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Sjaak Pouwels,1 Elijah E Sanches,1 Eylem Cagiltay,2 Rich Severin,3–5 Shane A Philips5,6 1Department of Surgery, Haaglanden Medical Center, The Hague, the Netherlands; 2University of Health Sciences Turkey, Sultan Abdulhamid Han Education and Research Hospital, Department of Endocrinology and Metabolic Diseases, Istanbul, Uskudar, 34668, Turkey; 3Department of Physical Therapy, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USA; 4Physical Therapy Program, Robbins College of Health and Human Sciences, Baylor University, Waco, TX, USA; 5Graduate Program in Rehabilitation Sciences, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USA; 6Department of Physical Therapy, Integrative Physiologic Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USACorrespondence: Sjaak PouwelsDepartment of Surgery, Haaglanden Medical Center, P.O. Box 432, 2501 CK, The Hague, the NetherlandsEmail Sjaakpwls@gmail.comAbstract: Nowadays, obesity and related comorbidities like type 2 diabetes, hypertension, dyslipidaemia and obstructive sleep apnoea syndrome are considered one of the medical challenges of the 21st century. Even with the rise of bariatric and metabolic surgery, obesity and metabolic syndrome are reaching endemic proportions. Even in 2020, obesity is still a growing problem. There is increasing evidence that next to bariatric surgery, exercise interventions in the perioperative period could give extra beneficial effects. In this regard, effects on anthropometrics, cardiovascular risk factors and physical fitness. The aim of this review is to summarise effects of preoperative and postoperative exercise, tools for screening and directions for future research and implementations.Keywords: obesity, exercise, bariatric surgery, metabolic surgery, postoperative outcomes

Fluorescent nanodiamonds are promising probes for nanoscale magnetic resonance measurements. Their physical properties predict them to have particularly useful applications in intracellular analysis. Before using them in intracellular experiments however, it should be clear whether diamond particles influence cell biology. While cytotoxicity has already been ruled out in previous studies, we consider the non-fatal influence of fluorescent nanodiamonds on the formation of reactive oxygen species (an important stress indicator and potential target for intracellular sensing) for the first time. We investigated the influence of different sizes, shapes and concentrations of nanodiamonds on the genetic and protein level involved in oxidative stress-related pathways of the HeLa cell, an important model cell line in research. The changes in viability of the cells and the difference in intracellular levels of free radicals, after diamond uptake, are surprisingly small. At lower diamond concentrations, the cellular metabolism cannot be distinguished from that of untreated cells. This research supports the claims of non-toxicity and includes less obvious non-fatal responses. Finally, we give a handhold concerning the diamond concentration and size to use for non-toxic, intracellular measurements in favour of (cancer) research in HeLa cells.

Abstract Background Physical inactivity is a major public health concern, exacerbated in countries with a (sub)tropical climate. The built environment can facilitate physical activity; however, current evidence is mainly from North American and European countries with activity-friendly climate conditions. This study explored associations between built environment features and physical activity in global tropical or subtropical dry or desert climate regions. Methods A systematic review of four major databases (Web of Science, Scopus, PubMed, and SportDISCUS) was performed. To be included, studies had to investigate associations between perceived or objective built environment characteristics and adult’s physical activity and had to be conducted in a location with (sub)tropical climate. Each investigated association was reported as one case and results were synthesized based upon perceived and objectively assessed environment characteristics as well as Western and non-Western countries. Study quality was evaluated using a tool designed for assessing studies on built environment and physical activity. Results Eighty-four articles from 50 studies in 13 countries with a total of 2546 built environment-physical activity associations were included. Design (connectivity, walking/cycling infrastructure), desirability (aesthetics, safety), and destination accessibility were the built environment characteristics most frequently associated with physical activity across the domains active transport, recreational physical activity, total walking and cycling, and moderate-to-vigorous physical activity, particularly if multiple attributes were present at the same time. Very few studies assessed built environment attributes specifically relevant to physical activity in (sub)tropical climates. Most studies were conducted in Western countries, with results being largely comparable with non-Western countries. Findings were largely generalizable across gender and age groups. Results from natural experiments indicated that relocating to an activity-friendly neighborhood impacted sub-groups differently. Conclusions Built environment attributes, including destination accessibility, connectivity, walking and cycling infrastructure, safety, and aesthetics, are positively associated with physical activity in locations with (sub)tropical climate. However, few studies focus on built environment attributes specifically relevant in a hot climate, such as shade or indoor recreation options. Further, there is limited evidence from non-Western countries, where most of the urban population lives in (sub)tropical climates. Policy makers should focus on implementing activity-friendly environment attributes to create sustainable and climate-resilient cities.

