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University campuses could become leaders in developing alternatives to policing for managing public health and safety, yet, nearly all campuses rely on campus or local police to respond to mental health emergencies. Herein, we present the available evidence for campus mobile crisis intervention teams (MCITs) as an alternative to policing, consider what colleges and universities can learn from existing community MCIT models, and propose initial steps for the development and implementation of a campus MCIT.

Background The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg). Objective We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study. Methods Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 μg, subjects who had received DBV712 250 μg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment. Results Of 213 eligible subjects who had received DBV712 250 μg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%). Conclusions These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.

Aims Anaemia and iron deficiency (ID) are frequently found in patients with chronic heart failure (CHF) and associated with adverse outcome. However, it is unclear whether absolute [transferrin saturation (TSAT) 100 μg/L) with and without anaemia had similar or different consequences for such patients. Methods and results Within this retrospective cohort study, 2223 patients (1601 men and 622 women) with CHF, referred to our department, between 2000 and 2018, were followed for a median time of 84 months. Anaemia was found in 393 patients and was an independent predictor for an adverse outcome [HR 2.164 (95% CI 1.865–2.512), P

Aims: Immune activation and disturbances of vitamin D metabolism are frequently encountered in patients with heart failure. Elevated fibroblast growth factor 23 (FGF23) levels as well as immune activation have been associated with a worse outcome in patients with heart failure. We evaluated the relationship of vitamin D metabolism and FGF23 levels with immune activation and its association with cardiac function and outcome in patients with heart failure. Methods and Results: In 149 patients with heart failure caused by nonischaemic cardiomyopathy, parameters of vitamin D metabolism (vitamin D, parathormone, phosphate, C-terminal FGF23, calcium), inflammation (hsCRP, neopterin) and cardiac function were investigated. Patients with elevated inflammatory parameters had significantly higher Ct-FGF23 levels (37.33 RU/mL vs. 17.60 RU/mL, p < 0.001). The highest Ct-FGF23 and phosphate levels were found in patients with elevated neopterin and hsCRP levels as well as in in patients with progressive heart failure. Patients with high Ct-FGF23 and neopterin levels (Ct-FGF23 > 22.60 RU/mL, neopterin > 6.90 nmol/L) had a significantly higher risk for adverse events compared to patients with low Ct-FGF23 and neopterin levels (HR 7.386, [95%CI 2.543 – 21.447], p < 0.001). Conclusions: Our study indicates a strong relationship of vitamin D metabolism, especially FGF23, with Th1 immune activation in patients with heart failure. Elevated Ct-FGF23 and neopterin levels are additive predictors for adverse cardiovascular events in patients with heart failure.

Immune activation coincides with disturbances in iron and vitamin D metabolism in patients with cardiomyopathy. In this study, we investigated whether there are differences regarding immune activation, iron and vitamin D metabolism between the different cardiomyopathy aetiologies. Patients and methods: Parameters of iron metabolism (haemoglobin, iron, transferrin, transferrin saturation, ferritin, hepcidin), vitamin D metabolism (Ct-FGF23, parathormone, phosphate, vitamin D) and immune activation (C-reactive protein and neopterin) were determined in 149 patients (98 men, 51 women) with non-ischaemic cardiomyopathy. Results: Patients with amyloid cardiomyopathy presented with higher neopterin, ferritin and hepcidin levels than other cardiomyopathy aetiologies. Furthermore, they showed the highest rate of cardiovascular events. C-reactive protein levels were significantly higher in patients with inflammatory cardiomyopathy. Patients with virus positive cardiomyopathy presented with significantly higher ferritin and Ct-FGF23 levels compared to patients with virus negative inflammatory cardiomyopathy. Conclusion: This study indicates that there are some differences regarding the extent of immune activation and inflammation as well as alterations in iron metabolism disorders between different cardiomyopathy aetiologies. Further studies with larger patient cohorts are needed to investigate these findings more precisely.

