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Purpose The purpose of this study was to examine the expression of glial derived neurotrophic factor (GDNF), the GDNF receptors GFRα1 and GFRα2, ciliary neurotrophic factor (CNTF), and the CNTF receptor CNTFRα in normal and glaucomatous human tissue. Methods Human retinas were collected from 8 donors that had been clinically diagnosed and treated for glaucoma, and also from 9 healthy control donors. Immunohistochemical analysis for each trophic factor and receptor was performed. The percent of each retinal section labeled with each antibody was quantified for the total retinal thickness, and separately for the retinal ganglion cell (RGC) complex + retinal nerve fiber layer (RNFL). The expression of each protein was correlated with measures of the subject's ocular histories. Results The percentage area immunopositive for GFRα2 was significantly decreased in the total retinal thickness containing all retinal layers and in the combined RGC complex + RNFL in glaucomatous eyes in both the peripapillary region and more peripheral retinal locations. We also observed a decrease in GFRα1 expression in the peripapillary RGC Complex + RNFL in glaucoma patients compared to healthy control patients. We also observed a relationship between GDNF and its receptors with several outcomes obtained from the medical record. No differences in CNTF or CNTFR labeling were observed. Conclusion Decreases in GDNF receptor expression in glaucomatous tissue may limit the potential for neuroprotective therapy by supplementation with GDNF.

Objective We sought to assess the association of hemoglobin A1c (HbA1c) with adverse perinatal outcomes in obese women with gestational diabetes mellitus (GDM). Study design This was a secondary analysis of a multicenter randomized controlled trial assessing early (14-20 weeks) versus routine (24-28 weeks) screening for GDM in obese women. Women were included if they were diagnosed with GDM at either time during pregnancy and had a HbA1c result available. The primary exposure was HbA1c at 24 to 28 weeks. The primary outcome was a composite of macrosomia, primary cesarean, pregnancy-induced hypertension, shoulder dystocia, neonatal hypoglycemia, or hyperbilirubinemia. Receiver operating characteristics (ROC) curves were used to assess the association of HbA1c with the composite outcome. The Liu method was used to select an optimal HbA1c cutoff, and the incidence of the outcome compared. Results Of 125 women with GDM, 93 (74%) had a HbA1c at 24 to 28 weeks and 103 (82.4%) had a HbA1c at 14 to 20 weeks. Baseline characteristics were balanced between groups above and below the cutoff. The area under the ROC curve for HbA1c and its association with the adverse perinatal composite outcome was 0.6 (95% confidence interval [CI]: 0.5-0.7). The frequency of the primary outcome was similar among women with low and high HbA1c at 24 to 28 weeks (adjusted relative risk, 1.12, 95% CI: 0.97-1.29). Compared with women with a decreasing HbA1c during pregnancy, women with a stable or increasing HbA1c did not have a significant increase in the primary adverse perinatal composite outcome. However, the frequency of preterm delivery was higher among women with stable or increasing HbA1c compared with those with a decreasing HbA1c (26.1 vs. 6.7%, p = 0.03). Conclusion A single HbA1c in women with GDM is not associated with a composite perinatal adverse outcome, but a HbA1c that increases or remains stable between 14 to 20 and 24 to 28 weeks is associated with an increase in preterm delivery. Key points · A single HbA1c in GDM is not associated with a composite perinatal adverse outcome.. · HbA1c that increases or remains stable may be associated with an increase in preterm delivery.. · HbA1c at 24 to 28 weeks was not significantly associated with the adverse perinatal composite outcome..

Blast-induced traumatic brain injury is the signature injury of modern military conflicts. To more fully understand the effects of blast exposure, we placed rats in different holder configurations, exposed them to blast overpressure, and assessed the degree of eye and brain injury. Anesthetized Long-Evans rats received blast exposures directed at the head (63 kPa, 195 dB-SPL) in either an "open holder" (head and neck exposed; n = 7), or an "enclosed holder" (window for blast exposure to eye; n = 15) and were compared to non-blast exposed (control) rats (n = 22). Outcomes included optomotor response (OMR), electroretinography (ERG), and spectral domain optical coherence tomography (SD-OCT) at 2, 4, and 6 months post-blast, and cognitive function (Y-maze) at 3 months. Spatial frequency and contrast sensitivity were reduced in ipsilateral blast-exposed eyes in both holders (p 0.01), while contralateral eyes showed greater deficits with the enclosed holder (p 0.05). Thinner retinas (p 0.001) and reduced ERG a- and b- wave amplitudes (p 0.05) were observed for both ipsilateral and contralateral eyes with the enclosed, but not the open, holder. Rats in the open holder showed cognitive deficits compared to rats in the enclosed holder (p 0.05). Overall, the animal holder configuration used in blast exposure studies can significantly affect outcomes. Enclosed holders may cause secondary damage to the contralateral eye by concussive injury or blast wave reflection off the holder wall. Open holders may damage the brain via rapid head movement (contrecoup injury). These results highlight additional factors to be considered when evaluating patients with blast exposure or developing models of blast injury.

Objective To compare the effectiveness of single-dose azithromycin, with or without amoxicillin, with placebo to prevent peripartum infection in laboring women. Methods We conducted a multicenter, three-group, double-blind randomized controlled trial of women with viable term nonanomalous pregnancies with either prolonged labor of 18 hours or longer or rupture of membranes for 8 hours or longer in Cameroon. Women with chorioamnionitis before randomization, study drug contraindications, or planned cesarean births were excluded. Women were randomized to oral azithromycin 1 g-placebo (group 1), oral azithromycin 1 g-oral amoxicillin 2 g (group 2), or placebo-placebo (group 3). All groups received usual care, including antibiotics given at the health care professional's discretion. The primary outcome was a composite of maternal peripartum infection or death from any cause up to 6 weeks postpartum. Two primary comparisons (group 1 vs group 3 and group 2 vs group 3) were planned. We estimated that 241 women per group (planning for 750 total) would provide 80% power at two-sided α=0.05 (0.025 per comparison) to detect a 50% effect size assuming 20% baseline composite infection rate. Results From January 6, 2018, to May 15, 2020, 6,531 women were screened, and 756 (253 in group 1, 253 in group 2, and 250 in group 3) were randomized. Baseline characteristics (including body mass index, duration of rupture of membranes or labor, and parity) were balanced across groups, except for maternal age. More than 60% of women in each group received usual-care antibiotics: more than 90% penicillin and approximately 50% for prolonged rupture of membranes across all study groups. Composite outcome incidences were similar in antibiotic groups 1 (6%) and 2 (7%) compared with placebo group 3 (10%) (RR 0.6, 95% CI 0.3-1.2; 0.7, 95% CI 0.4-1.3, respectively). Chorioamnionitis and wound infection were significantly lower in group 2 (3.2% vs 0.4% and 4% vs 0.8% respectively, both P=.02) compared with group 3. There were no differences in other maternal or neonatal outcomes including neonatal infection. Conclusion A single dose of oral azithromycin with or without amoxicillin for prolonged labor or rupture of membranes at term did not reduce maternal peripartum or neonatal infection. Observed lower than expected infection rates and frequent usual-care antibiotic use may have contributed to these findings. Clinical trial registration ClinicalTrials.gov, NCT03248297. Funding source Merck for Mothers Investigator Studies Program grant.

