A histological evaluation of peeling-induced skin changes in subcutaneous undermined preauricular facial skin flaps of 9 patients was performed. There were 3 treatment groups Trichloroacetic acid (TCA) 25%, TCA 40% and phenol/croton oil; 1 group served as control. Two independent evaluators determined the epidermal and dermal thickness and the depth of necrosis (μm). The percentual tissue damage due to the peeling was calculated and a one sample t-test for statistical significance was performed.
http://ift.tt/2tgUWOV
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Ετικέτες
Δευτέρα 26 Ιουνίου 2017
Histological case control study of peeling-induced skin changes of different peeling agents in surgically subcutaneous undermined skin flaps in facelift patients
Cranial bone structure in children with sagittal craniosynostosis: relationship with surgical outcomes
Whilst spring-assisted cranioplasty has become a widespread technique to correct scaphocephaly in children with sagittal synostosis, predicting head shape changes induced by the gradual opening of the springs remains challenging. The aim of this study was to explore the role of cranial bone structure on surgical outcomes.
http://ift.tt/2tQoXCf
The supraorbital region revisited – an anatomic exploration of the neuro-vascular bundle with regard to frontal migraine headache
Recent findings on the pathogenesis of frontal migraine headache support, besides a central vasogenic cause, an alternative peripheral mechanism involving compressed craniofacial nerves. Supported further by the efficiency of Botulinum Toxin injections as a new treatment option in frontal migraine headache patients.
http://ift.tt/2thadz3
US guided wire localization of malignant melanoma subcutaneous metastases
The American joint committee on cancer defines in transit (IT) metastases as any skin or subcutaneous nodule that is more than two centimetres away from the primary lesion but is not beyond the regional nodal basin. IT metastases usually present as cutaneous or subcutaneous nodules, which may or may not be pigmented. Occasionally the nodules are impalpable and are only picked up following imaging, thus making it difficult to isolate them perioperatively.
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Proximate composition and mineral contents in the body wall of two species of sea cucumber from Oman Sea
Abstract
The proximate composition and mineral contents of Stichopus horrens and Holothuria arenicola from Chabahar Bay were analyzed and investigated. During the present study, we aimed to demonstrate the nutritive value. The approximate percent composition of moisture, protein, fat, and ash were 92.8, 3.47, 0.4, and 3.33% in S. horrens and 93, 4.4, 0.6, and 2% in H. arenicola, respectively. Atomic absorption spectrophotometry of the ashes indicated the body wall of two species of sea cucumbers contained higher amounts of both macro minerals (92.5 mg/100 g Mg in S. horrens and 115 mg/100 g Mg in H. arenicola; 106.25 mg/100 g Ca in S. horrens and 83.25 mg/100 g Ca in H. arenicola) and trace elements (521.781 mg/100 g Fe in S. horrens; 60.354 mg/100 g Fe in H. arenicola, and 0.096 mg/100 g Zn in S. horrens; 0.04 mg/100 g Zn in H. arenicola). For both species, there were high content of protein and essential mineral. Also, they have low content of fat in the body wall of two species in the experiment.
http://ift.tt/2tfsz3l
Water dissociation on multimetallic catalysts
Publication date: 5 December 2017
Source:Applied Catalysis B: Environmental, Volume 218
Author(s): José L.C. Fajín, M. Natália D.S. Cordeiro, José R.B. Gomes
DFT based calculations were employed in the study of the dissociation of the water molecule onto copper and nickel (110) and (111) surface models, incorporating two additional metallic elements, because it was found previously that metal alloying leads to strong synergic effects in the catalysis of this reaction. The dissociation reaction was studied on the Pt/Ru/Ni, Pt/Ru/Cu, Rh/Ru/Cu, Ni/Ru/Cu and Al/Zn/Cu combinations, in a total of 25 trimetallic surfaces. Very low activation energy barriers for the dissociation of water were calculated on several of the surface models, suggesting that multimetallic surfaces can be interesting alternatives for catalyzing the dissociation of the water molecule, which is a crucial elementary step in the water gas shift reaction. Encouragingly, the calculations predict a facile dissociation of the water molecule onto the (AlZn)@Cu(111) catalyst model which is in agreement with recent experimental studies where it was found that a Cu0.5Zn0.5Al2O4 spinel oxide catalyst holds improved activity for the water gas shift reaction.
Graphical abstract
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Effect of preparation procedures on catalytic activity and selectivity of copper-based mixed oxides in selective catalytic oxidation of ammonia into nitrogen and water vapour
Publication date: 30 November 2017
Source:Applied Surface Science, Volume 423
Author(s): Magdalena Jabłońska, Marek Nocuń, Kinga Gołąbek, Regina Palkovits
The selective oxidation of ammonia into nitrogen and water vapour (NH3-SCO) was studied over Cu-Mg(Zn)-Al-(Zr) mixed metal oxides, obtained by coprecipitation and their subsequent calcination. The effect of acid-base properties of Cu-Mg-Al-Ox on catalytic activity was investigated by changing the Mg/Al molar ratio. Other Cu-containing oxides were prepared by rehydration of calcined Mg-Al hydrotalcite-like compounds or thermal decomposition of metal nitrate precursors. XRD, BET, NH3-TPD, H2-TPR, XPS, FTIR with adsorption of pyridine and CO as well as TEM techniques were used for catalysts characterization. The results of catalytic tests revealed a crucial role of easily reducible highly dispersed copper oxide species to obtain enhanced activity and N2 selectivity in NH3-SCO. The selective catalytic reduction of NO by NH3 (NH3-SCR) and in situ DRIFT of NH3 sorption indicated that NH3-SCO proceeds according to the internal selective catalytic reduction mechanism (i-SCR).
Graphical abstract
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Greenish yellow emission from wurtzite structured ZnS:Ce nanophosphor synthesized at low temperature
Publication date: December 2017
Source:Journal of Luminescence, Volume 192
Author(s): K.R. Bindu, E.I. Anila
Cerium doped ZnS nanoparticles were synthesized by aqueous colloidal precipitation method at 70°C and post sintering at 650°C. Their structural, morphological, and photoluminescence properties were investigated. Fourier transform infrared and X-ray diffraction were used to determine chemical bonding and crystal structure of the synthesized nanoparticles. A phase transformation from cubic to wurtzite structure was observed due to sintering at 650°C. Scanning electron microscope revealed that the sintered particles exhibit uneven blocky particles with irregular shape. The band-gap of the nanoparticles was determined from diffuse reflectance spectrum. For the sintered ZnS:Ce nanoparticles when excited at about 350nm, in addition to host UV emission, transitions from 2D to both 2F5/2 and 2F7/2 levels of Ce3+ in ZnS lattice were observed resulting in a broad greenish yellow emission band centered at 538nm.
