Biodiversity of protists and nematodes in the wild nonhuman primate gut

Documenting the natural diversity of eukaryotic organisms in the nonhuman primate (NHP) gut is important for understanding the evolution of the mammalian gut microbiome, its role in digestion, health and disease, and the consequences of anthropogenic change on primate biology and conservation. Despite the ecological significance of gut-associated eukaryotes, little is known about the factors that influence their assembly and diversity in mammals. In this study, we used an 18S rRNA gene fragment metabarcoding approach to assess the eukaryotic assemblage of 62 individuals representing 16 NHP species. We find that cercopithecoids, and especially the cercopithecines, have substantially higher alpha diversity than other NHP groups. Gut-associated protists and nematodes are widespread among NHPs, consistent with their ancient association with NHP hosts. However, we do not find a consistent signal of phylosymbiosis or host-species specificity. Rather, gut eukaryotes are only weakly structured by primate phylogeny with minimal signal from diet, in contrast to previous reports of NHP gut bacteria. The results of this study indicate that gut-associated eukaryotes offer different information than gut-associated bacteria and add to our understanding of the structure of the gut microbiome.Fil: Mann, Allison E.. University of British Columbia; CanadáFil: Mazel, Florent. University of British Columbia; CanadáFil: Lemay, Matthew A.. University of British Columbia; CanadáFil: Morien, Evan. University of British Columbia; CanadáFil: Billy, Vincent. University of British Columbia; CanadáFil: Kowalewski, Miguel Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia". Estación Biológica de Usos Múltiples (Sede Corrientes); ArgentinaFil: Di Fiore, Anthony. University of Texas at Austin; Estados UnidosFil: Link, Andrés. Universidad de los Andes; ColombiaFil: Goldberg, Tony L.. University of Wisconsin; Estados UnidosFil: Tecot, Stacey. University of Arizona; Estados UnidosFil: Baden, Andrea L.. City University Of New York. Hunter College; Estados UnidosFil: Gomez, Andres. University of Minnesota; Estados UnidosFil: Sauther, Michelle L.. State University of Colorado at Boulder; Estados UnidosFil: Cuozzo, Frank P.. Lajuma Research Centre; SudáfricaFil: Rice, Gillian A. O.. Dartmouth College; Estados UnidosFil: Dominy, Nathaniel J.. Dartmouth College; Estados UnidosFil: Stumpf, Rebecca. University of Illinois at Urbana; Estados UnidosFil: Lewis, Rebecca J.. University of Texas at Austin; Estados UnidosFil: Swedell, Larissa. University of Cape Town; Sudáfrica. City University of New York; Estados UnidosFil: Amato, Katherine. Northwestern University; Estados UnidosFil: Wegener Parfrey, Laura. University of British Columbia; Canad

Depression and health-related quality of life in ethnic minorities seeking care in general medical settings

Background: To examine ethnic groups differences in (a) prevalence of depressive disorders and (b) health related quality of life in fee-for-service and managed care patients (n=21 504) seeking care in general medical settings. Methods: Data are from the Medical Outcomes Study, a multi-site observational study of outpatient practices. The study screened patients of clinicians (family practice, internal medicine, cardiology, diabetology and endocrinology) for four chronic medical conditions; depression, coronary heart disease, hypertension and diabetes. A brief eight-item depression screener followed by the Diagnostic Interview Schedule-Depression Section (DIS) for screener positives identified depressed patients (n=2195). The Short Form Health Survey (SF-36) assessed health-related quality of life. Patient self-report determined ethnicity. Results: Before adjusting for demographic factors, African-Americans and Hispanics had highest rates of depressive symptoms. Asian-Americans had the lowest. adjusting for demographics (particularly gender and income), we found few statistically significant differences in prevalence or severity of depression. However, among the depressed, Whites were the most, and African-Americans the least likely to report suicidal ideation (p<0.01), and Hispanics and Whites were more likely to have melancholia (p<0.01). African-Americans reported the poorest quality of life. Limitations: DSM III criteria (though few changes in DSM IV), and relatively small sample size of Asian-Americans compared to other groups. Conclusions: Gender and socioeconomic status are more significant factors than ethnicity in determining risk for depressive disorder. However, ethnic differences in symptom presentation, and health-related quality of life could have clinical and social consequences, and merit further study.https://www.sciencedirect.com/science/article/pii/S016503279900069

Depression and health-related quality of life in ethnic minorities seeking care in general medical settings

