Intravenous lipopolysaccharide challenge in early versus mid-lactation dairy cattle. I: The immune and inflammatory responses.

Cows in early lactation (EL) are purportedly immune suppressed, which renders them more susceptible to disease. Thus, the study objective was to compare key biomarkers of immune activation from i.v. lipopolysaccharide (LPS) between EL and mid-lactation (ML) cows. Multiparous EL (20 ± 2 DIM; n = 11) and ML (131 ± 31 DIM; n = 12) cows were enrolled in a 2 × 2 factorial design and assigned to 1 of 2 treatments by lactation stage (LS): (1) EL (EL-LPS; n = 6) or ML (ML-LPS; n = 6) cows administered a single LPS bolus from Escherichia coli O55:B5 (0.09 µg/kg of body weight), or (2) pair-fed (PF) EL (EL-PF; n = 5) or ML (ML-PF; n = 6) cows administered i.v. saline. After LPS administration, cows were intensely evaluated for 3 d to analyze their response and recovery to LPS. Rectal temperature increased in LPS relative to PF cows (1.1°C in the first 9 h), and the response was more severe in EL-LPS relative to ML-LPS cows (2.3 vs. 1.3°C increase at 4 h post-LPS; respectively). Respiration rate increased only in EL-LPS cows (47% relative to ML-LPS in the first h post-LPS). Circulating tumor necrosis factor-α, IL-6, monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1ß, and IFN-γ-inducible protein-10 increased within the first 6 h after LPS and these changes were exacerbated in EL-LPS relative to ML-LPS cows (6.3-, 4.8-fold, 57%, 93%, 10%, and 61% respectively). All cows administered LPS had decreased circulating iCa relative to PF cows (34% at the 6 h nadir), but the hypocalcemia was more severe in EL-LPS than ML-LPS cows (14% at 6 h nadir). In response to LPS, neutrophils decreased regardless of LS, then increased into neutrophilia by 24 h in all LPS relative to PF cows (2-fold); however, the neutrophilic phase was augmented in EL- compared with ML-LPS cows (63% from 24 to 72 h). Lymphocytes and monocytes rapidly decreased then gradually returned to baseline in LPS cows regardless of LS; however, monocytes were increased (57%) at 72 h in EL-LPS relative to ML-LPS cows. Platelets were reduced (46%) in LPS relative to PF cows throughout the 3-d following LPS, and from 24 to 48 h, platelets were further decreased (41%) in EL-LPS compared with ML-LPS. During the 3-d following LPS, serum amyloid A (SAA), LPS-binding protein (LBP), and haptoglobin (Hp) increased in LPS compared with PF groups (9-fold, 72%, and 153-fold, respectively), and the LBP and Hp responses were more exaggerated in EL-LPS than ML-LPS cows (85 and 79%, respectively) whereas the SAA response did not differ by LS. Thus, our data indicates that EL immune function does not appear "suppressed," and in fact many aspects of the immune response are seemingly functionally robust.

Comparative MRI analysis of the forebrain of three sauropsida models.

The study of the brain by magnetic resonance imaging (MRI) allows to obtain detailed anatomical images, useful to describe specific encephalic structures and to analyze possible variabilities. It is widely used in clinical practice and is becoming increasingly used in veterinary medicine, even in exotic animals; however, despite its potential, its use in comparative neuroanatomy studies is still incipient. It is a technology that in recent years has significantly improved anatomical resolution, together with the fact that it is non-invasive and allows for systematic comparative analysis. All this makes it particularly interesting and useful in evolutionary neuroscience studies, since it allows for the analysis and comparison of brains of rare or otherwise inaccessible species. In the present study, we have analyzed the prosencephalon of three representative sauropsid species, the turtle Trachemys scripta (order Testudine), the lizard Pogona vitticeps (order Squamata) and the snake Python regius (order Squamata) by MRI. In addition, we used MRI sections to analyze the total brain volume and ventricular system of these species, employing volumetric and chemometric analyses together. The raw MRI data of the sauropsida models analyzed in the present study are available for viewing and downloading and have allowed us to produce an atlas of the forebrain of each of the species analyzed, with the main brain regions. In addition, our volumetric data showed that the three groups presented clear differences in terms of total and ventricular brain volumes, particularly the turtles, which in all cases presented distinctive characteristics compared to the lizards and snakes.

Intravenous lipopolysaccharide challenge in early versus mid-lactation dairy cattle. II: The production and metabolic responses.

