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81.
Sian Ellard Emma Kivuva Peter Turnpenny Karen Stals Matthew Johnson Weijia Xie Richard Caswell Hana Lango Allen 《European journal of human genetics : EJHG》2015,23(3):401-404
Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0–4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies. 相似文献
82.
Diana Lehmann Kathrin Schubert Pushpa R Joshi Steven A Hardy Helen A L Tuppen Karen Baty Emma L Blakely Christian Bamberg Stephan Zierz Marcus Deschauer Robert W Taylor 《European journal of human genetics : EJHG》2015,23(12):1735-1738
Pathogenic mitochondrial DNA (mtDNA) point mutations are associated with a wide range of clinical phenotypes, often involving multiple organ systems. We report two patients with isolated myopathy owing to novel mt-tRNAAla variants. Muscle biopsy revealed extensive histopathological findings including cytochrome c oxidase (COX)-deficient fibres. Pyrosequencing confirmed mtDNA heteroplasmy for both mutations (m.5631G>A and m.5610G>A) whilst single-muscle fibre segregation studies (revealing statistically significant higher mutation loads in COX-deficient fibres than in COX-positive fibres), hierarchical mutation segregation within patient tissues and decreased steady-state mt-tRNAAla levels all provide compelling evidence of pathogenicity. Interestingly, both patients showed very high-mutation levels in all tissues, inferring that the threshold for impairment of oxidative phosphorylation, as evidenced by COX deficiency, appears to be extremely high for these mt-tRNAAla variants. Previously described mt-tRNAAla mutations are also associated with a pure myopathic phenotype and demonstrate very high mtDNA heteroplasmy thresholds, inferring at least some genotype:phenotype correlation for mutations within this particular mt-tRNA gene. 相似文献
83.
Rebecka Hjort Emma Ahlqvist Per-Ola Carlsson Valdemar Grill Leif Groop Mats Martinell Bahareh Rasouli Anders Rosengren Tiinamaija Tuomi Bjørn Olav Åsvold Sofia Carlsson 《Diabetologia》2018,61(6):1333-1343
Aims/hypothesis
Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies.Methods
Analyses were based on incident cases of LADA (n?=?425) and type 2 diabetes (n?=?1420), and 1704 randomly selected control participants from a Swedish case–control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984–2008). We present adjusted ORs and HRs with 95% CI.Results
In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD.Conclusions/interpretation
Overweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.84.
Juvenile rhesus monkeys have lower type 2 cytokine responses than adults after primary infection with Schistosoma mansoni 总被引:3,自引:0,他引:3
Fallon PG Gibbons J Vervenne RA Richardson EJ Fulford AJ Kiarie S Sturrock RF Coulson PS Deelder AM Langermans JA Thomas AW Dunne DW 《The Journal of infectious diseases》2003,187(6):939-945
Adults and children have differences in their susceptibility to schistosomiasis. The relative influences of age-dependent innate resistance and acquired immunity in the differences between susceptibility to schistosomiasis are difficult to assess in humans. Therefore, we exposed juvenile and adult female rhesus monkeys to primary infection with Schistosoma mansoni. In contrast to the adult animals, the juvenile rhesus monkeys had low levels of interleukin (IL)-4 and IL-5 production by peripheral blood mononuclear cells after schistosome infection, as well as lower levels of parasite-antigen-specific antibody (IgG, IgM, and IgA) responses, and produced limited antigen-specific or total IgE. Juvenile animals had statistically nonsignificant increased worm burdens and tissue or fecal egg counts, compared with that of adults, whereas circulating schistosome antigens were significantly higher in infected juvenile monkeys. These results suggest that juvenile rhesus monkeys have reduced type 2 cytokine responses after primary schistosome infections and perhaps are more susceptible to parasite infection. 相似文献
85.
86.
Fibrinogen and Fibrin Clot Structure in Diabetes 总被引:3,自引:0,他引:3
Diabetes is associated with an increased risk of developing cardiovascular disease, which is not fully accounted for by the accumulation of classic cardiovascular risk factors in patients. Recent evidence has demonstrated fibrinogen to be a powerful independent risk marker for cardiovascular disease in the general population, and it is also likely to contribute toward the increased atherosclerotic risk in diabetes. The etiology of hyperfibrinogenemia in diabetes is likely to be multifactorial, and at present the mechanisms involved have not been clarified. However, insulin, insulin resistance and inflammation are likely to be involved, especially in type 2 diabetes. The influence of diabetes in determining an individual's atherothrombotic risk is likely to extend beyond that of elevated fibrinogen levels, and may also act via changes in the structure and function of the fibrin clot that forms. Further research is needed to determine the mechanisms underlying these changes, which may lead to development of future interventions to reduce the excessive vascular risk associated with this disease. 相似文献
87.
88.
Emma M. Smith Danelle Fuller Hina Mahmood 《Disability and rehabilitation. Assistive technology》2018,13(6):523-526
Purpose: To determine if older adult, novice wheelchair users who drive a power wheelchair with a JoyBar control complete maneuverability tasks in less time and with less error than those who drive a power wheelchair with a standard joystick control.Materials and methods: A parallel randomized controlled trial design conducted at a medical rehabilitation and research centre with ambulatory older adults aged 60 and above (n?=?27). The intervention was the JoyBar alternative wheelchair control. The primary outcome measure was total time to complete each of the two maneuverability tasks. The secondary outcome measure was total number of errors during each of the maneuverability tasks.Results: An independent, two sampled t-test was conducted and revealed that the JoyBar group took a greater amount of time to complete both maneuverability tasks than the control group (p?.05). No significant differences (p?.05) were found in rates of error on either task between the JoyBar and joystick groups.Conclusions: Maneuverability of a powered wheelchair by novice wheelchair users was not improved through the use of the JoyBar when compared to a standard wheelchair joystick, as measured by rates of error and time to complete maneuverability tasks.
