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David R Sinclair,1 David A Lubarsky,1 Michael M Vigoda,1 David J Birnbach,1 Eric A Harris,1 Vicente Behrens,1 Richard E Bazan,1 Steve M Williams,1 Kristopher Arheart,2 Keith A Candiotti1 1Department of Anesthesiology, Perioperative Medicine and Pain Management, 2Department of Public Health Sciences, Division of Biostatistics, University of Miami Miller School of Medicine, Miami, FL, USA Background: The purpose of this study was to propose a new crosswalk using the resource-based relative value system (RBRVS) that preserves the time unit component of the anesthesia service and disaggregates anesthesia billing into component parts (preoperative evaluation, intraoperative management, and postoperative evaluation). The study was designed as an observational chart and billing data review of current and proposed payments, in the setting of a preoperative holing area, intraoperative suite, and post anesthesia care unit. In total, 1,195 charts of American Society of Anesthesiology (ASA) physical status 1 through 5 patients were reviewed. No direct patient interventions were undertaken. Results: Spearman correlations between the proposed RBRVS billing matrix payments and the current ASA relative value guide methodology payments were strong (r=0.94–0.96, P

Samuel Maxwell Tom Williams,1 Rashid Ansumana,2 Jonathan Johnny,3 Ibrahim A Bakarr,3 Augustus Osborne1 1Department of Biological Sciences, School of Environmental Sciences, Njala University, Freetown, Sierra Leone; 2Department of Public Health, School of Community Health Sciences, Njala University, Freetown, Sierra Leone; 3Department of Wildlife Management and Conservation, School of Natural Resources Management, Njala University, Freetown, Sierra LeoneCorrespondence: Samuel Maxwell Tom Williams, Tel +23278462858, Email maxwell.williams@njala.edu.slBackground: Bats are considered wildlife species of public health concern, as they are known to host various pathogenic agents, and their interactions with humans are potential routes of pathogen spillover. A high level of knowledge on Bat-borne Zoonotic Diseases (BZD), their causative agents, signs, symptoms, mode and pattern of transmission, health attitudes, and practices towards the disorders are vital parameters in handling them. This study aimed to look into BZD knowledge, public attitudes, and behaviour.Methods: We surveyed the 14 chiefdoms of Moyamba district. A total of 421 participants were randomly sampled using closed-ended questionnaire. Simple linear regression analysis was used to determine the effects of gender, age, education, and livelihood opportunities on BZD knowledge (at 95% confidence interval and alpha value = 0.05). The findings were analysed and correlated with a scientific and public health perspective to assess the breadth of knowledge and awareness of BZD among the people of Moyamba district.Results: The findings from the study show a low level of knowledge on BZD among the people of the Moyamba district, with only 119 (28.3%) individuals that had some knowledge about BZD. Of those that knew about BZD, 94 (79.0%) had very little knowledge, 24 (20.2%) had a fair amount, and 1 (0.8%) had a great deal of knowledge about BZD. The primary mode of knowledge dissemination was through social media platforms.Conclusion: The level of knowledge about BZD is also very low. As a result of these findings, policymakers, health professionals, and environmental educators will be compelled to develop strategies to reduce the risk of BZD transmission in Sierra Leone’s population.Keywords: bat-borne zoonotic diseases, public health, transmission, Moyamba District, knowledge assessment, policymakers

