Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy.

Background: The alternative complement pathway plays a key role in the pathogenesis of IgA nephropathy. Iptacopan specifically binds to factor B and inhibits the alternative pathway.

Methods: In this phase 3, double-blind, randomized, placebo-controlled trial, we enrolled adults with biopsy-confirmed IgA nephropathy and proteinuria (defined as a 24-hour urinary protein-to-creatinine ratio of ≥1 [with protein and creatinine both measured in grams]) despite optimized supportive therapy.

Readmission Rates Among Acute Reperfusion Treatment Modalities for Patients With Ischemic Stroke.

Background And Purpose: Understanding various aspects associated with readmission after acute ischemic stroke (AIS) is an important priority. Our study aims to examine whether 60-day readmission rates differed among patients with AIS who were treated with different acute reperfusion treatment modalities along with associated clinical factors.

Methods: This is a retrospective analysis of a continuous cohort of patient with AIS, who received either intravenous recombinant tissue plasminogen activator (IV rtPA), endovascular treatment (EVT) or both, and were discharged alive.

Final report of the phase II NEXT/CNS-GCT-4 trial: GemPOx followed by marrow-ablative chemotherapy for recurrent intracranial germ cell tumors.

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).

Phase synchronization during the processing of taxonomic and thematic relations.

Semantic relations include "taxonomic" relations based on shared features and "thematic" relations based on co-occurrence in events. The "dual-hub" account proposes that the anterior temporal lobe (ATL) is functionally specialized for taxonomic relations and the inferior parietal lobule (IPL) for thematic relations. This study examined this claim by analyzing the intra- and inter-region phase synchronization of intracranial EEG data from electrodes in the ATL, IPL, and two subregions of the semantic control network: left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG).

Digital Therapeutic Device for Urinary Incontinence: A Longitudinal Analysis at 6 and 12 Months.

Objective: To evaluate the long-term efficacy of an 8-week regimen of pelvic floor muscle training guided by a motion-based digital therapeutic device compared with a standard home program in the treatment of stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (MUI).

Methods: The primary virtual trial was conducted from October 2020 to March 2021; 363 women with SUI or stress-predominant MUI were randomized to complete pelvic floor muscle training using the device (intervention group) or a standard home pelvic floor muscle training program (control group) for 8 weeks. Primary outcomes included change in UDI-6 (Urogenital Distress Inventory, Short Form) score and SUI episodes on a 3-day bladder diary.

miR-486 is essential for muscle function and suppresses a dystrophic transcriptome.

miR-486 is a muscle-enriched microRNA, or "myomiR," that has reduced expression correlated with Duchenne muscular dystrophy (DMD). To determine the function of miR-486 in normal and dystrophin-deficient muscles and elucidate miR-486 target transcripts in skeletal muscle, we characterized knockout mice ( KO). KO mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects were exacerbated in KO: (DKO) mice.

Digital Therapeutic Device for Urinary Incontinence: A Randomized Controlled Trial.

Objective: To evaluate whether pelvic floor muscle training using a motion-based digital intravaginal device is more effective than home pelvic floor muscle training for treatment of stress or stress-predominant mixed urinary incontinence (UI).

Methods: In a remote, virtually executed 8-week prospective randomized controlled superiority trial, women with stress or stress-predominant mixed UI were randomized to pelvic floor muscle training using a motion-based digital therapeutic device or a home training program using written and narrated instructions. Primary outcomes were change in UDI-6 (Urogenital Distress Inventory, Short Form) score and stress urinary incontinence (SUI) episodes on a 3-day bladder diary.

Lesion correlates of auditory sentence comprehension deficits in post-stroke aphasia.

Auditory sentence comprehension requires coordination of multiple levels of processing: auditory-phonological perception, lexical-semantic comprehension, syntactic parsing and discourse construction, as well as executive functions such as verbal working memory (WM) and cognitive control. This study examined the lesion correlates of sentence comprehension deficits in post-stroke aphasia, building on prior work on this topic by using a different and clinically-relevant measure of sentence comprehension (the Token Test) and multivariate (SCCAN) and connectome-based lesion-symptom mapping methods. The key findings were that lesions in the posterior superior temporal lobe and inferior frontal gyrus (pars triangularis) were associated with sentence comprehension deficits, which was observed in both mass univariate and multivariate lesion-symptom mapping.

Performance of a Vaginal Panel Assay Compared With the Clinical Diagnosis of Vaginitis.

Objective: To compare the performance of vaginitis diagnosis based on clinical assessment to molecular detection of organisms associated with bacterial vaginosis, vulvovaginal candidiasis, and Trichomonas vaginalis using a vaginal panel assay.

Methods: This cross-sectional diagnostic accuracy study included 489 enrolled participants from five collection sites where those with vaginitis symptoms had a vaginal assay swab collected during their visit and a clinical diagnosis made. The swab was later sent to a separate testing site to perform the vaginal panel assay.

Intracranial EEG evidence of functional specialization for taxonomic and thematic relations.

The dual-hub account posits that the neural organization of semantic knowledge is segregated by the type of semantic relation with anterior temporal lobe (ATL) specializing for taxonomic relations and inferior parietal lobule (IPL) for thematic relations. This study critically examined this account by recording intracranial EEG from an array of depth electrodes within ATL, IPL, and two regions within the semantic control network, inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG), while 17 participants with refractory epilepsy completed a semantic relatedness judgment task. We observed a significant difference between relation types in ATL and IPL approximately 600-800 ms after trial presentation, and no significant differences in IFG or pMTG.

Patient Perspectives on Gout and Gout Treatments: A Patient Panel Discussion That Informed the 2020 American College of Rheumatology Treatment Guideline.

