Adolescent pregnancy amongst displaced women in Bogota: playing between the barbs of structural violence-a qualitative study.

BACKGROUND: Colombia has high numbers of internally displaced people, forced to migrate due to the conflict. 1 in 3 displaced women undergo pregnancy during adolescence, compared to around 1 in 5 in the non-displaced population, alongside health and resource inequalities between these groups. There is limited qualitative information available from the perspectives of displaced women experiencing adolescent pregnancy. This research explores how structural violence may feature in their experiences. METHODS: Qualitative methods were used. Participants were recruited with purposive sampling, using key informants and snowball sampling technique. 14 semi-structured interviews were conducted in Ciudad Bolívar, Bogotá, involving 11 displaced women who began childbearing age 15-19 in the past 10 years, and 4 participants' mothers. Data was analysed using the theoretical framework of structural violence, and emergent themes categorised using thematic analysis. RESULTS: Pregnancy was considered advantageous in many ways, but this was contradicted by resulting disadvantages that ensued. Structural violence was embedded in life stories, manifesting in poverty and difficulties accessing reliable income, poor access to healthcare and education following pregnancy. Institutional and interpersonal discrimination confounded these challenges. CONCLUSIONS: Pregnancy during adolescence was a contradictory experience, representing both a safety net and a trap due to a complex interplay of structural and cultural violence in everyday survival. Policymakers must consider the importance of the context surrounding adolescent pregnancy and address systematic disadvantages affecting women in these positions.

The violent conflict in Colombia has left many people forced to leave their homes and become 'internally displaced'. Internally displaced women are more likely to become pregnant during their adolescence than non-displaced women. This work tries to understand more about the everyday lives of displaced women who experience adolescent pregnancy, through interviews. The interviews were analysed and results interpreted using the theory of 'structural violence'. Structural violence describes how social structures such as racism, sexism, war and poverty determine life choices, leading to suffering and inequality. The work found that pregnancy and motherhood in adolescence for displaced women was positive in many ways by bringing purpose, status and companionship. However, these women also experienced many challenges after pregnancy, such as exclusion from education and secure employment and difficulty accessing healthcare. This demonstrated that structural violence features in multiple interconnected forms in the daily lives of displaced adolescent mothers. The work urges policymakers to appreciate the complexity of context surrounding adolescent pregnancy and motherhood, and to address the structural disadvantages facing women in these situations.

[Juvenile Pompe disease: Undescribed genotype. First report in Quintana Roo]. / Enfermedad de Pompe juvenil: genotipo no descrito. Primer reporte en Quintana Roo.

Background: Pompe disease (PD) is a rare autosomal recessive genetic disorder (1 in 14,000) which affects the synthesis of acid alpha-glucosidase (AGA), leading to intralysosomal glycogen accumulation in muscle tissue. The clinical presentation is heterogeneous, with variable degrees of involvement and progression, classifiable based on the age of onset into infantile (classic or non-classic) and late-onset forms (juvenile or adult). The diagnostic test of choice is the enzymatic analysis of AGA, and the only pharmacological treatment is enzyme replacement therapy (ERT). This document aims to report a clinical case of late-onset PD. Clinical case: 14-year-old male who started at the age of 5 with postural alterations, gait changes, and decreased physical performance compared to his peers. A diagnostic evaluation was initiated in 2022 due to worsening neuromuscular symptoms, accompanied by dyspnea, tachycardia, and chest pain. A suspicion of a lysosomal storage myopathy was established, and through enzymatic determination of AGA the diagnosis of PD was confirmed. The study of the GAA gene revealed the association of 2 previously unreported genomic variants. ERT was initiated, resulting in clinical improvement. Conclusions: The age of symptom onset, severity of clinical presentation, and prognosis of the disease depend on the specific mutations involved. In this case, the identified genetic alterations are associated with different phenotypes. However, based on the clinical presentation, it is categorized as juvenile PD with an indeterminate prognosis.

