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Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Approximately 5% of Alzheimer's disease patients develop symptoms before age 65 (early-onset Alzheimer's disease), with either sporadic (sporadic early-onset Alzheimer's disease) or dominantly inherited (dominantly inherited Alzheimer's disease) presentations. Both sporadic early-onset Alzheimer's disease and dominantly inherited Alzheimer's disease are characterized by brain amyloid-β accumulation, tau tangles, hypometabolism and neurodegeneration, but differences in topography and magnitude of these pathological changes are not fully elucidated. In this study, we directly compared patterns of amyloid-β plaque deposition and glucose hypometabolism in sporadic early-onset Alzheimer's disease and dominantly inherited Alzheimer's disease individuals. Our analysis included 134 symptomatic sporadic early-onset Alzheimer's disease amyloid-Positron Emission Tomography (PET)-positive cases from the University of California, San Francisco, Alzheimer's Disease Research Center (mean ± SD age 59.7 ± 5.6 years), 89 symptomatic dominantly inherited Alzheimer's disease cases (age 45.8 ± 9.3 years) and 102 cognitively unimpaired non-mutation carriers from the Dominantly Inherited Alzheimer Network study (age 44.9 ± 9.2). Each group underwent clinical and cognitive examinations, 11C-labelled Pittsburgh Compound B-PET and structural MRI. 18F-Fluorodeoxyglucose-PET was also available for most participants. Positron Emission Tomography scans from both studies were uniformly processed to obtain a standardized uptake value ratio (PIB50-70 cerebellar grey reference and FDG30-60 pons reference) images. Statistical analyses included pairwise global and voxelwise group comparisons and group-independent component analyses. Analyses were performed also adjusting for covariates including age, sex, Mini-Mental State Examination, apolipoprotein ε4 status and average composite cortical of standardized uptake value ratio. Compared with dominantly inherited Alzheimer's disease, sporadic early-onset Alzheimer's disease participants were older at age of onset (mean ± SD, 54.8 ± 8.2 versus 41.9 ± 8.2, Cohen's d = 1.91), with more years of education (16.4 ± 2.8 versus 13.5 ± 3.2, d = 1) and more likely to be apolipoprotein ε4 carriers (54.6% ε4 versus 28.1%, Cramer's V = 0.26), but similar Mini-Mental State Examination (20.6 ± 6.1 versus 21.2 ± 7.4, d = 0.08). Sporadic early-onset Alzheimer's disease had higher global cortical Pittsburgh Compound B-PET binding (mean ± SD standardized uptake value ratio, 1.92 ± 0.29 versus 1.58 ± 0.44, d = 0.96) and greater global cortical 18F-fluorodeoxyglucose-PET hypometabolism (mean ± SD standardized uptake value ratio, 1.32 ± 0.1 versus 1.39 ± 0.19, d = 0.48) compared with dominantly inherited Alzheimer's disease. Fully adjusted comparisons demonstrated relatively higher Pittsburgh Compound B-PET standardized uptake value ratio in the medial occipital, thalami, basal ganglia and medial/dorsal frontal regions in dominantly inherited Alzheimer's disease versus sporadic early-onset Alzheimer's disease. Sporadic early-onset Alzheimer's disease showed relatively greater 18F-fluorodeoxyglucose-PET hypometabolism in Alzheimer's disease signature temporoparietal regions and caudate nuclei, whereas dominantly inherited Alzheimer's disease showed relatively greater hypometabolism in frontal white matter and pericentral regions. Independent component analyses largely replicated these findings by highlighting common and unique Pittsburgh Compound B-PET and 18F-fluorodeoxyglucose-PET binding patterns. In summary, our findings suggest both common and distinct patterns of amyloid and glucose hypometabolism in sporadic and dominantly inherited early-onset Alzheimer's disease.

