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Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing the same treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p, registered on 12/01/2018.

Introduction Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal diseases with frequent systemic complications that are incurable according to current knowledge. These diseases adversely affect various areas of life, lowering patients' quality of life. One of the most frequently reported symptoms is fatigue. Aim Translation and validation of the IBD-F patient self-assessment scale with a Polish IBD population. Material and methods After consent from the author of the questionnaire had been obtained, the questionnaire was translated using the forward- and back-translation method. After arriving at the final Polish version of the questionnaire and ensuring that the questions and statements were comprehensible, the questionnaire was validated with a group of 129 IBD patients. Results High values of intraclass correlation coefficient (ICC) were achieved for overall results in both parts of the IBD-F questionnaire between test and retest (values exceeding 0.75). A high Cronbach's α consistency coefficient was achieved for the entire IBD-F questionnaire, both in the test and in the retest (0.968 and 0.975, respectively). Broken down into parts, Cronbach's α coefficient for Section I (presence and severity of fatigue) of the IBD-F questionnaire was 0.883, and for Section II (impact of fatigue on the person's life) it was 0.966. All patients evaluating the Polish version of the IBD-F questionnaire deemed the content of the questions comprehensible. Conclusions The analysis of the results obtained, the Polish version of the IBD-F questionnaire was considered valid, reliable, and clinically useful.

Objective: The objective of this narrative review was to investigate the history of light therapy in hospital settings, with reference to physiotherapy and particularly in an Australian context.Types of articles and search method:a review of available literature was conducted on PubMed, Medline and Google Scholar using keywords light therapy, photobiomodulation, physiotherapy, low-level laser, heliotherapy. Physiotherapy textbooks from Sydney University Library were searched. Historical records were accessed from the San Hospital library. Interviews were conducted with the San Hospital Chief Librarian and a retired former Head Physiotherapist from Royal Prince Alfred Hospital.Summary: Historically, light treatment has been used in both medical and physiotherapy practice. From its roots in ancient Egypt, India, and Greece, through to medieval times, the modern renaissance in 'light as therapy ' was begun by Florence Nightingale who, in the 1850s, advocated the use of clean air and an abundance of sunlight to restore health. Modern light therapy (phototherapy) had a marked uptake in use in medicine in Scandinavia, America, and Australia from 1903, following the pioneering work of Niels Finsen in the late 19th century, which culminated in Dr Finsen receiving the Nobel Prize for Medicine for the treatment of tuberculosis scarring with ultraviolet (UV) light, and treatment of smallpox scarring with red light. Treatment with light, especially UVB light, has been widely applied by physiotherapists in hospitals for dermatological conditions since the 1950s, particularly in Australia, Scandinavia, USA, England and Canada. In parallel, light treatment in hospitals for hyperbilirubinemia was used for neonatal jaundice. Since the 1980s light was also used in the medical specialties of ophthalmology, dermatology, and cardiology. In more recent years in physiotherapy, light was mostly used as an adjunct to the management of orthopedic/rheumatological conditions. Since the 1990s, there has been global use of light, in the form of photobiomodulation for the management of lymphedema, including in supportive cancer care. Photobiomodulation in the form of low-level laser has been used by physiotherapists and pain doctors since the 1990s in the management of chronic pain. The use of light as therapy is exemplified by its use in the San Hospital in Sydney, where light therapy was introduced in 1903 (after Dr. John Harvey Kellogg visited Niels Finsen in Denmark) and is practiced by nurses, physiotherapists and doctors until the present day. The use of light has expanded into new and exciting practices including supportive cancer care, and treatment of depression, oral mucositis, retinopathy of prematurity, and cardiac surgery complications. Light is also being used in the treatment of neurological diseases, such as Parkinson's disease, traumatic brain injury, and multiple sclerosis. The innovative uses of light in physiotherapy treatment would not be possible without the previous experience of successful application of light treatment.Conclusion: Light therapy has had a long tradition in medicine and physiotherapy. Although it has fallen somewhat out of favour over the past decades, there has been a renewed interest using modern techniques in recent times. There has been continuous use of light as a therapy in hospitals in Australia, most particularly the San Hospital in Sydney where it has been in use for almost 120 years.

People living with HIV (PLWH) and substance use disorder (SUD) are particularly vulnerable to harmful health consequences of the global COVID-19 pandemic. The health and social consequences of the pandemic may exacerbate substance misuse and poor management of HIV among this population. This study compares substance use and HIV care before and during the pandemic using data collected weekly through an opioid relapse prevention and HIV management mobile-health intervention. We found that during the pandemic, PLWH and SUD have increased illicit substance use and contact with other substance-using individuals and decreased their confidence to stay sober and attend recovery meetings. The proportion of people missing their HIV medications also increased, and confidence to attend HIV follow-up appointments decreased. Optimal support for PLWH and SUD is critical during pandemics like COVID-19, as drug-related and HIV antiretroviral therapy (ART) non-adherence risks such as overdose, unsafe sexual behaviors, and transmission of infectious diseases may unfold.Personas con VIH y con trastornos por abuso de sustancias son más vulnerable a las consecuencias de la pandemia: COVID-19. Dentro estas poblaciones, las consecuencias sociales y de la salud, causadas por la pandemia, pueden exacerbar el mal uso de las sustancias, y la adherencia a los antiretrovirales. Este estudio compara el abuso de sustancias y el cuidado del VIH, antes y durante la pandemia, usando datos colectados semanal de otro programa que también investigo la prevención entre personas que han recaído con el uso de opioides y que tienen VIH. Nuestro análisis encuentra, que durante la pandemia, incrementaron el uso de sustancias ilícitas, y contacto con otras personas que usan sustancias, y perdieron la capacidad de mantenerse sobrios, y tambien dejaron de asistir reuniones de recuperación/apoyo. También, el porcentaje de personas con VIH no siguiendo con sus planes de tratamiento de VIH, incrementó; perdieron su motivacion en mantener sus citas médicos. Es muy crítico, durante una pandemia como COVID-19, tener recursos para personas que pertenecen a estas poblaciones, si no, casos de sobredosis, sexo sin protección y la transmisión de enfermedades infecciosas van a prevaler.

Background This study evaluated the efficacy, safety, and acceptability of a new ferrous sulfate oral solution (Tardyferon® 20 mg/mL) in young children with mild or moderate iron deficiency anemia (IDA). Methods This was a multicenter, national, single‐arm, open‐label study. Children aged 6–53 months presenting with mild or moderate IDA (i.e., blood hemoglobin (Hb) ranging from 7.0 to 10.9 g/dL and serum ferritin

