Outcomes of neoadjuvant chemotherapy and radical hysterectomy for locally advanced cervical cancer at Kigali University Teaching Hospital, Rwanda: a retrospective descriptive study.

BACKGROUND: Half of countries in Africa lack access to radiation (RT), which is essential for standard treatment of locally advanced cervical cancers. We evaluated outcomes for patients treated with neoadjuvant chemotherapy (NACT) followed by radical hysterectomy in settings where no RT is available. METHODS: We performed a retrospective descriptive study of all patients with FIGO stage IB2-IIA2 and some exceptional stage IIB cases who received NACT and surgery at Kigali University Teaching Hospital in Rwanda. Patients were treated with NACT consisting of carboplatin and paclitaxel once every 3 weeks for 3-4 cycles before radical hysterectomy. We calculated recurrence rates and overall survival (OS) rate was determined by Kaplan-Meier estimates. RESULTS: Between May 2016 and October 2018, 57 patients underwent NACT and 43 (75.4%) were candidates for radical hysterectomy after clinical response assessment. Among the 43 patients who received NACT and surgery, the median age was 56 years, 14% were HIV positive, and FIGO stage distribution was: IB2 (32.6%), IIA1 (7.0%), IIA2 (51.2%) and IIB (9.3%). Thirty-nine (96%) patients received 3 cycles and 4 (4%) received 4 cycles of NACT. Thirty-eight (88.4%) patients underwent radical hysterectomy as planned and 5 (11.6%) had surgery aborted due to grossly metastatic disease. Two patients were lost to follow up after surgery and excluded from survival analysis. For the remaining 41 patients with median follow-up time of 34.4 months, 32 (78%) were alive with no evidence of recurrence, and 8 (20%) were alive with recurrence. One patient died of an unrelated cancer. The 3-year OS rate for the 41 patients who underwent NACT and surgery was 80.8% with a recurrence rate of 20%. CONCLUSIONS: Neoadjuvant chemotherapy with radical hysterectomy is a feasible treatment option for locally advanced cervical cancer in settings with limited access to RT. With an increase in gynecologic oncologists skilled at radical surgery, this approach may be a more widely available alternative treatment option in countries without radiation facilities.

Burn and Trauma Burden and Screening for Interpersonal Violence During the COVID-19 Pandemic.

INTRODUCTION: Nationwide shelter-in-place (SIP) orders during the pandemic have had long-lasting effects, including increased rates of domestic violence and interpersonal violence. Screening for violence varies by institution, which tool is used, and when. Given increases in burn and trauma admissions over the course of the pandemic, we sought to examine trends at our institution during this time period to better guide care and anticipate system-level effects. METHODS: We performed a retrospective cohort study of pediatric burn and adult burn and trauma patients at our level 1 trauma/burn center between March-May 2019 and March-May 2020. Home safety screening was performed by nursing staff using a 1-part screening questionnaire. Patients presenting before March 15, 2020, were defined as "pre-SIP; " between March 16-May 19, 2020, were "during SIP; " and those after May 19, 2020, were designated as "post-SIP." Descriptive and chi-square statistics were used. Demographic, injury patterns, and screening information were collected. RESULTS: Blunt trauma comprised 60% of injuries, followed by burns (30%) then penetrating injury (7%). Over the entire time period analyzed, 1822 patients had documented home safety screening; ∼2% of patients screened reported a safety concern pre-SIP, compared to 3% of patients during SIP. There were higher rates of burns and penetrating injury during SIP compared to other periods (P ≤ 0.0001). Home safety screening rates were 94%-95% pre- and during SIP, but dropped to 85% post-SIP (P < 0.0001). Home safety concerns were reported almost 2% of the time pre-SIP and 3% during SIP (P = 0.016). CONCLUSIONS: We noted an increase in trauma and burns during and after SIP orders, consistent with the experiences of other institutions. Implementation of a nurse-driven screening process demonstrated high compliance with appropriate referrals. The burden of burn and traumatic injury remains significant, highlighting a need for continued psychosocial screening and the provision of psychosocial support resources in the acute trauma setting.

Gluten-induced Neurocognitive Impairment: Results of a Nationwide Study.

