Reciprocal and non-reciprocal effects of clinically relevant SETBP1 protein dosage changes.

Many genes in the human genome encode proteins that are dosage sensitive, meaning they require protein levels within a narrow range to properly execute function. To investigate if clinically relevant variation in protein levels impacts the same downstream pathways in human disease, we generated cell models of two SETBP1 syndromes: Schinzel-Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disease (SHD), where SGS is caused by too much protein, and SHD is caused by not enough SETBP1. Using patient and sex-matched healthy first-degree relatives from both SGS and SHD SETBP1 cases, we assessed how SETBP1 protein dosage affects downstream pathways in human forebrain progenitor cells.

Isthmoceles - Accuracy of imaging diagnosis and clinical correlation with histology: A prospective cohort study.

Background: Isthmoceles are a growing clinical concern.

Objectives: To evaluate the accuracy of diagnosis of isthmoceles by imaging and to correlate the dimensions with clinical symptoms and histopathology.

Materials And Methods: Prospective study of women (n=60) with ≥1 C-section undergoing hysterectomy.

Airflowing as an adjunctive treatment for periodontitis: A randomized controlled trial.

Backgound: The aim of this randomized controlled trial was to assess clinical and patient-reported outcomes of subgingival instrumentation (SI) with adjunctive use of erythritol airflowing (EAF) compared to SI alone in the treatment of periodontitis.

Methods: Twenty-six participants with Stage III/IV periodontitis requiring nonsurgical periodontal treatment were randomly allocated into two treatment groups: SI with EAF or SI alone. Clinical parameters of percentage of probing pocket depths (PPDs) of ≥5 mm, full mouth bleeding and plaque scores (FMBS and FMPS), and PPD values were recorded at baseline, and at 3 and 6 months posttreatment.

Anti-Ma2 encephalitis in a phenotypic female with XY gonadal dysgenesis: A case report.

Anti-Ma2 encephalitis is an autoimmune disorder that typically involves the brainstem, limbic system, and diencephalon. It can be paraneoplastic and is more common in males. We describe an unusual presentation of anti-Ma2 encephalitis in a patient with an XY chromosome and a female phenotype.

Enamel matrix derivative for alveolar ridge preservation: A randomized controlled trial.

Objective: The aims of this clinical trial were to evaluate the radiographic dimensional changes in alveolar ridge and patient-reported outcomes following tooth extraction and alveolar ridge preservation (ARP) using either deproteinized bovine bone mineral (DBBM) with EMD or DBBM alone.

Methods: Participants requiring at least one posterior tooth extraction and ARP were randomly allocated into two treatment groups: ARP using either DBBM with EMD or DBBM alone. Cone-beam computed tomography (CBCT) images were recorded immediately prior to extraction and at 6 months.

FOXG1 targets BMP repressors and cell cycle inhibitors in human neural progenitor cells.

FOXG1 is a critical transcription factor in human brain where loss-of-function mutations cause a severe neurodevelopmental disorder, while increased FOXG1 expression is frequently observed in glioblastoma. FOXG1 is an inhibitor of cell patterning and an activator of cell proliferation in chordate model organisms but different mechanisms have been proposed as to how this occurs. To identify genomic targets of FOXG1 in human neural progenitor cells (NPCs), we engineered a cleavable reporter construct in endogenous FOXG1 and performed chromatin immunoprecipitation (ChIP) sequencing.

Predictive Value of Ultrasound Imaging for Diagnosis and Surgery of Deep Endometriosis: A Systematic Review.

Objective: To calculate the predictive value and thus the clinical usefulness of transvaginal ultrasound (US) imaging for the management of deep endometriosis, knowing that the positive predictive value (PPV) varies with the prevalence and probably with the volume and location of the disease.

Data Sources: After registration on PROSPERO (CRD42022366323), PubMed was searched for all reports describing the diagnostic accuracy of US imaging for deep endometriosis published between January 1, 2000, and October 20, 2022.

Methods Of Study Selection: The 536 articles on "endometriosis AND US And diagnosis" were hand searched, and 30 reports describing sensitivity and specificity of deep endometriosis were found.

Reconsidering evidence-based management of endometriosis.

Background: Without an adequate animal model permitting experiments the pathophysiology of endometriosis remains unclear and without a non-invasive diagnosis, information is limited to symptomatic women. Lesions are macroscopically and biochemically variable. Hormonal medical therapy cannot be blinded since recognised by the patient and the evidence of extensive surgery is limited because of the combination of low numbers of interventions of variable difficulty with variable surgical skills.

New Understanding of Diagnosis, Treatment and Prevention of Endometriosis.

For 100 years, pelvic endometriosis has been considered to originate from the implantation of endometrial cells following retrograde menstruation or metaplasia. Since some observations, such as the clonal aspect, the biochemical variability of lesions and endometriosis in women without endometrium, the genetic-epigenetic (G-E) theory describes that endometriosis only begins after a series of cumulative G-E cellular changes. This explains that the endometriotic may originate from any pluripotent cell apart from the endometrium, that 'endometrium-like cells' can harbour important G-E differences, and that the risk is higher in predisposed women with more inherited incidents.

Hematologic malignancies of primary bone marrow involvement: a decade's experience in Bahrain.

