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Abstract Epilepsy imposes a substantial burden on the Democratic Republic of Congo (DRC). These challenges encompass the lack of comprehensive disease surveillance, an unresolved understanding of its pathophysiology, economic barriers limiting access to essential care, the absence of epilepsy surgical capabilities, and deeply ingrained societal stigmas. Notably, the national prevalence of epilepsy remains undetermined, with research primarily concentrating on infectious factors like Onchocerca volvulus, leaving other potential causes underexplored. Most patients lack insurance, incurring out‐of‐pocket expenses that often lead them to opt for traditional medicine rather than clinical care. Social stigma, perpetuated by common misconceptions, intensifies the social isolation experienced by individuals living with epilepsy. Additionally, surgical interventions are unavailable, and the accessibility of anti‐seizure medications and healthcare infrastructure remains inadequate. Effectively tackling these interrelated challenges requires a multifaceted approach, including conducting research into region‐specific factors contributing to epilepsy, increasing healthcare funding, subsidizing the costs of treatment, deploying mobile tools for extensive screening, launching awareness campaigns to dispel myths and reduce stigma, and promoting collaborations between traditional healers and medical practitioners to enhance local understanding and epilepsy management. Despite the difficulties, significant progress can be achieved through sustained and compassionate efforts to understand and eliminate the barriers faced by epilepsy patients in the region. This review outlines essential steps for alleviating the epilepsy burden in the DRC. Plain Language summary There are not enough resources to treat epilepsy in the DRC. PWEs struggle with stigma and the lack of money. Many of them still use traditional medicine for treatment and hold wrong beliefs about epilepsy. That is why there is a need for more resources to make the lives of PWEs better in the DRC.

Abstract Latent associations between low serum amylase and reduced plasma insulin levels and increased adiposity have been described previously in a small study of asymptomatic middle‐aged humans. In the present study, we sought to determine the nature of such changes during the longitudinal progression from metabolically normal to overt type 2 diabetes mellitus (T2DM) in nonhuman primates (NHPs), a disease that appears to be the same in both pathophysiology and underlying mechanisms as that which most commonly develops in middle‐aged adult humans. Amylase and lipase levels were characterized in 157 unrelated adult rhesus monkeys (Macaca mulatta); 38% developed T2DM while under study. In all monkeys, multivariable linear regression analysis revealed that amylase could be negatively predicted by % body fat (β −0.29; p = 0.002), age (β −0.27; p = 0.005), and HbA1c (β −0.18; p = 0.037). Amylase levels were positively predicted by lipase levels (β = 0.19; p = −0.024) in all NHPs included in the study. Amylase was significantly lower in NHPs with metabolic syndrome (p

Abstract To better understand how vocalisations are used during interactions of multiple individuals, studies are increasingly deploying on‐board devices with a microphone on each animal. The resulting recordings are extremely challenging to analyse, since microphone clocks drift non‐linearly and record the vocalisations of non‐focal individuals as well as noise. Here we address this issue with callsync, an R package designed to align recordings, detect and assign vocalisations to the caller, trace the fundamental frequency, filter out noise and perform basic analysis on the resulting clips. We present a case study where the pipeline is used on a dataset of six captive cockatiels (Nymphicus hollandicus) wearing backpack microphones. Recordings initially had a drift of ~2 min, but were aligned to within ~2 s with our package. Using callsync, we detected and assigned 2101 calls across three multi‐hour recording sessions. Two had loud beep markers in the background designed to help the manual alignment process. One contained no obvious markers, in order to demonstrate that markers were not necessary to obtain optimal alignment. We then used a function that traces the fundamental frequency and applied spectrographic cross correlation to show a possible analytical pipeline where vocal similarity is visually assessed. The callsync package can be used to go from raw recordings to a clean dataset of features. The package is designed to be modular and allows users to replace functions as they wish. We also discuss the challenges that might be faced in each step and how the available literature can provide alternatives for each step.

Abstract Aim To describe nurses' roles, involvement, and topics in shared decision‐making with older patients with dementia in acute hospitals. Design An integrative review. Methods A systematic search was performed until April 2022 in PubMed, PsychInfo, CINAHL, and Cochrane, followed by a manual search on the reference lists of relevant systematic reviews. Studies were independently screened, appraised using the Joanna Briggs Institute (JBI) methodology, and extracted by two reviewers. Results Nine studies were included. Nurses were involved as treatment team members, intermediates, or patient supporters. Nurses' roles were most explicit in the preparatory phase of shared decision‐making. The step of ‘developing tailor‐made options’ was limitedly identified. ‘Deliberating and trying options to reach a decision’ were described from an outsider's perspective in which nurses attempted to influence the decision. In conclusion, nurses primarily have a role in decision‐making by supplementing patient information. Patient and Public Contribution No Patient or Public Contribution.

