Short communication: Effect of yeast cell wall supplementation on peripheral leukocyte populations and mRNA expression of cytokines in lactating dairy cows.

This study was designed to examine the effect of yeast cell wall (YCW) supplementation on peripheral leukocyte populations and mRNA expression of cytokines in lactating dairy cows. Fourteen Holstein lactating cows were assigned to 1 of 2 treatments; the control group (n = 7) were fed a total mixed ration without supplementation and cows in the YCW group (n = 7) were fed a total mixed ration supplemented with YCW (SafMannan; Phileo, Lesaffre Animal Care, Lille, France; 10 g/cow per day). Blood samples were collected 3 times during the experimental period [wk 0 (before any treatment), wk 4, and wk 8]. Peripheral leukocyte populations and cytokine mRNA expression of peripheral blood monocular cells were measured using flow cytometry and real-time PCR, respectively. Among the peripheral leukocyte populations, TcR1-N12 + and CD14+ T cells increased at wk 4, and CD4+ T cells and CD8+ T cells increased at wk 4 and wk 8 with YCW supplementation. The mRNA level of IL8 tended to be increased in the YCW group at wk 4. Expression of IL12A was lower in the YCW group than in the control group before the experiment (wk 0) but no differences were observed at later time points (wk 4 and wk 8). Expression of IL12A decreased in the control group and increased in the YCW group. Expression of CCR2 increased at wk 4, and CCL2 and CCL3 were increased at wk 8 in the YCW group. Thus, YCW supplementation increased the mRNA expression of cytokines in peripheral blood mononuclear cells of lactating dairy cows.

Effects of butyrate supplementation on blood glucagon-like peptide-2 concentration and gastrointestinal functions of lactating dairy cows fed diets differing in starch content.

The objective of this study was to evaluate effects of butyrate supplementation on plasma concentration of glucagon-like peptide-2 (GLP-2), apparent total-tract digestibility, and responses to a grain challenge of lactating dairy cows fed diets differing in starch content. Eight Holstein cows averaging 58.6 ± 9.96 d in milk (4 primiparous cows fitted with rumen cannula and 4 multiparous intact cows) were blocked by parity and assigned to one of two 4 × 4 Latin squares balanced for carryover effects with a 2 × 2 factorial arrangement of treatments. Treatments were dietary starch content [20.6 vs. 27.5%, respectively, for low starch (LS) and high starch (HS)] and butyrate supplementation (butyrate vs. control) with 21-d periods. Butyrate was provided as Gustor BP70 WS (Norel, S.A., Madrid, Spain), containing 70% sodium butyrate and 30% fatty acid mixture, at 2% of dietary dry matter (providing butyrate at 1.1% of dietary dry matter), and control premix contained 70% wheat bran and 30% fatty acid mixture. Feeds, orts, and fecal samples were collected from d 17 to 19 to determine apparent total-tract nutrient digestibility. Blood and rumen fluid samples were collected on d 19. The baseline of dry matter intake (DMI) was determined as average DMI from d 17 to 19 for each cow, and cows were feed-restricted at 60% of the baseline DMI on d 20, and a grain challenge was conducted by providing steam-flaked corn grain at 0.6% of body weight, on an as-fed basis, in addition to each treatment diet on d 21, and blood and ruminal fluid samples were collected. The interaction of dietary starch content by butyrate supplementation was significant for plasma GLP-2 concentration, being greater for cows fed butyrate with the HS diet than those fed the other 3 diets. Cows fed butyrate increased n-butyrate concentration in the ruminal fluid and tended to increase dry matter and organic matter digestibility compared with the control. During the grain challenge, rumen endotoxin concentration increased over time and was higher for cows fed the HS diets compared with those fed LS diets. However, response variables related to inflammation were not affected by the grain challenge. However, serum haptoglobin, lipopolysaccharide-binding protein, and serum amyloid-A concentrations were greater for cows fed butyrate with the LS diet, but not for those fed the HS diet. These results indicate that butyrate supplementation may increase plasma GLP-2 concentration for cows fed HS diets, and total-tract digestibility regardless of dietary starch content. However, butyrate supplementation did not mitigate inflammation in this study.

Short communication: Effects of butyrate supplementation on the productivity of lactating dairy cows fed diets differing in starch content.

