Maternofetal Outcomes in Women With Congenital Uterine Anomalies.

Müllerian anomalies are congenital disorders that affect the female reproductive system, often leading to a range of obstetric complications. These anomalies include structural abnormalities such as arcuate, septate, unicornuate, and bicornuate uteri, which can impact fertility, pregnancy outcomes, and delivery methods. This case series presents five patients with different types of Müllerian anomalies, including septate, arcuate, and unicornuate uteri.

Pregnancy After Beating Thyroid Cancer: A Case Series.

Thyroid cancer is common among women of reproductive age and is a frequently occurring cancer during pregnancy, following breast cancer. Contributing factors include radiation exposure, iodine deficiency, and genetic conditions like multiple endocrine neoplasia type 2 (MEN2). Pregnancy significantly impacts thyroid function, leading to gland enlargement and altered thyroid stimulating hormone (TSH) levels due to hormonal changes, including elevated human chorionic gonadotropin (hCG) and estrogen.

CCR4 and CCR7 differentially regulate thymocyte localization with distinct outcomes for central tolerance.

Central tolerance ensures autoreactive T cells are eliminated or diverted to the regulatory T cell lineage, thus preventing autoimmunity. To undergo central tolerance, thymocytes must enter the medulla to test their T-cell receptors (TCRs) for autoreactivity against the diverse self-antigens displayed by antigen-presenting cells (APCs). While CCR7 is known to promote thymocyte medullary entry and negative selection, our previous studies implicate CCR4 in these processes, raising the question of whether CCR4 and CCR7 play distinct or redundant roles in central tolerance.

The initial age-associated decline in early T-cell progenitors reflects fewer pre-thymic progenitors and altered signals in the bone marrow and thymus microenvironments.

Age-related thymus involution results in decreased T-cell production, contributing to increased susceptibility to pathogens and reduced vaccine responsiveness. Elucidating mechanisms underlying thymus involution will inform strategies to restore thymopoiesis with age. The thymus is colonized by circulating bone marrow (BM)-derived thymus seeding progenitors (TSPs) that differentiate into early T-cell progenitors (ETPs).

Central tolerance is impaired in the middle-aged thymic environment.

One of the earliest hallmarks of immune aging is thymus involution, which not only reduces the number of newly generated and exported T cells, but also alters the composition and organization of the thymus microenvironment. Thymic T-cell export continues into adulthood, yet the impact of thymus involution on the quality of newly generated T-cell clones is not well established. Notably, the number and proportion of medullary thymic epithelial cells (mTECs) and expression of tissue-restricted antigens (TRAs) decline with age, suggesting the involuting thymus may not promote efficient central tolerance.

Age-Related Changes in Thymic Central Tolerance.

Thymic epithelial cells (TECs) and hematopoietic antigen presenting cells (HAPCs) in the thymus microenvironment provide essential signals to self-reactive thymocytes that induce either negative selection or generation of regulatory T cells (Treg), both of which are required to establish and maintain central tolerance throughout life. HAPCs and TECs are comprised of multiple subsets that play distinct and overlapping roles in central tolerance. Changes that occur in the composition and function of TEC and HAPC subsets across the lifespan have potential consequences for central tolerance.

A Genetic Mouse Model Recapitulates Immune Checkpoint Inhibitor-Associated Myocarditis and Supports a Mechanism-Based Therapeutic Intervention.

Immune checkpoint inhibitors (ICI) targeting CTLA4 or PD-1/PD-L1 have transformed cancer therapy but are associated with immune-related adverse events, including myocarditis. Here, we report a robust preclinical mouse model of ICI-associated myocarditis in which monoallelic loss of in the context of complete genetic absence of leads to premature death in approximately half of mice. Premature death results from myocardial infiltration by T cells and macrophages and severe ECG abnormalities, closely recapitulating the clinical and pathologic hallmarks of ICI-associated myocarditis observed in patients.

Interface residues of transient protein-protein complexes have extensive intra-protein interactions apart from inter-protein interactions.

