Pan-Cancer Analysis of Genomic Sequencing among the Elderly

Publication date: Available online 7 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Daniel R. Wahl, Paul Nguyen, Maria Santiago, Kasra Yousefi, Elai Davicioni, Dean A. Shumway, Corey Speers, Rohit Mehra, Felix Y. Feng, Joseph R. Osborne, Daniel E. Spratt
IntroductionWe hypothesized that elderly patients may have age-specific genetic abnormalities yet be underrepresented in currently available sequencing repositories, which could limit the impact of sequencing efforts for this population.Methods and MaterialsLeveraging The Cancer Genome Atlas (TCGA) data-portal, 9 tumor types were analyzed. Frequency distribution of cancer by age was determined and compared to Surveillance, Epidemiology, and End Results (SEER) data. Using the estimated median somatic mutational frequency of each tumor type, the samples needed beyond TCGA to detect a 10% mutational frequency were calculated. Micro-array data from a separate prospective cohort were obtained from primary prostatectomy samples to determine if elderly-specific transcriptomic alterations could be identified.ResultsOf the 5,236 TCGA samples, 73% were in patients younger than age 70. Comparing the distribution of TCGA samples by age to SEER data, patients <70 were well represented across most tumor types, but patients 80-99 years old were underrepresented in all cancers (median TCGA underrepresentation of 167%). All cancers (except colorectal) contained enough samples to detect a 10% mutational frequency in patients <60 years old. In contrast, no cancer type had enough samples for which a 10% mutational frequency could be detected in patients ≥80 years old. To further interrogate whether elderly patients with cancer were likely to harbor age-specific molecular abnormalities, we accessed transcriptomic data from a separate, larger database of over 2,000 prostate cancer samples. This analysis revealed significant differences in the expression of 10 genes in patients ≥70 years old compared to those younger than 70, of which 7 are involved in androgen signaling and/or DNA repair.ConclusionsElderly patients are underrepresented in genomic sequencing studies. Our data suggest the presence of elderly-specific molecular alterations. Further dedicated efforts to understand the biology of cancer among the elderly will be important moving forward.



http://ift.tt/2inOb4z

Using Proton Beam Therapy in the Elderly Population: A Snapshot of Current Perception and Practice

Publication date: Available online 6 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Juliette Thariat, Terence Sio, Pierre Blanchard, Samir Patel, Yusuke Demizu, Federico Ampil, Sebastien Guihard, Robert C. Miller, Ulf Karlsson, Marco Krengli, Huan Giap, Nam Nguyen
Allocation to advanced radiation technologies is challenged by the increasing proportion of elderly cancer patients. Current decision-making systems for proton therapy (PT) do not adequately address the clinical needs. Based on a survey among radiation oncologists, a gap was shown between chronological age and eventual PT allocation. It also pointed out a lack of systematic geriatric assessment and the potential for PT to limit the toxicity burden and hospital costs in the elderly.



http://ift.tt/2jnk8OT

The impact of IMRT on hospitalization outcomes in the SEER-Medicare population with anal squamous cell carcinoma

Publication date: Available online 7 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Erqi L. Pollom, Guanying Wang, Jeremy P. Harris, Albert C. Koong, Eran Bendavid, Jay Bhattacharya, Daniel T. Chang
PurposeWe examined the impact of intensity-modulated radiotherapy (IMRT) on hospitalization rate in the SEER-Medicare population with anal squamous cell carcinoma (SCC).MethodsWe performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We identified patients with non-metastatic anal SCC diagnosed between 2001 and 2011 and treated with chemoradiotherapy. We assessed the relation between IMRT and first hospitalization using a multivariate competing risk model as well as instrumental variable analysis, using provider IMRT affinity as our instrument.ResultsOf the 1,165 patients included in our study, 458 (39%) received IMRT. IMRT use increased over time, and was associated more with regional and provider characteristics, rather than patient characteristics. The 3- and 6-month cumulative incidences of first hospitalization were 41.9% (95% CI 37.3-46.4) and 47.6% (95% 43.0-52.2), and 46.7% (95% CI 43.0-50.4) and 52.1% (95% CI 48.4-55.7) for the IMRT and non-IMRT cohorts, respectively. IMRT was associated with a decreased hazard of first hospitalization compared to 3-D radiation techniques (HR 0.70, 95% CI 0.58-0.84, p=0.0002). Instrumental variable analysis suggested an even greater reduction in hospitalizations with IMRT after controlling for unmeasured confounders. There was a trend toward improved overall survival with IMRT, with an adjusted hazard ratio of 0.77 (95% CI 0.59-1.00, p=0.05).ConclusionThe use of IMRT is associated with reduced hospitalizations in elderly patients with anal squamous cell carcinoma. Further work is warranted to understand the long-term health and cost impact of IMRT, particularly for patient subgroups most at risk of toxicity and hospitalization.