The objective of this study was to evaluate the effects of butyrate supplementation on the dry matter intake (DMI), milk production, and blood metabolites of lactating dairy cows fed diets differing in starch content. Eight Holstein cows after peak lactation (58.6 ± 9.96 d in milk; mean ± SD) were blocked by parity and assigned to 1 of 2 Latin squares (4 × 4) balanced for carryover effects with a 2 × 2 factorial arrangement of treatments. Treatments differed by dietary starch content (20.6 vs. 27.5%) and butyrate supplementation (butyrate vs. control) with 21-d periods. Experimental diets contained 36 and 30% corn silage, 18 and 15% grass silage, and 46 and 55% concentrates, respectively, for low starch and high starch diets, on a dry matter (DM) basis. Butyrate was provided as Gustor BP70 WS (Norel S.A., Madrid, Spain), containing 70% sodium butyrate and 30% fatty acid mixture, at 2% of dietary DM (providing butyrate at 1.1% of dietary DM), and control premix contained 70% wheat bran and 30% fatty acid mixture. Interaction effects between dietary starch content and butyrate supplementation were not observed for primary response variables, and milk yield was not affected by treatment. Butyrate supplementation increased serum ß-hydroxybutyrate concentration compared with control (0.706 vs. 0.930 mM), but did not exceed 1.2 mM, a commonly accepted value for subclinical ketosis, and DMI was not affected. Cows fed butyrate had increased milk fat content (4.58 vs. 4.37%) and milk fat yield (1.51 vs. 1.42 kg/d), tended to have increased 4% fat-corrected milk yield (35.9 vs. 34.3 kg/d) and feed efficiency (1.56 vs. 1.50; 4% fat-corrected milk yield/DMI), and had decreased milk urea nitrogen (MUN) concentration (10.8 vs. 11.7 mg/dL) compared with control. Cows fed high starch diets tended to have increased DMI (23.3 vs. 22.5 kg/d), increased milk protein yield (1.13 vs. 1.05 kg/d), and decreased MUN concentration (10.3 vs. 12.2 mg/dL). Inclusion of butyrate at 1.1% of dietary DM increased milk fat production and decreased MUN concentration without affecting DMI or increasing the risk of subclinical ketosis, regardless of dietary starch content.

Prenatal profile of Pallister-Killian syndrome: Retrospective analysis of 114 pregnancies, literature review and approach to prenatal diagnosis.

Pallister-Killian syndrome (PKS) is a tissue limited mosaic disorder, characterized by variable degrees of neurodevelopmental delay and intellectual disability, typical craniofacial findings, skin pigmentation anomalies and multiple congenital malformations. The wide phenotypic spectrum of PKS in conjunction with the mosaic distribution of the i(12p) makes PKS an underdiagnosed disorder. Recognition of prenatal findings that should raise a suspicion of PKS is complicated by the fragmentation of data currently available in the literature and challenges in diagnosing a mosaic diagnosis on prenatal testing. Ultrasound anomalies, especially congenital diaphragmatic hernia, congenital heart defects, and rhizomelic limb shortening, have been related to PKS, but they are singularly not specific and are not present in all affected fetuses. We have combined prenatal data from 86 previously published reports and from our cohort of 114 PKS probands (retrospectively reviewed). Summarizing this data we have defined a prenatal growth profile and identified markers of perinatal outcome which collectively provide guidelines for early recognition of the distinctive prenatal profile and consideration of a diagnosis of PKS as well as for management and genetic counseling.

Effects of testosterone replacement therapy on metabolic syndrome among Japanese hypogonadal men: A subanalysis of a prospective randomised controlled trial (EARTH study).

We investigated the effects of testosterone replacement therapy (TRT) on metabolic factors among hypogonadal men with a metabolic syndrome. From the study population of the EARTH study, which was a randomised controlled study in Japan, 65 hypogonadal patients with a metabolic syndrome, comprising the TRT group (n = 32) and controls (n = 33), were included in this study analysis. The TRT group was administered 250 mg of testosterone enanthate as an intramuscular injection every 4 weeks for 12 months. Waist circumference, body mass index, body fat volume and blood pressure were measured in all patients at baseline and at 12 months. In addition, blood biochemical data, including total cholesterol, triglyceride (TG), HDL cholesterol, fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) levels, were also evaluated. Changes in these categories from baseline to 12 months were compared between the TRT and control groups, with significant differences observed in waist circumference, body fat percentage, FPG, TG and HbA1c levels. No significant differences were observed in other parameters. TRT for 1 year was associated with improvements in some metabolic factors among Japanese men with hypogonadism and metabolic syndrome.

