Low-level laser treatment stimulates hair growth via upregulating Wnt10b and β-catenin expression in C3H/HeJ mice

Abstract

This study was conducted in order to evaluate the role of low-level laser treatment (LLLT) in hair growth in C3H/HeJ mice. Healthy C57BL/6 mice were randomly divided into two groups: with and without low-level laser treatment. The skin color of each mouse was observed each day. Skin samples were collected for H&E, immunofluorescence, PCR, and western blot analysis, to observe the morphology of hair follicles and detect the expression levels of Wnt10b and β-catenin. Observation of skin color demonstrated that black pigmentation started significantly earlier in the laser group than in the control group. Hair follicle number in both groups showed no difference; however, the hair follicle length presented a significant difference. Wnt10b protein was detected on the second day in hair matrix cells in the LLLT group but not in the control group. PCR and western blot results both illustrated that expression of Wnt10b and β-catenin was significantly higher in the LLLT group than in the control group. Our study illustrated that low-level laser treatment can promote hair regrowth by inducing anagen phase of hair follicles via initiating the Wnt10b/β-catenin pathway.

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Preclinical study of a cost-effective photodynamic therapy protocol for treating oral candidoses

Abstract

Photodynamic therapy (PDT) is a promising treatment for oral candidoses. Its use as an alternative to antifungals prevents several adverse effects, including microbial resistance. However, most PDT protocols do not employ devices and consumables commonly available in dental practice, thus influencing treatment affordability. This study aimed to determine the efficacy of a PDT method based on light curing units' blue LEDs combined to a plaque-disclosing composition (5% erythrosine) against C. albicans in culture and in a murine model of oral candidosis. Standard and resistant fungal strains were tested in vitro in planktonic and biofilm forms. PDT (pre-irradiation time periods: 30 and 60 s; irradiation time: 3 min) was compared to control conditions without light and/or erythrosine. Mice with induced oral candidosis (n = 40) randomly received PDT or similar control conditions with subsequent C. albicans count. These mice underwent histological analysis, as well as 12 healthy mice submitted to experimental treatments. PDT completely inactivated C. albicans planktonic cells and biofilm. Control conditions presented minor differences (ANOVA, p < 0.05), with mean values ranging from 5.2 to 6.8 log10 (UFC/mL). Infected mice presented no significant difference in C. albicans counts consequent to treatments (ANOVA, p = 0.721), although the PDT protocol was able to enhance the inflammatory infiltrate in healthy mice. It can be concluded that the tested PDT protocol can inactivate C. albicans but still needs further investigation in order to achieve efficacy and safety.

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Pasireotide in an insulin-requiring diabetic acromegalic patient without worsening of hyperglycemia

Summary

Long-acting pasireotide is an effective treatment option for acromegaly, but it is associated with hyperglycemia, which could impact its use in patients with diabetes. We present a case of a 53-year-old man with acromegaly and type 2 diabetes mellitus (glycated hemoglobin (HbA_1c): 7.5%), who refused surgery to remove a pituitary macroadenoma and enrolled in a Phase 3 clinical trial comparing long-acting pasireotide and long-acting octreotide in acromegalic patients. The patient initially received octreotide, but insulin-like growth factor 1 (IGF-1) levels remained elevated after 12 months (383.9 ng/mL; 193.0 ng/mL; reference range: 86.5–223.8 ng/mL), indicating uncontrolled acromegaly. He switched to pasireotide 40 mg and subsequently increased to 60 mg. Within 6 months, IGF-1 levels normalized (193.0 ng/mL), and they were mostly normal for the next 62 months of treatment with pasireotide (median IGF-1: 190.7 ng/mL). Additionally, HbA_1c levels remained similar to or lower than baseline levels (range, 6.7% to 7.8%) during treatment with pasireotide despite major changes to the patient's antidiabetic regimen, which included insulin and metformin. Uncontrolled acromegaly can result in hyperglycemia due to an increase in insulin resistance. Despite having insulin-requiring type 2 diabetes, the patient presented here did not experience a long-term increase in HbA_1c levels upon initiating pasireotide, likely because long-term control of acromegaly resulted in increased insulin sensitivity. This case highlights the utility of long-acting pasireotide to treat acromegaly in patients whose levels were uncontrolled after long-acting octreotide and who manage diabetes with insulin.

Learning points

Long-acting pasireotide provided adequate, long-term biochemical control of acromegaly in a patient with insulin-requiring type 2 diabetes mellitus who was unresponsive to long-acting octreotide.

Glycemic levels initially increased after starting treatment with pasireotide but quickly stabilized as acromegaly became controlled.

Long-acting pasireotide, along with an appropriate antidiabetic regimen, may be a suitable therapy for patients with acromegaly who also have insulin-requiring type 2 diabetes mellitus.

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Positive clinical outcome in a patient with recalcitrant bullous pemphigoid treated with rituximab and intravenous immunoglobulin

Summary

A 41-year-old white man was treated for bullous pemphigoid (BP) for 4 years, using high-dose prednisone as well as ciclosporin and mycophenolate mofetil. Sustained clinical improvement was not observed. He suffered several serious side effects. Consequently, he was treated with a combination of rituximab (RTX) and intravenous immunoglobulin (IVIg). He received 12 infusions of RTX in 6 months and monthly IVIg until the end of the therapy. Within 5 weeks of this therapy, appearance of new lesions ceased. Within 8 weeks, all previous lesions resolved and previous medications were discontinued. No hospitalizations, relapses, infections or other serious adverse events occurred. The high levels of pathogenic autoantibody decreased and have remained undetectable. After three infusions of RTX, CD19+ B cells were undetectable and returned to normal levels within 18 months. The patient remains in complete clinical remission off all systemic therapy and free of disease for a 20-month follow-up.

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Survival Differences in Women with and without Autologous Breast Reconstruction after Mastectomy for Breast Cancer

Background: Breast reconstruction (BR) is an option for women who are treated with mastectomy; however, there has been concern regarding the oncologic safety of BR. In this study, we evaluated recurrences and mortality in women treated with mastectomy and compared outcomes in those treated with mastectomy alone to those with mastectomy plus transverse rectus adbominis (TRAM) flap BR. Methods: The prospective cohort study included women treated with mastectomy at Women's College Hospital from 1987 to 1997. Women with TRAM flap BR were matched to controls based on age and year of diagnosis, stage, and nodal status. Patients were followed from the date of diagnosis until death or date of last follow-up. Hazard ratios were generated to compare cases and controls for outcome variables using Cox's proportional hazards models. Results: Of 443 women with invasive breast cancer, 85 subjects had TRAM flap BR. Sixty-five of these women were matched to 115 controls. The mean follow-up was 11.2 (0.4–26.3) years. There were no significant differences between those with and without BR with weight, height, or smoking status. Women with TRAM flap were less likely to experience a distant recurrence compared to women without a TRAM flap (relative risk, 0.42; P = 0.0009) and were more likely to be alive (relative risk, 0.54; P = 0.03). Conclusions: Women who elect for TRAM flap BR after an invasive breast cancer diagnosis do have lower rates of recurrences and mortality than women treated with mastectomy alone. This cannot be explained by differences in various clinical or lifestyle factors.

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Establishing Content Validity of the CLEFT-Q: A New Patient-reported Outcome Instrument for Cleft Lip/Palate

Background: The CLEFT-Q is a new patient-reported outcome instrument designed to measure outcomes that matter to patients. The aim of this qualitative study was to establish content validity of the CLEFT-Q in patients who differ by age and culture. Methods: Patients aged between 6 and 29 years were recruited from plastic surgery clinics in Canada, India, Ireland, the Philippines, the Netherlands and the United States. Healthcare providers and other experts participated in a focus group or provided individual feedback. Input was sought on all aspects of the CLEFT-Q (item wording, instructions, and response options), and to identify missing content. Patient interviews and expert feedback took place between September 2013 and September 2014. Results: Sixty-nine patients and 44 experts participated. The first draft of the CLEFT-Q consisted of 163 items measuring 12 constructs. The first round of feedback identified 92 items that required revision. In total, 3 rounds of interviews, and the involvement of an artist to create pictures for 17 items, were needed to establish content validity. At the conclusion of cognitive interviews, the CLEFT-Q consisted of 13 scales (total 171 items) that measure appearance, health-related quality of life, and facial function. The mean Flesch-Kincaid readability statistic for items was 1.4 (0 to 5.2). Conclusion: Cognitive interviews and expert review allowed us to identify items that required re-wording, re-conceptualizing, or to be removed, as well as any missing items. This process was useful for refining the CLEFT-Q scales for further testing.

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Carbon nanotubes: Culprit or witness of air pollution?

Publication date: Available online 15 May 2017
Source:Nano Today
Author(s): Jelena Kolosnjaj-Tabi, Henri Szwarc, Fathi Moussa
The notorious PM2.5 (2.5μm diameter particulate matters) that can reach human lungs, considered as responsible for most deleterious effects of air pollution, are now unmasked. Anthropogenic carbon nanotubes and other carbon nanoparticles have been unambiguously identified as the major components of PM2.5 in alveolar macrophages of Parisian children. Soot and diesel particulate matter have recognized detrimental health effects. However, information on the health effects of anthropogenic carbon nanotubes, which are the main components of PM2.5 found within human alveolar cells, is still lacking. While nanotechnologists are focused on applications with a profit, notably in the field of nano-biomedicine, the health effects of nano-particulate pollutants attract little of their attention. In an attempt to bridge the research gaps between cutting-edge nanotechnologies, environmental studies and biomedical approaches, this opinion paper attempts to inform the nanotechnology community about critical issues related to airborne anthropogenic carbon nanotubes. The question that has to be urgently addressed is whether carbon nanotubes are the main culprit or act only as nano-vectors of carcinogenic polycyclic aromatic hydrocarbons and other toxic gaseous pollutants.

Graphical abstract

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Water splitting dye-sensitized solar cells

Publication date: Available online 15 May 2017
Source:Nano Today
Author(s): Pengtao Xu, Nicholas S. McCool, Thomas E. Mallouk
Research in artificial photosynthesis is driven by the goal of creating low-cost, integrated systems for the direct conversion of solar energy to high energy density fuels. Water-splitting dye-sensitized solar cells can in principle leverage the successful architecture, spectral tunability, and high quantum efficiency of regenerative photovoltaic dye cells toward this goal. In this article, we review the current development of both dye-sensitized photoanodes and photocathodes for water splitting. A detailed discussion of the individual components of photoanodes and photocathodes – semiconductors, sensitizers, and catalysts – is presented. We review experiments on the electron transfer kinetics that control the efficiency of water splitting, and highlight recent research on electrode architectures that can improve both the efficiency and stability of water-splitting dye cells.

Graphical abstract

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A rounded opacity silhouetting the left heart border and hilum

Pericardial incidentaloma: benign pericardial cyst

από Lin, A. N., Lin, S., Lin, K., Raju, F. στο BMJ Case Reports Last 6 Issues

Μετάφραση άρθρου

Description

A 73-year-old woman with hypertension and atrial fibrillation presented with head and neck injury after mechanical fall. During workup, chest X-ray anteroposterior view (figure 1) revealed a rounded opacity silhouetting the left heart border and hilum. Subsequent contrast-enhanced CT of the chest showed single, 6.4 cm, rounded, well-defined, thin-walled, non-enhanced, low attenuated (–20 and 20 Hounsfield Unit) and homogenous cyst-like structure at the left mediastinum connected to pericardial recesses and not attached to adjacent structures (figure 2A–C). Transthoracic echocardiogram ruled out left ventricular aneurysm, aortic aneurysm, solid tumour and outflow tracts obstruction. Although bronchogenic cyst, oesophageal duplication cyst, thymic tumour and mediastinal lymphoma were considered as possible differentials, radiological features such as CT appearance, homogenous attenuation, unrelated to the underlying structures favoured pericardial cyst. Since patient was asymptomatic, patient and family member were unwilling to undergo surgical removal and pathological confirmation. Follow-up with non-enhanced CT of...

