A review of single-cell transcriptomics and epigenomics studies in maternal and child health.

Single-cell sequencing technologies enhance our understanding of cellular dynamics throughout pregnancy. We outlined the workflow of single-cell sequencing techniques and reviewed single-cell studies in maternal and child health. We conducted a literature review of single cell studies on maternal and child health using PubMed. We summarized the findings from 16 single-cell atlases of the human and mammalian placenta across gestational stages and 31 single-cell studies on maternal exposures and complications including infection, obesity, diet, gestational diabetes, pre-eclampsia, environmental exposure and preterm birth. Single-cell studies provides insights on novel cell types in placenta and cell type-specific marks associated with maternal exposures and complications.

Single-cell sequencing technologies offer new biological insights on pregnancy at the cellular level. We reviewed these technologies and their applications in maternal and child health studies, including 16 placenta cell databases and 31 studies on health challenges during pregnancy such as COVID infection. New cell types and biological pathways among specific groups of cells were found.

Disparities in Sporadic Vestibular Schwannoma Initial Presentation Between a Public Safety Net Hospital and Tertiary Academic Medical Center at the Same Zip Code 2010 to 2020.

INTRODUCTION: Treatment of vestibular schwannoma (VS) has been extensively studied, but a gap in knowledge exists demonstrating how racial and socioeconomic status influence VS presentation. Our institution has a unique setting with a public safety net hospital (PSNH) and tertiary academic medical center (TAMC) in the same zip code, which we study to evaluate initial VS presentation disparities in patient populations presenting to these hospital settings. METHODS: Retrospective chart review was performed of all adult patients (n = 531) presenting 2010 to 2020 for initial VS evaluation at TAMC (n = 462) and PSNH (n = 69). Ethnicity, insurance, maximum tumor size, audiometry, initial treatment recommendation, treatment received, and follow up were recorded and statistical analysis performed to determine differences. RESULTS: Average age at diagnosis (51.7 ± 13.6 TAMC vs 52.3 ± 12.4 PSNH) and gender (58.4% TAMC vs 52.2% PSNH female) were similar. Patients' insurance (TAMC 75.9% privately insured vs PSNH 82% Medicaid) and racial/ethnic profiles (TAMC 67.7% White and 10.0% Hispanic/Latinx, vs PSNH 4.8% White but 59.7% Hispanic/Latinx) were significantly different. Tumor size was larger at PSNH (20.2 ± 13.3 mm) than TAMC (16.6 ± 10.0 mm). Hearing was more impaired at PSNH than TAMC (mean pure tone average 58.3 dB vs 43.9 dB, word recognition scores 52.3% vs 68.2%, respectively). Initial treatment recommendations and treatment received may include more than 1 modality. TAMC patients were offered 66.7% surgery, 31.2% observation, and 5.2% radiation, while PSNH patients offered 50.7% observation, 49.3% surgery, and 8.7% radiation. TAMC patients received 62.9% surgery, 32.5% observation, and 5.3% radiation, while PSNH patients received 36.2% surgery, 59.4% observation, and 14.5% radiation. Follow up and treatment at the same facility was not significantly different between hospitals. CONCLUSIONS: Hearing was worse and tumor size larger in patients presenting to PSNH. Despite worse hearing status and larger tumor size, the majority of PSNH patients were initially offered observation, compared to TAMC where most patients were initially offered surgery.

Evaluating Chlamydia trachomatis and Neisseria gonorrhoeae screening and treatment among asymptomatic pregnant women to prevent preterm birth and low birthweight in Gaborone, Botswana: A secondary analysis from a non-randomised, cluster-controlled trial.

