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This study was aimed to investigate the influence of verapamil-mediated inhibition of P-glycoprotein (P-gp) on the pharmacokinetics of ivermectin (IVM) given orally and subcutaneously (SC) to rabbits. Twenty New Zealand rabbits were allotted to 4 groups (n = 5) and received IVM either orally or SC (0.4 mg/kg) alone or co-administered with verapamil (2 mg/kg SC, 3 times at a 12-hr interval). Plasma, fecal, and urine samples were collected over 30 days after medication to assess IVM concentrations in these samples. No significant differences were observed in the pharmacokinetic parameters of IVM between oral and SC administrations. The area under the plasma concentration-time curve was higher (p less then .05) after IVM (oral)/verapamil treatment, compared with oral IVM alone. Moreover, the time to the Cmax of IVM was shorter (p less then .05), whereas the elimination half-life and the mean residence time were longer (p less then .05) in the presence of verapamil. The IVM/verapamil combination administered orally or SC reduced fecal IVM concentrations, compared with IVM alone. In conclusion, the significant changes by verapamil on the pharmacokinetics of IVM, likely due to the inhibition of a P-gp-mediated intestinal secretion, may change IVM's antinematodal activity.

Modern agricultural management approaches are often dependent on the application of chemicals, resulting in adverse impacts on human and environmental health. Therefore, for sustainable agriculture, there is a need to implement integrated agriculture practices that can maintain natural soil microbiome and enhance crop production. check details Various agricultural approaches influence crop production by impacting the functional bacterial community entailed in biogeochemical cycles, for example, nitrogen (N) cycle. This study aimed to assess the rhizospheric N cycling community of soybean under three agricultural practices, namely, conservation agriculture (CA), conventional treatment (CT), and organic agriculture (OA) for two consecutive years (2017 and 2018).

A field experiment was designed under soybean-wheat cropping system employing CA, CT, and OA modules that included different practices of tillage, crop bedding pattern, crop residue retention, and nutrient application. Assessment of bacterial communities contribu over the two consecutive years. The outcome revealed the mechanistic principle behind enhanced plant growth under conservation agriculture, and opened up the possibility of regulating the N cycling bacterial community to develop sustainable and productive agro-ecosystems. © 2020 Society of Chemical Industry.Multiple morphological abnormalities of the flagella (MMAF) is a genetically heterogeneous disorder leading to male infertility. Recent studies have revealed that DNAH17 variants are associated with MMAF, yet there is no functional evidence in support of their pathnogenicity. Here, we recruited two consanguineous families of Pakistani and Chinese origins, respectively, diagnosed with MMAF. Whole-exome sequencing identified novel homozygous DNAH17 variants, which led to loss of DNAH17 proteins, in the patients. Transmission electron microscope analyses revealed completely disorganized axonemal structure as the predominant anomaly and increased frequencies of missings of microtubule doublet(s) 4-7 in sperm flagella of patients. Similar to those found in patients, Dnah17-/- mice also displayed MMAF phenotype along with completely disorganized axonemal structures. Clusters of disorganized microtubules and outer dense fibers were observed in developing spermatids, indicating impaired sperm flagellar assembly. Besides, we also noticed many elongating spermatids with a deformed nuclear shape and abnormal step 16 spermatids that failed to spermiate, which subsequently underwent apoptosis in Dnah17-null mice. These findings present direct evidence establishing that DNAH17 is a MMAF-related gene in humans and mice, extend the clinical interpretations of DNAH17 variants, and highlight an essential and complex role of DNAH17 in spermatogenesis.Testosterone masculinizes male sexual behavior by providing organizational and activational effects during the perinatal and peripubertal periods and during adulthood, respectively. We revealed that the emission of ultrasonic vocalizations (USVs) and mounting behavior was regulated by different neural circuits. However, the detailed testosterone effects on these two behaviors have not been fully elucidated. Here, we evaluated the time-dependent effects of testosterone on USVs and mounting behavior in mice using a testosterone treatment model, in which females were treated with testosterone to assess the "gain-of-function" and a "loss-of-function" model. In the loss-of-function model, we used Ad4BP/SF-1ΔFLC/- male mice, in which testosterone production was abolished in prenatal and postnatal stages, and Ad4BP/SF-1ΔFLC/ΔFLC mice, in which testosterone production was markedly reduced only in prenatal stages. When testosterone was administered to female mice during the neonatal and peripubertal periods, but not during adulthood, USV emissions increased. Conversely, testosterone treatment in adult female mice increased the mounting behavior, but not USVs. In Ad4BP/SF-1ΔFLC/- mice, USVs and mounting behavior was completely absent. Ad4BP/SF-1ΔFLC/ΔFLC male mice displayed equivalent levels of USVs but less mounting behavior. Collectively, these results suggest that testosterone has dual regulatory roles in USV emissions and mounting behavior.

To investigate whether a radiomic MRI feature-based prediction model can differentiate oropharyngeal squamous cell carcinoma (SCC) according to the human papillomavirus (HPV) status.

Retrospective cohort study.

Pretreatment MRI data from 62 consecutive patients with oropharyngeal SCC were retrospectively reviewed, and chronologically allocated to training (n = 43) and test sets (n = 19). Enhancing tumors were semi-automatically segmented on each slice of the postcontrast T1WI to span the entire tumor volume, after registration of T2WI to postcontrast T1WI; 170 radiomic features were extracted from the entire tumor volume. Relevant features were selected and radiomics models were trained using least absolute shrinkage and selection operator (LASSO) logistic regression model with 10-fold cross-validation, after subsampling of training sets using synthetic minority over-sampling technique to mitigate data imbalance. The selected features, weighted by their respective coefficients, were combined linearly to yield a radiomics score.

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