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Lana Alhalaseh,1,* Hala Makahleh,1,* Bashayer Al-Saleem,1,* Farah Al-Omran,1,* Birgitte Schoenmakers2,* 1Department of Family and Community Medicine, School of Medicine, The University of Jordan, Amman, Jordan; 2Department of Public Health and Primary Care, Katholieke Universiteit Leuven, Leuven, Belgium*These authors contributed equally to this workCorrespondence: Lana Alhalaseh, P O Box 851182 Sweifieh, Amman, 11185, Jordan, Tel +962-798506513, Fax +962-6-5355 522, Email l.halaseh@ju.edu.joPurpose: Geriatric syndromes (GS) are prevalent in the older population, with an impact on morbidity and disability. This study aimed to investigate the prevalence of functional dependence and ten GS in community older adults and to examine the different associations between these syndromes and sociodemographic variables and their impact on functional dependence.Patients and Methods: A cross-sectional study of 342 outpatients seen at the geriatric clinic in the period 2015– 2023.Results: The mean age was 75± 7.4. One-third had functional dependence and 96.2% had at least one GS. The mean number of GS was 3.11± 1.74, ranging from 2.56± 1.67 in the 60s to 3.55± 1.70 in octogenarians. The most common GS found were polypharmacy (79.5%), musculoskeletal pain (49.7%), and Major Neurocognitive Disorder (MND) (32.7%). Polypharmacy was significantly associated with female sex and chronic pain, whereas sensory impairment was associated with male sex. MND, dizziness, and urinary incontinence were the only GS that significantly predicted functional dependence and were typically associated with increasing age.Conclusion: Functional dependence increases as individuals age, paralleled by increases in MND, urinary incontinence, dizziness, sensory impairment, and constipation. Notably, only MND, incontinence, depression, and dizziness were significant predictors of functional dependence. Consequently, it is imperative to screen older adults presenting with these syndromes for early signs of functional decline to optimize their function and avert subsequent dependence, morbidity, and mortality.Keywords: geriatric syndromes, functional dependence, elderly/older, ADL, Katz Index

Linguistic judgment experiments typically elicit judgments in terms of the acceptability or surface probability of a sentence. There is evidence that the dimension of the scale on which sentences are judged influences the outcome of the experiment, but to date this evidence is only limited. This is not a trivial matter, as the elicited judgment data are increasingly considered the basis for inferences about linguistic representation. The present study investigates whether the dimension of the scale influences judgments. Sentences are judged in one of three dimensions: acceptability, probability, or aesthetics. Two distinct sets of experimental items are tested; one with cases of stigmatized variation (violations of the prescriptive norm) and another with cases of non-stigmatized variation (middle-field scrambling) in Dutch. The results show that participants take into account the scale dimension, both in stigmatized and in non-stigmatized variation. The results for stigmatized variation reflect a certain degree of conscious reflection based on the judgment scale; the effects in non-stigmatized variation, by contrast, are only main effects of instruction without changes in the relative pattern of judgments between conditions. These findings corroborate the idea that linguistic judgments of non-stigmatized variation are not the result of introspection in the technical sense, but automatic, multi-dimensional responses to a stimulus.

