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Background/Aims Hypoxemia is a common side effect of propofol sedation during endoscopy. Applying mild positive airway pressure (PAP) using a nasal mask may offer a simple way to reduce such events and optimize the conditions for diagnostic and therapeutic upper gastrointestinal endoscopies. Methods We compared overweight patients (body mass index >25 kg/m2) with a nasal PAP mask or standard nasal cannula undergoing upper gastrointestinal endoscopies by non-anesthesiologists who provided propofol sedation. Outcome parameters included the frequency and severity of hypoxemic episodes. Results We analyzed 102 procedures in 51 patients with nasal PAP masks and 51 controls. Episodes of hypoxemia (oxygen saturation [SpO2]

Abstract Background Saudi Arabia is implementing a comprehensive health system transformation in health services provision, governance, and financing. Given the high burden of non-communicable diseases (NCD), a key objective of the transformation is to integrate NCD prevention and treatment into primary care. The study objectives were to assess primary care service use for treatment of NCDs, to quantify existing inequities in preventive services utilization, and to identify regional and sociodemographic factors associated with these inequities. Methods Using the 2019 Kingdom of Saudi Arabia World Health Survey, multivariable logistic regression models were conducted to identify predictors of utilization of primary care services for NCD prevention and treatment, unmet need among those with a diagnosis of diabetes, hypertension, or dyslipidemia, and unmet need in breast and cervical cancer screening. Results Among those with an NCD diagnosis, living in a high-income household was associated with a lower probability of having an unmet need compared to those in low-income households. Furthermore, rural residents were less likely to have an unmet need compared to urban residents (OR 0.58, p=0.029). Individuals without a perceived need for healthcare within the last 12 months had three times the probability of unmet need in comparison to those with such a perceived need (p

Abstract The consumption of antibiotics varies between and within countries. However, our understanding of the key drivers of antibiotic consumption is largely limited to observational studies. Using Indian data that showed substantial differences between states and changes over years, we conducted a quasi-experimental fixed-effects regression study to examine the determinants of private-sector antibiotic consumption. Antibiotic consumption decreased by 10.2 antibiotic doses per 1000 persons per year for every ₹1000 (US$12.9) increase in per-capita gross domestic product. Antibiotic consumption decreased by 46.4 doses per 1000 population per year for every 1% increase in girls’ enrollment rate in tertiary education. The biggest determinant of private sector antibiotic use was government spending on health—antibiotic use decreased by 461.4 doses per 1000 population per year for every US$12.9 increase in per-capita government health spending. Economic progress, social progress, and increased public investment in health can reduce private-sector antibiotic use.

Abstract Accurate localization of gliomas, the most common malignant primary brain cancer, and its different sub-region from multimodal magnetic resonance imaging (MRI) volumes are highly important for interventional procedures. Recently, deep learning models have been applied widely to assist automatic lesion segmentation tasks for neurosurgical interventions. However, these models are often complex and represented as “black box” models which limit their applicability in clinical practice. This article introduces new hybrid vision Transformers and convolutional neural networks for accurate and robust glioma segmentation in Brain MRI scans. Our proposed method, TransXAI, provides surgeon-understandable heatmaps to make the neural networks transparent. TransXAI employs a post-hoc explanation technique that provides visual interpretation after the brain tumor localization is made without any network architecture modifications or accuracy tradeoffs. Our experimental findings showed that TransXAI achieves competitive performance in extracting both local and global contexts in addition to generating explainable saliency maps to help understand the prediction of the deep network. Further, visualization maps are obtained to realize the flow of information in the internal layers of the encoder-decoder network and understand the contribution of MRI modalities in the final prediction. The explainability process could provide medical professionals with additional information about the tumor segmentation results and therefore aid in understanding how the deep learning model is capable of processing MRI data successfully. Thus, it enables the physicians’ trust in such deep learning systems towards applying them clinically. To facilitate TransXAI model development and results reproducibility, we will share the source code and the pre-trained models after acceptance at https://github.com/razeineldin/TransXAI .

