Grazing behavior of dairy cows under contrasting pasture allocation frequencies and areas.

This study aimed to compare grazing behavior of dairy cows with highly contrasting pasture allocation frequencies. The study ran from September 9, 2022, to December 2, 2022 (12 wk), during a time when daily pasture growth was expected to exceed daily herd intake. Three pasture allocation frequencies were compared, each with 11 spring-calving cows grazing a 4-ha farmlet. The allocations were high frequency rotational grazing (HFRG; 32.5 m2/cow per allocation and 4 allocations/d), rotational grazing with weekly allocations (7RG; 909 m2/cow per allocation and each allocated area continuously grazed over 7 d), and continuous grazing (CG; 1,818 m2/cow per allocation). Animal behavior was monitored using IceQube accelerometers (Peacock Technology) and CowManager ear tags (Agis Automatisering BV). Milk yield and composition were measured and pasture cover was estimated. Daily eating time was highest for CG animals, whereas lying time, lying bouts, and ruminating time were lowest, with no differences between HFRG and 7RG. There were no differences in fat- and protein-corrected milk yield between farmlets; however, estimated accumulated pasture yield was greater with more frequent allocations. Although milk production did not differ between treatment groups, this appeared to be achieved through greater eating times when allocated pasture less frequently, at the expense of time spent lying.

Identifying and predicting heat stress events for grazing dairy cows using rumen temperature boluses.

Heat stress events in dairy cows are associated with behavioral and physiological changes such as seeking shade, increased respiration rate and body temperature, reduced milk production, and psychological distress. Knowledge of the relationship between weather and animal responses to heat stress enables automated alerts using forecast weather, aiding early provision of shade or other mitigation practices. While numerous heat stress indices for cattle have been developed, these have limitations for cows exposed to wind and solar radiation (i.e., predominantly grazing outdoors or managed on pasture). To develop a predictive model for heat stress events in pasture-based dairy systems, rumen temperature data from smaXtec (smaXtec animal care GmbH, Graz, Austria) rumen boluses in 443 cows on 3 dairy farms in Northland, New Zealand, were used to identify heat stress events and these were matched with automated weather station data collected on or near the farm. Heat stress rate (HSR) was defined as the percentage of cows within an age-breed group having a rumen temperature greater than 3 standard deviations above an individual cow's mean and heat stress events were defined as HSR >25%. Single and multiple linear regression models, including published heat stress indices, were generally able to predict a high proportion of heat stress events (sensitivity 34%-68%), but were insufficiently discriminating, predicting also a high number of false positives (precision only 9%-27%). A machine learning algorithm, cubist, was the best performing model, predicting 79% of heat stress events with a precision of 52% for this dataset. Our proof-of-concept study demonstrates the potential of this approach, using climate data to predict and forecast heat stress events in pasture-based dairy systems. Further work should test the cubist model using independent data, refine dataset construction, investigate the value of including known animal variables such as cow age or breed, and incorporate other measures of heat stress such as respiration rate.

Cancellation and short postponement of primary hip or knee arthroplasty does not influence postoperative joint specific function or health related quality of life.

PURPOSE: The effect of cancellation and postponement of primary total hip arthroplasty (THA) or knee arthroplasty (TKA) on patient outcomes is unclear. The aim was to assess whether cancellation and delay to arthroplasty was associated with worse joint specific function and quality of life (QoL) 1-year postoperatively. METHODS: A single centre retrospective case-control study was performed for all patients planned to undergo THA or TKA in 2019. A total of 3133 arthroplasties were scheduled for 2019 (1484 THA, 1649 TKA), of which 344 (11.0%) were cancelled (136 THA [9.2%], 208 TKA [12.6%]). Pre-operative and one-year post-operative EuroQol (EQ-5D) and Oxford hip (OHS) or knee (OKS) scores were collected. RESULTS: The median time between the date of cancellation and the subsequent operation was 46.0 days for TKA and 45.5 days for THA. The cancelled group were more likely to be male (odds ratio [OR] 1.23, p = 0.03), older (mean difference [MD] 1.19, p = 0.03), with a higher ASA grade (OR 1.88 [ASA 3], OR 5.3 [ASA 4], p = 0.001) or planned for a TKA (OR 1.41, p = 0.003). There were no differences in pre-operative OKS (mean difference [MD] 0.19, p = 0.828) or EQ-5D (MD 0.028, p = 0.394) or in the one-year postoperative OKS (MD 1.51, p = 0.064) or EQ-5D (MD 0.041, p = 0.067) between groups undergoing TKA. However, cancelled THA patients had lower pre-operative OHS (MD 2.73, p = 0.018) and EQ-5D (MD 0.134, p = 0.0017) but at one-year postoperatively there was no difference in the absolute OHS (MD 2.07, p = 0.052) or EQ5D (MD 0.04, p = 0.142). The improvement in hip EQ-5D was greater (MD 0.096, p = 0.016) in the cancelled group. CONCLUSION: Cancellation and short delay did not influence joint specific outcome or QoL following THA or TKA at one-year. Preoperative hip specific pain, function and QoL were worse in cancelled THA patients, suggesting deterioration while waiting for their surgery, but this did not affect their postoperative outcome.