Anne Schoenmakers,1 Liesbeth Mieras,1 Teky Budiawan,2 Wim H van Brakel1 1NLR, Amsterdam, The Netherlands; 2NLR, Jakarta, IndonesiaCorrespondence: Anne Schoenmakers Email a.schoenmakers@nlrinternational.orgObjective: Annually, over 200,000 people are diagnosed with leprosy, also called Hansen’s disease. This number has been relatively stable over the past years. Progress has been made in the fields of chemoprophylaxis and immunoprophylaxis to prevent leprosy, with a primary focus on close contacts of patients. In this descriptive meta-analysis, we summarize the evidence and identify knowledge gaps regarding post-exposure prophylaxis against leprosy.Methods: A systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was conducted by searching the medical scientific databases Cochrane, Embase, Pubmed/MEDLINE, Research Gate, Scopus and Web of Science on Jan. 22, 2020, using a combination of synonyms for index terms in four languages: “leprosy” and “population” or “contacts” and “prevention” or “prophylaxis.” Subsequently, Infolep.org and Google Scholar were searched and the "snowball method" was used to retrieve other potentially relevant literature. The found articles were screened for eligibility using predetermined inclusion and exclusion criteria.Results: After deduplication, 1,515 articles were screened, and 125 articles were included in this descriptive meta-analysis. Immunoprophylaxis by bacillus Calmette-Guérin (BCG) vaccination is known to provide protection against leprosy. The protection it offers is higher in household contacts of leprosy patients compared with the general population and is seen to decline over time. Contact follow-up screening is important in the first period after BCG administration, as a substantial number of new leprosy patients presents three months post-vaccination. Evidence for the benefit of re-vaccination is conflicting. The World Health Organization (WHO) included BCG in its Guidelines for the Diagnosis, Treatment and Prevention of Leprosy by stating that BCG at birth should be maintained in at least all leprosy high-burden regions. Literature shows that several vaccination interventions with other immunoprophylactic agents demonstrate similar or slightly less efficacy in leprosy risk reduction compared with BCG. However, most of these studies do not exclusively focus on post-exposure prophylaxis. Two vaccines are considered future candidates for leprosy prophylaxis: Mycobacterium indicus pranii (MiP) and LepVax. For chemoprophylaxis, trials were performed with dapsone/acedapsone, rifampicin, and ROM, a combination of rifampicin, ofloxacin, and minocycline. Single-dose rifampicin is favored as post-exposure prophylaxis, abbreviated as SDR-PEP. It demonstrated a protective effect of 57% in the first two years after administration to contacts of leprosy patients. It is inexpensive, and adverse events are rare. The risk of SDR-PEP inducing rifampicin resistance is considered negligible, but continuous monitoring in accordance with WHO policies should be encouraged. The integration of contact screening and SDR-PEP administration into different leprosy control programs was found to be feasible and well accepted. Since 2018, SDR-PEP is included in the WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy.Conclusion: Progress has been made in the areas of chemoprophylaxis and immunoprophylaxis to prevent leprosy in contacts of patients. Investing in vaccine studies, like LepVax and MiP, and increasing harmonization between tuberculosis (TB) and leprosy research groups is important. SDR-PEP is promising as a chemoprophylactic agent, and further implementation should be promoted. More chemoprophylaxis research is needed on: enhanced medication regimens; interventions in varying (epidemiological) settings, including focal mass drug administration (fMDA); specific approaches per contact type; combinations with screening variations and field-friendly rapid tests, if available in the future; community and health staff education; ongoing antibiotic resistance surveillance; and administering chemoprophylaxis with SDR-PEP prior to BCG administration. Additionally, both leprosy prophylactic drug registration nationally and prophylactic drug availability globally at low or no cost are important for the implementation and further upscaling of preventive measures against leprosy, such as SDR-PEP and new vaccines.Keywords: leprosy, chemoprophylaxis, fMDA, immunoprophylaxis, MDA, prevention, post-exposure prophylaxis, SDR-PEP, rifampicin, vaccine, BCG, MiP, Mw, LepVax, M. leprae, neglected tropical diseases, NTDs

Liver X receptor-α (LXRα) regulates cellular cholesterol abundance and potently activates hepatic lipogenesis. Here we show that at least 1 in 450 people in the UK Biobank carry functionally impaired mutations in LXRα, which is associated with biochemical evidence of hepatic dysfunction. On a western diet, male and female mice homozygous for a dominant negative mutation in LXRα have elevated liver cholesterol, diffuse cholesterol crystal accumulation and develop severe hepatitis and fibrosis, despite reduced liver triglyceride and no steatosis. This phenotype does not occur on low-cholesterol diets and can be prevented by hepatocyte-specific overexpression of LXRα. LXRα knockout mice exhibit a milder phenotype with regional variation in cholesterol crystal deposition and inflammation inversely correlating with steatosis. In summary, LXRα is necessary for the maintenance of hepatocyte health, likely due to regulation of cellular cholesterol content. The inverse association between steatosis and both inflammation and cholesterol crystallization may represent a protective action of hepatic lipogenesis in the context of excess hepatic cholesterol.