Abstract Background Global migration has led to a sharp increase in the number of language‐discordant consultations (LDCs) in healthcare. Evidence on how healthcare providers (HCPs) meet migrant patients' needs while mitigating language barriers is lacking. Design Using purposive and snowball sampling, we recruited twenty‐seven Dutch HCPs (Mage = 45.07, SD = 11.46) and conducted semi‐structured interviews to collect qualitative, open‐ended data for identifying the communication strategies used with migrant patients in LDCs. We analysed the transcripts using deductive and inductive approaches (e.g., constant comparative method from Grounded Theory). Final pattern codes (i.e., key themes) were discussed among the research team until mutual agreement had been achieved. Results Five key themes emerged from the analyses: HCPs often ‘got‐by’ with (1) instrumental and (2) affective communication strategies used in language‐concordant consultations to start medical consultations. When some instrumental communication strategies were deemed ineffective (e.g., lingua franca, gesturing, etc.) to bridge language barriers, HCPs turned to (3) incorporating digital tools (e.g., Google Translate). When HCPs were unable to communicate with migrant patients at all, (4) informal, ad‐hoc and professional interpreters were involved. Finally, HCPs often (5) involved additional support to engage migrant patients to engage in treatment‐related behaviours. Discussion and Conclusions Our results highlight the importance of raising awareness among HCPs about using various combinations of different strategies. The development of a guideline indicating the optimal combination of communication strategies for different medical consultation goals may be useful in reshaping the current communication behaviour of HCPs in LDCs. Patient or Public Contribution HCPs were the study population involved in this qualitative study. Refugee health advisors, general practitioners and linguistic specialists (i.e., members of the Right2Health consortium) with experience with the Dutch healthcare system were involved throughout the development of this research. This includes a review of the research question, participant information sheet and interview topic guide as well as providing interpretations of the data and feedback to this manuscript.

Abstract Biologging devices are deployed on animals to collect ultra‐fine‐scale movement data that reveal subsecond patterns in locomotion or long‐term patterns in motion and space use. Often these two data types, although complementary, are rarely collected within the same study, given the limiting factors of memory space, power requirements and the need to retrieve stored data from animals. Biologging requires a revolutionary advancement in data networking to overcome these restrictions that constrain big data collection; for the continuous recording and remote download of fine‐scale movement and environmental data, from long‐term deployments and multiple individuals. Here, we adopt a strategy from the Internet of Things and develop the use of Wi‐Fi as a solution for big data biologging. Our ‘WildFi’ tag uses pre‐existing, or easy‐to‐set‐up, infrastructure in smartphones and Wi‐Fi gateways. We demonstrate the power of memory management and an embedded modular software architecture for functionality, including collective data retrieval at multiple gateways. We find that Wi‐Fi, together with smart embedded software, increases the retrieval efficiency of biologging data by orders of magnitude compared to other available systems: with a transmission speed of 230 kByte/s and range of ≤200 m that is 11 times faster than Bluetooth low energy and >3000 times faster than LoRaWAN. Case studies on a domestic dog (Canis lupus familiaris), aviary‐housed cockatiels (Nymphicus hollandicus) and free‐roaming pangolins (Smutsia temminckii) demonstrate the functionality of the WildFi tag for remote and robust autonomous Wi‐Fi data transmission under a range of conditions. Modularity in software and hardware allows for project‐specific tailoring beyond reconfiguring sampling parameters of a biologger, which we encourage with open‐source sharing of our architecture design. Enhanced communication between animal‐attached devices, Wi‐Fi infrastructure and smartphones, alongside smart and collaborative data retrieval, eases restrictions for big data collection in animal ecology.

