Non-genetic effects and repeatability estimates of semen production traits in Murrah buffalo bulls.

The objectives of this study were to determine the repeatability estimates and the effect of ejaculate, season, period, age, and bull on semen production traits in Murrah buffalo bulls maintained in an organized semen station. A data set comprising 54,268 ejaculates from 76 Murrah buffalo bulls collected across 12 years were analyzed. The analysis of variables included non-genetic factors as the fixed effects and bull as the random effect. The repeatability was estimated by the restricted maximum likelihood method (REML) using WOMBAT program. The overall least-squares means for semen volume, sperm concentration, total sperm/ejaculate, mass activity, individual motility, post-thaw motility, and frozen semen straws/ejaculate were 2.65 ml, 1222.04 million/ml, 3030.10 million, 2.64, 67.45%, 51.73%, and 128.80 doses. The repeatability estimates were 0.27, 0.25, 0.22, 0.28, 0.34, 0.27, and 0.23, respectively. The studied non-genetic factors influenced (P < 0.01) all seminal traits. Likewise, variation (P < 0.01) due to individual bull was also observed. The first ejaculate was superior in terms of ejaculate volume, sperm concentration, total sperm/ejaculate, and frozen semen straws than the second ejaculate. The south-west monsoon and summer seasons were the best seasons with better semen quality and frozen semen production. Compared to the remaining periods, during Period V (2014-2016), greater values for most seminal traits were found. Bulls above 8 years of age expressed higher semen production than the younger bulls below 4 years, whereas the best performance was observed in the age group of 12 years and above. The repeatability estimates were low to moderate ranging from 0.22 for total sperm/ejaculate to 0.34 for individual motility. A significant (P < 0.01) positive correlation was observed between the seminal traits except the negative correlation in semen volume and total sperm/ejaculate. It was concluded that all the non-genetic factors considered in this study exerted influence on studied seminal traits. Therefore, appropriate management practices can be applied to improve semen quality and quantity.

Supplementation of the diets with hydroponic maize fodder affects digestibility, puberty, sexual behavior, and semen characteristics in buck kids.

Hydroponics is one of the widely adopted technologies for fodder production in arid and semi-arid regions. In addition to the benefits such as shorter growth period and minimal water and land use, it also produces nutritious fodder that contains essential nutrients required for the growth and reproduction of livestock. This study was conducted to evaluate the effect of feeding hydroponic maize fodder on the reproductive performance of buck kids. Twenty-four Tellicherry buck kids aged around 3 months were randomly selected and allocated into three treatment groups, namely, control, treatment 1 (T1), and treatment 2 (T2). Experimental diets were formulated by replacing the concentrate with hydroponic maize fodder at 0% (control), 25% (T1), and 50% (T2) level. The buck kids supplemented with hydroponic maize fodder attained puberty earlier (T1, 246.50 ± 2.61 days; T2, 241.00 ± 2.06 days) (P < 0.05); had higher (P < 0.05) scrotal circumference, testicular volume, and fresh semen characteristics; and exhibited intense sexual behaviors than the non-supplemented kids. Furthermore, hydroponic maize fodder supplementation improved the digestibility of dry matter (DM) (P < 0.01), organic matter (OM) (P < 0.01), crude fiber (CF) (P < 0.05), ether extract (EE) (P < 0.01), and nitrogen-free extract (NFE) (P < 0.01) in the kids. In conclusion, hydroponic maize fodder feeding did not have any negative impact on the reproductive performance of kids. Furthermore, the hydroponic maize fodder supplementation enhanced the kids' nutrient digestibility and reproductive performance.

Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma.

BACKGROUND: Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. METHODS: Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers. RESULTS: In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47-0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65-1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13-0.70). CONCLUSIONS: SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS. CLINICAL TRIAL REGISTRATION: ISRCTN71070888; ClinialTrials.gov (NCT03529175).

Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer.

OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry. Functional and preclinical experiments, as well as expression analysis of stromal markers and gemcitabine metabolism pathways were performed in murine and human specimen to investigate the preclinical implications and the mechanism of gemcitabine accumulation. RESULTS: Gemcitabine accumulation was significantly enhanced in fibroblast-rich tumours compared with liver metastases and normal liver. In vitro, significantly increased concentrations of activated 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) and greatly reduced amounts of the inactive gemcitabine metabolite 2',2'-difluorodeoxyuridine were detected in PSCs and CAFs. Mechanistically, key metabolic enzymes involved in gemcitabine inactivation such as hydrolytic cytosolic 5'-nucleotidases (Nt5c1A, Nt5c3) were expressed at low levels in CAFs in vitro and in vivo, and recombinant expression of Nt5c1A resulted in decreased intracellular dFdCTP concentrations in vitro. Moreover, gemcitabine treatment in KPC mice reduced the number of liver metastases by >50%. CONCLUSIONS: Our findings suggest that fibroblast drug scavenging may contribute to the clinical failure of gemcitabine in desmoplastic PDAC. Metabolic targeting of CAFs may thus be a promising strategy to enhance the antiproliferative effects of gemcitabine.

Defect nonunion of a metatarsal bone fracture in a cow: successful management with bone plating and autogenous cancellous bone graft.