BackgroundPericonception lifestyle behaviors affect maternal, paternal, offspring, and transgenerational health outcomes. Previous research in other target populations has shown that personalized lifestyle interventions, in which face-to-face counseling and eHealth (“blended care”) are combined, may effectively target these lifestyle behaviors. ObjectiveWe aimed to assess the effectiveness of a periconceptional lifestyle intervention on the improvement of specific lifestyle components. MethodsA blended periconception lifestyle care approach was developed, combining the outpatient lifestyle counseling service “Healthy Pregnancy” with the eHealth platform “Smarter Pregnancy” (www.smarterpregnancy.co.uk) in which lifestyle was coached for 24 weeks. All couples contemplating pregnancy or already pregnant (≤12 weeks of gestation) who visited the outpatient clinics of the Department of Obstetrics and Gynecology at the Erasmus University Medical Center (Erasmus MC), Rotterdam, the Netherlands, between June and December 2018, were invited to participate. We measured changes in lifestyle behaviors at weeks 12 and 24 compared with baseline. Generalized estimating equations were used to analyze the changes in lifestyle behaviors over time. Subgroup analyses were performed for women with obesity (BMI ≥30 kg/m2), women pregnant at the start of the intervention, and those participating as a couple. ResultsA total of 539 women were screened for eligibility, and 450 women and 61 men received the blended periconception intervention. Among the participating women, 58.4% (263/450) were included in the preconception period. Moreover, 78.9% (403/511) of the included participants completed the online lifestyle coaching. At baseline, at least one poor lifestyle behavior was present in most women (379/450, 84.2%) and men (58/61, 95.1%). In the total group, median fruit intake increased from 1.8 to 2.2 pieces/day (P

Texts about fictional characters are often written in a third person singular (3SG) perspective. In a self-paced reading study, Child et al. (2018) found that emotional information is processed more easily when the narrative uses second person singular (2SG) rather than 3SG. In the current study, we explore how 2SG and 3SG are processed in Dutch. Because Dutch is a language with a formal-informal distinction in 2SG, we also contrast formal 2SG-V (e.g., u, 'you') to informal 2SG-T (e.g., jij, 'you') forms. We find a main effect of perspective on target processing, with 2SG read faster than 3SG. In contrast, spillover regions (three words following the target) are read slower following 2SG than 3SG, and spillover regions were read slower following 2SG-V than following 2SG-T. This means that processing emotional narratives through a 2SG perspectives induces a processing cost compared to 3SG perspectives, and this increases with formal 2SG.

Aortic aneurysms, which may dissect or rupture acutely and be lethal, can be a part of multisystem disorders that have a heritable basis. We report four patients with deficiency of selenocysteine-containing proteins due to selenocysteine Insertion Sequence Binding Protein 2 (SECISBP2) mutations who show early-onset, progressive, aneurysmal dilatation of the ascending aorta due to cystic medial necrosis. Zebrafish and male mice with global or vascular smooth muscle cell (VSMC)-targeted disruption of Secisbp2 respectively show similar aortopathy. Aortas from patients and animal models exhibit raised cellular reactive oxygen species, oxidative DNA damage and VSMC apoptosis. Antioxidant exposure or chelation of iron prevents oxidative damage in patients cells and aortopathy in the zebrafish model. Our observations suggest a key role for oxidative stress and cell death, including via ferroptosis, in mediating aortic degeneration.

Extreme response style (ERS), the tendency of participants to select extreme item categories regardless of the item content, has frequently been found to decrease the validity of Likert-type questionnaire results. For this reason, various item response theory (IRT) models have been proposed to model ERS and correct for it. Comparisons of these models are however rare in the literature, especially in the context of cross-cultural comparisons, where ERS is even more relevant due to cultural differences between groups. To remedy this issue, the current article examines two frequently used IRT models that can be estimated using standard software: a multidimensional nominal response model (MNRM) and a IRTree model. Studying conceptual differences between these models reveals that they differ substantially in their conceptualization of ERS. These differences result in different category probabilities between the models. To evaluate the impact of these differences in a multigroup context, a simulation study is conducted. Our results show that when the groups differ in their average ERS, the IRTree model and MNRM can drastically differ in their conclusions about the size and presence of differences in the substantive trait between these groups. An empirical example is given and implications for the future use of both models and the conceptualization of ERS are discussed.

Since their introduction, the notions of indistinguishability and non-malleability have been changed and extended by different authors to support different goals. In this paper, we propose new flavors of these notions, investigate their relative strengths with respect to previous notions, and provide the full picture of relationships (i.e., implications and separations) among the security notions for public-key encryption schemes. We take into account the two general security goals of indistinguishability and non-malleability, each in the message space, key space, and hybrid message-key space to find six specific goals, a couple of them, namely complete indistinguishability and key non-malleability, are new. Then for each pair of goals, coming from the indistinguishability or non-malleability classes, we prove either an implication or a separation, completing the full picture of relationships among all these security notions. The implications and separations are respectively supported by formal proofs (i.e., reductions) in the concrete-security framework and by counterexamples.