Background: Vedolizumab, a humanized antibody targeting the α4β7 integrin, was proven to be effective in the treatment of moderate-to-severe ulcerative colitis (UC) in randomized clinical trials. The aim of the POLONEZ study is to determine the demographic and clinical characteristics of the patients with UC treated with vedolizumab within the scope of the National Drug Program in Poland and to assess the real-world effectiveness and safety of vedolizumab in the study population. Here we report the demographic and clinical characteristics of these patients. Methods: This prospective study included adult patients eligible for UC treatment with vedolizumab who were recruited from 12 centers in Poland between February and November 2019. Collected data included sex, age, disease duration, presence of extraintestinal manifestations or comorbidities, status of previous biologic treatment, and current concomitant treatment. Disease extent was determined according to the Montreal classification, and disease activity was measured with the Mayo Score. Results: A total of 100 (55 biologic-naïve and 45 biologic-exposed) patients were enrolled in the study (51% female, median age 35 years). Among biologic-exposed patients (mostly infliximab-treated), 57% had failed to respond to the therapy. The disease duration was significantly shorter in biologic-naïve (median 5 years) than in biologic-exposed (8 years, p = 0.004) or biofailure patients (7 years, p = 0.04). In the overall population the median Total Mayo Score was 10. Disease extent and activity were similar between the subgroups. Conclusions: Our study indicates that patients treated with vedolizumab in Poland receive the drug relatively early after UC diagnosis, but their disease is advanced. More than half of the patients had not been treated with biologic drugs before initiating vedolizumab. The study was registered in ENCePP database (EUPAS34119). Lay summary Characteristics of patients treated for ulcerative colitis with vedolizumab in Poland Treatment of moderate-to-severe ulcerative colitis (UC) with the integrin antagonist vedolizumab became available within the Polish National Drug Program (NDP) in 2018. In this study, for the first time, we provide detailed demographic and clinical characteristics of 100 patients (median age 35 years, 51% female) treated with vedolizumab in Poland, of whom 55 were biologic-naïve and 45 biologic-exposed. The median duration of disease was 6 years. The disease duration was shorter in biologic-naïve than in biologic-exposed patients. Most patients were affected by extensive colitis (52%) or left-sided colitis (42%). Median disease activity was 10 according to the Total Mayo Score. Sixty-eight patients received concomitant systemic corticosteroids and 45 patients received immunomodulators. Our findings indicate that Polish patients receiving vedolizumab have a high disease activity and are treated relatively early after UC diagnosis. This might be due to the criteria for inclusion of a patient in the NDP.

The prevalence of herpes zoster (HZ) is high in patients with rheumatologic diseases. The incidence in patients with rheumatoid arthritis (RA) is at least twice as high as in healthy people. Nevertheless, little is known about humoral immunity against varicella zoster virus (VZV), in particular in patients with RA. We, therefore, aimed to retrospectively compare VZV antibody concentrations in a collective of patients with RA in a German outpatient clinic with age- and sex-matched controls without RA. We included n = 247 patients with RA from one single university centre as well as n = 250 age- and sex-matched controls from the in-house routine in this retrospective analysis. The concentration of VZV IgG antibody concentration was either available from the records or was measured using an enzyme-linked immunosorbent assay (ELISA). Additionally, avidity for specific IgG was analysed for some of the samples. The antibody concentrations have been compared between the two groups. Moreover, a consecutive subgroup analysis after stratification by age was performed. A total of 68.4% (n = 169) of the included patients were treated with conventional synthetic DMARDs, either as monotherapy or in combination. Biological originator DMARDs were used in 45.8% (n = 113) of the patients, with the majority (85%, n = 96) of them being on tumour necrosis factor (TNF)–inhibiting agents. As the main result of this study, antibody titres for VZV were found to be significantly lower in RA patients compared with healthy controls (p

Objective In light of the predicted shortage of surgeons, attrition from surgical residency is a significant problem. Prior data have shown that those who are happier are more productive, and those who are less well have higher rates of absenteeism. This study sought to identify the role of social belonging and its relationship to well-being and risk of attrition. Design Surgical residents were invited to participate in an online survey containing measures of social belonging (a 10-item scale adapted from previous studies), well-being (the Dupuy Psychological General Well-Being Scale, Beck Depression Inventory Short Form, and Maslach Burnout Inventory), and risk of attrition (indicated by frequency of thoughts of leaving the program). Setting We surveyed residents at 2 tertiary care centers, Stanford Health Care (2010, 2011, and 2015) and Washington University in St. Louis (2017). Participants Categorical general surgery residents, designated preliminary residents going into 7 surgical subspecialties, and nondesignated preliminary residents were included. Results One hundred sixty-nine residents responded to the survey for a response rate of 66%. Belonging was positively correlated with general psychological well-being (r = 0.56, p Conclusions Social belonging has a significant positive correlation with well-being and negative correlation with thoughts of leaving surgical training. Lack of social belonging appears to be a significant predictor of risk of attrition in surgical residency. Efforts to enhance social belonging may protect against resident attrition.

Purpose Previous Japanese studies have not compared health-related quality of life (HRQoL), work productivity and activity impairment, health care resource utilization (HRU), and costs in inflammatory bowel disease (IBD) patients with non-IBD controls, leading to insufficient evidence regarding IBD's true burden. The aim of this study was to examine the impact of IBD on patient-reported outcomes and costs among Japanese adults (≥18 years). Patients and methods This retrospective cross-sectional study used data from the 2012-2014 Japan National Health and Wellness Survey (N=83,505). HRQoL (SF-36v2), work productivity and activity impairment (work productivity and activity impairment-General Health Questionnaire), HRU, and annual costs were compared between respondents with IBD (n=441) and non-IBD controls (n=82,944), and within IBD subtypes (Crohn's disease [CD] and ulcerative colitis [UC]) using chi-square and ANOVA tests. Results Mental Component Summary (MCS), Physical Component Summary (PCS), and health state utility (Short-Form-6 Dimensions [SF-6D]) scores were significantly lower in IBD respondents than in controls (differences of 2.2 points, 2.6 points, and 0.041 points, respectively; all P

Introduction: The increase of elders on Brazilian population enticed a discussion about life quality and degenerativediseases among this populationAbstractThe anthropometric variables from the physical composition evaluated were the BMI (body mass index), waistcircumference (WC), waist-hip ratio (WHR) and bodyfat percentage (BF%)In comparison to the waist-hip ratio (WHR) measurement, 34% of the elders were classified at very high risk. In thebody fat percentage test (BF%) 54% were classified as below average, bad or very bad presenting risk of acquiring chronicdegenerative diseasesObjective: Evaluate the physical composition of elders who were put on a physical activity program at the city ofGuarulhos.Materials and methodology: The population studied were elders over 60 years old, being 450 woman and 46 men,totaling 496 subjects who exercised twice a weekIntroduction: The increase of elders on Brazilian population enticed a discussion about life quality and degenerativediseases among this populationAbstractThe anthropometric variables from the physical composition evaluated were the BMI (body mass index), waistcircumference (WC), waist-hip ratio (WHR) and bodyfat percentage (BF%)In comparison to the waist-hip ratio (WHR) measurement, 34% of the elders were classified at very high risk. In thebody fat percentage test (BF%) 54% were classified as below average, bad or very bad presenting risk of acquiring chronicdegenerative diseasesObjective: Evaluate the physical composition of elders who were put on a physical activity program at the city ofGuarulhosResults: in relation to the BMI, 33% of the elders were obese, being that 44% of them were overweight and only 26% ofthem were at normal range. The WC measure showed that 48% of them were at very high risk. Only 24% were classified as lowrisk subjects. In comparison to the waist-hip ratio (WHR) measurement, 34% of the elders were classified at very high risk. In thebody fat percentage test (BF%) 54% were classified as below average, bad or very bad presenting risk of acquiring chronicdegenerative diseases. Conclusion: There are inadequacies on the anthropometry of the subjects, showing a prevalence in obesity, and thatmost of the body fat is located at the abdominal region, being that anatomic place that indicates a higher susceptibility on eldersondeveloping chronic degenerative non-transmissible diseases