This study focuses on the functional and psychosocial consequences of facial weakness of patients with facioscapulohumeral muscular dystrophy (FSHD) and how they manage their daily lives. We conducted a qualitative study. Sixteen FSHD patients with varying degrees of facial weakness were interviewed using a semi-structured interview guide. Data were analyzed using the constant comparison approach based on the Straussian Grounded Theory. Reduced facial expression affected different aspects of a participant’s life, which is reinforced by fatigue. Particularly the younger participants described the confrontation with reduced facial expression as upsetting. The unpredictability of the progression of facial weakness makes many participants insecure and concerned. They generally tend to avoid discussing facial weakness with loved ones as well as with strangers. Patients would like the expert teams to shed more light on effective skill training and psychosocial support, especially for the younger patient group. A multidisciplinary approach is needed in addition to programs focusing on the individual aspects of facial weakness. As the experienced psychosocial effect is not commonly equal to the objective degree of facial weakness, we recommend a tailored approach. Finally, these programs should point out the importance of the patient’s own ingenuity.Implications for RehabilitationFacial weakness affects both activities and social participation in patients with facioscapulohumeral muscular dystrophy (FSHD), which is reinforced by fatigue.Many participants try to stay down to earth and focus on their ability to self-manage their obstacles regarding facial weakness.Thus, future treatment programs should have a multidisciplinary approach and should point out the importance of the patient’s own ingenuity. Facial weakness affects both activities and social participation in patients with facioscapulohumeral muscular dystrophy (FSHD), which is reinforced by fatigue. Many participants try to stay down to earth and focus on their ability to self-manage their obstacles regarding facial weakness. Thus, future treatment programs should have a multidisciplinary approach and should point out the importance of the patient’s own ingenuity.

The coronavirus disease 2019 (COVID-19) pandemic, caused by a novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged at the end of 2019 in China and affected the entire world population, either by infection and its health consequences, or by restrictions in daily life as a consequence of hygiene measures and containment strategies. As of September 2021, more than 231,000.000 infections and 4,740.000 deaths due to COVID-19 have been reported. The infections present with varied clinical symptoms and severity, ranging from asymptomatic course to fatal outcome. Several risk factors for a severe course of the disease have been identified, the most important being age, gender, comorbidities, lifestyle, and genetics. While most patients recover within several weeks, some report persistent symptoms restricting their daily lives and activities, termed as post-COVID. Over the past 18months, we have acquired significant knowledge as reflected by an almost uncountable number of publications on the nature of the underlying virus and its evolution, host responses to infection, modes of transmission, and different clinical presentations of the disease. Along this line, new diagnostic tests and algorithms have been developed paralleled by the search for and clinical evaluation of specific treatments for the different stages of the disease. In addition, preventive non-pharmacological measures have been implemented to control the spread of infection in the community. While an effective antiviral therapy is not yet available, numerous vaccines including novel vaccine technologies have been developed, which show high protection from infection and specifically from a severe course or death from COVID-19. In this review, we tried to provide an up-to-date schematic of COVID-19, including aspects of epidemiology, virology, clinical presentation, diagnostics, therapy, and prevention.

Objectives Rapid identification of infected subjects is a cornerstone for controlling a pandemic like the current one with the SARS-CoV-2. Easy to handle antigen tests can provide timely results, which is of particular importance in a primary care setting. However, concerns exist regarding their sensitivity, which led us to evaluate four commercially available tests in patients hospitalized for COVID-19. Methods We analyzed in parallel nasopharyngeal/oropharyngeal swabs from 154 consecutive patients admitted to our department with moderate to severe COVID-19, using quantitative RT-PCR (Cobas, Roche) and up to four antigen tests from different distributors. Antigen test results were linked to Ct (cycle threshold) values as markers for patients’ infectivity. Results We found that two out of four antigen tests correctly identified subjects with high viral loads (Ct ≤ 25), and three out of four tests detected more than 80% of subjects with a Ct ≤ 30, which is considered the threshold for infectivity. However, one test investigated had a poor clinical performance. When investigating subjects with Ct values >30, we found that the antigen test was still positive in up to 45% of those cases. Conclusion Most antigen tests had a sufficient sensitivity to identify symptomatic subjects infected with SARS-CoV-2 and with transmissible infection. On the other hand, antigen testing may not be suitable to identify loss of infectivity in COVID-19 subjects during follow-up. Newly introduced antigen tests need to be validated in a clinical or primary care setting to define their clinical usefulness.

Anemia and disturbances of iron metabolism are frequently encountered in patients with COVID-19 and associated with an adverse clinical course. We retrospectively analyzed 645 consecutive COVID-19 patients hospitalized at the Innsbruck University Hospital. Pre-existing anemia was associated with increased risk for in-hospital death. We further found that the decline in hemoglobin levels during hospital stay is more pronounced in patients with signs of hyperinflammation upon admission, the latter being associated with a nearly two-fold higher risk for new onset anemia within one week. Anemia prevalence increased from 44.3% upon admission to 87.8% in patients who were still hospitalized after two weeks. A more distinct decrease in hemoglobin levels was observed in subjects with severe disease, and new-onset anemia was associated with a higher risk for ICU admission. Transferrin levels decreased within the first week of hospitalization in all patients, however, a continuous decline was observed in subjects who died. Hemoglobin, ferritin, and transferrin levels normalized in a median of 122 days after discharge from hospital. This study uncovers pre-existing anemia as well as low transferrin concentrations as risk factors for mortality in hospitalized COVID-19 patients, whereas new-onset anemia during hospitalization is a risk factor for ICU admission. Anemia and iron disturbances are mainly driven by COVID-19 associated inflammation, and cure from infection results in resolution of anemia and normalization of dysregulated iron homeostasis.