Abstract Introduction The poorest in Burkina Faso face numerous barriers to healthcare access, including financial and geographic obstacles, as well as a high burden of chronic conditions and multimorbidity. This study estimates the average cost of providing curative outpatient consultations at first-level healthcare facilities to the poorest in Burkina Faso. It also estimates the budgetary impact of scaling up free access to these services nationwide. The findings provide essential evidence on cost structures to inform decision-makers in developing policies aimed at achieving universal health coverage and ensuring that no one is left behind. Methods We conducted a micro-costing study to estimate the economic costs of providing curative outpatient healthcare services to the poorest at first-level healthcare facilities, considering a health system perspective. We measured the consumption of capital costs (building and equipment) using survey data from 32 primary health facilities and recurrent costs (drugs and consumables) from medical records of 1380 poor patients in Diébougou district. These individuals were targeted and exempted from user fees through a community-based targeting approach. We obtained unit costs from official price lists, pharmacy registries, and expert interviews. We calculated the national budget for providing curative care services to the exempted poorest based on the average cost per first-level consultation. Results The estimated capital and recurrent costs of providing curative care services ranged between USD 0.59 - USD 0.61 and USD 2.58 - USD 5.00, respectively. The total cost ranged between USD 3.17 - USD 5.61 per first-level consultation. Providing curative care to the bottom 20% of the population, assuming 0.25 healthcare contacts per person per year, would result in an annual expense ranging from USD 2.77 M to USD 5.38 M (0.74-1.43% of the healthcare budget in 2019). With 2 healthcare contacts per person per year, costs increase to USD 22.19 M to USD 43.05 M (5.91-11.45% of the healthcare budget). Conclusion The results can inform policies aimed at expanding access to curative care for the poorest in Burkina Faso, contributing to the goals of universal health coverage and leaving no one behind. Further research is needed to enhance cost estimation and budgeting for higher-level care in the country.

Abstract Disease-modifying therapies for Alzheimer’s disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum. CSF and plasma trajectories were similar at presymptomatic stages, discriminating mutation carriers from non-carrier controls 10-20 years before the estimated onset of clinical symptoms, depending on the statistical model used. However, after symptom onset the rate of change in CSF NfL continued to increase steadily, whereas the rate of change in plasma NfL leveled off. Both plasma and CSF NfL changes were associated with grey-matter atrophy, but not with Aβ-PET changes, supporting a temporal decoupling of Aβ deposition and neurodegeneration. These observations support NfL in both CSF and blood as an early marker of neurodegeneration but suggest that NfL measured in the CSF may be better suited for monitoring clinical trial outcomes in symptomatic AD patients.

The new edition of Peter Singer’s “Animal Liberation” gives the author the opportunity to take stock of the improvements in the conditions of non-human animals, particularly in the European Union, and to emphasize the importance of the dissemination of this volume for their achievement. In addition, the article returns to discuss Singer’s theoretical approach to animal ethics, highlighting its various oscillations and some critical issues. The author, while distancing himself from utilitarianism (the moral theory advocated by Singer), points out that a good part of Singer’s moral reflection about non-human animals is convincing, so his contribution contains more lights than shadows.

Approximately 5% of Alzheimer's disease cases have an early age at onset (

The paper focuses on technological evolution applied to sports architecture, considered as urban infrastructures. A field of research – that has not been given its due importance both by architectural historiography and by technological culture – despite the fact that sports architecture has always represented privileged places of formal, technical and engineering experimentation. Some design experiences in the field of sports venues – from the twentieth century to the contemporary age – have instead represented significant steps of technological development. In particular, the latest generation of sports infrastructures, represent the architectural typology where it is possible to find, concentrated, paradigms such as those of resilience, flexibility, sustainability technologies for adaptive skins and many others innovative parameters.

Abstract Background The sustainability of diets consumed by African populations under socio-economic transition remains to be determined. This study developed and characterized a multi-dimensional Sustainable Diet Index (SDI) reflecting healthfulness, climate-friendliness, sociocultural benefits, and financial affordability using individual-level data of adults in rural and urban Ghana and Ghanaian migrants in Europe to identify the role of living environment in dietary sustainability. Methods We used cross-sectional data from the multi-centre Research on Obesity and Diabetes among African Migrants Study (N = 3169; age range: 25–70 years). For the SDI construct (0–16 score points), we used the Diet Quality Index-International, food-related greenhouse gas emission, the ratio of natural to processed foods, and the proportion of food expenditure from income. In linear regression analyses, we estimated the adjusted ß-coefficients and 95% confidence intervals (CIs) for the differences in mean SDI across study sites (using rural Ghana as a reference), accounting for sociodemographic and lifestyle factors. Results The overall mean SDI was 8.0 (95% CI: 7.9, 8.1). Participants in the highest SDI-quintile compared to lower quintiles were older, more often women, non-smokers, and alcohol abstainers. The highest mean SDI was seen in London (9.1; 95% CI: 8.9, 9.3), followed by rural Ghana (8.2; 95% CI: 8.0, 8.3), Amsterdam (7.9; 95% CI: 7.7, 8.1), Berlin (7.8; 95% CI: 7.6, 8.0), and urban Ghana (7.7; 95% CI: 7.5, 7.8). Compared to rural Ghana, the differences between study sites were attenuated after accounting for age, gender and energy intake. No further changes were observed after adjustment for lifestyle factors. Conclusion The multi-dimensional SDI describes four dimensions of dietary sustainability in this Ghanaian population. Our findings suggest that living in Europe improved dietary sustainability, but the opposite seems true for urbanization in Ghana.