Brachial plexus reconstruction (BPR) consists of the complex surgical restoration of nerve structures. To further understand the underlying motor cortex changes and evaluate neuroplasticity after a successful surgery, we performed a navigated transcranial magnetic stimulation (nTMS) study mapping the postoperative motor representation of the formerly plegic arm. We conducted a prospective nTMS study mapping the musculocutaneous nerve as a representative, prominent target of BPR including a patient (n = 8) and a control group (n = 10). Measurements like resting motor threshold (RMT), cortical motor area location, and size were taken. Mathematical analysis was performed using MATLAB 2022, statistical analysis was performed using SPSS 26, and nTMS mapping was performed using the Nexstim NBS 5.1 system. Mapping was feasible in seven out of eight patients. Median RMT on the affected hemisphere was 41% compared to 50% on the unaffected hemisphere and they were 37% and 36% on the left and right hemispheres of the control group. The motor area location showed a relocation of bicep brachii representation at the middle precentral gyrus of the corresponding contralateral hemisphere. Motor area size was increased compared to the control group and the patient’s unaffected, ipsilateral hemisphere. Understanding cortical reorganization is important for potential future treatments like therapeutic nTMS. The issue of motor neuroplasticity in patients with brachial plexus lesions is worth exploring in further studies.

Background: Research on medicines access and use is heterogeneous and can be challenging for decision- makers to interpret. Pharmaceutical policy is an additional component for study and is the foundation for the promotion of access and use of medicines. This systematic review summarizes findings from the literature on medicines policy, access and use over the past two decades in Mexico and identifies research gaps that should be addressed. Methods: A systematic review of the literature published between 2000 and 2022 was conducted to identify publications on medicines policy, access and use in Mexico. The study followed PRISMA Statement guidelines 2020. A narrative review including content analysis was conducted. Results: A total of 5057 articles were reviewed, of which 77 fit the inclusion criteria. Studies described the lack of an explicit national policy, a misalignment between the legal framework and reinforcement incentives, deficient policy documentation at the national level, and the absence of necessary medicines regulation and transparency. In terms of access to medicines, challenges related to supply, selection, acquisition, distribution and expenditure were noted. Regarding medicine use, key study findings included a lack of adherence to standard treatment guidelines, dispensing, lack of reliable information on medicines, lack of treatment adherence and harmful self-medication. Conclusion: The appropriate use of medicines and adequate access to them are priority topics for the formulation of Mexican pharmaceutical policy. It is critical that further research includes longitudinal studies of medicine access and use, and the consideration of studying the private sector as well as new methodological approaches. Many reported challenges related to access to and use of medicines have persisted across decades, suggesting a lack of effective research-to-practice knowledge transfer and policy implementation. This article is part of the Hospital pharmacy, rational use of medicines and patient safety in Latin America Special Issue: https://www.drugsincontext.com/special_issues/hospital-pharmacy-rational-use-of-medicines-and-patient-safety-in-latin-america/

ABSTRACTOur immune system possesses sophisticated mechanisms to cope with invading microorganisms, while pathogens evolve strategies to deal with threats imposed by host immunity. Human plasma protein α1-antitrypsin (AAT) exhibits pleiotropic immune-modulating properties by both preventing immunopathology and improving antimicrobial host defence. Genetic associations suggested a role for AAT in candidemia, the most frequent fungal blood stream infection in intensive care units, yet little is known about how AAT influences interactions between Candida albicans and the immune system. Here, we show that AAT differentially impacts fungal killing by innate phagocytes. We observed that AAT induces fungal transcriptional reprogramming, associated with cell wall remodelling and downregulation of filamentation repressors. At low concentrations, the cell-wall remodelling induced by AAT increased immunogenic β-glucan exposure and consequently improved fungal clearance by monocytes. Contrastingly, higher AAT concentrations led to excessive C. albicans filamentation and thus promoted fungal immune escape from monocytes and macrophages. This underscores that fungal adaptations to the host protein AAT can differentially define the outcome of encounters with innate immune cells, either contributing to improved immune recognition or fungal immune escape.

Violence is defined as "the intentional use of physical force or power, threatened or actual, against oneself, another person, or against a group or community, that either results in or has a high likelihood of resulting in injury, death, psychological harm, maldevelopment, or deprivation." Encompassed in this definition are multiple, interrelated forms of violence, including interpersonal firearm death and injury, but also the systems, policies, and practices enacted by those with power to advantage some groups while depriving others of meaningful opportunities for meeting their basic needs-known as "structural violence". Yet dominant violence prevention narratives too often ignore or deemphasize the deeply intertwined threads of structural violence with other forms of violence, leading to policies and practices that are frequently insufficient, and often harmful, for reducing interpersonal firearm violence and building community safety, particularly in minoritized and structurally marginalized communities. We highlight ways in which limited scrutiny of structural violence, the omission of its defining characteristics-power and deprivation-from functional characterizations and frameworks of interpersonal firearm violence, and the inadequate distribution of power and resources to those most impacted by violence to self-determine narratives of and solutions to interpersonal firearm violence grossly impacts how interpersonal firearm violence is collectively conceived, discussed, and addressed. Expanding dominant narratives of interpersonal firearm violence, guided by the wisdom and determination of those most impacted, such that the goal of prevention and intervention efforts is not merely the absence of violence but rather the creation of a community safety and health ecosystem is essential to meet this critical moment in firearm violence research and prevention.

