G9a Modulates Lipid Metabolism in CD4 T Cells to Regulate Intestinal Inflammation.

Background & Aims: Although T-cell intrinsic expression of G9a has been associated with murine intestinal inflammation, mechanistic insight into the role of this methyltransferase in human T-cell differentiation is ill defined, and manipulation of G9a function for therapeutic use against inflammatory disorders is unexplored.

Methods: Human naive T cells were isolated from peripheral blood and differentiated in vitro in the presence of a G9a inhibitor (UNC0642) before being characterized via the transcriptome (RNA sequencing), chromatin accessibility (assay for transposase-accessible chromatin by sequencing), protein expression (cytometry by time of flight, flow cytometry), metabolism (mitochondrial stress test, ultrahigh performance liquid chromatography-tandem mas spectroscopy) and function (T-cell suppression assay). The in vivo role of G9a was assessed using 3 murine models.

Detection of Anal Intraepithelial Neoplasia and Anal Squamous Cell Carcinoma on Colonoscopy.

The purpose of this case series is to review the endoscopic detection of anal intraepithelial neoplasia and anal squamous cell carcinoma including the role of rectal retroflexion and narrow-band imaging. Four cases of anal intraepithelial neoplasia were incidentally discovered in women aged 55-71 years. Anal lesions identified included sessile polyps, nodular mucosa, and circumferential polyps.

Harlequin Ichthyosis: A Fatal Case Report in Al-Medina, Saudi Arabia.

Harlequin ichthyosis (HI) is an autosomal recessive disorder. It is a fatal disease and many infants born with HI die shortly after birth. The incidence is extremely rare and is reported to be about 1 in 300,000 births.

Child-Turcotte-Pugh versus MELD-XI identify distinct high-risk populations for heart transplantation following ventricular assist device placement.

Background: Patients with end-stage heart failure frequently have significant congestive hepatopathy requiring hepatology assessment prior to heart transplantation listing. An elevated Model for End-stage Liver Disease score with modification to exclude INR (MELD-XI) has been associated with increased mortality following heart transplantation (HT). This study's primary aim was to examine whether Child-Turcotte-Pugh (CTP) classification is associated with post-transplant mortality in patients bridged to transplant with left ventricular assist devices.

Evaluation of Charcot Triad, Reynolds Pentad, and Tokyo Guidelines for Diagnosis of Cholangitis Secondary to Choledocholithiasis Across Patient Age Groups.

Objective: To determine the prevalence of Charcot triad, Reynolds pentad, and Tokyo Guidelines criteria and clinical outcomes among patients with cholangitis across different age groups.

Patients And Methods: We conducted a retrospective analysis of 257 consecutive hospitalized adult patients with acute cholangitis due to endoscopic retrograde cholangiopancreatography-confirmed choledocholithiasis between January 1, 2015, and December 31, 2019. Patients were divided into 3 age groups: less than 65 years, 65 to 79 years, and 80 years or older.

Fetal aortic valvuloplasty: first report of two cases from Saudi Arabia.

Background: Fetal aortic stenosis may progress to hypoplastic left heart syndrome (HLHS), which carries a poor prognosis. We report two infants with fetal aortic stenosis successfully treated with fetal aortic valvuloplasty (FAV) using balloon dilatation.

Case Presentation: Of five fetuses with aortic stenosis fulfilling the FAV criteria of severe aortic stenosis with a left ventricular length Z-score of ≥ - 2, retrograde flow in the transverse aortic arch, left-to-right flow across the foramen ovale, monophasic mitral inflow, and significant left ventricular dysfunction, we obtained permission for FAV in two fetuses.

Congenital anomalies and associated risk factors in a Saudi population: a cohort study from pregnancy to age 2 years.

Objective: To assess the three key issues for congenital anomalies (CAs) prevention and care, namely, CA prevalence, risk factor prevalence and survival, in a longitudinal cohort in Riyadh, Saudi Arabia.

Setting: Tertiary care centre, Riyadh, Saudi Arabia.

Participants: Saudi women enrolled during pregnancy over 3 years and their 28 646 eligible pregnancy outcomes (births, stillbirths and elective terminations of pregnancy for foetal anomalies).

Human regulatory T cells undergo self-inflicted damage via granzyme pathways upon activation.

Tregs hold great promise as a cellular therapy for multiple immunologically mediated diseases, given their ability to control immune responses. The success of such strategies depends on the expansion of healthy, suppressive Tregs ex vivo and in vivo following the transfer. In clinical studies, levels of transferred Tregs decline sharply in the blood within a few days of the transfer.

Molecular autopsy in maternal-fetal medicine.

PurposeThe application of genomic sequencing to investigate unexplained death during early human development, a form of lethality likely enriched for severe Mendelian disorders, has been limited.MethodsIn this study, we employed exome sequencing as a molecular autopsy tool in a cohort of 44 families with at least one death or lethal fetal malformation at any stage of in utero development. Where no DNA was available from the fetus, we performed molecular autopsy by proxy, i.