Abstract Background Access of all people to the healthcare they need, without financial hardship is the goal of Universal Health Coverage (UHC). As UHC initiatives expand, assessing the needs of vulnerable populations can reveal gaps in the system which may be covered by relevant policies. In this study we (i) identify the met and unmet primary healthcare needs of the poorest population of Khyber Pakhtunkhwa province (KP), Pakistan, and (ii) explore why the gaps exist. Methods We used Leveque’s Framework of Patient-centred Access to Healthcare to examine unmet primary healthcare (PHC) needs and their underlying causes for the poorest population in four districts of Khyber Pakhtunkhwa province, Pakistan. Using a triangulation mixed methods design, we analysed data from a quantitative household survey of744 households, 17 focus group discussions with household members and, 11 interviews with healthcare providers. Results Our results show that indicate that despite service utilization, PHC needs were not met, primarily due to prohibitively high costs at each stage of access. Furthermore, gaps in outreach and information (approachability), and varying availability of medicines and diagnostics at facilities (appropriateness) the supply side as well as difficulties in navigating the system (inability to perceive) and adhering to prescriptions (inability to engage) on the demand side, also led to unmet PHC needs. Going beyond utilization, our findings highlight that engagement with care is an important determinant of met needs for vulnerable populations. Conclusion Social health protection policies can contribute to advancing UHC for primary care. However, in our setting, enhancing communication and outreach, addressing gender and age disparities, and improving quality of care and health infrastructure are necessary to fully meet the needs of the poorest populations.

Background The coronavirus disease 2019 (COVID-19) pandemic has had a profound global impact, raising concerns about its long-term effects, particularly neurological complications. While studies have highlighted such complications in adults, there is a paucity of research focusing on children.

IntroductionBehavioral and Psychological Symptoms of Dementia (BPSD) are a heterogeneous set of psychological reactions and abnormal behaviors in people with dementia (PwD). Current assessment tools, like the Neuropsychiatric Inventory (NPI), only rely on caregiver assessment of BPSD and are therefore prone to bias.Materials and methodsA multidisciplinary team developed the BPSD-SINDEM scale as a three-part instrument, with two questionnaires administered to the caregiver (evaluating BPSD extent and caregiver distress) and a clinician-rated observational scale. This first instrument was tested on a sample of 33 dyads of PwD and their caregivers, and the results were qualitatively appraised in order to revise the tool through a modified Delphi method. During this phase, the wording of the questions was slightly changed, and the distress scale was changed into a coping scale based on the high correlation between extent and distress (r = 0.94). The final version consisted of three 17-item subscales, evaluating BPSD extent and caregiver coping, and the unchanged clinician-rated observational scale.ResultsThis tool was quantitatively validated in a sample of 208 dyads. It demonstrated good concurrent validity, with the extent subscale correlating positively with NPI scores (r = 0.64, p

Introduction Achieving universal health coverage (UHC) through an effective health financing system is a challenge for many low-income countries. Learning is key to success due to many uncertainties and unknowns. Using the case of translating strategic health purchasing into policy and practice in Burkina Faso, our study seeks to understand how policy learning can shape policy processes and outcomes.Methods We used a qualitative case study design and Dunlop and Radaelli’s conceptualisation of policy learning to identify which modes of learning did or did not occur, what helped or hindered them and the resulting policy outcomes. Dunlop and Radaelli frame policy learning as epistemic, reflexive, negotiative or hierarchical. We collected data through documentary review and in-depth individual interviews with 21 key informants. We analysed the data manually using pattern-matching techniques.Results The introduction of strategic health purchasing in Burkina Faso was initially seen as an opportunity to reduce the fragmentation of the health financing system by coupling a performance-based financing scheme and a user fee exemption policy. However, this has faltered, and our findings suggest that an inability to harness all modes of learning has led to blockages. Indeed, while reflective learning was present, epistemic, hierarchical and learning through bargaining were absent, preventing national policy actors from defending their own policy or scheme from reaching compromises. But thanks to facilitating processes led by a well-resourced organisation and contextual elements that encouraged the emergence of more pluralistic modes of learning, some progress was achieved in operationalising strategic health purchasing.Conclusions Some modes of learning seem to be overlooked in countries’ efforts to achieve UHC. Facilitation techniques and initiatives that encourage the use of all modes of learning, while supporting countries to take full ownership and responsibility for consolidating their own learning health systems, should be promoted.