The COVID-19 pandemic disrupted health care delivery of cancer screenings. The primary aim of our work was to evaluate the degree to which populations were accepting of home-based screenings for colorectal cancer (CRC) and cervical cancer (ie, primary human papillomavirus [HPV] testing). Three groups of adults having distinct health burdens that may affect acceptance of home-based cancer screening were identified through outpatient electronic medical records: those having survived a COVID-19 hospitalization; those having been positive for a non-COVID-19 respiratory illness; or those having type 2 diabetes. A total of 132 respondents (58% female) completed an online survey with hypothetical cases about their acceptance of home-based CRC or cervical cancer screening. Among women respondents, urine and vaginal screening for primary HPV testing was acceptable to 64% and 59%, respectively. Among both men and women, at-home CRC screening with fecal immunochemical test or Cologuard(®) was acceptable to 60% of the respondents. When adjusting for education, women with a positive attitude toward home-based urine and vaginal screening were 49 times and 23 times more likely, respectively, to have a positive attitude toward CRC screening. These findings indicate that home-based cancer screens for CRC and primary HPV testing are acceptable to men and women and may allow for greater compliance with screening in the future.

Objective: To describe the impact of pharmacy driven penicillin allergy assessments on de-labeling penicillin allergies and antibiotic streamlining opportunities for hospitalized patients. Design: Multi-center, retrospective case-series study. Setting: A health system of 4 non-teaching hospitals. Participants: Patients aged 18 years and older with a physician order for a pharmacist penicillin allergy assessment. Exclusion criteria consisted of patients with anaphylaxis or a type II penicillin allergy, anaphylaxis of any cause within 4 weeks, refusal of penicillin allergy skin test (PAST), antihistamine use within 24 hours, penicillin intolerance, immunosuppression or immunosuppressive medications, or skin conditions that could interfere with PAST. Interventions: The primary endpoint evaluated the number of de-labeled penicillin allergies after pharmacists provided penicillin allergy assessments. Secondary endpoints evaluated the percent of patients with antibiotics deescalated to beta-lactam antibiotics and classification of notable interventions made by pharmacists. Measurements and Main Results: There were 35 patients who met inclusion criteria. Twenty-four patients underwent both penicillin allergy skin testing and oral (PO) amoxicillin challenge. Five patients had allergies de-labeled only after a pharmacist interview. Four patients received only the PO amoxicillin challenge and 2 patients received only PAST. Penicillin allergies were de-labeled from the electronic health record (EHR) in 31 (89%) patients despite all testing negative for a penicillin allergy from PAST or a PO amoxicillin challenge. Four patients had the allergy re-added to the chart on subsequent admissions. No patients experienced a reaction from PAST, PO amoxicillin challenge, or subsequent beta-lactam antibiotics. Twenty-eight (80%) patients had their antibiotic therapy changed as a result of the allergy assessment. Seventeen patients were de-escalated onto beta-lactam antibiotics and aztreonam was stopped in 6 patients. Conclusion: Results from this study suggests that pharmacists expanding their scope of practice with PAST is a safe and effective allergy de-labeling tool. Pharmacist-driven penicillin allergy assessments could provide antibiotic cost savings and avoid aztreonam use. The study supports the need to emphasize education for patients and caretakers regarding allergy testing results to avoid relabeling in future hospital visits.

We sought to determine if variation in head circumference (HC) within the range of normal (5th-10th and 90th-95th percentile) is associated with poor neurodevelopmental outcomes (NDO), which defined as mild or moderate delay by Bayley II psychometrics (BSID-II).This is a secondary analysis of a randomized controlled trial assessing the benefits of magnesium for the prevention of cerebral palsy. Fetuses with a normal HC at birth defined as within 5th to 95th percentile were included. NDO were assessed at age 2 with BSID-II. Moderate delay was defined as a score70 and mild delay as85. HC was classified as small normal (5th-10th percentile), normal (10th-90th percentile), and large normal (90th-95th percentile). Logistic regression models adjusted for confounding. Linear regression models estimated the impact for every 1 cm of change in HC.Of 1,236 included infants, 111 (8%) had small normal HC; 1,058 (85%) had normal HC; and 67 (5%) had large normal HC. Baseline characteristics were similar between groups. There was no association with changes in HC within the range of normal and developmental indices. When considered as a continuous variable, every 1 cm increase in HC was also not associated with a significant change in developmental indices.Within the normal range (5th-95th percentile), changes in HC did not correlate with changes in NDO at 2 years as measured by Bayley II scales.· It is unknown if variations in normal HC are associated with poor neurodevelopmental outcomes.. · Alterations in HC within the range of normal (5th-95th percentile) are not associated with adverse NDO.. · When considered as a continuous variable, a 1 cm increase in HC is not associated with adverse NDO.. · Changes in HC within the range of normal do not appear to be a pathologic change altering NDO..

Background Patients with autism spectrum disorder (ASD) experience high rates of sleep disruption beginning early in life; however, the developmental consequences of this disruption are not understood. We examined sleep behavior and the consequences of sleep disruption in developing mice bearing C-terminal truncation mutation in the high-confidence ASD risk gene SHANK3 (Shank3ΔC). We hypothesized that sleep disruption may be an early sign of developmental divergence, and that clinically relevant Shank3WT/ΔC mice may be at increased risk of lasting deleterious outcomes following early life sleep disruption. Methods We recorded sleep behavior in developing Shank3ΔC/ΔC, Shank3WT/ΔC, and wild-type siblings of both sexes using a noninvasive home-cage monitoring system. Separately, litters of Shank3WT/ΔC and wild-type littermates were exposed to automated mechanical sleep disruption for 7 days prior to weaning (early life sleep disruption: ELSD) or post-adolescence (PASD) or undisturbed control (CON) conditions. All groups underwent standard behavioral testing as adults. Results Male and female Shank3ΔC/ΔC mice slept significantly less than wild-type and Shank3WT/ΔC siblings shortly after weaning, with increasing sleep fragmentation in adolescence, indicating that sleep disruption has a developmental onset in this ASD model. ELSD treatment interacted with genetic vulnerability in Shank3WT/ΔC mice, resulting in lasting, sex-specific changes in behavior, whereas wild-type siblings were largely resilient to these effects. Male ELSD Shank3WT/ΔC subjects demonstrated significant changes in sociability, sensory processing, and locomotion, while female ELSD Shank3WT/ΔC subjects had a significant reduction in risk aversion. CON Shank3WT/ΔC mice, PASD mice, and all wild-type mice demonstrated typical behavioral responses in most tests. Limitations This study tested the interaction between developmental sleep disruption and genetic vulnerability using a single ASD mouse model: Shank3ΔC (deletion of exon 21). The broader implications of this work should be supported by additional studies using ASD model mice with distinct genetic vulnerabilities. Conclusion Our study shows that sleep disruption during sensitive periods of early life interacts with underlying genetic vulnerability to drive lasting and sex-specific changes in behavior. As individuals progress through maturation, they gain resilience to the lasting effects of sleep disruption. This work highlights developmental sleep disruption as an important vulnerability in ASD susceptibility.

Delayed sleep-onset is a common problem among children and youth with intellectual and developmental disabilities. This case report describes the effects of a faded bedtime intervention on delayed ...

