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101.
102.
Gianetti E Hall JE Au MG Kaiser UB Quinton R Stewart JA Metzger DL Pitteloud N Mericq V Merino PM Levitsky LL Izatt L Lang-Muritano M Fujimoto VY Dluhy RG Chase ML Crowley WF Plummer L Seminara SB 《The Journal of clinical endocrinology and metabolism》2012,97(9):E1798-E1807
Context: A broad spectrum of GnRH-deficient phenotypes has been identified in individuals with both mono- and biallelic GNRHR mutations. Objective: The objective of the study was to determine the correlation between the severity of the reproductive phenotype(s) and the number and functional severity of rare sequence variants in GNRHR. Subjects: Eight hundred sixty-three probands with different forms of GnRH deficiency, 46 family members and 422 controls were screened for GNRHR mutations. The 70 subjects (32 patients and 38 family members) harboring mutations were divided into four groups (G1-G4) based on the functional severity of the mutations (complete or partial loss of function) and the number of affected alleles (monoallelic or biallelic) with mutations, and these classes were mapped on their clinical phenotypes. Results: The prevalence of heterozygous rare sequence variants in GNRHR was significantly higher in probands vs. controls (P < 0.01). Among the G1-G3 groups (homozygous subjects with successively decreasing severity and number of mutations), the hypogonadotropic phenotype related to their genetic load. In contrast, subjects in G4, with only monoallelic mutations, demonstrated a greater diversity of clinical phenotypes. Conclusions: In patients with GnRH deficiency and biallelic mutations in GNRHR, genetic burden defined by severity and dose is associated with clinical phenotype. In contrast, for patients with monoallelic GNRHR mutations this correlation does not hold. Taken together, these data indicate that as-yet-unidentified genetic and/or environmental factors may combine with singly mutated GNRHR alleles to produce reproductive phenotypes. 相似文献
103.
Children and adolescents who are forcibly displaced represent almost half the world's internally displaced and refugee populations. We undertook a two-part systematic search and review of the evidence-base for individual, family, community, and societal risk and protective factors for the mental health outcomes of children and adolescents. Here we review data for displacement to low-income and middle-income settings. We draw together the main findings from reports to identify important issues and establish recommendations for future work. We draw attention to exposure to violence as a well established risk factor for poor mental health. We note the paucity of research into predictor variables other than those in the individual domain and the neglect of other variables for the assessment of causal associations, including potential mediators and moderators identifiable in longitudinal work. We conclude with research and policy recommendations to guide the development and assessment of effective interventions. 相似文献
104.
L Fraenkel RL Street V Towle JR O'Leary L Iannone PH Van Ness TR Fried 《Journal of the American Geriatrics Society》2012,60(8):1434-1441
105.
Ollberding NJ Maskarinec G Conroy SM Morimoto Y Franke AA Cooney RV Wilkens LR Le Marchand L Goodman MT Hernandez BY Henderson BE Kolonel LN 《Blood》2012,119(24):5817-5823
This analysis examined the association of non-Hodgkin lymphoma (NHL) with prediagnostic carotenoid levels, a marker for a diet rich in fruits and vegetables. We conducted a nested case-control study within the Multiethnic Cohort with 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, and hours fasting before blood draw. Serum carotenoid levels were obtained by high-pressure liquid chromatography with photodiode array detection. Conditional logistic regression was used to calculate odds ratios (ORs) according to tertiles of serum carotenoids and trend tests using continuous variables. Higher total serum carotenoids (OR(T3 vs T1) = 0.66 [0.46-0.96]; P(trend) = .02), lycopene (OR = 0.54 [0.38-0.78]; P(trend) = .003), and α-cryptoxanthin (OR = 0.53 [0.36-0.78]; P(trend) = .003) were associated with a lower risk of NHL. For retinol (OR = 0.90 [0.61-1.33]; P(trend) = .04), a statistically significant inverse linear trend was detected. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex and ethnicity; heterogeneity with NHL subtype was detected only for β-carotene. Other carotenoids, including α-carotene, β-carotene, lutein, β-cryptoxanthin, and zeaxanthin, showed no association with risk. These data provide support for a protective role of carotenoid-rich fruits and vegetables in the etiology of NHL. 相似文献
106.