With >7000 species the order of rust fungi has a disproportionately large impact on agriculture, horticulture, forestry and foreign ecosystems. The infectious spores are typically dikaryotic, a feature unique to fungi in which two haploid nuclei reside in the same cell. A key example is Phakopsora pachyrhizi, the causal agent of Asian soybean rust disease, one of the world's most economically damaging agricultural diseases. Despite P. pachyrhizi's impact, the exceptional size and complexity of its genome prevented generation of an accurate genome assembly. Here, we sequence three independent P. pachyrhizi genomes and uncover a genome up to 1.25 Gb comprising two haplotypes with a transposable element (TE) content of ~93%. We study the incursion and dominant impact of these TEs on the genome and show how they have a key impact on various processes such as host range adaptation, stress responses and genetic plasticity.

The burden of firearm homicide in the United States is not evenly distributed across the population; rather, it disproportionately affects youth in disadvantaged and marginalized communities. Research is limited relevant to the impacts of exposure to firearm violence that occurs near where youth live or attend school - spatially proximate firearm violence - on youths mental health and whether those impacts vary by characteristics that shape youths risk for experiencing that exposure in the first place. Using a dataset linking the Fragile Families and Child Wellbeing Study with the Gun Violence Archive (N = 3086), we employed propensity score matching and multilevel stratification to examine average and heterogeneous associations between spatially proximate firearm homicide exposure and anxiety and depression among all youth and then separately for boys and girls. We found a statistically significant average association between firearm homicide exposure and symptoms of depression among youth. Furthermore, heterogeneous effects analyses yielded evidence that the average association is driven by youth, and particularly boys, who are the most disadvantaged and have the highest risk of firearm homicide exposure. The results of this study suggest that the accumulation of stressors associated with structural disadvantage and neighborhood disorder, coupled with exposure to spatially proximate and deadly firearm violence, may make boys and young men, particularly Black boys and young men, uniquely vulnerable to the mental health impacts of such exposure. Ancillary analyses of potential effect moderators suggest possible future areas of investigation.

BackgroundThough largely substance-naïve at enrollment, a proportion of the youth in the Adolescent Brain Cognitive Development (ABCD) Study are expected to initiate substance use (SU) as they transition into later adolescence. With annual data from youth 9-13 years-old, this study aims to describe their SU patterns over time. Here, prevalence rates of use are reported, along with predicted odds of use while analyzing common risk-factors associated with youth SU.MethodsThe ABCD Study® enrolled 11,876 participants at Baseline (ages 9-10) and has followed them annually. Data through half of the third follow-up visit are available (ages 12-13; n = 6,251). SU descriptives for al psychoactive substances over time are outlined. General estimating equations (GEEs) assessed whether sociodemographic factors, internalizing and externalizing symptoms, and parental SU problems were associated with SU between Baseline and Y2 follow-up.ResultsAcross time, alcohol and nicotine remain the most used substances. Yearly rates of any SU increased (past year use: 13.9% in Y1; 14% Y2, 18.4% Y3). Cumulatively, by Y3, 39.7% of the cohort reported experimenting (e.g., sipping alcohol) with SU within their lifetime, while 7.4% reported a "full use" (a full alcohol drink, nicotine use, cannabis use, or any other SU) in their lifetime (past-year: 1.9% alcohol, 2.1% nicotine, 1.1% cannabis, 1.2% other substances). GEEs revealed ongoing longitudinal associations between sociodemographic factors, greater externalizing symptoms, and parental drug problems with increased odds of initiating SU.ConclusionsAs ABCD participants transition into their teenage years, the cohort is initiating SU at increasing (though still low) rates.