Background In 2016, the U.S. Food and Drug Administration expressed concern that neurodevelopment may be negatively affected by anesthesia or sedation exposure in pregnancy or before three years of age. We examined the association between general anesthesia at the time of cesarean delivery and early childhood neurodevelopment. Methods A secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm delivery. Exposure was general compared to neuraxial anesthesia. The primary outcome was motor or mental delay at two years of age, assessed by Bayley Scales of Infant Development II (BSIDII). Secondary outcomes included BSIDII subdomains and perinatal outcomes. Multivariable logistic regression models were performed to control for confounders. Results Of 557 women undergoing cesarean delivery, 119 (21%) received general anesthesia. There were no differences in the primary composite outcome of developmental delay (aOR 0.93, 95% CI 0.61 to 1.43) or the BSIDII subdomains of mild, moderate, or severe mental delay, or mild or moderate motor delay. Severe motor delay was more common among infants exposed to general anesthesia (aOR 1.98, 95% CI 1.06 to 3.69). Infants exposed to general anesthesia had longer neonatal intensive care stays (51 vs 37 days, P=0.010). Conclusions General anesthesia for cesarean delivery was not associated with overall neurodevelopmental delay at two years of age, except for greater odds of severe motor delay. Future studies should evaluate this finding, as well as the impact of longer or multiple anesthetic exposures across all gestational ages on neurodevelopment.

The jet-flow overpressure chamber (OPC) has been previously reported as a model of blast-mediated traumatic brain injury (bTBI). However, rigorous characterization of the features of this injury apparatus shows that it fails to recapitulate exposure to an isolated blast wave. Through combined experimental and computational modeling analysis of gas-dynamic flow conditions, we show here that the jet-flow OPC produces a collimated high-speed jet flow with extreme dynamic pressure that delivers a severe compressive impulse. Variable rupture dynamics of the diaphragm through which the jet flow originates also generate a weak and infrequent shock front. In addition, there is a component of acceleration-deceleration injury to the head as it is agitated in the headrest. Although not a faithful model of free-field blast exposure, the jet-flow OPC produces a complex multi-modal model of TBI that can be useful in laboratory investigation of putative TBI therapies and fundamental neurophysiological processes after brain injury.

ObjectiveTo analyze the association between peri-ictal brainstem posturing semiologies with postictal generalized electroencephalographic suppression (PGES) and breathing dysfunction in generalized convulsive seizures (GCS).MethodsIn this prospective, multicenter analysis of GCS, ictal brainstem semiology was classified as (1) decerebration (bilateral symmetric tonic arm extension), (2) decortication (bilateral symmetric tonic arm flexion only), (3) hemi-decerebration (unilateral tonic arm extension with contralateral flexion) and (4) absence of ictal tonic phase. Postictal posturing was also assessed. Respiration was monitored with thoracoabdominal belts, video, and pulse oximetry.ResultsTwo hundred ninety-five seizures (180 patients) were analyzed. Ictal decerebration was observed in 122 of 295 (41.4%), decortication in 47 of 295 (15.9%), and hemi-decerebration in 28 of 295 (9.5%) seizures. Tonic phase was absent in 98 of 295 (33.2%) seizures. Postictal posturing occurred in 18 of 295 (6.1%) seizures. PGES risk increased with ictal decerebration (odds ratio [OR] 14.79, 95% confidence interval [CI] 6.18–35.39,p< 0.001), decortication (OR 11.26, 95% CI 2.96–42.93,p< 0.001), or hemi-decerebration (OR 48.56, 95% CI 6.07–388.78,p< 0.001). Ictal decerebration was associated with longer PGES (p= 0.011). Postictal posturing was associated with postconvulsive central apnea (PCCA) (p= 0.004), longer hypoxemia (p< 0.001), and Spo2recovery (p= 0.035).ConclusionsIctal brainstem semiology is associated with increased PGES risk. Ictal decerebration is associated with longer PGES. Postictal posturing is associated with a 6-fold increased risk of PCCA, longer hypoxemia, and Spo2recovery. Peri-ictal brainstem posturing may be a surrogate biomarker for GCS severity identifiable without in-hospital monitoring.Classification of EvidenceThis study provides Class III evidence that peri-ictal brainstem posturing is associated with the GCS with more prolonged PGES and more severe breathing dysfunction.

LAY SUMMARY: During the coronavirus disease 2019 (COVID-19) pandemic, cancer screening decreased precipitously; home screening for colorectal cancer diminished less than that for colonoscopy and breast and cervical cancer screening. The authors have highlighted approaches for home cancer screening in addition to telemedicine.

Background and Objectives: Family physicians play an important role in delivery of family planning services, but many factors impact scope of practice. One important factor is the development of subspecialties, such as the new subspecialty within obstetrics and gynecology called complex family planning (CFP). Methods: In 2019, we conducted a survey of family medicine department chairs as part of the Council of Academic Family Medicine Educational Research Alliance survey. We used descriptive statistics and logistic regression to test for associations between program and chair characteristics, knowledge of CFP, and attitudes regarding family planning services (complex contraceptive counseling, pregnancy options counseling, first trimester miscarriage management, and pregnancy termination). Results: The survey response rate was 54% (105/193). Only 8% of respondents were aware of the CFP subspecialty. The majority of chairs considered all queried family planning services as part of family medicine’s scope of practice, including pregnancy termination by medication abortion (77%) and by uterine aspiration (60%). Chairs of departments with a faculty champion in family planning had higher odds of advocating for all queried family planning services as part of family medicine scope of practice (OR 3.0, 1.1-8.2) than those without a faculty champion. Conclusions: Few chairs are aware of the new subspecialty of CFP, but most would advocate to maintain some form of abortion care in family medicine’s scope of practice. Given family medicine’s role in the health care safety net, supporting faculty champions in family planning is important to preserve access to family planning services for marginalized communities.

Significance Chronic neurodegeneration, a major cause of the long-term disabilities that afflict survivors of traumatic brain injury (TBI), is linked to an increased risk for late-life neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, vascular dementia, and chronic traumatic encephalopathy. Here, we report on the restoration of blood–brain barrier (BBB) structure and function by P7C3-A20 when administered 12 mo after TBI. This pharmacotherapy was associated with cessation of chronic neurodegeneration and recovery of normal cognitive function, benefits that persisted long after treatment cessation. Pharmacologic renewal of BBB integrity may thus provide a new treatment option for patients who have suffered a remote TBI, or other neurological conditions associated with BBB deterioration., Chronic neurodegeneration in survivors of traumatic brain injury (TBI) is a major cause of morbidity, with no effective therapies to mitigate this progressive and debilitating form of nerve cell death. Here, we report that pharmacologic restoration of the blood–brain barrier (BBB), 12 mo after murine TBI, is associated with arrested axonal neurodegeneration and cognitive recovery, benefits that persisted for months after treatment cessation. Recovery was achieved by 30 d of once-daily administration of P7C3-A20, a compound that stabilizes cellular energy levels. Four months after P7C3-A20, electron microscopy revealed full repair of TBI-induced breaks in cortical and hippocampal BBB endothelium. Immunohistochemical staining identified additional benefits of P7C3-A20, including restoration of normal BBB endothelium length, increased brain capillary pericyte density, increased expression of BBB tight junction proteins, reduced brain infiltration of immunoglobulin, and attenuated neuroinflammation. These changes were accompanied by cessation of TBI-induced chronic axonal degeneration. Specificity for P7C3-A20 action on the endothelium was confirmed by protection of cultured human brain microvascular endothelial cells from hydrogen peroxide-induced cell death, as well as preservation of BBB integrity in mice after exposure to toxic levels of lipopolysaccharide. P7C3-A20 also protected mice from BBB degradation after acute TBI. Collectively, our results provide insights into the pathophysiologic mechanisms behind chronic neurodegeneration after TBI, along with a putative treatment strategy. Because TBI increases the risks of other forms of neurodegeneration involving BBB deterioration (e.g., Alzheimer’s disease, Parkinson’s disease, vascular dementia, chronic traumatic encephalopathy), P7C3-A20 may have widespread clinical utility in the setting of neurodegenerative conditions.