Purpose To compare outcomes, between stemmed and stemless reverse shoulder arthroplasty (RSA) at a minimum follow-up of 5 years. Methods The authors retrospectively assessed a consecutive series of 45 patients that underwent RSA between September 2014 and October 2018 (23 stemless and 22 stemmed). All patients underwent plain anteroposterior and scapular Y-view radiographs for assessment immediately post-operatively and at final follow-up. At a minimum follow-up of 5 years, an independent observer assessed the clinical scores, including Constant score, QuickDASH score, and American Shoulder and Elbow Surgeons score. Results Of the 45 patients that underwent RSA, 5 patients died (11%), 2 were revised due to infection (4%), and 4 patients were lost to follow-up (9%). This left a final cohort of 34 patients (18 stemless and 16 stemmed). Significant differences between groups were found immediately post-operatively for lateralisation shoulder angle (LSA) (p = 0.021), but at 5 years post-operative for distalisation shoulder angle (DSA) (p = 0.017) and QuickDASH scores (p = 0.041) (Table 4), while the outcomes were comparable for absolute Constant scores, ASES score, and range of motion. Finally, stemless RSA had a 17% complication rate, while stemmed RSA had a 31% complication rate. Conclusion Stemless RSA had significantly more lateralisation, and significantly less distalisation, compared to stemmed RSA. Furthermore, at a 5-year follow-up, stemless RSA granted significantly greater QuickDASH scores. Finally, stemless RSA had comparable complication rates as stemmed RSA. The clinical relevance of this study is that stemless RSA is a safe alternative to stemmed RSA, while granting comparable or greater scores. Level of Evidence: III, Comparative Study

Abstract Background Chronic diseases, or non-communicable diseases (NCD), are conditions of long duration and often influenced and contributed by complex interactions of several variables, including genetic, physiological, environmental, and behavioral factors. These conditions contribute to death, disability, and subsequent health care costs. Primary and secondary school settings provide an opportunity to deliver relatively low cost and effective interventions to improve public health outcomes. However, there lacks systematic evidence on the cost-effectiveness of these interventions. Methods We systematically searched four databases (PubMed/Medline, Cochrane, Embase, and Web of Science) for published studies on the cost-effectiveness of chronic-disease interventions in school settings. Studies were eligible for inclusion if they assessed interventions of any chronic or non-communicable disease, were conducted in a school setting, undertook a full cost-effectiveness analysis and were available in English, Spanish, or French. Results Our review identified 1029 articles during our initial search of the databases, and after screening, 33 studies were included in our final analysis. The most used effectiveness outcome measures were summary effectiveness units such as quality-adjusted life years (QALYs) (22 articles; 67%) or disability-adjusted life years (DALYs) (4 articles; 12%). The most common health condition for which an intervention targets is overweight and obesity. Almost all school-based interventions were found to be cost-effective (30 articles; 81%). Conclusion Our review found evidence to support a number of cost-effective school-based interventions targeting NCDs focused on vaccination, routine physical activity, and supplement delivery interventions. Conversely, many classroom-based cognitive behavioral therapy for mental health and certain multi-component interventions for obesity were not found to be cost-effective.

Abstract The COVID-19 pandemic has dramatically threatened the Gulf Cooperation Council (GCC) countries which have a large proportion of foreign workers. The governments of GCC countries have proactively implemented a comprehensive set of policy measures, and up to our knowledge, a systematic analysis of qualitative and quantitative evidence on the government response is still lacking. We summarized the GCC countries’ government response and quantitatively measured that response using four indexes—the Government Response Index, the Stringency Index, the Vaccine Index, and the Initial Response Index, to analyse their response for future pandemic preparedness. Overall, the government response of all the GCC countries to the COVID-19 pandemic has been comprehensive, stringent, and timely. Notably, the GCC countries have implemented comprehensive vaccine policies. In addition, they have worked actively to protect foreign workers to improve their access to health services and secure their essential living conditions, regardless of their immigrant status. All the GCC countries dynamically adjusted their response to the evolving COVID-19 epidemiological burden and started to relax the stringency of the control policies after the Omicron wave, though the governments had different response magnitudes as measured by the four indexes. These findings have provided several important lessons for future pandemic response and preparedness for countries with similar economic, demographic, and health contexts in (1) prompt actions of containment and closure policies with dynamic adjusting, (2) strengthening health system policies, (3) comprehensive vaccination policies with universal access, (4) equitable and free access to testing, diagnosis, and treatment for all, and (5) strengthening the resilience of health systems.