OBJECTIVE: To evaluate the impact of screening and treating asymptomatic pregnant women for Chlamydia (C.) trachomatis and Neisseria (N.) gonorrhoeae infections on the frequency of preterm birth or low birthweight infants in Botswana. DESIGN: Non-randomised, cluster-controlled trial. SETTING: Four antenatal care clinics in Gaborone, Botswana. POPULATION: Pregnant women aged ≥15 years, attending a first antenatal care visit, ≤27 weeks of gestation and without urogenital symptoms were eligible. METHODS: Participants in the intervention clinics received screening (GeneXpert®, Cepheid) during pregnancy and at the postnatal visit. Participants in the standard-of-care clinics received screening at the postnatal visit only. We used multivariable logistic regression and post-estimation predictive margins analysis. Post-hoc analysis was conducted among sub-samples stratified by parity. MAIN OUTCOME MEASURES: Preterm birth (<37 weeks of gestation) and low birthweight (<2500 g). RESULTS: After controlling for parity, hypertension, antenatal care visits and clinic site, the predicted prevalence of preterm birth or low birthweight was lower in the intervention arm (11%) compared with the standard-of-care arm (16%) (adjusted odds ratio [aOR] 0.59; 95% confidence interval [CI] 0.28-1.24). In post-hoc analysis, the intervention was more effective than the standard-of-care (aOR 0.20; 95% CI 0.07-0.64) among nulliparous participants. CONCLUSION: A C. trachomatis and N. gonorrhoeae infection screening and treatment intervention among asymptomatic pregnant women may have reduced preterm birth or low birthweight outcomes, but results were not statistically significant. Post-hoc analysis found that the intervention reduced adverse outcomes among nulliparous participants.

A Novel Discriminating Tool for Microcytic Anemia in Childhood.

Accurate and timely interpretation of microcytic anemia can be diagnostically challenging in the primary care setting. We sought to develop a novel model for distinguishing iron-deficiency anemia from thalassemia trait in the modern pediatric population. Demographic history and red blood cell indices were retrospectively characterized for 76 children referred to our pediatric hematology clinic for evaluation of microcytic anemia. Statistically significant variables were sequentially added into a logistic regression model to develop the final model. The final discriminating model incorporates red cell distribution width, mean corpuscular hemoglobin concentration, and red blood cell values. Favorable predictive performance is seen in the initial (sensitivity 89.2%, specificity 92.3%) and external validation cohort (sensitivity 84.4%, specificity 88.9%). This novel tool may aid in determining the cause of hypochromic, microcytic anemia in the primary care setting. Finally, the study cohort reflects an underrepresented group in the development of screening tools, and thus offers generalizability.

Chronic kidney disease increases cost of care and readmission risk after shoulder arthroplasty.

BACKGROUND: Chronic kidney disease (CKD) is associated with adverse outcomes and higher costs after lower extremity arthroplasty from higher rates of infection, aseptic loosening, and transfusion and longer hospital length of stay (LOS). The purpose of this study was to compare health care utilization and 90-day encounter charges after shoulder arthroplasty (SA) in patients with and without renal disease. A secondary aim was to define the characteristics of patients with renal disease. METHODS: We conducted a retrospective cohort study of all patients who underwent primary SA from January 2015 to December 2019 by a single surgeon at a single institution. Patients without a baseline glomerular filtration rate (GFR) were excluded. We evaluated results for patients with CKD (GFR ≤59 mL/min/1.73 m2) and without CKD (GFR ≥60 mL/min/1.73 m2). Univariate regression was performed to assess the influence of CKD on health care utilization, including LOS, transfusion, and risk for emergency department (ED) revisit or readmission during the 90-day postoperative period. In addition, 90-day encounter charges, revisit charges, and ED charges for patients with CKD were compared with those for patients with normal renal function. Last, multivariable linear regression models were used to assess the effect of estimated GFR on total 90-day encounter charges. RESULTS: A total of 514 patients met the study inclusion criteria, with 125 having CKD and 389 having normal GFR. Patients with CKD were more likely to require transfusion (odds ratio: 16.2 [confidence interval: 1.9, 139.7], P = .011) despite similar intraoperative estimated blood loss (156.9 ± 132.5 mL vs. 153.8 ± 89.7 mL; P = .768). In addition, patients with CKD had longer LOS (2.8 ± 1.3 days vs. 2.3 ± 1.0 days; P < .001), had higher 90-day readmission rates (P = .001), were more likely to visit the ED within 90 days after SA (P = .018), and had higher total 90-day encounter charges ($37,769 ± $6901 vs. $35,684 ± $5312; P = .001). Each unit increase in eGFR independently reduced total encounter charges by $67 (-$132, -$2; P = .043); dialysis patients incurred higher total 90-day encounter charges compared with patients with less severe renal disease ($42,733 ± $8985 vs. $37,531 ± $6749; P = .002). Also, patients with CKD were older (73.2 ± 8.9 vs. 68.1 ± 9.4 years; P < .001); had a lower preoperative hemoglobin level (12.4 ± 1.5 g/dL vs. 13.4 ± 1.5 g/dL; P < .001), higher American Society of Anesthesiologists score (P < .001), and more preoperative comorbidities (5.9 ± 2.9 vs. 5.0 ± 3.1; P < .001); and were more likely to use opioids preoperatively (P = .043). CONCLUSION: Patients with CKD have a higher risk for blood transfusion, ED visits, and readmission after SA, with higher total 90-day encounter charges. Identifying and optimizing this patient population before surgery can reduce costs and improve outcomes, which benefits patients, physicians, institutions, and payors.

