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Abstract Hepatic graft‐versus‐host disease (HGVHD) contributes significantly to morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Clinical findings and liver biomarkers are neither sensitive nor specific. The relationship between clinical and histologic diagnoses of HGVHD was assessed premortem and at autopsy. Medical records from patients who underwent HSCT at the National Institutes of Health (NIH) Clinical Center between 2000 and 2012 and expired with autopsy were reviewed, and laboratory tests within 45 days of death were divided into 15‐day periods. Clinical diagnosis of HGVHD was based on Keystone Criteria or NIH Consensus Criteria, histologic diagnosis based on bile duct injury without significant inflammation, and exclusion of other potential etiologies. We included 37 patients, 17 of whom had a cholestatic pattern of liver injury and two had a mixed pattern. Fifteen were clinically diagnosed with HGVHD, two showed HGVHD on autopsy, and 13 had histologic evidence of other processes but no HGVHD. Biopsy or clinical diagnosis of GVHD of other organs during life did not correlate with HGVHD on autopsy. The diagnostic accuracy of the current criteria was poor (κ = −0.20). A logistic regression model accounting for dynamic changes included peak bilirubin 15 days before death, and an increase from period −30 (days 30 to 16 before death) to period −15 (15 days before death) showed an area under the receiver operating characteristic curve of 0.77. Infection was the immediate cause of death in 68% of patients. In conclusion, liver biomarkers at baseline and GVHD elsewhere are poor predictors of HGVHD on autopsy, and current clinical diagnostic criteria have unsatisfactory performance. Peak bilirubin and cholestatic injury predicted HGVHD on autopsy. A predictive model was developed accounting for changes over time. Further validation is needed.

Temozolomide (TMZ) can cross the blood‐brain barrier (BBB) and deliver methyl groups to the purine (guanine) bases of DNA, leading to mispairing during DNA replication and subsequent cell death. However, increased expression of the repair enzyme methyl guanine methyltransferase (MGMT), which removes methyl groups from purine bases, counteracts methylation by TMZ. We evaluated the anticancer potential of thymoquinone (TQ), a hydrophobic flavonoid that inhibits resistance and induces apoptosis in various cancer cells, both in vitro and in vivo. In vitro experiments showed that compared with the Hs683 and M059J cell lines, U251 cells were more sensitive to TMZ. Compared to U251 cells, U251R cells, a TMZ drug‐resistant strain established in this study, are characterized by increased expression of phosphorylated extracellular signal‐regulated kinase (p‐ERK) and MGMT. TQ treatments induced apoptosis in all cell lines. The p38 mitogen‐activated protein kinase signal pathway was mainly activated in U251 and U251R cells; however, p‐ERK and MGMT upregulation could not suppress TQ effects. Furthermore, si‐p38 pretreatment of U251R cells in TQ treatments inhibited cell apoptosis. We speculate that TQ contributed to the phosphorylation and activation of p38, but not of ERK‐induced apoptosis (irrespective of TMZ resistance). In vivo, U251R‐derived tumors subcutaneously inoculated in nude mice exhibited significant tumor volume reduction after TQ or TQ + TMZ cotreatments. High‐performance liquid chromatography assay confirmed the presence of TQ in murine brain tissues. Our findings demonstrate that TQ can effectively cross the BBB and function alone or in combination with TMZ to treat glioblastoma. [ABSTRACT FROM AUTHOR]

We conducted a cross-sectional study to investigate the associations between domestic pets and respiratory health in children. We randomly recruited 11,611 school children from Zhongshan, a southern city in China. Information about the respiratory symptoms and disease history of the recruited children, the status of domestic pets, and other related risk factors were collected from March to July 2016. We identified cat-keeping at home increases the risk of persistent cough (OR, 1.77; 95%CI, 1.03–3.05); poultry-keeping at home increases the risk of current asthma (OR, 3.87; 95%CI, 1.08–13.92) and allergic rhinitis (OR, 1.84; 95%CI, 1.01–3.37); sleeping with pets increases the risk of persistent phlegm (OR, 5.04; 95%CI, 1.05–24.28), doctor-diagnosed asthma (OR, 3.35; 95%CI, 1.31–8.57) and current asthma (OR, 4.94; 95%CI, 1.05–23.31) in children. Cat-keeping and molds on the wall of the house had the multiplicative and additive interaction in doctor-diagnosed asthma. In conclusion, pet-keeping increased the risk of respiratory symptoms in children. [ABSTRACT FROM AUTHOR]

Objective: To assess the influence of rs2910164 G/C single nucleotide polymorphism (SNP) of the miR-146a gene on its expression and susceptibility to gastric cancer., Methods: Fifty three gastric cancer patients and six gastric cancer cell lines were selected for determining the miR-146a expression by Taqman quantitative PCR. A model was constructed to assess the influence of miR-146a overexpression on the growth of AGS gastric cancer cells. A case-control study involving 417 gastric cancer patients and 420 cancer-free individuals was then conducted, and the allelic and genotypic frequencies of the rs2910164 G/C SNP were compared. The genotypes of all subjects were determined by using a Taqman allelic discrimination assay. A Taqman assay was also used to quantify mature and pri-miR-146a transcripts among 65 gastric cancer patients with known genotypes., Results: The expression of miR-146a was down-regulated among the 53 gastric cancer patients and six gastric cancer cell lines. Over-expression of miR-146a has suppressed the growth of gastric cancer by inhibiting the G1/S-phase transition of AGS cells. The case-control study showed that subjects with GC/CC genotypes had significantly lower risk for gastric cancer compared with those with GG genotype. In addition, miR-146a G/C SNP has significantly increased the level of mature miR-146a in those with GC/CC genotype compared with GG genotype., Conclusion: Down-regulation of miR-146a may play an important role in the pathogenesis of gastric cancer. The rs2910164 polymorphism of the miR-146a gene may reduce the risk of gastric cancer by influencing the processing of mature miR-146a.

Seasonal effects on post-partum ovarian activity, duration and intensity of sexual behaviour were determined for Holstein dairy cattle imported from a temperate climate into a tropical region. Animals were observed continuously during the cooler (temperature-humidity index (THI) < 25) and hotter (THI > 25) seasons for 2 years. They were restricted to a cement footing in the hotter season observation period in Year 1, but had access to both concrete and dirt footing during all other seasons. Sequential milk progesterone profiles provided an indication of when follicular phases occurred, and recorded sexual behaviour was compared with these to determine if oestrous signs accompanied ovulations. Most cows had normal ovarian cycles and ovulated regularly during both seasons, but quiet ovulations occurred with greater frequency during the hotter times of the year (P < 0.05). Demonstrations of sexual behaviour were affected by choice of footing rather than season. The actual time when cows stood passively and allowed herdmates to complete mounting ranged from 5.1 +/- 0.7 to 5.8 +/- 1 h with access to exercise yards and cement or dirt footing, but declined to only 1.3 +/- 1.1 h when animals were confined to cement (P < 0.05). Similarly, the total duration of oestrus and mean number of interactions were significantly (P < 0.05) reduced during the observation period conducted with cows confined to concrete footing. These findings further emphasize that the duration of oestrus in dairy cows in considerably shorter than the commonly quoted 18 h.