Genomic evaluation of feed efficiency in US Holstein heifers.

There is growing interest in improving feed efficiency traits in dairy cattle. The objectives of this study were to estimate the genetic parameters of residual feed intake (RFI) and its component traits [dry matter intake (DMI), metabolic body weight (MBW), and average daily gain (ADG)] in Holstein heifers, and to develop a system for genomic evaluation for RFI in Holstein dairy calves. The RFI data were collected from 6,563 growing Holstein heifers (initial body weight = 261 ± 52 kg; initial age = 266 ± 42 d) for 70 d, across 182 trials conducted between 2014 and 2022 at the STgenetics Ohio Heifer Center (South Charleston, OH) as part of the EcoFeed program, which aims to improve feed efficiency by genetic selection. The RFI was estimated as the difference between a heifer's actual feed intake and expected feed intake, which was determined by regression of DMI against midpoint MBW, age, and ADG across each trial. A total of 61,283 SNPs were used in genomic analyses. Animals with phenotypes and genotypes were used as training population, and 4 groups of prediction population, each with 2,000 animals, were selected from a pool of Holstein animals with genotypes, based on their relationship with the training population. All traits were analyzed using univariate animal model in DMU version 6 software. Pedigree information and genomic information were used to specify genetic relationships to estimate the variance components and genomic estimated breeding values (GEBV), respectively. Breeding values of the prediction population were estimated by using the 2-step approach: deriving the prediction equation of GEBV from the training population for estimation of GEBV of prediction population with only genotypes. Reliability of breeding values was obtained by approximation based on partitioning a function of the accuracy of training population GEBV and magnitudes of genomic relationships between individuals in the training and prediction population. Heifers had DMI (mean ± SD) of 8.11 ± 1.59 kg over the trial period, with growth rate of 1.08 ± 0.25 kg/d. The heritability estimates (mean ± SE) of RFI, MBW, DMI, and growth rate were 0.24 ± 0.02, 0.23 ± 0.02, 0.27 ± 0.02, and 0.19 ± 0.02, respectively. The range of genomic predicted transmitted abilities (gPTA) of the training population (-0.94 to 0.75) was higher compared with the range of gPTA (-0.82 to 0.73) of different groups of prediction population. Average reliability of breeding values from the training population was 58%, and that of prediction population was 39%. The genomic prediction of RFI provides new tools to select for feed efficiency of heifers. Future research should be directed to find the relationship between RFI of heifers and cows, to select individuals based on their lifetime production efficiencies.

Multiple-trait random regression modeling of feed efficiency in US Holsteins.

Residual feed intake (RFI) and feed saved (FS) are important feed efficiency traits that have been increasingly considered in genetic improvement programs. Future sustainability of these genetic evaluations will depend upon greater flexibility to accommodate sparsely recorded dry matter intake (DMI) records on many more cows, especially from commercial environments. Recent multiple-trait random regression (MTRR) modeling developments have facilitated days in milk (DIM)-specific inferences on RFI and FS, particularly in modeling the effect of change in metabolic body weight (MBW). The MTRR analyses, using daily data on the core traits of DMI, MBW, and milk energy (MilkE), were conducted separately for 2,532 primiparous and 2,379 multiparous US Holstein cows from 50 to 200 DIM. Estimated MTRR variance components were used to derive genetic RFI and FS and DIM-specific genetic partial regressions of DMI on MBW, MilkE, and change in MBW. Estimated daily heritabilities of RFI and FS varied across lactation for both primiparous (0.05-0.07 and 0.11-0.17, respectively) and multiparous (0.03-0.13 and 0.10-0.17, respectively) cows. Genetic correlations of RFI across DIM varied (>0.05) widely compared with FS (>0.54) within either parity class. Heritability estimates based on average lactation-wise measures were substantially larger than daily heritabilities, ranging from 0.17 to 0.25 for RFI and from 0.35 to 0.41 for FS. The partial genetic regression coefficients of DMI on MBW (0.11 to 0.16 kg/kg0.75 for primiparous and 0.12 to 0.14 kg/kg0.75 for multiparous cows) and of DMI on MilkE (0.45 to 0.68 kg/Mcal for primiparous and 0.36 to 0.61 kg/Mcal for multiparous cows) also varied across lactation. In spite of the computational challenges encountered with MTRR, the model potentially facilitates an efficient strategy for harnessing more data involving a wide variety of data recording scenarios for genetic evaluations on feed efficiency.

