Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine.

The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22).

Additive value of invasive haemodynamic assessment for predicting post-operative outcomes after Fontan.

Routine pre-Fontan cardiac catheterization remains standard practice at most centres. However, with advances in non-invasive risk assessment, an invasive haemodynamic assessment may not be necessary for all patients.Using retrospective data from patients undergoing Fontan palliation at our institution, we developed a multivariable model to predict the likelihood of a composite adverse post-operative outcome including prolonged length of stay ≥ 30 days, hospital readmission within 6 months, and death and/or transplant within 6 months.

Feeding Variation Among Infants in Acute Care Cardiology Units.

Infants with heart disease are at high risk of feeding difficulties and complications. Feeding practices amongst acute care cardiology units are not standardized. This study aims to describe feeding practices for infants at the time of discharge from a Pediatric Acute Care Cardiology Collaborative (PAC) center and practice variation between centers.

Complex ADHD Challenging Case: Managing Co-Occurring Attention-Deficit Hyperactivity Disorder and Congenital Heart Disease with a Limited Medication Formulary: A Case from Mexico.

DL is an 8-year-old Mexican boy with a posterior atrial septal defect and partial anomalous pulmonary venous return of the right lower pulmonary vein with resultant right heart dilation with normal right ventricular systolic and diastolic function and no arrhythmias. Surgical repair was deferred, and DL's condition was being medically managed with furosemide 0.5 mg/kg BID and spironolactone 0.

Generation of a Commercial-Scale Founder Population of Porcine Reproductive and Respiratory Syndrome Virus Resistant Pigs Using CRISPR-Cas.

Disease resistance genes in livestock provide health benefits to animals and opportunities for farmers to meet the growing demand for affordable, high-quality protein. Previously, researchers used gene editing to modify the porcine CD163 gene and demonstrated resistance to a harmful virus that causes porcine reproductive and respiratory syndrome (PRRS). To maximize potential benefits, this disease resistance trait needs to be present in commercially relevant breeding populations for multiplication and distribution of pigs.

Safety, tolerability, and immunogenicity of the Ebola Sudan chimpanzee adenovirus vector vaccine (cAd3-EBO S) in healthy Ugandan adults: a phase 1, open-label, dose-escalation clinical trial.

Background: Sudan Ebola virus can cause severe viral disease, with an average case fatality rate of 54%. A recent outbreak of Sudan Ebola virus in Uganda caused 55 deaths among 164 confirmed cases in the second half of 2022. Although vaccines and therapeutics specific for Zaire Ebola virus have been approved for use during outbreak situations, Sudan Ebola virus is an antigenically distinct virus with no approved vaccines available.

How Low Is Too Low? A Retrospective Analysis of Very Low LDL-C Levels in Veterans.

Background: Low-density lipoprotein cholesterol (LDL-C) can build up on the walls of blood vessels, leading to coronary heart disease. Medications used to lower LDL-C levels have demonstrated decreased risks of atherosclerotic cardiovascular disease, but currently, there is no consensus on how to define very low LDL-C levels. It is necessary for the body to have LDL-C to maintain proper brain function; however, the safety and effects of prolonged very low LDL-C levels are unknown.

Low-dose intravenous and subcutaneous CIS43LS monoclonal antibody for protection against malaria (VRC 612 Part C): a phase 1, adaptive trial.

Background: Human monoclonal antibodies might offer an important new approach to reduce malaria morbidity and mortality. In the first two parts of a three-part clinical trial, the antimalarial monoclonal antibody CIS43LS conferred high protection against parasitaemia at doses of 20 mg/kg or 40 mg/kg administered intravenously followed by controlled human malaria infection. The ability of CIS43LS to confer protection at lower doses or by the subcutaneous route is unknown.

Use of Rivaroxaban in Children with Congenital Heart Disease: A Single-Center Case Series.

Rivaroxaban is a direct oral anticoagulant approved for therapeutic and prophylactic anticoagulation in both adults and children. Studies on rivaroxaban use in pediatric patients with congenital heart disease (CHD) are limited. Currently, warfarin (oral) and enoxaparin (injection) are the primary options for pediatric outpatient anticoagulation.

Transcriptomic Response to Calcium in Normal Colon Organoids is Impacted by Colon Location and Sex.

Unlabelled: Observational studies indicate that calcium supplementation may protect against colorectal cancer. Stratified analyses suggest that this protective effect may differ based on anatomic subsite and sex, but these hypotheses have been difficult to test experimentally. Here, we exposed 36 patient-derived organoid lines derived from normal colon biopsies (21 right colons, 15 left colons) of unrelated subjects (18 female, 18 male) to moderate (1.

Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria.

Background: New approaches for the prevention and elimination of malaria, a leading cause of illness and death among infants and young children globally, are needed.

Methods: We conducted a phase 1 clinical trial to assess the safety and pharmacokinetics of L9LS, a next-generation antimalarial monoclonal antibody, and its protective efficacy against controlled human malaria infection in healthy adults who had never had malaria or received a vaccine for malaria. The participants received L9LS either intravenously or subcutaneously at a dose of 1 mg, 5 mg, or 20 mg per kilogram of body weight.

Current evidence for pharmacologic therapy following stage 1 palliation for single ventricle congenital heart disease.

Introduction: Infants with single ventricle congenital heart disease are vulnerable to complications between stage 1 and stage 2 of palliation. Pharmaceutical treatment during this period is varied and often dependent on institutional practices as there is little evidence supporting a particular treatment path.

Areas Covered: This review focuses on medical management of patients following stage I palliation.

Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial.