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Novel sulfonamide-containing 2-indolinones that selectively inhibit tumor-associated alpha carbonic anhydrases

Publication date: Available online 15 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Nilgün Karalı, Atilla Akdemir, Füsun Göktaş, Pınar Eraslan Elma, Andrea Angeli, Merih Kızılırmak, Claudiu T. Supuran
Human carbonic anhydrases IX and XII are upregulated in many tumors and form a novel target for new generation anticancer drugs. Here we report the synthesis of novel 2-indolinone derivatives with the sulfonamide group as a zinc binding moiety. Enzyme inhibition assays confirmed that the compounds showed selectivity against hCA IX and XII over the widely distributed off-targets hCA I and II. Molecular modelling studies were performed to suggest modes of binding for these compounds.

Graphical abstract

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Transient hemiparaesthesias and dysarthria

Mitral Stenosis

από Oehler, A. C., Sullivan, P. D., Mansoor, A. M. στο BMJ Case Reports Last 6 Issues

Μετάφραση άρθρου

Description

A previously healthy 29-year-old Mexican woman presented to an emergency department with transient hemiparaesthesias and dysarthria. There was no evidence of stroke on cross-sectional imaging of the head, and she was discharged without a clear diagnosis. Two days later, she returned with acute abdominal pain. Abdominal imaging revealed complete occlusion of the right renal artery, prompting emergency embolectomy. Following the procedure, she developed acute haemoptysis, dyspnoea and hypoxaemia. Chest imaging demonstrated evidence of pulmonary venous hypertension. Cardiac auscultation revealed an opening snap followed by a diastolic murmur with presystolic accentuation. These sounds were better appreciated in combination with phonocardiography, a technique supplanted by echocardiography in the 1970s1 that visualised heart sounds (video 1). An echocardiogram confirmed the presence of mitral stenosis (MS), unifying the syndrome of embolic phenomena, haemoptysis and pulmonary hypertension. She underwent successful mitral valve replacement and has since returned to normal...

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Assessment of perception, experience, and information-seeking behavior of the public of Ras Al-Khaimah, United Arab Emirates, toward usage and safety of complementary and alternative medicine

Sathvik Belagodu Sridhar, Atiqulla Shariff, Nour Al Halabi, Rand Sarmini, Lubab Arkan Harb

Journal of Pharmacy And Bioallied Sciences 2017 9(1):48-55

Aims and Objectives: This study was conducted to identify the different types of complementary and alternative medicine (CAM) used, reasons for the use of CAM, and the perceptions, experience, and information seeking-behavior toward usage and safety of CAM by the general public of Ras Al-Khaimah, UAE. Materials and Methods: This was a prospective cross-sectional study. A validated, self-administered, or interviewer-assisted survey questionnaire was used to collect the data. Data from 403 respondents satisfying inclusion criteria were collected and were analyzed using the Statistical Package for the Social Sciences version 24.0. Results: A majority of the respondents (218 [54.1%]) were females. The most commonly (210 [52.1%]) used CAM among the study respondents was herbal medicine. A total of 91 (22.6%) of the survey respondents mentioned that they receive conventional medications along with their CAM. Majority (213 [52.9%]) of the survey respondents opted for CAM to prevent illness. Good number (208 [51.6%]) of the survey respondents mentioned that CAM usage was beneficial in improving their health condition, and they (216 [53.6%]) do believe it as safe and effective. However, a small group (26 [6%]) of respondents reported side effects or complications with the use of CAM. Conclusion: Widespread use of CAM for different medical problems was evident in our study. Although majority of the CAM users believe it as safe and effective, CAM usage should be discussed with the health-care providers to understand the safety issues involved in the use of majority of CAM.

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Modulatory effects of Decalepis hamiltonii extract and its compounds on the antioxidant status of the aging rat brain

Ramachandregowda Sowbhagya, Siddhaghatta Kariyappa Anupama, Dundaiah Bhagyalakshmi, Santosh Anand, Tekupalli Ravikiran

Journal of Pharmacy And Bioallied Sciences 2017 9(1):8-15

Objective: The present study was aimed to investigate the neuroprotective effects of Decalepis hamiltonii (Dh) aqueous root extract and its compounds against age-related oxidative stress (OS) in the discrete regions of the rat brain. Materials and Methods: Male Wistar albino rats of 4- and 22-month-old were divided into control and six supplemented groups. The supplemented groups were orally administered with ellagic acid (EA), 4-hydroxyisophthalic acid (4-HIA), and Dh extract for 30 days. Results: Age-related decrease in antioxidant enzyme activities was noticed. The hippocampus was found to be more vulnerable to OS as seen by the elevation in the OS markers. Supplementation of the Dh extract, EA, and 4-HIA was found to be effective in up-regulating the antioxidant status. However, the extent of up-regulation was more evident in Dh supplemented animals. Conclusion: Our results suggest that Dh extract and its compounds exhibit neuroprotective effects against age-related OS and can be used as a dietary therapeutic intervention for the treatment of neurological disorders.

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Estimation of guggulsterone E and Z in the Guggul-based commercial formulations using high-performance thin-layer chromatography

Pramod Kumar Sairkar, Anjana Sharma, NP Shukla

Journal of Pharmacy And Bioallied Sciences 2017 9(1):1-7

Background: Guggulsterone (GS) is a plant steroid and bioactive compound present in gum Guggul of Commiphora wightii. An Indian herbal medicine system "Ayurveda" has a long history of use of gum Guggul and plant extract of C. wightii as medicine for the treatment of various illnesses. Complex nature, low availability, and inconsistency of phytoconstituents make its analysis of difficult tasks. Aims: In this work, six different Guggul-based herbal formulations were examined for estimation of GS and their isomers (E and Z) through high-performance thin-layer chromatography technique. Materials and Methods: For that various concentrations of standard E-GS and Z-GS (50 ng–250 ng/spot) with samples (20 μg/spot) were applied on silica gel coated aluminum plate and developed with the mobile phase of toluene: ethyl acetate: formic acid: methanol (6:2:1:0.5). The scanning was performed at 254 nm wavelength and the absorbance (scan) spectrum of E-GS and Z-GS peak was generated at 200 nm–400 nm wavelength range. Results and Conclusions: Rf value and scan spectrum pattern of the samples reveal that they contain either one form of GS (E-GS, Z-GS) or both. The quantity of E-GS and Z-GS within the samples was ranged from 0.230 ± 0.0040–0.926 ± 0.0168% to 0.537 ± 0.0026–0.723 ± 0.0177%, respectively.

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Moisture sorption–desorption characteristics and the corresponding thermodynamic properties of carvedilol phosphate

Ravikiran Allada, Arthanareeswari Maruthapillai, Kamaraj Palanisamy, Praveen Chappa

Journal of Pharmacy And Bioallied Sciences 2017 9(1):16-21

Aims: Carvedilol phosphate (CDP) is a nonselective beta-blocker used for the treatment of heart failures and hypertension. In this work, moisture sorption–desorption characteristics and thermodynamic properties of CDP have been investigated. Materials and Methods: The isotherms were determined using dynamic vapor sorption analyzer at different humidity conditions (0%–90% relative humidity) and three pharmaceutically relevant temperatures (20°C, 30°C, and 40°C). The experimental sorption data determined were fitted to various models, namely, Brunauer–Emmett–Teller; Guggenheim-Anderson-De Boer (GAB); Peleg; and modified GAB. Isosteric heats of sorption were evaluated through the direct use of sorption isotherms by means of the Clausius-Clapeyron equation. Statistical Analysis Used: The sorption model parameters were determined from the experimental sorption data using nonlinear regression analysis, and mean relative percentage deviation (P), correlation (Correl), root mean square error, and model efficiency were considered as the criteria to select the best fit model. Results: The sorption–desorption isotherms have sigmoidal shape – confirming to Type II isotherms. Based on the statistical data analysis, modified GAB model was found to be more adequate to explain sorption characteristics of CDP. It is noted that the rate of adsorption and desorption is specific to the temperature at which it was being studied. It is observed that isosteric heat of sorption decreased with increasing equilibrium moisture content. Conclusions: The calculation of the thermodynamic properties was further used to draw an understanding of the properties of water and energy requirements associated with the sorption behavior. The sorption–desorption data and the set of equations are useful in the simulation of processing, handling, and storage of CDP and further behavior during manufacture and storage of CDP formulations.

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Prevalence, pattern, and correlates of alcohol misuse among male patients attending rural primary care in India

Sanghamitra Pati, Subhashisa Swain, Sandeep Mahapatra, Mohammad Akhtar Hussain, Sandipana Pati

Journal of Pharmacy And Bioallied Sciences 2017 9(1):66-72

Background: There are limited data available on how the problem of alcohol use is detected in primary care setting in India. Particularly in Odisha, it has not been investigated yet. This study was conducted to determine the prevalence of drinking, drinking patterns, and quitting behavior among the male patients visiting a primary health-care facility in a district of Odisha. Methodology: A cross-sectional study was conducted among patients attending community health center (CHC), Buguda in the state of Odisha, India, from December 1, 2014, to February 31, 2015. Patients above 18 years of age, conscious, and willing to participate in the study were included in the study, while those with cognitive impairment and critically ill were excluded from the study. All eligible consecutive patients attending outpatient department of CHC were invited to participate while they came out after physician's consultation. A pilot study was conducted prior to the study. Informed verbal consent from each patient was obtained before the interview. The study was approved by the Institutional Ethics Committee of Indian Institute of Public Health, Bhubaneswar. Results: A total of 431 patients were interviewed. Our study showed 38% (95% confidence interval [CI]: 33.5%–42.7%) of respondents were alcoholic and of those 60% (95% CI: 51.4%–66.5%) were hazardous drinkers. One in five patients had a history of alcoholics in their family, and a similar proportion of participants were heavy workers. Smokers were eight times (adjusted odds ratio [AOR] =7.56; 4.03–14.52) more likely to be alcoholics as compared to nonsmokers (P

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Influence of milling process on efavirenz solubility

Erizal Zaini, Deni Wahyu, Maria Dona Octavia, Lili Fitriani

Journal of Pharmacy And Bioallied Sciences 2017 9(1):22-25

Introduction: The aim of this study was to investigate the influence of the milling process on the solubility of efavirenz. Materials and Methods: Milling process was done using Nanomilling for 30, 60, and 180 min. Intact and milled efavirenz were characterized by powder X-ray diffraction, scanning electron microscopy (SEM), spectroscopy infrared (IR), differential scanning calorimetry (DSC), and solubility test. Results: The X-ray diffractogram showed a decline on peak intensity of milled efavirenz compared to intact efavirenz. The SEM graph depicted the change from crystalline to amorphous habit after milling process. The IR spectrum showed there was no difference between intact and milled efavirenz. Thermal analysis which performed by DSC showed a reduction on endothermic peak after milling process which related to decreasing of crystallinity. Solubility test of intact and milled efavirenz was conducted in distilled water free CO2with 0.25% sodium lauryl sulfate media and measured using high-performance liquid chromatography method with acetonitrile: distilled water (80:20) as mobile phases. The solubility was significantly increased (P