Background: To examine ethnic groups differences in (a) prevalence of depressive disorders and (b) health related quality of life in fee-for-service and managed care patients (n=21 504) seeking care in general medical settings. Methods: Data are from the Medical Outcomes Study, a multi-site observational study of outpatient practices. The study screened patients of clinicians (family practice, internal medicine, cardiology, diabetology and endocrinology) for four chronic medical conditions; depression, coronary heart disease, hypertension and diabetes. A brief eight-item depression screener followed by the Diagnostic Interview Schedule-Depression Section (DIS) for screener positives identified depressed patients (n=2195). The Short Form Health Survey (SF-36) assessed health-related quality of life. Patient self-report determined ethnicity. Results: Before adjusting for demographic factors, African-Americans and Hispanics had highest rates of depressive symptoms. Asian-Americans had the lowest. adjusting for demographics (particularly gender and income), we found few statistically significant differences in prevalence or severity of depression. However, among the depressed, Whites were the most, and African-Americans the least likely to report suicidal ideation (p<0.01), and Hispanics and Whites were more likely to have melancholia (p<0.01). African-Americans reported the poorest quality of life. Limitations: DSM III criteria (though few changes in DSM IV), and relatively small sample size of Asian-Americans compared to other groups. Conclusions: Gender and socioeconomic status are more significant factors than ethnicity in determining risk for depressive disorder. However, ethnic differences in symptom presentation, and health-related quality of life could have clinical and social consequences, and merit further study

Increasing Immunization Rates Among Inner-City, African American Children: A Randomized Trial of Case Management

CONTEXT.— Immunization rates in the inner city remain lower than in the general US population, but efforts to raise immunization levels in inner-city areas have been largely untested. OBJECTIVE.— To assess the effectiveness of case management in raising immunization levels among infants of inner-city, African American families. DESIGN.— Randomized controlled trial with follow-up through 1 year of life. SETTING.— Low-income areas of inner-city Los Angeles, Calif. PATIENTS.— A representative sample of 419 African American infants and their families. INTERVENTIONS.— In-depth assessment by case managers before infants were 6 weeks of age, with home visits 2 weeks prior to when immunizations were scheduled and additional follow-up visits as needed. MAIN OUTCOME MEASURES.— Percentage of children with up-to-date immunizations at age 1 year, characteristics associated with improved immunization rates, and cost-effectiveness of case management intervention. RESULTS.— A total of 365 newborns were followed up to age 1 year. Overall, the immunization completion for the case management group was 13.2 percentage points higher than the control group (63.8% vs 50.6%; P=.01). In a logistic model, the case management effect was limited to the 25% of the sample who reported 3 or fewer well-child visits (odds ratio, 3.43; 95% confidence interval, 1.26-9.35); for them, immunization levels increased by 28 percentage points. Although for the case management group intervention was not cost-effective ($12022 per additional child immunized), it was better ($4546) for the 25% of the sample identified retrospectively to have inadequate utilization of preventive health visits. CONCLUSIONS.— A case management intervention in the first year of life was effective but not cost-effective at raising immunization levels in inner-city, African American infants. The intervention was demonstrated to be particularly effective for subpopulations that do not access well-child care; however, currently there are no means to identify these groups prospectively. For case management to be a useful tool to raise immunizations levels among high-risk populations, better methods of tracking and targeting, such as immunization registries, need to be developed

The prognostic significance of circulating tumor cells in head and neck and non-small-cell lung cancer

Tumor biopsy is the gold standard for the assessment of clinical biomarkers for treatment. However, tumors change dynamically in response to therapy, and there remains a need for a more representative biomarker that can be assayed over the course of treatment. Circulating tumor cells (CTCs) may provide clinically important and comprehensive tumoral information that is predictive of treatment response and outcome. Blood samples were processed for CTCs from 56 patients using the ClearCell FX system. Captured cells were phenotyped for CTC clusters and markers for immunotherapy (PD-L1) CTC chromosomal architecture (ALK, EGFR). CTCs were isolated in 11/23 (47.8%) of head and neck cancer (HNC) patients and 17/33 (51.5%) of non-small-cell lung cancer (NSCLC) patients. CTCs were determined to be PD-L1-positive in 6/11 (54.4%) HNC and 11/17 (64.7%) NSCLC cases, respectively. 3D chromosomal DNA FISH for ALK and EGFR molecular targets showed better resolution than in 2D when imaging CTCs. HNC CTC-positive patients had shorter progression-free survival (PFS) (hazard ratio[HR]: 4.946; 95% confidence internal[CI]:1.571-15.57; P\ua0=\ua00.0063), and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011-26.33; P\ua0=\ua00.0485). In the advanced stage NSCLC patient cohort, PFS was not found to be associated with CTCs prior to therapy ([HR]:2.246; 95% [CI]:0.9565-5.273; P\ua0=\ua00.0632), nor the presence of PD-L1 expression ([HR]:1.646; 95% [CI]:0.5128-5.283; P\ua0=\ua00.4023). This study demonstrated that CTCs are predictive of poorer outcomes in HNC and provides distinct and separate utility for CTCs in HNC and NSCLC, which may be more representative of the disease burden and overall survival than the parameters used to measure them

Targeting Metalloenzymes for Therapeutic Intervention

Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many others. The role of metalloenzymes in these processes also makes them central for the progression of many diseases and, as such, makes metalloenzymes attractive targets for therapeutic intervention. Increasing awareness of the role metalloenzymes play in disease and their importance as a class of targets has amplified interest in the development of new strategies to develop inhibitors and ultimately useful drugs. In this Review, we provide a broad overview of several drug discovery efforts focused on metalloenzymes and attempt to map out the current landscape of high-value metalloenzyme targets