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Abstract Introduction Population‐level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale‐up. Methods In 2015–2020, we measured VLS (

Background Obesity leads to an elevated risk of developing gastrointestinal disease such as gastric ulcers. Callistemon citrinus leaf extract has shown antioxidant, antimicrobial, hepatoprotective, and chemoprotective effects against colon cancer. The aim of this study is to evaluate the gastroprotective effect of C. citrinus leaf extract on indomethacin-induced gastric ulcers in obese rats. Methods Gastric ulcers were induced in female obese Wistar rats using a single oral dose of indomethacin (IND). In the first stage, the rats were fed with a high fat sugar diet (HFSD) for 15 weeks to induce obesity and, at the same time, the diet of the other group of animals included daily administration of ethanolic C. citrinus leaf extract (250 mg/kg) in addition to HFSD. In the second stage, gastric ulcers were induced with IND (30 mg/kg). The gastroprotective activity of C. citrinus, the inflammatory enzyme activities, and cytokines in the stomach were determined. Results C. citrinus produced a reduction of gastric lesions caused by IND. Myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) activities also decreased. Although inflammatory biomarkers such as TNFα, IL-6, AOPP, and leptin were significantly decreased by C. citrinus, adiponectin levels increased. Moreover, C. citrinus decreased weight gain and morphological and biochemical parameters. Conclusion The use of indomethacin in rats fed with a high fat-sugar diet increased gastric ulcers. Gastroprotective effect of C. citrinus in obese rats is attributed to the reduction of pro-inflammatory cytokines and the inflammatory enzymes.

Objectives: Wars and armed conflicts have a major impact on population health. As the discipline of public health aims to increase the health at population level, professionals play a significant role in dealing with war and armed conflict. There is need for research on prevention. This study aims to map the literature on existing public health approaches addressing the primary prevention of war and/or armed conflict.Methods: We performed a scoping review in the databases Web of Science, PubMed and Google Scholar, followed by a narrative synthesis.Results: We included 15 studies. We identified three main themes regarding preventive measures: 1) research on root causes of conflicts, surveillance and documentation of its health consequences; 2) education and awareness raising on the consequences of conflicts; and 3) interventions to change socio-economic and political conditions conducive to conflicts.Conclusion: A two-tiered conceptual framework emerges: For primary prevention of war, public health should promote human rights and the rule of law. To prevent armed conflict within states, public health should address the social determinants of health and aim to reduce poverty and inequity.

Since the world first approved gene therapeutics, nucleic acid-based therapies have gained prominence. Several strategies for DNA-based therapy have been approved, and numerous clinical trials for plasmid DNA (pDNA)-based vaccines are currently in development. Due to the rising interest in pDNA for vaccination and gene therapy, plasmid manufacturing must become more effective. One of the most critical steps is downstream processing, involving isolation and purification procedures. To comply with the regulatory guidelines, pDNA must be available as a highly purified, homogeneous preparation of supercoiled pDNA (sc pDNA). This process undertakes several challenges, primarily due to the diversity of molecules derived from the producer organism. In this study, different resins were tested for the adsorption and selective polishing of sc pDNA. To identify optimal pDNA adsorption conditions, batch and column assays were performed with different resins while promoting electrostatic and hydrophobic interactions. The effect of ionic strength, pH, and contact time were evaluated and optimized. Additionally, static and dynamic binding capacities were determined for the selected resins. Analytical chromatography and agarose gel electrophoresis were used to assess the selectivity of the most promising resins toward sc pDNA isoform. Also, genomic DNA, endotoxins, and proteins were quantified to characterize the final sc pDNA quality. At the same time, the recovery and purity yields were evaluated by quantification of sc pDNA after the purification procedure. Overall, the results of the chromatographic assays using agmatine- and arginine-based resins have shown promising potential for sc pDNA polishing. Both resins demonstrated excellent binding capacity for pDNA, with agmatine outperforming arginine-based resin in terms of capacity. However, arginine-based resin exhibited a superior pDNA recovery yield, reaching a notable 52.2% recovery compared to 10.09% from agmatine. Furthermore, both resins exhibited high relative purity levels above 90% for the sc pDNA. The comprehensive characterization of the recovered sc pDNA also revealed a significant reduction in gDNA levels, reinforcing the potential of these prototypes for obtaining high-quality and pure sc pDNA. These findings highlight the promising applications of both resins in scalable pDNA purification processes for gene therapy and biopharmaceutical applications.

