The constitutive capacity of human keratinocytes to kill Staphylococcus aureus is dependent on beta-defensin 3

Normal skin is often exposed to bacteria, including potent pathogens such as E. coli, Staphylococcus aureus, and Streptococcus sp., but these microbes usually do not cause skin inflammation or infection in healthy individuals. Therefore, we hypothesized that there must be a constitutive mechanism for rapid destruction and elimination of small numbers of bacteria which penetrate the stratum corneum from everyday activities. This study found that exposure of keratinocytes cultured from a number of individuals to S. aureus resulted in approximately 2-3 log better killing than by HaCaT cells within 1 hour. Killing required contact between the keratinocytes and the bacteria, but was not dependent on internalization. Contact between the bacteria and the keratinocytes resulted in rapid deposition of several antimicrobial peptides onto the bacteria, but only human beta-defensin (HBD) 3 accumulated at levels sufficient to account for killing when S. aureus were exposed to human skin explants. Blocking peptide binding of HBD3 inhibited killing of the bacteria, indicating an essential role for beta-defensin 3 in the constitutive killing of bacteria by normal keratinocytes.     

Season of birth and eating disorders

A statistically significant season of birth variation is found in an unselected nationwide sample of 1,939 eating disorders patients, with peak season of birth occurring in May. However, among younger patients (n = 882), peak season of birth is in March, which is statistically significantly different to that expected from the general population season of birth cycle. This finding may imply links between etiology of earlier-onset eating disorders and the psychoses; similar first quarter peak seasonal patterns of birth have been found in schizophrenic and affective psychoses—with birth peaks in January and February. In contrast, for the neuroses and personality disorders, birth peaks have been found to be in June and August, similar to the June birth peak found in this study for later-onset eating disorders (n = 1,057), which was not statistically significantly different to season of birth peaks expected from general population data. © 1996 by John Wiley & Sons, Inc.     

Maternal diet and the risk of hypospadias and cryptorchidism in the offspring

Male genital tract birth defects have been associated in previous studies with several prenatal exposures to environmental and dietary risk factors. The purpose of this study was to explore the association between hypospadias and cryptorchidism, and the dietary habits of an agricultural population in Italy. A population-based case-control study was conducted in the Sicilian Province of Ragusa. Cases (n = 90) and controls (n = 202) included births for the period 1998-2002. Data on dietary habits of the mothers, as well as health-related social, occupational and environmental exposures prior to and during the index birth, were collected through interviews. Adjusted odds ratios (OR) were calculated by logistic regression after adjustment for confounding variables. Increased ORs were observed for mothers of children with hypospadias who, during pregnancy, frequently consumed fish (OR = 2.33 [95% confidence interval (CI) 1.03, 5.31]) and market-purchased fruit (OR = 5.10 [95% CI 1.31, 19.82]). For cryptorchidism, increased risk was observed in mothers consuming liver (OR = 5.21 [95% CI 1.26, 21.50]), and smoked products (OR = 2.46 [95% CI 1.15, 5.29]). For the two malformations pooled together, increased risk was associated with maternal consumption of liver (OR = 4.38 [95% CI 1.34, 14.26]) and with frequent consumption of wine (OR = 1.98 [95% CI 1.01, 3.86]). This study suggests that some maternal dietary factors may play a role in the development of congenital defects of the male reproductive tract. In particular, our data indicate that further research may be warranted on the endocrine-disrupting effects resulting from the bioaccumulation of contaminants (fish, liver), pesticides (marketed fruit, wine) and/or potentially toxic food components (smoked products, wine, liver).     

Dissociation of mercaptoacetate's effects on feeding and fat metabolism by dietary medium- and long-chain triacylglycerols in rats

OBJECTIVE AND METHODS: Mercaptoacetate (MA) inhibits hepatic fatty acid oxidation (FAO) and stimulates feeding in rats fed fat-rich diets. To test whether the feeding stimulation by MA depends on hepatic FAO, we compared the effects of intraperitoneally injected MA (45.6 mg/kg body weight) with saline in rats fed diets containing 18% predominately long-chain triacylglycerols (LCTs; > or =90% 16 C) or 18% medium-chain triacylglycerols (MCTs; 51% 10-12 C). We hypothesized that, because medium-chain fatty acids reach the liver and are oxidized faster than long-chain fatty acids, if MA's feeding-stimulatory effect depends on hepatic FAO, MA should stimulate feeding more in MCT-fed rats than in LCT-fed rats. RESULTS: Although MA injected in mid-light phase stimulated feeding similarly in MCT- and LCT-fed rats, MA injected at light onset initially stimulated food intake (1 h) only in LCT- and not in MCT-fed rats. To investigate MA's metabolic effects during the initial hour, rats were sacrificed 30 min after light-onset injections. At this time plasma beta-hydroxybutyrate appeared to be higher in MCT- than in LCT-fed rats and to be increased by MA. In a final experiment, MA did not affect fatty acid content in liver and duodenum tissues but increased fatty acids in duodenal tissue mitochondria from 12 h-fasted rats fed chow. CONCLUSION: In light-onset tests, adaptation to the MCT diet increased hepatic FAO but not the feeding-stimulatory effect of MA in comparison with adaptation to the LCT diet, suggesting that at this time MA does not act in the liver to stimulate feeding or that this effect is not due to FAO inhibition. Inhibition of duodenal mitochondrial FAO may be another metabolic process through which MA stimulates feeding.     