Reliability of Phonemically Loaded Sentences in Spanish for Identifying Laryngeal Dystonia by Non-Spanish Speaking Speech-Language Pathologists.

INTRODUCTION: Laryngeal dystonia (LD) is a focal dystonia affecting the intrinsic laryngeal muscles. Clinical diagnosis requires subjective evaluation by experienced clinicians and is primarily based on auditory-perceptual assessment. Several speech tasks are widely accepted to elicit diagnosis specific auditory-perceptual symptoms of glottal stops in adductor LD or breathy breaks in abductor LD in spoken English. With the growing Spanish speaking population in the US and lack of Spanish speech tasks to assist in identifying LD in Spanish speaking subjects, assessing the reliability of phonemically loaded sentences in Spanish for use by non-Spanish speaking providers is critical. The first aim of this study was to develop and assess the reliability of a set of Spanish language phonemically loaded sentences designed to elicit signs and symptoms of LD. The second aim was to determine the effectiveness of non-Spanish speaking speech-language pathologists (SLPs) in identifying LD in Spanish speaking subjects using these stimuli. METHODS: Phonemically loaded sentences were developed for this study following current guidelines for assessment of LD. Voice samples were obtained from native Spanish speaking individuals. Participant-speakers included 20 people with LD and 20 people without LD who served as controls. All participant-speakers were assessed by a Spanish-speaking laryngologist. Audio samples were presented to non-Spanish speaking SLPs with expertise in working with people with LD who served as raters and classified the samples as either presence or absence of LD. Kappa and the intra-class correlation coefficient were calculated and mixed effects logistic regression was used for prediction. RESULTS: The inter and intra-rater reliability indicated statistically significant agreement. Sensitivity, specificity, and predictive values for the diagnosis of LD by the raters were overall strong. CONCLUSIONS: Findings demonstrate that non-Spanish speaking SLPs with expertise in the assessment and treatment of LD can reliably identify the presence of LD using Spanish language stimuli in Spanish-speaking individuals. This study supports the use of newly developed Spanish language phonemically loaded voiced and voiceless sentences by English speaking clinicians as an effective tool for identifying LD in Spanish speakers, perhaps mitigating diagnostic delays experienced by patients with LD.

Causes of Death Among Medical ICU Patients With Pneumonia Due to COVID-19 in a Safety-Net Hospital.

We sought to identify the primary causes of death of adult patients admitted to the medical ICU with symptomatic COVID-19 who ultimately suffered in-hospital mortality over the span of three major waves of COVID-19: Wild-type, alpha/epsilon, and delta. DESIGN: Retrospective single-center cohort study from March 2020 to December 2021. SETTING: One medical ICU in a 600-bed Tertiary Care Hospital in Los Angeles, CA. PATIENTS: Adult (n = 306) ICU patients admitted with symptomatic COVID-19 who suffered in-hospital mortality. INTERVENTIONS: None. MAIN RESULTS: Of the 306 patients with COVID-19 who died in the hospital, 86.3% were Hispanic/Latino. The leading cause of death was respiratory failure, occurring in 57.8% of patients. There was no significant change in the rate of pulmonary deaths across the three waves of COVID-19 in our study period. The mean time from symptom onset to admission was 6.5 days, with an average hospital length of stay of 18 days. This did not differ between pulmonary and other causes of death. Sepsis was the second most common cause of death at 23.9% with a significant decrease from the wild-type wave to the delta wave. Among patients with sepsis as the cause of death, 22% (n = 16) were associated with fungemia. There was no significant association between steroid administration and cause of death. Lastly, the alpha/epsilon wave from December 2020 to May 2021 had the highest mortality rate when compared with wild-type or delta waves. CONCLUSIONS: We found the primary cause of death in ICU patients with COVID-19 was acute respiratory failure, without significant changes over the span of three waves of COVID-19. This finding contrasts with reported causes of death for patients with non-COVID-19 acute respiratory distress syndrome, in which respiratory failure is an uncommon cause of death. In addition, we identified a subset of patients (5%) who died primarily due to fungemia, providing an area for further investigation.