To examine the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin-related kinase receptor-B (TrkB), in normal and glaucomatous human retinas.Human retinas were collected from 8 donors who had been clinically diagnosed and treated for glaucoma, and from 9 control donors. Immunohistochemical analysis for BDNF and TrkB was performed. The percent of each retina expressing BDNF and TrkB was quantified for the total retinal thickness, and separately for the retinal ganglion cell (RGC) complex + retinal nerve fiber layer (RNFL). The expression of each protein was correlated with clinical outcomes obtained from the subject's ocular histories.There was no significant difference in BDNF or TrkB expression when comparing glaucomatous and control retinas. Correlation analysis revealed a significant relationship between BDNF expression and the use of prostaglandin analogs. TrkB expression was highly correlated with the last-measured intraocular pressure (IOP), the use of carbonic anhydrase inhibitors, the use of beta blockers, and the total number of drugs used for the treatment of glaucoma.Topical drugs used to treat glaucoma were associated with an increase in retinal BDNF and TrkB expression in human retina, independent of IOP, which may represent molecular evidence of neuroprotective pathway activation.

Objective Nicotine is an established neuroteratogen, and prenatal tobacco exposure alters the structure of the developing nervous system. An association between prenatal tobacco exposure and impaired neurologic function is less well established. We examine the association between prenatal tobacco exposure and childhood neurodevelopment among infants born preterm. Study Design Secondary analysis of a multicenter randomized controlled trial assessing the benefits of magnesium sulfate for the prevention of cerebral palsy in preterm infants. Women were included if they delivered a singleton and nonanomalous infant before 37 weeks. Exposure was any self-reported prenatal tobacco use. Primary outcome was the original trial composite outcome of moderate or severe cerebral palsy at 2 years of age, or stillbirth, or infant death by 1 year of age. Secondary outcomes included components of the composite and mild cerebral palsy at 2 years, Bayley Scales of Infant Development II motor and mental scores, death before two years, and use of auditory aids or corrective lenses. Multivariable logistic regression models were performed to estimate adjusted odds ratios (aOR) with 95% confidence intervals. Results Of 1,826 women included, 503 (27.5%) used tobacco. Tobacco users were more likely to be older, unmarried, and white; have a prior preterm birth; have received no prenatal care; and to use illicit drugs or alcohol. Gestational age at delivery, betamethasone exposure, and magnesium exposure were not different between groups. There were no differences in the composite primary outcome or in rates of cerebral palsy by tobacco use. Moderate developmental delay was more common among tobacco exposed in bivariate but not adjusted analysis (20.5 vs. 15.9%, p = 0.035). In adjusted analysis, tobacco exposure was associated with increased use of corrective lenses (5.0 vs. 2.9%, aOR: 2.28, 95% confidence interval: 1.28–4.07). Conclusion Prenatal tobacco exposure is not associated with neurodevelopmental impairment in infants born preterm. However, tobacco exposure may be associated with impaired vision. Key Points

Objectives Hypoxia, or abnormally low blood‐oxygen levels, often accompanies seizures and may elicit brain structural changes in people with epilepsy which contribute to central processes underlying sudden unexpected death in epilepsy (SUDEP). The extent to which hypoxia may be related to brain structural alterations in this patient group remains unexplored. Methods We analyzed high‐resolution T1‐weighted magnetic resonance imaging (MRI) to determine brain morphometric and volumetric alterations in people with generalized tonic‐clonic seizures (GTCS) recorded during long‐term video‐electroencephalography (VEEG), recruited from two sites (n = 22), together with data from age‐ and sex‐matched healthy controls (n = 43). Subjects were sub‐divided into those with mild/moderate (GTCS‐hypox‐mild/moderate, n = 12) and severe (GTCS‐hypox‐severe, n = 10) hypoxia, measured by peripheral oxygen saturation (SpO2) during VEEG. Whole‐brain voxel‐based morphometry (VBM) and regional volumetry were used to assess group comparisons and correlations between brain structural measurements as well as the duration and extent of hypoxia during GTCS. Results Morphometric and volumetric alterations appeared in association with peri‐GTCS hypoxia, including volume loss in the periaqueductal gray (PAG), thalamus, hypothalamus, vermis, cerebellum, parabrachial pons, and medulla. Thalamic and PAG volume was significantly reduced in GTCS patients with severe hypoxia compared with GTCS patients with mild/moderate hypoxia. Brainstem volume loss appeared in both hypoxia groups, although it was more extensive in those with severe hypoxia. Significant negative partial correlations emerged between thalamic and hippocampal volume and extent of hypoxia, whereas vermis and accumbens volumes declined with increasing hypoxia duration. Significance Brain structural alterations in patients with GTCS are related to the extent of hypoxia in brain sites that serve vital functions. Although the changes are associative only, they provide evidence of injury to regulatory brain sites related to respiratory manifestations of seizures.

OBJECTIVE The study aimed to test the hypothesis that higher Edinburgh Postnatal Depression Scale (EPDS) scores are associated with increased pain scores and opioid use during postpartum hospitalization following cesarean section. STUDY DESIGN We conducted a retrospective cohort of English or Spanish-speaking women ≥18 years who had prenatal care for a singleton gestation and delivered by cesarean at ≥36 weeks within a tertiary center during 2017. Exclusions included women with fetal anomalies, intrauterine fetal demise, sickle cell disease, previously diagnosed pain disorders (e.g., chronic pain or fibromyalgia), substance use disorder (based on documented prescription or use of methadone or buprenorphine), or reoperation during hospital stay. Women without an EPDS recorded antenatally were also excluded. Major depressive symptoms (MDS) were defined as a documented antenatal EPDS ≥12. Women with and without MDS were compared, and multivariable linear regression models were generated to evaluate associations between MDS status and both pain scores and opioid use. RESULTS Of the 891 women meeting other inclusion criteria, 676 (76%) had documented antenatal EPDS scores, and 104 (15.4%) of those had MDS. Women with MDS were more likely to be use tobacco and have general anesthesia for cesarean delivery, but groups were otherwise similar. Women with MDS reported higher daily and average pain scores postpartum (2.4 vs. 1.7 average; p

Objective This study aimed to evaluate perinatal outcomes in women with a history of recurrent pregnancy loss. Study Design Retrospective cohort study of singleton and nonanomalous gestations at ≥ 20 weeks who delivered at our academic institution. The exposed group was defined as women with a history of ≥ 2 consecutive spontaneous abortions (SABs) at Results Of 17,670 women included, 235 (1.3%) had a history of ≥ 2 consecutive SABs. Compared with women with a history of ≤ 1 SAB, women with ≥ 2 consecutive SABs were not more likely to have a PTB (19.6 vs. 14.0%, p = 0.01, adjusted odds ratios (AOR): 0.91, 95% confidence interval [CI]: 0.62–1.33). However, they were more likely to deliver at an earlier mean gestational age (37.8 ± 3.4 vs. 38.6 ± 2.9 weeks, p Conclusion A history of ≥ 2 consecutive SABs was not associated with an increased incidence of PTB but may be associated with gestational diabetes in a subsequent pregnancy. Key Points

