ResearchPad - original-articles https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks]]> https://www.researchpad.co/article/elastic_article_13744 Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long‐term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients.Approach and ResultsEXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0‐52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0‐37.0]). Elevated levels of hepatic δ‐aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ‐aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization.ConclusionsPatients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day‐to‐day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. ]]> <![CDATA[Prognostic impact of pre-existing interstitial lung disease in non-HIV patients with <i>Pneumocystis</i> pneumonia]]> https://www.researchpad.co/article/elastic_article_12763 Pre-existing interstitial lung disease (ILD) is an independent prognostic risk factor for non- HIV Pneumocystis pneumonia (PCP). Prophylaxis for PCP is needed in patients with pre-existing ILD under immunosuppression. http://bit.ly/37BGZuK

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<![CDATA[Mobilising community networks for early identification of tuberculosis and treatment initiation in Cambodia: an evaluation of a seed-and-recruit model]]> https://www.researchpad.co/article/elastic_article_12762 A tuberculosis active case finding model that mobilises community networks using a seed-and-recruit approach is associated with early identification and treatment of TB, and is also more likely to find bacteriologically confirmed TB cases in Cambodia https://bit.ly/33PWqyR

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<![CDATA[Kidney manifestations of mild, moderate and severe coronavirus disease 2019: a retrospective cohort study]]> https://www.researchpad.co/article/elastic_article_12453 Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 3 million patients globally. Previous data from Wuhan city showed that acute kidney injury (AKI), proteinuria and hematuria occurred frequently in patients with severe COVID-19. However, the prevalence of kidney injury in milder cases remains unclear.MethodsThis retrospective study included two major consecutive cohorts of COVID-19 patients in Sichuan Province. Baseline characteristics, laboratory data including renal function, proteinuria and dipstick hematuria, and other laboratory parameters were collected. A subgroup of patients was followed up for 2–4 weeks to evaluate the short-term outcome of renal impairment.ResultsOverall, 168 COVID-19-positive patients were included in the study. The majority of patients (79.7%) were diagnosed with mild or moderate disease. Half of patients presented with fever; however, in The Tibetan cohort, fever only occurred in 13.4% of patients. On hospital admission, proteinuria and dipstick hematuria were noted in 18.4% and 17.4% of patients, respectively, while AKI only occurred in one patient. Further analysis showed that severe or critical COVID-19 was associated with higher risk of proteinuria [relative risk (RR) 7.37, 95% confidence interval (CI) 2.45–22.18, P = 3.8 × 10−4] and dipstick hematuria (RR 8.30, 95% CI 2.69–25.56, P = 2.3 × 10−4). Proteinuria, dipstick hematuria, or the combination of proteinuria and hematuria could significantly predict severe or critical severe COVID-19.ConclusionsProteinuria and dipstick hematuria are not uncommon in patients with COVID-19 infection, especially in severe or critical cases. ]]> <![CDATA[Burden of Healthcare-Associated Viral Respiratory Infections in Children’s Hospitals]]> https://www.researchpad.co/article/elastic_article_11646 Although healthcare-associated (HA) viral respiratory infections (VRIs) are common in pediatrics, no benchmark for comparison exists. We aimed to determine, compare, and assess determinants of unit-specific HA-VRI incidence rates in 2 children’s hospitals.MethodsThis study was a retrospective comparison of prospective cohorts. The Montreal Children’s Hospital and the Cohen Children’s Medical Center of New York perform prospective surveillance for HA-VRI using standardized definitions that require the presence of symptoms compatible with VRI and virus detection. Cases detected between April 1, 2010, and March 31, 2013, were identified using surveillance databases. Annual incidence rates were calculated, and a generalized estimating equation model was used to assess determinants of HA-VRI rates.ResultsThe overall HA-VRI rate during the 3-year study period was significantly higher at Montreal Children’s Hospital than that at Cohen Children’s Medical Center of New York (1.91 vs 0.80 per 1000 patient-days, respectively; P < .0001). Overall, the HA-VRI incidence rate was lowest in the neonatal intensive care unit. Rates in the pediatric intensive care, oncology, and medical/surgical units were similar. The most common etiology of HA-VRI at both institutions was rhinovirus (49% of cases), followed by parainfluenza virus and respiratory syncytial virus. Hospitals with less than 50% single rooms had HA-VRI rates 1.33 (95% confidence interval, 1.29–1.37) times higher than hospitals with more than 50% single rooms for a given unit type.ConclusionsHA-VRI rates were substantial but different among 2 children’s hospitals. Future studies should examine the effect of HA-VRI and evaluate best practices for preventing such infections. ]]> <![CDATA[Rates of Microbiologically Diagnosed Infection and Pathogen Detection in Hematopoietic Stem Cell Transplant Patients]]> https://www.researchpad.co/article/elastic_article_11643 Infections remain a significant cause of mortality in hematopoietic stem cell transplant patients. Evaluations of causes of infection are often unrevealing, and at some sites, increasing rates of antimicrobial resistance have been noticed. We performed a retrospective analysis of infection rates and microbiologic testing yield, or percent of tests ordered to diagnose an infection, in the first 100 days of 30 allogeneic and 56 autologous stem cell transplants performed at San Antonio Military Medical Center from July 2011 to April 2014. Blood stream infections were diagnosed in 11.6% with a yield of 6%. Urinary tract infections were diagnosed in 2.3% with a yield of 3%. Clostridium difficile infections were diagnosed in 9.3% and testing yield was 6%. Incidence of respiratory viruses was 5.8% with 4 rhinoviruses/enteroviruses and 1 influenza virus identified. One Proteus mirabilis urinary isolate was an extended spectrum beta-lactamase producer. Five patients, 13% of allogeneic and 4% of autologous patients, died within the first 100 days post-transplantation. History of bacteremia was present in 60% of patients who died; however, only one died due to a microbiologically diagnosed infection. Improved diagnostic tests and methods are needed to increase yield of detection of infection in hematopoietic stem cell transplant patients.

