Brief Virtual Workshop on Gambling Disorder to Raise Knowledge and Awareness Among Health Service Providers.

Gambling disorder is a "hidden disease" due to the lack of visible markers. It often negatively affects multiple domains of a person's life and predicts adverse physical, mental, social, and financial outcomes. Health service settings are suited for early detection of gambling disorder because of its comorbid medical conditions and due to the trust patients have in their health service providers (HSPs). However, HSPs often lack the knowledge needed to screen for this disorder and to make appropriate referrals. This paper reports a quasi-experimental wait-list control study (experimental group n = 18; wait-list control group n = 14), with cross-over and a twelve-week follow-up which assessed whether a brief virtual gambling disorder training entitled Gambling Know More could improve gambling disorder knowledge among HSPs. Results showed workshop participation caused a significant increase in gambling disorder knowledge immediately after the workshop and twelve weeks later. Participation in Gambling Know More bodes well for increasing early detection of gambling disorder and appropriate treatment referrals among HSPs. Findings have important policy implications for the training of HSPs.

Anti-racism structures in academic dentistry: Supporting underrepresented racially/ethnically diverse faculty.

OBJECTIVES: The purpose of this paper is to describe the racialized barriers to recruiting and retaining historically underrepresented racially/ethnically diverse (HURE) faculty at U.S. dental schools and the linkages of these barriers to structural racism to assist dental schools in eliminating these hurdles through an antiracism framework. METHODS: Data is used to describe the trends in the racial/ethnic composition of dental school faculty and the parity gaps by race/ethnicity between dentists and the U.S. POPULATION: Literature on the recruitment and retention of faculty of color at higher education institutions is reviewed to identify challenges and best practices. Barriers to the full participation of HURE faculty, outlined in the American Dental Education Association's Faculty Diversity Toolkit, are also identified. Research on antiracism frameworks is also investigated to denote their uses and key components. RESULTS: There is a critical shortage of HURE faculty at dental schools and active HURE dentists in the U.S. A history of racism and its legacy reinforce biases, stereotypes, and power structures that harm HURE faculty at U.S. dental schools. An anti-racism framework is needed to holistically eliminate inequities and racialized policies and practices that persists as barriers for HURE faculty. CONCLUSIONS: Increasing the representation of HURE dentists in the workforce and dental school faculty requires a major disruption to culture and institutional practices that mask centuries of structural racism embedded within complex academic systems. Dental schools must use antiracism models to create strategic initiatives that support a humanistic, equitable, and antiracism environment where HURE faculty can thrive.

Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell Function.

BACKGROUND & AIMS: One of the features of ulcerative colitis (UC) is a defect in the protective mucus layer. This has been attributed to a reduced number of goblet cells (GCs). However, it is not known whether abnormal GC mucus secretion also contributes to the reduced mucus layer. Our aims were to investigate whether GC secretion was abnormal in UC and exists as a long-term effect of chronic inflammation. METHODS: Colonoids were established from intestinal stem cells of healthy subjects (HS) and patients with UC. Colonoids were maintained as undifferentiated (UD) or induced to differentiate (DF) and studied as three-dimensional or monolayers on Transwell filters. Total RNA was extracted for quantitative real-time polymerase chain reaction analysis. Carbachol and prostaglandin E2 mediated mucin stimulation was examined by MUC2 IF/confocal microscopy and transmission electron microscopy. RESULTS: Colonoids from UC patients can be propagated over many passages; however, they exhibit a reduced rate of growth and transepithelial electrical resistance compared with HS. Differentiated UC colonoid monolayers form a thin and non-continuous mucus layer. UC colonoids have increased expression of secretory lineage markers ATOH1 and SPDEF, along with MUC2 positive GCs, but failed to secrete mucin in response to the cholinergic agonist carbachol and prostaglandin E2, which caused increased secretion in HS. Exposure to tumor necrosis factor α (5 days) reduced the number of GCs, with a greater percentage decrease in UC colonoids compared with HS. CONCLUSIONS: Chronic inflammation in UC causes long-term changes in GCs, leading to abnormal mucus secretion. This continued defect in GC mucus secretion may contribute to the recurrence in UC.