Ian Kudel,1 Markay Hopps,2 Joseph C Cappelleri,3 Alesia Sadosky,2 Kristen King-Concialdi,1 Ryan Liebert,1 Bruce Parsons,2 Patrick Hlavacek,2 Andrea H Alexander,2 Marco D DiBonaventura,4 John D Markman,5 John T Farrar,6 Brett R Stacey7 1Health Outcomes Practice, Kantar Health, New York, NY, USA; 2Pfizer Inc, New York, NY, USA; 3Pfizer Inc, Groton, CT, USA; 4Pfizer Inc, New York, NY, USA; 5University of Rochester Medical Center School of Medicine and Dentistry, Rochester, NY, USA; 6Department of Biostatistics and Epidemiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 7UW Center for Pain Relief, University of Washington, Seattle, WA, USA Background: The aim of this study was to identify the clinical characteristics, treatment usage, and health outcomes of US adults diagnosed with neuropathic pain (NeP) by experienced physicians. Methods: Adults with scores exceeding the threshold for probable NeP (painDETECT ≥19) and diagnosed with NeP by a qualified physician completed a questionnaire that included comorbid conditions, pain symptoms and experiences, medication use, health status (3-level EuroQol 5 Dimensions (EQ-5D-3L]: health utilities index and visual analog scale), pain severity and interference with functioning (Brief Pain Inventory), and work and activity impairment (Work Productivity and Activity Impairment questionnaire). Descriptive analyses were performed for each NeP subtype. Results: Participants (n=295) were predominantly female (64.4%), middle-aged (53.9%), and white (51.5%). Chronic low back pain was the most frequently diagnosed major NeP syndrome (n=166), followed by diabetic peripheral neuropathy (n=58), post-trauma neuropathy (n=47), post-surgical neuropathy (n=28), and central NeP (n=23). An additional 45 participants were diagnosed, but did not meet the criteria for the aforementioned subtypes. Participants could be diagnosed with multiple subtypes. Across each NeP subtype, patients reported high rates of comorbid disease, including arthritis (range: 39.1%–64.3%) and high blood pressure (range: 26.1%–69.0%), as well as symptomology that included numbness (range: 68.1%–91.4%) and changes in muscular strength (range: 24.1%–65.2%). The majority of patients reported back pain (range: 77.8%–95.7%) and arthritis/joint pain (range: 68.1%–78.6%). The most commonly reported types of NeP pain medication were non-steroidal anti-inflammatory drugs (range: 43.1%–70.2%), weak opioids (range: 22.2%–39.3%), and strong opioids (range: 8.7%–28.6%). All six NeP groups generally reported similar levels of dysfunction on all self-report measures. The most notable finding was that the EuroQol-5D-3L health utilities index scores for each of the six groups were lower than the US norms by a clinically important amount. Conclusion: These exploratory findings indicate that patients with NeP across different etiologies are medically complex and experience impaired function across multiple domains. Keywords: activity impairment, functional status, health-related quality of life, neuropathic pain, pain medication use, physician diagnosis, work impairment

Objective Anemia is an important global health challenge. We investigate anemia prevalence among Indigenous Shuar of Ecuador to expand our understanding of population-level variation, and to test hypotheses about how anemia variation is related to age, sex, and market integration. Methods Hemoglobin levels were measured in a total sample of 1650 Shuar participants (ages 6 months to 86 years) from 46 communities between 2008 and 2017 to compare anemia prevalence across regions characterized by different levels of market integration. Results Shuar anemia rates among children under 15 years (12.2%), adult women (10.5%), and adult men (5.3%) were less than half of those previously documented in other neo-tropical Indigenous populations. Anemia prevalence did not vary between more traditional and market integrated communities (OR = 0.47, p = .52). However, anemia was negatively associated with body mass index (OR = 0.47, p = .002). Conclusions Compared to other South American Indigenous populations, anemia prevalence is relatively low among Shuar of Ecuador and invariant with market integration. Understanding this pattern can provide valuable insights into anemia prevention among at-risk populations.

International audience; Pomegranate juice (PJ) is a rich source of ellagitannins (ETs), precursors of colonic metabolite urolithin A, which are believed to contribute to pomegranate’s neuroprotective effect. While many experimental studies involving PJ’s role in Alzheimer’s disease and hypoxic-ischemic brain injury have been conducted, our knowledge of pomegranate’s effects against Parkinson’s disease (PD) is very limited. Previously, we have reported that PJ treatment improved postural stability, which correlated well with enhancement of neuronal survival, protection against oxidative damage, and α-synuclein aggregation. Since olfactory and motor deficits are typical symptoms of PD, in this study, we aimed to investigate the capability of PJ to protect against olfactory, motoric, and neurochemical alterations. To evaluate its efficiency, Wistar rats were given a combined treatment with ROT (1.3 mg/kg b.w./day, s.c.) and PJ (500 mg/kg/day, p.o.) for 35 days. After this, we assessed the olfactory discrimination index (DI) and vertical and horizontal activities as well as levels of dopamine and its main metabolite 3,4-Dihydroxyphenylacetic acid (DOPAC) in the dissected midbrain of animals. Our findings provide the first evidence that PJ treatment protects against ROT-induced DA depletion in the midbrain, which correlates well with improved olfactory function and vertical activity as well as with the presence of urolithin A in the brain.

© The Author(s). 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly understood tissue function. As this factor is highly expressed in the stem and proliferative zones of the intestinal epithelium, we explore its role in this tissue. Results: Specific deletion of Smarcad1 in the mouse intestinal epithelium leads to colitis resistance and substantial changes in gene expression, including a striking increase of expression of several genes linked to innate immunity. Absence of Smarcad1 leads to changes in chromatin accessibility and significant changes in histone H3K9me3 over many sites, including genes that are differentially regulated upon Smarcad1 deletion. We identify candidate members of the gut microbiome that elicit a Smarcad1-dependent colitis response, including members of the poorly understood TM7 phylum. Conclusions: Our study sheds light onto the role of the chromatin remodeling machinery in intestinal epithelial cells in the colitis response and shows how a highly conserved chromatin remodeling factor has a distinct role in anti-microbial defense. This work highlights the importance of the intestinal epithelium in the colitis response and the potential of microbial species as pharmacological and probiotic targets in the context of inflammatory diseases., This work was supported by BBSRC Institute Strategic Programme Grants (BBS/E/B/000C0404, BBS/E/B/000C0405), a MRC project grant to PVW and MV (MR/N009398/1), a BBSRC-Fundação de Amparo à Pesquisa do Estado de São Paulo/FAPESP-Brazil Pump-priming award (BB/N013565/1,FAPESP#2015/50379-1), and a Newton Advanced Fellowship from the Royal Society to MARV and PVW (NAF\R1\180116).

Cytomegalovirus (CMV)-specific T cells expand with CMV reactivation and are probably prerequisite for control and protection. Given the critical role STAT5A phosphorylation (pSTAT5A) in T cell proliferation, this study presents a simple and sensitive flow cytometric-based pSTAT5A assay to quickly identify CMV-specific T cell proliferation. We determined pSTAT5A in T cells treated with CMV-specific peptide mix (pp65 + IE1 peptides) from 20 healthy adult subjects and three immunodeficient patients with CARMIL-2 mutation. After stimulation, the percentage of pSTAT5A+ T cells in CMV-seropositive (CMV+ ) subjects significantly increased from 3.0% ± 1.9% (unstimulated) to 11.4% ± 5.9% (stimulated) for 24 h. After 7 days of stimulation, the percentage of expanded T cells amounted to 26% ± 17.2%. Conversely, the percentage of pSTAT5A+ T cells and T cell proliferation from CMV-seronegative (CMV- ) subjects hardly changed (from 3.0% ± 1.3% to 3.7% ± 1.8% and from 4.3% ± 2.1% to 5.7% ± 1.7%, respectively). We analyzed the correlation between the percentage of pSTAT5A+ T cells versus (1) CMV-IgG concentrations versus (2) the percentage of expanded T cells and versus (3) the percentage of initial CMV-specific T cells. In immunodeficient patients with CARMIL-2 mutation, CMV-specific pSTAT5A and T cell proliferation were completely deficient. In conclusion, flow cytometric-based pSTAT5A assay represents an appropriate tool to quickly identify CMV-specific T cell proliferation and helps to understand dysfunctions in controlling other pathogens. Flow cytometric-based pSTAT5A assay may be a useful test in clinical practice and merits further validation in large studies.

