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1.
O'Bryant SE Xiao G Barber R Huebinger R Wilhelmsen K Edwards M Graff-Radford N Doody R Diaz-Arrastia R;Texas Alzheimer's Research & Care Consortium;Alzheimer's Disease Neuroimaging Initiative 《PloS one》2011,6(12):e28092
Context
There is no rapid and cost effective tool that can be implemented as a front-line screening tool for Alzheimer''s disease (AD) at the population level.Objective
To generate and cross-validate a blood-based screener for AD that yields acceptable accuracy across both serum and plasma.Design, Setting, Participants
Analysis of serum biomarker proteins were conducted on 197 Alzheimer''s disease (AD) participants and 199 control participants from the Texas Alzheimer''s Research Consortium (TARC) with further analysis conducted on plasma proteins from 112 AD and 52 control participants from the Alzheimer''s Disease Neuroimaging Initiative (ADNI). The full algorithm was derived from a biomarker risk score, clinical lab (glucose, triglycerides, total cholesterol, homocysteine), and demographic (age, gender, education, APOE*E4 status) data.Major Outcome Measures
Alzheimer''s disease.Results
11 proteins met our criteria and were utilized for the biomarker risk score. The random forest (RF) biomarker risk score from the TARC serum samples (training set) yielded adequate accuracy in the ADNI plasma sample (training set) (AUC = 0.70, sensitivity (SN) = 0.54 and specificity (SP) = 0.78), which was below that obtained from ADNI cerebral spinal fluid (CSF) analyses (t-tau/Aβ ratio AUC = 0.92). However, the full algorithm yielded excellent accuracy (AUC = 0.88, SN = 0.75, and SP = 0.91). The likelihood ratio of having AD based on a positive test finding (LR+) = 7.03 (SE = 1.17; 95% CI = 4.49–14.47), the likelihood ratio of not having AD based on the algorithm (LR−) = 3.55 (SE = 1.15; 2.22–5.71), and the odds ratio of AD were calculated in the ADNI cohort (OR) = 28.70 (1.55; 95% CI = 11.86–69.47).Conclusions
It is possible to create a blood-based screening algorithm that works across both serum and plasma that provides a comparable screening accuracy to that obtained from CSF analyses. 相似文献2.
Background
Mutations linked to early onset, familial forms of Alzheimer''s disease (FAD) are found most frequently in PSEN1, the gene encoding presenilin-1 (PS1). Together with nicastrin (NCT), anterior pharynx-defective protein 1 (APH1), and presenilin enhancer 2 (PEN2), the catalytic subunit PS1 constitutes the core of the γ-secretase complex and contributes to the proteolysis of the amyloid precursor protein (APP) into amyloid-beta (Aβ) peptides. Although there is a growing consensus that FAD-linked PS1 mutations affect Aβ production by enhancing the Aβ1–42/Aβ1–40 ratio, it remains unclear whether and how they affect the generation of APP intracellular domain (AICD). Moreover, controversy exists as to how PS1 mutations exert their effects in different experimental systems, by either increasing Aβ1–42 production, decreasing Aβ1–40 production, or both. Because it could be explained by the heterogeneity in the composition of γ-secretase, we purified to homogeneity complexes made of human NCT, APH1aL, PEN2, and the pathogenic PS1 mutants L166P, ΔE9, or P436Q.Methodology/Principal Findings
We took advantage of a mouse embryonic fibroblast cell line lacking PS1 and PS2 to generate different stable cell lines overexpressing human γ-secretase complexes with different FAD-linked PS1 mutations. A multi-step affinity purification procedure was used to isolate semi-purified or highly purified γ-secretase complexes. The functional characterization of these complexes revealed that all PS1 FAD-linked mutations caused a loss of γ-secretase activity phenotype, in terms of Aβ1–40, Aβ1–42 and APP intracellular domain productions in vitro.Conclusion/Significance
Our data support the view that PS1 mutations lead to a strong γ-secretase loss-of-function phenotype and an increased Aβ1–42/Aβ1–40 ratio, two mechanisms that are potentially involved in the pathogenesis of Alzheimer''s disease. 相似文献3.