Purpose The Sauve-Kapandji procedure (SK) combines a distal radioulnar joint (DRUJ) arthrodesis with the creation of an ulnar pseudarthrosis for the salvage of DRUJ instability or arthritis. Despite several published case series, there are limited data on postoperative functional outcomes. This study evaluates patient-reported outcomes of SK using a validated functional outcomes scale. Methods We performed a retrospective review of patients who underwent SK in 2 health care systems over 10 years (2008–2018). Preoperative and postoperative range of motion, Quick–Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores, and wrist plain film radiographic measurements were recorded. Preoperative and postoperative outcomes analyses and subgroup comparisons were performed. Results We included 57 patients in the study. Surgical indications included posttraumatic DRUJ arthritis (n = 35), rheumatoid arthritis (n = 10), degenerative DRUJ arthritis (n = 7), Madelung deformity (n = 3), psoriatic arthritis (n = 1), and giant cell tumor of bone (n = 1). During the first postoperative year, QuickDASH scores decreased from a mean of 52 before surgery to 28 at 12 months. The QuickDASH scores at final follow-up demonstrated significant improvement in patients with osteoarthritis and inflammatory arthritis. Supination significantly improved after surgery, from 48° to 74°, whereas wrist flexion, wrist extension, and pronation remained unchanged. Radiographically, significant postoperative decreases were seen in ulnar variance and McMurtry’s translation index. The postoperative complication rate was 21%, including revision osteotomy in 4 patients (7.0%) and hardware removal in 4 patients (7.0%). No DRUJ nonunions were seen. Conclusions The Sauve-Kapandji procedure for DRUJ salvage significantly improved patient-reported outcomes after 1 year and significantly improved supination. Similar functional improvements after SK were seen in both osteoarthritis and inflammatory arthritis. Type of study/level of evidence Therapeutic IV.

Objective The aim of this study is to assess the impact of a prolonged second stage of labor on maternal and neonatal outcomes by comparing women who had expectant management versus operative intervention beyond specified timeframes in the second stage of labor. Study Design Retrospective cohort including live singletons at ≥36 weeks who reached the second stage of labor. Expectant management (second stage >3, 2, 2, and 1 hour in nulliparas with an epidural, nulliparas without an epidural, multiparas with an epidural, and multiparas without an epidural, respectively) was compared with those who had an operative delivery (vaginal or cesarean) prior to these timeframes. The primary maternal outcome was a composite of postpartum hemorrhage, chorioamnionitis, operative complications, postpartum infections, and intensive care unit admission. The primary neonatal outcome was a composite of cord blood acidemia, 5-minute Apgar's score 1 day. Results Among 218 women, 115 (52.8%) had expectant management. Expectant management was associated with a significantly increased risk of the maternal composite (adjusted odds ratio [aOR]: 1.99, 95% confidence interval [CI]: 1.09–3.64) but not the neonatal composite (aOR: 1.54, 95% CI: 0.71–3.35). Conclusion Expectant management of a prolonged second stage was associated with a higher rate of adverse maternal outcomes, but the rate of adverse neonatal outcomes was not significantly increased.

The present study addressed the problem of overweight and obesity in students with autism spectrum disorder (ASD) through replication and social validation of a residential health and wellness intervention. The primary methods were (a) diet-nutrition, (b) exercise-physical activity, (c) health informatics monitoring, and (d) care provider training which were implemented as an intervention package with four adolescent students (16–19 years old) attending a residential school. The students lost between 9 and 59 lbs. (M = 28.5 lbs.) from baseline weights of 168–238 lbs. and had corresponding reduction in BMI. Three of the four students classified as obese preceding the intervention achieved non-obese status; one of them also reached non-overweight status by conclusion of the study. The fourth student was classified as overweight but not obese preceding intervention and subsequently achieved non-overweight status. Parents of the students rated the health and wellness intervention positively with regard to the procedures and outcomes. Results suggest that residential health and wellness interventions can be effective with adolescent students who have ASD and are overweight and obese. Further replication and component analyses of intervention methods are meaningful objectives for future research.

This study aimed to assess whether patient satisfaction differs between women beginning cervical ripening in the outpatient versus inpatient setting.We performed a planned secondary analysis evaluating patient satisfaction randomized to outpatient versus inpatient cervical ripening. In the original randomized controlled trial, low-risk parous women ≥39 weeks who required cervical ripening for induction and had reassuring fetal heart rate monitoring were included and randomized to inpatient versus outpatient ripening with a transcervical Foley's catheter. All women were then admitted to the labor ward on the following day. Patient satisfaction was evaluated using three separate surveys. The first two surveys, Six Simple Questions and Lady-X, were previously validated. The third survey used visual analog scales to assess overall pain experienced during Foley's placement, overall pain experienced during labor, how likely they would be to choose the same type of care for their next pregnancy, and how likely they would be to recommend their method of cervical ripening to friends/family.From May 2016 to October 2017, 129 women were randomized (outpatient, 65; inpatient, 64). Based on survey results, there was no difference in satisfaction between outpatient and inpatient cervical ripening with transcervical Foley's catheterization, with high satisfaction in both groups. Patients in both the outpatient and inpatient groups would choose the same type of care for their next pregnancy (on a scale of 1-7, median (25th-75th percentile): 7 [7-7] vs. 7 [6-7], respectively,Parous women's satisfaction does not differ between inpatient and outpatient cervical ripening with transcervical Foley's catheterization.· Outpatient cervical ripening may allow providers to incorporate the benefits of electively inducing women as well as decrease the time spent in the labor and delivery unit.. · Parous women's satisfaction does not differ between inpatient and outpatient cervical ripening with transcervical Foley.. · Additional prospective evaluation is warranted to further characterize patient preferences in relation to the location of cervical ripening..

We report the case of an 18-year-old girl who had autism spectrum disorder (ASD) and demonstrated persistent delayed sleep onset after going to bed in her group home at a residential school. Intervention consisted of a faded bedtime in which her customary time to bed was extended later into the night, then gradually made earlier as she started falling asleep more rapidly over the course of many weeks. By conclusion of the study and at a 1-month follow-up, the girl was falling asleep in less than 30 min after going to bed and sleeping an average of 8.4 hr each night. Compared with previous research with children in inpatient and home environments, the study found positive effects from a faded bedtime intervention without additional procedures, targeted an adolescent with ASD, and was conducted by care providers in a novel residence setting.

