Feasibility and Acceptability of Biofeedback-Based Virtual Reality System Use in Children and Adolescents Undergoing Surgery: Phase 1 of a Pilot Observational Study.

BACKGROUND: Biofeedback-based virtual reality (VR-BF) is a novel, nonpharmacologic method for teaching patients how to control their breathing, which in turn increases heart rate variability (HRV) and may reduce pain. Unlike traditional forms of biofeedback (BF), VR-BF is delivered through a gamified virtual reality environment, increasing the accessibility of BF. This is the first study to systematically integrate VR-BF use in the pediatric perioperative setting, with the ultimate goal of evaluating the efficacy of VR-BF to reduce pain, anxiety, and opioid consumption once feasibility and acceptability has been established. OBJECTIVE: The primary objective was to develop a clinical trial protocol for VR-BF use in the pediatric perioperative setting, including preoperative education/training and postoperative application of VR-BF in children undergoing surgery. A secondary objective was to evaluate the patient/parent experience with VR-BF. METHODS: A total of 23 patients (12-18 years of age) scheduled for surgery at Nationwide Children's Hospital were recruited using purposive sampling. Following training, participants independently completed a daily, 10-minute VR-BF session for seven days before surgery and during their inpatient stay. Participants could use VR-BF up to two weeks after hospital discharge. Patient and session-level data of VR-BF usage and achievement of target HRV parameters were measured to identify the optimal frequency and duration of sessions before and after surgery for this population. Standardized questionnaires and semi-structured interviews were conducted to obtain qualitative information about patients' experiences with VR-BF. RESULTS: Patient-level data indicated that the highest odds of achieving 1 session under target HRV parameters was after 4 sessions (OR 4 vs. 3 sessions=5.1, 95% CI 1.3-20.6; OR 3 vs. 2 sessions=16.6, 95% CI 1.2-217.0). Session-level data showed that a session duration of 9 to 10 minutes provided the greatest odds of achieving 1 session under target HRV parameters (OR 9 vs. 8 minutes=1.3, 95% CI 1.1-1.7; OR 8 vs. 7 minutes=1.4, 95% CI 1.1-1.8; OR 10 vs. 9 minutes=1.0, 95% CI 0.9-1.2). Qualitative data revealed patient satisfaction with the VR-BF technology, particularly in managing perioperative stress (n=17, 85%). Few patients reported VR-BF as beneficial for pain (n=8, 40%). CONCLUSIONS: Children and adolescents undergoing surgery successfully learned behavioral strategies with VR-BF with once-daily 10-minute sessions for 5 days. To integrate VR-BF as a therapeutic intervention in a subsequent clinical trial, patients will be instructed to complete three 10-minute sessions a day for 7 days after surgery. CLINICALTRIAL: ClinicalTrials.gov; NCT04943874; https://clinicaltrials.gov/ct2/show/NCT04943874.

Assessing structural models of neighborhood and family sociodemographic characteristics and their relations with externalizing psychopathology.

Externalizing psychopathology has been found to have small to moderate associations with neighborhood and family sociodemographic characteristics. However, prior studies may have used suboptimal operationalizations of neighborhood sociodemographic characteristics and externalizing psychopathology, potentially misestimating relations between these constructs. To address these limitations, in the current study we test different measurement models of these constructs and assess the structural relations between them. Using a population-representative sample of 2,195 twins and siblings from the Georgia Twin Study and data from the National Neighborhood Data Archive and 2000 U.S. Census, we assessed the fit of competing measurement models for family sociodemographic, neighborhood sociodemographic, and neighborhood environment characteristics. In structural models, we regressed a general externalizing dimension on different operationalizations of these variables separately and then simultaneously in a final model. Latent variable operationalizations of family sociodemographic, neighborhood sociodemographic, and neighborhood environment characteristics explained no more variance in broad externalizing psychopathology than other operationalizations. In an omnibus model, family sociodemographic characteristics showed a small association with externalizing psychopathology, while neighborhood sociodemographic and environmental characteristics did not. Family sociodemographic characteristics showed small associations with neighborhood sociodemographic and environmental characteristics, and neighborhood sociodemographic characteristics were moderately associated with neighborhood environment. These findings suggest that family sociodemographic characteristics are more associated with the development of broad externalizing psychopathology in youth than neighborhood sociodemographic characteristics and neighborhood environment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Role of Cytokines in Acute and Chronic Postsurgical Pain in Pediatric Patients after Major Musculoskeletal Surgeries.