The microbiota is attributed to be important for initial soil formation under extreme climate conditions, but experimental evidence for its relevance is scarce. To fill this gap, we investigated the impact of in situ microbial communities and their interrelationship with biocrust and plants compared to abiotic controls on soil formation in initial arid and semiarid soils. Additionally, we assessed the response of bacterial communities to climate change. Topsoil and subsoil samples from arid and semiarid sites in the Chilean Coastal Cordillera were incubated for 16 weeks under diurnal temperature and moisture variations to simulate humid climate conditions as part of a climate change scenario. Our findings indicate that microorganism-plant interaction intensified aggregate formation and stabilized soil structure, facilitating initial soil formation. Interestingly, microorganisms alone or in conjunction with biocrust showed no discernible patterns compared to abiotic controls, potentially due to water-masking effects. Arid soils displayed reduced bacterial diversity and developed a new community structure dominated by Proteobacteria, Actinobacteriota, and Planctomycetota, while semiarid soils maintained a consistently dominant community of Acidobacteriota and Proteobacteria. This highlighted a sensitive and specialized bacterial community in arid soils, while semiarid soils exhibited a more complex and stable community. We conclude that microorganism-plant interaction has measurable impacts on initial soil formation in arid and semiarid regions on short time scales under climate change. Additionally, we propose that soil and climate legacies are decisive for the present soil microbial community structure and interactions, future soil development, and microbial responses.

Extracellular vesicles (EVs) are membrane structures enclosed by a lipid bilayer that are released into the extracellular space by all types of cells. EVs are involved in many physiological processes by transporting biologically active substances. Interest in EVs for diagnostic biomarker research and therapeutic drug delivery applications has increased in recent years. The realization of the full therapeutic potential of EVs is currently hampered by the lack of a suitable technology for the isolation and purification of EVs for downstream pharmaceutical applications. Anion Exchange Chromatography (AEX) is an established method in which specific charges on the AEX matrix can exploit charges on the surface of EVs and their interactions to provide a productive and scalable separation and purification method. The established AEX method using Eshmuno® Q, a strong tentacle anion exchange resin, was used to demonstrate the principal feasibility of AEX-based isolation and gain insight into isolated EV properties. Using several EV analysis techniques to provide a more detailed insight into EV populations during AEX isolation, we demonstrated that although the composition of CD9/63/81 remained constant for tetraspanin positive EVs, the size distribution and purity changed during elution. Higher salt concentrations eluted larger tetraspanin negative vesicles.

The current trend in biopharmaceutical drug manufacturing is towards increasing potency and complexity of products such as peptide scaffolds, oligonucleotides and many more. Therefore, a universal affinity purification step is important in order to meet the requirements for cost and time efficient drug production. By using a self-splicing intein affinity tag, a purification template is generated that allows for a universal chromatographic affinity capture step to generate a tagless target protein without the use of proteases for further tag removal. This study describes the successful implementation of gp41-1-based split inteins in a chromatographic purification process for, e.g., E. coli-derived targets. The tagless target is generated in a single-step purification run. The on-column cleavage is induced by triggering a simple pH change in the buffer conditions without the need for additives such as Zn2+ or thiols. This system has proven to be reusable for at least ten purification cycles that use 150 mM H3PO4 as the cleaning agent.

Background: Nearly one in six children lived in war zones in 2023. Evidence-based psychosocial and parenting support has potential to mitigate negative impacts for parents and children co-exposed to war and displacement, especially in relation to mental health and harsh parenting reactions. In the current war in Ukraine, local mental health experts co-created and evaluated, with global experts, the effectiveness of psychosocial and parenting support groups, called ‘Hope Groups’ on improvements in mental health, positive parenting, and violence against children. This paper aimed to assess the effectiveness of psychosocial and parenting support groups, called 'Hope Groups,' on improvements in caregiver mental health, positive parenting, and prevention of violence against children, for families affected by the war in Ukraine, using a pre/post study design. Methods: Participants (n = 577) included Ukrainian caregivers, 66% (381) of whom were parents and co-residing caregivers of children ages 0–17, while the remaining 34% were non-resident informal caregivers. Internally displaced, externally displaced, and those living at-home in war-torn regions were invited to groups by trained Ukrainian peer facilitators. Using a pre-post design, we compared individual level frequency measures at three time-points – baseline, midline, and endline, to assess changes in 4 mental health, and 9 parenting and child health outcomes. We analyzed these outcomes using paired t-tests to compare outcomes at baseline-to-midline (after 4-sessions) and baseline-to-endline (after 10-sessions), which estimated the mean changes in days per week and associated percent change, during the respective periods; we quantified uncertainties using bias-corrected and accelerated (BCa) bootstrapping with 95% uncertainty ranges for baseline-midline and baseline-endline estimates. We used this same approach for stratified analyses to assess potential effect modification by displacement status and facilitator type. We further used linear models to adjust for age and sex. Findings: Compared to baseline, every mental health, parenting, and child health outcome improved significantly at midline and endline. Mental health ratings showed endline reductions in depressive symptoms of 56.8% (95% CI: -59.0,-54.3; -1.8 days/week), and increases in hopefulness, coping with grief, and self-care, ranging from 62.0% (95% CI: 53.6,71.3; 2.2 days/week) to 77.0% (95% CI: 66.3,88.3; 2.2 days/week). Significant improvements in parenting and child health outcomes included monitoring children, reinforcing positive behavior, supporting child development, protecting child, nonviolent discipline, and child verbalizing emotions. By endline, emotional violence, physical violence, and child despondency had dropped by 57.7% (95% CI: -63.0%,-51.9; -1.3 days/week), 64.0% (95% CI: -79.0,-39.5; -0.22 days/week), and 51.9% (95% CI: -45.1,-57.9; -1.2 days/week), respectively. Outcomes stratified by displacement status remained significant across all groups, as did those according to facilitator type (lay versus professional). Interpretation: This study demonstrates preliminary evidence, using a brief survey and pre-post design as is appropriate for acute and early protracted emergency settings, of the feasibility and effectiveness of Hope Groups for war-affected Ukrainian caregivers, on improved mental health, positive parenting, and reduced violence against children.