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<![CDATA[Multi-sensory potential of archives in dementia care]]> https://www.researchpad.co/article/elastic_article_10988 This paper aimed to review the potential for archival items to be used to support therapeutic interventions in dementia care, with a particular focus on olfactory stimuli. Archival research was used to identify objects and to re-create authentic historical product fragrances from Boots UK. Potentially therapeutic material and smells for people living with dementia were identified and olfactory profiles created. These were characterized by strong smells and items featuring well-known brands and distinctive packaging including carbolic soap and Old English Lavender talcum powder. A dataset of items has been created for use in future research studies.

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<![CDATA[Chronic kidney disease progression and mortality risk profiles in Germany: results from the Chronic Kidney Disease Outcomes and Practice Patterns Study]]> https://www.researchpad.co/article/elastic_article_10781 Chronic kidney disease (CKD) progression among German patients in a representative setting has not been described previously. The Verband Deutsche Nierenzentren and Chronic Kidney Disease Outcomes and Practice Patterns Study established a longitudinal observational cohort among German CKD patients to research variations in patient care and outcomes in real-world nephrology practices.MethodsA cohort of CKD Stages 3 (25%) and 4 (75%) patients was established from German nephrologist-run CKD clinics in 2013–16. Linear models were used to determine the estimated glomerular filtration rate (eGFR) slope during follow-up and Cox models were used to assess outcomes of end-stage kidney disease (ESKD) and death.ResultsA total of 1834 patients (median age 75 years, 58% male, 42% diabetics, median baseline eGFR 25 mL/min/1.73 m2) were followed for a median of 29 months. More than 50% had slow or no decline and 17% declined ≥5 mL/min/1.73 m2/year. After 4.5 years, the incidence of ESKD was 8% and of deaths without ESKD 16% among patients with eGFR ≥30 mL/min/1.73 m2 and 37% and 19% for eGFR <30 mL/min/1.73 m2. Adjusted models showed higher risks of ESKD or death for patients with worse kidney function at baseline, male sex, diabetes and higher blood pressure; a higher risk of ESKD with higher albuminuria; and a higher risk of death with older age or cardiovascular comorbidity.ConclusionsRoutine nephrology care of patients in Germany comprises mostly elderly patients, many with slow CKD progression. Identification of risk factors for CKD progression and mortality may help guide resources by closer follow-up of high-risk patients. ]]> <![CDATA[Calciprotein particle inhibition explains magnesium-mediated protection against vascular calcification]]> https://www.researchpad.co/article/elastic_article_10780 Phosphate (Pi) toxicity is a strong determinant of vascular calcification development in chronic kidney disease (CKD). Magnesium (Mg2+) may improve cardiovascular risk via vascular calcification. The mechanism by which Mg2+ counteracts vascular calcification remains incompletely described. Here we investigated the effects of Mg2+ on Pi and secondary crystalline calciprotein particles (CPP2)-induced calcification and crystal maturation.MethodsVascular smooth muscle cells (VSMCs) were treated with high Pi or CPP2 and supplemented with Mg2+ to study cellular