Graphical abstract
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NIR luminescent heterodinuclear [ZnII LnIII] complexes: Synthesis, crystal structures and photophysical properties
Publication date: December 2017
Source:Journal of Luminescence, Volume 192
Author(s): Nidhi Dwivedi, Sumit K. Panja, Abhineet Verma, Tomohisa Takaya, Koichi Iwata, Sailaja S. Sunkari, Satyen Saha
Two series of new 3d-4f heterodinuclear [ZnIILnIII] Schiff base complexes of general formula [Zn(µ-L1)(µ-CH3COO)Ln(NO3)2(S)] [Ln = Pr (1), Nd (2), Sm (3), Gd (4); S = MeOH; H2L1= N,N-bis(3-methoxysalicylidene)-1,4-diaminobutane] and [Zn(µ-L2)(µ-CH3COO)Ln(NO3)2(S)] [Ln= Pr (5), Nd (6), Sm (7), Gd (8), S= MeOH; H2L2= N,N-bis(3-ethoxysalicylidene)-1,4-diaminobutane] are synthesized and fully characterized. Complexes 1, 2, 3, 4, 5 & 7 are structurally characterized by single crystal X-ray crystallography. The crystallographic investigation indicates that the complexes contain 9 and 10-coordinated LnIII ions, while the ZnII ions always display a distorted square-pyramidal geometry. The crystal structure of the complexes are stabilized by inter molecular extended hydrogen bonding and C-H····π interactions resulting in supramolecular frameworks. Luminescence studies for the heterodinuclear compounds containing NdIII & SmIII reveal that the Zn-complex moiety acts as antenna for the emission from LnIII ions. In addition to the ligand-centered emission in the UV–Vis region, complex 2 (having NdIII) exhibits emission in NIR region also, thus resulting a new NIR emitting material.
Graphical abstract
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Fathers' feeding practices and children's weight status in Mexican American families
Source:Appetite, Volume 117
Author(s): Carlos Penilla, Jeanne M. Tschann, Julianna Deardorff, Elena Flores, Lauri A. Pasch, Nancy F. Butte, Steven E. Gregorich, Louise C. Greenspan, Suzanna M. Martinez, Emily Ozer
Mothers' feeding practices are associated with their children's weight status, but little is known about the associations between fathers' feeding practices and children's weight status. Moreover, there is a dearth of research on Latino fathers' feeding practices and children's weight status, even though Latino children suffer some of the highest obesity rates in the U.S. We examined the associations between fathers' feeding practices and child weight status, conditional on mothers' feeding practices, within 174 Mexican American families with children aged 8–10 years. Parents completed the Parental Feeding Practices Questionnaire, which consists of four subscales: positive involvement in child eating, pressure to eat, use of food to control behavior, and restriction of amount of food. To assess child weight status, body mass index (BMI) was calculated and converted to age- and gender-specific percentile scores (BMI z-score). We fit four sets of regression models, one set for each of the four parental feeding practices subscales, with child BMI z-score as the outcome variable. Fathers' pressure to eat (b = −0.20, p = 0.04; 95% CI: −0.39, −0.01) and use of food to control behavior (b = −0.36, p = 0.02; 95% CI: −0.65, −0.07) were associated with lower child BMI z-score, and restriction of amount of food (b = 0.56, p < 0.001; 95% CI: 0.27, 0.84) was associated with higher child BMI z-score, after accounting for mothers' feeding practices. Fathers' positive involvement in child eating was not associated with child BMI z-score. These findings provide empirical evidence that fathers' feeding practices are independently associated with children's weight status, even when mothers' feeding practices are taken into account, and suggest that fathers' feeding practices also matter in regard to children's weight status.
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Psychometric evaluation of the German version of the Intuitive Eating Scale-2 in a community sample
Source:Appetite, Volume 117
Author(s): Ulrike Alexandra Ruzanska, Petra Warschburger
Intuitive eating is based on a strong physical connection with the body, aligned to internal cues of hunger and satiety, and a low preoccupation with food. The aim of this study was to provide a German version of the Intuitive Eating Scale-2 (IES-2) and to examine its psychometric properties with data collected from 532 participants aged 18–91 years. The IES-2 was translated into German following the World Health Organization guidelines (2016). Cronbach's alpha as a measure of internal consistency was 0.89 for the IES-2 total score, as well as 0.73 - 0.92 for the IES-2 subscale scores. For group differences, the results were as hypothesized: men had higher IES-2 scores than women, and participants with under- and average weight showed higher IES-2 scores than participants with overweight and obesity. Participants without a dieting history had higher IES-2 scores than former or current dieters. In line with our hypotheses regarding construct validity, the IES-2 score had negative associations with emotional eating, restraint eating, external eating, binge eating and eating disorder symptomatology, as well as positive associations with self-efficacy and mental health-related quality of life. Second-order confirmatory factor analysis replicated the four-factor solution, with intuitive eating as a higher-order factor. These findings demonstrate that the German version of the IES-2 is a useful tool to assess intuitive eating in the general German population.
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Is there an advantage in onset of action with mixing lignocaine and bupivacaine?
Ever since Lidocaine (lignocaine) was first synthesised in 1943 and Bupivacaine first synthesised in 1957, surgeons have been mixing these two local anaesthetics. Lidocaine with its shorter duration of action has been linked (inaccurately) with a more rapid onset of action while the longer duration of Bupivacaine has again been suggested to have a slower onset of action. This erroneous extrapolation has led to many mixing the two to have an anaesthetic solution which might have rapid onset and long duration.
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Autoantibodies in juvenile-onset myositis: Their diagnostic value and associated clinical phenotype in a large UK cohort
Source:Journal of Autoimmunity
Author(s): Sarah L. Tansley, Stefania Simou, Gavin Shaddick, Zoe E. Betteridge, Beverley Almeida, Harsha Gunawardena, Wendy Thomson, Michael W. Beresford, Angela Midgley, Francesco Muntoni, Lucy R. Wedderburn, Neil J. McHugh
ObjectivesJuvenile myositis is a rare and heterogeneous disease. Diagnosis is often difficult but early treatment is important in reducing the risk of associated morbidity and poor outcomes. Myositis specific autoantibodies have been described in both juvenile and adult patients with myositis and can be helpful in dividing patients into clinically homogenous groups. We aimed to explore the utility of myositis specific autoantibodies as diagnostic and prognostic biomarkers in patients with juvenile-onset disease.MethodsUsing radio-labelled immunoprecipitation and previously validated ELISAs we examined the presence of myositis specific autoantibodies in 380 patients with juvenile-onset myositis in addition to, 318 patients with juvenile idiopathic arthritis, 21 patients with juvenile-onset SLE, 27 patients with muscular dystrophies, and 48 healthy children.ResultsAn autoantibody was identified in 60% of juvenile-onset myositis patients. Myositis specific autoantibodies (49% patients) were exclusively found in patients with myositis and with the exception of one case were mutually exclusive and not found in conjunction with another autoantibody. Autoantibody subtypes were associated with age at disease onset, key clinical disease features and treatment received.ConclusionsIn juvenile patients the identification of a myositis specific autoantibody is highly suggestive of myositis. Autoantibodies can be identified in the majority of affected children and provide useful prognostic information. There is evidence of a differential treatment approach and patients with anti-TIF1γ autoantibodies are significantly more likely to receive aggressive treatment with IV cyclophosphamide and/or biologic drugs, clear trends are also visible in other autoantibody subgroups.
