Search

Abstract Background Advanced prostate cancer leads to many symptoms, notably bone pain and lower urinary tract symptoms (LUTs); however, the degree and duration of pain relief, changes in LUTs severity and underlying factors associated with the extent of symptom relief remain inadequately understood. Surgical castration has proven effective in relieving both bone pain and urinary symptoms for metastatic prostate cancer patients. Objective To determine the extent and pattern of symptom relief in advanced prostate cancer patients following surgical castration at Muhimbili National Hospital (MNH). Methods We conducted a prospective cohort study for a period of 6 months involving men with advanced Prostate cancer (PCa) undergoing surgical castration at MNH and followed them for 30 days. The international prostate symptoms score tool was used to assess changes in LUTs, and the pain rating scale was used for assessing changes in bone pain symptoms before and after surgery. Logistic regression model was used to determine factors associated with complete bone pain relief. Results A total of 210 participants with a mean age of 72.3 years were recruited. The LUTS score showed a decrease of 7.1 points after surgical castration (95% CI: 6.4 to 7.7, p

Abstract Background The burden of chronic non-communicable diseases (NCDs) is a growing public health concern. The availability of cost-of-illness data, particularly public healthcare costs for NCDs, is limited in Sub-Saharan Africa (SSA), yet such data evidence is needed for policy action. Objective The objective of this study was to estimate the economic burden of type 2 diabetes (T2D) on Kenya’s public healthcare system in 2021 and project costs for 2045. Methods This was a cost-of-illness study using the prevalence-based bottom-up costing approach to estimate the economic burden of T2D in the year 2021. We further conducted projections on the estimated costs for the year 2045. The costs were estimated corresponding to the care, treatment, and management of diabetes and some diabetes complications based on the primary data collected from six healthcare facilities in Nairobi and secondary costing data from previous costing studies in low and middle-income countries (LMICs). The data capture and costing analysis were done in Microsoft Excel 16, and sensitivity analysis was conducted on all the parameters to estimate the cost changes. Results The total cost of managing T2D for the healthcare system in Kenya was estimated to be US$ 635 million (KES 74,521 million) in 2021. This was an increase of US$ 2 million (KES 197 million) considering the screening costs of undiagnosed T2D in the country. The major cost driver representing 59% of the overall costs was attributed to T2D complications, with nephropathy having the highest estimated costs of care and management (US$ 332 million (KES 36, 457 million). The total cost for T2D was projected to rise to US$ 1.6 billion (KES 177 billion) in 2045. Conclusion This study shows that T2D imposes a huge burden on Kenya’s healthcare system. There is a need for government and societal action to develop and implement policies that prevent T2D, and appropriately plan care for those diagnosed with T2D.

Abstract Background The aim of this study was to explore predictors associated with reasons for visiting an oral healthcare professional (OHP) and satisfaction with OHPs in the Netherlands among the Indian migrants and the host population. Methods A random sample was obtained for this cross-sectional questionnaire study. Variables were classified according to the Andersen Behavioural Model of Health Services Utilization. Multivariable binary logistic regression analysis was conducted to identify significant predictors for reasons for visiting an oral healthcare professional (OHP) (routine checkups and preventive care or visiting only for pain and/or treatment) and satisfaction with OHPs (satisfied or dissatisfied). Results The sample consisted of 391 participants (Indian migrants = 147 and host population = 244). Indian migrants with higher internal locus of control (LoC) [OR = 7.73 (95% CI: 2.13;27.99)], more trust in OHPs [OR = 4.12 (95% CI:1.68;10.14)] and higher integration level [OR = 1.09 (95% CI:1.03;1.17)] had higher odds of visiting an OHP for routine checkups and preventive care. In the host population, having dental insurance [OR = 2.64 (95% CI:1.00;6.95)] was significantly associated with increased odds of visiting an OHP for routine checkups and preventive care. For satisfaction, Indians with low paid jobs [OR = 16.26 (95% CI:2.83;93.36)] and those with higher integration levels [OR = 1.29 (95% CI:1.16;1.42)] had higher odds of being satisfied with the Dutch OHPs. Among the host population, those with more trust in OHPs [OR = 2.86 (95% CI:1.19;6.88)] had higher odds of being satisfied. Conclusion Our study emphasize that integration levels and trust emerged as two crucial factors, policy makers can leverage upon to improve access to care for Indian migrants. Clinical trial N.A as this is a survey based cross sectional study.

Abstract The organosulfur compound dimethylsulfoniopropionate (DMSP) has key roles in stress protection, global carbon and sulfur cycling, chemotaxis, and is a major source of climate-active gases. Saltmarshes are global hotspots for DMSP cycling due to Spartina cordgrasses that produce exceptionally high concentrations of DMSP. Here, in Spartina anglica, we identify the plant genes that underpin high-level DMSP synthesis: methionine S-methyltransferase (MMT), S-methylmethionine decarboxylase (SDC) and DMSP-amine oxidase (DOX). Homologs of these enzymes are common in plants, but differences in expression and catalytic efficiency explain why S. anglica accumulates such high DMSP concentrations and other plants only accumulate low concentrations. Furthermore, DMSP accumulation in S. anglica is consistent with DMSP having a role in oxidative and osmotic stress protection. Importantly, administration of DMSP by root uptake or over-expression of Spartina DMSP synthesis genes confers plant tolerance to salinity and drought offering a route for future bioengineering for sustainable crop production.

Abstract Background The sustainability of diets consumed by African populations under socio-economic transition remains to be determined. This study developed and characterized a multi-dimensional Sustainable Diet Index (SDI) reflecting healthfulness, climate-friendliness, sociocultural benefits, and financial affordability using individual-level data of adults in rural and urban Ghana and Ghanaian migrants in Europe to identify the role of living environment in dietary sustainability. Methods We used cross-sectional data from the multi-centre Research on Obesity and Diabetes among African Migrants Study (N = 3169; age range: 25–70 years). For the SDI construct (0–16 score points), we used the Diet Quality Index-International, food-related greenhouse gas emission, the ratio of natural to processed foods, and the proportion of food expenditure from income. In linear regression analyses, we estimated the adjusted ß-coefficients and 95% confidence intervals (CIs) for the differences in mean SDI across study sites (using rural Ghana as a reference), accounting for sociodemographic and lifestyle factors. Results The overall mean SDI was 8.0 (95% CI: 7.9, 8.1). Participants in the highest SDI-quintile compared to lower quintiles were older, more often women, non-smokers, and alcohol abstainers. The highest mean SDI was seen in London (9.1; 95% CI: 8.9, 9.3), followed by rural Ghana (8.2; 95% CI: 8.0, 8.3), Amsterdam (7.9; 95% CI: 7.7, 8.1), Berlin (7.8; 95% CI: 7.6, 8.0), and urban Ghana (7.7; 95% CI: 7.5, 7.8). Compared to rural Ghana, the differences between study sites were attenuated after accounting for age, gender and energy intake. No further changes were observed after adjustment for lifestyle factors. Conclusion The multi-dimensional SDI describes four dimensions of dietary sustainability in this Ghanaian population. Our findings suggest that living in Europe improved dietary sustainability, but the opposite seems true for urbanization in Ghana.

