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Visualizing micro- and nano-scale biological entities requires high-resolution imaging and is conventionally achieved via optical microscopic techniques. Optical diffraction limits their resolution to ∼200 nm. This limit can be overcome by using ions with ∼1 MeV energy. Such ions penetrate through several micrometers in tissues, and their much shorter de Broglie wavelengths indicate that these ion beams can be focused to much shorter scales and hence can potentially facilitate higher resolution as compared to the optical techniques. Proton microscopy with ∼1 MeV protons has been shown to have reasonable inherent contrast between sub-cellular organelles. However, being a transmission-based modality, it is unsuitable for in vivo studies and cannot facilitate three-dimensional imaging from a single raster scan. Here, we propose proton-induced acoustic microscopy (PrAM), a technique based on pulsed proton irradiation and proton-induced acoustic signal collection. This technique is capable of label-free, super-resolution, 3D imaging with a single raster scan. Converting radiation energy into ultrasound enables PrAM with reflection mode detection, making it suitable for in vivo imaging and probing deeper than proton scanning transmission ion microscopy (STIM). Using a proton STIM image of HeLa cells, a coupled Monte Carlo+k-wave simulations-based feasibility study has been performed to demonstrate the capabilities of PrAM. We demonstrate that sub-50 nm lateral (depending upon the beam size and energy) and sub-micron axial resolution (based on acoustic detection bandwidth and proton beam pulse width) can be obtained using the proposed modality. By enabling visualization of biological phenomena at cellular and subcellular levels, this high-resolution microscopic technique enhances understanding of intricate cellular processes.

Abstract Fibrinogen, a blood plasma protein with a key role in hemostasis and thrombosis, is highly susceptible to post-translational modifications (PTMs), that significantly influence clot formation, structure, and stability. These PTMs, which include acetylation, amidation, carbamylation, citrullination, dichlorination, glycation, glycosylation, guanidinylation, hydroxylation, homocysteinylation, malonylation, methylation, nitration, oxidation, phosphorylation and sulphation, can alter fibrinogen biochemical properties and affect its functional behavior in coagulation and fibrinolysis. Oxidation and nitration are notably associated with oxidative stress, impacting fibrin fiber formation and promoting the development of more compact and resistant fibrin networks. Glycosylation and glycation contribute to altered fibrinogen structural properties, often resulting in changes in fibrin clot density and susceptibility to lysis, particularly in metabolic disorders like diabetes. Acetylation and phosphorylation, influenced by medications such as aspirin, modulate clot architecture by affecting fiber thickness and clot permeability. Citrullination and homocysteinylation, although less studied, are linked to autoimmune conditions and cardiovascular diseases, respectively, affecting fibrin formation and stability. Understanding these modifications provides insights into the pathophysiology of thrombotic disorders and highlights potential therapeutic targets. This review comprehensively examines the current literature on fibrinogen PTMs, their specific sites, biochemical pathways, and their consequences on fibrin clot architecture, clot formation and clot lysis.

Abstract Background The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019. Results The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF. Conclusion This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services.

Abstract Background In Brazil, the prevalence of mental disorders is heterogeneous, with most studies conducted in large cities with high population density. This study aimed to assess the prevalence of mental disorders and psychiatric comorbidities among young adults (22–23 years old) and adults (37–38 years old) from Ribeirão Preto, a city located in the Northeast of the São Paulo state, with approximately 700,000 inhabitants, and to explore associations with sociodemographic variables, suicide risk, and health service usage. Second, we aimed to evaluate the performance of the Self-Report Questionnaire (SRQ-20) as a screening tool for mental disorders to be applied to the local population. Methods Participants from the 1978/1979 and 1994 Ribeirão Preto birth cohorts were evaluated using the Mini International Neuropsychiatric Interview (MINI) and the SRQ-20 at mean ages of 22–23, and 37–38 years, respectively. Results Our sample comprised 1,769 individuals from the 1978/1979 cohort and 1,037 from the 1994 cohort. The prevalence of mental disorders ranged from 28.6% (1978/79) to 31% (1994), with frequent comorbid diagnoses (42.7% and 43.3%, respectively). Men and women had a similar prevalence of mental disorders in the younger cohort, while women had a higher prevalence in the older cohort. Low educational attainment was associated with higher rates of diagnosis. In both cohorts, alcohol and other psychoactive substance use was higher among those with a psychiatric diagnosis. Although those with a psychiatric diagnosis were less satisfied with their own health, only one-fifth had seen a mental health professional in the previous year. A psychiatric diagnosis increased the suicide risk by 5.6 to 9.1 times. Regarding the SRQ-20, the best cutoff points were 5/6 for men and 7/8 for women, with satisfactory performance. Conclusions The prevalence and comorbidity of mental disorders were high in both cohorts and comparable to those in larger Brazilian cities. However, few individuals with a diagnosis had sought specialized care. These data suggest that the mental health gap is still significant in Brazil.