BackgroundImproving neighborhood walkability is critical for sustainable and livable urban development and is associated with increased physical activity. The Neighborhood Environment Walkability Scale-Abbreviated (NEWS-A) is a tool for assessing neighborhood walkability among adults. Currently, no Arabic version is available for this important walkability scale.ObjectiveTo translate the NEWS-A to Arabic, culturally adapt, and pre-test it for adults.MethodsThe NEWS-A was translated and culturally adapted using Cross-cultural Survey Guidelines and then pre-tested using 65 households selected randomly from the neighborhoods of three districts in Riyadh. After answering the survey, 55 participants took part in a semi-structured cognitive interview, which sought their understanding of the words in the Arabic questionnaire, the clarity of each item, and their suggestions for improvement.ResultsTranslation and adaptation of NEWS-A to Arabic resulted in adding two items (mosque and healthcare center) to section B of the scale (stores, facilities, and other things in your neighborhood) and one related item to section C (access to services). The total individual items became 57 instead of the original 54 items in the English version. Also, we added “ATM machine” to item 14 (Bank/credit union) in section B. In addition, the overall results of the cognitive interview showed that most of the participants understood the intended meaning of the questionnaire (99.5%). Further, 99.8% of the respondents stated that the items were not difficult to comprehend, while 100% of the sample indicated that the sentences were comfortable and not sensitive to them.ConclusionTranslating, adapting, and pre-testing the NEWS-A resulted in retaining all the original items and adding three additional items. The Arabic NEWS-A provides an important tool for future research on neighborhood environment walkability among adults.

Abstract Transitioning to a green economy is urgently needed to achieve the climate targets by the end of this century. Here we investigate alternative pathways for the transition of the global economy from one dominated by the fossil-fueled (brown) sector to one dominated by the low-emission (green) sector. We modify a well-known integrated assessment model of climate change and economy to consider three transition pathways: Linear, Delayed, and Fast. Our results indicate that the main burden of the green transition lies on capital formation, accumulation, and transfers facilitated by full R&D investment in the green sector’s productivity. We also find that transition pathways rely on different mechanisms to achieve their targets. The Delayed pathway relies on the combination of higher green capital investment and an increase in green capital productivity through R&D investment, while the Fast pathway requires substantial transfers of capital from the brown sector coupled with high abatement efforts.

Abstract Background Lumbar spine pathology (LSP) is a common source of low back or leg pain, and paraspinal muscle in these patients demonstrates fatty and fibrotic infiltration, and cellular degeneration that do not reverse with exercise‐based rehabilitation. However, it is unclear of this lack of response is due to insufficient exercise stimulus, or an inability to mount a growth response. The purpose of this study was to compare paraspinal muscle gene expression between individuals with LSP who do and do not undergo an acute bout of resistance exercise. Methods Paraspinal muscle biopsies were obtained from 64 individuals with LSP undergoing spinal surgery. Eight participants performed an acute bout of machine‐based lumbar extension resistance exercise preoperatively. Gene expression for 42 genes associated with adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic pathways was measured, and differential expression between exercised and non‐exercised groups was evaluated for (a) the full cohort, and (b) an age, gender, acuity, and etiology matched sub‐cohort. Principal components analyses were used to identify gene expression clustering across clinical phenotypes. Results The exercised cohort demonstrated upregulation of inflammatory gene IL1B, inhibition of extracellular matrix components (increased MMP3&9, decreased TIMP1&3, COL1A1) and metabolic/adipogenic genes (FABP4, PPARD, WNT10B), and downregulation of myogenic (MYOD, ANKRD2B) and atrophic (FOXO3) genes compared to the non‐exercised cohort, with similar patterns in the matched sub‐analysis. There were no clinical phenotypes significantly associated with gene expression profiles. Conclusion An acute bout of moderate‐high intensity resistance exercise did not result in upregulation of myogenic genes in individuals with LSP. The response was characterized by mixed metabolic and fibrotic gene expression, upregulation of inflammation, and downregulation of myogenesis.