Introducción: la enfermedad de Pompe (EP) es un padecimiento genético autosómico recesivo poco frecuente (1:14,000) que afecta la síntesis de alfa-glucosidasa ácida (AGA) y condiciona un depósito de glucógeno intralisosomal en tejido muscular. La presentación clínica es heterogénea, con grados variables de afectación y progresión, clasificable según la edad de aparición en infantil (clásica y no clásica) y de inicio tardío (juvenil o de adultez). La prueba diagnóstica de elección es el análisis enzimático de AGA y el único tratamiento farmacológico es la terapia de reemplazo enzimático (TRE). Este documento tiene como objetivo reportar un caso clínico de EP de inicio tardío. Caso clínico: paciente de sexo masculino de 14 años que comenzó a los 5 años con alteraciones de la postura, marcha y desempeño físico. Se inició protocolo de estudio ante agravamiento de los síntomas neuromusculares, a los que se agregaron disnea, taquicardia y dolor torácico. Se sospechó de una miopatía metabólica de depósito lisosomal y mediante determinación enzimática de AGA se confirmó el diagnóstico de EP. El estudio molecular del gen GAA reportó una asociación de 2 variantes genómicas no descritas previamente. Se empleó la TRE con mejoría clínica. Conclusiones: la edad de inicio del cuadro clínico, severidad y pronóstico dependen de las mutaciones presentadas. En este caso, las alteraciones genéticas encontradas están relacionadas con diferentes fenotipos; no obstante, por clínica es categorizado como una EP juvenil con pronóstico indeterminado.

Functional and structural assessment of an experimental section gap graded modified with sugarcane bagasse ash.

Gap-graded aggregate combined with asphalt rubber presents a high-performance alternative for roads with heavy traffic loads, offering advantages over conventional mixtures in terms of permanent deformation (rutting), fatigue life, and texture. In this study, the conventional filler in the well-established mixture was substituted with sugarcane bagasse bottom ash (SCBA) at a proportion of 5% of the total mineral aggregates. The objective was to enhance the mechanical performance of the asphalt coating while ensuring proper disposal of this waste material. Compared to conventional filler, SCBA is less dense, has smaller dimensions, and exhibits greater roughness, thereby affecting the volumetric parameters of the Marshall mix design. Consequently, the volume of voids in mineral aggregates and voids filled with asphalt increased while maintaining the same volume of air voids (5.3%). Consequently, there was a notable increase in Marshall Stability (40%) and Indirect Tensile Test (22%) mechanical parameters. Following laboratory analysis, the modified mixtures were applied as asphalt coating on a high-traffic highway (BR-158). Field specimens revealed an 18% increase in the Resilience Modulus (4088 MPa; 3478 MPa). Additionally, its Flow Number exhibited a 73% increase (16,707; 9681), and its permanent deformation rate was 28% lower within 10,000 cycles in the dynamic creep test. This was further supported by an 11% reduction in permanent deformation rate in the Hamburg Wheel Tracking Device (HWTD) within 20,000 cycles (3.2 mm; 3.6 mm). In conclusion, the partial replacement of conventional filler with sugarcane bagasse ash within the established granulometric range has demonstrated technical feasibility both in laboratory and field settings.

Predictors of permanent pacemaker implantation for transcatheter self-expandable aortic valve implant in the cusp overlap era.