Study Objective: To determine if baseline cytokines and their changes over postoperative days 0-2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery. Design: Prospective, observational, longitudinal nested study. Setting: University-affiliated quaternary children's hospital. Patients: Subjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure. Measurements: Demographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and after (up to two weeks) surgery, using Luminex bead arrays. After data preparation, relationships between pre- and post-surgical cytokine concentrations with acute (% time in moderate-severe pain over POD0-2) and chronic (pain score>3/10 beyond 3 months post-surgery) pain were analyzed. After adjusting for covariates, univariate/multivariate regression analyses were conducted to associate baseline cytokine concentrations with postoperative pain, and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes. Main Results: Analyses included 3,164 measures of 16 cytokines from 112 subjects (median age 15.3, IQR 13.5-17.0, 54.5% female, 59.8% pectus). Acute postsurgical pain was associated with higher baseline concentrations of GM-CSF (ß=0.95, SE 0.31; p=.003), IL-1ß (ß=0.84, SE 0.36; p=.02), IL-2 (ß=0.78, SE 0.34; p=.03), and IL-12 p70 (ß=0.88, SE 0.40; p=.03) and longitudinal postoperative elevations in GM-CSF (ß=1.38, SE 0.57; p=.03), IFNγ (ß=1.36, SE 0.6; p=.03), IL-1ß (ß=1.25, SE 0.59; p=.03), IL-7 (ß=1.65, SE 0.7, p=.02), and IL-12 p70 (ß=1.17, SE 0.58; p=.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (ß= -0.39, SE 0.17; p=.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (ß= -0.57, SE 0.26; p=.03), IL-8 (ß= -0.68, SE 0.24; p=.006), and IL-13 (ß= -0.48, SE 0.22; p=.03). Furthermore, higher odds for CPSP were found for females (vs. males) for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNFα, and for pectus (vs. spine) surgery for IL-8 and IL-10. Conclusion: We identified pro-inflammatory cytokines associated with increased acute postoperative pain and anti-inflammatory cytokines associated with lower CPSP risk, with potential to serve as predictive and prognostic biomarkers.

Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats.

Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues; both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1,645 genetically diverse heterogeneous stock (HS) rats. We tested HS rats in a Pavlovian conditioned approach task, in which we characterized the individual responses to food-associated stimuli ("cues"). Rats exhibited either cue-directed "sign-tracking" behavior or food-cup directed "goal-tracking" behavior. We then used the conditioned reinforcement procedure to determine whether rats would perform a novel operant response for unrewarded presentations of the cue. We found that these measures were moderately heritable (SNP heritability, h2 = .189-.215). GWAS identified 14 quantitative trait loci (QTLs) for 11 of the 12 traits we examined. Interval sizes of these QTLs varied widely. 7 traits shared a QTL on chromosome 1 that contained a few genes (e.g. Tenm4, Mir708) that have been associated with substance use disorders and other mental health traits in humans. Other candidate genes (e.g. Wnt11, Pak1) in this region had coding variants and expression-QTLs in mesocorticolimbic regions of the brain. We also conducted a Phenome-Wide Association Study (PheWAS) on other behavioral measures in HS rats and found that regions containing QTLs on chromosome 1 were also associated with nicotine self-administration in a separate cohort of HS rats. These results provide a starting point for the molecular genetic dissection of incentive salience and provide further support for a relationship between attribution of incentive salience and drug abuse-related traits.

The effect of single low-dose primaquine treatment for uncomplicated Plasmodium falciparum malaria on hemoglobin levels in Ethiopia: a longitudinal cohort study.