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Implementation of a School‐Based Educational Program to Increase Breast Cancer Awareness and Promote Intergenerational Transmission of Knowledge in a Rural Mexican Community
AbstractBackground.Rural women have limited access to breast cancer education, which partially contributes to late diagnosis and treatment. In this pilot study, we tested the feasibility of implementing a school‐based breast cancer educational program for adolescents in a rural Mexican community. We hypothesized that the adolescents' knowledge on breast cancer would increase as a result of the program, and that there would be intergenerational transmission of that knowledge to their older female relatives.Materials and Methods.Female adolescents from a rural middle school received the educational program. The program would be considered feasible and acceptable if more than 75% reported being satisfied with its contents. Changes in knowledge in the students and their relatives were evaluated using baseline and 4 months follow‐up questionnaires.Results.One hundred twenty‐six students were enrolled. The program was considered acceptable by 96% of the participants. The students' knowledge regarding breast cancer increased significantly from baseline to 4 months follow‐up (63% to 82%). One hundred ninety‐four female relatives completed the initial knowledge questionnaires. The relatives' knowledge regarding breast cancer showed a significant increase from baseline to 4 months follow‐up (55% to 61%).Conclusion.Implementing breast cancer educational programs for adolescents in rural communities is feasible and acceptable. The program increased the adolescents' knowledge on breast cancer, and promoted the intergenerational transmission of that knowledge to their female relatives. Intergenerational transmission of knowledge represents a potential method for providing population‐based health awareness education globally.Implications for Practice.In limited‐resource settings, education is a valuable tool for achieving early detection and downstaging of breast cancer. Unfortunately, rural women lack access to educational opportunities and information about breast cancer, which is a factor contributing to late diagnosis and treatment. In this study, we demonstrated that implementing a school‐based breast cancer educational program for female adolescents in a rural Mexican community was feasible, acceptable, and increased their knowledge about breast cancer. Furthermore, the program encouraged the transmission of information to the students' older relatives. Intergenerational transmission of knowledge represents a novel and potentially effective tool in cancer education and promotion.
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Pregabalin for the Prevention of Oxaliplatin‐Induced Painful Neuropathy: A Randomized, Double‐Blind Trial
AbstractLessons Learned. Pregabalin is a medication that can decrease neuronal hyperexcitability, relieve neuropathic pain, and reach stable plasma levels after a titration period of only a few days.Its use during oxaliplatin infusions was not able to decrease the incidence of chronic, oxalipaltin‐related neuropathic pain, compared with placebo.Background.Patients with colorectal cancer (CRC) receiving oxaliplatin (OXA) develop acute and chronic painful oxaliplatin‐induced peripheral neuropathy (OXAIPN). Acute and chronic OXA‐related neuropathies have different pathophysiological bases, but both lead to a common phenomenon: central sensitization (CS) of nociceptive neuronal networks, leading to increased sensitivity (hyperlgesia, allodynia) in the somatosensory system, the common ground of chronic neuropathic pain. Because CS is related to increased risk of painful OXAIPN, we hypothesized that preemptive use of the anti‐hyperalgesic drug pregabaline (known to decrease CS) during OXA infusions would decrease the incidence of chronic OXAIPN.Methods.Pain‐free, chemotherapy‐naïve CRC patients receiving at least one cycle of modified‐FLOX [5‐FU(500mg/m2)+leucovorin(20mg/m2)/week for] 6weeks+Oxaliplatin(85mg/m2) at weeks 1‐3‐5 every 8 weeks] were randomized (1:1) into the study. Patients received either pregabalin or placebo for 3 days before and 3 days after each OXA infusion and were followed for up to 6 months. Clinical assessments were performed at baseline, at the end of chemotherapy, and after the follow‐up period. The main outcome was average pain at the last visit assessed by the visual analogic scale (0–10) item of the Brief Pain Inventory (BPI). Secondary endpoints were presence of neuropathic pain according to the Douleur Neuropathique‐4 (DN‐4), pain dimensions (short‐ form McGill Pain Questionnaire [MPQ]), Neuropathic Pain Symptom Inventory (NPSI), and changes in nerve conduction studies (NCS) and side effect profile.Results.One hundred ninety‐nine patients (57.0 ± 10.7 years old, 98 female, 101 male) were randomized. Data from 56 patients were not included in the analyses (as they did not receive at least one full cycle of modified FLOX). Data from 78 patients in the pregabalin group and 65 patients in the placebo group were retained for analyses. At the last visit, pain intensity in the pregabalin group was 1.03 (95% confidence interval [CI] = 0.79–1.26), and 0.85 (95% CI = 0.64–1.06) in the placebo group, which did not reach significance. Scores from the BPI, MPQ, DN‐4, NPSI, and NCS and side‐effect profiles and incidence of death did not differ between groups. Quality of life (QoL) score did not differ between groups (placebo = 76.9 ± 23.1, pregabalin group 79.4 ± 20.6). Mood scores were not significantly different between groups (placebo 9.7 [8.1–11.2]; pregabalin 6.8 [5.6–8.0]).Conclusion.The preemptive use of pregabalin during OXA infusions was safe, but did not decrease the incidence of chronic pain related to OXAIPN.
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Immune‐Related Adverse Events as a Biomarker in Non‐Melanoma Patients Treated with Programmed Cell Death 1 Inhibitors
AbstractBackground.The programmed death 1 (PD‐1) checkpoint inhibitors (CKIs) can lead to immune‐related adverse events (irAEs). We sought to evaluate whether the development of irAEs correlates with treatment response in non‐melanoma malignancies.Materials and Methods.We conducted a retrospective study of patients who received anti‐PD‐1 CKI monotherapy at Fox Chase Cancer Center. Endpoints included overall response rate (ORR), time to next therapy or death (TTNTD), and overall survival (OS). Fisher's exact tests and logistic regression models were used to determine the association between irAE incidence and ORR, and Kaplan‐Meier curves with log‐rank tests and Cox regression models were used for the comparison of TTNTD and OS.Results.Between November 2011 and November 2016, 160 patients were treated with >1 dose of an anti‐PD‐1 CKI. Seventy‐three (46%) were treated on a clinical trial. Immune‐related adverse events were noted in 64 patients (40%), with steroids required in 36 (23%). Of the 142 patients evaluable for clinical response, 28 patients (20%) achieved a partial response at first scan. An association between irAEs and ORR was seen in clinical trial patients (p = .007), but not in non‐trial patients (p = .13). When controlling for clinical trial participation and cancer type using multivariate analysis, low‐grade irAEs had higher ORR (p = .017) and longer TTNTD (p = .008). No association between irAE incidence and OS was seen (p = .827). Immune‐related adverse events that required steroid treatment were marginally associated with increased TTNTD (p = .05, hazard ratio 0.62) but were not associated with OS (p = .13).Conclusion.We demonstrate several positive associations between the development of irAEs and clinical outcomes in non‐melanoma patients treated with PD‐1 CKIs, for which further validation is required.Implications for Practice.This study evaluated whether the development of immune‐related adverse events in non‐melanoma patients treated with programmed cell death 1 checkpoint inhibitors correlates with improved clinical outcomes. The results indicate that for a subset of patients, in particular those with low‐grade immune‐related adverse events, immune‐related adverse events predicted for an improved response rate and longer time to next therapy or death.