Abstract Uncertainty can be classified as either aleatoric (intrinsic randomness) or epistemic (imperfect knowledge of parameters). The majority of frameworks assessing infectious disease risk consider only epistemic uncertainty. We only ever observe a single epidemic, and therefore cannot empirically determine aleatoric uncertainty. Here, we characterise both epistemic and aleatoric uncertainty using a time-varying general branching process. Our framework explicitly decomposes aleatoric variance into mechanistic components, quantifying the contribution to uncertainty produced by each factor in the epidemic process, and how these contributions vary over time. The aleatoric variance of an outbreak is itself a renewal equation where past variance affects future variance. We find that, superspreading is not necessary for substantial uncertainty, and profound variation in outbreak size can occur even without overdispersion in the offspring distribution (i.e. the distribution of the number of secondary infections an infected person produces). Aleatoric forecasting uncertainty grows dynamically and rapidly, and so forecasting using only epistemic uncertainty is a significant underestimate. Therefore, failure to account for aleatoric uncertainty will ensure that policymakers are misled about the substantially higher true extent of potential risk. We demonstrate our method, and the extent to which potential risk is underestimated, using two historical examples.

Caffeine is a compound found in the leaves, seeds and fruits of plants such as coffee and guarana. The aim of the systematic review was to determine the influence of caffeine on cardiorespiratory functions and physical performance. The method was the collection of relevant literature in the period from 2011-2022, and their analysis. The results clearly show the benefit and positive influence of caffeine on both investigated areas. The recommended consumption of caffeine should be higher than 75mg in order to expect positive changes and effects. Also, doses above 600mg should not be exceeded due to side effects, especially on the heart. It is necessary to consume caffeine for at least 45 minutes before the planned activity to ensure complete absorption. Caffeine is a very powerful supplement, it is only necessary to take care of the method and amount of dosage.

Abstract Lead halide perovskites are new key materials in various application areas such as high efficiency photovoltaics, lighting, and photodetectors. Doping with Mn, which is known to enhance the stability, has recently been reported to lead to ferromagnetism below 25 K in methylammonium lead iodide (MAPbI3) mediated by superexchange. Two most recent reports confirm ferromagnetism up to room temperature but mediated by double exchange between Mn2+ and Mn3+ ions. Here we investigate a wide concentration range of MAMn x Pb1−x I3 and Mn-doped triple-cation thin films by soft X-ray absorption, X-ray magnetic circular dichroism, and quantum interference device magnetometry. The X-ray absorption lineshape shows clearly an almost pure Mn2+ configuration, confirmed by a sum-rule analysis of the dichroism spectra. A remanent magnetization is not observed down to 2 K. Curie-Weiss fits to the magnetization yield negative Curie temperatures. All data show consistently that significant double exchange and ferromagnetism do not occur. Our results show that Mn is not suitable for creating ferromagnetism in lead halide perovskites.

Abstract The number of tRNA isodecoders has increased dramatically in mammals, but the specific molecular and physiological reasons for this expansion remain elusive. To address this fundamental question we used CRISPR editing to knockout the seven-membered phenylalanine tRNA gene family in mice, both individually and combinatorially. Using ATAC-Seq, RNA-seq, ribo-profiling and proteomics we observed distinct molecular consequences of single tRNA deletions. We show that tRNA-Phe-1-1 is required for neuronal function and its loss is partially compensated by increased expression of other tRNAs but results in mistranslation. In contrast, the other tRNA-Phe isodecoder genes buffer the loss of each of the remaining six tRNA-Phe genes. In the tRNA-Phe gene family, the expression of at least six tRNA-Phe alleles is required for embryonic viability and tRNA-Phe-1-1 is most important for development and survival. Our results reveal that the multi-copy configuration of tRNA genes is required to buffer translation and viability in mammals.

