Nevin Manimala

J Dairy Sci. 2023 Oct 6:S0022-0302(23)00717-8. doi: 10.3168/jds.2023-23741. Online ahead of print.

ABSTRACT

The aim of this study was to infer the effects of heat stress (HS) of dams during late gestation on direct and maternal genetic parameters for traits related to milk production and milk quality parameters (90,558 records) in Italian browns Swiss cattle (12,072 cows in 617 herds). Daily Average Temperature-humidity indices (THI) during the last 56 d of pregnancy were calculated, using the climate data from the nearest public weather station for each herd. Heat load effects were considered as the average across the entire periods considering a thermoneutrality condition for data below the THI 60. For parameter estimation a random regression model using the second order Legendre polynomial regression coefficient for THI considering both animal and maternal effect for heat load. Direct heritability increased sharply from THI 60 to 65, then decreased gradually up to THI ∼72, and sharply thereafter. Maternal heritability showed a different trend, with values close to 0 up until to THI 65 and slightly increasing toward extreme THI values. The study suggests a lower threshold of THI 60 for the onset of heat stress. Higher heritability values indicate greater selective efficiency in the THI range of 65-70, even if an higher standard deviation value have been detected. The effects of high THI during intrauterine life varied among traits with different heritability levels. Genetic correlations for milk, fat and protein content at 60 THI with increasing value of environmental variable, remained constant (∼0.90) until THI >75, where they slightly decreased (∼0.85). Fat and protein yields, as well as milk and ECM, showed correlations dropping to 0.80 around THI 67-68 and stabilizing between 0.75 and 0.85 at extreme THI values. Maternal component correlations dropped close to zero, with negative values for protein content at THI 65-70. Antagonism between direct and maternal components was stronger for intermediate THI values but less divergent for extremes. G x E interaction was observed, indicating the selection of resilient animals would be theoretically possible. The application of climate variables in selection schemes should in the future take into account above all the dimensions of the genetic correlations to be able to decide between the simple inclusion of the environmental effect in the statistical models rather than a real parallel genetic evaluation.

PMID:37806626 | DOI:10.3168/jds.2023-23741

J Dairy Sci. 2023 Oct 6:S0022-0302(23)00722-1. doi: 10.3168/jds.2023-23851. Online ahead of print.

ABSTRACT

Mastitis is one of the most significant diseases in dairy cows and causes several economic losses. Somatic cell count (SCC) is often used as an indirect diagnostic tool for mastitis, especially for subclinical mastitis (SCM) where no symptoms or signs can be detected. Streptococcus agalactiae is one of the main causes of contagious mastitis, while Prototheca spp. is an alga inducing environmental mastitis that is not always correlated with increased milk SCC. The aim of this study was to evaluate the changes in the metabolomic profile of blood in relation to subclinical intramammary infection (sIMI) in dairy cows. In addition, differences due to the etiologic agent causing mastitis were also considered. Forty Holstein-Friesian dairy cows in mid and late lactation were enrolled in this study with a cross-sectional design. Based on the bacteriological examination of milk, the animals were divided into 3 groups: Group CTR (control group; n = 16); Group A (affected by SCM with IMI of Streptococcus agalactiae; n = 17); and Group P (affected by SCM with IMI of Prototheca spp.; n = 7). Blood samples were collected in tubes containing clot activator from jugular vein. The serum aliquot was stored until metabolomic analysis by ¹H-NMR. Statistical analysis was conducted fitting a linear model with the group as fixed effect and SCC as covariate. Forty-two metabolites were identified and among them, 10 were significantly different among groups. Group A and P showed greater level of His and lactose, and lower level of acetate, Asn, and dimethylamine compared with Group CTR. Group A showed high level of Val, while the Group P showed also high level of Cit and methylguanidine, and lower level of 3-hydroxybutyrate, acetone, allantoin, carnitine, citrate, and ethanol. These metabolites were related to ruminal fermentations, energy metabolism, urea synthesis and metabolism, immune and inflammatory response, and mammary gland permeability. These results are suggestive of a systemic involvement of sIMI and that the metabolic profile of animals with SCM undergoes changes related to the etiological agent of mastitis.

PMID:37806625 | DOI:10.3168/jds.2023-23851

J Dairy Sci. 2023 Oct 6:S0022-0302(23)00718-X. doi: 10.3168/jds.2023-23772. Online ahead of print.