Background: Protein-protein interactions are crucial for normal biological processes and to regulate cellular reactions that affect gene expression and function. Several previous studies have emphasized the roles of residues at the interface of protein-protein complexes in conferring stability and specificity to the complex. Interface residues in a protein are well known for their interactions with sidechain and main chain atoms with the interacting protein.

Role of Aspirin in High Pulsatility Index of Uterine Artery: A Consort Study.

Background: Preeclampsia is a heterogeneous disorder prevalent in 3-10% of pregnant women globally. The etiology is multifactorial. There is a initial stage of endothelial dysfunction and placental ischemia (Stage 1); this leads to maternal syndrome of hypertension, edema, and proteinuria (Stage 2).

Role of Gene Polymorphism in Recurrent Implantation Failure and Preeclampsia.

This is a rare case of gene polymorphism causing thrombophilia and recurrent implantation failure following intrauterine insemination. gene encodes plasminogen activator inhibitor type 1 and inhibits fibrinolysis, or clot dissolution. The 4G variant results in increased expression of SERPINE1 and consequently higher inhibition of fibrinolysis, thus leading to thrombophilia.

Efficacy of transcutaneous electrical nerve stimulation in the treatment of chronic pelvic pain.

Background: Chronic pelvic pain is prevalent in 2% of women population globally. The etiology is multifactorial. Even in the absence of pelvic pathology, there is a subgroup of women who do not respond to analgesic and anti-inflammatory therapy.

Spatio-temporal profile, phenotypic diversity, and fate of recruited monocytes into the post-ischemic brain.

Background: A key feature of the inflammatory response after cerebral ischemia is the brain infiltration of blood monocytes. There are two main monocyte subsets in the mouse blood: CCR2Ly6C "inflammatory" monocytes involved in acute inflammation, and CX3CR1Ly6C "patrolling" monocytes, which may play a role in repair processes. We hypothesized that CCR2Ly6C inflammatory monocytes are recruited in the early phase after ischemia and transdifferentiate into CX3CR1Ly6C "repair" macrophages in the brain.

Retroperitoneal approach for dissection of inflamed pelvic viscera in acute pelvic inflammatory disease- case report.

Tubo-ovarian abscesses can rupture spontaneously after a manual examination or an accidental trauma. A critically ill patient with septic peritonitis will only deteriorate if timely surgical removal of pus is not done. The operation of choice is removal of free pus, together with the abscess, the uterus, the tubes and usually, the ovaries.

Using pharmacophore models to gain insight into structural binding and virtual screening: an application study with CDK2 and human DHFR.

This study provides results from two case studies involving the application of the HypoGenRefine algorithm within Catalyst for the automated generation of excluded volume from ligand information alone. A limitation of pharmacophore feature hypothesis alone is that activity prediction is based purely on the presence and arrangement of pharmacophoric features; steric effects remained unaccounted. Recently reported studies have illustrated the usefulness of combining excluded volumes to the pharmacophore models.

Isolated dissections and dissecting aneurysms of the posterior inferior cerebellar artery: topic and literature review.

Isolated dissections of the posterior inferior cerebellar artery (PICA) are rare. Thus, no large series of cases have been reported in the literature. Due to limited knowledge regarding the natural history of these lesions and the lack of high-quality evidence supporting various treatment options, management is controversial and practice parameters are ill defined.

Hemodynamic response changes in cerebrovascular disease: implications for functional MR imaging.

Background And Purpose: Patients with cerebrovascular occlusive disease may develop compensatory changes in local cerebral vasculature with a resultant loss of vascular reactivity. These alterations can affect the blood oxygen level-dependent (BOLD) signal that is the basis for functional MR imaging. We investigated the BOLD signal in patients with unilateral cerebrovascular disease to ascertain the clinical utility of functional MR imaging in these patients.

Evaluation of a novel shape-based computational filter for lead evolution: application to thrombin inhibitors.

A novel shape-feature-based computational method is described and used to rapidly filter compound libraries. The computational model, built using three-dimensional conformations of active and inactive molecules, consists of a collection of whole molecule shapes and chemical feature positions that are ranked according to their correlation with activity. A small ensemble of these shapes and features is used to filter virtual compound libraries.