Laser treatment of cutaneous angiokeratomas: A systematic review

Abstract

Angiokeratomas can present therapeutic challenges, especially in cases of extensive lesions, where traditional surgical methods carry high risks of scarring and hemorrhage. Argon, pulsed dye (PDL), neodymium-doped yttrium aluminum garnet (Nd:YAG), copper vapor, potassium titanyl phosphate, carbon dioxide, and erbium-doped yttrium aluminum garnet (Er:YAG) lasers have emerged as alternative options. To review the use and efficacy of lasers in treating angiokeratomas. A PubMed search identified randomized clinical trials, cohort studies, case series, and case reports involving laser treatment of cutaneous angiokeratomas. Twenty-five studies were included. Quality ratings were assigned using the Oxford Centre for Evidence-Based Medicine scheme. Several laser modalities are effective in treating multiple variants of angiokeratomas. Vascular lasers like PDL, Nd:YAG, and argon are the most studied and of these, PDL offers the safest side effect profile. Nd:YAG may be more effective for hyperkeratotic angiokeratomas. Combination treatment with multiple laser modalities has also demonstrated some success. Lasers are a promising treatment option for angiokeratomas, but current use is limited by the lack of treatment guidelines. There are limited high quality studies comparing laser treatments to each other and to non-laser options. Additional studies are needed to establish guidelines and to optimize laser parameters.

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Monopolar radiofrequency treatment in Asian skin: An update

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Cosmeceutical effect of ethyl acetate fraction of Kombucha tea by intradermal administration in the skin of aged mice

Summary

Background/purpose

Natural ingredients have been always an interesting approach to prolong youthful appearance of skin. One of the natural compounds is Kombucha tea (KT), which has been mainly used as an energy drink in Asian countries for a long time. Previous reports indicated that it has pharmaceutical and favorable wound repairing effects. The beneficial properties of KT are thought to be mainly due to the presence of fermentation products such as flavonoids and other polyphenols with inhibition of hydrolytic and oxidative enzymes and anti-inflammatory effects. These properties prompted us to study the anti-aging potential of KT and investigate its effective fraction in aged mice,

Methods

Kombucha tea was fractionated into chloroform, butanol, and ethyl acetate, and flavonoid content was determined. Young and old mice were used as control. KT ethyl acetate fraction (KEAf), which had the highest flavonoid content, was intradermally administered to old mice.

Results

Administration of KEAf significantly increased the collagen content, NAD⁺/NADH level, and concomitantly improved skin connective tissue abnormalities in the aged skin. No sensitivity or irritation was observed.

Conclusion

This finding suggested that KEAf can be a suitable candidate as a cosmetic product to improve aging-related skin abnormalities and regeneration of aged skin.

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Skin care and cosmeceuticals: Attitudes and trends among trainees and educators

Summary

Introduction

Patients often seek skin care recommendations from their dermatologist. The objective of this study was to determine the degree of education dermatology residents receive on skin care and cosmeceutical products, the source of education, and the attitude of trainees and their educators toward skin care and cosmeceuticals.

Methods

A cross-sectional survey of dermatology residents and faculty via an online survey administered June 2015 and August 2015, respectively.

Results

In total, 104 dermatology residents and 50 dermatology faculty members completed the survey. Among the dermatology residents and faculty, equal distribution was represented across the country. The majority of residents and faculty (62% and 69%, respectively) report discussing skin care with up to 25% of their patients. Among resident participants, 76.5% "agree or strongly agree" that skin care and cosmeceutical education should be part of their education and the majority of residents (74.5%) report their education has been "too little or nonexistent" during residency. In contrast, the majority of the faculty (60%) reports their resident education is "just the right amount or too much" (P < .001).

Conclusions

Skin care and cosmeceutical recommendations are often discussed in dermatology visits. Dermatology residents feel that education on these products should be a part of their residency training.

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Clinical Thyroidology for the Public – Highlighted Article

From Clinical Thyroidology for the Public: Overall, thyroid blood testing has steadily increased over the past few decades, corresponding with rising healthcare costs. Many thyroid tests are overused and may be inappropriate for the type of thyroid condition suspected. Read More….

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Standardised noxious stimulation-guided individual adjustment of remifentanil target-controlled infusion to prevent haemodynamic responses to laryngoscopy and surgical incision: A randomised controlled trial

BACKGROUND The surgical plethysmographic index (SPI) is one of the available indexes of the nociception–antinociception (NAN) balance. Individually adjusting the NAN balance to prevent somatic responses to noxious stimulation remains a challenge. OBJECTIVES To assess whether guiding remifentanil administration according to the SPI response to a calibrated noxious stimulus (NANCAL) can blunt the haemodynamic response to tracheal intubation and surgical incision. DESIGN Prospective randomised multicentre controlled study. SETTING Two Belgian university hospitals from January 2014 to April 2015. PATIENTS After ethic review board approval and informed consent, 48 American Society of Anesthesiologists I or II adult patients scheduled for surgery under general anaesthesia were enrolled. INTERVENTIONS Patients were randomly assigned to a SPI group, where remifentanil effect-site concentration was adjusted according to NANCAL, or a control group, where it was fixed at 4 ng ml−1. Propofol concentration was always adjusted to maintain the bispectral index close to 40. NANCAL consisted of a 100 Hz, 60 mA electrical tetanic stimulation during 30 s at the wrist before tracheal intubation and before surgical incision. MAIN OUTCOME MEASURES The primary endpoint was the efficacy of the NANCAL-guided remifentanil administration to prevent the haemodynamic response to tracheal intubation and surgical incision. The secondary aim was to compare the ability of SPI, analgesia nociception index, pupil diameter and mean arterial pressure response to NANCAL to predict the haemodynamic response to tracheal intubation and surgical incision. RESULTS Our SPI response to NANCAL-based correcting scheme for remifentanil administration was not superior to a fixed remifentanil concentration at blunting the haemodynamic response to tracheal intubation or surgical incision. Among all tested NAN balance indices, only mean arterial pressure had significant predictive ability with regard to the haemodynamic response to surgical incision. CONCLUSION Further research is needed to define the best NANCAL stimulus and the best remifentanil correcting scheme to help individualised tailoring of antinociception for each specific subpopulation of surgical patients. TRIAL REGISTRATION Clinicaltrials.gov NCT: 02884310; http://ift.tt/2B2PCiQ. Correspondence to Aline Defresne, MD, Department of Anaesthesia and Intensive Care Medicine, CHR Citadelle, Bd du 12eme de Ligne, 1, 4000 Liege, Belgium E-mail: adefresne@chu.ulg.ac.be © 2017 European Society of Anaesthesiology

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EACPT News

Publication date: October 2017
Source:Clinical Therapeutics, Volume 39, Issue 10





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Factors Associated with Type 2 Diabetes Mellitus Treatment Choice Across Four European Countries

Publication date: Available online 4 November 2017
Source:Clinical Therapeutics
Author(s): Edith M. Heintjes, Jetty A. Overbeek, Gillian C. Hall, Daniel Prieto-Alhambra, Francesco Lapi, Niklas Hammar, Irene D. Bezemer
PurposeThe aim of this analysis was to identify factors associated with the choice of type 2 diabetes mellitus (T2DM) therapy at the time of intensification of antidiabetic treatment across 4 European countries.MethodsAntidiabetic drug prescription/dispensing records and patients' characteristics were obtained from the electronic health care records of patients with T2DM from the Netherlands (NL), Italy, and Spain (ES) (all, 2007–2011); and the United Kingdom (UK; 2008–2012). Oral monotherapy was defined as first-line; oral dual therapy, as second-line; >2 oral treatments or oral combined with an injectable, as third-line; and injectables only, as fourth-line treatment. Treatment intensification was defined as the start of a higher line of treatment. Comedication, comorbidities, clinical parameters, and other factors associated with treatment choice were identified using multivariate relative risk estimation by Poisson regression with robust error variance.FindingsIn the 5-year study period, 485,120 patients (79% of the treated T2DM population) underwent treatment intensification. Changes in treatment choice were clearly visible over the study period, such as a decline in the use of thiazolidinediones (NL, ES, UK) and increases in the use of dipeptidyl peptidase-4 inhibitors (DPP4i) (NL, ES, UK) and glucagon-like peptide-1 receptor agonists (UK). With first-line treatment, advanced age and renal comorbidity were associated with the use of sulfonylureas (SUs; all countries), whereas high body mass index (BMI) was inversely associated with SU use in the United Kingdom and Spain. With second-line treatment, advanced age was associated with metformin + SU use (all countries); and renal comorbidity with SU + DPP4i use in the United Kingdom and the Netherlands. High BMI was associated with metformin + thiazolidinedione (TZD) use in the United Kingdom and Spain, and with metformin + DPP4i in the United Kingdom. With third-line treatment, advanced age and renal comorbidity were associated with the use of SU + insulin (NL, ES, UK). Hemoglobin A1c >8.5% was positively associated, and high BMI was inversely associated, with the use of any third-line combination containing insulin. Across treatment lines TZD and metformin were negatively associated with renal and cardiac morbidity. Second and third line treatment choices strongly depended on prior treatments. With fourth-line treatment, women were more likely to receive glucagon-like peptide-1 receptor agonists than were men in the United Kingdom and Spain.ImplicationsThe results suggest that the main factors driving treatment choice at any stage of intensification were age, hemoglobin A1c, BMI, renal and cardiac morbidity, and treatment history. These drivers were consistent with guidelines on, and contraindications of, specific medications. Differences between countries were generally consistent with, but not solely attributable to, differences in local guidelines and reimbursement policies.