ABSTRACT

Information on dry matter intake (DMI) and energy balance (EB) at the animal and herd level is important for management and breeding decisions. However, routine recording of these traits at commercial farms can be challenging and costly. Fourier-transform mid-infrared (FT-MIR) spectroscopy is a non-invasive technique applicable to a large cohort of animals that is routinely used to analyze milk components and is convenient for predicting complex phenotypes that are typically difficult and expensive to obtain on a large scale. We aimed to develop prediction models for EB and use the predicted phenotypes for genetic analysis. First, we assessed prediction equations using 4,485 phenotypic records from 167 Holstein cows from an experimental station. The phenotypes available were body weight (BW), milk yield (MY) and milk components, weekly-averaged DMI, and FT-MIR data from all milk samples available. We implemented mixed models with Bayesian approaches and assessed them through 50 randomized replicates of a 5-fold cross-validation. Second, we used the best prediction models to obtain predicted phenotypes of EB (EBp) and DMI (DMIp) on 5 commercial farms with 2,365 phenotypic records of MY, milk components and FT-MIR data, and BW from 1,441 Holstein cows. Third, we performed a GWAS and estimated heritability and genetic correlations for energy content in milk (EnM), BW, DMIp, and EBp using the genomic information available on the cows from commercial farms. The highest correlation between the predicted and observed phenotype (r_y,y^) was obtained with DMI (0.88) and EB (0.86), while predicting BW was, as anticipated, more challenging (0.69). In our study, models that included FT-MIR information performed better than models without spectra information in the 3 traits analyzed, with increments in prediction correlation ranging from 5 to 10%. For the predicted phenotypes calculated by the prediction equations and data from the commercial farms the heritability ranged between 0.11 and 0.16 for EnM, predicted DMI (DMIp) and predicted EB (EBp), and 0.42 for BW. The genetic correlation between EnM and BW was -0.17, with DMIp was 0.40 and with EBp was -0.39. From the GWAS, we detected one significant QTL region for EnM, and 3 for BW, but none for DMIp and EBp. The results obtained in our study support previous evidence that FT-MIR information from milk samples contribute to improve the prediction equations for DMI, BW, and EB, and these predicted phenotypes may be used for herd management and contribute to the breeding strategy for improving cow performance.

PMID:37806624 | DOI:10.3168/jds.2023-23772

Am J Obstet Gynecol. 2023 Oct 6:S0002-9378(23)00730-5. doi: 10.1016/j.ajog.2023.09.100. Online ahead of print.

ABSTRACT

BACKGROUND: The US Food and Drug Administration (FDA) supports innovations to facilitate new indications for high-risk human papillomavirus (HPV) testing. This report describes the retrospective testing of stored specimens and analysis of existing data to efficiently and cost-effectively support a new indication for the Onclarity HPV assay (Becton, Dickinson and Company; BD Life Sciences Integrated Diagnostic Solutions; Sparks, MD, USA). The performance of this index test was compared to a predicate test, the cobas HPV assay (Roche Diagnostics; Indianapolis, IN, USA). Both HPV assays are based on real-time polymerase chain reaction (PCR) platforms that detect the presence of 14 high-risk HPV genotypes. The predicate assay reports HPV16 and 18 as individual results and the other 12 HPV genotypes as one pooled result. The index assay reports nine, independent results (HPV 16, 18, 31, 33/58, 35/39/68, 45, 51, 52, 56/59/66). The index and predicate assays are both FDA-approved for cervical cancer screening but at the time that this study was initiated, the index HPV assay was not approved for use with cervical specimens collected in PreservCyt (Hologic, Inc.; San Diego, CA, USA) liquid-based cytology (LBC) media.

OBJECTIVES: The performance of the index HPV assay was compared to the predicate HPV assay for detection of cervical intraepithelial neoplasia grades 2 or 3 or worse (≥CIN2 or ≥CIN3) using PreservCyt LBC specimens collected from women ages 21-65 years. The ability of the index test’s extended genotyping to stratify ≥CIN2 or ≥CIN3 risks, using these specimens, was also evaluated.