Background: To interrupt residual malaria transmission and achieve successful elimination of P. falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of hemolysis in patients with G6PD deficiency (G6PDd), PQ use is not as common. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency. Methods: An observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and hemoglobin (Hb) concentrations. G6PD levels were masured by a quantiative biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone. Results: A total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 14) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to -0.47) in patients treated with ACT alone (P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PD deficiency group (-0.56 g/dL) than in the G6PD normal group (-0.39 g/dL); however, there was no statistically significant difference (P = 0.359). Overall, D14 losses were 0.10 g/dl (95% CI = -0.00 to 0.20) and 0.05 g/dl (95% CI = -0.123 to 0.22) in patients with and without SLD-PQ, respectively (P = 0.412). Conclusions: Our findings showed that single low-dose primaquine (SLD-PQ) treatment for uncomplicated P. falciparum malaria is safe and does not increase the risk of hemolysis in G6PDd patients. This evidence suggests that the wider deployment of SLD-PQ for P. falciparum is part of a global strategy for eliminating P. falciparum malaria.

Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.

Background: SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs). However, emerging variants coupled with waning immunity, immunosenescence, and variability of vaccine efficacy undermine vaccine effectiveness. We therefore need to update our understanding of the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Methods: The current study focuses on a subset of participants from a longitudinal study of consented NHRs and HCWs who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine after FDA approval in Fall 2023. NHRs were classified based on whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. Results: The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). Following XBB.1.5 monovalent vaccination, there was a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers of 17.3 (95% confidence interval [CI] 9.3, 32.4) and 11.3 (95% CI 5, 25.4) in NHRs with and without interval infection, respectively. The GMFR in HCWs was 13.6 (95% CI 8.4,22). Similarly, we noted a robust GMFR in JN.1-specific neutralizing antibody titers of 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) among NHRs with and without interval infection, and a GMFR of 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher neutralizing antibody titers across all analyzed strains following XBB.1.5 monovalent vaccination, compared to NHRs without interval infection. Conclusion: The XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs. This response was more pronounced in individuals known to be infected with SARS-CoV-2 since bivalent vaccination. Impact Statement: All authors certify that this work entitled " Broad immunogenicity to prior strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents " is novel. It shows that the XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers in both nursing home residents and healthcare workers to XBB and BA.28.6/JN.1 strains. This work is important since JN.1 increased from less than 0.1% to 94% of COVID-19 cases from October 2023 to February 2024 in the US. This information is timely given the CDC's latest recommendation that adults age 65 and older receive a Spring 2024 XBB booster. Since the XBB.1.5 monovalent vaccine produces compelling immunogenicity to the most prevalent circulating JN.1 strain in nursing home residents, our findings add important support and rationale to encourage vaccine uptake. Key Points: Emerging SARS-CoV-2 variants together with waning immunity, immunosenescence, and variable vaccine efficacy reduce SARS-CoV-2 vaccine effectiveness in nursing home residents.XBB.1.5 monovalent vaccination elicited robust response in both XBB.1.5 and JN.1 neutralizing antibodies in nursing home residents and healthcare workers, although the absolute titers to JN.1 were less than titers to XBB.1.5Why does this paper matter? Among nursing home residents, the XBB.1.5 monovalent SARS-CoV-2 vaccine produces compelling immunogenicity to the JN.1 strain, which represents 94% of all COVID-19 cases in the U.S. as of February 2024.

Radiation of pain: Psychophysical evidence for a population coding mechanism.

