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Background The accurate and independent measurement of blood pressure (BP) by patients is essential for home BP monitoring (HBPM) and determining the quality of hypertension (HTN) control. This study aimed to evaluate the BP self-measurement techniques of hypertensive patients and their accuracy in accordance with established guidelines. We sought to identify the common errors that patients make and suggest improvements that can be implemented in the primary healthcare setting to increase the reliability of HBPM conducted by hypertensive patients. Methods One hundred patients diagnosed with HTN completed a questionnaire inquiring about their health and demographic data and BP monitoring practices. Patients were then observed and filmed while measuring their BP on their own devices in five primary healthcare centres in Kraków, Poland. The correctness of their techniques was assessed in accordance with the European Society of Hypertension guidelines on HBPM. Results Only 3% of patients measured their BP without error; 60% made three or more errors. The most frequent error, made by 76% of subjects, was incorrect sphygmomanometer cuff placement (above or below heart level, or/and the indicator mark was not aligned with the brachial artery). Regarding patients’ previous instruction for the correct use of their devices, 36% of patients referred to their monitor’s user manual, 22% did not receive any prior assistance, and only 29% were adequately counselled by physicians on how to measure their BP correctly. Conclusions Our findings suggest that primary healthcare physicians and their personnel often do not adequately instruct patients on how to measure their BP correctly. Therefore, healthcare systems must provide patients with more adequate training and reference materials on the best practices of BP monitoring.

In this retrospective cohort study, we characterize the health profile of preterm males with Duchenne muscular dystrophy. Major clinical milestones (ambulation cessation, assisted ventilation use, and onset of left ventricular dysfunction) and corticosteroids use in males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using Kaplan-Meier survival curves and Cox proportional hazards modeling. The adjusted risk of receiving any respiratory intervention among preterm males with Duchenne muscular dystrophy was 87% higher than among the corresponding full-term males with Duchenne muscular dystrophy. The adjusted risks for ambulation cessation and left ventricular dysfunction were modestly elevated among preterm compared to full-term males, but the 95% confidence intervals contained the null. No difference in the start of corticosteroid use between preterm and full-term Duchenne muscular dystrophy males was observed. Overall, the disease course seems to be similar between preterm and full-term males with Duchenne muscular dystrophy; however, pulmonary function seems to be affected earlier among preterm males with Duchenne muscular dystrophy.

Mississippi ranks as the nation's least-healthy state. There is a shortage of trained preventive medicine (PM) physicians in the state. The Department of Preventive Medicine at The University of Mississippi Medical Center was reinstated in 2015 to address this need. Initial PM residency accreditation was awarded in November of 2017 with subsequent notification of 10-year accreditation status in April of 2020 allowing up to 4 PGY-2 and 4 PGY-3 resident positions per year. The residency experiences provided by the program are varied and unique due to the program being housed in both the School of Medicine and the School of Population Health. Preventive medicine residents have the opportunity to complete the American College of Lifestyle Medicine's Lifestyle Medicine Residency Curriculum. Through our diverse didactic and clinical experiences, we are optimistic that our program will continue to attract, train, and retain PM physicians for our state.

Introduction: Previous studies indicated variability in the prevalence of Duchenne and Becker muscular dystrophies (DBMD) by racial/ethnic groups. The Centers for Disease Control and Prevention’s (CDC) Muscular Dystrophy Surveillance, Tracking, and Research network (MD STARnet) conducts muscular dystrophy surveillance in multiple geographic areas of the USA and continues to enroll new cases. This provides an opportunity to continue investigating differences in DBMD prevalence by race and ethnicity and to compare the impact of using varying approaches for estimating prevalence. Objective: To estimate overall and race/ethnicity-specific prevalence of DBMD among males aged 5–9 years and compare the performance of three prevalence estimation methods. Methods: The overall and race/ethnicity-specific 5-year period prevalence rates were estimated with MD STARnet data using three methods. Method 1 used the median of 5-year prevalence, and methods 2 and 3 calculated prevalence directly with different birth cohorts. To compare prevalence between racial/ethnic groups, Poisson modeling was used to estimate prevalence ratios (PRs) with non-Hispanic (NH) whites as the referent group. Comparison between methods was also conducted. Results: In the final population-based sample of 1,164 DBMD males, the overall 5-year prevalence for DBMD among 5–9 years of age ranged from 1.92 to 2.48 per 10,000 males, 0.74–1.26 for NH blacks, 1.78–2.26 for NH whites, 2.24–4.02 for Hispanics, and 0.61–1.83 for NH American Indian or Alaska Native and Asian or Native Hawaiian or Pacific Islander (AIAN/API). The PRs for NH blacks/NH whites, Hispanics/NH whites, and NH AIAN/API/NH whites were 0.46 (95% CI: 0.36–0.59), 1.37 (1.17–1.61), and 0.61 (0.40–0.93), respectively. Conclusions: In males aged 5–9 years, compared to the prevalence of DBMD in NH whites, prevalence in NH blacks and NH AIAN/API was lower and higher in Hispanics. All methods produced similar prevalence estimates; however, method 1 produced narrower confidence intervals and method 2 produced fewer zero prevalence estimates than the other two methods.

Objectives To describe a residency retreat curriculum established to improve wellness and reduce burnout within a radiology residency. Methods A wellness retreat was created and implemented within a large academic medical center's radiology residency. The retreat curriculum was designed by a Radiology Residency Wellness Committee and was supported by departmental funding. The retreat curriculum centered on 3 strategies for success: teambuilding and bonding, Design Thinking, and guided reflection. A questionnaire was distributed at the end of the retreat, asking 12 questions in 5-point Likert format to assess resident satisfaction with different components of the retreat, as well as open-ended questions to more deeply assess the effects of the retreat on the residency experience and personal wellness in our radiology residency. Questionnaire results were summarized using frequency and percentages. Open-ended responses were qualitatively analyzed using the constant comparative method. Results Thirty-seven of 41 residents (90%) in our radiology residency participated in the retreat. Thirty-five of the 37 residents (95%) participated in the postretreat questionnaire, with 33 of 37 residents (89%) completing the entire questionnaire. Thirty-two of 33 responders (97%) anticipated the retreat would improve their residency experience, and 27 of 33 responders (82%) indicated the retreat would improve their personal wellness. Based upon the open-ended responses, improved camaraderie was the major benefit of the retreat cited by the majority of residents. Conclusion A departmentally sponsored radiology residency retreat may improve personal wellness and reduce burnout.

Objective The popliteofibular ligament (PFL) is an important stabilizer of the knee found within the posterolateral corner (PLC) of the joint. Injuries to the PLC can cause substantial patient morbidity. Accurate PFL visualization has been historically challenging, impeding injury diagnosis and treatment. The gold standard for in vivo PFL visualization is magnetic resonance imaging (MRI), but this procedure has slice thickness limitations, is costly, and is subject to longer wait times. Ultrasonographic (US) PFL assessment is a potentially viable alternative to MRI. This study aimed to determine the viability of US PFL assessment. Materials and methods Ten fresh-frozen lower limb specimens were evaluated for the presence and morphometric characteristics of the PFL via US using an 18.0-MHz linear transducer. The cadavers were then dissected and reassessed for the presence and morphometric characteristics of the PFLs for comparison with US findings. Moreover, the fracture of the fibular styloid process near the site of the insertion of the PFL (the arcuate sign) was simulated and assessed via US. Results The PFL was visualized and measured in all ten knees via both US and cadaveric assessments. There were no statistically significant differences in PFL morphometric characteristics determined via US examination and dissection. The fibular styloid fracture was easily identified in US examination. Conclusion US imaging is a viable alternative for accurate and effective assessment of the normal PFL. Moreover, the arcuate sign can be evaluated via US.