BackgroundThe Middle East and North Africa (MENA) region faces unique challenges in promoting physical activity and reducing sedentary behaviors, as the prevalence of insufficient physical activity is higher than the global average. Mobile technologies present a promising approach to delivering behavioral interventions; however, little is known about the effectiveness and user perspectives on these technologies in the MENA region. ObjectiveThis study aims to evaluate the effectiveness of mobile interventions targeting physical activity and sedentary behaviors in the MENA region and explore users’ perspectives on these interventions as well as any other outcomes that might influence users’ adoption and use of mobile technologies (eg, appropriateness and cultural fit). MethodsA systematic search of 5 databases (MEDLINE, Embase, CINAHL, Scopus, and Global Index Medicus) was performed. Any primary studies (participants of all ages regardless of medical condition) conducted in the MENA region that investigated the use of mobile technologies and reported any measures of physical activity, sedentary behaviors, or user perceptions were included. We conducted a narrative synthesis of all studies and a meta-analysis of randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to assess the quality of the included RCTs; quality assessment of the rest of the included studies was completed using the relevant Joanna Briggs Institute critical appraisal tools. ResultsIn total, 27 articles describing 22 interventions (n=10, 37% RCTs) and 4 (15%) nonexperimental studies were included (n=6141, 46% women). Half (11/22, 50%) of the interventions included mobile apps, whereas the other half examined SMS. The main app functions were goal setting and self-monitoring of activity, whereas SMS interventions were primarily used to deliver educational content. Users in experimental studies described several benefits of the interventions (eg, gaining knowledge and receiving reminders to be active). Engagement with the interventions was poorly reported; few studies (8/27, 30%) examined users’ perspectives on the appropriateness or cultural fit of the interventions. Nonexperimental studies examined users’ perspectives on mobile apps and fitness trackers, reporting several barriers to their use, such as perceived lack of usefulness, loss of interest, and technical issues. The meta-analysis of RCTs showed a positive effect of mobile interventions on physical activity outcomes (standardized mean difference=0.45, 95% CI 0.17-0.73); several sensitivity analyses showed similar results. The trim-and-fill method showed possible publication bias. Only 20% (2/10) of the RCTs measured sedentary behaviors; both reported positive changes. ConclusionsThe use of mobile interventions for physical activity and sedentary behaviors in the MENA region is in its early stages, with preliminary evidence of effectiveness. Policy makers and researchers should invest in high-quality studies to evaluate long-term effectiveness, intervention engagement, and implementation outcomes, which can inform the design of culturally and socially appropriate interventions for countries in the MENA region. Trial RegistrationPROSPERO CRD42023392699; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=392699

The host environment is of critical importance for antibiotic efficacy. By impacting bacterial machineries, stresses encountered by pathogens during infection promote the formation of phenotypic variants that are transiently insensitive to the action of antibiotics. It is assumed that these recalcitrant bacteria-termed persisters-contribute to antibiotic treatment failure and relapsing infections. Recently, we demonstrated that host reactive nitrogen species (RNS) transiently protect persisters against the action of β-lactam antibiotics by delaying their regrowth within host cells. Here, we discovered that RNS intoxication of persisters also collaterally sensitizing them to fluoroquinolones during infection, explaining the higher efficiency of fluoroquinolones against intramacrophage Salmonella. By reducing bacterial respiration and the proton-motive force, RNS inactivate the AcrAB efflux machinery of persisters, facilitating the accumulation of fluoroquinolones intracellularly. Our work shows that target inactivity is not the sole reason for Salmonella persisters to withstand antibiotics during infection, with active efflux being a major contributor to survival. Thus, understanding how the host environment impacts persister physiology is critical to optimize antibiotics efficacy during infection.

Digital therapeutics (DTx) are a new class of intervention involving evidence-based software applications and have been used in neurology and psychiatry. To assess the potential of DTx in urology, we conducted a survey to assess the current prevalence of the digital infrastructure required for DTx, areas of support expected by patients, and requirements for uptake. Between November 2022 and January 2023, we conducted an anonymized survey at two German academic centers among patients with urologic conditions. We found that among patients aged

Abstract Background As Saudi Arabia is expected to face population aging in the future, the burden of diseases arising from inadequate physical activity (PA) and excess sedentary behavior (SB) may subsequently increase without successful interventions. The present study critically reviews the global literature on the effectiveness of PA interventions targeting community-dwelling older adults to draw on lessons and applications for future interventions in Saudi Arabia. Methods This umbrella review of systematic reviews included interventions designed to increase PA and/or reduce SB in community-dwelling older adults. We conducted searches in July 2022 in two electronic databases—PubMed and Embase—and identified relevant peer-reviewed systematic reviews in English. Results Fifteen systematic reviews focusing on community-dwelling older adults were included. Several reviews reported that PA- or SB-based interventions, including eHealth interventions (such as automated advice, tele-counseling, digital PA coaching, automated PA tracking and feedback, online resources, online social support, and video demonstrations), mHealth interventions, and non-eHealth interventions (such as goal setting, individualized feedback, motivational sessions, phone calls, face-to-face education, counseling, supervised exercise sessions, sending educational materials to participants’ homes, music, and social marketing programs), were effective in the short term (e.g., ≤ 3 months) but with wide heterogeneity in findings and methodologies. There were limited studies on PA- and SB-based interventions that could be effective for one year or more after the intervention. Most reviews were heavily skewed toward studies carried out in Western communities, limiting their generalizability to Saudi Arabia and other parts of the world. Conclusion There is evidence that some PA and SB interventions may be effective in the short term, but high-quality evidence regarding long-term effects is lacking. The cultural, climate, and environmental barriers related to PA and SB in Saudi Arabia require an innovative approach and research to evaluate such interventions in older individuals in the long term.