Most immunometabolic research utilizes mid-lactation (ML) cows. Cows in early lactation (EL) are in a presumed state of immune suppression/dysregulation and less is known about how they respond to a pathogen. Study objectives were to compare the production and metabolic responses to i.v. lipopolysaccharide (LPS) and to differentiate between the direct effects of immune activation and the indirect effects of illness-induced hypophagia in EL and ML cows. Cows in EL (n = 11; 20 ± 2 d in milk) and ML (n = 12; 131 ± 31 d in milk) were enrolled in a 2 × 2 factorial design containing 2 experimental periods (P). During P1 (3 d), cows were fed ad libitum and baseline data were collected. At the initiation of P2 (3 d), cows were randomly assigned to 1 of 2 treatments by lactation stage (LS): (1) EL (EL-LPS; n = 6) or ML (ML-LPS; n = 6) cows administered i.v. a single bolus of 0.09 µg LPS/kg of body weight; Escherichia coli O55:B5 or (2) pair-fed (PF) EL (EL-PF; n = 5) or ML (ML-PF; n = 6) cows administered i.v. saline. Administering LPS decreased dry matter intake (DMI) and this was more severe in EL-LPS than ML-LPS cows (34 and 11% relative to baseline, respectively). By design, P2 DMI patterns were similar in the PF groups compared with their LPS counterparts. Milk yield decreased following LPS (42% on d 1 relative to P1) and despite an exacerbated decrease in EL-LPS cows on d 1 (25% relative to ML-LPS), remained similar between LS from d 2-3. EL-LPS had increased milk fat content, but no difference in protein and lactose percentages compared with ML-LPS cows. Further, cumulative ECM yield was increased (21%) in EL-LPS compared with ML-LPS cows. During P2, EL-LPS cows had a more intense increase in milk urea nitrogen (MUN) and blood urea nitrogen (BUN) than ML-LPS and EL-PF cows. Administering LPS did not cause hypoglycemia in either EL-LPS or ML-LPS cows, but glucose was increased (33%) in EL-LPS compared with EL-PF. Hyperinsulinemia occurred post-LPS, and insulin was further increased in ML-LPS than EL-LPS cows (2.2-fold at 12 h peak). During P2, circulating glucagon increased only in EL-LPS cows (64% relative to all other groups). Both EL groups had increased NEFA at 3 and 6 h post-LPS from baseline (56%), but NEFA in EL-LPS cows gradually returned to baseline thereafter and were reduced relative to EL-PF until 36 h (50% from 12 to 24 h). Alterations in ß-hydroxybutyrate (BHB) did not differ between ML groups, but EL-LPS had reduced BHB compared with EL-PF from 24 to 72 h (51%). Results indicate that there are distinct LS differences in the anorexic and metabolic responses to immune activation. Collectively, EL cows are more sensitive to the catabolic effects of LPS than ML cows, but these exacerbated metabolic responses appear coordinated to fuel an augmented immune system while simultaneously supporting milk synthesis.

Intramammary lipopolysaccharide challenge in early versus mid-lactation dairy cattle: immune, production, and metabolic responses.

Study objectives were to compare the immune response, metabolism and production following intramammary lipopolysaccharide (IMM LPS) administration in early and mid-lactation cows. Early (E-LPS; n = 11; 20 ± 4 d in milk [DIM]) and mid- (M-LPS; n = 10; 155 ± 40 DIM) lactation cows were enrolled in an experiment consisting of 2 periods (P). During P1 (5 d) cows were fed ad libitum and baseline data were collected, including liver and muscle biopsies. At the beginning of P2 (3 d) cows received 10 mL sterile saline containing 10 µg of LPS from Escherichia coli O111:B4/mL into the left rear quarter of the mammary gland, and liver and muscle biopsies were collected at 12 h post-LPS. Tissues were analyzed for metabolic flexibility, which measures substrate switching capacity from pyruvic acid to palmitic acid oxidation. Data were analyzed with the MIXED procedure in SAS 9.4. Rectal temperature was assessed hourly for the first 12 h post-LPS and every 6 h thereafter for the remainder of P2. All cows developed a febrile response following LPS, but E-LPS had a more intense fever than M-LPS cows (0.7°C at 5 h after LPS). Blood samples were collected at 0, 3, 6, 9, 12, 24, 36, 48, and 72 h post-LPS for analysis of systemic inflammation and metabolism parameters. Total serum Ca decreased after LPS (26% at 6 h nadir) but did not differ by lactation stage (LS). Circulating neutrophils decreased, then increased post-LPS in both LS, but E-LPS had exaggerated neutrophilia (56% from 12 to 48 h) compared with M-LPS. Haptoglobin increased after LPS (15-fold) but did not differ by LS. Many circulating cytokines were increased post-LPS, and IL-6, IL-10, TNF-α, MCP-1, and IP-10 were further augmented in E-LPS compared with M-LPS cows. Relative to P1, all cows had reduced milk yield (26%) and dry matter intake (DMI; 14%) on d 1 that did not differ by lactation stage (LS). Somatic cell score increased rapidly in response to LPS regardless of LS and gradually decreased from 18 h onwards. Milk component yields decreased after LPS. However, E-LPS had increased fat (11%) and tended to have increased lactose (8%) yield compared with M-LPS cows throughout P2. Circulating glucose was not affected by LPS. Nonesterified fatty acids (NEFA) decreased in E-LPS (29%) but not M-LPS cows. ß-hydroxybutyrate (BHB) slightly increased (14%) over time post-LPS regardless of LS. Insulin increased after LPS in all cows, but E-LPS had blunted hyperinsulinemia (52%) compared with M-LPS cows. Blood urea nitrogen (BUN) increased after LPS and the relative change in BUN was elevated in E-LPS cows compared with M-LPS cows (36 and 13%, respectively, from 9 to 24 h). During P1, metabolic flexibility was increased in liver and muscle in early lactating cows compared with mid-lactation cows, but 12 h post-LPS, metabolic flexibility was reduced and did not differ by LS. In conclusion, IMM LPS caused severe immune activation and E-LPS cows had a more intense inflammatory response compared with M-LPS cows, but the effects on milk synthesis was similar between LS. Some parameters of the E-LPS metabolic profile suggest continuation of metabolic adjustments associated with early lactation to support both a robust immune system and milk synthesis.