STUDY DESIGN: The New Mexico HPV Pap Registry was used to select an age- and cytology-stratified random sample of 19,879 women undergoing opportunistic cervical screening and follow-up in routine clinical practice across New Mexico. A random subset of PreservCyt specimens from 4,820 of these women was selected for paired testing by the index and predicate HPV assays within age and cytology strata and included women with or without cervical biopsy follow-up. Point estimate differences and ratios were calculated for cervical disease detection and positivity rates, respectively, with 95% confidence intervals (95% CI) to determine statistical significance. The cumulative risk of ≥CIN2 or ≥CIN3, with up to five-years follow-up, was estimated for the index assay using Kaplan-Meier methods.

RESULTS: Five-year cumulative ≥CIN3 detection was 5.6% and 4.6% for the index and predicate assay, respectively (difference=1.0% [.5% to 1.5%]). The ≥CIN3 positivity rate within <1-year for the index and predicate assay was 95.3% and 94.5%, respectively (ratio=1.01 [.98 to 1.06]). The ≥CIN3 cumulative positivity rates for the index and predicate assays were also similar at five-years. Among cases of ≥CIN3, positive agreement between the index and predicate assay for HPV16 and HPV18, was 100% (95%CI=95.0% to 100%), and 90.9% (95%CI=62.3% to 98.4%), respectively. HPV16 carried the highest ≥CIN2/3 risk, followed by HPV18/31/33/58/52/45, and then HPV35/56/59/51/56/59/66.

CONCLUSIONS: The index and predicate HPV assays demonstrated equivalent performance, and extended HPV genotyping, using the index assay, provided effective ≥CIN2 and ≥CIN3 risk stratification, supporting a new indication for use of the index assay with PreservCyt.

PMID:37806613 | DOI:10.1016/j.ajog.2023.09.100

Am J Pharm Educ. 2023 Oct 6:100599. doi: 10.1016/j.ajpe.2023.100599. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the impact of a critical care pharmacy elective (CCPE) on student performance in other courses in the Doctor of Pharmacy curriculum that emphasize clinical reasoning and decision-making.

METHODS: This is a retrospective, cohort study including all students from the 2019-2021 graduating classes enrolled in required courses, Pharmacotherapy and Integrated Patient Cases (IPC). Students were divided for comparison based on completion of the CCPE. The primary outcome was outstanding performance, defined by a final course grade 90% or above, in Pharmacotherapy and IPC. Baseline characteristics and outcomes were analyzed using descriptive statistics and the Chi-squared test or two-sided t-test for categorical and continuous variables, respectively. Binary logistic regression models were constructed to identify variables associated with the primary outcome.

RESULTS: Of 377 students included, 129 (34%) completed the CCPE. Baseline characteristics were similar between both groups, except more females completed the CCPE. Students that completed the CCPE were not more likely to demonstrate outstanding performance in Pharmacotherapy III (20% vs. 30%) or Pharmacotherapy IV (27% vs. 24%), but were more likely in IPC (34% vs 23%). In the adjusted analysis, CCPE students were almost twice as likely to exhibit outstanding performance in IPC.

CONCLUSION: Students that completed the CCPE were more likely to demonstrate outstanding performance in IPC, but not in either of the Pharmacotherapy courses. Students may benefit from practicing clinical reasoning earlier in the curriculum to build up to effective and efficient clinical decision-making. Implications of course structure on student performance should be further explored.

PMID:37806556 | DOI:10.1016/j.ajpe.2023.100599

Neuroscience. 2023 Oct 6:S0306-4522(23)00441-4. doi: 10.1016/j.neuroscience.2023.09.017. Online ahead of print.

