Effects of one-hour daily outdoor access on milk yield and composition and behaviors of tethered dairy cows.

Objective: We investigated the effects of outdoor access for one-hour per day (ODA) on milk yield and composition and behaviors of tethered dairy cows. Methods: Eleven all-day tethered dairy cows were treated the ODA for two weeks. To evaluate the effect of ODA on milk yield, we first calculated the average daily milk yield of each cow for three days during two weeks before the ODA, three days before the ODA, three days at the end of the ODA, and three days during two weeks after the ODA. We then compared the milk yield change during the ODA with that for two weeks before and two weeks after the ODA. The effects of ODA on milk compositions and behaviors were evaluated by comparing the average values for each composition and behavior for the three days before the ODA and the last three days of the ODA. Results: The decrease of milk yield during the two weeks of ODA was significantly higher than that during the two weeks before ODA (p<0.01). The milk fat rate was significantly higher during ODA than before ODA (p<0.05). Lactose rate was significantly lower during ODA than before ODA (p<0.05). The concentrations of milk urea nitrogen, ketone bodies, and free fatty acids in the milk were significantly higher during ODA than before ODA (p<0.05). The mean total duration per day of lying during ODA was significantly lower than that before ODA (p<0.05). The walking steps per one-hour outdoor access were 158.4 ± 54.7. The social behavior during the one-hour outdoor access of the 11 cows was 53 times/h/herd. . Conclusion: Our results suggested that ODA promotes the express of normal behavior in dairy cows, but even one hour of ODA decreases milk production in cows, which may drop producers' profits without some financial supplementation.

Prognostic Model of Baseline Medications plus Neutrophil-to-lymphocyte Ratio in Patients with Advanced Non-small-cell Lung Cancer Receiving Immune Checkpoint Inhibitor plus Platinum Doublet: A Multicenter Retrospective Study.

Background: Association between baseline medications plus neutrophil-to-lymphocyte ratio (NLR) and the effectiveness of immune checkpoint inhibitor (ICI) plus platinum doublet remains unknown, despite several reported prognostic models. We used real-world data to investigate whether baseline medications plus NLR predict survival outcomes in patients with advanced non-small-cell lung cancer (NSCLC) receiving ICI plus platinum doublet. Methods: This multicenter, retrospective, observational study conducted in Japan between December 2018 and March 2021 used real-world data of consecutive patients with advanced NSCLC who received ICI (pembrolizumab or atezolizumab) plus platinum doublet as first-line treatment. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The prognostic score for baseline medications plus NLR was weighted by regression ß coefficients and used to categorize patients into good, intermediate, and poor prognoses groups. In addition, time-dependent receiver operating characteristic curve analyses and univariable and multivariable Cox proportional hazards models were constructed. Results: Overall, 241 patients were included. Poor prognosis was significantly associated with worse PFS (hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.08-2.94; P = 0.025) and OS (HR: 3.59; 95% CI: 2.05-6.28; P < 0.001) than good prognosis. Harrell's C-index for this prognostic model was 0.648. Conclusions: Baseline medication plus NLR could predict progressively worse survival outcomes in patients with advanced NSCLC receiving ICI plus platinum doublet and could be used as a prognostic index for poor outcomes.

The Successful Treatment of Metastatic Extraosseous Ewing Sarcoma with Pazopanib.

The clinical efficacy and outcomes of pazopanib treatment for metastatic extraosseous Ewing sarcoma remain unclear. We herein report a case of heavily pre-treated metastatic extraosseous Ewing sarcoma in which pazopanib treatment achieved a significant improvement. A 17-year-old girl was referred to our hospital due to metastatic extraosseous Ewing sarcoma. The initial cytotoxic chemotherapy was temporarily effective, however, her disease eventually progressed, and she was subsequently treated with pazopanib. The recurrent tumor showed a marked response to pazopanib therapy; the therapeutic effect has lasted for more than 26 months. The present case suggests that pazopanib may be a therapeutic option for extraosseous Ewing sarcoma.

Negative regulation of cellular Ca2+ mobilization by ryanodine receptor type 3 in mouse mesenteric artery smooth muscle.