http://ift.tt/2inVfhH

Cerebral cortex regions selectively vulnerable to radiation dose-dependent atrophy

Publication date: Available online 6 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Tyler M. Seibert, Roshan Karunamuni, Samar Kaifi, Jeffrey Burkeen, Michael Connor, AnithaPriya Krishnan, Nathan S. White, Nikdokht Farid, Hauke Bartsch, Vyacheslav Murzin, Tanya T. Nguyen, Vitali Moiseenko, James B. Brewer, Carrie R. McDonald, Anders M. Dale, Jona A. Hattangadi-Gluth
Purpose/Objectives: Neurologic deficits after brain radiotherapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy.Materials/MethodsWe measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. Study patients had high-resolution, volumetric MRI (T1-weighted; T2 FLAIR) prior to and one year after RT. Semi-automated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region pre-RT and at one year. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, two primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α=0.05 using two-tailed tests.ResultsCortical atrophy was significantly associated with radiation dose in the entorhinal (p=0.01) and inferior parietal ROIs (p=0.02). In contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (p≤0.002).ConclusionsAreas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients develop deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.

Teaser

Neurologic deficits after brain radiotherapy typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We used quantitative MRI to see whether areas of cerebral cortex involved in higher-order cognition are more vulnerable to radiation dose-dependent atrophy. At one year after radiotherapy, higher-order "association cortex" regions demonstrated dose-dependent atrophy, while "primary cortex" regions did not.


http://ift.tt/2jniSeC

ASCENDE-RT: An Analysis of Treatment-Related Morbidity for A Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to A Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer

Publication date: Available online 6 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Sree Rodda, Scott Tyldesley, W. James Morris, Mira Keyes, Ross Halperin, Howard Pai, Michael McKenzie, Graeme Duncan, Gerard Morton, Jeremy Hamm, Nevin Murray
PurposeTo report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing two methods of dose escalation for high- and intermediate-risk prostate cancer.Materials and MethodsASCENDE-RT enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy (ADT), pelvic irradiation to 46 Gy followed by a dose escalated-external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GU and GI morbidity and information on urinary continence, catheter use, and erectile function. Excluding 15 who received non-protocol treatment and correcting 14 crossovers events, leaves 195 men who actually received a DE-EBRT boost and 188 a LDR-PB boost. Median follow up is 6.5 years.ResultsLDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5 years, the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB versus 5.2% for DE-EBRT (p <0.001). Compared to the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% versus 2.2%, p =0.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% versus 3.2% for LDR-PB and DE-EBRT (p =0.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% versus 2.2%). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5 years versus 37% after DE-EBRT (p =0.30).ConclusionsIncidence of acute and late GU morbidity was higher following LDR-PB boost and there was a non-significant trend for worse GI morbidity as well. No differences in the frequency of erectile dysfunction were observed.



http://ift.tt/2i24hjC

Antimicrobial activity and acute toxicity of ozonated lomefloxacin solution

Abstract

Lomefloxacin (LOM) is a synthetic antimicrobial from the fluoroquinolone family (FQ) used as a veterinary and human drug. Once in the environment, LOM may pose a risk to aquatic and terrestrial microorganisms due to its antimicrobial activity. This study evaluated the effect of ozonation of LOM (500 μg L⁻¹), the residual antimicrobial activity against Escherichia coli and acute toxicity against Vibrio fischeri. In addition, degradation products were investigated by UHPLC-MS/MS and proposed. Ozonation was carried out varying the applied ozone dose from 0 to 54.0 mg L⁻¹ O₃ and pH values of 3, 7, and 11. Ozonation was most efficient at pH 11 and led to 92.8% abatement of LOM in a 9-min reaction time (54.0 mg L⁻¹ O₃ applied ozone dose). Ozonation at pH 3 was able to degrade 80.4% of LOM. At pH 7, 74.3% of LOM was degraded. Although the LOM concentration and the antimicrobial activity of the solution dropped as ozone dose increased (antimicrobial activity reduction of 95% at pH 11), toxicity to V. fischeri increased for pH 7 and 11 (i.e., 65% at pH 7 and 75% at pH 11). The reduction in antimicrobial activity may be related to the oxidation of piperazinyl and the quinolone moiety. The formation of intermediates depended on the oxidant (hydroxyl radicals or/and molecular O₃) that acted the most in the process.