Hypertensive disorders of pregnancy and occurrence of ADHD, ASD, and epilepsy in the child: A meta-analysis.

AIM: To synthesize epidemiologic literature pertaining to the association between preeclampsia (PE), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and epilepsy. METHOD: A systematic search of PubMed and Embase was performed supplemented by hand-searching of reference lists of eligible studies. Two independent reviewers screened abstracts following a prepared protocol. Data extraction and quality appraisal using the Newcastle Ottawa Scale were performed by an independent reviewer. PRISMA guidelines were followed throughout. Random-effects meta-analyses were performed. Adjusted pooled Odds Ratios and their 95% confidence intervals were reported. RESULTS: Fifteen out of 121 identified studies were eligible for inclusion. Six reported adjusted estimates for ADHD, resulting in a pooled odds ratio of 1.29 (95% CI: 1.20, 1.38). Eight reported adjusted estimates for ASD, resulting in a pooled odds ratio of 1.27 (95% CI:1.22, 1.32). Three reported adjusted estimates for epilepsy, resulting in a pooled odds ratio of 1.35 (95% CI: 1.12, 1.63). INTERPRETATION: Intrauterine exposure to PE increased the risk of ADHD, ASD, and epilepsy, though it is unclear whether the true association is with pre-term birth. To our knowledge, this is the first meta-analysis to quantify the association between PE and epilepsy. The results of this meta-analysis can inform screening strategies among children born to preeclamptic mothers for early identification and treatment.

The clinical relevance of human papillomavirus negative status in unsatisfactory cervical cytology.

PURPOSE: The aim of this study was to evaluate the clinical relevance of high-risk human papillomavirus (HR-HPV) negativity at the time of unsatisfactory cervical cytology. METHODS: In this retrospective observational study, records were reviewed for patients who had unsatisfactory cervical cytology with HR-HPV testing performed from January 2015 through September 2019 at a large teaching hospital. Pathology results of follow-up cervical cytology and biopsies were assessed. RESULTS: Of 1282 patients with unsatisfactory cervical cytology and negative HR-HPV testing, repeat cytology was negative for intraepithelial lesion (NIL) in 952 (75%) patients, unsatisfactory in 273 (22%) patients, and abnormal in 41 (3%) patients. Median follow-up time was 91 days. The concordance of HR-HPV status between initial unsatisfactory cervical cytology and subsequent satisfactory cervical cytology was 96.3% for HR-HPV negative patients and 68.8% for HR-HPV positive patients. Compared to women who were HR-HPV negative, women who were HR-HPV positive on initial unsatisfactory cytology were at higher risk of subsequent cervical intraepithelial neoplasia (CIN) 2 or greater (odds ratio = 4.91, 95% confidence interval: 1.34-18.03 for E6/E7 mRNA positivity alone; odds ratio = 46.13, 95% confidence interval: 13.45-158.01 for HR-HPV genotype 16 or 18/45 positivity). CONCLUSION: In the 3 month follow-up of patients with unsatisfactory cervical cytology and negative HR-HPV testing, approximately 3% had abnormal cytology but no cases of HPV related pathology of CIN 2 or greater were found. There was high concordance of negative HR-HPV testing results with those on follow-up satisfactory cervical cytology.

Assessing the efficacy of magnesium oxide and riboflavin as preventative treatment of migraines in pregnancy.