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Prevalence of exposure to secondhand smoke among higher secondary school students in Ernakulam District, Kerala, Southern India

PS Rakesh, Jishnu Satheesh Lalu, K Leelamoni

Journal of Pharmacy And Bioallied Sciences 2017 9(1):44-47

Introduction: The association between secondhand smoke and health outcomes, such as frequent respiratory infections, ischemic heart disease, lung cancer, asthma, and stroke, has long been established. The study aimed to estimate the prevalence of secondhand smoking exposure among higher secondary school students in Ernakulam district, Kerala, Southern India. Materials and Methods: A structured questionnaire was administered to all students from four randomly selected higher secondary schools in Ernakulam district. Descriptive statistics was done using frequencies and percentages. Univariate and multivariate analyses were done for factors associated with household exposure to tobacco smoke generating odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 629 students participated in the study. The prevalence of ever smokers was 11.9% and of current smokers was 5.2%. Among the study participants, 23.2% were exposed to secondhand smoking from a family member and 18.8% from friends. Lower educational status of father was associated with the household exposure to secondhand smoke (adjusted OR 4.51 [95% CI 1.66–12.22]). More than half of the study participants (56.3%) reported that they were exposed to cigarette smoke in past 1 week in a public place and 10.2% in closed public places. Nearly one-third of the students reported that they have seen somebody smoking inside school campus in the past 30 days. Conclusion: Exposure to secondhand smoke at home, schools, and public places was higher among the late adolescent higher secondary school students in Ernakulam district. The findings underscore the urgent need for increased efforts to implement the strategies to reduce secondhand smoke exposure among adolescents.

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Chromatographic isolation and spectroscopic identification of phytoconstituents of jujuba seeds (Zizyphus jujuba Mill.)

Md Manowwar Alam, Abuzer Ali, Mohammad Ali, Showkat R Mir

Journal of Pharmacy And Bioallied Sciences 2017 9(1):26-32

Background: The seeds of Zizyphus jujuba Mill. (Rhamnaceae) are astringent, aphrodisiac, tonic; used to cure cough, asthma, vomiting, burning sensation, biliousness, leucorrhoea, and eye infections in traditional systems of medicine. Materials and Methods: The methanol extract of seeds of Z. jujuba was partitioned into petroleum ether and water soluble fractions. Isolation of compounds was performed by silica gel column chromatography. The structures of isolated compounds were established on the basis of spectral studies and chemical reactions. Results: Chromatographic separation of methanolic extract of seeds yielded three new phyto-constituents characterized as 3, 5, 7-trimethoxy-8, 3′, 4′, 5′-tetrahydroxy flavone-6-oxy hexahydrobisabolene ether (4), 1, 9-dihydroxy tetrahydrogeranyl-8-oxy-O-β-D-glucuronopyranoside (5) and terahydrogeranyl-8-oxy-O-β-D-glucuronopyranosyl (2a→1b)-O-β-D-glucofuranosyl (2b→1c)-O-β-D-glucofuranosyl (2c→1d)-O-β-D-glucopyranosyl (2d→1e)-O-β-D-glucopyranosyl (2c→f)-O-β-D-glucopyranosyl-2f-benzoate (6) along with five known compounds, palmitoyl palmitoleoyl arachidoyl glyceride (1), tetratriacontenoic acid (2), palmitoyl oleoyl linolenoyl glyceride (3), hexanyl tetraglucoside (7) and pentasaccharide (8). Conclusion: This is the first report of saturated monoterpene and sesquiterpene derivatives from jujuba seeds.

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Efficacy and tolerability of antihypertensive drugs in diabetic and nondiabetic patients

Maria Aslam, Mobasher Ahmad, Fizza Mobasher

Journal of Pharmacy And Bioallied Sciences 2017 9(1):56-65

Objectives of the Study: The aim of the study was to compare the efficacy and tolerability of different classes of antihypertensive drugs in diabetic and nondiabetic patients (NDPs) with essential hypertension. Material and Methods: The study was conducted in Mayo Hospital, Punjab Institute of Cardiology, and National Defence Hospital, Lahore, Pakistan, on 200 hypertensive patients with diabetes and 230 hypertensive patients without (Three hospitals) diabetes. Both male and female patients of age between 30 and 80 years with systolic blood pressure (SBP) above 130 mmHg and diastolic blood pressure (DBP) above 80 mmHg were enrolled in the study. Angiotensin converting enzyme inhibitors (ACEI), beta-blocker (βB), calcium-channel blocker (CCB), diuretics (D), angiotensin receptor blocker (ARB) as well as α-blocker classes of antihypertensive drugs were used. These drugs were used as monotherapy as well as combination therapy. The study was conducted for 4 months (July–October). After 4 months, patients were assessed for efficacy by monitoring blood pressure (BP) and tolerability by assessing safety profile on renal function, liver function as well as lipid profile. Results: Significant control in mean BP by all drug groups was observed in "both groups that is patients with diabetes and without diabetes." The efficacy and tolerability data revealed that in diabetic patients with hypertension, the highest decrease in SBP and DBP was observed using monotherapy with ACEI, two-drug combination therapy with ACEI plus diuretic, ARBs plus diuretic, ACEI plus CCBs, three-drug combination therapy with ACEI plus CCBs plus diuretic, and four drug combination therapy with ACEI plus CCBs plus diuretic plus βBs, ARB's plus CCBs plus diuretic plus βBs while in NDPs, monotherapy with diuretic, two-drug combination therapy with ACEI plus CCBs, ACEI plus βBs, three-drug combination therapy with βBs plus ACEI plus D was found more effective in controlling SBP as well as DBP. Adverse effects observed were dry cough, pedal edema, dizziness, muscular cramps, constipation, palpitations, sweating, vertigo, tinnitus, paresthesia, and sexual dysfunction. Conclusion: All classes of antihypertensives were found to control blood pressure significantly in both groups of patients that is diabetic patients with hypertesion and non-diabetic patients with hypertension.

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Evaluation of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage

R Sunil Kumar, Ramesh Balenahalli Narasingappa, Chandrashekar G Joshi, Talakatta K Girish, Ummiti JS Prasada Rao, Ananda Danagoudar

Journal of Pharmacy And Bioallied Sciences 2017 9(1):33-43

Objective: The present study aims to evaluate antioxidants and protective role of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage. Materials and Methods: The total and profiles of flavonoids were identified and quantified through reversed-phase high-performance liquid chromatography. In vitro antioxidant activity was determined using standard antioxidant assays. The protective role of C. tora extracts against oxidative stress-induced DNA and cell membrane damage was examined by electrophoretic and scanning electron microscopic studies, respectively. Results: The total flavonoid content of CtEA was 106.8 ± 2.8 mg/g d.w.QE, CtME was 72.4 ± 1.12 mg/g d.w.QE, and CtWE was 30.4 ± 0.8 mg/g d.w.QE. The concentration of flavonoids present in CtEA in decreasing order: quercetin >kaempferol >epicatechin; in CtME: quercetin >rutin >kaempferol; whereas, in CtWE: quercetin >rutin >kaempferol. The CtEA inhibited free radical-induced red blood cell hemolysis and cell membrane morphology better than CtME as confirmed by a scanning electron micrograph. CtEA also showed better protection than CtME and CtWE against free radical-induced DNA damage as confirmed by electrophoresis. Conclusion: C. tora contains flavonoids and inhibits oxidative stress and can be used for many health benefits and pharmacotherapy.

http://ift.tt/2qLywUF

Marfan syndrome

T Sivasankari, Philips Mathew, Ravi David Austin, Sakthi Devi

Journal of Pharmacy And Bioallied Sciences 2017 9(1):73-77

Marfan syndrome (MFS) is the autosomal dominant-inherited multisystem connective-tissue disorder, with a reported incidence of 1 in 10,000 individuals and equal distribution in both genders. The main clinical manifestation of this disorder consists of an exaggerated length of the upper and lower limbs, hyperlaxity, scoliosis, alterations in the cardiovascular and pulmonary systems, and atypical bone overgrowth. Orofacial manifestations such as high-arched palate, hypodontia, long narrow teeth, bifid uvula, mandibular prognathism, and temporomandibular disorders are also common. Early diagnosis of MFS is essential to prevent the cardiovascular complications and treatment of orofacial manifestations, thus to increase the quality of life of the patient.

http://ift.tt/2qLKTjG

Detection of HER2 Amplification in Circulating Tumor Cells of HER2-Negative Gastric Cancer Patients

Abstract

A key to the successful use of targeted cancer therapy is the ability to preselect patients who are likely to benefit from the treatment according to molecular markers. Assessment for predicting therapy response is mostly done using tumor biopsies. However, these might not truly represent all of the patient's malignant cells because of tumor heterogeneity and/or clonal evolution during disease progression. One potential strategy that can complement primary tumor biopsy is the analysis of circulating tumor cells (CTCs). In this study, we analyzed CTCs of patients with gastric cancer (GC) to find those who were likely to benefit from trastuzumab therapies. We developed an imaging-based method that enabled CTC identification simultaneously with evaluation of HER2 gene amplification (the 3D–IF-FISH method). Then we performed a study enrolling 101 GC patients in whom we analyzed CTCs by both 3D–IF-FISH and an FDA-approved CellSearch system. As compared with the CellSearch system, 3D–IF-FISH methods identified a higher number of patients whose primary tumors were HER2- but who had HER2+ CTCs, suggesting that the 3D–IF-FISH method is effective in preselecting patients for trastuzumab therapies. To demonstrate this, we performed an exploratory clinical study to evaluate the clinical benefits of trastuzumab treatment for advanced GC patients (n = 15) whose primary tumors were HER2-, but whose CTCs showed HER2 amplification. An interim evaluation after the first stage showed that these preselected patients had response rates comparable to those reported in the trastuzumab-plus-chemotherapy arm of the ToGA study. The present study offers a new, non-invasive strategy to select patients who are likely to benefit from trastuzumab-based therapies, despite their primary biopsy being HER2-negative. (UMIN ID: UMIN000008622).

http://ift.tt/2rkSgLL

The development and use of a drug-induced immunosuppressed rat-model to screen Phela for mechanism of immune stimulation