Background: In a 2-y intervention targeting increased physical activity and healthy eating in primary school children, the adjusted body mass index (BMI) z score was 0.26 units (95% CI: 0.21, 0.32) lower in intervention than in control children. Few obesity prevention initiatives in children have undertaken follow-up analyses.Objective: The objective was to determine whether differences in BMI persisted ~2 y after the cessation of the intervention.Design:All children who had at least one measurement of height and weight at any time during the study (baseline and years 1 or 2) were invited to participate in follow-up measurements (height and weight).Results: Five hundred fifty-four of 727 eligible children (76%) participated. Children who refused to participate (n = 14) or had moved from the study area (n = 159) did not differ from the remaining participants in baseline age, sex, or BMI. The mean BMI z score (and 95% CI) remained significantly lower in intervention children at follow-up in the whole group (n = 554; -0.17; -0.25, -0.08) and in the group who underwent at least 1 (n = 389; -0.19; -0.24, -0.13) or 2 (n = 256; -0.21; -0.29, -0.14) full years of intervention. Intervention children were less likely to be overweight, but only in those who were present for the full intervention (n = 256; RR: 0.81; 95% CI: 0.69, 0.94).Conclusion: Despite the main intervention initiative (school-based activity coordinators charged with the responsibility of enhancing physical activity and promoting healthy eating) being discontinued at the end of the intervention, continued benefits to BMI remained apparent in intervention children ~2 y later. © American Society for Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: Developing effective strategies for obesity prevention in children is urgently required. OBJECTIVE: We determined the effectiveness of a 2-y controlled community-based intervention to prevent excessive weight gain in 5-12-y-old children by enhancing opportunities for healthy eating and noncurricular physical activity. DESIGN: Children (n = 730) from 4 intervention and 3 control schools underwent measurements of height, weight, waist circumference, blood pressure, diet, and physical activity at baseline and at 1 and 2 y. Intervention components included nutrition education that targeted reductions in sweetened drinks and increased fruit and vegetable intake and activity coordinators who managed an activity program that focused on noncurricular lifestyle-based activities (eg, community walks). RESULTS: Body mass index (BMI; in kg/m(2)) z score was significantly lower in intervention children than in control children by a mean of 0.09 (95% CI: 0.01, 0.18) after 1 y and 0.26 (95% CI: 0.21, 0.32) at 2 y, but the prevalence of overweight did not differ. Waist circumference was significantly lower at 2 y (-1 cm), and systolic blood pressure was reduced at 1 y (-2.9 mm Hg). An interaction existed between intervention group and overweight status (P = 0.029), such that mean BMI z score was reduced in normal-weight (-0.29; 95% CI: -0.38, -0.21) but not overweight (-0.02; 95% CI: -0.16, 0.12) intervention children relative to controls. Intervention children consumed fewer carbonated beverages (67% of control intake; P = 0.04) and fruit juice or drinks (70%; P = 0.03) and more fruit (0.8 servings/3 d; P < 0.01). CONCLUSION: A relatively simple approach, providing activity coordinators and basic nutrition education in schools, significantly reduces the rate of excessive weight gain in children, although this may be limited to those not initially overweight. This trial was registered at Australian Clinical Trials Registry as #12605000578606. Copyright © 2007 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Objective: The extent to which lifestyle must be altered to improve insulin sensitivity has not been established. This study compares the effect on insulin sensitivity of current dietary and exercise recommendations with a more intensive intervention in normoglycemic insulin-resistant individuals.Research Design and Methods: Seventy-nine normoglycemic insulin-resistant (determined by the euglycemic insulin clamp) men and women were randomized to either a control group or one of two combined dietary and exercise programs. One group (modest level) was based on current recommendations and the other on a more intensive dietary and exercise program. Insulin sensitivity was measured using a euglycemic insulin clamp, body composition was measured using dual-energy X-ray absorptiometry, and anthropometry and aerobic fitness were assessed before and after a 4-month intervention period. Four-day dietary intakes were recorded, and fasting glucose, insulin, and lipids were measured.Results: Only the intensive group showed a significant improvement in insulin sensitivity (23% increase, P=0.006 vs. 9% in the modest group, P=0.23). This was associated with a significant improvement in aerobic fitness (11% increase in the intensive group, P=0.02 vs. 1% in the modest group, P=0.94) and a greater fiber intake, but no difference in reported total or saturated dietary fat.Conclusions: Current clinical dietary and exercise recommendations, even when vigorously implemented, did not significantly improve insulin sensitivity; however, a more intensive program did. Improved aerobic fitness appeared to be the major difference between the two intervention groups, although weight loss and diet composition may have also played an important role in determining insulin sensitivity. [ABSTRACT FROM AUTHOR]