http://ift.tt/2inUmWD

Removal of organic matter and electricity generation of sediments from Progreso, Yucatan, Mexico, in a sediment microbial fuel cell

Abstract

Sediment microbial fuel cells (SMFCs) are devices that generate electrical energy through sediments rich in organic matter (OM). The present study assessed the potential of sediments collected at two sites in Yucatan, Mexico, (the swamp of Progreso port and Yucalpetén dock) to be used in these electrochemical devices. Sediments were collected during the rainy and winter seasons and were monitored in the SMFC for 120 days through electrochemical and physicochemical characterization. OM removal in the SMFC ranged from 8.1–18.01%, generating a maximum current density of 232.46 mA/cm² and power density of 95.85 mW/cm². SUVA analysis indicated that with a young soil, the ratio E4/E6 presented evidence directly related to the degradation of aromatic and aliphatic compound formation, implying humification and, therefore, sediment enrichment.

http://ift.tt/2jnjW29

Can toxicants used against cotton mealybug Phenacoccus solenopsis be compatible with an encyrtid parasitoid Aenasius bambawalei under laboratory conditions?

Abstract

The cotton mealybug, Phenacoccus solenopsis Tinsley (Sternorrhyncha: Pseudococcidae) is a serious pest of various cultivated plants in Pakistan. Recent reports show that the parasitoid Aenasius bambawalei Hayat (Hymenoptera: Encyrtidae) is a good biocontrol agent of the pest. Compatibleness is important in any IPM programme, and the insecticide used must have little or no effects on the biological control agent. This study investigated the compatibility of neem treatments and a commercial insecticide, imidacloprid on A. bambawalei. Bioassays were laid out in a completely randomized design (CRD) under laboratory conditions. Results showed that the adult stage of the parasitoid was more susceptible to the commercial insecticide imidacloprid than the concealed pupal stage. Moreover, on the basis of the International Organization for Biological Control (IOBC) toxicity categories of the commercial insecticide, imidacloprid was moderately toxic throughout the study period (Ex >80%) while neem was slightly toxic after 24 h of use (Ex <80%). Results also suggest that A. bambawalei release should be delayed for at least 1 week after neem treatments. Because imidacloprid destroys A. bambawalei, it might cause resurgence of P. solenopsis; thus, farmers should avoid integrating the insecticide in the control of P. solenopsis.

http://ift.tt/2inUmG7

Variation in dermatologist visits by sociodemographic characteristics

Publication date: Available online 6 January 2017
Source:Journal of the American Academy of Dermatology
Author(s): Andrew Mulcahy, Ateev Mehrotra, Karen Edison, Lori Uscher-Pines
BackgroundAccess to dermatologists is an ongoing concern for Medicaid enrollees. Understanding current use is a key step toward designing and implementing policies to improve access.ObjectiveWe sought to quantify how often Medicaid enrollees visit dermatologists and receive treatment for skin-related conditions compared with patients with other coverage or without health insurance.MethodsWe conducted a retrospective cross-sectional analysis of multiyear federal survey data (Medical Expenditure Panel Survey). The sample included Medical Expenditure Panel Survey respondents younger than 65 years from 2008 to 2012.ResultsIn unadjusted comparisons, we found that 1.4% of Medicaid enrollees had an ambulatory visit to a dermatologist annually, compared with 1.2% of uninsured individuals and 5.5% of individuals with private coverage. In adjusted models, we found that health insurance source, age, sex, race/ethnicity, and geography are associated with the likelihood of having visits to a dermatologist. Compared with individuals with private coverage, Medicaid enrollees are less likely to receive a diagnosis for a skin condition by any provider and are less than half as likely to have skin-related diagnoses made by dermatologists.LimitationsWe have relatively few Medical Expenditure Panel Survey respondents for a subset of specific diagnoses.ConclusionsOur findings emphasize the need for efforts to reduce disparities in access to dermatologists.



http://ift.tt/2jdTRhG

Lesions on the back of hands and female gender predispose to stigmatization in patients with psoriasis