Sei J. Lee Christine S. Ritchie Kristine Yaffe Irena Stijacic Cenzer Deborah E. Barnes 《PloS one》2014,9(12)
Background
Mild cognitive impairment is often a precursor to dementia due to Alzheimer''s disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment.Objective
To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings.Design and Participants
382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer''s Disease Neuroimaging Initiative (ADNI), a multi-site, longitudinal, observational study.Main Predictors Measures
Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales.Main Outcome Measure
Progression to probable Alzheimer''s disease.Key Results
Subjects had a mean (SD) age of 75 (7) years and 43% progressed to probable Alzheimer''s disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]). The optimism-corrected Harrell''s c-statistic was 0.71(95% CI: 0.68–0.75). Fourteen percent of subjects with low risk scores (0–2 points, n = 124) converted to probable Alzheimer''s disease over 3 years, compared to 51% of those with moderate risk scores (3–8 points, n = 223) and 91% of those with high risk scores (9–16 points, n = 35).Conclusions
An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer''s disease and may help clinicians differentiate between mild cognitive impairment patients at low vs. high risk of progression. 相似文献4.
Letenneur L Pérès K Fleury H Garrigue I Barberger-Gateau P Helmer C Orgogozo JM Gauthier S Dartigues JF 《PloS one》2008,3(11):e3637
Background
Herpes Simplex Virus (HSV) infection has been proposed as a possible risk factor of Alzheimer''s Disease (AD) notably because it is neurotropic, ubiquitous in the general population and able to establish lifelong latency in the host. The fact that HSV was present in elderly subjects with AD suggests that the virus could be a co-factor of the disease. We investigated the risk of developing AD in anti-HSV immunoglobulin G (IgG) positive subjects (indicator of a lifelong infection to HSV) and IgM-positive subjects (indicator of primary infection or reactivation of the virus) in a longitudinal population-based cohort of elderly subjects living in the community.Methods
Cox proportional hazard models were used to study the risk of developing AD according to the presence or not of anti-HSV IgG and IgM antibodies, assessed in the sera of 512 elderly initially free of dementia followed for 14 years.Results
During the follow-up, 77 incident AD cases were diagnosed. Controlled for age, gender, educational level and Apolipoprotein E4 (APOE4) status, IgM-positive subjects showed a significant higher risk of developing AD (HR = 2.55; 95% CI [1.38–4.72]), although no significant increased risk was observed in IgG-positive subjects (HR = 1.67; 95%CI [0.75–3.73]). No modification effect with APOE4 status was found.Conclusion
Reactivation of HSV seropositivity is highly correlated with incident AD. HSV chronic infection may therefore be contributive to the progressive brain damage characteristic of AD. 相似文献5.
Lee TC Glynn RJ Peña JM Paynter NP Conen D Ridker PM Pradhan AD Buring JE Albert MA 《PloS one》2011,6(12):e27670
Objectives
We prospectively examined whether socioeconomic status (SES) predicts incident type II diabetes (diabetes), a cardiovascular risk equivalent and burgeoning public health epidemic among women.Methods
Participants include 23,992 women with HbA1c levels <6% and no CVD or diabetes at baseline followed from February 1993 to March 2007. SES was measured by education and income while diabetes was self-reported.Results
Over 12.3 years of follow-up, 1,262 women developed diabetes. In age and race adjusted models, the relative risk of diabetes decreased with increasing education (<2 years of nursing, 2 to <4 years of nursing, bachelor''s degree, master''s degree, and doctorate: 1.0, 0.7 [95% Confidence Interval (CI), 0.6–0.8], 0.6 (95% CI, 0.5–0.7), 0.5 (95% CI, 0.4–0.6), 0.4 (95% CI, 0.3–0.5); ptrend<0.001). Adjustment for traditional and non-traditional cardiovascular risk factors attenuated this relationship (education: ptrend = 0.96). Similar associations were observed between income categories and diabetes.Conclusion
Advanced education and increasing income were both inversely associated with incident diabetes even in this relatively well-educated cohort. This relationship was largely explained by behavioral factors, particularly body mass index. 相似文献6.