To compare the diagnostic performance and inter-reader agreement of an abbreviated (5 min) MR protocol compared to a complete (25 min) protocol, for evaluation of suspected tibial bone stress injury. This IRB-approved retrospective study consisted of 95 consecutive MR examinations in 88 patients with suspected tibial bone stress injury. Three musculoskeletal radiologists independently classified all examinations utilizing both an abbreviated protocol consisting only of axial T2-weighted images with fat suppression, and after a washout period again classified the complete examinations. Accuracy was calculated as proportion of cases classified exactly, within 1 grade, within 2 grades, and also utilizing a simplified “clinically relevant” classification combining grades 2, 3, and 4A into a single group. Significance testing was performed with the chi-test, and a post-hoc power analysis was performed. Inter-reader agreement was calculated with Kendall’s coefficient of concordance, with significance testing performed utilizing the z-test after bootstrapping to obtain the standard error. There was no significant difference in accuracy of grading tibial bone stress injuries between complete and abbreviated examinations. For complete exams, pooled exact accuracy was 47.8%; accuracy within 1 grade was 82.8%; and accuracy within 2 grades was 96.1%. For the abbreviated protocol, corresponding accuracies were 50.2, 82.0, and 93.9%. With the “clinically relevant” simplified classification, accuracy was 58.6% for complete exams and 64.2% for abbreviated exams. There was no significant difference in inter-reader agreement, with substantial agreement demonstrated for both complete (Kendall coefficient of concordance 0.805) and abbreviated examinations (coefficient of 0.767).

OBJECTIVE: Research has not examined the use of health care by patients with myotonic muscular dystrophy (MMD), but it would provide insights into this population, which is prone to comorbidities and high service needs. This study is an analysis of this understudied subgroup, using a unique linked dataset to examine the characteristics and healthcare utilization patterns for people with MMD. METHODS: This analysis used 3 South Carolina datasets (2009–2014). The subjects included individuals with at least 1 encounter with an International Classification of Diseases, Ninth Revision, Clinical Modification code of 359.21. The variables included sex, race, visit type, payer, and diagnoses. The analyses examined characteristics and number of encounters. RESULTS: The subjects were predominately female, white, and 45 to 64 years old. A total of 44.6% of the study population had at least 1 inpatient visit, whereas 64.2% had at least 1 emergency department visit. A majority of the subjects had at least 1 office visit (55.0%), and most (85.3%) did not have a home health encounter. CONCLUSIONS: Investigation of the reasons for these inpatient and emergency department encounters may be helpful in identifying ways to deliver high-quality care.

Amyotrophic lateral sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) share clinical, neuropathological, and genetic features. This includes common genetic disease-causing mutations such as the expanded G4C2 repeat in the C9orf72 gene (C9-ALS/FTLD) and cytoplasmic and insoluble protein depositions of the TDP-43 in degenerating regions of the brain and spinal cord. Proposed mechanisms of toxicity in C9-ALS/FTLD are the production of repeat expansion transcripts and their dipeptide repeat proteins (DPRs) products which are hypothesized to drive nucleocytoplasmic transport defects. The nuclear pore complex (NPC) regulates nucleocytoplasmic trafficking by creating a selectivity and permeability barrier comprised of phenylalanine glycine nucleoporins (FG nups). However, the relationship between FG nups and TDP-43 pathology remains elusive. Here, we define two mechanisms through which TDP-43 promotes Nup62 nuclear depletion and cytoplasmic in C9-ALS/FTLD and sALS/FTLD. In C9-ALS/FTLD, poly-GR initiates the formation of TDP-43 containing stress granules (SGs) that trigger the nuclear loss and recruitment of Nup62 in vitro and in vivo. When colocalized, cytoplasmic TDP-43:Nup62 assemblies mature into insoluble inclusions through an interaction within the TDP-43 nuclear localization sequence (NLS) suggesting Nup62 promotes deleterious phase transitions. Absent of poly-GR, aberrant TDP-43 phase transitions in the cytoplasm recruits and mislocalizes Nup62 into pathological inclusions. The result of these cytoplasmic Nup62 and TDP-43 interactions are pathological and insoluble TDP-43:Nup62 assemblies that are observed in C9-ALS/FTLD and sALS/FTLD CNS tissue.

The aim of this study was to review the literature on the innervation of the wrist with an emphasis on pathological and therapeutic aspects. The nerves involved in wrist innervation and their mechanoreceptor endings are described. The literature over the past 30 years includes several topics that are still subjects of discussion and debate and require further research.

Background: The popliteofibular ligament (PFL) is a static stabilizer of the posterolateral corner of the knee, preventing varus angulation, tibial rotation, and posterior translation. The PFL is anatomically variable, and there is no current review that outlines its prevalence rate and morphological variations. Purpose: To investigate the anatomic prevalence and morphological qualities of the PFL in various global patient populations via a meta-analysis of relevant literature involving both cadaveric dissections and patient-based research using magnetic resonance imaging (MRI) scans. Study Design: Meta-analysis. Methods: We pooled literature data detailing PFL prevalence rates and performed a retrospective MRI study of 100 knees to determine the overall PFL prevalence. Data searches and analyses were performed according to Anatomical Quality Assurance and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results: There were 30 cadaveric studies and 11 MRI studies (including our radiological investigation), representing a total of 1595 lower limbs. The meta-analysis of cadaveric studies showed a higher prevalence of the PFL than the meta-analysis of MRI studies, with 98.4% (95% CI, 97.5%-99.2%) and 89.0% (95% CI, 73.9%-98.6%), respectively. Our MRI investigation reported a PFL prevalence of 92.0%. Conclusion: The PFL was found to be a constant or rarely absent anatomic structure of the human knee according to the analysis of cadaveric dissection studies, and it was identified notably less on MRI, albeit not significantly. Increasing PFL anatomic knowledge, including awareness of its prevalence and morphological diversity, will improve injury diagnoses, treatment methods, and prognoses.

Background The marginal artery of Drummond (MA) is an anatomically variable blood vessel that forms a major anastomotic network between the superior and inferior mesenteric arteries. It vascularizes the transverse and descending colons and is a major contributor to the collateral circulation of left-colic structures. Purpose To conduct a systematic review of the MA and highlight the current understanding of its anatomy and role in physiological and pathological vascularization. Methods The major online databases (Pubmed, Google Scholar, Embase, and Web of Science) were systematically assessed to reveal all available literature pertaining to the MA. Articles judged relevant by the authors were used for the final review. Results The MA is a key player in the collateral circulation of left-colic structures in the setting of pathological processes affecting their normal vascularization. It helps to maintain perfusion in the event of obstructions and atherosclerosis, and in the cases of obliteration or congenital absence of the mesenteric vessels, it sustains adequate vascularization of the left-colon. The MA has come into increasing prominence as surgeons have become more aware of both iatrogenic injuries to it and its value in mitigating the effects of reduced patency of the mesenteric vessels. Conclusions The MA continues to become more important to surgeons as both an obstacle and an opportunity in abdominal procedures. Further exploration of its anatomical variability, for example through embryological and dissection studies, will further improve treatment outcomes during abdominal surgery.