Aims: To compare the effects of prone and supine sleep position on the main physiological responses to mild asphyxia: increase in ventilation and arousal.Methods: Ventilatory and arousal responses to mild asphyxia (hypercapnia/hypoxia) were measured in 53 healthy infants at newborn and 3 months of age, during quiet sleep (QS) and active sleep (AS), and in supine and prone sleep positions. The asphyxial test mimicked face down rebreathing by slowly altering the inspired air: CO(2), maximum 5% and O(2), minimum 13.5%. The change in ventilation with inspired CO(2) was measured over 5-6 minutes of the test. The slope of a linear curve fit relating inspired CO(2) to the logarithm of ventilation was taken as a quantitative measure of ventilatory asphyxial sensitivity (VAS). Sleep state and arousal were determined by behavioural criteria.Results: At 3 months of age, prone positioning in AS lowered VAS (0.184 prone v 0.269 supine, p = 0.050). At newborn age, sleep position had no effect on VAS. Infants aged 3 months were twice as likely to arouse to the test than newborns (p = 0.013). Placing infants prone as opposed to supine increased the chances of arousal 1.57-fold (p = 0.035).Conclusion: Our findings show 3 month old babies sleeping prone compared to supine have poorer ventilatory responses to mild asphyxia, particularly in AS, but the increased prevalence of arousal is a protective factor. [ABSTRACT FROM AUTHOR]

BACKGROUND: A central fat pattern has adverse health implications in both children and adults. Because adiposity tracks from childhood into adulthood, the ability of simple anthropometric techniques to correctly measure truncal adiposity in childhood needs to be assessed. OBJECTIVES: We sought to assess the validity of waist circumference, waist-to-hip ratio (WHR), and the conicity index as indicators of trunk fat mass in children and adolescents. DESIGN: Trunk fat mass (kg) was measured with dual-energy X-ray absorptiometry in 278 girls and 302 boys aged 3-19 y. Receiver operating characteristic (ROC) curves and areas under the curves (AUCs) for the ROCs were calculated to compare the relative abilities of the anthropometric measures to correctly identify children with high trunk fat mass (z score for our study population of > or =1). RESULTS: The 80th percentile for waist circumference correctly identified 89% of girls and 87% of boys with high trunk fat mass (sensitivity) and 94% of girls and 92% of boys with low trunk fat mass (specificity). Waist circumference performed significantly better as an index of trunk fat mass than did WHR or the conicity index, as shown by the AUCs in girls and boys, respectively: waist circumference AUCs = 0.97 and 0.97, conicity index AUCs = 0.80 and 0.81, and WHR AUCs = 0.73 and 0.71. Our cutoffs for high trunk fat mass and high waist circumference are provided for both sexes for each year of age. CONCLUSION: Waist circumference provides a simple yet effective measure of truncal adiposity in children and adolescents. Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Presents information on a study which identified the effects of advancing age on lactose malabsorption in women and determined whether lactose malabsorbers have lower bone mineral density or display faster bone loss than lactose absorbers. Background to the study; Methods; Results; Conclusions.

Focuses on the impact of the distribution and organization of frontal cortex-projecting dopamine (DA) neurons in non-human primates. Exhibition of the mesencephalic distribution of neurons; Compartmentalization of the mesofrontal DA system; Heterogeneity of cognitive and affective symptoms.

The objective of this study was to determine whether overweight insulin resistant individuals who lost weight and improved cardiovascular risk factors during a 4-month lifestyle intervention could sustain these lifestyle changes in the long-term. Seventy-nine insulin resistant adults were randomised to a control group or either a modest or intensive lifestyle intervention group for 4-months. Thereafter the two intervention groups were combined and all participants were followed-up at 8, 12 and 24 months. Anthropometry, blood pressure, fasting glucose, lipids, insulin and aerobic fitness were measured and dietary intake was assessed. An interview was conducted to determine factors which participants perceived facilitated or hindered maintenance of healthy lifestyle habits. Seventy-two (91.1%), sixty-nine (87.3%) and sixty-two (78.5%) participants were retained at 8, 12 and 24-month respectively. At 4-months the adjusted difference in weight between the modest and control groups was -3.4 kg (95% CI -5.4, -1.3) p=0.002 and intensive and control groups was -4.7 kg (-6.9, -2.4) p=0.0001 respectively. At 2-years there were no significant differences for weight when the initial 3 groups were compared or when the combined intervention group was compared with the control group. At 2-years, 64% of participants reported that more frequent follow-up would have helped them to maintain healthy lifestyle habits. Even intensive counselling for 4-months with 4-monthly and then yearly monitoring were not enough for maintaining lifestyle changes sufficient to sustain weight loss. More frequent monitoring for an indefinite period was perceived by two-thirds of participants as necessary for them to maintain their initial lifestyle changes. [ABSTRACT FROM AUTHOR]