BackgroundInsufficient physical activity (PA) was estimated to cause 4.8% of deaths and 2.6% of disability-adjusted life-years (DALYs) due to noncommunicable diseases in Saudi Arabia in 2019. While Saudi Arabia is already achieving great improvements, we predict the health and economic burden of insufficient PA up to 2040 to present a case for policy makers to invest more in the uptake of PA.MethodsUsing a population health model to estimate avoidable health loss, we identified four causes of health loss related to low PA (cardiovascular diseases, diabetes, breast cancer, and colorectal cancer) and estimated the deaths and DALYs from these causes. We projected the expected disease burden until 2040 under alternative assumptions about future PA levels and trends by using three health scenarios: baseline (no change in 2019 PA levels), intervention (81% of the population achieving sufficient PA levels), and ideal (65% of population: moderate PA, 30%: high PA, and 5%: inactive). We applied an "intrinsic value" approach to estimate the economic impact of each scenario.ResultsOverall, we estimate that between 2023 and 2040, about 80,000 to 110,000 deaths from all causes and 2.0 million to 2.9 million DALYs could be avoided by increasing PA levels in Saudi Arabia. The average annual economic loss from insufficient PA is valued at 0.49% to 0.68% of the current gross domestic product, with an average of US$5.4 billion to US$7.6 billion annually till 2040. The most avoidable disease burden and economic losses are expected among males and because of ischemic heart disease.ConclusionsThis study highlights that low PA levels will have considerable health and economic impacts in Saudi Arabia if people remain inactive and do not start following interventions. There is an urgent need to develop innovative programs and policies to encourage PA among all age and sex groups.

Background Physical inactivity among the general population is of great concern in public health. Objective This narrative review aims to identify promising physical activity (PA) public policies based on the best available evidence from the literature. Methods The study is a narrative synthesis of ‘reviews of reviews’ of public policies designed to increase physical activity among either (a) youths or (b) the community at large. We searched the literature for reviews of reviews of public policies of any country relevant to physical activity, physical inactivity, or sedentary behaviour published since 1 January 2000, in four databases. Results Based on 12 reviews of reviews published between 2011 and 2022, we identified seven potentially effective PA public policies. Six of the seven were youth-based public policies that would be implemented in schools. The seventh was a policy aimed at establishing and promoting walking groups. Conclusions Policymakers seeking to increase PA should consider focusing on school-based PA policies and community-based walking groups, as this is where the evidence base is greatest. To implement these policies, pilot studies to assess the efficacy of such programmes in local communities should first be conducted due to methodological limitations in the underlying literature and questions of generalisability and reproducibility.

The concept of an integrated power‐to‐gas (P2G) process was demonstrated for renewable energy storage by converting renewable electrical energy to synthetic fuels. Such a dynamically integrated process enables direct production of synthetic natural gas (SNG) from CO2 and H2O. The produced SNG can be stored or directly injected into the existing natural gas network. To study process integration, operating parameters of the high‐temperature solid oxide electrolysis cell (SOEC) producing syngas (H2+CO) mixtures through co‐electrolysis and a fixed bed reactor for syngas methanation of such gas mixtures were first optimized individually. Reactor design, operating conditions, and enhanced SNG selectivity were the main targets of the study. SOEC experiments were performed on state‐of‐the‐art button cells. Varying operating conditions (temperature, flow rate, gas mixture and current density) emphasized the capability of the system to produce tailor‐made syngas mixtures for downstream methanation. Catalytic syngas methanation was performed using hydrotalcite‐derived 20 %Ni‐2 %Fe/(Mg,Al)Ox catalyst and commercial methanation catalyst (Ni/Al2O3) as reference. Despite water in the feed mixture, SNG with high selectivity (≥90 %) was produced at 300 °C and atmospheric pressure. An adequate rate of syngas conversion was obtained with H2O contents up to 30 %, decreasing significantly for 50 % H2O in the feed. Compared to the commercial catalyst, 20 %Ni‐2 %Fe/(Mg,Al)Ox enabled a higher rate of COx conversion. [ABSTRACT FROM AUTHOR]