Introduction: The data on the pattern of primary hematologic malignancies in Bahrain is sparse, although previously published studies suggested rising trends in their incidence. This study aimed to compare with regional and world data and identify any changing trends.

Methods: A retrospective cross-sectional chart analysis study was done on all cases of primary hematologic malignancies of bone marrow origin of Bahraini nationals presenting during the 10-year period from January 2005 to December 2014 at the sole oncology referral center in Bahrain during the study period.

Kabuki syndrome stem cell models reveal locus specificity of histone methyltransferase 2D (KMT2D/MLL4).

Kabuki syndrome is frequently caused by loss-of-function mutations in one allele of histone 3 lysine 4 (H3K4) methyltransferase KMT2D and is associated with problems in neurological, immunological and skeletal system development. We generated heterozygous KMT2D knockout and Kabuki patient-derived cell models to investigate the role of reduced dosage of KMT2D in stem cells. We discovered chromosomal locus-specific alterations in gene expression, specifically a 110 Kb region containing Synaptotagmin 3 (SYT3), C-Type Lectin Domain Containing 11A (CLEC11A), Chromosome 19 Open Reading Frame 81 (C19ORF81) and SH3 And Multiple Ankyrin Repeat Domains 1 (SHANK1), suggesting locus-specific targeting of KMT2D.

FOXG1 dose tunes cell proliferation dynamics in human forebrain progenitor cells.

Heterozygous loss-of-function mutations in Forkhead box G1 (FOXG1), a uniquely brain-expressed gene, cause microcephaly, seizures, and severe intellectual disability, whereas increased FOXG1 expression is frequently observed in glioblastoma. To investigate the role of FOXG1 in forebrain cell proliferation, we modeled FOXG1 syndrome using cells from three clinically diagnosed cases with two sex-matched healthy parents and one unrelated sex-matched control. Cells with heterozygous FOXG1 loss showed significant reduction in cell proliferation, increased ratio of cells in G0/G1 stage of the cell cycle, and increased frequency of primary cilia.

Pathogenesis Based Diagnosis and Treatment of Endometriosis.

Understanding the pathophysiology of endometriosis is changing our diagnosis and treatment. Endometriosis lesions are clones of specific cells, with variable characteristics as aromatase activity and progesterone resistance. Therefore the GE theory postulates GE incidents to start endometriosis, which thus is different from implanted endometrium.

Developmental refinement of visual callosal inputs to ferret area 17.

Corticocortical connections link visual cortical areas in both the ipsilateral and contralateral hemispheres. We studied the postnatal refinement of callosal connections linking multiple cortical areas with ferret area 17 during the period from just before eye opening (4 weeks) to 10 weeks of age. We aimed to determine (1) whether callosal projections from multiple visual cortical areas to area 17 refine with a similar rate and (2) whether the refinement of callosal projections parallels that of intrahemispheric cortical circuits.

Large variations in disease severity, death and ICU admission of 2993 patients infected with SARS-CoV-2: The potential impact of genetic vulnerability.

Background: The COVID-19 pandemic has had an immeasurable impact, affecting healthcare systems, the global economy, and society. Exploration of trends within the existing COVID-19 data may guide directions for further study and novel treatment development. As the world faces COVID-19 disease, it is essential to study its epidemiological and clinical characteristics further to better understand and aid in its detection and containment.

Factors affecting pedestrian behaviors at signalized crosswalks: An empirical study.

Introduction: Safety of pedestrians depends, among other factors, on their behavior while crossing the road. This study aims to assess behaviors of pedestrians at signalized crosswalks.

Method: Following a literature review and a pilot study, 25 vital pedestrian crossing factors and behaviors were determined.

Visual Corticocortical Inputs to Ferret Area 18.

Visual cortical areas in the adult mammalian brain are linked by a network of interareal feedforward and feedback circuits. We investigated the topography of feedback projections to ferret () area 18 from extrastriate areas 19, 21, and Ssy. Our objective was to characterize the anatomical organization of the extrastriate feedback pool to area 18.

Retention in the endoplasmic reticulum is the underlying mechanism of some hereditary haemorrhagic telangiectasia type 2 ALK1 missense mutations.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterised by vascular dysplasia and increased bleeding that affect 1 in 5,000 people world-wide. Pathology is linked to mutations in genes encoding components of the heteromeric transforming growth factor-beta receptor (TGF-beta) and SMAD signalling pathway. Indeed HHT1 and HHT2 result from mutations in the genes encoding endoglin and activin-like kinase 1 (ALK1), TGF-beta receptor components.

Defective cellular trafficking of missense NPR-B mutants is the major mechanism underlying acromesomelic dysplasia-type Maroteaux.

Natriuretic peptides (NPs) comprise a family of structurally related but genetically distinct hormones that regulate a variety of physiological processes such as cardiac growth, blood pressure, axonal pathfinding and endochondral ossification leading to the formation of vertebrae and long bones. The biological actions of NPs are mediated by natriuretic peptide receptors (NPRs) A, B and C that are located on the cell surface. Mutations in NPR-B have been shown to cause acromesomelic dysplasia-type Maroteaux (AMDM), a growth disorder in humans and severe dwarfism in mice.