7.
Background
There are approximately 3 million people aged 50 and older in sub-Saharan Africa who are HIV-positive. Despite this, little is known about the characteristics of older adults who are on treatment and their treatment outcomes.Methods
A retrospective cohort analysis was performed using routinely collected data with Malawi Ministry of Health monitoring tools from facilities providing antiretroviral therapy services in Zomba district. Patients aged 25 years and older initiated on treatment from July 2005 to June 2010 were included. Differences in survival, by age group, were determined using Kaplan–Meier survival plots and Cox proportional hazards regression models.Results
There were 10,888 patients aged 25 and older. Patients aged 50 and older (N = 1419) were more likely to be male (P<0.0001) and located in rural areas (P = 0.003) than those aged 25–49. Crude survival estimates among those aged 50–59 were not statistically different from those aged 25–49 (P = 0.925). However, survival among those aged 60 and older (N = 345) was worse (P = 0.019) than among those 25–59. In the proportional hazards model, after controlling for sex and stage at initiation, survival in those aged 50–59 did not differ significantly from those aged 25–49 (hazard ratio 1.00 (95% CI: 0.79 to 1.27; P = 0.998) but the hazard ratio was 1.46 (95% CI: 1.03 to 2.06; P = 0.032) for those aged 60 and older compared to those aged 25–49.Conclusions
Treatment outcomes of those aged 50–59 are similar to those aged 25–49. A better understanding of how older adults present for and respond to treatment is critical to improving HIV services. 相似文献8.
Background
Forensic medicine has been largely by-passed by the tide of health systems research and evidence based medicine. Murder victims form a central part of forensic medical examiners'' case load, and women murdered by intimate partners are an important subgroup, representing the most severe form and consequence of intimate partner violence. Our aim was to describe the epidemiology of female murder in South Africa (by intimate and non-intimate partners); and to describe and compare autopsy findings, forensic medical management of cases and the contribution of these to legal outcomes.Methods
We did a retrospective national study in a proportionate random sample of 25 medico-legal laboratories to identify all homicides in 1999 of women aged 14 years and over. Data were abstracted from the mortuary file and autopsy report, and collected from a police interview.Findings
In 21.5% of cases the perpetrator was convicted. Factors associated with a conviction for the female murders included having a history of intimate partner violence 1.18 (95%CI: 0.16–2.20), weapon recovered 1.36 (95% CI:0.58–2.15) and a detective visiting the crime scene 1.57 (95% CI:0.14–3.00). None of the forensic medical activities increased the likelihood of a conviction.Conclusion
The findings raise important questions about the role of forensic medicine in these cases. 相似文献9.