Abstract Background In Saudi Arabia, stay-at-home orders to address the coronavirus disease 2019 (COVID-19) pandemic between March 15 and 23, 2020 and eased on May 28, 2020. We conducted a scoping review to systematically describe physical activity and sedentary behavior in Saudi Arabia associated with the timing of the lockdown. Methods We searched six databases on December 13, 2021 for articles published in English or Arabic from 2018 to the search date. Studies must have reported data from Saudi Arabia for any age and measured physical activity or sedentary behavior. Results Overall, 286 records were found; after excluding duplicates, 209 records were screened, and 19 studies were included in the review. Overall, 15 studies were cross-sectional, and 4 studies were prospective cohorts. Three studies included children and adolescents (age: 2–18 years), and 16 studies included adults (age: 15–99 years). Data collection periods were

Economic shocks test the resilience of families around the world. Lockdowns, extended periods of unemployment, and inflation challenge the capabilities of private households to maintain their living standards whilst keeping their budgets in balance. Asset poverty is a concept invoked frequently to measure the capacity of private households to mitigate income loss by relying exclusively on their savings. In contrast to conventional asset poverty measures, we quantify the combined cushioning effect of private and public safety nets. Highlighting the importance of public safety nets and familial networks, this article devises a modified concept of asset poverty: Rather than purely simulating a household’s asset decumulation without replacement income, the modified indicator accounts for replacement income in a static setting. The empirical assessment of modified asset poverty in Europe and America combines harmonised microdata on household finances with simulations of institutional rules set by social insurance systems. Our results reveal how differences in social relations and institutional rules shape cross‐country variation in the vulnerability of private households. We find that, in contrast to the US, where the asset poverty of families is particularly low, households in most European countries are less vulnerable because generous social security systems coexist with low private assets. However, in some European countries, benefit generosity decreases the longer income losses last, exposing time dynamics in vulnerability. Complementing social insurance mechanisms, in countries such as Greece, households are more likely to receive financial support from family or friends. Cross‐national heterogeneity in vulnerability suggests that a shock may have different implications across countries.

Abstract Background Conditions affecting skeletal muscle, such as chronic rotator cuff tears, low back pain, dystrophies, and many others, often share changes in muscle phenotype: intramuscular adipose and fibrotic tissue increase while contractile tissue is lost. The underlying changes in cell populations and cell ratios observed with these phenotypic changes complicate the interpretation of tissue-level transcriptional data. Novel single-cell transcriptomics has limited capacity to address this problem because muscle fibers are too long to be engulfed in single-cell droplets and single nuclei transcriptomics are complicated by muscle fibers’ multinucleation. Therefore, the goal of this project was to evaluate the potential and challenges of a spatial transcriptomics technology to add dimensionality to transcriptional data in an attempt to better understand regional cellular activity in heterogeneous skeletal muscle tissue. Methods The 3′ Visium spatial transcriptomics technology was applied to muscle tissue of a rabbit model of rotator cuff tear. Healthy control and tissue collected at 2 and 16 weeks after tenotomy was utilized and freshly snap frozen tissue was compared with tissue stored for over 6 years to evaluate whether this technology is retrospectively useful in previously acquired tissues. Transcriptional information was overlayed with standard hematoxylin and eosin (H&E) stains of the exact same histological sections. Results Sequencing saturation and number of genes detected was not affected by sample storage duration. Unbiased clustering matched the underlying tissue type-based on H&E assessment. Connective-tissue-rich areas presented with lower unique molecular identifier counts are compared with muscle fibers even though tissue permeabilization was standardized across the section. A qualitative analysis of resulting datasets revealed heterogeneous fiber degeneration–regeneration after tenotomy based on (neonatal) myosin heavy chain 8 detection and associated differentially expressed gene analysis. Conclusions This protocol can be used in skeletal muscle to explore spatial transcriptional patterns and confidently relate them to the underlying histology, even for tissues that have been stored for up to 6 years. Using this protocol, there is potential for novel transcriptional pathway discovery in longitudinal studies since the transcriptional information is unbiased by muscle composition and cell type changes.

