1,328 research outputs found
Matched cohort study of germline BRCA mutation carriers with triple negative breast cancer in brightness
Observers in an accelerated universe
If the current acceleration of our Universe is due to a cosmological
constant, then a Coleman-De Luccia bubble will nucleate in our Universe. In
this work, we consider that our observations could be likely in this framework,
consisting in two infinite spaces, if a foliation by constant mean curvature
hypersurfaces is taken to count the events in the spacetime. Thus, we obtain
and study a particular foliation, which covers the existence of most observers
in our part of spacetime.Comment: revised version, accepted in EPJ
Progressive Structural Defects in Canine Centronuclear Myopathy Indicate a Role for HACD1 in Maintaining Skeletal Muscle Membrane Systems
Mutations in HACD1/PTPLA cause recessive congenital myopathies in humans and dogs. Hydroxyacyl-coA dehydratases are required for elongation of very long chain fatty acids, and HACD1 has a role in early myogenesis, but the functions of this striated muscle-specific enzyme in more differentiated skeletal muscle remain unknown. Canine HACD1 deficiency is histopathologically classified as a centronuclear myopathy (CNM). We investigated the hypothesis that muscle from HACD1-deficient dogs has membrane abnormalities in common with CNMs with different genetic causes. We found progressive changes in tubuloreticular and sarcolemmal membranes and mislocalized triads and mitochondria in skeletal muscle from animals deficient in HACD1. Furthermore, comparable membranous abnormalities in cultured HACD1-deficient myotubes provide additional evidence that these defects are a primary consequence of altered HACD1 expression. Our novel findings, including T-tubule dilatation and disorganization, associated with defects in this additional CNM-associated gene provide a definitive pathophysiologic link with these disorders, confirm that dogs deficient in HACD1 are relevant models, and strengthen the evidence for a unifying pathogenesis in CNMs via defective membrane trafficking and excitation-contraction coupling in muscle. These results build on previous work by determining further functional roles of HACD1 in muscle and provide new insight into the pathology and pathogenetic mechanisms of HACD1 CNM. Consequently, alterations in membrane properties associated with HACD1 mutations should be investigated in humans with related phenotypes
Accuracy of both virtual and printed 3-dimensional models for volumetric measurement of alveolar clefts prior to alveolar bone grafting compared to a validated algorithm:a preliminary investigation
Feasibility of a lifestyle intervention in early pregnancy to prevent deterioration of glucose tolerance
<p>Abstract</p> <p>Background</p> <p>In conjunction with the growing prevalence of obesity and the older age of pregnant women gestational diabetes (GDM) is a major health problem.</p> <p>The aim of the study was to evaluate if a lifestyle intervention since early pregnancy is feasible in improving the glucose tolerance of women at a high-risk for GDM in Finland.</p> <p>Methods</p> <p>A 75-g oral glucose tolerance test (OGTT) was performed in early pregnancy (n = 102). Women at high risk for GDM (n = 54) were randomized at weeks 8-12 from Apr 2005 to May 2006 to a lifestyle intervention group (n = 27) or to a close follow-up group (n = 27). An OGTT was performed again at weeks 26-28 for the lifestyle intervention and close follow-up groups.</p> <p>Results</p> <p>The values of the OGTT during the second trimester did not differ between the lifestyle intervention and close follow-up groups. In the lifestyle intervention group three women had GDM in the second trimester and respectively one woman in the close follow up group. Insulin therapy was not required in both groups. The intervention resulted in somewhat lower weight gain 11.4 ± 6.0 kg vs. 13.9 ± 5.1 kg, p = 0.062, adjusted by the prepregnancy weight.</p> <p>Conclusions</p> <p>Early intervention with an OGTT and simple lifestyle advice is feasible. A more intensive lifestyle intervention did not offer additional benefits with respect to glucose tolerance, although it tended to ameliorate the weight gain.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01130012">NCT01130012</a></p
The Expression of ERCC1, RRM1, and BRCA1 in Breast Cancer According to the Immunohistochemical Phenotypes