A Minimal Nontrivial Example of Higher Order Evidence.

Higher order evidence (evidence about evidence) allows epidemiologists and other health data scientists to account for measurement error in validation data. Here, to illustrate the use of higher order evidence, we provide a minimal nontrivial example of estimating the proportion and show how higher order evidence can be used to construct sensitivity analyses. The proposed method provides a flexible approach to account for multiple levels of distortion in the results of epidemiologic studies.

Depression: an individual-level early warning indicator of virologic failure in HIV patients in South Africa.

OBJECTIVE: To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa. DESIGN: A matched case-control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site. Participants were interviewed while clinical, pharmacy refill, laboratory, and objective pharmacological data were obtained. Multivariate conditional logistic regression models were constructed using model selection to identify factors associated with VF. Significant determinants of VF were identified using an alpha level of 0.05. RESULTS: In a full conditional model, higher cumulative ART adherence, quantified using tenofovir-diphosphate concentrations in dried blood spots (OR 0.26) and medication possession ratio (OR 0.98) were protective against VF, whereas an increase in total depression score (OR 1.20) was predictive of VF. CONCLUSION: This analysis demonstrates the importance of depression as a key individual-level early warning indicator of VF. Efforts to address mental health concerns among patients with people living with HIV could improve virologic suppression.

OBJECTIF: Identifier les indicateurs d'alerte précoce au niveau individuel de l'échec virologique chez les patients séropositifs recevant un traitement antirétroviral (TAR) en Afrique du Sud. MÉTHODE: Une étude cas-témoins appariée de personnes avec et sans échec virologique (FV, pour l'anglais « virologic failure ¼) (>5 mois sous ART et charge virale plasmatique du VIH-1 >1 000 copies/ml) a été menée entre juin 2014 et juin 2018. Sur les 1 000 participants inscrits dans la cohorte parente, 96 ont présenté une FV et 199 témoins supplémentaires ont été identifiés dans la cohorte parentale et appariés 1:2 (certains appariés 1:3) pour le sexe, l'âge, la durée du TAR et le site. Les participants ont été interrogés pendant que des données cliniques, de renouvellement de pharmacie, de laboratoire et pharmacologiques objectives ont été obtenues. Des modèles de régression logistique conditionnelle multivariée ont été construits à l'aide d'une sélection de modèles pour identifier les facteurs associés à la FV. Les déterminants significatifs de la FV ont été identifiés à l'aide d'un niveau alpha de 0,05. RÉSULTATS: Dans un modèle conditionnel complet, une observance cumulative plus élevée du TAR, quantifiée à l'aide des concentrations de ténofovir-diphosphate dans les gouttes de sang séché (OR 0,26) et du ratio de possession de médicaments (OR 0,98) protégeait contre la FV, tandis qu'une augmentation du score de dépression totale (OR 1,20) était prédictive de la FV. CONCLUSION: Cette analyse démontre l'importance de la dépression en tant qu'indicateur précoce clé au niveau individuel de la FV. Les efforts visant à résoudre les problèmes de santé mentale chez les personnes vivant avec le VIH pourraient améliorer la suppression virologique.

An exploration into the sleep of workers on block-calving, pasture-based dairy farms.

