Sexual Health Behaviors by Age 17 and Lower Urinary Tract Symptoms at Age 19: PLUS Research Consortium Analysis of ALSPAC Data.

Purpose: We examined how antecedent sexual health factors affect lower urinary tract symptoms (LUTS) in adolescent women.

Methods: We analyzed 1,941 adolescent women from the Avon Longitudinal Study of Parents and Children at age 19. At ages 15 and 17, participants reported use of oral contraceptives (OCs), history of sexual intercourse, number of sexual partners, and condom use.

Continuation Versus Discontinuation of Buprenorphine in the Perioperative Setting: A Retrospective Study.

Background Buprenorphine use continues to grow for the management of opioid use disorder (OUD) and chronic pain management. In the face of this increase in use, perioperative buprenorphine management continues to have conflicting recommendations with no consensus on optimal management. We examined the effects of holding versus continuing perioperative buprenorphine in patients on chronic buprenorphine therapy to seek an answer to whether it should be continued or discontinued in the perioperative period.

A transgenic Alx4-CreER mouse to analyze anterior limb and nephric duct development.

Background: Genetic tools to study gene function and the fate of cells in the anterior limb bud are very limited.

Results: We describe a transgenic mouse line expressing CreER from the Aristaless-like 4 (Alx4) promoter that induces recombination in the anterior limb. Cre induction at embryonic day 8.

Number of Social Determinants of Health and Fatal and Nonfatal Incident Coronary Heart Disease in the REGARDS Study.

Background: Social determinants of health (SDH) are individually associated with incident coronary heart disease (CHD) events. Indices reflecting social deprivation have been developed for population management, but are difficult to operationalize during clinical care. We examined whether a simple count of SDH is associated with fatal incident CHD and nonfatal myocardial infarction (MI).

School Toileting Environment, Bullying, and Lower Urinary Tract Symptoms in a Population of Adolescent and Young Adult Girls: Preventing Lower Urinary Tract Symptoms Consortium Analysis of Avon Longitudinal Study of Parents and Children.

Objectives: To examine whether the school toilet environment at age 13, including bullying at toilets, is associated with female lower urinary tract symptoms (LUTS) at ages 13 and 19, as little is known about the association among school toilet environment, voiding behaviors, and LUTS in adolescent girls.

Methods: The sample comprised 3962 female participants from the Avon Longitudinal Study of Parents and Children. At age 13, participants reported on 7 school toilet environment characteristics and a range of LUTS items.

SARS-CoV-2: Is it the newest spark in the TORCH?

Amid the rapidly evolving global coronavirus disease 2019 (COVID-19) pandemic that has already had profound effects on public health and medical infrastructure globally, many questions remain about its impact on child health. The unique needs of neonates and children, and their role in the spread of the virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) should be included in preparedness and response plans. Fetuses and newborn infants may be uniquely vulnerable to the damaging consequences of congenitally- or perinatally-acquired SARS-CoV-2 infection, but data are limited about outcomes of COVID-19 disease during pregnancy.

Using health-related quality of life to predict cardiovascular disease events.

Purpose: Although strong associations between self-reported health and mortality exist, quality of life is not conceptualized as a cardiovascular disease (CVD) risk factor. Our objective was to assess the independent association between health-related quality of life (HRQOL) and incident CVD.

Methods: This study used the REasons for Geographic And Racial Differences in Stroke data, which enrolled 30,239 adults from 2003 to 2007 and followed them over 10 years.

Role for intraflagellar transport in building a functional transition zone.

Genetic disorders caused by cilia dysfunction, termed ciliopathies, frequently involve the intraflagellar transport (IFT) system. Mutations in IFT subunits-including IFT-dynein motor DYNC2H1-impair ciliary structures and Hedgehog signalling, typically leading to "skeletal" ciliopathies such as Jeune asphyxiating thoracic dystrophy. Intriguingly, IFT gene mutations also cause eye, kidney and brain ciliopathies often linked to defects in the transition zone (TZ), a ciliary gate implicated in Hedgehog signalling.

Physical Activity and Incidence of Heart Failure in Postmenopausal Women.

Objectives: This study prospectively examined physical activity levels and the incidence of heart failure (HF) in 137,303 women, ages 50 to 79 years, and examined a subset of 35,272 women who, it was determined, had HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF).

Background: The role of physical activity in HF risk among older women is unclear, particularly for incidence of HFpEF or HFrEF.

Methods: Women were free of HF and reported ability to walk at least 1 block without assistance at baseline.

A Screen for Modifiers of Cilia Phenotypes Reveals Novel MKS Alleles and Uncovers a Specific Genetic Interaction between osm-3 and nphp-4.

Nephronophthisis (NPHP) is a ciliopathy in which genetic modifiers may underlie the variable penetrance of clinical features. To identify modifiers, a screen was conducted on C. elegans nphp-4(tm925) mutants.

KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome.

Background: Joubert syndrome (JBTS) and related disorders are defined by cerebellar malformation (molar tooth sign), together with neurological symptoms of variable expressivity. The ciliary basis of Joubert syndrome related disorders frequently extends the phenotype to tissues such as the eye, kidney, skeleton and craniofacial structures.

Results: Using autozygome and exome analyses, we identified a null mutation in KIAA0556 in a multiplex consanguineous family with hallmark features of mild Joubert syndrome.

Primary cilia enhance kisspeptin receptor signaling on gonadotropin-releasing hormone neurons.

Most central neurons in the mammalian brain possess an appendage called a primary cilium that projects from the soma into the extracellular space. The importance of these organelles is highlighted by the fact that primary cilia dysfunction is associated with numerous neuropathologies, including hyperphagia-induced obesity, hypogonadism, and learning and memory deficits. Neuronal cilia are enriched for signaling molecules, including certain G protein-coupled receptors (GPCRs), suggesting that neuronal cilia sense and respond to neuromodulators in the extracellular space.