Publication date: 12 July 2017
Source:Journal of Ethnopharmacology, Volume 206
Author(s): Makhotso Rose Lekhooa, Andrew Walubo, Jan B. du Plessis, Motlalepula Gilbert Matsabisa
Ethnopharmacology relevancyPhela, is code name for a medicinal product made from four South African traditional medicinal plants (Clerodendrum glabrum E. Mey, Polianthes tuberosa (Linn.), Rotheca myricoides (Hochst.) Steane & Mabb. and Senna occidentalis (L.) Link). All these plants have established traditional use in a wide spectrum of diseases. Phela is under development for use as an immune booster in immunocompromised patients, which includes patients with the human immunodeficiency virus (HIV). Already several studies, both pre-clinical and clinical, have shown that Phela is a safe and effective immune booster. Despite some studies on the action of Phela, the mechanism of action by Phela is still not known. Understanding the mechanism of action will enable safer and effective use of the drug for the right indications. Unfortunately, there is no well characterized test-system for screening products for immune stimulant activity. Therefore, the objective of this study was to use Phela as the test article, to develop and validate a rat-model (test system) by which to screen medicines for immune stimulant activity.Material and methodsFirst, the batch of Phela used was authenticated by high performance liquid chromatography (HPLC) techniques; analytical methods for the immunosuppressant drugs, cyclosporine A (CsA), cyclophosphamide (CP) and dexamethasone (Dex) were developed and validated; and a slide-A-Lyzer dialysis was used to test for potential interactions in rat plasma of Phela with CsA, CP and Dex. Thereafter, using Sprague Dawley (SD) rats and in separate experiments, the effective dose of Phela in the study animals was determined in a dose ranging study with levamisole, a known immune stimulant as the positive control; the appropriate doses for immunosuppression by CsA, CP and Dex were determined; the time to reach 'established immunosuppression' with each drug was determined (it was also the time for intervention with Phela); and eventually, the effect of Phela on the immune system was tested separately for each drug induced immunosuppression. The immune system was monitored by observing for changes in plasma profiles of IL-2, IL-10, IgG, IgM, CD4 and CD8 cell counts at appropriate intervals, while in addition to function tests, the kidneys, liver, spleen, thymus, were weighed and examined for any pathology.ResultsThe chromatographic fingerprint certified this batch of Phela as similar to the authentic Phela. There was no significant interaction between Phela and CsA, CP and Dex. The effective dose of Phela was determined to be 15.4mg/kg/day. Phela led to a moderate increase in the immune parameters in the normal rats. Co-administration of Phela 15mg/kg/day orally for 21 days with CsA led to stoppage and reversal of the immunosppressive effects of CsA that were exhibited as increased IL-2, IL-10, CD4 and CD8 counts, implying that Phela stimulates the cell mediate immunity (CMI). For CP, Phela led to stoppage and reversal, though moderate, of CP-induced suppression of IL-10, IgM and IgG only, implying that Phela stimulates the humoral immunity (HI) too. Phela had no effect on Dex induced immunosuppression. Stimulation of the CMI means that Phela clinical testing programme should focus on diseases or disorders that compromise the CMI, e.g., HIV and TB. The stimulation of the HI immunity means that Phela may stimulate existing memory cells to produce antibodies.ConclusionThe present study has revealed Phela's mechanism of action as mainly by stimulation of the CMI, implying that the use of Phela as immune booster in HIV patients is appropriate; and that using Phela as the test product, a rat model for screening medicinal products for immune stimulation has been successfully developed and validated, with a hope that it will lead to the testing of other related medicinal products.

Graphical abstract

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Tropical ulcer plant treatments used by Papua New Guinea's Apsokok nomads

Publication date: 9 June 2017
Source:Journal of Ethnopharmacology, Volume 205
Author(s): Thomas A.K. Prescott, Peter Homot, Fionnuala T. Lundy, Rui Fang, Sheila Patrick, Rodrigo Cámara-Leret, Robert Kiapranis
Ethnopharmacological relevanceThe tropical ulcer is a debilitating bacterial infection that is common in Papua New Guinea. Deploying healthcare infrastructure to remote and inaccessible rainforest locations is not practical, therefore local plants may be the best treatment option. Here we present an ethnobotanical survey of the tropical ulcer plant medicines used by the semi-nomadic Apsokok who roam the remote central mountains of Papua New Guinea's West New Britain Province. In vitro biological activity in assays relevant to tropical ulcer wound healing is also presented.Materials and methodsFocus groups and semi-structured interviews were used to acquire information on the uses of plants, vouchers of which were identified by comparison with authentic herbarium specimens. Antibacterial disc diffusion assays with Staphylococcus aureus and Fusobacterium ulcerans, MMP-9 enzyme inhibition and dermal fibroblast stimulation assays were carried out on plant saps and aqueous extracts of plant material. LC-MS was used to identify known plant metabolites.ResultsThe ethnobotanical survey identified sixteen species that were used to treat tropical ulcers, all of which were applied topically. A subset of twelve species were investigated further in vitro. Four species produced zones of inhibition with S. aureus, all 12 species provided low level inhibition of MMP-9 and 8 species stimulated dermal fibroblast proliferation, although cytotoxicity occurred at higher concentrations. The extract of Homalium foetidum Benth. inhibited S. aureus and MMP-9 while at lower sub-cytotoxic concentrations stimulated fibroblast proliferation. Trans-3-O-p-coumaroylquinic acid cis-3-O-p-coumaroylquinic acid were detected in the aqueous extract of H. foetidum.ConclusionsTopical application of plant saps to wounds results in very high localised concentrations of plant metabolites which is likely to result in inhibition of MMP proteases. H. foetidum is a candidate plant for tropical ulcer treatment in remote areas.

Graphical abstract

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Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib

Background.

This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice.

Materials and Methods.

We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan.

Results.

The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7–14.2) and 26.9 months (21.2–32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] ≥2), smoking index (≥20 pack-years), liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV) infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3 [0.11–0.83], p = .02; 2.69 [1.60–4.51], p < .001; 1.92 [1.24–2.97], p = .003; 2.26 [1.34–3.82], p = .002; 3.38 [1.85–7.78], p < .001, respectively). However, brain metastasis (BM) at initial diagnosis or intracranial progression during gefitinib treatment had no impact on OS (1.266 [0.83–1.93], p = .275 and 0.75 [0.48–1.19], p = .211, respectively).

Conclusion.

HCV infection, performance status (ECOG ≥2), newly diagnosed advanced NSCLC without prior operation, and liver metastasis predicted poor OS in EGFR mutation-positive advanced NSCLC patients treated with first-line gefitinib; however, neither BM at initial diagnosis nor intracranial progression during gefitinib treatment had an impact on OS. The Oncologist 2017;22:1–9

Implications for Practice.

The finding that chronic hepatitis C virus (HCV) infection might predict poor overall survival (OS) in epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer (NSCLC) patients treated with first-line gefitinib may raise awareness of benefit from anti-HCV treatment in this patient population. Brain metastasis in the initial diagnosis or intracranial progression during gefitinib treatment is not a prognostic factor for OS. This study, which enrolled a real-world population of NSCLC patients, including sicker patients who were not eligible for a clinical trial, may have impact on guiding usual clinical practice.

http://ift.tt/2rkQVVk

Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture-Based Assay of Circulating Tumor DNA

ALK rearrangements have been observed in 0.05%–2.5% of patients with colorectal cancers (CRCs) and are predicted to be oncogenic drivers largely mutually exclusive of KRAS, NRAS, or BRAF alterations. Here we present the case of a patient with metastatic CRC who was treatment naïve at the time of molecular testing. Initial ALK immunohistochemistry (IHC) staining was negative, but parallel genomic profiling of both circulating tumor DNA (ctDNA) and tissue using similar hybrid capture-based assays each identified an identical STRN-ALK fusion. Subsequent ALK IHC staining of the same specimens was positive, suggesting that the initial result was a false negative. This report is the first instance of an ALK fusion in CRC detected using a ctDNA assay. The Oncologist 2017;22:1–6

Key Points.

Current guidelines for colorectal cancer (CRC) only recommend genomic assessment of KRAS, NRAS, BRAF, and microsatellite instability (MSI) status.

ALK rearrangements are rare in CRC, but patients with activating ALK fusions have responded to targeted therapies

ALK rearrangements can be detected by genomic profiling of ctDNA from blood or tissue, and this methodology may be informative in cases where immunohistochemistry (IHC) or other standard testing is negative.

http://ift.tt/2qLraR7

Immunotherapy for Head and Neck Squamous Cell Carcinoma: A Review of Current and Emerging Therapeutic Options

Advances in the field of cancer immunotherapy have occurred rapidly over the past decade. Exciting results from clinical trials have led to new treatment options and improved survival for patients with a myriad of solid tumor pathologies. However, questions remain unanswered regarding duration and timing of therapy, combination regimens, appropriate biomarkers of disease, and optimal monitoring of therapeutic response. This article reviews emerging immunotherapeutic agents and significant clinical trials that have led to advancements in the field of immuno-oncology for patients with head and neck squamous cell carcinoma. The Oncologist 2017;22:1–15

Implications for Practice: This review article summarizes recently developed agents that harness the immune system to fight head and neck squamous cell carcinoma. A brief review of the immune system and its role in cancer development is included. Recently completed and emerging therapeutic trials centering on the immune system and head and neck cancer are reviewed.

http://ift.tt/2rkFmO7

A Case of Metastatic Atypical Neuroendocrine Tumor with ALK Translocation and Diffuse Brain Metastases

A challenge in precision medicine requires identification of actionable driver mutations. Critical to such effort is the deployment of sensitive and well-validated assays for mutation detection. Although identification of such alterations within the tumor tissue remains the gold standard, many advanced non-small cell lung cancer cases have only limited tissue samples, derived from small biopsies or fine-needle aspirates, available for testing. More recently, noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA) have become an alternative method for identifying molecular biomarkers and screening patients eligible for targeted therapies. In this article, we present a case of a 52-year-old never-smoking male who presented with widely metastatic atypical neuroendocrine tumor to the bones and the brain. Molecular genotyping using DNA harvested from a bone metastasis was unsuccessful due to limited material. Subsequent ctDNA analysis revealed an ALK translocation. The clinical significance of the mutation in this particular cancer type and therapeutic strategies are discussed. The Oncologist 2017;22:1–6

Key Points.

To our knowledge, this index case represents the first reported ALK translocation identified in an atypical carcinoid tumor.

Liquid biopsy such as circulating tumor DNA is a feasible alternative platform for identifying sensitizing genomic alterations.

Second-generation ALK inhibitors represent a new paradigm for treating ALK-positive patients with brain metastases.