The spread of pain across body locations remains poorly understood but may provide important insights into the encoding of sensory features of noxious stimuli by populations of neurons. In this psychophysical experiment, we hypothesized that more intense noxious stimuli would lead to spread of pain, but more intense light stimuli would not produce perceptual radiation. Fifty healthy volunteers participated in this study wherein four intensities of noxious stimuli (43, 45, 47 and 49°C) were applied to glabrous (hand) and hairy skin (forearm) skin with 5s and 10s durations. Also, four different intensities of visual stimuli displayed on the target bodily area were utilized as a control. Participants provided pain (and light) spatial extent ratings as well as pain (and light) intensity ratings. In the extent rating procedure, participants adjusted the extent of the square displayed on the screen with the extent of pain (or light) which they experienced. Pain extent ratings showed statistically significant radiation of pain indicated by 12.42× greater spatial spread of pain (pain extent) than the area of the stimulation with 49°C (p < 0.001), in contrast to visual ratings which closely approximated the size of the stimulus (1.22×). Pain radiation was more pronounced in hairy than glabrous skin (p < 0.05) and was more pronounced with longer stimulus duration (p < 0.001). Pain intensity explained, on average, only 14% of the pain radiation variability. The relative independence of the pain radiation from perceived pain intensity indicates that distinct components of population coding mechanisms may be involved in the spatial representation of pain versus intensity coding.

Agreement between three noninvasive temperature monitoring devices during spinal anaesthesia for caesarean delivery: a prospective observational study.

Hypothermia during obstetric spinal anaesthesia is a common and important problem, yet temperature monitoring is often not performed due to the lack of a suitable, cost-effective monitor. This study aimed to compare a noninvasive core temperature monitor with two readily available peripheral temperature monitors during obstetric spinal anaesthesia. We undertook a prospective observational study including elective and emergency caesarean deliveries, to determine the agreement between affordable reusable surface temperature monitors (Welch Allyn SureTemp® Plus oral thermometer and the Braun 3-in-1 No Touch infrared thermometer) and the Dräger T-core© (using dual-sensor heat flux technology), in detecting thermoregulatory changes during obstetric spinal anaesthesia. Predetermined clinically relevant limits of agreement (LOA) were set at ± 0.5 °C. We included 166 patients in our analysis. Hypothermia (heat flux temperature < 36 °C) occurred in 67% (95% CI 49 to 78%). There was poor agreement between devices. In the Bland-Altman analysis, LOA for the heat flux monitor vs. oral thermometer were 1.8 °C (CI 1.7 to 2.0 °C; bias 0.5 °C), for heat flux monitor vs. infrared thermometer LOA were 2.3 °C (CI 2.1 to 2.4 °C; bias 0.4 °C) and for infrared vs. oral thermometer, LOA were 2.0 °C (CI 1.9 to 2.2 °C; bias 0.1 °C). Error grid analysis highlighted a large amount of clinical disagreement between methods. While monitoring of core temperature during obstetric spinal anaesthesia is clinically important, agreement between monitors was below clinically acceptable limits. Future research with gold-standard temperature monitors and exploration of causes of sensor divergence is needed.

Total robotic liver transplant: the final frontier of minimally invasive surgery.

The use of robotic surgery in transplantation is increasing; however, robotic liver transplantation (RLT) remains a challenging undertaking. To our knowledge, this is a report of the first RLT in North America and the first RLT using a whole graft from a deceased donor in the world. This paper describes the preparation leading to the RLT and the surgical technique of the operation. The operation was performed in a 62-year-old man with hepatitis C cirrhosis and hepatocellular carcinoma with a native Model for End-Stage Liver Disease score of 10. The total console time for the operation was 8 hours 30 minutes, and the transplant hepatectomy took 3 hours 30 minutes. Warm ischemia time was 77 minutes. Biliary reconstruction was performed in a primary end-to-end fashion and took 19 minutes to complete. The patient had an uneventful recovery without early allograft dysfunction or surgical complications and continues to do well after 6-months follow-up. This paper demonstrates the feasibility of this operation in highly selected patients with chronic liver disease. Additional experience is required to fully understand the role of RLT in the future of transplant surgery. Narrated video is available at https://youtu.be/TkjDwLryd3I.

Patient Satisfaction in Neurosurgery Clinic.