calcification. The effect of Mg2+ on CPP maturation, morphology and composition was studied by medium absorbance, electron microscopy and energy dispersive spectroscopy. To translate our findings to CKD patients, the effects of Mg2+ on calcification propensity (T50) were measured in sera from CKD patients and healthy controls.ResultsMg2+ supplementation prevented Pi-induced calcification in VSMCs. Mg2+ dose-dependently delayed the maturation of primary CPP1 to CPP2 in vitro. Mg2+ did not prevent calcification and associated gene and protein expression when added to already formed CPP2. Confirmatory experiments in human serum demonstrated that the addition of 0.2 mmol/L Mg2+ increased T50 from healthy controls by 51 ± 15 min (P < 0.05) and CKD patients by 44 ± 13 min (P < 0.05). Each further 0.2 mmol/L addition of Mg2+ led to further increases in both groups.ConclusionsOur results demonstrate that crystalline CPP2 mediates Pi-induced calcification in VSMCs. In vitro, Mg2+ delays crystalline CPP2 formation and thereby prevents Pi-induced calcification. ]]> <![CDATA[Predicting kidney failure risk after acute kidney injury among people receiving nephrology clinic care]]> https://www.researchpad.co/article/elastic_article_10779 Outcomes after acute kidney injury (AKI) are well described, but not for those already under nephrology clinic care. This is where discussions about kidney failure risk are commonplace. We evaluated whether the established kidney failure risk equation (KFRE) should account for previous AKI episodes when used in this setting.MethodsThis observational cohort study included 7491 people referred for nephrology clinic care in British Columbia in 2003–09 followed to 2016. Predictors were previous Kidney Disease: Improving Global Outcomes–based AKI, age, sex, proteinuria, estimated glomerular filtration rate (eGFR) and renal diagnosis. Outcomes were 5-year kidney failure and death. We developed cause-specific Cox models (AKI versus no AKI) for kidney failure and death, stratified by eGFR (</≥30 mL/min/1.73 m2). We also compared prediction models comparing the 5-year KFRE with two refitted models, one with and one without AKI as a predictor.ResultsAKI was associated with increased kidney failure (33.1% versus 26.3%) and death (23.8% versus 16.8%) (P  < 0.001). In Cox models, AKI was independently associated with increased kidney failure in those with an eGFR ≥30 mL/min/1.73 m2 {hazard ratio [HR] 1.35 [95% confidence interval (CI) 1.07–1.70]}, no increase in those with eGFR <30 mL/min/1.73 m2 ([HR 1.05 95% CI 0.91–1.21)] and increased mortality in both subgroups [respective HRs 1.89 (95% CI 1.56–2.30) and 1.43 (1.16–1.75)]. Incorporating AKI into a refitted kidney failure prediction model did not improve predictions on comparison of receiver operating characteristics (P = 0.16) or decision curve analysis. The original KFRE calibrated poorly in this setting, underpredicting risk.ConclusionsAKI carries a poorer long-term prognosis among those already under nephrology care. AKI may not alter kidney failure risk predictions, but the use of prediction models without appreciating the full impact of AKI, including increased mortality, would be simplistic. People with kidney diseases have risks beyond simply kidney failure. This complexity and variability of outcomes of individuals is important. ]]> <![CDATA[The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia]]> https://www.researchpad.co/article/elastic_article_10777

