Effect of video angle on detection of induced front limb lameness in horses.

BACKGROUND: Lameness examinations are commonly performed in equine medicine. Advancements in digital technology have increased the use of video recordings for lameness assessment, however, standardization of ideal video angle is not available yielding videos of poor diagnostic quality. The objective of this study was to evaluate the effect of video angle on the subjective assessment of front limb lameness. A randomized, blinded, crossover study was performed. Six horses with and without mechanically induced forelimb solar pain were recorded using 9 video angles including horses trotting directly away and towards the video camera, horses trotting away and towards a video camera placed to the left and right side of midline, and horses trotting in a circle with the video camera placed on the inside and outside of the circle. Videos were randomized and assessed by three expert equine veterinarians using a 0-5 point scoring system. Objective lameness parameters were collected using a body-mounted inertial sensor system (Lameness Locator®, Equinosis LLC). Interobserver agreement for subjective lameness scores and ease of grading scores were determined. RESULTS: Induction of lameness was successful in all horses. There was excellent agreement between objective lameness parameters and subjective lameness scores (AUC of the ROC = 0.87). For horses in the "lame" trials, interobserver agreement was moderate for video angle 2 when degree of lameness was considered and perfect for video angle 2 and 9 when lameness was considered as a binary outcome. All other angles had no to fair agreement. For horses in the "sound" trials, interobserver agreement was perfect for video angle 5. All other video angles had slight to moderate agreement. CONCLUSIONS: When video assessment of forelimb lameness is required, a video of the horse trotting directly towards the video camera at a minimum is recommended. Other video angles may provide supportive information regarding lameness characteristics.

Cord blood DNA methylation of immune and lipid metabolism genes is associated with maternal triglycerides and child adiposity.

OBJECTIVE: Fetal exposures may impact offspring epigenetic signatures and adiposity. The authors hypothesized that maternal metabolic traits associate with cord blood DNA methylation, which, in turn, associates with child adiposity. METHODS: Fasting serum was obtained in 588 pregnant women (27-34 weeks' gestation), and insulin, glucose, high-density lipoprotein cholesterol, triglycerides, and free fatty acids were measured. Cord blood DNA methylation and child adiposity were measured at birth, 4-6 months, and 4-6 years. The association of maternal metabolic traits with DNA methylation (429,246 CpGs) for differentially methylated probes (DMPs) and regions (DMRs) was tested. The association of the first principal component of each DMR with child adiposity was tested, and mediation analysis was performed. RESULTS: Maternal triglycerides were associated with the most DMPs and DMRs of all traits tested (261 and 198, respectively, false discovery rate < 0.05). DMRs were near genes involved in immune function and lipid metabolism. Triglyceride-associated CpGs were associated with child adiposity at 4-6 months (32 CpGs) and 4-6 years (2 CpGs). One, near CD226, was observed at both timepoints, mediating 10% and 22% of the relationship between maternal triglycerides and child adiposity at 4-6 months and 4-6 years, respectively. CONCLUSIONS: DNA methylation may play a role in the association of maternal triglycerides and child adiposity.

Incidence and risk factors for complications associated with equine general anaesthesia for elective magnetic resonance imaging.

BACKGROUND: Complications are a practical consideration for elective magnetic resonance imaging (MRI) studies performed under general anaesthesia but relatively little is known about their distribution and risk factors. OBJECTIVES: To describe the incidence of complications associated with MRI performed under general anaesthesia at a large referral facility and evaluate potential risk factors for these complications. STUDY DESIGN: Retrospective case-control study. METHODS: Patient information and details of the MRI procedure were collected retrospectively from medical records of all horses that had undergone an MRI under general anaesthesia at the University of Pennsylvania, New Bolton Center, between September 2005 and April 2012. Complications and categorical variables were examined by chi-squared or Fisher's exact tests as appropriate. A mixed-effects logistic regression approach was used to evaluate associations between explanatory variables and the outcome variable (complications or pyrexia). A univariable screen was used to select variables (likelihood ratio test p < 0.2) for inclusion in the multivariable analysis. Statistical significance was inferred when p ≤ 0.05. RESULTS: Complications were noted after MRI in 51 (17.4%) of 293 events eligible for inclusion. Complications included pyrexia (n = 35), pneumonia (n = 14), colic (n = 10), facial/nerve paralysis (n = 6), diarrhoea (n = 4), and other (n = 3). The odds of developing a post-anaesthetic complication were significantly decreased in horses that received peri-anaesthetic antimicrobials (OR 0.29, 95% CI 0.14-0.63, p = 0.002). Increased age (OR 0.87, 95% CI, 0.76-0.99, p = 0.03) and peri-anaesthetic antimicrobial administration (OR 0.23, 95% CI 0.08-0.65, p = 0.005) were associated with a decreased odds of developing pyrexia. MAIN LIMITATIONS: Single centre retrospective design. CONCLUSIONS: Potential complications including pyrexia, pneumonia and colic should be recognised when pursuing MRI under general anaesthesia. The administration of peri-anaesthetic antimicrobials decreased the odds of a complication and warrants consideration, particularly in horses that might be classified as high risk.