Brown K Fraser G Ramsay M Shanley R Cowley N van Wijgerden J Toff P Falconer M Hudson M Green J Kroll JS Vincent C Sevdalis N 《PloS one》2011,6(5):e19381
Background and Objective
Continued suboptimal measles-mumps-rubella (MMR) vaccine uptake has re-established measles epidemic risk, prompting a UK catch-up campaign in 2008–09 for children who missed MMR doses at scheduled age. Predictors of vaccine uptake during catch-ups are poorly understood, however evidence from routine schedule uptake suggests demographics and attitudes may be central. This work explored this hypothesis using a robust evidence-based measure.Design
Cross-sectional self-administered questionnaire with objective behavioural outcome.Setting and Participants
365 UK parents, whose children were aged 5–18 years and had received <2 MMR doses before the 2008–09 UK catch-up started.Main Outcome Measures
Parents'' attitudes and demographics, parent-reported receipt of invitation to receive catch-up MMR dose(s), and catch-up MMR uptake according to child''s medical record (receipt of MMR doses during year 1 of the catch-up).Results
Perceived social desirability/benefit of MMR uptake (OR = 1.76, 95% CI = 1.09–2.87) and younger child age (OR = 0.78, 95% CI = 0.68–0.89) were the only independent predictors of catch-up MMR uptake in the sample overall. Uptake predictors differed by whether the child had received 0 MMR doses or 1 MMR dose before the catch-up. Receipt of catch-up invitation predicted uptake only in the 0 dose group (OR = 3.45, 95% CI = 1.18–10.05), whilst perceived social desirability/benefit of MMR uptake predicted uptake only in the 1 dose group (OR = 9.61, 95% CI = 2.57–35.97). Attitudes and demographics explained only 28% of MMR uptake in the 0 dose group compared with 61% in the 1 dose group.Conclusions
Catch-up MMR invitations may effectively move children from 0 to 1 MMR doses (unimmunised to partially immunised), whilst attitudinal interventions highlighting social benefits of MMR may effectively move children from 1 to 2 MMR doses (partially to fully immunised). Older children may be best targeted through school-based programmes. A formal evaluation element should be incorporated into future catch-up campaigns to inform their continuing improvement. 相似文献10.
Objective
It may be possible to thrombolyse ischaemic stroke (IS) patients up to 6 h by using penumbral imaging. We investigated whether a perfusion CT (CTP) mismatch can help to select patients for thrombolysis up to 6 h.Methods
A cohort of 254 thrombolysed IS patients was studied. 174 (69%) were thrombolysed at 0–3 h by using non-contrast CT (NCCT), and 80 (31%) at 3–6 h (35 at 3–4.5 h and 45 at 4.5–6 h) by using CTP mismatch criteria. Symptomatic intracerebral haemorrhage (SICH), the mortality and the modified Rankin Score (mRS) were assessed at 3 months. Independent determinants of outcome in patients thrombolysed between 3 and 6 h were identified.Results
The baseline characteristics were comparable in the two groups. There were no differences in SICH (3% v 4%, p = 0.71), any ICH (7% v 9%, p = 0.61), or mortality (16% v 9%, p = 0.15) or mRS 0–2 at 3 months (55% v 54%, p = 0.96) between patients thrombolysed at 0–3 h (NCCT only) or at 3–6 h (CTP mismatch). There were no significant differences in outcome between patients thrombolysed at 3–4.5 h or 4.5–6 h. The NIHSS score was the only independent determinant of a mRS of 0–2 at 3 months (OR 0.89, 95% CI 0.82–0.97, p = 0.007) in patients treated using CTP mismatch criteria beyond 3 h.Conclusions
The use of a CTP mismatch model may help to guide thrombolysis decisions up to 6 h after IS onset. 相似文献11.
Context
The treatment for transsexualism is sex reassignment, including hormonal treatment and surgery aimed at making the person''s body as congruent with the opposite sex as possible. There is a dearth of long term, follow-up studies after sex reassignment.Objective
To estimate mortality, morbidity, and criminal rate after surgical sex reassignment of transsexual persons.Design
A population-based matched cohort study.Setting
Sweden, 1973-2003.Participants
All 324 sex-reassigned persons (191 male-to-females, 133 female-to-males) in Sweden, 1973–2003. Random population controls (10∶1) were matched by birth year and birth sex or reassigned (final) sex, respectively.Main Outcome Measures
Hazard ratios (HR) with 95% confidence intervals (CI) for mortality and psychiatric morbidity were obtained with Cox regression models, which were adjusted for immigrant status and psychiatric morbidity prior to sex reassignment (adjusted HR [aHR]).Results
The overall mortality for sex-reassigned persons was higher during follow-up (aHR 2.8; 95% CI 1.8–4.3) than for controls of the same birth sex, particularly death from suicide (aHR 19.1; 95% CI 5.8–62.9). Sex-reassigned persons also had an increased risk for suicide attempts (aHR 4.9; 95% CI 2.9–8.5) and psychiatric inpatient care (aHR 2.8; 95% CI 2.0–3.9). Comparisons with controls matched on reassigned sex yielded similar results. Female-to-males, but not male-to-females, had a higher risk for criminal convictions than their respective birth sex controls.Conclusions
Persons with transsexualism, after sex reassignment, have considerably higher risks for mortality, suicidal behaviour, and psychiatric morbidity than the general population. Our findings suggest that sex reassignment, although alleviating gender dysphoria, may not suffice as treatment for transsexualism, and should inspire improved psychiatric and somatic care after sex reassignment for this patient group. 相似文献12.