Laparoscopic procedures require the creation of pneumoperitoneum. CO2, which must be cold and dry, is the standard gas used in such surgeries. The type of gas used, its temperature, and moisture may change the peritoneal surface and cause systemic and local oxidative stress. Our objective is to evaluate the influence of pneumoperitoneum heating on the occurrence of histological lesions in the peritoneum, inflammation, plasma oxidative stress, and on the mesothelial surface in patients undergoing video-assisted ovariohysterectomy. Twenty canine females were included and distributed evenly into two groups: heated CO2 (HG) and unheated CO2 (UHG). The biomarkers of inflammation and oxidative stress were evaluated before insufflation (T0), at 30 min (T1), and at 60 min (T2) of exposure to CO2. Biopsies of the peritoneal tissue for histological evaluation were performed at T0 and T2. Regarding plasma parameters, acetylcholinesterase (AChE) showed a greater activity in the HG at T1 ( p = 0.0268 ) and T2 ( p = 0.0423 ); in turn, butyrylcholinesterase (BChE) showed a greater activity at T2 in the HG ( p = 0.0175 ) compared with T0. Catalase activity (CAT) was different between HG times; it was higher at T1 ( p = 0.0253 ). There was a decrease in the levels of substances reactive to thiobarbituric acid (TBARS) ( p = 0.0117 ) and in glutathione (GSH) ( p = 0.0114 ) between T0 and T2 in the UHG. Regarding tissue oxidative stress, the CAT in the HG showed a greater activity at T2 than T1 ( p = 0.0150 ). By comparing the groups at each time, there was a difference only at T2 ( p = 0.0288 ), being greater in the HG. Regarding the activity of superoxide dismutase (SOD) in the HG, there was a difference between T2 in relation to T0 and T1 ( p = 0.0181 ); finally, there was an increase only at T1 ( p = 0.0287 ) in the UHG when comparing groups at the same time. There were no differences in the histological parameters evaluated. Our study demonstrates that the heating of CO2 generates a greater inflammatory response and forms reactive oxygen species (ROS) at the plasma and peritoneal levels.

Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present with different disease severity. Here, we determined 171 microRNAomes from 58 hospitalised COVID-19 patients (Cohort 1) and levels of 25 cytokines and chemokines (CC) in the same samples. Combining microRNA (miRNA) and CC measurements allowed for discrimination of severe cases with greater accuracy than using miRNA or CC levels alone. Severity group-specific associations between miRNAs and COVID-19-associated CC (e.g. IL6, CCL20) or clinical hallmarks of COVID-19 (e.g. neutrophilia, hypoalbuminemia) separated patients with similar CC levels but different disease severity. Critically, analysis of an independent cohort of 108 patients from a different centre (Cohort 2) demonstrated feasibility of CC/miRNA profiling in leftover blood samples with similar severe disease CC and miRNA profiles, and revealed CCL20, IL6, IL10, and miR-451a as key correlates of fatal COVID-19. These findings highlight that systemic miRNA/CC networks underpin severe COVID-19. Funding: The study was funded by the UKRI MRC/NIHR award to the UK Coronavirus Immunology Consortium (UK-CIC, MR/V028448/1). Sample collection at Manchester NHS Trusts was supported by the NIHR Manchester Biomedical Research Centre (TH and AS) and 3M Global Giving award (JRG and TH). Sample collection at York and Scarborough NHS Trust was supported by the Wellcome Trust (ISSF grant WT204829 through the Centre for Future Health at the University of York) and the Hull York Medical School. JRG is supported by a senior fellowship by The Kennedy Trust for Rheumatology Research. This report contains independent research supported by the North West Lung Centre Charity and the NIHR Manchester Clinical Research Facility at Wythenshawe Hospital. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: For the cohort 1, ethics approval was obtained from the North West-Haydock Research Ethics Committee for ManARTS (reference 15/NW/0409) and from the Wales Research Ethics Committee 4 for NCARC (reference 18/WA/0368). For the cohort 2, ethics approval was obtained from Yorkshire & The Humber - Leeds West Research Ethics Committee (REC reference 19/YH/0394 with approved 26 SA002 amendment of IRAS project 269597).

With data quality issues with administrative claims and medically derived datasets, a dataset derived from a combination of sources may be more effective for research. The purposes of this article is to link an EMR-based data warehouse with state administrative data to study individuals with rare diseases; to describe and compare their characteristics; and to explore research with the data. These methods included subjects with diagnosis codes for one of three rare diseases from the years 2009-2014; Spina Bifida, Muscular Dystrophy, and Fragile X Syndrome. The results from the combined data provides additional information that each dataset, by itself, would not contain. The simultaneous examination of data such as race/ethnicity, physician and other outpatient visit data, charges and payments, and overall utilization was possible in the combined dataset. It is also discussed that combining such datasets can be a useful tool for the study of populations with rare diseases.

Background Obesity affects nearly half of adults in the United States and is contributing substantially to a pandemic of obesity-associated chronic conditions such as type 2 diabetes, hypertension, and arthritis. The obesity-associated chronic condition pandemic is particularly severe in low-income, medically underserved, predominantly African-American areas in the southern United States. Little is known regarding the impact of geographic, income, and racial disparities in continuity of care on major health outcomes for patients with obesity-associated chronic conditions. Objective The aim of this study is to assess, among patients with obesity-associated chronic conditions, and within this group, patients with type 2 diabetes, (1) whether continuity of care is associated with lower overall and potentially preventable emergency department and hospital utilization, (2) the effect of geographic, income, and racial disparities on continuity of care and on health care utilization, (3) whether continuity of care particularly protects individuals at risk for disparities from adverse health outcomes, and (4) whether characteristics of health systems are associated with higher continuity of care and better outcomes. Methods Using 2015-2018 data from 4 practice-based research networks participating in the Southern Obesity and Diabetes Coalition, we will conduct a retrospective cohort analysis and distributed meta-analysis. Patients with obesity-associated chronic conditions and with type 2 diabetes will be assessed within each health system, following a standardized study protocol. The primary study outcomes are overall and preventable emergency department visits and hospitalizations. Continuity of care will be calculated at the facility level using a modified version of the Bice-Boxerman continuity of care index. Race will be assessed using electronic medical record data. Residence in a low-income area or a health professional shortage area respectively will be assessed by linking patient residence ZIP codes to the Centers for Medicare & Medicaid Services database. Results In 4 regional health systems across Tennessee, Mississippi, Louisiana, and Arkansas, a total of 53 adult hospitals were included in the study. A total of 147,889 patients with obesity-associated chronic conditions who met study criteria were identified in these health systems, of which 45,453 patients met the type 2 diabetes criteria for inclusion. Results are expected by the end of 2020. Conclusions This study should reveal whether health system efforts to increase continuity of care for patients with obesity and diabetes have potential to improve outcomes and reduce costs. Analyzing disparities in continuity of care and their effect on major health outcomes can help demonstrate how to improve care and use of health care resources for vulnerable patients with obesity-associated chronic conditions, and within this group, patients with type 2 diabetes. Better understanding of the association between continuity and health care utilization for these vulnerable populations will contribute to the development of higher-value health systems in the southern United States. International Registered Report Identifier (IRRID) DERR1-10.2196/20788

Psychiatric disorders are prevalent in dermatology patients. Psychodermatology is the body of knowledge at the intersection of psychiatry and dermatology practice. The purpose of this literature review was to assess the knowledge, attitudes, and practices of health care professionals regarding psychodermatology. A search of relevant articles was conducted in PubMed, CINAHL, ERIC, and PsychInfo databases using a comprehensive set of search terms. Studies were included if (1) study participants were health care professionals, (2) studies contained data that could be extracted, and (3) studies were published in peer-reviewed journals. A review of study findings was conducted. A total of nine studies were included in the review. Studies were conducted in several countries. Findings from the review confirmed that providers frequently reported psychocutaneous disorders in their practice. There were, however, gaps and variations in providers' knowledge base and level of comfort treating these patients. Further, providers acknowledged a lack of training in the practice of psychodermatology. The findings from this review suggest that health care professionals from multiple areas of the world may lack a full understanding, level of comfort, and proper training in psychodermatology. Improving the knowledge base and increasing level of comfort in treating psychodermatological disorders can improve the practice of psychodermatology amongst providers. Further, addressing knowledge and comfort level among providers through training and continuing education may improve outcomes for patients with psychocutaneous disorders.