Abstract Background The safety, tolerability, and immunogenicity of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% (dual-vial unit of human immunoglobulin 10% and recombinant human hyaluronidase [rHuPH20]) were assessed in children with primary immunodeficiency diseases (PIDs). Methods This phase 4, post-authorization, prospective, interventional, multicenter study (NCT03116347) conducted in the European Economic Area, enrolled patients aged 2 to < 18 years with a documented PID diagnosis who had received immunoglobulin therapy for ≥ 3 months before enrollment. New fSCIG 10% starters underwent fSCIG 10% dose ramp-up for ≤ 6 weeks (epoch 1) before receiving fSCIG 10% for ≤ 3 years (epoch 2); patients pretreated with fSCIG 10% entered epoch 2 directly. The primary outcome was the number and rate (per infusion) of all noninfectious treatment-related serious and severe adverse events (AEs). Results In total, 42 patients were enrolled and dosed (median [range] age: 11.5 [3–17] years; 81% male; 23 new starters; 19 pretreated). Overall, 49 related noninfectious, treatment-emergent AEs (TEAEs) were reported in 15 patients; most were mild in severity (87.8%). No treatment-related serious TEAEs were reported. Two TEAEs (infusion site pain and emotional distress) were reported as severe and treatment-related in a single new fSCIG 10% starter. The rate of local TEAEs was lower in pretreated patients (0.1 event/patient-year) versus new starters (1.3 events/patient-year). No patients tested positive for binding anti-rHuPH20 antibodies (titer of ≥ 1:160). Conclusions No safety signals were identified, and the incidence of local AEs declined over the duration of fSCIG 10% treatment. This study supports fSCIG 10% long-term safety in children with PIDs. Trial registration number (ClinicalTrials.gov) NCT03116347.

Gene mutations linked to diseases like cancer may be caused by exposure to environmental chemicals. The X-linked phosphatidylinositol glycan class A (PIG-A) gene, required for glycosylphosphatidylinositol (GPI) anchor biosynthesis, is a key target locus for in vitro genetic toxicity assays. Various organisms and cell lines may respond differently to genotoxic agents. Here, we compared the mutagenic potential of directly genotoxic ethyl methane sulfonate (EMS) to metabolically activated pro-mutagenic polycyclic aromatic hydrocarbons (PAHs). The two classes of mutagens were compared in an in vitro PIG-A gene mutation test using the metabolically active murine hepatoma Hepa1c1c7 cell line and the human TK6 cell line, which has limited metabolic capability. Determination of cell viability is required for quantifying mutagenicity. Two common cell viability tests, the MTT assay and propidium iodide (PI) staining measured by flow cytometry, were evaluated. The MTT assay overestimated cell viability in adherent cells at high benzo[a]pyrene (B[a]P) exposure concentrations, so PI-based cytotoxicity was used in calculations. The spontaneous mutation rates for TK6 and Hepa1c1c7 cells were 1.87 and 1.57 per million cells per cell cycle, respectively. TK6 cells exposed to 600 µM and 800 µM EMS showed significantly higher mutation frequencies (36 and 47 per million cells per cell cycle, respectively). Exposure to the pro-mutagen benzo[a]pyrene (B[a]P, 10 µM) did not increase mutation frequency in TK6 cells. In Hepa1c1c7 cells, mutation frequencies varied across exposure groups (50, 50, 29, and 81 per million cells per cell cycle when exposed to 10 µM B[a]P, 5-methylcholanthrene (5-MC), chrysene, or 16,000 µM EMS, respectively). We demonstrate that the choice of cytotoxicity assay and cell line can determine the outcome of the Pig-A mutagenesis assay when assessing a specific mutagen.

Abstract Background Data regarding rural youths’ experience with firearms, including safety training, is highly limited despite their frequent presence in homes. Our objective was to investigate rural adolescents’ use of firearms and whether they had received formal firearm training. Methods A convenience sample of 2021 National FFA (formerly Future Farmers of America) Convention & Expo attendees were given an anonymous survey at the University of Iowa Stead Family Children’s Hospital injury prevention booth. The survey explored their use of rifles/shotguns and handguns and whether they had completed a certified firearm safety course. Descriptive and comparative analyses, including multivariable logistic regression analyses, were performed on compiled data. Results 3206 adolescents ages 13–18 years participated with 45% reporting they lived on a farm or ranch. The vast majority of participants (85%) had fired a rifle/shotgun; 43% reported firing them > 100 times. Of those that had fired rifles/shotguns, 41% had done so before 9 years old. Most had also fired a handgun (69%), with 23% having fired handguns > 100 times. Of those that had fired handguns, 44% had done so before 11 years. Average age for first firing rifles/shotguns was 9.5 (SD 3.1) years, and 11.1 (SD 3.0) years for handguns. Males, non-Hispanic Whites, and those living on farms or in the country had significantly greater percentages who had fired a rifle/shotgun or a handgun. Significant differences were also seen by U.S. census region. Over half (64%) reported having gone hunting. Of those that had used a firearm, 67% had completed a firearm safety training course. Overall, 23% were/had been members of a school or club shooting team and of these, 87% had taken a safety course. Conclusions Most FFA member participants had fired both rifles/shotguns and handguns, many at very young ages. Significant differences in firearm use were noted by demographic factors including the home setting (i.e., farms and ranches) and their U.S. census region. Nearly one-third of adolescent firearm users had not received formal safety training. Promoting firearm safety should include advising families on when it is developmentally appropriate to introduce youth to firearms and on the importance of firearm safety training.

Abstract Background Head injuries are the most common cause of death in some motorized vehicles for which helmet use can significantly decrease the risk. Our objective was to determine rural adolescents’ attitudes regarding helmets and their use while riding ATVs, motorcycles and dirt bikes. Methods A convenience sample of 2022 Iowa FFA (formerly Future Farmers of America) Leadership Conference attendees were surveyed. After compilation, data were imported into the statistical program, R ( https://www.R-project.org/ ). Descriptive statistics, contingency table, logistic regression and non-parametric alternatives to ANOVA analyses were performed. Results 1331 adolescents (13–18 years) participated. One half lived on a farm, 21% lived in the country/not on a farm and 28% were from towns. Nearly two-thirds (65%) owned an ATV with 77% of all having ridden one in the past year. Farm residents had the highest ATV ownership (78%) and having ridden (80%) proportions, both p

Abstract While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy (“PRINCE”, NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.

Abstract Background Plasmodium falciparum erythrocyte membrane protein‐1 (PfEMP‐1) is important in malaria pathogenicity as it mediates Pf‐infected erythrocytes cytoadherence to host endothelial microvasculature receptors. Naturally acquired antibodies against specific PfEMP‐1 antigens may be beneficial in clinical malaria protection. This study determined antibodies to DBLα2, CIDRα1, DBLβ12, and DBLγ6 domains of PfEMP‐1 in children with P. falciparum malaria in Tamale, Ghana. Methods Sixty P. falciparum‐infected children, and 30 controls, aged 1–12 years were recruited for this case‐control study from April to July 2023 in Northern Ghana. Participants with uncomplicated malaria had asexual P. falciparum in peripheral blood and Hb ≥ 5.0 g/dL, and severe malaria was diagnosed when participants had Hb

Previously institutionalized adolescents show increased risk for psychopathology, though placement into high-quality foster care can partially mitigate this risk. White matter (WM) structure is associated with early institutional rearing and psychopathology in youth. Here we investigate associations between WM structure and psychopathology in previously institutionalized youth. Adolescent psychopathology data were collected using the MacArthur Health and Behavior Questionnaire. Participants underwent diffusion MRI, and data were processed using fixel-based analyses. General linear models investigated interactions between institutionalization groups and psychopathology on fixel metrics. Supplementary analyses also examined the main effects of psychopathology and institutionalization group on fixel metrics. Ever–Institutionalized children included 41 randomized to foster care (Mage=16.6), and 40 to care-as-usual (Mage=16.7)). In addition, 33 participants without a history of institutionalization were included as a reference group (Mage=16.9). Ever–Institutionalized adolescents displayed altered general psychopathology–fixel associations within the cerebellar peduncles, inferior longitudinal fasciculi, corticospinal tract, and corpus callosum, and altered externalizing–fixel associations within the cingulum and fornix. Our findings indicate brain–behavior associations reported in the literature may not be generalizable to all populations. Previously institutionalized youth may develop differential brain development, which in turn leads to altered neural correlates of psychopathology that are still apparent in adolescence.

