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1.
Theriogenology ; 223: 53-58, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38678696

ABSTRACT

Mares enrolled in assisted reproductive technologies (ARTs) programs are often treated with non-steroidal anti-inflammatory drugs (NSAIDs), particularly phenylbutazone (Bute), due to chronic lameness. The current study was performed to determine the effect of Bute administration on the developmental competence of in vitro-matured equine oocytes subjected to Intracytoplasmic Sperm Injection (ICSI). In a Preliminary Study, immature cumulus-oocyte complexes (COCs) recovered by post-mortem ovary harvested from two healthy mares (n = 2) treated for 10 days with Bute (4.4 mg/kg, PO, BID), and four non-treated healthy mares (n = 4), were matured in vitro and subjected to Piezo-driven ICSI. Lower oocyte in vitro maturation [Bute: 25% (3/12) vs. Control: 61% (28/46)] and blastocyst rates [Bute: 0% (0/12) vs. Control: 18% (5/28)] were observed in the Bute-treated when compared to the Control mares (P < 0.05). In the Main Experiment, a group of healthy mares (n = 9) received a daily dose of Bute (4.4 mg/kg, orally, SID) for 10 days. A control group of mares (n = 10) was treated with an equal volume of placebo. Mares in both groups were subjected to ultrasound-guided transvaginal oocyte aspiration (TVA) on days 3, 33, and 77 following the last dose of Bute (PT). Recovered COCs from both mare groups were matured in vitro and subjected to Piezo-driven ICSI. By day-3 PT, oocyte in vitro maturation rate was similar between mare groups [Bute: 65% (36/55) vs. Control: 67% (78/116); P > 0.05], while oocyte recovery [Bute: 53% (55/103) vs. Control: 70% (116/166)], cleavage [Bute: 31% (11/36) vs. Control: 62% (48/78)] and blastocyst rates [Bute: [0%] (0/36) vs. Control: 28% (22/78)] were significantly different (P < 0.05). By day 33 PT and 77 PT, differences on oocyte recovery, in vitro maturation, cleavage, and blastocyst rates were not observed between mare groups. In summary, the administration of Bute for 10 consecutive days (4.4 mg/kg, PO, SID, or BID) is associated with a decrease in the ability of immature equine oocytes to undergo in vitro-maturation (Preliminary Study) and develop to the blastocyst stage following ICSI (Preliminary Study and Main Experiment). This negative effect appeared to be transient, as 30- and 77-days post-treatment, no differences on in vitro maturation, cleavage or blastocyst rates were observed.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Blastocyst , In Vitro Oocyte Maturation Techniques , Oocytes , Phenylbutazone , Sperm Injections, Intracytoplasmic , Animals , Horses , Sperm Injections, Intracytoplasmic/veterinary , Sperm Injections, Intracytoplasmic/methods , Female , In Vitro Oocyte Maturation Techniques/veterinary , In Vitro Oocyte Maturation Techniques/methods , Oocytes/drug effects , Oocytes/physiology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Phenylbutazone/pharmacology , Blastocyst/drug effects , Embryonic Development/drug effects
2.
J Am Vet Med Assoc ; 262(5): 692-697, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38382193

ABSTRACT

OBJECTIVE: Advancements in artificial intelligence (AI) and large language models have rapidly generated new possibilities for education and knowledge dissemination in various domains. Currently, our understanding of the knowledge of these models, such as ChatGPT, in the medical and veterinary sciences is in its nascent stage. Educators are faced with an urgent need to better understand these models in order to unleash student potential, promote responsible use, and align AI models with educational goals and learning objectives. The objectives of this study were to evaluate the knowledge level and consistency of responses of 2 platforms of ChatGPT, namely GPT-3.5 and GPT-4.0. SAMPLE: A total of 495 multiple-choice and true/false questions from 15 courses used in the assessment of third-year veterinary students at a single veterinary institution were included in this study. METHODS: The questions were manually entered 3 times into each platform, and answers were recorded. These answers were then compared against those provided by the faculty members coordinating the courses. RESULTS: GPT-3.5 achieved an overall performance score of 55%, whereas GPT-4.0 had a significantly (P < .05) greater performance score of 77%. Importantly, the performance scores of both platforms were significantly (P < .05) below that of the veterinary students (86%). CLINICAL RELEVANCE: Findings of this study suggested that veterinary educators and veterinary students retrieving information from these AI-based platforms should do so with caution.

3.
J Alzheimers Dis Rep ; 8(1): 57-73, 2024.
Article in English | MEDLINE | ID: mdl-38312533

ABSTRACT

Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are typically associated with very different clinical and neuroanatomical presentations; however, there is increasing recognition of similarities. Objective: To examine memory and executive functions, as well as cortical thickness, and glucose metabolism in AD and bvFTD signature brain regions. Methods: We compared differences in a group of biomarker-defined participants with Alzheimer's disease and a group of clinically diagnosed participants with bvFTD. These groups were also contrasted with healthy controls (HC). Results: As expected, memory functions were generally more impaired in AD, followed by bvFTD, and both clinical groups performed more poorly than the HC group. Executive function measures were similar in AD compared to bvFTD for motor sequencing and go/no-go, but bvFTD had more difficulty with a set shifting task. Participants with AD showed thinner cortex and lower glucose metabolism in the angular gyrus compared to bvFTD. Participants with bvFTD had thinner cortex in the insula and temporal pole relative to AD and healthy controls, but otherwise the two clinical groups were similar for other frontal and temporal signature regions. Conclusions: Overall, the results of this study highlight more similarities than differences between AD and bvFTD in terms of cognitive functions, cortical thickness, and glucose metabolism. Further research is needed to better understand the mechanisms mediating this overlap and how these relationships evolve longitudinally.

