Exploring Peripheral and Cardiac Immune Responses in a Pneumosepsis Mouse Model with Group A Streptococcus.

(Group A Streptococcus, GAS) is a human pathogen that causes local and systemic infections of the skin and mucous membranes. However, GAS is also found asymptomatically in the nasopharynx of infants. GAS infections, including pharyngitis and invasive pneumosepsis, pose significant public health concerns.

A Rare Case of Superior Mesenteric Artery Thrombosis With Gangrenous Bowel in a Patient With Mitral Valve Replacement in a Hypocoagulable State.

Acute thromboembolism of the superior mesenteric artery (SMA) causing mesenteric ischemia has a grave prognosis with high mortality rates. Its rarity and non-specific symptoms often lead to delayed diagnosis and increased morbidity. Early signs can include pain out of proportion to physical findings, with abdominal distension, tenderness, and guarding appearing only in later stages when bowel necrosis has occurred.

Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency.

The importance of calcium (Ca2+) as a second messenger in T cell signaling is exemplified by genetic deficiencies of STIM1 and ORAI1, which abolish store-operated Ca2+ entry (SOCE) resulting in combined immunodeficiency (CID). We report five unrelated patients with de novo missense variants in ITPR3, encoding a subunit of the inositol 1,4,5-trisphosphate receptor (IP3R), which forms a Ca2+ channel in the endoplasmic reticulum (ER) membrane responsible for the release of ER Ca2+ required to trigger SOCE, and for Ca2+ transfer to other organelles. The patients presented with CID, abnormal T cell Ca2+ homeostasis, incompletely penetrant ectodermal dysplasia, and multisystem disease.

Serum Proteomic Predictors of Calcification of Solitary Cysticercus Granuloma.

Solitary cysticercus granulomas (SCG), prevalent among Indian patients with new-onset seizures, either resolve completely or transform into calcified granulomas. This study aimed to identify serum proteins through liquid chromatography-tandem mass spectrometry that could predict calcification of SCGs in 20 patients with SCG with at least 6-months of follow-up. At a median follow-up of 14 months, the SCG had calcified (n = 5), resolved (n = 11), or persisted (n = 4).

Mass Spectrometry Identifies Taenia solium Proteins in Sera of Patients With and Without Parenchymal Neurocysticercosis.

Neurocysticercosis (NCC), a major cause of global acquired epilepsy, results from Taenia solium larval brain infection. T. solium adult worms release large numbers of infective eggs into the environment contributing to high levels of exposure in endemic areas.

De novo missense variants in HDAC3 leading to epigenetic machinery dysfunction are associated with a variable neurodevelopmental disorder.

Histone deacetylase 3 (HDAC3) is a crucial epigenetic modulator essential for various developmental and physiological functions. Although its dysfunction is increasingly recognized in abnormal phenotypes, to our knowledge, there have been no established reports of human diseases directly linked to HDAC3 dysfunction. Using trio exome sequencing and extensive phenotypic analysis, we correlated heterozygous de novo variants in HDAC3 with a neurodevelopmental disorder having variable clinical presentations, frequently associated with intellectual disability, developmental delay, epilepsy, and musculoskeletal abnormalities.

Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome.

The shift to a genotype-first approach in genetic diagnostics has revolutionized our understanding of neurodevelopmental disorders, expanding both their molecular and phenotypic spectra. Kleefstra syndrome (KLEFS1) is caused by EHMT1 haploinsufficiency and exhibits broad clinical manifestations. EHMT1 encodes euchromatic histone methyltransferase-1-a pivotal component of the epigenetic machinery.

Delivery of a national prenatal exome sequencing service in England: a mixed methods study exploring healthcare professionals' views and experiences.

Introduction: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during the first 2 years of its delivery in the NHS.

Methods: A survey ( = 159) and semi-structured interviews ( = 63) with healthcare professionals, including clinical geneticists, FM specialists, and clinical scientists (interviews only) were used to address: 1) Views on the pES service; 2) Capacity and resources involved in offering pES; 3) Awareness, knowledge, and educational needs; and 4) Ambitions and goals for the future.