The Learning Health System Competency Appraisal Inventory (LHS-CAI): A novel tool for assessing LHS-focused education needs.

There is increasing interest in health care organizations functioning as learning health systems (LHSs) to improve the quality and efficiency of health care delivery while generating new knowledge. Individuals must be trained in associated concepts and competencies and subsequently positioned (or embedded) within the delivery system for maximum effect as they perform their scholarship. Potential researchers within LHSs come from many different training backgrounds; therefore, each LHS scholar requires a goal-directed plan tailored to his or her needs. There are few tools available to guide development, training, or evaluation of individuals interested in becoming leaders of research in LHSs. In this paper, we present a newly developed tool for guiding the training of such researchers, the Learning Health Systems Competency Appraisal Inventory (LHS-CAI). The LHS-CAI is modeled after the Clinical Research Appraisal Index (CRAI) used within Clinical and Translational Science Award sites across the United States. The LHS-CAI is a tool for trainees at all levels to use with their mentors in an interactive manner. The tool can then identify areas in which more training is needed and at what level to ensure success as a researcher within LHSs. We further modified the CRAI format to better leverage the LHS-CAI as a key part of an LHS scholar's individual development plan. To implement the LHS-CAI, we have identified key points within the Minnesota Learning Health System Mentored Career Development Program (MN-LHS) at which assessment of expertise for each competency would be useful to LHS scholars, mentors, and program leaders. Scholars in this program come from various clinical and academic backgrounds but are all targeting their career trajectories toward leading embedded LHS research. They will reevaluate their expertise upon completion of the program, with comparison to baseline serving as a key program evaluation tool. The LHS-CAI is currently being implemented with the first cohort of scholars in the MN-LHS program.

Intestinal stem cell-derived enteroids from morbidly obese patients preserve obesity-related phenotypes: Elevated glucose absorption and gluconeogenesis.

OBJECTIVE: The mechanisms behind the efficacy of bariatric surgery (BS) for treating obesity and type 2 diabetes, particularly with respect to the influence of the small bowel, remain poorly understood. In vitro and animal models are suboptimal with respect to their ability to replicate the human intestinal epithelium under conditions induced by obesity. Human enteroids have the potential to accelerate the development of less invasive anti-obesity therapeutics if they can recapitulate the pathophysiology of obesity. Our aim was to determine whether adult stem cell-derived enteroids preserve obesity-characteristic patient-specific abnormalities in carbohydrate absorption and metabolism. METHODS: We established 24 enteroid lines representing 19 lean, overweight, or morbidly obese patients, including post-BS cases. Dietary glucose absorption and gluconeogenesis in enteroids were measured. The expression of carbohydrate transporters and gluconeogenic enzymes was assessed and a pharmacological approach was used to dissect the specific contribution of each transporter or enzyme to carbohydrate absorption and metabolism, respectively. RESULTS: Four phenotypes representing the relationship between patients' BMI and intestinal dietary sugar absorption were found, suggesting that human enteroids retain obese patient phenotype heterogeneity. Intestinal glucose absorption and gluconeogenesis were significantly elevated in enteroids from a cohort of obese patients. Elevated glucose absorption was associated with increased expression of SGLT1 and GLUT2, whereas elevated gluconeogenesis was related to increased expression of GLUT5, PEPCK1, and G6Pase. CONCLUSIONS: Obesity phenotypes preserved in human enteroids provide a mechanistic link to aberrant dietary carbohydrate absorption and metabolism. Enteroids can be used as a preclinical platform to understand the pathophysiology of obesity, study the heterogeneity of obesity mechanisms, and identify novel therapeutics.

Cholinergic-induced anion secretion in murine jejunal enteroids involves synergy between muscarinic and nicotinic pathways.