GOALS: This study aimed to understand the neurocognitive symptoms associated with gluten exposure in individuals with self-reported celiac disease (CD) and nonceliac gluten sensitivity (NCGS). BACKGROUND: While gluten-induced neurocognitive impairment (GINI; eg, "celiac fog" or "brain fog") is commonly described by individuals with CD and NCGS, there are little data regarding the prevalence and symptoms associated with these experiences. STUDY: A 9-question online survey was accessed by 1396 individuals (1143 with CD; 253 with NCGS). Forced choice and free-response questions were asked of participants to obtain a description of neurocognitive symptoms experienced after gluten ingestion. Free-response answers were coded using a coding structure developed based on the Health-Related Quality of Life Instrument. RESULTS: The majority of survey participants (89% of CD and 95% of NCGS) reported having GINI symptoms. When describing symptoms, the most common word descriptors for both groups were difficulty concentrating, forgetfulness, and grogginess. Timing of symptoms, including onset and symptom peak, were similar across the 2 groups. Coding of free responses found the most common references were to cognitive, physical, psychological, and overall quality of life impacts. CONCLUSIONS: This survey suggests that GINI is common and may be severe in both individuals with CD and NCGS. Cognitive impairment and decline in physical functioning may be similar to that occurring in other illnesses, such as lupus. Clinical follow-up with both individuals with CD and NCGS should include assessment of GINI symptoms. Further research is warranted, including the development of a patient-reported outcome measure including neurocognitive effects of gluten exposure.

Rapid Implementation of Telehealth Services During the COVID-19 Pandemic.

Telehealth is an important tool utilized to provide remote clinical care and has increased in prevalence during the coronavirus disease of 2019 (COVID-19) pandemic. It allows providers to conduct safe, timely, and high-quality ambulatory care for patients without increasing risk of disease exposure for both parties. Major organizations including the Centers for Disease Control and Prevention and American College of Obstetrics and Gynecology have released recommendations encouraging the use of telehealth systems for patient care. In obstetrics and gynecology, practice of telehealth has not been commonplace and no practical procedural guidelines have been published. The authors have created such guidelines for use of telehealth in a moderate-risk academic generalist practice in response to the COVID-19 pandemic. This document highlights the process to determine which obstetrics and gynecology patients are candidates for telehealth, the frequency of follow-up, and the technical aspects of designing and delivering a de novo telehealth system. The guidelines were vital in providing structure amid a sudden transition in an academic setting while ensuring patient and provider safety.

Review of the enhanced recovery pathway for children: perioperative anesthetic considerations.

PURPOSE: Enhanced recovery after surgery (ERAS) pathways have been used for two decades to improve perioperative recovery in adults. Nevertheless, little is known about their effectiveness in children. The purpose of this review was to consider pediatric ERAS pathways, review the literature concerned with their potential benefit, and compare them with adult ERAS pathways. SOURCE: A PubMed literature search was performed for articles that included the terms enhanced recovery and/or fast track in the pediatric perioperative period. Pediatric patients included those from the neonatal period through teenagers and/or youths. PRINCIPAL FINDINGS: The literature search revealed a paucity of articles about pediatric ERAS. This lack of academic investigation is likely due in part to the delayed acceptance of ERAS in the pediatric surgical arena. Several pediatric studies examined individual components of adult-based ERAS pathways, but the overall study of a comprehensive multidisciplinary ERAS protocol in pediatric patients is lacking. CONCLUSION: Although adult ERAS pathways have been successful at reducing patient morbidity, the translation, creation, and utility of instituting pediatric ERAS pathways have yet to be realized.

The Role of Primary Motor Cortex (M1) Glutamate and GABA Signaling in l-DOPA-Induced Dyskinesia in Parkinsonian Rats.