Abstract Coronavirus disease (COVID-19) is a contagious respiratory disease caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, a global COVID-19 pandemic was declared by the World Health Organization (WHO). As of February 2023, almost 670 million cases and 6,8 million deaths have been confirmed worldwide. Coronaviruses, including SARS-CoV-2, contain a single-stranded RNA genome enclosed in a viral capsid consisting of four structural proteins: the nucleocapsid (N) protein, in the ribonucleoprotein core, the spike (S) protein, the envelope (E) protein, and the membrane (M) protein, embedded in the surface envelope. In particular, the E protein is a poorly characterized viroporin with high identity amongst all the β-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) and a low mutation rate. Here, we focused our attention on the study of SARS-CoV-2 E and M proteins, and we found a general perturbation of the host cell calcium (Ca2+) homeostasis and a selective rearrangement of the interorganelle contact sites. In vitro and in vivo biochemical analyses revealed that the binding of specific nanobodies to soluble regions of SARS-CoV-2 E protein reversed the observed phenotypes, suggesting that the E protein might be an important therapeutic candidate not only for vaccine development, but also for the clinical management of COVID designing drug regimens that, so far, are very limited.

Abstract Prostate cancer is the most commonly diagnosed malignancy and the third leading cause of cancer deaths. GWAS have identified variants associated with prostate cancer susceptibility; however, mechanistic and functional validation of these mutations is lacking. We used CRISPR‐Cas9 genome editing to introduce a missense variant identified in the ELAC2 gene, which encodes a dually localised nuclear and mitochondrial RNA processing enzyme, into the mouse Elac2 gene as well as to generate a prostate‐specific knockout of Elac2. These mutations caused enlargement and inflammation of the prostate and nodule formation. The Elac2 variant or knockout mice on the background of the transgenic adenocarcinoma of the mouse prostate (TRAMP) model show that Elac2 mutation with a secondary genetic insult exacerbated the onset and progression of prostate cancer. Multiomic profiling revealed defects in energy metabolism that activated proinflammatory and tumorigenic pathways as a consequence of impaired noncoding RNA processing and reduced protein synthesis. Our physiologically relevant models show that the ELAC2 variant is a predisposing factor for prostate cancer and identify changes that underlie the pathogenesis of this cancer.

Background: According to the definition of the German Federal Statistical Office, about every fourth person living in Germany has a so-called migration background (MB), i.e., the person or at least one of their parents was born without German citizenship. However, MB has been defined differently in many studies. Also, the MB summarises people in different living situations, making differentiated analysis in health science more difficult. This article formulates recommendations for the collection and analysis of migration-related, as well as social and structural, determinants of health. Indicators for capturing relevant determinants of health: As part of the Improving Health Monitoring in Migrant Populations project (IMIRA), the previous approaches to operationalise and measure migration-related determinants were revised based on literature research and exchange formats, such as workshops, meetings, congress contributions, etc. Instead of MB, the country of birth of the respondents and their parents, duration of residence, citizenship(s), residence status, and German language proficiency should be recorded as minimum indicators and analysed as individual variables. Further social and structural determinants, such as socioeconomic position, working and housing conditions, or self-reported discrimination, should be included. Conclusions: In order to describe health inequalities and to specifically identify the needs of people with a history of migration, a mutual and differentiated consideration of migration-related and social determinants of health is essential.

Datio in solutum, ispunjenje obveze davanjem umjesto isplate, važan je institut ugovornog obveznog prava. Dužnik će tim putem ispuniti svoju ugovornu obvezu na drukčiji način od ugovorenoga, no uvijek uz suglasnost i pristanak vjerovnika. Datio in solutum je, stoga pravni posao, ugovor. Ispunjenjem ovoga drugog (drugotnog) predmeta obveze - obveza prestaje kada vjerovnik to primi. No, nije svako primanje uvijek isto i problem nastaje kada to primanje nije i fizičko primanje novca (na što najčešće glasi izvorna, prvotna obveza). Slučajevi davanja mjenice, zemljišnoknjižnoga prijenosa prava vlasništva na nekretninama ili stjecanja dionica kao primjera ispunjenja drugotnih obveza vrlo zorno pokazuju nastali problem. Ne bi se, naime, smjelo dogoditi da je ugovor izvršen, da je vjerovnik primio drugotnu obvezu, a da efektivno nije dobio ništa.