Abstract Diet‐induced obesity, the metabolic syndrome, type 2 diabetes (DIO/MetS/T2DM), and their adverse sequelae have reached pandemic levels. In mice, DIO/MetS/T2DM initiation involves diet‐dependent increases in lipids that activate hepatic atypical PKC (aPKC) and thereby increase lipogenic enzymes and proinflammatory cytokines. These or other hepatic aberrations, via adverse liver‐to‐muscle cross talk, rapidly impair postreceptor insulin signaling to glucose transport in muscle. The ensuing hyperinsulinemia further activates hepatic aPKC, which first blocks the ability of Akt to suppress gluconeogenic enzyme expression, and later impairs Akt activation, further increasing hepatic glucose production. Recent findings suggest that hepatic aPKC also increases a proteolytic enzyme that degrades insulin receptors. Fortunately, all hepatic aberrations and muscle impairments are prevented/reversed by inhibition or deficiency of hepatic aPKC. But, in the absence of treatment, hyperinsulinemia induces adverse events, some by using “spare receptors” to bypass receptor defects. Thus, in brain, hyperinsulinemia increases Aβ‐plaque precursors and Alzheimer risk; in kidney, hyperinsulinemia activates the renin–angiotensin–adrenal axis, thus increasing vasoconstriction, sodium retention, and cardiovascular risk; and in liver, hyperinsulinemia increases lipogenesis, obesity, hepatosteatosis, hyperlipidemia, and cardiovascular risk. In summary, increases in hepatic aPKC are critically required for development of DIO/MetS/T2DM and its adverse sequelae, and therapeutic approaches that limit hepatic aPKC may be particularly effective.

Background We compared the dementia incidence rate between users and nonusers of oral anticoagulants (OACs) in a large cohort of primary care patients with atrial fibrillation. Methods and Results We performed a retrospective study using an Australia‐wide primary care data set, MedicineInsight. Patients aged ≥18 years and newly diagnosed with atrial fibrillation between January 1, 2010, and December 31, 2017, and with no recorded history of dementia or stroke were included and followed until December 31, 2018. We applied a propensity score for 1:1 pair matching of baseline covariates and Cox regression for comparing the dementia incidence rates for OAC users and nonusers. Data were analyzed for 18 813 patients with atrial fibrillation (aged 71.9±12.6 years, 47.1% women); 11 419 had a recorded OAC prescription for at least 80% of their follow‐up time. During the mean follow‐up time of 3.7±2.0 years, 425 patients (2.3%; 95% CI, 2.1%–2.5%) had a documented diagnosis of dementia. After propensity matching, the incidence of dementia was significantly lower in OAC users (hazard ratio [HR], 0.59; 95% CI, 0.44–0.80; P

Abstract Increasing human population growth, exurban development, and associated habitat fragmentation is accelerating the isolation of many natural areas and wildlife populations across the planet. In Tanzania, rapid and ongoing habitat conversion to agriculture has severed many of the country's former wildlife corridors between protected areas. To identify historically linked protected areas, we investigated the genetic structure and gene flow of African savanna elephants in Tanzania using microsatellite and mitochondrial DNA markers in 688 individuals sampled in 2015 and 2017. Our results indicate distinct population genetic structure within and between ecosystems across Tanzania, and reveal important priority areas for connectivity conservation. In northern Tanzania, elephants sampled from the Tarangire‐Manyara ecosystem appear marginally, yet significantly isolated from elephants sampled from the greater Serengeti ecosystem (mean FST = 0.03), where two distinct subpopulations were identified.Unexpectedly, elephants in the Lake Manyara region appear to be more closely related to those across the East African Rift wall in the Ngorongoro Conservation Area than they are to the neighboring Tarangire subpopulations. We concluded that the Rift wall has had a negligible influence on genetic differentiation up to this point, but differentiation may accelerate in the future because of ongoing loss of corridors in the area. Interestingly, relatively high genetic similarity was found between elephants in Tarangire and Ruaha although they are separated by >400 km. In southern Tanzania, there was little evidence of female‐mediated gene flow between Ruaha and Selous, probably due to the presence of the Udzungwa Mountains between them. Despite observing evidence of significant isolation, the populations of elephants we examined generally exhibited robust levels of allelic richness (mean AR = 9.96), heterozygosity (mean µHE = 0.73), and effective population sizes (mean Ne = 148). Our results may inform efforts to restore wildlife corridors between protected areas in Tanzania in order to facilitate gene flow for long‐term survival of elephants and other species.