Childhood overweight and obesity (OW/OB) is increasingly centered in low- and middle-income countries (LMICs) as rural populations experience market integration and lifeway change. Most explanatory studies have relied on imprecise estimates of children's energy expenditure, restricting understanding of the relative effects of changes in diet and energy expenditure on the development of OW/OB in transitioning contexts.This study used gold-standard measurements of children's energy expenditure to investigate the changes that underlie OW/OB and the nutrition/epidemiologic transition.Cross-sectional data were collected from "rural" (n = 43) Shuar forager-horticulturalist children and their "peri-urban" (n = 34) Shuar counterparts (age 4-12 y) in Amazonian Ecuador. Doubly labeled water measurements of total energy expenditure (TEE; kcal/d), respirometry measurements of resting energy expenditure (REE; kcal/d), and measures of diet, physical activity, immune activity, and market integration were analyzed primarily using regression models.Peri-urban children had higher body fat percentage (+8.1%, P 0.001), greater consumption of market-acquired foods (multiple P 0.001), lower concentrations of immune activity biomarkers (multiple P 0.05), and lower REE (-108 kcal/d, P = 0.002) than rural children. Despite these differences, peri-urban children's TEE was indistinguishable from that of rural children (P = 0.499). Moreover, although sample-wide IgG concentrations and household incomes predicted REE (both P 0.05), no examined household, immune activity, or physical activity measures were related to children's overall TEE (all P 0.09). Diet and energy expenditure associations with adiposity demonstrate that only reported consumption of market-acquired "protein" and "carbohydrate" foods predicted children's body fat levels (multiple P 0.05).Despite underlying patterns in REE, Shuar children's TEE is not reliably related to market integration and-unlike dietary measures-does not predict adiposity. These findings suggest a leading role of changing dietary intake in transitions to OW/OB in LMICs.

Background:SARS-CoV-2, the virus causing corona virus disease 2019 (COVID-19), has been demonstrated to infect the gastrointestinal tract and might therefore be a source of infection for the surgical team during abdominal operations. One of the most common surgical procedures performed is appendectomy. However, reports of virologic testing of appendiceal tissue specimens in COVID-19 patients are lacking. We sought to determine whether SARS-CoV-2 is present in the appendectomy specimen of a patient with COVID-19. Case presentation:A female patient presented to the emergency department of our tertiary care academic hospital with lower abdominal pain, fever, nausea, and vomiting. She was admitted to the gynecological floor because of suspected pelvic inflammatory disease. Due to worsening symptoms, a laparoscopy was performed the next day and a severely inflamed appendix was detected. Laparoscopic appendectomy was performed without complications. A few hours postoperatively, the patient was tested positive for corona virus disease 2019 (COVID 19). Real-time reverse transcription polymerase chain reaction analysis targeting the SARS-CoV-2 E-gene was performed on the appendectomy specimen. SARS-CoV-2 could not be detected. During her hospital stay, the patient developed mild respiratory symptoms while the postoperative course was otherwise uncomplicated. Conclusions:The absence of SARS-CoV-2 in the appendectomy specimen of our case adds to the preliminary available evidence indicating that appendectomy in COVID-19 patients with mild disease carries probably a low risk of infection by aerosols generated during the procedure.

This narrative review analyses the Australian Guideline (2018) for the treatment of knee osteoarthritis (KOA) developed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The Guideline recommended against the use low-level laser therapy (LLLT). Why this conclusion was reached is discussed in this review in the context of evidence provided in other systematic reviews, the latest of which was published in 2019 and which provided strong support for LLLT for knee OA. We evaluated the reference list cited for the recommendation “against” LLLT and compared this with reference lists of systematic reviews and studies published before and after the publication date of the Guideline. Eight randomised controlled trials (RCTs) of LLLT were cited in the Guideline the latest of which was published in 2012. There were seventeen additional RCTs, five of which together with one systematic review were located in the year of publication, 2018. The most recent systematic review in 2019 included 22 RCTs in its analysis. Discordance with the levels of evidence and recommendations was identified. Although GRADE methodology is said to be robust for systematically evaluating evidence and developing recommendations, many studies were not identified in the Guideline. In contrast, the latest systematic review and meta-analysis provides robust evidence for supporting the use of LLLT in knee OA. The conflict between guidelines based on opinion and evidence based on meta-analysis is highlighted. Given the totality of the evidence, we recommend that the Australian Guideline should be updated immediately to reflect a “for” recommendation.

Oculocutaneous albinism (OCA) is a genetic disorder characterized by skin, hair, and eye hypopigmentation due to a reduction or absence of melanin. Clinical manifestations include vision problems and a high susceptibility to skin cancer. In its non-syndromic form, OCA is associated with six genes and one chromosomal region. Because OCA subtypes are not always clinically distinguishable, molecular analysis has become an important tool for classifying types of OCA, which facilitates genetic counseling and can guide the development of new therapies. We studied eight Brazilian individuals aged 1.5–18 years old with clinical diagnosis of OCA. Assessment of ophthalmologic characteristics showed results consistent with albinism, including reduced visual acuity, nystagmus, and loss of stereoscopic vision. We also observed the appearance of the strabismus and changes in static refraction over a 2-year period. Dermatologic evaluation showed that no participants had preneoplastic skin lesions, despite half of the participants reporting insufficient knowledge about skin care in albinism. Whole-exome and Sanger sequencing revealed eight different mutations: six in the TYR gene and two in the SLC45A2 gene, of which one was novel and two were described in a population study but were not previously associated with the OCA phenotype. We performed two ophthalmological evaluations, 2 years apart; and one dermatological evaluation. To the best of our knowledge, this is the first study to perform clinical follow-up and genetic analysis of a Brazilian cohort with albinism. Here, we report three new OCA causing mutations.

The aim of this study was to compare the protective effects of chokeberry juice and silymarin against chemical-induced liver fibrosis in rats. Liver fibrosis was induced by CCl4 administered two days a week for six weeks. Two groups of rats were co-treated with chokeberry juice, 10 mL/kg/day. or silymarin as a positive control, 100 mg/kg/day for six weeks. Hepatic lipid peroxidation was suppressed by 50% and the activity of hepatic antioxidant enzymes was increased by 19%&ndash, 173% in rats co-treated with CCl4 and substances tested as compared to rats administered CCl4 alone. Hepatic hydroxyproline was decreased by 24% only in rats treated with silymarin. The messenger RNA (mRNA) expression levels of fibrosis-related molecules, procollagen I, &alpha, SMA, TIMP-1, TGF&beta, and TNF&alpha, which were significantly increased in the liver of CCl4-treated rats, were not modulated by substances tested. Histological evaluation revealed a slight protective effect of silymarin against fibrosis. However, in CCl4 + chokeberry-treated rats, the density of vacuolated hepatocytes was significantly lower than that in silymarin administered animals. Chokeberry juice did not demonstrate an antifibrotic effect in the applied experimental model of fibrosis, and the effect of the known antifibrotic agent, silymarin, was very limited.