Lack of Methylation Changes in GJB2 and RB1 Non-coding Regions of Cochlear Implant Patients with Sensorineural Hearing Loss.

Objective: Recent advances in epigenetic studies continue to reveal novel mechanisms of gene regulation and control, however little is known on the role of epigenetics in sensorineural hearing loss (SNHL) in humans. We aimed to investigate the methylation patterns of two regions, one in RB1 and another in GJB2 in Filipino patients with SNHL compared to hearing control individuals. Methods: We investigated an RB1 promoter region that was previously identified as differentially methylated in children with SNHL and lead exposure. Additionally, we investigated a sequence in an enhancer-like region within GJB2 that contains four CpGs in close proximity. Bisulfite conversion was performed on salivary DNA samples from 15 children with SNHL and 45 unrelated ethnically-matched individuals. We then performed methylation-specific real-time PCR analysis (qMSP) using TaqMan® probes to determine percentage methylation of the two regions. Results: Using qMSP, both our cases and controls had zero methylation at the targeted GJB2 and RB1 regions. Conclusion: Our study showed no changes in methylation at the selected CpG regions in RB1 and GJB2 in the two comparison groups with or without SNHL. This may be due to a lack of environmental exposures to these target regions. Other epigenetic marks may be present around these regions as well as those of other HL-associated genes.

Gastrointestinal Dysfunction in Genetically Defined Neurodevelopmental Disorders.

Gastrointestinal symptoms are common in most forms of neurodevelopment disorders (NDDs) such as in autism spectrum disorders (ASD). The current patient-reported outcome measures with validated questionnaires used in the general population of children without NDDS cannot be used in the autistic individuals. We explore here the multifactorial pathophysiology of ASD and the role of genetics and the environment in this disease spectrum and focus instead on possible diagnostics that could provide future objective insight into the connection of the gut-brain-microbiome in this disease entity. We provide our own data from both humans and a zebrafish model of ASD called Phelan-McDermid Syndrome. We hope that this review highlights the gaps in our current knowledge on many of these profound NDDs and that it provides a future framework upon which clinicians and researchers can build and network with other interested multidisciplinary specialties.

Interobserver agreement of lateral and oblique radiography and standing cone beam CT of the caudal cervical articular process joints of horses.

Caudal cervical articular process joint osteoarthritis (CAPJ OA) leads to career-altering clinical signs in the horse. Oblique radiographs and standing cone beam computed tomography (CBCT) facilitate the assessment of this area, however, the variability of interpretation of these images is currently unknown. This retrospective, secondary analysis, methods comparison study investigated interobserver agreement between clinicians and modality in grades of CAPJ OA on lateral and oblique radiographs and CBCT. We hypothesized that agreement between clinicians' grades of CAPJ OA would be lowest for oblique radiographs and highest for CBCT, and agreement between grades of CAPJ OA would be low for all pairs of modalities. Horses underwent lateral and oblique radiography and CBCT of the CAPJs of C5-C6 and C6-C7. Radiographs and CBCT images were graded retrospectively by four blinded clinicians using 3-point scales. Cohen's kappa analysis was used to evaluate interobserver agreement between grades of CAPJ OA, and agreement between grades of CAPJ OA between different modalities was explored using kappa-weighted analysis. Agreement between clinicians' grades of CAPJ OA was moderate for lateral radiographs (0.49), and fair for oblique radiographs (0.23) and CBCT (0.36). For all modalities, agreement was slight to fair between clinicians for CAPJs with grade 1 (normal, 0.21-0.32) or 2 (mild, 0.13-0.36) CAPJ OA, and moderate to substantial for grade 3 (moderate to severe, 0.45-0.77) CAPJ OA. Agreement between grades of CAPJ OA was fair for all pairs of modalities. This study provides important information regarding the inconsistency of interpretation of mild CAPJ OA on radiographs and CBCT amongst clinicians.