Carbapenems are important therapeutic agents for treating infections caused by multidrug-resistant Gram-negative bacteria. Mandatory reporting of carbapenem-resistant Gram-negative bacteria (CR-GN) can allow for a better understanding of the changing CR-GN burden and can help facilitate intervention. In November 2011, identification of CR-GN with acquired carbapenem resistance became notifiable in Hesse, Germany. Hesse is one of the 16 German federal states, with a population of 6.1 million. We report on CR-GN notified between 1 January and 8 April 2013, when reporting requirements were changed. During this period, 549 CR-GN were isolated from 525 patients. Of these, 67.0% (368/549) were . The remaining 181 CR-GN comprised 59 (32.6%) , 53 (29.3%) , 28 (15.5%) spp., 20 (11.5%) , and 21 (11.6%) other CR-GN. Seventy-three (13.3%) CR-GN were reported to harbour a carbapenemase. Fourteen different carbapenemase types were reported, with the most frequent being OXA-23 (n=18), OXA-48 (n= 16), VIM-2 (n=12), VIM-1 (n=11), and NDM (n=5). Our results suggest the widespread presence of CR-GN, a high diversity of identified carbapenemases, autochthonous transmissions, and regional differences in incidence for the different species and carbapenemases, even in the absence of major outbreaks of infection.

Objectives: The role of sleep quality is not yet fully understood in the context of posttraumatic stress disorder (PTSD) following exposure to community violence. Thus, the primary aim of this study is to examine the mediating effect of sleep quality in the relationship between community violence exposure and posttraumatic stress symptoms. Methods: Utilizing a cross-sectional survey administered to an online opt-in panel of adults in the United States in 2023 (age ≥ 18 years) (N = 342), respondents reported on their exposure to community violence, sleep quality, and posttraumatic stress symptoms. Covariate-adjusted regressions were used to test these relationships. Results: Directly experiencing community violence was associated with poorer sleep quality (β = 0.11, 95 % CI [0.02, 0.20], p = 0.022) and posttraumatic stress symptoms (β = 0.33, 95 % CI [0.17, 0.48], p = < 0.001), and poorer sleep quality predicted greater posttraumatic stress symptoms (β = 0.74, 95 % CI [0.58, 0.91], p = 0

IntroductionWhile the effectiveness of cognitive-behavioral stress management trainings (SMTs) is well-documented, the underlying mechanisms, especially in an occupational context, are not fully understood. We tested whether SMT-induced improvements in stress management skills, particularly in the mastery of changing cognitions, may explain beneficial SMT effects.MethodsOur non-randomized controlled trial comprised 108 employees of a German health insurance company, with 65 of them participating in a cognitive-behavioral SMT and 43 participating in an alternative control training (AT). As outcome variables, we repeatedly assessed stress-related (functional stress management skills, relaxation, stress reactivity, exhaustion), work-related (job dissatisfaction), and specific-context-related (social support, trait anger) measures at baseline, 2 weeks, and 3 months after the trainings. Functional stress management skills and, in particular, a subscale assessing perceived mastery of changing cognitions (“cognitive-strategies-and-problem-solving”) were tested as mediators of change.ResultsRepeated measures (M)AN(C)OVAs and complementary multigroup latent difference models confirmed improvements in all outcomes in the SMT-group compared to the AT-group (p's ≤ 0.015). Multivariate mediation path analyses revealed that, regarding mechanisms of change, the subscale cognitive-strategies-and-problem-solving was identified as the most important mediator for all outcomes (95% CIs for expected increases in SMT- vs. AT-group = [lower limits (LLs) ≥ 0.004]; 95% CIs for expected decreases in the SMT- vs. AT-group = [upper limits(ULs) ≤ −0.078]) except for job dissatisfaction.DiscussionOur findings confirm that employees can effectively learn to master stress reduction techniques and consequently lower the resulting burden. Moreover, beneficial SMT effects seem to result from improvements in functional stress management skills, particularly in the ability to change cognitions. This points to the importance of training cognitive techniques.

BackgroundWhile aldosterone plays an important role in blood pressure regulation, its role in essential hypertension (EHT) remains unclear. Here, we systematically investigated the secretion of biologically-active free aldosterone in saliva in response to awakening (AldAR) and during the day (AldDay) in EHT compared to normotensive controls (NT).MethodsIn 30 men with EHT and 30 age-matched NT, AldAR saliva samples were collected immediately after awakening and 15, 30, 45, and 60 min thereafter and AldDay samples were collected from 08:30–22:00 h on two consecutive days.ResultsOver the course of the day, men with EHT had higher repeated AldDay levels compared to NT (p = .002) with higher concentrations in the morning hours (p's ≤ .047), a steeper decline over the course of the day (p's ≤ .018), and similar concentrations in the evening (p's ≥ .21). Regarding AldAR, we observed higher concentrations in EHT at awakening (p = .017) and borderline higher concentrations at 15 min (p = .086). No differences were found 30–60 min after awakening (p's ≥ .34). Analyses with repeated and aggregated AldAR levels resulted in borderline significantly higher free aldosterone in EHT (p's ≤ .077). Complementary analyses confirmed linear associations between higher blood pressure and higher AldAR and AldDay levels.ConclusionsOur data point to elevated salivary free aldosterone secretion in EHT over the course of the day, particularly in the morning hours. As the free aldosterone fraction is considered biologically active, our data may point to a biological mechanism underlying EHT.