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Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA‐3 Results
AbstractBackground.The efficacy and safety of palbociclib, a cyclin‐dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET).Patients and Methods.One hundred eight premenopausal endocrine‐refractory women ≥18 years with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) ABC were among 521 women randomized 2:1 (347:174) to fulvestrant (500 mg) ± goserelin with either palbociclib (125 mg/day orally, 3 weeks on, 1 week off) or placebo. This analysis assessed whether the overall tolerable safety profile and significant progression‐free survival (PFS) improvement extended to premenopausal women. Potential drug‐drug interactions (DDIs) and ovarian suppression with goserelin were assessed via plasma pharmacokinetics and biochemical analyses, respectively. (ClinicalTrials.gov identifier: NCT01942135)Results.Median PFS for premenopausal women in the palbociclib (n = 72) versus placebo arm (n = 36) was 9.5 versus 5.6 months, respectively (hazard ratio, 0.50, 95% confidence interval: 0.29–0.87), and consistent with the significant PFS improvement in the same arms for postmenopausal women. Any‐grade and grade ≤3 neutropenia, leukopenia, and infections were among the most frequent adverse events reported in the palbociclib arm with concurrent goserelin administration. Hormone concentrations were similar between treatment arms and confirmed sustained ovarian suppression. Clinically relevant DDIs were not observed.Conclusion.Palbociclib combined with fulvestrant and goserelin was an effective and well‐tolerated treatment for premenopausal women with prior endocrine‐resistant HR+/HER2− ABC. Inclusion of both premenopausal and postmenopausal women in pivotal combination ET trials facilitates access to novel drugs for young women and should be considered as a new standard for clinical trial design.Implications for Practice.PALOMA‐3, the first registrational study to include premenopausal women in a trial investigating a CDK4/6 inhibitor combined with endocrine therapy, has the largest premenopausal cohort reported in an endocrine‐resistant setting. In pretreated premenopausal women with hormone receptor–positive advanced breast cancer, palbociclib plus fulvestrant and goserelin (luteinizing hormone–releasing hormone [LHRH] agonist) treatment almost doubled median progression‐free survival (PFS) and significantly increased the objective response rate versus endocrine monotherapy, achieving results comparable to those reported for chemotherapy without apparently interfering with LHRH agonist‐induced ovarian suppression. The significant PFS gain and tolerable safety profile strongly support use of this regimen in premenopausal women with endocrine‐resistant disease who could possibly delay chemotherapy.
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Ruthenium complex exerts antineoplastic effects that are mediated by oxidative stress without inducing toxicity in Walker-256 tumor-bearing rats
Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Carlos Eduardo Alves de Souza, Helen de Morais Alves de Souza, Maria Carolina Stipp, Claudia Rita Corso, Claudia Martins Galindo, Carolina Riverin Cardoso, Rosangela Locatelli Dittrich, Edneia Amancio de Souza Ramos, Giseli Klassen, Rose Maria Carlos, Sílvia Maria Suter Correia Cadena, Alexandra Acco
The present study evaluated the in vivo antitumor effects and toxicity of a new Ru(II) compound, cis-(Ru[phen]2[ImH]2)2+ (also called RuphenImH [RuC]), against Walker-256 carcinosarcoma in rats. After subcutaneous inoculation of Walker-256 cells in the right pelvic limb, male Wistar rats received 5 or 10mgkg−1 RuC orally or intraperitoneally (i.p.) every 3 days for 13 days. A positive control group (2mgkg−1 cisplatin) and negative control group (vehicle) were also used. Tumor progression was checked daily. After treatment, tumor weight, plasma biochemistry, hematology, oxidative stress, histology, and tumor cell respiration were evaluated. RuC was effective against tumors when administered i.p. but not orally. The highest i.p. dose of RuC (10mgkg−1) significantly reduced tumor volume and weight, induced oxidative stress in tumor tissue, reduced the respiration of tumor cells, and induced necrosis but did not induce apoptosis in the tumor. No clinical signs of toxicity or death were observed in tumor-bearing or healthy rats that were treated with RuC. These results suggest that RuC has antitumor activity through the modulation of oxidative stress and impairment of oxidative phosphorylation, thus promoting Walker-256 cell death without causing systemic toxicity. These effects make RuC a promising anticancer drug for clinical evaluation.
Graphical abstract
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Multiple functional strategies for amplifying sensitivity of amperometric immunoassay for tumor markers: A review
Source:Biosensors and Bioelectronics, Volume 98
Author(s): Zhongxue Tang, Zhanfang Ma
Multiple functional strategies have shown great potential in ultrasensitive amperometric immunoassays for tumor markers, which promote conductivity and signal multiple amplification. The sensitivity of amperometric immunoassays is significantly affected by the conductivity and specific area of the sensing interface as well as the electrochemical activity of redox species. Thus, these strategies are generally based on integrating various materials together and endowing immunosensing systems with many advantages, such as large specific area, high electrochemical activity, good conductivity, biocompatibility, and catalytic performance. Owing to the rapid development of functional materials (such as conductive hybrids, catalytic hybrids, enzyme-like materials, highly electrochemical active species, redox nanocomposites, porous materials, hydrogels, and metal-organic framework) and new bioactive substances (including new blocking agents and receptors like peptides and oligonucleotide chains), the sensitivity of related biosensors is usually higher than that of traditional ones, indicating that multiple functional strategies are promising in amperometric immunoassays. Herein, we provide an overview of recent advances in multiple functional strategies that have proven to dramatically enhance the sensitivity of amperometric immunoassays, which incorporate the following materials: (1) conductive nanomaterials hybrids; (2) catalytic nanomaterials hybrids; (3) new redox materials; (4) three-dimensional porous materials; (5) new receptors and blocking agents.
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In situ grown DNA nanotail-templated silver nanoclusters enabling label-free electrochemical sensing of terminal deoxynucleotidyl transferase activity
Source:Biosensors and Bioelectronics, Volume 98
Author(s): Yufang Hu, Qingqing Zhang, Zhiyong Guo, Sui Wang, Chunnuan Du, Chunyang Zhai
A novel label-free electrochemical strategy was established based on the unique electro-catalytic activity of graphene oxide (GO)-supported terminal deoxynucleotidyl transferase (TdT)-generated C-rich DNA nanotail-templated silver nanoclusters (DNA-AgNCs). TdT can catalyze the deoxycytidine triphosphate (dCTP) to the 3′-OH terminus of single-stranded DNA (ssDNA) with no template; then, in the presence of Ag(I), TdT-generated C-rich DNA sequence was employed for the synthetic template of AgNCs because of the formed complexes of nitrogen atoms of cytosine based with silver atoms. We proved that in situ grown DNA nanotail-templated AgNCs can be adsorbed on GO-modified electrode and possess high electro-catalytic activity to H2O2 reduction, presenting a good electrochemical indicator for signal readout. Under optimal conditions, the proposed biosensor could be employed for quantitatively monitoring TdT activity and within a dynamic range from 0.4 to 90U/mL and a low limit of detection is 0.08U/mL. With high sensitivity and excellent selectivity, this strategy offers a facile, convenient and specific electrochemical method for TdT activity detection and its relevant inhibitors screening. It holds a promising potential in the practical application of TdT-based biochemical research, disease diagnosis and drug discovery.
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Dietary Supplements as Surrogate of Mediterranean Diet in Healthy Smoking Subjects
Rejuvenation Research , Vol. 0, No. 0.
