Health Status and Health Care Access of Farm and Rural Populations

Rural residents have higher rates of age-adjusted mortality, disability, and chronic disease than their urban counterparts, though mortality and disability rates vary more by region than by metro status. Contributing negatively to the health status of rural residents are their lower socioeconomic status, higher incidence of both smoking and obesity, and lower levels of physical activity. Contributing negatively to the health status of farmers are the high risks from workplace hazards, which also affect other members of farm families who live on the premises and often share in the work; contributing positively are farmers’ higher socioeconomic status, lower incidence of smoking, and more active lifestyle. Both farm and rural populations experience lower access to health care along the dimensions of affordability, proximity, and quality, compared with their nonfarm and urban counterparts.Health Economics and Policy, agriculture safety and health, electronic health records, farmer health, health, health care access, health care affordability, health care quality, health disparities, health IT, health status, mortality, rural health, telehealth, uninsured,

E2F1 induces phosphorylation of p53 that is coincident with p53 accumulation and apoptosis

It has been proposed that the E2F1 transcription factor serves as a link between the Rb/E2F proliferation pathway and the p53 apoptosis pathway by inducing the expression of p19ARF, a protein that regulates p53 stability. We find that although p19ARF contributes to p53 accumulation in response to E2F expression, p19ARF is not required for E2F1-mediated apoptosis. E2F1 can signal p53 phosphorylation in the absence of p19ARF, similar to the observed modifications to p53 in response to DNA damage. These modifications are not observed in the absence of p19ARF following expression of E2F2, an E2F family member that does not induce apoptosis in mouse embryo fibroblasts but can induce p19ARF and p53 protein expression. p53 modification is found to be crucial for E2F1-mediated apoptosis, and this apoptosis is compromised when E2F1 is coexpressed with a p53 mutant lacking many N- and C-terminal phosphorylation sites. Additionally, E2F1-mediated apoptosis is abolished in the presence of caffeine, an inhibitor of phosphatidylinositol 3-kinase-related kinases that phosphorylate p53. These findings suggest that p53 phosphorylation is a key step in E2F1-mediated apoptosis and that this modification can occur in the absence of p19ARF

Does undertaking an intercalated BSc influence first clinical year exam results at a London medical school?

Background: Intercalated BScs (iBScs) are an optional part of the medical school curriculum in many Universities. Does undertaking an iBSc influence subsequent student performance? Previous studies addressing this question have been flawed by iBSc students being highly selected. This study looks at data from medical students where there is a compulsory iBSc for non-graduates. Our aim was to see whether there was any difference in performance between students who took an iBSc before or after their third year (first clinical year) exams.Methods: A multivariable analysis was performed to compare the third year results of students at one London medical school who had or had not completed their iBSc by the start of this year (n = 276). A general linear model was applied to adjust for differences between the two groups in terms of potential confounders (age, sex, nationality and baseline performance).Results: The results of third year summative exams for 276 students were analysed (184 students with an iBSc and 92 without). Unadjusted analysis showed students who took an iBSc before their third year achieved significantly higher end of year marks than those who did not with a mean score difference of 4.4 (0.9 to 7.9 95% CI, p = 0.01). (overall mean score 238.4 "completed iBSc" students versus 234.0 "not completed", range 145.2 - 272.3 out of 300). There was however a significant difference between the two groups in their prior second year exam marks with those choosing to intercalate before their third year having higher marks. Adjusting for this, the difference in overall exam scores was no longer significant with a mean score difference of 1.4 (-4.9 to +7.7 95% CI, p = 0.66). (overall mean score 238.0 "completed iBSc" students versus 236.5 "not completed").Conclusions: Once possible confounders are controlled for (age, sex, previous academic performance) undertaking an iBSc does not influence third year exam results. One explanation for this confounding in unadjusted results is that students who do better in their second year exams are more likely to take an iBSc before their third year

siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a primary regulator of transferrin uptake