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Publication date: Available online 3 November 2017 Source:Clinical Therapeutics Author(s): Laura...

Publication date: Available online 3 November 2017
Source:Clinical Therapeutics
Author(s): Laura S. Madore, Sarbattama Sen




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Erratum to 'Clinical Therapeutics Supplement: The Proceedings of the 13th Congress of the European Association for Clinical Pharmacology and Therapeutics' Clin Ther. 2017;39:e1-e110

Publication date: Available online 3 November 2017
Source:Clinical Therapeutics





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Canagliflozin in Conjunction With Sulfonylurea Maintains Glycemic Control and Weight Loss Over 52 Weeks: A Randomized, Controlled Trial in Patients With Type 2 Diabetes Mellitus

Publication date: Available online 3 November 2017
Source:Clinical Therapeutics
Author(s): Jean-François Yale, John Xie, Stephen E. Sherman, Claude Garceau
PurposeOur aim was to investigate the long-term efficacy and safety of canagliflozin, a sodium−glucose co-transporter 2 inhibitor, added to background sulfonylurea (SU) monotherapy for patients with type 2 diabetes mellitus.MethodsThe CANagliflozin cardioVascularAssessment Study (CANVAS) was a double-blind, placebo-controlled cardiovascular outcomes study that randomly assigned participants to receive placebo or canagliflozin 100 or 300 mg once daily in addition to routine therapy. CANVAS included a prespecified SU substudy of patients taking background doses of SU monotherapy; data from the primary efficacy evaluation at 18 weeks have been published previously. We performed a retrospective analysis of the SU substudy at 52 weeks to measure long-term efficacy and safety of canagliflozin used with an SU. The primary objective of the long-term extension was to assess the change from baseline to 52 weeks in glycosylated hemoglobin (HbA1c).FindingsA total of 215 patients were included in the 52-week extension study. Patients receiving both 100-mg and 300-mg doses of canagliflozin achieved a sustained reduction in HbA1c relative to patients receiving placebo (−0.61% [95% CI, −0.941% to −0.282%] and −0.66% [95% CI, −0.993% to −0.332%], respectively), regardless of baseline HbA1c, duration of diabetes, SU dose, estimated glomerular filtration rate, or body mass index. A sustained reduction in fasting plasma glucose was also found in both 100-mg and 300-mg groups, relative to the placebo group (−2.04 mmol/L [95% CI, −2.778 to −1.299 mmol/L] and −1.88 mmol/L [95% CI, −2.623 to −1.146 mmol/L], respectively). Weight was reduced significantly at 52 weeks in both 100-mg and 300-mg groups, relative to placebo (−1.9% [95% CI, −3.2% to −0.7%] and −2.0% [95% CI, −3.2% to –0.7%], respectively). Reduction in systolic blood pressure was also reported for both dose groups relative to the placebo group, but there was no clear difference in HDL-C, LDL-C, or triglyceride levels. Canagliflozin was generally well tolerated. While documented hypoglycemia occurred in 14% of patients on placebo, the frequency of hypoglycemia with the addition of canagliflozin was similar. There was an increased frequency of genital mycotic infections in both men (5.1%) and women (10.4%) in both canagliflozin groups combined, relative to the placebo group (0%), and their frequency increased in the higher-dose group. There was a slightly higher rate of renal impairment in those treated with canagliflozin versus placebo (2.1% vs 0%).ImplicationsAfter 52 weeks, patients receiving canagliflozin added to background SU had sustained reductions in HbA1c and fasting plasma glucose, without increasing hypoglycemia and body weight; safety findings were generally consistent with the known safety profile of the drug. ClinicalTrials.gov identifier: NCT01032629.



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Lipid Management After First Diagnosis of Coronary Artery Disease: Contemporary Results From an Observational Cohort Study

Publication date: Available online 2 November 2017
Source:Clinical Therapeutics
Author(s): Christoph Waldeyer, Moritz Seiffert, Nils Staebe, Julian Braetz, Rebecca Kohsiack, Francisco Ojeda, Niklas Schofer, Mahir Karakas, Tanja Zeller, Christoph Sinning, Benedikt Schrage, Dirk Westermann, Karsten Sydow, Stefan Blankenberg, Fabian J. Brunner, Renate B. Schnabel
PurposeAlthough the efficacy of lipid-lowering medication (LLM) in patients with coronary artery disease (CAD) is well established, the majority of patients fail to achieve their LDL-C goals. The evidence for measurement of LDL-C to achieve these goals is limited. The goal of the present study, therefore, was to analyze ambulatory LLM management in relation to performance of LDL-C measurements and achieved LDL-C levels after the initial diagnosis of CAD.MethodsThe study followed up a subcohort of 200 patients with newly diagnosed CAD of the INTERCATH trial, an observational study including patients undergoing coronary angiography. In addition to baseline information, data were collected on LLM, performance of lipid measurements, and laboratory results at a minimum of 6 months' postdischarge.FindingsThe mean age of the sample was 67.9 years, and 36.0% were women. In 34.5% of all patients, no measurement of LDL-C levels was performed during follow-up. We found no differences in baseline characteristics between patients with and without LDL-C measurements during follow-up. In patients with measurement of LDL-C levels, the frequency of intensification of statin medication according to LDL-C reduction was higher compared with those patients without LDL-C measurement (23.6% vs 4.3%; P < 0.001); all other categories of intensity adjustment were comparable. In patients with 3 LDL-C measurements, achieved LDL-C levels were significantly lower (mean, 81 mg/dL), and a higher proportion reached an LDL-C level <70 mg/dL (44.7%) compared with patients with 1 (95 mg/dL [P = 0.013]; 21.8%) or 2 (91 mg/dL [P = 0.037]; 28.9%) LDL-C measurements despite comparable LDL-C levels at baseline. Ezetimibe was used in 3.5% of the entire study cohort.ImplicationsWe found no differences in patient characteristics between patients with and without LDL-C measurements after being newly diagnosed with CAD. Performance and frequency of LDL-C measurements were clearly associated with better, higher frequency of intensification of statin medication, lower achieved LDL-C levels, and a higher proportion of patients achieving the LDL-C goal of <70 mg/dL. These results suggest an important role of LDL-C measurements for secondary prevention after the initial diagnosis of CAD.



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A Randomized, Multicenter, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and the Tolerability of a Triple Combination of Amlodipine/Losartan/Rosuvastatin in Patients With Comorbid Essential Hypertension and Hyperlipidemia

Publication date: Available online 14 November 2017
Source:Clinical Therapeutics
Author(s): Hae-Young Lee, Seok-Yeon Kim, Kee-Joon Choi, Byung-Su Yoo, Dong-Hun Cha, Hae Ok Jung, Dong-Ryeol Ryu, Joon Hyouk Choi, Kwang Je Lee, Tae Ho Park, Ju Hyeon Oh, Sang Min Kim, Ji-Yong Choi, Kye Hun Kim, Jaemin Shim, Woo-Shik Kim, Si-Wan Choi, Dae-Gyun Park, Pil-Sang Song, Taek-Jong Hong, Moo-Yong Rhee, Seung-Woon Rha, Seung Woo Park
PurposeThe objective of this study was to evaluate the efficacy and tolerability of a triple combination of amlodipine/losartan/rosuvastatin in patients with hypertension and hypercholesterolemia.MethodsA randomized, multicenter, double-blind, placebo-controlled study was conducted. Eligible patients with hypertension and a sitting diastolic blood pressure (SiDBP) of >90 mm Hg and LDL-C levels <250mg/dL were screened. After a 4-week run-in period with therapeutic lifestyle changes and losartan potassium 100mg once daily, patients who met both blood pressure criteria (80 mm Hg ≤ SiDBP < 110 mm Hg) and the LDL-C level criteria (defined in the National Cholesterol Education Program Adult Treatment Panel III cardiovascular risk categories) were randomized to 1 of 3 groups and treated once daily for 8 weeks: losartan potassium 100mg + rosuvastatin 20mg treatment (L/R 100/20) group, amlodipine camsylate 5mg + losartan potassium 100mg treatment (A/L 5/100) group, and amlodipine 5mg+ losartan potassium 100mg + rosuvastatin 20mg (A/L/R 5/100/20) group. The primary efficacy variables were the percent change in LDL-C in the A/L/R 5/100/20 and A/L 5/100 groups and the mean change of SiDBP in the A/L/R 5/100/20 and L/R 100/20 groups after 8 weeks of treatment, relative to baseline values.FindingsA total of 146 patients were enrolled and the demographic characteristics were similar among the 3 treatment groups. After 8 weeks of treatment, the mean (SD) percent change in LDL-C was significantly greater in the A/L/R group than in the A/L group (–48.40% [2.77%] vs –6.70% [3.00%]; P < 0.0001). Moreover, the mean change in SiDBP was significantly greater in the A/L/R group than in the L/R group (–9.75 [0.92] mm Hg vs –1.73 [1.03] mm Hg; P < 0.0001). SiDBP and LDL-C reductions in the A/L/R group were comparable to reductions in the A/L and L/R groups, respectively. Ten adverse events were reported in 7 patients (4.83%), and 1 patient from the A/L group (0.69%) experienced 2 adverse drug reactions (tachycardia and face edema), which were mild and resolved without specific treatment. There were no clinically significant tolerability issues during the treatment period.ImplicationsTriple combination therapy with amlodipine/losartan/rosuvastatin can be an effective therapeutic strategy in patients with hypertension combined with dyslipidemia. These findings will form the foundation of the future development of a single-pill triple combination. ClinicalTrials.gov identifier: NCT02899455.