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Dataset on lipid profile of bovine oocytes exposed to Lα-phosphatidylcholine during in vitro maturation investigated by MALDI mass spectrometry and gas chromatography-flame ionization detection
Publication date: August 2017
Source:Data in Brief, Volume 13
Author(s): Alessandra A. Vireque, Christina R. Ferreira, Rafael R. Hatanaka, Alessandra Tata, Katia Roberta A. Belaz, Vanessa G. Santos, Marcos N. Eberlin, Marcos Felipe Silva de Sá, Rui A. Ferriani, Ana Carolina J.S. Rosa e Silva
Data presented in this article are related with the research article entitled "Effect of soybean phosphatidylcholine on lipid profile of bovine oocytes matured in vitro" [1]. This article describes the differences in the relative abundance of the lipid ions detected by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) in control and Lα-phosphatidylcholine-treated oocytes. In addition, the fatty acids (FA) content in pure Lα-phosphatidylcholine supplement and oocytes was analyzed by gas chromatography-flame ionization detection (GC-FID). The dataset provides information and inputs for further studies aiming to optimize in vitro maturation conditions and cryotolerance of mammalian oocytes.
http://ift.tt/2sU9osX
Vitamin D and Cardiovascular Disease: Controversy Unresolved
Abstract
Vitamin D deficiency is typically caused by inadequate cutaneous synthesis secondary to decreased exposure to sunlight. Serum levels of 25-hydroxyvitamin D l <20 ng/ml are diagnostic of vitamin D deficiency. Vitamin D has various cardiovascular pleiotropic effects by activating its nuclear receptor in cardiomyocytes and vascular endothelial cells and by regulating the renin-angiotensin-aldosterone system, adiposity, energy expenditure, and pancreatic cell activity. In humans, vitamin D deficiency is associated with the following: vascular dysfunction; arterial stiffening; left ventricular hypertrophy; and worsened metrics of diabetes, hypertension, and hyperlipidemia. It is also linked with worse cardiovascular morbidity and mortality. However, meta-analyses of vitamin D supplementation trials have failed to show clear improvements in blood pressure, insulin sensitivity, or lipid parameters, thus suggesting that the link between vitamin D deficiency and cardiovascular disease may be an epiphenomenon. Ongoing larger randomized trials will clarify whether monitoring and supplementation of vitamin D play roles in cardiovascular protection.
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Procedural Experience for Transcatheter Aortic Valve Replacement and Relation to Outcomes: The STS/ACC TVT Registry
AbstractBackground
Transcatheter aortic valve replacement (TAVR) has been introduced into U.S. clinical practice with efforts to optimize outcomes and minimize the learning curve.
ObjectivesThe goal of this study was to assess the degree to which increasing experience during the introduction of this procedure, separated from other outcome determinants including patient and procedural characteristics, is associated with outcomes.
MethodsThe authors evaluated the association of hospital TAVR volume and patient outcomes for TAVR by using data from 42,988 commercial procedures conducted at 395 hospitals submitting to the Transcatheter Valve Therapy Registry from 2011 through 2015. Outcomes assessed included adjusted and unadjusted in-hospital major adverse events.
ResultsIncreasing site volume was associated with lower in-hospital risk-adjusted outcomes, including mortality (p < 0.02), vascular complications (p < 0.003), and bleeding (p < 0.001) but was not associated with stroke (p = 0.14). From the first case to the 400th case in the volume–outcome model, risk-adjusted adverse outcomes declined, including mortality (3.57% to 2.15%), bleeding (9.56% to 5.08%), vascular complications (6.11% to 4.20%), and stroke (2.03% to 1.66%). Vascular and bleeding volume–outcome associations were nonlinear with a higher risk of adverse outcomes in the first 100 cases. An association of procedure volume with risk-adjusted outcomes was also seen in the subgroup having transfemoral access.
ConclusionsThe initial adoption of TAVR into practice in the United States showed that increasing experience was associated with better outcomes. This association, whether deemed a prolonged learning curve or a manifestation of a volume–outcome relationship, suggested that concentrating experience in higher volume heart valve centers might be a means of improving outcomes. (STS/ACC Transcatheter Valve Therapy Registry [TVT Registry]; NCT01737528)
http://ift.tt/2tNOAnj
Temporal Trends in Transcatheter Aortic Valve Replacement in France: FRANCE 2 to FRANCE TAVI
AbstractBackground
Transcatheter aortic valve replacement (TAVR) is standard therapy for patients with severe aortic stenosis who are at high surgical risk. However, national data regarding procedural characteristics and clinical outcomes over time are limited.
ObjectivesThe aim of this study was to assess nationwide performance trends and clinical outcomes of TAVR during a 6-year period.
MethodsTAVRs performed in 48 centers across France between January 2013 and December 2015 were prospectively included in the FRANCE TAVI (French Transcatheter Aortic Valve Implantation) registry. Findings were further compared with those reported from the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry, which captured all TAVRs performed from January 2010 to January 2012 across 34 centers.
ResultsA total of 12,804 patients from FRANCE TAVI and 4,165 patients from FRANCE 2 were included in this analysis. The median age of patients was 84.6 years, and 49.7% were men. FRANCE TAVI participants were older but at lower surgical risk (median logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE]: 15.0% vs. 18.4%; p < 0.001). More than 80% of patients in FRANCE TAVI underwent transfemoral TAVR. Transesophageal echocardiography guidance decreased from 60.7% to 32.3% of cases, whereas more recent procedures were increasingly performed in hybrid operating rooms (15.8% vs. 35.7%). Rates of Valve Academic Research Consortium–defined device success increased from 95.3% in FRANCE 2 to 96.8% in FRANCE TAVI (p < 0.001). In-hospital and 30-day mortality rates were 4.4% and 5.4%, respectively, in FRANCE TAVI compared with 8.2% and 10.1%, respectively, in FRANCE 2 (p < 0.001 for both). Stroke and potentially life-threatening complications, such as annulus rupture or aortic dissection, remained stable over time, whereas rates of cardiac tamponade and pacemaker implantation significantly increased.
ConclusionsThe FRANCE TAVI registry provided reassuring data regarding trends in TAVR performance in an all-comers population on a national scale. Nonetheless, given that TAVR indications are likely to expand to patients at lower surgical risk, concerns remain regarding potentially life-threatening complications and pacemaker implantation. (Registry of Aortic Valve Bioprostheses Established by Catheter [FRANCE TAVI]; NCT01777828)
http://ift.tt/2teoAnX
Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015
AbstractBackground
The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world.
ObjectivesThe GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden.
MethodsCVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility.
ResultsIn 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75.
ConclusionsCVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.
http://ift.tt/2teXQ6C
The Cardiovascular Effects of Cocaine
Abstract
Cocaine is the leading cause for drug–abuse-related visits to emergency departments, most of which are due to cardiovascular complaints. Through its diverse pathophysiological mechanisms, cocaine exerts various adverse effects on the cardiovascular system, many times with grave results. Described here are the varied cardiovascular effects of cocaine, areas of controversy, and therapeutic options.
http://ift.tt/2tOiwzp
Arterial Remodeling After Bioresorbable Scaffolds and Metallic Stents
AbstractBackground
Although previous observational studies have documented late luminal enlargement and expansive remodeling following implantation of a bioresorbable vascular scaffold (BVS), no comparison with metallic stents has been conducted in a randomized fashion.
ObjectivesThis study sought to compare vessel remodeling patterns after either Absorb BVS or Xience metallic drug-eluting stent (DES) implantation (Abbott Vascular, Santa Clara, California) and determine the independent predictors of remodeling.
MethodsIn the ABSORB II randomized trial, 383 lesions (n = 359) were investigated by intravenous ultrasound both post-procedure and at 3-year follow-up. According to vessel and lumen area changes over 3 years, we categorized 9 patterns of vessel remodeling that were beyond the reproducibility of lumen and vessel area measurements.
ResultsThe relative change in mean vessel area was significantly greater with the BVS compared to the DES (6.7 ± 12.6% vs. 2.9 ± 11.5%; p = 0.003); the relative change in mean lumen area was significantly different between the 2 arms (1.4 ± 19.1% vs. –1.9 ± 10.5%, respectively; p = 0.031). Multivariate analysis indicated that use of the BVS, female sex, balloon-artery ratio >1.25, expansion index ≥0.8, previous percutaneous coronary intervention, and higher level of low-density lipoprotein cholesterol were independent predictors of expansive remodeling. Furthermore, in the BVS arm, necrotic core pre-procedure was an independent determinant of expansive remodeling.