A two-and-half-year-old cow was presented with a defect nonunion of the right metatarsal III/IV bone following a severely comminuted open fracture two months previously. The animal underwent open fixation using a 4.5 mm, broad, 10-hole, dynamic compression plate and autogenous cancellous bone graft collected from the contralateral iliac shaft. The animal started partial weight bearing after the third postoperative day and resumed complete weight bearing after the 10th day. Fracture healing was complete and the implants were removed after the 120th postoperative day. Stable fixation by means of a bone plate in conjunction with a cancellous bone graft facilitated complete healing and restoration of the bone column of the defect and the metatarsal fracture. The animal made a complete recovery.

Cylindrical luminescent solar concentrators with near-infrared quantum dots.

We investigate the performance of cylindrical luminescent solar concentrators (CLSCs) with near-infrared lead sulfide quantum dots (QDs) in the active region. We fabricate solid and hollow cylinders from a composite of QDs in polymethylmethacrylate, prepared by radical polymerization, and characterize sample homogeneity and optical properties using spectroscopic techniques. We additionally measure photo-stability and photocurrent outputs under both laboratory and external ambient conditions. The experimental results are in good agreement with theoretical calculations which demonstrate that the hollow CLSCs have higher absorption of incident radiation and lower self-absorption compared to solid cylindrical and planar geometries with similar geometric factors, resulting in a higher optical efficiency.

Modeling the formation of in vitro filopodia.

Filopodia are bundles of actin filaments that extend out ahead of the leading edge of a crawling cell to probe its upcoming environment. In vitro experiments (Vignjevic et al. in J Cell Biol 160:951-962, 2003) have determined the minimal ingredients required for the formation of filopodia from the dendritic-like morphology of the leading edge. We model these experiments using kinetic aggregation equations for the density of growing bundle tips. In mean field, we determine the bundle size distribution to be broad for bundle sizes smaller than a characteristic bundle size above which the distribution decays exponentially. Two-dimensional simulations incorporating both bundling and cross-linking measure a bundle size distribution that agrees qualitatively with mean field. The simulations also demonstrate a nonmonotonicity in the radial extent of the dendritic region as a function of capping protein concentration, as was observed in experiments, due to the interplay between percolation and the ratcheting of growing filaments off a spherical obstacle.

Evaluation of a nested PCR targeting IS6110 of Mycobacterium tuberculosis for detection of the organism in the leukocyte fraction of blood samples.

PURPOSE: Tuberculosis poses a serious health problem in resource-poor settings such as India. Polymerase chain reaction (PCR) is presently seen as a promising alternative to conventional smear microscopy and culture techniques. Undiagnosed fever is a condition where the aetiology could include tuberculosis in a significant percentage. This paper evaluates a nested PCR (nPCR) using Hotstar Taq for the detection of M. tuberculosis in patients with febrile illness using insertion element, IS6110 as a target. MATERIAL AND METHODS: A total of 355 samples (301 HIV status unknown and 54 HIV seropositives) from patients primarily with febrile illness were tested for the presence of M. tuberculosis. Blood culture was done in a commercial automated blood culture system and nPCR in DNA extracts from buffy coat samples. Hotstar Taq polymerase was used to enhance the sensitivity of nPCR and the lower limit of detection was determined by using cloned plasmid. RESULTS: Among the patients tested, 2% were positive by automated culture system and 6.8% of patients were positive by nPCR. Majority of the positives were from HIV seropositive individuals. The sensitivity of the nPCR was 100% and the specificity was 95.1%. The lower limit of detection was less than 1 genome copy per microlitre. Among the nPCR positives, patients from rural community were significantly higher than from the peri-urban community. CONCLUSIONS: The nPCR had a high sensitivity and specificity on buffy coat samples using Hotstar Taq polymerase in the reaction mix. Thus the technique is a valuable tool in the diagnosis of tuberculosis.

Effects of epidural ketamine-xylazine combination on the clinicophysiological and haematobiochemical parameters of uraemic and healthy goats.

Xylazine-ketamine combination was evaluated for its efficacy and safety after epidural administration in uraemic and healthy goats. The combination (xylazine 0.025 mg/kg and ketamine 2.5 mg/kg) was administered to uraemic (n = 6) and healthy (n = 6) animals in the lumbosacral epidural space. The combination was evaluated in terms of clinical, physiological, haematological and biochemical parameters. The onset of analgesia was faster in healthy animals than in uraemic animals. Xylazine and ketamine produced complete analgesia of tail, perineum, inguinal and thigh regions in all animals of both groups. However, healthy animals showed longer duration of complete analgesia than did uraemic animals. Greater ataxia was recorded in healthy animals than in uraemic animals. The heart rate showed a significant decrease in both groups; however, respiratory rate and rectal temperature did not show any significant changes. Haemoglobin, packed cell volume and total leukocyte count decreased non-significantly in both groups. Total leukocyte count was significantly higher in uraemic animals. A significantly higher value of urea nitrogen and creatinine was recorded in uraemic animals. The blood electrolytes (Na+, K+ and Cl-) and blood gases (PO2 and PCO2) did not show any significant changes in both groups; however, base excess was significantly higher in uraemic animals. The effects produced by the combination on different systems were transient and values normal as the effect of the drugs wore off. The results suggest that the combination when used epidurally in uraemic goats produced effective and safe surgical analgesia.