Divertor components for ITER and even beyond will be subjected to cyclic steady state heat loads with a duration of several minutes to hours, repeatedly occurring slow transients during reattachment or ramp-up and down, as well as heat loads during ELMs applying a combination of low cycle fatigue and creep as well as high cycle fatigue via thermal shock loads. While for the qualification of components the duration of the fatigue cycles up to now has been kept small, i.e., close to the required time to reach thermal saturation which is 10 s for typical divertor components, creep in these components has not yet been assessed.In this study divertor tungsten monoblock mock-up manufactured via hot radial pressing in the ITER-like geometry consisting of 4 monoblocks and quality checked via ultrasonic testing are exposed to high heat flux loads in the electron beam facility JUDITH 2 using a high temperature cooling circuit with controlled water chemistry. Thereby, cyclic loads up to 1000 cycles with a duration of 10 to 600 s and a power density of 20 MW/m2 were applied, representing strike point loading conditions in DEMO during strike point sweeping scenarios. Each of the tungsten monoblocks is loaded individually providing the possibility to study different scenarios on one single mock-up. The aim is to assess the performance and degradation of performance due to the applied loads, which is supported by characterization via metallography, profilometry, SEM and hardness testing after the high heat flux tests.

We report an unusual constellation of diseases in a 32-year-old woman with neurofibromatosis type 1 (NF1) diagnosed with the recently described precursor entity of malignant peripheral nerve sheath tumor (MPNST), the so-called atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP) and a large symptomatic cervical arteriovenous fistula. An [18F] 2-Fluoro-2-deoxy-D-glucose PET/CT (FDG-PET/CT) was performed to detect and stage a conspicuous symptomatic cervical tumor. The FDG-PET/CT showed high FDG uptake in one of the multiple known tumorous lesions associated with peripheral nerves. However, no relevant FDP uptake was observed in this affected cervical area. After digital subtraction angiography, the cervical mass turned out to be a widespread arteriovenous fistula of the vertebral artery. This was successfully treated using endovascular embolization. Subsequently, magnet resonance imaging (MRI) of the FDG-positive tumor revealed a well-enhanced homogeneous mass of the sciatic nerve measuring 5.2×2.4×2.8 cm. Microsurgical gross total tumor resection was performed using ultrasound. The final histopathological diagnosis was ANNUBP transformed from neurofibroma. The patient benefited excellently from the surgery; no recurrence or metastasis has been observed since resection. According to imaging, ANNUBP can be characterized as a well-enhanced homogeneous mass on MRI, displaying high uptake on FDG-PET/CT and hypoechogenic in ultrasound.

Background & Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identifying ideal candidates remains a challenge. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating marker of immune activation that has previously been associated with liver inflammation, but its prognostic value in patients receiving TIPS is unknown. In the present study, we evaluated the potential clinical relevance of suPAR levels in patients undergoing TIPS insertion. Methods: suPAR concentrations were measured by ELISA in hepatic vein (HV) and portal vein (PV) blood samples from 99 patients (training cohort) as well as peripheral venous blood samples from an additional 150 patients (validation cohort) undergoing TIPS placement. The association between suPAR levels and patient outcomes was assessed using Kaplan-Meier methods and Cox-regression analyses. Results: suPAR concentrations were significantly higher in HV samples compared to PV samples and correlated with PV concentration, the presence of ascites, renal injury, and consequently with the Child-Pugh and MELD scores. Patients with lower suPAR levels had significantly better short- and long-term survival after TIPS insertion, which remained robust after adjustment for confounders in multivariate Cox-regression analyses. Sensitivity analysis showed an improvement in risk prediction in patients stratified by Child-Pugh or MELD scores. In an independent validation cohort, higher levels of suPAR predicted poor transplant-free survival after TIPS, particularly in patients with Child-Pugh A/B cirrhosis. Conclusion: suPAR is largely derived from the injured liver and its levels are predictive of outcome in patients undergoing TIPS. suPAR, as a surrogate of hepatic inflammation, may be used to stratify care in patients following TIPS insertion. Impact and implications: Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identification of the ideal candidates remains challenging. We show that soluble urokinase plasminogen activator receptor (suPAR), a circulating marker of immune activation that can easily be measured in routine clinical practice, is a novel marker to identify patients who will benefit from TIPS and those who will not.