Acetylcholine induces robust electrogenic anion secretion in mammalian intestine and it has long been hypothesized that it mediates the epithelial response through the M3 and, to a lesser extent, the M1 muscarinic receptors in the mouse. However, nicotinic receptors have recently been identified in intestinal enterocytes by quantitative real-time (qRT)-PCR/RNAseq, although any direct influence on intestinal transport has not been identified. We tested the hypothesis that cholinergic-induced anion secretion in the intestine is a result of both muscarinic and nicotinic pathways that are intrinsic to the intestinal epithelia. We developed a method to generate mouse jejunal enteroid monolayers which were used to measure active electrogenic anion secretion by the Ussing chamber/voltage-clamp technique. Here, we show that the cholinergic agonist carbachol (CCh) and the muscarinic agonist bethanechol (BCh) stimulate short-lived, concentration-dependent anion secretion in the epithelial cell-only enteroid monolayers. The muscarinic antagonist atropine completely inhibited CCh- and BCh-induced secretion, while the nicotinic antagonist hexamethonium reduced the CCh response by ~45%. While nicotine alone did not alter anion secretion, it increased the BCh-induced increase in short-circuit current in a concentration-dependent manner; this synergy was prevented by pretreatment with hexamethonium. In addition to being sensitive to hexamethonium, monolayers express both classes of cholinergic receptor by qRT-PCR, including 13 of 16 nicotinic receptor subunits. Our findings indicate that an interaction between muscarinic and nicotinic agonists synergistically stimulates anion secretion in mouse jejunal epithelial cells and identify a role for epithelial nicotinic receptors in anion secretion.

Drug-impregnated, pressurized gas expanded liquid-processed alginate hydrogel scaffolds for accelerated burn wound healing.

While the benefits of both hydrogels and drug delivery to enhance wound healing have been demonstrated, the highly hydrophilic nature of hydrogels creates challenges with respect to the effective loading and delivery of hydrophobic drugs beneficial to wound healing. Herein, we utilize pressurized gas expanded liquid (PGX) technology to produce very high surface area (~200 m2/g) alginate scaffolds and describe a method for loading the scaffolds with ibuprofen (via adsorptive precipitation) and crosslinking them (via calcium chelation) to create a hydrogel suitable for wound treatment and hydrophobic drug delivery. The high surface area of the PGX-processed alginate scaffold facilitates >8 wt% loading of ibuprofen into the scaffold and controlled in vitro ibuprofen release over 12-24 h. In vivo burn wound healing assays demonstrate significantly accelerated healing with ibuprofen-loaded PGX-alginate/calcium scaffolds relative to both hydrogel-only and untreated controls, demonstrating the combined benefits of ibuprofen delivery to suppress inflammation as well as the capacity of the PGX-alginate/calcium hydrogel to maintain wound hydration and facilitate continuous calcium release to the wound. The use of PGX technology to produce highly porous scaffolds with increased surface areas, followed by adsorptive precipitation of a hydrophobic drug onto the scaffolds, offers a highly scalable method of creating medicated wound dressings with high drug loadings. STATEMENT OF SIGNIFICANCE: While medicated hydrogel-based wound dressings offer clear advantages in accelerating wound healing, the inherent incompatibility between conventional hydrogels and many poorly water-soluble drugs of relevance in wound healing remains a challenge. Herein, we leveraged supercritical fluids-based strategies to both process and subsequently impregnate alginate, followed by post-crosslinking to form a hydrogel, to create a very high surface area alginate hydrogel scaffold loaded with high hydrophobic drug contents (here, >8 wt% ibuprofen) without the need for any pore-forming additives. The impregnated scaffolds significantly accelerated burn wound healing while also promoting regeneration of the native skin morphology. We anticipate this approach can be leveraged to load clinically-relevant and highly bioavailable dosages of hydrophobic drugs in hydrogels for a broad range of potential applications.

ADEA Faculty Diversity Toolkit: A Comprehensive Approach to Improving Diversity and Inclusion in Dental Education.