The rise in population density, vehicle ownership, and urban development has significantly influenced travel demand and altered travel patterns, leading to traffic congestion in rapidly growing urban centers such as Accra, Ghana. The traditional approach of expanding roadways to accommodate rising traffic is no longer environmentally sustainable. Instead, the emphasis has shifted toward travel demand management (TDM) strategies as a more sustainable solution. This study aimed to investigate a range of TDM strategies that can be adopted in Accra to improve traffic flow through the lenses of everyday road users. The study employed a questionnaire survey and a stratified sampling technique to gather data from 615 respondents for relative importance index (RII) ranking and Chi-square statistical analysis. The findings revealed that the topmost preferred strategies were mass transit improvements, walking and cycling improvements, and alternative work schedules. Notably, mass transit improvements emerged as the most preferred strategy. Conversely, strategies like efficient parking pricing, congestion pricing, and higher fuel and road taxes for private vehicles ranked lowest, garnering minimal preference. The study also revealed a statistically significant correlation between variables such as age, education level, marital status, income level, and mode of transportation and all the selected TDM preferences. However, no significant relationship was found between gender or car ownership and any of the selected TDM preferences. The study provides valuable insights into road users’ preferences for TDM strategies that can aid in planning future urban mobility systems to proactively manage travel demand, alleviate congestion, and promote sustainable transportation options for the city’s residents.

The calcium/calmodulin-dependent protein kinase II-beta (CAMK2B) gene is important for calcium signaling and glutamatergic synapses, which impacts neuroplasticity and learning. Mutations in the CAMK2B gene, which cause autosomal dominant mental retardation 54 (Online Mendelian Inheritance in Man # 617799), can have multisystemic clinical impact. Due to the rarity of CAMK2B mutations at present, case reports about patients with CAMK2B mutations are limited. The present case report describes a patient with CAMK2B-related disorder confirmed by whole exome sequencing and adds to the current information in the literature. We review three case reports in literature with detailed descriptions of patients presenting with mutations in the CAMK2B gene. While there is a broad spectrum of phenotypic presentations, there appears to be an emerging neurobehavioral phenotype. Optimal management of patients will require attention to behavioral issues as well as involvement of neuropsychiatric expertise along with other supports for development and vision abnormalities.

Abstract Introduction To achieve quality midwifery education, understanding the experiences of midwifery educators and students in implementing a competency-based pre-service curriculum is critical. This study explored the experiences of and barriers to implementing a pre-service curriculum updated with emergency obstetric and newborn care (EmONC) skills by midwifery educators, students and mentors in Kenya. Methods This was a nested qualitative study within the cluster randomised controlled trial investigating the effectiveness of an EmONC enhanced midwifery curriculum delivered by trained and mentored midwifery educators on the quality of education and student performance in 20 colleges in Kenya. Following the pre-service midwifery curriculum EmONC update, capacity strengthening of educators through training (in both study arms) and additional mentoring of intervention-arm educators was undertaken. Focus group discussions were used to explore the experiences of and barriers to implementing the EmONC-enhanced curriculum by 20 educators and eight mentors. Debrief/feedback sessions with 6–9 students from each of the 20 colleges were conducted and field notes were taken. Data were analysed thematically using Braun and Clarke’s six step criteria. Results Themes identified related to experiences were: (i) relevancy of updated EmONC-enhanced curriculum to improve practice, (ii) training and mentoring valued as continuous professional development opportunities for midwifery educators, (iii) effective teaching and learning strategies acquired – peer teaching (teacher-teacher and student-student), simulation/scenario teaching and effective feedback techniques for effective learning and, (iv) effective collaborations between school/academic institution and hospital/clinical staff promoted effective training/learning. Barriers identified were (i) midwifery faculty shortage and heavy workload vs. high student population, (ii) infrastructure gaps in simulation teaching – inadequate space for simulation and lack of equipment inventory audits for replenishment (iii) inadequate clinical support for students due to inadequate clinical sites for experience, ineffective supervision and mentoring support, lack/shortage of clinical mentors and untrained hospital/clinical staff in EmONC and (iv) limited resources to support effective learning. Conclusion Findings reveal an overwhelmed midwifery faculty and an urgent demand for students support in clinical settings to acquire EmONC competencies for enhanced practice. For quality midwifery education, adequate resources and regulatory/policy directives are needed in midwifery faculty staffing and development. A continuous professional development specific for educators is needed for effective student teaching and learning of a competency-based pre-service curriculum.

Abstract Background Honey bees are the principal commercial pollinators. Along with other arthropods, they are increasingly under threat from anthropogenic factors such as the incursion of invasive honey bee subspecies, pathogens and parasites. Better tools are needed to identify bee subspecies. Genomic data for economic and ecologically important organisms is increasing, but in its basic form its practical application to address ecological problems is limited. Results We introduce HBeeID a means to identify honey bees. The tool utilizes a knowledge-based network and diagnostic SNPs identified by discriminant analysis of principle components and hierarchical agglomerative clustering. Tests of HBeeID showed that it identifies African, Americas-Africanized, Asian, and European honey bees with a high degree of certainty even when samples lack the full 272 SNPs of HBeeID. Its prediction capacity decreases with highly admixed samples. Conclusion HBeeID is a high-resolution genomic, SNP based tool, that can be used to identify honey bees and screen species that are invasive. Its flexible design allows for future improvements via sample data additions from other localities.

Abstract Deployment of ultracold atom interferometers (AI) into space will capitalize on quantum advantages and the extended freefall of persistent microgravity to provide high-precision measurement capabilities for gravitational, Earth, and planetary sciences, and to enable searches for subtle forces signifying physics beyond General Relativity and the Standard Model. NASA’s Cold Atom Lab (CAL) operates onboard the International Space Station as a multi-user facility for fundamental studies of ultracold atoms and to mature space-based quantum technologies. We report on pathfinding experiments utilizing ultracold 87Rb atoms in the CAL AI. A three-pulse Mach–Zehnder interferometer was studied to understand the influence of ISS vibrations. Additionally, Ramsey shear-wave interferometry was used to manifest interference patterns in a single run that were observable for over 150 ms free-expansion time. Finally, the CAL AI was used to remotely measure the Bragg laser photon recoil as a demonstration of the first quantum sensor using matter-wave interferometry in space.

Abstract Tuberculosis (TB) remains a leading cause of death, but antibiotic treatments for tuberculous meningitis, the deadliest form of TB, are based on those developed for pulmonary TB and not optimized for brain penetration. Here, we perform first-in-human dynamic 18F-pretomanid positron emission tomography (PET) in eight human subjects to visualize 18F-pretomanid biodistribution as concentration-time exposures in multiple compartments (NCT05609552), demonstrating preferential brain versus lung tissue partitioning. Preferential, antibiotic-specific partitioning into brain or lung tissues of several antibiotics, active against multidrug resistant (MDR) Mycobacterium tuberculosis strains, are confirmed in experimentally-infected mice and rabbits, using dynamic PET with chemically identical antibiotic radioanalogs, and postmortem mass spectrometry measurements. PET-facilitated pharmacokinetic modeling predicts human dosing necessary to attain therapeutic brain exposures. These data are used to design optimized, pretomanid-based regimens which are evaluated at human equipotent dosing in a mouse model of TB meningitis, demonstrating excellent bactericidal activity without an increase in intracerebral inflammation or brain injury. Importantly, several antibiotic regimens demonstrate discordant activities in brain and lung tissues in the same animal, correlating with tissue antibiotic exposures. These data provide a mechanistic basis for the compartmentalized activities of antibiotic regimens, with important implications for developing treatments for meningitis and other infections in compartments with unique antibiotic penetration.