UNLABELLED: Long-term treatment of Parkinson's disease with l-DOPA almost always leads to the development of involuntary movements termed l-DOPA-induced dyskinesia. Whereas hyperdopaminergic signaling in the basal ganglia is thought to cause dyskinesia, alterations in primary motor cortex (M1) activity are also prominent during dyskinesia, suggesting that the cortex may represent a therapeutic target. The present study used the rat unilateral 6-hydroxydopamine lesion model of Parkinson's disease to characterize in vivo changes in GABA and glutamate neurotransmission within M1 and determine their contribution to behavioral output. 6-Hydroxydopamine lesion led to parkinsonian motor impairment that was partially reversed by l-DOPA. Among sham-lesioned rats, l-DOPA did not change glutamate or GABA efflux. Likewise, 6-hydroxydopamine lesion did not impact GABA or glutamate among rats chronically treated with saline. However, we observed an interaction of lesion and treatment whereby, among lesioned rats, l-DOPA given acutely (1 d) or chronically (14-16 d) reduced glutamate efflux and enhanced GABA efflux. Site-specific microinjections into M1 demonstrated that l-DOPA-induced dyskinesia was reduced by M1 infusion of a D1 antagonist, an AMPA antagonist, or a GABAA agonist. Overall, the present study demonstrates that l-DOPA-induced dyskinesia is associated with increased M1 inhibition and that exogenously enhancing M1 inhibition may attenuate dyskinesia, findings that are in agreement with functional imaging and transcranial magnetic stimulation studies in human Parkinson's disease patients. Together, our study suggests that increasing M1 inhibitory tone is an endogenous compensatory response designed to limit dyskinesia severity and that potentiating this response is a viable therapeutic strategy. SIGNIFICANCE STATEMENT: Most Parkinson's disease patients will receive l-DOPA and eventually develop hyperkinetic involuntary movements termed dyskinesia. Such symptoms can be as debilitating as the disease itself. Although dyskinesia is associated with dynamic changes in primary motor cortex physiology, to date, there are no published studies investigating in vivo neurotransmitter release in M1 during dyskinesia. In parkinsonian rats, l-DOPA administration reduced M1 glutamate efflux and enhanced GABA efflux, coincident with the emergence of dyskinetic behaviors. Dyskinesia could be reduced by local M1 modulation of D1, AMPA, and GABAA receptors, providing preclinical support for the notion that exogenously blunting M1 signaling (pharmacologically or with cortical stimulation) is a therapeutic approach to the treatment of debilitating dyskinesias.

Opioid Prescribing for the Treatment of Acute Pain in Children on Hospital Discharge.

BACKGROUND: The epidemic of nonmedical use of prescription opioids has been fueled by the availability of legitimately prescribed unconsumed opioids. The aim of this study was to better understand the contribution of prescriptions written for pediatric patients to this problem by quantifying how much opioid is dispensed and consumed to manage pain after hospital discharge, and whether leftover opioid is appropriately disposed of. Our secondary aim was to explore the association of patient factors with opioid dispensing, consumption, and medication remaining on completion of therapy. METHODS: Using a scripted 10-minute interview, parents of 343 pediatric inpatients (98% postoperative) treated at a university children's hospital were questioned within 48 hours and 10 to 14 days after discharge to determine amount of opioid prescribed and consumed, duration of treatment, and disposition of unconsumed opioid. Multivariable linear regression was used to examine predictors of opioid prescribing, consumption, and doses remaining. RESULTS: Median number of opioid doses dispensed was 43 (interquartile range, 30-85 doses), and median duration of therapy was 4 days (interquartile range, 1-8 days). Children who underwent orthopedic or Nuss surgery consumed 25.42 (95% confidence interval, 19.16-31.68) more doses than those who underwent other types of surgery (P < .001), and number of doses consumed was positively associated with higher discharge pain scores (P = .032). Overall, 58% (95% confidence interval, 54%-63%) of doses dispensed were not consumed, and the strongest predictor of number of doses remaining was doses dispensed (P < .001). Nineteen percent of families were informed how to dispose of leftover opioid, but only 4% (8 of 211) did so. CONCLUSIONS: Pediatric providers frequently prescribed more opioid than needed to treat pain. This unconsumed opioid may contribute to the epidemic of nonmedical use of prescription opioids. Our findings underscore the need for further research to develop evidence-based opioid prescribing guidelines for physicians treating acute pain in children.

Parkinson's disease iron deposition caused by nitric oxide-induced loss of ß-amyloid precursor protein.