The benefits of sufficient and high-quality sleep for people are well documented. Insufficient sleep increases the risk of accidents, injuries, and negative health implications for people. This is especially relevant for farmers, as they work with large animals and machinery. Dairy farming often requires early start times and long days, particularly over the high workload calving period in block calving, pasture-based systems. However, there is little published data quantifying the sleep quantity and quality of farmers over this period. In this study, the sleep patterns of workers (n = 33) on 10 New Zealand dairy farms was measured for 90 d over the spring calving period using a sleep measuring device (OuraTM ring, Oura Health Ltd., Oulu, Finland). Total sleep time (TST) averaged 6 h 15 min, lower than the required 7 to 9 h for optimal wellbeing and cognitive functioning. TST decreased over the calving period and was significantly correlated with both sleep start and wake times. Factors such as work start time, farm location, and role on farm influenced sleep quantity and quality; indicating adjusting these on-farm factors could positively impact TST. Further research is required to better understand sleep and its effect on dairy farmers, over both the calving period and the remaining months of the year.

Characterizing hepatitis B virus infection in children in the Democratic Republic of Congo to inform elimination efforts.

Objective: Despite global reductions in hepatitis B virus (HBV) prevalence, an estimated 6.2 million children are infected, two-thirds of whom live in the WHO Africa region. We sought to characterize childhood HBV to inform elimination efforts in the Democratic Republic of Congo (DRC), one of the largest and most populous African countries. Methods: Using the most recent (2013-14) nationally representative Demographic and Health Survey in the DRC, we analyzed HBV surface antigen (HBsAg) on dried blood spots and associated survey data from children aged 6-59 months. We estimated HBsAg-positivity prevalence nationally, regionally, and by potential correlates of infection. We evaluated spatial variation in HBsAg-positivity prevalence, overall and by age, sex, and vaccination status. Findings: Using data from 5,679 children, we found national HBsAg-positivity prevalence was 1.3% (95% CI: 0.9%-1.7%), but ranged from 0.0% in DRC's capital city province, Kinshasa, to 5.6% in northwestern Sud-Ubangi Province. Prevalence among boys (1.8%, 95% CI: 1.2%-2.7%) was double that among girls (0.7%, 95%CI: 0.4%-1.3%). Tetanus antibody-negativity, rurality, and lower household wealth were also significantly associated with higher HBsAg-positivity prevalence. We observed no difference in prevalence by age. Children had higher HBsAg-positivity odds if living with ≥1 HBsAg-positive adult household member (OR: 2.3, 95%CI: 0.7-7.8), particularly an HBsAg-positive mother (OR: 7.2, 95%CI:1.6-32.2). Conclusion: In the largest national survey of HBV among children and household contacts in the DRC, we found that childhood HBV prevalence was 10-60 times the global target of 0.1%. We highlight specific regions and populations for further investigation and focused prevention efforts.

Impact of endophyte-infected tall fescue seed consumption on endocrine changes associated with intake regulation and post-absorptive metabolism in growing steers.

Fescue toxicosis is a syndrome occurring from the consumption of endophyte-infected tall fescue and results in substantial economic losses to the beef industry primarily from reduced growth accompanied by decreased dry matter intake (DMI); however, the associations characterizing this reduction in DMI have yet to be elucidated. The objective of this experiment was to identify endocrine changes associated with intake regulation post-consumption of endophyte-infected tall fescue seed (E+). Twelve Holstein steers were stratified by body weight and assigned to 1 of 3 treatments (n=4): 0 ppm ergovaline (ERV), 1.8 ppm ERV, or 2.7 ppm ERV. Treatments were achieved by combining differing proportions of ground E+ and non-endophyte-infected tall fescue seed. Steers were adapted to their diets for 7 d followed by a 7 d DMI collection period. Within treatment, steers were assigned to a sampling day (d 16 or d 17). Blood samples were collected every 20 min for 8 h, beginning 1 h before feeding. Intake data was analyzed using the MIXED procedure of SAS 9.4 (SAS Inst. Inc., Cary, NC) with treatment, day, and the interaction as fixed effects. Hormone and metabolite data were analyzed with the fixed effect of treatment, time, and the interaction including time as a repeated measure and orthogonal contrasts. Dry matter intake was linearly decreased with increasing ERV in the diet (P < 0.001). Insulin and leptin concentrations exhibited a quadratic effect (P = 0.018 and P = 0.005) with insulin concentrations highest for the 2.7 ppm treatment and leptin concentrations highest for the 1.8 ppm treatment. No differences were detected for active ghrelin or ß-hydroxybuytrate concentrations among treatment groups. Further, steers consuming both the 1.8 and 2.7 ppm ERV treatments had lower prolactin concentrations compared to the 0 ppm treatment (quadratic, P= 0.019). Glucose concentrations had a tendency for a linear increase as ERV concentrations increased (P = 0.091). A treatment × time interaction (P = 0.002) was noted in NEFA concentrations, with the 1.8 ppm ERV treatment showing increased pre-feeding concentrations, and the 2.7 ppm ERV treatment exhibiting elevated NEFA concentrations as time post-feeding progressed. The results suggest that E+ consumption reduces intake likely through alterations in intake-related hormones and post-absorptive metabolism and contributes to our current understanding of E+ effects on intake reduction while providing avenues for future research.