Population demographic shifts in the United States and Canada have led to an increasingly diverse postsecondary student population. However, the largely homogenous dental faculty in the United States and Canada does not reflect the rapidly changing student body and the diverse patient population academic dentistry has been called to serve. Therefore, recruitment and retention of diverse dental faculty in dental education must be a priority. Substantial evidence also indicates improved outcomes for faculty, students, and institutions when faculty diversity on campus is increased. Beyond the positive impact faculty diversity can deliver to the learning and working environments of an academic institution, a variety of regulatory bodies mandate good faith efforts to maintain a diverse faculty, including the Commission on Dental Accreditation (CODA) standards for dental schools and dental therapy education programs. To assist its member institutions with answering the call for improved faculty diversity, the American Dental Education Association (ADEA) worked with its members to develop the ADEA Faculty Diversity Toolkit (ADEA FDT), a landmark evidence-based resource designed to assist dental education with the design and implementation of faculty recruitment and retention initiatives that can be tailored to their unique needs. This article provides an overview of the changing landscape of the United States and Canadian populations, shares the historic homogeneity of dental education faculty, provides an overview of some of the benefits associated with faculty diversity and highlights the challenges and barriers related to recruiting and retaining diverse faculty. Most importantly, it introduces the ADEA FDT and the need for dental schools and allied dental programs to use the Toolkit as a proactive resource in increasing and maintaining faculty diversity. Furthermore, it provides an overview of how to utilize and adapt the highlighted best practices and model programs to improve faculty diversity on their campuses.

Problematic women: psychology, gender, and health in North America / Mulheres problemáticas: psicologia, gênero e saúde na América do Norte / Mujer problemática: psicología, género y salud en América del Norte

Taking its cue from the medical field, psychology has long been curious about the relationship between biological sex and illness just as societies have long been interested in regulating women's bodies. From 19th Century gender differences scholarship through 20th century activism this article introduces the gendered history of psychology and health. Offering a general overview of the past and more recent feminist present within a North American framework. Taking as its base foundation the intellectual shifts away from an exclusively individualistic lens towards one that now emphasizes systems and society; referred to as the difference between a "women-as-problem" and a "women-in-context" approach. Topics addressed include early gender differences scholarship, mental health costs and gendered violence; dual impact of the paradigms of masculinity, perversity in medicating and treating a woman's psychological condition which result from living in a patriarchal societies; constructs of female sexual dysfunction, and more. We encourage South American scholars to take up the call to more thoroughly explore and expand on the histories of gendered health and psychology within regional and historical time sensitive contexts.

Frente ao campo da medicina, a psicologia tem dedicado discussões sobre a relação entre sexo biológico e doença, assim como as sociedades que, há algum tempo, se interessam em regular o corpo das mulheres. Este artigo apresenta a história de gênero da psicologia e da saúde, a partir das pesquisas de diferenças de gênero do século XIX, por meio do ativismo do século XX. Além de oferecer uma perspectiva sobre o feminismo presente no quadro norte-americano, sobre o diálogo entre presente e passado. Sendo assim, A reflexão se desloca de uma produção intelectual com lente exclusivamente individualista para uma que agora enfatiza os sistemas e a sociedade; referido como a diferença entre uma abordagem "mulheres como problema" e "mulheres em contexto". Os tópicos abordados incluem a relação de diferenças de gênero com bolsas de estudos, custos de saúde mental e violência de gênero; impacto duplo dos paradigmas da masculinidade, perversidade em medicar e tratar a condição psicológica de uma mulher que resulta de viver em sociedades patriarcais; construtos da disfunção sexual feminina e mais. Encorajamos pesquisadores da América do Sul para fomentarem as discussões exploratórias e profundas da história de saúde e psicologia de gênero - dentro de contextos regionais e históricos, sensíveis ao tempo,

Siguiendo la propuesta del campo de la medicina, la psicología ha sentido curiosidad por la relación entre el sexo biológico y la enfermedad así como las sociedades han estado interesadas desde hace tiempo en regular los cuerpos de las mujeres. Desde las diferencias de género en subsidios en el siglo XIX hasta el activismo en el siglo XX, este artículo introduce la historia de género de la psicología y la salud. Ofrece una visión general del pasado y del más reciente feminismo en un ámbito norteamericano. Tomando como su base fundamental el intelectual se aleja de una lente exclusivamente individualista hacia una que enfatiza los sistemas y la sociedad; se refiere a la diferencia entre los enfoques "mujeres-como-problema" y "mujeres-en-contexto". Los temas abordados incluyen subsidios anticipados considerando las diferencias de género, costos de salud mental y violencia de género; doble impacto de los paradigmas de la masculinidad, la perversidad en medicar y tratar de la condición psicológica de una mujer que resulta de vivir en una sociedad patriarcal; constructos de la disfunción sexual femenina, y más. Alentamos a los académicos sudamericanos a que atiendan al llamado para explorar y expandir profundamente las historias de salud y psicología de género en contextos regionales e históricos sensibles al tiempo.

