BACKGROUND Clodronate is a non-nitrogenated bisphosphonate approved for use in horses. There are no peer-reviewed published reports describing the pharmacokinetics or evaluating renal health indices and urinary excretion patterns in conjunction with plasma and synovial fluid concentration following the systemic administration of clodronate to horses. OBJECTIVES Describe clodronate concentrations in plasma, urine and synovial fluid and evaluate the effects on renal indices after intramuscular administration to healthy horses. STUDY DESIGN Experimental study with repeated measures. METHODS Six healthy adult horses received a single intramuscular dose of clodronate (1.8 mg/kg). Blood, synovial fluid and urine were collected prior to and after administration of clodronate up to 72, 48 and 168 hours respectively. Drug concentrations were measured using LC-MS/MS and noncompartmental pharmacokinetic analysis was performed. Renal function indices were also evaluated. RESULTS Clodronate was quantifiable for up to 24 hf clodronate, values were never above the normal reference range. Further studies are warranted in horses undergoing exercise and those undergoing multiple dosing schemes. © 2020 EVJ Ltd.The Family Adaptability and Cohesion Scale IV (FACES-IV) was developed to capture the balanced and unbalanced levels of cohesion and flexibility in families. Although this measure has been shown to be valid and reliable, its length at 62 items limits utility and uptake in clinical and research settings. This paper details the development of a shorter form of the FACES-IV (the FACES-IV Short Form) using two studies. In the first study, three item-level analyses were used to identify 24 items that provided the best measurement of each of the scales of the FACES-IV. In the second study, the reliability, and convergent and divergent validity of the short form was tested. Results suggest that the FACES-IV-SF is a valid and reliable measure that adheres to the theory underlying the original FACES-IV but may be better utilized in clinical and research settings due to its brevity. © 2020 American Association for Marriage and Family Therapy.Mandibular mobility accompanying gape change in Northern and Antarctic minke whales was investigated by manipulating jaws of carcasses, recording jaw movements via digital instruments (inclinometers, accelerometers, and goniometers), and examining osteological and soft tissue movements via computed tomography (CT)-scans. We investigated longitudinal (α) rotation of the mandible and mediolateral displacement at the symphysis (Ω1 ) and temporomandibular joint (Ω2 ) as the mouth opened (Δ). Results indicated three phases of jaw opening. In the first phase, as gape increased from zero to 8°, there was slight ( less then 1°) α and Ω rotation. As gape increased between 20 and 30°, the mandibles rotated slightly laterally (Mean 3°), the posterior condyles were slightly medially displaced (Mean 4°), and the anterior ends at the symphysis were laterally displaced (Mean 3°). In the third phase of jaw opening, from 30° to full (≥90°) gape, these motions reversed mandibles rotated medially (Mean 29°), condyles were laterally displaced (Mean 14°), and symphyseal ends were medially displaced (Mean 1°). Movements were observed during jaw manipulation and analyzed with CT-images that confirmed quantitative inclinometer/accelerometer data, including the unstable intermediate (Phase 2) position. Together these shifting movements maintain a constant distance for adductor muscles stretched between the skull's temporal fossa and mandible's coronoid process. Mandibular rotation enlarges the buccal cavity's volume as much as 36%, likely to improve prey capture in rorqual lunge feeding; it may strengthen and stabilize jaw opening or closure, perhaps via a simple locking or unlocking mechanism. Rotated lips may brace baleen racks during filtration. Mandibular movements may serve a proprioceptive mechanosensory function, perhaps via the symphyseal organ, to guide prey engulfment and water expulsion for filtration. © 2020 Wiley Periodicals, Inc.Pyrazoline-linked carboxamide derivatives were designed, synthesized, and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer activity, and apoptotic and cardiomyopathy toxicity. Compounds 6m and 6n inhibit EGFR kinase at a concentration of 6.5 ± 2.91 and 3.65 ± 0.54 µM, respectively. Some of these compounds showed effects on proliferation, which were also then evaluated against four different human cancer cell lines, that is, MCF-7 (breast cancer), A549 (non-small-cell lung tumor), HCT-116 (colon cancer), and SiHa cells (cancerous tissues of the cervix uteri). The results showed that certain synthetic compounds showed significant inhibitor activity; compounds 6m and 6n were more cytotoxic than doxorubicin against A549 cancer cells, with IC50 values of 10.3 ± 1.07 and 4.6 ± 0.57 µM, respectively. Additionally, compounds 6m and 6n induced apoptosis in A549 cancer cells, as evidenced by 4',6-diamidino-2-phenylindole (DAPI) staining and phase-contrast microscopy. Potency to induce apoptosis by compound 6n was further confirmed by fluorescence-activated cell sorting using Annexin V-FITC and propidium iodide labeling. Compound 6n showed normal cardiomyocytes with no marked sign of pyknotic nuclei in cardiomyopathy and also normal histological appearance of the renal cortex when compared with that of control. Results of molecular docking studies suggested that compounds 6m and 6n can bind to the hinge region of the adenosine triphosphate-binding site of EGFR kinase, like the standard drug erlotinib. Therefore, the present study suggests that compounds 6m and 6n have potent in vitro antitumor activities against the human non-small-cell lung tumor cell line A549, which can be further explored in other cancer cell lines and in animal studies. © 2020 Deutsche Pharmazeutische Gesellschaft.NEW FINDINGS What is the central question of this study? Are sex-difference in the central airways present in healthy paediatric patients. What is the main finding and its importance? In patients ≤12 years we found no sex-differences in central airway luminal area. After 14 years, the males had significantly larger central airway luminal areas than the females.  https://www.selleckchem.com/products/choline-hydroxide.html  The sex-differences were minimized, but preserved when correcting for height. Luminal area is the main determinant of airway resistance and our finding could help explain sex-differences in pulmonary system limitations to exercise in paediatric patients. ABSTRACT Cross-sectional airway area is the main determinant of resistance to airflow in the respiratory system. In paediatric patients ( 0.05). However, in patients greater than age ≥14 yr the cross-sectional areas were larger in the males compared to females in most airway sites. For instance, the cross-sectional size of the trachea was 25% (218± 44 vs. 163±24 mm2 , P  less then  0.01) larger in males vs.