Mouse spermatogenic cells are known to contain at least two isoforms of cytoplasmic poly(A)-binding proteins, PABPC1 and PABPC2 (previously known as PABPT). In this study, we have characterized PABPC1 and PABPC2. PABPC2 was present in pachytene spermatocytes and round spermatids, whereas elongating spermatids still included PABPC1. These two proteins are capable of binding mRNA poly(A) tails nonspecifically and of directly associating with each other and with several translational regulators, including EIF4G1, PAIP1, PAIP2, and PIWIL1 (previously known as MIWI). Moreover, both PABPC1 and PABPC2 exhibited the ability to enhance translation of a reporter mRNA in vitro. Despite these similarities, PABPC2 was distinguished from PABPC1 by the absence of PABPC2 in actively translating polyribosomes of testicular cells. PABPC1 was distributed in polyribosomes and in translationally inactive messenger ribonucleoprotein particles. Most importantly, PABPC2 and PIWIL1 were noticeably enriched in the chromatoid body of round spermatids. These results suggest that PABPC2 may function in translational repression during spermatogenesis.

Introduction To investigate the efficacy and safety of trelagliptin 25 mg in patients with type 2 diabetes mellitus with severe renal impairment or end‐stage renal disease. Materials and Methods This multicenter, randomized, phase 3 study comprised a 12‐week double‐blind phase followed by a 40‐week open‐label phase. Patients had type 2 diabetes mellitus with severe renal impairment (creatinine clearance <30 mL/min) or end‐stage renal disease (undergoing hemodialysis), and were receiving diet and/or exercise therapy with/without one antidiabetic drug. Results Patients were randomized to trelagliptin (A/A, n = 55) or placebo (P/A, n = 52; double‐blind phase). Both groups received trelagliptin in the open‐label phase. The least square mean change (95% confidence interval [CI]) from baseline in hemoglobin A1c at the end of the double‐blind phase was −0.71% (95% CI −0.885, −0.542) and 0.01% (95% CI −0.170, 0.183) in the A/A and P/A groups, respectively (intergroup least square means difference −0.72%, 95% CI −0.966, −0.473; P < 0.0001). Mean hemoglobin A1c decreased after trelagliptin treatment in the P/A group to similar levels observed in the A/A group and remained comparable in both groups versus baseline up to week 52. In the double‐blind phase, the incidence of treatment‐emergent adverse events (TEAEs) was 72.7% and 61.5% in the A/A and P/A group, respectively; most TEAEs were mild‐to‐moderate, except in one patient (P/A group), who experienced two severe TEAEs. The incidence of serious TEAEs was 7.3% and 3.8% in the A/A and P/A group, respectively. Conclusions Once‐weekly trelagliptin 25 mg was efficacious, with no major safety concerns, and represents a meaningful treatment option in this patient population.

Doctors in any department should have at least minimum knowledge of Kampo medicines. However, doctors who specialize in neurology often have inadequate knowledge of Kampo medicines. The efficacy of Kampo medicines in treating intractable diseases such as neurodegenerative diseases is not adequately understood and needs to be investigated in the future. On the other hand, Kampo medicines are often effective for treating common symptoms such as headache, dysesthesia, pain, and vertigo, encountered in daily medical practice. Because many patients suffer from these symptoms, the impact of these symptoms on our society is not small, even though the causes of these symptoms are not crucial. Having the skill to prescribe even a dozen or so Kampo medicines (for example, goshuyuto, goreisan, goshajinkigan, sokeikakketsuto) increases the treatment options and may be very beneficial in daily medical practice. In this article, I provide instructions on the use of representative Kampo medicines and present some case reports to elucidate their use. Amassing and sharing clinical experiences regarding the use of Kampo medicines would strengthen the medical evidences of Kampo medicines.

Aim Several weeks of treatment with an antidepressive agent may be required before efficacy is demonstrated in patients with major depressive disorder. This study investigated the predictive value of early partial improvement with vortioxetine for treatment response and remission. Methods This was a post hoc analysis of an 8-week, randomized, double-blind, placebo-controlled, Phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20–75 years with recurrent major depressive disorder and a Montgomery–Åsberg Depression Rating Scale (MADRS) score of at least 26. The key outcomes were the predictive value of early partial improvement (reduction in MADRS total score of ≥20% from baseline to week 2) with vortioxetine for MADRS response (≥50% decrease in score from baseline) and remission (decrease in score to ≤10) at week 8. Results Relevant data were available for 478 patients; 62/158 patients receiving placebo, 71/162 receiving vortioxetine 10 mg, and 66/158 receiving vortioxetine 20 mg were early improvers. Early improvers receiving vortioxetine (10 mg or 20 mg) were more likely than non-early improvers to achieve a week 8 response (71.2–73.2% vs 29.7–38.0%) or remission (50.7–51.5% vs 17.4–18.7%). Positive predictive values for response and remission with vortioxetine were ~70% and ~50%, respectively; negative predictive values were ~70% and ~80%, respectively. Conclusion Improvement with vortioxetine may be predicted by early partial improvement in MADRS score. Some patients may benefit from longer-term treatment even without early improvement, another finding that may aid clinical decision-making. ClinicalTrials.gov registration for primary study: NCT02389816.

We aimed to explore the efficacy and safety of once‐weekly trelagliptin 100 mg as an add‐on therapy to insulin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control. Patients with haemoglobin A1c (HbA1c) 7.5% to 10.0% who were receiving 8 to 40 units of insulin per day were randomized to receive, with insulin, trelagliptin 100 mg (A/A, n = 116) or placebo (P/A, n = 124) for a 12‐week double‐blind (DB) phase, after which all received trelagliptin for a 40‐week open‐label phase. Primary endpoints were HbA1c change from baseline to the end of the DB phase and adverse events (AEs).HbA1c significantly decreased in the A/A group vs the P/A group at the end of the DB phase (least square mean difference, −0.63% [95% CI, −0.83 to −0.44]: P < .0001). The frequency of treatment‐emergent AEs during the DB phase was 44.0% in the A/A group and 47.6% in the P/A group. No patient experienced severe hypoglycaemia during trelagliptin treatment. Once‐weekly trelagliptin 100 mg therapy with insulin demonstrated a significant reduction in HbA1c. Long‐term treatment was well‐tolerated, with no clinically significant hypoglycaemia, suggesting that trelagliptin with insulin is a meaningful treatment option in this patient population.