Elevation of both neuronal iron and nitric oxide (NO) in the substantia nigra are associated with Parkinson's disease (PD) pathogenesis. We reported previously that the Alzheimer-associated ß-amyloid precursor protein (APP) facilitates neuronal iron export. Here we report markedly decreased APP expression in dopaminergic neurons of human PD nigra and that APP(-/-) mice develop iron-dependent nigral cell loss. Conversely, APP-overexpressing mice are protected in the MPTP PD model. NO suppresses APP translation in mouse MPTP models, explaining how elevated NO causes iron-dependent neurodegeneration in PD.

An Analysis of 34,218 Pediatric Outpatient Controlled Substance Prescriptions.

BACKGROUND: Prescription errors are among the most common types of iatrogenic errors. Because of a previously reported 82% error rate in handwritten discharge narcotic prescriptions, we developed a computerized, web-based, controlled substance prescription writer that includes weight-based dosing logic and alerts to reduce the error rate to (virtually) zero. Over the past 7 years, >34,000 prescriptions have been created by hospital providers using this platform. We sought to determine the ongoing efficacy of the program in prescription error reduction and the patterns with which providers prescribe controlled substances for children and young adults (ages 0-21 years) at hospital discharge. METHODS: We examined a database of 34,218 controlled substance discharge prescriptions written by our institutional providers from January 1, 2007 to February 14, 2014, for demographic information, including age and weight, type of medication prescribed based on patient age, formulation of dispensed medication, and amount of drug to be dispensed at hospital discharge. In addition, we randomly regenerated 2% (700) of prescriptions based on stored data and analyzed them for errors using previously established error criteria. Weights that were manually entered into the prescription writer by the prescriber were compared with the patient's weight in the hospital's electronic medical record. RESULTS: Patients in the database averaged 9 ± 6.1 (range, 0-21) years of age and 36.7 ± 24.9 (1-195) kg. Regardless of age, the most commonly prescribed opioid was oxycodone (73%), which was prescribed as a single agent uncombined with acetaminophen. Codeine was prescribed to 7% of patients and always in a formulation containing acetaminophen. Liquid formulations were prescribed to 98% of children <6 years of age and to 16% of children >12 years of age (the remaining 84% received tablet formulations). Regardless of opioid prescribed, the amount of liquid dispensed averaged 106 ± 125 (range, 2-3240) mL, and the number of tablets dispensed averaged 51 ± 51 (range, 1-1080). Of the subset of 700 regenerated prescriptions, all were legible (drug, amount dispensed, dose, patient demographics, and provider name) and used best prescribing practice (e.g., no trailing zero after a decimal point, leading zero for doses <1). Twenty-five of the 700 (3.6%) had incorrectly entered weights compared with the most recent weight in the chart. Of these, 14 varied by 10% or less and only 2 varied by >15%. Of these, 1 resulted in underdosing (true weight 80 kg prescribed for a weight of 50 kg) and the other in overdosing (true weight 10 kg prescribed for a weight of 30 kg). CONCLUSIONS: A computerized prescription writer eliminated most but not all the errors common to handwritten prescriptions. Oxycodone has supplanted codeine as the most commonly prescribed oral opioid in current pediatric pain practice and, independent of formulation, is dispensed in large quantities. This study underscores the need for liquid opioid formulations in the pediatric population and, because of their abuse potential, the urgent need to determine how much of the prescribed medication is actually used by patients.

Effects of the beta-adrenergic receptor antagonist Propranolol on dyskinesia and L-DOPA-induced striatal DA efflux in the hemi-parkinsonian rat.

Dopamine (DA) replacement therapy with L-DOPA continues to be the primary treatment of Parkinson's disease; however, long-term therapy is accompanied by L-DOPA-induced dyskinesias (LID). Several experimental and clinical studies have established that Propranolol, a ß-adrenergic receptor antagonist, reduces LID without affecting L-DOPA's efficacy. However, the exact mechanisms underlying these effects remain to be elucidated. The aim of this study was to evaluate the anti-dyskinetic profile of Propranolol against a panel of DA replacement strategies, as well as elucidate the underlying neurochemical mechanisms. Results indicated that Propranolol, in a dose-dependent manner, reduced LID, without affecting motor performance. Propranolol failed to alter dyskinesia produced by the D1 receptor agonist, SKF81297 (0.08 mg/kg, sc), or the D2 receptor agonist, Quinpirole (0.05 mg/kg, sc). These findings suggested a pre-synaptic mechanism for Propranolol's anti-dyskinetic effects, possibly through modulating L-DOPA-mediated DA efflux. To evaluate this possibility, microdialysis studies were carried out in the DA-lesioned striatum of dyskinetic rats and results indicated that co-administration of Propranolol (20 mg/kg, ip) was able to attenuate L-DOPA- (6 mg/kg, sc) induced DA efflux. Therefore, Propranolol's anti-dyskinetic properties appear to be mediated via attenuation of L-DOPA-induced extraphysiological efflux of DA.