Single-cell multiomics provides comprehensive insights into gene regulatory networks, cellular diversity, and temporal dynamics. Here, we introduce nanoSPLITS (nanodroplet SPlitting for Linked-multimodal Investigations of Trace Samples), an integrated platform that enables global profiling of the transcriptome and proteome from same single cells via RNA sequencing and mass spectrometry-based proteomics, respectively. Benchmarking of nanoSPLITS demonstrates high measurement precision with deep proteomic and transcriptomic profiling of single-cells. We apply nanoSPLITS to cyclin-dependent kinase 1 inhibited cells and found phospho-signaling events could be quantified alongside global protein and mRNA measurements, providing insights into cell cycle regulation. We extend nanoSPLITS to primary cells isolated from human pancreatic islets, introducing an efficient approach for facile identification of unknown cell types and their protein markers by mapping transcriptomic data to existing large-scale single-cell RNA sequencing reference databases. Accordingly, we establish nanoSPLITS as a multiomic technology incorporating global proteomics and anticipate the approach will be critical to furthering our understanding of biological systems., Competing Interests: Competing interests: J.C.B., J.W.B, and A.S. are employees of Scienion/Cellenion. Y.Z. is an employee of Genentech Inc. and shareholder of Roche Group. Battelle Memorial Institute has submitted a U.S. patent application for the design of nanoSPLITS devices and the associated operation methods (Application number: 17/954,834, filed 09/28/2022; Inventors: Y.Z., J.M.F., L.M.M., and L.P.T.; Status of application: Pending). Other authors declare no other competing interests., (© 2024. Battelle Memorial Institute, Scienion US Inc. and Cellenion SASU 2024.)

Multiplexed bimolecular profiling of tissue microenvironment, or spatial omics, can provide deep insight into cellular compositions and interactions in healthy and diseased tissues. Proteome-scale tissue mapping, which aims to unbiasedly visualize all the proteins in a whole tissue section or region of interest, has attracted significant interest because it holds great potential to directly reveal diagnostic biomarkers and therapeutic targets. While many approaches are available, however, proteome mapping still exhibits significant technical challenges in both protein coverage and analytical throughput. Since many of these existing challenges are associated with mass spectrometry-based protein identification and quantification, we performed a detailed benchmarking study of three protein quantification methods for spatial proteome mapping, including label-free, TMT-MS2, and TMT-MS3. Our study indicates label-free method provided the deepest coverages of ∼3500 proteins at a spatial resolution of 50 μm and the highest quantification dynamic range, while TMT-MS2 method holds great benefit in mapping throughput at >125 pixels per day. The evaluation also indicates both label-free and TMT-MS2 provides robust protein quantifications in identifying differentially abundant proteins and spatially covariable clusters. In the study of pancreatic islet microenvironment, we demonstrated deep proteome mapping not only enables the identification of protein markers specific to different cell types, but more importantly, it also reveals unknown or hidden protein patterns by spatial coexpression analysis., Competing Interests: Conflict of interest Y. Z. is an employee of Genentech Inc. and shareholder of Roche Group. A. I. N. and F. Y. receive royalties from the University of Michigan for the sale of MSFragger and IonQuant software licenses to commercial entities. All license transactions are managed by the University of Michigan Innovation Partnerships office and all proceeds are subject to university technology transfer policy. The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Collection of hematopoietic progenitor cell products [HPC(A)] is deferred if the donor is symptomatic and tests positive for Covid-19. However, donor questionnaires are subjective and may miss minimally symptomatic donors. Alternatively, myalgia associated with Covid-19 infection can be falsely dismissed as an adverse effect of granulocyte stimulating factor (Filgrastim) administered prior to product collection. The likelihood of donors with an underlying acute but minimally symptomatic infection undergoing successful product collection is significant. In these circumstances, it is less known whether Covid-19 infection results in product viremia or alters the clinical outcome of transplant. We aimed to evaluate the above question by studying a donor whose product was collected during acute Covid-19 infection. Aliquots of the product tested negative for SARS-CoV-2 RNA by reverse-transcriptase polymerase chain reaction assay (RT-PCR). Importantly, the donor received an autologous stem cell transplant using the product collected at the time of infection, and their case will be described in this report. We describe one of the very few reports of successful transplant of HPC(A) product collected during acute Covid-19 infection., (© 2024. The Author(s).)