Preparation and In Vitro Characterization of -Loaded Alginate Particles as a Promising Delivery Tool for Periodontal Probiotic Therapy.

Probiotic microorganisms are used in a variety of food supplements and medical formulations to promote human health. In periodontal therapy, probiotics are mainly used in the form of gels, tablets or rinses that often tend to leak from the periodontal pocket, resulting in a strongly reduced therapeutic effect. In this pilot in vitro study, we present biodegradable alginate-based particles as an alternative, highly efficient system for a periodontal delivery of probiotic bacteria to the inflammation site.

Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties.

Background: The initial idea of functional tissue replacement has shifted to the concept that injected cells positively modulate myocardial healing by a non-specific immune response of the transplanted cells within the target tissue. This alleged local modification of the scar requires assessment of regional properties of the left ventricular wall in addition to commonly applied measures of global morphological and functional parameters. Hence, we aimed at investigating the effect of cardiac cell therapy with cardiovascular progenitor cells, so-called cardiac induced cells, on both global and regional properties of the left ventricle by a multimodal imaging approach in a mouse model.

A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3.

PPFIA3 encodes the protein-tyrosine phosphatase, receptor-type, F-polypeptide-interacting-protein-alpha-3 (PPFIA3), which is a member of the LAR-protein-tyrosine phosphatase-interacting-protein (liprin) family involved in synapse formation and function, synaptic vesicle transport, and presynaptic active zone assembly. The protein structure and function are evolutionarily well conserved, but human diseases related to PPFIA3 dysfunction are not yet reported in OMIM. Here, we report 20 individuals with rare PPFIA3 variants (19 heterozygous and 1 compound heterozygous) presenting with developmental delay, intellectual disability, hypotonia, dysmorphisms, microcephaly or macrocephaly, autistic features, and epilepsy with reduced penetrance.

Role of neutrophil-lymphocyte ratio as a prognostic marker for type 2 diabetic nephropathy among Indians.

Diabetic nephropathy/diabetic kidney disease (DKD) is one of the leading causes of renal failure. Early identification of the development or progression of diabetic nephropathy using appropriate screening and diagnostic tools is very important in order to provide timely and proper management. Inflammation plays a crucial role in development and progression of diabetic nephropathy.

CCR2 macrophage response determines the functional outcome following cardiomyocyte transplantation.

Background: The immune response is a crucial factor for mediating the benefit of cardiac cell therapies. Our previous research showed that cardiomyocyte transplantation alters the cardiac immune response and, when combined with short-term pharmacological CCR2 inhibition, resulted in diminished functional benefit. However, the specific role of innate immune cells, especially CCR2 macrophages on the outcome of cardiomyocyte transplantation, is unclear.

Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes.

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn -/- mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits.

New Approaches in Heart Research: Prevention Instead of Cardiomyoplasty?

Cardiovascular diseases are the leading cause of death in industrialized nations. Due to the high number of patients and expensive treatments, according to the Federal Statistical Office (2017) in Germany, cardiovascular diseases account for around 15% of total health costs. Advanced coronary artery disease is mainly the result of chronic disorders such as high blood pressure, diabetes, and dyslipidemia.

Cardiac cell therapies for the treatment of acute myocardial infarction in mice: systematic review and meta-analysis.

Backgound Aims: This meta-analysis aims at summarizing the whole body of research on cell therapies for acute myocardial infarction (MI) in the mouse model to bring forward ongoing research in this field of regenerative medicine. Despite rather modest effects in clinical trials, pre-clinical studies continue to report beneficial effects of cardiac cell therapies for cardiac repair following acute ischemic injury. Results: The authors' meta-analysis of data from 166 mouse studies comprising 257 experimental groups demonstrated a significant improvement in left ventricular ejection fraction of 10.