The gut-lung axis: Protozoa join the party.

The gut microbiota is a powerful influencer of systemic immunity, with its impact on distal organs like the lungs garnering increasing attention. In this issue of Cell, Burrows et al. report that a gut protozoan plays a key role in shaping the immunological steady state of the lung.

Preference for HIV Pre-exposure Prophylaxis Access Among Men who Have Sex With Men in China: A Discrete Choice Experiment.

Background: HIV pre-exposure prophylaxis (PrEP) is highly effective but not widely used by men who have sex with men (MSM; 27%) in China.

Methods: In June 2023, an online cross-sectional survey with a discrete choice experiment (DCE) was distributed to PrEP-eligible MSM in China who were at least 18 years old. The DCE explored attributes of PrEP modality (daily pill, on-demand pill, injections, implants), clinical care model (same-day, 2-visit, telehealth prescription), medication pickup (clinic, community health center, pharmacy, MSM-focused community-based organization, home delivery), enhanced support (self-management, smartphone app, text reminder, anonymous peer support group), and cost.

Antiseizure Medications in Poststroke Seizures: A Systematic Review and Network Meta-Analysis.

Background And Objectives: The most effective antiseizure medications (ASMs) for poststroke seizures (PSSs) remain unclear. We aimed to determine outcomes associated with ASMs in people with PSS.

Methods: We systematically searched electronic databases for studies on patients with PSS on ASMs.

An optimized plasmalogen modulating dietary supplement provides greater protection in a male than female mouse model of dilated cardiomyopathy.

We previously reported that plasmalogens, a class of phospholipids, were decreased in a setting of dilated cardiomyopathy (DCM). Plasmalogen levels can be modulated via a dietary supplement called alkylglycerols (AG) which has demonstrated benefits in some disease settings. However, its therapeutic potential in DCM remained unknown.

Challenges of symptom management in interstitial lung disease: dyspnea, cough, and fatigue.

Introduction: Interstitial lung disease (ILD) is a broad group of conditions characterized by fibrosis of the lung parenchyma. Idiopathic pulmonary fibrosis (IPF) is the most common subvariant. IPF is marked by considerable symptom burden of dyspnea, cough and fatigue that is often refractory to optimal disease-directed treatment.

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Six months of hybrid closed-loop therapy improves diabetes-specific positive well-being, and reduces diabetes distress and fear of hypoglycemia: secondary analysis of a randomized controlled trial.

Introduction: This analysis aimed to investigate diabetes-specific psychological outcomes among adults with type 1 diabetes (T1D) using hybrid closed-loop (HCL) versus standard therapy.

Research Design And Methods: In this multicenter, open-label, randomized, controlled, parallel-group clinical trial, adults with T1D were allocated to 26 weeks of HCL (MiniMed™ 670G) or standard therapy (insulin pump or multiple daily injections without real-time continuous glucose monitoring). Psychological outcomes (awareness and fear of hypoglycemia; and diabetes-specific positive well-being, diabetes distress, diabetes treatment satisfaction, and diabetes-specific quality of life (QoL)) were measured at enrollment, mid-trial and end-trial.

Ward-delivered nasal high-flow oxygen and non-invasive ventilation are safe for people with acute respiratory failure: a cohort study.

Background And Aims: Ward-delivered non-invasive respiratory supports (NIRS) (conventional oxygen therapy (COT), high-flow nasal oxygen (HFNO), continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV)), are often used to treat hospitalised patients with acute respiratory failure (ARF) both in high acuity and general wards. This study aimed to describe the processes of care adopted and examine patient outcomes from a specialist, ward-delivered NIRS service caring for people with COVID-19 in general wards or in a respiratory care unit (RCU).

Methods: A cohort study was undertaken including all consecutive patients admitted to a quaternary hospital with ARF secondary to COVID-19 and requiring ward-delivered NIRS between 28 February 2020 and 18 March 2022.

Prediction accuracy of discrete choice experiments in health-related research: a systematic review and meta-analysis.

Background: Discrete choice experiments (DCEs) are increasingly used to inform the design of health products and services. It is essential to understand the extent to which DCEs provide reliable predictions outside of experimental settings in real-world decision-making situations. We aimed to compare the prediction accuracy of stated preferences with real-world choices, as modelled from DCE data.

Blood Group B May Reduce Risk of Rebleeding in Patients With Upper Gastrointestinal Haemorrhage due to Peptic Ulcer Disease.

Risk stratification tools for the prediction of complications in patients with upper gastrointestinal haemorrhage are crucial for appropriate management. Blood group status has been associated with the risk of bleeding, thrombosis and risk of peptic ulcer disease (PUD). We assessed the influence of blood group status on rebleeding and other complications in 699 patients with PUD bleeding.

Exploring artificial intelligence for differentiating early syphilis from other skin lesions: a pilot study.

Background: Early diagnosis of syphilis is vital for its effective control. This study aimed to develop an Artificial Intelligence (AI) diagnostic model based on radiomics technology to distinguish early syphilis from other clinical skin lesions.