Multi-Omic Signatures of Sarcoidosis and Progression in Bronchoalveolar Lavage Cells.

Introduction: Sarcoidosis is a heterogeneous, granulomatous disease that can prove difficult to diagnose, with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential genomic biomarkers. Methods: Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of diagnosis and phenotype, adjusting for age, sex, and smoking. We built a supervised multi-omics model using a subset of features from each dataset. Results: We identified 46,812 CpGs, 1,842 mRNAs, and 5 miRNAs associated with sarcoidosis versus controls and 1 mRNA, SEPP1 - a protein that supplies selenium to cells, associated with disease progression. Our integrated model emphasized the prominence of the PI3K/AKT1 pathway in sarcoidosis, which is important in T cell and mTOR function. Novel immune related genes and miRNAs including LYST, RGS14, SLFN12L, and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression/methylation of IL20RB, ABCC11, SFSWAP, AGBL4, miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis. Conclusions: Leveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic/prognostic biomarkers and/or drug targets, although future testing will be required for confirmation.

Sex-based differences in placental DNA methylation profiles related to gestational age: an NIH ECHO meta-analysis.

The placenta undergoes many changes throughout gestation to support the evolving needs of the foetus. There is also a growing appreciation that male and female foetuses develop differently in utero, with unique epigenetic changes in placental tissue. Here, we report meta-analysed sex-specific associations between gestational age and placental DNA methylation from four cohorts in the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Programme (355 females/419 males, gestational ages 23-42 weeks). We identified 407 cytosine-guanine dinucleotides (CpGs) in females and 794 in males where placental methylation levels were associated with gestational age. After cell-type adjustment, 55 CpGs in females and 826 in males were significant. These were enriched for biological processes critical to the immune system in females and transmembrane transport in males. Our findings are distinct between the sexes: in females, associations with gestational age are largely explained by differences in placental cellular composition, whereas in males, gestational age is directly associated with numerous alterations in methylation levels.

Multiomic Signatures of Chronic Beryllium Disease Bronchoalveolar Lavage Cells Relate to T-Cell Function and Innate Immunity.

Chronic beryllium disease (CBD) is a Th1 granulomatous lung disease preceded by sensitization to beryllium (BeS). We profiled the methylome, transcriptome, and selected proteins in the lung to identify molecular signatures and networks associated with BeS and CBD. BAL cell DNA and RNA were profiled using microarrays from CBD (n = 30), BeS (n = 30), and control subjects (n = 12). BAL fluid proteins were measured using Olink Immune Response Panel proteins from CBD (n = 22) and BeS (n = 22) subjects. Linear models identified features associated with CBD, adjusting for covariation and batch effects. Multiomic integration methods identified correlated features between datasets. We identified 1,546 differentially expressed genes in CBD versus control subjects and 204 in CBD versus BeS. Of the 101 shared transcripts, 24 have significant cis relationships between gene expression and DNA methylation, assessed using expression quantitative trait methylation analysis, including genes not previously identified in CBD. A multiomic model of top DNA methylation and gene expression features demonstrated that the first component separated CBD from other samples and the second component separated control subjects from remaining samples. The top features on component one were enriched for T-lymphocyte function, and the top features on component two were enriched for innate immune signaling. We identified six differentially abundant proteins in CBD versus BeS, with two (SIT1 and SH2D1A) selected as important RNA features in the multiomic model. Our integrated analysis of DNA methylation, gene expression, and proteins in the lung identified multiomic signatures of CBD that differentiated it from BeS and control subjects.

Associations between child filaggrin mutations and maternal diet with the development of allergic diseases in children.