A cluster randomized trial on the effect of a multifaceted intervention improved the technical quality of diabetes care by primary care physicians: The Japan Diabetes Outcome Intervention Trial-2 (J-DOIT2).

AIMS: To evaluate the effect of multifaceted interventions using the Achievable Benchmark of Care (ABC) method for improving the technical quality of diabetes care in primary care settings. METHODS: We conducted a 1-year cluster randomized controlled trial in 22 regions divided into an intervention group (IG) or control group (CG). Physicians in the IG received a monthly report of their care quality, with the top 10% quality of diabetes care scores for all physicians being the achievable benchmark. The change in quality-of-care scores between the IG and CG during follow-up was analysed using a generalized linear model considering clustering. RESULTS: A total of 2199 patients were included. Their mean (sd) age was 56.5 ± 5.9 years and the mean (sd) HbA1c level was 56.4 ± 13.3 mmol/mol (7.4 ± 1.2%). The quality-of-care score in the CG changed from 50.2%-point at baseline to 51%-point at 12 months, whereas the IG score changed from 49.9%-point to 69.6%-point, with statistically significant differences between the two groups during follow-up [the effect of intervention was 19.0%-point (95% confidence interval 16.7%- to 21.3%-point; P < 0.001)]. CONCLUSIONS: Multifaceted intervention, measuring quality-of-care indicators and providing feedback regarding the quality of diabetes care to physicians with ABC, was effective for improving the technical quality of care in patients with Type 2 diabetes in primary care settings. ( TRIAL REGISTRATION: umin.ac.jp/ctr as UMIN000002186).

High precision optical cavity length and width measurements using double modulation.

We use doubly phase modulated light to measure both the length and the linewidth of an optical resonator with high precision. The first modulation is at RF frequencies and is set near a multiple of the free spectral range, whereas the second modulation is at audio frequencies to eliminate offset errors at DC. The light in transmission or in reflection of the optical resonator is demodulated while sweeping the RF frequency over the optical resonance. We derive expressions for the demodulated power in transmission, and show that the zero crossings of the demodulated signal in transmission serve as a precise measure of the cavity linewidth at half maximum intensity. We demonstrate the technique on two resonant cavities, with lengths 16 m and a 4 km, and achieve an absolute length accuracy as low as 70 ppb. The cavity width for the 16 m cavity was determined with an accuracy of approximately 6000 ppm. Through an analysis of the systematic errors we show that this result could be substantially improved with the reduction of technical sources of uncertainty.

Cyclic mechanical pressure-loading alters epithelial homeostasis in a three-dimensional in vitro oral mucosa model: clinical implications for denture-wearers.

Denture-wearing affects the quality and quantity of epithelial cells in the underlying healthy oral mucosa. The physiologic mechanisms, however, are poorly understood. This study aimed to compare histologic changes and cellular responses of an epithelial cell layer to cyclic mechanical pressure-loading mimicking denture-wearing using an organotypic culture system to develop a three-dimensional in vitro oral mucosa model (3DOMM). Primary human oral keratinocytes and fibroblasts were serially grown in a monolayer culture, and cell viability was measured under continuous cyclic mechanical pressure (50 kPa) for 7 days (cycles of 60 min on, 20 s off to degas and inject air). Upon initiation of an air-liquid interface culture for epithelial stratification, the cyclic pressure, set to the mode above mentioned, was applied to the 3DOMMs for 7 days. Paraffin-embedded 3DOMMs were examined histologically and immunohistochemically. In the monolayer culture, the pressure did not affect the viability of oral keratinocytes or fibroblasts. Few histologic changes were observed in the epithelial layer of the control and pressure-loaded 3DOMMs. Immunohistochemical examination, however, revealed a significant decrease in Ki-67 labelling and an increase in filaggrin and involucrin expression in the suprabasal layer of the pressure-loaded 3DOMMs. Pressure-loading attenuated integrin ß1 expression and increased matrix metalloproteinase-9 activity. Incomplete deposition of laminin and type IV collagen beneath the basal cells was observed only in the pressure-loaded 3DOMM. Cyclic pressure-loading appeared to disrupt multiple functions of the basal cells in the 3DOMM, resulting in a predisposition towards terminal differentiation. Thus, denture-wearing could compromise oral epithelial homeostasis.