Effects of a multispecies direct-fed microbial on gastrointestinal permeability during feed restriction in a growing heifer model.

The objectives were to evaluate the effects of a 4-strain direct-fed microbial (DFM) on gastrointestinal tract (GIT) permeability and inflammation during feed restriction (FR) in heifers. Holstein heifers (n = 32; mean ± standard deviation; 295 ± 25 kg body weight; 287 ± 17 d of age) were used in an experiment conducted in 2 replicates (16/replicate). Heifers were randomly assigned to 1 of 2 top-dressed dietary treatments: (1) control (CON; 10 g/d dried lactose; n = 16) or (2) DFM containing a commercial blend of Lactobacillus animalis, Propionibacterium freudenreichii, Bacillus licheniformis, and Bacillus subtilis at 11.8 × 109 cfu/d (PRO; 10 g/d 4-strain DFM; n = 16). The trial consisted of 2 experimental periods (P): P1 (14 d) served as baseline for P2 (5 d), when all heifers were restricted to 40% of their P1 dry matter intake (DMI). On P1 d 12 and P2 d 2 and 5, GIT permeability was evaluated using oral chromium (Cr)-EDTA. By design, FR decreased DMI (60%) and body weight (∼18 kg) in all heifers. Regardless of treatment, during FR, all heifers had decreased circulating glucose, ß-hydroxybutyrate, insulin, and l-lactate (4, 14, 45, and 19%, respectively), but increased nonesterified fatty acids, serum amyloid A, and haptoglobin (3.0-, 1.7-, and 5.0-fold, respectively). Circulating white blood cells, neutrophils, lymphocytes, and basophils decreased (4, 7, 5, and 6%, respectively), whereas eosinophils increased (41%) during P2 irrespective of dietary treatment. Circulating IFN-γ inducible protein-10 increased (23%) during FR compared with P1 regardless of treatment. Plasma Cr area under the curve increased in all heifers on d 2 and 5 (10 and 14%, respectively) of P2 relative to P1, but this was unaltered by dietary treatment. In summary, FR compromised GIT barrier function and stimulated an inflammatory response, but this did not appear to be ameliorated by PRO.

Effects of a multistrain Bacillus-based direct-fed microbial on gastrointestinal permeability and biomarkers of inflammation during and following feed restriction in mid-lactation Holstein cows.

Objectives were to evaluate the effects of a multistrain Bacillus-based (Bacillus subtilis and Bacillus pumilus blend) direct-fed microbial (DFM) on production, metabolism, inflammation biomarkers and gastrointestinal tract (GIT) permeability during and following feed restriction (FR) in mid-lactation Holstein cows. Multiparous cows (n = 36; 138 ± 53 DIM) were randomly assigned to 1 of 3 dietary treatments: 1) control (CON; 7.5 g/d rice hulls; n = 12), 2) DFM10 (10 g/d Bacillus DFM, 4.9 × 109 cfu/d; n = 12) or 3) DFM15 (15 g/d Bacillus DFM, 7.4 × 109 cfu/d; n = 12). Before study initiation, cows were fed their respective treatments for 32 d. Cows continued to receive treatments during the trial, which consisted of 3 experimental periods (P): P1 (5 d) served as baseline for P2 (5 d), during which all cows were restricted to 40% of P1 dry matter intake (DMI), and P3 (5 d), a "recovery" where cows were fed ad libitum. On d 4 of P1 and on d 2 and 5 of P2, GIT permeability was evaluated in vivo using the oral paracellular marker chromium (Cr)-EDTA. As anticipated, FR decreased milk production, decreased insulin, glucagon, and BUN but increased nonesterified fatty acids. During recovery, DMI rapidly increased on d 1 then subsequently decreased (4.9 kg) on d 2 before returning to baseline whereas milk yield slowly increased but remained decreased (13%) relative to P1. DFM10-fed cows had increased DMI and milk yield relative to DFM15 during P3 (10%). Overall, milk lactose content was increased in DFM cows relative to CON (0.10 percentage units), and DFM10 cows tended to have increased lactose yield relative to CON and DFM15 during P3 (8 and 10%, respectively). No overall treatment differences were observed for other milk composition variables. Circulating glucose was quadratically increased in DFM10 cows compared with CON and DFM15 during FR and recovery. Plasma Cr area under the curve was increased in all cows on d 2 (9%) and 5 (6%) relative to P1. Circulating lipopolysaccharide binding protein (LBP), serum amyloid A (SAA), and haptoglobin (Hp) increased in all cows during P2 compared with baseline (31%, 100%, and 9.0-fold, respectively). Circulating Hp concentrations continued to increase during P3 (274%). Overall, circulating LBP and Hp tended to be increased in DFM15 cows relative to DFM10 (29 and 81%, respectively), but no treatment differences were observed for SAA. Following feed reintroduction during P3, fecal pH initially decreased (0.62 units), but returned to baseline levels whereas fecal starch markedly increased (2.5-fold) and remained increased (82%). Absolute quantities of a fecal Butyryl-CoA CoA transferase (But) gene associated with butyrate synthesis, collected by fecal swab were increased in DFM10 cows compared with CON and DFM15-fed cows. In summary, FR increased GIT permeability, caused inflammation, and decreased production. Feeding DFM10 increased some key production and metabolism variables and upregulated a molecular biomarker of microbial hindgut butyrate synthesis, while DFM15 appeared to augment immune activation.