Abstract COVID‐19 causes severe disease with poor outcomes. We tested the hypothesis that early SARS‐CoV‐2 viral infection disrupts innate immune responses. These changes may be important for understanding subsequent clinical outcomes. We obtained residual nasopharyngeal swab samples from individuals who requested COVID‐19 testing for symptoms at drive‐through COVID‐19 clinical testing sites operated by the University of Utah. We applied multiplex immunoassays, real‐time polymerase chain reaction assays and quantitative proteomics to 20 virus‐positive and 20 virus‐negative samples. ACE‐2 transcripts increased with infection (OR =17.4, 95% CI [CI] =4.78–63.8) and increasing viral N1 protein transcript load (OR =1.16, CI =1.10–1.23). Transcripts for two interferons (IFN) were elevated, IFN‐λ1 (OR =71, CI =7.07–713) and IFN‐λ2 (OR =40.2, CI =3.86–419), and closely associated with viral N1 transcripts (OR =1.35, CI =1.23–1.49 and OR =1.33 CI =1.20–1.47, respectively). Only transcripts for IP‐10 were increased among systemic inflammatory cytokines that we examined (OR =131, CI =1.01–2620). We found widespread discrepancies between transcription and translation. IFN proteins were unchanged or decreased in infected samples (IFN‐γ OR =0.90 CI =0.33–0.79, IFN‐λ2,3 OR =0.60 CI =0.48–0.74) suggesting viral‐induced shut‐off of host antiviral protein responses. However, proteins for IP‐10 (OR =3.74 CI =2.07–6.77) and several interferon‐stimulated genes (ISG) increased with viral load (BST‐1 OR =25.1, CI =3.33–188; IFIT1 OR =19.5, CI =4.25–89.2; IFIT3 OR =245, CI =15–4020; MX‐1 OR =3.33, CI =1.44–7.70). Older age was associated with substantial modifications of some effects. Ambulatory symptomatic patients had an innate immune response with SARS‐CoV‐2 infection characterized by elevated IFN, proinflammatory cytokine and ISG transcripts, but there is evidence of a viral‐induced host shut‐off of antiviral responses. Our findings may characterize the disrupted immune landscape common in patients with early disease.

Abstract Objective The objective of this study is to report the results of the genetic analysis in a large and well‐characterized population with pediatric‐onset epilepsies and to identify those who could benefit from precision medicine treatments. Methods In this retrospective observational study, we consecutively recruited patients with pediatric‐onset epilepsy observed at a tertiary neurological center over a time span of 7 years, collecting clinical and laboratory findings. Following in‐depth diagnostic process to exclude possible structural and metabolic causes of the disease, patients with a suspected genetically determined etiology underwent next‐generation sequencing (NGS) screening with panels for the analysis of target genes causative of epilepsy. Results We detected likely pathogenic or pathogenic variants (classes IV and V) in 24% of the 562 patients who underwent genetic investigations. By the evaluation of patients' data, we observed that some features (onset of epilepsy before one year old, presence of neurological deficits, psychomotor delay/cognitive disability, and malformative aspects at brain MRI) were significantly associated with class IV or V variants. Moreover, statistical analysis showed that the diagnostic yield resulted higher for patients affected by Progressive Myoclonic Epilepsy (PME) and with early onset developmental and epileptic encephalopathies (DEE), compared with focal epilepsies, genetic generalized epilepsies, DEE with onset at/after 1 y.o., and unclassified epileptic syndromes. According to the results of the genetic screening, up to 33% of patients carrying class IV or V variants resulted potentially eligible for precision medicine treatments. Significance The large‐scale application of NGS multigene panels of analysis is a useful tool for the molecular diagnosis of patients with pediatric‐onset epilepsies, allowing the identification of those who could benefit from a personalized therapeutic approach. Plain Language Summary The analysis of patients with pediatric‐onset epilepsy using advanced technologies for the screening of all the implicated genes allows the identification of the cause of diseases in an ever‐increasing number of cases. Understanding the pathogenic mechanisms could, in some cases, guide the selection and optimization of appropriate treatment approaches for patients.

Abstract Background Exercise is widely considered to have beneficial impact on skeletal muscle aging. In addition, there are also several studies demonstrating a positive effect of exercise on muscular dystrophies. Oculopharyngeal muscular dystrophy (OPMD) is a late‐onset autosomal dominant inherited neuromuscular disorder caused by mutations in the PAPBN1 gene. These mutations consist in short (1‐8) and meiotically stable GCN trinucleotide repeat expansions in its coding region responsible for the formation of PAPBN1 intranuclear aggregates. This study aims to characterize the effects of two types of chronic exercise, resistance and endurance, on the OPMD skeletal muscle phenotype using a relevant murine model of OPMD. Methods In this study, we tested two protocols of exercise. In the first, based on endurance exercise, FvB (wild‐type) and A17 (OPMD) mice underwent a 6‐week‐long motorized treadmill protocol consisting in three sessions per week of running 20 cm/s for 20 min. In the second protocol, based on resistance exercise generated by chronic mechanical overload (OVL), surgical removal of gastrocnemius and soleus muscles was performed, inducing hypertrophy of the plantaris muscle. In both types of exercise, muscles of A17 and FvB mice were compared with those of respective sedentary mice. For all the groups, force measurement, muscle histology, and molecular analyses were conducted. Results Following the endurance exercise protocol, we did not observe any major changes in the muscle physiological parameters, but an increase in the number of PABPN1 intranuclear aggregates in both tibialis anterior (+24%, **P = 0.0026) and gastrocnemius (+18%, ****P