Abstract One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-confidence autism risk genes within the mouse brain for proximity-based endogenous proteomics, achieving the identification of high-specificity spatial proteomes. The resulting native proximity proteomes are enriched for human genes dysregulated in the brain of autistic individuals, and reveal proximity interactions between proteins from high-confidence risk genes with those of lower-confidence that may provide new avenues to prioritize genetic risk. Importantly, the datasets are enriched for shared cellular functions and genetic interactions that may underlie the condition. We test this notion by spatial proteomics and CRISPR-based regulation of expression in two autism models, demonstrating functional interactions that modulate mechanisms of their dysregulation. Together, these results reveal native proteome networks in vivo relevant to autism, providing new inroads for understanding and manipulating the cellular drivers underpinning its etiology.

Background: Capitellar osteochondritis dissecans (OCD) lesions are common in athletes. Osteochondral autograft transfer (OAT) is one possible treatment option, though outcomes including return to sport (RTS) data are limited to small series. The purpose of this study was to systematically review RTS following OAT for capitellar OCD lesions. Our secondary objectives were to evaluate patient-reported outcomes (PROs), range of motion (ROM), and complications after OAT. Methods: PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature were searched for peer-reviewed articles on “osteochondral autograft transfer” and related terms for capitellar OCD lesions. Articles were included if they reported an RTS rate and had a follow-up time point of at least 12 months. Data on RTS rates, PRO measures, complications, and ROM were extracted. Articles were assessed for methodological quality using the Methodological Index for Non-randomized Studies criteria. Results: Six hundred sixty-six articles were retrieved, and 24 articles (470 patients) met the inclusion criteria. In total, 454/470 patients (97%) returned to sports following OAT for OCD. The RTS rate ranged from 79% to 100%. Return to previous level of performance ranged from 10% to 100%. Timmerman-Andrews postoperative scores (range = 169-193) were most often reported, with 87% of patients showing scores within the excellent range. Disabilities of the Arm, Shoulder, and Hand and Japanese Orthopedic Association scores were also excellent postoperatively for all studies reporting, with higher scores among centralized lesions vs. lateral. Conclusions: Following OAT for capitellar OCD lesions, RTS rates are high; however, athletes should be counseled on the potential of a return to lower performance or the need to change positions. Lateral lesion location may negatively impact outcomes. PRO scores are typically excellent and postoperative ROM consistently improves. This information helps counsel patients regarding expectations and outcomes of OAT for OCD of the capitellum.

Objective: To examine the association of left atrial (LA) function with incident chronic kidney disease (CKD) and assess the clinical utility of adding LA function to a CKD risk prediction equation. Patients and Methods: We included 4002 Atherosclerosis Risk in Communities study participants without prevalent CKD (mean ± SD age, 75±5 years; 58% female, 18% Black). Left atrial function (reservoir, conduit, and contractile strain) was evaluated by 2D-echocardiograms on 2011 to 2013. Chronic kidney disease was defined as greater than 25% decline in estimated glomerular filtration rate of less than 60 mL/min/1.73 m2, end-stage kidney disease, or hospital records. Cox proportional hazards models were used. Risk prediction and decision curve analyses evaluated 5-year CKD risk by diabetes status. Results: Median follow-up was 7.2 years, and 598 participants developed incident CKD. Incidence rate for CKD was 2.29 per 100 person-years. After multivariable adjustments, the lowest quintile of LA reservoir, conduit, and contractile strain (vs highest quintile) had a higher risk of CKD (hazard ratios [95% CIs]: 1.94 [1.42-2.64], 1.62 [1.19-2.20], and 1.49 [1.12-1.99]). Adding LA reservoir strain to the CKD risk prediction equation variables increased the C-index by 0.026 (95% CI: 0.005-0.051) and 0.031 (95% CI: 0.006-0.058) in participants without and with diabetes, respectively. Decision curve analysis found the model with LA reservoir strain had a higher net benefit than the model with CKD risk prediction equation variables alone. Conclusion: Lower LA function is independently associated with incident CKD. Adding LA function to the CKD risk prediction enhances prediction and yields a higher clinical net benefit. These findings suggest that impaired LA function may be a novel risk factor for CKD.

Abstract Background Severe Plasmodium falciparum malarial anemia is still the principal cause of death in children in underdeveloped countries. An imbalance between proinflammatory and anti‐inflammatory cytokines is associated with malaria progression. This study evaluated circulating levels of selected inflammatory cytokines among malaria‐infected children in Ghana. Methods This case‐control study was conducted at Tamale Teaching Hospital, Ghana. One hundred and twenty children with malaria and 60 controls, aged 12−144 months were selected from April to July, 2023 for the study. Malaria was diagnosed through microscopy, full blood count was measured using hematology analyzer, and cytokines were measured using enzyme‐linked immunosorbent assay. Results Malaria‐infected children had higher tumor necrosis factor alpha (TNF‐α) (p

Abstract Background The yeast Komagataella phaffii is widely used for manufacturing recombinant proteins, but secreted titers of recombinant proteins could be improved by genetic engineering. In this study, we hypothesized that cellular resources could be redirected from production of endogenous proteins to production of recombinant proteins by deleting unneeded endogenous proteins. In non-model microorganisms such as K. phaffii, however, genetic engineering is limited by lack gene annotation and knowledge of gene essentiality. Results We identified a set of endogenous secreted proteins in K. phaffii by mass spectrometry and signal peptide prediction. Our efforts to disrupt these genes were hindered by limited annotation of essential genes. To predict essential genes, therefore, we designed, transformed, and sequenced a pooled library of guide RNAs for CRISPR-Cas9-mediated knockout of all endogenous secreted proteins. We then used predicted gene essentiality to guide iterative disruptions of up to 11 non-essential genes. Engineered strains exhibited a ~20× increase in the production of human serum albumin and a twofold increase in the production of a monoclonal antibody. Conclusions We demonstrated that disruption of as few as six genes can increase production of recombinant proteins. Further reduction of the endogenous proteome of K. phaffii may further improve strain performance. The pooled library of secretome-targeted guides for CRISPR-Cas9 and knowledge of gene essentiality reported here will facilitate future efforts to engineer K. phaffii for production of other recombinant proteins and enzymes.

Abstract Non-human primates remain the most useful and reliable pre-clinical model for many human diseases. Primate breath profiles have previously distinguished healthy animals from diseased, including non-human primates. Breath collection is relatively non-invasive, so this motivated us to define a healthy baseline breath profile that could be used in studies evaluating disease, therapies, and vaccines in non-human primates. A pilot study, which enrolled 30 healthy macaques, was conducted. Macaque breath molecules were sampled into a Tedlar bag, concentrated onto a thermal desorption tube, then desorbed and analyzed by comprehensive two-dimensional gas chromatography-time of flight mass spectrometry. These breath samples contained 2,017 features, of which 113 molecules were present in all breath samples. The core breathprint was dominated by aliphatic hydrocarbons, aromatic compounds, and carbonyl compounds. The data were internally validated with additional breath samples from a subset of 19 of these non-human primates. A critical core consisting of 23 highly abundant and invariant molecules was identified as a pragmatic breathprint set, useful for future validation studies in healthy primates.