Methods: The study collected 260 images of skin lesions caused by various skin infections, including 115 syphilis and 145 other infection types.

Targeted sequencing of bacteria using CRISPR-Cas9 enrichment and Oxford Nanopore Technologies.

Unlabelled: Sequencing DNA directly from patient samples enables faster pathogen characterization compared to traditional culture-based approaches, but often yields insufficient sequence data for effective downstream analysis. CRISPR-Cas9 enrichment is designed to improve the yield of low abundance sequences but has not been thoroughly explored with Oxford Nanopore Technologies (ONT) for use in clinical bacterial epidemiology. We designed CRISPR-Cas9 guide RNAs to enrich the human pathogen , by targeting multi-locus sequence type (MLST) and transfer RNA (tRNA) genes, as well as common antimicrobial resistance (AMR) genes and the resistance-associated integron gene .

Risk of Adverse Pregnancy Outcomes Associated With Antiseizure Medications and Their Indications: A Systematic Review and Meta-Analysis.

Background And Objectives: Aside from congenital malformations and impaired postnatal neurodevelopment, risks associated with antiseizure medication (ASM) use during pregnancy have been sparsely investigated, particularly outside of epilepsy. We aimed to assess these risks through a systematic literature review and meta-analysis, including ASM exposure for indication.

Methods: We searched MEDLINE, EMBASE, and Cochrane for studies including pregnant women on ASMs for any indication and untreated pregnant women, investigating obstetric complications and fetal/neonatal complications other than congenital malformations and impaired neurodevelopment.

Integrated Approaches for the Delivery of Maternal and Child Health Services with Childhood Immunization Programs in Low- and Middle-Income Countries: Systematic Review Update 2011-2020.

: The integration of maternal and child health services (MCH) with routine immunization is an important global health strategy, particularly in low- and middle-income countries (LMICs). However, evidence is lacking regarding the best practices for service integration and the effect of integration on immunization and linked health service outcomes. : We searched publication databases and gray literature for articles published between 2011 and 2020 that include approaches to integrating MCH services with immunizations during the first two years of life in LMICs.

TRAPPopathies: Severe Multisystem Disorders Caused by Variants in Genes of the Transport Protein Particle (TRAPP) Complexes.

The TRAPP (TRAnsport Protein Particle) protein complex is a multi-subunit complex involved in vesicular transport between intracellular compartments. The TRAPP complex plays an important role in endoplasmic reticulum-to-Golgi and Golgi-to-plasma membrane transport, as well as autophagy. TRAPP complexes comprise a core complex, TRAPPI, and the association of peripheral protein subunits to make two complexes, known as TRAPPII and TRAPPIII, which act as Guanine Nucleotide Exchange Factors (GEFs) of Rab11 and Rab1, respectively.

Cardiovascular effects of tirzepatide.

Tirzepatide is a first-in-class dual agonist at receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) for the treatment of T2D and obesity with unprecedented efficacy for glycaemic control and reductions in body weight as well as improvements in blood pressure and lipid profile compared with placebo and GLP-1 receptor agonists. To date, clinical trials of tirzepatide have fulfilled the requirement by regulatory authorities of demonstrated cardiovascular safety in high-risk patients. Whether cardiovascular benefits will be found with dual GLP-1/GIP receptor agonists remains uncertain, and the contribution of GIP receptor activation to cardiovascular risk has not been established.

Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats; establishment of human leukemia xenograft models.

Background: Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan.

Exposure to Perinatal Trauma Modifies Nociception and Gene Expression in the Prefrontal Cortex and Hypothalamus of Adolescent Rats.

The perinatal period encompasses a critical window for neurodevelopment that renders the brain highly responsive to experience. Trauma, such as intimate partner violence (IPV) and early life stress/neglect, during this period negatively affects physical and mental health outcomes, including increasing ones risk for chronic pain. Although epigenetic programming likely contributes, the mechanisms that drive the relationship between perinatal trauma and adverse health outcomes, are not fully understood.

Achieving better engagement with care and support for young people living with HIV in Australia: a mixed-method enquiry.

Young people aged 18-29 are considered "adult" within the Australian HIV health service context. However, evidence increasingly defines this age group as distinct from the broader adult population such that the needs of young people living with HIV may be overlooked in the context of HIV service design and delivery. This analysis draws on the Young + Positive study, a national study in Australia that documented the perspectives of young people (aged 18-29) living with HIV.

Update on inborn errors of immunity.

Ever since the first description of an inherited immunodeficiency in 1952 in a boy with gammaglobulin deficiency, new insights have progressed rapidly in disorders that are now referred to as inborn errors of immunity. In a field where fundamental molecular biology, genetics, immune signaling, and clinical care are tightly intertwined, 2022-24 saw a multitude of advances. Here we report a selection of research updates with a main focus on (1) diagnosis and screening, (2) new genetic defects, (3) susceptibility to severe coronavirus disease 2019 infection and impact of vaccination, and (4) treatment.