Cohort profile: the potentially preventable burden of community-acquired pneumonia in South African adults in the era of widespread PCV13 immunisation and antiretroviral therapy roll-out, before and during the COVID-19 pandemic - the multicentre, multimethod PotPrev Study.

Purpose: In the setting of an established childhood pneumococcal vaccination programme with immediate initiation and treatment of antiretroviral therapy (ART) for people living with HIV (PLWH), the risk of adult pneumococcal community-acquired pneumonia (CAP) is not recently described. We aimed to investigate CAP incidence, recurrence, mortality, risk factors and microbiology before and during the COVID-19 pandemic.

Participants: Adults aged ≥18 years were enrolled in three South African provinces from March 2019 to October 2021, with a brief halt during the initial COVID-19 lockdown.

Rapid microfluidic perfusion system enables controlling dynamics of intracellular pH regulated by Na/H exchanger NHE1.

pH regulation of eukaryotic cells is of crucial importance and influences different mechanisms including chemical kinetics, buffer effects, metabolic activity, membrane transport and cell shape parameters. In this study, we develop a microfluidic system to rapidly and precisely control a continuous flow of ionic chemical species to acutely challenge the intracellular pH regulation mechanisms and confront predictive models. We monitor the intracellular pH dynamics in real-time using pH-sensitive fluorescence imaging and establish a robust mathematical tool to translate the fluorescence signals to pH values.

Wernicke Encephalopathy Presenting With Syndrome of Inappropriate Antidiuretic Hormone.

Wernicke encephalopathy is a well-described neurological complication of thiamine deficiency that is classically characterized by a triad of mental confusion, ophthalmoplegia, and gait ataxia. Although most commonly linked to alcoholism and thiamine deficiency in adults, it can present in pediatric patients. Wernicke encephalopathy presenting as dysnatremias is not well described.

Costs of Influenza Illness and Acute Respiratory Infections by Household Income Level: Catastrophic Health Expenditures and Implications for Health Equity.

Background: Seasonal influenza illness and acute respiratory infections can impose a substantial economic burden in low- and middle-income countries (LMICs). We assessed the cost of influenza illness and acute respiratory infections across household income strata.

Methods: We conducted a secondary analysis of data from a prior systematic review of costs of influenza and other respiratory illnesses in LMICs and contacted authors to obtain data on cost of illness (COI) for laboratory-confirmed influenza-like illness and acute respiratory infection.

A Small-Particle Aerosol Model of Ebolavirus Zaire Infection in Ferrets.

The Ebola virus (EBOV) causes severe disease in humans, and animal models are needed to evaluate the efficacy of vaccines and therapeutics. While non-human primate (NHP) and rodent EBOV infection models have been well characterized, there is a growing need for an intermediate model. Here, we provide the first report of a small-particle aerosol (AE) EBOV ferret model and disease progression compared with the intramuscular (IM) EBOV ferret model.

A generalised catalytic model to assess changes in risk for multiple reinfections with SARS-CoV-2.

Background: Monitoring trends in multiple infections with SARS-CoV-2, following several pandemic waves, provides insight into the biological characteristics of new variants, but also necessitates methods to understand the risk of multiple reinfections.

Objectives: We generalised a catalytic model designed to detect increases in the risk of SARS-CoV-2 reinfection, to assess the population-level risk of multiple reinfections.

Methods: The catalytic model assumes the risk of reinfection is proportional to observed infections and uses a Bayesian approach to fit model parameters to the number of nth infections among individuals that occur at least 90 days after a previous infection.

EGFR status assessment using reflex testing targeted next-generation sequencing for resected non-squamous non-small cell lung cancer.

EGFR status assessment is mandatory for adjuvant decision-making of resected stage IB-IIIA non-squamous non-small cell lung cancer (NS-NSCLC). It is questionable whether single-gene RT-PCR versus next-generation sequencing (NGS) should be used for this evaluation. Moreover, co-occurring mutations have an impact on tumor behavior and may influence future therapeutic decision-making.

Effect of improving food security on parenting practices and caregiver-adolescent relationships: qualitative findings of an income-generating agricultural intervention in rural Kenya.

Background: Despite the recognised links between food insecurity and parenting, few studies have evaluated the perceived impacts of livelihood or food security interventions on parental practices, intra-household functioning, adolescent behaviour and psychosocial outcomes in HIV-affected households in sub-Saharan Africa.

Aims: The study aimed to understand the perceived effects of food security on parenting practices and how this was experienced by both adolescent girls (aged 13-19 years) and their caregivers in rural Kenya.

