Linezolid Pharmacokinetics and Its Association with Adverse Drug Reactions in Patients with Drug-Resistant Pulmonary Tuberculosis.

We evaluated the relationship between the pharmacokinetic parameters of linezolid (LZD) and development of adverse drug reactions (ADRs) in patients with pulmonary drug-resistant tuberculosis. A prospective cohort of adults with pulmonary multidrug-resistant tuberculosis with additional resistance to fluoroquinolone (MDR-TBFQ+) received treatment with bedaquiline, delamanid, clofazimine, and LZD. Blood samples were collected during weeks 8 and 16 at eight time points over 24 h. The pharmacokinetic parameters of LZD were measured using high-performance liquid chromatography and associated with ADRs. Of the 165 MDR-TBFQ+ patients on treatment, 78 patients developed LZD-associated anemia and 69 developed peripheral neuropathy. Twenty-three patients underwent intense pharmacokinetic testing. Plasma median trough concentration was 2.08 µg/mL and 3.41 µg/mL, (normal <2 µg/mL) and AUC0-24 was 184.5 µg/h/mL and 240.5 µg/h/mL at weeks 8 and 16, respectively, showing a linear relationship between duration of intake and plasma levels. Nineteen patients showed LZD-associated ADRs-nine at week 8, twelve at week 16, and two at both weeks 8 and 16. Thirteen of the nineteen had high plasma trough and peak concentrations of LZD. A strong association between LZD-associated ADRs and plasma LZD levels was noted. Trough concentration alone or combinations of trough with peak levels are potential targets for therapeutic drug monitoring.

Metabolomics-a powerful tool in livestock research.

Advancements in the Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) along with recent developments in omics sciences have resulted in a better understanding of molecular mechanisms and pathways associated with the physio-pathological state of the animal. Metabolomics is a post-genomics tool that deals with small molecular metabolites in a given set of time which provides clear information about the status of an organism. Recently many researchers mainly focus their research on metabolomics studies due to its valuable information in the various fields of livestock management and precision dairying. The main aim of the present review is to provide an insight into the current research output from different sources and application of metabolomics in various areas of livestock including nutri-metabolomics, disease diagnosis advancements, reproductive disorders, pharmaco-metabolomics, genomics studies, and dairy production studies. The present review would be helpful in understanding the metabolomics methodologies and use of livestock metabolomics in various areas in a brief way.

Perioperative outcomes in dogs and cats undergoing pancreatic surgery: 81 cases (2008-2019).

OBJECTIVES: To identify and describe the type and frequency of perioperative factors in dogs and cats undergoing pancreatic surgery under referral care. METHODS: Medical records from a small animal surgical referral practice were retrospectively reviewed to identify dogs and cats that underwent pancreatic surgery between 2008 and 2019. Inclusion criteria included complete medical record, histopathology results and follow-up of at least 14 days postoperatively or until death. Variables collected included signalment, history, presenting complaint, preoperative diagnostic results, intraoperative complications, surgical findings/procedures, postoperative complications and histopathology results. Cases were excluded if pertinent information or a histopathology report was missing from the medical record. The frequency of these variables was reported. RESULTS: There were 81 client-owned animals identified that met the inclusion criteria (57 dogs and 24 cats). The most common pancreatic procedure performed in dogs was partial pancreatectomy 63.2% (36/57) and in cats was pancreatic biopsy 62.5% (15/24). The most common histologic diagnosis in dogs was pancreatic islet cell carcinoma 50.9% (29/57) and in cats was pancreatitis 41.7% (10/24). The overall mortality rate was 13.6% (11/81), with a 10.5% (6/57) mortality rate in dogs and a 20.8% (5/24) mortality rate in cats. CLINICAL SIGNIFICANCE: In this series of dogs and cats, pancreatic surgery under referral care carried a low to moderate mortality rate.

Differences in milk metabolites in Malnad Gidda (Bos indicus) cows reared under pasture-based feeding system.