Background Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-μg peanut protein (Viaskin™ Peanut 250 μg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children. Objective To examine the safety of VP250 in children, using a study design approximating potential real-world use. Methods REALISE is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported. Results Three hundred ninety-three children were randomized 3:1 to receive VP250 (n=294) or placebo (n=99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued due to adverse events. Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall adverse event rates were similar among participants with and without history of peanut anaphylaxis. Conclusions In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

Objective:Anemia is often found in patients with coronary artery disease (CAD) or acute coronary syndrome (ACS) and related to disease severity. Our study investigated the relationship between anemia, iron homeostasis and inflammation in CAD and examined their influence on the outcome of patients.Patients and Methods:Markers of immune activation (neopterin, interleukin [IL]-12, IL-6, high sensitive C-reactive protein (hsCRP), fibrinogen, serum amyloid A [SAA]) and iron metabolism (ferritin, transferrin saturation, hemoglobin) were determined in 2,082 patients (68.7 % men, median age 63 years) from the Ludwigshafen Risk and cardiovascular Health (LURIC) cohort. Patients were followed-up for a median of 9.81 years.Results:960 patients (46.1 %) presented with chronic CAD, 645 patients (31.0 %) had an ACS, and 477 patients (22.9 %) presented with no CAD in coronary angiography (CAG). Anemia (n= 357, 17.1 %) was associated with disease severity (reflected by more progressed stenosis in CAG, CCS, and NYHA classes, and a lower LV-EF), a higher cardio-cerebrovascular event rate and higher levels of inflammatory markers. Interestingly, anemia was only predictive for an adverse outcome in patients with elevated inflammatory markers. Accordingly, anemia of chronic disease (ACD) was associated with a higher cardio-cerebrovascular event-rate in the subsequent 2 years as compared to patients with other types of anemia or without anemia (14.3 vs. 6.1 vs. 4.0%,p< 0.001).Conclusions:This study confirms that anemia and immune activation are strongly related to cardiovascular disease progression and an adverse outcome. Our data suggest that the association of anemia with disease severity and outcome might mainly be due to underlying inflammation.

Summary Background SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin–angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19. Methods ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUCSOFA), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596. Findings Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66–80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00–2·00) vs 1·00 (0·00–3·00); p=0·12). Discontinuation was associated with a significantly lower AUCSOFA (0·00 [0·00–9·25] vs 3·50 [0·00–23·50]; p=0·040), mean SOFA score (0·00 [0·00–0·31] vs 0·12 [0·00–0·78]; p=0·040), and 30-day SOFA score (0·00 [10–90th percentile, 0·00–1·20] vs 0·00 [0·00–24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group. Interpretation Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options. Funding Austrian Science Fund and German Center for Cardiovascular Research.

Organ transplantation survival rates have continued to improve over the last decades, mostly due to reduction of mortality early after transplantation. The advancement of the field is facilitating a liberalization of the access to organ transplantation with more patients with higher risk profile being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of marginal donors. In this regard, hypothermic and normothermic machine perfusion are recognized as one of the most important developments in the modern era. Owing to these developments, novel non-invasive tools for the assessment of organ quality are on the horizon. Hyperspectral imaging represents a potentially suitable method capable of evaluating tissue morphology and organ perfusion prior to transplantation. Considering the changing environment, we here discuss the hypothetical combination of organ machine perfusion and hyperspectral imaging as a prospective feasibility concept in organ transplantation.

This study evaluates the predictive value of circulating inflammatory markers, especially neopterin, in patients with coronavirus disease 2019 (COVID-19). Within this retrospective analysis of 115 hospitalized COVID-19 patients, elevated neopterin levels upon admission were significantly associated with disease severity, risk for intensive care unit admission, need for mechanical ventilation, and death. Therefore, neopterin is a reliable predictive marker in patients with COVID-19 and may help to improve the clinical management of patients.

Food allergy is increasingly prevalent and poses a life-threatening risk to those afflicted. The health care costs associated with food allergies are also increasing. Current and emerging treatments for food allergies aim at protecting against reactions caused by accidental ingestion and increasing the food allergen reaction threshold, although this protection is often temporary. In the future, ideal biologic therapies would target key mediators of the type II immune pathway, essential in development of the atopic march to prevent development of food allergies. Biologics offering long-term protection against allergic reactions to food are needed, and several agents are already in development.