An inducible CiliaGFP mouse model for in vivo visualization and analysis of cilia in live tissue.

Background: Cilia are found on nearly every cell type in the mammalian body, and have been historically classified as either motile or immotile. Motile cilia are important for fluid and cellular movement; however, the roles of non-motile or primary cilia in most tissues remain unknown. Several genetic syndromes, called the ciliopathies, are associated with defects in cilia structure or function and have a wide range of clinical presentations.

TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis.

Background: We have shown previously that murine gammaherpesvirus 68 (γHV68) infection exacerbates established pulmonary fibrosis. Because Toll-like receptor (TLR)-9 may be important in controlling the immune response to γHV68 infection, we examined how TLR-9 signaling effects exacerbation of fibrosis in response to viral infection, using models of bleomycin- and fluorescein isothiocyanate-induced pulmonary fibrosis in wild-type (Balb/c) and TLR-9-/- mice.

Results: We found that in the absence of TLR-9 signaling, there was a significant increase in collagen deposition following viral exacerbation of fibrosis.

Assessing the pathogenic potential of human Nephronophthisis disease-associated NPHP-4 missense mutations in C. elegans.

A spectrum of complex oligogenic disorders called the ciliopathies have been connected to dysfunction of cilia. Among the ciliopathies are Nephronophthisis (NPHP), characterized by cystic kidney disease and retinal degeneration, and Meckel-Gruber syndrome (MKS), a gestational lethal condition with skeletal abnormalities, cystic kidneys and CNS malformation. Mutations in multiple genes have been identified in NPHP and MKS patients, and an unexpected finding has been that mutations within the same gene can cause either disorder.

Role of epidermal primary cilia in the homeostasis of skin and hair follicles.

Skin and hair follicle morphogenesis and homeostasis require the integration of multiple signaling pathways, including Hedgehog (Hh) and Wingless (Wnt), and oriented cell divisions, all of which have been associated with primary cilia. Although studies have shown that disrupting dermal cilia causes follicular arrest and attenuated Hh signaling, little is known about the role of epidermal cilia. Here, epidermal cilia function was analyzed using conditional alleles of the ciliogenic genes Ift88 and Kif3a.

Utilization of conditional alleles to study the role of the primary cilium in obesity.

Ciliopathies are a group of human diseases that involve dysfunction of the cilium. Human patients with mutations in ciliary proteins can exhibit a wide range of phenotypes, one of which is obesity. This is seen in patients with Bardet-Biedl syndrome (BBS) and Alström syndrome (ALMS).

Insulin therapy in diabetes mellitus: how can the currently available injectable insulins be most prudently and efficaciously utilised?

The era of animal source insulins has passed and human recombinant DNA insulins are gradually being replaced because of the superior efficacy of insulin analogues. Analogue insulins are available in both rapid- and long-acting preparations. Currently available rapid-acting insulins are lispro, aspart and glulisine, and the currently available long-acting analogue basal insulins are detemir and glargine.

Advantages of a third-generation beta-blocker in patients with diabetes mellitus.

beta-Blocker use improves outcomes even more for the patient with diabetes mellitus than for the patient without diabetes with a history of acute myocardial infarction or coronary artery disease. beta-Blockers facilitate shifting the metabolism of the myocardium away from free fatty acid toward glucose utilization, thereby reducing the cardiac workload and myocardial ischemia. beta-Blockers are also able to reverse the fetal gene induction program to reverse myocardial remodeling and improve ventricular function.

Type 2 diabetes mellitus: what is the optimal treatment regimen?

Treatment options for type 2 diabetes mellitus currently consist of insulin sensitizers, alpha-glucosidase inhibitors, secretagogues, and insulin. However, the emphasis on initial therapy has been shifting from secretagogues and alpha-glucosidase inhibitors to insulin sensitizers such as metformin and the thiazolidinediones (TZDs). This article outlines the benefits of treatment with sensitizers vis à vis alpha-glucosidase inhibitors and secretagogues as part of a comprehensive treatment algorithm for type 2 diabetes.

Laparoscopically assisted anorectal pull-through for high imperforate anus--a new technique.

Background/purpose: This report describes a new technique of laparoscopically assisted anorectal pull-through (LAARP) for repair of high imperforate anus. The procedure utilizes minimal perineal dissection, preservation of the distal rectum, and accurate placement of the rectum within the levator ani and external anal sphincter muscle complex.

Methods: Sharp dissection and cautery was used laparoscopically to expose the rectal pouch down to the urethral or vaginal fistula, which was clipped distally and divided.

Comparison of anti-epileptic drug levels in different cases of sudden death.

Sudden unexplained death syndrome (SUDS) in epilepsy is identified as death in an epileptic individual with no anatomic cause found at autopsy. SUDS appears to be associated with subtherapeutic levels of anticonvulsants. Sudden death with no demonstrable cause at autopsy accounts for 5% to 30% of deaths in epileptic individuals.

Evidence for altered proliferative ability of progenitors of urothelial cells in interstitial cystitis.

Secondary cultures of basal urothelial cells isolated from patients with stress incontinence (7 patients), neurogenic bladder (2 patients), interstitial cystitis (IC) (27 patients), bladder rupture (1 patient) and bacterial cystitis (3 patients) grew under growth restricting conditions. All groups displayed reproducible colony size distribution, reflecting the proliferative potential distribution in the population of progenitor cells seeded. The percentage of large colonies (> 6 cells/colony), progeny of basal cells with high proliferative potential, was low in cultures from control patients with stress incontinence, neurogenic bladder or bladder rupture.