Targeting tumor cell motility and proliferation is an extremely important challenge in the prevention of metastasis and improving the effectiveness of cancer treatment. We recently published data revealing that DMU-214, the metabolite of firmly cytotoxic resveratrol analogue DMU-212, exerted significantly higher biological activity than the parent compound in ovarian cancer cells. The aim of the present study was to assess the molecular mechanism of the potential anti-migration and anti-proliferative effect of DMU-214 in ovarian cancer cell line SKOV-3. We showed that DMU-214 reduced the migratory capacity of SKOV-3 cells. The microarray analysis indicated ontology groups of genes involved in processes of negative regulation of cell motility and proliferation. Furthermore, we found DMU-214 triggered changes in expression of several migration- and proliferation-related genes (SMAD7, THBS1, IGFBP3, KLF4, Il6, ILA, SOX4, IL15, SRF, RGCC, GPR56) and proteins (GPR56, RGCC, SRF, SMAD7, THBS1), which have been shown to interact to each other to reduce cell proliferation and motility. Our study showed for the first time that DMU-214 displayed anti-migratory and anti-proliferative activity in SKOV-3 ovarian cancer cells. On the basis of whole transcriptome analysis of these cells, we provide new insight into the role of DMU-214 in inhibition of processes related to metastasis.

Pomegranate juice is a rich source of ellagitannins (ETs) believed to contribute to a wide range of pomegranate&rsquo, s health benefits. While a lot of experimental studies have been devoted to Alzheimer disease and hypoxic-ischemic brain injury, our knowledge of pomegranate&rsquo, s effects against Parkinson&rsquo, s disease (PD) is very limited. It is suggested that its neuroprotective effects are mediated by ETs-derived metabolites&mdash, urolithins. In this study, we examined the capability of pomegranate juice for protection against PD in a rat model of parkinsonism induced by rotenone. To evaluate its efficiency, assessment of postural instability, visualization of neurodegeneration, determination of oxidative damage to lipids and &alpha, synuclein level, as well as markers of antioxidant defense status, inflammation, and apoptosis, were performed in the midbrain. We also check the presence of plausible active pomegranate ETs-derived metabolite, urolithin A, in the plasma and brain. Our results indicated that pomegranate juice treatment provided neuroprotection as evidenced by the postural stability improvement, enhancement of neuronal survival, its protection against oxidative damage and &alpha, synuclein aggregation, the increase in mitochondrial aldehyde dehydrogenase activity, and maintenance of antiapoptotic Bcl-xL protein at the control level. In addition, we have provided evidence for the distribution of urolithin A to the brain.

OBJECTIVES This study investigates bone density across the life course among Bolivian Tsimane and Ecuadorian Shuar of Amazonia. Both groups are rural, high-fertility forager-horticulturalists, with high lifetime physical activity levels. We test whether Tsimane and Shuar bone density patterns are different from each other, and if both groups are characterized by lower osteoporosis risk compared to U.S. references. METHODS Anthropometric and calcaneal bone density data, obtained via quantitative ultrasonometry (QUS), were collected from 678 Tsimane and 235 Shuar (13-92 years old). Population and sex differences in QUS values (estimated bone mineral density, speed of sound, broadband ultrasound attenuation) by age group were assessed using Mann-Whitney U tests. Age-related change and age at peak QUS value were determined using polynomial regressions. One-way analyses of covariance assessed population-level differences in QUS values by age group adjusting for body mass index. Participants aged 50+ years at elevated osteoporosis risk were identified using a T score

Introduction: The aim of this study was to assess the therapeutic effect and the safety of pre surgical treatment with long-acting octreotide in patients with acromegaly. Material and methods: This project was conducted in 25 centres across Poland as a non interventional, multicentre, observational study in patients with acromegaly, in which long-acting octreotide (Sandostatin® LAR®) was administered before surgery. They were 148 patients included into the study: 88 females and 60 males aged 18–86 years (51.3 ± 13.4). Results: Eighty patients completed the study (underwent tumour surgery). The CRF included: baseline visit, four follow-up visits every three months before surgery, and two follow-up visits every three months after surgery. Sandostatin® LAR® was administered every four weeks. The efficacy measures were as follows: change of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, number of patients fulfilling criteria of cure, and change of adenoma (micro- and macroadenomas) size during the treatment. Normalisation of GH and IGF-1 concentrations were obtained in 42.4 and 49.1% of patients at the end of medical therapy, respectively. Normalisation of GH and IGF-1 concentrations were obtained in 77.9 and 83.8% of patients after surgery, respectively. Reduction of microadenoma size was documented in 58.8% of patients, and in 70% of patients with macroadenomas at the end of medical therapy. In 74.0% of patients no pituitary tumour was shown on MRI after surgery. Conclusion: In conclusion, we have shown good surgical outcome in patients with acromegaly after pre-treatment with somatostatin analogue, and good tolerance and safety of the therapy, supporting the national recommendation for pre-surgical treatment with longacting somatostatin analogues in acromegaly patients.

BackgroundSoil-transmitted helminth (STH) infections have many negative health outcomes (e.g., diarrhea, nutritional deficiencies) that can also exacerbate poverty. These infections are generally highest among low-income populations, many of which are also undergoing market integration (MI; increased participation in a market-based economy). Yet the direct impact of MI-related social and environmental changes on STH infection patterns is poorly understood, making it unclear which lifestyle factors should be targeted to better control disease spread. This cross-sectional study examines if household infrastructure associated with greater MI is associated with lower STH burdens among Indigenous Ecuadorian Shuar.MethodsKato-Katz fecal smears were used to determine STH infection status and intensity (n = 620 participants; 308 females, 312 males, aged 6 months-86 years); Ascaris lumbricoides (ascarid) and Trichuris trichiura (whipworm) were the primary infection types detected. Structured interviews assessing lifestyle patterns (e.g., measures of household infrastructure) measured participant MI. Multilevel regression analyses and zero-inflated negative binomial regression models tested associations between MI measures and STH infection status or intensity, controlling for individual and community characteristics.ResultsParticipants residing in more market-integrated households exhibited lower infection rates and intensities than those in less market integrated households. Parasite infection status and T. trichiura infection intensity were lower among participants living in houses with wood floors than those with dirt floors, while individuals using well or piped water from a spring exhibited lower A. lumbricoides infection intensities compared to those using river or stream water. Unexpectedly, latrine type was not significantly related to STH infection status or intensity. These results suggest that sources of exposure differ between the two helminth species.ConclusionsThis study documents associations between household measures and STH infection among an Indigenous population undergoing rapid MI. These findings can help healthcare programs better target interventions and reduce STH exposure among at-risk populations.

Background Integrated molecular profiling has identified intrinsic expression-based bladder cancer molecular subtypes. Despite frequent histological diversity, robustness of subtypes in paired conventional (urothelial) and squamous components of the same bladder tumor has not been reported. Objective To assess the impact of histological heterogeneity on expression-based bladder cancer subtypes. Design, setting, and participants We performed clinically applicable, targeted DNA and/or RNA sequencing (multiplexed DNA and RNA sequencing [mxDNAseq and mxRNAseq, respectively]) on 112 formalin-fixed paraffin-embedded (FFPE) bladder cancer samples, including 12 cases with paired urothelial/squamous components and 21 bladder cancer cell lines. Outcome measurements and statistical analysis Unsupervised hierarchical and consensus clustering of target gene expression enabled derivation of basal/luminal molecular subtyping. Results and limitation Across 21 bladder cancer cell lines, our custom mxRNAseq panel was highly concordant with whole transcriptome sequencing, and assessed targets robustly determined expression-based basal/luminal subtypes from The Cancer Genome Atlas data (in silico) and internally sequenced FFPE tissues. Frequent deleterious TP53 (56%) and activating hotspot PIK3CA (30%) somatic mutations were seen across 69 high-quality tissue samples. Potentially targetable focal ERBB2 (6%) or EGFR (6%) amplifications were also identified, and a novel subgene copy-number detection approach is described. Combined DNA/RNA analysis showed that focally amplified samples exhibit outlier EGFR and ERBB2 expression distinct from subtype-intrinsic profiles. Critically, paired urothelial and squamous components showed divergent basal/luminal status in three of 12 cases (25%), despite identical putatively clonal prioritized somatic genomic alterations. Limitations include lack of profiled paired normal tissues for formal somatic alteration determination, and the need for formal analytical and clinical validation. Conclusions Our results support the feasibility of clinically relevant integrative bladder cancer profiling and challenge the intrinsic nature of expression subtypes in histologically diverse bladder cancers. Patient summary A targeted RNA sequencing assay is capable of assessing gene expression-based subtypes in individual components of clinical bladder cancer tissue specimens. Different histological components of the same tumor may yield divergent expression profiles, suggesting that expression-based subtypes should be interpreted with caution in heterogeneous cancers.