Infections with SARS-CoV-2 can result in severe clinical manifestations. As such patients present with systemic inflammation, we studied the prevalence and predictive value of anemia of inflammation (AI) or functional iron deficiency (FID), originating from immune-mediated alterations of iron homeostasis. Within this retrospective analysis of 259 hospitalized patients with COVID-19, we found that, upon admission, 24.7% were anemic, with the majority suffering from AI (68.8%). Anemia was associated with a significantly higher in-hospital mortality (OR 3.729 (95%CI 1.739&ndash, 7.995), p = 0.001) but not an increased frequency of intensive care unit (ICU) admission or need for mechanical ventilation. FID was present in 80.0% of patients upon admission, linked to more advanced inflammation and associated with significantly longer hospital stay. Notably, a ferritin/transferrin ratio &gt, 10 predicted a five-fold higher risk of ICU admission and an eight-fold higher risk of the need for mechanical ventilation. Anemia and alterations of iron homeostasis are highly prevalent in hospitalized COVID-19 patients. Iron metabolism biomarkers and hemoglobin can contribute to risk stratification of patients, as initial anemia is associated with increased mortality, whereas alterations of iron homeostasis with a higher ferritin/transferrin ratio reflect more advanced inflammation and predicts subsequent insufficient pulmonary oxygenation with the need for ICU admission and mechanical ventilation.

Food allergy is increasing in prevalence, and management focuses on strict avoidance of known allergens and appropriately treating reactions. Any reaction has the potential to result in anaphylaxis, which can be fatal. Children spend a significant amount of time in the childcare or school setting, and interactions between families, school personnel, and clinicians are important to ensure the health and safety of children with allergies and asthma. This review examines current food allergy guidelines and legislation, an assessment of allergen-free schools, the importance of written anaphylaxis action plans, training and education of school personnel, emerging treatment options, and the social implications of having food allergies. As the clinical use and research into food allergen immunotherapy continues to expand, an additional level of education and management is required of school personnel and caregivers. Food allergy has both medical and social implications, which are magnified in the school setting.

Context The ratio of clinicians to patients has been associated with health outcomes in many medical contexts but has not been explored in collegiate sports medicine. The relationship between administrative and financial oversight models and staffing is also unknown. Objective To (1) evaluate staffing patterns in National Collegiate Athletic Association sports medicine programs and (2) investigate whether staffing was associated with the division of competition, Power 5 conference status, administrative reporting structure (medical or athletic department), or financial structure (medical or athletic department). Design Cross-sectional study. Setting Collegiate sports medicine programs. Patients or Other Participants Representatives of 325 universities. Main Outcome Measure(s) A telephone survey was conducted during June and July 2015. Participants were asked questions regarding the presence and full-time equivalence of the health care providers on their sports medicine staff. The number of athletes per athletic trainer was determined. Results Responding sports medicine programs had 0.5 to 20 full-time equivalent staff athletic trainers (median = 4). Staff athletic trainers at participating schools cared for 21 to 525 athletes per clinician (median = 100). Both administrative and financial oversight from a medical department versus the athletics department was associated with improved staffing across multiple metrics. Staffing levels were associated with the division of competition; athletic trainers at Division I schools cared for fewer athletes than athletic trainers at Division II or III schools, on average. The support of graduate assistant and certified intern athletic trainers varied across the sample as did the contributions of nonphysician, nonathletic trainer health care providers. Conclusions In many health care settings, clinician : patient ratios are associated with patient health outcomes. We found systematic variations in clinician : patient ratios across National Collegiate Athletic Association divisions of competition and across medical versus athletics organizational models, raising the possibility that athletes' health outcomes vary across these contexts. Future researchers should evaluate the relationships between clinician : patient ratios and athletes' access to care, care provision, health care costs, health outcomes, and clinician job satisfaction.

BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; PCONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