BACKGROUND: Predictors of permanent pacemaker implantation (PPMI) after self-expanding transcatheter aortic valve implant (TAVI) were described. Is unknown if PPMI predictors remain in the era of high implants using the cusp overlap (COP). METHODS: Single-center, prospective, consecutive case series of patients undergoing self-expanding TAVI with the COP approach. The status of PPMI and other clinical events were ascertained at 30 days. RESULTS: A total of 261 patients were included (84% with Evolut, n = 219). Implant depth >4 mm was infrequent (13.8%). TAVI depth (OR 1.259; p = 0.005), first or second-degree auriculo-ventricular block (OR 3.406; p = 0.033), right-bundle (OR 15.477; p < 0.0001), and incomplete left-bundle branch block (OR 7.964; p = 0.036) were found to be independent predictors of PPMI. The risk of PPMI with deep implant and no electrical disturbances was 3%, and 0% with high implant and no prior electrical disturbances. Those who received PPMI had no statistically significant increased risk of death, myocardial infarction, stroke, bleeding events, or vascular complications at 30 days, but longer hospital stay (mean difference 1.43 days more, p = 0.003). CONCLUSIONS: Implant depth and prior conduction abnormalities remain the main predictors of PPMI using self-expanding TAVI in the COP era. Patients with high implants and no prior conduction abnormalities may be candidates for early discharge after uneventful self-expanding TAVI, while the rest may need inpatient monitoring regardless of achieving a high implant. The need for PPMI was associated with longer hospital stays.

Thirty Years of Midwifery Education in the Rural and Diverse State of New Mexico.

The purpose of this article is to discuss the evolution of the University of New Mexico (UNM) Nurse-Midwifery Education Program, its impact on New Mexico communities, and the vision moving forward for the program in a rural and culturally diverse state. New Mexico has a rich history of community-based midwifery and the UNM Nurse-Midwifery Education Program, founded in 1991, is rooted in this tradition. Graduates are prepared to practice in rural and underserved communities, advance birth equity, and decrease perinatal health disparities. Faculty have advanced the program mission to improve the health and well-being of New Mexico families through diversifying the midwifery workforce, growing community collaboration, and engaging in research and scholarship activities aimed at promoting access to care. Program faculty recognize the critical need to address factors underpinning the rising maternal morbidity and mortality crisis, including rurality, poverty, and structural racism. These efforts have yielded positive results, with 60% of program graduates serving New Mexico communities and increasingly diverse midwifery student cohorts (70% of currently enrolled students). Efforts to support midwifery student success are bolstered through a recently awarded Health Resources and Services Administration Maternity Care Nursing Workforce Expansion grant. Through such endeavors, the program will continue to strive toward social justice and human dignity.

Peritraumatic Dissociation Partially Mediates the Influence of Lifetime Trauma Exposure on Prospective PTSD Symptoms.

Higher lifetime trauma exposure and increased peritraumatic dissociation (PD) are well-known predictors of Post-Traumatic Stress Disorder (PTSD) symptoms following new trauma (prospective PTSD symptoms). The interplay between those factors, however, is not well established. In this study, we aimed to assess whether PD mediates the influence of lifetime trauma exposure on prospective PTSD symptoms. A total of 387 adults visiting five emergency departments who had experienced a traumatic event within 72 hours completed baseline assessments on lifetime trauma exposure count and PD. PTSD symptoms were assessed 1 month later. Structural equation modeling was used to examine the mediation effect of PD in the relationship between lifetime trauma exposure count and 1-month PTSD symptoms. We found that PD mediated the association between lifetime trauma exposure count and 1-month PTSD symptoms, even after accounting for some confounders. However, the mediation was partial, accounting for 17.9% of the lifetime trauma exposure count's total effect. While this finding is significant, it also suggests that additional mechanisms beyond PD play a role in explaining the influence of higher lifetime trauma exposure on prospective PTSD symptoms. These findings provide valuable insights into the complex dynamics of PTSD development and call for further research to explore complementary factors and preventive strategies.

Hydroelectric Plant Safety: Real-Time Monitoring Utilizing Fiber-Optic Sensors.