4.
Equine Vet J ; 56(3): 522-534, 2024 May.
Article in English | MEDLINE | ID: mdl-37341387

ABSTRACT

BACKGROUND: Information on the management and health of US senior horses (≥15 years of age) is currently limited. OBJECTIVES: Provide information on (1) primary use of US senior horses, (2) reasons and risk factors for horse retirement, (3) exercise management, (4) prevalence of low muscle mass and (5) risk factors for, and owner-perceived consequences of, low muscle mass. STUDY DESIGN: Online survey. METHODS: Survey responses from 2717 owners of U.S.-resident senior horses (≥15 years of age) were analysed descriptively and inferentially, using ordered and binomial logistic regression, ANOVA and the Kruskal-Wallis test. RESULTS: The most frequently reported primary uses were pleasure riding/driving (38.5%) and full retirement (39.8%). Most horses (61.5%) were retired between 15 and 24 years of age, with health problems being the main reason. Age, female sex, Thoroughbred breed and various medical conditions were identified as risk factors for retirement. In working horses (i.e., those not retired or semi-retired), exercise intensity was negatively associated with age. The owner-reported prevalence of low muscle mass in all horses was 17.2% (95%CI = 15.7-18.7). In those affected by low muscle mass, the ability to work and welfare-related aspects were commonly perceived to be impaired. Increasing age, sex (gelding), pituitary pars intermedia dysfunction, osteoarthritis, laminitis and primary use (retired and semi-retired vs. use for competition) were identified as risk factors for owner-reported low muscle mass. MAIN LIMITATIONS: Potential response, recall and sampling bias. Causal relationships cannot be established. CONCLUSIONS: Although structured exercise into old age may provide health benefits (as seen in elderly people), a large proportion of horses were fully retired in the current study. Senior horses were mainly retired for health problems and characterising these problems may aid in extending their work/active life. Low muscle mass was perceived to affect horses' welfare and ability to work, and identification of prevention and treatment strategies is therefore warranted.


Subject(s)
Horse Diseases , Retirement , Male , Animals , Female , Horses , Horse Diseases/epidemiology , Horse Diseases/therapy , Risk Factors , Surveys and Questionnaires , Muscles
5.
mBio ; 14(5): e0204923, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37747229

ABSTRACT

IMPORTANCE: Bacteria such as GBS can cause infections during pregnancy leading to preterm births, stillbirths, and neonatal infections. The interaction between host and bacterial factors during infections in the placenta is not fully understood. GBS secretes a hyaluronidase enzyme that is thought to digest host hyaluronan into immunosuppressive disaccharides that dampen TLR2/4 signaling, leading to increased bacterial dissemination and adverse outcomes. In this study, we show that GBS HylB mediates immune suppression and promotes bacterial infection during pregnancy that requires TLR2, TLR4, and IL-10. Understanding the interaction between host and bacterial factors can inform future therapeutic strategies to mitigate GBS infections.


Subject(s)
Pregnancy Complications, Infectious , Streptococcal Infections , Pregnancy , Female , Infant, Newborn , Humans , Hyaluronoglucosaminidase/genetics , Toll-Like Receptor 2 , Interleukin-10/genetics , Streptococcus agalactiae , Pregnancy Complications, Infectious/microbiology , Streptococcal Infections/microbiology
6.
Front Neurol ; 14: 1214083, 2023.
Article in English | MEDLINE | ID: mdl-37731852

ABSTRACT

Composite cognitive measures in large-scale studies with biomarker data for amyloid and tau have been widely used to characterize Alzheimer's disease (AD). However, little is known about how the findings from these studies translate to memory clinic populations without biomarker data, using single measures of cognition. Additionally, most studies have utilized voxel-based morphometry or limited surface-based morphometry such as cortical thickness, to measure the neurodegeneration associated with cognitive deficits. In this study, we aimed to replicate and extend the biomarker, composite study relationships using expanded surface-based morphometry and single measures of cognition in a memory clinic population. We examined 271 clinically diagnosed symptomatic individuals with mild cognitive impairment (N = 93) and Alzheimer's disease dementia (N = 178), as well as healthy controls (N = 29). Surface-based morphometry measures included cortical thickness, sulcal depth, and gyrification index within the "signature areas" of Alzheimer's disease. The cognitive variables pertained to hallmark features of Alzheimer's disease including verbal learning, verbal memory retention, and language, as well as executive function. The results demonstrated that verbal learning, language, and executive function correlated with the cortical thickness of the temporal, frontal, and parietal areas. Verbal memory retention was correlated to the thickness of temporal regions and gyrification of the inferior temporal gyrus. Language was related to the temporal regions and the supramarginal gyrus' sulcal depth and gyrification index. Executive function was correlated with the medial temporal gyrus and supramarginal gyrus sulcal depth, and the gyrification index of temporal regions and supramarginal gyrus, but not with the frontal areas. Predictions of each of these cognitive measures were dependent on a combination of structures and each of the morphometry measurements, and often included medial temporal gyrus thickness and sulcal depth. Overall, the results demonstrated that the relationships between cortical thinning and cognition are widespread and can be observed using single measures of cognition in a clinically diagnosed AD population. The utility of sulcal depth and gyrification index measures may be more focal to certain brain areas and cognitive measures. The relative importance of temporal, frontal, and parietal regions in verbal learning, language, and executive function, but not verbal memory retention, was replicated in this clinic cohort.