Emerging studies indicate that some COVID-19 patients suffer from persistent symptoms including breathlessness and chronic fatigue; however the long-term immune response in these patients presently remains ill-defined. Here we describe the phenotypic and functional characteristics of B and T cells in healthy individuals and individuals with acute or convalescent COVID-19. We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed long-term alterations with persistence of a cytotoxic programme evident in CD8+ T cells as well as elevated production of type-1 cytokines and IL-17. Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/ IL-10 cytokine imbalance in response to toll-like receptor activation, skewed towards a pro-inflammatory phenotype. Whereas the frequency of IL-10+ B cells was restored in a subset of convalescent patients, IL-6 production remained elevated. Our data are the first to define long-term alterations in the lymphocyte compartment of previously hospitalized COVID-19 patients, at up to 19 weeks of convalescence, and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes. We propose that alterations in B and T cell function following hospitalisation with COVID-19 could impact long-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients. Funding: This study was funded by the BBSRC (BB/M025977/1 to JEK, BB/S01103X/1 to TNS), by the Lister Institute (Prize Fellowship to JEK), by PTDF (SHS/1327/18 to HAS), The Wellcome Trust (202865/Z/16/Z to TH), The Kennedy Trust for Rheumatology Research (Rapid Response Award to JRG) and Versus Arthritis (FAM and JEK studentship). This report is independent research supported by the North West Lung Centre Charity and the NIHR Manchester Clinical Research Facility at Wythenshawe Hospital. We acknowledge the Manchester Allergy, Respiratory and Thoracic Surgery Biobank for supporting this project and thank the study participants for their contribution. Ethical Approval: Ethical approval obtained from the National Research Ethics Service (REC reference 15/NW/0409 for ManARTS and 18/WA/0368 for NCARC). Informed consent was obtained from each patient, clinical information was extracted from written/electronic medical records including demographic data, presenting symptoms, comorbidities, radiographic findings, vital signs, and laboratory data. Declaration of Interest: None to declare.

The objective of this study was to investigate whether males who were born preterm took longer to receive a Duchenne muscular dystrophy diagnosis than term males. Data for males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using a Kaplan-Meier estimator. The first signs and symptoms were noted at a median age of 2 years in both groups. Median age when first signs and symptoms prompted medical evaluation was 2.59 years among preterm and 4.01 years among term males. Median age at definitive diagnosis was 4.25 years and 4.92 years for preterm and term males, respectively. Neither difference was statistically significant. Preterm males tended to be seen for their initial medical evaluation earlier than term males, though they were not diagnosed significantly earlier. It may take clinicians longer after the initial evaluation of preterm males to arrive at a Duchenne muscular dystrophy diagnosis.

Background Limited research has evaluated the relationship between dietary behavior and mortality among those with mobility limitations. Objective To examine the association between dietary behavior and mortality in a national sample of American adults with mobility limitations. Methods Data from the 2003–2006 National Health and Nutrition Examination Survey were utilized. Participants were followed through 2011. Based on self-report, analyzed participants included those with mobility limitations (N = 1369). Dietary behavior was assessed from the alternate healthy eating index (AHEI). Results For the sample, 108,010 person-months occurred with an all-cause mortality rate of 2.07 per 1000 person-months. Dietary behavior was associated with reduced all-cause mortality risk when expressed both as a continuous variable and binary variable (i.e., meeting dietary guidelines). With regard to the latter, and after adjustments, those meeting dietary guidelines (vs. not) had a 40% reduced hazard of all-cause death (HR = 0.60; 95% CI: 0.38–0.97; P = 0.03). Conclusion Among adults with mobility limitations, and thus, who unable to engage in sufficient physical activity, dietary behavior may have survival benefits.

Background The relationship between older age and extraintestinal manifestations (EIMs) in patients with inflammatory bowel disease (IBD) remains unknown. Aims This study aims to determine whether older age is associated with increased risk of EIMs in IBD patients. Methods This was a retrospective study of IBD patients seen at the McMaster University Medical Centre, in Hamilton, ON, Canada from 2012–2020. Patients were identified to have the primary outcome of interest if their gastroenterologist documented the presence of any EIM either during the baseline assessment or during the period of follow up. The independent variable, age at start of follow-up, was dichotomized into two categories age >=40 vs. Results A total of 995 IBD patients (625 with CD) were considered for the regression analysis, all for whom the EIM status was recorded. Out of the 995 patients, 270 patients reported at least one EIM – 99 with arthritis/arthralgia, 79 with dermatologic manifestations, 16 with ophthalmic manifestations, 30 with liver manifestations, and 116 with other EIMs. A univariate regression analysis foundincreased odds of EIMs in older patientsas compared to younger patients (odds ratio (OR) 1.41 (95% CI, 1.05 – 1.89)). In the multivariate regression analysis, current biologic use was found to have a significant relationship with odds of having EIMs (OR 1.49; 95% CI, 1.06 – 2.09). After adjustment for biologic use, patients aged 40 or over had 1.46 times higher odds of having EIMs (95% CI 1.03 – 2.05). A sub-analysis of individual EIM categoriesdid not show a significant association with older age. Conclusions Older age is associated with increased risk of EIMs in IBD patients. Patients with EIMs were also more likely to be treated with biological therapies. Clinicians should inquire about the presence of EIMs in older IBD patients. Funding Agencies None

Introduction Ambulatory care sensitive conditions (ACSCs) can be seen as failure of access or management in primary care settings. Identifying factors associated with ACSCs for individuals with an Intellectual Disability (ID) provide insight into potential interventions. Method To assess the association between emergency department (ED) ACSC visits and a number of demographic and health characteristics of South Carolina Medicaid members with ID. A retrospective cohort of adults with ID was followed from 2001 to 2011. Using ICD-9-CM codes, four ID subgroups, totalling 14 650 members, were studied. Results There were 106 919 ED visits, with 21 214 visits (19.8%) classified as ACSC. Of those, 82.9% were treated and released from EDs with costs averaging $578 per visit. People with mild and unspecified ID averaged greater than one ED visit per member year. Those with Down syndrome and other genetic cause ID had the lowest rates of ED visits but the highest percentage of ACSC ED visits that resulted in inpatient hospitalisation (26.6% vs. an average of 16.8% for other subgroups). When compared with other residential types, those residing at home with no health support services had the highest ED visit rate and were most likely to be discharged back to the community following an ED visit (85.2%). Adults residing in a nursing home had lower rates of ED visits but were most likely to be admitted to the hospital (38.9%) following an ED visit. Epilepsy and convulsions were the leading cause (29.6%) of ACSC ED visits across all subgroups and residential settings. Conclusion Prevention of ACSC ED visits may be possible by targeting adults with ID who live at home without health support services.