Effects of bethanechol chloride and distigmine bromide on postvoiding residual volume in patients with underactive bladder.

AIM: The efficacy of cholinergic drugs for reduction of post-voiding residual volume (PVR) in patients with underactive bladder is still controversial. This study was performed to examine whether cholinergic drugs have such an effect on PVR. METHODS: Patients with underactive bladder treated for more than two months with cholinergic drugs, which were later discontinued, were extracted retrospectively based on their charts. The changes in PVR, cholinesterase activity (ChE), renal function, and voiding function before and after discontinuation of cholinergic drugs were reviewed and analyzed. RESULTS: Twenty-nine patients were included in this study. In multiple linear regression analysis, the discontinuation of distigmine bromide (DB) was indicated as a significant covariate for PVR increase and ChE increase, while bethanechol chloride (BC) was not a significant covariate. The increase in ChE was significantly correlated with both PVR and voided volume after discontinuation of cholinergic drugs. CONCLUSION: DB could reduce PVR via a decrease in ChE. However, BC at doses up to 60 mg did not reduce PVR. DB may be recommended for the reduction of PVR in patients with underactive bladder.

Development of advanced photon calibrator for Kamioka gravitational wave detector (KAGRA).

The Kamioka Gravitational wave detector (KAGRA) cryogenic gravitational-wave observatory has commenced joint observations with the worldwide gravitational wave detector network. Precise calibration of the detector response is essential for accurately estimating parameters of gravitational wave sources. A photon calibrator is a crucial calibration tool used in laser interferometer gravitational-wave observatory, Virgo, and KAGRA, and it was utilized in joint observation 3 with GEO600 in Germany in April 2020. In this paper, KAGRA implemented three key enhancements: a high-power laser, a power stabilization system, and remote beam position control. KAGRA employs a 20 W laser divided into two beams that are injected onto the mirror surface. By utilizing a high-power laser, the response of the detector at kHz frequencies can be calibrated. To independently control the power of each laser beam, an optical follower servo was installed for power stabilization. The optical path of the photon calibrator's beam positions was controlled using pico-motors, allowing for the characterization of the detector's rotation response. Additionally, a telephoto camera and quadrant photodetectors were installed to monitor beam positions, and beam position control was implemented to optimize the mirror response. In this paper, we discuss the statistical errors associated with the measurement of relative power noise. We also address systematic errors related to the power calibration model of the photon calibrator and the simulation of elastic deformation effects using finite element analysis. Ultimately, we have successfully reduced the total systematic error from the photon calibrator to 2.0%.

Nerve growth factor derived from bronchial epithelium after chronic mite antigen exposure contributes to airway hyperresponsiveness by inducing hyperinnervation, and is inhibited by in vivo siRNA.

BACKGROUND: Bronchial asthma is a chronic allergic airway inflammatory disease. Neurotrophins, including nerve growth factor (NGF), play an important role in the pathogenesis of asthma. However, the effects of NGF derived from epithelium on airway hyperresponsiveness (AHR) after antigen sensitization/exposure remain uncertain. OBJECTIVE: In this study, we examined the role of NGF on AHR after chronic antigen exposure and the effect of inhibiting NGF by in vivo siRNA on AHR exacerbation. METHODS: We generated chronic mouse models of bronchial asthma using house-dust mite antigen (Dermatophagoides pteronyssinus; Dp). NGF concentrations in bronchoalveolar lavage fluid (BALF), lung histopathology, hyperresponsiveness, and related neuronal peptides and cytokines in supernatants of lung homogenates were determined. RESULTS: NGF in BALF was increased in a dose- and time-dependent manner, and was expressed primarily in bronchial epithelium. Nerve fibres and substance P-positive fibres were detected in subepithelium of Dp-sensitized and challenged mice over 4 weeks of mite antigen exposure. AHR was positively correlated with NGF concentration and nerve fibre innervation. AHR, modulation of innervation, and increased substance P were inhibited by in vivo administration of siRNA that targeted NGF, although the inhibition of NGF did not affect allergic inflammation and subepithelial fibrosis. CONCLUSION AND CLINICAL RELEVANCE: These findings suggest that NGF derived from bronchial and alveolar epithelium plays an important role in AHR after chronic exposure to mite antigen. NGF inhibition could potentially manage bronchial asthma, including AHR.