Background: Advances in therapeutic drugs have increased life-expectancies for HIV-infected individuals, but the need for an effective vaccine remains. We assessed safety and immunogenicity of HIV-1 vaccine, Trimer 4571 (BG505 DS-SOSIP.664) adjuvanted with aluminum hydroxide (alum), in HIV-negative adults.

Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial.

Background: Western (WEEV), eastern (EEEV), and Venezuelan (VEEV) equine encephalitis viruses are mosquito-borne pathogens classified as potential biological warfare agents for which there are currently no approved human vaccines or therapies. We aimed to evaluate the safety, tolerability, and immunogenicity of an investigational trivalent virus-like particle (VLP) vaccine, western, eastern, and Venezuelan equine encephalitis (WEVEE) VLP, composed of WEEV, EEEV, and VEEV VLPs.

Methods: The WEVEE VLP vaccine was evaluated in a phase 1, randomised, open-label, dose-escalation trial at the Hope Clinic of the Emory Vaccine Center at Emory University, Atlanta, GA, USA.

Menthol and flavored tobacco products in LMICs: A growing menace.

Introduction: High income jurisdictions are banning menthol/flavored cigarettes and other tobacco products because they attract young people and create dependence. This study explores the importance of menthol and other flavored tobacco products for tobacco markets in low- and middle-income countries (LMICs), identifies countries where the menthol/flavor share is particularly high or rapidly growing, and identifies strategies tobacco companies are using to develop menthol/flavor markets.

Methods: Research involved analysis of menthol/flavor market data from 2005 to 2019, a systematic review of academic literature, and a scoping exercise with our advocate contacts in LMICs.

Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial.

Adeno-associated viral vector-mediated transfer of DNA coding for broadly neutralizing anti-HIV antibodies (bnAbs) offers an alternative to attempting to induce protection by vaccination or by repeated infusions of bnAbs. In this study, we administered a recombinant bicistronic adeno-associated virus (AAV8) vector coding for both the light and heavy chains of the potent broadly neutralizing HIV-1 antibody VRC07 (AAV8-VRC07) to eight adults living with HIV. All participants remained on effective anti-retroviral therapy (viral load (VL) <50 copies per milliliter) throughout this phase 1, dose-escalation clinical trial ( NCT03374202 ).

Trends in the Number of Authors and Institutions in Papers Published in AJPE 2015-2019.

To investigate the number of authors and unique institutions per paper published in the (AJPE) in 2015 through 2019, and to examine the number of authors and unique institutions for papers that were nominated for the Rufus A. Lyman Award in the same period. Articles published in AJPE from 2015 through 2019 were reviewed.

Adapting Interstage Home Monitoring with the use of Telemedicine During the COVID-19 Pandemic.

Pediatric single ventricle patients have seen dramatic improvements in overall outcomes over the past several decades. This is attributed to the development of home monitoring programs for interstage patients. In today's current COVID-19 pandemic, the use of telemedicine has allowed providers to care for these patients and support their families effectively while minimizing the risk of COVID-19 exposure.

Transcriptome-wide Effects of Aspirin on Patient-derived Normal Colon Organoids.

Mechanisms underlying aspirin chemoprevention of colorectal cancer remain unclear. Prior studies have been limited because of the inability of preclinical models to recapitulate human normal colon epithelium or cellular heterogeneity present in mucosal biopsies. To overcome some of these obstacles, we performed aspirin treatment of colon organoids derived from normal mucosal biopsies to reveal transcriptional networks relevant to aspirin chemoprevention.

A Monoclonal Antibody for Malaria Prevention.

Background: Additional interventions are needed to reduce the morbidity and mortality caused by malaria.

Methods: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with . Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria.

Primary prevention of prescription opioid diversion: a systematic review of medication disposal interventions.

: In the U.S., 50-75% of nonmedical users of prescription opioids obtain their pills through diversion by friends or relatives.

A Functional Variant on 9p21.3 Related to Glioma Risk Affects Enhancer Activity and Modulates Expression of CDKN2B-AS1.

Genome-wide association studies have identified SNPs associated with glioma risk on 9p21.3, but biological mechanisms underlying this association are unknown. We tested the hypothesis that a functional SNP on 9p21.

Gerbode defect following surgical mitral valve replacement and tricuspid valve repair: a case report.

Background: Gerbode defect is a congenital or acquired communication between the left ventricle and right atrium. While the defect is becoming a more well-recognized complication of cardiac surgery, it presents a diagnostic and therapeutic challenge for providers. This case highlights the predisposing factors and imaging features that may assist in the diagnosis of Gerbode defect, as well as potential approaches to treatment.

Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci.

Background & Aims: The association of genetic variation with tissue-specific gene expression and alternative splicing guides functional characterization of complex trait-associated loci and may suggest novel genes implicated in disease. Here, our aims were as follows: (1) to generate reference profiles of colon mucosa gene expression and alternative splicing and compare them across colon subsites (ascending, transverse, and descending), (2) to identify expression and splicing quantitative trait loci (QTLs), (3) to find traits for which identified QTLs contribute to single-nucleotide polymorphism (SNP)-based heritability, (4) to propose candidate effector genes, and (5) to provide a web-based visualization resource.

Methods: We collected colonic mucosal biopsy specimens from 485 healthy adults and performed bulk RNA sequencing.

The Association of Fetal Congenital Cardiac Defects and Placental Vascular Malperfusion.

Objectives: Abnormal early angiogenesis appears to impact both placental disorders and fetal congenital heart defects (CHD). We sought to assess the association of placental perfusion defects (PPD) and fetal (CHD).

Methods: Singleton pregnancies with isolated severe fetal CHD were compared to controls without congenital anomalies or maternal malperfusion (MVM) risk factors.