Fetal over- and undernutrition differentially program thyroid axis adaptability in adult sheep.

OBJECTIVE: We aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early-life postnatal overnutrition modulates implications of prenatal programming. DESIGN: Twin-pregnant sheep (n = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months-of-age, twin lambs received a conventional (CONV) or an obesogenic, high-carbohydrate high-fat (HCHF) diet. Subgroups were slaughtered at 6-months-of-age. Remaining lambs were fed a low-fat diet until 2½ years-of-age (adulthood). METHODS: Serum hormone levels were determined at 6 months- and 2½ years-of-age. At 2½ years-of-age, feed intake capacity (intake over 4-h following 72-h fasting) was determined, and an intravenous thyroxine tolerance test (iTTT) was performed, including measurements of heart rate, rectal temperature and energy expenditure (EE). RESULTS: In the iTTT, the LOW and nutritionally mismatched NORM:HCHF and HIGH:CONV sheep increased serum T3, T3:T4 and T3:TSH less than NORM:CONV, whereas TSH was decreased less in HIGH, NORM:HCHF and LOW:HCHF. Early postnatal exposure to the HCHF diet decreased basal adult EE in NORM and HIGH, but not LOW, and increased adult feed intake capacity in NORM and LOW, but not HIGH.Conclusions: The iTTT revealed a differential programming of central and peripheral HPT axis function in response to late fetal malnutrition and an early postnatal obesogenic diet, with long-term implications for adult HPT axis adaptability and associated consequences for adiposity risk.

Cerebral Venous Sinus Thrombosis during Everest Expedition: A Case Report and Review of the Literature.

Cerebral venous sinus thrombosis (CVST) is a rare but serious disorder that is associated with a poor clinical outcome. We report a 35-year-old man who had a severe headache and diplopia while climbing Mount Everest. His MR venography showed right transverse and right sigmoid sinus thrombosis. He improved on anticoagulant and symptomatic measures. Cerebral venous sinus thrombosis at high altitude is discussed.

Late gestation under- and overnutrition have differential impacts when combined with a post-natal obesogenic diet on glucose-lactate-insulin adaptations during metabolic challenges in adolescent sheep.

AIM: To determine whether late gestation under- and overnutrition programme metabolic plasticity in a similar way, and whether metabolic responses to an obesogenic diet in early post-natal life depend on the foetal nutrition history. METHODS: In a 3 × 2 factorial design, twin-pregnant ewes were for the last 6 weeks of gestation (term = 147 days) assigned to HIGH (N = 13; 150 and 110% of energy and protein requirements, respectively), NORM (N = 9; 100% of requirements) or LOW (N = 14; 50% of requirements) diets. The twin offspring were raised on high-carbohydrate-high-fat (HCHF; N = 35) or conventional (CONV; N = 35) diets from 3 days to 6 months of age (around puberty). Then intravenous glucose (GTT; overnight fasted), insulin (ITT; fed) and propionate (gluconeogenetic precursor; PTT; both fed and fasted) tolerance tests were conducted to evaluate (hepatic) metabolic plasticity. RESULTS: Prenatal malnutrition differentially impacted adaptations of particularly plasma lactate followed by glucose, cholesterol and insulin. This was most clearly expressed during PTT in fasted lambs and much less during ITT and GTT. In fasted lambs, propionate induced more dramatic increases in lactate than glucose, and HIGH lambs became more hyperglycaemic, hyperlactataemic and secreted less insulin compared to the hypercholesterolaemic LOW lambs. Propionate-induced insulin secretion was virtually abolished in fasted HCHF lambs, but upregulated in fasted compared to fed CONV lambs. HCHF lambs had the greatest glucose-induced insulin secretory responses. CONCLUSION: Prenatal malnutrition differentially programmed glucose-lactate metabolic pathways and cholesterol homeostasis. Prenatal overnutrition predisposed for hyperglycaemia and hyperlactataemia, whereas undernutrition predisposed for hypercholesterolaemia upon exposure to an obesogenic diet. Prenatal overnutrition (not undernutrition) interfered with pancreatic insulin secretion by non-glucose-dependent mechanisms.

Late gestation over- and undernutrition predispose for visceral adiposity in response to a post-natal obesogenic diet, but with differential impacts on glucose-insulin adaptations during fasting in lambs.