ABSTRACT Transient global amnesia (TGA) is a rare, temporary, sudden-onset disturbance in anterograde episodic memory with unclear pathophysiology. Previous brain volumetric analysis in TGA patients showed varied results. Objective: To explore brain morphometry, hypothesizing that patients with TGA exhibit structural alterations. Methods: A case-control study was performed involving TGA subjects (n=50) and matched healthy controls (n=50). Both groups underwent a 3D-T1 weighted structural MRI on a 3T scanner, and voxel-based morphometry (VBM), region-based morphometry (RBM), and surface-based morphometry (SBM) were analyzed. Results: After performing the VBM, RBM, and SBM analyses, no consistent and statistically significant differences were found after applying multiple corrections. Conclusion: Despite previous studies showing volumetric changes in TGA patients, our results differ from this. The discrepancy could be due to sample size and timing of MRI scans. While our findings do not explain TGA pathophysiology, they support a network dysfunction as a possible mechanism and discards a structural alteration as a predisposing factor for TGA.

ObjectiveThe aim of the study was to characterize drug prescription patterns in elderly patients hospitalized in acute wards as a function of cognitive status and staff training.MethodsWe recorded clinical parameters reflecting health status and drug prescriptions at admission, during hospital stay, and at discharge before and after a short staff training on the needs of aged cognitively impaired patients. Participants aged 65 and older had a Mini-Mental State Examination (MMSE) score ≥16. The number of prescriptions, sedative and anticholinergic load, and drug–drug interactions were evaluated. Of the 116 older patients analyzed, 59 patients were cognitively impaired, and 57 were cognitively normal with an MMSE value > 24. Fifty-nine patients (28 CN, 31 CI) were assisted by the hospital health staff after training.ResultsParticipants presented a widespread polypharmacy. Cognitively impaired patients received more prescriptions, more inappropriate prescriptions, had a greater sedative load, and were exposed to more interactions. Staff training had no effect on the prescription pattern.ConclusionThe results suggest that hospitalized cognitively impaired patients are overprescribed psychotropic drugs and have an excessive sedative and anticholinergic load. Interventions designed to improve dementia care practices in health staff that are not also designed to manage drug polypharmacy do not modify prescription patterns.

IntroductionLiquid biopsy is gaining momentum for diagnosis and surveillance of cancer patients. Indeed, head and neck squamous cell carcinoma (HNSCC) is burdened with poor prognosis and high recurrence rates after treatment. It is therefore crucial to be able to detect minimal residual disease early after radical treatment or relapse, so surgery can be performed when the disease is still resectable. In this scenario, aim of this study is to create a liquid biopsy-based pipeline able to detect somatic tumor mutations in a cohort of HNSCC-affected patients undergoing follow-up after surgical intervention.MethodsOur cohort included 17 patients diagnosed with HNSCC over 4 years. The first saliva sample was collected before surgery while the rest were collected during the subsequent visits, according to the follow-up schedule. Salivary DNA (sDNA) was extracted, and a 52-gene next generation sequencing (NGS)-based panel was used for somatic variants detection.Results41.2% of samples collected before surgery bore a deleterious variant (n=7/17). Overall, 29.2% of samples harbored at least a pathogenic variant (n=21/72). The most frequently mutated genes were TP53 (80%), FBXW7 (8%), PDGFRA (4%) and PTEN (4%). Finally, three patients experienced a loco-regional relapse by clinical evaluations, anticipated in 67% of cases by the molecular one (n=2/3).DiscussionOur data indicate that sDNA could aid in the monitoring of patients’ follow-up as low-frequency somatic mutations could be assessed from the saliva of HNSCC patients. Prospectively, these results suggest that salivary-based liquid biopsy might pave the way for personalized molecular therapies based on mutational data.