ABSTRACT

Hypertensive individuals are at a high risk of stroke, and thus, prevention of stroke in hypertensive patients is essential. Metabolomics and lipidomics can be used to identify diagnostic biomarkers and conduct early assessments of stroke risk in hypertensive populations. In this study, serum samples were collected from 30 hypertensive ischemic stroke (IS), 30 matched hypertensive and 30 matched healthy participants. Metabolomics and lipidomics analyses were conducted via liquid chromatography-tandem mass spectrometry, and the data were analyzed using multivariate and univariate statistical methods. A random forest algorithm and binary logistic regression were used to screen the biomarkers and establish diagnostic model. We detected 21 differential metabolites and 38 differential lipids between the hypertensive IS and healthy group. Moreover, we found 18 differential metabolites and 31 differential lipids between the hypertensive IS and hypertension group. In particular, the following seven metabolites or lipids distinguished the hypertensive IS from the healthy group: 4-hydroxyphenylpyruvic acid, cafestol, phosphatidylethanolamine (PE) (18:0p/18:2), PE (16:0e/20:4), (O-acyI)-1-hydroxy fatty acid (36:3), PE (16:0p/20:3) and PE (18:1p/18:2) (rep). The following seven biomarkers distinguished the hypertensive IS from the hypertension group: diglyceride (DG) (20:1/18:2), PE (18:0p/18:2), PE (16:0e/22:5), phosphatidylcholine (40:7), dimethylphosphatidylethanolamine (50:3), DG (18:1/18:2), and 4-hydroxyphenylpyruvic acid. The aforementioned panels had good diagnostic and predictive ability for hypertensive IS. Our study determines the metabolomic and lipidomic profiles of hypertensive IS patients and thereby identifies potential biomarkers of the presence of IS in hypertensive populations.

PMID:37806545 | DOI:10.1016/j.neuroscience.2023.09.017

J Ethnopharmacol. 2023 Oct 6:117249. doi: 10.1016/j.jep.2023.117249. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Cola nitida (Vent.) Schott & Endl. are among the common medicinal plants employed in traditional medicine for treating diabetes and its complications.

AIM OF THE STUDY: The present study investigated the effect of Cola nitida infusion on the expression of key genes involved in insulin signaling vis-à-vis Insulin receptor substrate 1 (IRS-1), tumor protein P53 gene, glucose transporter type 4 (GLUT4), phosphoinositide 3-kinases (PI3K) and B-cell lymphoma-2 (BCL2) in skeletal muscles of type 2 diabetic (T2D) rats.

METHODS: T2D rats were administered C. nitida infusion at low and high doses (150 and 300 mg/kg bodyweight, respectively), while a high dose of the infusion was administered to a normal toxicological group. Metformin served as the standard antidiabetic drug. The rats were sacrificed at the end of the experimental period. Their psoas muscles were harvested and assayed for the expressions of IRS1, P53, GLUT4, PI3K and BCL2. The studied genes were further subjected to enrichment analysis using the ShinyGO 0.76 online software.

RESULTS: Induction of T2D upregulated the expressions of IRS-1, p53, PI3K and BCL2 in psoas muscles, while concomitantly downregulating GLUT4 expression. These expressions were significantly reversed in T2D rats treated with C. nitida infusion, and statistically significant compared to metformin. Gene enrichment analysis revealed the genes were linked to intrinsic pathways and biological processes involved in insulin resistance. The infusion further improved muscle glucose uptake, ex vivo. Molecular docking and molecular dynamics stimulation of C. nitida infusion phytoconstituents, caffeine and theobromine with IRS-1, P53, GLUT4, PI3K and BCL2 revealed a strong binding affinity as evident by the RMSD and RMSF values.

CONCLUSION: These results indicate the potentials of C. nitida infusion to improve glucose homeostasis in skeletal muscles of diabetic rats.

PMID:37806534 | DOI:10.1016/j.jep.2023.117249

World Neurosurg. 2023 Oct 6:S1878-8750(23)01410-9. doi: 10.1016/j.wneu.2023.10.015. Online ahead of print.

ABSTRACT

OBJECTIVE: Cervical microendoscopic laminoforaminotomy (MELF) has been proven to be an effective, motion preserving procedure for the surgical treatment of cervical radiculopathy. Cervical four (C4) radiculopathies are often unrecognized by the initial evaluating physician and may be misdiagnosed as axial neck pain. In this study, we compare MELF to anterior cervical disc fusion (ACDF) for C4 radiculopathy in the largest series of minimally invasive foraminotomy for C4 radiculopathy to date.

METHODS: This is a single-institution retrospective chart review of 42 cases for C4 radiculopathy, 21 MELF and 21 ACDF. Primary outcome measures were length of surgery, length of hospital stay, and time to return to work. Secondary outcome measures were VAS neck pain and reoperation rate.

RESULTS: All patients were diagnosed with a unilateral C4 radiculopathy using MRI or steroid injections. The length of surgery, and length of hospital stay were significantly decreased in the MELF group compared to ACDF. VAS neck pain significantly decreased for patients in both groups, but the difference between MELF and ACDF was not statistically significant. There were no major complications. No patient underwent revision at the index level or adjacent levels in the MELF group.