Effects of androgen deprivation therapy on elderly men with high-risk prostate cancer: PROSARC observational study.

INTRODUCTION: Prostatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient's quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation. We present data from an interim analysis. MATERIALS AND METHODS: PROSARC is a national (Spain) prospective observational study (May-2022-May-2025) still in progress in 2 hospitals. It includes patients with high-risk PC, aged ≥70 years, non-candidates for local treatment and scheduled to start androgen deprivation therapy. The following variables are analyzed: comorbidity, frailty (Fried frailty phenotype criteria), osteoporosis, sarcopenia (EWGSOP2), fat mass and muscle mass, before treatment and after 6 months of follow-up. RESULTS: A 6-month follow-up was completed by 12/25 included patients (mean age, 84 years), with a high baseline prevalence of pre-frailty/frailty (67.7%), sarcopenia (66.7%) and osteoporosis (25%). Treatment did not significantly alter these variables or comorbidity. We observed changes in body mass index (p=0.666), decreased mean value of appendicular muscle mass (p=0.01) and increased percentage of fat mass (p=0.012). CONCLUSION: In patients with high-risk PC, advanced age and a considerable prevalence of osteoporosis, frailty and sarcopenia, androgen deprivation (ADT; 6 months) produces decreased muscle mass without impact on the incidence of the known adverse effects of androgen deprivation.

Vulnerabilidad y determinantes sociales en diabetes / Vulnerability and social determinants in diabetes

Los determinantes sociales de la salud influyen significativamente en el desarrollo y en la progresión de enfermedades crónicas como la diabetes tipo2 (DM2). Este artículo examina los determinantes sociales clave, incluidos la educación, la estabilidad económica, el vecindario, así como la procedencia, la raza o la religión, que afectan a las personas con DM2. También se explora el papel del género como determinante social, enfatizando la necesidad de consideraciones específicas de género en la gestión y en la investigación de la DM2. Además, se analiza el impacto de la pobreza en los resultados de salud, destacando la relación bidireccional entre pobreza y enfermedad. Las medidas integrales que abordan estos determinantes son cruciales para mejorar la salud y el bienestar de las personas con DM2. Abordar las desigualdades sociales a través de intervenciones específicas puede contribuir a mejores resultados de tratamiento y a una atención médica equitativa (AU)

Social determinants of health significantly influence the development and progression of chronic diseases such as type2 diabetes (T2DM). This article examines key social determinants including education, economic stability, neighborhood, and factors such as ethnicity, race, or religion that impact individuals with T2DM. The role of gender as a social determinant is also explored, emphasizing the need for gender-specific considerations in T2DM management and research. Additionally, the impact of poverty on health outcomes is analyzed, highlighting the bidirectional relationship between poverty and disease. Comprehensive measures addressing these determinants are crucial to improving the health and well-being of individuals with T2DM. Addressing social inequalities through targeted interventions can contribute to better treatment outcomes and equitable healthcare (AU)

Effects of Bacillus subtilis PB6 supplementation on production, metabolism, inflammatory biomarkers, and gastrointestinal tract permeability in transition dairy cows.

Objectives were to evaluate the effects of Bacillus subtilis PB6 (BSP) on gastrointestinal tract permeability, metabolism, inflammation, and production parameters in periparturient Holstein cows. Multiparous cows (n = 48) were stratified by previous 305-d mature equivalent milk yield and parity and assigned to 1 of 2 top-dressed dietary treatments 21 d before expected calving through 63 DIM: (1) control (CON; 13 g/d calcium carbonate; n = 24) or (2) BSP (13 g/d BSP; CLOSTAT, Kemin Industries, Des Moines, IA; n = 24). Gastrointestinal tract permeability was evaluated in vivo using the oral paracellular marker chromium (Cr)-EDTA. Effects of treatment, time, and treatment × time were assessed using PROC MIXED of SAS version 9.4 (SAS Institute Inc.). Prepartum dry matter intake (DMI) was unaffected by treatment; however, BSP supplementation decreased postpartum DMI relative to CON (0.7 kg). Milk yield, energy-corrected milk (ECM), fat-corrected milk (FCM), and solids-corrected milk (SCM) increased in BSP cows compared with CON (1.6, 1.8, 1.6, and 1.5 kg, respectively). Decreased DMI and increased production collectively improved feed efficiency of milk yield, ECM, FCM, and SCM for BSP cows (6, 5, 5, and 5%, respectively). No treatment differences were observed for concentrations of milk fat, protein, total solids, somatic cell count, somatic cell score, body weight, or body condition score. Milk urea nitrogen concentrations decreased (5%), whereas milk protein and lactose yield increased (5 and 2%, respectively) with BSP supplementation. Prepartum fecal pH did not differ among treatments; conversely, postpartum fecal pH was increased with BSP supplementation (0.09 pH units). Prepartum fecal dry matter percentage, starch, acetic acid, propionic acid, butyric acid, and ethanol did not differ among treatments. Postpartum concentrations of the aforementioned fecal parameters were also unaffected by treatment, but fecal propionic acid concentration was decreased (24%) in BSP cows relative to CON. Circulating glucose, nonesterified fatty acids, l-lactate, and insulin were similar between treatments both pre- and postpartum. Prepartum ß-hydroxybutyrate (BHB) did not differ between treatments, but postpartum BSP supplementation decreased (21%) circulating BHB relative to CON. Regardless of treatment, inflammatory markers (serum amyloid A and haptoglobin) peaked immediately following parturition and progressively decreased with time, but this pattern was not influenced by treatment. Postpartum lipopolysaccharide binding protein tended to be decreased on d 3 in BSP relative to CON cows (19%). Neither treatment nor time affected Cr-EDTA area under the curve. In summary, supplementing BSP had no detectable effects prepartum, but increased key postpartum production parameters. Bacillus subtilis PB6 consistently increased postpartum fecal pH and decreased fecal propionate concentrations but did not appear to have an effect on gastrointestinal tract permeability.