Summary: Platelets are anucleate blood cells that contain mitochondria and regulate blood clotting in response to injury. Mitochondria contain their own gene expression machinery that relies on nuclear-encoded factors for the biogenesis of the oxidative phosphorylation system to produce energy required for thrombosis. The autonomy of the mitochondrial gene expression machinery from the nucleus is unclear, and platelets provide a valuable model to understand its importance in anucleate cells. Here, we conditionally delete Elac2, Ptcd1, or Mtif3 in platelets, which are essential for mitochondrial gene expression at the level of RNA processing, stability, or translation, respectively. Loss of ELAC2, PTCD1, or MTIF3 leads to increased megakaryocyte ploidy, elevated circulating levels of reticulated platelets, thrombocytopenia, and consequent extended bleeding time. Impaired mitochondrial gene expression reduces agonist-induced platelet activation. Transcriptomic and proteomic analyses show that mitochondrial gene expression is required for fibrinolysis, hemostasis, and blood coagulation in response to injury.

Objetivo: Describir las características del uso de una app preventiva en la población peruana durante su primer año de operaciones, en el periodo comprendido entre el 2019 y 2020. Materiales y métodos: Estudio de tipo descriptivo, transversal y retrospectivo, donde se revisó la base de datos de la app preventiva Salud Total respecto a las características demográficas y forma de uso en la población peruana durante su primer año de operaciones. Se analizaron las variables sociodemográficas (sexo y edad) y las formas de uso (los datos de salud ingresados, los hallazgos patológicos encontrados, la recurrencia de uso y el tipo y la cantidad de servicios solicitados). El análisis y procesamiento de los datos descriptivos se realizaron con el programa Microsoft Excel. Resultados: El número de usuarios que descargaron y se registraron en la app fue 9737 personas. Con respecto al sexo, la proporción fue similar, y el grupo etario predominante fue entre 21 y 50 años. Se obtuvieron 2304 datos de salud que los usuarios registraron voluntariamente, de los cuales los más reportados fueron el peso y la talla (45,3 %), seguidos de la presión arterial (20,4 %), la hemoglobina (17,1 %) y la circunferencia abdominal. Se encontraron hallazgos patológicos en los datos registrados tales como la presión arterial elevada (25,7 %) y el peso elevado (58,5 %), entre otros. Asimismo, los usuarios solicitaron por medio de la app un total de 1072 servicios de salud de diversos tipos, entre los cuales destacan la atención médica (58 %) y el laboratorio clínico (32 %). Conclusiones: Los usuarios pudieron registrarse e interactuar con una app preventiva con el fin de controlar su bienestar, y la usaron tanto para añadir sus datos de salud como para solicitar servicios médicos de forma remota, lo que puede significar una nueva herramienta de intervención para direccionar acciones preventivas, la atención oportuna de enfermedades y una nueva fuente de datos para la investigación en salud.

Background. Based on the fundamental principles of training, the methodology that each coach develops in the planning of sessions can be effective in improving the performance of their athletes. Study purpose. Therefore, the general objective pursued in this study was to find out the type of work carried out by the coaching staffs in their different teams/clubs. Materials and methods. For this work, a descriptive cross-sectional study was carried out on a sample of 517 coaches from different divisions and nationalities. To characterise the sample, descriptive measures were used and Pearson’s chi-square was used to study whether there is a relationship between the variables studied. All statistical analyses were performed with Stata and statistical significance was always set at a p-value < 0.05. Results. The results indicated that the methodology preferred by the coaches for working on the technique was the Coerver and analytical methods. The global and analytical methods were the most used on average by the coaches for tactical work. The coaches, regardless of the division or category in which they train, indicated that strength is the most important capacity to work on. Conclusions. The results of this study can be very useful for future coaching staffs when distributing training sessions and workloads.

(1) Background: Sport goals, although widely recognised as crucial for motivation and performance in sport, are multifaceted and can be difficult to measure directly. The present research aims to validate the 3 × 2 achievement goals questionnaire of Mascret in Spanish in a population of athletes. (2) Method: By using a latent factor approach, it is possible to identify the underlying dimensions of these goals and to better understand how they are structured. For this purpose, this questionnaire has been translated and compared with the life satisfaction scale. An exploration of the multifaceted nature of sport goals has been carried out using structural equation modelling. A total of 580 athletes (463 males and 216 females, M = 21.5, SD = 2.36) from different sport disciplines and from 12 autonomous communities in Spain participated in the research. (3) Results: The results show that the questionnaire presents a high scale reliability and that all items contribute significantly to the internal consistency of the scale. (4) Conclusions: The adaptation of this scale to the Spanish population of athletes can be a valid and useful tool to measure and understand motivation and goals in the sport context.