CONCLUSION: We demonstrate that C4 radiculopathy can be identified with appropriate history, physical exam, and targeted nerve root injections. When identified, these radiculopathies that fail conservative therapy can be effectively treated with cervical microendoscopic laminoforaminotomy, with comparable outcomes to ACDF. The length of surgery and length of stay are reduced when compared to ACDF.

PMID:37806518 | DOI:10.1016/j.wneu.2023.10.015

J Foot Ankle Surg. 2023 Oct 6:S1067-2516(23)00247-8. doi: 10.1053/j.jfas.2023.09.014. Online ahead of print.

ABSTRACT

Hammertoe deformity is a common forefoot pathology, characterized by a progressive deformity with dorsiflexion of the proximal phalanx on the metatarsal head at the metatarsal phalangeal joint (MTPJ) and plantarflexion of the intermediate phalanx on the proximal phalanx at the proximal interphalangeal joint (PIPJ). While there literature available discussing open techniques for hammertoe correction, there is a lack of publications discussing minimally invasive techniques, therefore the objective of this retrospective comparative study is to evaluate minimally invasive versus open hammertoe surgery in terms of time to osseous union, complications, recurrence, and return to full activity. Sixty eight feet amongst 41 patients met the inclusion criteria and were surveyed. Among the 68 feet, 54 feet (124 toes) underwent minimally invasive hammertoe correction and 14 feet (22 toes) underwent open hammertoe correction. Time to osseous union (weeks) in the MIS group was 8.76 ± 2.31 weeks with similar outcomes to the open group with union at 8.42 ± 2.31 (p=0.65). Return to activity (weeks) was 10.47 ± 3.45 in the MIS group and 9.92 ± 3.03 in the open group with no statistical significance (p=0.62). There was 4 recurrent hammertoe deformities in the MIS group (3.23%) with no recurrent hammertoes in the open group (0%). In the MIS group 5 hammertoes had unplanned hardware removal (4.03%) compared to 0 in the open group. There was no statistical significance for both recurrence and unplanned hardware removal (p=1). Overall, we concluded that both techniques are equivocal with no detectable statistical difference.

PMID:37806485 | DOI:10.1053/j.jfas.2023.09.014

Environ Res. 2023 Oct 6:117312. doi: 10.1016/j.envres.2023.117312. Online ahead of print.

ABSTRACT

BACKGROUND: Polybrominated biphenyls (PBBs), a class of endocrine disrupting chemicals, were the main chemicals present in one of the largest industrial accidents in the United States. We investigated the association between serum PBB-153 levels and autoimmune disorders among members of the Michigan PBB Registry.

METHODS: Eight hundred and ninety-five members of the registry had both a serum PBB-153 measurement and had completed one or more questionnaires about autoimmune disorders. Autoimmune disorders were examined collectively and within specific organ systems. Sex-stratified unadjusted and adjusted log-binomial models were used to examine the association between tertiles of serum PBB-153 levels and autoimmune disorders. Models were adjusted by lifestage at exposure (in utero, childhood, adulthood), smoking history (never, past, current), and total serum lipid levels (continuous). We utilized cubic spline models to investigate non-linearity between serum PBB-153 levels and the prevalence of autoimmune disorders.

RESULTS: Approximately 12.9% and 20.7% of male and female participants reported having one or more autoimmune disorders, respectively. After adjustment for potential confounders, we observed no association between PBB-153 tertiles and the composite classification of ‘any autoimmune disorder’ in either sex. We observed some evidence for an association between serum PBB-153 levels and rheumatoid arthritis in males and females; however, this was not statistically significant in females. We also observed some evidence for an association between serum PBB-153 levels and neurological- and thyroid-related autoimmune disorders in females, but again this was not statistically significant. Additionally, we identified dose-response curves for serum PBB-153 levels and the prevalence of autoimmune disorders that differed by lifestage of exposure and sex.

CONCLUSIONS: We observed some evidence that increasing serum PBB-153 levels were associated with three specified autoimmune disorders. Studies focusing on these three autoimmune disorders and the potential non-linear trend differences by lifestage of exposure warrant further investigation.

PMID:37806482 | DOI:10.1016/j.envres.2023.117312