The milk and milk products from cows reared under grazing system are believed to be healthier and hence have high demand compared to milk from cows reared in the non-grazing system. However, the effect of grazing on milk metabolites, specifically lipids has not been fully understood. In this study, we used acetonitrile precipitation and methanol:chloroform methods for extracting the milk metabolites followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) run to identify the different metabolites between the milk of grazing and non-grazing early lactating Malnad Gidda cows. Various carbohydrates, amino acids, nucleosides and vitamin derivatives were found to be differentially abundant in grazing cows. A total of 35 metabolites were differentially regulated (fold change above 1.5) between the two groups. Tyrosyl-threonine, histidinyl-cysteine, 1-methyladenine, L-cysteine and selenocysteine showed fold change above 3 in grazing cows. The lipid profile of milk showed a lesser difference between grazing and non-grazing cows as compared to polar metabolites. To the best of our knowledge, this is the largest inventory of milk metabolomics data of an Indian cattle (Bos indicus) breed. We believe that our study would help to emerge a field of Nutri-metabolomics and veterinary omics research.

Diabetogenic diet-induced insulin resistance associates with lipid droplet proteins and adipose tissue secretome, but not with sexual dimorphic adipose tissue fat accumulation in wistar rats.

The role of sexual dimorphic adipose tissue fat accumulation in the development of insulin resistance is well known. However, whether vitamin A status and/or its metabolic pathway display any sex- or depot (visceral/subcutaneous)-specific pattern and have a role in sexual dimorphic adipose tissue development and insulin resistance are not completely understood. Therefore, to assess this, 5 weeks old Wistar male and female rats of eight from each sex were provided either control or diabetogenic (high fat, high sucrose) diet for 26 weeks. At the end, consumption of diabetogenic diet increased the visceral fat depots (p < 0.001) in the males and subcutaneous depot (p < 0.05) in the female rats, compared to their sex-matched controls. On the other hand, it caused adipocyte hypertrophy (p < 0.05) of visceral depot (retroperitoneal) in the females and subcutaneous depot of the male rats. Although vitamin A levels displayed sex- and depot-specific increase due to the consumption of diabetogenic diet, the expression of most of its metabolic pathway genes in adipose depots remained unaltered. However, the mRNA levels of some of lipid droplet proteins (perilipins) and adipose tissue secretory proteins (interleukins, lipocalin-2) did display sexual dimorphism. Nonetheless, the long-term feeding of diabetogenic diet impaired the insulin sensitivity, thus affected glucose clearance rate and muscle glucose-uptake in both the sexes of rats. In conclusion, the chronic consumption of diabetogenic diet caused insulin resistance in the male and female rats, but did not corroborate with sexual dimorphic adipose tissue fat accumulation or its vitamin A status.

Delineating the influence of picolinic acid on Eu(iii) sorption by γ-alumina.

The present study aims at understanding the sorption mechanism of Eu(iii) by γ-alumina in the presence of picolinic acid (PA), a decontaminating agent used in the nuclear industry, through batch sorption studies, spectroscopy and surface complexation modeling. PA is weakly sorbed by γ-alumina, with the sorption increasing with pH up to 4.5 and decreasing with further increase in pH. Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) measurements indicate that PA forms an inner sphere surface complex on γ-alumina. The presence of PA does not affect Eu(iii) sorption by γ-alumina at low [Eu(iii)], while it drastically reduces Eu(iii) sorption at high [Eu(iii)]. Similar Eu(iii) sorption profiles with different addition sequences of Eu(iii) and PA suggest identical Eu(iii) surface species for Eu(iii) sorption on γ-alumina in the presence of PA which has been validated by time resolved fluorescence spectroscopy (TRFS). TRFS measurements of Eu(iii) sorbed on γ-alumina in the absence (binary systems) and presence of PA (ternary systems) exhibited two components 1 & 2. The lifetime value of component 1 in ternary systems is enhanced compared to that in binary systems signifying the formation of new surface species containing Eu(iii), PA and the γ-alumina surface whereas the similarity of component 2 in both the binary and ternary systems reveals an almost identical coordination environment of Eu(iii) in the two types of system. Using the spectroscopic information obtained from TRFS, Eu(iii) sorption, at high [Eu(iii)], in ternary systems has been successfully modeled by considering Eu(iii) bridged PA surface species at both low and high affinity sites of γ-alumina. At low [Eu(iii)] both PA and Eu(iii) bridged ternary surface complexes only at high affinity sites of γ-alumina could describe the Eu(iii) sorption adequately.