ConclusionsExpansive vessel wall remodeling was more frequent and intense with the BVS than the metallic DES and could be determined by patient baseline characteristics and periprocedural factors. The clinical effect of the observed lumen and vessel remodeling must be investigated in further large clinical studies to optimize the clinical outcome of patients and lesions treated by bioresorbable scaffolds. (ABSORB II Randomized Controlled Trial; NCT01425281)
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Treating Specialty and Outcomes in Newly Diagnosed Atrial Fibrillation: From the TREAT-AF Study
AbstractBackground
Atrial fibrillation (AF) occurs in many clinical contexts and is diagnosed and treated by clinicians across many specialties. This approach has resulted in treatment variations.
ObjectivesThe goal of this study was to evaluate the association between treating specialty and AF outcomes among patients newly diagnosed with AF.
MethodsUsing data from the TREAT-AF (Retrospective Evaluation and Assessment of Therapies in AF) study from the Veterans Health Administration, patients with newly diagnosed, nonvalvular AF between 2004 and 2012 were identified who had at least 1 outpatient encounter with primary care or cardiology within 90 days of the AF diagnosis. Cox proportional hazards regression was used to evaluate the association between treating specialty and AF outcomes.
ResultsAmong 184,161 patients with newly diagnosed AF (age 70 ± 11 years; 1.7% women; CHA2DS2-VASc score 2.6 ± 1.7), 40% received cardiology care and 60% received primary care only. After adjustment for covariates, cardiology care was associated with reductions in stroke (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.86 to 0.96; p < 0.001) and death (HR: 0.89; 95% CI: 0.88 to 0.91; p < 0.0001) and increases in hospitalizations for AF/supraventricular tachycardia (HR: 1.38; 95% CI: 1.35 to 1.42; p < 0.0001) and myocardial infarction (HR: 1.03; 95% CI: 1.00 to 1.05; p < 0.04). The propensity-matched cohort had similar results. In mediation analysis, oral anticoagulation prescription within 90 days of diagnosis may have mediated reductions in stroke but did not mediate reductions in survival.
ConclusionsIn patients with newly diagnosed AF, cardiology care was associated with improved outcomes, potentially mediated by early prescription of oral anticoagulation therapy. Although hypothesis-generating, these data warrant serious consideration and study of health care system interventions at the time of new AF diagnosis.
http://ift.tt/2teDN8w
External validation of leukocytosis and neutrophilia as a prognostic marker in anal carcinoma treated with definitive chemoradiation
Source:Radiotherapy and Oncology
Author(s): Antoine Schernberg, Florence Huguet, Laurence Moureau-Zabotto, Cyrus Chargari, Eleonor Rivin Del Campo, Michel Schlienger, Alexandre Escande, Emmanuel Touboul, Eric Deutsch
PurposeTo validate the prognostic value of leukocyte disorders in anal squamous cell carcinoma (SCC) patients receiving definitive concurrent chemoradiation.Materials and methodsBi-institutional clinical records from consecutive patients treated between 2001 and 2015 with definitive chemoradiation for anal SCC were retrospectively reviewed. Prognostic value of pretreatment leukocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as leukocyte or neutrophil count exceeding 10G/L and 7G/L, respectively.ResultsWe identified 133 patients, treated in two institutions. Eight% and 7% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year overall survival (OS) and progression-free survival (PFS) were 88% and 77%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS (p<0.01), locoregional control (LRC) and Distant Metastasis Control (DMC) (p<0.05), also after stratification by each institution. In multivariate analysis, leukocytosis and neutrophilia remained as independent risk factors associated with poorer OS, PFS, LRC and DMC (p<0.05).ConclusionThis study validates leukocytosis and neutrophilia as independent prognostic factors in anal SCC patients treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters are clinically relevant biomarkers to be considered for further clinical investigations.
http://ift.tt/2sJl1ob
The incidence of symptomatic brain metastases from extra-pulmonary small cell carcinoma: Is there a role for prophylactic cranial irradiation in a clinically relevant population cohort?
Source:Radiotherapy and Oncology
Author(s): Alex De Caluwé, Gale Bowering, Alan Nichol, Fred Hsu
Background and purposeTo examine the incidence and outcomes of patients with brain metastases from extra-pulmonary small cell carcinoma (EPSCC) and assess the indication for prophylactic cranial irradiation (PCI).Materials and methodsA Provincial cancer registry was used to conduct a retrospective, population-based study of patients diagnosed with EPSCC between January 1997 and December 2011. The primary end point was the incidence of brain metastases. The secondary endpoint was overall survival. A "PCI Eligible" cohort was defined to provide an estimation of the incidence of brain metastases in clinically relevant patients.ResultsIn 287 patients, the primary sites were 21% gastrointestinal, 34% genito-urinary, 14% gynecologic, 5% head/neck and 25% unknown primary. Thirty-five (12.5%) patients had brain metastases: 12 (4.2%) at initial diagnosis and 23 (8%) later in the disease course. In PCI Eligible patients, the 3-year cumulative incidence of new brain metastases was 5.5% for M0 stage disease and 26.3% for M1 disease. There was no significant difference in the incidence of brain metastases between primary sites.ConclusionsThe incidence of brain metastases in patients with EPSCC is comparatively low, even in a cohort of patients that were suitable for PCI. Based on our analysis, we cannot recommend PCI for patients with EPSCC.
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Quality of compounded hydrocortisone capsules used in the treatment of children
Objectives
Due to the lack of paediatric-licensed formulations, children are often treated with individualized pharmacy-compounded adult medication. An international web-based survey about the types of medication in children with adrenal insufficiency (AI) revealed that the majority of paediatric physicians are using pharmacy-compounded medication to treat children with AI. Observations of loss of therapy control in children with congenital adrenal hyperplasia with compounded hydrocortisone capsules and regained control after prescribing a new hydrocortisone batch led to this 'real world' evaluation of pharmacy-compounded paediatric hydrocortisone capsules.
MethodsCapsule samples were collected randomly from volunteering parents of treated children suffering from congenital adrenal hyperplasia from all over Germany. Analysis of net mass and hydrocortisone content by high-performance liquid chromatography with ultraviolet (HPLC-UV) detection method was performed based on the European Pharmacopeia.
ResultsIn a total of 61 batches that were sent, 5 batches could not be analysed because of missing dose information, insufficient number of capsules or were not possible to be evaluated. Fifty-six batches containing 1125 capsules were evaluated. 21.4% of the batches revealed insufficiency in uniformity of net mass or drug content and additional 3.6% failed because they did not contain the labelled drug.