Background Following promising results to increase survival and reduce treatment burden in intracranial non-germinomatous germ cell tumors (NGGCTs), we conducted a European study using dose-intense chemotherapy followed by risk-adapted radiotherapy. Methods All patients received 4 courses of cisplatin/etoposide/ifosfamide. Non-metastatic patients then received focal radiotherapy only (54 Gy); metastatic patients received 30 Gy craniospinal radiotherapy with 24 Gy boost to primary tumor and macroscopic metastatic sites. Results Patients with localized malignant NGGCT (n = 116) demonstrated 5-year progression-free survival (PFS) and overall survival (OS) of 0.72 ± 0.04 and 0.82 ± 0.04, respectively. Primary tumor sites were: 67 pineal, 35 suprasellar, 5 bifocal, 9 others. One patient died postsurgery in clinical remission; 3 patients progressed during treatment and 27 (23%) relapsed afterward. Fourteen were local, 6 combined, and 7 distant relapses (outside radiation field). Seventeen of the 27 relapsed patients died of disease. Patients with metastatic disease (n = 33) demonstrated 5-year PFS and OS of 0.68 ± 0.09 and 0.75 ± 0.08, respectively; 1 patient died following progression on treatment and 9 (27%) relapsed afterward (5 local, 1 combined, 3 distant). Only one metastatic patient with recurrence was salvaged. Multivariate analysis identified diagnostic alpha-fetoprotein level (serum and/or cerebrospinal fluid level >1000 ng/mL, 19/149 patients, of whom 11 relapsed; P < 0.0003) and residual disease following treatment, including after second-look surgery (n = 52/145 evaluable patients, 26 relapsed; P = 0.0002) as significant prognostic indicators in this cohort. Conclusion In localized malignant NGGCT, craniospinal radiotherapy could be avoided without increased relapses outside the radiotherapy field. Chemotherapy and craniospinal radiotherapy remain the gold standard for metastatic disease.

Each year in the United States, about 4000 deaths are attributed to cervical cancer, and over 40,000 deaths are attributed to breast cancer (U.S. Cancer Statistics Working Group, 2015). The purpose of this study was to identify predictors of full, partial, and no screening for breast and cervical cancer among women with and without intellectual disability (ID) who are within the age group for screening recommended by the U.S. Preventive Service Task Force (USPSTF), while accounting for changes in recommendations over the study period. Women with ID and an age matched comparison group of women without ID were identified using merged South Carolina Medicaid and Medicare files from 2000 to 2010. The sample consisted of 9406 and 16,806 women for mammography screening and Papanicolaou (Pap) testing adherence, respectively. We estimated multinomial logistic regression models and determined that women with ID were significantly less likely than women without ID to be fully adherent compared to no screening with mammography recommendations (adjusted odds ratio [AOR]: 0.63, 95% confidence interval [CI] 0.55–0.72), and Pap testing recommendations (AOR: 0.17, 95% CI 0.16–0.19). For the 70% of women with ID for whom we had residential information, those who lived in a group home, medical facility, or supervised community living setting were more likely to be fully adherent with both preventive services than those living alone or with family members. For both outcomes, women residing in a supervised nonmedical community living setting had the highest odds of full adherence, adjusting for other covariates.

Compared to aerobic-based physical activity, less research has evaluated the effects of muscle-strengthening physical activity (MSPA) on mortality. Additionally, limited research has evaluated this among adults with mobility limitations, which was this study's purpose. Data from the 2003-2006 NHANES, with follow-up through 2011, were used (analyzed in 2016). MSPA was assessed via self-report, with all-cause, CVD-specific, and cancer-specific mortality assessed as the outcome variables. Analyses were limited to adults with mobility limitations (N=1411), assessed via a validated questionnaire. After adjustments, those meeting MSPA guidelines (vs. not) had a 38% reduced hazard of all-cause death (HR=0.62; 95% CI: 0.41-0.95). Results were similar for CVD-specific mortality (HR=0.46; 95% CI: 0.23-0.97) and cancer-specific mortality (HR=0.27; 95% CI: 0.06-1.20). Meeting MSPA guidelines is associated with reduced all-cause and cause-specific mortality among adults with mobility limitations. This is an encouraging observation as adults with mobility limitations may be unable to engage in sufficient amounts of aerobic-based physical activity. Thus, promotion of MSPA among this population may be of critical importance.

We aimed to retrospectively assess treatments/outcomes, including the value of high-dose-chemotherapy and autologous-stem-cell-rescue (HDC+AuSCR) and re-irradiation, in a large, European patient-cohort with relapsed intracranial germ-cell-tumors (GCTs) receiving uniform first-line therapy, including radiotherapy as standard-of-care. Fifty-eight UK/German patients (48 male/10 female) with relapsed intracranial-GCTs [13 germinoma/45 non-germinomatous GCT(NGGCT)] treated 1996-2010 as per the SIOP-CNS-GCT-96 protocol were evaluated. For germinoma, six patients relapsed with germinoma and five with NGGCT (one palliative, one teratoma patient excluded). Five-year overall-survival (OS) for the whole-group (n=11) was 55%. Four of six germinoma relapses and two of five relapsing with NGGCT were salvaged; patients were salvaged with either standard-dose-chemotherapy (SDC) and re-irradiation or HDC+AuSCR with/without re-irradiation. Of 45 relapsed NGGCT patients, 13 were excluded (3 non-protocol adherence, 5 teratoma, 5 palliation). Five-year OS for the remaining 32 relapsed malignant NGGCT patients treated with curative intent was 9%(95%CI: 2-26%). By treatment received, 5-year OS for the 10 patients receiving SDC and 22 patients treated with intention for HDC+AuSCR was 0%(0-0%) and 14%(3-36%), respectively. The three relapsed NGGCT survivors had raised HCG markers alone; two received additional irradiation. Patients with relapsed germinoma had better 5-year OS than those with relapsed NGGCT (55%vs.9%; p=0.007). Patients with relapsed germinoma were salvaged both with SDC and re-irradiation or HDC+AuSCR with/without re-irradiation; which both represent valid treatment options. Outcomes for malignant relapse following initial diagnosis of NGGCT were exceptionally poor; the few survivors received thiotepa-based HDC+AuSCR, which is a treatment option at first malignant relapse for such patients, with further surgery/irradiation where feasible. This article is protected by copyright. All rights reserved.

Purpose Studies have shown that children with muscular dystrophy are at increased risk for falls, however there is insufficient information about what predicts the first and subsequent events. The purpose of this study was to describe the experience of injury with emphasis on identifying risk factors for fall-related injuries. Methods We studied 269 boys with muscular dystrophy describing their injury experience and identifying risk and protective factors associated with 281 non-simultaneous injuries and 127 falls that resulted in Emergency Department visits and/or inpatient hospitalization during the period 1998-2014. We used a Cox model to estimate the predictors of an initial fall and a zero-inflated Poisson model to identify the predictors for the number of falls. Results Falls accounted for the greatest number of injury occurrences; The most frequent injury type was contusion. The factors that were protective for falls were steroid use, wheelchair use, or having a heart condition. Baseline age was negatively associated with the risk of having any fall, but not significantly related to subsequent falls. Conclusion Wheelchair use and heart conditions associated with reduced risk of falls likely reflects decreased mobility. Clinicians should help families identify factors associated with falls among those who remain ambulatory.

We conducted a series of studies on multiple forms of repetitive behavior displayed by four children with autism spectrum disorder. Study 1 showed that each participant’s highest probability repetitive behavior persisted in the absence of social consequences, thereby meeting the functional definition of stereotypy. Study 2 showed that preferred, structurally matched stimulation decreased each participant’s targeted (highest probability) stereotypy, as well as their non-targeted (lower probability) stereotypy. Study 3 showed that for three participants, non-contingent access to preferred stimulation decreased immediate and, to some extent, subsequent engagement in targeted and non-targeted stereotypy. For the fourth participant, non-contingent access to preferred stimulation decreased immediate engagement in the targeted stereotypy, but increased subsequent engagement in non-targeted stereotypy; this subsequent increase was attenuated by reducing the duration of access to the preferred stimulus. Study 4 showed that a trial-based differential reinforcement of other behavior (DRO) procedure systematically increased the period of time for which the targeted stereotypy was not displayed for three of three participants. In addition, results showed that the participants’ non-targeted stereotypy either decreased or was unchanged when DRO was provided for the targeted stereotypy.