7.
Foot Ankle Orthop ; 8(3): 24730114231184189, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37484537

ABSTRACT

Background: The rising prevalence of obesity among American adults has disproportionately affected Black adults and women. Furthermore, body mass index (BMI) has historically been used as a relative contraindication to many total joint arthroplasty (TJA) procedures, including total ankle arthroplasty. The purpose of this study was to investigate potential disparities in patient eligibility for total ankle arthroplasty based on race, ethnicity, sex, and age by applying commonly used BMI cutoffs to the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Methods: Patients in the ACS-NSQIP database who underwent TAA from 2011 to 2020 were retrospectively reviewed in a cross-sectional analysis. BMI cutoffs of <50, <45, <40, and <35 were then applied. The eligibility rate for TAA was examined for each BMI cutoff, and findings were stratified by race, ethnicity, sex, and age. Independent t tests, chi-squared tests, and Fisher exact tests were performed to compare differences at an α = 0.05. Results: A total of 1215 of 1865 TAA patients (65.1%) were included after applying the exclusion criteria. Black patients had disproportionately lower rates of eligibility at the most stringent BMI cutoff of <35 (P = .004). Hispanic patients had generally lower rates of eligibility across all BMI cutoffs. In contrast, Asian American and Pacific Islander patients had higher rates of eligibility at the BMI cutoffs of <35 (P = .033) and <40 (P = .039), and White non-Hispanic patients had higher rates of eligibility across all BMI cutoffs. Females had lower eligibility rates across all BMI cutoffs. Ineligible patients were also younger compared to eligible patients across all BMI cutoffs. Conclusion: Stringent BMI cutoffs may disproportionately disqualify Black, female, and younger patients from receiving total ankle arthroplasty. Level of Evidence: Level III, retrospective cross-sectional study.

8.
PLoS Pathog ; 19(6): e1011490, 2023 06.
Article in English | MEDLINE | ID: mdl-37384812

ABSTRACT

Although hemolytic lipids have been discovered from many human pathogens including Group B Streptococcus (GBS), strategies that neutralize their function are lacking. GBS is a leading cause of pregnancy-associated neonatal infections, and adult GBS infections are on the rise. The GBS hemolytic lipid toxin or granadaene, is cytotoxic to many immune cells including T and B cells. We previously showed that mice immunized with a synthetic nontoxic analog of granadaene known as R-P4 had reduced bacterial dissemination during systemic infection. However, mechanisms important for R-P4 mediated immune protection was not understood. Here, we show that immune serum from R-P4-immunized mice facilitate GBS opsonophagocytic killing and protect naïve mice from GBS infection. Further, CD4+ T cells isolated from R-P4-immunized mice proliferated in response to R-P4 stimulation in a CD1d- and iNKT cell-dependent manner. Consistent with these observations, R-P4 immunized mice lacking CD1d or CD1d-restricted iNKT cells exhibit elevated bacterial burden. Additionally, adoptive transfer of iNKT cells from R-P4 vaccinated mice significantly reduced GBS dissemination compared to adjuvant controls. Finally, maternal R-P4 vaccination provided protection against ascending GBS infection during pregnancy. These findings are relevant in the development of therapeutic strategies targeting lipid cytotoxins.


Subject(s)
Natural Killer T-Cells , Streptococcal Infections , Humans , Pregnancy , Female , Adult , Animals , Mice , Vaccination , Lymphocyte Activation , Lipids , Antigens, CD1d
9.
Vet Clin North Am Equine Pract ; 39(2): 197-210, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37169618

ABSTRACT

Abdominal sonography is currently a routine procedure in the evaluation of colic in the horse. This imaging technique is used in both the assessment of the horse presented in the emergency setting with acute colic and the assessment of the horse presented for chronic or recurrent colic in the nonemergency setting. Sonography for colic evaluation is used by specialists in different disciplines and by general practitioners in the ambulatory and hospital settings. In this review, we will focus on indications and clinical interpretation of findings as well as recent developments in abdominal sonography.


Subject(s)
Colic , Horse Diseases , Horses , Animals , Colic/diagnostic imaging , Colic/surgery , Colic/veterinary , Horse Diseases/diagnostic imaging , Horse Diseases/surgery , Hospitals
10.
Equine Vet J ; 55(3): 376-388, 2023 May.
Article in English | MEDLINE | ID: mdl-35834170

ABSTRACT

The bacterium Rhodococcus equi causes pneumonia in foals that is prevalent at breeding farms worldwide. In the absence of an effective vaccine, transfusion of commercial plasma from donor horses hyperimmunised against R. equi is used by many farms to reduce the incidence of pneumonia among foals at farms where the disease is endemic. The effectiveness of hyperimmune plasma for controlling R. equi pneumonia in foals has varied considerably among reports. The purposes of this narrative review are: (1) to review early studies that provided a foundational basis for the practice of transfusion of hyperimmune plasma that is widespread in the United States and in many other countries; (2) to summarise current knowledge of hyperimmune plasma for preventing R. equi pneumonia; (3) to provide an interpretive summary of probable explanations for the variable results among studies evaluating the effectiveness of transfusion of hyperimmune plasma for reducing the incidence of R. equi pneumonia; (4) to review mechanisms by which hyperimmune plasma might mediate protection; and (5) to consider risks of transfusing foals with hyperimmune plasma. Although the weight of evidence supports the practice of transfusing foals with hyperimmune plasma to prevent R. equi pneumonia, many important gaps in our knowledge of this topic remain including the volume/dose of hyperimmune plasma to be transfused, the timing(s) of transfusion, and the mechanism(s) by which hyperimmune plasma mediates protection. Transfusing foals with hyperimmune plasma is expensive, labour-intensive, and carries risks for foals; therefore, alternative approaches for passive and active immunisation to prevent R. equi pneumonia are greatly needed.