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Neonatal Weight Gain on Minute or Large Amounts of Donor Milk

Publication date: Available online 1 November 2017
Source:Clinical Therapeutics
Author(s): Sergio Verd, Gemma Ginovart




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Long-term Clinical and Cost Outcomes of a Pharmacist-managed Risk Factor Management Clinic in Singapore: An Observational Study

Publication date: Available online 1 November 2017
Source:Clinical Therapeutics
Author(s): She Hui Tan, Kwee Keng Kng, Sze Mian Lim, Alexandre Chan, Jason Kwok Kong Loh, Joyce Yu-Chia Lee
PurposeFew studies have determined the benefits of pharmacist-run clinics within a tertiary institution, and specifically on their capability to improve clinical outcomes as well as reduce the cost of illness. This study was designed to investigate the effectiveness of a pharmacist-managed risk factor management clinic (RFMP) in an acute care setting through the comparison of clinical (improvement in glycosylated hemoglobin level) and cost outcomes with patients receiving usual care.MethodsThis single-center, observational study included patients aged ≥21 years old and diagnosed with type 2 diabetes mellitus (DM) who received care within the cardiology department of a tertiary institution between January 1, 2014, and December 31, 2015. The intervention group comprised patients who attended the RFMP for 3 to 6 months, and the usual-care group comprised patients who received standard cardiologist care. Univariate analysis and multiple linear regression were conducted to analyze the clinical and cost outcomes.FindingsA total of 142 patients with DM (71 patients in the intervention group and 71 patients in the usual-care group) with similar baseline characteristics were included. After adjusting for differences in baseline systolic blood pressure and triglyceride levels, the mean reduction in glycosylated hemoglobin level at 6 months from baseline in the intervention group was significantly lower by 0.78% compared with the usual-care group. Patients in the usual-care group had a significantly higher risk of hospital admissions within the 12 months from baseline compared with the intervention group (odds ratio, 3.84 [95% CI, 1.17–12.57]; P = 0.026). Significantly lower mean annual direct medical costs were also observed in the intervention group (US $8667.03 [$17,416.20] vs US $56,665.02 [$127,250.10]; P = 0.001).ImplicationsThe pharmacist-managed RFMP exhibited improved clinical outcomes and reduced health care costs compared with usual care within a tertiary institute.



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Musings on Social Media and GIST (Gastrointestinal Stromal Cancer)

Publication date: Available online 1 November 2017
Source:Clinical Therapeutics
Author(s): Richard J. Shader




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“I’m Home(screen)!”: Social Media in Health Care Has Arrived

Publication date: Available online 1 November 2017
Source:Clinical Therapeutics
Author(s): Laura T. Housman
In more than a decade, the adoption and use of some type of social media among American adults has risen from 5% in 2005 to nearly 70% in 2016. The reigning social media platform by usage, Facebook, has 142% more American adult users than the second most utilized social media platform, Instagram, which was purchased by Facebook in March 2012. Of the 68% of American adult Facebook users, more than three quarters visit the site daily. Although social media applications (apps) such as Facebook and Instagram are the clear draw among users, health care apps are beginning to gain traction as well. In 2017, 32% of consumers now have at least 1 health app on their smartphones or tablets, doubling over the past 4 years. Although having an app should not be confused with using an app, having an app downloaded and available for use is a step closer to ongoing adoption. Mobile apps in health care are being used for ordering and scheduling health care services, as well as tracking and managing aspects of health and wellness. An incredible opportunity now exists to connect and leverage social media to enhance the impact of health care, particularly in the areas of drug development, clinical trial recruitment, and therapy administration and adherence, in which dose reminders, sharing of side effects and response, and the accessibility of patients to one another has both a context and a platform. This commentary serves as an introduction to the ways that social media and mobile health care apps are being used in real-world settings as tools to advance the development and effectiveness of clinical therapeutics.



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#PatientVoiceMatters: How Social Media Is Bringing Patients and Biopharmaceutical Companies Together to Improve Drug Development

Publication date: Available online 31 October 2017
Source:Clinical Therapeutics
Author(s): Stella Stergiopoulos




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Improving Patient Involvement in the Drug Development Process: Case Study of Potential Applications from an Online Peer Support Network

Publication date: Available online 31 October 2017
Source:Clinical Therapeutics
Author(s): Amrutha Anand, Helen Jane Brandwood, Matt Jameson Evans
To date, social media has been used predominantly by the pharmaceutical industry to market products and to gather feedback and comments on products from consumers, a process termed social listening. However, social media has only been used cautiously in the drug development cycle, mainly because of regulations, restrictions on engagement with patients, or a lack of guidelines for social media use from regulatory bodies. Despite this cautious approach, there is a clear drive, from both the industry and consumers, for increased patient participation in various stages of the drug development process. The authors use the example of HealthUnlocked, one of the world's largest health networks, to illustrate the potential applications of online health communities as a means of increasing patient involvement at various stages of the drug development process. Having identified the willingness of the user population to be involved in research, numerous ways to engage users on the platform have been identified and explored. This commentary describes some of these approaches and reports how online health networks that encourage people to share their experiences in managing their health can, in turn, enable rapid patient engagement for clinical research within the constraints of industry regulation.



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Patient-Reported Outcomes in Patients with Type 2 Diabetes Treated with Dulaglutide Added to Titrated Insulin Glargine (AWARD-9)

Publication date: Available online 27 October 2017
Source:Clinical Therapeutics
Author(s): Maria Yu, Kate Van Brunt, Zvonko Milicevic, Oralee Varnado, Kristina S. Boye
PurposeThis 28-week, randomized, double-blind study compared a once-weekly injection of dulaglutide 1.5 mg to placebo, both added to titrated once-daily insulin glargine (with or without metformin), in patients with type 2 diabetes mellitus and inadequate glycemia control (control defined as hemoglobin A1c, ≥7% and ≤10.5%). Patient-reported outcomes were assessed as an exploratory objective to further understand patients' physical, psychological, and social aspects of well-being and injection-device experience.MethodsPatients not naive to injectable therapy were randomly assigned (1:1) to receive dulaglutide/glargine or placebo/glargine; glargine was titrated to a fasting plasma glucose target of 71 to 99 mg/dL. The Impact of Weight on Self-Perceptions (IW-SP), the EQ-5D-5L (measure of health status), the 18-item Diabetes Health Profile (DHP-18), and the Medication Device Delivery Assessment (MDDAB) instruments for assessing the dulaglutide Single-Use Pen (SUP) and glargine-delivery device were administered at baseline and 28 weeks, and also at 6 or 12 weeks for some measures. A mixed model for repeated measures was used for analyzing changes from baseline scores.FindingsAt 28 weeks, improvements observed in the transformed total scores on the IW-SP and DHP-18 Disinhibited Eating domain were significantly greater with dulaglutide/glargine compared with placebo/glargine (least squares mean differences, +6.06 [P = 0.019] and –4.50 [P = 0.017], respectively). There were no significant overall between-treatment differences in quality of life as measured by the EQ-5D-5L or the Barriers to Activities and Psychological Distress domains of the DHP-18. Of all patients, 95% reported that overall, the dulaglutide SUP was "easy" or "very easy" to use at 28 weeks. Device-features scores showed that most patients liked the dulaglutide SUP features, with the 3 highest-rated items relating specifically to features of the needle (not having to touch the needle, not having to attach the needle, and automatic insertion). The majority of patients (~90%) "agreed" or "strongly agreed" that they were satisfied with the overall dulaglutide SUP injection experience at 28 weeks.ImplicationsDulaglutide/glargine-treated patients had greater improvements in weight-related quality-of-life measures compared with placebo/glargine-treated patients, which may be clinically relevant when evaluating treatment options for insulin-requiring patients who often gain weight with insulin monotherapy. Results from the MDDAB indicated overall satisfaction with the dulaglutide SUP injection experience, which may be an important factor in some patients when initiating parenteral therapy. ClinicalTrials.gov identifier: NCT02152371.



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Management of Allergic Rhinitis: A Review for the Community Pharmacist

Publication date: Available online 25 October 2017
Source:Clinical Therapeutics
Author(s): J. Russell May, William K. Dolen
PurposeAllergic rhinitis is a highly prevalent disease affecting the quality of life of millions of North Americans. The management of allergic rhinitis includes allergen avoidance, pharmacotherapy, and immunotherapy. Current pharmacologic options include oral and intranasal antihistamines, intranasal corticosteroids, oral and intranasal decongestants, oral and intranasal anticholinergics, and leukotriene receptor antagonists. Second-generation oral antihistamines and intranasal corticosteroids are the mainstays of treatment, with practice guidelines recommending intranasal corticosteroids as first-line treatment for moderate to severe allergic rhinitis.MethodsClinical trials studying a widely used intranasal corticosteroid, fluticasone propionate, in comparison with second-generation oral antihistamines, cetirizine, loratadine, or montelukast, were selected to support the comparative review of the efficacy and tolerability of these 2 classes of medications. Studies evaluating the combination of fluticasone propionate with an oral antihistamine were also included to review the efficacy and tolerability of combination therapy to treat allergic rhinitis.FindingsStudies comparing fluticasone propionate with cetirizine had mixed findings; fluticasone propionate was found to have equal or greater efficacy in reducing nasal symptom scores. Combination therapy of fluticasone propionate and the oral antihistamine, loratadine, was found to have efficacy comparable with that of intranasal corticosteroid alone.ImplicationsMany of these medications are available over the counter in the pharmacy, and the community pharmacist plays an important role as part of the patient's health care team in managing this disease. Pharmacotherapy is patient-specific, based on type, duration, and severity of symptoms, comorbidities, prior treatment, and patient preference. This article aims to provide an overview of the pathophysiology, available treatment options, guideline recommendations, and role of the pharmacist for this disease.



