Mitochondria transfer can enhance the murine embryo development

Purpose To evaluate the effect of mitochondrial transfer on embryonic development. Materials and methods Mitochondria concentrates were collected from murine hepatocytes and fertilized murine zygotes from young and older mice in the 2PN stage were subjected to mitochondrial transfer and cultured in vitro to evaluate the embryonic development. Results After extended in vitro culture, 37.65% and 20.91% embryos from the young mice developed to the blastocyst stage in the injected and control groups respectively, which is statistically significant. There was no difference in terms of hatching rates (1.76% and 1.82% respectively). Zygotes from the older mice (> 20 weeks old) that received mitochondrial transfer also had a better developmental outcome than the control group (54.35% and 18.92% developed to morula stage, 43.48% and 8.11% developed to the blastocyst stage respectively), which is statistically significant. Conclusions Our results for the murine model provide direct scientific evidence that mitochondrial transfer improves embryonic development. However, potential risks such as mitochondrial heteroplasmy, nuclear-mitochondrial interaction and epigenetic aspects all deserve further evaluation before mitochondrial transfer is applied clinically

Trajectory of functional outcome and health status after moderate-to-major trauma in Hong Kong: A prospective 5 year cohort study

Background Trauma care systems in Asia have been developing in recent years, but there has been little long-term outcome data from injured survivors. This study aims to evaluate the trajectory of functional outcome and health status up to five years after moderate to major trauma in Hong Kong. Methods We report the five year follow up results of a multicentre, prospective cohort from the trauma registries of three regional trauma centres in Hong Kong. The original cohort recruited 400 adult trauma patients with ISS ≥ 9. Telephone follow up was conducted longitudinally at seven time points, and the extended Glasgow Outcome Scale (GOSE) and Short-Form 36 (SF36) were tracked. Results 119 out of 309 surviving patients (39%) completed follow up after 5 years. The trajectory of GOSE, PCS and MCS showed gradual improvements over the seven time points. 56/119 (47.1%) patients reported a GOSE = 8 (upper good recovery), and the mean PCS and MCS was 47.8 (95% CI 45.8, 49.9) and 55.8 (95% CI 54.1, 57.5) respectively at five years. Univariate logistic regression showed change in PCS - baseline to 1 year and 1 year to 2 years, and change in MCS - baseline to 1 year were associated with GOSE = 8 at 5 years. Linear mixed effects model showed differences in PCS and MCS were greatest between 1-month and 6-month follow up. Conclusions After injury, the most rapid improvement in PCS and MCS occurred in the first six to 12 months, but further recovery was still evident for MCS in patients aged under 65 years for up to five years

Playing The Hypothesis Testing Minority Game In The Maximal Reduced Strategy Space

Hypothesis Testing Minority Game (HMG) is a variant of the standard Minority Game (MG) that models the inertial behavior of agents in the market. In the earlier study of our group, we find that agents cooperate better in HMG than in the standard MG when strategies are picked from the full strategy space. Here we continue to study the behavior of HMG when strategies are chosen from the maximal reduced strategy space. Surprisingly, we find that, unlike the standard MG, the level of cooperation in HMG depends strongly on the strategy space used. In addition, a novel intermittency dynamics is also observed in the minority choice time series in a certain parameter range in which the orderly phases are characterized by a variety of periodic dynamics. Remarkably, all these findings can be explained by the crowd-anticrowd theory.Comment: 12 pages, 7 figures, to appear in Physica

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

Prevalence and Correlates of PrEP Awareness and Use Among Black Men Who Have Sex with Men and Women (MSMW) in the United States

Men who have sex with men and women (MSMW), including those who are Black, experience HIV-related disparities compared to men who have sex with men only (MSMO). Few studies have assessed the prevalence and correlates of pre-exposure prophylaxis (PrEP) awareness and use among Black MSMW. We recruited MSM ≥ 18 attending Black Gay Pride events between 2014–2017. We conducted multivariable logistic regressions to assess differences in PrEP awareness and use among HIV-negative Black MSM (n = 2398) and within Black MSMW (n = 419). MSMW were less likely than MSMO to report PrEP awareness (p < 0.001). Among PrEP-aware MSM, MSMW were more likely than MSMO to report PrEP use (p < 0.05). MSMW receiving gay community support were more likely to be PrEP-aware (p < 0.01). MSMW reporting any past-year STI diagnoses were more likely to report PrEP use (p < 0.01). Findings suggest that PrEP awareness campaigns tailored for Black MSMW, concomitant with STI-to-PrEP interventions, will facilitate greater PrEP uptake in this population

Lack of Evidence for Human-to-Human Transmission of Avian Influenza A (H9N2) Viruses in Hong Kong, China 19991

In April 1999, isolation of avian influenza A (H9N2) viruses from humans was confirmed for the first time. H9N2 viruses were isolated from nasopharyngeal aspirate specimens collected from two children who were hospitalized with uncomplicated, febrile, upper respiratory tract illnesses in Hong Kong during March 1999. Novel influenza viruses have the potential to initiate global pandemics if they are sufficiently transmissible among humans. We conducted four retrospective cohort studies of persons exposed to these two H9N2 patients to assess whether human-to-human transmission of avian H9N2 viruses had occurred. No serologic evidence of H9N2 infection was found in family members or health-care workers who had close contact with the H9N2-infected children, suggesting that these H9N2 viruses were not easily transmitted from person to person

Towards good practice guidelines for the contour method of residual stress measurement

Accurate measurement of residual stress in metallic components using the contour method relies on the achievement of a good quality cut, on the appropriate measurement of the deformed cut surface and on the robust analysis of the measured data. There is currently no published standard or code of practice for the contour method. As a first step towards such a standard, this study draws on research investigations addressing the three main steps in the method: how best to cut the specimens; how to measure the deformation contour of the cut surface; and how to analyse the data. Good practice guidance is provided throughout the text accompanied by more detailed observations and advice tabulated in Appendi

In search of disorders: internalizing symptom networks in a large clinical sample.

Background The co‐occurrence of internalizing disorders is a common form of psychiatric comorbidity, raising questions about the boundaries between these diagnostic categories. We employ network psychometrics in order to: (a) determine whether internalizing symptoms cluster in a manner reflecting DSM diagnostic criteria, (b) gauge how distinct these diagnostic clusters are and (c) examine whether this network structure changes from childhood to early and then late adolescence. Method Symptom‐level data were obtained for service users in publicly funded mental health services in England between 2011 and 2015 (N = 37,162). A symptom network (i.e. Gaussian graphical model) was estimated, and a community detection algorithm was used to explore the clustering of symptoms. Results The estimated network was densely connected and characterized by a multitude of weak associations between symptoms. Six communities of symptoms were identified; however, they were weakly demarcated. Two of these communities corresponded to social phobia and panic disorder, and four did not clearly correspond with DSM diagnostic categories. The network structure was largely consistent by sex and across three age groups (8–11, 12–14 and 15–18 years). Symptom connectivity in the two older age groups was significantly greater compared to the youngest group and there were differences in centrality across the age groups, highlighting the age‐specific relevance of certain symptoms. Conclusions These findings clearly demonstrate the interconnected nature of internalizing symptoms, challenging the view that such pathology takes the form of distinct disorders

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

7th Drug hypersensitivity meeting: part two

No abstract availabl