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<![CDATA[Modulation of Post-Traumatic Immune Response Using the IL-1 Receptor Antagonist Anakinra for Improved Visual Outcomes]]> https://www.researchpad.co/article/elastic_article_10495 The purpose of this study was to characterize acute changes in inflammatory pathways in the mouse eye after blast-mediated traumatic brain injury (bTBI) and to determine whether modulation of these pathways could protect the structure and function of retinal ganglion cells (RGC). The bTBI was induced in C57BL/6J male mice by exposure to three 20 psi blast waves directed toward the head with the body shielded, with an inter-blast interval of one hour. Acute cytokine expression in retinal tissue was measured through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) four hours post-blast. Increased retinal expression of interleukin (lL)-1β, IL-1α, IL-6, and tumor necrosis factor (TNF)α was observed in bTBI mice exposed to blast when compared with shams, which was associated with activation of microglia and macroglia reactivity, assessed via immunohistochemistry with ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein, respectively, one week post-blast. Blockade of the IL-1 pathway was accomplished using anakinra, an IL-1RI antagonist, administered intra-peritoneally for one week before injury and continuing for three weeks post-injury. Retinal function and RGC layer thickness were evaluated four weeks post-injury using pattern electroretinogram (PERG) and optical coherence tomography (OCT), respectively. After bTBI, anakinra treatment resulted in a preservation of RGC function and RGC structure when compared with saline treated bTBI mice. Optic nerve integrity analysis demonstrated a trend of decreased damage suggesting that IL-1 blockade also prevents axonal damage after blast. Blast exposure results in increased retinal inflammation including upregulation of pro-inflammatory cytokines and activation of resident microglia and macroglia. This may explain partially the RGC loss we observed in this model, as blockade of the acute inflammatory response after injury with the IL-1R1 antagonist anakinra resulted in preservation of RGC function and RGC layer thickness.

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<![CDATA[Cerium Oxide Nanoparticles Improve Outcome after <i>In Vitro</i> and <i>In Vivo</i> Mild Traumatic Brain Injury]]> https://www.researchpad.co/article/elastic_article_10489 Mild traumatic brain injury results in aberrant free radical generation, which is associated with oxidative stress, secondary injury signaling cascades, mitochondrial dysfunction, and poor functional outcome. Pharmacological targeting of free radicals with antioxidants has been examined as an approach to treatment, but has met with limited success in clinical trials. Conventional antioxidants that are currently available scavenge a single free radical before they are destroyed in the process. Here, we report for the first time that a novel regenerative cerium oxide nanoparticle antioxidant reduces neuronal death and calcium dysregulation after in vitro trauma. Further, using an in vivo model of mild lateral fluid percussion brain injury in the rat, we report that cerium oxide nanoparticles also preserve endogenous antioxidant systems, decrease macromolecular free radical damage, and improve cognitive function. Taken together, our results demonstrate that cerium oxide nanoparticles are a novel nanopharmaceutical with potential for mitigating neuropathological effects of mild traumatic brain injury and modifying the course of recovery.