Abstract Background Recent years have seen a growing interest in the use of digital tools for delivering person-centred mental health care. Experience Sampling Methodology (ESM), a structured diary technique for capturing moment-to-moment variation in experience and behaviour in service users’ daily life, reflects a particularly promising avenue for implementing a person-centred approach. While there is evidence on the effectiveness of ESM-based monitoring, uptake in routine mental health care remains limited. The overarching aim of this hybrid effectiveness-implementation study is to investigate, in detail, reach, effectiveness, adoption, implementation, and maintenance as well as contextual factors, processes, and costs of implementing ESM-based monitoring, reporting, and feedback into routine mental health care in four European countries (i.e., Belgium, Germany, Scotland, Slovakia). Methods In this hybrid effectiveness-implementation study, a parallel-group, assessor-blind, multi-centre cluster randomized controlled trial (cRCT) will be conducted, combined with a process and economic evaluation. In the cRCT, 24 clinical units (as the cluster and unit of randomization) at eight sites in four European countries will be randomly allocated using an unbalanced 2:1 ratio to one of two conditions: (a) the experimental condition, in which participants receive a Digital Mobile Mental Health intervention (DMMH) and other implementation strategies in addition to treatment as usual (TAU) or (b) the control condition, in which service users are provided with TAU. Outcome data in service users and clinicians will be collected at four time points: at baseline (t0), 2-month post-baseline (t1), 6-month post-baseline (t2), and 12-month post-baseline (t3). The primary outcome will be patient-reported service engagement assessed with the service attachment questionnaire at 2-month post-baseline. The process and economic evaluation will provide in-depth insights into in-vivo context-mechanism-outcome configurations and economic costs of the DMMH and other implementation strategies in routine care, respectively. Discussion If this trial provides evidence on reach, effectiveness, adoption, implementation and maintenance of implementing ESM-based monitoring, reporting, and feedback, it will form the basis for establishing its public health impact and has significant potential to bridge the research-to-practice gap and contribute to swifter ecological translation of digital innovations to real-world delivery in routine mental health care. Trial registration ISRCTN15109760 (ISRCTN registry, date: 03/08/2022).

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.

We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer’s disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, expression of pluripotency markers, and maintains a normal karyotype.

BackgroundImportant insights into the early pathogenesis of Alzheimer's disease can be provided by studies of autosomal dominant Alzheimer's disease and Down syndrome. However, it is unclear whether the timing and spatial distribution of amyloid accumulation differs between people with autosomal dominant Alzheimer's disease and those with Down syndrome. We aimed to directly compare amyloid changes between these two groups of people.MethodsIn this cross-sectional study, we included participants (aged ≥25 years) with Down syndrome and sibling controls who had MRI and amyloid PET scans in the first data release (January, 2020) of the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study. We also included carriers of autosomal dominant Alzheimer's disease genetic mutations and non-carrier familial controls who were within a similar age range to ABC-DS participants (25-73 years) and had MRI and amyloid PET scans at the time of a data freeze (December, 2020) of the Dominantly Inherited Alzheimer Network (DIAN) study. Controls from the two studies were combined into a single group. All DIAN study participants had genetic testing to determine PSEN1, PSEN2, or APP mutation status. APOE genotype was determined from blood samples. CSF samples were collected in a subset of ABC-DS and DIAN participants and the ratio of amyloid β42 (Aβ42) to Aβ40 (Aβ42/40) was measured to evaluate its Spearman's correlation with amyloid PET. Global PET amyloid burden was compared with regards to cognitive status, APOE ɛ4 status, sex, age, and estimated years to symptom onset. We further analysed amyloid PET deposition by autosomal dominant mutation type. We also assessed regional patterns of amyloid accumulation by estimated number of years to symptom onset. Within a subset of participants the relationship between amyloid PET and CSF Aβ42/40 was evaluated.Findings192 individuals with Down syndrome and 33 sibling controls from the ABC-DS study and 265 carriers of autosomal dominant Alzheimer's disease mutations and 169 non-carrier familial controls from the DIAN study were included in our analyses. PET amyloid centiloid and CSF Aβ42/40 were negatively correlated in carriers of autosomal dominant Alzheimer's disease mutations (n=216; r=-0·565; p

Background and purposeClinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation.MethodLogistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number.ResultsFrom March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p