BACKGROUND: National commercial surveys are used to assess patient satisfaction. However, the information obtained does not always correspond to the clinical situation and therefore may be inadequate to help improve a specific patient experience when through no fault of its design, results in low response rates and inadequate specifics. OBJECTIVE: The objective is to investigate patient satisfaction using real-time in-person patient experience survey responses at the end of a neurosurgical clinic visit and review the results from these survey responses and those from national commercial survey responses provided by the hospital for the ability to affect change. METHODS: This is a prospective study from October 2023 to December 2023 during which a paper copy of 10 questionnaires derived from a national commercial outpatient clinical survey was given to every unique patient who was neurologically capable of filling it out at the end of his or her neurosurgery clinic visit. The electronic medical record was used to collect patient demographics and details of the clinic visit. National commercial survey responses from July 2022 to November 2023 provided by the hospital were reviewed. RESULTS: A total of 149 patients were seen in the neurosurgery clinic from October 2023 to December 2023, 121 patients were given the in-person patient satisfaction survey, and the response rate was 100%. The mean age was 46.5 years with females constituted 45.5% of the patient sample. The visit type included 46 (38.0%) new patients, 53 (43.8%) returning patients, and 22 (18.2%) post-op patients, of which 45.5% presented with cranial pathologies. Comparing the patient satisfaction level between those seen by one provider and those seen by two providers, such as resident, or mid-level with attending, patients seen by two providers were less satisfied with "feeling respected by the providers" (4.92 vs. 4.64, p=0.0088), "feeling listened to by the providers" (4.84 vs. 4.50, p=0.0180), and "feeling appreciated that the providers discussed illness prevention" (4.72 vs. 4.29, p=0.0232). Due to a lack of necessary information from our national commercial outpatient clinic survey responses provided by the hospital, a direct comparison between the in-person survey and our national commercial outpatient clinic survey was not made. CONCLUSIONS: Patient satisfaction surveys when not given in real-time in-person run the risk of low response rate and lack of specifics to help guide providers in quality improvement. Our data supports the use of real-time in-person patient satisfaction surveys that not only increase response rate but also provide useful information to help improve patient experience.

Epidemiology of Plasmodium vivax in Duffy negatives and Duffy positives from community and health centre collections in Ethiopia.

BACKGROUND: Malaria remains a significant cause of morbidity and mortality in Ethiopia with an estimated 3.8 million cases in 2021 and 61% of the population living in areas at risk of malaria transmission. Throughout the country Plasmodium vivax and Plasmodium falciparum are co-endemic, and Duffy expression is highly heterogeneous. The public health significance of Duffy negativity in relation to P. vivax malaria in Ethiopia, however, remains unclear. This study seeks to explore the prevalence and rates of P. vivax malaria infection across Duffy phenotypes in clinical and community settings. METHODS: A total of 9580 and 4667 subjects from community and health facilities from a malaria endemic site and an epidemic-prone site in western Ethiopia were enrolled and examined for P. vivax infection and Duffy expression from February 2018 to April 2021. Association between Duffy expression, P. vivax and P. falciparum infections were examined for samples collected from asymptomatic community volunteers and symptomatic subjects from health centres. RESULTS: Infection rate of P. vivax among Duffy positives was 2-22 fold higher than Duffy negatives in asymptomatic volunteers from the community. Parasite positivity rate was 10-50 fold higher in Duffy positives than Duffy negatives among samples collected from febrile patients attending health centres and mixed P. vivax and P. falciparum infections were significantly more common than P. vivax mono infections among Duffy negative individuals. Plasmodium vivax parasitaemia measured by 18sRNA parasite gene copy number was similar between Duffy positives and Duffy negatives. CONCLUSIONS: Duffy negativity does not offer complete protection against infection by P. vivax, and cases of P. vivax in Duffy negatives are widespread in Ethiopia, being found in asymptomatic volunteers from communities and in febrile patients from health centres. These findings offer evidence for consideration when developing control and intervention strategies in areas of endemic P. vivax and Duffy heterogeneity.

Antithrombotic Therapy for VTE Disease: Compendium and Review of CHEST Guidelines 2012-2021.