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<![CDATA[Influence of Blood–Brain Barrier Integrity on Brain Protein Biomarker Clearance in Severe Traumatic Brain Injury: A Longitudinal Prospective Study]]> https://www.researchpad.co/article/elastic_article_10486 Brain protein biomarker clearance to blood in traumatic brain injury (TBI) is not fully understood. The aim of this study was to analyze the effect that a disrupted blood–brain barrier (BBB) had on biomarker clearance. Seventeen severe TBI patients admitted to Karolinska University Hospital were prospectively included. Cerebrospinal fluid (CSF) and blood concentrations of S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE) were analyzed every 6–12 h for ∼1 week. Blood and CSF albumin were analyzed every 12–24 h, and BBB integrity was assessed using the CSF:blood albumin quotient (QA). We found that time-dependent changes in the CSF and blood levels of the two biomarkers were similar, but that the correlation between the biomarkers and QA was lower for NSE (ρ = 0.444) than for S100B (ρ = 0.668). Because data were longitudinal, we also conducted cross correlation analyses, which indicated a directional flow and lag-time of biomarkers from CSF to blood. For S100B, this lag-time could be ascribed to BBB integrity, whereas for NSE it could not. Upon inferential modelling, using generalized least square estimation (S100B) or linear mixed models (NSE), QA (p = 0.045), time from trauma (p < 0.001), time from trauma2 (p = 0.023), and CSF biomarker levels (p = 0.008) were independent predictors of S100B in blood. In contrast, for NSE, only time from trauma was significant (p < 0.001). These findings are novel and important, but must be carefully interpreted because of different characteristics between the two proteins. Nonetheless, we present the first data that indicate that S100B and NSE are cleared differently from the central nervous system, and that both the disrupted BBB and additional alternative pathways, such as the recently described glymphatic system, may play a role. This is of importance both for clinicians aiming to utilize these biomarkers and for the pathophysiological understanding of brain protein clearance, but warrants further examination.

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<![CDATA[rhIGF-1/BP3 Preserves Lung Growth and Prevents Pulmonary Hypertension in Experimental Bronchopulmonary Dysplasia]]> https://www.researchpad.co/article/elastic_article_10247 Rationale: Antenatal factors, such as chorioamnionitis, preeclampsia, and postnatal injury, are associated with an increased risk for bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) after preterm birth. IGF-1 (insulin-like growth factor-1) is markedly decreased in normal preterm infants, but whether IGF-1 treatment can prevent BPD or PH is unknown.

Objectives: To evaluate whether postnatal treatment with rhIGF-1 (recombinant human IGF-1)/BP3 (binding peptide 3) improves lung growth and prevents PH in two antenatal models of BPD induced by intraamniotic exposure to endotoxin (ETX) or sFlt-1 (soluble fms-like tyrosine kinase 1), and in a postnatal model due to prolonged hyperoxia.

Methods: ETX or sFlt-1 were administered into the amniotic sac of pregnant rats at Embryonic Day 20 to simulate antenatal models of chorioamnionitis and preeclampsia, respectively. Pups were delivered by cesarean section at Embryonic Day 22 and treated with rhIGF-1/BP3 (0.02–20 mg/kg/d intraperitoneal) or buffer for 2 weeks. Study endpoints included radial alveolar counts (RACs), vessel density, and right ventricular hypertrophy (RVH). Direct effects of rhIGF-1/BP3 (250 ng/ml) on fetal lung endothelial cell proliferation and tube formation and alveolar type 2 cell proliferation were studied by standard methods in vitro.

Measurements and Main Results: Antenatal ETX and antenatal sFlt-1 reduced RAC and decreased RVH in infant rats. In both models, postnatal rhIGF-1/BP3 treatment restored RAC and RVH to normal values when compared with placebo injections. rhIGF-1/BP3 treatment also preserved lung structure and prevented RVH after postnatal hyperoxia. In vitro studies showed that rhIGF-1/BP3 treatment increased lung endothelial cell and alveolar type 2 cell proliferation.

Conclusions: Postnatal rhIGF-1/BP3 treatment preserved lung structure and prevented RVH in antenatal and postnatal BPD models. rhIGF-1/BP3 treatment may provide a novel strategy for the prevention of BPD in preterm infants.