AIM: To investigate if late gestation under- or overnutrition has similar adverse impacts on visceral adiposity, metabolic and endocrine function in sheep, and if subsequent exposure to a high-fat diet in early post-natal life exaggerates the prenatal programming outcomes later in life. METHODS: Thirty-six twin-pregnant ewes were fed a NORM (fulfilling 100% of daily requirements for energy and protein), LOW (50% of NORM) or HIGH diet (150% of energy and 110% of protein requirements) during the last 6 weeks of gestation (term = 147 days). Post-natally, the twin lambs were subjected to a high-fat or a moderate diet until 6 months of age (around puberty), where metabolic and endocrine adaptability to fasting was examined, and subgroups of animals were killed. RESULTS: Animals exposed to either prenatal under- or overnutrition had reduced subcutaneous fat deposition when fed a high-fat diet, resulting in higher ratios of mesenteric and peri-renal fat relative to subcutaneous fat compared to controls. This was not related to prenatal influences on plasma glucose or insulin. Irrespective of the prenatal diet, high-fat-fed lambs underwent changes resembling the metabolic syndrome with higher plasma glucose, cholesterol, non-esterified fatty acids, triglyceride and lactate combined with abdominal obesity. Peri-renal fat appeared to be a particular target of a high-fat diet post-natally. CONCLUSION: Both prenatal under- and overnutrition predisposed for abdominal adiposity, apparently by reducing the expandability of subcutaneous adipose tissue and induced differential physiological adaptations to fasting. This study does not suggest that exposure to gestational overnutrition will provide a protective effect against development of hyperglycaemia later in life.

Intrauterine growth curves for singleton live babies in Paropakar Maternity and Women's Hospital in Nepal.

BACKGROUND: To construct birth weight, crown heel length and head circumference centile chart referenced to gestational age for Nepalese infants. METHODS: The study was conducted over a period of six months. It included consecutive live births from 28 to 42 weeks of gestation. Their birth weight, crown-heel length and head circumference were recorded. Smoothed percentile values along with curves were created using the Lambda Mu Sigma (LMS) method. The curves were compared with one of the Indian study. RESULTS: A total of 9710 newborns were measured. The mean birth weight, crown-heel length, head circumference at 40 weeks were 3023g, 49.22cm and 33.61cm respectively. Smoothed percentile values calculated gave the cutoffs for defining small and large gestational age for Nepalese newborns. Comparison with Indian study showed significant difference (p<0.01) in weight. The Indian babies weighed less than Nepalese babies. CONCLUSIONS: The referenced growth standards help in clinical assessment, defining and identifying high risk newborns, thus, leading to improved care and management of neonates. It should help public health policy makers to track population difference due to several factors, intervene and find response over time.

Percutaneous K wire fixation of fifth metacarpal neck fracture--new and simple technique.

BACKGROUND: Isolated fractures of metacarpals and phalanges are the commonest injuries affected upper extremity, which constitute about 10% of skeletal fractures in general. Fifth metacarpal (boxer's fractures) being the most common. The objective of this study was to investigate the outcome of treatment of the displaced neck and sub-capital fractures of the fifth metacarpal by percutaneous K wire fixation. METHODS: An observational study was conducted in the department of orthopedics Patan hospital as an outpatient procedure from January 2010 to January 2012. All adult patients with unilateral fracture of neck of fifth metacarpal bone were included. Whose physis was open, having previous hand injury or diseases causing deformity or impaired hand function and when fracture was more than 7 days old, were excluded from the study. RESULTS: Twenty eight of 35 patients obtained anatomic reduction, and 7 patients had 2/3 apposition of bone end and no rotational deformity. Follow-up was available for only 30 patients. The follow-up time was up to 12 weeks. The head/shaft angle of the fifth metacarpal was 60.60 degrees ±9.39 degrees preoperatively, and 14.20 degrees ±7.32 degrees postoperatively, and 15.60 degrees ±6.95 degrees in 12 weeks postoperatively. The difference between preoperative and postoperative angles was highly significant. The range of motion of the metacarpal joint was 86.73 degrees ±6.13 degrees postoperatively, which was not significantly different compared with that of uninjured side which was 90.93 degrees ±3.18. The difference between preoperative and postoperative angles was highly significant. The range of motion of the metacarpal joint was not significantly different compared with that of uninjured side. The average union time was 5.46 weeks ±1.22. CONCLUSIONS: This method under consideration does not disturb the fracture site itself, the Kirschner wire being introduced in retrograde fashion makes it easier to correctly place the wire, which gives reasonably stable fixation, gives excellent results in a high proportion of selected cases. Local anesthesia is an added advantage.