Women with spinal cord injury (SCI) may face barriers that result in disparities in receipt of recommended mammography and Papanicolaou testing.South Carolina.South Carolina women with SCI were identified using International Classification of Diseases codes in 2000-2010 Medicaid and Medicare billing data.Receipt of mammography and Pap testing was determined using procedure billing codes. Partial proportional odds models were estimated to examine the association between SCI and adherence with screening recommendations from the United States Preventive Services Task Force. Each individual's screening experience was classified as full adherence, partial adherence, or no screening.The cohort for mammography consisted of 3,173 women with SCI and 6,433 comparison women without SCI. The cohort for Pap testing consisted 5,025 women with SCI and 9,538 comparison women. Women with SCI were less likely to have full adherence with mammography recommendations (aOR = 0.69, 95% CI 0.64, 0.76) and Pap test recommendations (aOR = 0.53, 95% CI 0.49, 0.57). They were more likely to have no mammography screening (aOR = 1.44, 95% CI 1.33, 1.57) and no Pap testing (aOR = 1.89, 95% CI 1.77, 2.03) than women without SCI.Using longitudinal data with multiple outcome levels, women with SCI were less likely to be fully adherent with receipt of recommended breast and cervical cancer screenings and more likely to have no screenings during the eligible years when compared to women without SCI.

Chronic inflammation is associated with increased risk of cancer, cardiovascular disease (CVD), and diabetes. The role of pro-inflammatory diet in the risk of cancer mortality and CVD mortality in prediabetics is unclear. We examined the relationship between diet-associated inflammation, as measured by dietary inflammatory index (DII) score, and mortality, with special focus on prediabetics. This prospective cohort study used data from the Third National Health and Nutrition Examination Survey (NHANES III). We categorized 13,280 eligible participants, ages 20–90 years, according to glycosylated hemoglobin (HgbA1c) level and identified 2681 with prediabetes, defined as a glycosylated hemoglobin percentage of 5.7–6.4. Computation of DII scores and all statistical analyses were conducted in 2015. The DII was computed based on baseline dietary intake assessed using 24-h dietary recalls (1988–1994). Mortality was determined from the National Death Index records through 2006. Over follow-up ranging between 135 and 168 person-months, a total of 3016 deaths were identified, including 676 cancer, 192 lung cancer, 176 digestive-tract cancer, and 1328 CVD deaths. Cox proportional hazard regression was used to estimate hazard ratios. The prevalence of prediabetes was 20.19 %. After controlling for age, sex, race, HgbA1c, current smoking, physical activity, BMI, and systolic blood pressure, DII scores in tertile III (vs tertile I) was significantly associated with mortality from all causes (HR 1.39, 95 % CI 1.13, 1.72), CVD (HR 1.44, 95 % CI 1.02, 2.04), all cancers (HR 2.02, 95 % CI 1.27, 3.21), and digestive-tract cancer (HR 2.89, 95 % CI 1.08, 7.71). Findings for lung cancer (HR 2.01, 95 % CI 0.93, 4.34) suggested a likely effect. These results were moderately enhanced after additional adjustment for serum low-density lipoprotein and triglyceride and following eliminating deaths during the first year. A pro-inflammatory diet, as indicated by higher DII scores, is associated with an increased risk of all-cause, CVD, all-cancer, and digestive-tract cancer mortality among prediabetic subjects.

Swallow and breathing are highly coordinated behaviors reliant on shared anatomical space and neural pathways. Incremental ascent to high altitudes results in hypoxia/hypocapnic conditions altering respiratory drive, however it is not known whether these changes also alter swallow. We examined the effect of incremental ascent (1045 m, 3440 m and 4371 m) on swallow motor pattern and swallow-breathing coordination in seven healthy adults. Submental surface electromyograms (sEMG) and spirometry were used to evaluate swallow triggered by saliva and water infusion. Swallow-breathing phase preference was different between swallows initiated by saliva versus water. With ascent, saliva swallows changed to a dominate pattern of occurrence during the transition from inspiration to expiration. Additionally, water swallows demonstrated a significant decrease in submental sEMG duration and a shift in submental activity to earlier in the apnea period, especially at 4371 m. Our results suggest that there are changes in swallow-breathing coordination and swallow production that likely increase airway protection with incremental ascent to high altitude. The adaptive changes in swallow were likely due to the exposure to hypoxia and hypocapnia, along with airway irritation.

Both diet and physical activity have been shown to be associated with reduced risk for mortality. The current study examined the individual and combined effects of the inflammatory quality of diet and physical activity levels on mortality risk.Data from the 1999-2004 National Health and Nutrition Examination Survey were used (N = 10,610 adults 20-85 years). Participants were followed through 2011, entailing a median follow-up time of 9.6 yrs. Dietary patterns were assessed using the Dietary Inflammatory Index (DII®), with a higher score indicative of greater diet-related inflammation. Habitual physical activity was assessed via a 30-day recall of leisure-time physical activity as well as objectively via up to seven days of accelerometry assessment. Four lifestyle groups were created: 1) unfavorable DII and inactive (referent); 2) unfavorable DII and active; 3) favorable DII and inactive; and 4) favorable DII and active.Those who had a low DII score (favorable) and who self-reported being active had a 39% reduced hazard of all-cause mortality (HR = 0.61; 95% CI: 0.49-0.76) when compared to those with a higher DII and were inactive. Results based on accelerometer-assessed physical activity indicate a 65% reduced hazard (HR = 0.35; 95% CI: 0.17-0.74). DII and physical activity also were individually associated with mortality in the expected direction. Specifically, DII was positively associated (HR = 1.08; 95% CI: 1.04-1.13) and physical activity inversely associated (HR = 0.97; 95% CI: 0.94-0.99) with all-cause mortality risk.The combination of consuming a more anti-inflammatory diet and having adequate levels of physical activity is associated with a reduced risk of mortality. Additional replicative work is warranted.

Measurements of central and peripheral respiratory chemoreflexes are important in the context of high altitude as indices of ventilatory acclimatization. However, respiratory chemoreflex tests have many caveats in the field, including considerations of safety, portability and consistency. This overview will (a) outline commonly utilized tests of the hypoxic ventilatory response (HVR) in humans, (b) outline the caveats associated with a variety of peak response HVR tests in the laboratory and in high altitude fieldwork contexts, and (c) advance a novel index of steady-state chemoreflex drive (SS-CD) that addresses the many limitations of other chemoreflex tests. The SS-CD takes into account the contribution of central and peripheral respiratory chemoreceptors, and eliminates the need for complex equipment and transient respiratory gas perturbation tests. To quantify the SS-CD, steady-state measurements of the pressure of end-tidal (PET)CO2 (Torr) and peripheral oxygen saturation (SpO2; %) are used to quantify a stimulus index (SI; PETCO2/SpO2). The SS-CD is then calculated by indexing resting ventilation (L/min) against the SI. SS-CD data are subsequently reported from 13 participants during incremental ascent to high altitude (5160 m) in the Nepal Himalaya. The mean SS-CD magnitude increased approximately 96% over 10 days of incremental exposure to hypobaric hypoxia, suggesting that the SS-CD tracks ventilatory acclimatization. This novel SS-CD may have future utility in fieldwork studies assessing ventilatory acclimatization during incremental or prolonged stays at altitude, and may replace the use of complex and potentially confounded transient peak response tests of the HVR in humans.