Effects of cashew nut shell extract supplementation on production, rumen fermentation, metabolism, and inflammatory biomarkers in transition dairy cows.

Cashew nut shell extract (CNSE) is a byproduct of the cashew nut industry, containing bioactive compounds that alter rumen fermentation patterns. Therefore, study objectives were to evaluate the effects of CNSE (59% anacardic acid and 18% cardol) on production, rumen fermentation variables, metabolism, and inflammation in transition dairy cows. A total of 51 multiparous Holstein cows were used in a randomized design and assigned to treatment based on their previous 305-d mature equivalent milk and parity. Cows were assigned to 1 of 2 treatments 21 d before expected calving: (1) CON (control diet; n = 17) or (2) CNSE-5.0 (control diet and 5.0 g/d CNSE granule [containing 50% CNSE]; n = 34). Following parturition, 17 cows (preselected at initial treatment assignment) from the CNSE-5.0 treatment were reallocated into a third treatment group: CNSE-2.5 (control diet and 2.5 g/d CNSE granule; n = 17), resulting in 3 total treatments postpartum: (1) CON, (2) CNSE-2.5, and (3) CNSE-5.0. Prepartum rumen pH was unaltered by treatment; however, postpartum rumen pH was increased (0.31 units) in CNSE cows relative to CON. Prepartum rumen ammonia N concentration tended to be decreased (34%) in CNSE-5.0 cows compared with CON, and there tended to be a quadratic effect on postpartum ammonia N, as it was decreased in CNSE-2.5 compared with CON and CNSE-5.0. Prepartum dry matter intake (DMI) was unaffected by treatment; however, postpartum DMI was increased (8%) in CNSE cows relative to CON. No treatment differences were observed in pre- or postpartum digestibility measurements. Milk and protein yields from cows fed CNSE tended to be increased (6% and 7%, respectively) relative to CON. No treatment differences were detected for energy-corrected milk, feed efficiency, body weight, body condition score, energy balance, milk composition, milk urea nitrogen, or somatic cell count. Prepartum fecal pH decreased (0.12 units) in CNSE-5.0 cows relative to CON cows but was similar between treatments postpartum. Supplementing CNSE did not affect prepartum glucose, nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), or insulin. However, prepartum circulating blood urea nitrogen tended to be decreased and glucagon was decreased in CNSE-5.0 cows compared with CON (9 and 20%, respectively). Additionally, CNSE supplementation decreased glucose and insulin concentrations postpartum relative to CON cows (6% and 20%, respectively). Quadratic effects were detected for postpartum circulating NEFA and BHB such that their levels were increased in CNSE-2.5 cows relative to CON and CNSE-5.0. Pre- and postpartum circulating serum amyloid A, lipopolysaccharide-binding protein, and haptoglobin were unaffected by treatment. Overall, CNSE influenced some key rumen fermentation variables, altered postabsorptive metabolism, and increased production parameters in transition dairy cows.

[Vulnerability and social determinants in diabetes]. / Vulnerabilidad y determinantes sociales en diabetes.

Social determinants of health significantly influence the development and progression of chronic diseases such as type2 diabetes (T2DM). This article examines key social determinants including education, economic stability, neighborhood, and factors such as ethnicity, race, or religion that impact individuals with T2DM. The role of gender as a social determinant is also explored, emphasizing the need for gender-specific considerations in T2DM management and research. Additionally, the impact of poverty on health outcomes is analyzed, highlighting the bidirectional relationship between poverty and disease. Comprehensive measures addressing these determinants are crucial to improving the health and well-being of individuals with T2DM. Addressing social inequalities through targeted interventions can contribute to better treatment outcomes and equitable healthcare.

Effects of abomasally infused rumen fluid from corn-challenged donor cows on production, metabolism, and inflammatory biomarkers in healthy recipient cows.