Method: We conducted semi-structured, individual interviews with 62 caregiver-adolescent dyads who were participants in the adolescent (NCT03741634), a sub-study of adolescent girls and caregivers with a household member participating in the agricultural and finance intervention trial (NCT01548599).

Impact of neoadjuvant therapy on angioplastic lobectomy: a retrospective study.

Objectives: The efficacy of neoadjuvant therapy (NT) prior to angioplastic lobectomy (AL) in non-small cell lung cancer is unclear. This study assessed its impact on morbidity, mortality and 5-year survival.

Methods: We retrospectively analysed 114 patients who underwent AL at 2 tertiary centres from January 2000 to December 2020.

Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages (the PSERENADE project): a global surveillance analysis.

Background: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages.

Methods: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%.

Phylodynamics for HIV Prevention: A Miami-Dade Case Study.

Background: To date, HIV molecular epidemiology (HIV ME) has been primarily used to identify clusters of related infections (cluster detection and response [CDR]) and then address interventions to these clusters. Community groups have raised concern regarding CDR regarding privacy and ethical concerns. Here we demonstrate how an alternative approach to HIV ME can provide public health benefit.

Epidemiological and clinicopathological characteristics of vascular-limited renal AL amyloidosis.

Background And Hypothesis: Kidney involvement, along with cardiac disease, is the most frequent manifestation of systemic AL amyloidosis usually resulting in nephrotic-range proteinuria. Rarely, deposits predominantly or exclusively affect the intrarenal arterioles or arteries, these vascular-limited forms following a distinct clinical course, but very little is known about these forms. Our work plan at better characterizing renal vascular limited AL amyloidosis.

Efficacy and Safety of Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor T-Cell for the Treatment of Relapsed and Refractory AL Amyloidosis.

Purpose: The use of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy for AL amyloidosis (AL) is limited owing to patient frailty. HBI0101 anti-BCMA CART was the first proof of concept for its applicability to AL. This report addresses the AL patient cohort treated to date within the phase Ia/Ib clinical trial (ClinicalTrials.

Merkel Cell Carcinoma and Immunosuppression, UV Radiation, and Merkel Cell Polyomavirus.

Importance: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer. Quantifying the contribution of major potentially modifiable risk factors to the burden of MCC may inform prevention efforts.

Objective: To estimate the population attributable fraction of MCC cases in the US that were attributable to major immunosuppressing conditions (eg, HIV, solid organ transplant, chronic lymphocytic leukemia [CLL]), ambient UV radiation [UVR] exposure, and Merkel cell polyomavirus [MCPyV]).

Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens.

Background: Heightened levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain elevated after virologic suppression by antiretroviral therapy (ART). As new combinations of ART become available, an evaluation of their effects on immune activation and inflammation is warranted. Additionally, it remains unknown whether transient increases in viral load ("blips") during ART are associated with increases in inflammation.

The HUSH epigenetic repressor complex silences PML nuclear body-associated HSV-1 quiescent genomes.

Herpes simplex virus 1 (HSV-1) latently infected neurons display diverse patterns in the distribution of the viral genomes within the nucleus. A key pattern involves quiescent HSV-1 genomes sequestered in promyelocytic leukemia nuclear bodies (PML NBs) forming viral DNA-containing PML-NBs (vDCP NBs). Using a cellular model that replicates vDCP NB formation, we previously demonstrated that these viral genomes are chromatinized with the H3.

"The leadership shown by nurses gave me such a boost": health resources used by nurses who experienced COVID-19 pandemic stressors.

Purpose: To thoroughly describe 1) the stressors experienced by nurses during the first waves of the COVID-19 pandemic, 2) the extent to which experiencing these stressors affected nurses' psychological and physical health and 3) the health resources nurses used to protect and maintain their psychological and physical health during this period.

Method: We used a theory-driven descriptive qualitative design and conducted seven focus groups of 2-5 nurses (total = 23 nurses) distinguished by their degree of contact with COVID-19 patients hospitalized in Switzerland.

Results: A thematic analysis identified three main themes and their respective sub-themes: 1) Lived experiences and stressors (Living in a strange world; Hard work alone behind closed doors; Contaminating or being contaminated; Living at home behind closed doors; A war of attrition after the first wave); 2) Health (Everything is fine; Multiple traumas; Stress; Long-term exhaustion); 3) Resources (Societal and institutional resources; Direct relational resources; Resources specific to individuals).

Discovery of novel cyclopentane carboxylic acids as potent and selective inhibitors of Na1.7.

Discovery efforts leading to the identification of cyclopentane carboxylic acid 31, a potent inhibitor of Na1.7 that showed high selectivity over Na1.5 and exhibited robust analgesic effects in an inherited erythromelalgia (IEM) transgenic mouse assay, are described herein.