Background
Management of febrile neutropenic episodes (FE) is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT) in FE for initial diagnosis of infection and reassessment in persistent fever.Methods
PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples): 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS), 68 clinically documented infections (CDI, 35%; 39 deep-seated), and 61 fever of unexplained origin (FUO, 31.5%).Results
At fever onset median PCT was 190 pg/mL (range 30–26''800), without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80–86350) vs. FUO (205, 33–771; p<0.001). PCT >500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570–771). A PCT peak >500 pg/mL (1196, 524–11950) occurred beyond 3 days of persistent fever in 17/21 (81%) invasive fungal diseases (IFD). This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1–23) vs. 10 (3–22; p = 0.026), respectively.Conclusion
While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses. 相似文献13.
Background
The associations of glycemic load (GL) and glycemic index (GI) with the risk of cardiovascular diseases (CVD) are not well-established, particularly in men, and may be modified by gender.Objective
To assess whether high dietary GL and GI increase the risk of CVD in men and women.Methods
A large prospective cohort study (EPIC-MORGEN) was conducted within the general Dutch population among 8,855 men and 10,753 women, aged 21–64 years at baseline (1993–1997) and free of diabetes and CVD. Dietary intake was assessed with a validated food-frequency questionnaire and GI and GL were calculated using Foster-Powell''s international table of GI. Information on morbidity and mortality was obtained through linkage with national registries. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for incident coronary heart disease (CHD) and stroke, while adjusting for age, CVD risk factors, and dietary factors.Results
During a mean follow-up of 11.9 years, 581 CHD cases and 120 stroke cases occurred among men, and 300 CHD cases and 109 stroke cases occurred among women. In men, GL was associated with an increased CHD risk (adjusted HR per SD increase, 1.17 [95% CI, 1.02–1.35]), while no significant association was found in women (1.09 [0.89–1.33]). GI was not associated with CHD risk in both genders, while it was associated with increased stroke risk in men (1.27 [1.02–1.58]) but not in women (0.96 [0.75–1.22]). Similarly, total carbohydrate intake and starch intake were associated with a higher CHD risk in men (1.23 [1.04–1.46]; and 1.24 [1.07–1.45]), but not in women.Conclusion
Among men, high GL and GI, and high carbohydrate and starch intake, were associated with increased risk of CVD. 相似文献14.