The present study characterized the effect of multiple myeloma (MM) on work productivity, health care resource usage, and out of pocket costs (OOPCs) and examined the association of adherence with quality of life (QoL) and productivity loss.The present cross-sectional study included 162 patients categorized by their 4-item Morisky Medication Adherence Scale (MMAS-4) score (4 vs. ≤ 3). Online surveys included the Work Productivity and Activity Impairment questionnaire, Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM), and MM-specific questions.On average, patients reported FACT-MM scores of 98.5 ± 29.3, absenteeism of 18.3% ± 17.8%, presenteeism of 51.8% ± 30.2%, overall work productivity impairment of 57.3% ± 31.7%, and activity impairment of 49.9% ± 29.5% in the previous 7 days. During the previous 3 months, the mean OOPCs were $709 ± $1307; prescription medications accounted for 55% of these costs. Patients attended 4.1 ± 4.6 visits to oncologists or hematologists during that time, which accounted for 45% of the OOPCs. Patients spent an average of 6.8 ± 8.3 hours at MM-related monthly appointments, and 35.2% reported frustration while at the doctor's office. Patients with an MMAS-4 score of 4 reported higher FACT-MM scores (106.9 vs. 89.2; P .001). Patients with an MMAS-4 score of ≤ 3 reported greater activity impairment (56.5% vs. 39.8%; P = .015) and feeling overwhelmed or frustrated with rescheduling MM appointments (64.0% vs. 26.0%; P = .002).MM was associated with significant workplace and functional impairment, high OOPCs, and frequent office visits. High medication adherence was associated with better outcomes across these domains. As survival for patients with MM improves, patient QoL should be considered to enhance these outcomes.

Introduction Usage patterns and effectiveness of a longer-acting formulation of insulin glargine at a strength of 300 units per milliliter (Gla-300) have not been studied in real-world clinical practice. This study evaluated differences in dosing and clinical outcomes before and after Gla-300 treatment initiation in patients with type 2 diabetes starting or switching to treatment with Gla-300 to assess whether the benefits observed in clinical trials translate into real-world settings. Methods This was a retrospective observational study using medical record data obtained by physician survey for patients starting treatment with insulin glargine at a strength of 100 units per milliliter (Gla-100) or Gla-300, or switching to treatment with Gla-300 from treatment with another basal insulin (BI). Differences in dosing and clinical outcomes before versus after treatment initiation or switching were examined by generalized linear mixed-effects models. Results Among insulin-naive patients starting BI treatment, no difference in the final titrated dose was observed in patients starting Gla-300 treatment versus those starting Gla-100 treatment [least-squares (LS) mean 0.43 units per kilogram vs 0.44 units per kilogram; P = 0.77]. Both groups had significant hemoglobin A1c level reductions (LS mean 1.21 percentage points for Gla-300 and 1.12 percentage points for Gla-100 ; both P

Background: The HER family of proteins (EGFR, HER2, HER3 and HER4) have long been thought to be therapeutic targets for bladder cancer, but previous clinical trials targeting these proteins have been disappointing. Second generation agents may be more effective. Objective: The aim of this study was to evaluate responses to two second-generation irreversible tyrosine kinase inhibitors, dacomitinib and afatinib, in bladder cancer cell lines. Methods: Cell lines were characterized by targeted next generation DNA sequencing, RNA sequencing, western blotting and flow cytometry. Cell survival responses to dacomitinib or afatinib were determined using (3-[4,5-dimethylthioazol-2-yl]-2,5-diphenyl tetrazolium bromide) (MTT) or [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and phenazine methosylfate (PMS) cell survival assays. Results: Only two cell lines of 12 tested were sensitive to afatinib. Sensitivity to afatinib was significantly associated with mutation in either HER2 or HER3 (p

Introduction. This study was conducted on a population of patients with inflammatory bowel disease (IBD) and was based on an assessment of the prevalence and severity of depression and anxiety symptoms in various clinical aspects. The psychological features of IBD patients are very important in the perception of symptoms, but crucial as triggers of IBD or as a releasing factor for IBD symptoms recurrence. Methods. The study included 130 patients with IBD, including 68 with Crohn’s disease (CD) and 62 with ulcerative colitis (UC). The severity of anxiety and depression symptoms were examined by the Hospital Anxiety and Depression Scale (HADS). Patients were also subjected to assessment of anthropometric attributes, clinical factors, quality of life, and symptoms of the disease, with dedicated clinical scales. Results. The occurrence of significant symptoms of anxiety was estimated at 45.5% in patients with CD and 30.5% in the UC patients. Significant depressive symptoms related to 20.5% of people with CD and 17.5% of patients with UC. The parameters of anxiety and depression showed significant associations with parameters of quality of life, BMI, and the scales describing the exacerbation of the diseases. Conclusions. The analyses did not reveal significant differences in the severity and prevalence of symptoms of anxiety and depression in subgroups with IBD. The expansion of relevant symptoms of anxiety and depression in this population was greater than in the general population. In addition, there was a significant correlation between parameters of HADS and clinical factors.

We conduct a field experiment to analyze barriers disabled students face when entering higher education institutions. Fictitious high-school graduates request information regarding the admission process and special accommodations to ease studying. Potential applicants randomly reveal one of four impairment types. Response rates are similar for all four conditions. Evaluating response contents reveals differential treatment by impairment type. Students with depression or dyslexia are provided less information and services compared to students with physical impairments or students with no disability. Our results suggest that general information deficits about health conditions exist. Psychological and learning impairments are less often recognized as disabilities.

Introduction. We aimed to investigate survivin and its splice variants DEx3 and 2B expressions in pituitary adenomas and normal pituitary glands using immunohistochemistry. Material and methods. The study group consisted of eight pituitary adenomas: five of non-functional tumors, two of GH-secreting tumors, and one PRL-secreting tumor. Eight healthy pituitary tissue samples obtained after autopsy served as controls. Results. Survivin expression was found in 87.5% of the study group and 100% of the controls. A positive staining of survivin 2B was found in 62.5% of pituitary adenomas and 100% of controls. Survivin DEx3 was recognized in 25% of pituitary adenomas and 12.5% of normal pituitary glands. There was significantly lower immunoreactivity of survivin 2B in pituitary adenomas when compared with normal pituitary glands (p = 0.0498). Conclusions: Survivin and its splice variants might be involved to some extent in benign tumor growth of pituitary adenomas. However, survivin cannot be regarded as a candidate for targeted therapy or molecular biomarker of pituitary adenomas.

