DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Brief Report: Cystatin C Provides Substantially Higher Glomerular Filtration Rate Estimates Than Creatinine in a Subset of Black People With HIV on Current Antiretroviral Regimens.

Background: In African populations, estimated glomerular filtration rate by cystatin C (eGFRcys) is better aligned with gold-standard GFR measurements than eGFR by creatinine (eGFRcr). Moreover, eGFRcys is unaffected by the effects of antiretroviral therapy (ART) on tubular secretion and may thus provide better estimates of GFR in people with HIV on ART.

Setting: Observational cohort study of people of African ancestry living with suppressed HIV RNA on ART in London, United Kingdom.

Tocilizumab and rituximab for systemic sclerosis interstitial lung disease: a real-world cohort analysis.

Objectives: Systemic sclerosis (SSc)-interstitial lung disease (ILD) is one of the leading causes of mortality in SSc. Data from randomised controlled trials (RCTs) supports rituximab and tocilizumab monotherapy but there is limited data regarding their use for those who fail standard immunomodulatory therapies.

Methods: SSc patients treated with rituximab or tocilizumab were retrospectively identified in a single centre cohort.

Weight discrimination partially mediates the longitudinal relationship between Body Mass Index and pain.

Pain is common among individuals with high Body Mass Index (BMI). This study investigated weight discrimination as a mediator of the longitudinal relationship between BMI and the presence of moderate/severe pain among adults from the English Longitudinal Study of Ageing (ELSA) cohort. ELSA is a longitudinal study of middle-aged and older adults living in England.

Treatment strategies for limited-stage small cell carcinoma of the esophagus: evidence from a Chinese multicenter cohort study and the American SEER database.

Background: The rare incidence of small cell carcinoma of the esophagus (SCCE) makes prospective studies difficult to conduct, the efficacy of existing standard treatment regimens for SCCE is therefore highly controversial. This study aimed to explore differences in the efficacy of three different treatment regimens [upfront surgery, neoadjuvant chemotherapy (NCT), and chemoradiotherapy (CRT)] in patients with limited-stage SCCE (LS-SCCE).

Methods: In total, 483 patients with LS-SCCE were screened from five centers from June 2001 to June 2020, and 128 patients with LS-SCCE were screened from the Surveillance, Epidemiology, and End Results (SEER) database.

Impact of CT-angiography derived plaque characteristics on cardiac events in patients with a negative invasive fractional flow reserve.

Background: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for chronic coronary syndromes (CCS) improves outcomes compared with angiography-guided PCI, however cardiac events still occur during long-term follow-up of FFR-negative patients. In the PREVENT study preventive PCI reduced cardiac-events in lesions which were FFR-negative (FFR > 0.80) and had intracoronary imaging defined vulnerable plaque.

Treatments for RYR1-related disorders.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary objective To analyse the benefits and harms of pharmacological or other interventions (e.g.

Childhood interstitial lung disease survivors in adulthood: a European collaborative study.

Background: Interstitial lung disease (ILD) is rarer in children (chILD) than adults, but with increasing diagnostic awareness, more cases are being discovered. chILD prognosis is often poor, but increasing numbers are now surviving into adulthood.

Aim: To characterize chILD-survivors and identify their impact on adult-ILD centers.

Non-Surgical Approaches to the Management of the Intrathoracic Goiter-A Systematic Review.

Background: Intrathoracic goiters (ITGs) are usually managed by surgical excision, However, over recent years, non-surgical strategies are emerging as an alternatives for treating this condition.

Methods: A systematic review of research published since 2017 in the PubMed database was conducted and a total of 39 articles were retrieved, along with methodological issues and future directions in the research on ITGs.

Results: Several non-surgical treatments exist, including radio-iodine ablation (RIA) and mini-invasive approaches, such as transcervical microwave ablation (TcMA), transcervical radiofrequency ablation (TcRfA), or selective embolization of the thyroid arteries (SETA).

Pathogenic PDE12 variants impair mitochondrial RNA processing causing neonatal mitochondrial disease.

Pathogenic variants in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial function. Within this group, an increasing number of families have been identified, where Mendelian genetic disorders implicate defective mitochondrial RNA biology. The PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs.