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Moving Beyond Conventional Clinical Trial End Points in Treatment-Refractory Metastatic Colorectal Cancer: A Composite Quality-of-Life and Symptom Control End Point

Publication date: Available online 25 October 2017
Source:Clinical Therapeutics
Author(s): Jun Gong, Daniel Wu, Jeremy Chuang, Richard Tuli, John Simard, Andrew Hendifar
PurposeThis review highlights the evidence supporting symptom control and quality-of-life (QOL) measures as predictors of survival in treatment-refractory metastatic colorectal cancer (mCRC) and describes a composite symptom control and QOL end point recently reported in a Phase III trial that may serve as a more reasonable end point of efficacy in this population.MethodsA literature search was conducted using MEDLINE to identify clinical studies (including case series and observational, retrospective, and prospective studies) that reported the predictive value of QOL measures for survival in mCRC. The search was limited by the following key words: quality of life, survival, and colorectal cancer. We then performed a second search limited to studies of randomized and Phase III design in mCRC to identify studies that used QOL assessments as their primary end points. A manual search was also performed to include additional studies of potential relevance.FindingsThere is increasing evidence to support that symptom control and QOL measures are predictors of survival in treatment-refractory mCRC and can serve as an alternative but equally as important end point to survival in this population. A recent large, randomized Phase III trial using a composite primary end point of lean body mass, pain, anorexia, and fatigue reported the feasibility in evaluating benefit in mCRC beyond conventional clinical trial end points.ImplicationsFuture studies in treatment-refractory mCRC may be better served by evaluating improvement in symptom control and QOL, which may otherwise serve as the best predictor of survival in last-line treatment settings.



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Examining and Enabling the Role of Health Care Providers as Patient Engagement Facilitators in Clinical Trials

Publication date: Available online 25 October 2017
Source:Clinical Therapeutics
Author(s): Kenneth A. Getz
PurposeThe Tufts Center for the Study of Drug Development conducted a study among practicing physicians and nurses (health care providers) across multiple specialties to assess their attitudes and experiences with referring patients into clinical trials and to supplement the body of scholarly research focused primarily on referral practices among oncology-based health care providers.MethodsA total of 755 physicians and 1255 nurses completed online surveys in late 2015 and early 2016.FindingsThe results of the study indicate that a high percentage of multispecialty nurses and physicians is interested in referring their patients to appropriate clinical trials, are familiar with the clinical trial process, and are comfortable providing clinical trial information to, and discussing clinical trial opportunities with, their patients. Study results also indicate, however, that health care providers refer only a small number of patients each year largely because of the inability to access clinical trial information and the lack of sufficient information and time to evaluate and confidently discuss clinical trial options with their patients.ImplicationsMany reasons for choosing not to refer patients appear addressable, particularly through effective but presently –underused communication leveraging social media communities and using liaisons who can act as a bridge between clinical care and clinical research.



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Understanding the Patient Experience with Carcinoid Syndrome: Exit Interviews from a Randomized, Placebo-Controlled Study of Telotristat Ethyl

Publication date: Available online 23 October 2017
Source:Clinical Therapeutics
Author(s): Lowell Anthony, Claire Ervin, Pablo Lapuerta, Matthew H. Kulke, Pamela Kunz, Emily Bergsland, Dieter Hörsch, David C. Metz, Janice Pasieka, Nick Pavlakis, Marianne Pavel, Martyn Caplin, Kjell Öberg, John Ramage, Emily Evans, Qi Melissa Yang, Shanna Jackson, Karie Arnold, Linda Law, Dana B. DiBenedetti
PurposeTelotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in TELESTAR, a Phase III study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview substudy was conducted to provide insight into the patient experience in TELESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful.MethodsParticipating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at the end of the double-blind treatment period. Patients and interviewers were blinded to treatment.FindingsAll 35 interviewed participants reported diarrhea and/or excessive BMs at baseline. Patients reported that these symptoms negatively affected emotional, social, physical, and occupational well-being. Prespecified criteria for treatment response (achieving ≥30% reduction in BM frequency for at least 50% of the days) were met by 8 of 26 patients taking telotristat ethyl and 1 of 9 patients taking placebo. All 8 patients taking telotristat ethyl described clinically meaningful reductions in BM frequency and were very satisfied with the ability of the study drug to control their carcinoid syndrome symptoms. Overall, reports of being very satisfied were observed in 12 patients taking telotristat ethyl and 0 taking placebo.ImplicationsPatient interviews revealed that TELESTAR patients, at baseline, were significantly affected by their high BM frequency. Patient reports of their clinical trial experience supported the significance of the primary end point and clinical responder analysis in TELESTAR, helping identify and understand clinically meaningful change produced by telotristat ethyl.



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Long-Term Systemic Corticosteroid Exposure: A Systematic Literature Review

Publication date: Available online 19 October 2017
Source:Clinical Therapeutics
Author(s): J. Bradford Rice, Alan G. White, Lauren M. Scarpati, George Wan, Winnie W. Nelson
PurposeWhile corticosteroids are relatively inexpensive and commonly used as treatment for a variety of conditions, long-term use is known to be associated with certain toxicities. Prior systematic reviews have revealed an increased risk for costly adverse events (AEs), including bone fracture, infection, and gastrointestinal bleeding. The objective of this study was to conduct a systematic literature review of recent publications on the burden of long-term corticosteroid exposure, specifically, to summarize the AEs and economic impact of long-term corticosteroid use and to reveal data gaps for additional research.MethodsThe Ovid search platform was used to access scientific literature databases. The search strategy targeted the use of corticosteroids and economic outcomes research. Articles were restricted to those published between 2007 and 2016 to cover publications since prior reviews; conference abstracts and articles assessing pediatrics were excluded. Titles and abstracts resulting from inclusion criteria were screened, and reviewers independently extracted relevant information from the relevant full-text articles.FindingsThe literature review included 32 articles, with 75% focusing on autoimmune diseases, asthma, or lung diseases. Included articles were 14 database analyses, 6 simulations, 6 clinical trials, 3 systematic literature reviews, 2 patient surveys, and 1 chart review. Commonly-cited AEs associated with long-term corticosteroid exposure included hypertension (prevalence >30%); bone fracture (21%–30%); cataract (1%–3%); nausea, vomiting, and other gastrointestinal conditions (1%–5%); and metabolic issues (eg, weight gain, hyperglycemia, and type 2 diabetes; cases had 4-fold the risk of controls). Association of dose and duration with increased AE risk is not well-quantified. AEs like peptic ulcer and myocardial infarction are particularly costly to payers (1-year cost of $21,825 and $26,472, respectively, in year-2009 USD). The few articles assessing the economic impact of corticosteroid use have found dose-related increases in health care resource utilization and costs, with per-annum incremental costs relative to nonusers ranging from $5700 in low-dose users (<7.5 mg/d) to $29,000 in high-dose users (>15 mg/d). Adherence to treatment guidelines on avoiding AEs (eg, prescribing of oral bisphosphonates, calcium, and vitamin D) remains low.ImplicationsAlthough doses of long-term corticosteroids have fallen over the past several decades in response to AEs, dose reduction may not be a sufficient solution. Numerous AEs, some very costly, persist among long-term corticosteroid users, suggesting a need for further research to fill current data gaps, as well as a potential need for alternative treatment options.



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Differences in Adverse Event Reporting Rates of Therapeutic Failure Between Two Once-daily Extended-release Methylphenidate Medications in Canada: Analysis of Spontaneous Adverse Event Reporting Databases