Seizures are due to excessive, synchronous neuronal firing in the brain and are characteristic of epilepsy, the fourth most prevalent neurological disease. We report handling-induced and spontaneous seizures in mice deficient for CD39, a cell-surface ATPase highly expressed on microglial cells. CD39-/- mice with handling-induced seizures had normal input-output curves and paired-pulse ratio measured from hippocampal slices and lacked microgliosis, astrogliosis or overt cell loss in the hippocampus and cortex. As expected, however, the cerebrospinal fluid of CD39-/- mice contained increased levels of ATP and decreased levels of adenosine. To determine if immune activation was involved in seizure progression, we challenged mice with lipopolysaccharide (LPS) and measured the effect on microglia activation and seizure severity. Systemic LPS challenge resulted in increased cortical staining of Iba1/CD68 and gene array data from purified microglia predicted increased expression of interleukin-8, triggering receptor expressed on myeloid cells 1, p38, pattern recognition receptors, death receptor, nuclear factor-κB , complement, acute phase, and interleukin-6 signalling pathways in CD39-/- versus CD39+/+ mice. However, LPS treatment did not affect handling-induced seizures. In addition, microglia-specific CD39 deletion in adult mice was not sufficient to cause seizures, suggesting instead that altered expression of CD39 during development or on non-microglial cells such as vascular endothelial cells may promote the seizure phenotype. In summary, we show a correlation between altered extracellular ATP/adenosine ratio and a previously unreported seizure phenotype in CD39-/- mice. This work provides groundwork for further elucidation of the underlying mechanisms of epilepsy.

Oral food challenges are an integral part of an allergist's practice and are used to evaluate the presence or absence of allergic reactivity to foods. A work group within the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology was formed to update a previously published oral food challenge report. The intention of this document was to supplement the previous publication with additional focus on safety, treatment of IgE-mediated allergic reactions, guidance for challenges in infants and adults, psychosocial considerations for children and families participating in an oral food challenge, specific guidance for baked milk or baked egg challenges, masking agents and validated blinding recipes for common food allergens, and recommendations for conducting and interpreting challenges in patients with suspected food protein–induced enterocolitis syndrome. Tables and figures within the report and an extensive online appendix detail age-specific portion sizes, appropriate timing for antihistamine discontinuation, serum and skin test result interpretation, written consents, and instructional handouts that may be used in clinical practice.

Background The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. Objective ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. Methods Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non–daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. Results Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non–daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non–daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. Conclusions Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

Anemia often coincides with depression and impaired quality of life (QoL) in cancer patients. Sustained immune activation can lead to the development of anemia. Furthermore, it also may go along with changes in tryptophan and phenylalanine metabolism. The aim of our pilot study was to study the relationship between anemia, immune-mediated changes in amino acid metabolism, and the QoL and mood of cancer patients. Questionnaires to measure QoL and depression were completed by 152 patients with solid tumors. Hemoglobin, parameters of immune activation as well as tryptophan and phenylalanine metabolism were determined in the patients&rsquo, sera. Anemic patients (51.7%) presented with higher inflammatory markers, and a higher tryptophan breakdown with lower tryptophan concentrations. They reported an impaired QoL and had higher depression scores. Patients with an impaired QoL (65.8%) also suffered from more fatigue and impaired physical, emotional, and social functioning. They, furthermore, presented with higher concentrations of inflammatory markers (C-reactive protein (CRP) and neopterin) as well as higher tryptophan degradation (in men) and higher phenylalanine concentrations (in women). Sixty-one patients (40.1%) had (mostly mild) depression. In these patients, a higher degree of Th1 immune activation was found. The results of our study suggest that cancer-related anemia goes along with an impaired QoL, which is also associated with immune-mediated disturbances of tryptophan and phenylalanine metabolism.

Activation of the steroidogenic enzyme CYP11A1 was shown to be necessary for the development of peanut-induced intestinal anaphylaxis and IL-13 production in allergic mice. We determined if levels of CYP11A1 in peripheral blood T cells from peanut-allergic (PA) children compared to non-allergic controls were increased and if levels correlated to IL-13 production and oral challenge outcomes to peanut. CYP11A1 mRNA and protein levels were significantly increased in activated CD4+ T cells from PA patients. In parallel, IL-13 production was significantly increased; IFNγ levels were not different between groups. There were significant correlations between expression levels of CYP11A1 mRNA and levels of IL13 mRNA and protein, levels of serum IgE anti-Ara h 2 and to outcomes of peanut challenge. The importance of CYP11A1 on cytokine production was tested using a CYP11A1 CRISPR/Cas9 KO plasmid or an inhibitor of enzymatic CYP11A1 activity. Inhibition of CYP11A1 activation in patient cells treated with the inhibitor, aminoglutethimide, or CD4+ T cell line transfected with the CYP11A1 KO plasmid resulted in reduced IL-13 production. These data suggest that the CYP11A1-CD4+Tcell-IL-13 axis in activated CD4+ T cells from PA children is associated with development of PA reactions. CYP11A1 may represent a novel target for therapeutic intervention in PA children.