Background
Auto-antibodies with specificity to self-antigens have been implicated in a wide variety of neurological diseases, including Parkinson''s (PD) and Alzheimer''s diseases, being sensitive indicators of neurodegeneration and focus for disease prevention. Of particular interest are the studies focused on the auto-immune responses to amyloidogenic proteins associated with diseases and their applications in therapeutic treatments such as vaccination with amyloid antigens and antibodies in PD, Alzheimer''s disease and potentially other neurodegeneration ailments.Methodology/Principal Findings
Generated auto-antibodies towards the major amyloidogenic protein involved in PD Lewy bodies – α-synuclein and its amyloid oligomers and fibrils were measured in the blood sera of early and late PD patients and controls by using ELISA, Western blot and Biacore surface plasmon resonance. We found significantly higher antibody levels towards monomeric α-synuclein in the blood sera of PD patients compared to controls, though the responses decreased with PD progression (P<0.0001). This indicates potential protective role of autoimmunity in maintaining the body homeostasis and clearing protein species whose disbalance may lead to amyloid assembly. There were no noticeable immune responses towards amyloid oligomers, but substantially increased levels of IgGs towards α-synuclein amyloid fibrils both in PD patients and controls, which subsided with the disease progression (P<0.0001). Pooled IgGs from PD patients and controls interacted also with the amyloid fibrils of Aβ (1–40) and hen lysozyme, however the latter were recognized with lower affinity. This suggests that IgGs bind to the generic amyloid conformational epitope, displaying higher specificity towards human amyloid species associated with neurodegeneration.Conclusions/Significance
Our findings may suggest the protective role of autoimmunity in PD and therefore immune reactions towards PD major amyloid protein – α-synuclein can be of value in the development of treatment and diagnostic strategies, especially during the early disease stages. 相似文献15.
Ingrid D. C. van Balkom Michaeline Bresnahan Pieter Jelle Vuijk Jan Hubert Ezra Susser Hans W. Hoek 《PloS one》2012,7(9)
Objective
The aim of this study was to examine paternal age in relation to risk of autism spectrum disorders (ASDs) in a setting other than the industrialized west.Design
A case-control study of Aruban-born children (1990–2003). Cases (N = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only such clinic in Aruba; gender and age matched controls (N = 347) were gathered from public health records. Parental age was defined categorically (≤29, 30–39, 40–49, ≥50y). The analysis was made, using conditional logistic regression.Results
Advanced paternal age was associated with increased risk of ASDs in offspring. In comparison to the youngest paternal age group (≤29y), risk of autism increased 2.18 times for children born from fathers in their thirties, 2.71 times for fathers in their forties, and 3.22 thereafter.Conclusion
This study, part of the first epidemiologic study of autism in the Caribbean, contributes additional evidence, from a distinctive sociocultural setting, of the risk of ASD associated with increased paternal age. 相似文献16.
Objective
The paper projects the contribution to 2011–2015 international targets of three major pandemics by programs in 140 countries funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest external financier of tuberculosis and malaria programs and a major external funder of HIV programs in low and middle income countries.Design
Estimates, using past trends, for the period 2011–2015 of the number of persons receiving antiretroviral (ARV) treatment, tuberculosis case detection using the internationally approved DOTS strategy, and insecticide-treated nets (ITNs) to be delivered by programs in low and middle income countries supported by the Global Fund compared to international targets established by UNAIDS, Stop TB Partnership, Roll Back Malaria Partnership and the World Health Organisation.Results
Global Fund-supported programs are projected to provide ARV treatment to 5.5–5.8 million people, providing 30%–31% of the 2015 international target. Investments in tuberculosis and malaria control will enable reaching in 2015 60%–63% of the international target for tuberculosis case detection and 30%–35% of the ITN distribution target in sub-Saharan Africa.Conclusion
Global Fund investments will substantially contribute to the achievement by 2015 of international targets for HIV, TB and malaria. However, additional large scale international and domestic financing is needed if these targets are to be reached by 2015. 相似文献17.
Background
When preparing for fertilization, oocytes undergo meiotic maturation during which structural changes occur in the endoplasmic reticulum (ER) that lead to a more efficient calcium response. During meiotic maturation and subsequent fertilization, the actin cytoskeleton also undergoes dramatic restructuring. We have recently observed that rearrangements of the actin cytoskeleton induced by actin-depolymerizing agents, or by actin-binding proteins, strongly modulate intracellular calcium (Ca2+) signals during the maturation process. However, the significance of the dynamic changes in F-actin within the fertilized egg has been largely unclear.Methodology/Principal Findings
We have measured changes in intracellular Ca2+ signals and F-actin structures during fertilization. We also report the unexpected observation that the conventional antagonist of the InsP3 receptor, heparin, hyperpolymerizes the cortical actin cytoskeleton in postmeiotic eggs. Using heparin and other pharmacological agents that either hypo- or hyperpolymerize the cortical actin, we demonstrate that nearly all aspects of the fertilization process are profoundly affected by the dynamic restructuring of the egg cortical actin cytoskeleton.Conclusions/Significance
Our findings identify important roles for subplasmalemmal actin fibers in the process of sperm-egg interaction and in the subsequent events related to fertilization: the generation of Ca2+ signals, sperm penetration, cortical granule exocytosis, and the block to polyspermy. 相似文献18.