Characterization of antisperm antibody binding patterns in relation to sperm phenotypic attributes and field fertility in dairy bulls.

To test our hypothesis that antisperm antibodies (ASA) might alter sperm phenotypic attributes thus leading to sub-fertility/infertility in bulls, ASA were generated in crossbred male calves by immunizing with sperm two times. Cryopreserved spermatozoa from crossbred bulls (n = 24) with different field fertility ratings were incubated with ASA and different patterns of ASA immunolocalization were studied. In addition, sperm membrane integrity, acrosomal integrity and cryo-capacitation status were also assessed. Immunolocalization of sperm antigens using antisperm antibody revealed three major patterns (Acrosomal-AR, apical-AP and, acrosome and tail-AT). The proportion of ASA reactive spermatozoa was significantly (P < 0.05) higher in low- and medium-fertile bulls compared to high-fertile bulls. Among the three patterns, the proportion of spermatozoa with AR pattern was significantly (P < 0.05) higher in low- and medium-fertile bulls compared to high-fertile bulls. The proportion of membrane and acrosome intact spermatozoa was significantly (P < 0.05) higher in high-fertile bulls compared to medium- and low-fertile bulls. There were no significant differences in the proportion of cryo-capacitated spermatozoa among high-, medium- and low-fertile bulls. The relationship between ASA reactive spermatozoa and conception rates (CR) of bulls was highly (P < 0.01) significant and negative. Similarly, AR and AT pattern were also significantly (P < 0.01) and negatively related to CR of bulls. The reactivity of spermatozoa with ASA was also significantly (P < 0.01) and negatively related to the membrane and acrosome integrity of spermatozoa. It was concluded that the proportion of spermatozoa responding to ASA was higher in low-compared to high-fertile bulls and ASA localization in sperm acrosomal area was negatively related to sperm membrane and acrosomal integrity and bull fertility.

Monitoring foot surface temperature using infrared thermal imaging for assessment of hoof health status in cattle: A review.

Detection of lameness early in cows is important from the animal welfare point of view and for reducing economic losses. Currently, many studies are being conducted for assessment of hoof health status by measuring the surface temperature of skin in cattle and other animal species in different parts of the world. Infrared Thermography (IRT) is able to detect lesions of hooves associated with lameness by measuring the changes in coronary band and hoof skin surface temperature. The surface temperature of a lame limb will be increased when the hoof has lesion(s). IRT has been used as a non-invasive diagnostic tool for early detection of hoof lesions based on the temperature difference between affected and non-affected hoof and maximum foot temperature on the regions of interest. In spite of having many potential applications in cattle production, factors affecting the temperature readings in thermograms must also are considered while taking images. Standard operating procedures must be established before taking thermographs under different circumstances, by considering all the factors that affect its normal function. IRT may help in minimising the cost of veterinary services, low yield, compromised fertility and culling expenses, where lameness cannot be resolved in early stages.

WITHDRAWN: Glue versus suture for mesh fixation in inguinal hernia repair.

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Vitamin A deficiency induces endoplasmic reticulum stress and apoptosis in pancreatic islet cells: Implications of stearoyl-CoA desaturase 1-mediated oleic acid synthesis.