In the context of hydroelectric plants, this article emphasizes the imperative of robust monitoring strategies. The utilization of fiber-optic sensors (FOSs) emerges as a promising approach due to their efficient optical transmission, minimal signal attenuation, and resistance to electromagnetic interference. These optical sensors have demonstrated success in diverse structures, including bridges and nuclear plants, especially in challenging environments. This article culminates with the depiction of the development of an array of sensors featuring Fiber Bragg Gratings (FBGs). This array is designed to measure deformation and temperature in protective grids surrounding the turbines at the Santo Antônio Hydroelectric Plant. Implemented in a real-world scenario, the device identifies deformation peaks, indicative of water flow obstructions, thereby contributing significantly to the safety and operational efficiency of the plant.

Sustainable Electromagnetic Prototype for Detecting Internal Deterioration in Building Walls.

The aim of this study was to develop a sustainable electromagnetic prototype to detect the interior deterioration of walls in buildings in order to mitigate uncertainty as it is a challenge to observe the interior state of walls without utilising destructive procedures. The method used was experimental, developmental and quantitative in its approach. The inductance, electric current, modulated frequency and power of the electromagnetic field were used to penetrate the constructed specimens, which were built of materials such as concrete, brick, adobe, plaster and fine sand and had walls with a thickness of less than 300 millimetres. The results show that the optimum value of the magnetic field was 0.18 µT, which was sufficient to penetrate 150 mm with densities between 1.0 and 2.4 g/cm3 and porosities between 11 and 60%. The current and wave each had a coefficient of determination R2 = 0.8914, and the average inductance value was 184 µH, which was established with an air core of radius 9.75 cm and with 19 turns with AWG-25 wire. The frequency-modulated signal ranged in the audible zone between 10 and 22 kHz. The presented prototype detects the interior deterioration of the walls of the building, and the signal is reflected on a metallic guide on the opposite side of the wall with a reading error of 5%. The use of this prototype does not represent a risk to the operator or the environment.

Effects of riparian vegetation restoration and environmental context on ecosystem functioning in tropical streams of southeastern Brazil.

Tropical stream ecosystems are under increasing human pressure, making the development of effective restoration approaches and expanding knowledge in this field urgent. This study evaluated the impact of riparian vegetation restoration and environmental context on stream ecosystem functioning by measuring key ecosystem functions - gross primary production (GPP), ecosystem respiration (ER), and nutrient uptake of ammonium and soluble reactive phosphorus - across ten tropical streams in southeastern Brazil. The streams represented a gradient from clearcut areas (impacted reaches) to relatively pristine conditions (reference reaches), including intermediate stages of vegetation recovery (restored reaches). In the short-term (~15-20 years after restoration), restoration led to reduced GPP akin to reference reaches. Yet, ER did not show the anticipated increase, suggesting a longer timeframe is necessary for restored streams to emulate the functional characteristics of reference reaches. Additionally, the restored reaches did not achieve the nutrient uptake efficiencies observed in both impacted and reference reaches, pointing to a partial recovery of ecosystem function. This study suggests that while riparian vegetation restoration contributes positively to certain aspects of stream function, environmental variables less related to this type of restoration, such as discharge and hydromorphology, significantly influence stream ecosystem functioning, highlighting the importance of considering environmental context in restoration efforts. A more holistic approach, possibly encompassing broader hydromorphological and habitat enhancements, is needed to fully restore ecological processes in these vital ecosystems. These insights are critical for informing future tropical stream restoration projects, advocating the use of ecosystem function metrics as comprehensive indicators of ecological recovery and restoration success.

Exploring the electronic structure of knotted proteins: the case of two ornithine transcarbamylase family.