Background: The recommended gestational age to deliver pregnancies complicated by diabetes ranges from 34 to 39 weeks of gestation. The objective of this study was to determine the optimal gestational age for delivery of patients with diabetes to minimize perinatal death. Methods: We extracted a population-based cohort of singleton, nonanomalous infants of diabetic pregnancies from the Missouri birth registry for the period January 1, 1989 to December 31, 2005 and compared perinatal outcomes of planned deliveries at 37, 38, 39, and 40 weeks to expectant management. Planned deliveries were identified by induction or cesarean delivery without documented medical or obstetric indications. The primary outcome was perinatal death, defined as stillbirth or neonatal death within 28 days of birth. Secondary outcomes were independent stillbirth, independent neonatal death, and a composite adverse neonatal event of assisted ventilation >30 minutes, birth injury, seizures, or 5-minute Apgar score ≤3. Groups were compared using t test and chi-square as appropriate. Results: In 4,905 diabetic pregnancies reaching 37 weeks, 1,012 (20.6%) patients were insulin dependent. Overall, the risk of perinatal death at any gestational age examined was low (3/1,000 births or lower), as was the risk of the adverse perinatal outcome (

IntroductionUsing screen counts, women 50-64 yo have lower cancer screening rates for cervical and colorectal cancers compared to all other age ranges. The primary aim of this paper is to present cervical cancer and CRC screenings per woman and determine the predictors of being up-to-date for both.MethodsWe used the Behavioral Risk Factor Surveillance System (BRFSS), an annual survey to guide health policy in the US, to explore the up-to-date status of dual cervical and colorectal cancer screening for women 50-64 yo. We categorized women into four mutually exclusive categories: up-to-date for dual screening, each single-screen, or neither screen. Multinomial multivariate regression modeling was used to evaluate the predictors of each category.ResultsAmong women ages 50-64 yo, dual screening was reported for 58.7% (57.6-59.9), cervical cancer screening alone (27.0% (25.9-28.1), CRC screening alone (5.3% (4.8-5.8), and neither screen (9% (8.4-9.6). Age, race, education, income, and chronic health conditions were significantly associated with dual screening compared to neither screen. Hispanic women compared to non-Hispanic White women were more likely to be up-to-date with cervical cancer screening than dual screening (aOR 1.38 (1.08, 1.77). By comparison to younger women, those 60-64 years are significantly more likely to be up-to-date with CRC screening than dual screening (aOR 1.75 (1.30, 2.34)).ConclusionsScreening received by each woman shows a much lower rate of dual screening than prior single cancer screening rates. Addressing dual screening strategies rather than single cancer screening programs for women 50-64 years may increase both cancer screening rates.Graphical AbstractScreening rates differ by calculation approach. A better population metric for cancer prevention is to consider the screens each woman has received. Our data show much lower cervical cancer and CRC screening rates than a single screen calculation.TweetWomen 50-64 years old lack dual cervical and colorectal cancer screening. Women who screen for only one cancer of the two, screen for cervical cancer almost five times more often than colorectal cancer.Lay SummaryRoutine cervical and colorectal cancer (CRC) screenings can detect early, treatable, curable cancers. Using the responses to the 2018 Behavioral Risk Factor Surveillance Survey (BRFSS) we approached prevention by what the woman has received rather than by how many screens were done. We showed that women 50-64 years old were only up-to-date for both cervical and CRC screening 59% of the time, whereas, by traditional screening calculations, our data showed 86% of women were up-to-date for cervical cancer screening and 64% were up to date with CRC screening, irrespective of any other cancer screenings.

Neonatal survival requires precise control of breathing and cardiovascular action, with fatal consequences or severe injury without support. Prematurity presents multiple opportunities to disrupt cardiorespiratory regulation, leading to expressions of apnea of prematurity, periodic breathing, and inappropriate cardiovascular responses to apnea. Failed breathing control can result from altered breathing drives, typically arising from untimely development of sensory or motor coordination processes. Some drives, such as temperature, are a special concern in neonates with low body mass, enhancing susceptibility to rapid body cooling. Chemical drives, such as pH or CO2 or O2, may be inadequately developed; in some conditions, such as congenital central hypoventilation syndrome (CCHS), breathing responses to CO2 or low O2 may be reduced or absent, and coupling of cardiovascular responses to breathing changes are abolished. Sleep states exert profound influences on both chemical and temperature drives, with rapid eye movement (REM) sleep potentially modifying descending temperature influences, and state transitions significantly altering respiratory responses to chemical stimuli. In addition, neonates spend the majority of time in REM sleep, a state which induces a generalized inhibition of skeletal muscle activity that abolishes muscle tone to upper airway and thoracic wall muscles, enhancing the likelihood for obstructive sleep apnea. Although disrupted regulatory drives can often be replaced by positive (or negative) pressure ventilation, such as continuous positive airway pressure or enhanced by manipulating neurotransmitter action via caffeine, those approaches may exert negative consequences in the long term; the lungs of neonates, especially premature infants, are fragile, and easily injured by positive pressure. The consequences of caffeine use, acting directly on neural receptors, although seemingly innocuous in the near-term, may have long-term concerns and disrupts the integrity of sleep. The developmental breathing field needs improved means to support ventilation when one or more drives to respiration fail, and when the cardiovascular system, depending heavily on interactions with breathing, is compromised. Neuromodulatory procedures which manipulate the vestibular system to stabilize breathing or use tactile or proprioceptive stimuli to activate long-established reflexive mechanisms coupling limb movement with respiratory efforts can provide support for central and obstructive apnea, as well as for periodic breathing and cardiovascular action, particularly during sleep.

Cerebellar stimulation reduces seizures in animals and in humans with drug-resistant epilepsy. In a pilot safety and feasibility study, we applied continuous cutaneous vibratory stimulation (limb proprioceptive cerebellar stimulation) to foot limb proprioceptive receptors to activate cerebellar, pontine, and thalamic structures in drug-resistant epilepsy patients for 8-h nocturnally up to 6-months after a 4-week pre-treatment control baseline. Seizure frequency was evaluated during the baseline control period, and at 6, 12, and 24 weeks after the control recordings. Five-subjects completed at least the first 6-week treatment. At 12-weeks, the median reduction in seizure frequency was −27.8% (mean reduction = −22.3%). Two subjects continued for 24 weeks, with a decline of −44.1 and −45.4%. This pilot study provides support for further clinical studies into the safety and efficacy of limb proprioceptive cerebellar stimulation for epilepsy.

Background:Women 50–65 years of age have the lowest cervical and colorectal cancer (CRC) screening rates among ages recommended for screening. The primary aim of this work is to determine how cancer risk perceptions and provider communication behaviors, in addition to known demographic factors, influence the uptake of both cervical and CRC screening or a single screen among women in southeast Michigan.Methods:Fourteen health services and communication behavior questions were adapted from the Health Information National Trends Survey (HINTS) and administered to a multiethnic sample of adults in southeast Michigan. The outcome variable was self-reported up-to-date cervical cancer and/or CRC screening as defined by the United States Preventive Services Task Force (USPSTF). Demographic and cancer risk/communication behavior responses of the four screening populations (both tests, one test, no tests) were analyzed with multinomial regression for all comparisons.Results:Of the 394 respondents, 54% were up to date for both cervical and CRC screening, 21% were up to date with only cervical cancer screening and 12% were up to date for only CRC screening. Of the 14 risk perception and communication behavior questions, only ‘Did your primary care physician (PCP) involve you in the decisions about your health care as much as you wanted?’ was significantly associated with women having both screens compared to only cervical cancer screening (aOR 1.67; 95% CI: 1.08, 2.57). The multivariate model showed age, and Middle East and North African (MENA) ethnicity and Black race, in addition to PCP-patient dyad decision-making to be associated with the cancer screenings women completed.Conclusions:Optimizing PCP-patient decision-making in health care may increase opportunities for both cervical cancer and CRC screening either in the office or by self-sampling. Understanding the effects of age and the different interventional strategies needed for MENA women compared to Black women will inform future intervention trials aimed to increase both cancer screenings.Funding:This work was supported by NIH through the Michigan Institute for Clinical and Health Research UL1TR002240 and by NCI through The University of Michigan Rogel Cancer Center P30CA046592-29-S4 grants.

SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system. SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt βII-spectrin function and disturb cytoskeletal organization and dynamics.