BACKGROUND: Filaggrin (FLG) loss-of-function mutations in children and maternal diet in pregnancy have been implicated in child allergy outcomes. This paper studies the questions: "do FLG mutations modify the effect of maternal diet on the odds of development of allergic diseases?" and "which factor leads to the highest rate of diagnosis allergic diseases over time, maternal diet, or FLG mutations?". METHODS: Exact logistic regressions studied effect modification. Cox proportional hazard models compared the rate of allergic disease development in three groups (N = 624): (1) children with FLG mutation, (2) children without FLG mutation whose mothers did not eat an allergy preventive diet, and (3) children without FLG mutation whose mothers ate an allergy preventive diet. Maternal diet was classified using a validated index. RESULTS: Cox models showed the development of atopic dermatitis, asthma, and wheeze was significantly higher for children in group 1 versus 3 (HR = 2.40 [1.32, 4.37], HR = 2.29 [1.05, 4.97], and HR 2.10 [1.004, 4.38], respectively), but not significantly higher for children in group 1 versus 2 (HR = 1.30 [0.74, 2.29], HR = 1.27 [0.61, 2.63], and HR = 1.29 [0.65, 2.58], respectively). Development of allergic rhinitis was significantly higher for group 1 versus 2 and 3 (1 vs. 2: HR = 2.29 [1.10, 4.76]; 1 vs. 3: HR = 3.21 [1.46, 7.08]). There was no significant effect modification for any outcome. CONCLUSION: Children with FLG mutation had similar risk of atopic dermatitis, asthma, and wheeze as children without an FLG mutation whose mothers did not eat an allergy preventive diet during pregnancy. Child FLG mutation did not modify the effect of maternal diet. The results suggest that maternal diet in pregnancy, a modifiable risk factor, could be a target for preventive interventions.

Treatment and outcome of eight horses with limb cellulitis and septic tendonitis or desmitis.

OBJECTIVE: To report the clinical features, treatment, and outcome in horses with cellulitis and concurrent septic tendonitis and/or desmitis. STUDY DESIGN: Short case series. METHODS: Medical records from 2000 to 2019 were reviewed, identifying horses with cellulitis and concurrent septic tendonitis and/or desmitis based on sonographic examination and positive bacterial culture. Signalment, ultrasonographic results, bacterial culture, treatment, duration of hospitalization, and complications were recorded. Long-term outcome data were obtained from follow-up examinations and/or telephone interviews. Successful outcome was defined as return to intended use. RESULTS: Eight horses met the inclusion criteria. All infections occurred in hindlimbs, with septic suspensory ligament in six of eight horses, and septic superficial digital flexor tendon in one of eight horses. Surgical debridement was performed in six of eight horses. All horses were treated with systemic and regional intravenous antimicrobials and were discharged from the hospital. Long-term follow-up was available in seven of eight horses. Of these, four horses returned to their intended athletic function, two horses returned to their intended function as a broodmare or pasture pet, and one horse is still rehabilitating. CONCLUSION: Septic tendonitis or desmitis is a rare but possible sequela of limb cellulitis. Based on the findings in this study, prognosis for return to athletic function is fair to good for horses diagnosed with cellulitis and concurrent septic tendonitis or desmitis.

The Gut-Brain-Microbiome Axis and Its Link to Autism: Emerging Insights and the Potential of Zebrafish Models.

Research involving autism spectrum disorder (ASD) most frequently focuses on its key diagnostic criteria: restricted interests and repetitive behaviors, altered sensory perception, and communication impairments. These core criteria, however, are often accompanied by numerous comorbidities, many of which result in severe negative impacts on quality of life, including seizures, epilepsy, sleep disturbance, hypotonia, and GI distress. While ASD is a clinically heterogeneous disorder, gastrointestinal (GI) distress is among the most prevalent co-occurring symptom complex, manifesting in upward of 70% of all individuals with ASD. Consistent with this high prevalence, over a dozen family foundations that represent genetically distinct, molecularly defined forms of ASD have identified GI symptoms as an understudied area with significant negative impacts on quality of life for both individuals and their caregivers. Moreover, GI symptoms are also correlated with more pronounced irritability, social withdrawal, stereotypy, hyperactivity, and sleep disturbances, suggesting that they may exacerbate the defining behavioral symptoms of ASD. Despite these facts (and to the detriment of the community), GI distress remains largely unaddressed by ASD research and is frequently regarded as a symptomatic outcome rather than a potential contributory factor to the behavioral symptoms. Allowing for examination of both ASD's impact on the central nervous system (CNS) as well as its impact on the GI tract and the associated microbiome, the zebrafish has recently emerged as a powerful tool to study ASD. This is in no small part due to the advantages zebrafish present as a model system: their precocious development, their small transparent larval form, and their parallels with humans in genetics and physiology. While ASD research centered on the CNS has leveraged these advantages, there has been a critical lack of GI-centric ASD research in zebrafish models, making a holistic view of the gut-brain-microbiome axis incomplete. Similarly, high-throughput ASD drug screens have recently been developed but primarily focus on CNS and behavioral impacts while potential GI impacts have not been investigated. In this review, we aim to explore the great promise of the zebrafish model for elucidating the roles of the gut-brain-microbiome axis in ASD.