We studied the expression of BRCA1, ERCC1, and RRM1 which play an important role in DNA repair systems in breast cancer. Immunohistochemical staining for EGFR, BRCA1, ERCC1, and RRM1 were performed by using a tissue microarray made from 230 breast cancer patients. Patients were classified into luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) types according to ER, PR, and HER-2 expression. The expression of ERCC1, RRM1, and BRCA1 were correlated (P < 0.05). The expression level of ERCC1 was the lowest in TNBC type (P = 0.031), ERCC1 negativity was more prominent in TNBC and luminal B groups than luminal A and HER-2 groups (P = 0.013). Cases with EGFR overexpression showed high expression of RRM1 and BRCA1 (P = 0.046, and 0.004, respectively). In conclusion, the expression of ERCC1 is particularly lower in TNBCs than other types of breast cancers
Discussing Depression with Vietnamese American Patients
Background Asian patients preferentially seek mental health care from their primary care providers but are unlikely to receive it. Primary care providers need culturally-informed strategies for addressing stigmatizing illnesses. Methods 11 Vietnamese American community members participated in semi-structured interviews. Interviews were audio-taped and transcribed. The grounded theory approach was used for qualitative coding and thematic analysis. Results Vietnamese community members describe experiences with depression under four themes: (1) Stigma and face; (2) Social functioning and the role of the family; (3) Traditional healing and beliefs about medications; and (4) Language and culture. Based on this data, we offer suggestions for improving culturally-informed care for Vietnamese Americans. Disucssion Our study adds to the research aimed at improving communication and health care relationships between physicians and Vietnamese American patients. Physicians should learn to tailor their interviewing style to the increasingly diverse patient population
HIV Risks and Seroprevalence Among Mexican American Injection Drug Users in California
Latinos in the United States are an ethnically diverse group disproportionately affected by HIV/AIDS. We describe HIV seroprevalence, HIV risk behaviors and utilization of health services among Mexican American injection drug users (IDUs) in California (n = 286) and compare them to White (n = 830) and African American (n = 314) IDUs. Study participants were recruited from syringe exchange programs (n = 24) in California. HIV seroprevalence among Mexican Americans (0.5%) was dramatically lower than Whites (5%) and African Americans (8%). Mexican Americans reported fewer sex-related risks than Whites and African Americans though injection-related risks remained high. Compared to Whites, Mexican Americans were more likely to participate in drug treatment during a 6 month period (AOR 1.5, 95% CI 1.1, 2.0) but less likely to receive any health care (AOR 0.6, 95% CI 0.5, 0.8). Exploring cultural and structural factors among Mexican American IDUs may offer new insights into how to maintain low rates of HIV seroprevalence and reduce barriers to health care utilization
MAPping out distribution routes for kinesin couriers
In the crowded environment of eukaryotic cells, diffusion is an inefficient distribution mechanism for cellular components. Long-distance active transport is required and is performed by molecular motors including kinesins. Furthermore, in highly polarized, compartmentalized and plastic cells such as neurons, regulatory mechanisms are required to ensure appropriate spatio-temporal delivery of neuronal components. The kinesin machinery has diversified into a large number of kinesin motor proteins as well as adaptor proteins that are associated with subsets of cargo. However, many mechanisms contribute to the correct delivery of these cargos to their target domains. One mechanism is through motor recognition of subdomain-specific microtubule (MT) tracks, sign-posted by different tubulin isoforms, tubulin post-translational modifications (PTMs), tubulin GTPase activity and MT associated proteins (MAPs). With neurons as a model system, a critical review of these regulatory mechanisms is presented here, with particular focus on the emerging contribution of compartmentalised MAPs. Overall, we conclude that – especially for axonal cargo – alterations to the MT track can influence transport, although in vivo, it is likely that multiple track-based effects act synergistically to ensure accurate cargo distribution
Tamoxifen-Independent Recombination in the RIP-CreER Mouse
The inducible Cre-lox system is a valuable tool to study gene function in a spatial and time restricted fashion in mouse models. This strategy relies on the limited background activity of the modified Cre recombinase (CreER) in the absence of its inducer, the competitive estrogen receptor ligand, tamoxifen. The RIP-CreER mouse (Tg (Ins2-cre/Esr1) 1Dam) is among the few available β-cell specific CreER mouse lines and thus it has been often used to manipulate gene expression in the insulin-producing cells of the endocrine pancreas
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