- Implications for rehabilitation
Clients who are new to powered wheelchair use may perform maneuverability tasks faster, with equivalent accuracy, using a standard joystick versus the JoyBar.
Clients who use a JoyBar may require adjustments to the programming of their wheelchair to ensure optimal performance.
Additional training may be required to achieve proficiency in maneuverability tasks with a JoyBar versus a standard joystick.
89.
90.
Scott D. Rhodes Lilli Mann Florence M. Simán Eunyoung Song Jorge Alonzo Mario Downs Emma Lawlor Omar Martinez Christina J. Sun Mary Claire O’Brien Beth A. Reboussin Mark A. Hall 《American journal of public health》2015,105(2):329-337
Objectives. We sought to understand how local immigration enforcement policies affect the utilization of health services among immigrant Hispanics/Latinos in North Carolina.Methods. In 2012, we analyzed vital records data to determine whether local implementation of section 287(g) of the Immigration and Nationality Act and the Secure Communities program, which authorizes local law enforcement agencies to enforce federal immigration laws, affected the prenatal care utilization of Hispanics/Latinas. We also conducted 6 focus groups and 17 interviews with Hispanic/Latino persons across North Carolina to explore the impact of immigration policies on their utilization of health services.Results. We found no significant differences in utilization of prenatal care before and after implementation of section 287(g), but we did find that, in individual-level analysis, Hispanic/Latina mothers sought prenatal care later and had inadequate care when compared with non-Hispanic/Latina mothers. Participants reported profound mistrust of health services, avoiding health services, and sacrificing their health and the health of their family members.Conclusions. Fear of immigration enforcement policies is generalized across counties. Interventions are needed to increase immigrant Hispanics/Latinos’ understanding of their rights and eligibility to utilize health services. Policy-level initiatives are also needed (e.g., driver’s licenses) to help undocumented persons access and utilize these services.Federal immigration enforcement policies have been increasingly delegated to state and local jurisdictions, leading to increased enforcement activities by local police. This shift has resulted largely from the implementation of 2 federal initiatives: section 287(g) of the Immigration and Nationality Act and the Secure Communities program. Section 287(g) authorizes Immigration and Custom Enforcement to enter into agreements with state and local law enforcement agencies to enforce federal immigration law during their regular, daily law enforcement activities. The original intention was to “target and remove undocumented immigrants convicted of violent crimes, human smuggling, gang/organized crime activity, sexual-related offenses, narcotics smuggling and money laundering.”1 Added to the Immigration and Nationality Act in 1996, section 287(g) was not widely used in its first decade, but its use accelerated in the mid- to late 2000s.2,3The Secure Communities program differs from section 287(g) in that it does not authorize local enforcement bodies to arrest individuals for federal immigration violations. Instead, when individuals are arrested for nonimmigration matters, the Secure Communities program facilitates the sharing of local arrestees’ fingerprints and information with Immigration and Custom Enforcement and the Federal Bureau of Investigation, which checks them against immigration databases. If these checks reveal that an individual is unlawfully present in the United States or otherwise removable because of a criminal conviction, Immigration and Custom Enforcement takes enforcement action.4Some evidence suggests that both section 287(g) and the Secure Communities program contribute to Hispanic/Latino immigrants’ general mistrust of local law enforcement and fear of utilizing a variety of public services, such as police protection and emergency services.2,5–7 Although many immigrant Hispanics/Latinos in the United States experience barriers to care because of a lack of bilingual and bicultural services, low health literacy, insufficient public transportation, and limited knowledge of available health services,8–12 studies have suggested that individuals lacking legal status may have more difficulty obtaining health services and may experience worse health outcomes than do individuals with legal status.13–18 Among immigrant Hispanics/Latinos, the fear of deportation, a lack of required forms of documentation, interaction with law enforcement personnel, and racial profiling are factors also associated with reduced utilization of health services and worse health.6,19–22 Such fears lead to incomplete sequences of care,19,20,23,24 promote the use of nonstandard and unsafe contingencies for care,16,25–27 and contribute to public health hazards, as immigrants delay preventive care or treatment.13,22,28 These fears further affect long-term health outcomes as immigrant Hispanics/Latinos alter their physical activity, food purchasing behaviors, and food consumption because of concerns about being in public.29 They may withhold information from health care providers19 and experience high levels of stress, leading to compromised mental health.20,30,31The Patient Protection and Affordable Care Act bars undocumented or recent legal immigrants from receiving financial assistance for health insurance32; thus, many will continue to remain uninsured and dependent on public health services and free clinics for a significant portion of their care. Because these services are associated with government authority, there is the potential that increasing immigration enforcement policies will deter noncitizens from seeking needed care, not only to their detriment but also to the detriment of public health.Currently there is little research examining the impact of recent immigration enforcement policies on the access to and utilization of health care, and there has been a call to better understand the public health impact of current immigration policies and their enforcement.29 Through mixed methods, we explored the effect of local immigration enforcement policies on access to and utilization of health services among immigrant Hispanics/Latinos in North Carolina. We analyzed vital records data to determine whether there were differences in utilization of prenatal services by Hispanic/Latina mothers pre- and postimplementation of section 287(g), and we conducted focus groups and in-depth interviews with Hispanics/Latinos living in counties that had implemented section 287(g) and in “sanctuary” counties, counties in which leaders, including politicians and clergy, have spoken out against the program. 相似文献