Publication date: Available online 6 January 2017
Source:Journal of the American Academy of Dermatology
Author(s): Marlena Hawro, Marcus Maurer, Karsten Weller, Romuald Maleszka, Anna Zalewska-Janowska, Andrzej Kaszuba, Zofia Gerlicz-Kowalczuk, Tomasz Hawro
BackgroundPsoriasis vulgaris is characterized by disfiguring and stigmatizing skin lesions. The links among lesions distribution, severity, and stigmatization remain unclear.ObjectiveWe sought to investigate if the involvement of visible and sensitive areas is linked to stigmatization.MethodsIn all, 115 patients with psoriasis vulgaris were assessed for disease severity, skin lesions distribution, itch, and stigmatization using the Feelings of Stigmatization Questionnaire. Quality of life was assessed with the Dermatology Life Quality Index and the World Health Organization Quality of Life-BREF.ResultsThe localization of psoriatic lesions on the back of hands was related to higher stigmatization levels (P = .011, total score of the Feelings of Stigmatization Questionnaire), but not the involvement of nails, the palms, the face, or the genital area nor overall disease severity. All patients reported some level of stigmatization, regardless of the localization of lesions and type of psoriasis. Higher levels of stigmatization characterized patients who claimed not to be able to hide their lesions by clothing (P = .025), women (P = .001), and the unemployed (P = .004). Stigmatization was the strongest predictor of quality of life impairment.LimitationsOnly hospitalized patients were included.ConclusionsPsoriatic lesions on the back of hands are debilitating and warrant effective treatment. Special attention should be paid to female patients, who are more sensitive to stigmatization.



http://ift.tt/2hZKkyz

Sex Differences in Hazard Ratio During Drug Treatment of Non–Small-cell Lung Cancer in Major Clinical Trials: A Focused Data Review and Meta-analysis

Publication date: Available online 7 January 2017
Source:Clinical Therapeutics
Author(s): Lishi Wang, Yanhong Cao, Mingji Ren, Amei Chen, Jinglin Cui, DiaJun Sun, Weikuan Gu
PurposeUnderstanding how sex impacts the efficacy of anticancer agents is a crucial step toward personalized and precision medicine. This review and meta-analysis evaluated sex differences in hazard ratios (HRs) of progression-free survival and overall survival in representative Phase III clinical trials of non–small-cell lung cancer (NSCLC).MethodsData were extracted from 24 large-scale clinical trials that included 12,000 male and 7000 female patients. The data were examined for HR differences between subgroups by sex, smoking status, and age, and for potential sex–smoking status, sex–age, and sex–drug interactions, during cancer treatment.FindingsSummarized information revealed variations in the influences of sex, smoking status, and age on the efficacy of drugs used for the treatment of NSCLC. The male and female subgroups had different HR values. Smoking status, age, and the percentage of female patients in a treatment group had no influence on the sex HR. The sex difference was supported by a set of data collected from all journals.ImplicationsThe findings from this meta-analysis are important for assessing potential toxicity during drug treatment in both sexes. The outcomes measures of a drug in clinical application should be specified by subpopulation, such as males versus females, as a first step in personalized medicine.



http://ift.tt/2inRZmr

Drugs and Medical Devices: Adverse Events and the Impact on Women’s Health

Publication date: Available online 7 January 2017
Source:Clinical Therapeutics
Author(s): Jennifer L. Carey, Nathalie Nader, Peter R. Chai, Stephanie Carreiro, Matthew K. Griswold, Katherine L. Boyle
A large number of medications and medical devices removed from the market by the US Food and Drug Administration over the past 4 decades specifically posed greater health risks to women. This article reviews the historical background of sex and gender in clinical research policy and describes several approved drugs and devices targeted for use in women that have caused major morbidity and mortality. The intended population for the medications and devices, population affected, approval process, and the basic and legal actions taken against the medication/drug company are also discussed. It is recognized that women are still at risk for harm from unsafe medications and devices, and continued improvements in legislation that promotes inclusion of sex and gender into the design and analysis of research will improve safety for both men and women.



http://ift.tt/2jnjhh6

The thyroid, the eyes and the gut: a possible connection

Abstract

Introduction

Graves' disease (GD) is an autoimmune disorder responsible for 60–90% of thyrotoxicosis, with an incidence of 1 to 2 cases per 1000 population per year in England. Graves' orbitopathy (GO) is the most frequent extrathyroidal manifestation, not provoked directly by abnormal thyroid hormone levels, but by the consequence of the underlying autoimmune process. The aetiology of autoimmune disorders is due to an interplay between susceptibility genes and environmental factors, such as infections and stress. What triggers the autoimmune reaction to a specific site of the body is not yet clearly understood. The lack of knowledge in GD and GO pathogenesis implicates therapies that only limit damage but do not prevent disease onset.