Subacute rumen acidosis may cause postruminal intestinal barrier dysfunction, but this does not appear to be due to increased hindgut fermentation. Alternatively, intestinal hyperpermeability may be explained by the plethora of potentially harmful substances (e.g., ethanol, endotoxin, and amines) produced in the rumen during subacute rumen acidosis, which are difficult to isolate in traditional in vivo experiments. Therefore, objectives were to evaluate whether abomasal infusion of acidotic rumen fluid collected from donor (Donor) cows elicits systemic inflammation or alters metabolism or production in healthy recipients. Ten rumen-cannulated lactating dairy cows [249 ± 63 d in milk; 753 ± 32 kg of body weight (BW)] were randomly assigned to 1 of 2 abomasal infusion treatments: (1) healthy rumen fluid (HF; 5 L/h; n = 5) or (2) acidotic rumen fluid (AF; 5 L/h; n = 5) infused. Eight rumen-cannulated cows [4 dry, 4 lactating (lactating = 391 ± 220 d in milk); 760 ± 70 kg of BW] were used as Donor cows. All 18 cows were acclimated to a high-fiber diet (46% neutral detergent fiber; 14% starch) during an 11-d prefeeding period during which rumen fluid was collected for the eventual infusion into HF cows. During period (P) 1 (5 d), baseline data were obtained and on d 5 Donor were corn-challenged (2.75% BW ground corn after 16 h of 75% feed restriction). Cows were fasted until 36 h relative to rumen acidosis induction (RAI), and data were collected through 96 h RAI. At 12 h RAI, an additional 0.50% BW of ground corn was added, and acidotic fluid collections began (7 L/Donor every 2 h; 6 M HCl was added to collected fluid until pH was between 5.0 and 5.2). On d 1 of P2 (4 d), HF/AF cows were abomasally infused with their respective treatments for 16 h, and data were collected for 96 h relative to the first infusion. Data were analyzed in SAS (SAS Institute Inc.) using PROC MIXED. Following the corn challenge in the Donor cows, rumen pH only mildly decreased at nadir (pH = 5.64 at 8 h RAI) and remained above the desired threshold for both acute (5.2) and subacute (5.6) acidosis. In contrast, fecal and blood pH markedly decreased to acidotic levels (nadir = 4.65 and 7.28 at 36 and 30 h RAI, respectively), and fecal pH remained below 5 from 22 to 36 h RAI. In Donor cows, dry matter intake remained decreased through d 4 (36% relative to baseline) and serum amyloid A and lipopolysaccharide-binding protein markedly increased by 48 h RAI in Donor cows (30- and 3-fold, respectively). In cows that received the abomasal infusions, fecal pH decreased in AF from 6 to 12 h relative to the first infusion (7.07 vs. 6.33) compared with HF; however, milk yield, dry matter intake, energy-corrected milk, rectal temperature, serum amyloid A, and lipopolysaccharide-binding protein were unaffected. Overall, the corn challenge did not cause subacute rumen acidosis but markedly decreased fecal and blood pH and stimulated a delayed inflammatory response in the Donor cows. Abomasal infusion of rumen fluid from corn-challenged Donor cows decreased fecal pH but did not cause inflammation, nor did it create an immune-activated phenotype in recipient cows.

Effects of hindgut acidosis on production, metabolism, and inflammatory biomarkers in previously immune-activated lactating dairy cows.

Previous stressors and systemic inflammation may increase the intestine's susceptibility to hindgut acidosis (HGA). Therefore, our experimental objectives were to evaluate the effects of isolated HGA on metabolism, production, and inflammation in simultaneously immune-activated lactating cows. Twelve rumen-cannulated Holstein cows (118 ± 41 d in milk; 1.7 ± 0.8 parity) were enrolled in a study with 3 experimental periods (P). Baseline data were collected during P1 (5 d). On d 1 of P2 (2 d), all cows received an i.v. lipopolysaccharide (LPS) bolus (0.2 µg/kg of body weight; BW). During P3 (4 d), cows were randomly assigned to 1 of 2 abomasal infusion treatments: (1) control (LPS-CON; 6 L of H2O/d; n = 6) or (2) starch infused (LPS-ST; 4 kg of corn starch + 6 L of H2O/d; n = 6). Treatments were allocated into 4 equal doses (1.5 L of H2O or 1 kg of starch and 1.5 L of H2O, respectively) and administered at 0000, 0600, 1200, and 1800 h daily. Additionally, both treatments received i.v. LPS on d 1 and 3 of P3 (0.8 and 1.6 µg/kg of BW, respectively) to maintain an inflamed state. Effects of treatment, time, and their interaction were assessed. Repeated LPS administration initiated and maintained an immune-activated state, as indicated by increased circulating white blood cells (WBC), serum amyloid A (SAA), and LPS-binding protein (LBP) during P2 and P3 (29%, 3-fold, and 50% relative to P1, respectively) for both abomasal infusion treatments. Regardless of abomasal treatment, milk yield and dry matter intake were decreased throughout P2 and P3 but with lesser severity following each LPS challenge (54, 44, and 37%, and 49, 42, and 40% relative to baseline on d 1 of P2, d 1 and d 3 of P3, respectively). As expected, starch infusions markedly decreased fecal pH (5.56 at nadir vs. 6.57 during P1) and increased P3 fecal starch relative to LPS-CON (23.7 vs. 2.4% of dry matter). Neither LPS nor starch infusions altered circulating glucose, insulin, nonesterified fatty acids, or ß-hydroxybutyrate, although LPS-ST cows had decreased blood urea nitrogen throughout P3 (16% relative to LPS-CON). Despite the striking reduction in fecal pH, HGA had no additional effect on circulating WBC, SAA, or LBP. Thus, in previously immune-activated dairy cows, HGA did not augment the inflammatory state, as indicated by a lack of perturbations in production, metabolism, and inflammatory biomarkers.