Abstract Background Legislative bodies across the country have increasingly allowed off-road vehicles (ORVs) including all-terrain vehicles (ATVs) and utility task vehicles (UTVs) on public roads, an environment for which they are not designed. In 2004, Iowa gave individual counties the discretion to pass ordinances allowing ORVs on public roadways. The objective of this study was to evaluate the relationship between the passage of ORV ordinances and ORV crash rates, especially on public roads. Methods An Iowa ORV roadway ordinance database and an Iowa ORV crash database (2002–2018) for all 99 counties were compiled. Crashes for which county location could not be determined were excluded. Utilizing a zero-inflated Poisson model, correcting for background crash frequency trends and population, investigators compared the relative rates of crashes after ordinance passage to time points before ordinance implementation and to counties without such ordinances. Sub-analyses, including that focused on more recent years (2008–2018), were also performed. Results Forty-five county ORV roadway ordinances went into effect between 2011 and 2018 and 2,347 crashes (69%) met inclusion criteria. Adjusted for year, there was a 58% greater ORV crash rate in counties after passing an ORV roadway ordinance (incidence rate ratio (IRR) 1.58, 95% CI 1.32–1.90). Roadway crashes (n = 834) increased 48% after ordinance passage (IRR 1.48, 95% CI 1.14–1.94). This roadway crash association remained statistically significant when analysis was limited to the years 2008–2018 (IRR 1.39, CI 1.06–1.83, n = 544); to ATV crashes only (IRR 1.70, CI 1.20–2.40, n = 683); and to ATV crashes excluding counties with UTV-only ordinances (IRR 1.74, CI 1.40–2.15, n = 2,011). Conclusions ORV roadway and total crashes increased significantly after implementation of county ordinances allowing ORVs on public roadways and when compared to counties without such ordinances. It is likely that these increased crashes have resulted in more injuries and possibly deaths. Results from this study may help inform policymakers as they consider legislation regarding ORV usage on public roads.

Abstract Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) were initially recommended as oral anti-diabetic drugs to treat type 2 diabetes (T2D), by inhibiting SGLT2 in proximal tubule and reduce renal reabsorption of sodium and glucose. While many clinical trials demonstrated the tremendous potential of SGLT2i for cardiovascular diseases. 2022 AHA/ACC/HFSA guideline first emphasized that SGLT2i were the only drug class that can cover the entire management of heart failure (HF) from prevention to treatment. Subsequently, the antiarrhythmic properties of SGLT2i have also attracted attention. Although there are currently no prospective studies specifically on the anti-arrhythmic effects of SGLT2i. We provide clues from clinical and fundamental researches to identify its antiarrhythmic effects, reviewing the evidences and mechanism for the SGLT2i antiarrhythmic effects and establishing a novel paradigm involving intracellular sodium, metabolism and autophagy to investigate the potential mechanisms of SGLT2i in mitigating arrhythmias. Graphical abstract

Abstract YAP plays a vital role in controlling growth and differentiation in various cell lineages. Although the expression of YAP in mice testicular and spermatogenic cells suggests its role in mammalian spermatogenesis, the role of YAP in the development of human male germ cells has not yet been determined. Using an in vitro model and a gene editing approach, we generated human spermatogonia stem cell-like cells (hSSLCs) from human embryonic stem cells (hESCs) and investigated the role of YAP in human spermatogenesis. The results showed that reducing YAP expression during the early stage of spermatogenic differentiation increased the number of PLZF+ hSSLCs and haploid spermatid-like cells. We also demonstrated that the up-regulation of YAP is essential for maintaining spermatogenic cell survival during the later stages of spermatogenic differentiation. The expression of YAP that deviates from this pattern results in a lower number of hSSLCs and an increased level of spermatogenic cell death. Taken together, our result demonstrates that the dynamic expression pattern of YAP is essential for human spermatogenesis. Modulating the level of YAP during human spermatogenesis could improve the production yield of male germ cells derived from hESCs, which could provide the optimization method for in vitro gametogenesis and gain insight into the application in the treatment of male infertility.

Abstract In East Africa, community-based conservation models (CBCMs) have been established to support the conservation of wildlife in fragmented landscapes like the Tarangire Ecosystem, Tanzania. To assess how different management approaches maintained large herbivore populations, we conducted line distance surveys and estimated seasonal densities of elephant, giraffe, zebra, and wildebeest in six management units, including three CBCMs, two national parks (positive controls), and one area with little conservation interventions (negative control). Using a Monte-Carlo approach to propagate uncertainties from the density estimates and trend analysis, we analyzed the resulting time series (2011–2019). Densities of the target species were consistently low in the site with little conservation interventions. In contrast, densities of zebra and wildebeest in CBCMs were similar to national parks, providing evidence that CBCMs contributed to the stabilization of these migratory populations in the central part of the ecosystem. CBCMs also supported giraffe and elephant densities similar to those found in national parks. In contrast, the functional connectivity of Lake Manyara National Park has not been augmented by CBCMs. Our analysis suggests that CBCMs can effectively conserve large herbivores, and that maintaining connectivity through CBCMs should be prioritized.

Abstract The development of neural circuits has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, periodic EEG power features and aperiodic components were examined from longitudinal EEGs collected from 592 healthy 2–44 month-old infants, revealing age-dependent nonlinear changes suggestive of distinct milestones in early brain maturation. Developmental changes in periodic peaks include (1) the presence and then absence of a 9-10 Hz alpha peak between 2-6 months, (2) nonlinear changes in high beta peaks (20-30 Hz) between 4-18 months, and (3) the emergence of a low beta peak (12-20 Hz) in some infants after six months of age. We hypothesized that the emergence of the low beta peak may reflect maturation of thalamocortical network development. Infant anesthesia studies observe that GABA-modulating anesthetics do not induce thalamocortical mediated frontal alpha coherence until 10-12 months of age. Using a small cohort of infants (n = 23) with EEG before and during GABA-modulating anesthesia, we provide preliminary evidence that infants with a low beta peak have higher anesthesia-induced alpha coherence compared to those without a low beta peak.

Abstract We present the first machine learning-based autonomous hyperspectral neutron computed tomography experiment performed at the Spallation Neutron Source. Hyperspectral neutron computed tomography allows the characterization of samples by enabling the reconstruction of crystallographic information and elemental/isotopic composition of objects relevant to materials science. High quality reconstructions using traditional algorithms such as the filtered back projection require a high signal-to-noise ratio across a wide wavelength range combined with a large number of projections. This results in scan times of several days to acquire hundreds of hyperspectral projections, during which end users have minimal feedback. To address these challenges, a golden ratio scanning protocol combined with model-based image reconstruction algorithms have been proposed. This novel approach enables high quality real-time reconstructions from streaming experimental data, thus providing feedback to users, while requiring fewer yet a fixed number of projections compared to the filtered back projection method. In this paper, we propose a novel machine learning criterion that can terminate a streaming neutron tomography scan once sufficient information is obtained based on the current set of measurements. Our decision criterion uses a quality score which combines a reference-free image quality metric computed using a pre-trained deep neural network with a metric that measures differences between consecutive reconstructions. The results show that our method can reduce the measurement time by approximately a factor of five compared to a baseline method based on filtered back projection for the samples we studied while automatically terminating the scans.