Subject(s)
Actinomycetales Infections , Horse Diseases , Pneumonia, Bacterial , Rhodococcus equi , Animals , Horses , Actinomycetales Infections/prevention & control , Actinomycetales Infections/veterinary , Horse Diseases/prevention & control , Horse Diseases/epidemiology , Pneumonia, Bacterial/prevention & control , Pneumonia, Bacterial/veterinary , Pneumonia, Bacterial/epidemiology , Enzyme-Linked Immunosorbent Assay/veterinary
11.
Article in English | MEDLINE | ID: mdl-36367308

ABSTRACT

Alzheimer's disease is primarily known for deficits in learning and retaining new information. This has long been associated with pathological changes in the mesial temporal lobes. The role of the frontal lobes in memory in Alzheimer's disease is less well understood. In this study, we examined the role of the frontal lobes in learning, recognition, and retention of new verbal information, as well as the presence of specific errors (i.e., intrusions and false-positive errors). Participants included one hundred sixty-seven patients clinically diagnosed with amnestic mild cognitive impairment or suspected Alzheimer's disease dementia who were administered the California Verbal Learning Test and completed high-resolution MRI. We confirmed the role of the mesial temporal lobes in learning and retention, including the volumes of the hippocampus, entorhinal cortex, and parahippocampal gyrus. In addition, false-positive errors were associated with all volumes of the mesial temporal lobes and widespread areas within the frontal lobes. Errors of intrusion were related to the supplementary motor cortex and hippocampus. Most importantly, the mesial temporal lobes interacted with the frontal lobes for learning, recognition, and memory errors. Lower volumes in both regions explained more performance variance than any single structure. This study supports the interaction of the frontal lobes with the temporal lobes in many aspects of memory in Alzheimer's disease.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/diagnosis , Temporal Lobe/diagnostic imaging , Temporal Lobe/pathology , Recognition, Psychology , Hippocampus , Magnetic Resonance Imaging , Frontal Lobe/diagnostic imaging , Frontal Lobe/pathology , Verbal Learning , Neuropsychological Tests
12.
Front Cell Infect Microbiol ; 13: 1299644, 2023.
Article in English | MEDLINE | ID: mdl-38239507

ABSTRACT

Background: Preterm birth is a leading cause of neonatal mortality, which is often complicated by intrauterine infection and inflammation. We have established a nonhuman primate model of Group B Streptococcus (GBS, Streptococcus agalactiae) infection-associated preterm birth. Immune checkpoints are modulators of the immune response by activating or suppressing leukocyte function and are understudied in preterm birth. The objective of this study was to spatially profile changes in immune protein expression at the maternal-fetal interface during a GBS infection with a focus on immune checkpoints. Methods: Twelve nonhuman primates (pigtail macaques, Macaca nemestrina) received a choriodecidual inoculation of either: 1) 1-5 X 108 colony forming units (CFU) of hyperhemolytic/hypervirulent GBS (GBSΔcovR, N=4); 2) an isogenic/nonpigmented strain (GBS ΔcovRΔcylE, N=4); or, 3) saline (N=4). A Cesarean section was performed at preterm labor or 3 days after GBS infection or 7 days after saline inoculation. Nanostring GeoMx® Digital Spatial Profiling technology was used to segment protein expression within the amnion, chorion, and maternal decidua at the inoculation site using an immuno-oncology panel targeting 56 immunoproteins enriched in stimulatory and inhibitory immune checkpoint proteins or their protein ligands. Statistical analysis included R studio, Kruskal-Wallis, Pearson and Spearman tests. Results: Both inhibitory and stimulatory immune checkpoint proteins were significantly upregulated within the chorioamniotic membranes and decidua (VISTA, LAG3, PD-1, CD40, GITR), as well as their ligands (PD-L1, PD-L2, CD40L; all p<0.05). Immunostaining for VISTA revealed positive (VISTA+) cells, predominantly in the chorion and decidua. There were strong correlations between VISTA and amniotic fluid concentrations of IL-1ß, IL-6, IL-8, and TNF-α (all p<0.05), as well as maternal placental histopathology scores (p<0.05). Conclusion: Differential regulation of multiple immune checkpoint proteins in the decidua at the site of a GBS infection indicates a major perturbation in immunologic homeostasis that could benefit the host by restricting immune-driven pathologies or the pathogen by limiting immune surveillance. Protein expression of VISTA, an inhibitory immune checkpoint, was upregulated in the chorion and decidua after GBS infection. Investigating the impact of innate immune cell expression of inhibitory immune checkpoints may reveal new insights into placental host-pathogen interactions at the maternal-fetal interface.


Subject(s)
Premature Birth , Streptococcal Infections , Infant, Newborn , Animals , Humans , Pregnancy , Female , Streptococcus agalactiae/physiology , Placenta , Immune Checkpoint Proteins/metabolism , Up-Regulation , Cesarean Section , Streptococcal Infections/pathology , Primates
13.
Ann Clin Microbiol Antimicrob ; 21(1): 43, 2022 Oct 13.
Article in English | MEDLINE | ID: mdl-36229877

