Methodology for Analysis of Diet Grit Size on Molar Attrition for Fourche Maline and Caddo People

Using the Murphy (1959) system for scoring the degree of dentin exposure, Fourche Maline (Woodland) molars show a greater attrition rate than Caddo (Mississippian) molars. Archeological evidence suggests that this differential in attrition rates is caused by the use of stone grinders for food preparation in the Fourche Maline culture and their absence among the Caddo. Analysis of scratches on the occlusal surface of molars from these samples confirms this hypothesis. Several techniques for observing these scratches and reconstructing the grit sizes and grit particle frequencies responsible for this differential abrasion are evaluated

In vitro fertilization is associated with an increased risk of borderline ovarian tumours

Objectives: To compare the risk of borderline ovarian tumours in women having in vitro fertilization (IVF) with women diagnosed with infertility but not having IVF. Methods: This was a whole-population cohort study of women aged 20–44 years seeking hospital infertility treatment or investigation in Western Australia in 1982–2002. Using Cox regression, we examined the effects of IVF treatment and potential confounders on the rate of borderline ovarian tumours. Potential confounders included parity, age, calendar year, socio-economic status, infertility diagnoses including pelvic inflammatory disorders and endometriosis and surgical procedures including hysterectomy and tubal ligation. Results: Women undergoing IVF had an increased rate of borderline ovarian tumours with a hazard ratio (HR) of 2.46 (95% confidence interval [CI] 1.20–5.04). Unlike invasive epithelial ovarian cancer, neither birth (HR 0.89; 95% CI 0.43–1.88) nor hysterectomy (1.02; 0.24–4.37) nor sterilization (1.48; 0.63–3.48) appeared protective and the rate was not increased in women with a diagnosis of endometriosis (HR 0.31; 95% CI 0.04–2.29). Conclusions: Women undergoing IVF treatment are at increased risk of being diagnosed with borderline ovarian tumours. Risk factors for borderline ovarian tumours appear different from those for invasive ovarian cancer

Are We Making Progress in Medical Education?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75582/1/j.1525-1497.2006.00446.x.pd

Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels

The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease aggressiveness. We aimed to identify novel genetic and biomolecular mechanisms regulating scuPAR levels. Elevated serum scuPAR levels were identified in asthma (n=514) and chronic obstructive pulmonary disease (COPD; n=219) cohorts when compared to controls (n=96). In these cohorts, a genome-wide association study of serum scuPAR levels identified a human plasma kallikrein gene (KLKB1) promoter polymorphism (rs4253238) associated with serum scuPAR levels in a control/asthma population (P=1.17×10−7), which was also observed in a COPD population (combined P=5.04×10−12). Using a fluorescent assay, we demonstrated that serum KLKB1 enzymatic activity was driven by rs4253238 and is inverse to scuPAR levels. Biochemical analysis identified that KLKB1 cleaves scuPAR and negates scuPAR's effects on primary human bronchial epithelial cells (HBECs) in vitro. Chymotrypsin was used as a proproteolytic control, while basal HBECs were used as a control to define scuPAR-driven effects. In summary, we reveal a novel post-translational regulatory mechanism for scuPAR using a hypothesis-free approach with implications for multiple human diseases

Gallbladder Cancer Incidence Among American Indians and Alaska Natives, US, 1999–2004

BACKGROUND. Gallbladder cancer (GBC) is rare; however, it disproportionately affects the American Indian and Alaska Natives (AI/AN) population. The purpose of the study was to characterize GBC among AI/AN in the US population. METHODS. Cases of GBC diagnosed between 1999 and 2004 and collected by state-based cancer registries were included. Registry records were linked with Indian Health Service (IHS) administration records to decrease race misclassification of AI/AN. GBC rates and/or percent distributions for AI/AN and non-Hispanic whites (NHW) were calculated by sex, IHS region, age, and stage for all US counties and IHS Contract Health Service Delivery Area (CHSDA) counties, in which approximately 56% of US AI/AN individuals reside. RESULTS. In CHSDA counties, the GBC incidence rate among AI/AN was 3.3 per 100,000, which was significantly higher than that among NHW (P \u3c .05). Rates varied widely among IHS regions and ranged from 1.5 in the East to 5.5 in Alaska. Rates were higher among AI/AN females than males in all regions, except the Northern Plains. Higher percentages of GBC were diagnosed among AI/AN aged CONCLUSIONS. To the authors’ knowledge to date, this is the most comprehensive study of GBC incidence among AI/AN in the US. The accurate characterization of GBC in this population could help inform the development of interventions aimed at reducing morbidity and mortality from this diseas

Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development

Inhalation of Ultrafine Particles Alters Blood Leukocyte Expression of Adhesion Molecules in Humans

Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter ~ 25 nm, geometric standard deviation ~ 1.6), for 2 hr, in three separate protocols: 10 μg/m(3) at rest, 10 and 25 μg/m(3) with exercise, and 50 μg/m(3) with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 μg/m(3) UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 μg/m(3) UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4(+) T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed

Understanding factors influencing home pregnancy test use among women in western Kenya: A qualitative analysis

BackgroundThere are limited data on home pregnancy test use among women in low-and-middle-income countries. A prior survey found that only 20% of women in western Kenya used a home pregnancy test to confirm their pregnancies before going to antenatal care. This qualitative study aims to understand why women do not use home pregnancy tests in early pregnancy.MethodsFrom April 2021 to July 2021, we interviewed women from four antenatal care clinics in Homa Bay and Siaya counties. We recruited women previously enrolled in the PrEP Implementation for Mothers in Antenatal care (PrIMA) study, a cluster-randomized trial that evaluated the best approaches to implementing PrEP in maternal and child health clinics in Western Kenya (NCT03070600). Interviews were conducted via phone, audio recorded, translated, and transcribed verbatim. We coded and analyzed the transcripts to capture factors influencing women's capability, opportunity, and motivation to use home pregnancy tests.ResultsWe conducted 48 semistructured interviews with women aged 21–42 years. Twenty-seven women did not use a home pregnancy test in their most recent pregnancy. Seventeen of these women reported not using a home pregnancy test before. Lack of knowledge, mistrust in the accuracy of tests, preferring to rely on signs and symptoms of pregnancy or get a test from the health facility, cost, and accessibility were key barriers to home pregnancy test use.ConclusionImproving the uptake of home pregnancy testing during early pregnancy will require efforts to enhance community knowledge of test use and associated benefits and reduce cost burdens by making tests more affordable and accessible