Effects of hindgut acidosis on inflammation, metabolism, and productivity in lactating dairy cows fed a high-fiber diet.

Hindgut acidosis (HGA) may cause or contribute to the inflammatory state of transition dairy cows by compromising the intestinal barrier. Previous experiments isolating the effects of HGA on inflammatory metrics have generated inconsistent results, which may be explained by acclimation to low- versus high-starch diets. Thus, study objectives were to evaluate the effects of HGA in cows acclimated to a high-fiber diet. Ten rumen-cannulated Holstein cows (38 ± 5 kg/d milk yield; 243 ± 62 d in milk; 1.6 ± 1.1 parity; 663 ± 57 kg of body weight) were enrolled in a study with 2 experimental periods (P). Before P1, all cows were acclimated to a high-fiber, low-starch diet (50% neutral detergent fiber, 15% starch) for 17 d. During P1 (4 d), baseline data were collected for use as covariates. During P2 (7 d), cows were assigned to 1 of 2 abomasal infusion treatments: (1) control (CON; 1.5 L of H2O/infusion; n = 4) or (2) starch infused (ST; 1 kg of corn starch + 1.5 L of H2O/infusion; n = 6). All cows were infused with their respective treatments every 6 h daily at 0000, 0600, 1200, and 1800 h, such that ST cows received a total of 4 kg of corn starch/d. Starch infusions successfully induced HGA, as indicated by a marked decrease in fecal pH (1.2 units) relative to CON. However, in contrast to our assumptions, infusing starch had no deleterious effects on milk yield, energy-corrected milk, or voluntary dry matter intake during P2. Milk protein, lactose, their yields, fat yield, and somatic cell score remained unaffected by starch infusions, whereas milk fat content and urea nitrogen were decreased in ST relative to CON (8 and 17%, respectively). Overall, circulating glucose and ß-hydroxybutyrate concentrations remained similar between treatments, but starch infusions decreased nonesterified fatty acids on d 3 relative to CON. Blood urea nitrogen decreased throughout P2 in ST (38%) relative to CON. In contrast to our hypothesis, HGA did not alter circulating serum amyloid A or lipopolysaccharide binding protein, nor did it affect rectal temperature. In summary, HGA moderately altered metabolism but did not affect production or elicit an inflammatory response in lactating dairy cows previously acclimated to a high-fiber diet.

Effects of hindgut acidosis on production, metabolism, and inflammatory biomarkers in feed-restricted lactating dairy cows.

Study objectives were to evaluate the effects of hindgut acidosis (HGA) on production, metabolism, and inflammation in feed-restricted (FR) dairy cows. Twelve rumen-cannulated cows were enrolled in a study with 3 experimental periods (P). During P1 (5 d), baseline data were collected. During P2 (2 d), all cows were FR to 40% of their baseline feed intake. During P3 (4 d), cows remained FR and were assigned to 1 of 2 abomasal infusion treatments: (1) control (FR-CON; 6 L of H2O/d; n = 6) or (2) starch (FR-ST; 4 kg of corn starch + 6 L of H2O/d; n = 6). Respective treatments were partitioned into 4 equal doses (1 kg of corn starch/infusion) and were abomasally infused daily at 0000, 0600, 1200, and 1800 h. All 3 P were analyzed independently and the effects of treatment, time, and treatment × time were assessed using PROC MIXED, and P1 and P2 data were analyzed using the treatments cows were destined to be assigned to during P3. Hallmark production and metabolic responses to feed restriction were observed in both treatments, including decreased milk yield (39%) and energy-corrected milk (32%), circulating glucose (12%), insulin (71%), and increased circulating nonesterified fatty acids (3.2-fold) throughout both P2 and P3, relative to P1. However, despite a marked reduction in fecal pH (0.96 units), the aforementioned metrics were unaltered by HGA. During P3, starch infusions increased circulating ß-hydroxybutyrate, with the most pronounced increase occurring on d 2 (81% relative to FR-CON). Further, feed restriction decreased blood urea nitrogen during P2 (17% relative to P1) in both treatments, and this was exacerbated by starch infusions during P3 (31% decrease relative to FR-CON). In contrast to our hypothesis, neither feed restriction nor HGA increased circulating acute-phase proteins (serum amyloid A and lipopolysaccharide binding protein) relative to P1 or FR-CON, respectively. Thus, despite marked reductions in fecal pH, prior feed restriction did not appear to increase the susceptibility to HGA.

The Effects of Cumulative and Noncumulative Exams Within the Context of Interteaching.

Interteaching is a behavioral teaching method that has been empirically shown to increase student learning outcomes. The present study investigated the effect of combining interteaching with cumulative versus noncumulative exams in two sections of an online asynchronous class. Interteaching was used in both sections of the course. The noncumulative exam section experienced weekly exams with test questions that only covered material learned in that week of class. The cumulative exam section was given weekly exams in which half of the questions were from material learned that current week and the other half were cumulative up to that point in the class. This was followed by a cumulative final exam given to both groups. All exam questions were multiple choice. On average, students in the cumulative exam group scored 4.91% higher on the final exam than students in the noncumulative exam group. Students exposed to weekly cumulative exams also earned more As and Bs on the final compared to the noncumulative exam group. Overall, our experiment provides evidence that interteaching may be further improved when combined with cumulative weekly exams.