Publication date: October 2017
Source:Clinical Therapeutics, Volume 39, Issue 10
Author(s): Laura Park-Wyllie, Judy van Stralen, Genaro Castillon, Stephen E. Sherman, Doron Almagor
PurposeOur study evaluated adverse events of therapeutic failure (and specifically reduced duration of action) with the use of a branded product, Osmotic Release Oral System (OROS) methylphenidate, which is approved for the treatment of attention deficit/hyperactivity disorder, and a generic product (methylphenidate, methylphenidate ER-C), which was approved for marketing in Canada based on bioequivalence to OROS methylphenidate. This study was initiated following reports that some US-marketed generic methylphenidate ER products had substantially higher reporting rates of therapeutic failure than did the referenced brands.MethodsThrough methodology similar to that used by the US Food and Drug Administration to investigate the issue with the US-marketed generic, reporting rates were calculated from cases of therapeutic failure identified in the Canadian Vigilance Adverse Reaction Online database for a 1-year period beginning 8 months after each product launch. Corresponding population exposure was estimated from the number of tablets dispensed. An in-depth analysis of narratives of individual case safety reports (ICSRs) with the use of the generic product was conducted in duplicate by 2 physicians to assess causality and to characterize the potential safety risk and clinical pattern of therapeutic failure. Similar secondary analyses were conducted on the US-marketed products.FindingsReporting rates of therapeutic failure with the use of methylphenidate ER-C (generic) and OROS methylphenidate (brand name) were 411.5 and 37.5 cases per 100,000 patient-years, respectively (reporting rate ratio, 10.99; 95% CI, 5.93–22.21). In-depth analysis of narratives of 230 ICSRs of therapeutic failure with the Canadian-marketed generic determined that all ICSRs were either probably (60 [26%]) or possibly (170 [74%]) causally related to methylphenidate ER-C. Clinical symptoms suggestive of overdose were present in 31 reports of loss of efficacy (13.5%) and occurred primarily in the morning, and premature loss of efficacy (shorter duration of action) was described in 98 cases (42.6%) and occurred primarily in the afternoon. Impacts on social functioning, such as disruption in work or school performance or adverse social behaviors, were found in 51 cases (22.2%).ImplicationsThe ~10-fold higher reporting rate of therapeutic failure with the generic product relative to its reference product in the present Canadian study resembles findings with US-marketed generic products. While these results should be interpreted with caution due to the limitations of spontaneous adverse event reporting, which may confound comparisons across products, similar findings nonetheless led the US Food and Drug Administration to declare in 2014 that 2 methylphenidate ER generic products in the United States were neither bioequivalent nor interchangeable with OROS methylphenidate—their reference product. Our results indicate a potential safety issue with the Canadian-marketed generic and suggest a need for further investigation by Health Canada.



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Oral and Maxillofacial Radiology

Publication date: Available online 6 November 2017
Source:Radiologic Clinics of North America
Author(s): Dania Tamimi




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Imaging of Odontogenic Infections

Publication date: Available online 21 October 2017
Source:Radiologic Clinics of North America
Author(s): Shaza Mardini, Anita Gohel

Teaser

Odontogenic infections represent a common clinical problem in patients of all ages. The presence of teeth enables the direct spread of inflammatory products from dental caries, trauma, and/or periodontal disease into the maxilla and mandible. The radiographic changes seen depend on the type and duration of the inflammatory process and host body response. Imaging plays a central role in identifying the source of infection and the extent of the disease spread and in detecting any complications. Many different imaging modalities can be used. The radiographic features associated with acute and chronic inflammatory processes are discussed.


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Malignant Lesions in the Dentomaxillofacial Complex

Publication date: Available online 19 October 2017
Source:Radiologic Clinics of North America
Author(s): Susan M. White

Teaser

Malignancies in the maxillofacial region are rare but comprise a broad spectrum of lesions. Given the potential for malignancies to mimic dental/sinus/temporomandibular joint pathology or remain asymptomatic, the judicious radiologist will be familiar with the initial and unique malignant changes affecting the dentition, periodontium, and supporting osseous structures on conventional film, dental, and sinus imaging. This article is meant to serve as a complement to the many excellent texts dedicated to advanced imaging techniques for the staging of known malignancies. The lesions discussed are a representative sample of malignancies involving hard tissues of the maxillofacial complex but are far from complete.


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Fibroosseous and Other Lesions of Bone in the Jaws

Publication date: Available online 19 October 2017
Source:Radiologic Clinics of North America
Author(s): Mansur Ahmad, Laurence Gaalaas

Teaser

Fibroosseous lesions in the jaws have similar histologic and radiographic features. Despite their similarity, management varies significantly. In this article, common fibroosseous lesions and key radiographic features are described. Many of the fibroosseous lesions are diagnosed radiographically, without performing histologic examinations. For some of the fibroosseous lesions, for example, periapical osseous dysplasia, histologic examination is contraindicated. Cherubism and fibrous dysplasia have specific radiographic findings; these conditions can be diagnosed radiographically. Accurate diagnosis conditions is essential; some conditions do not require any intervention, while others require surgical resection. Patient demographics, for example, age, gender, and race, play important roles in diagnosis.


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Radiology of Implant Dentistry

Publication date: Available online 16 October 2017
Source:Radiologic Clinics of North America
Author(s): Asma'a Abdurrahman Al-Ekrish

Teaser

The article presents an overview of the goal of imaging at each stage of implant therapy and the usefulness and limitations of multidetector computed tomography (MDCT) in achieving those goals. Various MDCT protocols of use in implant imaging also are presented, with an emphasis on dose reduction and the use of iterative reconstruction techniques. Also discussed are options for viewing and analysis of CT images, issues related to appropriate image reformatting and interpretation, interactive treatment planning, and transfer of information from the images to the surgical field during implant surgery using surgical guides and CT-guided navigation systems.


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The protected survivor model: Using resistant successful cognitive aging to identify protection in the very old

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Jeremy M. Silverman, James Schmeidler
For some cardiovascular risk factors, association with risk for cognitive impairment observed in early old age is reduced, or paradoxically even reversed, as age of outcome increases. Successful cognitive aging is intact cognition in the oldest-old; we define resistant successful cognitive aging as successful cognitive aging despite high risk. The protected survivor model posits that a minority of the general population has a protective factor that mitigates the negative effect of a risk factor on successful cognitive aging for the unprotected majority. As age increases, differential failure rates increase the proportion of survivors with protection. Among the unprotected, the proportion with low risk increases, but among those with protection, high risk and low risk do not differ. Due to differential mortality, half the survivors are eventually protected – a majority among those with high risk, and a minority among those with low risk. According to the protective survivor model, an example of Simpson's paradox, the association of the risk factor with survival does not change within an individual, but the association in the surviving population changes as its age increases.We created quantitative illustrations of a simplified protected survivor model applied to successful cognitive aging to explain how the usual association of a risk factor with cognitive decline is reversed in the very old. In the illustrations, probability of subsequent survival was higher for survivors with high risk (mostly protected) than low risk (mostly not protected), an example of Simpson's paradox. Resistance to disease despite the presence of risk factors is consistent with the presence of countervailing protection. Based on the protected survivor model, we hypothesize that studies seeking protective factors against cognitive decline will be more effective by limiting a successful cognitive aging sample to resistant successful cognitive aging – to contrast with a sample without successful cognitive aging.



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Trigeminal long-term potentiation as a cellular substrate for migraine

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Dong-ho Youn
Most previous studies suggest that the subnucleus caudalis (Vc) of spinal trigeminal nucleus (Vsp) plays a key role in the generation and maintenance of migraine, a type of primary headache, by participating in the trigeminovascular system. Furthermore, the excitability of the Vc with the stimulation of the peripheral nociceptive fibers innervating the intracranial vessels or dura matter is regarded as a main cellular substrate for migraine. Here, a revised hypothesis is introduced, reinforcing the previous hypothesis and complementing it. This hypothesis suggests that, besides the Vc, much broader areas of the trigeminal sensory nuclei (Vsn), i.e., the principal sensory nucleus (Vp), the oralis nucleus (Vo), and the interpolaris nucleus (Vi), contribute to process and integrate pain signals generated in the head. In addition, the plasticity of synaptic transmission between nuclei or subnuclei in the Vsn, in particular, the Vsp, can be a cellular model for migraine, in the same way as the hippocampal synaptic plasticity is a model for learning and memory. This hypothesis will contribute to the discovery of new therapeutic tools for patients with migraine.



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Comparison of geographic distributions of Irritable Bowel Syndrome with Inflammatory Bowel Disease fail to support common evolutionary roots

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Andrew Szilagyi, Xiaoqing Xue
Irritable Bowel Syndrome (IBS) shares overlapping symptoms and some features of pathogenesis with Inflammatory Bowel Diseases (IBD: Crohn's disease [CD], and Ulcerative Colitis [UC]). Geographic markers such as latitude/sunshine and more recently lactase population distributions are found to be correlated with IBD. As a result of clinical and pathogenic similarities between the 2 conditions, some authorities questioned whether a connection exists between them. We compare IBS directly with IBD, and indirectly with geographic markers associated with IBD, in order to evaluate possible evolutionary links between IBS and IBD. Similar correlations may link IBS as a precursor to IBD and possibly other conditions which are geographically connected with IBD. Data from four systematic reviews on IBD incidence and prevalence, IBS prevalence, and lactase distributions were included. Pearson's correlations were used for comparisons, with IBD values log-transformed because of skewed distribution. The articles provided 18–28 complete set of national data. Direct comparison between IBS and IBD showed no significant correlations (r = −0.14, r = −0.06 for CD and UC prevalence, r = −0.10 for CD incidence). Indirect comparisons also failed to show correlations of IBS with lactase distributions (r = −0.17), sunshine (r = −0.2) or latitude (r = 0.097); however, there was significant correlation between lactase distributions and CD incidence (r = −0.84), prevalence (r = −0.55) and UC prevalence (r = −0.59). Both sunshine (r= −0.53) and latitude (r = 0.58) are also significantly related to CD incidence. It is concluded that IBS and IBD do not follow similar global geographic patterns. This suggests a lack of an evolutionary genetic background coincident with emergence of lactase persistence. As well, vitamin D has no obvious impact on development of IBS. Similarities with IBD may result from sub groups (not yet identified) within the current Rome criteria of IBS. Alternatively limited intestinal gut–brain responses to host microbial interactions may result in similar overlap features in both.