The CHEST Antithrombotic Therapy for Venous Thromboembolism Disease evidence-based guidelines are now updated in a more frequent, focused manner. Guidance statements from the most recent full guidelines and two subsequent updates have not been gathered into a single source. An international panel of experts with experience in prior antithrombotic therapy guideline development reviewed the 2012 CHEST antithrombotic therapy guidelines and its two subsequent updates. All guideline statements and their associated patient, intervention, comparator, and outcome questions were assembled. A modified Delphi process was used to select statements considered relevant to current clinical care. The panel further endorsed minor phrasing changes to match the standard language for guidance statements using the modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) format endorsed by the CHEST Guidelines Oversight Committee. The panel appended comments after statements deemed as relevant, including suggesting that statements be updated in future guidelines because of interval evidence. We include 58 guidance statements from prior versions of the antithrombotic therapy guidelines, with updated phrasing as needed to adhere to contemporary nomenclature. Statements were classified as strong or weak recommendations based on high-certainty, moderate-certainty, and low-certainty evidence using GRADE methodology. The panel suggested that five statements are no longer relevant to current practice. As CHEST continues to update guidance statements relevant to antithrombotic therapy for VTE disease, this article serves as a unified collection of currently relevant statements from the preceding three guidelines. Suggestions have been made to update specific statements in future publications.

Social health in young women with chronic pain.

Introduction: Chronic pain may negatively affect social functioning, but no study to date has examined the specific social impact of different chronic pain conditions in young women, and whether living with multiple chronic overlapping pain conditions (COPCs) differently influences social domains. Objectives: This study aimed to assess social functioning (social isolation, hostility, informational support satisfaction, social roles, emotional support, friendships, and family relationships) among young women with chronic pain compared with pain-free controls and to test whether the number of COPCs influenced the extent of social burden. Methods: Participants aged 18 to 30 years with a physician-confirmed diagnoses of migraine, fibromyalgia, or temporomandibular disorder (TMD) and pain-free controls were invited to participate from across the United States. After confirming eligibility, participants completed a 1-hour REDCap online questionnaire assessing social functioning. Results: One hundred four participants (mean age 24.54 ± 3.35 years) were included (n = 26 with TMD, n = 25 with fibromyalgia, n = 25 with migraine, and n = 28 controls). All 3 chronic pain groups combined reported worse functioning than controls on friendship (P = 0.038), social isolation (P = 0.002), and social roles (P < 0.001). There were no differences on social variables between the 3 chronic pain groups (all P's > 0.05). Compared with those with 3 COPCs, participants with 1 condition reported better family relationships (P = 0.024). Conclusions: Experience of chronic pain-regardless of the specific pain condition-may negatively affect some areas of social functioning in young women.

Multi-view representation learning for tabular data integration using inter-feature relationships.

OBJECTIVE: An applied problem facing all areas of data science is harmonizing data sources. Joining data from multiple origins with unmapped and only partially overlapping features is a prerequisite to developing and testing robust, generalizable algorithms, especially in healthcare. This integrating is usually resolved using meta-data such as feature names, which may be unavailable or ambiguous. Our goal is to design methods that create a mapping between structured tabular datasets derived from electronic health records independent of meta-data. METHODS: We evaluate methods in the challenging case of numeric features without reliable and distinctive univariate summaries, such as nearly Gaussian and binary features. We assume that a small set of features are a priori mapped between two datasets, which share unknown identical features and possibly many unrelated features. Inter-feature relationships are the main source of identification which we expect. We compare the performance of contrastive learning methods for feature representations, novel partial auto-encoders, mutual-information graph optimizers, and simple statistical baselines on simulated data, public datasets, the MIMIC-III medical-record changeover, and perioperative records from before and after a medical-record system change. Performance was evaluated using both mapping of identical features and reconstruction accuracy of examples in the format of the other dataset. RESULTS: Contrastive learning-based methods overall performed the best, often substantially beating the literature baseline in matching and reconstruction, especially in the more challenging real data experiments. Partial auto-encoder methods showed on-par matching with contrastive methods in all synthetic and some real datasets, along with good reconstruction. However, the statistical method we created performed reasonably well in many cases, with much less dependence on hyperparameter tuning. When validating feature match output in the EHR dataset we found that some mistakes were actually a surrogate or related feature as reviewed by two subject matter experts. CONCLUSION: In simulation studies and real-world examples, we find that inter-feature relationships are effective at identifying matching or closely related features across tabular datasets when meta-data is not available. Decoder architectures are also reasonably effective at imputing features without an exact match.