Overweight and obesity are common in patients with facioscapulohumeral dystrophy (FSHD) and myotonic dystrophy type 1 (DM1). Lifestyle change is often challenging for patients with neuromuscular diseases, especially to increase physical activity. When lifestyle changes have not been effective, bariatric surgery is a treatment option. However, very little is known about the benefits and risks in patients with neuromuscular disorders. This study therefore aims to obtain insight into the patients' perspectives and experiences, the outcome, effects and risks of bariatric surgery in these disorders. We performed a qualitative study, consisting of 14 in-depth interviews with six patients (three FSHD and three DM1; five women, one man; aged range 31-47 years), four relatives, three bariatric surgeons and one general practitioner. The study used a qualitative descriptive method. Four themes were formulated: (1) overweight as burden; (2) bariatric surgery as last option; (3) not your standard patient; and (4) a different life, a different me. This study shows that bariatric surgery has beneficial physical and mental effects for most patients with FSHD and DM1, and does not influence the muscular disease course. Bariatric surgery is feasible in patients with FSHD and DM1, but specific precautions and a suitable follow-up including tailored dietary and training advices are required. (C) 2018 Elsevier B.V. All rights reserved.

Inflammation and immune activation play an important role in the pathogenesis of cardiac remodelling in patients with heart failure. The aim of this study was to assess whether biomarkers of inflammation and immune activation are linked to disease severity and the prognosis of heart failure patients. In 149 patients (65.8% men, median age 49.7 years) with heart failure from nonischaemic cardiomyopathy, the biomarkers neopterin and C-reactive protein were tested at the time of diagnosis. Patients were followed-up for a median of 58 months. During follow-up, nineteen patients died, five had a heart transplantation, two needed a ventricular assistance device, and twenty-one patients had to be hospitalised because of heart failure decompensation. Neopterin concentrations correlated with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations (rs = 0.399, p < 0.001) and rose with higher New York Heart Association (NYHA) class (I: 5.60 nmol/L, II: 6.90 nmol/L, III/IV: 7.80 nmol/L, p = 0.033). Higher neopterin levels were predictive for an adverse outcome (death or hospitalisation due to HF decompensation), independently of age and sex and of established predictors in heart failure such as NYHA class, NT-proBNP, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LV-EF) (HR 2.770; 95% CI 1.419–5.407; p = 0.003). Patients with a neopterin/eGFR ratio ≥ 0.133 (as a combined marker for immune activation and kidney function) had a more than eightfold increased risk of reaching an endpoint compared to patients with a neopterin/eGFR ratio ≤0.065 (HR 8.380; 95% CI 2.889–24.308; p < 0.001). Neopterin is associated with disease severity and is an independent predictor of prognosis in patients with heart failure.

IMPORTANCE: There are currently no approved treatments for peanut allergy. OBJECTIVE: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n = 356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein. INTERVENTIONS: Daily treatment with peanut patch containing either 250 μg of peanut protein (n = 238) or placebo (n = 118) for 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs). RESULTS: Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% [95% CI, 12.4%-29.8%; P

SALAMONSON Y., RAMJAN L., LOMBARDO L., LANSER L.H., FERNANDEZ R. & GRIFFITHS R. (2011) Diversity and demographic heterogeneity of Australian nursing students: a closer look. International Nursing Review59, 59–65 Background: In the last decade, there has been a rapid growth of international students undertaking nursing studies in Australian universities. At the same time, nursing courses continue to attract local students from a diversity of backgrounds. Aim: The aim of this study is to examine first year nursing students by enrolment classification and country of birth: i) international; ii) local, overseas-born; and iii) local, Australian-born student, and demographic differences of academic performance at the 12-month follow-up. Methods: A prospective, correlational design was used to identify nursing student characteristics as predictors of academic performance in a large university in the western region of Sydney. Results: Of the 806 students enrolled in the course, 540 (67%) completed the survey and consented to data linkage. Fifty-six per cent of the 540 participants were born overseas, of which 38% were local and 18% were international students. Local, overseas-born students originated from 55 different countries, in contrast to international students who were representative of only 16 different countries. International students were younger, spent less time in paid work and were more likely to have a close friend in the same course. Although age was positively related to academic performance, local, overseas-born and international enrolment classifications, and hours in paid work during semester were negatively associated to academic performance. Conclusion: This study has taken a closer look at an important issue that requires further examination, given that international and local, overseas-born students were two distinctive groups. Although both groups underperformed academically compared with Australian-born students, the differences in characteristics between local, overseas-born students and international students suggest that these two student groups are likely to experience different challenges during their nursing studies in Australia.

A tremendous increase in the number of female athletes of all ages and abilities has occurred in the past 35 years. In general, sports and athletic competition produce healthier and happier women. However, explosion in participation has revealed clear gender-specific injuries and medical conditions unique to the female athlete. This article focuses on the latest advances in our knowledge of the female athlete triad and the relationship between athletic-associated amenorrhea and endothelial dysfunction. Treatment of vascular dysfunction with folic acid is also discussed.