ObjectiveThis study aimed to review health-enhancing physical activity (HEPA) policies and initiatives introduced in Saudi Arabia (SA) since 2016 and identify the gaps in their design and implementation.MethodsA combination of methods was used, including semi-structured interviews with key informants from relevant entities (such as those from the ministries of health, education, sports, tourism, and other regulatory bodies) and a review of policy/initiative documents provided by them. Stakeholder mapping led by local experts and snowball sampling supported the identification of key informants. Three existing frameworks—the World Health Organization’s HEPA Policy Audit Tool, the Global Observatory for Physical Activity (PA) Policy Inventory, and the European Monitoring Framework for PA Indicators—were used to develop data collection instruments.ResultsThe review identified 44 policies/initiatives from different sectors. The Saudi Sports for All Federation is the leader in PA promotion and community sports development. However, there is a lack of multisectoral agenda and governance structures for PA promotion. The overlap between initiatives by different key informants results in duplication of efforts, including initiatives to promote PA among the general public led by competitive professional sports and community-based sports.ConclusionThe study findings indicate that several policies/initiatives have been implemented in SA since 2016. However, there is a need to focus on the challenges or barriers that affect the sustainability of policies/initiatives. A system-based approach can help build on sectoral synergies, thereby accelerating progress in engaging the Saudi population with PA.

Introduction: Rotator cuff tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration, which is not improved upon with surgical repair, highlighting the need to better understand the underlying biology impairing more favorable outcomes.Methods: In this study, we collected supraspinatus muscle tissue from 6 month old female rabbits who had undergone unilateral tenotomy for 8 weeks at 1, 2, 4, or 8 weeks post-repair (n = 4/group). RNA sequencing and enrichment analyses were performed to identify a transcriptional timeline of rotator cuff muscle adaptations and related morphological sequelae.Results: There were differentially expressed (DE) genes at 1 (819 up/210 down), 2 (776/120), and 4 (63/27) weeks post-repair, with none at 8 week post-repair. Of the time points with DE genes, there were 1092 unique DE genes and 442 shared genes, highlighting that there are changing processes in the muscle at each time point. Broadly, 1-week post-repair differentially expressed genes were significantly enriched in pathways of metabolism and energetic activity, binding, and regulation. Many were also significantly enriched at 2 weeks, with the addition of NIF/NF-kappaB signaling, transcription in response to hypoxia, and mRNA stability alongside many additional pathways. There was also a shift in transcriptional activity at 4 weeks post-repair with significantly enriched pathways for lipids, hormones, apoptosis, and cytokine activity, despite an overall decrease in the number of differentially expressed genes. At 8 weeks post-repair there were no DE genes when compared to control. These transcriptional profiles were correlated with the histological findings of increased fat, degeneration, and fibrosis. Specifically, correlated gene sets were enriched for fatty acid metabolism, TGF-B-related, and other pathways.Discussion: This study identifies the timeline of transcriptional changes in muscle after RC repair, which by itself, does not induce a growth/regenerative response as desired. Instead, it is predominately related to metabolism/energetics changes at 1 week post-repair, unclear or asynchronous transcriptional diversity at 2 weeks post-repair, increased adipogenesis at 4 weeks post-repair, and a low transcriptional steady state or a dysregulated stress response at 8 weeks post-repair.

This study aims to evaluate the abdominal aortic atherosclerotic plaque index (API)’s predictive role in patients with pre-operatively or post-operatively developed chronic kidney disease (CKD) treated with robot-assisted partial nephrectomy (RAPN) for renal cell carcinoma (RCC). One hundred and eighty-three patients (134 with no pre- and post-operative CKD (no CKD) and 49 with persistent or post-operative CKD development (post-op CKD)) who underwent RAPN between January 2019 and January 2022 were deemed eligible for the analysis. The API was calculated using dedicated software by assessing the ratio between the CT scan atherosclerotic plaque volume and the abdominal aortic volume. The ROC regression model demonstrated the influence of API on CKD development, with an increasing effect according to its value (coefficient 0.13; 95% CI 0.04–0.23; p = 0.006). The Model 1 multivariable analysis of the predictors of post-op CKD found that the following are independently associated with post-op CKD: Charlson Comorbidity Index (OR 1.31; p = 0.01), last follow-up (FU) Δ%eGFR (OR 0.95; p < 0.01), and API ≥ 10 (OR 25.4; p = 0.01). Model 2 showed API ≥ 10 as the only factor associated with CKD development (OR 25.2; p = 0.04). The median follow-up was 22 months. Our results demonstrate API to be a strong predictor of post-operative CKD, allowing the surgeon to tailor the best treatment for each patient, especially in those who might be at higher risk of CKD.

