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.

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.

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.

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.

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.

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.

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.

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.

Celecoxib significantly reduces opioid use after shoulder arthroplasty.

BACKGROUND: The opioid crisis has illuminated the risks of opioid use for pain management, with renewed interest in reducing opioid consumption after common orthopedic procedures. Anti-inflammatory medication is an important component of multimodal pain management for patients undergoing orthopedic surgery. The purpose of this study was to evaluate the effect of celecoxib on pain control and opioid use after shoulder surgery. METHODS: Patients scheduled for either total shoulder replacement (group 1) or rotator cuff repair (group 2) were candidates for the study. The exclusion criteria included allergy to celecoxib, coagulopathy, use of anticoagulants, baseline use of long-acting opioids, and a history of medical conditions such as myocardial infarction or stroke. Consenting patients were randomized by type of procedure using block randomization to receive either placebo or celecoxib 1 hour prior to the procedure and for 3 weeks postoperatively. The primary outcome measure assessed was opioid utilization as measured by morphine-equivalent dose (MED). Secondary outcome measures included pain scores at 3 and 6 weeks postoperatively. Data were analyzed using multiple linear regression. RESULTS: Of 1081 patients scheduled for either total shoulder replacement or rotator cuff repair from February 2014 to February 2018, 78 were enrolled for arthroplasty (group 1, with 39 receiving celecoxib and 39 receiving placebo) and 79 were enrolled for rotator cuff repair (group 2, with 40 receiving celecoxib and 39 receiving placebo). Compared with the placebo arm, patients prescribed celecoxib took fewer MEDs by -168 (95% confidence interval [CI], -272 to -64; P < .01) at 3 weeks in the total population and by -197.7 (95% CI, -358 to -38; P = .02) in the arthroplasty group. Similarly, at 6 weeks, total MEDs used was -199 (95% CI, -356 to -42; P < .01) in the total population and -270 (95% CI, -524 to -16; P = .04) in the arthroplasty group. No statistically significant differences in opioid consumption were found between study arms in the cuff repair group, at either 3 or 6 weeks. Of note, preoperative opioid use was statistically associated with higher levels of opioid use in the total population and group 1 at 3 and 6 weeks (P < .01 for all) but not in group 2 (P > .05 for both). CONCLUSIONS: Use of morphine equivalents was statistically significantly less at 3 and 6 weeks in patients who took celecoxib in the total population and in the arthroplasty group. Patients prescribed celecoxib for 3 weeks after shoulder surgery took less opioid medication for pain at 3 and 6 weeks. Multimodal pain control using celecoxib is an effective way to reduce postoperative opioid use in shoulder arthroplasty patients. Preoperative opioid use is associated with higher levels of opioid use after shoulder arthroplasty.

Preseason shoulder range of motion screening and in-season risk of shoulder and elbow injuries in overhead athletes: systematic review and meta-analysis.

OBJECTIVE: To characterise whether preseason screening of shoulder range of motion (ROM) is associated with the risk of shoulder and elbow injuries in overhead athletes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Six electronic databases up to 22 September 2018. ELIGIBILITY CRITERIA: Inclusion criteria were (1) overhead athletes from Olympic or college sports, (2) preseason measures of shoulder ROM, (3) tracked in-season injuries at the shoulder and elbow, and (4) prospective cohort design. Exclusion criteria were (1) included contact injuries, (2) lower extremity, spine and hand injuries, and (3) full report not published in English. RESULTS: Fifteen studies were identified, and they included 3314 overhead athletes (baseball (74.6%), softball (3.1%), handball (16.1%), tennis (2.0%), volleyball (2.0%) and swimming (2.2%)). Female athletes are unrepresented (12% of the overall sample). Study quality ranged from 11 to 18 points on a modified Downs and Black checklist (maximum score 21, better quality). In one study, swimmers with low (<93°) or high (>100°) shoulder external rotation were at higher risk of injuries. Using data pooled from three studies of professional baseball pitchers, we showed in the meta-analysis that shoulder external rotation insufficiency (throwing arm <5° greater than the non-throwing arm) was associated with injury (odds ratio=1.90, 95% confidence interval 1.24 to 2.92, p<0.01). CONCLUSION: Preseason screening of shoulder external rotation ROM may identify professional baseball pitchers and swimmers at risk of injury. Shoulder ROM screening may not be effective to identify handball, softball, volleyball and tennis players at risk of injuries. The results of this systematic review and meta-analysis should be interpreted with caution due to the limited number of studies and their high degree of heterogeneity. PROSPERO REGISTRATION NUMBER: CRD42017072895.

Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles.

Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10-6), and immune genes (OR = 1.82, p = 7.34 × 10-18), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. "Cytokine-cytokine receptor interaction" was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.