Effects of dietary antioxidant supplementation on metabolism and inflammatory biomarkers in heat-stressed dairy cows.

Heat-stress-induced inflammation may be ameliorated by antioxidant supplementation due to the purported effects of increased production of reactive oxygen species or oxidative stress on the gastrointestinal tract barrier. Thus, study objectives were to evaluate whether antioxidant supplementation [AGRADO Plus 2.0 (AP); EW Nutrition] affects metabolism and inflammatory biomarkers in heat-stressed lactating dairy cows. Thirty-two mid-lactation multiparous Holstein cows were assigned to 1 of 4 dietary-environmental treatments: (1) thermoneutral (TN) conditions and fed a control diet (TN-CON; n = 8), (2) TN and fed a diet with AP (10 g antioxidant; n = 8), (3) heat stress (HS) and fed a control diet (HS-CON; n = 8), or (4) HS and fed a diet with AP (HS-AP; n = 8). The trial consisted of a 23-d prefeeding phase and 2 experimental periods (P). Respective dietary treatments were top-dressed starting on d 1 of the prefeeding period and continued daily throughout the duration of the experiment. During P1 (4 d), baseline data were collected. During P2 (7 d), HS was artificially induced using an electric heat blanket (Thermotex Therapy Systems Ltd.). During P2, the effects of treatment, day, and treatment-by-day interaction were assessed using PROC MIXED of SAS (SAS Institute Inc.). Heat stress (treatments 3 and 4) increased rectal, vaginal, and skin temperatures (1.2°C, 1.1°C, and 2.0°C, respectively) and respiration rate (33 breaths per minute) relative to TN cows. As expected, HS decreased dry matter intake, milk yield, and energy-corrected milk yield (32%, 28%, and 28% from d 4 to 7, respectively) relative to TN. There were no effects of AP on body temperature indices or production. Milk fat, protein, and lactose concentrations remained unaltered by HS or AP; however, milk urea nitrogen was increased during HS regardless of AP supplementation (26% relative to TN). Circulating glucose remained unchanged by HS, AP, or time. Additionally, HS decreased circulating glucagon (29% from d 3 to 7 relative to TN), but there was no additional effect of AP. There was a tendency for nonesterified fatty acid concentrations to be increased in HS-AP cows throughout P2 (60% relative to TN-CON), whereas it remained similar in all other treatments. Blood urea nitrogen increased for both HS treatments from d 1 to 3 before steadily decreasing from d 5 to 7, with the overall increase being most pronounced in HS-CON cows (27% relative to TN-CON). Further, supplementing AP decreased blood urea nitrogen in HS-AP on d 3 relative to HS-CON (15%). Circulating serum amyloid A tended to be and lipopolysaccharide binding protein was increased by HS, but neither acute-phase protein was affected by AP. Overall, AP supplementation appeared to marginally alter metabolism but did not meaningfully alter inflammation during HS.

Plasma levels of efavirenz and frequency of the CYP2B6 516G>T polymorphism in people living with HIV-1 in Mexico.

Efavirenz (EFV) is a widely used antiretroviral, due to its safety, efficacy, and low cost. However, plasma concentrations have been related with an increased risk of virological failure and the appearance of serious adverse reactions. EFV is metabolized by Cytochrome P450, the main isoenzyme involved is CYP2B6 and the most relevant genetic polymorphisms found in several populations has been the CYP2B6 516G> T. The aim of this study was to identify the frequency of the CYP2B6 516G>T polymorphism and its effect on the plasma concentration of efavirenz (EFV) in a group of people living with HIV (PLWH) and undergoing EFV treatment in Morelos, Mexico. Ninety-six PLWH undergoing EFV treatment, at a daily dose of 600 mg orally in combination with other antiretrovirals (ARVs), were included in this study. The CYP2B6 516G>T polymorphism was detected using PCR-RFLP. The plasma concentrations of EFV were evaluated by high-resolution liquid chromatography coupled to a mass-mass detector, using a protein precipitation method. The median plasma EFV concentration was 4.6 µg/mL (IQR = 4.64) and 64.6% of the subjects had concentrations above the therapeutic range. The CYP2B6 516G>T genotype findings were as follows: 46.9% of the population presented the wild-type genotype (GG), while 45.8 % and 7.3 % showed the heterozygote (GT) and the polymorphic homozygote (TT) genotype, respectively. The homozygote G had the lowest plasma concentrations of EFV (median = 4.1 µg/mL and IQR = 1.7 µg/mL), followed by those with the GT genotype (median = 5.1 µg/mL and IQR = 3.0 µg/mL). Participants with the homozygous T genotype had the highest EFV concentrations (median = 9.7 µg/mL and IQR = 5.8 µg/mL). In conclusion, the CYP2B6 516G>T polymorphism was associated with plasma levels of EFV in PLWH undergoing ARV treatment. EFV plasma concentrations at 600mg doses were outside the therapeutic range in most subjects.