Objective: The objective of this study was to understand patient perspectives to inform the voting process for the 2020 American College of Rheumatology (ACR) gout treatment guideline.

Methods: We conducted a panel meeting of eight patients with gout in Birmingham, Alabama. Patients were referred to the project by private and academic rheumatologists in the Birmingham area.

Development of a computerized paediatric intensive care unit septic shock pathway: improving user experience.

The purpose of this study was to understand the user experience with a computerized septic shock protocol relative to the workflow of Paediatric Intensive Care Unit clinicians. The need for data-driven, condition-specific, computerized protocols in the intensive care unit helps improve decision-making at the bedside. PICU clinicians were interviewed and given pre-and post-implementation surveys asking their opinions on the current PICU septic shock protocol, as well as the current electronic health record being used at [Paediatric Academic Medical Center].

Teen Driving Education in a Pediatric Emergency Department: Effectiveness of a Toolkit.

Objectives: In the United States, the leading cause of death for adolescents aged 16 to 24 years is motor vehicle crashes, with Alabama ranked as the second-worst state in the nation for teen driving deaths. We sought to determine the efficacy of teenage driving education within the setting of the pediatric emergency department and to assess the driving habits of teenagers and their parents and their understanding of the Alabama Graduated Driver's License (GDL) law.

Methods: Surveys were administered to noncritically ill teenagers aged 13 to 19 years and their parents who presented to the children's emergency department.

Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy.

MEGF10 myopathy is a rare inherited muscle disease that is named after the causative gene, MEGF10. The classic phenotype, early onset myopathy, areflexia, respiratory distress and dysphagia, is severe and immediately life-threatening. There are no disease-modifying therapies.

Strength and Temporal Variance of the Default Mode Network to Investigate Chronic Mild Traumatic Brain Injury in Service Members with Psychological Trauma.

Background: There is a significant number of military personnel with a history of mild traumatic brain injury (mTBI) who suffer from comorbid posttraumatic stress symptoms (PTS). Although there is evidence of disruptions of the default mode network (DMN) associated with PTS and mTBI, previous studies have only studied static connectivity while ignoring temporal variability of connectivity.

Objective: To assess DMN disrupted or dysregulated neurocircuitry, cognitive functioning, and psychological health of active-duty military with mTBI and PTS.

VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles.

Background: The next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659-tezacaftor-ivacaftor), was developed to restore the function of Phe508del CFTR protein in patients with cystic fibrosis.

Methods: We evaluated the effects of VX-659-tezacaftor-ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659-tezacaftor-ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del-MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del-Phe508del genotype).

The NOTCH1/SNAIL1/MEF2C Pathway Regulates Growth and Self-Renewal in Embryonal Rhabdomyosarcoma.

Tumor-propagating cells (TPCs) share self-renewal properties with normal stem cells and drive continued tumor growth. However, mechanisms regulating TPC self-renewal are largely unknown, especially in embryonal rhabdomyosarcoma (ERMS)-a common pediatric cancer of muscle. Here, we used a zebrafish transgenic model of ERMS to identify a role for intracellular NOTCH1 (ICN1) in increasing TPCs by 23-fold.

2017 Update of the Drug Resistance Mutations in HIV-1.

The 2017 edition of the IAS-USA drug resistance mutations list updates the figures last published in November 2015. The mutations listed are those that have been identified by specific criteria for evidence and drugs described. The figures are designed to assist practitioners in identifying key mutations associated with resistance to antiretroviral drugs and, therefore, in making clinical decisions regarding antiretroviral therapy.

Rate of shunt revision as a function of age in patients with shunted hydrocephalus due to myelomeningocele.

OBJECTIVE It is generally accepted that cerebrospinal fluid shunts fail most frequently in the first years of life. The purpose of this study was to describe the risk of shunt failure for a given patient age in a well-defined cohort with shunted hydrocephalus due to myelomeningocele (MMC). METHODS The authors analyzed data from their institutional spina bifida research database including all patients with MMC and shunted hydrocephalus.

Syndecan-1 (CD138) Suppresses Apoptosis in Multiple Myeloma by Activating IGF1 Receptor: Prevention by SynstatinIGF1R Inhibits Tumor Growth.

Syndecan-1 (Sdc1/CD138) expression is linked to disease severity in multiple myeloma, although the causal basis for this link remains unclear. Here we report that capture of the IGF1 receptor (IGF1R) by Sdc1 suppresses ASK1-dependent apoptosis in multiple myeloma cells. Sdc1 binds two different fractions of IGF1R, one that is constitutively active and a second that is activated by IGF1 ligand.

Therapeutic Error Calls Among Older Adults Reported to a Regional Poison Control Center in Alabama.

Objectives: Although Americans aged 65 years and older account for only 13.0% of the population, they consume one-third of all prescription medications each year. Increased life expectancy, age-related deterioration in health, and polypharmacy lead to a significant risk of potential medication errors.

Pulmonary Artery Pressure-Guided Heart Failure Management Reduces 30-Day Readmissions.

Background: This study examines the impact of pulmonary artery pressure-guided heart failure (HF) care on 30-day readmissions in Medicare-eligible patients.

Methods And Results: The CardioMicroelectromechanical system (CardioMEMS) Heart Sensor Allows Monitoring of Pressures to Improve Outcomes in New York Heart Association Class III Heart Failure Patients (CHAMPION) Trial included 550 patients implanted with a permanent MEMS-based pressure sensor in the pulmonary artery. Subjects were randomized to a treatment group (uploaded pressures were made available to investigators) or a control group (uploaded pressures were not made available to investigators).