Device Prototype for Vaginal Delivery of Extremely Preterm Fetuses in the Breech Presentation.

Vaginal delivery is typically avoided in the extremely preterm breech population due to the concern of entrapment by the cervix of the aftercoming head. A mechanical device concept is presented to enable vaginal delivery by preventing retraction of the cervix against the fetus during delivery. The two-part device was designed to dilate the cervix, prevent prolapse of small fetal parts and maintain sufficient dilation during delivery. The two-part device was designed and manufactured with the following modules: an inflatable saline-filled cervical balloon for dilation and a cervical retractor composed of semirigid beams to stabilize the cervix and maintain adequate dilation. The device was tested using a cervical phantom designed to simulate the compressive force the cervix exerts. The cervical balloon reached a maximum dilation of 8.5 cm, after which there was leakage of saline from the balloon. While this dilation was less than the target goal of 10 cm, the leaking was attributed to prototype manufacturing defects, which could be resolved with further development. The cervical retractor was able to withstand between 1-3 kPa. Although estimates of cervical pressure values can be upward of 30 kPa, there are no in vivo measurements to formally identify the pressure values for patients in preterm labor. This device serves as a viable proof-of-concept for utilizing an inflatable balloon device to prevent cervical retraction in the setting of extremely preterm vaginal breech delivery. Further manufacturing improvements and design changes could improve the device for continued development and testing.

Preconceptional Lipid-Based Nutrient Supplementation in 2 Low-Resource Countries Results in Distinctly Different IGF-1/mTOR Placental Responses.

BACKGROUND: Preconceptional maternal small-quantity lipid-based nutrient supplementation (SQLNS) improved intrauterine linear growth in low-resource countries as demonstrated by the Women First Preconception Maternal Nutrition Trial (WF). Fetal growth is dependent on nutrient availability and regulated by insulin-like growth factor 1 (IGF-1) through changes in placental transfer capacity, mediated by the mechanistic target of rapamycin (mTOR) pathway. OBJECTIVES: Our objective was to evaluate the role of placental mTOR and IGF-1 signaling on fetal growth in women from 2 low-resource countries with high rates of stunting after they received preconceptional SQLNS. METHODS: We studied 48 women from preconception through delivery who were from Guatemala and Pakistan and received SQLNS or not, as part of the WF study. Placental samples were obtained at delivery (control, n = 24; SQLNS, n = 24). Placental protein or mRNA expression of eukaryotic translation initiation factor binding protein-1 (4E-BP1), ribosomal protein S6 (rpS6), AMP-activated protein kinase α (AMPKA), IGF-1, insulin-like growth factor receptor (IGF-1R), and pregnancy associated plasma protein (PAPP)-A, and DNA methylation of the IGF1 promoter were determined. Maternal serum IGF-1, insulin-like growth factor binding protein (IGFBP)-3, IGFBP-4, IGFBP-5, PAPP-A, PAPP-A2, and zinc were measured. RESULTS: Mean ± SEM maternal prepregnancy BMI differed between participants in Guatemala (26.5 ± 1.3) and Pakistan (19.8 ± 0.7) (P < 0.001). In Pakistani participants, SQLNS increased the placental rpS6(T37/46):rpS6 ratio (1.5-fold) and decreased the AMPKA(T172):AMPKA ratio. Placental IGF1 mRNA expression was positively correlated with birth length and birth weight z-scores. Placental PAPP-A (30-fold) and maternal serum zinc (1.2-fold) increased with SQLNS. In Guatemalan participants SQLNS did not influence placental mTOR signaling. Placental IGF-1R protein expression was positively associated with birth length and birth weight z-scores. SQLNS increased placental PAPP-A (40-fold) and maternal serum IGFBP-4 (1.6-fold). CONCLUSIONS: In Pakistani pregnant women with poor nutritional status, preconceptional SQLNS activated placental mTOR and IGF-1 signaling and was associated with improved fetal growth. In contrast, in Guatemalan women SQLNS did not activate placental nutrient-sensing pathways. In populations experiencing childhood stunting, preconceptional SQLNS improves placental function and fetal growth only in the context of poor maternal nutrition. This trial was registered at clinicaltrials.gov as NCT01883193.