Material and methods

We performed on PubMed and the Cochrane Library a literature search for the articles published until July 2016 by using the search terms 'graves disease' and 'microbiome', 'orbitopathy' and 'autoimmune pathogenesis'. Reference lists of relevant studies were hand-searched for additional studies.

Conclusion

In this scenario, a Marie Sklodowska–Curie funded project INDIGO (http://ift.tt/2jnacVg) is investigating the role of the gut bacteria in GD and GO pathogenesis. The gut is the first and the widest area of bacteria access, with the highest concentration of T cells in the human body and trained to react to microorganisms. Interestingly, all the environmental factors involved in GD and GO pathogenesis can alter the balance within the microorganisms located in the gut, and influence the immune system, in particular the proportions of regulatory Treg and inflammatory TH17 cells. It is hoped that investigating GD and GO pathogenesis from this novel aspect will identify new targets for prevention and treatment.

http://ift.tt/2i1OW2g

Development of Highly-Sensitive Detection System in 19F NMR for Bioactive Compounds Based on the Assembly of Paramagnetic Complexes with Fluorinated Cubic Silsesquioxanes

Publication date: Available online 7 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Takahiro Kakuta, Hayato Narikiyo, Jong-Hwan Jeon, Kazuo Tanaka, Yoshiki Chujo
This manuscript reports the detection system with ¹⁹F NMR probes for bioactive amine compounds at sub-micro molar concentrations. Water-soluble fluorinated polyhedral oligomeric silsesquioxane (POSS) derivatives were prepared, and the paramagnetic Ni-porphyrin (NiPor) with the fluorinated POSS (F-POSS) was adsorbed in the buffer. By adding the series of amine derivatives to the homogeneous dispersion containing the POSS-NiPor complexes, the changes in the signal intensity were evaluated. It was clearly observed from homogeneous dispersions that the signal intensity of ¹⁹F NMR decreased especially in the presence of ethanediamine and hexylamine. From the dynamic light scattering measurements, it was revealed that the assembly of the F-POSS complexes was dramatically induced by the amine compounds when the signal intensity decreased. According to these data, it is proposed that the signal reduction of ¹⁹F NMR from the POSS-NiPor complexes could be induced via the strong paramagnetic relaxation enhancement from NiPor in the assembly. Finally, based on the signal reduction by the assembly, we can detect the amine derivatives under 1 μM concentration which is similar sensitivity to the conventional fluorescence probes. Our system is valid to monitor the distribution of the bio-active molecules at cellular concentrations.

Graphical abstract

http://ift.tt/2i1MRUf

Bath-PUVA therapy improves impaired resting regulatory T cells and increases activated regulatory T cells in psoriasis

Publication date: Available online 6 January 2017
Source:Journal of Dermatological Science
Author(s): Ryoji Kubo, Shinnosuke Muramatsu, Yoko Sagawa, Chiyo Saito, Saori Kasuya, Akiko Nishioka, Emi Nishida, Sayuri Yamazaki, Akimichi Morita
BackgroundBath-psoralen plus ultraviolet light A (PUVA) therapy is an effective, safe, and inexpensive treatment for psoriasis. Psoriasis might be due to an unbalanced ratio of Th17 cells and regulatory T cells (Treg). The Treg functional ratio is significantly lower in patients with psoriasis compared with controls and is inversely correlated with the Psoriasis Area and Severity Index score. We previously reported that bath-PUVA therapy significantly increases the number of Treg and restores Treg function to almost normal in most patients with psoriasis.ObjectivesWe examined the effects of bath-PUVA therapy on three distinct Foxp3⁺ subsets: activated Treg (aTreg), resting Treg (rTreg), and cytokine-secreting non-suppressive T cells.MethodsWe enrolled 15 patients with psoriasis and 11 healthy controls. We examined aTreg, rTreg, and cytokine-secreting non-suppressive T cells in peripheral blood obtained from the psoriasis patients before and after every fifth bath-PUVA therapy session.ResultsLevels of aTreg, which are considered to have the strongest suppressive activity in patients with psoriasis, were significantly increased in the early bath-PUVA therapy sessions, and then diminished. Levels of rTreg were lower in psoriasis patients than in healthy controls, and increased during bath-PUVA therapy.ConclusionsBath-PUVA therapy induced aTreg and rTreg concomitantly with an improvement in the psoriatic lesions, suggesting a mechanism for the effectiveness of bath-PUVA therapy for psoriasis patients.



