Incidence and Risk Factors for Hypertension among Children with Nephrotic Syndrome.

Objectives: To determine incidence and risk factors for hypertension in childhood nephrotic syndrome.

Study Design: Using data from the Insight into Nephrotic Syndrome (INSIGHT) study, a prospective observational childhood nephrotic syndrome cohort from Toronto, Canada, we evaluated hypertension incidence and time-to-hypertension overall and stratified by 1) steroid-resistance or steroid-sensitivity, and 2) frequently-relapsing, steroid dependent, or infrequently-relapsing. Hypertension was defined as stage 1-2 hypertensive blood pressure on two consecutive visits or anti-hypertensive medication initiation.

Social networks and COVID-19 vaccination intention in Dutch middle-aged and older adults in 2020: Insights into individual, interpersonal, community, and societal determinants - The SaNAE study.

Background: Social networks, our social relationships, influence the spread of infectious diseases and preventive behaviors such as vaccination. Here, we aimed to assess which individual, interpersonal (social network characteristics), community and societal factors are associated with coronavirus disease 2019 (COVID-19) vaccination intention during the second wave of the COVID-19 pandemic in 2020, prior to vaccine availability.

Methods: This cross-sectional study collected primary data from 5,001 community-dwelling adults aged 40 years and older in the Netherlands, using an online questionnaire from August and November 2020.

Orthopaedic trauma residency programs: Perspectives from different countries across the world.

The ability to manage the myriad of musculoskeletal conditions successfully requires multiple years of training. Access to and completion of orthopaedic surgical training entails an often grueling, highly regulated path to certification to practice. Although the world is more connected than ever, the question is whether the local certification criteria for medical specialists leads to a generic residency program and a similar training in all countries.

Genetic modulation of the gene reduces anxiety-related behavior in mice.

The expanding field of precision gene editing using CRISPR/Cas9 has demonstrated its potential as a transformative technology in the treatment of various diseases. However, whether this genome-editing tool could be used to modify neural circuits in the central nervous system (CNS), which are implicated in complex behavioral traits, remains uncertain. In this study, we demonstrate the feasibility of noninvasive, intranasal delivery of adeno-associated virus serotype 9 (AAV9) vectors containing CRISPR/Cas9 cargo within the CNS resulting in modification of the receptor gene.

Vertigoheel promotes rodent cognitive performance in multiple memory tests.

Introduction: Cognitive impairment associated with old age or various brain disorders may be very disabling for affected individuals, placing their carers and public health services under considerable stress. The standard-of-care drugs produce only transient improvement of cognitive impairment in older people, so the search for novel, safe and effective therapeutics that would help to reverse or delay cognitive impairment is warranted. Repurposing pharmacological therapies with well-established safety record for additional indications is a promising recent trend in drug development.

Differences in mobile food market customer outcomes between 2019 and 2021.

Objectives: To evaluate the outcomes of increasing mobile market service from mostly biweekly in 2019 to weekly in 2021.

Design: Repeated, cross-sectional customer intercept surveys.

Sample: Mobile market customers in Summers 2019 (N = 302) and 2021 (N = 72).

Development and validation of a questionnaire to measure the severity of pain, functional limitations, and reduction of sports ability for german-speaking patients with osteochondral lesions of the ankle (OCLA-G).

Background: There is no patient-reported functional scale specific for osteochondral lesion of the ankle (OCLA). Therefore, the objectives of this study were to develop a questionnaire that measures symptom severity, function, and sports capacity in patients with osteochondral lesions of the ankle and to determine the psychometric properties of the tool in German language (OCLA-G).

Methods: The OCLA-G questionnaire was developed according to the COSMIN guidelines.

Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial.

Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.

Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.

Lenalidomide induced pneumonitis.

Introduction: Iatrogenic lung injury is a very rare, albeit serious complication with antineoplastic therapy, including immunomodulatory drugs. Pneumonitis typically presents clinically with symptoms such as cough, dyspnea, fever, and hypoxemia. Radiographic evaluation often demonstrates diffuse, patchy infiltrates and ground-glass opacities.

Association of glial tau pathology and LATE-NC in the ageing brain.

Ageing-related pathologies of the brain include neurofibrillary tangles, argyrophilic grains, ageing-related tau astrogliopathy (ARTAG), limbic-predominant age-related TDP-43 encephalopathy-neuropathological change (LATE-NC), vascular pathology and corpora amylacea. This study used an unbiased approach to evaluate a broad range of pathologies in an unselected European community-dwelling ageing cohort of 101 individuals (77-90 years). Pathological alterations observed included neurofibrillary tangles and corpora amylacea in all cases, ARTAG (79%), Thal amyloid-β phase >1 (60%), cerebral amyloid angiopathy (39%), Lewy bodies (22%), LATE-NC (21%), oligodendroglial tau-positive coiled bodies (33%), and argyrophilic grains (15%).

Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer.

Clinical trials reporting the robust antitumor activity of immune checkpoint inhibitors (ICIs) in microsatellite instability-high (MSI-H) solid tumors have used tissue-based testing to determine the MSI-H status. This study assessed if MSI-H detected by a plasma-based circulating tumor DNA liquid biopsy test predicts robust response to ICI in patients with pancreatic ductal adenocarcinoma (PDAC). Retrospective analysis of patients with PDAC and MSI-H identified on Guardant360 from October 2018 to April 2021 was performed; clinical outcomes were submitted by treating providers.

Implementing a fluid volume management program to decrease intra-dialytic hypotensive events in a paediatric in-centre haemodialysis unit: a quality improvement project.