Proyl isomerase Pin1 facilitates ubiquitin-mediated degradation of cyclin-dependent kinase 10 to induce tamoxifen resistance in breast cancer cells.

Endocrine therapies that inhibit estrogen receptor (ER)-α signaling are the most common and effective treatment for ER-α-positive breast cancer. However, the use of these agents is limited by the frequent development of resistance. The aim of this study was to elucidate the mechanisms by which downregulation of CDK10 expression confers resistance to tamoxifen in breast cancer. Here, we show that peptidyl-prolyl isomerase Pin1 downregulates CDK10 protein as a result of its interaction with and ubiquitination of CDK10, thereby affecting CDK10-dependent Raf-1 phosphorylation (S338). Pin1(-/-) mouse embryonic fibroblasts (MEFs) show higher CDK10 expression than Pin1(+/+) MEFs, whereas CDK10 protein was downregulated in the rescued Pin1(-/-) MEFs after reexpression of Pin1. Pin1 silencing in SKBR-3 and MCF7 cells increased the CDK10 expression. In human tamoxifen-resistant breast cancer and tamoxifen-resistant MCF7 cells, immunohistochemical staining and immunoblotting analysis shows an inverse correlation between the expression of CDK10 and the degree of tamoxifen resistance. There was also a positive correlation between the high level of P-Raf-1 (Ser338) and Pin1 in human tamoxifen-resistant breast cancer and tamoxifen-resistant MCF7 (TAMR-MCF7) cells. Importantly, 4-OH tamoxifen (4-OHT), when used in combination with overexpressed CDK10 or Raf-1 inhibitor, increased cleaved PARP and DNA fragmentation to inhibit cologenic growth of MCF7 cells and Tamoxifen-resistant MCF7 cells, respectively. On the basis of these findings, we suggest that the Pin1-mediated CDK10 ubiquitination is a major regulator of tamoxifen-resistant breast cancer cell growth and survival.

Status of intestinal parasitosis among hospital visiting patients in Deukhury Valley, Dang, Nepal.

Intestinal parasitosis is highly prevalent among the general population in Nepal. This study aimed to assess the status of intestinal parasitosis among patients attending Deukhury Community Hospital, Lamahi, Dang, situated in the mid western region of Nepal. A total of 210 stool samples examined by direct smear technique were reported. The overall prevalence of intestinal parasitic infection was found to be 21.4% (M = 23.5% vs F = 19.3%). Children < 15 yrs age were infected more often as compared to > 60 yrs and 15-60 yrs aged people. Among adults, Entamoeba histolytica infection was found to be very high compared to high helminthic infection found among children. Finding showed that, the prevalence was significantly high (68.8%) among people having low socio-economic status compared to others (31.1%) (p < 0.05). Among various parasites detected, E. histolytica was the most common parasite (48.8%) followed by helminths, mainly Ascaris lumbricoides (31.1%), hookworm (13.3%), Trichuris trichiura (4.4%) and Taenia species (2.2%) respectively in the locality.

Pattern of poisoning cases in a hospital in a Terai district of central Nepal.

Poisoning is a major global health problem and is one of the major causes of hospitalization through emergency. The objective of this study is to evaluate the characteristics of poisoning cases admitted to emergency department over a one year period. A hospital based study was carried out in the emergency department, Mahendra Adarsha Chikitsalaya, Chitwan analyzing the data of the poisoning cases attended for one year duration by searching all the medical records. A total of 921 poisoning cases presented to emergency department in the year 2007. The female to male ratio was 1.17:1. Most of poisoning occurred in the age group 15-24 years. Snake bite was the commonest form of poisoning amongst all cases. By occupation, 46.0% cases were in farmers. Accidental poisoning prevailed over intentional poisoning. Seasonal trend revealed maximum cases being in summer (42.4%). Poisoning shows seasonal trend and hence proper intervention is required in community level.

The effect of cattle manure cultivation on moisture content and survival of Escherichia coli.

A new practice whereby wet slurry is added daily to the cattle manure bedding at the barn and cultivated has been developed in Israel. The objective of the present study was to examine the effect of manure cultivation on the persistence of Escherichia coli in a model system. A cow manure-derived E. coli strain was tagged with green fluorescence protein (GFP) and antibiotic resistance markers and was used to inoculate cow manure in 10-L buckets. After 3 successive cycles of inoculation and cultivation, wet slurry was added during an additional 2 cycles. After 32 d, the cultivated and noncultivated manure contained 677 ± 14 and 505 ± 2 g·kg(-1) DM, respectively. The cultivated manure remained drier compared with the noncultivated manure after the addition of wet slurry, and its texture remained lumpy compared with the compact, cohesive, and sticky texture of the noncultivated manure. Throughout the experiment, the counts of the tagged E. coli were less (P < 0.05) and disappeared faster in the cultivated than in the noncultivated manure. These results support the hypothesis that daily cultivation of manure may result in reduced incidence of mastitis and improves the welfare and performance of dairy cows.