Context Callistemon citrinus Skeels (Myrtaceae) exhibits many biological activities.Objective This study analyzes for the first time, the toxicity, obesogenic, and antioxidant effects of C. citrinus in rats fed with a high fat-fructose diet (HFFD).Materials and methods Four studies using male Wistar rats were conducted: (a) 7 groups (n = 3): control (corn oil) and ethanol extract of C. citrinus leaf (single oral dose at 100–4000 mg/kg) for acute toxicity; (b) 2 groups (n = 8): control (corn oil) and C. citrinus (1000 mg/kg/day) for 28 days for subacute toxicity; (c) 3 groups (n = 4) with single oral dose of lipid emulsion: control (lipid emulsion), C. citrinus and orlistat (250 and 50 mg/kg, respectively) for lipid absorption; (d) 4 groups (n = 6): control (normal diet) and 3 groups fed with HFFD: HFFD only, C. citrinus and simvastatin (oral dose 250 and 3 mg/kg, respectively) for 13 weeks. Antioxidant enzymes and biomarkers were evaluated and inhibition of pancreatic lipase was determined in vitro.Results Toxicological studies of C. citrinus showed no differences in biochemical parameters and lethal dose (LD50) was higher than 4000 mg/kg. C. citrinus inhibited pancreatic lipase activity, with IC50 of 392.00 µg/mL, and decreased lipid absorption by 70%. Additionally, it reduced the body weight 22%, restored the activities of antioxidant enzymes, and reduced the biomarkers of oxidative stress.Conclusions Callistemon citrinus showed an effect against oxidative stress by reducing biomarkers and induced antioxidant system, without toxic effects.

Up to 40% of neuro-oncological patients already deal with high levels of distress under conventional circumstances. Due to COVID-19, pandemic hospital visitor rules have been restricted and patients did not receive the same level of supporting caregiver network as before COVID. The aim of the present study was to analyse the impact of the COVID pandemic on the prevalence of distress, anxiety and depression in neuro-oncological patients. Patients admitted for brain tumour surgery were screened regarding distress, anxiety and depression. Furthermore, aspects of patients’ quality of life and clinical data were covered. Retrospectively available data of patients treated pre-pandemic (group A) and throughout the COVID-19 pandemic (group B) were statistically analysed using Chi-square tests and independent-sample t-tests, and regression analysis was performed to support statistical findings. Data from 110 patients were available. In all, 48 patients were included pre-COVID-19 and 62 during the COVID-19 pandemic. The authors found no significant difference between pre-COVID-19 prevalence of distress (p = 0.112), anxiety (p = 0.385) or depression (p = 0.084). Regression analyses additionally did not show any significant influence of COVID-19 on the above analysed parameter. Analyses of our cohort’s data could not underline the negative impact of COVID-19 restrictions, shortcuts of professional and remodelled caregiver support on psycho-oncological outcomes.

Sleep-disordered breathing is a risk factor for Alzheimer’s disease. Here the authors use mesopontine tegmentum lesion to model sleep disordered breathing in a mouse model of Alzheimer’s disease, and find that some features of the Alzheimer’s disease-like phenotype are exacerbated.

Abstract Background Neuropathic pain is experienced worldwide by patients suffering from nerve injuries, infectious or metabolic diseases or chemotherapy. However, the treatment options are still limited because of low efficacy and sometimes severe side effects. Recently, the deficiency of FKBP51 was shown to relieve chronic pain, revealing FKBP51 as a potential therapeutic target. However, a specific and potent FKBP51 inhibitor was not available until recently which hampered targeting of FKBP51. Methods In this study, we used the well-established and robust spared nerve injury model to analyze the effect of SAFit2 on nerve injury-induced neuropathic pain and to elucidate its pharmacodynamics profile. Therefore, the mice were treated with 10 mg/kg SAFit2 after surgery, the mice behavior was assessed over 21 days and biochemical analysis were performed after 14 and 21 days. Furthermore, the impact of SAFit2 on sensory neurons and macrophages was investigated in vitro. Results Here, we show that the FKBP51 inhibitor SAFit2 ameliorates nerve injury-induced neuropathic pain in vivo by reducing neuroinflammation. SAFit2 reduces the infiltration of immune cells into neuronal tissue and counteracts the increased NF-κB pathway activation which leads to reduced cytokine and chemokine levels in the DRGs and spinal cord. In addition, SAFit2 desensitizes the pain-relevant TRPV1 channel and subsequently reduces the release of pro-inflammatory neuropeptides from sensory neurons. Conclusions SAFit2 ameliorates neuroinflammation and counteracts enhanced neuronal activity after nerve injury leading to an amelioration of nerve injury-induced neuropathic pain. Based on these findings, SAFit2 constitutes as a novel and promising drug candidate for the treatment of nerve injury-induced neuropathic pain.