ConclusionsCompounded medication is a possible cause of variation of steroid doses in children with adrenal insufficiency or congenital adrenal hyperplasia, putting these vulnerable patients at risk of poor disease control and adrenal crisis. These data may apply to other individualized compounded oral medication as well, emphasizing the need for development of licensed paediatric formulations approved by regulatory authorities.
http://ift.tt/2tdZTbd
Effect of different nitrogen forms on the toxicity of Zn in wheat seedling root: a modeling analysis
Abstract
Heavy metal stress in culture media is always rhizotoxic. Our study aims to investigate the role of negative potential (ψ 0) at root cell membrane surface (CMs) on modeling Zn2+ toxicity to wheat seedling roots and to examine the effects of different nitrogen forms (NH4+ and NO3−) on ψ 0 and Zn rhizotoxicity. Solution culture experiments were conducted to measure the root elongation and Zn accumulation under Zn2+ exposure. The role of two nitrogen forms in affecting Zn2+ toxicity was compared, giving particular consideration to ψ 0 and Zn2+ activities at CMs ({Zn2+}0). Results showed that NH4+ alleviates Zn2+ rhizotoxicity and NO3− increases Zn2+ rhizotoxicity. In modeling the rhizotoxicity, root length correlated better with {Zn2+}0 than {Zn2+}b, and the predictive accuracy (r 2) of NH4+ treatment increased from 0.748 to 0.917 when incorporation of {Zn2+}0 and {Ca2+}0 into analysis. Oppositely, ψ 0 played a limited role in modeling Zn2+ rhizotoxicity and bioavailability in NO3− treated medium (r 2 = 0.609). Moreover, higher concentration of Zn in roots was found in NO3− treatment, compared with the NH4+ treatment. ψ 0 rather than the rhizotoxicity data correlated better with Zn accumulation especially in the NO3− treatment (r 2 > 0.7), which meant the electrical driving force at CMs playing a dominant role in modeling the metal accumulation. In conclusion, the alleviatory role of NH4+ on Zn toxicity and uptake was well explained and modeled by electrostatic effects at CMs. Though our data do not explore mechanisms for the NO3−-Zn2+ interactions, we propose that ψ 0 worked better in affecting the driving force for root Zn uptake, than influencing metal bioavailability at CMs.
http://ift.tt/2seeK0t
Evaluation of air pollution tolerance index and anticipated performance index of plants and their application in development of green space along the urban areas
Abstract
Air pollution due to vehicular emissions has become one of the most serious problems in the whole world and has resulted in huge threat to both the environment and the health of living organisms (plants, humans, animals, microorganisms). Plants growing along the roadsides get affected at the maximum as they are the primary recipients to different air pollutants and show varied levels of tolerance and sensitivity. Taking this into account, the present work was based on assessment of seasonal variation in air pollution tolerance index (APTI) and anticipated performance index (API) of four roadside plants, namely, Alstonia scholaris, Nerium oleander, Tabernaemontana coronaria, and Thevetia peruviana belonging to family Apocynaceae. APTI was calculated by the determination of four important biochemical parameters, viz., pH, relative water content (RWC), total chlorophyll (TChl), and ascorbic acid (AsA) content of leaves. The leaf samples were collected from plants growing at seven different sites of Amritsar (Punjab), India, for pre-monsoon and post-monsoon seasons. Highest APTI (82.14) was reported in N. oleander during the pre-monsoon season while the lowest was recorded in T. coronaria (18.59) in the post-monsoon season. On the basis of API score, A. scholaris was anticipated to be an excellent performer during the pre-monsoon and post-monsoon seasons followed by N. oleander, T. coronaria, and T. peruviana. Linear regression analysis and Pearson's correlation coefficient depicted significant positive correlation between APTI and ascorbic acid content during the pre-monsoon and post-monsoon seasons.
http://ift.tt/2sIQXsO
Histamine H 4 receptor signalling in tongue cancer and its potential role in oral carcinogenesis - a short report
Abstract
Purpose
Recent reports indicate that histamine and its novel, high-affinity histamine H4 receptor (H4R) play a role in carcinogenesis, and thus H4R signalling has become a focus of increasing interest in the pathogenesis of many cancers. The roles of H4R in oral epithelial dysplasia (OED) and oral tongue squamous cell carcinoma (OTSCC) are unknown. The purpose of this study was to assess H4R expression in OTSCC patients and in OTSCC-derived cell lines.
Methods
Biopsies taken from OED, OTSCC and healthy oral mucosa were studied by immunostaining. Primary human oral keratinocytes (HOKs) and two OTSCC-derived cell lines (HSC-3 and SCC-25) were used for the in vitro studies. Quantitative real-time PCR was used to measure oncogene expression in the stimulated HOKs.
Results
We found that H4R-immunoreactivity was significantly reduced in the OED and OTSCC samples, especially in the samples with higher histopathological grades and noticeably increased mast cell counts. The presence of H4R in HSC-3 cells had clearly waned, in contrast to the HOKs. Gene expression data indicated that histamine-relevant inflammatory and environmental elements may participate in the regulation of oncogenes.
Conclusions
Our results suggest an association between H4R and oral carcinogenesis. Furthermore, our findings raise a potential implication of histamine-mediated factors in the regulation of oncogenes, possibly via mast cells, as crucial components of the tumor microenvironment. The identification of new elements that govern oral cancer development is highly relevant for the development of novel therapeutic approaches in OTSCC.
http://ift.tt/2rU9vUh
Progesterone suppresses the invasion and migration of breast cancer cells irrespective of their progesterone receptor status - a short report
Abstract
Purpose
Pre-operative progesterone treatment of breast cancer has been shown to confer survival benefits to patients independent of their progesterone receptor (PR) status. The underlying mechanism and the question whether such an effect can also be observed in PR negative breast cancer cells remain to be resolved.
Methods
We performed proteome profiling of PR-positive and PR-negative breast cancer cells in response to progesterone using a phospho-kinase array platform. Western blotting was used to validate the results. Cell-based phenotypic assays were conducted using PR-positive and PR-negative breast cancer cells to assess the effect of progesterone.
Results
We found that progesterone induces de-phosphorylation of 12 out of 43 kinases tested, which are mostly involved in cellular invasion and migration regulation. Consistent with this observation, we found through cell-based phenotypic assays that progesterone inhibits the invasion and migration of breast cancer cells independent of their PR status.
Conclusion
Our results indicate that progesterone can inhibit breast cancer cell invasion and migration mediated by the de-phosphorylation of kinases. This inhibition appears to be independent of the PR status of the breast cancer cells. In a broader context, our study may provide a basis for an association between progesterone treatment and recurrence reduction in breast cancer patients, thereby providing a lead for modelling a randomized in vitro study.
http://ift.tt/2tcube2
Development of a Perfusion Platform for Dynamic Cultivation of in vitro Skin Models
Reconstructed skin models are suitable test systems for toxicity testing and for basic investigations on (patho-)physiological aspects of human skin. Reconstructed human skin, however, has clear limitations such as the lack of immune cells and a significantly weaker skin barrier function compared to native human skin. Potential reasons for the latter might be the lack of mechanical forces during skin model cultivation which is performed classically in static well-plate setups. Mechanical forces and shear stress have a major impact on tissue formation and, hence, tissue engineering. In the present work, a perfusion platform was developed allowing dynamic cultivation of in vitro skin models. The platform was designed to cultivate reconstructed skin at the air-liquid interface with a laminar and continuous medium flow below the dermis equivalent. Histological investigations confirmed the formation of a significantly thicker stratum corneum compared to the control cultivated under static conditions. Moreover, the skin differentiation markers involucrin and filaggrin as well as the tight junction proteins claudin 1 and occludin showed increased expression in the dynamically cultured skin models. Unexpectedly, despite improved differentiation, the skin barrier function of the dynamically cultivated skin models was not enhanced compared with the skin models cultivated under static conditions.