Putting out the welcome mat-targeting outreach efforts under the Affordable Care Act: Evidence from the Minnesota Community Application Agent Program.

CONTEXT: An evaluation of the Minnesota Community Application Agent (MNCAA) Program was conducted for the MN Minnesota Department of Human Services and funded by the Health Resources and Services Administration's State Health Access Program grant. OBJECTIVE: The MNCAA evaluation assessed effectiveness in reaching disparate populations, explored overall program value, and sought lessons applicable to the Navigator programs required under the Affordable Care Act. DESIGN: Mixed-methods approach using quantitative analysis of tracking and payment data and interviews with key informants to elicit "lessons learned" about the MNCAA program. SETTING: The MNCAA program offers incentive payments and technical assistance to community partner organizations that assist individuals in applying for public health care coverage. PARTICIPANTS: A total of 140 unique community organizations participated in the MNCAA program in 2008 to 2012. Outreach staff and directors from participating MNCAAs and state/local government officials were interviewed. MAIN OUTCOME MEASURE(S): The article highlights a strategy for targeting outreach to individuals eligible for Medicaid coverage or subsidies under the Affordable Care Act by presenting evaluation findings from a unique outreach program to increase access to care for vulnerable populations in Minnesota. RESULTS: Almost two-thirds of applicants were successfully enrolled but lengthy waiting periods persisted. Seventy percent of applications came from health care organizations. Only 13% of applicants assisted by MNCAAs were new to public health care programs. Most MNCAAs believed that the incentive payment-$25 per successful enrollee-was insufficient. CONCLUSIONS: Significant expertise in enrolling individuals in public health care programs exists within a core group of community organizations. Incentives to leverage the capacity of community organizations must be accompanied by recruiting and training. Outreach providers and navigators also need timely access to client information. More investment in financial incentives will be required.

Legal Authority for Infectious Disease Reporting in the United States: Case Study of the 2009 H1N1 Influenza Pandemic.

Tracking of infectious diseases is a public health core function essential to disease prevention and control. Each state mandates reporting of certain infectious diseases to public health authorities. These laws vary by state, and the variation could affect the ability to collect critical information. The 2009 H1N1 influenza pandemic served as a case study to examine the legal authority in the 50 states; Washington, DC; and New York City for mandatory infectious disease reporting, particularly for influenza and new or emerging infectious diseases. Our study showed reporting laws to be generally present and functioning well; nevertheless, jurisdictions should be mindful of their mandated parameters and review the robustness of their laws before they face a new or emerging disease outbreak.

ss3sim: an R package for fisheries Stock Assessment simulation with stock synthesis.

Simulation testing is an important approach to evaluating fishery stock assessment methods. In the last decade, the fisheries stock assessment modeling framework Stock Synthesis (SS3) has become widely used around the world. However, there lacks a generalized and scriptable framework for SS3 simulation testing. Here, we introduce ss3sim, an R package that facilitates reproducible, flexible, and rapid end-to-end simulation testing with SS3. ss3sim requires an existing SS3 model configuration along with plain-text control files describing alternative population dynamics, fishery properties, sampling scenarios, and assessment approaches. ss3sim then generates an underlying 'truth' from a specified operating model, samples from that truth, modifies and runs an estimation model, and synthesizes the results. The simulations can be run in parallel, reducing runtime, and the source code is free to be modified under an open-source MIT license. ss3sim is designed to explore structural differences between the underlying truth and assumptions of an estimation model, or between multiple estimation model configurations. For example, ss3sim can be used to answer questions about model misspecification, retrospective patterns, and the relative importance of different types of fisheries data. We demonstrate the software with an example, discuss how ss3sim complements other simulation software, and outline specific research questions that ss3sim could address.

Expert panel reviews of research centers: the site visit process.