Lenalidomide, adriamycin, dexamethasone for induction followed by stem-cell transplant in newly diagnosed myeloma

In this paper, we examine patterns of self-reported diagnosis of noncommunicable diseases (NCDs) and prevalences of algorithm/measured test-based, undiagnosed, and untreated NCDs in China, Ghana, India, Mexico, Russia, and South Africa. Nationally representative samples of older adults aged ≥50 years were analyzed from wave 1 of the World Health Organization's Study on Global Ageing and Adult Health (2007–2010; n = 34,149). Analyses focused on 6 conditions: angina, arthritis, asthma, chronic lung disease, depression, and hypertension. Outcomes for these NCDs were: 1) self-reported disease, 2) algorithm/measured test-based disease, 3) undiagnosed disease, and 4) untreated disease. Algorithm/measured test-based prevalence of NCDs was much higher than self-reported prevalence in all 6 countries, indicating underestimation of NCD prevalence in low- and middle-income countries. Undiagnosed prevalence of NCDs was highest for hypertension, ranging from 19.7% (95% confidence interval (CI): 18.1, 21.3) in India to 49.6% (95% CI: 46.2, 53.0) in South Africa. The proportion untreated among all diseases was highest for depression, ranging from 69.5% (95% CI: 57.1, 81.9) in South Africa to 93.2% (95% CI: 90.1, 95.7) in India. Higher levels of education and wealth significantly reduced the odds of an undiagnosed condition and untreated morbidity. A high prevalence of undiagnosed NCDs and an even higher proportion of untreated NCDs highlights the inadequacies in diagnosis and management of NCDs in local health-care systems.

The role of CYP1A1 and CYP1B1 enzymes in the biotransformation and biological activity of the methylated resveratrol analogue, 3,4,5,4′-tetramethoxystilbene (DMU-212) is still elusive. Our recently published data have shown that one of the metabolites of DMU-212, 3′-hydroxy-3,4,5,4′-tetramethoxystilbene (DMU-214) exerts more potent cytotoxic effects in A-2780 ovarian cancer cell line, as compared to the parent compound. Hence, this study aims to elucidate whether the biological activity of DMU-212 is related to its biotransformation to DMU-214. Furthermore, we aimed to assess which enzymes of CYP1 family are involved in the biotransformation of DMU-212. The human ovarian cancer cell lines A-2780, A-2780CYP1A1(−) and non-cancerous human ovarian surface epithelial (HOSE) cells were employed in the present study. In contrary to other authors’ suggestions we have found that CYP1A1 is the major enzyme of CYP1 family involved in the metabolic activation of DMU-212. Since the distinctly weaker anti-proliferative effects of DMU-212 against HOSE and A-2780CYP1A1(−) cells have been associated with the lack of the expression of CYP1A1, we suggest that the biological activity of the parent compound may be related to its metabolic activation to DMU-214 and the level of this enzyme.

Grit, a measure of perseverance, has been shown to predict resident well-being. In this study we assess the relationship between grit and attrition.We collected survey data from residents in a single institution over two consecutive years. All residents in general surgery were invited to participate (N = 115). Grit and psychological well-being were assessed using validated measures. Risk of attrition was measured using survey items.73 residents participated (63% response rate). Grit was positively correlated with general psychological well-being (r = 0.30, p 0.05) and inversely correlated with depression (r = -0.25, p 0.05) and risk of attrition (r = -0.37, p 0.01). In regression analyses, grit was positively predictive of well-being (B = 0.77, t = 2.96, p 0.01) and negatively predictive of depression (B = -0.28 t = -2.74, p 0.01) and attrition (B = -0.99, t = -2.53, p 0.05).Attrition is a costly and disruptive problem in residency. Grit is a quick, reliable measure which appears to be predictive of attrition risk in this single-institution study.

ZusammenfassungDie Hand-Fuß-Mund-Krankheit (HFMK) ist ein gut bekanntes pädiatrisches Krankheitsbild. Zunehmend wird vor allem aus dem asiatischen und amerikanischen Raum von Coxsackievirus A6 (CVA6)-assoziierten Erscheinungsbildern berichtet. Die besondere Herausforderung hierbei stellt die Abgrenzung zu oftmals ähnlich imponierenden mitunter gefährlichen Krankheitsbildern, wie Herpesvirus- oder Staphylokokken-Superinfektionen, dar. Das CVA6-assoziierte Erscheinungsbild ist in dieser Arbeit anhand eines Fallbeispiels und einer Zusammenfassung literaturbekannter Daten beschrieben. Es ist klinisch gekennzeichnet durch ausgedehnte vesikulobullöse und erosive Läsionen, her -pesähnelndes Ekzem, Gianotti-Crosti-ähnelnde Ausschläge sowie petechiale und purpurfarbene Läsionen. Wobei die sonst typischen Manifestationsorte wie Hand- und Fußinnenflächen eher ausgespart sind. Typischerweise gehen die Hautbefunde mit Juckreiz und späteren Nagelplattenablösungen einher, bei sonst geringer Komplikationsrate. Die Diagnostik erfolgt über Virus-PCR. Die Therapie erfolgt symptomatisch. Eine Prophylaxe mittels trivalentem anti-HFMK-Impfstoff ist in Erprobung.

The aim of this study was to evaluate the proportion of patients with acromegaly who remained on long-term lanreotide depot after completion of an open-label multicenter phase III clinical trial (SALSA: A Multi Center Open Label Study to Assess the Ability of Subjects With Acromegaly or Their Partners to Administer Somatuline Autogel), compare baseline and long-term follow-up symptoms scores, and correlate scores with individual longitudinal clinical outcomes.Records of all subjects previously enrolled at the Massachusetts General Hospital site of SALSA were reviewed. Those who remained on lanreotide were interviewed and asked to complete a questionnaire that they had filled out in SALSA in 2007 regarding their current symptomatology and injection side effects, as well as to complete the Acromegaly Quality of Life Questionnaire. Furthermore, clinical, biochemical, and radiographic data related to acromegaly and its comorbidities were tracked throughout follow-up.Six out of 7 patients chose to remain on lanreotide, and 5 of them continued lanreotide depot through last follow-up, for up to 8 years or in 1 case until death. In all cases, lanreotide remained well tolerated, and insulin-like growth factor-1 levels and pituitary imaging remained well controlled on stable doses. While comorbidities persisted or developed, the self-reported symptom score after up to 8 years of therapy showed a significant decrease in frequency or resolution in symptoms that were reported at baseline.This study shows a significant decrease in frequency or resolution in self-reported symptoms in well-controlled patients receiving long-term lanreotide therapy.AcroQoL = Acromegaly Quality of Life Questionnaire GH = growth hormone GI = gastrointestinal IGF-1 = insulin-like growth factor-1 SALSA = A Multi Center Open Label Study to Assess the Ability of Subjects With Acromegaly or Their Partners to Administer Somatuline Autogel.

Fatal Zoonotic Viral Infection after Transplantation Evidence of Borna disease virus 1 infection in humans is limited; in this report, donor-derived Borna virus encephalitis is shown to occur in three solid-organ transplant recipients.

Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (P = 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.

Forager-horticulturalist children do not spend more calories than industrialized children, but they do spend calories differently., Children’s metabolic energy expenditure is central to evolutionary and epidemiological frameworks for understanding variation in human phenotype and health. Nonetheless, the impact of a physically active lifestyle and heavy burden of infectious disease on child metabolism remains unclear. Using energetic, activity, and biomarker measures, we show that Shuar forager-horticulturalist children of Amazonian Ecuador are ~25% more physically active and, in association with immune activity, have ~20% greater resting energy expenditure than children from industrial populations. Despite these differences, Shuar children’s total daily energy expenditure, measured using doubly labeled water, is indistinguishable from industrialized counterparts. Trade-offs in energy allocation between competing physiological tasks, within a constrained energy budget, appear to shape childhood phenotypic variation (e.g., patterns of growth). These trade-offs may contribute to the lifetime obesity and metabolic health disparities that emerge during rapid economic development.