Higher outdoor mosquito density and Plasmodium infection rates in and around malaria index case households in low transmission settings of Ethiopia: Implications for vector control.

BACKGROUND: Understanding the clustering of infections for persistent malaria transmission is critical to determining how and where to target specific interventions. This study aimed to determine the density, blood meal sources and malaria transmission risk of anopheline vectors by targeting malaria index cases, their neighboring households and control villages in Arjo-Didessa, southwestern Ethiopia. METHODS: An entomological study was conducted concurrently with a reactive case detection (RCD) study from November 2019 to October 2021 in Arjo Didessa and the surrounding vicinity, southwestern Ethiopia. Anopheline mosquitoes were collected indoors and outdoors in index case households and their surrounding households (neighboring households), as well as in control households, using pyrethrum spray cache (PSC) and U.S. Centers for Disease Control and Prevention (CDC) light traps. Adult mosquitoes were morphologically identified, and speciation in the Anopheles gambiae complex was done by PCR. Mosquito Plasmodium infections and host blood meal sources were detected by circumsporozoite protein enzyme-linked immunosorbent assay (CSP-ELISA) and cytochrome b-based blood meal PCR, respectively. RESULTS: Among the 770 anopheline mosquitoes collected, An. gambiae sensu lato (A. gambiae s.l.) was the predominant species, accounting for 87.1% (n = 671/770) of the catch, followed by the Anopheles coustani complex and Anopheles pharoensis, which accounted for 12.6% (n = 97/770) and 0.26% (n = 2/770) of the catch, respectively. From the sub-samples of An. gambiae s.l.analyzed with PCR, An. arabiensis and Anopheles amharicus were identified. The overall mean density of mosquitoes was 1.26 mosquitoes per trap per night using the CDC light traps. Outdoor mosquito density was significantly higher than indoor mosquito density in the index and neighboring households (P = 0.0001). The human blood index (HBI) and bovine blood index (BBI) of An. arabiensis were 20.8% (n = 34/168) and 24.0% (n = 41/168), respectively. The overall Plasmodium sporozoite infection rate of anophelines (An. arabiensis and An. coustani complex) was 4.4% (n = 34/770). Sporozoites were detected indoors and outdoors in captured anopheline mosquitoes. Of these CSP-positive species for Pv-210, Pv-247 and Pf, 41.1% (n = 14/34) were captured outdoors. A significantly higher proportion of sporozoite-infected mosquitoes were caught in index case households (5.6%, n = 8/141) compared to control households (1.1%, n = 2/181) (P = 0.02), and in neighboring households (5.3%, n = 24/448) compared to control households (P = 0.01). CONCLUSIONS: The findings of this study indicated that malaria index cases and their neighboring households had higher outdoor mosquito densities and Plasmodium infection rates. The study also highlighted a relatively higher outdoor mosquito density, which could increase the potential risk of outdoor malaria transmission and may play a role in residual malaria transmission. Thus, it is important to strengthen the implementation of vector control interventions, such as targeted indoor residual spraying, long-lasting insecticidal nets and other supplementary vector control measures such as larval source management and community engagement approaches. Furthermore, in low transmission settings, such as the Arjo Didessa Sugarcane Plantation, providing health education to local communities, enhanced environmental management and entomological surveillance, along with case detection and management by targeting of malaria index cases and their immediate neighboring households, could be important measures to control residual malaria transmission and achieve the targeted elimination goals.

Genetic disruption of the bacterial raiA motif noncoding RNA causes defects in sporulation and aggregation.