Background: Intra-dialytic hypotension (IDH) is the most common serious adverse event in paediatric haemodialysis (HD). Repeated IDH results in chronic multi-organ damage and increased mortality. At the Hospital for Sick Children, Toronto, retrospective data from all in-centre HD sessions revealed frequently occurring IDH events (16.

Recombinant botulinum neurotoxin serotype A1 in vivo characterization.

Clinically used botulinum neurotoxins (BoNTs) are natural products of Clostridium botulinum. A novel, recombinant BoNT type A1 (rBoNT/A1; IPN10260) has been synthesized using the native amino acid sequence expressed in Escherichia coli and has previously been characterized in vitro and ex vivo. Here, we aimed to characterize rBoNT/A1 in vivo and evaluate its effects on skeletal muscle.

Underserved and Undermeasured: a Mixed-Method Analysis of Family-Centered Care and Care Coordination for Low-Income Minority Families of Children with Autism Spectrum Disorder.

This study examined how a racially and socioeconomically diverse group of caregivers of children with autism spectrum disorder (ASD) responds to national standard measures of family-centered care (FCC) and care coordination (CC) and what aspects of quality care are missing from these measures. Based on survey and interview data collected from 70 caregivers who have a child with ASD that receive services at a community-based autism clinic located in Atlanta, GA, we compared proportions of answers to FCC and CC questions to national and state representative data using chi-square analyses and contextualized our findings through a thematic analysis of qualitative interviews. Compared to national- and state-level data, the Atlanta autism clinic data had a higher percentage of participants who identified as Black, relied on public health insurance, and lived below 200% of the federal poverty line.

Progression of Gender Dysphoria in Children and Adolescents: A Longitudinal Study.

Background And Objectives: The progression of gender-expansive behavior to gender dysphoria and to gender-affirming hormonal treatment (GAHT) in children and adolescents is poorly understood.

Methods: A cohort of 958 gender-diverse (GD) children and adolescents who did not have a gender dysphoria-related diagnosis (GDRD) or GAHT at index were identified. Rates of first GDRD and first GAHT prescription were compared across demographic groups.

Author Correction: A Small Compound Targeting Prohibitin with Potential Interest for Cognitive Deficit Rescue in Aging mice and Tau Pathology Treatment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The use of the dynamic weight bearing test to assess the effects of acute, intramuscularly administered botulinum neurotoxin type A1 in rats.

Assessing the efficacy of botulinum neurotoxin (BoNT) is essential given the growing number of BoNT products used in the clinic. Here, we evaluated the dynamic weight bearing (DWB) test for sensitivity to paralytic effects of BoNT-A following intramuscular administration. The toxin was administered into the gastrocnemius lateralis as a single bolus or into the gastrocnemius lateralis and medialis as two boluses.

Temperatures, diagnostics and treatment in pediatric cancer patients with fever in neutropenia, NCT01683370.

In pediatric oncology, there is no evidence-based definition of the temperature limit defining fever (TLDF), which itself is essential for the definition of fever in chemotherapy-induced severe neutropenia (FN). Lowering the TLDF can increase the number of FN episodes diagnosed. This prospective, single center observational study collected data on all temperature measurements, complete blood counts (CBCs), and measures of diagnostics and therapy performed at and after FN diagnosis in pediatric oncology patients using a high standard TLDF (39 °C ear temperature).

A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma.

Background: MET signaling is a well described mechanism of resistance to anti-EGFR therapy, and MET overexpression is common in head and neck squamous cell carcinomas (HNSCCs). In the current trial, the authors compared the oral MET inhibitor tivantinib (ARQ197) in combination with cetuximab (the TC arm) versus a control arm that received cetuximab monotherapy (C) in patients with recurrent/metastatic HNSCC.

Methods: In total, 78 evaluable patients with cetuximab-naive, platinum-refractory HNSCC were enrolled, including 40 on the TC arm and 38 on the C arm (stratified by human papillomavirus [HPV] status).

A Small Compound Targeting Prohibitin with Potential Interest for Cognitive Deficit Rescue in Aging mice and Tau Pathology Treatment.

Neurodegenerative diseases, including Alzheimer's and Parkinson's disease, are characterized by increased protein aggregation in the brain, progressive neuronal loss, increased inflammation, and neurogenesis impairment. We analyzed the effects of a new purine derivative drug, PDD005, in attenuating mechanisms involved in the pathogenesis of neurodegenerative diseases, using both in vivo and in vitro models. We show that PDD005 is distributed to the brain and can rescue cognitive deficits associated with aging in mice.

Discovery of BNC375, a Potent, Selective, and Orally Available Type I Positive Allosteric Modulator of α7 nAChRs.

Positive allosteric modulators (PAMs) of α7 nAChRs can have different properties with respect to their effects on channel kinetics. Type I PAMs amplify peak channel response to acetylcholine but do not appear to influence channel desensitization kinetics, whereas Type II PAMs both increase channel response and delay receptor desensitization. Both Type I and Type II PAMs are reported in literature, but there are limited reports describing their structure-kinetic profile relationships.

Chronic Traumatic Encephalopathy (CTE) Is Absent From a European Community-Based Aging Cohort While Cortical Aging-Related Tau Astrogliopathy (ARTAG) Is Highly Prevalent.

This study determined the prevalence of chronic traumatic encephalopathy (CTE) and cortical aging-related tau astrogliopathy (ARTAG) in a European community-based population (n = 310). The frontal, parietal, and temporal cortices, representing initial stages of CTE were assessed. No case fulfilling CTE consensus criteria was found.