Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus.

Prevalence of opioid dependence in Scotland 2015-2020: A multi-parameter estimation of prevalence (MPEP) study.

Background And Aims: Drug-related deaths in Scotland more than doubled between 2011 and 2020. To inform policymakers and understand drivers of this increase, we estimated the number of people with opioid dependence aged 15-64 from 2014/15 to 2019/20.

Design: We fitted a Bayesian multi-parameter estimation of prevalence (MPEP) model, using adverse event rates to estimate prevalence of opioid dependence jointly from Opioid Agonist Therapy (OAT), opioid-related mortality and hospital admissions data.

The immunobiology of SARS-CoV-2 infection and vaccine responses: potential influences of cross-reactive memory responses and aging on efficacy and off-target effects.

Immune responses to both SARS-CoV-2 infection and its associated vaccines have been highly variable within the general population. The increasing evidence of long-lasting symptoms after resolution of infection, called post-acute sequelae of COVID-19 (PASC) or "Long COVID," suggests that immune-mediated mechanisms are at play. Closely related endemic common human coronaviruses (hCoV) can induce pre-existing and potentially cross-reactive immunity, which can then affect primary SARS-CoV-2 infection, as well as vaccination responses.

Regulation of human and mouse bystander T cell activation responses by PD-1.

Bystander activation of memory T cells occurs via cytokine signaling alone in the absence of T cell receptor (TCR) signaling and provides a means of amplifying T cell effector responses in an antigen-nonspecific manner. While the role of Programmed Cell Death Protein 1 (PD-1) on antigen-specific T cell responses is extensively characterized, its role in bystander T cell responses is less clear. We examined the role of the PD-1 pathway during human and mouse non-antigen-specific memory T cell bystander activation and observed that PD-1+ T cells demonstrated less activation and proliferation than activated PD-1- populations in vitro.

Internally versus externally trained residents and fellows hired as attendings at a large integrated healthcare system: a 20-year retrospective study.

Background: There remains a question of whether graduates trained internally are different than those trained elsewhere. We examine the difference between physicians trained within our Graduate Medical Education (GME) programs versus physicians trained elsewhere. Our large integrated healthcare system is unique in addressing this objective due to its large physician labor hiring needs across different specialties of GME graduates.

Aging augments obesity-induced thymic involution and peripheral T cell exhaustion altering the "obesity paradox".

Introduction: The incidence of obesity, a condition characterized by systemic chronic inflammation, has reached pandemic proportions and is a poor prognostic factor in many pathologic states. However, its role on immune parameters has been diverse and at times contradictory. We have previously demonstrated that obesity can result in what has been called the "obesity paradox" which results in increased T cell exhaustion, but also greater efficacy of immune checkpoint blockade in cancer treatment.

Activation status dictates the function of unlicensed natural killer cells in mice and humans.

Natural killer (NK) cells are involved in innate defense against viral infection and cancer. NK cells can be divided into subsets based on the ability of different receptors to bind to major histocompatibility (MHC) class 1 molecules, resulting in differential responses upon activation in a process called "licensing" or "arming." NK cells expressing receptors that bind self-MHC are considered licensed due to an augmented effector lytic function capability compared with unlicensed subsets.

Increased efficacy of dual proinflammatory cytokine blockade on acute GVHD while maintaining GVT effects.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curative option for treating a variety of hematologic diseases, but acute and chronic graft-versus-host disease (GVHD) remain major barriers limiting efficacy. Acute gut GVHD occurs with marked increases in proinflammatory cytokines (including TNF and IL-6), which we recently demonstrated was exacerbated in obesity resulting in severe gastrointestinal pathology. Given the pleiotropic and overlapping effects of these 2 cytokines, we assessed the impact of dual TNF and IL-6R blockade on GVHD as well as graft-versus tumor (GVT) effects in different mouse GVHD models.

Point-of-care ultrasound in obstetrics.

Point-of-care ultrasound, or PoCUS, where imaging is undertaken at the bedside, clinic or emergency department (ED) by the clinician overseeing treatment, is a rapid form of assessment that may be undertaken alongside or as an alternative to traditional, formal ultrasound performed by a radiology service. PoCUS reduces the time to diagnosis, thus allowing lifesaving treatment to be initiated. This is particularly relevant in Obstetrics and Gynaecology (OBGYN), where delayed diagnosis of pregnancy complications is often fatal or highly debilitating to the mother or fetus.

Gallbladder Polyps: Real or Imagined?

The finding of gallbladder polyps on imaging studies prompts further workup. Imaging results are often discordant with final pathology. The goal of this study is to compare polypoid lesions of the gallbladder found on preoperative ultrasound (US) with final pathologic diagnosis after cholecystectomy to help guide clinical decision-making.

Small Bowel Obstructions in a Virgin Abdomen: Is an Operation Mandatory?