Food allergy is increasing in prevalence; as a result, there is intense focus on developing safe and effective therapies. Current methods of specific immunotherapy include oral, sublingual, and epicutaneous, while nonspecific methods that have been investigated include: Chinese herbal medicine, probiotics, and anti-IgE antibodies. Although some studies have demonstrated efficacy in inducing desensitization, questions regarding safety and the potential for achieving immune tolerance remain. Although some of these therapies demonstrate promise, further investigation is required before their incorporation into routine clinical practice.

Mammalian retinal ganglion cells (RGCs) do not normally regenerate their axons through an injured optic nerve, but can be stimulated to do so by activating macrophages intraocularly. In a cell culture model of this phenomenon, we found that a small molecule that is constitutively present in the vitreous, acting in concert with macrophage-derived proteins, stimulates mature rat RGCs to regenerate their axons if intracellular cAMP is elevated. In lower vertebrates, RGCs regenerate their axons spontaneouslyin vivo, and in culture, the most potent axon-promoting factor for these cells is a molecule that resembles the small vitreous-derived growth factor from the rat. This molecule was isolated chromatographically and was shown by mass spectrometry to be a carbohydrate. In agreement with this finding,d-mannose proved to be a potent axon-promoting factor for rat RGCs (ED50∼10 μm); this response was cAMP-dependent and was augmented further by macrophage-derived proteins. Goldfish RGCs showed far less selectivity, responding strongly to eitherd-mannose ord-glucose in a cAMP-independent manner. These findings accord well with the success or failure of optic nerves to regenerate in higher and lower vertebratesin vivo. The axon-promoting effects of mannose are highly specific and are unrelated to energy metabolism or glycoprotein synthesis.

Item does not contain fulltext STUDY DESIGN: A clinical practice guideline. OBJECTIVES: To assist physiotherapists in decision making and to improve the efficacy and uniformity of care for patients with whiplash-associated disorders Grades I and II. SUMMARY OF BACKGROUND DATA: Whiplash constitutes a considerable problem in health care. Many interventions are used in physiotherapy practice, despite increasing evidence for the use of active interventions. There is still no clinical practice guideline for the management of patients with whiplash-associated disorders. METHOD OF DEVELOPMENT: A computerized literature search of Medline, Cinahl, Cochrane Controlled Trial Register, Cochrane Database of Systematic Reviews, and the Database of the Dutch National Institute of Allied Health Professions was performed to search for information about the diagnostic process and the therapeutic process in whiplash patients. When no evidence was available, consensus between experts was achieved to develop the guideline. Practicing physiotherapists reviewed the clinical applicability and feasibility of the guideline, and their comments were used to improve it. RECOMMENDATIONS: The diagnostic process consists of systematic history taking and a physical examination supported by reliable and valid assessment tools to document symptoms and functional disabilities. The primary goals of treatment are a quick return to normal activities and the prevention of chronicity. Active interventions such as education, exercise therapy, training of functions, and activities are recommended according to the length of time since the accident and the rate of recovery. The biopsychosocial model is used to address the consequences of whiplash trauma. CONCLUSIONS: Scientific evidence for the diagnosis and physiotherapeutic management of whiplash is sparse; therefore, consensus is used in different parts of the guideline. The guideline reflects the current state of knowledge of the effective and appropriate physiotherapy in whiplash patients. More and better research is necessary to validate this guideline in the future.

SSc-associated pulmonary hypertension (SSc-PH) has a worse prognosis compared with SSc without PH (SSc-nonPH). Iron deficiency (ID) was previously associated with worse clinical outcome and survival in other types of PH, but ID effects in SSc-PH are unknown. Therefore we investigated the prevalence and clinical significance of ID in systemic sclerosis patients with and without PH.Body iron status was determined in SSc-PH (n = 47) and SSc-nonPH patients (n = 122). ID was defined by circulating soluble transferrin receptor (sTfR) levels28.1 nmol/l. Clinical and exercise parameters were compared between the groups. Four-year survival after iron measurements was determined.ID prevalence was 46.1% in SSc-PH compared with 16.4% in SSc-nonPH patients (P0.001). Overall hepcidin levels were high compared with reference values and related to sTfR, but not with IL-6 (P = 0.82). Six-minute walking distance and maximal achieved work at ergometry was lower in SSc-PH compared with SSc-nonPH patients (P0.001 and P0.01, respectively) and was even further reduced in case of ID (P(interaction)0.05). In addition, ID SSc-PH patients had a poorer survival compared with non-ID patients [hazard ratio (HR) 0.34, 95% CI 0.14, 0.82, P0.05) and a similar trend was observed in SSc-nonPH patients (HR 0.16, 95% CI 0.02, 1.11, P = 0.06).ID is more prevalent in SSc-PH than in SSc-nonPH patients and is associated with exercise impairment in both SSc-PH and SSc-nonPH. In addition, ID SSc-PH patients have a significantly worse survival compared with non-ID patients.