A virtual reality simulator for teaching and evaluating dental procedures.

OBJECTIVES: We present a dental training system with a haptic interface that allows dental students or experts to practice dental procedures in a virtual environment. The simulator is able to monitor and classify the performance of an operator into novice or expert categories. The intelligent training module allows a student to simultaneously and proactively follow the correct dental procedures demonstrated by an intelligent tutor. METHODS: The virtual reality (VR) simulator simulates the tooth preparation procedure both graphically and haptically, using a video display and haptic device. We evaluated the performance of users using hidden Markov models (HMMs) incorporating various data collected by the simulator. We implemented an intelligent training module which is able to record and replay the procedure that was performed by an expert and allows students to follow the correct steps and apply force proactively by themselves while reproducing the procedure. RESULTS: We find that the level of graphics and haptics fidelity is acceptable as evaluated by dentists. The accuracy of the objective performance assessment using HMMs is encouraging with 100 percent accuracy. CONCLUSIONS: The simulator can simulate realistic tooth surface exploration and cutting. The accuracy of automatic performance assessment system using HMMs is also acceptable on relatively small data sets. The intelligent training allows skill transfer in a proactive manner which is an advantage over the passive method in a traditional training. We will soon conduct experiments with more participants and implement a variety of training strategies.

Substance use among medical students in Kathmandu valley.

INTRODUCTION: Substance use including tobacco and alcohol is the most important cause of preventable morbidity, disability, and premature mortality. The study aims to specify the prevalence and the pattern of use of different substance. METHODS: A cross sectional study was performed amongst first year and final year students in four medical colleges in Kathmandu using self administered anonymous questionnaire.Data collectedfrom 446 students were analyzed. RESULTS: Prevalence of substance use was found to be 60.3% among the medical students. Alcohol (57.6%) was the substance most prevalently used followed by tobacco (27.58%) and cannabis (12.8%). Mean age of first exposure was 17.94 (Confidence interval: 17.91-17.97). There was significant difference in the useof tobacco and cannabis amongst final year students than first year students. Male and female differed significantly in use of every substance except for benzodiazepine. Medical college, college and school were place of first exposure in 17.26%, 15.92% and 13.23% of the cases respectively. Family history was associated with substance use in medical students and was statistically significant (P<0.0001).Experimentation was the major reason for the use of most of the substances. CONCLUSIONS: Substance use is prevalent in male medical students of both first and final year. Hence steps should be initiated early in school, college and medical college to prevent substance use.

Conservation reaches new heights.

PIP: The conservation program with the management assistance of the Woodlands Mountain Institute in 2 contiguous parks, the Mount Everest National Park in Nepal and the Qomolangma Nature Reserve in China, in 2 countries is described. The focus is on conservation of the complex ecosystem with sustainable development by showing local people how to benefit from the park without environmental damage. Cultural diversity is as important as biological diversity. The area has been designated by UNESCO as a World Heritage Site with the "last pure ecological seed" of the Himalayas. The regional geography and culture are presented. Population growth has impacted natural resources through overgrazing, cultivation of marginal land, and deforestation; future plans to build a dam and road bordering the nature reserve pose other threats. Proposed management plans for the Makalu-Barun Nature Park (established in November 1991) and Conservation Area include a division of the park into nature reserve areas free of human activity, protected areas which permit traditional land use, and special sites and trail for tourists and religious pilgrims. The conservation area will act as a buffer for the park and provide economic opportunities; further subdivisions include land use for biodiversity protection, community forest and pasture, agroforestry, and agriculture and settlement. Efforts will be made to increase the welfare of women and local people; proposed projects include the introduction of higher milk-producing animals for stall feeding. Also proposed is a cultural and natural history museum. 70% of the project's resources will be directed to local community participation in consultation and park maintenance. The project is a model of how conservation and protection of natural resources can coexist with local economic development and participation; an integration of preservation of biological diversity, mountain wisdom, and the value of local people as resources for conservation.^ieng