Human recombinant interleukin-6 improves the morphological quality of cryopreserved in vitro produced bovine blastocysts.

This work explored whether a well-characterized recombinant human interleukin-6 (hIL6) protein will influence in vitro produced (IVP) bovine embryo development and survival after cryopreservation. Cumulus oocyte complexes were collected from abattoir derived ovaries, matured for 24 h, and fertilized using pooled semen from Holstein bulls. Embryos were treated with 0, 25, 50, or 100 ng/mL hIL6 on day 5 post-fertilization. An increase in ICM cell numbers was observed in each hIL6 treatment, with the lowest hIL6 treatment having the same magnitude of response as the middle and highest hIL6 concentration. No effects on TE cell numbers were observed. The second study involved cryopreserving (via slow freezing) of hIL6-treated blastocysts, then examining post-thaw blastocyst survival by incubating for 24 h in the absence of hIL6 treatments. Blastocyst re-expansion and hatching rates were unaffected by any of the IL6 treatments, however, increases in both ICM and TE cell numbers were detected at 24 h post-thawing in blastocysts exposed to 100 ng/mL hIL6 but not lower concentrations before freezing. A reduction in the percentage of TUNEL-positive TE cells was observed after thawing in blastocysts exposed to 25, 50 and 100 ng/mL hIL6 before cryopreservation. No treatment-dependent changes in TUNEL-positive ICM cells were observed. In summary, hIL6 supplementation improves ICM cell numbers in bovine blastocysts to a degree that is commensurate with what has been observed when using bovine recombinant IL6. This positive effect of hIL6 on ICM cell numbers is maintained after freezing and thawing, and a novel improvement in post-thaw TE cell numbers occur in hIL6 treated embryos. This positive effect on TE cell numbers is attributed, at least in part, to an hIL6-dependent reduction in TE cell apoptosis.

Impact of preovulatory follicle maturity on oocyte metabolism and embryo development.

Improved oocyte competence for embryo development and pregnancy was observed following ovulation of preovulatory follicles with greater physiological maturity, as indicated by estradiol production, prior to the gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) surge. It was hypothesized that follicular fluid from preovulatory follicles of greater maturity better supports the maturing oocyte's metabolic requirements and improves embryo development. The objective was to determine if differences in preovulatory follicular fluid due to follicle maturity influence oocyte metabolism during in vitro maturation (IVM) and affect embryo development. Bovine preovulatory follicular fluid was collected 18 h after a GnRH-induced LH surge. Serum estradiol concentration at GnRH administration categorized follicles as greater or lesser maturity. Immature bovine oocytes were submitted to 24 h IVM in medium supplemented with 20% follicular fluid from preovulatory follicles of greater or lesser maturity. Embryo development was recorded. Oocyte maturation media and media conditioned by developing embryos were submitted for metabolomics. A randomized block design was utilized to determine differences in embryo development and media metabolites (P ≤ 0.05). Blastocysts from oocytes matured in greater vs. lesser maturity follicular fluid had a more moderate rate of development (P = 0.01). At the conclusion of 24 h IVM, abundance of 66 metabolites differed between greater and lesser follicle maturity treatments. Nine metabolites differed in media conditioned by developing embryos. Metabolome results suggest improved amino acid, purine, and glucose metabolism, followed by a more efficient rate of embryo development, in oocytes matured in greater vs lesser maturity follicular fluid.

A novel neurotropic microsporidium from the swamp guppy Micropoecilia picta from Grenada, West Indies.