The objective was to determine whether hyoid bone elevation induced by an anterior mandibular positioning appliance (AMP) predicts the effectiveness of the AMP in patients with obstructive sleep apnea (OSA). Fifteen patients (12 males and 3 females) underwent polysomnographic recordings and lateral cephalograms before and after AMP use of at least 6 months. Measurements of sleep variables and upper airway morphology were compared between pre-AMP and with-AMP states. The AMP appliance reduced apnea-hypopnea indices (AHI) ~53% (33.77 ± 3.29 vs. 15.85 ± 3.78, P = 0.0013). Cephalograms of the oropharyngeal airway showed that the hyoid bone moved superiorly toward the inferior mandibular border (Δ H-MP) ~5 mm (23.4 ± 1.44 vs. 18.27 ± 1.86, P = 0.0377), with the AMP inserted in the oral cavity; no airway measurement other than hyoid bone position changed. No significant correlations emerged between AHI improvement (Δ AHI) and amounts of hyoid elevation (Δ H-MP) when all patients were pooled. However, when the samples were subcategorized, the correlation coefficients increased significantly (P < 0.01) in both subgroups. This outcome suggests the presence of two distinct types among the “Good-Responders” to AMP appliance use. Overall use of the AMP appliance is effective; however, the effectiveness of the appliance appears to depend on the mode of hyoid elevations, likely resulting from muscle responsiveness in patients with AMP use. The results suggest that Δ H-MP measurements may be a useful marker to segregate patients with tongue and hyoid muscles responsive to AMP from those not-so-responsive.

Appalachian women 18 to 26 years old have high baseline seropositivity rates for at least 1 of the 4 human papillomavirus vaccine–related types, but low vaccine-relevant type infections. Supplemental digital content is available in the text., Background Key informants of the Appalachian community questioned whether their unique environmental stressors would alter their immune response to human papillomavirus (HPV) infections. The primary aim of this study is to determine predictors of HPV seroprevalence to at least 1 of the 4 vaccine-related HPV types before vaccination using a psychoneuroimmunologic model in Appalachian women. Method Women aged 18 to 26 years (n = 185) who had not received HPV vaccination provided cervical HPV DNA and blood samples. Human papillomavirus DNA was identified through Hybrid Capture 2 assay and then genotyped for HPV types 6, 11, 16, and 18 by Roche Linear Array. Competitive Luminex Immunoassay measured the type-specific antibodies to HPV types 6, 11, 16, and 18 in milli-Merck units per milliliter. Nine psychoneuroimmunology scales measuring attributes of stress were self-completed. Results Human papillomavirus DNA was detected in 50% (92/183) of participants, with only 14% (26/183) positive for HPV-6/11/16/18 DNA. Seropositivity for at least one anti–HPV-6/11/16 or 18, on the other hand, was present in 35% (64/183) of women, with only 10% (19/183) concomitantly infected and seropositive for the vaccine-related types. The Perceived Stress Scale was not a strong predictor of HPV seropositivity. Conclusions Both HPV infection and vaccine-related HPV type seropositivity is common among Appalachian women aged 18 to 26 years. The anticipated effect of environmental stressors on HPV seropositivity was not seen when multiple predictors were considered.

Purpose The purpose of this study was to examine the influence of genetic background on the retinal ganglion cell (RGC) response to blast-mediated traumatic brain injury (TBI) in Jackson Diversity Outbred (J:DO), C57BL/6J and BALB/cByJ mice. Methods Mice were subject to one blast injury of 137 kPa. RGC structure was analyzed by optical coherence tomography (OCT), function by the pattern electroretinogram (PERG), and histologically using BRN3A antibody staining. Results Comparison of the change in each group from baseline for OCT and PERG was performed. There was a significant difference in the J:DOΔOCT compared to C57BL/6J mice (P = 0.004), but not compared to BALB/cByJ (P = 0.21). There was a significant difference in the variance of the ΔOCT in J:DO compared to both C57BL/6J and BALB/cByJ mice. The baseline PERG amplitude was 20.33 ± 9.32 µV, which decreased an average of -4.14 ± 12.46 µV following TBI. Baseline RGC complex + RNFL thickness was 70.92 ± 4.52 µm, which decreased an average of -1.43 ± 2.88 µm following blast exposure. There was not a significant difference in the ΔPERG between J:DO and C57BL/6J (P = 0.13), although the variances of the groups were significantly different. Blast exposure in J:DO mice results in a density change of 558.6 ± 440.5 BRN3A-positive RGCs/mm2 (mean ± SD). Conclusions The changes in retinal outcomes had greater variance in outbred mice than what has been reported, and largely replicated herein, for inbred mice. These results demonstrate that the RGC response to blast injury is highly dependent upon genetic background.

Highlights • Middle Eastern/North African (MENA) women in the US have the lowest up-to-date screening rate of colorectal and cervical cancer of all races/ethnicities at 18%. • Any chronic health condition doubles the likelihood of having both below the belt screens compared to neither screen. • Women without insurance are more likely to only have cervical cancer compared to both colorectal and cervical cancer up-to-date screens. • 54% of women 50–65 years old are up-to-date with both colorectal and cervical cancer screening., Middle Eastern/North Africa (MENA) women are often not identified in cancer screening studies. The aim of this study was to determine the rates and predictors of cervical and colorectal cancer (CRC) screening for women 50–65 years of three race/ethnicities. White, black and MENA women of Southeast Michigan were surveyed once in 2019 for demographics, health care barriers, chronic diseases, and cancer screening updates using in-person, telephone, and online methods. Descriptive statistics and multivariate multinomial logistic regression were used to predict up-to-date colorectal cancer and cervical cancer screening. All analyses were adjusted by local population weights for comparability and generalizability. 394 women participated with 54% up-to-date on both screenings, 21% for cervical cancer screening alone, and 12% for CRC alone. Women more likely to be up-to-date for only cervical cancer screening compared to both cancer screens are younger (aOR 0.83 (95% CI 0.76, 0.92), are of MENA descent (7.97 (2.46, 25.76) and have no insurance (9.41 (1.07, 82.92). There are no predictors for women being up-to-date for CRC screening alone compared to both screens. Among women 50–65 years old, being up-to-date in cervical cancer screening is unrelated to being up-to-date for CRC screening. Compared to Healthy People 2020, there are significant gaps in cervical and CRC screening among women 50–65 years old of all races, but particularly among women of MENA descent who are even less likely to have CRC screening than cervical cancer screening.

