Donor-specific immune senescence as a candidate biomarker of operational tolerance following liver transplantation in adults: Results of a prospective, multicenter cohort study.

Immunosuppression can be withdrawn from selected liver transplant recipients, although robust clinical predictors of tolerance remain elusive. The Immune Tolerance Network ITN056ST study (OPTIMAL; NCT02533180) assessed clinical outcomes and mechanistic correlates of phased immunosuppression withdrawal (ISW) in nonautoimmune, nonviral adult liver transplant recipients. Enrolled subjects were ≥3 years posttransplant with minimal/absent inflammation or fibrosis on a screening liver biopsy.

Prader-Willi syndrome: guidance for children and transition into adulthood.

Prader-Willi syndrome (PWS) is a rare orphan disease and complex genetic neurodevelopmental disorder, with a birth incidence of approximately 1 in 10,000-30,000. Management of people with PWS requires a multi-disciplinary approach, ideally through a multi-disciplinary team (MDT) clinic with community support. Hypotonia, poor feeding and faltering growth are characteristic features in the neonatal period, followed by hyperphagia and risk of rapid weight gain later in childhood.

Examining the utility of near infrared light as pre-exposure therapy to mitigate temporary noise-induced hearing loss in humans.

Introduction: This study sought to determine the effect of Occupational Safety and Health Administration (OSHA) compliant noise on auditory health and assess whether pre-noise near infrared (NIR) light therapy can mitigate the effects of noise exposure.

Methods: Over four visits, participants ( = 30, NCT#: 03834714) with normal hearing completed baseline hearing health assessments followed by exposure to open ear, continuous pink noise at 94 dBA for 15 min. Immediately thereafter, post-noise hearing tests at 3000, 4000, and 6000 Hz and distortion product otoacoustic emissions (DPOAEs) were conducted along with the Modified Rhyme Test (MRT), Masking Level Difference Test (MLD), and Fixed Level Frequency Tests (FLFT) [collectively referred to as the Central and Peripheral Auditory Test Battery (CPATB)] to acquire baseline noise sensitivity profiles.

Transitioning from global to local computational strategies during brain-machine interface learning.

When learning to use a brain-machine interface (BMI), the brain modulates neuronal activity patterns, exploring and exploiting the state space defined by their neural manifold. Neurons directly involved in BMI control (i.e.

Immunosuppression withdrawal in living-donor renal transplant recipients following induction with antithymocyte globulin and rituximab: Results of a prospective clinical trial.

Durable tolerance in kidney transplant recipients remains an important but elusive goal. We hypothesized that adding B cell depletion to T cell depletion would generate an immune milieu postreconstitution dominated by immature transitional B cells, favoring tolerance. The Immune Tolerance Network ITN039ST Research Study of ATG and Rituximab in Renal Transplantation was a prospective multicenter pilot study of live donor kidney transplant recipients who received induction with rabbit antithymocyte globulin and rituximab and initiated immunosuppression (IS) withdrawal (ISW) at 26 weeks.

Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study.

Objective: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS).

Methods: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score.

Medications for opioid use disorder in rural primary care practices: Patient and provider experiences.

Introduction: The opioid epidemic has exacted a significant toll in rural areas, yet adoption of medications for opioid use disorder (MOUD) lags. The Rural Access to Medication Assisted Treatment in Pennsylvania (RAMP) Project facilitated adoption of MOUD in rural primary care clinics. The purpose of this study was to gain a better understanding of the barriers and facilitators operating at multiple levels to access or provide MOUD in rural Pennsylvania.

Evaluation of the usability, content, readability and cultural appropriateness of online alcohol and other drugs resources for Aboriginal and Torres Strait Islander Peoples in New South Wales, Australia.

Objectives: This study aimed to analyse the usability, content, readability and cultural appropriateness of alcohol and other drugs (AODs) resources for Aboriginal and Torres Strait Islander Peoples in New South Wales (NSW), Australia.