The Association Between Inhaled Nitric Oxide Treatment and ICU Mortality and 28-Day Ventilator-Free Days in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: To investigate the association between inhaled nitric oxide treatment and ICU mortality and 28-day ventilator-free days in pediatric acute respiratory distress syndrome. DESIGN: Retrospective cohort study. A propensity score for inhaled nitric oxide treatment was developed and used in the analysis. SETTING: Two quaternary care PICUs. PATIENTS: Children with pediatric acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 499 children enrolled in this study with 143 (28.7%) receiving inhaled nitric oxide treatment. Children treated with inhaled nitric oxide were more likely to have a primary diagnosis of pneumonia (72% vs 54.8%; p < 0.001), had a higher initial oxygenation index (median 16.9 [interquartile range, 10.1-27.3] vs 8.5 [interquartile range, 5.8-12.2]; p < 0.001), and had a higher 72-hour maximal Vasoactive-Inotrope Score (median 15 [interquartile range, 6-25] vs 8 [interquartile range, 0-17.8]; p < 0.001) than those not receiving inhaled nitric oxide. Mortality was higher in the inhaled nitric oxide treatment group (25.2% vs 16.3%; p = 0.02), and children in this group had fewer 28-day ventilator-free days (10 d [interquartile range, 0-18 d] vs 17 d (interquartile range 5.5-22 d]; p < 0.0001). We matched 176 children based on propensity score for inhaled nitric oxide treatment. In the matched cohort, inhaled nitric oxide treatment was not associated with mortality (odds ratio, 1.3 [95% CI, 0.56-3.0]) or 28-day ventilator-free days (incidence rate ratio, 0.91 [95% CI, 0.80-1.04]). These results remained consistent in the entire study cohort when the propensity score for inhaled nitric oxide treatment was used for either inverse probability weighting or stratification in regression modeling with the exception that subjects treated with inhaled nitric oxide were more likely to have 0 ventilator-free days (p ≤ 0.02). In secondary analysis stratified by oxygenation response, inhaled nitric oxide treatment was not associated with mortality or 28-day ventilator-free days in children with a positive oxygenation response (all p > 0.2) CONCLUSIONS:: Treatment with inhaled nitric oxide in pediatric acute respiratory distress syndrome is not associated with improvement in either mortality or ventilator-free days and may be associated with harm. Further prospective trials are required to define the role of inhaled nitric oxide treatment in pediatric acute respiratory distress syndrome.

A transient placental source of serotonin for the fetal forebrain.

Serotonin (5-hydroxytryptamine or 5-HT) is thought to regulate neurodevelopmental processes through maternal-fetal interactions that have long-term mental health implications. It is thought that beyond fetal 5-HT neurons there are significant maternal contributions to fetal 5-HT during pregnancy but this has not been tested empirically. To examine putative central and peripheral sources of embryonic brain 5-HT, we used Pet1(-/-) (also called Fev) mice in which most dorsal raphe neurons lack 5-HT. We detected previously unknown differences in accumulation of 5-HT between the forebrain and hindbrain during early and late fetal stages, through an exogenous source of 5-HT which is not of maternal origin. Using additional genetic strategies, a new technology for studying placental biology ex vivo and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source. We uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor in both mice and humans. This study reveals a new, direct role for placental metabolic pathways in modulating fetal brain development and indicates that maternal-placental-fetal interactions could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes.

So You Think You Don't Plunge? An Assessment of Far Cortex Drill Tip Plunging Based on Level of Training.

INTRODUCTION: Drill bit tip plunging past the far cortex places critical anatomical structures at risk. This study measured plunging past the far cortex based on level of training. The time required for screw placement when a depth gauge was used to measure bone tunnel depth was compared to the time required for screw placement when bone tunnel depth was measured in real time. MATERIALS AND METHODS: Thirty orthopedic surgery staff with 1-37 years of experience applied 10-hole plates to cadaveric limbs. Procedures were performed using two different drilling systems. Time and plunge depth were recorded. RESULTS: Penetration past the far cortex ranged from an average of 11.9 mm in the novice group to an average of 6.1 mm in the experienced group (P <0.001). The time required to drill and place a screw decreased by an average of 14 seconds per screw when depth gauge use was eliminated. CONCLUSIONS: Penetration past the far cortex occurred at all levels of training, but decreased with increased levels of experience. Real time measurement of bone tunnel length decreased total drilling time. The time saved with real time measurement decreased with increased level of experience.

Evaluation of risk-factor-based screening for thyroid peroxidase antibody positivity in pregnancy.