Skin Pharmacol Physiol 2017;30:180-189
http://ift.tt/2rTxpz5
Gabapentin Prevents Progressive Increases in Excitatory Connectivity and Epileptogenesis Following Neocortical Trauma
http://ift.tt/2sT5QHw
Neuroinflammation and Tau Interact with Amyloid in Predicting Sleep Problems in Aging Independently of Atrophy
http://ift.tt/2s9bY19
Sex differences in brain mitochondrial metabolism: influence of endogenous steroids and stroke
Abstract
Steroids are neuroprotective and growing body of evidence indicates that mitochondria are a potential target of their effects. The mitochondria are the site of cellular energy synthesis, regulate oxidative stress and play a key role in cell death after brain injury and neurodegenerative diseases. After a summary of the literature on the general functions of mitochondria and the effects of sex steroid administrations on mitochondrial metabolism, we will summarize and discuss our recent findings concerning sex differences in brain mitochondrial function in physiological and pathological conditions. To analyze the influence of endogenous sex steroids, oxidative phosphorylation system, mitochondrial oxidative stress and brain steroid levels were compared between male and female mice, either intact or gonadectomized. Our results show that females have higher mitochondrial respiration and lower oxidative stress as compared to males and these differences were suppressed by ovariectomy but not orchidectomy. We have also shown that the decrease in brain mitochondrial respiration induced by ischaemia/reperfusion is different according to sex. In both sexes, treatment with progesterone reduced the ischaemia/reperfusion-induced mitochondrial alterations. Our findings point to sex differences in brain mitochondrial function under physiological conditions, and after stroke, and identify mitochondria as a target of the neuroprotective properties of progesterone. Thus, it is necessary to investigate sex specificity in brain physio-pathological mechanisms, especially when mitochondria impairment is involved.
This article is protected by copyright. All rights reserved.
http://ift.tt/2u8aOQi
Effects of central administration of resistin on renal sympathetic nerve activity in rats fed a high fat diet; a comparison with leptin
Abstract
Resistin acts centrally to increase renal sympathetic nerve activity (RSNA). This is similar to leptin. In high fat fed animals, the sympatho-excitatory effects of leptin are retained, in contrast to the reduced actions of leptin on dietary intake. In the present study we investigated whether the sympatho-excitatory actions of resistin were influenced by a high fat diet. Further, since resistin and leptin combined can induce a greater sympatho-excitatory response than each alone in rats fed a normal chow diet, we investigated whether a high fat diet (22%) could influence this centrally mediated interaction. MAP, HR and RSNA were recorded before and for 3 hours after intracerebroventricular saline (control) (n=5), leptin (7 μg; n=4), resistin (7 μg; n=5) and leptin and resistin combined (n=6). Leptin alone and resistin alone significantly increased RSNA (71±16%, 62±4% respectively). When leptin and resistin were combined there was a significantly greater increase in RSNA (195±41%) compared to either hormone alone. MAP and HR responses were not significantly different between hormones. When the responses in high fat fed rats were compared to normal chow fed rats, there were no significant differences in the maximum RSNA responses. The findings indicate that sympatho-excitatory effects of resistin on RSNA are not altered by high fat feeding, including the greater increase in RSNA observed when resistin and leptin are combined. Our results suggest that diets rich in fat do not induce resistance to the increase in RSNA induced by resistin alone or in combination with leptin.
This article is protected by copyright. All rights reserved.
http://ift.tt/2ta02eZ
Endocrine influence on neuroinflammation: the use of reporter systems
Abstract
Most of the ageing-associated pathologies are coupled with a strong inflammatory component that accelerates the progress of the physio-pathological functional decline related to ageing. The currently available pharmacological tools for the control of neuroinflammation present several side effects which restrict their application, particularly in chronic disorders. The discovery of the potential anti-inflammatory action exerted by endogenous estrogens and that activation of ERα results in a significant decrease of inflammation at the cellular level and in models of inflammatory diseases, prompted us to embark in a series of studies aimed at the generation of reporter systems allowing to i.) understand the anti-inflammatory action of estrogens at molecular level, ii.) evaluate the extent to which the action of this steroid hormone was relevant in models of pathologies characterized by a strong inflammatory component and iii.) investigate the efficacy of novel, synthetic estrogens endowed of anti-inflammatory activity. To this aim, we conceived the NFkB-luc2 reporter mouse, a model characterized by dual reporter genes for fluorescence and bioluminescence imaging under the control of a synthetic DNA able to bind the transcription factor (TF) NFkB, the master regulator of the expression of most of the cytokines responsible for the initial phase of acute inflammation. We here summarize the philosophy that has driven our research in the past years and some of the results obtained so far.
This article is protected by copyright. All rights reserved.
http://ift.tt/2u7QVc1
Scholar : These new articles for Cogent Arts & Humanities are available online
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Surveillance of anal carcinoma after radiochemotherapy
Abstract
Background
Surveillance after radiochemotherapy of anal carcinoma (ACa) with curative intent is recommended in guidelines, but data regarding the effectiveness of follow-up are lacking. We aimed to assess the performance of an ACa surveillance program in a real-life setting.
Methods
We retrospectively summarized clinical history, physical findings, and follow-up investigations (endoanal ultrasound, endoscopy, CT scan) obtained during 42 months (±27 months) from 80 patients after radiochemotherapy of ACa.
Results
In 7/80 cases (8.8%) an incomplete response to therapy was identified at or before the 6‑month time point after the end of treatment; 4 of the 7 cases were identified during scheduled follow-up. In 6 cases (7.5%), recurrent disease was found after the 6‑month time point. Recurrence was systemic in 5 cases and local/inguinal in 1 case. In 3 of the 6 cases (50%), recurrence was identified during scheduled follow-up. In one asymptomatic patient, a single liver metastasis was detected during scheduled follow-up and the patient remains free of disease 19 months after surgery. Surveillance resulted in a high rate of false-positive findings (70 findings in 604 investigations), of which only 14 could be confirmed.
Conclusion
Scheduled follow-up after treatment of ACa detected recurrent disease at systemic sites, enabling potentially curative treatment in a single case. Effectiveness of abdominal imaging during follow-up after ACa treatment should be tested in a prospective trial.
http://ift.tt/2u7trUg
Automation of radiation treatment planning
Abstract
Background
Intensity-modulated radiotherapy (IMRT) techniques are now standard practice. IMRT or volumetric-modulated arc therapy (VMAT) allow treatment of the tumor while simultaneously sparing organs at risk. Nevertheless, treatment plan quality still depends on the physicist's individual skills, experiences, and personal preferences. It would therefore be advantageous to automate the planning process. This possibility is offered by the Pinnacle3 treatment planning system (Philips Healthcare, Hamburg, Germany) via its scripting language or Auto-Planning (AP) module.
Materials and methods
AP module results were compared to in-house scripts and manually optimized treatment plans for standard head and neck cancer plans. Multiple treatment parameters were scored to judge plan quality (100 points = optimum plan). Patients were initially planned manually by different physicists and re-planned using scripts or AP.
Results and discussion
Script-based head and neck plans achieved a mean of 67.0 points and were, on average, superior to manually created (59.1 points) and AP plans (62.3 points). Moreover, they are characterized by reproducibility and lower standard deviation of treatment parameters. Even less experienced staff are able to create at least a good starting point for further optimization in a short time. However, for particular plans, experienced planners perform even better than scripts or AP. Experienced-user input is needed when setting up scripts or AP templates for the first time. Moreover, some minor drawbacks exist, such as the increase of monitor units (+35.5% for scripted plans).
Conclusion
On average, automatically created plans are superior to manually created treatment plans. For particular plans, experienced physicists were able to perform better than scripts or AP; thus, the benefit is greatest when time is short or staff inexperienced.
http://ift.tt/2ta64fp
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