Paratransit users have reportedly been unsatisfied with the quality of service that they receive. Efforts at replacing the service or formalizing operations to meet users’ mobility needs have faced challenges or outrightly resisted. Approaches such as providing travel information and deploying interventions along the roadway infrastructure where the government has authority have been suggested. Deploying any of these approaches will require insights from empirical data. The study considered a key measure of service quality to users and operators alike – travel time. It investigated factors affecting the travel time of paratransit at the route and segment levels. A travel time survey that employed a mobile app (Trands) onboard paratransit vehicle was used to collect travel time, stop, and other related information on a selected route. The backward stepwise regression technique was used to determine factors affecting paratransit travel were. Dwell time, signal delay, recurrent congestion index (RCI), non-trip stops, and deviation from route were significant variables at the route level. All the factors affecting segment travel were also part of those involving route travel time except the segment length. Interestingly, deviation from the route increased overall travel time, which is against its logic. Insights gained from the study were used in suggesting proposals that can reduce travel time and improve the service quality of paratransit.

Abstract Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [18F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose – 2-[18F]fluoro-2-deoxytrehalose ([18F]FDT) – is a mechanism-based reporter of Mycobacteria-selective enzyme activity in vivo. Use of [18F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb-mediated processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [18F]FDT from the most globally-abundant organic 18F-containing molecule, [18F]FDG. The full, pre-clinical validation of both production method and [18F]FDT now creates a new, bacterium-selective candidate for clinical evaluation. We anticipate that this distributable technology to generate clinical-grade [18F]FDT directly from the widely-available clinical reagent [18F]FDG, without need for either custom-made radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer.

Abstract Future socioeconomic climate pathways have regional water-quality consequences whose severity and equity have not yet been fully understood across geographic and economic spectra. We use a process-based, terrestrial-freshwater ecosystem model to project 21st-century river nitrogen loads under these pathways. We find that fertilizer usage is the primary determinant of future river nitrogen loads, changing precipitation and warming have limited impacts, and CO2 fertilization-induced vegetation growth enhancement leads to modest load reductions. Fertilizer applications to produce bioenergy in climate mitigation scenarios cause larger load increases than in the highest emission scenario. Loads generally increase in low-income regions, yet remain stable or decrease in high-income regions where agricultural advances, low food and feed production and waste, and/or well-enforced air pollution policies balance biofuel-associated fertilizer burdens. Consideration of biofuel production options with low fertilizer demand and rapid transfer of agricultural advances from high- to low-income regions may help avoid inequitable water-quality outcomes from climate mitigation.

Previous research has revealed that daily variations in human neurobehavioral functions are driven in part by the endogenous circadian system. The objective of this study was to explore whether there exists a circadian influence on performance regarding a risky decision-making task and to determine whether the performance changes with sleep deprivation (SD). Thirteen participants underwent a 39 h constant routine (CR) protocol, during which they remained awake in constant conditions and performed the BART (balloon analogue risk task) every two hours. The mean pumps (gains) (p < 0.001) and balloons popped (losses) (p = 0.003) exhibited variation during the CR. The reaction time (RT) also showed significant variation across the CR (p < 0.001), with slower mean RTs in the morning hours following SD. A greater risk propensity was observed around midday before SD and a lower risk propensity after 29.5 h of being awake. The sensitivity to punishment varied during the CR, but did not follow a predictable trend. Further research using real monetary incentives and neurophysiological measures is warranted to elucidate these findings.

Abstract This study focused on how historical contextualisation is reflected in 12 history textbooks for primary schools in Ghana. The study employed a content analysis design to analyse how historical contextualisation is reflected in history textbooks. A multi-stage sampling technique was used in selecting 12 textbooks to represent the 6 classes in the Ghanaian primary school. A thematic matrix was developed from historical thinking frameworks to collect data from the textbooks. Microsoft Excel functions were used to rate the textbooks on a scale of 0–5, depending on the amount of evidence of historical contextualisation. Descriptive statistics and Maton’s (2013) principle of shift in the Semantic Wave were used in the analysis to determine the level of evidence of historical contextualisation in the textbooks. The study established that historical contextualisation is reflected in the history textbooks used in the study. This study contributes to understanding how textbook writers incorporate historical contextualisation within textbook narratives to meet history curriculum requirements. It gives an understanding of how historical contextualisation is needed in history textbooks to promote historical reasoning among textbook users such as teachers and students. Possible implications of the findings are discussed in the main text.

BackgroundCOVID-19 disruptions including lockdowns and prioritization of COVID-19 control programs in Africa in 2020–2022 contributed to reductions in malaria control activities including malaria diagnosis, treatment and resistance monitoring. This study investigated the malaria burden and distribution on the background of active transmission of SARS-CoV-2 in Southern Ghana; utilizing community health education and medical screening (CHEMS) approach to determine epidemiological overlaps in COVID-19 and malaria.MethodsBetween October–December 2022, prospective cross-sectional surveys, with CHEMS were conducted in Greater Accra and Central regions, where 994 participants enrolled either at a hospital or community setting provided demographic and clinical data including history of clinical malaria infection and antimalarial treatment in the past 2 weeks. Of this study population, 953 provided nasal/throat swabs for COVID-19 RT-PCR testing, with a subset of 136 participants also providing finger-prick blood for malaria RDT testing.ResultsThe study population comprised of 73.6% adults, with 54.6% COVID-19 vaccination rate. Overall, 18.1% of participants had a history of clinical malaria, which was associated (adjusted odds ratio > 1.50, p-value ≤0.022) with COVID-19 symptoms and positivity, study area and hospital setting, suggestive of overlaps in the epidemiological risk for malaria. On a background of widespread SARS-CoV-2 infections (12–37%), malaria parasitaemia was detected in 6%, with 2% being co-infections with SARS-CoV-2. Among the malaria positives, 9.5% had a history of antimalarial treatment, which suggested that their infections were recrudescent parasitaemia.ConclusionThe epidemiological and clinical overlap between malaria and COVID-19 within the hospital and community settings underscores the need for accurate case diagnosis to inform effective clinical treatments. Innovative surveillance programs, with community engagement are needed to maximize control interventions including treatment of asymptomatic malaria infections.

The fundamental organization of the human brain is established before birth, with rapid growth continuing over the first postnatal years. Children exposed before or after birth to various biological (e.g., substance exposure) or psychosocial hazards (e.g., maltreatment) are at elevated likelihood of deviating from a typical developmental trajectory, which in turn can be associated with psychological, behavioral, and physical health sequelae. In the HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, brain, physical, biological, cognitive, behavioral, social, and emotional development is being examined starting in pregnancy and planned through age 10 (data are sampled at varying degrees of granularity depending on age, with more dense sampling earlier in life). HBCD aims to determine the short- and long-term impacts of a variety of both harmful and protective factors, including prenatal substance use, on developmental trajectories through early childhood. Organized as a nationwide consortium across 27 sites, the HBCD Study will collect multimodal data that will be made publicly available on a yearly basis, through a data use application and approval process. Here we provide an overview of the HBCD Study design, sampling, protocol development, and data management. Data collected through HBCD will be fundamental to informing future prenatal and early childhood interventions and policies to promote wellbeing and resilience in all children.

Abstract There is limited quantitative evidence of the effects of socio‐economic shocks on biological resource use. Focusing on wild meat hunting, a substantial livelihood and food source in tropical regions, we evaluated the impacts of the shock from Nigeria's coronavirus disease (COVID‐19) lockdown on species exploitation around a global biodiversity hotspot. Using a 3‐year quantitative dataset collected during and after the lockdown (covering 1008 hunter‐months) and matching by time of year, we found that successful hunting trip rates were more frequent during the lockdown, with a corresponding increase in the monthly number, mass, and value of animals caught. Moreover, hunters consumed a larger proportion of wild meat and sold less during lockdown, compared to non‐lockdown periods. These results suggest that local communities relied on wild meat to supplement reduced food and income during the lockdown, buffering the COVID‐19's socio‐economic shock. Our findings also indicate that wild species may be especially vulnerable to increased hunting pressure during socio‐economic shocks.