OBJECTIVE: To determine whether risk-factor-based screening for thyroid dysfunction in pregnancy performs well for detecting thyroid peroxidase antibodies (TPOAb), a marker for autoimmune thyroid disease. STUDY DESIGN: We prospectively evaluated pregnant women for thyroid dysfunction using The Endocrine Society's eleven screening questions. Serum was analysed for TPOAb. RESULT: We enrolled 546 women. TPOAb positivity was higher in women with a personal (odds ratio (OR) = 8·0; 95% confidence interval (CI) = 1·7-37·4; P = 0·02) or family history of thyroid disease (OR = 2·7; 95% CI = 1·3-5·7; P = 0·02). There was no association between the number of positive responses and TPOAb positivity (P = 0·41). Risk-factor-based screening missed 18 women (33%) with TPOAb. CONCLUSION: One-third of women with TPOAb were missed by the case-finding method. A personal or family history of thyroid disease was most strongly associated with TPOAb positivity.

Trial Promoter: A Web-Based Tool for Boosting the Promotion of Clinical Research Through Social Media.

BACKGROUND: Scarce information about clinical research, in particular clinical trials, is among the top reasons why potential participants do not take part in clinical studies. Without volunteers, on the other hand, clinical research and the development of novel approaches to preventing, diagnosing, and treating disease are impossible. Promising digital options such as social media have the potential to work alongside traditional methods to boost the promotion of clinical research. However, investigators and research institutions are challenged to leverage these innovations while saving time and resources. OBJECTIVE: To develop and test the efficiency of a Web-based tool that automates the generation and distribution of user-friendly social media messages about clinical trials. METHODS: Trial Promoter is developed in Ruby on Rails, HTML, cascading style sheet (CSS), and JavaScript. In order to test the tool and the correctness of the generated messages, clinical trials (n=46) were randomized into social media messages and distributed via the microblogging social media platform Twitter and the social network Facebook. The percent correct was calculated to determine the probability with which Trial Promoter generates accurate messages. RESULTS: During a 10-week testing phase, Trial Promoter automatically generated and published 525 user-friendly social media messages on Twitter and Facebook. On average, Trial Promoter correctly used the message templates and substituted the message parameters (text, URLs, and disease hashtags) 97.7% of the time (1563/1600). CONCLUSIONS: Trial Promoter may serve as a promising tool to render clinical trial promotion more efficient while requiring limited resources. It supports the distribution of any research or other types of content. The Trial Promoter code and installation instructions are freely available online.

Clinical Risk Factors Do Not Predict Shoulder Dystocia.

Objective: To compare 2 different risk factor models for the prediction of shoulder dystocia. Study Design: We performed a retrospective study of women with vaginal deliveries at a single institution over an 8-year period. Two distinct multivariable logistic regression models were used to evaluate the occurrence of shoulder dystocia: a traditional model used information based on birthweight and macrosomia, and a clinical model used information based on esti-mated fetal weight and suspected macrosomia. Results: Of the 13,998 deliveries analyzed, there were 221 cases of shoulder dystocia (1.6%). In addition to the macrosomia or suspected macrosomia variables, the final models included prolonged second stage of labor, diabetes status, and oxytocin use. Neither model was highly sensitive or highly specific, and neither demonstrated a cutoff threshold that yielded a clinically viable PPV. Conclusion: Despite the presence of 1 or more risk factors for shoulder dystocia, its occurrence remains largely an unpredictable clinical event.

Genetic and epigenetic mechanisms collaborate to control SERPINA3 expression and its association with placental diseases.

SERPINA3 (Serpin peptidase inhibitor clade A member 3), also known as a1-antichymotrypsin, is a serine protease inhibitor involved in a wide range of biological processes. Recently, it has been shown to be up-regulated in human placental diseases in association with a hypomethylation of the 5' region of the gene. In the present study, we show that the promoter of SERPINA3 is transcriptionally activated by three transcription factors (TFs) (SP1, MZF1 and ZBTB7B), the level of induction being dependent on the rs1884082 single nucleotide polymorphism (SNP) located inside the promoter, the T allele being consistently induced to a higher level than the G, with or without added TFs. When the promoter was methylated, the response to ZBTB7B was allele specific (the G allele was strongly induced, while the T allele was strongly down-regulated). We propose an adaptive model to explain the interest of such a regulation for placental function and homeostasis. Overexpression of SERPINA3 in JEG-3 cells, a trophoblast cell model, decreased cell adhesion to the extracellular matrix and to neighboring cells, but protects them from apoptosis, suggesting a way by which this factor could be deleterious at high doses. In addition, we show in different human populations that the T allele appears to predispose to Intra Uterine Growth Restriction (IUGR), while a G allele at a second SNP located in the second exon (rs4634) increases the risk of preeclampsia. Our results provide mechanistic views inside the involvement of SERPINA3 in placental diseases, through its regulation by a combination of epigenetic, genetic and TF-mediated regulations.

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.