Outcome Measures: The content of 30 AOD resources for Aboriginal and Torres Strait Islander Peoples was analysed according to the following criteria: general characteristics; elements of graphical design and written communication; thoroughness and content; readability (Flesch-Kincaid grade level (FKGL), Gunning Fog index (Fog), Simplified Measure of Gobbledygook and Flesch Reading Ease); and cultural appropriateness.

Results: Most resources displayed good usability, depicted by the use of headings and subheadings (n=27), superior writing style (n=19), relevant visuals (n=19) and use of colour support (n=30).

Persistent SARS-CoV-2-specific immune defects in kidney transplant recipients following third mRNA vaccine dose.

Kidney transplant recipients (KTRs) show poorer response to SARS-CoV-2 mRNA vaccination, yet response patterns and mechanistic drivers following third doses are ill-defined. We administered third monovalent mRNA vaccines to n = 81 KTRs with negative or low-titer anti-receptor binding domain (RBD) antibody (n = 39 anti-RBD; n = 42 anti-RBD), compared with healthy controls (HCs, n = 19), measuring anti-RBD, Omicron neutralization, spike-specific CD8%, and SARS-CoV-2-reactive T cell receptor (TCR) repertoires. By day 30, 44% anti-RBD remained seronegative; 5% KTRs developed BA.

Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial.

Context: Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if not controlled.

Objective: The primary end point was change from baseline in hyperphagia using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Other end points included Global Impression Scores, and changes in body composition, behaviors, and hormones.

Selective decrease of donor-reactive T after liver transplantation limits T therapy for promoting allograft tolerance in humans.

Promoting immune tolerance to transplanted organs can minimize the amount of immunosuppressive drugs that patients need to take, reducing lifetime risks of mortality and morbidity. Regulatory T cells (T) are essential for immune tolerance, and preclinical studies have shown their therapeutic efficacy in inducing transplantation tolerance. Here, we report the results of a phase 1/2 trial (ARTEMIS, NCT02474199) of autologous donor alloantigen-reactive T (darT) therapy in individuals 2 to 6 years after receiving a living donor liver transplant.

Long-term Outcomes With Islet-Alone and Islet-After-Kidney Transplantation for Type 1 Diabetes in the Clinical Islet Transplantation Consortium: The CIT-08 Study.

Objective: To determine long-term outcomes for islet-alone and islet-after-kidney transplantation in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia.

Research Design And Methods: This was a prospective interventional and observational cohort study of islet-alone (n = 48) and islet-after-kidney (n = 24) transplant recipients followed for up to 8 years after intraportal infusion of one or more purified human pancreatic islet products under standardized immunosuppression. Outcomes included duration of islet graft survival (stimulated C-peptide ≥0.

Formation of Supported Lipid Bilayers (SLBs) from Buffers Containing Low Concentrations of Group I Chloride Salts.

Supported lipid bilayers (SLBs) are a useful tool for studying the interactions between lipids and other biomolecules that make up a cell membrane. SLBs are typically formed by the adsorption and rupture of vesicles from solution. Although it is known that many experimental factors can affect whether SLB formation is successful, there is no comprehensive understanding of the mechanism.

Validation and Concordance Analysis of a New Lateral Flow Assay for Detection of Antigen in Urine.

Histoplasmosis is a major cause of mortality in people living with HIV (PLHIV). Rapid methods to diagnose disease could dramatically decrease the time to initiate treatment, resulting in reduced mortality. The aim of this study was to validate a MiraVista Diagnostics (MVD) urine antigen lateral flow assay (MVD LFA) for the detection of antigen (Ag) in urine and compare this LFA against the MVista  Ag quantitative enzyme immunoassays (MVD EIA).

Effect of spinal cord injury on neural encoding of spontaneous postural perturbations in the hindlimb sensorimotor cortex.