Brief treatment with a highly selective immunoproteasome inhibitor promotes long-term cardiac allograft acceptance in mice.

Constitutive proteasomes (c-20S) are ubiquitously expressed cellular proteases that degrade polyubiquitinated proteins and regulate cell functions. An isoform of proteasome, the immunoproteasome (i-20S), is highly expressed in human T cells, dendritic cells (DCs), and B cells, suggesting that it could be a potential target for inflammatory diseases, including those involving autoimmunity and alloimmunity. Here, we describe DPLG3, a rationally designed, noncovalent inhibitor of the immunoproteasome chymotryptic subunit β5i that has thousands-fold selectivity over constitutive β5c.

Tiam1/Rac1 complex controls Il17a transcription and autoimmunity.

RORγt is a master transcription factor of Th17 cells and considered as a promising drug target for the treatment of autoimmune diseases. Here, we show the guanine nucleotide exchange factor, Tiam1, and its cognate Rho-family G protein, Rac1, regulate interleukin (IL)17A transcription and autoimmunity. Whereas Tiam1 genetic deficiency weakens IL-17A expression partially and inhibits the development of experimental autoimmune encephalomyelitis (EAE), deletion of Rac1 in T cells exhibits more robust effects on Th17 cells and EAE.

Identification of embryonic lethal genes in humans by autozygosity mapping and exome sequencing in consanguineous families.

Background: Identifying genetic variants that lead to discernible phenotypes is the core of Mendelian genetics. An approach that considers embryonic lethality as a bona fide Mendelian phenotype has the potential to reveal novel genetic causes, which will further our understanding of early human development at a molecular level. Consanguineous families in which embryonic lethality segregates as a recessive Mendelian phenotype offer a unique opportunity for high throughput novel gene discovery as has been established for other recessive postnatal phenotypes.

Effect of consanguinity on birth defects in Saudi women: results from a nested case-control study.

Background: The role of consanguinity in the etiology of structural birth defects outside of chromosomal and inherited disorders has always been debated. We studied the independent role of consanguinity on birth defects in Saudi women with a high prevalence of consanguineous marriages.

Methods: This case and control study was nested within a 3-year prospective cohort study to examine patterns of fetal and neonatal malformations in Saudi women at Prince Sultan Military Medical City (PSMMC), Riyadh -Saudi Arabia.

BCL6 controls Th9 cell development by repressing Il9 transcription.

The transcriptional repressor B cell lymphoma 6 (BCL6) is required for the development of Th follicular cells, and it has been shown to suppress Th2 cell differentiation. We demonstrate that BCL6 is a key regulator of Th9 cell development. BCL6 expression is transiently downregulated in polarized Th9 cells, and forced expression of BCL6 in Th9 cells impairs Th9 cell differentiation.

Vaginoscopic resection of vaginal septum.

We report the resection of a vaginal septum while preserving the virginity of a 12-year-old girl with Herlyn-Werner-Wunderlich Syndrome (HWWS) having a didelphys uterus, obstructed hemivagina, and an ipsilateral renal agenesis with follow-up at 18 months. Successful resection of the vaginal septum with conservation of the hymenal ring and complete drainage of both the hematocolpos and the hematometra were achieved. Cyclic dysmenorrhea and pelvic pain were completely resolved on follow-up visits at 4, 6, and 18 months.

Fetus-in-fetu. Imaging and pathology.

Fetus-in-fetu (FIF), also known as endoparasitic twin, is a form of asymmetric fetal duplication in which the abnormal developing embryo parasitizes the normal co-twin by attaching internally. Here, we report a case of FIF presented as an intra-abdominal cystic mass, which was first detected during an antenatal ultrasound examination of a 32-year-old Saudi mother. At 34 weeks and 4 days of gestation, she had spontaneous labor and delivered a baby boy.

Prevalence and pattern of alternative medicine use: the results of a household survey.

Background And Objectives: Alternative medicine (AM) encompasses all forms of therapies that fall outside the mainstream of medical practice. Its popularity is on the increase. Because previous surveys were limited and not generalizable, we estimated the prevalence, pattern and factors associated with use of AM in the community.

Multiple pregnancy and preterm labor.

Objective: Multiple gestations are high risk pregnancies, which may be complicated by pre-maturity, low birth weight infants, pre-eclampsia, anemia, postpartum hemorrhage, intrauterine growth restriction, neonatal morbidity and high perinatal, neonatal and infant mortality. This study was carried out to determine the incidence and effect of multiple pregnancies on pre-term labor in tertiary care hospitals.

Methods: Retrospective case record analysis of 375 cases of multiple pregnancies that were reported at Armed Forces Hospital and King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, between January 2000 and December 2001.