Objectives: Few studies have assessed whether refugees’ health is associated with accommodation characteristics. We aimed to devise a typology of refugee accommodation based on variables on the accommodation and its physical context before assessing its association with health in multivariate analyses.Methods: We performed a cluster analysis based on a hierarchal, agglomerative clustering algorithm using Euclidean Distance and Ward’s method. We analysed accommodation clusters based on number of inhabitants, degree of housing deterioration, urbanity of location (urban/rural distinction), and remoteness (walking distance to shops, medical or administrative services). In total, we analysed health and accommodation data of 412 refugees and asylum seekers from 58 different accommodation facilities in the federal state of Baden-Württemberg in the south-west of Germany.Results: Accommodations with a moderate occupation, lowest levels of deterioration, and a central urban location showed the best health outcomes in terms of subjective general health status, depression, and generalized anxiety disorder (GAD). Associations were strongest for GAD and weakest for depression.Conclusion: Our findings inform policymakers on layout and location of refugee collective accommodation centres.

A subset of mitochondrial transcripts is not flanked by tRNAs and thus does not conform to the canonical mode of processing. Here, Clemente et al. demonstrate that phosphatase activity of ANGEL2 is required for correct processing of these transcripts.

Machine learning of multi-modal data, including transcriptomic, proteomic, structural and physical interaction, predicts genes and molecular pathways involved in RNA methylation in humans.

This paper presents methods for the actuation, measurement, and control of a magnetic resonance imaging- and radiation-compatible single-axis translatory actuation system. As an exemplary demanding use case, the axis is developed for a robotic phantom for evaluating emitted radiation doses of radiotherapy devices. For this, the robot has to follow given three-dimensional trajectories of patients’ movements with an accuracy of 200 µm. For enabling use of magnetic resonance imaging, actuation of the robot is realized by hydraulic transmission without any metal parts or electrical components at the imaging side. The hydraulic axis is developed, built-up, and tested. In order to compensate for deviations from the targeted actuation trajectory resulting from tolerances, friction, and non-linearities in the system, a combination of photogrammetric measurement and iterative learning control is applied. The developed photogrammetric system is capable of determining the robot’s position with systematic errors of 35 µm and stochastic errors of 0.3 µm. Different types of iterative learning control methods are applied, parameterized, and tested. With this, the hydraulically actuated axis is able to follow given trajectories with maximum errors below 130 µm.

Enterococcus faecalis es un microorganismo considerado como agente etiológico de diferentes procesos infecciosos, tales como: infecciones de la piel, osteomielitis, neumonía, infecciones del tracto urinario, endocarditis, entre otros, siendo los pacientes nosocomiales una población más vulnerable a esta bacteria. El objetivo del presente estudio fue evaluar la actividad antibacteriana in vitro de extractos metanólicos y clorofórmicos de las plantas Peperomia galioides, Otholobium mexicanum, Zingiber officinale y Rosmarinus officinalis frente a Enterococcus faecalis ATCC 29212, Enterococcus faecalis ATCC 51299 (resistente a la vancomicina) y una cepa clínica de Enterococcus faecalis. Para la evaluación de esta bioactividad se utilizó la metodología de microdilución y puntos de corte establecidos por la CLSI (2021) para Enterococcus faecalis y los resultados obtenidos se expresaron en IC50. El IC50 de mayor interés se obtuvo con el extracto clorofórmico de Otholobium mexicanum frente a la cepa clínica, siendo de 2.050 μg/mL, considerándose como muy activo. El IC50 más destacable de Peperomia galioides se obtuvo con el extracto clorofórmico frente a la cepa clínica con un valor de 8.248 μg/mL, considerándolo como ligeramente activo. Para Rosmarinus officinalis, solo el extracto metanólico mostró una ligera actividad antibacteriana con un IC50 de 20.234 μg/mL frente a Enterococcus faecalis ATCC 29212. Finalmente, todos los extractos de Zingiber officinale no mostraron actividad frente a las concentraciones probadas de las diferentes cepas de Enterococcus faecalis. Los resultados obtenidos son de gran relevancia ya que pueden ser aplicados para la producción de antimicrobianos a partir de fuentes naturales que podrían tener aplicación dentro de la industria farmacéutica, veterinaria o agrícola.