A novel microsporidium was observed in wild swamp guppies Micropoecilia picta from Levera Pond within Levera National Park Grenada, West Indies. Initial observations indicated similarity with Pseudoloma neurophilia, an important pathogen in zebrafish Danio rerio. P. neurophilia exhibit broad host specifity, including members of the family Poecillidae, and both parasites infect the central nervous system. However, spore morphology and molecular phylogeny based on rDNA showed that the swamp guppy microsporidium (SGM) is distinct from P. neurophilia and related microsporidia (Microsporidium cerebralis and M. luceopercae). Spores of the SGM were smaller than others in the clade (3.6 µm long). Differences were also noted in histology; the SGM formed large aggregates of spores within neural tissues along with a high incidence of numerous smaller aggregates and single spores within the surface tissue along the ventricular spaces that extended submeninx, whereas P. neurophilia and M. cerebralis infect deep into the neuropile and cause associated lesions. Analysis of small subunit ribosomal DNA sequences showed that the SGM was <93% similar to these related microsporidia. Nevertheless, one of 2 commonly used PCR tests for P. neurophilia cross reacted with tissues infected with SGM. These data suggest that there could be other related microsporidia capable of infecting zebrafish and other laboratory fishes that are not being detected by these highly specific assays. Consequently, exclusive use of these PCR tests may not accurately diagnose other related microsporidia infecting animals in laboratory and ornamental fish facilities.

Characteristics of TB cases without documented sputum culture in the United States, 2011-2021.

Culture-based diagnostics are the gold standard for diagnosing pulmonary TB (PTB). We characterized culture practices by comparing cases with documented sputum culture to those without.Using multivariable logistic regression, we examined associations between PTB case characteristics and no documented sputum culture reported to the U.S. National TB Surveillance System during 2011-2021.Among 69,538 PTB cases analyzed, no sputum culture attempt was documented for 5,869 (8%). Non-sputum culture specimens were documented for 54%, 80%, and 89% of cases without documented sputum culture attempts among persons aged <15 years, 15-64, and 65+ years, respectively; bronchial fluid and lung tissue were common non-sputum specimens among cases in persons >15 years old. Having no documented sputum culture was associated with age <15 years (aOR 23.84, 99% CI 20.09-28.27) or ≥65 years (aOR 1.22, 99% CI 1.07-1.39), culture of a non-sputum specimen (aOR 6.57, 99% CI 5.93-7.28), residence in a long-term care facility (aOR 1.58, 99% CI 1.23-2.01), and receiving TB care outside of a health department (aOR 1.79, 99% CI 1.61-1.98).Inability to obtain sputum from children and higher diagnostic suspicion for disease processes that require tissue-based diagnostics could explain these findings..

5-hydroxytryphophan mitigates ergot alkaloid-induced suppression of serotonin and feed intake in cattle.

The impact of ergot toxicosis on livestock industries is detrimental and treatments are needed in many countries. The objective of this study was to evaluate the effects of acute exposure to ergot alkaloids and 5-hydroxytryptophan (5-HTP) supplementation on feed intake, serotonin metabolism, and blood metabolites in cattle. Eight Holstein steers (538 ±â€…18 kg) fitted with ruminal cannulas were used in a replicated 4 × 4 Latin Square design experiment with a 2 × 2 factorial treatment structure. The treatments were the combination of 0 (E-) or 15 µg ergovaline/kg BW (E+) and 0 (5HTP-) or 0.5 mg of 5-hydroxy-l-tryptophan/kg BW (5HTP+) administered daily for 6 d. Toxic endophyte-infected tall fescue seed was used to supply the daily dose of ergovaline. Endophyte-free seed was used to equalize seed intake between treatments. Ground seed was placed into the rumen immediately before feeding. The 5-HTP was dissolved in water and infused into the abomasum via the reticulo-omasal orifice. Blood was collected from a jugular vein catheter at 0, 1, 2, 4, 8, and 24 h after treatment administration. Ergovaline without 5-HTP (E+/5HTP-) decreased dry matter intake (DMI) in comparison to steers without ergovaline and 5-HTP (E-/5HTP-). However, 5-HTP infusion in association with ergovaline (E+/5HTP+) normalized the DMI. Although E + did not affect (P > 0.05) the area under the curve (AUC) of serum 5-HTP, 5-hydroxyindoleacetic acid, tryptophan, and kynurenine, serum and plasma serotonin concentrations were decreased (P < 0.05). The infusion of 5-HTP increased (P < 0.05) the AUC of serum 5-HTP, serum and plasma serotonin, and serum 5-hydroxyindoleacetic acid. In conclusion, acute exposure to ergot alkaloids reduced DMI and circulating serotonin in cattle but 5-HTP administration showed potential to normalize both circulating serotonin and feed intake.