CONTEXT: Geometrical knots are rare structural arrangements in proteins in which the polypeptide chain ties itself into a knot, which is very intriguing due to the uncertainty of their impact on the protein properties. Presently, classical molecular dynamics is the most employed technique in the few studies found on this topic, so any information on how the presence of knots affects the reactivity and electronic properties of proteins is even scarcer. Using the electronic structure methods and quantum chemical descriptors analysis, we found that the same amino-acid residues in the knot core have statistically larger values for the unknotted protein, for both hard-hard and soft-soft interaction descriptors. In addition, we present a computationally feasible protocol, where we show it is possible to separate the contribution of the geometrical knot to the reactivity and other electronic structure properties. METHODS: In order to investigate these systems, we used PRIMoRDiA, a new software developed by our research group, to explore the electronic structure of biological macromolecules. We evaluated several local quantum chemical descriptors to unveil relevant patterns potentially originating from the presence of the geometrical knot in two proteins, belonging to the ornithine transcarbamylase family. We compared several sampled structures from these two enzymes that are highly similar in both tertiary structure and function, but one of them has a knot whereas the other does not. The sampling was carried out through molecular dynamics simulations using ff14SB force field along 50 ns, and the semiempirical convergence was performed with PM7 Hamiltonian.

Spatial heterogeneity in climate change effects across Brazilian biomes.

We present a methodology designed to study the spatial heterogeneity of climate change. Our approach involves decomposing the observed changes in temperature patterns into multiple trend, cycle, and seasonal components within a spatio-temporal model. We apply this method to test the hypothesis of a global long-term temperature trend against multiple trends in distinct biomes. Applying this methodology, we delve into the examination of heterogeneity of climate change in Brazil-a country characterized by a spectrum of climate zones. The findings challenge the notion of a global trend, revealing the presence of distinct trends in warming effects, and more accelerated trends for the Amazon and Cerrado biomes, indicating a composition between global warming and deforestation in determining changes in permanent temperature patterns.

Dengue virus non-structural protein 3 inhibits mitochondrial respiration by impairing complex I function.

Dengue virus (DENV) infection is known to affect host cell metabolism, but the molecular players involved are still poorly known. Using a proteomics approach, we identified six DENV proteins associated with mitochondria isolated from infected hepatocytes, and most of the peptides identified were from NS3. We also found an at least twofold decrease of several electron transport system (ETS) host proteins. Thus, we investigated whether NS3 could modulate the ETS function by incubating recombinant DENV NS3 constructs in mitochondria isolated from mouse liver. We found that NS3pro (NS3 protease domain), but not the correspondent catalytically inactive mutant (NS3proS135A), impairs complex I (CI)-dependent NADH:ubiquinone oxidoreductase activity, but not the activities of complexes II, III, IV, or V. Accordingly, using high-resolution respirometry, we found that both NS3pro and full-length NS3 decrease the respiratory rates associated with malate/pyruvate oxidation in mitochondria. The NS3-induced impairment in mitochondrial respiration occurs without altering either leak respiration or mitochondria's capacity to maintain membrane potential, suggesting that NS3 does not deeply affect mitochondrial integrity. Remarkably, CI activity is also inhibited in DENV-infected cells, supporting that the NS3 effects observed in isolated mitochondria may be relevant in the context of the infection. Finally, in silico analyses revealed the presence of potential NS3 cleavage sites in 17 subunits of mouse CI and 16 subunits of human CI, most of them located on the CI surface, suggesting that CI is prone to undergo proteolysis by NS3. Our findings suggest that DENV NS3 can modulate mitochondrial bioenergetics by directly affecting CI function. IMPORTANCE: Dengue virus (DENV) infection is a major public health problem worldwide, affecting about 400 million people yearly. Despite its importance, many molecular aspects of dengue pathogenesis remain poorly known. For several years, our group has been investigating DENV-induced metabolic alterations in the host cells, focusing on the bioenergetics of mitochondrial respiration. The results of the present study reveal that the DENV non-structural protein 3 (NS3) is found in the mitochondria of infected cells, impairing mitochondrial respiration by directly targeting one of the components of the electron transport system, the respiratory complex I (CI). NS3 acts as the viral protease during the DENV replication cycle, and its proteolytic activity seems necessary for inhibiting CI function. Our findings uncover new nuances of DENV-induced metabolic alterations, highlighting NS3 as an important player in the modulation of mitochondria function during infection.