Abstract Background The COVID-19 pandemic and its collateral damage severely impact health systems globally and risk to worsen the malaria situation in endemic countries. Malaria is a leading cause of morbidity and mortality in Ghana. This study aims to describe the potential effects of the COVID-19 pandemic on malaria cases observed in health facilities in the Northern Region of Ghana. Methods Monthly routine data from the District Health Information Management System II (DHIMS2) of the Northern Region of Ghana were analysed. Overall outpatient department visits (OPD) and malaria case rates from the years 2015–2019 were compared to the corresponding data of the year 2020. Results Compared to the corresponding periods of the years 2015–2019, overall visits and malaria cases in paediatric and adult OPDs in northern Ghana decreased in March and April 2020, when major movement and social restrictions were implemented in response to the pandemic. Cases slightly rebounded afterwards in 2020, but stayed below the average of the previous years. Malaria data from inpatient departments showed a similar but more pronounced trend when compared to OPDs. In pregnant women, however, malaria cases in OPDs increased after the first COVID-19 wave. Conclusions The findings from this study show that the COVID-19 pandemic affects the malaria burden in health facilities of northern Ghana, with declines in inpatient and outpatient rates except for pregnant women. They may have experienced reduced access to insecticide-treated nets and intermittent preventive malaria treatment in pregnancy, resulting in subsequent higher malaria morbidity. Further data, particularly from community-based studies and ideally complemented by qualitative research, are needed to fully determine the impact of the pandemic on the malaria situation in Africa.

The ability to alter the genomes of living cells is key to understanding how genes influence the functions of organisms and will be critical to modify living systems for useful purposes. Here, the authors use computational design to discover Cas9 enzymes with increased activity.

Abstract Background Populations have varying needs and expectations concerning health care that result from diversity characteristics such as a migrant background, gender identity, disability, and age. These needs and expectations must be considered to ensure adequate utilization and quality of health services. Approaches to address diversity do exist, however, little is known about the extent to which they are implemented by health care facilities. The present study aims to examine, which measures and structures hospitals in Germany employ to address diversity, as well as which barriers they encounter in doing so. Methods A mixed-mode survey among administration managers of all registered German hospitals (excluding rehabilitation hospitals; n = 1125) was conducted between May and October 2019 using pen-and-paper and online questionnaires. Results were analyzed descriptively. Results Data from n = 112 hospitals were available. While 57.1% of hospitals addressed diversity in their mission statement and 59.9% included diversity considerations in quality management, dedicated working groups and diversity commissioners were less prevalent (15.2% each). The majority of hospitals offered multi-lingual admission and exit interviews (59.8%), treatments or therapies (57.1%), but only few had multi-lingual meal plans (12.5%) and seminars or presentations (11.6%). While 41.1% of the hospitals offered treatment and/or nursing exclusively by staff of the same sex, only 17.0% offered group therapies for both sexes separately. According to the managers, the main barriers were a lack of financial resources (54.5%), a lack of incentives from the funding providers (49.1%), and organizational difficulties (45.5%). Other reported barriers were a lack of conviction of the necessity among decision makers (28.6%) and a lack of motivation among staff members (19.6%). Conclusions Administration managers from only a small proportion of hospitals participated in our survey on diversity sensitivity. Even hospitals of those who did are currently not adequately addressing the diversity of staff members and patients. Most hospitals address diversity on an ideational level, practical measures are not widely implemented. Existing measures suggest that most hospitals have no overarching concept to address diversity in a broader sense. The main reported barriers relate to economic aspects, a lack of support in organizing and implementing corresponding measures and a lack of awareness or motivation.

Abstract Background The mapping of immigration-related health inequalities remains challenging, since immigrant populations constitute a heterogenous socially constructed group whose health experiences differ by social determinants of health. In spite of the increasing awareness that population mobility and its effects on health are highly gendered, an explicit gender perspective in epidemiology is often lacking or limited. Methods To map inequalities in self-reported physical and mental health in Germany at the intersections of sex, gendered practices and immigration status, we used data from the German Socioeconomic Panel (SOEP) and applied an intercategorical intersectional approach conducting multilevel linear regression models. We differentiated between sex (male/female) as reported in the survey and gendered social practices, quantified through a gender score (on a femininity-masculinity continuum). Results We included 20,897 participants in our analyses. We saw an intersectional gradient for physical and mental health. Compared to the reference group, i.e. non-immigrant males with masculine gendered practices, physical and mental health steadily decreased in the intersectional groups that did not embody one or more of these social positions. The highest decreases in health were observed in the intersectional group of immigrant females with feminine gendered practices for physical health (-1,36; 95% CI [-2,09; -0,64]) and among non-immigrant females with feminine practices for mental health (-2,51; 95% CI [-3,01; -2,01]). Conclusions Patterns of physical and mental health vary along the intersectional axes of sex, gendered practices and immigration status. These findings highlight the relevance of intersections in describing population health statuses and emphasise the need to take them into account when designing public health policies aiming at effectively reducing health inequalities.