Aims
To evaluate the associations of age at menarche and the leg length-to-sitting-height ratio, markers of adolescent growth, with risk of diabetes in later life.Materials and Methods
Information from 69,385 women and 55,311 men, aged 40–74 years from the Shanghai Women''s Health Study and Shanghai Men''s Health Study, were included in the current analyses. Diabetes status was ascertained through biennial in person follow-up. Cox models, with age as the time scale, were used.Results
There were 2369 cases of diabetes (1831 women; 538 men) during an average of 7.3 and 3.6 years of follow-up of the women and men, respectively. In females, menarche age was inversely associated with diabetes risk after adjustment for birth cohort, education, and income (HR = 0.95, 0.92–0.98). In both genders, leg length-to-sitting-height ratio was inversely related to diabetes (HR = 0.88, 0.80–0.97 for men; HR = 0.91, 0.86–0.96 for women) after adjustment for birth cohort, education, and income. Further adjustment for adult BMI at study enrollment completely eliminated the associations of age at menarche (HR = 0.99, 0.96–1.02) and the leg length-to-sitting-height ratio (HR = 1.00, 0.91–1.10 for men; HR = 1.01, 0.96–1.07 for women) with diabetes risk.Conclusions
Our study suggests that markers of an early age at peak height velocity, i.e. early menarche age and low leg-length-to-sitting height ratio, may be associated with diabetes risk later in life and this association is likely to be mediated through obesity. 相似文献19.
Background and Objective
Emerging evidence from biological and epidemiological studies has suggested that body iron stores and heme-iron intake may be related to the risk of type 2 diabetes (T2D). We aimed to examine the association of body iron stores and heme-iron intake with T2D risk by conducting a systematic review and meta-analysis of previously published studies.Research Design and Methods
Systematic review and subsequent meta-analysis were conducted by searching MEDLINE database up to June 22, 2012 to identify studies that analyzed the association of body iron stores or dietary heme-iron intake with T2D risk. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled risk estimates, while the heterogeneity among studies was examined using the I2 and Q statistic.Results
The meta-analysis included 16 high-quality studies: 12 studies analyzed ferritin levels (4,366 T2D patients and 41,091 controls) and 4 measured heme-iron intake (9,246 T2D patients and 179,689 controls). The combined relative risk (RR) comparing the highest and lowest category of ferritin levels was 1.66 (95% CI: 1.15–2.39) for prospective studies, 2.29 (95% CI: 1.48–3.54) for cross-sectional studies with heterogeneity (Q = 14.84, p = 0.01, I2 = 66.3%; Q = 44.16, p<0.001, I2 = 88.7%). The combined RR comparing the highest and lowest category of heme-iron intake was 1.31 (95% CI: 1.21–1.43) with heterogeneity (Q = 1.39, p = 0.71, I2 = 0%). No publication bias was found. Additional 15 studies that were of good quality, had significant results, and analyzed the association between body iron stores and T2D risk were qualitatively included in the systematic review.Conclusions
The meta-analysis and systematic review suggest that increased ferritin levels and heme-iron intake are both associated with higher risk of T2D. 相似文献20.
Kranzer K van Schaik N Karmue U Middelkoop K Sebastian E Lawn SD Wood R Bekker LG 《PloS one》2011,6(9):e25244