Abstract Thyroid cancer is the most common endocrine carcinoma and, among its different subtypes, the papillary subtype (PTC) is the most frequent. Generally, PTCs are well differentiated, but a minor percentage of PTCs are characterized by a worse prognosis and more aggressive behavior. Phytochemicals, naturally found in plant products, represent a heterogeneous group of bioactive compounds that can interfere with cell proliferation and the regulation of the cell cycle, taking part in multiple signaling pathways that are often disrupted in tumor initiation, proliferation, and progression. In this work, we focused on 15,16-dihydrotanshinone I (DHT), a tanshinone isolated from Salvia miltiorrhiza Bunge (Danshen). We first evaluated DHT biological effect on PTC cells regarding cell viability, colony formation ability, and migration capacity. All of these parameters were downregulated by DHT treatment. We then investigated gene expression changes after DHT treatment by performing RNA-seq. The analysis revealed that DHT significantly reduced the Wnt signaling pathway, which plays a role in various diseases, including cancer. Finally, we demonstrate that DHT treatment decreases protein levels of β-catenin, a final effector of canonical Wnt signaling pathway. Overall, our data suggest a possible use of this nutraceutical as an adjuvant in the treatment of aggressive papillary thyroid carcinoma.

The extent to which the pathophysiology of autosomal dominant Alzheimer's disease corresponds to the pathophysiology of 'sporadic' late onset Alzheimer's disease is unknown, thus limiting the extrapolation of study findings and clinical trial results in autosomal dominant Alzheimer's disease to late onset Alzheimer's disease. We compared brain MRI and amyloid PET data, as well as CSF concentrations of amyloid-β42, amyloid-β40, tau and tau phosphorylated at position 181, in 292 carriers of pathogenic variants for Alzheimer's disease from the Dominantly Inherited Alzheimer Network, with corresponding data from 559 participants from the Alzheimer's Disease Neuroimaging Initiative. Imaging data and CSF samples were reprocessed as appropriate to guarantee uniform pipelines and assays. Data analyses yielded rates of change before and after symptomatic onset of Alzheimer's disease, allowing the alignment of the ∼30-year age difference between the cohorts on a clinically meaningful anchor point, namely the participant age at symptomatic onset. Biomarker profiles were similar for both autosomal dominant Alzheimer's disease and late onset Alzheimer's disease. Both groups demonstrated accelerated rates of decline in cognitive performance and in regional brain volume loss after symptomatic onset. Although amyloid burden accumulation as determined by PET was greater after symptomatic onset in autosomal dominant Alzheimer's disease than in late onset Alzheimer's disease participants, CSF assays of amyloid-β42, amyloid-β40, tau and p-tau181 were largely overlapping in both groups. Rates of change in cognitive performance and hippocampal volume loss after symptomatic onset were more aggressive for autosomal dominant Alzheimer's disease participants. These findings suggest a similar pathophysiology of autosomal dominant Alzheimer's disease and late onset Alzheimer's disease, supporting a shared pathobiological construct.

Introduction Universal health coverage (UHC) is a global priority, ensuring equitable access to quality healthcare services without financial hardship. Many countries face challenges in progressing towards UHC. Health financing is pivotal for advancing UHC by raising revenues, enabling risk-sharing through pooling of funds and allocating resources. Digital technologies in the healthcare sector offer promising opportunities for health systems. In low-income and middle-income countries (LMICs), digital technologies for health financing (DTHF) have gained traction, supporting these three main functions of health financing for UHC. As existing information on DTHF in LMICs is limited, our scoping review aims to provide a comprehensive overview of DTHF in LMICs. Our objectives include identifying and describing existing DTHF, exploring evaluation approaches, examining their positive and negative effects, and investigating facilitating factors and barriers to implementation at the national level.Methods and analysis Our scoping review follows the six stages proposed by Arksey and O’Malley, further developed by Levac et al and the Joanna Briggs Institute. The reporting adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews framework. Eligibility criteria for studies reflect the three core elements of the search: (1) health financing, (2) digital technologies and (3) LMICs. We search multiple databases, including Medline via PubMed, EMBASE via Ovid, the Web of Science Core Collection, CENTRAL via Cochrane and the Global Index Medicus by the WHO. The extracted information is synthesised from both quantitative and qualitative studies.Ethics and dissemination As our scoping review is based solely on information gathered from previously published studies, documents and publicly available scientific literature, ethical clearance is not required for its conduct. The findings are presented and discussed in a peer-reviewed article, as well as shared at conferences relevant to the topic.