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<![CDATA[Blue care: a systematic review of blue space interventions for health and wellbeing]]> https://www.researchpad.co/article/elastic_article_10219 There is increasing interest in the potential use of outdoor water environments, or blue space, in the promotion of human health and wellbeing. However, therapeutic nature-based practices are currently outpacing policy and the evidence base for health or wellbeing benefits of therapeutic interventions within blue space has not been systematically assessed. This systematic review aims to address the gap in understanding the impacts of blue space within existing interventions for targeted individuals. A systematic review was carried out, searching Google Scholar, SCOPUS, PubMed, etc. through to August 2017. Only blue space interventions were included that were specifically designed and structured with a therapeutic purpose for individuals with a defined need and did not include nature-based promotion projects or casual recreation in the outdoors. Thirty-three studies met the inclusion criteria and were assessed. Overall, the studies suggest that blue care can have direct benefit for health, especially mental health and psycho-social wellbeing. The majority of papers found a positive or weak association between blue care and health and wellbeing indicators. There was also some evidence for greater social connectedness during and after interventions, but results were inconsistent and mixed across studies with very few findings for physical health. This is the first systematic review of the literature on blue care. In summary, it has been shown that mental health, especially psycho-social wellbeing, can be improved with investment in blue spaces. Key areas for future research include improving understanding of the mechanisms through which blue care can improve public health promotion.

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<![CDATA[Histologic patterns of liver injury induced by anti-PD-1 therapy]]> https://www.researchpad.co/article/elastic_article_10192 Nivolumab and pembrolizumab—two monoclonal antibodies that block human programmed cell death-1 (PD-1)—have been successfully used to treat patients with multiple advanced malignancies. The histologic patterns of hepatic toxicity induced by anti-PD-1 treatment have not been well studied and the aim of this study was to explore them.MethodsEight patients with advanced malignancies who were treated with either nivolumab or pembrolizumab were identified from five institutions. These patients had no history of underlying liver disease and a viral hepatitis panel was negative in all patients.ResultsSeven of eight patients exhibited mild to moderate gastrointestinal symptoms such as abdominal pain, fatigue, nausea, vomiting, and jaundice after anti-PD-1 treatment. Significant elevations in liver-chemistry tests were detected in all patients. Six cases (6/8) demonstrated an acute lobular hepatitis pattern of histologic injury. The remaining two cases showed different histologic patterns of injury: steatohepatitis with mild cholestasis (1/8) and pure acute cholestatic injury (1/8). No case showed typical features of autoimmune hepatitis. The liver function recovered in all eight cases after cessation of anti-PD-1 agents and with immunosuppressive therapy.ConclusionsOur study suggests that screening patients for abnormal liver-function tests prior to anti-PD-1 therapy as well as periodic monitoring of liver-function tests are necessary to prevent severe liver injury. Rather than causing classical autoimmune hepatitis, PD-1 inhibitors appear to produce an immune-mediated nonspecific acute hepatitis. Drug cessation, without steroid therapy, may therefore be sufficient in some patients. ]]> <![CDATA[A peer navigation intervention to prevent HIV among mixed immigrant status Latinx GBMSM and transgender women in the United States: outcomes, perspectives and implications for PrEP uptake]]> https://www.researchpad.co/article/elastic_article_10138 The Latinx population in the United States is disproportionately affected by HIV. Our community-based participatory research partnership developed, implemented and evaluated a Spanish-language peer navigation intervention designed to increase HIV testing and condom use among social networks of immigrant Spanish-speaking Latinx gay, bisexual and other men who have sex with men (GBMSM) and transgender women (TW). We randomized 21 social networks of Latinx GBMSM and TW, ages 18–55 years, to the intervention, known as HOLA, or a waitlist control group. Social network participants (n = 166) completed structured assessments at baseline and 12-month follow-up (24 months after baseline). Follow-up retention was 95%. Individual in-depth interviews with a sample of participants documented their intervention-related experiences, needs, and priorities to inform future research. At follow-up, HOLA participants reported increased HIV testing (adjusted odds ratio = 8.3; 95% CI = 3.0–23.0; P < 0.0001). All study participants reported increased condom use; there was no significant difference between HOLA and waitlist control participants. In-depth interviews identified critical intervention elements and impacts and community needs and priorities. The HOLA intervention is effective for increasing HIV testing among Latinx GBMSM and TW, an initial step within the HIV prevention and care continua, and may be adaptable to promote pre-exposure prophylaxis uptake.