Casein kinase II subunit alpha (CSNK2A1), a serine/threonine kinase, phosphorylates multiple protein substrates and is involved in diverse cellular and biological processes. Implicated in various human diseases, high-performing antibodies would help evaluate its potential as a therapeutic target and benefit the scientific community. In this study, we have characterized ten CSNK2A1 commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.

Rab10 is a small GTPase involved in cargo transport from the trans-Golgi network to the plasma membrane and endocytic recycling back to the cell membrane. It has garnered significant interest in neurodegenerative disease research, particularly due to its phosphorylation by the LRRK2 kinase. This relationship underscores the importance of Rab10 in cellular processes related to disease pathology, specifically Parkinson’s disease. The accessibility of renewable and selective antibodies against Rab10 would advance research efforts, enabling further understanding of its function and implications in disease. Here, we have characterized eight Rab10 commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.

Abstract With rapid development and mature of single‐cell measurements, single‐cell biology and pathology become an emerging discipline to understand the disease. However, it is important to address concerns raised by clinicians as to how to apply single‐cell measurements for clinical practice, translate the signals of single‐cell systems biology into determination of clinical phenotype, and predict patient response to therapies. The present Perspective proposes a new system coined as the clinical artificial intelligent single‐cell (caiSC) with the dynamic generator of clinical single‐cell informatics, artificial intelligent analyzers, molecular multimodal reference boxes, clinical inputs and outs, and AI‐based computerization. This system provides reliable and rapid information for impacting clinical diagnoses, monitoring, and prediction of the disease at the single‐cell level. The caiSC represents an important step and milestone to translate the single‐cell measurement into clinical application, assist clinicians’ decision‐making, and improve the quality of medical services. There is increasing evidence to support the possibility of the caiSC proposal, since the corresponding biotechnologies associated with caiSCs are rapidly developed. Therefore, we call the special attention and efforts from various scientists and clinicians on the caiSCs and believe that the appearance of the caiSCs can shed light on the future of clinical molecular medicine.

Aim of the study: Short stay processes are incentives to unburden chronically stressed healthcare systems. The aim of this study is to analyze financial implications of day admission (DAS) and outpatient strategies for colon resections in a prospective payment system (PPS) using Diagnosis Related Group (DRG) coding. Methods: Consecutive patients undergoing left and right colonic resections between January 1, 2019 and December 31, 2020 were included. Medico-economic evaluations of the virtual outpatient and day admission surgery groups based on predefined criteria were compared to the identical group of patients who underwent surgery in the actual traditional inpatient setting. In a second step, postoperative complications of the virtual outpatient group were assessed. Cost-revenue analysis was performed using a micro-costing approach including direct medical costs. Results: Overall (N = 257), 97 (37.7%) colectomies would have been potentially eligible for an outpatient strategy. The global costs of the actual inpatient strategy totaled USD 3 634 392 with a global revenue of USD 3 571 069, corresponding to a cost coverage rate of 98%. The result of the virtual DAS strategy would have been a net loss of USD 15 800 (coverage rate of 99%) due to 4 low length of stay outliers triggering a reimbursement reduction and preventing a positive net result of USD 16 208. The pilot reference outpatient case’s revenue and cost amounted to respectively USD 7479 and USD 6911 (cost coverage of 108%). Conclusion: From both any given hospital and healthcare system point of view, elective outpatient colectomy for selected patients is the most cost-saving option. However, in a prospective payment system implemented to avoid bad incentives, the latter can unintentionally disadvantage best performing hospitals and impede widespread adoption of high-value strategies.

Background: Uterine fibroids, or Leiomyoma is a type of Smooth Muscle Tumors of the uterus (SMTs) and are common in the black race. Giant uterine fibroids, on the other hand, are uncommon and may occur during patient dissimulation. Dissimulation may occur because of a dread of surgery and hospitals visits, fear of surgical death, chronic intake of herbal concussion, and a religio-traditional strong belief system on instant healing following prayers, among others. Myths like belief of defecating the uterine fibroids, some herbs that can melt them away, and the belief that such illness may follow ancestral curses can fuel dissimulation. The surgical approach can be a source of challenge, careful case selection considering the size and number of tumors can be helpful. Case report: We present a 35-year-old nulligravida who presented to the clinic with a 14-year history of progressive abdominal swelling. Examination revealed a firm mass with a symphysio-fundal height of 55 cm. She subsequently had an open abdominal myomectomy with all the myoma nodules weighing 12.9 kg in total! Histology confirmed uterine fibroid. Conclusion: It is possible to offer open myomectomy in patients with giant uterine fibroid following careful patient selection with a consent for possible hysterectomy. Dissimulation can be minimized with repetitive counseling of patients. The choice of surgery depends on the size and number of uterine fibroids, but surgical approach does not necessarily influence fecundity.

BackgroundIn addition to conventional treatment and modifications in physical activity and diet, alternative strategies have been investigated to manage, prevent, or delay diabetes in humans. In this regard, one strategy has relied on the immunomodulatory properties of mycobacteria, whereby Bacillus Calmette–Guerin, an attenuated live strain of Mycobacterium bovis, has been shown to improve glycemic control in patients with diabetes and to alleviate hyperglycemia in selected murine models of diabetes. A novel heat-killed (HK) whole-cell preparation of Mycobacterium aurum (M. aurum) is currently under development as a potential food supplement; nevertheless, its potential bioactivity remains largely unknown. Thus, the present study investigated the potential prophylactic anti-diabetic effects of HK M. aurum in streptozotocin (STZ)–induced diabetic mice.MethodsMice were divided into three groups: the STZ-induced diabetic group was injected with a single intraperitoneal high dose of STZ, the HK M. aurum–treated diabetic group was prophylactically treated with three doses of HK M. aurum 6 weeks before STZ injection, and the control non-diabetic group was given three intradermal injections of borate-buffered saline and an intraperitoneal injection of citrate buffer. Liver lactate dehydrogenase (LDH), uncoupling protein 2 (UCP2), and glucose transporter 2 (GLUT2) and skeletal muscle LDH, UCP3, and GLUT4 protein expression levels in different mouse groups were determined by Western blot.ResultsOur results indicated that HK M. aurum did not cause any significant changes in glycemic levels of normal non-diabetic mice. Prophylactic administration of three doses of HK M. aurum to diabetic mice resulted in a significant reduction in their blood glucose levels when compared to those in control diabetic mice. Prophylactic treatment of diabetic mice with HK M. aurum significantly restored their disturbed protein expression levels of liver UCP2 and LDH as well as of skeletal muscle UCP3. On the other hand, prophylactic treatment of diabetic mice with HK M. aurum had no significant effect on their liver GLUT2 and skeletal muscle GLUT4 and LDH protein expression levels.ConclusionsOur findings provide the first evidence that HK M. aurum possesses a hyperglycemia-lowering capacity and might support its future use as a food supplement for the amelioration of diabetes.

Summary: Adaptation of the circadian clock to the environment is essential for optimal health, well-being, and performance. Animal models demonstrate that a high-fat diet impairs circadian adaptation to advances of the light-dark cycle; it is unknown whether this occurs in humans. Utilizing a natural experiment that occurs when humans must advance their behaviors to an earlier hour for daylight saving time (DST), we measured the influence of diet on sleep/wake timing relative to dim-light melatonin onset time. Students with a lower-fat diet rapidly altered their sleep-wake timing to match the imposed time change, whereas those with a high-fat diet were slower to adapt to the time change. Moreover, a faster shift in timing after DST was associated with higher general health, lower body mass index, and higher grade point average. These data suggest that diet may influence the speed of sleep and circadian adaptation, which could have implications for health and performance.