PURPOSE: The purpose of this study is to assess the efficacy of magnesium oxide (MgO) alone and, secondarily, MgO plus riboflavin as preventive treatment of migraines in pregnancy. We hypothesize that MgO alone will be effective for the majority of patients and, when clinically indicated, the addition of riboflavin will result in further benefit. METHODS: This was a retrospective cohort study of pregnant patients treated for migraines between 2015 and 2020. We evaluated pre-/post-differences in the following primary outcomes: migraine frequency, severity, and duration. Secondary outcomes included associated migraine symptoms. RESULTS: Of 203 total patients, 117 received MgO alone and 86 received MgO plus riboflavin. There were no significant differences in baseline demographics between the two groups. There was a statistically significant decrease in migraine frequency, severity, and duration in the groups receiving MgO alone and MgO plus riboflavin (p < 0.01 for all). In total, 154 patients reported migraine-associated symptoms, of which 119 (77%) improved after treatment, 18 (12%) did not improve, and 17 (11%) patients' data were missing. The MgO plus riboflavin group had a lower gestational age at treatment initiation and was more likely to receive treatment prior to pregnancy (p < 0.01). Significant differences were observed for several baseline migraine symptoms, including photophobia, phonophobia, nausea, and vomiting, which were more common in the group receiving MgO plus riboflavin (p < 0.05 for all). CONCLUSION: Migraine frequency, severity, and duration all decreased with MgO alone and MgO plus riboflavin in this pregnancy cohort. Associated symptoms also significantly decreased for both groups.

Internalized HIV-related stigma in women of color obtaining care at an HIV specialty center in Los Angeles County, California.

The current study examined the role of internalized HIV-related stigma in antiretroviral therapy adherence, viral load, and retention in care among women of color living with HIV in Los Angeles County, California. African American and Hispanic/Latino women 18 years of age and older completed a one-time brief survey between September 2017 and February 2018. Descriptive statistics, and univariable and multivariable logistic regressions were used to analyze the data. Seventy-six participants enrolled in the study and 74 completed the entire survey. Seventy-six percent of respondents were Hispanic/Latino, 24% were African American, 71% were unemployed, and 54% had less than a high school education. Thirty-five percent were defined as having "high" stigma with a score in the upper quartile of the scale. Being unemployed, having a high school education or less, and not meeting the Health Resources and Services Administration's annual retention in care measure were associated with "high" stigma. When controlling for education and employment status, those reporting "high" stigma vs. "low" stigma were 18.8 times more likely to not meet the criteria for annual retention in care (OR = 18.8, 95% CI = 1.9-189.2, p = 0.013). Stigma-reduction interventions targeting healthcare settings may be necessary to improve patient retention and engagement in care.

Understanding Delayed Presentation to Emergency Care in Pediatric Patients With Neutropenic Fever.

We investigated social and logistic factors eg, distance from the medical center, language barriers, other children to care for, number of caregivers, etc.) for families to delay seeking immediate emergency care for neutropenic fever in a retrospective cohort study of all pediatric hematology-oncology patients who presented for fever in the setting of neutropenia to our emergency department or clinic from 2015 to 2020. Patients with a history of at least 2 prior admissions for neutropenic fever waited more often for a second fever before presenting versus those without such history (odds ratio 5.00, 95% CI 1.26 to 19.84, P =0.04). No other significant associations were found.

Characteristics and Sodium Pentobarbital Concentrations of Equine Mortality Compost Piles in the Upper Midwest.

Recent changes in rendering availability for chemically-euthanized animals have created a need to explore composting as an equine mortality management method. The objectives of this study were to evaluate equine mortality composting in the Upper Midwest during fall and spring, document sodium pentobarbital concentrations throughout the process, and determine nutrient content of finished compost. During each season, four horses were euthanized by intravenous administration of sodium pentobarbital. Carcasses were positioned at the center of a woodchip and shavings base and covered with a 2:1 mixture of horse stall waste and cattle feedlot waste. Data loggers were placed at 46- and 91cm depths to record pile temperatures every 8 hours. At turning (44-50 days) and trial conclusion (181-216 days), compost piles were sampled for sodium pentobarbital and nutrient composition. Piles contained large bones after 6 months of composting. Sodium pentobarbital remained detectable at trial conclusion (<0.002-1.49 mg kg1 dry matter); however, composting reduced the estimated quantities of sodium pentobarbital by ≥94% (P ≤ .001). Compost from each season met ideal land application values for organic matter (45%-48%), pH (7.3-7.6), and electrical conductivity (3.3-3.4 mm hos cm-1). Low NPK and high C:N ratio (20-30) indicate compost could partially replace synthetic fertilizers when land applied. These findings suggest equine mortality composting is an effective management practice during fall and spring in the Upper Midwest. While remaining sodium pentobarbital residues were minimal, further research is needed to determine environmental implications of composting chemically-euthanized equines.