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Medroxyprogesterone acetate drives M2 macrophage differentiation toward a phenotype of decidual macrophage

Publication date: Available online 15 May 2017
Source:Molecular and Cellular Endocrinology
Author(s): Yung-Chieh Tsai, Joseph T. Tseng, Chia-Yih Wang, Mei-Tsz Su, Jyun-Yuan Huang, Pao-Lin Kuo
M1 macrophage differentiation plays a crucial role in enhanced inflammation during pregnancy, which may lead to pregnancy complications. Therefore, modulation of macrophage differentiation toward the M2 phenotype is desirable to ensure a successful pregnancy. Medroxyprogesterone acetate (MPA) is a potent progestin with an anti-inflammatory property, but its effect on macrophage differentiation is unknown. This study aimed to examine whether MPA can induce an M2 macrophage differentiation by using the human monocytes cell line THP-1 or primary monocytes. THP-1 cells were primed with phorbol-12-myristate-13 acetate (PMA) to initiate macrophage differentiation. By incubating with MPA, the cells (denoted as MPA-pTHP-1) underwent M2 macrophage differentiation with downregulations of CD11c, IL-1β and TNF-α, and upregulations of CD163 and IL-10; while cells incubated with progesterone (P4) did not show the M2 phenotype. Primary monocytes treated with MPA also had the same M2 phenotype. Moreover, M1 macrophages derived from IFN-γ/LPS-treated THP-1 cells, which had high levels of IL-1b and iNOS, and low levels of IL-10 and IDO, were reversed to the M2 phenotype by the MPA treatment. We also found that the MPA-pTHP-1 promoted the decidualization of endometrial stromal cells and the invasion of trophoblast cells. To mimic conditions of exposure to various pathogens, MPA-pTHP-1 cells were stimulated by different types of TLR ligands. We found they produced lower levels of IL-1β and TNF-α, as well as a higher level of IL-10, compared to untreated cells. Finally, we found the level of phosphorylated ERK in the MPA-pTHP-1 cells was increased, but its IL-10 production was suppressed by either the progesterone/glucocorticoid antagonist (Mifepristone) or MEK inhibitor (U0126). Taken together, MPA could drive monocyte differentiation toward an M2 phenotype that mimics decidual macrophages. This finding holds great potential to combat chronic endometrial inflammation.



http://ift.tt/2pEzYYJ

Reproductive factors, exogenous hormone use, and risk of pancreatic cancer in postmenopausal women

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Geoffrey C. Kabat, Victor Kamensky, Thomas E. Rohan
IntroductionThe epidemiologic literature on menstrual and reproductive factors associated with pancreatic cancer has yielded weak and inconsistent evidence of an association. Furthermore, few cohort studies have examined the association of exogenous hormone use, including type and duration, with this disease. The aim of this study was to assess the association of these exposures with risk of pancreatic cancer in a large cohort of postmenopausal women.MethodsWe used data from the Women's Health Initiative on 1003 cases of pancreatic cancer diagnosed among 158,298 participants over 14.3 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations of interest.ResultsBeing parous vs. nulliparous was associated with reduced risk (HR=0.84, 95% CI 0.70–1.00), and women who had 1–2 and 3–4 births were at decreased risk compared to nulliparous women, whereas women who had >5 births showed no decrease in risk. Compared to women who gave birth between the ages of 20–29, women who gave birth at age 30 or above were at increased risk (HR 1.23, 95% CI 1.00–1.53, p for trend 0.003). Other reproductive factors and exogenous hormone use were not associated with risk.ConclusionsTogether with the existing literature on this topic, our results suggest that reproductive and hormonal exposures are unlikely to play an important role in the etiology of pancreatic cancer.



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Anticipatory Coarticulation and the Minimal Planning Unit of Speech.

Author: Liu, Qiang; Kawamoto, Alan H.; Payne, Katherine K.; Dorsey, Genvieve N.

DOI: 10.1037/xhp0000443

Publication Date: POST AUTHOR CORRECTIONS, 11 May 2017

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The Long and Winding Road After FDA Approval: A Medical Device Industry Perspective.

Author: Stein, Kenneth M. MD

Page: 1877-1878

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India and the Coronary Stent Market: Getting the Price Right.

Author: Wadhera, Priya MS; Alexander, Thomas MD; Nallamothu, Brahmajee K. MD, MPH

Page: 1879-1881

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Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus.

Author: Young, Lawrence H. MD; Viscoli, Catherine M. PhD; Curtis, Jeptha P. MD; Inzucchi, Silvio E. MD; Schwartz, Gregory G. MD; Lovejoy, Anne M. PAC; Furie, Karen L. MD; Gorman, Mark J. MD; Conwit, Robin MD; Abbott, J. Dawn MD; Jacoby, Daniel L. MD; Kolansky, Daniel M. MD; Pfau, Steven E. MD; Ling, Frederick S. MD; Kernan, Walter N. MD; for the IRIS Investigators

Page: 1882-1893

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New Hope For People With Dysglycemia and Cardiovascular Disease Manifestations: Reduction of Acute Coronary Events With Pioglitazone.

Author: Ryden, Lars MD, PhD; Mellbin, Linda MD, PhD

Page: 1894-1896

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Quality of Care at Hospitals Identified as Outliers in Publicly Reported Mortality Statistics for Percutaneous Coronary Intervention.

Author: Waldo, Stephen W. MD; McCabe, James M. MD; Kennedy, Kevin F. MS; Zigler, Corwin M. PhD; Pinto, Duane S. MD; Yeh, Robert W. MD, MSc

Page: 1897-1907

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Response to Outlier Status: Lessons From Public Reporting for Percutaneous Coronary Intervention.

Author: Joynt, Karen E. MD, MPH

Page: 1908-1910

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Serial Measurement of High-Sensitivity Troponin I and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus in the EXAMINE Trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care).

Author: Cavender, Matthew A. MD, MPH; White, William B. MD; Jarolim, Petr MD, PhD; Bakris, George L. MD; Cushman, William C. MD; Kupfer, Stuart MD; Gao, Qi MS; Mehta, Cyrus R. PhD; Zannad, Faiez MD; Cannon, Christopher P. MD; Morrow, David A. MD, MPH

Page: 1911-1921

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[beta]2-Glycoprotein I/IgA Immune Complexes: A Marker to Predict Thrombosis After Renal Transplantation in Patients With Antiphospholipid Antibodies.

Author: Serrano, Manuel MD *; Martinez-Flores, Jose A. PhD *; Perez, Dolores BS; Garcia, Florencio MD, PhD; Cabrera, Oscar MD; Pleguezuelo, Daniel MD; Paz-Artal, Estela MD, PhD; Morales, Jose M. MD, PhD; Gonzalez, Esther MD, PhD; Serrano, Antonio MD, PhD

Page: 1922-1934

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Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells.

Author: Choi, Bongkun PhD *; Lee, Sahmin MD, PhD *; Kim, Sang-Min MS; Lee, Eun-Jin PhD; Lee, Sun Ro BS; Kim, Dae-Hee MD, PhD; Jang, Jeong Yoon MD; Kang, Sang-Wook PhD; Lee, Ki-Up MD; Chang, Eun-Ju PhD +; Song, Jae-Kwan MD, PhD +

Page: 1935-1950

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A Rock and a Hard Place: Chiseling Away at the Multiple Mechanisms of Aortic Stenosis.

Author: Aikawa, Elena MD, PhD; Libby, Peter MD

Page: 1951-1955

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Stress Testing in Asymptomatic Aortic Stenosis.

Author: Redfors, Bjorn MD, PhD; Pibarot, Philippe DVM, PhD; Gillam, Linda D. MD, MPH; Burkhoff, Daniel MD, PhD; Bax, Jeroen J. MD, PhD; Lindman, Brian R. MD, MSCI; Bonow, Robert O. MD, MS; O'Gara, Patrick T. MD; Leon, Martin B. MD; Genereux, Philippe MD

Page: 1956-1976

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Winter Is Coming After a Cardiac Arrest.

Author: Fernandez-Vega, Ana MD; Martinez-Losas, Pedro MD; Noriega, Francisco J. MD, PhD; Fernandez-Ortiz, Antonio MD, PhD; Biagioni, Corina MD; Cruz-Utrilla, Alejandro MD; Martinez-Vives, Pablo MD; Garcia-Arribas, Daniel MD; Viana-Tejedor, Ana MD, PhD

Page: 1977-1978

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Primary Prevention With Statin Therapy in the Elderly: New Meta-Analyses From the Contemporary JUPITER and HOPE-3 Randomized Trials.

Author: Ridker, Paul M MD; Lonn, Eva MD; Paynter, Nina P. PhD; Glynn, Robert ScD; Yusuf, Salim MD

Page: 1979-1981

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Primary Stable Microvascular Angina: A Long-Term Clinical Follow-Up Study.

Author: Lanza, Gaetano Antonio MD; Filice, Monica MD; De Vita, Antonio MD; Lamendola, Priscilla MD; Villano, Angelo MD; Spera, Francesco MD; Golino, Michele MD; Rota, Elisabetta MD; Argiro, Alessia MD; Crea, Filippo MD

Page: 1982-1984

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Letter by Ma et al Regarding Article, "Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial".

Author: Ma, Lei-Lei MD; Kong, Fei-Juan MD; Ge, Jun-Bo MD

Page: e1042-e1043

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Response by Wiberg et al to Letter Regarding Article, "Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial".

Author: Wiberg, Sebastian MD; Hassager, Christian MD, DMSc; Kjaergaard, Jesper MD, PhD, DMSc

Page: e1044-e1045

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Letter by Tuncez et al Regarding Article, "Identifying Patients at Risk for Prehospital Sudden Cardiac Arrest at the Early Phase of Myocardial Infarction: The e-MUST Study (Evaluation en Medecine d'Urgence des Strategies Therapeutiques des infarctus du myocarde)".

Author: Tuncez, Abdullah MD; Ates, Muhammed Salih MD; Tezcan, Huseyin MD

Page: e1046-e1047

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Response by Karam et al to Letter Regarding Article, "Identifying Patients at Risk for Prehospital Sudden Cardiac Arrest at the Early Phase of Myocardial Infarction: The e-MUST Study (Evaluation en Medecine d'Urgence des Strategies Therapeutiques des infarctus du myocarde)".

Author: Karam, Nicole MD, MPH; Bataille, Sophie MD; Marijon, Eloi MD, PhD; Tafflet, Muriel MPH; Lapostolle, Frederic MD; Spaulding, Christian MD, PhD; Jouven, Xavier MD, PhD *; Lambert, Yves MD *; For the e-MUST Study Investigators

Page: e1048-e1049

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Letter by Rottenberg Regarding Article, "Conventional Versus Compression-Only Versus No Bystander Cardiopulmonary Resuscitation for Pediatric Out-of-Hospital Cardiac Arrest".

Author: Rottenberg, Eric M. AAS

Page: e1050-e1051

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Biophysical study of bevacizumab structure and bioactivity under thermal and pH-stresses

Publication date: 15 July 2017
Source:European Journal of Pharmaceutical Sciences, Volume 105
Author(s): Flávia Sousa, Bruno Sarmento, Maria Teresa Neves-Petersen
The evaluation of the structural stability and bioactivity of monoclonal antibodies (mAb) is a crucial step in the development of mAb therapeutic based products, since immunogenicity needs to be avoided. In the present work, a study was carried out to understand the changes on the structure and bioactivity of mAbs induced by different pH and temperature values. Structural changes of bevacizumab were monitored using fluorescence spectroscopy, circular dichroism (CD) and Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). The secondary and tertiary structural content was monitored at six different pH values and at room temperature, upon heating up to 85°C and upon cooling down to 20°C. Furthermore, the temperature induced conformational changes were continuously monitored from 20°C to 85°C using fluorescence spectroscopy and circular dichroism, allowing to monitor the melting temperature of the protein at different pH values. The results showed that the thermal denaturation of bevacizumab was irreversible at all pH value. The conformational changes induced by pH were higher at extreme pH values (5, 9 and 10) than neutral pH. Thermal stability studies showed that pH6 was the pH that confer bevacizumab the highest structural stability. These studies were confirmed by in vitro studies, where bevacizumab's bioactivity was measured by cell viability/proliferation at all pH values at room temperature, and it was found a higher bioactivity for pH6. Biophysical and biological studies were correlated in order to understand the importance of the modifications in bevacizumab structural content on its bioactivity. However, a decrease in bevacizumab's bioactivity was observed for pH8, 9 and 10. Overall, this work demonstrated the usefulness of the spectroscopy techniques for estimating the stability of therapeutic mAb during formulation development.

