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101.
Chen JM, Férec C, Cooper DN. Revealing the human mutome. The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database). However, for a variety of reasons, this figure is likely to represent only a small proportion of the clinically relevant genetic variants that remain to be identified in the human genome (the ‘mutome’). With the advent of next‐generation sequencing, we are currently witnessing a revolution in medical genetics. In particular, whole‐genome sequencing (WGS) has the potential to identify all disease‐causing or disease‐associated DNA variants in a given individual. Here, we use examples of recent advances in our understanding of mutational/pathogenic mechanisms to guide our thinking about possible locations outwith gene‐coding sequences for those disease‐causing or disease‐associated variants that are likely so often to have been overlooked because of the inadequacy of current mutation screening protocols. Such considerations are important not only for improving mutation‐screening strategies but also for enhancing the interpretation of findings derived from genome‐wide association studies, whole‐exome sequencing and WGS. An improved understanding of the human mutome will not only lead to the development of improved diagnostic testing procedures but should also improve our understanding of human genome biology. 相似文献
102.
PG Kareru JM Keriko GM Kenji GT Thiong'o AN Gachanja HN Mukiira 《African journal of traditional, complementary, and alternative medicines》2010,7(3):214-218
In this study, Tithonia diversifolia Helms. (A Gray), Aloe secundiflora (Miller) and Azadirachta indica (A. Juss) plant extracts were used to make herbal soaps while Thevetia peruviana (Schum) seed oil was used to make a herbal lotion for skincare. The soaps were tested for the growth inhibition of Escherichia coli, and Candida albicans. The lotion was evaluated against Staphylococcus aureus and E.coli. Although Tithonia diversifolia soap exhibited the highest inhibitory effect on the test bacterial strains, it had the least inhibition against C. albicans. Results from this study indicated that the ‘Tithonia diversifolia’ soap would have superior skin protection against the tested bacteria but would offer the least skin protection against C. albicans. The herbal lotion inhibited S. aureus and E. coli in a concentration dependent manner, however, the inhibitory effect was more pronounced on S. aureus. 相似文献
103.
Cristóbal Esteban José M Quintana Javier Moraza Myriam Aburto Urko Aguirre José I Aguirregomoscorta Susana Aizpiri Luis V Basualdo Alberto Capelastegui 《BMC medicine》2010,8(1):28
Background
Forced expiratory volume in one second (FEV1) is used to diagnose and establish a prognosis in chronic obstructive pulmonary disease (COPD). Using multi-dimensional scores improves this predictive capacity.Two instruments, the BODE-index (Body mass index, Obstruction, Dyspnea, Exercise capacity) and the HADO-score (Health, Activity, Dyspnea, Obstruction), were compared in the prediction of mortality among COPD patients. 相似文献104.
Broman G Quintana M Lindberg T Jansson E Kaijser L 《European journal of applied physiology》2006,98(2):117-123
Deep water running with wet vest is a safe form of exercise for elderly with mobility limitations. However, it is not known to what extent their aerobic power may be improved. Therefore, the aim was to assess the effects of high intensity deep water interval training with vest in elderly women. Twenty-nine healthy women 69 ± 4 years old participated. They performed a graded maximal exercise test on the cycle ergometer. They were randomly assigned to a control or to a training group. A submaximal exercise test on the cycle ergometer was executed only by the training group. They trained in deep water running/walking wearing a vest two times a week for 8 weeks. The target heart rate was 75% of maximal heart rate and the training consisted of several short working periods and resting intervals. After the intervention the heart rate at rest was 8% lower for the training group (P<0.01). Their heart rate at submaximal exercise was 3% less (P<0.01), their maximal oxygen uptake was raised by 10% (P<0.01), and their maximal ventilation was increased 14% (P<0.01). The values for the control group were unaltered after the period of intervention. In conclusion, high intensity deep water running with vest improves submaximal work capacity, maximal aerobic power, and maximal ventilation with the effects transferable to land-based activities in elderly women. 相似文献
105.