Lymphocyte Subset Ratio Cannot Diagnose Immune Failure of a TKA.

BACKGROUND: Up to 20% of patients are dissatisfied following total knee arthroplasty (TKA), most often due to pain and/or stiffness. The differential diagnosis includes immune reaction to the prosthesis. However, there is no consensus on diagnostic criteria for immune failure, an allergic reaction, to a TKA. Histologic evaluation could provide evidence as to whether an allergic reaction caused TKA failure. A recent study showed an increase in CD4+ lymphocytes compared to CD8+ lymphocytes in patients lymphocyte transformation testing (LTT) + for Ni. This finding is consistent with Ni sensitization, but can lymphocyte subsets be used to diagnose immune failure on a case-by-case basis? METHODS: Periprosthetic tissues from 18 revision cases of well-fixed, aseptic, but painful and/or stiff primary TKAs were analyzed. Six patients LTT- for Ni were matched as a cohort for age, sex, and body mass index (BMI), to 12 patients LTT + for Ni. Periprosthetic tissue biopsies underwent immunohistochemical IHC staining for CD4+ and CD8+ lymphocyte subsets and were compared by LTT status. The immunohistochemicalIHC results were also compared with periprosthetic histology. RESULTS: There was no relationship between LTT status and mean CD4+ cells/hpf or CD4+:CD8+ lymphocyte ratio. No relationship was found between LTT stimulation index (continuous or categorical) and CD4+:CD8+ ratio or aseptic lymphocyte-dominant vasculitis-associated lesion ALVAL score. CONCLUSION: Lymphocytes in periprosthetic tissue are highly variable in number, subtype ratio, and location, and have no relationship to LTT result or ALVAL score on a case-by-case basis. Based on these results, lymphocyte subsets cannot diagnose immune failure. Further work is needed to determine criteria for the diagnosis of immune failure of a TKA.

Geographic variation in the use of continuous outpatient inotrope infusion therapy and beta blockers.

BACKGROUND: Continuous outpatient inotrope infusion therapy (COIIT) can be used as palliative or interim treatment in patients with advanced heart failure (AHF). Despite widespread use, there is a relative lack of data informing best practices. This study aimed to examine whether patterns of COIIT use differed by region and to explore whether observed differences influenced clinical outcomes. METHODS: Retrospective study of AHF patients receiving COIIT from May 2009 through June 2016. The primary outcome was regional difference, the secondary outcome was persistence (duration) on therapy. Cox proportional hazards model was used to calculate hazard ratios for treatment regimens. RESULTS: There were 3,286 patients, mean (SD) age 61.9 (14.4) years and 74.0% (2,433) male. Inotrope selection and beta blocker use varied by region by chi square (χ2 (21) = 166.9, p < 0.001). Persistence was greater on milrinone compared to dobutamine (HR (for discontinuation) 0.54, CI 0.41-0.70, p < 0.001). Concurrent beta-blocker was associated with greater persistence for patients receiving milrinone (HR 0.13, CI 0.08-0.20, p < 0.001) and dobutamine (HR 0.36, CI 0.18-0.71, p < 0.001). CONCLUSIONS: Patterns of COIIT use varied by region, and variations in use were associated with differences in clinical outcomes.

Effects of water quality on growth performance and health of nursery pigs.