ABSTRACT

Group B streptococci (GBS) are bacteria that can cause preterm birth and invasive neonatal disease. Heterogeneous expression of virulence factors enables GBS to exist as both commensal bacteria and to become highly invasive. A molecular epidemiological study comparing GBS bacterial traits, genotype and host characteristics may indicate whether it is possible to predict the risk of perinatal invasive GBS disease and more accurately target intrapartum antibiotic prophylaxis. A total of 229 invasive GBS isolates from Swedish pregnant women or neonates were assessed for virulence and phenotypic traits: hemolysis zone, hemolytic pigment (Granada agar), Streptococcus B Carrot Broth (SBCB) assay, CAMP factor, and hyaluronidase activity. Genes regulating hemolytic pigment synthesis (covR/covS, abx1, stk1, stp1) were sequenced. Of the virulence factors and phenotypes assessed, a Granada pigment or SBCB score ≥ 2 captured more than 90% of EOD isolates with excellent inter-rater reliability. High enzyme activity of hyaluronidase was observed in 16% (36/229) of the invasive GBS isolates and notably, in one case of stillbirth. Hyaluronidase activity was also significantly higher in GBS isolates obtained from pregnant/postpartum individuals versus the stillbirth or neonatal invasive isolates (p < 0.001). Sequencing analysis found that abx1 (g.T106I), stk1 (g.T211N), stp1 (g.K469R) and covS (g.V343M) variants were present significantly more often in the higher (Granada pigment score ≥ 2) versus lower pigmented isolates (p < 0.001, each variant). Among the 203 higher Granada pigment scoring isolates, 22 (10.8%) isolates had 3 of the four sequence variants and 10 (4.9%) had 2 of the four sequence variants. Although heterogeneity in GBS virulence factor expression was observed, the vast majority were more highly pigmented and contained several common sequence variants in genes regulating pigment synthesis. High activity of hyaluronidase may increase risk for stillbirth and invasive disease in pregnant or postpartum individuals. Our findings suggest that testing for GBS pigmentation and hyaluronidase may, albeit imperfectly, identify pregnant people at risk for invasive disease and represent a step towards a personalized medical approach for the administration of intrapartum antibiotic prophylaxis.


Subject(s)
Premature Birth , Streptococcal Infections , Agar/metabolism , Agar/therapeutic use , Anti-Bacterial Agents/therapeutic use , Female , Genotype , Humans , Hyaluronoglucosaminidase/genetics , Hyaluronoglucosaminidase/metabolism , Hyaluronoglucosaminidase/therapeutic use , Infant, Newborn , Phenotype , Pregnancy , Pregnant Women , Premature Birth/drug therapy , Reproducibility of Results , Stillbirth , Streptococcal Infections/microbiology , Streptococcus agalactiae , Sweden/epidemiology , Virulence/genetics , Virulence Factors/genetics , Virulence Factors/metabolism
14.
Foot Ankle Spec ; : 19386400221127836, 2022 Oct 08.
Article in English | MEDLINE | ID: mdl-36210764

ABSTRACT

BACKGROUND: Mobility limitations are well linked to increased morbidity and mortality. Older patients with chronic pathologies of the foot and ankle can suffer from significant mobility limitations; however, the magnitude of limitation experienced by this cohort is not well characterized. Conversely, the effects of congestive heart failure (CHF) on patient mobility are routinely assessed via the New York Heart Association (NYHA) classification. New York Heart Association classification is determined by a patient's physical activity limitation and is strongly correlated to functional status. We hypothesized that non-emergent conditions of the foot and ankle would be as mobility limiting as CHF. METHODS: Life-Space Mobility Assessments (LSAs) were prospectively collected from orthopaedic patients at their preoperative visits and from CHF patients at a cardiology clinic. Patients over the age of 50 years were included in this study. Congestive heart failure patients NYHA class II or greater were included. The non-emergent foot and ankle cohort included Achilles tendonitis, ankle joint cartilage defects, ankle arthritis, subtalar arthritis, and midfoot arthritis. Patient demographics and LSA scores were analyzed using Mann-Whitney U and chi-squared tests. RESULTS: A total of 96 elderly, non-emergent foot and ankle operative patients and 45 CHF patients met inclusion criteria. All medical comorbidities, except smoking status, were significantly more prevalent in the CHF cohort. No statistical difference was observed between CHF and preoperative foot and ankle LSA scores (56.1 vs 62.4, P = .320). Life-Space Mobility Assessment scores in the foot and ankle cohort were significantly improved relative to CHF patients, at 6-month and 1-year postoperative visits (P = .028, P < .0001, respectively). CONCLUSION: Non-emergent ankle, hindfoot, and midfoot pathology is associated with similar mobility limitation to that of NYHA class II and III CHF. Older patients undergoing elective foot and ankle procedures exceeded the mobility of CHF patients at 6 months post-operation, and the mobility gains persisted at 1-year post-operation. LEVELS OF EVIDENCE: Level II: Prospective cohort study.