The prevalence of renal cell carcinoma (RCC) is increasing due to advanced imaging techniques. Surgical resection is the standard treatment, involving complex radical and partial nephrectomy procedures that demand extensive training and planning. Furthermore, artificial intelligence (AI) can potentially aid the training process in the field of kidney cancer. This review explores how artificial intelligence (AI) can create a framework for kidney cancer surgery to address training difficulties. Following PRISMA 2020 criteria, an exhaustive search of PubMed and SCOPUS databases was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on AI’s role in kidney cancer surgical training. On the other hand, all non-original articles and articles published in any language other than English were excluded. Two independent reviewers assessed the articles, with a third party settling any disagreement. Study specifics, AI tools, methodologies, endpoints, and outcomes were extracted by the same authors. The Oxford Center for Evidence-Based Medicine’s evidence levels were employed to assess the studies. Out of 468 identified records, 14 eligible studies were selected. Potential AI applications in kidney cancer surgical training include analyzing surgical workflow, annotating instruments, identifying tissues, and 3D reconstruction. AI is capable of appraising surgical skills, including the identification of procedural steps and instrument tracking. While AI and augmented reality (AR) enhance training, challenges persist in real-time tracking and registration. The utilization of AI-driven 3D reconstruction proves beneficial for intraoperative guidance and preoperative preparation. Artificial intelligence (AI) shows potential for advancing surgical training by providing unbiased evaluations, personalized feedback, and enhanced learning processes. Yet challenges such as consistent metric measurement, ethical concerns, and data privacy must be addressed. The integration of AI into kidney cancer surgical training offers solutions to training difficulties and a boost to surgical education. However, to fully harness its potential, additional studies are imperative.

ABSTRACT Purpose: Contrast-enhanced CT scan is the standard staging modality for patients with bladder cancer undergoing radical cystectomy (RC). Involvement of lymph nodes (LN) determines prognosis of patients with bladder cancer. The detection of LN metastasis by CT scan is still insufficient. Therefore, we investigated various CT scan characteristics to predict lymph node ratio (LNR) and its impact on survival. Also, pre-operative CT scan characteristics might hold potential to risk stratify cN+ patients. Materials and Methods: We analyzed preoperative CT scans of patients undergoing RC in a tertiary high volume center. Retrospectively, local tumor stage and LN characteristics such as size, morphology (MLN) and number of loco-regional LN (NLN) were investigated and correlation to LNR and survival was analyzed. CT scan characteristics were used to develop a risk stratification using Kaplan-Maier and multivariate analysis. Results: 764 cN0 and 166 cN+ patients with complete follow-up and imaging data were included in the study. Accuracy to detect LN metastasis and locally advanced tumor stage in CT scan was 72% and 62%. LN larger than 15mm in diameter were significantly associated with higher LNR (p=0.002). Increased NLN correlated with decreased CSS and OS (p=0.001: p=0.002). Furthermore, CT scan based scoring system precisely differentiates low-risk and high-risk profiles to predict oncological outcome (p 15mm significantly correlated with higher LNR. Identification of increased loco-regional LN was associated with worse survival. For the first time, precise risk stratification based on computed-tomography findings was developed to predict oncological outcome for clinical lymph node-positive patients undergoing RC.

Genetically susceptible bacteria can escape the action of bactericidal antibiotics through antibiotic tolerance or persistence. However, one major difference between the two phenomena is their distinct penetrance within an isogenic population. While with antibiotic persistence, susceptible and persister cells co-exist, antibiotic tolerance affects the entire bacterial population. Here, we show that antibiotic tolerance can be achieved in numerous non-specific ways in vitro and during infection. More importantly, we highlight that, due to their impact on the entire bacterial population, these tolerance-inducing conditions completely mask persistence and the action of its molecular determinants. Finally, we show that even though tolerant populations display a high survival rate under bactericidal drug treatment, this feature comes at the cost of having impaired proliferation during infection. In contrast, persistence is a risk-limiting strategy that allows bacteria to survive antibiotic treatment without reducing the ability of the population to colonize their host. Altogether, our data emphasise that the distinction between these phenomena is of utmost importance to improve the design of more efficient antibiotic therapies.

Abstract Background Docetaxel (D) or secondary hormonal therapy (SHT) each combined with androgen deprivation therapy (ADT) represent possible treatment options in males with metastasized hormone‐sensitive prostate cancer (mHSPC). Real‐world data comparing different protocols are lacking yet. Thus, our objective was to compare the efficacy and safety of abiraterone acetate (AA)+ADT versus D+ADT in mHSPC. Methods In a retrospective multicenter analysis including males with mHSPC treated with either of the aforementioned protocols, overall survival (OS), progression‐free survival 1 (PFS1), and progression‐free survival 2 (PFS2) were assessed for both cohorts. Median time to event was tested by Kaplan–Meier method and log‐rank test. The Cox‐proportional hazards model was used for univariate and multivariate regression analyses. Results Overall, 196 patients were included. The AA+ADT cohort had a longer PFS1 in the log‐rank testing (23 vs. 13 mos., p