Host methylation predicts SARS-CoV-2 infection and clinical outcome.

BACKGROUND: Since the onset of the SARS-CoV-2 pandemic, most clinical testing has focused on RT-PCR1. Host epigenome manipulation post coronavirus infection2-4 suggests that DNA methylation signatures may differentiate patients with SARS-CoV-2 infection from uninfected individuals, and help predict COVID-19 disease severity, even at initial presentation. METHODS: We customized Illumina's Infinium MethylationEPIC array to enhance immune response detection and profiled peripheral blood samples from 164 COVID-19 patients with longitudinal measurements of disease severity and 296 patient controls. RESULTS: Epigenome-wide association analysis revealed 13,033 genome-wide significant methylation sites for case-vs-control status. Genes and pathways involved in interferon signaling and viral response were significantly enriched among differentially methylated sites. We observe highly significant associations at genes previously reported in genetic association studies (e.g. IRF7, OAS1). Using machine learning techniques, models built using sparse regression yielded highly predictive findings: cross-validated best fit AUC was 93.6% for case-vs-control status, and 79.1%, 80.8%, and 84.4% for hospitalization, ICU admission, and progression to death, respectively. CONCLUSIONS: In summary, the strong COVID-19-specific epigenetic signature in peripheral blood driven by key immune-related pathways related to infection status, disease severity, and clinical deterioration provides insights useful for diagnosis and prognosis of patients with viral infections.

Host methylation predicts SARS-CoV-2 infection and clinical outcome.

BACKGROUND: Since the onset of the SARS-CoV-2 pandemic, most clinical testing has focused on RT-PCR1. Host epigenome manipulation post coronavirus infection2-4 suggests that DNA methylation signatures may differentiate patients with SARS-CoV-2 infection from uninfected individuals, and help predict COVID-19 disease severity, even at initial presentation. METHODS: We customized Illumina's Infinium MethylationEPIC array to enhance immune response detection and profiled peripheral blood samples from 164 COVID-19 patients with longitudinal measurements of disease severity and 296 patient controls. RESULTS: Epigenome-wide association analysis revealed 13,033 genome-wide significant methylation sites for case-vs-control status. Genes and pathways involved in interferon signaling and viral response were significantly enriched among differentially methylated sites. We observe highly significant associations at genes previously reported in genetic association studies (e.g. IRF7, OAS1). Using machine learning techniques, models built using sparse regression yielded highly predictive findings: cross-validated best fit AUC was 93.6% for case-vs-control status, and 79.1%, 80.8%, and 84.4% for hospitalization, ICU admission, and progression to death, respectively. CONCLUSIONS: In summary, the strong COVID-19-specific epigenetic signature in peripheral blood driven by key immune-related pathways related to infection status, disease severity, and clinical deterioration provides insights useful for diagnosis and prognosis of patients with viral infections.

Viral infections affect the body in many ways, including via changes to the epigenome, the sum of chemical modifications to an individual's collection of genes that affect gene activity. Here, we analyzed the epigenome in blood samples from people with and without COVID-19 to determine whether we could find changes consistent with SARS-CoV-2 infection. Using a combination of statistical and machine learning techniques, we identify markers of SARS-CoV-2 infection as well as of severity and progression of COVID-19 disease. These signals of disease progression were present from the initial blood draw when first walking into the hospital. Together, these approaches demonstrate the potential of measuring the epigenome for monitoring SARS-CoV-2 status and severity.

Inflammatory cytokines in horses with cervical articular process joint osteoarthritis on standing cone beam computed tomography.