Previously, we reported that vitamin A deficiency resulted in the reduction of stearoyl-CoA desaturase 1 (SCD1) and monounsaturated fatty acid (MUFA) levels, which corroborated with attenuation of high fructose-induced hepatic steatosis. Here, we aimed at assessing the effect of vitamin A deficiency on SCD1, MUFA levels and their impact on pancreas' structure and functions. Male weanling Wistar rats fed one of the four diets, namely control (Con), vitamin A-deficient (VAD), highfructose (HFr) and vitamin A-deficient diet with highfructose (VADHFr) for 16 weeks period. Compared to the control, feeding of VAD diet (alone or with HFr) resulted in pancreatic intra-islet vessel dilation and reduced plasma insulin, glucagon and C-peptide levels, however, glucose levels decreased only in VADHFr group. In line with plasma levels, VAD diet-fed animals displayed lower immunostaining for insulin and glucagon, which corroborated with increased apoptotic staining observed in the islet regions, possibly due to increased cellular stress, as indicated by high immunostaining for endothelial nitric oxide synthase (eNOS) and CCAAT/Enhancer-binding protein homologues protein (CHOP). On the other hand, it significantly decreased the SCD1 protein, which corroborated with reduced MUFA levels, particularly, oleic acid (C18:1), when compared to the control and HFr groups. In conclusion, chronic vitamin A deficiency altered the structure and functions of pancreas by diminishing the islet cells, possibly by inducing cellular stress-mediated apoptosis and decreasing SCD1-mediated oleic acid (C18:1) synthesis. Thus, the data suggest that unlike liver, the reduction in SCD1 and MUFA levels in the pancreas exerts deleterious effects on its functions and perturb the overall cellular metabolism.

Metabolic and immunological changes in transition dairy cows: A review.

Smooth transition from pregnancy to lactation is important for high productive and reproductive performance during later postpartum period in dairy animals. On the other hand, the poor transition often leads to huge economic loss to dairy farmers due to compromised production and reproduction. Therefore, understanding the causes and consequence of metabolic changes during the transition period is very important for postpartum health management. In this review, metabolic changes with reference to negative energy balance in transition cow and its effect on health and reproduction during the later postpartum period in dairy animals are discussed besides the role of metabolic inflammation in postpartum performance in dairy animals.

Efficacy of corrective exercise strategy in subjects with hyperkyphosis.

BACKGROUND: Age-related hyperkyphosis causes deleterious effects on health, physical function, and quality of life. Recently, health care providers recognized it as a major health concern. OBJECTIVE: To identify the effect of corrective exercise strategy on hyperkyphosis and compare it with that of conventional exercise. METHODS: Subjects were randomly categorized into two groups. Each group comprised 30 subjects. Group A received the corrective exercise strategy, and group B received conventional exercises for 8 weeks of the study duration (15 repetitions of each exercise for three sessions/day for a total duration of 45 min and 4 days/week. Pre- and post-interventional hyperkyphosis were analyzed according to posture number using the Posture Pro 8 postural analysis software. In addition, pectoralis minor flexibility was assessed using the ruler scale method in centimeters. RESULTS: Both groups showed highly significant postural alteration and changes in pectoralis minor muscle length (p< 0.001)CONCLUSIONS:The corrective exercise strategy seems to promote scapular stability and produce a more upright posture of the upper thoracic spine.

Influence of clinical mastitis and its treatment outcome on reproductive performance in crossbred cows: A retrospective study.