Background Food allergy is a significant public health concern in the United States, especially in the pediatric population. It places substantial clinical and economic burdens on the health care system. Exposure to antibiotics in early childhood is thought to increase the risk of subsequent food allergy. Objective To examine the impact of exposure to antibiotics early in life on time to development of food allergy. Methods We conducted a population-based matched cohort study using Medicaid data from 28 states. Antibiotic nonusers were matched 1:1 to antibiotic users on date of birth, sex, race, and state. A Cox proportional hazards regression model was used to evaluate the effect of antibiotic exposure on time to development of food allergy. Sensitivity analyses were performed to assess the robustness of study findings. Results We matched 500,647 antibiotic nonusers to 500,647 antibiotic users in the Medicaid pediatric population. In the adjusted Cox proportional hazards regression analysis, antibiotic exposure was significantly associated with faster development of food allergy (hazard ratio, 1.40; 95% CI, 1.34-1.45). The magnitude and significance of the association between antibiotic exposure and food allergy did not change in the sensitivity analyses. A significant association between antibiotic exposure and faster development of food allergy was found in 17 of 28 states. Conclusion Compared with antibiotic nonusers, children with antibiotic prescription had an increased risk of food allergy.

Introduction: Transitioning from adolescence to adulthood can be problematic for individuals with rare disabilities such as muscular dystrophy (MD). Methods: We identified a cohort of 220 individuals with MD and 440 matched comparison individuals and measured emergency room (ER) and inpatient (IP) encounters for the years 2000 through 2010, using all-payer hospital discharge uniform billing data. We compared ER and IP use rates for people with and without MD, and for 15–19-year-olds with MD to 20–24-year-olds with MD. Results: ER and IP use rates were significantly higher among individuals with MD than the comparison group. In addition, ER and IP use rates were significantly higher in the 20–24-year age group than in the 15–19-year group. Conclusions: Additional research is needed to determine whether increased ER and IP use in young adults is attributable to difficulties in healthcare transition versus increased disease severity. Muscle Nerve 52: 714–721, 2015

The authors investigated 48 deaths (7% death rate) among 690 adolescents and young adults with spina bifida in South Carolina during 2000–2010. The authors used Medicaid and other administrative data and a retrospective cohort design that included people with spina bifida identified using ICD-9 codes. Cox regression models with time-dependent and time-invariant covariates, and Kaplan–Meier survival curves were constructed. The authors found that 21.4% of the study group had a skin ulcer during the study period and individuals with skin ulcers had significantly higher mortality than those without ulcers (P < .0001). People who had their first skin ulcer during adolescence had higher mortality than those who had the first skin ulcer during young adulthood (P = .0002; hazard ratio = 10.70, 95% confidence interval for hazard ratio: 3.01, 38.00) and those without skin ulcers, controlling for other covariates. This study showed that age at which individuals first had a skin ulcer was associated with mortality.

Diabetic nephropathy (DN) is characterized by interstitial inflammation and fibrosis, which is the result of chronic accumulation of extracellular matrix produced by activated fibroblasts in the renal tubulointerstitium. Renal proximal tubular epithelial cells (PTECs), through the process of epithelial-to-mesenchymal transition (EMT), are the source of fibroblasts within the interstitial space, and loss of E-cadherin has shown to be one of the earliest steps in this event. Here, we studied the effect of the anti-diabetic agent sodium tungstate (NaW) in the loss of E-cadherin induced by transforming growth factor (TGF) β-1, the best-characterized in vitro EMT promoter, and serum from untreated or NaW-treated diabetic rats in HK-2 cell line, a model of human kidney PTEC. Our results showed that both TGFβ-1 and serum from diabetic rat induced a similar reduction in E-cadherin expression. However, E-cadherin loss induced by TGFβ-1 was not reversed by NaW, whereas sera from NaW-treated rats were able to protect HK-2 cells. Searching for soluble mediators of NaW effect, we compared secretion of TGFβ isoforms and vascular endothelial growth factor (VEGF)-A, which have opposite actions on EMT. One millimolar NaW alone reduced secretion of both TGFβ-1 and -2, and stimulated secretion of VEGF-A after 48 h. However, these patterns of secretion were not observed after diabetic rat serum treatment, suggesting that protection from E-cadherin loss by serum from NaW-treated diabetic rats originates from an indirect rather than a direct effect of this salt on HK-2 cells, via a mechanism independent of TGFβ and VEGF-A functions.

Background Tight junction proteins (TJPs) and dendritic cells (DC) are critical in the pathogenesis of inflammatory bowel diseases. The ileal pouch formed by restorative proctocolectomy provides a unique human model for studying the pathogenesis of inflammatory bowel diseases. Data implicate the microbiota in the pathogenesis of pouchitis, while the role of innate immune factors remains unclear. We performed longitudinal and cross-sectional studies of patients after restorative proctocolectomy and assessed TJP and DC characteristics in the ileal pouch. Methods Mucosal biopsies were taken from the ileal pouch of patients with ulcerative colitis (UC) and familial adenomatous polyposis (n = 8). Of patients with UC, one group (n = 5) was followed longitudinally over the first year after ileostomy closure, another group had pouchitis (n = 15), and another group no inflammation (n = 18). Dendritic cell phenotype and epithelial cell TJP expression were assessed using flow cytometric analysis. Results Increased epithelial expression of the "pore-forming" TJP claudin 2, and DC expression of gut-homing markers CCR 9 and integrin β7, occurred early after ileostomy closure. In patients with UC with pouchitis, epithelial expression of ZO-1 and claudin 1 were reduced, DC were activated with increased CD40, and Toll-like receptor 4 expression increased. In pouchitis, DC expressing CCR 9 were decreased, whereas DC expressing β7 increased. Conclusions Abnormalities were found in TJP expression in the pouch of patients with UC, in particular, increased expression of the pore-forming claudin 2 as an early event in the development of pouch inflammation and an aberrant DC phenotype was characterized in the ileal pouch of patients with UC.

The clinical signs of infection in dogs with Neospora caninum are usually associated with neurological disorders and are seen in young dogs. In this brief case report we observed multifocal ulcerative and exudative skin nodules on the neck and pelvic limbs of a 10-year-old cocker spaniel dog. Infection with N. caninum was diagnosed on the basis of cytology and examination of skin tissues by PCR. The dog initially responded to treatment with clindamycin and then relapsed; the dog died. Infection with N. caninum may have been due in part to immune suppression due to hyperadrenocorticism; which either allowed for the development of a primary infection or reactivation of a latent infection by N. caninum with the occurrence of skin lesions.