Surface matches prevail over distant analogs during retrieval.

Laboratory studies using a reception paradigm have found that memory items sharing similar entities and relations with a working memory cue (surface matches) are easier to retrieve than items sharing only a system of abstract relations (structural matches). However, the naturalistic approach has contended that the observed supremacy of superficial similarity could have originated in a shallow processing of somewhat inconsequential stories, as well as in the inadvertent inclusion of structural similarity during the construction of surface matches. We addressed the question of which kind of similarity dominates retrieval through a hybrid paradigm that combines the ecological validity of the naturalistic production paradigm with the experimental control of the reception paradigm. In Experiment 1 we presented participants with a target story that maintained either superficial or structural similarities with two popular movies that had received a careful processing prior to the experimental session. Experiment 2 replicated the same procedure with highly viralized public events. In line with traditional laboratory results, surface matches were significantly better retrieved than structural matches, confirming the supremacy of superficial similarities during retrieval.

Characterization of Nano- and Microstructures of Native Potato Starch as Affected by Physical, Chemical, and Biological Treatments.

Modifying starch allows for improvements in its properties to enable improved uses in food matrices, bioplastics, and encapsulating agents. In this research, four varieties of native potato starch were modified by acid treatment, enzymatic treatment, and ethanol precipitation, and their physicochemical, structural, thermal, and techno-functional characteristics were analyzed. According to FT-IR analysis, no influence of the modified starches on the chemical groups was observed, and by scanning electron microscopy (SEM), spherical and oval shapes were observed in the acid and enzymatic treatments, with particle sizes between 27 and 36 µm. In particular, the ethanolic precipitation treatment yielded a different morphology with a particle size between 10.9 and 476.3 nm, resulting in a significant decrease in gelatinization temperature (DSC) and more pronounced crystallites (XRD). On the other hand, the enzymatic treatment showed higher values for z-potential (ζ), and the acid treatment showed lower mass loss (TGA). Acid and ethanolic treatments affected the dough properties compared to native starches. The techno-functional properties showed a decrease in the water absorption index, an increase in the water solubility index, and varied swelling power behaviors. In conclusion, the modification of potato starches through acid, enzymatic, and ethanolic precipitation treatments alters their physicochemical properties, such as swelling capacity, viscosity, and thermal stability. This in turn affects their molecular structure, modifying morphology and the ability to form gels, which expands their applications in the food industry to improve textures, stabilize emulsions, and thicken products. Furthermore, these modifications also open new opportunities for the development of bioplastics by improving the biodegradability and mechanical properties of starch-based plastic materials.

Stress and the Consumption of Ultra-Processed Foods during COVID-19's Social Distancing: Are Mental Disorders Mediators in This Association? ELSA-Brasil Results.

The COVID-19 pandemic exacerbated various determinants of mental disorders. Several behavioral changes were observed given this increase, including harmful health consequences, such as excessive consumption of ultra-processed foods (UPFs). To assess this relationship, we investigated the meditational role of symptoms of mental disorders (anxiety and depression) in the association between stress resulting from social distancing during the COVID-19 pandemic and the consumption of UPFs in 3884 Brazilian public employees in a supplementary study of the ELSA-Brasil study. Structural equation models (SEMs) were estimated to assess the direct and indirect effects mediated by symptoms of mental disorders. The results suggested a significant and positive mediational effect of the symptoms of mental disorders on the association between the stress resulting from social distancing and the consumption of UPFs. These findings contribute to informing the need for policies and early interventions in potentially stressful situations, with a focus on the promotion of mental health, and may thus help prevent or reduce the consumption of unhealthy foods.

Policies that support working parents and gender health equity: needed research and methodological challenges.