Some grass species have a symbiotic relationship with an endophytic fungus that produces toxic ergot alkaloids which have detrimental impacts on herbivores. Ergot alkaloids have a significant impact on livestock production causing annual loss to the livestock industry that likely exceeds $1 billion. Effective treatment for this toxicosis is still needed. The objective of this study was to evaluate the effects of acute exposure to ergot alkaloids and 5-hydroxytryptophan supplementation on feed intake, serotonin metabolism, and blood metabolites in cattle. We found that 5-hydroxytryptophan administration has the potential to normalize both circulating serotonin and feed intake reduced by ergot alkaloid consumption.

Levodopa attenuates the feed intake reduction caused by ergot alkaloids in cattle.

Consumption of ergot alkaloids from endophyte-infected tall fescue results in losses to the livestock industry in many countries and a means to mitigate these losses is needed. The objective of this study was to evaluate intra-abomasal infusion of the dopamine precursor, levodopa (L-DOPA), on dopamine metabolism, feed intake, and serum metabolites of steers exposed to ergot alkaloids. Twelve Holstein steers (344.9 ±â€…9.48 kg) fitted with ruminal cannula were housed with a cycle of heat challenge during the daytime (32 °C) and thermoneutral at night (25 °C). The steers received a basal diet of alfalfa cubes containing equal amounts of tall fescue seed composed of a mixture of endophyte-free (E-) or endophyte-infected tall fescue seeds (E+) equivalent to 15 µg ergovaline/kg body weight (BW) for 9 d followed by intra-abomasal infusion of water (L-DOPA-) or levodopa (L-DOPA+; 2 mg/kg BW) for an additional 9 d. Afterward, the steers were pair-fed for 5 d to conduct a glucose tolerance test. The E+ treatment decreased (P = 0.005) prolactin by approximately 50%. However, prolactin increased (P = 0.050) with L-DOPA+. Steers receiving E+ decreased (P < 0.001) dry matter intake (DMI); however, when supplemented with L-DOPA+ the decrease in DMI was less severe (L-DOPA × E, P = 0.003). Also, L-DOPA+ infusion increased eating duration (L-DOPA × E, P = 0.012) when steers were receiving E+. The number of meals, meal duration, and intake rate were not affected (P > 0.05) by E+ or L-DOPA+. The L-DOPA+ infusion increased (P < 0.05) free L-DOPA, free dopamine, total L-DOPA, and total dopamine. Conversely, free epinephrine and free norepinephrine decreased (P < 0.05) with L-DOPA+. Total epinephrine and total norepinephrine were not affected (P > 0.05) by L-DOPA+. Ergot alkaloids did not affect (P > 0.05) circulating free or total L-DOPA, dopamine, or epinephrine. However, free and total norepinephrine decreased (P = 0.046) with E+. Glucose clearance rates at 15 to 30 min after glucose infusion increased with L-DOPA+ (P < 0.001), but not with E+ (P = 0.280). Administration of L-DOPA as an agonist therapy to treat fescue toxicosis provided a moderate increase in DMI and eating time and increased plasma glucose clearance for cattle dosed with E+ seed.

Fescue has become the dominant cool-season perennial grass in the southeastern region of the United States and is also found in other countries. Endophytes from a plant­fungus symbiotic relationship produce toxic alkaloids that have caused significant annual economic losses to the livestock industry. Treatments to alleviate this toxicosis are still demanded. This study evaluates the infusion of the dopamine precursor, levodopa (L-DOPA), to mitigate the toxicosis caused by ergot alkaloids. When L-DOPA was infused, eating duration increased and the decrease in feed intake caused by ergot alkaloids was less severe. Additionally, circulating dopamine and glucose clearance increased with L-DOPA. These results suggest that L-DOPA has the potential to aid in the mitigation of the toxicosis caused by ergot alkaloids.

Magnitude and persistence of higher estrus-associated temperatures in beef heifers and suckled cows.