Summary: Background: Neuroimaging studies often quantify tau burden in standardized brain regions to assess Alzheimer disease (AD) progression. However, this method ignores another key biological process in which tau spreads to additional brain regions. We have developed a metric for calculating the extent tau pathology has spread throughout the brain and evaluate the relationship between this metric and tau burden across early stages of AD. Methods: 445 cross-sectional participants (aged ≥ 50) who had MRI, amyloid PET, tau PET, and clinical testing were separated into disease-stage groups based on amyloid positivity and cognitive status (older cognitively normal control, preclinical AD, and symptomatic AD). Tau burden and tau spatial spread were calculated for all participants. Findings: We found both tau metrics significantly elevated across increasing disease stages (p

Abstract Background There is limited understanding of how universal health coverage (UHC) schemes such as publicly-funded health insurance (PFHI) benefit women as compared to men. Many of these schemes are gender-neutral in design but given the existing gender inequalities in many societies, their benefits may not be similar for women and men. We contribute to the evidence by conducting a gender analysis of the enrolment of individuals and households in India’s national PFHI scheme, Rashtriya Swasthya Bima Yojana (RSBY). Methods We used data from a cross-sectional household survey on RSBY eligible families across eight Indian states and studied different outcome variables at both the individual and household levels to compare enrolment among women and men. We applied multivariate logistic regressions and controlled for several demographic and socio-economic characteristics. Results At the individual level, the analysis revealed no substantial differences in enrolment between men and women. Only in one state were women more likely to be enrolled in RSBY than men (AOR: 2.66, 95% CI: 1.32-5.38), and this pattern was linked to their status in the household. At the household level, analyses revealed that female-headed households had a higher likelihood to be enrolled (AOR: 1.36, 95% CI: 1.14-1.62), but not necessarily to have all household members enrolled. Conclusion Findings are surprising in light of India’s well-documented gender bias, permeating different aspects of society, and are most likely an indication of success in designing a policy that did not favour participation by men above women, by mandating spouse enrolment and securing enrolment of up to five family members. Higher enrolment rates among female-headed households are also an indication of women’s preferences for investments in health, in the context of a conducive policy environment. Further analyses are needed to examine if once enrolled, women also make use of the scheme benefits to the same extent as men do. India is called upon to capitalise on the achievements of RSBY and apply them to newer schemes such as PM-JAY.

Behavioural phenotype and autism-related traits of 38 patients affected by Cornelia de Lange syndrome (CdLS) were assessed using a specific neuropsychiatric protocol. Subsequently, we search for possible genotype-phenotype correlations comparing individuals with NIPBL variants and patients with negative molecular results. Firstly results showed a higher percentage of subjects with normal intellectual quotient (IQ) and borderline IQ; adaptive skills were lower than expected for age in all participants. 39.5% of the sample presented with autism spectrum disorder (ASD), NIPBL mutated individuals demonstrated a worse trend in comparison with the clinical diagnosis group. non-truncating individuals displayed no ASD and better communication abilities than truncating individuals. Findings increase our awareness of the strengths and weaknesses points in CdLS individuals.

Abstract Background “Brain-predicted age” estimates biological age from complex, nonlinear features in neuroimaging scans. The brain age gap (BAG) between predicted and chronological age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD), in which AD progression is highly predictable with minimal confounding age-related co-pathology. Methods We modeled BAG in 257 deeply-phenotyped ADAD mutation-carriers and 179 non-carriers from the Dominantly Inherited Alzheimer Network using minimally-processed structural MRI scans. We then tested whether BAG differed as a function of mutation and cognitive status, or estimated years until symptom onset, and whether it was associated with established markers of amyloid (PiB PET, CSF amyloid-β-42/40), phosphorylated tau (CSF and plasma pTau-181), neurodegeneration (CSF and plasma neurofilament-light-chain [NfL]), and cognition (global neuropsychological composite and CDR-sum of boxes). We compared BAG to other MRI measures, and examined heterogeneity in BAG as a function of ADAD mutation variants, APOE ε4 carrier status, sex, and education. Results Advanced brain aging was observed in mutation-carriers approximately 7 years before expected symptom onset, in line with other established structural indicators of atrophy. BAG was moderately associated with amyloid PET and strongly associated with pTau-181, NfL, and cognition in mutation-carriers. Mutation variants, sex, and years of education contributed to variability in BAG. Conclusions We extend prior work using BAG from sporadic AD to ADAD, noting consistent results. BAG associates well with markers of pTau, neurodegeneration, and cognition, but to a lesser extent, amyloid, in ADAD. BAG may capture similar signal to established MRI measures. However, BAG offers unique benefits in simplicity of data processing and interpretation. Thus, results in this unique ADAD cohort with few age-related confounds suggest that brain aging attributable to AD neuropathology can be accurately quantified from minimally-processed MRI.