This article summarizes the 2023 International Continence Society (ICS) Workshop 5 focused on neurologically mediated chronic pelvic pain (CPP) (Workshop 5). A team of experts share practical advice and tools for assessment, diagnosis and management relevant to pudendal neuropathy or other nerve entrapment, central nervous system diagnoses such as herniated disc, radiculopathy, Tarlov cyst, tethered cord, hip confounders, and systemic neuropathy such as small fiber neuropathy, neuroinflammatory disease (e.g. Lyme, Multiple Sclerosis) and central sensitization.

Background Achieving disease control is the goal of asthma management. Serum or sputum eosinophil counts have been known traditional means of assessing eosinophilic airway inflammation in asthma, which is vital in predicting response to corticosteroid therapy which ultimately promotes control of the disease. Evidence suggests that fraction of exhaled nitric oxide (FeNO) may be a more useful non-invasive surrogate biomarker for the assessment of eosinophilic airway inflammation and could help with the timely adjustment of inhaled corticosteroid therapy in the uncontrolled asthma patient. The relationship between FeNO and other markers of airway inflammation has been variable in literature, with limited data in sub-Saharan Africa where FeNO testing is very sparse. We sought to define the relationship between FeNO levels, serum eosinophil counts, spirometry measures and symptom control among asthma patients.Materials and methods The study was conducted at the Asthma Clinic of a large tertiary hospital. This study included 82 patients with physician-diagnosed asthma being regularly managed at the clinic. All participants were taken through the asthma control test (ACT), had FeNO and spirometry measurements taken according to the American Thoracic Society (ATS) guidelines. Blood samples were obtained from all participants for serum eosinophil counts. Correlation coefficient was used to ascertain the relationship between FeNO levels and serum eosinophil counts, ACT scores, and spirometry measurements. Logistic regression was used to examine the association between high FeNO and abnormal FEV1 percentage predicted (50 ppb) was associated with an over fivefold increased risk of having an abnormal FEV1 percentage predicted.Conclusion FeNO levels significantly correlated with the ACT scores, serum eosinophil counts and FEV1% predicted among the asthma patients who were on inhaled corticosteroid therapy. High FeNO was significantly associated with abnormal FEV1 percentage predicted. We suggest that the point of care assessment of FeNO is a reliable marker of eosinophilic inflammation in our cohort of patients and together with ‘ACT scores’ in our asthma clinics could increase asthma control rates.

Abstract Background Midwifery education is under-invested in developing countries with limited opportunities for midwifery educators to improve/maintain their core professional competencies. To improve the quality of midwifery education and capacity for educators to update their competencies, a blended midwifery educator-specific continuous professional development (CPD) programme was designed with key stakeholders. This study evaluated the feasibility of this programme in Kenya and Nigeria. Methods This was a mixed methods intervention study using a concurrent nested design. 120 randomly selected midwifery educators from 81 pre-service training institutions were recruited. Educators completed four self-directed online learning (SDL) modules and three-day practical training of the blended CPD programme on teaching methods (theory and clinical skills), assessments, effective feedback and digital innovations in teaching and learning. Pre- and post-training knowledge using multiple choice questions in SDL; confidence (on a 0–4 Likert scale) and practical skills in preparing a teaching a plan and microteaching (against a checklist) were measured. Differences in knowledge, confidence and skills were analysed. Participants’ reaction to the programme (relevance and satisfaction assessed on a 0–4 Likert scale, what they liked and challenges) were collected. Key informant interviews with nursing and midwifery councils and institutions’ managers were conducted. Thematic framework analysis was conducted for qualitative data. Results 116 (96.7%) and 108 (90%) educators completed the SDL and practical components respectively. Mean knowledge scores in SDL modules improved from 52.4% (± 10.4) to 80.4% (± 8.1), preparing teaching plan median scores improved from 63.6% (IQR 45.5) to 81.8% (IQR 27.3), and confidence in applying selected pedagogy skills improved from 2.7 to 3.7, p 0.05). Qualitatively, educators found the programme educative, flexible, convenient, motivating, and interactive for learning. Internet connectivity, computer technology, costs and time constraints were potential challenges to completing the programme. Conclusion The programme was feasible and effective in improving the knowledge and skills of educators for effective teaching/learning. For successful roll-out, policy framework for mandatory midwifery educator specific CPD programme is needed.

Abstract Background Despite recent advancements in migraine treatment, some patients continue to endure significant disease burden. Due to the controlled nature of randomized trials in migraine prevention, many real-world patients with comorbidities or prior exposure to certain therapies are excluded. Capturing evidence of the effectiveness of treatment in real-world clinical settings can further shape treatment paradigms. The objective of this study was to develop a comprehensive understanding of both patients’ and physicians’ real-world experiences with eptinezumab for chronic migraine (CM). Methods REVIEW (Real-world EVidence and Insights into Experiences With eptinezumab) is an observational, multi-site (n = 4), US-based study designed to evaluate real-world experiences of patients treated with eptinezumab and their treating physicians. Patients were ≥ 18 years of age, with a diagnosis of CM, who had completed ≥ 2 consecutive eptinezumab infusion cycles (≥ 6 months of exposure). The study included a retrospective chart review, a patient survey, and a semi-structured physician interview that assessed patient and/or physician satisfaction with elements of daily living / well-being, migraine symptomology, and perspectives of the eptinezumab infusion experience. Results Of the 94 patients enrolled, 83% (78/94) were female, the mean age was 49.2 years, and the mean time since migraine diagnosis was 15.4 years. Before eptinezumab treatment, patients experienced a mean of 8 self-reported “good” days/month, which increased to 18 after treatment. Most patients took, on average, ≥ 10 days/month of prescription and/or over-the-counter medication (81% [75/93] and 66% [61/93], respectively) to treat migraine attacks before eptinezumab treatment, which dropped to 26% (24/93) and 23% (21/93) following eptinezumab treatment. Prior to receiving eptinezumab, 62% (58/93) of patients indicated being at least slightly concerned about infusions; after eptinezumab infusion, this dropped to 14% (13/93). These patient survey findings were consistent with physician responses. Conclusion This real-world evidence study demonstrated high overall satisfaction with the effectiveness of eptinezumab treatment for CM among most patients and their physicians.

Abstract Background Contraceptive use dynamics continue to be of priority in sub-Saharan Africa because of persistently high levels of fertility. This paper focuses on the use of barrier versus non-barrier contraceptive use in sub-Saharan Africa hypothesizing that the HIV pandemic in the region would be responsible for increases in the use of barrier methods over time. Methods This paper uses Demographic and Heath Survey (DHS) data from 32 countries to conduct extensive analysis of trends in contraceptive use and method mix that refers to the distribution of contraceptive methods use among the sexually active population. The paper examines how contraceptive method mix dynamics have changed over time and whether the trends differ by marital status and gender using cross-tabulations. It furthers examines the determinants of method choice using logistic regressions. Results The findings indicate that the use of barrier methods, most markedly for unmarried women and men, rose substantially between the late 1980s and late 2000s in the region in tandem with trends in HIV prevalence. The results further show marked differences in method mix by gender with men being more likely to report barrier method use than women. Conclusions The findings indicate shifting preferences in contraceptive choice. The time trend analyses highlight the importance of expanding the focus of contraceptive use studies beyond women in this context as the study finds differing trends for men. Graphical Abstract