Though conventionally not considered standard of care, nonoperative management of patients with small bowel obstruction (SBO) without previous abdominal operations, so called "virgin abdomens," (VA) is presently being practiced. We aimed to determine outcomes of patients with VA undergoing operative and nonoperative management of SBO. A retrospective review of patients with SBO was performed; outcomes of patients with VA were analyzed.

Optimal control of insects through sterile insect release and habitat modification.

This paper develops an optimal control framework for an ordinary differential equation model to investigate the introduction of sterile mosquitoes to reduce the incidence of mosquito-borne diseases. Existence of a solution given an optimal strategy and the optimal control is determined in association with the negative effects of the disease on the population while minimizing the cost due to this control mechanism. Numerical simulations have shown the importance of effects of the bounds on the release of sterile mosquitoes and the bounds on the likelihood of egg maturation.

A decade of selective use of adjustable cutting seton combined with fistulotomy for anal fistula.

Previous studies have demonstrated that the division of sphincter muscle in the treatment of anal fistula may precipitate fecal incontinence. Cutting setons may pose a particular risk of unrecoverable injury to the sphincter apparatus. To evaluate if the use of an adjustable cutting seton mitigates this risk, we performed a retrospective review of all patients operated on for anal fistulae in a 10-year period by a single surgeon.

Predicting performance on the American Board of Surgery qualifying and certifying examinations: a multi-institutional study.

Background: We sought to determine whether US Medical Licensing Examination (USMLE) Step 1 score, American Board of Surgery (ABS) In-Training Examination (ABSITE) score, and other variables are associated with failing the ABS qualifying and certifying examinations. Identifying such factors may assist in the early implementation of an academic intervention for at-risk residents.

Design: Retrospective review.

BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis.

Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation.

Differential expression and regulation by activin of the neurotrophins BDNF and NT4 during human and mouse ovarian development.

The tropomyosin-related kinase (Trk) B neurotrophin receptor is essential for ovarian germ cell survival and primordial follicle formation, but the contributions of its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), are unknown. We have investigated their expression and regulation in developing human and mouse ovaries. BDNF expression increased with increasing gestation, expression of human NTF4 and of both Ntf5 and Bdnf in the mouse was unchanged.

Views of surgery program directors on the current ACGME and proposed IOM duty-hour standards.

Purpose: The purpose of this study was to survey the experiences of surgery program directors with the current Accreditation Council for Graduate Medical Education (ACGME) duty-hour standards and views of the Institute of Medicine (IOM) proposed duty-hour recommendations.

Methods: A total of 118 program directors (47.6% of all surgery programs in the US) responded to the survey.

Prostaglandin E2 as a regulator of germ cells during ovarian development.

Context: The formation of primordial follicles occurs during fetal life yet is critical to the determination of adult female fertility. Prior to this stage, germ cells proliferate, enter meiosis, and associate with somatic cells. Growth and survival factors implicated in these processes include activin A (INHBA), the neurotrophins BDNF and NT4 (NTF5), and MCL1.

Blasting neuroblastoma using optimal control of chemotherapy.

A mathematical model is used to investigate the effectiveness of the chemotherapy drug Topotecan against neuroblastoma. Optimal control theory is applied to minimize the tumor volume and the amount of drug utilized. The model incorporates a state constraint that requires the level of circulating neutrophils (white blood cells that form an integral part of the immune system) to remain above an acceptable value.

N- and E-cadherin expression in human ovarian and urogenital duct development.

Objective: To investigate expression of N- and E-cadherin in the developing human ovary.

Design: The expression of N- and E-cadherin was analyzed in 18 human fetal ovaries between 8 and 20 weeks' gestation using immunohistochemistry. Fetal human male and rat urogenital tracts were used for comparison of expression.

Operative strategy can reduce the incidence of major bile duct injury in laparoscopic cholecystectomy.

Major bile duct injury (BDI) rates remain in the range of 0.3 to 0.5 per cent for laparoscopic cholecystectomy (LC).

Early laparoscopic cholecystectomy is the preferred management of acute cholecystitis.

Hypothesis: Early laparoscopic cholecystectomy (LC) results in a shorter length of stay and acceptable conversion and complication rates when compared with antibiotic therapy plus interval LC or percutaneous cholecystostomy in patients admitted to a surgical service because of acute cholecystitis. However, actual practice does not conform to current evidence.

Design: Retrospective cohort study.

Activin signals via SMAD2/3 between germ and somatic cells in the human fetal ovary and regulates kit ligand expression.

Ovarian germ cell survival is dependent upon the formation of primordial follicles, which occurs during fetal life in the human. Activin contributes to germ cell proliferation and survival at this time. SMADs2 and 3 are central elements in the activin signalling pathway and thus indicate sites of activin action.