Higher estrus-associated temperatures (HEAT) are a hallmark feature in sexually active females. The overarching aim of this study was to characterize the variability, magnitude, and persistence of HEAT in heifers and suckled beef cows as well as identify associated factors when occurring during thermoneutral conditions at the onset of the spring breeding season. In both heifers and cows, estrus was induced using a 7-d controlled internal drug release (CIDR)-PGF2α protocol. Vaginal temperature after prostaglandin F2α administration was recorded every 5 min using a Thermochron iButton affixed to a blank CIDR (containing no progesterone). Estrus was defined as when a heifer first stood to be mounted or when a cow had an Estrotect patch score of 3 or 4. Level of HEAT varied among individual animals. When comparing common HEAT variables using a mixed model with date nested within a year, maximum HEAT (39.9 ±â€…0.1 and 40.0 ±â€…0.1 °C) and duration (15.5 ±â€…0.8 and 15.4 ±â€…0.7) were similar in heifers and cows, respectively. However, the magnitude and persistence of HEAT differed. Total area under the HEAT curve was 117.1 ±â€…13.5 and 158.7 ±â€…12.3 for heifers vs cows, respectively (P = 0.0571). Further, 42.9% of heifers and 49% of cows had maximum HEAT ≥ 40 °C which persisted up to 6.5 and 10 h, respectively. When ambient conditions were predominantly thermoneutral, temperature humidity index had minimal impact on HEAT (mixed model, repeated measures over time). Toward identifying associated factors with different aspects of HEAT using best fit hierarchical linear regression models, baseline vaginal temperature and baseline duration were the most highly associated independent variables. Follicle size, estradiol and progesterone levels, and other available animal-related variables (e.g., age, weight, hair coat score) explained only a small amount of variation in HEAT. In summary, level of HEAT varies in estrus females even under thermoneutral conditions. Because HEAT can persist for an extended time, direct effects on fertility important components are unavoidable. Whether HEAT is a good or bad component of the periovulatory microenvironment is the basis of ongoing and future studies.

When striving for a pregnancy, estrus is a critically important event. Higher estrus-associated temperatures (HEAT) are a hallmark feature in sexually active females. The importance of HEAT for pregnancy, however, remains unclear. Toward filling this critical knowledge gap, efforts described in the current study focused on examining variability of HEAT in individual animals, 2) defining the magnitude and persistence of HEAT, 3) identifying HEAT-associated factors, and 4) examining the similarity of HEAT between heifers and suckled beef cows when occurring at the onset of a spring breeding season. Although the magnitude and persistence of HEAT varied, 42.9% of heifers and 49% of cows reached temperatures ≥ 40 °C which in some cases persisted up to 6.5 and 10 h, respectively. When attempting to identify factors that could explain why some females exhibiting estrus remained hot for an extended time, available animal and environmental data contributed little. Even so, because HEAT can persist for an extended time, direct effects on fertility important components are unavoidable. Whether too much HEAT is good or bad for pregnancy is the basis of ongoing and future studies.

Oviduct and endometrial epithelium improve in vitro produced bovine embryo developmental kinetics.

In brief: Standard in vitro produced (IVP) bovine embryo culture media limit embryonic development. Culturing IVP bovine embryos in standard IVP bovine embryo culture media conditioned with oviduct and/or endometrial cells improves blastocyst formation and reduces the time to formation. Abstract: In vitro embryo production in cattle greatly impacts blastomere biochemistry, embryo rate of development and pre- and post-transfer survival. In vivo, the bovine embryo migrates through the oviduct isthmus before entering the uterus on approximately day 4 of development where it remains unattached within the uterine lumen until day 20 of gestation. During this time, the embryo is sequentially exposed to oviduct followed by endometrial secretions that support embryonic development. Considering this, we tested the effect of culturing in vitro produced (IVP) bovine embryos sequentially in oviduct epithelial- (OEp; days 1-3) followed by endometrial epithelial- (EEp) or EEp and fibroblast cell (EEp/F; days 4-8)-conditioned media on embryonic development using a time-lapse monitoring system. Compared to control, culturing IVP embryos in EEp- or EEp/F-conditioned media without prior culture in OEp-conditioned media increased blastocyst formation (P < 0.05) and reduced the time to blastocyst formation (P < 0.05). Culturing IVP bovine embryos in OEp-conditioned media followed by EEp- or EEp/F-conditioned media, however, had the greatest impact on embryo developmental kinetics and increased morula and blastocyst formation (P < 0.05) and reduced time to formation (P < 0.05). Day 8 blastocyst cell numbers, diameter and quality were not significantly different, although, blastocyst quality scores were less (indicative of better quality) for all cell-conditioned media compared to control. In conclusion, IVP bovine embryo development may be improved using a sequential embryo culture system involving bovine oviduct followed by endometrial cell-conditioned media.

Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma.

Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma.