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Nature exposure sufficiency and insufficiency: The benefits of environmental preservation

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): John R. Reddon, Salvatore B. Durante
Increasing industrialization, urbanization, and a failure of many world leaders to appreciate the consequences of climate change are deleteriously impacting quality of life as well as diminishing the prospects for long term survival. Economic competitiveness and corporate profitability often pre-empt environmental concerns. The calving of an iceberg in Antarctica and the hurricane activity in the Caribbean during 2017 are unfortunate illustrations of the continuing escalation of environmental issues. We provide historical and current evidence for the importance of Nature Exposure (NE) and introduce the continuum Nature Exposure Sufficiency (NES) and Insufficiency (NEI). Insufficiency includes impoverished environments (e.g., slums and prisons) where nature exposure is very limited. Nature Exposure Sufficiency (NES) is an optimal amount of exposure to nature where many benefits such as reinvigoration can be obtained by everyone. NES also has several benefits for individuals with various health conditions such as arthritis, dementia, or depression. The benefits of NE are not just derivable from parks, forests, and other natural settings. Interiors of buildings and homes can be enhanced with plants and even pictures or objects from nature. Additionally, there is abundant evidence indicating that virtual and artificial environments depicting nature can provide substantial NE and therefore contribute to general wellbeing. Besides the difficulty in achieving cooperation amongst nations, corporations, and other collectives in developing and implementing long range plans to deal with climate change, there is also sometimes an aversion at the individual level whereby people are unwilling to experience nature due to insects and other discomforts. Such individuals are often averse to supplanting the comforts of home, even temporarily, with inadequate facilities that are seemingly less pleasant than their typical dwellings. We propose using the term Nature Exposure Aversion (NEA) to describe such behavior and propose that the aversion is largely due to conditioning. Such behavior may be addressed through desensitization in virtual environments which in turn may contribute to an endorsement of the view that climate change is occurring and must be dealt with. The issues of Nature Exposure Sufficiency and Insufficiency are intertwined with the sustainability of the planet and future planning and efforts to deal with the environment. If the outcome is unfavorable, the descent of civilization will be more rapid than the ascent.



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An exploration of the hypothesis that testosterone is implicated in the psychological functioning of women with polycystic ovary syndrome (PCOS)

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): J.A. Barry, F. Qu, P.J. Hardiman
One of the diagnostic features of polycystic ovary syndrome (PCOS) is elevation of the androgen, testosterone. It is known that women with PCOS are more likely to suffer from psychological problems, especially anxiety and depression, than other women. However, little is known of how much of this is due to testosterone, and if so, what the mechanism(s) might be.This study explores the hypothesis that testosterone impacts women with PCOS both directly and indirectly, via testosterone currently in the bloodstream and through prenatal exposure. It is hypothesised that direct effects occur when testosterone acts directly upon receptors; indirect effects occur where the impact of testosterone is mediated via another variable; activational effects are ephemeral and are caused by testosterone in the bloodstream; organizational effects occur prenatally and cause permanent changes.Four pathways are hypothesised in this paper: 1/ a direct and activational pathway which improves mental rotation ability; 2/ an indirect and activational pathway, whereby distress is caused when the physiological symptoms of testosterone are experienced as embarrassing or otherwise disturbing; 3/ an indirect and organizational effect on mood, where elevated prenatal testosterone predisposes women with PCOS to low blood sugar levels and thus low mood; 4/ and finally, it is suggested that the pathway from biology to psychology can be travelled in reverse, with a direct activational effect of relaxation training on the reduction of adrenal androgens.Testing these hypotheses has important implications for our understanding of PCOS, and our ability to treat this condition more effectively.



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Blood flow restriction training as a prehabilitation concept in total knee arthroplasty: A narrative review about current preoperative interventions and the potential impact of BFR

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Alexander Franz, Fina Pauline Queitsch, Michael Behringer, Constantin Mayer, Rüdiger Krauspe, Christoph Zilkens
Osteoarthritis of the knee is one of the most commonly diagnosed joint ailments and responsible for increased rates of total knee arthroplasty surgeries worldwide. Whereas the surgical approach is able to diminish the perceived knee pain of concerned patients', the postoperative recovery is often accompanied by persistent skeletal muscle dysfunctions and atrophy, which is responsible for functional deficits for up to several years. Recent findings indicate that surgery induced adverse effects on skeletal muscles are largely associated with the use of pneumatic tourniquets, wherefore several studies try to reduce tourniquet use in orthopedic surgery. However, due to comparable incidence of muscle impairment and increased surgical challenge, the most frequently applied surgical technique in TKA is still associated with the use of tourniquets. When attenuating TKA induced adverse effects, the preoperative preparation of patients by specific exercises (called prehabilitation) was able to enhance preoperative overall fitness through associated accelerated recovery. Based on patients' limited functional activity, prehabilitation techniques have to be particularly designed to allow regular adherence. The present paper is based on a narrative review of current literature, and provides a novel hypothesis by which blood flow restriction exercises (BFR) are able to improve patients' compliance to prehabilitation. BFR training is characterized by the application of low-resistance exercise with similar intensities as daily living tasks in association with a suppression of venous blood flow in an extremity, achieving significant morphological and neuromuscular adaptations in skeletal muscles. In addition, preoperative enhancements in muscle health with corresponding benefits in overall fitness, BFR induced molecular alterations could also be able to interfere with TKA induced pathological signaling. Therefore, based on the known major impact of BFR on skeletal muscle physiology, the present paper aims to illustrate the potential beneficial impact of BFR training as a prehabilitation concept to promote patients regular adherence to preoperative exercises and thus achieve an accelerated recovery and increases in patients' satisfaction.



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Autoimmunity against a glycolytic enzyme as a possible cause for persistent symptoms in Lyme disease

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Paolo Maccallini, Serena Bonin, Giusto Trevisan
Some patients with a history of Borrelia burgdorferi infection develop a chronic symptomatology characterized by cognitive deficits, fatigue, and pain, despite antibiotic treatment. The pathogenic mechanism that underlines this condition, referred to as post-treatment Lyme disease syndrome (PTLDS), is currently unknown. A debate exists about whether PTLDS is due to persistent infection or to post-infectious damages in the immune system and the nervous system. We present the case of a patient with evidence of exposure to Borrelia burgdorferi sl and a long history of debilitating fatigue, cognitive abnormalities and autonomic nervous system issues. The patient had a positive Western blot for anti-basal ganglia antibodies, and the autoantigen has been identified as γ enolase, the neuron-specific isoenzyme of the glycolytic enzyme enolase. Assuming Borrelia own surface exposed enolase as the source of this autoantibody, through a mechanism of molecular mimicry, and given the absence of sera reactivity to α enolase, a bioinformatical analysis was carried out to identify a possible cross-reactive conformational B cell epitope, shared by Borrelia enolase and γ enolase, but not by α enolase. Taken that evidence, we hypothesize that this autoantibody interferes with glycolysis in neuronal cells, as the physiological basis for chronic symptoms in at least some cases of PTLDS. Studies investigating on the anti-γ enolase and anti-Borrelia enolase antibodies in PTLDS are needed to confirm our hypotheses.



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Nigral depigmentation reflects monoamine exhaustion as initial step to Parkinson’s disease

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Thomas Müller, Willi Kohlhepp
This hypothesis discusses exposure and response to various stressors as cause for chronic neurodegeneration. Predisposing genetic and environmental factors in conjunction with exposure to exogenous and endogenous toxins cause stress, which consumes dopamine and related biogenic amines. To compensate monoamine exhaustion, conversion of endogenous levodopa to dopamine by tyrosine hydroxylase is up regulated. Concomitantly, tyrosine mediated levodopa degradation to dopaquinone is reduced. Dopaquinone is the essential precursor of neuromelanin. Its deficiency may cause irreversible nigral fading as initial feature of Parkinson's disease.



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Etiological mechanism of iridocorneal endothelial (ICE) syndrome may involve infection of herpes simplex virus (HSV) and integration of viral genes into human genome

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Fei Li, Yaoming Liu, Yi Sun, Xiulan Zhang
Iridocorneal (ICE) syndrome is a rare ocular disease characterized by abnormal proliferation of corneal endothelial cells, progressive obstruction of irido-corneal angle and atrophy of iris. ICE syndrome progressed slowly, but can cause serious complications such as secondary glaucoma in late stage. Because the etiology of ICE syndrome is not clear, there is still no effective treatment in clinical practice. Previous studies have detected herpes simplex virus (HSV) DNA inside patient's aqueous humor. However, no further explanation for HSV-related etiology of ICE syndrome was established. Besides, construction of animal models using HSV all failed, leaving behind a blank space about how HSV infection finally led to ICE syndrome. By summarizing findings from previous studies, we came up with a hypothesis about etiology of ICE syndrome: HSV infection initiated ICE syndrome by integration of viral genetic material into human genome. Infection of HSV changed activity and morphology of endothelial cells, making them regain the ability of mitosis. Proof of such hypothesis will provide a theoretical foundation for construction of animal models and effective intervention of the disease.