AIM: Evaluation of the effect of clinical mastitis (CM) and its treatment outcome on the reproductive performance in crossbred cows retrospectively. MATERIALS AND METHODS: Datasets of 835 lactating cows affected with CM during a period of 12 years (2001-2012) were considered for this study. Mastitis treatment related data and reproductive parameters such as days to first detected heat (DTFDH), days to first insemination (DTFI), days open (DO), and number of services per conception (SC) were collected from mastitis treatment and artificial insemination registers, respectively. Data were analyzed by ANOVA using SPSS 20 software. The means were compared with the Duncan's multiple comparison post-hoc test. RESULTS: CM affected cows had significantly (p<0.05) higher DTFDH, DTFI, DO and SC compared to clinically healthy cows. Cows diagnosed with a single episode of CM had significantly (p<0.05) delayed DTFDH while, DO and SC were significantly higher (p<0.05) in cows diagnosed by multiple episodes of CM. SC was significantly (p<0.05) higher in cows diagnosed with both relapse and recurrence. Severe CM affected cows had significantly (p<0.05) altered reproductive parameters. The reproductive parameters were altered to high extent when CM occurred during the breeding period. CONCLUSION: CM-affected cows had higher DTFDH, DTFI, DO and SC compared to clinically healthy cows. The negative effects of CM on reproduction parameters were higher when CM occurred during the breeding period.

Mastitis effects on reproductive performance in dairy cattle: a review.

The reproductive performance of dairy animals is influenced by several factors, and accumulating lines of evidence indicate that mastitis is one of the determinants. Most of the published information relating mastitis with reproduction has evolved based on retrospective approach rather than controlled clinical studies. The complex nature of both mastitis and reproduction could be a limiting factor for understanding their relationship in detail. In this review, we analyzed the available retrospective studies on the effects of clinical mastitis on reproductive function and explained the possible mechanisms by which mastitis affects reproduction in dairy animals.

Differential expression of ISG 15 mRNA in peripheral blood mononuclear cells of nulliparous and multiparous pregnant versus non-pregnant Bos indicus cattle.

Embryonic mortality is found to be the main source of reproductive wastage in domestic ruminants. Many genes are involved in the growth and development of the embryo, and the interferon-stimulated gene 15 (ISG 15) is one of the major gene stimulated by interferon tau, the maternal recognition of pregnancy signal in ruminants. In this study, both genomic and cDNA sequences of ISG 15 from Bos indicus (Deoni breed) were amplified and characterized. The genomic sequence of Deoni ISG 15 exhibited 99% identity with Bos taurus and 97% identity with that of Bos mutus and Bubalus bubalis. Moreover qRT-PCR analysis revealed constitutive expression of the ISG 15 mRNA in peripheral blood mononuclear cells of Deoni heifers and multiparous cows during early pregnancy. Fourteen Deoni heifers and fifteen multiparous Deoni cows were synchronized for timed AI by CIDR-Ovsynch protocol, and six animals were kept as cyclic control in each group. Blood samples were collected on days 7, 14, 16, 18, 21, 30 and 45 from the day of AI. Pregnancy was confirmed by plasma progesterone level through ELISA. A significantly higher expression of ISG 15 mRNA was found on day 16 (p < .05) and day 18 (p < .05) of pregnancy in nulliparous heifers. Although in multiparous Deoni cows ISG 15 expression was greater in pregnant cows, difference was statistically non-significant. The result of this study indicates that ISG 15 gene expression is upregulated during 16-18 days of pregnancy and could be used as an early pregnancy marker in dairy cows especially in heifers.

Infrared thermography: A potential noninvasive tool to monitor udder health status in dairy cows.

The animal husbandry and livestock sectors play a major role in the rural economy, especially for the small and marginal farmers. India has the largest livestock population in the world and ranks first in the milk production. Mastitis is the most common and expensive infectious disease in dairy cattle. The global economic losses per year due to mastitis amounts to USD 35 billion and for Indian dairy industry ₹6000 crores per year. Early detection of mastitis is very important to reduce the economic loss to the dairy farmers and dairy industry. Automated methods for early and reliable detection of mastitis are currently in focus under precision dairying. Skin surface temperature is an important indicator for the diagnosis of cow's illnesses and for the estimation of their physiological status. Infrared thermography (IRT) is a simple, effective, on-site, and noninvasive method that detects surface heat, which is emitted as infrared radiation and generates pictorial images without causing radiation exposure. In human and bovine medicine, IRT is used as a diagnostic tool for assessment of normal and physiological status.