BACKGROUND: Standing cone beam computed tomography (CT) provides cross-sectional imaging of the caudal cervical articular process joints (CAPJs) in the sedated horse, though the clinical implications of osteoarthritis (OA) identified on CT in this location are unknown. Increases in concentrations of intra-synovial cytokines could lend support to the clinical significance of CAPJ OA identified on this imaging modality. OBJECTIVES: Investigate the presence and concentration of intra-synovial inflammatory cytokines in CAPJs with and without standing cone beam CT evidence of OA using an equine specific multiplex assay. STUDY DESIGN: Prospective clinical study. METHODS: Standing cone beam CT of C5-6 and C6-7 was performed on horses with CAPJ OA and control horses. Synovial fluid samples of the CAPJs of C5-6 and C6-7 were obtained bilaterally using ultrasound guidance and analysed for concentrations of IFN-γ, IL-1ß, IL-6, IL-10, IL-17 and TNFα with the Milliplex® multi-analyte profiling kit. CT Images were retrospectively graded using a novel grading scheme. Significant differences between concentrations of inflammatory cytokines between joints with different categories of osteoarthritis severity were explored using a Wilcoxon rank-sum test or Kruskal-Wallis test. RESULTS: Concentrations of intra-synovial cytokines were higher in joints with moderate to severe OA when compared to joints with no or mild OA, with differences in concentrations of IL-17 reaching statistical significance (P = .007). MAIN LIMITATIONS: Limitations include discrepancy in number, age, and breed between control and OA populations, use of a novel grading scheme, and lack of a histologic gold-standard to confirm the presence and severity of CAPJ OA. CONCLUSIONS: Differences in inflammatory cytokines between caudal CAPJs with and without evidence of moderate to severe osteoarthritis on standing cone beam CT exist. This finding lends support to the clinical relevance of a diagnosis of moderate to severe CAPJ OA in the caudal cervical vertebral column as identified with this imaging modality.

Integrating family and friend support, information technology, and diabetes education in community-centric diabetes self-management.

OBJECTIVE: Diabetes self-management (DSM) education, social support, and information technology interventions can improve patient engagement and health. A major challenge is animating, integrating, and accessing resources in under-resourced, rural communities. Set in an island community in Hawai'i, this study piloted a program that integrated friend-and-family support, community health services, telehealth-enabled DSM education, and mobile technologies by activating the community's social capital to support the program. MATERIALS AND METHODS: An action research approach informed the design and implementation of a community-based DSM program that included: friends and family support, telehealth classes, personalized consultations, Bluetooth-enabled blood glucose monitors, and text messaging support. Outcomes were evaluated using biometric data, surveys, interviews, and participant observations. RESULTS: The study spanned 9 months with 7 dyads, each with 1 individual with type 2 diabetes and a friend or family member. Six of the 7 participants with diabetes experienced reduced hemoglobin A1c percentages, with 3 reducing by more than 1%. The seventh participant maintained a hemoglobin A1c level within American Diabetes Association recommended ranges. DSM knowledge and self-care behaviors improved overall. Interviews and participant observations highlighted program strengths and social challenges associated with the interpersonal relationships between the members of the dyads. CONCLUSIONS: A community-centric diabetes program can enhance understanding of diabetes etiology, DSM activities, and communication skills for effective disease management support in under-resourced rural communities. Social capital among community members, leveraged with health information technology, can catalyze and integrate limited health system resources for DSM and social support as a cost-effective strategy to develop community-centric chronic healthcare management initiatives.

Long-term outcome and effect of diagnostic analgesia in horses undergoing interspinous ligament desmotomy for overriding dorsal spinous processes.

OBJECTIVE: To report the long-term outcome of horses treated with interspinous ligament desmotomy (ISLD) for pain associated with overriding dorsal spinous processes (ORDSP) and determine the influence of preoperative diagnostic analgesia on long-term outcome. STUDY DESIGN: Retrospective study. ANIMALS: Eighteen horses. METHODS: Data were collected from horses presenting for ISLD to the University of Pennsylvania New Bolton Center between January 2013 and May 2018. Follow-up of ≥3 months postsurgically was obtained from the owner, trainer, or referring veterinarian. Long-term improvement was compared between horses that improved with diagnostic analgesia presurgically and horses that did not undergo diagnostic analgesia presurgically by using a χ2 test. Univariate logistic regression was used to test associations between long-term improvement and independent variables. RESULTS: Clinical signs had improved in 13 of 18 horses at long-term follow-up (median, 14.5 months; range, 3-57). Clinical signs improved in nine of 10 horses responding to diagnostic analgesia but only in four of eight horses that did not undergo diagnostic analgesia (χ2 [1], N = 18) = 3.55; P = .06). Although the likelihood of long-term improvement increased with prior diagnostic analgesia (odds ratio = 6.3; 95% confidence interval = 0.73, 55.0; P = .09), it did not reach statistical significance. CONCLUSION: A higher proportion of horses experienced long-term improvement in clinical signs after ISLD when horses responding to preoperative diagnostic analgesia were compared with horses that were not tested. CLINICAL SIGNIFICANCE: This study provides some evidence to support the use of diagnostic analgesia in conjunction with clinical examination for identification of clinically relevant ORDSP.