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Hypothesis for the cause and therapy of neurodegenerative diseases

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Philip Serwer
The cause and therapy of neurodegenerative diseases remain unsolved puzzles. These diseases are correlated with presence of beta sheet-rich amyloid assemblies. Here, I derive and assemble puzzle pieces to obtain a loose end-tying hypothesis for cause with direct implications for therapy. I use the following extrapolations to find connectable puzzle pieces: (a) the traditional extrapolation that amyloid/amyloid precursors cause disease, (b) a recent extrapolation that amyloid-forming proteins, some of which are virus protein homologs, are components of an empirically obscure innate immune system that counters insults, including those by both viruses and bacteria, (c) a new extrapolation that various insults produce assemblies with structural features in common and that amyloid-forming, innate immune system proteins recognize these features and, then, counter insults by co-assembly, (d, 1) a second new extrapolation that beta sheet is a common structural feature and is extended during insult-neutralizing co-assembly and (d, 2) an appendix, derived from studies of phages T3 and T4, that most insult-produced assemblies are obscure to current biochemical analysis. The hypothesis is the following. One function of amyloid-forming proteins is non-classical innate immunity to biological insults. This immunity works via beta sheet-extending co-assembly of amyloid-forming proteins with beta sheet-containing insult products. For example, co-assembly with beta sheet-containing viral assembly intermediates inhibits virus production. Amyloid-forming proteins cause neurodegenerative disease when errant, typically overproduced. Other innate immunity systems sometimes exacerbate symptoms. This hypothesis suggests the following therapy, based on manipulating Nature's chemistry. First, conduct directed evolution to obtain low-pathogenicity, chronic symptom-producing viruses with assembly intermediates that co-assemble with and destabilize both amyloid and amyloid sub-assemblies. Then, infect patients with these viruses.



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Recently discovered interstitial cells “telocytes” as players in the pathogenesis of uterine leiomyomas

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Ivan Varga, Martin Klein, Ladislav Urban, Ludovit Danihel, Stefan Polak, Ludovit Danihel
Uterine telocytes are interstitial cells characterized by a very long cytoplasmic prolongations, which form a 3D network, functionally integrating a wide variety of different cells. Leiomyomas (uterine fibroids) are benign tumors, which pose a huge threat concerning various health problems in women affected by this condition. The exact cause of leiomyomas development is, however, still largely unknown. Therefore, in an attempt to clarify their etiology, we performed an immunohistochemical characterization of telocytes in leiomyomas as well as in normal myometrium. Tissue samples of intramural leiomyomas from 26 women (age 46.26 ± 11.07) were immunohistochemically stained for the expression of c-kit (CD117) antigen, one of the markers of telocytes. C-kit (CD117) antigen is useful for a routine immunohistochemical identification of uterine telocytes in histological sections of myometrium. In normal, healthy myometrium the c-kit positive telocytes occupy approximately 2.2% of the area of a tissue slide, contrasting with no detectable c-kit positive cells within leiomyomas. As telocytes are thought to be key players in the regulation of tissue homoeostasis, our data suggest that uterine telocyte loss may have important implications in the pathogenesis of leiomyomas. In addition, we supposed to summarize three hypotheses on the association of the cells telocytes loss within the myometrium and formation of leiomyomas. These hypotheses include the loss of telocytes' functions as "sex hormone sensors" and regulators of smooth muscle cells cycle; the role of telocytes as progenitor cells for the development of leiomyomas; and the hypothesis of decreased angiogenesis after telocytes' loss with subsequent hypoxia (as a key factor for leiomyomas development).



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Betacaryophyllene – A phytocannabinoid as potential therapeutic modality for human sepsis?

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Angel Meza, Christian Lehmann
Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units. The endogenous cannabinoid system (ECS) plays an important role in inflammation. Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis. Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R. We propose BCP administration as novel treatment to reduce hyper-inflammation in human sepsis.



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Recurrent and disseminated pityriasis versicolor: A novel clinical form consequent to Malassezia-host interaction?

Publication date: November 2017
Source:Medical Hypotheses, Volume 109
Author(s): Karina Romero-Sandoval, Anderson Alves Costa, Maria Glória Teixeira Sousa, Celia Regina Furucho, Neusa Valente, Paulo R. Criado, Valeria Aoki, Gil Benard
Pityriasis versicolor is a superficial fungal infection caused by Malassezia spp. The aim of this study is to propose the definition of a new clinical entity: the recurrent and disseminated pityriasis versicolor (RDPV). All patients with RDPV were enrolled over an eight-month period. Clinical and epidemiological data were obtained, Malassezia (M.) species were isolated in cultures and identified by phenotypic and molecular characterization, skin biopsies were taken from active lesions, serum levels of immunoglobulin E were obtained and therapeutic schemes were evaluated. A total of 16 patients were included (11 male, 5 female). The most frequently isolated species were M. japonica (n = 3) and M. furfur (n = 3). This is the first study that isolates M. japonica in patients with pityriasis versicolor; interestingly, those were recalcitrant patients. Seven patients (43.8%) had no cure with any of the proposed treatments; among those, 5 (71.4%) had increased serum IgE levels. The most effective treatment was itraconazole 200 mg daily for 28 days. The RDPV has very different features from the classic form, including a poor response to treatment, and the isolation of different Malassezia species; therefore, we propose a hypothesis for the definition of a new clinical condition (RDPV), which could be a result of the interaction Malassezia-host.



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Micro-calibration of space and motion by photoreceptors synchronized in parallel with cortical oscillations: A unified theory of visual perception

Publication date: January 2018
Source:Medical Hypotheses, Volume 110
Author(s): Ravinder Jerath, Shannon M. Cearley, Vernon A. Barnes, Mike Jensen
A fundamental function of the visual system is detecting motion, yet visual perception is poorly understood. Current research has determined that the retina and ganglion cells elicit responses for motion detection; however, the underlying mechanism for this is incompletely understood. Previously we proposed that retinogeniculo-cortical oscillations and photoreceptors work in parallel to process vision. Here we propose that motion could also be processed within the retina, and not in the brain as current theory suggests. In this paper, we discuss: 1) internal neural space formation; 2) primary, secondary, and tertiary roles of vision; 3) gamma as the secondary role; and 4) synchronization and coherence. Movement within the external field is instantly detected by primary processing within the space formed by the retina, providing a unified view of the world from an internal point of view. Our new theory begins to answer questions about: 1) perception of space, erect images, and motion, 2) purpose of lateral inhibition, 3) speed of visual perception, and 4) how peripheral color vision occurs without a large population of cones located peripherally in the retina. We explain that strong oscillatory activity influences on brain activity and is necessary for: 1) visual processing, and 2) formation of the internal visuospatial area necessary for visual consciousness, which could allow rods to receive precise visual and visuospatial information, while retinal waves could link the lateral geniculate body with the cortex to form a neural space formed by membrane potential-based oscillations and photoreceptors. We propose that vision is tripartite, with three components that allow a person to make sense of the world, terming them "primary, secondary, and tertiary roles" of vision. Finally, we propose that Gamma waves that are higher in strength and volume allow communication among the retina, thalamus, and various areas of the cortex, and synchronization brings cortical faculties to the retina, while the thalamus is the link that couples the retina to the rest of the brain through activity by gamma oscillations. This novel theory lays groundwork for further research by providing a theoretical understanding that expands upon the functions of the retina, photoreceptors, and retinal plexus to include parallel processing needed to form the internal visual space that we perceive as the external world.



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Environmental factors influencing the link between childhood ADHD and risk of adult coronary artery disease

Publication date: Available online 15 November 2017
Source:Medical Hypotheses
Author(s): Keith Fluegge, Kyle Fluegge
Yorbik et al. reported novel findings regarding a hypothesized relationship between childhood attention-deficit hyperactivity disorder (ADHD) and later risk for coronary heart disease in adulthood. The authors found that mean platelet volume (MPV), a marker of platelet reactivity and a presumable biomarker in patients with cardiovascular disease, was significantly elevated in children with ADHD compared to healthy controls. The mechanistic importance of this novel discovery remains unknown and warrants clarification. We have made the novel proposition that environmental exposure to the agricultural and combustion air pollutant, nitrous oxide (N2O), may be an etiological contributor to neurodevelopmental disorders. Clinical studies suggest that N2O may enhance platelet hyperaggregation, possibly via its biphasic role as an MAO inhibitor especially at trace levels of exposure or via the generation of oxidative stress. Therefore, this correspondence briefly details the hypothesis that altered biochemical profiles in neurodevelopmental disorders, derived from chronic environmental exposure to the agricultural and combustion air pollutant, N2O, may promote coronary artery disease in adulthood.



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The concept of ferrofluid preheating in the treatment of cancer by magnetic hyperthermia of tissues

Publication date: Available online 13 November 2017
Source:Medical Hypotheses
Author(s): I. Malaescu, P.C. Fannin, C.N. Marin, D. Lazic
The frequency dependence of the complex magnetic susceptibility, χ(ω)=χ'(ω)-i χ''(ω), of a water-based magnetic fluid with magnetite particles, over the frequency range 500 kHz to 2 MHz and at three different temperatures of 30 °C, 40 °C and 50 °C are presented. Based on these experimental measurements, the dependence on frequency, f=(ω/2π) Hz, of the heating rate, ΔT/Δt, of the ferrofluid has been evaluated at these stated temperatures and alternating magnetic field of different amplitudes, Ho = 200 A/m, 400 A/m, 600 A/m, 800 A/m and 1 kA/m.The results show that the preheating of the ferrofluid sample at the desired operating temperature has the advantage of using lower levels of H0 during over a shorter time period, as opposed to the case of an unheated sample. This concept of preheating a sample, has major significance for the treatment of cancer by magnetic hyperthermia in that the patient is subjected to lower values of H0, over the time period of the treatment.