A survey of 1,804 human dicer-generated signaling siRNAs using automated quantitative imaging identified the phosphatidylinositol-3,4,5-trisphosphate-mTOR signaling pathway as a primary regulator of iron-transferrin uptake

Acute Changes in Sleep Duration on Eating Behaviors and Appetite-Regulating Hormones in Overweight/Obese Adults

There is considerable interest in the role of sleep in weight regulation, yet few studies have examined this relationship in overweight/obese (OW/OB) adults. Using a within-subject, counterbalanced design, 12 OW/OB women were studied in lab with two nights of short (5 hr time in bed [TIB]) and two nights of long (9 hr TIB) sleep. Hunger, consumption at a buffet, and fasting hormone levels were obtained. Significant polysomnographic differences occurred between conditions in total sleep time and sleep architecture (ps < .001). Percent energy from protein at the buffet increased following short sleep. No differences were observed for total energy intake or measured hormones. Further research is needed to determine how lengthening sleep impacts weight regulation in OW/OB adults

The Trail, 1964-11-12

https://soundideas.pugetsound.edu/thetrail_all/1898/thumbnail.jp

The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease.

BACKGROUND: Rituximab is a B cell depleting anti-CD20 monoclonal antibody. CD20 is not expressed on mature plasma cells and accordingly rituximab does not have immediate effects on immunoglobulin levels. However, after rituximab some patients develop hypogammaglobulinaemia. METHODS: We performed a single centre retrospective review of 177 patients with multisystem autoimmune disease receiving rituximab between 2002 and 2010. The incidence, severity and complications of hypogammaglobulinaemia were investigated. RESULTS: Median rituximab dose was 6 g (1-20.2) and total follow-up was 8012 patient-months. At first rituximab, the proportion of patients with IgG <6 g/L was 13% and remained stable at 17% at 24 months and 14% at 60 months. Following rituximab, 61/177 patients (34%) had IgG <6 g/L for at least three consecutive months, of whom 7/177 (4%) had IgG <3 g/L. Low immunoglobulin levels were associated with higher glucocorticoid doses during follow up and there was a trend for median IgG levels to fall after ≥ 6 g rituximab. 45/115 (39%) with IgG ≥ 6 g/L versus 26/62 (42%) with IgG <6 g/L experienced severe infections (p=0.750). 6/177 patients (3%) received intravenous immunoglobulin replacement therapy, all with IgG <5 g/L and recurrent infection. CONCLUSIONS: In multi-system autoimmune disease, prior cyclophosphamide exposure and glucocorticoid therapy but not cumulative rituximab dose was associated with an increased incidence of hypogammaglobulinaemia. Severe infections were common but were not associated with immunoglobulin levels. Repeat dose rituximab therapy appears safe with judicious monitoring

BLM and BRCA1-BARD1 coordinate complementary mechanisms of joint DNA molecule resolution

The Bloom syndrome helicase BLM interacts with topoisomerase IIIα (TOP3A), RMI1, and RMI2 to form the BTR complex, which dissolves double Holliday junctions and DNA replication intermediates to promote sister chromatid disjunction before cell division. In its absence, structure-specific nucleases like the SMX complex (comprising SLX1-SLX4, MUS81-EME1, and XPF-ERCC1) can cleave joint DNA molecules instead, but cells deficient in both BTR and SMX are not viable. Here, we identify a negative genetic interaction between BLM loss and deficiency in the BRCA1-BARD1 tumor suppressor complex. We show that this is due to a previously overlooked role for BARD1 in recruiting SLX4 to resolve DNA intermediates left unprocessed by BLM in the preceding interphase. Consequently, cells with defective BLM and BRCA1-BARD1 accumulate catastrophic levels of chromosome breakage and micronucleation, leading to cell death. Thus, we reveal mechanistic insights into SLX4 recruitment to DNA lesions, with potential clinical implications for treating BRCA1-deficient tumors