In this issue of AJE, Platt et al (Am J Epidemiol. XXXX;XXX(XX):XXXX-XXXX) shed new light on the potential for supportive employment benefits, including family leave, flexible work hours, and employer provided or subsidized child-care to mitigate depression risk among full-time working mothers. The authors use a longitudinal study design and rigorous methods to carefully consider potential sources of bias, and, more broadly, their article underscores the importance of employment benefits as a social determinant of mental health for working mothers. In this commentary, we discuss some of the policy context surrounding employer benefits that support parenting, particularly around paid versus unpaid family leave laws and ordinances. We consider the ways in which the policy context impacts larger structural inequities and the potential implications for internal and external validity.

Psychological distress, health-promoting lifestyle and sociodemographic factors in Honduran university students: a structural equation model.

This study sought to analyze an explanatory model on the relationship among sociodemographic factors, health-promoting lifestyle behaviors and psychological distress (depression, anxiety and stress) in college students. This is an observational, analytical and cross-sectional study conducted on a national sample of 4203 students who entered a macro university in Honduras in 2021, 2022 and 2023. We used a sociodemographic survey, the Health-Promoting Lifestyle Profile (HPLP-II) and the Depression, Anxiety and Stress Scales (DASS-21). Univariate analysis and a multivariate structural equation model were conducted. The average HPLP-II score was 117.45 (±â€…23.41), and the average DASS-21 score was 20.06 (±â€…14.16). The multivariate model showed a good data fit (comparative fit index = 0.951; Tucker-Lewis index = 0.957; root mean square error of approximation = 0.067 [90% CI = 0.067-0.068]). Results indicate that being a woman (ß = 0.11; p < 0.001) and being enrolled in biological and health sciences (ß = 0.09; p < 0.001) significantly predict HPLP-II scores. Furthermore, being a woman (ß = 0.17; p < 0.001), age (ß = 0.10; p < 0.001) and having pre-existing medical conditions (ß = 0.16; p < 0.001) significantly explain part of the variance of DASS-21. A significant reverse relationship between health-promoting behavior and psychological distress was shown (r = -0.36; p < 0.001). This study identifies protective and risky sociodemographic factors linked to health-promoting lifestyle behaviors and psychological distress. Our findings have implications for developing comprehensive intervention policies and strategies to promote health in higher education settings.

The iceberg of dementia risk: empirical and conceptual arguments in favor of structural interventions for brain health.

While pharmacological interventions for dementia struggle to demonstrate improved outcomes for patients and at-risk populations, non-pharmacological lifestyle interventions have been proposed as a tool to achieve dementia risk reduction. In this review, it is argued that lifestyle modification alone is a surface-level intervention from the point of view of fair and far-reaching dementia prevention. Below the tip of this "iceberg of dementia risk," there are living conditions and social structures that represent deeper contributions to risk in the population. It is argued that alongside lifestyle modification, activist research and structural interventions are needed to make our society fairer and more dementia-resilient.

Molecular Basis of MC1R Activation: Mutation-Induced Alterations in Structural Dynamics.

The MC1R protein is a receptor found in melanocytes that plays a role in melanin synthesis. Mutations in this protein can impact hair color, skin tone, tanning ability, and increase the risk of skin cancer. The MC1R protein is activated by the alpha-melanocyte-stimulating hormone (α-MSH). Previous studies have shown that mutations affect the interaction between MC1R and α-MSH; however, the mechanism behind this process is poorly understood. Our study aims to shed light on this mechanism using molecular dynamics (MD) simulations to analyze the Asp84Glu and Asp294His variants. We simulated both the wild-type (WT) protein and the mutants with and without ligand. Our results reveal that mutations induce unique conformations during state transitions, hindering the switch between active and inactive states and decreasing cellular levels of cAMP. Interestingly, Asp294His showed increased ligand affinity but decreased protein activity, highlighting that tighter binding does not always lead to increased activation. Our study provides insights into the molecular mechanisms underlying the impact of MC1R mutations on protein activity.

Low-pass whole genome sequencing as a cost-effective alternative to chromosomal microarray analysis for low- and middle-income countries.

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.