Physiological functions of type 3 ryanodine receptors (RyR3) in smooth muscle (SM) tissues are not well understood, in spite of their wide expression. However, the short isoform of RyR3 is known to be a dominant-negative variant (DN-RyR3), which may negatively regulate functions of both RyR2 and full-length (FL) RyR3 by forming hetero-tetramers. Here, functional roles of RyR3 in the regulation of Ca2+ signaling in mesenteric artery SM cells (MASMCs) were examined using RyR3 homozygous knockout mice (RyR3-/-). Quantitative PCR analyses suggested that the predominant RyR3 subtype in MASMs from wild-type mice (RyR3+/+) was DN-RyR3. In single MASMCs freshly isolated from RyR3-/-, the EC50 of caffeine to induce Ca2+ release was lower than that in RyR3+/+ myocytes. The amplitude and frequency of Ca2+ sparks and spontaneous transient outward currents in MASMCs from RyR3-/- were all larger than those from RyR3+/+. Importantly, mRNA and functional expressions of voltage-dependent Ca2+ channel and large-conductance Ca2+-activated K+ (BK) channel in MASMCs from RyR3-/- were identical to those from RyR3+/+. However, in the presence of BK channel inhibitor, paxilline, the pressure rises induced by BayK8644 in MA vascular beds of RyR3-/- were significantly larger than in those of RyR3+/+. This indicates that the negative feedback effects of BK channel activity on intracellular Ca2+ signaling was enhanced in RyR3-/-. Thus, RyR3, and, in fact, mainly DN-RyR3, via a complex with RyR2 suppresses Ca2+ release and indirectly regulated membrane potential by reducing BK channel activity in MASMCs and presumably can affect the regulation of intrinsic vascular tone.

Ryanodine receptor type 3 does not contribute to contractions in the mouse myometrium regardless of pregnancy.

Ryanodine receptor type 3 (RyR3) is expressed in myometrial smooth muscle cells (MSMCs). The short isoform of RyR3 is a dominant negative variant (DN-RyR3) and negatively regulates the functions of RyR2 and full-length (FL)-RyR3. DN-RyR3 has been suggested to function as a major RyR3 isoform in non-pregnant (NP) mouse MSMCs, and FL-RyR3 may also be upregulated during pregnancy (P). This increase in the FL-RyR3/DN-RyR3 ratio may contribute to the strong contractions by MSMCs for parturition. In the present study, spontaneous contractions by the myometrium in NP and P mice were highly susceptible to nifedipine but were not affected by ryanodine. Ca2+ image analyses under a voltage clamp revealed that the influx of Ca2+ through voltage-dependent Ca2+ channels did not cause the release of Ca2+ from the sarcoplasmic reticulum (SR). Cytosolic Ca2+ concentrations ([Ca2+]cyt) in MSMCs were not affected by caffeine. Despite the abundant expression of large conductance Ca2+-activated K+ channels in MSMCs, spontaneous transient outward currents were not observed in the resting state because of the substantive lack of Ca2+ sparks. Quantitative PCR and Western blot analyses indicated that DN-RyR3 was strongly expressed in the NP myometrium, while the expression of FL-RyR3 and DN-RyR3 was markedly reduced in the P myometrium. The messenger RNA (mRNA) expression of RyR2 and RyR1 was negligible in the NP and P myometria. Moreover, RyR3 knockout mice may become pregnant and deliver normally. Thus, we concluded that none of the RyR subtypes, including RyR3, play a significant role in the regulation of [Ca2+]cyt in or contractions by mouse MSMCs regardless of pregnancy.

Outcomes of the implementation of the computer-assisted HBView system for the prevention of hepatitis B virus reactivation in chemotherapy patients: a retrospective analysis.

BACKGROUND: Screening for hepatitis B virus (HBV) infection is recommended worldwide for patients receiving systemic chemotherapy in accordance with clinical guidelines, but compliance varies by country and facility. Alert systems may be useful for promoting screening, but it is unclear how effective such systems are. In this study, we investigated HBV screening procedures and their incorporation into treatment regimens following the implementation of an alert system. METHODS: An alert system was introduced at our hospital in April 2012. The rates of HBV screening in the periods before and after the introduction of the alert system (September 2010 to March 2012 and April 2012 to October 2013, respectively) were investigated. We collected data on hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), and HBV-DNA testing in patients. As a result of this analysis, we developed a system in which pharmacists would intervene to check and confirm whether HBV screening had occurred in patients scheduled to begin treatment with chemotherapy. We named our project the "HBView" project, and the rate of HBV screening and the number of times pharmacists intervened was studied during specific time periods before and after the HBView project commenced (July 2013 to December 2013 and January 2014 to June 2014, respectively). RESULTS: After introducing the alert system, the percentage of patients tested for HBsAb/HBcAb and HBV-DNA increased significantly, from 71.6 % to 84.9 % and from 44.5 % to 69.7 %, respectively. However, the rate of compliance with HBV testing guidelines was not 100 % after interventions. The numbers of patients who were not screened but should have been before and after the introduction of HBView were 6 and 17, respectively. Two patients at risk of HBV reactivation were identified after intervention by pharmacists; their intervention thus prevented HBV reactivation. CONCLUSIONS: Compliance with clinical HBV screening guidelines was not sufficiently improved after the introduction of the automatic alert system; however, the HBView project proved useful in reinforcing the automatic alert system.