Yuri Quintana Bradley Crotty Darren Fahy Lewis Lipsitz Roger B. Davis Charles Safran 《BMC medical informatics and decision making》2018,18(1):105
Background
Longevity creates increasing care needs for healthcare providers and family caregivers. Increasingly, the burden of care falls to one primary caregiver, increasing stress and reducing health outcomes. Additionally, little has been published on adults’, over the age of 75, preferences in the development of health information sharing with family members using online platforms. This study aims to assess a novel, Internet based, family-centric communication and collaboration platform created to address the information needs of elders and their informal caregivers in a community setting.Methods
This study is an internet-based, open prospective cohort study, enrolling dyad pairs of one adult over the age of 75 with one informal caregiver. Dyads will be offered to use the InfoSAGE online platform without prospective assignment. Participants will consent using an online process that enables participation from any location and shares important study and privacy details. The platform will enable the capture of search queries and tracking of functions such as tasks and discussions. Surveys every six months assess health status, health and social needs, and caregiver burden using validated instruments over a two-year period. We will use a mixed methods approach, utilizing qualitative survey data along with website usage analytic data.Discussion
Analysis of the longitudinal usage and survey data will help to examine the patterns of family communication and health information seeking as the central older adult ages. We will use the study data to inform design recommendations relevant to a complex mixture of users, with special consideration to the needs of older adult users and potential physical limitations.106.
Luana Alves Dummer Fabricio Rochedo Conceio Leandro Quintana Nizoli Carina Martins de Moraes Andra Ramos Rocha Lorena Leonardo de Souza Talita Roos Telmo Vidor Fbio Pereira Leivas Leite 《Journal of virological methods》2009,161(1):84-90
Meningoencephalitis caused by Bovine herpesvirus type 5 (BoHV-5) is responsible for heavy economic losses in the cattle industry. As in other Alphaherpesviruses, the envelope glycoprotein IV (gD), which mediates penetration into host cells, is one of the major candidate antigens for a recombinant vaccine, since it induces a strong and persistent immune response. The DNA coding for a truncated form of BoHV-5 gD (tgD) has been cloned into the Pichia pastoris expression vector pPICZαB to allow protein secretion into the medium. After induction with methanol, a 55 kDa protein was obtained. Enzyme deglycosylation with Endo H showed a smaller size band in SDS-PGAE, with 50 kDa, suggesting that tgD has N-linked oligosaccharides and that it is not hyperglycosylated. The 55 kDa protein was recognized by several polyclonal antibodies, including polyclonal antibody anti-tgD and polyclonal antibodies of different animal species immunized with BoHV-5 and BoHV-1. This is the first report of BoHV-5 gD expression in yeast. It was shown that the recombinant truncated form of BoHV-5 gD has antigenic and immunogenic properties similar to the native BoHV-5 gD. Expression of tgD as a secreted protein allows simple and inexpensive purification methods that can be used for further studies to evaluate its immunogenicity in cattle. 相似文献
107.
Rocio Ramos‐Medina Aurea García‐Segovia Juana Gil Javier Carbone Angel Aguarón de la Cruz Ansgar Seyfferth Bárbara Alonso Jorge Alonso Juan A. León Diana Alecsandru Elena Meliá Elena Carrillo de Albornoz Daniel Ordoñez Isabel Santillán Victoria Verdú Jose Maria Garcia Ruiz de Morales Marcos López‐Hoyos Arturo López Larios Almudena Sampalo Pedro Caballero Luis Ortiz Quintana Eduardo Fernández‐Cruz Silvia Sánchez‐Ramón 《American journal of reproductive immunology (New York, N.Y. : 1989)》2014,71(5):458-466
108.