Use of transcutaneous ultrasonography to characterize ovarian status, size distribution, and hierarchical status of follicles in Japanese quail (Coturnix coturnix japonica).

The present study was undertaken to evaluate the ovarian status of matured breeding female Japanese quail by means of B Mode portable ultrasound scanning. Active ovaries in various stages of hierarchical development and different morphological structure were observed. The large yellow follicles appeared as a cluster of dark circles with various intensity of hyperechoic concentric ring. Sonographically, these follicles were classified into F1, F2, and F3 measuring 16.20 ± 0.06 mm, 12.48 ± 0.09 mm, and 7.95 ± 0.16 mm, respectively. A comparative study on preslaughter and postslaughter ovarian follicular status revealed accuracy of follicles less than 10 mm, 10-15 mm, 15-18 mm, and greater than 18 mm as 26.31%, 78.9%, 93.75%, and 100%, respectively, with an overall accuracy of 71%. This is the first report on the application of transcutaneous ultrasonographic technique to monitor ovarian status on Japanese quail reporting that the ovarian follicular activity and morphological structure can be monitored nonintrusively throughout quail life which can used as model for reproductive and biomedical research.

Potential of acute phase proteins as predictor of postpartum uterine infections during transition period and its regulatory mechanism in dairy cattle.

Among the various systemic reactions against infection or injury, the acute phase response is the cascade of reaction and mostly coordinated by cytokines-mediated acute phase proteins (APPs) production. Since APPs are sensitive innate immune molecules, they are useful for early detection of inflammation in bovines and believed to be better discriminators than routine hematological parameters. Therefore, the possibility of using APPs as a diagnostic and prognostic marker of inflammation in major bovine health disorders including postpartum uterine infection has been explored by many workers. In this review, we discussed specifically importance of postpartum uterine infection, the role of energy balance in uterine infections and potential of APPs as a predictor of postpartum uterine infections during the transition period and its regulatory mechanism in dairy cattle.

Investigation of body and udder skin surface temperature differentials as an early indicator of mastitis in Holstein Friesian crossbred cows using digital infrared thermography technique.

AIM: The objective of this study was to investigate the ability of infrared thermography (IRT) technique and its interrelationship with conventional mastitis indicators for the early detection of mastitis in Holstein Friesian (HF) crossbred cows. MATERIALS AND METHODS: A total of 76 quarters of lactating HF crossbred (Bos indicus × Bos taurus) cows (n=19) were monitored for body temperature (i.e., eye temperature) and udder skin surface temperature (USST) before milking using forward-looking infrared (FLIR) i5 camera. Milk samples were collected from each quarter and screened for mastitis using Somatic Cell Count (SCC), Electrical Conductivity (EC), and California mastitis test. Thermographic images were analyzed using FLIR Quick Report 1.2 image analysis software. Data on body and USST were compiled and analyzed statistically using SPSS 16.0 and Sigmaplot 11. RESULTS: The mean±standard deviation (SD) body (37.23±0.08°C) and USST (37.22±0.04°C) of non-mastitic cow did not differ significantly; however, the mean USST of the mastitis-affected quarters were significantly higher than the body temperature and USST of unaffected quarters (p<0.001). The mean±SD USST of the subclinical mastitis (SCM) and clinical mastitis-affected quarters were 38.08±0.17 °C and 38.25±0.33 °C, respectively, which is 0.72 and 1.05 °C higher than the USST temperature of unaffected quarters. The USST was positively correlated with EC (r=0.95) and SCC (r=0.93). The receiver operating characteristic curve analysis revealed a higher sensitivity for USST in early prediction of SCM with a cut-off value of >37.61°C. CONCLUSION: It is concluded that infrared thermal imaging technique could be used as a potential noninvasive, quick cow-side diagnostic technique for screening and early detection of SCM and clinical mastitis in crossbred cows.