Graphical abstract

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Glucosamine modulates propranolol pharmacokinetics via intestinal permeability in rats

Publication date: 15 July 2017
Source:European Journal of Pharmaceutical Sciences, Volume 105
Author(s): Hanadi A. Al Shaker, Nidal A. Qinna, Mujtaba Badr, Mahmoud M.H. Al Omari, Nasir Idkaidek, Khalid Z. Matalka, Adnan A. Badwan
Propranolol (PROP) undergoes extensive first-pass metabolism by the liver resulting in a relatively low bioavailability (13–23%); thus, multiple oral doses are required to achieve therapeutic effect. Since some studies have reported that glucosamine (GlcN) can increase the bioavailability of some drugs, therefore, it is aimed to study whether GlcN can change the pharmacokinetic parameters of PROP, thus modulating its bioavailability. When PROP was orally co-administered with GlcN (200mg/kg) to rats, PROP area under curve (AUC) and maximum concentration (Cmax) were significantly decreased by 43% (p<0.01) and 33% (p<0.05), respectively. In line with the in vivo results, in silico simulations confirmed that GlcN decreased rat intestinal effective permeability (Peff) and increased PROP clearance by 50%. However, in situ single pass intestinal perfusion (SPIP) experiments showed that GlcN significantly increased PROP serum levels (p<0.05). Furthermore, GlcN decreased PROP disposition/distribution into cultured hepatocytes in concentration dependent manner. Such change in the interaction pattern between GlcN and PROP might be attributed to the environment of the physiological buffer used in the in vitro experiments (pH7.2) versus the oral administration and thus, enhanced PROP permeability. Nevertheless, such enhancement was not detected when everted gut sacks were incubated with both drugs at the same pH in vitro. In conclusion, GlcN decreased PROP serum levels in rats in a dose-dependent manner. Such interaction might be attributed to decreased intestinal permeability and enhanced clearance of PROP in the presence of GlcN. Further investigations are still warranted to explain the in vitro inhibitory action of GlcN on PROP hepatocytes disposition and the involvement of GlcN in the intestinal and hepatic metabolizing enzymes of PROP at different experimental conditions.

Graphical abstract

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The relationships between sensation seeking and a spectrum of e-cigarette use behaviors: Cross-sectional and longitudinal analyses specific to Texas adolescents

Publication date: October 2017
Source:Addictive Behaviors, Volume 73
Author(s): Kathleen R. Case, Melissa B. Harrell, Adriana Pérez, Alexandra Loukas, Anna V. Wilkinson, Andrew E. Springer, MeLisa R. Creamer, Cheryl L. Perry
IntroductionSensation seeking is strongly associated with cigarette use in adolescents. However, few studies have investigated its relationship with adolescent e-cigarette use. This study examined cross-sectional and longitudinal associations between sensation seeking and a variety of e-cigarette use behaviors among Texas adolescents.MethodsThis study utilized two waves of data collected 6months apart through the Texas Adolescent Tobacco and Marketing Surveillance System (TATAMS) in 2014–2015 (n=2,488/N=461,069). TATAMS employs a complex probability-sampling design and is representative of students in 6th, 8th and 10th grades from five counties surrounding the four largest cities in Texas (Houston, Dallas/Ft. Worth, San Antonio, Austin). Weighted multivariable logistic regression was used to examine the cross-sectional and longitudinal associations between sensation seeking and susceptibility to e-cigarette use, ever e-cigarette use, and current (past 30day) e-cigarette use.ResultsIn the cross-sectional analyses, higher mean sensation seeking scores were associated with higher odds of both susceptibility to e-cigarette use and ever e-cigarette use (AOR=1.25, 95% CI=1.07, 1.47; AOR=1.24, 95% CI=1.08, 1.43, respectively). For the longitudinal analyses, only the association between higher mean sensation seeking scores and transition to ever e-cigarette use remained statistically significant (AOR=1.45, 95% CI=1.01, 2.08). There were no significant associations between sensation seeking and current e-cigarette use in either the cross-sectional or longitudinal analyses.ConclusionsHigher sensation seeking scores were consistently and significantly related to experimentation with e-cigarette use among Texas adolescents. Future interventions (e.g., communication campaigns) should target high sensation seeking adolescents to reduce initiation of e-cigarette use among this population.



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Cognitive avoidance and aversive cues related to tobacco in male smokers

Publication date: October 2017
Source:Addictive Behaviors, Volume 73
Author(s): Ji Sun Hong, Sun Mi Kim, Hye Yeon Jung, Kyoung Doo Kang, Kyung Joon Min, Doug Hyun Han
BackgroundTreatment using aversive conditioning has been suggested for smoking cessation. The efficacy of this method is thought to be associated with cognitive avoidance. We compare differences in avoidance traits and patterns of associated brain activation in response to cues that induce cravings versus aversion between smokers and non-smokers.MethodsFifteen smokers and fifteen non-smokers completed cue reactivity tasks while undergoing functional magnetic resonance imaging (fMRI) to examine brain responses to craving-inducing cues (Cr) and aversion-inducing cues (Av). Participant avoidant traits were also assessed.ResultsActivation of the left frontal subcallosal gyrus in response to Cr was greater in smokers than in non-smokers. Smokers showed less activation in the right temporal lobe in response to Av than did non-smokers. Brain activation in response to Cr in the left frontal subcallosal gyrus was positively correlated with Fagerstrom Test for Nicotine Dependence (FTND) scores in smokers. Brain activation in response to Av in the right temporal lobe was negatively correlated with the Korean Version of the Cognitive Avoidance Questionnaire (KCAQ) scores in non-smokers.ConclusionsCognitive avoidance in smokers during aversive stimulation might result in sustaining addictive behaviors. On the other hand, non-smokers may be able to emotionally confront the adverse effects of smoking.



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Scaffold protein JLP mediates TCR-initiated CD4+T cell activation and CD154 expression

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Qi Yan, Cheng Yang, Qiang Fu, Zhaowei Chen, Shan Liu, Dou Fu, Rahmat N. Rahman, Ryota Nakazato, Katsuji Yoshioka, Sam K.P. Kung, Guohua Ding, Huiming Wang
CD4⁺ T-cell activation and its subsequent induction of CD154 (CD40 ligand, CD40L) expression are pivotal in shaping both the humoral and cellular immune responses. Scaffold protein JLP regulates signal transduction pathways and molecular trafficking inside cells, thus represents a critical component in maintaining cellular functions.Its role in regulating CD4⁺ T-cell activation and CD154 expression, however, is unclear. Here, we demonstrated expression of JLP in mouse tissues of lymph nodes, thymus, spleen, and also CD4⁺ T cells. Using CD4+ T cells from jlp-deficient and jlp-wild-type mice, we demonstrated that JLP-deficiency impaired T-cell proliferation, IL-2 production, and CD154 induction upon TCR stimulations, but had no impacts on the expression of other surface molecules such as CD25, CD69, and TCR. These observed impaired T-cell functions in the jlp-/- CD4⁺ T cells were associated with defective NF-AT activation and Ca²⁺ influx, but not the MAPK, NF-κB, as well as AP-1 signaling pathways. Our findings indicated that, for the first time, JLP plays a critical role in regulating CD4⁺ T cells response to TCR stimulation partly by mediating the activation of TCR-initiated Ca²⁺/NF-AT.



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Pattern recognition receptors and coordinated cellular pathways involved in tuberculosis immunopathogenesis: Emerging concepts and perspectives

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Abhishek Mishra, Shamim Akhtar, Chinnaswamy Jagannath, Arshad Khan
Pattern Recognition Receptors (PRRs) play a central role in the recognition of numerous pathogens, including Mycobacterium tuberculosis, resulting in activation of innate and adaptive immune responses. Besides Toll Like Receptors, C-type Lectin Receptors and Nod Like Receptors are now being recognized for their involvement in inducing immune response against M. tuberculosis infection. Although, a functional redundancy of the PRRs has also been reported in many studies, emerging evidences support the notion that a cooperative and coordinated response generated by these receptors is critical to sustain the full immune control of M. tuberculosis infection. Many of the PRRs are now found to be involved in various cellular host defenses, such as inflammasome activation, phagosome biogenesis, endosomal trafficking, and antigen processing pathways that are all very critical for an effective immune response against M. tuberculosis. In support, polymorphism in several of these receptors has also been found associated with increased susceptibility to tuberculosis in humans. Nonetheless, increasing evidences also show that in order to enhance its intracellular survival, M. tuberculosis has also evolved multiple strategies to subvert and reprogram PPR-mediated immune responses. In light of these findings, this review analyzes the interaction of bacterial and host factors at the intersections of PRR signaling pathways that could provide integrative insights for the development of better vaccines and therapeutics for tuberculosis.



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Calcitonin protects chondrocytes from lipopolysaccharide-induced apoptosis and inflammatory response through MAPK/Wnt/NF-κB pathways

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Lai-Bo Zhang, Zhen-Tao Man, Wei Li, Wei Zhang, Xian-Quan Wang, Shui Sun
Calcitonin (CT) is an anti-absorbent, which has long been used for treatment of osteoporosis. However, little information is available about the effects of CT on osteoarthritis (OA). This study was mainly aimed to explore the effects of CT on the treatment of OA, as well as the underlying mechanisms. Chondrocytes were isolated from immature mice and then were incubated with lipopolysaccharide (LPS), CT, small interfering (si) RNA against bone morphogenetic protein (BMP)-2, and/or the inhibitors of MAPK/Wnt/NF-κB pathway. Thereafter, cell viability, apoptosis, nitric oxide (NO) and inflammatory factors productions, and expression levels of cartilage synthesis protein key factors, cartilage-derived morphogenetic protein (CDMP) 1, SRY (sex-determining region Y)-box 9 protein (SOX9), and MAPK/Wnt/NF-κB pathways key factors were determined. CT significantly reversed LPS-induced cell viability decrease, apoptosis increase, the inflammatory factors and NO secretion, the abnormally expression of cartilage synthesis proteins and the activation of MAPK/Wnt/NF-κB pathways (P<0.05). In addition, we observed that administration of the inhibitors of MAPK/Wnt/NF-κB pathways statistically further increased the levels of CDMP1 and SOX9 (P<0.05). Suppression of BMP-2 decreased the levels of CDMP1 and SOX9 and activated MAPK/Wnt/NF-κB pathways, and could partially abolish CT-modulated the expression changes in CDMP1 and SOX9, and MAPK/Wnt/NF-κB pathways key factors (P<0.05). The results showed that CT protects chondrocytes from LPS-induced apoptosis and inflammatory response by regulating BMP-2 and thus blocking MAPK/Wnt/NF-κB pathways.



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Chronic stress impairs the local immune response during cutaneous repair in gilthead sea bream (Sparus aurata, L.)