15.
Foot Ankle Int ; 43(11): 1501-1510, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36050924

ABSTRACT

BACKGROUND: Ankle arthrodesis has been the mainstay treatment for end-stage ankle arthritis. The popularity of total ankle arthroplasty (TAA) has been on the rise due to improved implant design and postoperative outcomes. The purpose of this study was to describe the basic epidemiology and trends of annual procedure volumes and incidence in the general American population as well as in different population subgroups from 2009 to 2019. We hypothesize that the incidence of TAA has significantly risen while the median length of hospital stay has decreased nationwide. METHODS: The IBM MarketScan database was queried for patients who underwent TAA from January 2009 to December 2019 based on Current Procedural Terminology coding. Population estimates from the US Census Bureau were used to calculate the annual incidence of TAA. Procedural volume and incidence were calculated for annual sums, gender, age subgroups, inpatient and outpatient TAA, as well as in four statistical geographic regions in the United States. Median length of hospital stay was calculated and trended annually for inpatient TAA. RESULTS: A total of 41,060 primary TAAs were identified in the database from 2009 to 2019, in which 52.5% were performed in males. Annual volumes increased by 136.1%, from 2180 to 5147 procedures nationwide. Incidence reported per 100 000 population increased by 120.8%. Both inpatient and outpatient procedures have increased, by 242.5% and 86.6%, respectively. Median length of hospital stay decreased from 3 days in 2009 to 1 day in 2019 and did not differ between genders. Growth in incidence was demonstrated in males and females above the age of 54 years with the largest growth in annual incidence found between 65 and 74 years. Incidence rose in the South and West of the United States by 111.8% and 136.5%, respectively. CONCLUSION: We found that annual volumes and incidence rates of primary TAA has increased between 2009 and 2019. Although both inpatient and outpatient surgery have become more frequent, inpatient volumes and incidence have increased almost 3 times more than those of outpatient surgery. Length of hospital stay decreased over the study years. When adjusted for the same study period, the cumulative annual growth rates of TAA were found to be 2 times greater than total knee arthroplasty and 3.6 times greater than total hip arthroplasty. LEVEL OF EVIDENCE: Level III, retrospective database review.


Subject(s)
Ankle , Arthroplasty, Replacement, Ankle , Humans , Female , United States/epidemiology , Male , Middle Aged , Incidence , Retrospective Studies , Ankle/surgery , Ankle Joint/surgery , Arthroplasty, Replacement, Ankle/methods
16.
Foot Ankle Spec ; : 19386400221118894, 2022 Sep 19.
Article in English | MEDLINE | ID: mdl-36124436

ABSTRACT

BACKGROUND: While first metatarsophalangeal joint (MTPJ) arthrodesis is a common and effective procedure, there is a paucity of studies examining obesity's effect on outcomes of 1st MTPJ arthrodesis. This study's purpose was to evaluate patient-reported outcomes following 1st MTPJ arthrodesis in obese versus non-obese patients. METHODS: A retrospective cohort study of 94 patients undergoing first MTPJ fusion over the age of 18 with a diagnosis of hallux valgus or hallux rigidus was performed. Surgical and postoperative outcomes were examined preoperatively and at 6 and 12 months follow-up via Visual Analog Pain scale (VAS), and Short Form 36 (SF-36) surveys, and data were stratified into 2 patient groups: BMI < 30 (n = 62, mean age 63.9 ± 9.1 and ≥ 30 (n = 32, mean age 61.9 ± 8.4). RESULTS: Average overall VAS and SF-36 physical component scores improved significantly at 6 months (P < .001, .006) and 1 year postoperative visits (P < .001, .007) with no differences in survey scores, outcomes, or complications between weight groups. CONCLUSION: Our study showed first MTPJ fusion improves short-term pain and physical quality-of-life in arthritic obese and non-obese patients without differences in nonunion, complications, or patient-reported measures. LEVEL OF EVIDENCE: Level III, Prognostic, Case-Control Study.

17.
J Clin Invest ; 132(20)2022 10 17.
Article in English | MEDLINE | ID: mdl-36006736

ABSTRACT

Invasive bacterial infections remain a major cause of human morbidity. Group B streptococcus (GBS) are Gram-positive bacteria that cause invasive infections in humans. Here, we show that factor XIIIA-deficient (FXIIIA-deficient) female mice exhibited significantly increased susceptibility to GBS infections. Additionally, female WT mice had increased levels of FXIIIA and were more resistant to GBS infection compared with isogenic male mice. We observed that administration of exogenous FXIIIA to male mice increased host resistance to GBS infection. Conversely, administration of a FXIIIA transglutaminase inhibitor to female mice decreased host resistance to GBS infection. Interestingly, male gonadectomized mice exhibited decreased sensitivity to GBS infection, suggesting a role for gonadal androgens in host susceptibility. FXIIIA promoted GBS entrapment within fibrin clots by crosslinking fibronectin with ScpB, a fibronectin-binding GBS surface protein. Thus, ScpB-deficient GBS exhibited decreased entrapment within fibrin clots in vitro and increased dissemination during systemic infections. Finally, using mice in which FXIIIA expression was depleted in mast cells, we observed that mast cell-derived FXIIIA contributes to host defense against GBS infection. Our studies provide insights into the effects of sexual dimorphism and mast cells on FXIIIA expression and its interactions with GBS adhesins that mediate bacterial dissemination and pathogenesis.


Subject(s)
Factor XIIIa , Streptococcal Infections , Androgens/metabolism , Animals , Factor XIIIa/metabolism , Female , Fibrin/metabolism , Fibronectins/genetics , Fibronectins/metabolism , Humans , Male , Mast Cells/metabolism , Mice , Streptococcal Infections/genetics , Streptococcus agalactiae/metabolism , Transglutaminases/metabolism
18.
Vet Dermatol ; 33(4): 338-e79, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35635294