http://ift.tt/2inDT4v

Yogurt consumption in infancy is inversely associated with atopic dermatitis and food sensitization at 5 years of age: a hospital-based birth cohort study

Publication date: Available online 6 January 2017
Source:Journal of Dermatological Science
Author(s): Tetsuo Shoda, Masaki Futamura, Limin Yang, Masami Narita, Hirohisa Saito, Yukihiro Ohya
BackgroundSeveral studies have suggested that habitual yogurt consumption is associated with favorable outcomes for health issues in children. However, the effects of yogurt consumption on allergic diseases and sensitization in children remain poorly understood.ObjectiveThis prospective birth cohort study aimed to investigate for associations between habitual yogurt consumption in infancy and development of allergic diseases/sensitization at 5 years of age.MethodsData were obtained from the Tokyo Children's Health, Illness and Development (T-CHILD) study. A total of 1,550 children were born to the recruited women. Consumption of yogurt by children during infancy was determined by using questionnaires completed at 12 months of age. Outcome data for children were collected from the questionnaires and medical check-ups completed at 5 years of age. Possible associations between habitual yogurt consumption in infancy and allergic diseases/sensitization were analyzed by multiple logistic regression analyses.ResultsWe analyzed the data for 1,166 children whose parents responded at 5 years of age. Habitual yogurt consumption in infancy and atopic dermatitis at 5 years of age were significantly associated (UKWP criteria: aOR, 0.70; 95% CI, 0.51–0.97; P=0.03). Children with habitual yogurt consumption in infancy were less likely to be sensitized to food allergens (aOR, 0.53; 95% CI, 0.31–0.93; P=0.03), but no associations were seen in regard to any other allergens.ConclusionsOur study demonstrated that habitual consumption of yogurt in infancy has the potential to prevent development of atopic dermatitis and food sensitization, but not other allergic diseases, at 5 years of age.



http://ift.tt/2jmXVjT

Immunohistochemistry in the workup of prostate biopsies: Frequency, variation and appropriateness of use among pathologists practicing at an academic center

Publication date: Available online 7 January 2017
Source:Annals of Diagnostic Pathology
Author(s): Sameer Al Diffalha, Mohanad Shaar, Güliz A. Barkan, Eva M. Wojcik, Maria M. Picken, Stefan E. Pambuccian
ObjectivesWe studied the frequency, inter-pathologist variation, appropriateness and utility of immunohistochemistry (IHC) performed on prostate biopsies (PB) to determine the significance of foci of suspicious glands or atypical small acinar proliferations (ASAP).MethodsWe calculated the rate of IHC use and diagnostic rate of ASAP and adenocarcinoma in PB from 01/01/2008 to 06/30/2015 for individual pathologists working in a tertiary academic institution, and correlated them with the pathologists' experience, subspecialization and PB volume with the aim of determining the interpathologist variation and appropriateness of use of IHC according to recently published recommendations, and the usefulness of IHC to resolve foci of ASAP as either benign or adenocarcinoma.ResultsIHC was used in 966/2652 (36.4%, 95% CI 33.4–39.4%) PB cases and 1915 of 16,359 (11.7%, 95% CI 11.2%–12.2%) of PB blocks and allowed definitive diagnosis of either benign or malignant in 75.8% (95% CI 73.9–77.7%) of blocks. By pathologist, IHC use rates varied more than twofold (22.8–50.5%); higher use was found for pathologists with genitourinary pathology specialization, higher PB volume and more experience, and correlated with higher rates of both ASAP and adenocarcinoma diagnoses. The use of IHC stains was considered appropriate in 822/966 (85.1%, 95% CI 82.9–87.4%) cases.ConclusionsDespite the fact that the use of IHC stains was considered useful and deemed appropriate in the majority of cases, it showed wide variation between pathologists, suggesting monitoring of IHC use rates may be useful to standardize its use.



http://ift.tt/2jew559

Myoepithelioma of Soft Tissue: A Cytological-Pathological Correlation with Literature Review