Attitudes to mesalamine questionnaire: a novel tool to predict mesalamine nonadherence in patients with IBD.

OBJECTIVES: Poor adherence to mesalamine is common and driven by a combination of lifestyle and behavioral factors, as well as health beliefs. We sought to develop a valid tool to identify barriers to patient adherence and predict those at risk for future nonadherence. METHODS: A 10-item survey was developed from patient-reported barriers to adherence. The survey was administered to 106 patients with ulcerative colitis who were prescribed mesalamine, and correlated with prospectively collected 12-month pharmacy refills (medication possession ratio (MPR)), urine levels of salicylates, and self-reported adherence (Morisky Medication Adherence Scale (MMAS)-8). RESULTS: From the initial 10-item survey, 8 items correlated highly with the MMAS-8 score at enrollment. Computer-generated randomization produced a derivation cohort of 60 subjects and a validation cohort of 46 subjects to assess the survey items in their ability to predict future adherence. Two items from the patient survey correlated with objective measures of long-term adherence: their belief in the importance of maintenance mesalamine even when in remission and their concerns about side effects. The additive score based on these two items correlated with 12-month MPR in both the derivation and validation cohorts (P<0.05). Scores on these two items were associated with a higher risk of being nonadherent over the subsequent 12 months (relative risk (RR) =2.2, 95% confidence interval=1.5-3.5, P=0.04). The area under the curve for the performance of this 2-item tool was greater than that of the 10-item MMAS-8 score for predicting MPR scores over 12 months (area under the curve 0.7 vs. 0.5). CONCLUSIONS: Patients' beliefs about the need for maintenance mesalamine and their concerns about side effects influence their adherence to mesalamine over time. These concerns could easily be raised in practice to identify patients at risk of nonadherence (Clinical Trial number NCT01349504).

Delays in Cervical Cancer Treatment Initiation for Patients Living With or Without HIV in Botswana: An Observational Cohort Analysis (2015-2019).

PURPOSE: To assess delays in treatment initiation of chemoradiation or radiation alone for patients with advanced stage cervical cancer in Botswana. METHODS AND MATERIALS: Females with locally advanced cervical cancer (stages IB2-IVB) were prospectively enrolled in an observational cohort study from 2015 to 2019. We evaluated delays at 30, 60, 90, 120, 150, and 180 or greater days between the date of diagnosis and treatment initiation. Factors associated with overall survival were modeled with multivariable Cox proportional hazards regression (aHR). Associations between delays in cervical cancer treatment initiation were evaluated via univariable logistic regression. RESULTS: Among the 556 patients included (median age = 47.9 years), 386 (69.4%) were females living with HIV with a median CD4 count of 448.0 cells/µL (IQR, 283.0-647.5 cells/µL) at diagnosis. Most patients had stages 2 (38.1%) or 3 (34.5%) cervical cancer. Early-stage patients experienced longer delays in treatment initiation compared to late-stage patients (P = .033). Early-stage patients with delays ≥90 days and pathology diagnosis between 2016 and 2019 (aHR, 0.34; P < .001) versus <90 days had a decreased risk of mortality, and those with delays ≥90 days and pathology diagnosis before 2016 (aHR, 5.67; P = .022) versus <90 days had an increased risk of mortality. Late-stage patients with delays ≥120 days and pathology diagnosis between 2018 and 2019 (aHR, 1.98; P = .025) versus <120 days had an increased risk of mortality. Early-stage patients with pathology diagnosis between 2016 and 2019 (odds ratio, 2.32; P = .043) versus before 2016 were more likely to experience delays ≥90 days, and late-stage patients who traveled >100 km to the treatment facility (odds ratio, 2.83; P < .001) versus <100 km were more likely to experience delays ≥120 days. CONCLUSIONS: Delays in care are common in Botswana, particularly for those living farther from the treatment clinic and at advanced stages. This paper is among the first to show an association between treatment delays and worsened overall survival at advanced stages of cervical cancer, highlighting the need for interventions to help patients receive timely care in global settings.