ABSTRACT

BACKGROUND: The existence of antibodies against cross-reactive carbohydrate determinants (CCDs) has been studied extensively in humans, and more recently, in dogs and cats. These antibodies can reduce the specificity of in vitro serum allergen tests. OBJECTIVES: To investigate the prevalence of anti-CCD immunoglobulin (Ig)E in both allergic and nonallergic horses as well as evaluate its potential impact on serum allergen testing. ANIMALS: Twenty-one allergic and 21 nonallergic horses. METHODS AND MATERIALS: Sera were analysed for anti-CCD IgE utilising a commercial CHO enzyme-linked immunosorbent assay (ELISA). An allergen specific Fc-ε receptor ELISA then was performed to evaluate polysensitisation, both with and without the addition of a proprietary anti-CCD blocking solution. RESULTS: Antibodies against CCD were detected in 30 of 42 horses. There was no statistically significant difference (p = 0.18) between the allergic and healthy groups in regard to anti-CCD prevalence. Horses with anti-CCD IgE exhibited more polysensitisation on serum allergen tests than horses without anti-CCD IgE in all allergen groups except mites. Polysensitisation was statistically significant at the 95% confidence interval for grasses (p <0.03), weeds (p = 0.02) and stinging insects (p = 0.0005). This was found to be true across both study groups. Inhibition with an anti-CCD blocking solution resulted in a 43% average reduction in polysensitisation. CONCLUSION AND CLINICAL IMPORTANCE: The prevalence of anti-CCD IgE of horses in this study coincides with the prevalence detected in pollen-sensitised people. Horses with anti-CCD IgE exhibited more positive reactions on serum allergen tests. By minimising potential artifactual polysensitisation, inclusion of an anti-CCD blocker may facilitate identification of allergen-specific IgE.


Contexte - L'existence d'anticorps contre les déterminants glucidiques à réaction croisée (CCD) a été largement étudiée chez l'homme et, plus récemment, chez le chien et le chat. Ces anticorps peuvent réduire la spécificité des tests d'allergènes sériques in vitro. Objectifs - Étudier la prévalence de l'immunoglobuline anti-CCD (Ig)E chez les chevaux allergiques et non allergiques et évaluer son impact potentiel sur les tests d'allergènes sériques. Animaux - Vingt et un chevaux allergiques et 21 chevaux non allergiques. Matériels et méthodes - Les sera ont été analysés pour les IgE anti-CCD en utilisant un dosage immuno-enzymatique CHO commercial (ELISA). Un ELISA du récepteur Fc-ε spécifique à l'allergène a ensuite été réalisé pour évaluer la polysensibilisation, avec et sans l'ajout d'une solution exclusive de blocage anti-CCD. Résultats - Des anticorps anti-CCD ont été détectés chez 30 des 42 chevaux. Il n'y avait pas de différence statistiquement significative (P = 0,18) entre les groupes allergiques et sains en ce qui concerne la prévalence anti-CCD. Les chevaux avec des IgE anti-CCD ont montré plus de polysensibilisation aux tests d'allergènes sériques que les chevaux sans IgE anti-CCD dans tous les groupes d'allergènes à l'exception des acariens. La polysensibilisation était statistiquement significative à l'intervalle de confiance de 95 % pour les graminées (P < 0,03), les herbacées (P = 0,02) et les insectes piqueurs (P = 0,0005). Cela s'est avéré vrai dans les deux groupes d'étude. L'inhibition avec une solution de blocage anti-CCD a entraîné une réduction moyenne de 43 % de la polysensibilisation. Conclusion et importance clinique - La prévalence des IgE anti-CCD des chevaux dans cette étude coïncide avec la prévalence détectée chez les personnes sensibilisées au pollen. Les chevaux avec des IgE anti-CCD ont présenté des réactions plus positives aux tests d'allergènes sériques. En minimisant la polysensibilisation artificielle potentielle, l'inclusion d'un bloqueur anti-CCD peut faciliter l'identification des IgE spécifiques de l'allergène.


Introducción- la existencia de anticuerpos contra los determinantes de carbohidratos de reacción cruzada (CCD) se ha estudiado ampliamente en humanos y, más recientemente, en perros y gatos. Estos anticuerpos pueden reducir la especificidad de las pruebas de alérgenos séricos in vitro. Objetivos - Investigar la prevalencia de inmunoglobulina (Ig)E anti-CCD tanto en caballos alérgicos como no alérgicos, así como evaluar su impacto potencial en las pruebas de alérgenos séricos. Animales- veintiún caballos alérgicos y 21 no alérgicos. Métodos y materiales- los sueros se analizaron para detectar IgE anti-CCD utilizando un ensayo comercial inmunoabsorbente ligado a enzimas (ELISA) para CHO. A continuación, se realizó un ELISA del receptor Fc-ε específico del alérgeno para evaluar la polisensibilización, con y sin la adición de una solución de bloqueo anti-CCD patentada. Resultados- se detectaron anticuerpos contra CCD en 30 de 42 caballos. No hubo diferencia estadísticamente significativa (P = 0,18) entre los grupos alérgicos y sanos con respecto a la prevalencia de anti-CCD. Los caballos con IgE anti-CCD exhibieron más polisensibilización en las pruebas de alérgenos séricos que los caballos sin IgE anti-CCD en todos los grupos de alérgenos excepto los ácaros. La polisensibilización fue estadísticamente significativa en el intervalo de confianza del 95 % para pastos (P < 0,03), malas hierbas (P = 0,02) e insectos picadores (P = 0,0005). Se encontró que esto fue similar en ambos grupos de estudio. La inhibición con una solución de bloqueo anti-CCD resultó en una reducción promedio del 43 % en la polisensibilización. Conclusión e importancia clínica - La prevalencia de IgE anti-CCD de los caballos en este estudio coincide con la prevalencia detectada en personas sensibilizadas al polen. Los caballos con IgE anti-CCD exhibieron más reacciones positivas en las pruebas de alérgenos en suero. La inclusión de un bloqueador anti-CCD puede facilitar la identificación de IgE específica de alérgeno al minimizar la posible polisensibilización artificial.