Several structured noncoding RNAs in bacteria are essential contributors to fundamental cellular processes. Thus, discoveries of additional ncRNA classes provide opportunities to uncover and explore biochemical mechanisms relevant to other major and potentially ancient processes. A candidate structured ncRNA named the "raiA motif" has been found via bioinformatic analyses in over 2,500 bacterial species. The gene coding for the RNA typically resides between the raiA and comFC genes of many species of Bacillota and Actinomycetota. Structural probing of the raiA motif RNA from the Gram-positive anaerobe Clostridium acetobutylicum confirms key features of its sophisticated secondary structure model. Expression analysis of raiA motif RNA reveals that the RNA is constitutively produced but reaches peak abundance during the transition from exponential growth to stationary phase. The raiA motif RNA becomes the fourth most abundant RNA in C. acetobutylicum, excluding ribosomal RNAs and transfer RNAs. Genetic disruption of the raiA motif RNA causes cells to exhibit substantially decreased spore formation and diminished ability to aggregate. Restoration of normal cellular function in this knock-out strain is achieved by expression of a raiA motif gene from a plasmid. These results demonstrate that raiA motif RNAs normally participate in major cell differentiation processes by operating as a trans-acting factor.

Environmental enrichment promotes adaptive responding during tests of behavioral regulation in male heterogeneous stock rats.

Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host of maladaptive behavioral traits associated with a range of neuropsychiatric disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This maladaptive dysregulation of behavior is influenced by genetic and environmental factors. For example, environmental enrichment produces beneficial neurobehavioral effects in animal models of such disorders. The present study determined the effects of environmental enrichment on a range of measures related to behavioral regulation using a large cohort of male, outbred heterogeneous stock (HS) rats as subjects. Subjects were reared from late adolescence onwards either in pairs in standard housing with minimal enrichment (n = 200) or in groups of 16 in a highly enriched environment consisting of a large multi-level cage filled with toys, running wheels, and shelters (n = 64). Rats were subjected to a battery of tests, including: (i) locomotor response to novelty, (ii) light reinforcement, (iii) social reinforcement, (iv) reaction time, (v) a patch-depletion foraging test, (vi) Pavlovian conditioned approach, (vii) conditioned reinforcement, and (viii) cocaine conditioned cue preference. Results indicated that rats housed in the enriched environment were able to filter out irrelevant stimuli more effectively and thereby regulate their behavior more efficiently than standard-housing rats. The dramatic impact of environmental enrichment suggests that behavioral studies using standard housing conditions may not generalize to more complex environments that may be more ethologically relevant.

Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocytic and Blood Stages.

New therapeutics are a priority for preventing and eliminating Plasmodium vivax (Pv) malaria because of its easy transmissibility and dormant stages in the liver. Relapses due to the dormant liver stages are the major contributor to reoccurring Pv. Therefore, therapies that reduce the establishment of dormant parasites and blood-stage infection are important for controlling this geographically widespread parasite. Here, we isolated 12 human monoclonal antibodies (humAbs) from the plasma of a Pv-exposed individual that recognized Pv apical membrane antigen 1 (PvAMA1). PvAMA1 is important for both sporozoite invasion of hepatocytes and merozoite invasion of reticulocytes. We identified one humAb, 826827, that blocked invasion of human erythrocytes using a transgenic P. falciparum line expressing PvAMA1 (IC 50 = 3 µg/mL) and all Pv clinical isolates in vitro . This humAb also inhibited sporozoite invasion of a human hepatocyte cell line and primary human hepatocytes (IC 50 of 0.3 - 3.7 µg/mL). The crystal structure of recombinant PvAMA1 with the antigen-binding fragment of 826827 at 2.4 Å resolution shows that the humAb partially occupies the highly conserved hydrophobic groove in PvAMA1 that binds its known receptor, RON2. HumAb 826827 binds to PvAMA1 with higher affinity than RON2, accounting for its potency. To our knowledge, this is the first reported humAb specific to PvAMA1, and the PvAMA1 residues it binds to are highly conserved across different isolates, explaining its strain-transcendent properties.