Estradiol enhances cholecystokinin-dependent lipid-induced satiation and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats

Part of the mechanism through which estradiol, acting via estrogen receptor (ERalpha) signaling, inhibits feeding in rats and mice is increasing the satiating potency of cholecystokinin (CCK) acting on peripheral CCK-1 receptors. Ingested lipid is a principal secretagogue of intestinal CCK, and intraduodenal lipid infusions elicit CCK-mediated satiation in animals and humans. Here we tested whether estradiol affects the satiating potency of intraduodenal lipid infusions in ovariectomized rats and, using c-Fos immunocytochemistry, searched for potential brain sites of ERalpha involved. Food-deprived ovariectomized rats with open gastric cannulas sham fed 0.8 m sucrose 2 d after estradiol (estradiol benzoate, 10 mug, sc) or vehicle injection. Estradiol markedly increased the satiating potency of intraduodenal infusions of Intralipid but not the satiating potency of L-phenylalanine (10 min infusions, 0.44 ml/min, 0.13 kcal/ml), which in male rats satiates via a CCK-independent mechanism. Estradiol had no significant effect in rats pretreated with the CCK-1 receptor antagonist Devazepide (1 mg/kg, ip). The effect of estradiol on intraduodenal Intralipid-induced satiation was mirrored by selective increases in the number of cells expressing c-Fos immunoreactivity in a circumscribed region of the nucleus tractus solitarius (NTS), just caudal to the area postrema (cNTS) but not elsewhere in the NTS or the hypothalamic paraventricular or arcuate nuclei. In addition, a significant proportion of cNTS c-Fos-positive cells also expressed ERalpha. These data provide behavioral and cellular evidence that estradiol-ERalpha signaling in cNTS neurons increases the satiating potency of endogenous CCK released in response to ingested lipid.     

Genetic testing in sudden unexpected natural death in the young: New York City Office of Chief Medical Examiner’s experience and perspective

Postmortem genetic testing is a diagnostic tool that is becoming increasingly utilized. The benefits and limitations of genetic testing in cases of sudden, unexpected death in the young (≤ 40 years old) are reviewed from the perspective of the Office of Chief Medical Examiner of the City of New York, whose Molecular Genetics Laboratory, accredited by College of American Pathologists, has had 15 years of postmortem testing experience. Challenges to the interpretation and communication of testing results are highlighted, and opportunities for improving testing yield are discussed for age groups across the lifespan, from infancy to adulthood.     

Morbidity and mortality conferences in general surgery: a narrative systematic review

BackgroundIn medical and surgical departments around the world, morbidity and mortality conferences (MMC) serve dual roles: they are cornerstones of quality-improvement programs and provide timely opportunities for education within the urgent context of clinical care. Despite the widespread adoption of MMCs, adverse events and preventable errors remain high or incompletely characterized, and opportunities to learn from and adjust to these events are frequently lost. This review examines the published literature on strategies to improve surgical MMCs.MethodsWe searched OVID Medline, PubMed, Embase and CENTRAL. We defined our combination of search terms using a PICO (population, intervention, comparison, outcome) model, focusing on the use of MMCs in general surgery.ResultsThe MMC literature focused on 5 themes: educational value, error analysis, case selection and representation, attendance and dissemination. Strategies used to increase educational value included limiting case presentation time to 15–20 minutes, mandatory brief literature reviews, increasing audience interaction, and standardizing presentations using a PowerPoint template or SBAR (situation, background, assessment, recommendation) format. Interventions to improve error analysis included focused discussion on causative factors and taxonomic error analysis. Case selection was improved by using an electronic clinical registry, such as the National Surgery Quality Improvement Program, to better capture incidence of morbidity and mortality. Attendance was improved with teleconferencing. Dissemination strategies included MMC newsletters, incorporating MMCs into plan-do-check-act cycles, and surgeon report cards.ConclusionGreater standardization of best practices may increase the quality improvement and educational impact of MMCs and provide a baseline to measure the effect of new MMC format innovations on the clinical and educational performance of surgical systems.     

Axillary pseudoaneurysm post core needle biopsy

Imaging‐guided Core Needle Biopsy (CNB) is a procedure for tissue sampling in case of suspicious findings, such as breast masses and abnormal lymph nodes. It provides definitive diagnosis with a high accuracy rate and generally with no significant complications. To our knowledge, this is the first case report to document a pseudoaneurysm of the axilla after CNB. An illustrative case and a diagnostic and therapeutic literature review are presented.