Susceptibility to Theiler''s virus-induced demyelination. Mapping of the gene within the H-2D region

Demyelination induced by Theiler's virus was examined in mouse strains with congeneic recombinant haplotypes. Light and electron microscopy of spinal cord sections from mice with s, q, v, p, and f H-2D alleles showed perivascular inflammation and primary demyelination. The presence of susceptible haplotypes in the K or I region did not correlate with pathologic abnormalities. The Qa, Tla, PgK, and UpG genes did not appear to be critical in determining susceptibility to disease. However, mutation in the H-2D genes altered the susceptibility to virus-induced demyelination. B10.D2dm1 mice, which have deletions in the 3' end of Dd and the 5' end of Ld, showed prominent demyelination and clinical deficits. In contrast, BALB/c-dm2, which have a deletion of the entire L gene, showed no pathologic changes. Central nervous system virus titers correlated with susceptibility to demyelination; both resistant and susceptible strains had a strong humoral immune response to the virus. The findings in the congeneic recombinant mice and in mice mutant in the H-2D region strongly suggest that at least one of the genes critical for determining virus-induced demyelination maps to the 3' end of the H-2D gene.     

High expression levels of IKK alpha and IKK beta are necessary for the malignant properties of liver cancer

IKK-NF-kappa B signaling is regarded as an important factor in hepatocarcinogenesis and a potential target for liver cancer therapy.Therefore,in this study,we analyzed the expression of mRNAs encoding components and targets of NF-kappa B signaling including IKK alpha,IKK beta,RANK,RANKL,OPG,CyclinD3,mammary serine protease inhibitor(Maspin),CyclinD1,c-FLIP,Bcl-x1,Stat3,Cip1 and Cip2 by real-time PCR in 40 patients with liver cancer.After statistical analysis,7 indices including IKK alpha,IKK beta,RANK,Maspi...     

Orexigenic peptides and alcohol intake: differential effects of orexin, galanin, and ghrelin

BACKGROUND: The question is which hypothalamic systems for food intake might play a role in ethanol intake and contribute to alcohol abuse. The peptide orexin was found to exhibit similar properties to galanin in its relation to dietary fat and may therefore be similar to galanin in having a stimulatory effect on alcohol intake. METHODS: Rats were trained to drink 10% ethanol, implanted with brain cannulas, and then injected in the paraventricular nucleus (PVN), lateral hypothalamus (LH), or nucleus accumbens (NAc) with galanin, orexin-A, and for comparison, ghrelin. Ethanol, food, and water intake were measured at 1, 2, and 4 hours postinjection. RESULTS: In the PVN, both orexin and galanin significantly increased ethanol intake, whereas ghrelin increased food intake. In the LH, orexin again induced ethanol intake, while ghrelin increased eating. In the NAc, orexin failed to influence ethanol intake but did stimulate food intake. CONCLUSIONS: In ethanol-drinking rats, injection of orexin or galanin into the appropriate locus in the hypothalamus induced significant ethanol intake instead of food intake. Ghrelin, as a positive control, failed to influence ethanol intake at the same hypothalamic sites. In the NAc, as an anatomical control, orexin augmented eating but not ethanol intake. Thus orexin and galanin in the hypothalamus selectively stimulated ethanol intake at sites where other studies have shown that both ethanol and fat increase expression of the endogenous peptides. Thus, a neural circuit that evolved with the capability to augment food intake is apparently co-opted by ethanol and may serve as a potential positive feedback circuit for alcohol abuse.     

Weight gain model in prepubertal rats: prediction and phenotyping of obesity-prone animals at normal body weight

OBJECTIVE: Male Sprague-Dawley rats maintained from birth on a high-fat diet were examined to determine whether a specific measure before puberty can identify and allow one to characterize prepubertal rats at normal weight with high vs low risk for adult obesity. MATERIALS AND METHODS: Measures from weaning (day 21) to around puberty (day 45) were taken of weight gain, absolute body weight and daily energy intake on a high-fat diet and related to the amount of body fat accumulated at maturity (80-100 days of age). Rats identified by a specific prepubertal measure as obesity-prone (OP) vs obesity-resistant (OR) were then characterized before and after puberty. RESULTS: Prepubertal weight gain from days 30 to 35 of age was the strongest and earliest positive correlate of ultimate body fat accrual in adult rats. The highest (8-10 g/day) compared to lowest (5-7 g/day) weight-gain scores identified accurately and reproducibly distinct OP and OR subgroups at day 35 that became obese or remained lean, respectively, as adults. The OP rats with rapid prepubertal weight gain and 50% greater adiposity at maturity (day 100) exhibited the expected phenotype of already-obese rats. These included elevated levels of leptin, insulin, triglycerides and glucose, increased galanin (GAL) peptide levels in the paraventricular nucleus (PVN) and reduced neuropeptide Y (NPY) levels in the arcuate nucleus (ARC). Before puberty (day 35), the OP rats with normal fat pad weights, energy intake and endocrine profile similar to OR rats exhibited these disturbances characteristic of obese rats. They had decreased capacity for fat oxidation in muscle, increased GAL expression in PVN and reduced expression of NPY and agouti-related protein in ARC. CONCLUSION: Prepubertal weight gain can identify OP rats on day 35 when they have minimal body fat but exhibit specific metabolic and neurochemical disturbances expected to promote obesity and characteristics of already-obese adult rats.     