Jain P Javdan M Feger FK Chiu PY Sison C Damle RN Bhuiya TA Sen F Abruzzo LV Burger JA Rosenwald A Allen SL Kolitz JE Rai KR Chiorazzi N Sherry B 《Haematologica》2012,97(4):599-607
Background
The levels and clinical relevance of Th17 cells and other interleukin-17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome.Design and Methods
Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry. Interleukin-17A-producing cells were analyzed in formalin-fixed, paraffin-embedded spleen and lymph node sections using immunohistochemistry and immunofluorescence.Results
The absolute numbers of Th17 cells in peripheral blood mononuclear cells and the percentages of Th17 cells in spleen cell suspensions were higher in patients with chronic lymphocytic leukemia than in healthy subjects; in six out of eight paired chronic lymphocytic leukemia blood and spleen sample comparisons, Th17 cells were enriched in spleen suspensions. Circulating Th17 levels correlated with better prognostic markers and longer overall survival of the patients. Two “non-Th17” interleukin-17-expressing cells were identified in chronic lymphocytic leukemia spleens: proliferating cells of the granulocytic lineage and mature mast cells. Granulocytes and mast cells in normal spleens did not express interleukin-17. Conversely, both chronic lymphocytic leukemia and healthy lymph nodes contained similar numbers of interleukin-17+ mast cells as well as Th17 cells.Conclusions
Th17 cells are elevated in chronic lymphocytic leukemia patients with better prognostic markers and correlate with longer survival. Furthermore, non-Th17 interleukin-17A-expressing cells exist in chronic lymphocytic leukemia spleens as maturing granulocytes and mature mast cells, suggesting that the microenvironmental milieu in leukemic spleens promotes the recruitment and/or expansion of Th17 and other IL-17-expressing cells. The pathophysiology of Th17 and non-Th17-interleukin-producing cells in chronic lymphocytic leukemia and their distributions and roles in this disease merit further study. 相似文献107.
ABSTRACT This article examines the neurocognitive sequelae of repeated exposure to hypoxemia in apnea (breath-hold) divers. A brief review of the literature on the physiological and neurological adaptations involved in the “human diving reflex” is presented. The results from a neuropsychological investigation of N = 21 elite apnea divers are evaluated. Standard neuropsychological tests, with known sensitivity to mild brain insults, included speed of visuo-motor responding, speed of language comprehension, response inhibition, and visual and verbal attention and recall tasks. Results indicated that the breath-hold divers performed tasks within the average range compared to norms on all tests, suggesting that 1–20 years of repeated exposure to hypoxemia including multiple adverse neurological events did not impact on performance on standard neuropsychological tasks. The results are discussed in relation to implications for clinical conditions such as sleep apnea, respiratory disorders, altitude sickness, and recreational apnea activities. 相似文献
108.
Katrina Tatton‐Brown Anne Murray Sandra Hanks Jenny Douglas Ruth Armstrong Siddharth Banka Lynne M. Bird Carol L. Clericuzio Valerie Cormier‐Daire Tom Cushing Frances Flinter Marie‐Line Jacquemont Shelagh Joss Esther Kinning Sally Ann Lynch Alex Magee Vivienne McConnell Ana Medeira Keiichi Ozono Michael Patton Julia Rankin Debbie Shears Marleen Simon Miranda Splitt Volker Strenger Kyra Stuurman Clare Taylor Hannah Titheradge Lionel Van Maldergem I. Karen Temple Trevor Cole Sheila Seal Childhood Overgrowth Consortium Nazneen Rahman 《American journal of medical genetics. Part A》2013,161(12):2972-2980
109.
110.
BackgroundThe Seattle Heart Failure Model (SHFM) is a multivariable model with proven prognostic value. Cardiopulmonary exercise testing (CPX) and neurohormonal markers (eg, B-type natriuretic peptide [BNP]) are also well accepted assessment techniques in the HF population and have both demonstrated robust prognostic value. The purpose of this investigation was to assess the combined prognostic value of the SHFM and CPX.Methods and ResultsThis study included all 453 patients enrolled in the Multicenter In-Sync Randomized Clinical Evaluation (MIRACLE) trial. Baseline SHFM and CPX were used. Both peak oxygen consumption (VO2) and ventilatory efficiency (VE/VCO2) were determined. In a univariate Cox proportional model analysis, SHFM and log-transformed peak VE/VCO2 were stronger predictors of 6-month mortality (both P < .001) than log-transformed BNP (P = .013) or peak VO2 (P = .066). In a multivariable Cox proportional hazards model, neither peak VO2 nor BNP were independent predictors when added to the SHFM (P > .1). Conversely, peak VE/VCO2 was a strong independent predictor when added to the SHFM, with an increase in the Cox proportional hazards model Wald χ2 from 22.7 for SHFM alone to 33.8 with inclusion of log-transformed peak VE/VCO2 (P < .0001) and significant changes in the net reclassification improvement and integrated discrimination index (both P < .002).ConclusionsThese results indicate that the SHFM and peak VE/VCO2 work synergistically to improve prognostic resolution. Further investigation is needed to continue to optimize multivariable prognostic models in patients with HF, a chronic disease population that continues to suffer from a high adverse event rate despite advances in medical care. 相似文献