Site visits are used extensively in a variety of settings within the evaluation community. They are especially common in making summative value decisions about the quality and worth of research programs/centers. However, there has been little empirical research and guidance about how to appropriately conduct evaluative site visits of research centers. We review the processes of two site visit examples using an expert panel review: (1) a process to evaluate four university research centers and (2) a process to review a federally sponsored research center. A set of 14 categories describing the expert panel review process was obtained through content analysis and participant observation. Most categories were addressed differently through the two processes highlighting the need for more research about the most effective processes to use within different contexts. Decisions about how to structure site visits appear to depend on the research context, practical considerations, the level at which the review is being conducted and the intended impact of the report. Future research pertaining to the selection of site visitors, the autonomy of the visitors in data collection and report writing, and the amount and type of information provided would be particularly valuable.

Improving geriatric transitional care through inter-professional care teams.

OBJECTIVES: The aim of this study was to examine the impact of the use of an inter-professional care team on patient length of stay and payer charges in a geriatric transitional care unit. METHODS: An analysis of de-identified administrative records for transitional care patients for the 12-month period (2003-2004) cared for by the inter-professional team (n = 163) and cared for by traditional single provider care model (n = 176) was carried out. We conducted logistic regression on length of stay and charges controlling for patient demographics and acuity levels. RESULTS: The inter-professional care team patients had significantly shorter lengths of stay, fewer patient days and lower total charges. Patient diagnosis and acuity were similar across groups. CONCLUSION: This study provides empirical evidence of the impact of an inter-professional care model in providing cost-effective transitional care in a nursing home setting. Evidence of shorter lengths of stay, shorter patient days and lower charges suggests benefit in the development and financing of inter-professional care teams for transitional care services.

The unique character of involvement in multi-site evaluation settings.

As the number of large federal programs increases, so, too, does the need for a more complete understanding of how to conduct evaluations of such complex programs. The research literature has documented the benefits of stakeholder participation in smaller-scale program evaluations. However, given the scope and diversity of projects in multi-site program evaluations, traditional notions of participatory evaluation do not apply. The purpose of this research is to determine the ways in which stakeholders are involved in large-scale, multi-site STEM evaluations. This article describes the findings from a survey of 313 program leaders and evaluators and from follow-up interviews with 12 of these individuals. Findings from this study indicate that attendance at meetings and conferences, planning discussions within the project related to use of the program evaluation, and participation in data collection should be added to the list of activities that foster feelings of evaluation involvement among stakeholders. In addition, perceptions of involvement may vary according to breadth or depth of evaluation activities, but not always both. Overall, this study suggests that despite the contextual challenges of large, multi-site evaluations, it is feasible to build feelings of involvement among stakeholders.

Localization of LGR7 (relaxin receptor) mRNA and protein in rat forebrain: correlation with relaxin binding site distribution.

Discrete neuronal populations in brain express relaxin and relaxin-3, and molecular studies have identified former-orphan, G-protein-coupled receptors LGR7 and GPCR135 as their native receptors. To better understand the role of central relaxin systems, we began to assess the anatomic distribution of these receptors and ligands in brain. This study documents the widespread distribution of LGR7 mRNA and LGR7-like immunoreactivity (LI) throughout adult rat forebrain areas shown to contain specific [33P]-relaxin binding sites. High densities of LGR7 mRNA hybridization were detected in deep layers of neocortex, hypothalamic paraventricular and supraoptic nuclei and within hippocampal subiculum and CA3, the basolateral amygdala and subfornical organ. Low to moderate hybridization was detected in septum, midline thalamic nuclei, arcuate and supramammillary nuclei, and regions of the midbrain pons. Complementary expression of LGR7-LI was observed in cortical pyramidal neurons, hypothalamic magnocellular neurons, and hippocampal pyramidal and interneurons. These findings provide further evidence for actions of relaxin as a modulator in somatosensory, autonomic, and neuroendocrine pathways.

A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy.