An experiment was conducted to determine the effects of providing drinking water of differing qualities on growth performance and health of nursery pigs. Weanling pigs (n = 450; 150 pigs/group; 10 pigs/pen) were assigned randomly to one of three experimental groups consisting of three water sources of varying qualities: 1) Water source A containing 1,410 ppm hardness (CaCO3 equivalent), 1,120 ppm sulfates, and 1,500 ppm total dissolved solids (TDS); 2) Water source B containing 909 ppm hardness (CaCO3 equivalent), 617 ppm sulfates, and 1,050 ppm TDS; and 3) Water source C containing 235 ppm hardness (CaCO3 equivalent), 2 ppm sulfates, and 348 ppm TDS. Pigs were provided ad libitum access to their respective water sources for the duration of the study which began at weaning (21 d of age) and ended 40 d later (61 d of age). Individual pig weights were recorded weekly along with feed intake on a pen basis. Occurrences of morbidity and mortality were recorded daily. Subjective fecal scores were assigned on a pen basis and blood samples were used to evaluate blood chemistry, cytokine concentrations, and phagocytic activity. A differential sugar absorption test was used to assess intestinal permeability. Fecal grab samples were used to establish diet digestibility, and drinking behavior was video-recorded to assess pigs' acceptance of water sources provided. The statistical model considered fixed effects of water source, room, and their interaction with the random effect of pen. A repeated measures analysis was conducted to determine the effects of water quality over time. There were no differences (P > 0.440) among water sources in average daily gain (A, 0.46 kg/d; B, 0.46 kg/d; C, 0.47 kg/d) or average daily feed intake (A, 0.68 kg/d; B, 0.69 kg/d; C, 0.71 kg/d). Overall mortality of pigs was 0.44% and did not differ across the three water sources. There were no differences in apparent total tract digestibility of the diet, intestinal permeability, immune parameters, or blood chemistry attributable to quality of water consumed by pigs. Pigs did not show an aversion to the water sources provided, because total time pigs spent at the drinker did not differ (P > 0.750) among water sources on days 1 through 3 of the experiment. These data indicate that the water sources of differing quality studied did not affect growth performance or health of nursery pigs.

Evaluation of Fracture Resistance of Zirconia Modification/Polishing Around Implant Abutments.

Subcrestal placement of implants may have interproximal bone proximity issues that interfere with the submucosal contour of implant-supported zirconia restorations during delivery of the restorations. Modification of the mesial distal submucosal areas may be necessary to fully seat the restoration without impingement of the interproximal bone. Our aim was to determine if modification of submucosal cervical contour of implant supported zirconia-titanium base (Zi-Ti base) restorations resulted in a significant change in fracture strength compared with Zi-Ti base restorations without any modification near the cervical submucosal area. Implant Zi-Ti base restorations designed in the form of a maxillary premolar were made for the Straumann implant lab analog. Zirconia samples were cemented onto the Ti-base and the test group (N = 20) underwent recontouring and polishing at the junction of the Zi-Ti base cervical areas. The control group (N = 20) did not undergo any modifications. All 40 samples underwent fracture testing with an Instron machine. We assessed differences between modified and unmodified implants restorations using a 2-tailed t test for independent samples. Fracture strength values (N) ranged from 4354.68 to 6412.49 in the test group (N = 20) and from 5400.31 to 6953.22 in the control group (N = 20). The average fracture strength in the control group (6154.84 ± 320.50) was higher than in the modified group (5593.13 ± 486.51; P < .001). Modification of submucosal contour significantly decreased fracture strength. However, the average fracture strength exceeded the masticatory forces of humans.

Modifiable risk factors increase length of stay and 90-day cost of care after shoulder arthroplasty.