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Ana Patrícia Mateus, Liliana Anjos, João R. Cardoso, Deborah M. Power
Scale removal in fish triggers a damage-repair program to re-establish the lost epidermis and scale and an associated local immune response. In mammals, chronic stress is known to delay wound healing and to modulate the cutaneous stress axis, but this is unstudied in teleost fish the most successful extant vertebrates. The present study was designed to test the hypothesis that chronic stress impairs cutaneous repair in teleost fish as a consequence of suppression of the immune response. The hypothesis was tested by removing the scales and damaging the skin on one side of the body of fish previously exposed for 4 weeks to a chronic crowding stress and then evaluating cutaneous repair for 1 week. Scale removal caused the loss of the epidermis although at 3days it was re-established. At this stage the basement membrane was significantly thicker (p=0.038) and the hypodermis was significantly thinner (p=0.016) in the regenerating skin of stressed fish relative to the control fish. At 3days, stressed fish also had a significantly lower plasma osmolality (p=0.015) than control fish indicative of reduced barrier function. Chronic stress caused a significant down-regulation of the glucocorticoid receptor (gr) in skin before damage (time 0, p=0.005) and of star at 3 and 7days (p<0.05) after regeneration relative to control fish. In regenerating skin key transcripts of cutaneous repair, pcna, colivα1 and mmp9, and the inflammatory response, tgfβ1, csf-1r, mpo and crtac2, were down-regulated (p<0.05) by chronic stress. Irrespective of chronic stress and in contrast to intact skin many hyper pigmented masses, putative melanomacrophages, infiltrated the epidermis of regenerating skin. This study reveals that chronic stress suppresses the local immune response to scale removal and impairs the expression of key transcripts of wound healing. Elements of the stress axis were identified and modulated by chronic stress during cutaneous repair in gilthead seabream skin.



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Dose Escalation Study of Lithium With Oxaliplatin and Capecitabine in Advanced Oesophago-Gastric or Colorectal Cancer

Conditions:   Colorectal Neoplasms;   Stomach Neoplasm;   Esophageal Neoplasms
Interventions:   Drug: Lithium;   Drug: Oxaliplatin;   Drug: Capecitabine
Sponsors:   Cancer Trials Ireland;   University College Cork
Not yet recruiting - verified May 2017

http://ift.tt/2rjynUP

Ruxolitinib in Operable Head and Neck Cancer

Condition:   Head and Neck Squamous Cell Carcinoma
Intervention:   Drug: Ruxolitinib
Sponsors:   University of California, San Francisco;   Incyte Pharmaceuticals
Not yet recruiting - verified May 2017

http://ift.tt/2qlaDm3

Safety Study of SEA-CD40 in Cancer Patients

Conditions:   Cancer;   Carcinoma;   Carcinoma, Non-Small-Cell Lung;   Carcinoma, Squamous Cell;   Hematologic Malignancies;   Hodgkin Disease;   Lymphoma;   Lymphoma, B-Cell;   Lymphoma, Follicular;   Lymphoma, Large B-Cell, Diffuse;   Lymphoma, Non-Hodgkin;   Melanoma;   Neoplasms;   Neoplasm Metastasis;   Neoplasms, Head and Neck;   Neoplasms, Squamous Cell;   Non-Small Cell Lung Cancer;   Non-Small Cell Lung Cancer Metastatic;   Non-small Cell Carcinoma;   Squamous Cell Cancer;   Squamous Cell Carcinoma;   Squamous Cell Carcinoma of the Head and Neck;   Squamous Cell Neoplasm
Interventions:   Drug: SEA-CD40 monotherapy regimen;   Drug: Pembrolizumab;   Drug: SEA-CD40 combination therapy regimen
Sponsor:   Seattle Genetics, Inc.
Recruiting - verified May 2017

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Direct Medical Cost Associated with Colorectal Cancer in North of Jordan

Publication date: Available online 15 May 2017
Source:Current Problems in Cancer
Author(s): Qais Alefan, Rana Malhees, Nizar Mhaidat
BackgroundColorectal cancer (CRC) is mainly characterized as the malignant and impaired growth of rectal cells in the intestinal region. Direct medical cost is related to resources, which are directly used in treating the patient that mainly includes the cost of drugs, diagnostic, treatment, follow up, rehabilitation and hospital admission.ObjectiveThis study aimed to estimate and analyze direct medical costs attributable to CRC in Jordan.MethodsA retrospective analysis of a cohort patients treated for CRC data has been performed to determine direct medical costs attributable to CRC in Jordan. The prevalence-based approach has been used in addition to the "bottom up" approach to accumulate one-year time costs of CRC. Demographic, clinical, and economic data have been collected and analyzed using SPSS for windows. Costs were estimated by a bottom-up approach, in which each service component was identified and valued at the most detailed level, in order to provide greater transparency and reliability in economic evaluation of health care services.ResultsThis study quantified the economic burden associated with CRC by Jordanian patients in KAUH from the perspective of health care providers (public sector). Total CRC cost in the year 2014 was estimated to JD 695,608, and the most expensive stage for all sites was stage 4 reaching a cost of JD 518,894. Advanced disease stages were associated with an increase in total cost and chemotherapy costs.ConclusionResults of this study propose that direct medical costs associated with CRC are considerable. The majority of the cost was devoted for medications, primarily chemotherapy. Advanced stages were associated with higher cost and largest number of patients.



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Facial emotion processing in pediatric social anxiety disorder: relevance of situational context

Publication date: Available online 15 May 2017
Source:Journal of Anxiety Disorders
Author(s): Daniela Schwab, Anne Schienle
Social anxiety disorder (SAD) typically begins in childhood. Previous research has demonstrated that adult patients respond with elevated late positivity (LP) to negative facial expressions. In the present study on pediatric SAD, we investigated responses to negative facial expressions and the role of social context information. Fifteen children with SAD and 15 non-anxious controls were first presented with images of negative facial expressions with masked backgrounds. Following this, the complete images which included context information, were shown. The negative expressions were either a result of an emotion-relevant (e.g., social exclusion) or emotion-irrelevant elicitor (e.g., weight lifting). Relative to controls, the clinical group showed elevated parietal LP during face processing with and without context information. Both groups differed in their frontal LP depending on the type of context. In SAD patients, frontal LP was lower in emotion-relevant than emotion-irrelevant contexts. We conclude that SAD patients direct more automatic attention towards negative facial expressions (parietal effect) and are less capable in integrating affective context information (frontal effect).



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Wasted Food, Wasted Nutrients: Nutrient Loss from Wasted Food in the United States and Comparison to Gaps in Dietary Intake

Publication date: Available online 15 May 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Marie L. Spiker, Hazel A.B. Hiza, Sameer M. Siddiqi, Roni A. Neff
BackgroundPrevious research has estimated that wasted food in the United States contains between 1,249 and 1,400 kcal per capita per day, but little is known about amounts of other nutrients embedded in the 31% to 40% of food that is wasted.ObjectiveThis research aimed to calculate the nutritional value of food wasted at the retail and consumer levels in the US food supply, and contextualize the amount of nutrient loss in terms of gaps between current and recommended intakes and estimated food recovery potential.DesignData from the National Nutrient Database for Standard Reference were used to calculate the nutritional value of retail- and consumer-level waste of 213 commodities in the US Department of Agriculture Loss-Adjusted Food Availability data series for 27 nutrients in 2012.ResultsFood wasted at the retail and consumer levels of the US food supply in 2012 contained 1,217 kcal, 33 g protein, 5.9 g dietary fiber, 1.7 μg vitamin D, 286 mg calcium, and 880 mg potassium per capita per day. Using dietary fiber as an example, 5.9 g dietary fiber is 23% of the Recommended Dietary Allowance for women. This is equivalent to the fiber Recommended Dietary Allowance for 74 million adult women. Adult women in 2012 underconsumed dietary fiber by 8.9 g/day, and the amount of wasted fiber is equivalent to this gap for 206.6 million adult women.ConclusionsThis was the first study to document the loss of nutrients from wasted food in the US food supply, to our knowledge. Although only a portion of discarded food can realistically be made available for human consumption, efforts to redistribute surplus foods where appropriate and prevent food waste in the first place could increase the availability of nutrients for Americans, while saving money and natural resources.



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Last Nail in the Coffin for Propensity Scores in Observational Cardiovascular Studies?

http://ift.tt/2ql11qN

Influence of Direct Oral Anticoagulants on Rates of Oral Anticoagulation for Atrial Fibrillation

AbstractBackground

Oral anticoagulation (OAC) with warfarin is underused for atrial fibrillation (AF). The availability of direct oral anticoagulants (DOACs) may improve overall OAC rates in AF patients, but a large-scale evaluation of their effects has not been conducted.

Objectives

This study assessed the effect of DOAC availability on overall OAC rates for nonvalvular AF.

Methods

Between April 1, 2008 and September 30, 2014, we identified 655,000 patients with nonvalvular AF and a CHA₂DS₂-VASc score of >1 in the National Cardiovascular Data Registry PINNACLE registry. Temporal trends in overall OAC and individual warfarin and DOAC use were analyzed. Multivariable hierarchical logistic regression identified patient factors associated with OAC and DOAC use. Practice variation of OAC and DOAC use was also assessed.

Results

Overall OAC rates increased from 52.4% to 60.7% among eligible AF patients (p for trend <0.01). Warfarin use decreased from 52.4% to 34.8% (p for trend <0.01), and DOAC use increased from 0% to 25.8% (p for trend <0.01). An increasing CHA₂DS₂-VASc score was associated with higher OAC use (odds ratio [OR]: 1.06; 95% confidence interval [CI]: 1.05 to 1.07), but with lower DOAC use (OR: 0.97; 95% CI: 0.96 to 0.98). Significant practice variation was present in OAC use (median odds ratio [MOR]: 1.52; 95% CI: 1.45 to 1.57) and in DOAC use (MOR: 3.58; 95% CI: 3.05 to 4.13).

Conclusions

Introduction of DOACs in routine practice was associated with improved rates of overall OAC use for AF, but significant gaps remain. In addition, there is significant practice-level variation in OAC and DOAC use.

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Achieving a Maximally Tolerated {beta}-Blocker Dose in Heart Failure Patients: Is There Room for Improvement?

Abstract

Heart failure (HF) is associated with significant morbidity and mortality. Although initially thought to be harmful in HF, beta-adrenergic blockers (β-blockers) have consistently been shown to reduce mortality and HF hospitalization in chronic HF with reduced ejection fraction. Proposed mechanisms include neurohormonal blockade and heart rate reduction. A new therapeutic agent now exists to target further heart rate lowering in patients who have been stable on a "maximally tolerated β-blocker dose," but this definition and how to achieve it are incompletely understood. In this review, the authors summarize published reports on the mechanisms by which β-blockers improve clinical outcomes. The authors describe differences in doses achieved in landmark clinical trials and those observed in routine clinical practice. They further discuss reasons for intolerance and the evidence behind using β-blocker dose and heart rate as therapeutic targets. Finally, the authors offer recommendations for clinicians actively initiating and up-titrating β-blockers that may aid in achieving maximally tolerated doses.

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New Treatment Options Fail to Close the Anticoagulation Gap in Atrial Fibrillation

http://ift.tt/2pPESxp

JACC Instructions for Authors

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Lean Body Mass Is the Predominant Anthropometric Risk Factor for Atrial Fibrillation

AbstractBackground

Obesity is repeatedly emphasized as a risk factor for atrial fibrillation or flutter (AF). However, the underlying evidence may be questioned, as the obvious correlations between various anthropometric measures hamper identification of the characteristics that are biologically driving AF risk, and recent studies suggest that fat carries limited or no independent risk of AF.

Objectives

This study sought to assess mutually adjusted associations among AF risk and height, weight, body mass index, hip and waist circumference, waist-to-hip ratio, and bioelectrical impedance-derived measures of fat mass, lean body mass, and fat percentage.

Methods

Anthropometric measures and self-reported life-style information were collected from 1993 to 1997 in a population-based cohort including 55,273 persons age 50 to 64 years who were followed in Danish registers until June 2013.

