Pughschou0136

Mutations at sites crucial for the interaction between RAD51 and BRC domains impair the ability of BRCA2 homologous recombination. We aimed to clarify whether BRCA2 BRC domain-associated mutation correlates with sensibility of platinum-based chemotherapy and survival in high-grade serous ovarian cancer (HGSOC).

We identified BRCA2 BRC domain mutations by sequencing PCR-amplified amplicons of genomic DNA isolated from tumor tissues and peripheral blood leukocytes (PBL)in 113 patients with advanced EOC, and assessed platinum-free interval (PFI), progression-free survival (PFS) and overall survival (OS).

21.23% (24 of 113) cases with somatic missense mutation but not germline mutation were identified. Among 24 cases with mutation, 33.3% (8 of 24) cases with nonsense mutation (C-terminal truncation) significantly prolonged median PFI (37 vs 8 months,P=0.000), PFS (43 vs 14 months, p=0.000) and OS (56 vs 31 months, P=0.002); 66.7% (16 of 24) cases with missense mutation also prolonged median PFI (15 vs 8 months, P=0.044), PFS (21 vs 14 months, P=0.049) and OS (38 vs 31 months, P=0.037), compared to those without any mutation.

Somatic mutations in BRCA2 BRC domain confer a higher sensitivity to platinum-based therapy and are associated with a favourable survival in HGSOC.

Somatic mutations in BRCA2 BRC domain confer a higher sensitivity to platinum-based therapy and are associated with a favourable survival in HGSOC.

To confirm that WHO weight-for-length Z-scores (zWFL) and WHO body mass index Z-scores (zBMI) in infancy are associated with adiposity and cardiometabolic measures at 8-10 years old and to compare the predictive ability of the two methods.

WFL and BMI Z-scores at 6, 12, and 18 months of age were computed using data extracted from health booklets, among participants in the Quebec Adipose and Lifestyle InvesTigation in Youth prospective cohort (n = 464). Outcome measures at 8-10 years included adiposity, lipid profile, blood pressure, and insulin dynamics. The relationships between zWFL, zBMI and each outcome were estimated using multivariable linear regression models. Outcome prediction at 8-10 years was compared between the two methods using eta-squared and the Lin concordance correlation.

zWFL and zBMI were associated with all measures of adiposity at 8-10 years. Associations with other cardiometabolic measures were less consistent. For both zWFL and zBMI across infancy, eta-squared were highly similar and the Lin coefficients were markedly high (> 0.991) for all outcomes.

There was no evidence that zBMI and zWFL in infancy differed in their ability to predict adiposity and cardiometabolic measures in childhood. This lends support to the sole use of zBMI for growth monitoring and screening of overweight and obesity from birth to 18 years.

There was no evidence that zBMI and zWFL in infancy differed in their ability to predict adiposity and cardiometabolic measures in childhood. This lends support to the sole use of zBMI for growth monitoring and screening of overweight and obesity from birth to 18 years.King Cobra (Ophiophagus hannah) bite is well-known for its potentially fatal neurotoxicity. However, fatalities still occur, despite specific antivenom and respiratory support. Cardiovascular disturbances, which have attracted little attention in published reports of O. hannah envenoming, could contribute to fatality. We present two cases of confirmed O. hannah envenoming in Southern Vietnam in which there were cardiac abnormalities including arrhythmias and electrocardiographic changes, as well as elevated markers of myocardial damage. Cardiac pacing was required. One patient developed critical multi-organ dysfunctions partly explained by extensive necrotizing fasciitis/myositis originating from an Aeromonas sobria wound infection. This resulted in rhabdomyolysis, disseminated intravascular coagulation and acute kidney injury. Specific antivenom reversed neurotoxic effects of envenoming. Additional therapeutic interventions included antibiotics, surgical debridement, continuous renal replacement therapy and therapeutic plasma exchange. Both patients eventually made full recoveries. Apart from the critical problem of rapidly evolving and severe neurotoxicity, our case reports also emphasises the risk of cardiotoxic envenoming, and the complications of an overwhelming secondary bacterial wound infection. Selleck ALK inhibitor We suggest a practical approach to diagnosis and management.There is currently no data regarding the toxicity or the in vivo effects of the venom the Aegaeobuthus nigrocinctus species, since it has not been studied thus far according to the best of our knowledge. In the present study, and for the first time, the median lethal dose, the in vivo toxic effects, the histological changes in some of the vital organs were all determined as well as an assessment was made of the histological, biochemical and haematological changes which were caused by the venom injected in mice. The median lethal dose (LD50) of the scorpion venom for mice was found to be 0.38 mg/kg in terms of body weight. The results of the study show that the A. nigrocintus is a potentially lethal scorpion. The evidence related to the venom indicated that it could cause tissue injury in some vital organs. In conclusion, this scorpion venom could cause significant medical complications, and may lead to death, regarding at-risk patients. Therefore, health professionals should be aware of the various scorpion species in their regions and should follow current medical approaches concerning scorpion envenomation.Synthetic opioids have been implicated as the single greatest contributor to rising drug-related fatalities in recent years. This study evaluated mu-opioid receptor (MOR) mediated effects of seven fentanyl-related substances that have emerged in the recreational drug marketplace, and for which there are no existing or only limited in vivo data. Adult male Swiss Webster mice were administered fentanyl-related substances and their effects on nociception and locomotion as compared to MOR agonist standards were observed. In locomotor activity tests, morphine (100, 180 mg/kg), fentanyl (1, 10 mg/kg), beta-methylfentanyl (10 mg/kg), para-methoxyfentanyl (10 mg/kg), fentanyl carbamate (100 mg/kg), and 3-furanylfentanyl (10 mg/kg), elicited significant (p ≤ 0.05) dose-dependent increases in locomotion. However, para-methylfentanyl and beta'-phenylfentanyl did not produce significant effects on locomotion at doses up to 100 mg/kg and phenylfentanyl (100 mg/kg) significantly decreased locomotion. In warm-water tail-withdrawal tests, all substances produced significant dose-dependent increases in antinociception with increasing ED50 values (95% CI) of fentanyl [0.