Rationale: Currently, there is some ambiguity over the role of postictal generalized electro-encephalographic suppression (PGES) as a biomarker in sudden unexpected death in epilepsy (SUDEP). Visual analysis of PGES, known to be subjective, may account for this. In this study, we set out to perform an analysis of PGES presence and duration using a validated signal processing tool, specifically to examine the association between PGES and seizure features previously reported to be associated with visually analyzed PGES.Methods: This is a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of SUDEP in adult patients with intractable epilepsy. We studied videoelectroencephalogram (vEEG) recordings of generalized convulsive seizures (GCS) in a cohort of patients in whom respiratory and vEEG recording were carried out during the evaluation in the epilepsy monitoring unit. A validated automated EEG suppression detection tool was used to determine presence and duration of PGES.Results: We studied 148 GCS in 87 patients. PGES occurred in 106/148 (71.6%) seizures in 70/87 (80.5%) of patients. PGES mean duration was 38.7 ± 23.7 (37; 1–169) seconds. Presence of tonic phase during GCS, including decerebration, decortication and hemi-decerebration, were 8.29 (CI 2.6–26.39, p = 0.0003), 7.17 (CI 1.29–39.76, p = 0.02), and 4.77 (CI 1.25–18.20, p = 0.02) times more likely to have PGES, respectively. In addition, presence of decerebration (p = 0.004) and decortication (p = 0.02), older age (p = 0.009), and hypoxemia duration (p = 0.03) were associated with longer PGES durations.Conclusions: In this study, we confirmed observations made with visual analysis, that presence of tonic phase during GCS, longer hypoxemia, and older age are reliably associated with PGES. We found that of the different types of tonic phase posturing, decerebration has the strongest association with PGES, followed by decortication, followed by hemi-decerebration. This suggests that these factors are likely indicative of seizure severity and may or may not be associated with SUDEP. An automated signal processing tool enables objective metrics, and may resolve apparent ambiguities in the role of PGES in SUDEP and seizure severity studies.

BackgroundWomen 50-65 years old have the lowest cervical and colorectal cancer (CRC) screening rates amongst ages recommended for screening. The primary aim of this work is to determine how cancer risk perceptions and provider communication behaviors, in addition to known demographic factors, influence the uptake of both cervical and CRC screening or a single screen among women in southeast Michigan.Methods14 health services and communication behavior questions were adapted from the Health Information National Trends Survey (HINTS) and administered to a multiethnic sample of adults in southeast Michigan. The outcome variable was self-reported up to date cervical and/or CRC screening as defined by the United States Preventive Services Task Force (USPSTF). Demographic and cancer risk/communication behavior responses of the four screening status categories (both tests, one test, no tests) were analyzed with multinomial regression for all comparisons.ResultsOf the 394 respondents, 54% were up to date for both cervical and CRC screening, 21% were up to date with only cervical cancer screening and 12% were up to date for only CRC screening. Of the 14 risk perception and communication behaviors only, Did your primary care physician (PCP) involve you in the decisions about your health care as much as you wanted? was significantly associated with women having both screens compared to only cervical cancer screening (aOR 1.67 (95% CI: 1.08, 2.57). The control variables included in the model, also significant, were MENA and Black races compared to white women and age.ConclusionsScreening behavior for both cancers is different than a single screen and associated with the woman’s perception of the physician involving her in her care as much as she wanted. In addition, educational programs are needed for MENA women.

Prostate cancer cells are characterized by a remarkably low proliferative rate and the production of high levels of prostate-specific proteases. Protein-based toxins are attractive candidates for prostate cancer therapy because they kill cells via proliferation-independent mechanisms. However, the non-specific cytotoxicity of these potent cytotoxins must be redirected to avoid toxicity to normal tissues. Prostate-Specific Membrane Antigen (PSMA) is membrane-bound carboxypeptidase that is highly expressed by prostate cancer cells. Potent dipeptide PSMA inhibitors have been developed that can selectively deliver and concentrate imaging agents within prostate cancer cells based on continuous PSMA internalization and endosomal cycling. On this basis, we conjugated a PSMA inhibitor to the apoptosis-inducing human protease Granzyme B and the potent Pseudomonas exotoxin protein toxin fragment, PE35. We assessed selective PSMA binding and entrance into tumor cell to induce cell death. We demonstrated these agents selectively bound to PSMA and became internalized. PSMA-targeted PE35 toxin was selectively toxic to PSMA producing cells in vitro. Intratumoral and intravenous administration of this toxin produced marked tumor killing of PSMA-producing xenografts with minimal host toxicity. These studies demonstrate that urea-based PSMA inhibitors represent a simpler, less expensive alternative to antibodies as a means to deliver cytotoxic proteins to prostate cancer cells.

In the past ten years, insurance funding has become a primary source of payment for applied behavior analytic services for individuals with autism spectrum disorders. The increased accessibility of...

Several subjective and direct methods have been used to measure and assess sleep patterns and problems among children and youth with autism spectrum disorder (ASD). In this paper, we describe the design, operating functions, and application of a computer-assisted system of sleep monitoring and data recording to improve measurement integrity of overnight care providers at a residential school. Descriptive and longitudinal evaluation conducted over a four-year evaluation period revealed that care providers averaged 91% implementation integrity with the system. A subsequent social validity assessment through survey questionnaire found that care providers uniformly rated the system as easy to learn, understand, and implement. We discuss the advantages of the system for sleep measurement and assessment of children and youth who have ASD and receive services in residential-care settings.

Objective The objective of this study was to evaluate the association between the method of maternal glycemic control after antenatal corticosteroid, administration and maternal hyperglycemia and neonatal morbidity among women with diabetes.Study Design This was a retrospective cohort study of women with pregestational diabetes who received antenatal corticosteroids and delivered in Results Of 52 eligible women, only 1 (1.9%) had adequate maternal glycemic control. There was no significant association between the method of glycemic control and maternal hyperglycemia or neonatal morbidity. There was no association between maternal glucose and neonatal morbidity; however, neonates with composite morbidity were more likely to be born to women who received less insulin.Conclusion Maternal glycemic control among women with diabetes was poor after the antenatal corticosteroid administration, regardless of glycemic control method. Neither the method of maternal glycemic control nor the degree of control was associated with neonatal morbidity.

Snakebites in pregnancy can result in significant maternal and fetal harm; however, the literature to guide management of this rare obstetric complication remains limited. We describe our approach to envenomation in pregnancy based on the currently available evidence. A 27-year-old G2P1 female presented at 27 weeks’ gestation after suffering a copperhead snakebite. She received antivenom and antenatal steroids without adverse maternal or fetal event. Antenatal testing was reassuring throughout admission, and she was discharged home with plans for close outpatient surveillance. She later developed preterm premature rupture of membranes and preterm labor, with delivery of a live infant at 33 weeks’ gestation. The risk of adverse maternal and fetal outcomes following snake envenomation in pregnancy may warrant closer antenatal surveillance than has been previously described.

Objective Late-night eating during pregnancy is associated with greater risk for gestational diabetes. The purposes of this study were to describe reasons why women engage in late-night eating and to understand perceptions about changing this behavior. Design Focus groups using a semi-structured interview script. Setting Urban university-affiliated obstetric clinic. Participants Low-income black women (n = 18) with overweight/obesity at entry to prenatal care. Phenomenon of Interest Late-night eating. Analysis Exhaustive approach coding responses to specific questions. Results Individual and interpersonal contributors to late-night eating included hunger, altered sleep patterns, fetal movement, and the influence of others. Food choices were largely driven by taste and convenience. Some women reported that they could alter nightly eating patterns, whereas others would consider changing only if late-night eating were associated with a severe illness or disability for the child. Conclusions and Implications There was considerable heterogeneity among the participants of this study regarding reasons for late-night eating during pregnancy and attitudes toward changing this behavior. Although the themes identified from this study cannot be generalized, they may be useful to inform future studies. Future research might develop strategies to overcome individual and social factors that contribute to late-night eating during pregnancy.

In this study, four children with autism were assessed to determine their preference choices for toothbrushes and toothpastes included during self-care skills teaching sessions. For two of the chil...

Opioid use disorders during pregnancy are a major risk factor for pregnancy-associated deaths. Women with opioid use disorders also experience increases in the incidence of cardiac arrest, renal failure, cesarean delivery, and blood transfusion. As such there is a tremendous need by obstetricians to