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“The origin of endometriosis-associated ovarian cancer from uterine neoplastic lesions”

Publication date: Available online 13 November 2017
Source:Medical Hypotheses
Author(s): Elisabetta Garavaglia, Cristina Sigismondi, Ferrari Stefano, Massimo Candiani
Endometriosis is a risk factor for type I epithelial ovarian cancer but an issue to be clarified is the site of origin of endometriosis associated ovarian cancer.Here we proposed that the uterus may be the organ of origin of ovarian endometrioid cancer associated with endometriosis. Thus, the first neoplastic transformation would characterize the uterine cells migrating in the pelvis via retrograde menstruation and they would implant secondarily on the ovary. Supporting this hypothesis, an higher incidence of synchronous precancerous and cancerous endometrial pathology in patients affected by ovarian endometrioid cancer associated with endometriosis was showed. Moreover, uterineendometrial type I carcinoma resembles endometriosis associated endometrioid ovarian cancer in behavior and prognosis. This hypothesis is also supported by epidemiologic evidence showing a protective effect for tubal ligation and oral contraceptive use for endometriosis associated endometrioid ovarian cancer. Endometriosis and endometrioid ovarian carcinoma might represent two distinct biological entities characterized by the same organ of origin (the uterus), the same pathogenetic mechanism (transtubal reflux) and the same target organ (the ovary). By shifting the early events of ovarian carcinogenesis to the endometrium, prevention approaches as salpingectomy/tubal ligation and intervention at uterine corpus level may play an important role.



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The Pruritus of Cholestasis: from Bile Acids to Opiate Agonists: Relevant After all these Years

Publication date: Available online 6 November 2017
Source:Medical Hypotheses
Author(s): Nora V. Bergasa
The pruritus of cholestasis is a maddening complication of liver disease. Increased opioidergic tone contributes to the pruritus of cholestasis, as evidenced by the amelioration of the symptom by opiate antagonists. Obeticholic acid, an agonist of the farnesoid receptor, has been approved for the treatment of primary biliary cholangitis, a disease characterized by cholestasis; this drug is associated with pruritus, the cause of which is unknown. In animal models, bile acids, which accumulate in the body as a result of cholestasis, have been reported to cause scratching behavior mediated by the TGR2 receptor, in an opioid-dependent manner, in laboratory animals. As obeticholic acid also binds to TGR2, the pruritus caused by this drug is likely to be mediated by the opioid system. Lisophosphatidic acid, which has been reported to be increased in patients with cholestasis and pruritus, has been described to cause scratching behavior that is prevented by an opiate antagonist in laboratory animals, suggesting an opioid-receptor mediated mechanism of scratching. In summary, evidence continues to support a role of the endogenous opioid system in the pathogenesis of the pruritus of cholestasis



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Title page/Editorial Board

Publication date: November 2017
Source:Medical Hypotheses, Volume 109





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Neuroprotective potential of high-dose biotin

Publication date: November 2017
Source:Medical Hypotheses, Volume 109
Author(s): Mark F. McCarty, James J. DiNicolantonio
A recent controlled trial has established that high-dose biotin supplementation – 100 mg, three times daily – has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS. But biotin's ability to boost cGMP synthesis in the brain may have broader neuroprotective potential. In many types of neurons and neural cells, cGMP exerts neurotrophic-mimetic effects – entailing activation of the PI3K-Akt and Ras-ERK pathways – that promote neuron survival and plasticity. Hippocampal long term potentiation requires nitric oxide synthesis, which in turn promotes an activating phosphorylation of CREB via a pathway involving cGMP and protein kinase G (PKG). In Alzheimer's disease (AD), amyloid beta suppresses this mechanism by inhibiting sGC activity; agents which exert a countervailing effect by boosting cGMP levels tend to restore effective long-term potentiation in rodent models of AD. Moreover, NO/cGMP suppresses amyloid beta production within the brain by inhibiting expression of amyloid precursor protein and BACE1. In conjunction with cGMP's ability to oppose neuron apoptosis, these effects suggest that high-dose biotin might have potential for the prevention and management of AD. cGMP also promotes neurogenesis, and may lessen stroke risk by impeding atherogenesis and hypertrophic remodeling in the cerebral vasculature. The neuroprotective potential of high-dose biotin likely could be boosted by concurrent administration of brain-permeable phosphodiesterase-5 inhibitors.



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The Founding Fathers of the International Neuroendocrine Society (INS)

Abstract

It seems appropriate in this Special Issue of Journal of Neuroendocrinology, which marks the new Pan American Neuroendocrine Society (PANS), to recognize the first group of international scientists who were linked by their common purpose to promote neuroendocrinology throughout the world.

This article is protected by copyright. All rights reserved.

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Scholar : These new articles for Comparative Legal History are available online

The online platform for Taylor & Francis Online content New for Comparative Legal History and online now on Taylor & Francis Online: Book Review Martin Luthers Reformation und das Recht. Die Entwicklung der Theologie Luthers und ihre Auswirkung auf das Recht unter den Rahmenbedingungen der Reichsreform und der Territorialstaatsbildung im Kampf mit Rom und den "Schwärmern" Mathias Schmoeckel Pages: 1-4 | DOI: 10.1080/2049677X.2017.1401795 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Comparative analysis of the protective effects of curcumin and N -acetyl cysteine against paracetamol-induced hepatic, renal, and testicular toxicity in Wistar rats

Abstract

This study aimed to investigate the possible protective role of curcumin (CUR) vs. N-acetyl cysteine (NAC) against paracetamol (PCM)-induced oxidative damage and impairment of liver, kidney, and testicular functions, as well as hematotoxicity, in albino rats. A large single dose of PCM induced lipid peroxidation along with a significant decline in glutathione content and catalase activity in the liver, kidneys, and testicles. The apparent oxidative damage was associated with evident hepatic, renal, and testicular dysfunction, which was confirmed in histopathological lesions, and increased serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities. PCM decreased serum total protein, albumin, and globulin contents; increased bilirubin, urea, and creatinine contents; and induced hematotoxicity. PCM also reduced the sperm cell count, sperm motility, and alive sperm rate and increased the sperm abnormality rate. Pretreatment of PCM-intoxicated animals with CUR or NAC substantially alleviated the increase in malondialdehyde and maintained the antioxidants at control levels. These pretreatments also minimized liver, kidney, and testicular histopathological changes and normalized their functions. CUR similarly mitigated the PCM hemato- and hepatotoxicity compared with NAC. However, it exhibited a pronounced nephroprotection, rather than reproductive protection as did NAC. Our findings demonstrate that a large single dose of PCM is not only associated with hepatotoxicity but also nephrotoxicity and reproductive toxicity. Both CUR and NAC administration provided substantial organ protection with pronounced efficacy against PCM nephrotoxicity with CUR and reproductive toxicity with NAC, which was possibly mediated through their antioxidant activities, as well as their specific characteristics.

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Characterization and valorization of biomass char: a comparison with biomass ash

Abstract

Organic matter derived from living, or recently living plant and animal, which can be used as fuel is called as biomass. It includes wood and agricultural waste such as dead plant etc. In India, majority of population depends largely upon agriculture as their primary source of income. Following every harvest, a huge amount of biomass is generated. It is mostly discarded as "agro waste"; however, recently, several uses of biomass and its derivatives have been reported. Thermochemical processing of biomass in absence of oxygen produces biomass char and flue gases which are of economic importance. However, it is necessary to characterize the physical and chemical properties of these components so as to utilize their potential benefit to the fullest. In this study, six different biomass remains that include mustard plant, groundnut plant, cotton plant, wheat plant, pigeon peas, and groundnut shell were pyrolyzed at 650 °C, in vertical downdraft fixed-bed biomass reactor. The flue gases were characterized in detail by gas chromatography. X-ray fluorescence, proximate, and ultimate analyses were performed on all BMC (biomass char) samples, and properties such as porosity, particle density, bulk density, point of zero charge, surface pH, surface charges, water-absorption capacity, and BET surface area were determined. SEM and FTIR were also carried out on all BMC samples. Our results showed that the surface area of biomass char varies from 38 to 138 m²/g. The solution pH for all BMC exceeds 8.6, thus confirmed the alkaline nature. Comparison between combustion products produced in the presence (biomass ash) and absence of oxygen (biomass char) is presented. BMC finds applications in agriculture, soil neutralizer, adsorbent, and soil additive. They have high amount of carbon and can act as a rich carbon source for the soil. Flue gases released contain methane and hydrogen which can also improve economic value for the char formation process.

http://ift.tt/2zf4gWJ

The micronucleus test for the oral mucosa: global trends and new questions

Abstract

This study reviews global trends in the publication of papers on the micronucleus test of the exfoliated cells of the oral mucosa in mammals as an approach for environmental biomonitoring. This test has been widely used due to its precision for the detection of chromosome damage. Our temporal analysis showed a significant increase (p < 0.05) in the publication of papers on the oral mucosa over the past 33 years. Brazil was the country that published most papers (24% of the total), followed by India (16%), the USA (10%), Mexico (7%), and Turkey (6%). A further 30 countries contributed the other 37% of the papers. Overall, 99% of the micronucleus studies involved human subjects, and only 1% involved other mammals. As many wild mammals are subject to the same environmental pressures as humans, in particular chemical pollution, it seems likely that many species are equally susceptible to genotoxicogical damage. We emphasize the importance of applying this technique to the analysis of the oral mucosa of wild mammals, as well as the evaluation of its effectiveness, as observed in humans, and the expansion of the available approaches to the monitoring of environmental quality.

http://ift.tt/2mFQnLr