Introduction Colorectal cancer (CRC) is a major cause of mortality. Dendritic cells (DC) promote tumour immunity or tolerance dictated by tissue microenvironment. Proximal colon (right-sided) CRC has lower incidence but poorer prognosis than distal colon (left-sided) CRC. This may be due to immunological differences between the proximal and distal colon. However, cellular and molecular studies on these differences especially in CRC are scarce. We aimed to characterise the immune activity in both compartments. Method Activation and migration of DC from human mucosal and tumour biopsies in health and CRC were investigated using flow-cytometry, immunohistology. Functional studies were performed using migration assay techniques. E-Cadherin, a tumour dissemination inhibitor was determined by real time PCR in a separate group of tumours from anaemic CRC patient. Results Co-stimulatory molecules (CD40/CD86) were expressed on more DC from proximal than distal colon in health and CRC (p=0.03; p=0.01 respectively). In CRC, DC from proximal mucosa and tumour showed increased skin-homing (CLA) and ILT3 (marker for immature DC) indicating reduced potential to focus immune activity to this compartment (p=0.03; p=0.01 respectively). CRC-DC showed increased CCR7 (lymph node homing) with greater migration but with negative correlation with tumour size. E-Cadherin mRNA fold-change was significantly lower on proximal tumour cells compared with those in the distal compartment. Functional studies using supernatants from normal mucosae or tumours reproduced the above changes in CRC-DC; changes thus reflected changed gut micro-environment in CRC. Conclusion Higher immune activity, in proximal colon, may underlie lower tumour incidence but higher tumour aggression due to tumour evolution in immunologically active microenvironment. This may have an impact on colorectal cancer treatment, for example, optimisation of current therapies based on the anatomical site of the colorectal tumour. Hence, establishment of standardised management for colon cancer by tumour location is needed. Reference . Bernardo D, et al., Chemokine (C-C Motif) Receptor2 Mediates Dendritic Cell Recruitment to the Human Colon but Is Not Responsible for Differences Observed in Dendritic Cell Subsets, Phenotype, and Function Between the Proximal and Distal Colon. Cell Mol Gastroenterol Hepatol2016;2(1):22–39. Disclosure of Interest None Declared

Limited research has evaluated the individual and combined associations of physical activity (PA), cardiorespiratory fitness (CRF) and muscle strengthening activities (MSA) on generalized anxiety, panic and depressive symptoms. We evaluated this topic in a representative sample of young (20-39 years) adults, with considerations by sex.Data from the 1999-2004 National Health and Nutrition Examination Survey (N = 2088) were used. Generalized anxiety, panic and depressive symptoms were assessed via self-report as well as using the Generalized Anxiety Disorder, Panic Disorder, and Depressive Disorders modules of the automated version of the World Health Organization Composite International Diagnostic Interview (CIDI-Auto 2.1). PA and MSA were assessed via validated self-report questionnaires and CRF was determined via a submaximal treadmill-based test. An index variable was created summing the number (range = 0-3) of these parameters for each participant. For example, those meeting PA guidelines, MSA guidelines and having moderate-to-high CRF were classified as having an index score of 3.MSA was not independently associated with generalized anxiety, panic and depressive symptoms, but those with higher levels of PA and CRF had a reduced odds of these symptoms (ranging from 40 to 46% reduced odds). Compared to those with an index score of 0, those with an index score of 1, 2, and 3, respectively, had a 39%, 54% and 71% reduced odds of having generalized anxiety, panic and depressive symptoms. Results were consistent across both sexes.PA and CRF, but not MSA, were independently associated with generalized anxiety, panic and depressive symptoms. There was evidence of an additive association between PA, CRF, and MSA on these symptoms.

Although the basic paradigm of the U.S. federal drug policy targeting the supply and demand reduction has not changed since its enactment in 1970, there have been seriously undesirable disparate treatments and impacts among various population groups. Although U.S. Congress could not define what is discrimination, it did provide two major criteria for the assessment of discriminatory practices as follows: (a) disparate treatment-basing a key decision on association with any of the five prohibited individual's demographic classifications (race, color, religion, sex, or national origin); and (b) disparate impact-correlation between any of the five prohibited demographic classifications and the key outcomes. In reference to those criteria, this article describes evidence-based indicators of national failure of the Comprehensive Drug Abuse Prevention and Control Act.

Objective This update of a 2008 guideline from the American Academy of Otolaryngology-Head and Neck Surgery Foundation provides evidence-based recommendations to benign paroxysmal positional vertigo (BPPV), defined as a disorder of the inner ear characterized by repeated episodes of positional vertigo. Changes from the prior guideline include a consumer advocate added to the update group; new evidence from 2 clinical practice guidelines, 20 systematic reviews, and 27 randomized controlled trials; enhanced emphasis on patient education and shared decision making; a new algorithm to clarify action statement relationships; and new and expanded recommendations for the diagnosis and management of BPPV. Purpose The primary purposes of this guideline are to improve the quality of care and outcomes for BPPV by improving the accurate and efficient diagnosis of BPPV, reducing the inappropriate use of vestibular suppressant medications, decreasing the inappropriate use of ancillary testing such as radiographic imaging, and increasing the use of appropriate therapeutic repositioning maneuvers. The guideline is intended for all clinicians who are likely to diagnose and manage patients with BPPV, and it applies to any setting in which BPPV would be identified, monitored, or managed. The target patient for the guideline is aged ≥18 years with a suspected or potential diagnosis of BPPV. The primary outcome considered in this guideline is the resolution of the symptoms associated with BPPV. Secondary outcomes considered include an increased rate of accurate diagnoses of BPPV, a more efficient return to regular activities and work, decreased use of inappropriate medications and unnecessary diagnostic tests, reduction in recurrence of BPPV, and reduction in adverse events associated with undiagnosed or untreated BPPV. Other outcomes considered include minimizing costs in the diagnosis and treatment of BPPV, minimizing potentially unnecessary return physician visits, and maximizing the health-related quality of life of individuals afflicted with BPPV. Action Statements The update group made strong recommendations that clinicians should (1) diagnose posterior semicircular canal BPPV when vertigo associated with torsional, upbeating nystagmus is provoked by the Dix-Hallpike maneuver, performed by bringing the patient from an upright to supine position with the head turned 45° to one side and neck extended 20° with the affected ear down, and (2) treat, or refer to a clinician who can treat, patients with posterior canal BPPV with a canalith repositioning procedure. The update group made a strong recommendation against postprocedural postural restrictions after canalith repositioning procedure for posterior canal BPPV. The update group made recommendations that the clinician should (1) perform, or refer to a clinician who can perform, a supine roll test to assess for lateral semicircular canal BPPV if the patient has a history compatible with BPPV and the Dix-Hallpike test exhibits horizontal or no nystagmus; (2) differentiate, or refer to a clinician who can differentiate, BPPV from other causes of imbalance, dizziness, and vertigo; (3) assess patients with BPPV for factors that modify management, including impaired mobility or balance, central nervous system disorders, a lack of home support, and/or increased risk for falling; (4) reassess patients within 1 month after an initial period of observation or treatment to document resolution or persistence of symptoms; (5) evaluate, or refer to a clinician who can evaluate, patients with persistent symptoms for unresolved BPPV and/or underlying peripheral vestibular or central nervous system disorders; and (6) educate patients regarding the impact of BPPV on their safety, the potential for disease recurrence, and the importance of follow-up. The update group made recommendations against (1) radiographic imaging for a patient who meets diagnostic criteria for BPPV in the absence of additional signs and/or symptoms inconsistent with BPPV that warrant imaging, (2) vestibular testing for a patient who meets diagnostic criteria for BPPV in the absence of additional vestibular signs and/or symptoms inconsistent with BPPV that warrant testing, and (3) routinely treating BPPV with vestibular suppressant medications such as antihistamines and/or benzodiazepines. The guideline update group provided the options that clinicians may offer (1) observation with follow-up as initial management for patients with BPPV and (2) vestibular rehabilitation, either self-administered or with a clinician, in the treatment of BPPV.

Squamous cell carcinoma is the most common carcinoma in the oral cavity. Resection of these cancers often requires reconstruction. Nasolabial flaps are a robust and reliable local flap that provide a satisfactory outcome. We report two cases where an epidermoid cyst developed within the scar of the nasolabial flap and review the literature.