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<![CDATA[Implementation of initiatives to prevent student stress: process evaluation findings from the Healthy High School study]]> https://www.researchpad.co/article/elastic_article_10136 Process evaluation of public health interventions is important for understanding intervention results and can help explain why interventions succeed or fail. This study evaluated implementation of a school-based intervention combining educational and environmental strategies to prevent stress among Danish high school students. We investigated dose delivered, dose received, fidelity, appreciation, barriers and facilitators at the 15 intervention schools using mixed methods and multiple data sources: questionnaires among students, teachers and school coordinators; semi-structured interviews with school coordinators; telephone interviews with student counsellors; and focus group interviews with students and teachers. Implementation varied by schools and classes. Half of the intervention schools delivered the environmental strategies. For the educational strategies, dose delivered differed according to intervention provider. Students reported a lower dose received compared with dose delivered reported by school staff. Overall, student counsellors, school coordinators and students—especially those with low perceived stress—were satisfied with the stress preventive initiatives while teacher satisfaction varied. Five main barriers and three facilitators for implementation were identified. The use of multiple data sources and data methods created new knowledge of the implementation process which is important for the interpretation of effect evaluation and development of future interventions.

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<![CDATA[The TLR9 Agonist Cobitolimod Induces IL10-Producing Wound Healing Macrophages and Regulatory T Cells in Ulcerative Colitis]]> https://www.researchpad.co/article/elastic_article_10038 The topically applied Toll-like receptor 9 [TLR9] agonist cobitolimod is a first-in-class DNA-based oligonucleotide with demonstrated therapeutic efficacy in clinical trials with ulcerative colitis [UC] patients. We here characterized its anti-inflammatory mechanism in UC.MethodsLuminal cobitolimod administration was evaluated in an experimental dextran sodium sulfate [DSS]-induced colitis model. Cultured blood and mucosal cells from UC patients were treated with cobitolimod and analysed via microarray, quantitative real-time PCR, ELISA and flow cytometry. Intestinal slides of cobitolimod-treated UC patients were analysed by immunohistochemistry.ResultsCobitolimod administration markedly suppressed experimental colitis activity, and microarray analyses demonstrated mucosal IL10 upregulation and suppression of IL17 signalling pathways. Cobitolimod treatment was associated with significant induction of mucosal IL10+Tr1 and Treg cells and suppression of Th17 cells. TLR9 knockout mice indicated that cobitolimod requires TLR9 signalling for IL10 induction. In UC patients, mucosal TLR9 levels correlated with severity of inflammation. Cobitolimod inhibited IL17A and IL17F, but increased IL10 and FoxP3 expression in cultured intestinal UC T cells. Cobitolimod-mediated suppression of intestinal IL17+T cells was abrogated by IL10 blockade. Furthermore, cobitolimod led to heightened IL10 production by wound healing macrophages. Immunohistochemistry in intestinal biopsies of cobitolimod-treated UC patients indicated increased presence of IL10+mononuclear and regulatory T cells, as well as reduction of IL17+cells.ConclusionActivation of TLR9 via cobitolimod might represent a novel therapeutic approach in UC, as it suppresses Th17 cells and induces anti-inflammatory IL10+macrophages and regulatory T cells, thereby modifying the dysregulated intestinal cytokine balance.PodcastThis article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast ]]>