Contexto - A existência de anticorpos contra determinantes de carboidratos de reação cruzada (CCDs) tem sido estudada extensivamente em humanos, e, mas recentemente, em cães e gatos. Estes anticorpos podem reduzir a especificidade de testes alérgicos sorológicos in vitro. Objetivos - Investigar a prevalência de imunoglobulina (Ig)E tanto em cavalos alérgicos quanto em cavalos não alérgicos e avaliar o seu potencial impacto no teste alérgico sorológico. Animais - Vinte e um cavalos alérgicos e 21 não alérgicos. Métodos e materiais - O soro foi testado para IgE anti-CCD utilizando um ensaio imunoenzimático CHO comercial (ELISA). Um ELISA alérgeno-específico para receptor Fc-ε foi realizado para avaliar polissensibilização, com e sem a adição de uma solução de bloqueio anti-CCD. Resultados - Anticorpos anti-CCD foram encontrados em 30 de 42 cavalos. Não houve diferença estatística significativa (P = 0,18) entre os grupos alérgico e saudável quanto à prevalência de anti-CCD. Cavalos com IgE anti-CCD exibiram mais polissensibilização no teste alérgico sorológico que cavalos sem IgE anti-CCD em todos os grupos alergênicos, exceto ácaros. Polissensibilização foi estatisticamente significativa em um intervalo de confiança de 95% para gramíneas (P < 0,03), herbáceas (P = 0,02) e insetos que picam (P = 0,0005). Isto foi verdadeiro para os dois grupos estudados. Inibição com uma solução bloqueadora de anti-CCD resultou em uma redução média de 43% na polissensibilização. Conclusão e importância clínica - A prevalência de IgE anti-CCD em cavalos nesse estudo coincide com a prevalência detectada em pessoas sensibilizadas a pólen. Equinos com IgE anti-CCD apresentaram mais reações positivas nos testes alérgicos sorológicos. Minimizando uma potencial polissensibilização a partir da utilização de um bloqueador de anti-CCD pode facilitar a identificação de IgE alérgeno-específica.


Subject(s)
Horse Diseases , Hypersensitivity , Allergens , Animals , Carbohydrates , Cross Reactions , Horse Diseases/epidemiology , Horses , Humans , Hypersensitivity/epidemiology , Hypersensitivity/veterinary , Immunoglobulin E , Prevalence
19.
Am J Vet Res ; 83(5): 419-425, 2022 Feb 02.
Article in English | MEDLINE | ID: mdl-35113795

ABSTRACT

OBJECTIVE: To compare the inflammatory response of murine macrophages exposed to the enteric microbiome of obese horses versus nonobese horses. SAMPLE: Fecal samples from 12 obese horses (body condition score ≥ 7/9) and 12 nonobese horses (body condition score 4 to 5/9) with similar dietary management. PROCEDURES: Fecal supernatant was prepared from frozen fecal samples. RAW 264.7 macrophage cells were exposed to the fecal extract. Inflammatory cytokine (interleukin-1ß, tumor necrosis factor-α, and interleukin-6) gene expression was quantified via real-time quantitative reverse transcription PCR assay, and cytokine concentration was quantified via ELISA. Lipopolysaccharide was evaluated in fecal extract via chromo-limulus amoebocyte lysate assay. RESULTS: Compared with fecal extracts from nonobese horses, fecal extracts from obese horses presented higher concentrations of lipopolysaccharide and induced a heightened expression of the proinflammatory cytokines interleukin-1ß, tumor necrosis factor-α, and interleukin-6 from macrophages. CLINICAL RELEVANCE: The increased levels of inflammatory markers induced in murine macrophages by the microbiome of obese horses in vitro suggested important differences in the enteric microbial composition of these horses, compared with nonobese horses. Overall, this study showed that the microbiome may play a role in mediating an inflammatory response within the gastrointestinal tract of obese horses. Mechanisms of obesity in the horse have not been fully elucidated. Improved understanding of the pathophysiology of disease will guide future research into potential diagnostic and therapeutic interventions for equine obesity.


Subject(s)
Horse Diseases , Rodent Diseases , Animals , Cytokines/genetics , Cytokines/metabolism , Horse Diseases/pathology , Horses , Interleukin-1beta/genetics , Interleukin-6 , Lipopolysaccharides/pharmacology , Macrophages , Mice , Obesity/veterinary , Plant Extracts , Tumor Necrosis Factor-alpha/genetics
20.
Foot Ankle Spec ; : 19386400211065967, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-35037505

ABSTRACT

BACKGROUND: The effects of preoperative depression following ankle fracture surgery remains unknown. The purpose of this study is to investigate the relationship between preoperative depression and outcomes following ankle fracture surgery. METHODS: This retrospective study used the Truven MarketScan database to identify patients who underwent ankle fracture surgery from January 2009 to December 2018. Patients with and without a diagnosis of preoperative depression were identified based on International Classification of Diseases (ICD) codes. Chi-squared and multivariate analyses were performed to determine the association between preoperative depression and postoperative complications following ankle fracture surgery. RESULTS: In total, 107,897 patients were identified for analysis, 13,981 of whom were diagnosed with depression (13%). Preoperative depression was associated with the increased odds for postoperative infection (odds ratio [OR]: 1.33, confidence interval [CI]: 1.20-1.46), wound complications (OR: 1.13, CI: 1.00-1.28), pain-related postoperative emergency department visits (OR: 1.58, CI: 1.30-19.1), 30-day and 90-day readmissions (OR: 1.08, CI: 1.03-1.21 and OR: 1.13, CI: 1.07-1.18), sepsis (OR: 1.39, CI: 1.12-1.72), and postoperative development of complex regional pain syndrome (OR: 1.46, CI: 1.18-1.81). CONCLUSION: Preoperative depression is associated with increased complications following ankle fracture surgery. Further studies are warranted to investigate the degree to which depression is a modifiable risk factor. LEVEL OF EVIDENCE: 3.

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