Paul JM Savelkoul Fabrizio De Mattia Yuedan Li Erik‐Jan Kamsteeg Irene BM Konings Peter van der Sluijs Peter MT Deen 《Human mutation》2009,30(10):E891-E903
Vasopressin regulates human water homeostasis by re‐distributing homotetrameric aquaporin‐2 (AQP2) water channels from intracellular vesicles to the apical membrane of renal principal cells, a process in which phosphorylation of AQP2 at S256 by cAMP‐dependent protein kinase A (PKA) is thought to be essential. Dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, is caused by AQP2 gene mutations. Here, we investigated a reported patient case of dominant NDI caused by a novel p.R254Q mutation. Expressed in oocytes, AQP2‐p.R254Q appeared to be a functional water channel, but was impaired in its transport to the cell surface to the same degree as AQP2‐p.S256A, which mimics non‐phosphorylated AQP2. In polarized MDCK cells, AQP2‐p.R254Q was retained and was distributed similarly to that of unstimulated wt‐AQP2 or AQP2‐p.S256A. Upon co‐expression, AQP2‐p.R254Q interacted with, and retained wt‐AQP2 in intracellular vesicles. In contrast to wild‐type AQP2, forskolin did not increase AQP2‐p.R254Q phosphorylation at S256 or its translocation to the apical membrane. Mimicking constitutive phosphorylation in AQP2‐p.R254Q with the p.S256D mutation, however, rescued its apical membrane expression. These date indicate that a lack of S256 phosphorylation is the sole cause of dominant NDI here, and thereby, p.R254Q is a loss of function instead of a gain of function mutation in dominant NDI. © 2009 Wiley‐Liss, Inc. 相似文献
109.
del Amo J Pérez-Hoyos S Moreno A Quintana M Ruiz I Cisneros JM Ferreros I González C García de Olalla P Pérez R Hernández I 《Journal of acquired immune deficiency syndromes (1999)》2006,41(5):624-631
OBJECTIVE: To study trends in progression to AIDS, all-cause mortality, and cause-specific mortality (AIDS-related, liver disease, and hemorrhagic complications) over calendar periods with different exposure to highly active antiretroviral therapy (HAART) in a cohort of hemophiliacs in Spain, taking into account the competing risks of the causes of death. METHODS: Multicenter cohort of HIV-infected hemophiliacs. HIV seroconversion was estimated using mathematic techniques for interval-censored data from 1979 through 1985. Rates of AIDS and cause-specific death were calculated by Poisson regression, allowing for late entry, for the periods 1985 through 1992, 1993 through 1996, 1997 through 2000 (early HAART), and 2001 through 2003 (late HAART), also allowing for competing risks. RESULTS: Of 585 subjects, 44% were younger than 15 years of age, 82% had severe hemophilia, 86% had type A hemophilia, and the median seroconversion date was October 1982. Calendar period and age at HIV seroconversion strongly influenced AIDS and death rates. Compared with 1993 through 1996, decreases of 75% (relative risk [RR] = 0.25, 95% confidence interval [CI]: 0.14 to 0.43) and 72% (RR = 0.28, 95% CI: 0.12 to 0.63) in the RR of AIDS were observed in early and late HAART. For all-cause mortality, 72% (RR = 0.28, 95% CI: 0.18 to 0.42) and 83% (RR = 0.17, 95% CI: 0.09 to 0.33) decreases were observed by 1997 through 2000 and 2001 through 2003. For liver-related deaths, increases were observed in the late-HAART period (RR = 2.80, 95% CI: 0.94 to 8.36) compared with 1993 through 1996, but using competing risks, this RR was substantially reduced (RR = 1.70, 95% CI: 0.57 to 5.04). DISCUSSION: Major reductions in AIDS and death rates were observed from 1997 to 2003 in hemophiliacs. These survival improvements are largely attributable to decreases in AIDS-related deaths and have been accompanied by increases in liver disease death rates, which are overestimated if competing risks are not taken into account. 相似文献