Body image and Black African women: A comparative study of Kenya and Nigeria.

Very few cross-national studies on body image focus on Black African women. In this study, a comparative analytical approach and sociocultural theory framework was utilized in examining measures of body image among 209 Kenyan and Nigerian women aged 18-69 (M = 34.4, SD = 7.81). We examined both weight-related and non-weight-related aspects of appearance, including hair texture, skin tone, and other racialized features. The regional samples were compared on scores of internalized Eurocentric beauty ideals, skin color satisfaction, objectified body consciousness, racialized body image satisfaction, and other demographic metrics. Kenyan and Nigerian women showed differences across multiple body image measures. Nigerian women showed thinner body ideals compared to Kenyan women and also endorsed higher skin color satisfaction, racialized body dissatisfaction, and internalized Eurocentric beauty idealization. Kenyan women showed higher levels of objectified body consciousness. An indirect effect of nationality was observed with internalized Eurocentric beauty ideals mediating differences in racialized body dissatisfaction and objectified body shame. Attention to regional variation in appearance satisfaction may deepen understandings of the particular sociocultural influences impacting body image among populations of Black African women.

Optimizing Respiratory Therapy Resources by De-Implementing Low-Value Care.

BACKGROUND: Our institution was experiencing a respiratory therapy staffing crisis during the COVID-19 pandemic, in part due to excessive workload. We identified an opportunity to reduce burden by limiting use of 3% hypertonic saline and/or N-acetylcysteine nebulizer therapies (3%HTS/NAC). METHODS: Leveraging the science of de-implementation, we established a policy empowering respiratory therapists to discontinue 3%HTS/NAC not meeting the American Association for Respiratory Care (AARC) Clinical Practice Guideline: Effectiveness of Pharmacologic Airway Clearance Therapies in Hospitalized Patients. After a 3-month period of educating physicians and advanced practice practitioners the policy went to into effect. Outcomes measured included monthly number of treatments, orders, and full-time employees associated with administering nebulized 3%HTS/NAC. RESULTS: Post policy activation, the monthly mean 3%HTS/NAC treatments were significantly reduced to 547.5 ± 284.3 from 3,565.2 ± 596.4 (P < .001) as were the associated monthly mean of full-time employees, 0.8 ± 0.41 from 5.1 ± 0.86 (P < .001). The monthly mean 3%HTS/NAC orders also fell to 93.8 ± 31.5 from 370.0 ± 46.9 (P < .001). Monthly mean non-3%HTS/NAC treatments remained stable; post policy was 3,089.4 ± 611.4 and baseline 3,279.6 ± 695.0 (P = 1.0). CONCLUSIONS: Implementing a policy that empowers respiratory therapists to promote adherence to AARC Clinical Guidelines reduced low-value therapies, costs, and staffing needs.

Serotonin transporter inhibition attenuates l-DOPA-induced dyskinesia without compromising l-DOPA efficacy in hemi-parkinsonian rats.