BACKGROUND: Baseline health conditions can negatively impact cost of care and risk of complications after joint replacement, necessitating additional care and incurring higher costs. Bundled payments have been used for hip and knee replacement and the Centers for Medicare & Medicaid Services (CMS) is testing bundled payments for upper extremity arthroplasty. The purpose of this study was to determine the impact of predefined modifiable risk factors (MRFs) on total encounter charges, hospital length of stay (LOS), related emergency department (ED) visits and charges, and related hospital readmissions within 90 days after shoulder arthroplasty. METHODS: We queried the electronic medical record (EPIC) for all shoulder arthroplasty cases under DRG 483 within a regional 7-hospital system between October 2015 and December 2019. Data was used to calculate mean LOS, total 90-day charges, related emergency department (ED) visits and charges, and related hospital readmissions after shoulder arthroplasty. Data for patients who had 1 or more MRFs, defined as anemia (hemoglobin < 10 g/dL), malnutrition (albumin < 3.4 g/dL), obesity (BMI > 40), uncontrolled diabetes (random glucose > 180 mg/dL or glycated hemoglobin > 8.0%), tobacco use (International Classification of Diseases, Tenth Revision, code indicating patient is a smoker), and opioid use (opioid prescription within 90 days of surgery), were evaluated as potential covariates to assess the relationship between MRFs and total encounter charges, LOS, ED visits, ED charges, and hospital readmissions. RESULTS: A total of 1317 shoulder arthroplasty patients were identified. Multivariable analysis demonstrated that anemia (+$19,847, confidence interval [CI] $15,743, $23,951; P < .001), malnutrition (+$5850, CI $3712, $7988; P < .001), and obesity (+$2762, CI $766, $4758, P = .007) independently contributed to higher charges after shoulder arthroplasty. Mean LOS was higher in patients with anemia (5.0 ± 4.0 days vs. 2.2 ± 1.6 days, P < .001), malnutrition (3.7 ± 2.8 days vs. 2.2 ± 1.5 days, P < .001), and uncontrolled diabetes (2.8 ± 2.8 days vs. 2.3 ± 1.7 days, P = .019). Univariate risk factors associated with a significant increase in total 90-day encounter charges included anemia (+$19,345, n = 37, P < .001), malnutrition (+$6971, n = 116, P < .001), obesity (+$2615, n = 184, P = .011), and uncontrolled diabetes (+$4377, n = 66, P = .011). Univariate risk for readmission within 90 days was higher in patients with malnutrition (odds ratio 3.0, CI 1.8, 4.9; P < .001). CONCLUSION: Malnutrition, obesity, and anemia contribute to significantly higher costs after shoulder arthroplasty. Medical strategies to optimize patients before shoulder arthroplasty are warranted to reduce total 90-day encounter charges, length of stay, and risk of readmission within 90 days of surgery. Optimizing patient health before shoulder surgery will positively impact outcomes and cost containment for patients, institutions, and payors after shoulder arthroplasty.

Epigenetic Dysregulation of Trophoblastic Gene Expression in Gestational Trophoblastic Disease.

Gestational trophoblastic diseases (GTDs) have not been investigated for their epigenetic marks and consequent transcriptomic changes. Here, we analyzed genome-wide DNA methylation and transcriptome data to reveal the epigenetic basis of disease pathways that may lead to benign or malignant GTDs. RNA-Seq, mRNA microarray, and Human Methylation 450 BeadChip data from complete moles and choriocarcinoma cells were bioinformatically analyzed. Paraffin-embedded tissues from complete moles and control placentas were used for tissue microarray construction, DNMT3B immunostaining and immunoscoring. We found that DNA methylation increases with disease severity in GTDs. Differentially expressed genes are mainly upregulated in moles while predominantly downregulated in choriocarcinoma. DNA methylation principally influences the gene expression of villous trophoblast differentiation-related or predominantly placenta-expressed genes in moles and choriocarcinoma cells. Affected genes in these subsets shared focal adhesion and actin cytoskeleton pathways in moles and choriocarcinoma. In moles, cell cycle and differentiation regulatory pathways, essential for trophoblast/placental development, were enriched. In choriocarcinoma cells, hormone biosynthetic, extracellular matrix-related, hypoxic gene regulatory, and differentiation-related signaling pathways were enriched. In moles, we found slight upregulation of DNMT3B protein, a developmentally important de novo DNA methylase, which is strongly overexpressed in choriocarcinoma cells that may partly be responsible for the large DNA methylation differences. Our findings provide new insights into the shared and disparate molecular pathways of disease in GTDs and may help in designing new diagnostic and therapeutic tools.

An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized, Controlled, Parallel-Arm Study.

There has been increasing interest in time-restricted eating to attain intermittent fasting's metabolic benefits. However, a more extended daily fast poses many challenges. This study was designed to evaluate the effects of a 200-calorie fasting-mimicking diet (FMD) energy bar formulated to prolong ketogenesis and mitigate fasting-associated side effects. A randomized, controlled study was conducted comparing the impact of consuming an FMD bar vs. continued water fast, after a 15-h overnight fast. Subjects in the FMD group showed a 3-h postprandial beta-hydroxybutyrate (BHB) level and 4-h postprandial BHB area under the curve (AUC0-4) that were non-inferior to those who continued with the water fast (p = 0.891 and p = 0.377, respectively). The postprandial glucose AUC0-4 in the FMD group was non-inferior to that in the water fast group (p = 0.899). A breakfast group served as a control, which confirmed that the instrument used in home glucose and ketone monitoring functioned as expected. The results indicate that FMD bar consumption does not interfere with the physiological ketogenesis associated with overnight fasting and could be used to facilitate the practice of time-restricted eating or intermittent fasting.