Two lifestyle factors emerge as strongly associated with bacterial vaginosis: systemic contraceptives appear protective, whereas douching is linked to an increase in prevalence. The temporal relationship between douching and bacterial vaginosis needs further clarification.

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The reliability of classification of cerebral palsy (CP) in low‐birth weight children was assessed by using clinical and research study records sampled from population‐based cohort studies in the USA, the Netherlands, Canada, and Germany. Records of neurological examination findings and functional motor assessments were submitted to up to five pediatricians with expertize in CP diagnosis, who grouped children into categories referred to as‘disabling’CP,‘non‐disabling’CP, and no CP. Each study provided between 31 and 51 records of children assessed between 2 and 8 years of age, approximately equally divided among the three groupings. The discrimination between‘any CP’and‘no CP’was only fair (mean Kappa coefficients 0.37 to 0.69). However, when more detailed information describing motor function was used, children with‘disabling’CP could be distinguished, on the basis of records, from those without CP or with‘non‐disabling’CP with good to excellent reliability (mean Kappa coefficients 0.69 to 0.88). Because of the substantially higher agreement observed when these functional distinctions are made, we recommend that reports or comparisons of rates of CP should include levels of motor function of children with CP, and not simply total CP, among the outcomes of interest.

Background Delayed excretion of methotrexate can lead to life‐threatening toxicity that may result in treatment cessation, irreversible organ damage, and death. Various factors have been demonstrated to influence the pharmacokinetic process of methotrexate, including genetic and nongenetic factors. Methods We investigated the genetic factors primarily related to the metabolic pathway of methotrexate in children with acute lymphoblastic leukemia with delayed elimination, defined as C44‐48h ≥ 1.0μmol/L in this study. A total of 196 patients (delayed excretion group: 98; normal excretion group: 98) who received CCCG‐ALL‐2015 protocol after propensity score‐matched analysis were included in the study. Twenty‐eight target single‐nucleotide polymorphisms (SNPs) were analyzed by multiplex polymerase chain reaction and sequencing, and 25 SNPs were finally included in the study. Results The genotype distribution of SLCO1B1 rs2306283 SNP was different between the delayed and normal excretion groups. SLCO1B1 rs2306283 AA carriers had a significantly lower methotrexate C44‐48h/D ratio than GG carriers in both groups. Furthermore, compared with the normal excretion group, SLCO1B1 rs2306283 AG and GG were risk factors for developing oral mucositis (odds ratio [OR]: 2.13; 95% confidence interval [CI]: 1.11‐4.08; P < .001), hepatotoxicity (OR: 2.12; 95% CI: 1.26‐3.56; P < .001), and myelosuppression (OR: 1.21; 95% CI: 1.04‐1.41; P = .005) in delayed excretion group. Conclusions The results from this study indicate the potential role of SLCO1B1 rs2306283 as a pharmacogenomic marker to guide and optimize methotrexate treatment for delayed elimination in children with acute lymphoblastic leukemia.

BackgroundKoumine is an alkaloid monomer found abundantly in Gelsemium plants. It has been shown to reverse thermal hyperalgesia and mechanical allodynia induced by sciatic nerve chronic constriction injury (CCI) in rats in a dose-dependent manner. Interestingly, this effect is mediated by elevated allopregnanolone levels in the spinal cord (SC). Since 3α-hydroxysteroid oxidoreductase (3α-HSOR), the key synthetase of allopregnanolone, is responsible for allopregnanolone upregulation in the SC, the objective of the present study was to investigate the role of its expression in the SC in koumine-induced analgesia using a rat model of neuropathic pain following peripheral nerve injury.ResultsTime-course investigations of immunohistochemistry and real-time polymerase chain reaction revealed that the immunoreactivity and mRNA expression of 3α-HSOR markedly increased in a time-dependent manner in the SC of koumine-treated CCI rats. Furthermore, 3α-HSOR activity in the SC of koumine-treated CCI rats increased by 15.8% compared to the activity in untreated CCI rats. Intrathecal injection of medroxyprogesterone acetate, a selective 3α-HSOR inhibitor, reversed the analgesic effect of koumine on CCI-induced mechanical pain perception. Our results confirm that koumine alleviates neuropathic pain in rats with CCI by enhancing 3α-HSOR mRNA expression and bioactivity in the SC.ConclusionThis study demonstrates that 3α-HSOR is an important molecular target of koumine for alleviating neuropathic pain. Koumine may prove a promising compound for the development of novel analgesic agents effective against intractable neuropathic pain.

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