Long-term dopamine replacement therapy with l-DOPA in Parkinson's disease often leads to the development of abnormal involuntary movements known as l-DOPA-induced dyskinesia. Growing evidence suggests that, following dopamine cell loss, serotonin neurons acting as surrogates for dopaminergic processes take up l-DOPA, convert it to dopamine and release it in an unregulated fashion that precipitates dyskinesia. Although most studies have focused on serotonin 5-HT(1) receptor stimulation as an antidyskinetic strategy, targeting the serotonin transporter modulation of dopamine activity has been overlooked. Therefore, in the current study, selective serotonin reuptake inhibitors were tested for their ability to reduce l-DOPA- and apomorphine-induced dyskinesia. In Experiments 1 and 2, hemi-parkinsonian rats were primed with l-DOPA until stable dyskinesia developed. Rats in Experiment 1 were administered the selective serotonin reuptake inhibitors paroxetine, citalopram or fluoxetine, followed by l-DOPA. Abnormal involuntary movements and forepaw adjusting steps were recorded to determine the effects of these compounds on dyskinesia and motor performance, respectively. Brains were collected on the final test day, after which striatal and raphe monoamines were examined via high-performance liquid chromatography. In Experiment 2, dyskinesias were measured after selective serotonin reuptake inhibitors and apomorphine. Serotonin reuptake inhibitors dose-dependently attenuated l-DOPA- but not apomorphine-induced dyskinesia, and preserved l-DOPA efficacy. Neurochemically, serotonin transporter inhibition enhanced striatal and raphe serotonin levels and reduced its turnover, indicating a potential mechanism of action. The present results support targeting serotonin transporters to improve Parkinson's disease treatment and provide further evidence for the role of the serotonin system in l-DOPA's effects.

Three-dimensional atlas of iron, copper, and zinc in the mouse cerebrum and brainstem.

Atlases depicting molecular and functional features of the brain are becoming an integral part of modern neuroscience. In this study we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS) to quantitatively measure iron (Fe), copper (Cu), and zinc (Zn) levels in a serially sectioned C57BL/6 mouse brain (cerebrum and brainstem). Forty-six sections were analyzed in a single experiment of approximately 158 h in duration. We constructed a 46-plate reference atlas by aligning quantified images of metal distribution with corresponding coronal sections from the Allen Mouse Brain Reference Atlas. The 46 plates were also used to construct three-dimensional models of Fe, Cu, and Zn distribution. This atlas represents the first reconstruction of quantitative trace metal distribution through the brain by LA-ICPMS and will facilitate the study of trace metals in the brain and help to elucidate their role in neurobiology.

Risk Behavioral Contexts in Adolescence of Obese Adults.

PURPOSE: Previous research suggests that poor nutrition, physical activity, sleep, and social/emotional climate are associated with weight gain. However, few empirical studies have examined how these factors relate to each other in adolescents who are later obese. Are these factors uniformly present, or do some co-occur or occur independently? This study seeks to identify subgroups of obese individuals at ages 24-32 years who exhibited unique, co-occurring behavioral and emotional contexts for obesity at ages 14-17 years. METHODS: To identify subgroups of behavioral and contextual profiles in adolescence, the study applies latent class analysis to a sample of individuals who were obese in the fourth wave of the National Longitudinal Study of Adolescent to Adult Health (Add Health, N = 1,889). The study then explored covariates (e.g., gender, race) of class membership. RESULTS: Considerable heterogeneity exists in risk profiles of adolescents obese as adults. For example, 21.1 percent of the sample is in a class with no differentiating risk factors, whereas two classes containing 22.1 percent of the sample exhibit high levels of depression, and nearly all the emotional factors are considered. Although some covariates are predictive of class membership, clear patterns are difficult to discern. However, poor physical health is clearly predictive of membership in the classes exhibiting a high risk of depression. DISCUSSION: Clinicians should be aware that at younger ages, people who are ultimately obese display a range of factors linked to obesity. Although some exhibit behaviors such as high screen time and processed food consumption, others exhibit mainly poor social/emotional climate.

Effect of implementing an enhanced recovery protocol for pediatric colorectal surgery on complication rate, length of stay, and opioid use in children.

Introduction In the past two decades, Enhanced Recovery After Surgery (ERAS) pathways for adults have improved efficiency of care and decreased length of stay (LOS) without increasing postoperative complications. The effects of enhanced recovery pathways for children are less well known. In this retrospective cohort study, we evaluated the effects of an enhanced recovery protocol (ERP) implementation in children undergoing colorectal surgery. Methods We introduced a colorectal ERP in 2017. Children and young adults (ages 2-22 years) were divided into pre-intervention (2014-2016) and post-intervention groups (2017-2019) for analysis. We abstracted data, including demographics, primary surgery, LOS, postoperative pain scores, and postoperative complications. Results A total of 432 patients were included. Of those,148 (34%) were pre-ERP implementation and 284 (66%) were post-ERP implementation. Post-ERP patients experienced significantly shorter LOS (5.7 vs. 8.3 days, p<0.01); required less intraoperative local anesthetic (9.5% vs. 38.5%, p<0.01) because 55% of patients received an epidural and 18% received an abdominal plane block; and used less postoperative opioid (62.5% vs. 98.7%, p<0.01) than did pre-ERAS patients. After protocol implementation, average pain scores were lower on postoperative day 1 (3.6 vs. 4.5, p<0.05) and across the hospitalization (3.0 vs. 4.0, p<0.01). Conclusion Enhanced recovery pathways decrease LOS, opioid use, and postoperative pain scores for children undergoing colorectal surgery and should be considered for this patient population.