Self-Induced Nasal Septal Perforation: Rhinotillexomania-A Different Entity From Nose Picking.

Background: Nose picking is a common habit that rarely leads to mutilating self-injury. It is important to distinguish between rhinotillexomania (compulsive nose picking) as a disease and nose picking that results in or contributes to nasal septal perforation (NSP). The aim of this study is to investigate the impact of rhinotillexomania and NSP repair on sinonasal symptoms and quality of life (QoL).

"Shifting sands in cystic fibrosis": impacts of CFTR modulators on reproductive health in people with cystic fibrosis and challenges related to exposure.

Introduction: Mutation-specific disease modifying drugs such as the triple combination Elexacaftor/Tezacaftor/Ivacaftor (ETI), are associated with significant improvements in physical health. Reproductive health and a pursuit of parenthood are of increased relevance; a dramatic increase in childbirth rates for females with CF has already been observed.

Areas Covered: Fertility in males and females with CF, and any subsequent impact of CFTR modulator therapy, is reviewed.

Interventions in women with type 2 diabetes mellitus in the pre-pregnancy, pregnancy and postpartum periods to optimise care and health outcomes: A systematic review.

Aims: Type 2 diabetes is a chronic condition affecting increasing numbers of women of reproductive age. Recent UK data show more severe adverse offspring outcomes (stillbirth, neonatal death) than in infants of those with Type 1 diabetes. This systematic review aimed to evaluate randomised controlled trials (RCTs) undertaken in the pre-pregnancy, pregnancy and the postpartum periods in women with Type 2 diabetes, to optimise care and health outcomes.

An update on autophagy disorders.

Macroautophagy is a highly conserved cellular pathway for the degradation and recycling of defective cargo including proteins, organelles, and macromolecular complexes. As autophagy is particularly relevant for cellular homeostasis in post-mitotic tissues, congenital disorders of autophagy, due to monogenic defects in key autophagy genes, share a common "clinical signature" including neurodevelopmental, neurodegenerative, and neuromuscular features, as well as variable abnormalities of the eyes, skin, heart, bones, immune cells, and other organ systems, depending on the expression pattern and the specific function of the defective proteins. Since the clinical and genetic resolution of EPG5-related Vici syndrome, the paradigmatic congenital disorder of autophagy, the widespread use of massively parallel sequencing has resulted in the identification of a growing number of autophagy-associated disease genes, encoding members of the core autophagy machinery as well as related proteins.

Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis in and Vici syndrome patients.

Epilepsy is a common neurological condition that arises from dysfunctional neuronal circuit control due to either acquired or innate disorders. Autophagy is an essential neuronal housekeeping mechanism, which causes severe proteotoxic stress when impaired. Autophagy impairment has been associated to epileptogenesis through a variety of molecular mechanisms.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XI - Milk supplement/replacement formulas for infants and toddlers with CMA - Systematic review.

Background: Cow's milk allergy (CMA) is the most complex and common food allergy in infants. Elimination of cow's milk from the diet and replacement with a specialized formula for infants with cow's milk allergy who cannot be breastfed is an established approach to minimize the risk of severe allergic reactions while avoiding nutritional deficiencies. Given the availability of multiple options, such as extensively hydrolyzed cow's milk-based formula (eHF-CM), aminoacid formula (AAF), hydrolyzed rice formula (HRF), and soy formula (SF), there is some uncertainty regarding which formula might represent the most suitable choice with respect to health outcomes.

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) in 2024.

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018 and updated in 2022. Recently, the European Society of Cardiology (ESC) published the guidelines for the management of acute coronary syndrome in 2023.

Working conditions during pregnancy: a survey of 3590 European anaesthesiologists and intensivists.

Background: Pregnancy adds challenges for healthcare professionals, regardless of gender. We investigated experiences during pregnancy, attitudes towards pregnant colleagues, family planning decisions, and awareness of regulations among European anaesthesiologists and intensivists.

Methods: A cross-sectional online survey was conducted among 3590 anaesthesiologists and intensivists from 47 European countries.