Publication date: Available online 6 January 2017
Source:Annals of Diagnostic Pathology
Author(s): Oleksandr Kravtsov, Jason Chang, Donald Hackbarth, Tamara Giorgadze
Myoepitheliomas of soft tissue are rare tumors with variable morphologic, immunohistochemical and molecular profiles and therefore are diagnostically challenging for pathologists. We report a case in a 60-year-old male with a painless slowly growing 3cm mass on left medial forefoot. Core biopsy of the mass showed a neoplastic proliferation of plasmacytoid tumor cells, consistent with myoepithelioma of soft tissue. Immunohistochemical stains demonstrated positivity of the tumor cells for cytokeratin AE1/AE3, CK18, S-100 protein and myosin heavy chain (SMMS-1), supporting the diagnosis. Fine-needle aspiration was performed intraoperatively before the resection of the mass. Air-dried Diff-Quik stained cytology slides showed singly scattered and loosely cohesive clusters of plasmacytoid and spindle cells with dense basophilic cytoplasm, distinct cytoplasmic borders, and round to oval mildly pleomorphic nuclei with smooth nuclear membrane. Scattered naked nuclei, binucleated tumor cells, as well as tumor cells with wispy elongated cytoplasm were also seen. Occasional clusters of cells were intimately associated with metachromatic fibrillary stromal material. Histologic examination of the resected tumor confirmed the diagnosis of myoepithelioma. Molecular studies showed absence of EWSR1 rearrangement. Cytological differential diagnosis, clinical, histological, immunohistochemical, and molecular features of soft tissue myoepitheliomas are discussed in this study.



http://ift.tt/2i0nrLD

Controlling water transport in carbon nanotubes

Publication date: Available online 6 January 2017
Source:Nano Today
Author(s): Kunli Goh, Yuan Chen
Water transport inside carbon nanotubes (CNTs) shows a wealth of unique nanofluidic phenomena, which can be exploited as solutions for many global challenges. However, translating this potential into practical applications remains questionable to date. Recently, a work by Secchi and coworkers provides confirmatory evidence of radius-dependent water slippage inside an individual CNT. This article therefore puts into perspective two key takeaways, namely, nanoconfinement and electronic structures of CNT, as promising approaches to control ultrafast water transport inside CNTs.

Graphical abstract

http://ift.tt/2jmZgHj

Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats

Publication date: March 2017
Source:International Immunopharmacology, Volume 44
Author(s): Palani Dinesh, MahaboobKhan Rasool
The current study was designed to investigate the therapeutic potential of berberine on monosodium urate (MSU) crystal stimulated RAW 264.7 macrophages and in MSU crystal induced rats. Our results indicate that berberine (25, 50 and 75μM) suppressed the levels of pro-inflammatory cytokines (interleukin–1beta (IL-1β) and tumor necrosis factor alpha (TNFα)) and intracellular reactive oxygen species in MSU crystal stimulated RAW 264.7 macrophages. The mRNA expression levels of IL-1β, caspase 1, nucleotide–binding oligomerization domain–like receptor pyrin domain containing 3 (NLRP3), thioredoxin interacting protein (TXNIP) and kelch–like ECH–associated protein 1 (Keap1) were found downregulated with the upregulation of nuclear factor erythroid–2–related factor 2 (Nrf2) transcription factor and its associated anti-oxidant enzymes: Heme oxygenase I (HO–1), superoxide dismutase (SOD1), glutathione peroxidase (GPx), NADPH quinone oxidoreductase–1 (NQO1) and catalase (CAT) in MSU crystal stimulated RAW 264.7 macrophages upon berberine treatment. Subsequently, western blot analysis revealed that berberine decreased the protein expression of IL-1β and caspase 1 and increased Nrf2 expression in RAW 264.7 macrophages. Immunofluorescence analysis also explored increased expression of Nrf2 in MSU crystal stimulated RAW 264.7 macrophages by berberine treatment. In addition, the paw edema, pain score, pro-inflammatory cytokines (IL-1β and TNFα) and articular elastase activity were found significantly reduced in berberine (50mg/kgb·wt) administered MSU crystal-induced rats. Conclusively, our current findings suggest that berberine may represent as a potential candidate for the treatment of gouty arthritis by suppressing inflammatory mediators and activating Nrf2 anti-oxidant pathway.



http://ift.tt/2iNaKme