Stage and outcomes of invasive cervical cancer patients in Botswana: A prospective cohort study from 2013 to 2020.

Objective: To present the stage distribution, patterns of care, and outcomes of patients from Botswana with invasive cervical cancer, living with or without HIV. Methods: Between 2013 and 2020, women with cervical cancer were prospectively enrolled in an observational cohort study. Results: A total of 1,043 patients were enrolled; 69% were women living with HIV. The median age of the cohort was 47 years (interquartile range [IQR] 40-58 years), with women living with HIV presenting at a younger age compared to women without HIV (44 versus 61 years, p < 0.001). Among women living with HIV, the median CD4 count at the time of cancer diagnosis was 429.5 cells/µL (IQR 240-619.5 cells/µL), 13% had a detectable viral load, and 95% were on antiretroviral therapy. In regard to treatment, 6% (n = 58) underwent surgery, 33% (n = 341) received radiation therapy, 51% (n = 531) received chemoradiation, and 7% (n = 76) did not receive treatment. Stage distribution in the cohort was as follows: I 17% (n = 173), II 37% (n = 388), III 35% (n = 368), and IV 8% (n = 88). For all patients, 2-year OS was 67%. In multivariable Cox regression, worse OS was associated with stage: II (HR 1.91, p = 0.007), III (HR 3.99, p < 0.001), and IV (HR 5.06, p < 0.001) compared to stage I. Improved OS was associated with hemoglobin > 10 g/dL (HR 0.51, p < 0.001) compared to Hb ≤ 10 g/dL. Conclusions: Among women in Botswana with cervical cancer, most patients presented with stage II or III disease warranting radiation therapy or chemoradiation. While two-thirds of cervical cancer patients were women living with HIV, HIV did not impact OS.

What Does He Think? Male Knowledge and Attitudes Regarding Long-Acting Reversible Contraception.

STUDY OBJECTIVE: Contraceptive counseling, especially regarding long-acting reversible contraception (LARC), has generally been directed at women. However, male partners and peers may influence contraceptive decision making. As there were no published studies examining male perceptions of LARC in the United States, this study investigated male knowledge and attitudes regarding LARC. DESIGN: An anonymous electronic cross-sectional survey collecting qualitative and quantitative data was administered from May to September 2018. SETTING: Participants were recruited via university e-mail listservs and in-person at a campus student organization fair at the University of Illinois at Chicago in Chicago (UIC), Illinois. PARTICIPANTS: University students identifying as male and 18-24 years of age. INTERVENTIONS: None. MAIN OUTCOMES MEASURED: Knowledge of LARC, perceptions of LARC, interest in learning about LARC. RESULTS: Participants (n = 97) were predominantly heterosexual (83.5%) men. Of those who were sexually active (63.9%), 98.4% reported female partners trying to avoid pregnancy. The most commonly used methods of contraception were oral contraceptive pills (48.4%) and/or condoms (80.6%). The majority (76.3%) of participants had not heard of LARC. Absence of prior LARC use by a partner was associated with knowledge deficits about LARC (odds ratio = 0.26, 95% confidence interval = 0.70-1.00); however, this association was not seen with other contraceptive methods. Participants familiar with LARC were generally neutral to very supportive of LARC (87.0%). Additionally, 80.4% of participants were interested in learning more about LARC. CONCLUSION: Males 18-24 years of age had limited knowledge of LARC, with an interest in learning more about LARC. This information could shape interventions to bridge knowledge gaps, ultimately helping women to make supported contraceptive choices.