Assessment of Cellulose Nanofiber-Based Elastase Biosensors to Inflammatory Disease as a Function of Spacer Length and Fluorescence Response.

Inflammatory disease biomarker detection has become a high priority in point-of-care diagnostic research in relation to chronic wounds, with a variety of sensor-based designs becoming available. Herein, two primary aspects of biosensor design are examined: (1) assessment of a cellulose nanofiber (CNF) matrix derived from cotton ginning byproducts as a sensor transducer surface; and (2) assessment of the relation of spacer length and morphology between the CNF cellulose backbone and peptide fluorophore as a function of sensor activity for porcine pancreatic and human neutrophil elastases. X-ray crystallography, specific surface area, and pore size analyses confirmed the suitability of CNF as a matrix for wound care diagnostics. Based upon the normalized degree of substitution, a pegylated-linker connecting CNF transducer substrate to peptide fluorophore showed the greatest fluorescence response, compared to short- and long-chain alkylated linkers.

A retrospective cohort study evaluating pregnancy outcomes in women with MIDD.

AIMS: The most common pathogenic mitochondrial mutation associated with mitochondrial disease is m.3243A>G. Increased obstetric complications, such as spontaneous abortion, gestational diabetes (GDM), preterm delivery, and preeclampsia, have been reported in women carrying this mutation. We aimed to determine the fetal and maternal outcomes in pregnant women with mitochondrial disease. METHODS: We retrospectively studied the obstetric and perinatal outcomes in 88 pregnancies of 26 women with genetically confirmed mitochondrial disease (m.3243A>G in the MTTL1 gene (n = 25); m.12258C>A in the MT-TS2 gene (n = 1)). Outcomes included pregnancy related complications, mode of delivery, gestational age at delivery and birthweight. RESULTS: Mean heteroplasmy rate was 18%. The miscarriage rate was higher than background at 25%. 21 pregnancies (24%) were complicated by GDM; 9 pregnancies (13.6%) had a preterm delivery and 2 of them (3%) an extreme premature delivery < 32 weeks. One woman had preeclampsia and one had a postpartum hemorrhage. The caesarean section (CS) rate was 20%. For every unit increase in maternal heteroplasmy levels there was a 26% increased risk of undergoing an assisted operative vaginal delivery (OR 1.26, 95% CI 1.04-1.53, P = 0.002, Bonferroni corrected P = 0.005) and an 18% increased risk of undergoing a CS (OR 1.18, 95% CI 1.01-1.39, P = 0.01, Bonferroni corrected P = 0.03) compared to a spontaneous vaginal delivery. There was a statistical significant correlation between maternal and offspring heteroplasmy levels. Spearman correlation rho = 0.96, 95% CI 0.78-0.99, P = 0.0002. CONCLUSION: Women with mitochondrial disease appear to have more frequent obstetric complications including miscarriage and GDM. Pre-pregnancy diagnosis of m.3243A>G will enable the counseling of women and increase awareness of possible obstetric complications.

Preparation and Activity of Hemostatic and Antibacterial Dressings with Greige Cotton/Zeolite Formularies Having Silver and Ascorbic Acid Finishes.

The need for prehospital hemostatic dressings that exert an antibacterial effect is of interest for prolonged field care. Here, we consider a series of antibacterial and zeolite formulary treatment approaches applied to a cotton-based dressing. The design of the fabric formulations was based on the hemostatic dressing TACGauze with zeolite Y incorporated as a procoagulant with calcium and pectin to facilitate fiber adherence utilizing silver nanoparticles, and cellulose-crosslinked ascorbic acid to confer antibacterial activity. Infra-red spectra were employed to characterize the chemical modifications on the dressings. Contact angle measurements were employed to document the surface hydrophobicity of the cotton fabric which plays a role in the contact activation of the coagulation cascade. Ammonium Y zeolite-treated dressings initiated fibrin equal to the accepted standard hemorrhage control dressing and showed similar improvement with antibacterial finishes. The antibacterial activity of cotton-based technology utilizing both citrate-linked ascorbate-cellulose conjugate analogs and silver nanoparticle-embedded cotton fibers was observed against Staphylococcus aureus and Klebsiella pneumoniae at a level of 99.99 percent in the AATCC 100 assay. The hydrogen peroxide levels of the ascorbic acid-based fabrics, measured over a time period from zero up to forty-eight hours, were in line with the antibacterial activities.