Results

During a median of 17 years of follow-up, 3,868 persons developed AF. Adjusted hazard ratios per population SD difference (HRs) showed highly statistically significant, positive associations for all 9 anthropometric measures (HRs ranging from 1.08 [95% confidence interval (CI): 1.05 to 1.12] for waist-to-hip ratio to 1.37 [95% CI: 1.33 to 1.42] for lean body mass). Pairwise mutual adjustment of the 9 measures left the association for lean body mass virtually unchanged (lowest HR: 1.33 [95% CI: 1.28 to 1.39] when adjusting for height), whereas no other association remained substantial when adjusted for lean body mass (highest HR: 1.05 [95% CI: 1.01 to 1.10] for height).

Conclusions

Lean body mass was the predominant anthropometric risk factor for AF, whereas no association was observed for either of the obesity-related anthropometric measures after adjustment for lean body mass.

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Man Helping Man: In Memoriam: A Tribute to Leonard S. Dreifus, MD

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Atrial Fibrillation and Body Composition: Is it Fat or Lean That Ultimately Determines the Risk?

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Off-Label Use of Non-Vitamin K Antagonist Oral Anticoagulants

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Clinical Significance of Lipid-Rich Plaque Detected by Optical Coherence Tomography: A 4-Year Follow-Up Study

AbstractBackground

Lipid-rich plaque (LRP) is thought to be a precursor to cardiac events. However, its clinical significance in coronary arteries has never been systematically investigated.

Objectives

This study investigated the prevalence and clinical significance of LRP in the nonculprit region of the target vessel in patients undergoing percutaneous coronary intervention (PCI).

Methods

The study included 1,474 patients from 20 sites across 6 countries undergoing PCI, who had optical coherence tomography (OCT) imaging of the target vessel. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, acute myocardial infarction, and ischemia-driven revascularization. Patients were followed for up to 4 years (median of 2 years).

Results

Lipid-rich plaque was detected in nonculprit regions of the target vessel in 33.6% of patients. The cumulative rate of nonculprit lesion-related MACE (NC-MACE) over 48 months in patients with LRP was higher than in those without LRP (7.2% vs. 2.6%, respectively; p = 0.033). Acute coronary syndrome at index presentation (risk ratio: 2.538; 95% confidence interval [CI]: 1.246 to 5.173; p = 0.010), interruption of statin use ≥1 year (risk ratio: 4.517; 95% CI: 1.923 to 10.610; p = 0.001), and LRP in nonculprit regions (risk ratio: 2.061; 95% CI: 1.050 to 4.044; p = 0.036) were independently associated with increased NC-MACE. Optical coherence tomography findings revealed that LRP in patients with NC-MACE had longer lipid lengths (p < 0.001), wider maximal lipid arcs (p = 0.023), and smaller minimal lumen areas (p = 0.003) than LRPs in patients without MACE.

Conclusions

Presence of LRP in the nonculprit regions of the target vessel by OCT predicts increased risk for future NC-MACE, which is primarily driven by revascularization for recurrent ischemia. Lipid-rich plaque with longer lipid length, wider lipid arc, and higher degree of stenosis identified patients at higher risk of future cardiac events. (The Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538)

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At Arms Length: Radiation Safety During Radial Percutaneous Coronary Intervention

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Predicting the Vulnerable Patient Using Intravascular Imaging

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Pulmonary Hypertension in Infants, Children, and Young Adults

Abstract

Pulmonary hypertension (PH) in neonates, infants, children, adolescents, and young adults is a complex condition that can be associated with several cardiac, pulmonary, and systemic diseases contributing to morbidity and mortality. The underlying pulmonary hypertensive vascular disease (PHVD) is characterized by inflammation, pulmonary vascular remodeling, and angio-obliteration leading to elevated pulmonary arterial pressure and resistance, right ventricular dysfunction, left ventricular compression, and subsequent heart failure. Recent advancements in PH-targeted therapies and interventional-surgical procedures have contributed to the improvement in quality of life and survival in PH/PHVD. This paper gives an update on recent developments in the diagnosis and treatment of children and young adults with PH. The focus is on the heterogeneous etiology/pathophysiology of PH in the young, and particularly on PHVD associated with congenital heart disease. Moreover, new pharmacological, surgical, and interventional therapies and their practical application in progressive/severe pulmonary arterial hypertension with inadequate response to conventional pharmacotherapy are discussed.

http://ift.tt/2pPMkIZ

Reproductive Factors and Incidence of Heart Failure Hospitalization in the Womens Health Initiative

AbstractBackground

Reproductive factors reflective of endogenous sex hormone exposure might have an effect on cardiac remodeling and the development of heart failure (HF).

Objectives

This study examined the association between key reproductive factors and the incidence of HF.

Methods

Women from a cohort of the Women's Health Initiative were systematically evaluated for the incidence of HF hospitalization from study enrollment through 2014. Reproductive factors (number of live births, age at first pregnancy, and total reproductive duration [time from menarche to menopause]) were self-reported at study baseline in 1993 to 1998. We employed Cox proportional hazards regression analysis in age- and multivariable-adjusted models.

Results

Among 28,516 women, with an average age of 62.7 ± 7.1 years at baseline, 1,494 (5.2%) had an adjudicated incident HF hospitalization during an average follow-up of 13.1 years. After adjusting for covariates, total reproductive duration in years was inversely associated with incident HF: hazard ratios (HRs) of 0.99 per year (95% confidence interval [CI]: 0.98 to 0.99 per year) and 0.95 per 5 years (95% CI: 0.91 to 0.99 per 5 years). Conversely, early age at first pregnancy and nulliparity were significantly associated with incident HF in age-adjusted models, but not after multivariable adjustment. Notably, nulliparity was associated with incident HF with preserved ejection fraction in the fully adjusted model (HR: 2.75; 95% CI: 1.16 to 6.52).

Conclusions

In post-menopausal women, shorter total reproductive duration was associated with higher risk of incident HF, and nulliparity was associated with higher risk for incident HF with preserved ejection fraction. Whether exposure to endogenous sex hormones underlies this relationship should be investigated in future studies.

http://ift.tt/2pPMnVb

Late Anthracycline-Related Cardiotoxicity in Low-Risk Breast Cancer Patients

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Understanding Hormones, Menopause, and Heart Failure: Still a Work in Progress

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Reply: Last Nail in the Coffin for Propensity Scores in Observational Cardiovascular Studies?

http://ift.tt/2pQ0GZA

Radiation Exposure and Vascular Access in Acute Coronary Syndromes: The RAD-Matrix Trial

AbstractBackground

It remains unclear whether radial access increases the risk of operator or patient radiation exposure compared to transfemoral access when performed by expert operators.

Objectives

This study sought to determine whether radial access increases radiation exposure.

Methods

A total of 8,404 patients, with or without ST-segment elevation acute coronary syndrome, were randomly assigned to radial or femoral access for coronary angiography and percutaneous intervention, and collected fluoroscopy time and dose-area product (DAP). RAD-MATRIX is a radiation sub-study of the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) trial. We anticipated that 13 or more operators, each wearing a thorax (primary endpoint), wrist, and head (secondary endpoints) lithium fluoride thermoluminescent dosimeter, and randomizing at least 13 patients per access site, were needed to establish noninferiority of radial versus femoral access.

Results

Among 18 operators, performing 777 procedures in 767 patients, the noninferiority primary endpoint was not achieved (p value for noninferiority = 0.843). Operator equivalent dose at the thorax (77 μSv) was significantly higher with radial than femoral access (41 μSv; p = 0.02). After normalization of operator radiation dose by fluoroscopy time or DAP, the difference remained significant. Radiation dose at wrist or head did not differ between radial and femoral access. Thorax operator dose did not differ for right radial (84 μSv) compared to left radial access (52 μSv; p = 0.15). In the overall MATRIX population, fluoroscopy time and DAP were higher with radial compared to femoral access: 10 min versus 9 min (p < 0.0001) and 65 Gy·cm² versus 59 Gy·cm² (p = 0.0001), respectively.

Conclusions

Compared to femoral access, radial access is associated with greater operator and patient radiation exposure when performed by expert operators in current practice. Radial operators and institutions should be sensitized towards radiation risks and adopt adjunctive radioprotective measures. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX; NCT101433627)

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Alcohol and Atrial Fibrillation: Mitigating the Risk

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Obituaries & Dedications

Publication date: April 2017
Source:Seminars in Cancer Biology, Volume 43





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Editorial Board & Publication Information

Publication date: April 2017
Source:Seminars in Cancer Biology, Volume 43





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Insulin receptor substrate signaling controls cardiac energy metabolism and heart failure

The heart is an insulin-dependent and energy-consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth and survival. Heart failure is highly associated with insulin resistance, and heart failure patients suffer from the cardiac energy deficiency and structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics and impairing cardiac contractility. Recent studies demonstrated that insulin receptor substrates 1 and 2 (IRS-1,-2) are major mediators of both insulin and insulin-like growth factor-1 (IGF-1) signaling responsible for myocardial energetics, structure, function and organismal survival. Importantly, the insulin receptor substrates (IRS) play an important role in the activation of the phosphatidylinositide-3-dependent kinase (PI-3K) that controls Akt and Foxo1 signaling cascade, regulating the mitochondrial function, cardiac energy metabolism and the renin–angiotensin system. Dysregulation of this branch in signaling cascades by insulin resistance in the heart through the endocrine system promotes heart failure, providing a novel mechanism for diabetic cardiomyopathy. Therefore, targeting this branch of IRS->PI-3K->Foxo1 signaling cascade and associated pathways may provide a fundamental strategy for the therapeutic and nutritional development in control of metabolic and cardiovascular diseases. In this review, we focus on insulin signaling and resistance in the heart and the role energetics play in cardiac metabolism, structure and function.

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Effect of androgen on Kiss1 expression and luteinizing hormone release in female rats

Hyperandrogenic women have various grades of ovulatory dysfunction, which lead to infertility. The purpose of this study was to determine whether chronic exposure to androgen affects the expression of kisspeptin (ovulation and follicle development regulator) or release of luteinizing hormone (LH) in female rats. Weaned females were subcutaneously implanted with 90-day continuous-release pellets of 5α-dihydrotestosterone (DHT) and studied after 10 weeks of age. Number of Kiss1-expressing cells in both the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) was significantly decreased in ovary-intact DHT rats. Further, an estradiol-induced LH surge was not detected in DHT rats, even though significant differences were not observed between DHT and non-DHT rats with regard to number of AVPV Kiss1-expressing cells or gonadotrophin-releasing hormone (GnRH)-immunoreactive (ir) cells in the presence of high estradiol. Kiss1-expressing and neurokinin B-ir cells were significantly decreased in the ARC of ovariectomized (OVX) DHT rats compared with OVX non-DHT rats; pulsatile LH secretion was also suppressed in these animals. Central injection of kisspeptin-10 or intravenous injection of a GnRH agonist did not affect the LH release in DHT rats. Notably, ARC Kiss1-expressing cells expressed androgen receptors (ARs) in female rats, whereas only a few Kiss1-expressing cells expressed ARs in the AVPV. Collectively, our results suggest excessive androgen suppresses LH surge and pulsatile LH secretion by inhibiting kisspeptin expression in the ARC and disruption at the pituitary level, whereas AVPV kisspeptin neurons appear to be directly unaffected by androgen. Hence, hyperandrogenemia may adversely affect ARC kisspeptin neurons, resulting in anovulation and menstrual irregularities.

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