Objective: The objective of this review is to consider the dual effects of microbiome and photobiomodulation (PBM) on human health and to suggest a relationship between these two as a novel mechanism. Background: PBM describes the use of low levels of visible or near-infrared (NIR) light to heal and stimulate tissue, and to relieve pain and inflammation. In recent years, PBM has been applied to the head as an investigative approach to treat diverse brain diseases such as stroke, traumatic brain injury (TBI), Alzheimer's and Parkinson's diseases, and psychiatric disorders. Also, in recent years, increasing attention has been paid to the total microbial population that colonizes the human body, chiefly in the gut and the mouth, called the microbiome. It is known that the composition and health of the gut microbiome affects many diseases related to metabolism, obesity, cardiovascular disorders, autoimmunity, and even brain disorders. Materials and methods: A literature search was conducted for published reports on the effect of light on the microbiome. Results: Recent work by our research group has demonstrated that PBM (red and NIR light) delivered to the abdomen in mice, can alter the gut microbiome in a potentially beneficial way. This has also now been demonstrated in human subjects. Conclusions: In consideration of the known effects of PBM on metabolomics, and the now demonstrated effects of PBM on the microbiome, as well as other effects of light on the microbiome, including modulating circadian rhythms, the present perspective introduces a new term “photobiomics” and looks forward to the application of PBM to influence the microbiome in humans. Some mechanisms by which this phenomenon might occur are considered.

Children starting school older consistently exhibit better educational outcomes. In this paper, we underscore child development as a mechanism driving this effect. Using unique administrative data on health examinations, we study the causal effect of school starting age (SSA) on a child's probability of being diagnosed with special educational needs in early grades. Results show that children with higher SSA are less likely to develop behavioral problems and speech impediments, whereas learning disabilities, ADHD, and dyslexia/dyscalculia remain unaffected. Importantly, these effects only arise after primary school entry and are not due to preexisting health conditions. We also find that teachers tend to over-refer relatively young children to special needs services, but this over-referring behavior is not driving the results, which are based on psychologists' diagnoses. The SSA effect persists throughout compulsory schooling, resulting in higher test scores and better quality vocational training contracts. However, SSA does not affect employment, earnings, or disability insurance benefits at labor market entry.

The evidence for non-specific effects (NSE) of vaccinations on all-cause morbidity and mortality among children is growing. However, our understanding of the underlying mechanisms is still limited. One hypothesis is that NSE are mediated by antibody titers. We used data of 2,123 children from the population-based birth cohort study LISA conducted in Germany to explore whether routine childhood vaccinations and the individual infection history in the first 2 years of life are associated with unrelated antibody titers. We selected 19 exposures (infections and vaccinations) and investigated their association with levels of 12 IgG antibody titers at the age of 2 years. Based on univariable analyses (ANOVA), we identified 21 crude associations between exposures and titers (p < 0.05), while 11 (95%-CI: 6, 17) spurious associations were expected due to multiple testing. In exploratory multivariable analyses, we observed associations between seven investigated IgG titers and 10 exposures; either administered vaccines [e.g., higher anti-hRSV IgG titer in BCG-vaccinated children (regression-coefficient in standard-deviation-units: 0.38; 95%-CI: 0.12, 0.65)] or infections [e.g., higher anti-measles IgG titer in children with reported chickenpox (0.44; 95%-CI: 0.08, 0.80)]. Our results indicate the existence of associations between immunogenic exposures and unrelated antibody titers. Further studies investigating the underlying immunological mechanisms are required.

Introduction Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract, which can significantly deteriorate everyday functioning. We are, however, still lacking simple methods to assess the influence of IBD on patients' disability. IBD Disk is a new graphical tool that allows for a quick assessment of the influence of IBD on different aspects of everyday life. Aim To present the adaptation process of the IBD Disk in Poland. Material and methods The Polish IBD Working Group together with the Institute of Translational Medicine in Birmingham (United Kingdom) and a professional translational agency performed a translation and re-translation of the Polish version of the IBD Disk. After full agreement was achieved, the final Polish version was accepted. In the next step, its understandability and ease of use was assessed by using a semiquantitative scale (scale from 1 to 10, where "1" means very easy to use, "10" means - very difficult to use). Results In the initial translation phase, the concordance between translation agency and experts was very high. In the re-translation phase only some stylistic and grammatical corrections were made. In the final step the general assessment of understandability of all items of the tool was high. Moreover, patients with IBD assessed the ease of use of the IBD Disk as very easy (median: 1.5 points, 95% confidence interval: 1.0-2.0). Conclusions The Polish adaptation of IBD Disk directly reflects the original English version. Thus, it can be further used in the validation process among Polish IBD patients.

INTRODUCTION AND OBJECTIVES:We conducted a phase II trial to evaluate combination therapy with BCG and Sunitinib for prevention of recurrence and progression of high-risk NMIBC with a primary endpoint of 3-month complete response (CR). We hypothesized that adding Sunitinib to BCG could increase the initial CR to therapy by synergistic inhibition of the VEGF pathway. We also measured urine levels of various biomarkers throughout treatment to identify trends that predict and/or explain a response to therapy.METHODS:Patients with high-grade clinical ≤T1N0M0 NMIBC who had not received BCG within 12 months of diagnosis were deemed eligible. Patients received a 6-week induction BCG course followed by 28 days of Sunitinib. CR was determined by biopsy and cytology. Urine samples were collected from patients before and after both BCG and Sunitinib. Urine biomarker levels were measured using a multiplexed bead assay for angiopoietin 2 (AP-2), fibroblast growth factor 2 (FGF-2), interleukin 8 (IL-8), and VEGF-A, -C,...

Objectives Prior studies of erectile dysfunction (ED) tend to narrowly focus on relationships with specific comorbidities, rather than evaluating a more comprehensive array of risk factors and assessing naturalistic patterns among them. This study identifies natural clusters of male characteristics from a general population sample per country, quantifies ED dynamics in these profiles and compares profiles across the US, Italy, Brazil and China samples. Methods National Health and Wellness Survey 2015 and 2016 patient-reported data on men aged 40-70 years (USA n = 15,652; Italy n = 2,521; Brazil n = 2,822; China n = 5,553) were analysed. Hierarchical agglomerative clustering identified clusters where predictors included demographics, health characteristics/behaviours, ED risk factors and provider visits in the past 6 months. Multinomial logistic regression assessed the independent utility of variables in predicting cluster membership, compared with the healthiest control cluster per country. Results Different natural clusters were found across countries, with four clusters for the USA, Italy and China and three clusters for Brazil. Age, income, employment, health behaviours and ED risk factors predicted different cluster membership across countries. In the USA, Italy and Brazil, younger clusters were predicted by ED, unhealthy behaviours and ED risk factors. Unique cluster profiles were identified in China, with ED and ED risk factors (aside from hypertension) not predicting cluster membership, while socio-demographics and health behaviours were strongly predictive. Conclusions Natural cluster profiles revealed notable ED rates among adult males of age 40-70 in four different countries. Clusters were mainly predicted by unhealthy behaviours, ED risk factors and ED, regardless of level or presence of positive health characteristics and behaviours. This analysis identified meaningful subgroups of men with heightened ED risk factors, which can help healthcare providers to better recognise specific populations with the greatest need for intervention.