Adverse trends in the reproductive health of male fish, including testis abnormalities and intersex gonads, have been increasingly reported over recent years. These effects have been associated with the exposure of fish to natural, synthetic, and xenobiotic estrogens present in the aquatic environment. A novel in vivo test system using transgenic zebrafish has been developed to rapidly determine the effects of estrogenic chemicals on critical life stages and sensitive target organs in the fish. In the transgenic zebrafish, an estrogen binding sequence linked to a TATA box and luciferase reporter gene was stably introduced. Binding of a substance to endogenous estrogen receptors (ER) and the subsequent transactivation of the ER result in luciferase gene induction that is easily measured in tissue lysates. Exposure to estradiol (E2) during juvenile stages of the transgenic zebrafish revealed the period of gonad differentiation to be the most responsive early life stage. In adult male transgenic zebrafish, the testis was the most sensitive and responsive target tissue to estrogens. Partial sequences of zebrafish estrogen receptor subtypes and were cloned for the first time and were found to be differentially expressed in developing fish and tissues of adult male zebrafish. The transgenic zebrafish assay is a promising new tool to rapidly determine the estrogenic potency of chemicals in vivo.

Objective: To study early motor and cognitive symptoms in Huntington disease. Design: A follow-up cohort study after a DNA test procedure in which gene carriers and noncarriers were identified among people genetically at risk for Huntington disease. Setting: Leiden University Medical Center, Department of Neurology, Leiden, the Netherlands, in cooperation with the Clinical Genetics Center Leiden and the Department of Medical Psychology and Psychotherapy, Erasmus University Rotterdam, Rotterdam, the Netherlands. Participants: Thirty-three individuals: 9 unaffected gene carriers, 6 gene carriers with motor symptoms, and 18 noncarriers of the gene for Huntington disease. Main Outcome Measures: A neuropsychologic examination covering a broad area of cognitive functioning, reaction time procedures, and motor tasks. Results: The neuropsychologic assessment showed no significant differences between presymptomatic gene carriers and noncarriers. Three motor tasks differentiated between these 2 groups on a liberal.05 P level (analysis of variance followed by the Student t test). The affected gene carriers performed less well than the presymptomatic gene carriers and the noncarriers in 10 motor tasks and 7 cognitive tasks. These differences were significant at P Conclusion: Motor symptoms play a more prominent and unequivocal role than cognitive symptoms in early stages of Huntington disease.

Paragangliomas (glomus tumors) comprise 15% of all neoplasms at the skull base. Despite extensive growth, these tumors usually do not secrete active biogenic substances into the circulation in sufficient quantities to produce symptoms. When they do secrete large amounts of catecholamines, they will cause symptoms that mimic a pheochromocytoma. The still confusing nomenclature of paragangliomas is reviewed, and the clinical work-up, surgical treatment, and follow-up of five patients with catecholamine-secreting paragangliomas of temporal bone (3), infratemporal fossa (1), and nasopharynx (1) are presented and discussed.

Summary: The relationship between cognitive deterioration and abnormalities detected by magnetic resonance imaging (MRI) was investigated to determine the radiological correlates of cognitive deterioration in hereditary cerebral hemorrhage with amyloidosis- Dutch type (HCHWA-D). Twenty HCHWA-D subjects (12 patients who had suffered one or more strokes and eight who had not suffered a stroke) were studied with MRI and underwent extensive neuropsychological examination. On MRI the number of focal lesions was counted, and white matter hyperintensities (WMHs) were scored semiquantitatively. A significant correlation between cognitive deterioration and WMH score and number of focal lesions was found. However, cognitive deterioration, WMH score, and the number of focal lesions all increase with age, and therefore their mutual correlation can be explained as an age effect. This study shows that cognitive deterioration in HCHWA-D is not correlated with abnormalities detected by MRI (number of focal lesions and subcortical WMHs) independently of age. Although a contribution of white matter changes and/or focal lesions, possibly in combination with age, to cognitive deterioration cannot be excluded. Cognitive deterioration in these HCHWA-D patients is probably primarily the result of chronic damage of amyloid angiopathy to the brain, to which may be superimposed cognitive impairment from focal cerebral hemorrhage or infarction