BACKGROUND: This report describes preliminary results of a study of glomerular number and volume and their associations, in kidneys of people coming to autopsy. METHODS: Both kidneys were weighed at autopsy and the right kidney was perfusion-fixed and sub-sampled for stereological estimation of total glomerular number, and of mean renal corpuscle volume, using the physical disector/fractionator combination. RESULTS: The 78 kidneys studied so far were from Australian Aborigines, Australian non-Aborigines, US blacks and US whites, ages newborn to 84 years. Glomerular number ranged almost ninefold (from 210,332 to 1,825,380), with mean (SD) of 784,909 (314,686); it decreased throughout adult life (r=-0.32, P=0.009). Mean renal corpuscle volume varied 5.6-fold in adults and was inversely correlated with glomerular number (r=-0.38, P=0.001). Total renal corpuscle volume varied in adults by a factor of 15.8. Kidney weight correlated with body surface area (BSA) at all ages (r=0.76, P < 0.001); it varied 3.4-fold among adults, while kidney weight/m2 varied 3.7-fold. The percentage of sclerosed glomeruli varied from 0 to 23%, and it correlated strongly with age (r=0.58, P < 0.001). Females had smaller kidneys than males, and, marginally, fewer glomeruli. There were no significant variations by ethnic group. CONCLUSIONS: These extraordinary ranges of glomerular number and size among ostensibly "normal" people, and their inverse relationship, probably have important implications for susceptibility to renal insufficiency. People with low glomerular (nephron) numbers are likely to be particularly predisposed, with the process marked by compensatory hypertrophy of residual nephrons, which, in turn, accelerates their obsolescence. Much, however, remains to be done, including evaluation of history, clinical features, accompanying pathology, detailed renal morphology, and further pursuit of potentially defining characteristics in high risk groups.

Programming effects of short prenatal exposure to cortisol.

Recent studies have linked fetal exposure to a suboptimal intrauterine environment with adult hypertension. The aims of this study were twofold: 1) to see whether cortisol treatment administered to the ewe for 2 days at 27 days of gestation (term approximately 150 days) resulted in high blood pressure in offspring; 2) to study the effect of the same treatment on gene expression in the brain at 130 days of gestation and in lambs at 2 months of age. Mean arterial pressure was significantly higher in the adult female and male offspring of sheep treated with cortisol than in the control group (females: 89+/-2 mmHg vs. 81+/-2; P<0.05 and males: 102+/-4 mmHg vs. 91+/-3; P<0.05). Prenatal cortisol treatment led to up-regulation of angiotensinogen, AT1, MR, and GR mRNA in the hippocampus in fetuses at 130 days of gestation but not in the animals at 2 months of age. This is the first evidence that short prenatal exposure to cortisol programmed high blood pressure in the adult female and male offspring of sheep. Altered gene expression in the hippocampus could have a significant effect on the development of the hippocampus, and on postnatal behavior.

Glomerular size and glomerulosclerosis: relationships to disease categories, glomerular solidification, and ischemic obsolescence.

In focal segmental glomerulosclerosis (FSGS), a biphasic change in glomerular size is described in which glomeruli are enlarged with early glomerulosclerosis. Hyperperfusion of larger glomeruli is believed to contribute to progressive glomerular injury. This study was undertaken to investigate whether similar alterations in glomerular size can be found in other renal diseases. Volumes of sclerotic and nonsclerotic glomeruli were estimated in renal biopsy specimens using the Weibel and Gomez method (1962). Glomerulosclerosis was graded on individual glomeruli from 0 to 4, with 0 as no sclerosis and 4 as 76% to 100% sclerosis. Primary and secondary FSGS showed a biphasic change in which grade 2 glomeruli were 50% larger than grade 0 glomeruli and grades 3 and 4 glomeruli were solidified and smaller than grade 0 glomeruli. In essential hypertension, no increase in glomerular size was seen with early glomerulosclerosis, and the latter stages consisted of ischemic obsolescence in which collapsed tufts were 50% smaller than solidified glomeruli of FSGS. Grade 0 glomeruli of membranous glomerulonephritis (MGN) were significantly larger than grade 0 glomeruli of FSGS, and no significant difference in size was seen between grades 0 and 2 glomerulosclerosis. Solidified diabetic glomeruli maintained a large size with grades 3 and 4 sclerosis. Glomeruloscleroses of FSGS, hypertension, MGN, and diabetes have stereologically distinct features. A biphasic change in glomerular size is characteristic of primary and secondary FSGS, but not hypertension, in which tuft collapse supports reduced rather than increased perfusion in the pathogenesis of its glomerular obsolescence.