Background Burkina Faso has been implementing financing reforms towards universal health coverage (UHC) since 2006. Recently, the country introduced a performance-based financing (PBF) program as well as user fee removal (gratuité) policy for health services aimed at pregnant and lactating women and children under 5. We aim to assess the effect of gratuité and PBF policies on facility-based out-of-pocket expenditures (OOPEs) for outpatient services.Methods Our study is a controlled pre- and post-test design using healthcare facility data from the PBF program’s impact evaluation collected in 2014 and 2017. We compared OOPE related to primary healthcare use incurred by children under 5 and individuals above 5 to assess the effect of the gratuité policy on OOPE. We further compared OOPE incurred by individuals residing in PBF districts and non-PBF districts to estimate the effect of the PBF on OOPE. Effects were estimated using difference-in-differences models, distinguishing the estimation of the probability of incurring OOPE from the estimation of the magnitude of OOPE using a generalized linear model (GLM).Results The proportion of children under 5 incurring OOPE declined significantly from 90% in 2014 to 3% in 2017. Concurrently, mean OOPE also decreased. Differences in both the probability of incurring OOPE and mean OOPE between PBF and non-PBF facilities were small. Our difference in differences estimates indicated that gratuité produced an 84% (CI -86%, -81%) reduction in the probability of incurring OOPE and reduced total OOPE by 54% (CI 63%, 42%). We detected no significant effects of PBF, either in reducing the probability of incurring OOPE or in its magnitude.Conclusion User fee removal is an effective demand-side intervention for enhancing financial accessibility. As a supplyside intervention, PBF appears to have limited effects on reducing financial burden.

Background Digital information management systems for health financing are implemented on the assumption that digitalization, among other things, enables strategic purchasing. However, little is known about the extent to which these systems are adopted as planned to achieve desired results. This study assesses the levels of, and the factors associated with the adoption of the Insurance Management Information System (IMIS) by healthcare providers in Tanzania.Methods Combining multiple data sources, we estimated IMIS adoption levels for 365 first-line health facilities in 2017 by comparing IMIS claim data (verified claims) with the number of expected claims. We defined adoption as a binary outcome capturing underreporting (verified

Abstract Background The government-subsidized health insurance scheme Seguro Integral de Salud (“SIS”) was introduced in Peru initially to provide coverage to uninsured and poor pregnant women and children under five years old and was later extended to cover all uninsured members of the population following the Peruvian Plan Esencial de Aseguramiento Universal – “PEAS” (Essential UHC Package). Our study aimed to analyze the extent to which the introduction of SIS has increased equity in access and quality by comparing the utilization of maternal healthcare services among women with different insurance coverages. Methods Relying on the 2021 round of the nationally-representative survey “ENDES” (Encuesta Nacional Demográfica y de Salud Familiar), we analyzed data for 19,181 women aged 15–49 with a history of pregnancy in the five years preceding the survey date. We used a series of logistic regressions to explore the association between health insurance coverage (defined as No Insurance, SIS, or Standard Insurance) and a series of outcome variables measuring access to and quality of all services along the available maternal healthcare continuum. Results Only 46.5% of women across all insurance schemes reported having accessed effective ANC prevention. Findings from the adjusted logistic regression confirmed that insured women were more likely to have accessed ANC services compared with uninsured women. Our findings indicate that women in the “SIS” group were more likely to have accessed six ANC visits (aOR = 1.40; 95% CI 1.14–1.73) as well as effective ANC prevention (aOR = 1.32; 95% CI 1.17–1.48), ANC education (aOR = 1.59; 95% CI 1.41–1.80) and ANC screening (aOR = 1.46; 95% CI 1.27–1.69) during pregnancy, compared with women in the “Standard Insurance” group [aOR = 1.35 (95% CI 1.13–1.62), 1.22 (95% CI 1.04–1.42), 1.34 (95% CI 1.18–1.51) and 1.31(95% CI 1.15–1.49)] respectively. In addition, women in the “Standard Insurance” group were more likely to have received skilled attendance at birth (aOR = 2.17, 95% CI 1.33–3.55) compared with the women in the “SIS” insurance group (aOR = 2.12; 95% CI 1.41–3.17). Conclusions Our findings indicate the persistence of inequities in access to maternal healthcare services that manifest themselves not only in the reduced utilization among the uninsured, but also in the lower quality of service coverage that uninsured women received compared with women insured under “Standard Insurance” or “SIS”. Further policy reforms are needed both to expand insurance coverage and to ensure that all women receive the same access to care irrespective of their specific insurance coverage.