Background: With the success of chimeric antigen receptor T-cell (CAR-T) and similar cellular-based therapies, the demand for collection of autologous mononuclear cells by apheresis (MNC(A)) from blood by apheresis has increased. From an apheresis technical standpoint, the collection of MNC(A) is relatively straightforward, especially when compared with collection of hematopoietic progenitor cells (HPC(A)). Most of the collection for MNC(A) are performed for the commercial entities, who use the product for manufacturing cellular therapeutics. We have noticed discrepancies in the handling and apheresis processes required by different companies in obtaining essentially the same product (all companies in the study manufacture CAR-T-based products). We have analyzed the MNC collection requirements from all FDA-approved CAR-T cellular products and some investigational products collected at University of Nebraska Medical Center. We identified discrepancies in the process and suggested mitigation strategies., Methods: Step-by-step analysis of the collection requirements. Review of the current guidelines and recommendations on this issue., Results: Multiple discrepancies in the collection process have been identified, even in the products collected for the same company. Practical approach of satisfying all the requirements based on University of Nebraska Medical Center experience has been suggested., Conclusion: The current recommendations from multiple sources were reviewed in discussion., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary, or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expressed genes (DEGs) and differentially methylated positions (DMPs)., Methods: Transcriptome and DNAm data were obtained from PBMC RNA and DNA of Kenyan children (n = 8) before, during, and 6 weeks following uncomplicated malaria. DEGs and DMPs between time points were detected using cell-type adjusted modeling with Cibersortx or IDOL, respectively., Results: Most major cell types and principal components had moderate to high correlation between the two deconvolution methods (r = 0.60-0.96). Estimates of cell-type proportions and DEGs or DMPs were largely unaffected by the method, with the greatest discrepancy in the estimation of neutrophils., Conclusion: Variation in cell-type proportions is captured similarly by both transcriptomic and methylome deconvolution methods for most major cell types., (© 2024. The Author(s).)

Background: The Human Proteome Project has credibly detected nearly 93% of the roughly 20,000 proteins which are predicted by the human genome. However, the proteome is enigmatic, where alterations in amino acid sequences from polymorphisms and alternative splicing, errors in translation, and post-translational modifications result in a proteome depth estimated at several million unique proteoforms. Recently mass spectrometry has been demonstrated in several landmark efforts mapping the human proteoform landscape in bulk analyses. Herein, we developed an integrated workflow for characterizing proteoforms from human tissue in a spatially resolved manner by coupling laser capture microdissection, nanoliter-scale sample preparation, and mass spectrometry imaging., Results: Using healthy human kidney sections as the case study, we focused our analyses on the major functional tissue units including glomeruli, tubules, and medullary rays. After laser capture microdissection, these isolated functional tissue units were processed with microPOTS (microdroplet processing in one-pot for trace samples) for sensitive top-down proteomics measurement. This provided a quantitative database of 616 proteoforms that was further leveraged as a library for mass spectrometry imaging with near-cellular spatial resolution over the entire section. Notably, several mitochondrial proteoforms were found to be differentially abundant between glomeruli and convoluted tubules, and further spatial contextualization was provided by mass spectrometry imaging confirming unique differences identified by microPOTS, and further expanding the field-of-view for unique distributions such as enhanced abundance of a truncated form (1-74) of ubiquitin within cortical regions., Conclusions: We developed an integrated workflow to directly identify proteoforms and reveal their spatial distributions. Where of the 20 differentially abundant proteoforms identified as discriminate between tubules and glomeruli by microPOTS, the vast majority of tubular proteoforms were of mitochondrial origin (8 of 10) where discriminate proteoforms in glomeruli were primarily hemoglobin subunits (9 of 10). These trends were also identified within ion images demonstrating spatially resolved characterization of proteoforms that has the potential to reshape discovery-based proteomics because the proteoforms are the ultimate effector of cellular functions. Applications of this technology have the potential to unravel etiology and pathophysiology of disease states, informing on biologically active proteoforms, which remodel the proteomic landscape in chronic and acute disorders., Competing Interests: Competing interests YZ is an employee of Genentech Inc. and shareholder of Roche. All other authors declare that they have no competing interests.