Supraspinal signals play a significant role in compensatory responses to postural perturbations. Although the cortex is not necessary for basic postural tasks in intact animals, its role in responding to unexpected postural perturbations after spinal cord injury (SCI) has not been studied. To better understand how SCI impacts cortical encoding of postural perturbations, the activity of single neurons in the hindlimb sensorimotor cortex (HLSMC) was recorded in the rat during unexpected tilts before and after a complete midthoracic spinal transection.

The Occurrence of Subspecies Positive Milk Antibody ELISA Results in Dairy Cattle under Varying Time Periods after Skin Testing for Bovine Tuberculosis.

Enzyme-linked immunosorbent assays (ELISA) are used to screen cows for subspecies (MAP) infections, informing Johne's disease (JD) management practices in dairy herds. The causative agent of bovine tuberculosis (bTB), , and MAP share multiple antigens. Moreover, subspecies is used in the single intradermal cervical comparative tests (SICCT) that are routinely used in early detection of cows infected with bTB.

Hearing Status of Children and Adolescents With Familial Adenomatous Polyposis.

Background/aim: Chemopreventative therapeutics may be helpful in familial adenomatous polyposis (FAP) management; however, prospective chemopreventative studies are complicated by potential ototoxicity and pre-existing hearing loss. The aim of this study was to establish and compare baseline hearing status of children and adolescents with FAP and their unaffected siblings.

Patients And Methods: Twenty FAP pediatric patients with documented mutation of the adenomatous polyposis coli (APC) gene and nine unaffected sibling controls underwent baseline hearing evaluation, including audiometry, speech perception testing, and middle and inner ear physiologic measures.

Using citizen science to engage the public in monitoring workplace breastfeeding support in Australia.

Issue Addressed: Returning to work is a major barrier to continued breastfeeding. While many large organisations in Australia have policies to support breastfeeding and expressing at work, it is not known how these are implemented in practice, what support is available in smaller workplaces or to what extent workplace support meets the needs of breastfeeding mothers.

Methods: This pilot study trialled a citizen science approach where members of the public provided photographs and descriptions of breastfeeding facilities and support within their workplaces.

A noninferiority design for a delayed calcineurin inhibitor substitution trial in kidney transplantation.

Improving long-term kidney transplant outcomes requires novel treatment strategies, including delayed calcineurin inhibitor (CNI) substitution, tested using informative trial designs. An alternative approach to the usual superiority-based trial is a noninferiority trial design that tests whether an investigational agent is not unacceptably worse than standard of care. An informative noninferiority design, with biopsy-proven acute rejection (BPAR) as the endpoint, requires determination of a prespecified, evidence-based noninferiority margin for BPAR.

Efficacy and Safety of Immunosuppression Withdrawal in Pediatric Liver Transplant Recipients: Moving Toward Personalized Management.

Background And Aims: Tolerance is transplantation's holy grail, as it denotes allograft health without immunosuppression and its toxicities. Our aim was to determine, among stable long-term pediatric liver transplant recipients, the efficacy and safety of immunosuppression withdrawal to identify operational tolerance.

Approach And Results: We conducted a multicenter, single-arm trial of immunosuppression withdrawal over 36-48 weeks.

Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes.

Allogeneic islet transplant offers a minimally invasive option for β cell replacement in the treatment of type 1 diabetes (T1D). The CIT consortium trial of purified human pancreatic islets (PHPI) in patients with T1D after kidney transplant (CIT06), a National Institutes of Health-sponsored phase 3, prospective, open-label, single-arm pivotal trial of PHPI, was conducted in 24 patients with impaired awareness of hypoglycemia while receiving intensive insulin therapy. PHPI were manufactured using standardized processes.

Avoidance of CNI and steroids using belatacept-Results of the Clinical Trials in Organ Transplantation 16 trial.

Immunosuppression devoid of corticosteroids has been investigated to avoid long-term comorbidities. Likewise, alternatives to calcineurin inhibitors have been investigated as a strategy to improve long-term kidney function following transplanion. Costimulatory blockade strategies that include corticosteroids have recently shown promise, despite their higher rates of early acute rejection.