Determinants and Policy Implications of Male Circumcision in the United States

Objective. We sought to determine whether lack of state Medicaid coverage for infant male circumcision correlates with lower circumcision rates.Methods. We used data from the Nationwide Inpatient Sample on 417 282 male newborns to calculate hospital-level circumcision rates. We used weighted multiple regression to correlate hospital circumcision rates with hospital-level predictors and state Medicaid coverage of circumcision.Results. The mean neonatal male circumcision rate was 55.9%. When we controlled for other factors, hospitals in states in which Medicaid covers routine male circumcision had circumcision rates that were 24 percentage points higher than did hospitals in states without such coverage (P < .001). Hospitals serving greater proportions of Hispanic patients had lower circumcision rates; this was not true of hospitals serving more African Americans. Medicaid coverage had a smaller effect on circumcision rates when a hospital had a greater percentage of Hispanic births.Conclusions. Lack of Medicaid coverage for neonatal male circumcision correlated with lower rates of circumcision. Because uncircumcised males face greater risk of HIV and other sexually transmitted infections, lack of Medicaid coverage for circumcision may translate into future health disparities for children born to poor families covered by Medicaid.Three recent randomized clinical trials in South Africa, Kenya, and Uganda found that male circumcision reduces a man''s risk of becoming infected with HIV through contact with a female partner by 55% to 76%.^1–3 These results are consistent with meta-analyses based on observational studies in Africa^4,5 and the United States.^6,7The recent randomized clinical trial findings prompted the American Academy of Pediatrics (AAP) to form a committee in June 2007 to review its position on male circumcision.⁸ In 1999 the AAP had adopted a neutral stance, stating that the medical benefits were not compelling enough to recommend routine neonatal circumcision. In the wake of the AAP statement, several states withdrew Medicaid coverage for routine, nontherapeutic circumcision. Currently, 16 state Medicaid plans do not cover the procedure. In 2006, legislators in Hawaii and Vermont introduced resolutions challenging the need for state funding of routine male circumcision.⁹In view of the striking results from the African clinical trials, it is timely to examine the impact of US hospital- and state-level policies on domestic rates of male circumcision. In particular, we hypothesized that male circumcision rates would be higher in states in which the Medicaid program pays for routine circumcision.     

Ockham's razor or Hickam's dictum: a right atrial mass following excision of left atrial myxoma

We report a case of a 54-year-old man presenting with a rightatrial mass 7 months after undergoing a left atrial myxoma excisionsurgery. The differential diagnosis included recurrent myxomaor thrombus. The patient underwent repeat open sternotomy oncardiopulmonary bypass. Histopathological evaluation of themass revealed an organizing thrombus. This report is, to ourknowledge, the first that demonstrates right atrial thrombusshortly following excision of left atrial myxoma.     

Folate Levels in Patients Hospitalized with Coronavirus Disease 2019

We aimed to investigate the prevalence of decreased folate levels in patients hospitalized with Coronavirus Disease 2019 (COVID-19) and evaluate their outcome and the prognostic signifi-cance associated with its different levels. In this retrospective cohort study, data were obtained from the electronic medical records at the Sheba Medical Center. Folic acid levels were available in 333 out of 1020 consecutive patients diagnosed with COVID-19 infection hospitalized from January 2020 to November 2020. Thirty-eight (11.4%) of the 333 patients comprising the present study population had low folate levels. No significant difference was found in the incidence of acute kidney injury, hypoxemia, invasive ventilation, length of hospital stay, and mortality be-tween patients with decreased and normal-range folate levels. When sub-dividing the study population according to quartiles of folate levels, similar findings were observed. In conclusion, decreased serum folate levels are common among hospitalized patients with COVID-19, but there was no association between serum folate levels and clinical outcomes. Due to the important role of folate in cell metabolism and the potential pathologic impact when deficient, a follow-up of folate levels or possible supplementation should be encouraged in hospitalized COVID-19 patients. Fur-ther studies are required to assess the prevalence and consequences of folate deficiency in COVID-19 patients.