Abstract The electrical outputs of single-layer antiferromagnetic memory devices relying on the anisotropic magnetoresistance effect are typically rather small at room temperature. Here we report a new type of antiferromagnetic memory based on the spin phase change in a Mn-Ir binary intermetallic thin film at a composition within the phase boundary between its collinear and noncollinear phases. Via a small piezoelectric strain, the spin structure of this composition-boundary metal is reversibly interconverted, leading to a large nonvolatile room-temperature resistance modulation that is two orders of magnitude greater than the anisotropic magnetoresistance effect for a metal, mimicking the well-established phase change memory from a quantum spin degree of freedom. In addition, this antiferromagnetic spin phase change memory exhibits remarkable time and temperature stabilities, and is robust in a magnetic field high up to 60 T.

Introduction: Burns are tissue injuries caused by contact with heat sources. They represent a global public health problem. They have major impacts on children. The severity and intensity of burns are related to the etiological agent and their consequences are a major obstacle for the patient. Method: The study analyzed data on hospital admissions for burns in children from 2012 to 2022, using information from SIH-SUS. Hospitalization rates per 100,000 inhabitants were calculated for each year, considering dependent variables. The researchers used standardized coefficients and simple linear regression to analyze the data. Results: Data from 91,091 hospitalizations for burns in children, 0-14 years old, were included. There was stability in the general hospitalization rate (mean rate 17.963; ß = 0.119; p = 0.163). In females there was an increasing trend (mean rate 14.346; ß = 0.169; p = 0.029); in males, there was stability (mean rate 21.426; ß = 0.069; p = 0.504). Females behaved with stability in all age groups; the male with an increase in the range 0-4 years (mean rate 42.264; ß = 0.613; p = 0.003), stability in the range 5-9 years (mean rate 14.189; ß = -0.21; p = 0.867) and reduction in the range 10-14 years (mean rate 9.871; ß = -0.328; p = 0.007). The South Region demonstrated an increasing trend (mean rate 26.952; ß = 1.091; p = 0.001). Conclusion: There was stability in the general hospitalization rate. The female sex tended towards increase and the male towards stability. There was stability in Brazilian regions, except in the South.

Objective: There are very few reports on the prevalence of diabetic retinopathy (DR) in children and youth with type-1 diabetes (T1D). Studies have also found very low rates of referral for DR screening in children and youth with T1D. We conducted this study to determine the prevalence of DR, to study the reliability of ISPAD screening recommendations and to identify predictors of DR, its progression and regression in Indian children and youth with T1D. Methods: This study included 882 children and youth with T1D. Demographic data, anthropometry, blood pressure, sexual maturity rating, ophthalmological examination (slit lamp for cataract) and biochemical measurements were performed using standard protocols. Fundus images were captured using the Forus Health 3netra classic digital non-mydriatic fundus camera by the same experienced operator. De-identified images were assessed by a senior grader and ophthalmologist (Belfast Ophthalmic Reading Center). Severity of DR was graded as per the UK National Health Service (NHS) DR classification scale. Result: We report 6.4% and 0.2% prevalence of DR and cataract in Indian children and youth with T1D, respectively. All the subjects with DR had early non-proliferative DR. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Presence of hypertension and older age were significant predictors of DR ( P

IntroductionPsychosocial stress during pregnancy has long-lasting and important consequences in the following generations, as it can affect intrauterine development. The impact on the developing immune system is notoriously important due to the associated morbidity and mortality in the first years of life. Little attention has been given to the role of violence during pregnancy (VDP), especially its impact on infant infectious morbidity.MethodsWe analyzed data from two Brazilian birth cohorts (n = 2,847) in two distinct cities (Ribeirão Preto and São Luís), collected during pregnancy and at the beginning of the second year of life. The association between VDP and infection in infancy was analyzed with structural equation modeling, using the WHO-VAW questionnaire as exposure and a latent variable for infection as the outcome.ResultsVDP was reported by 2.48% (sexual), 11.56% (physical), and 45.90% (psychological) of the mothers. The models presented an adequate fit. In the city of São Luís, VDP was significantly associated with the latent construct for infection (standardized beta = 0.182; p = 0.022), while that was not the case for the Ribeirão Preto sample (standardized beta = 0.113; p = 0.113). Further analyses showed a gradient effect for the different dimensions of the exposure, from psychological to physical and sexual violence.ConclusionOur results suggest an association of VDP with infant morbidity in a poorer socioeconomic setting, and highlight the importance of considering the different dimensions of intimate partner violence. These findings may have important implications for the comprehension of global health inequalities and of the effects of gender-based violence.

Investigamos a influência da depressão materna (DM) nas dimensões comunicativas e motoras do neurodesenvolvimento infantil, por meio de um estudo longitudinal e descritivo. Foram avaliadas 1.555 díades mãe-bebê de duas cidades brasileiras com características sociodemográficas discrepantes: Ribeirão Preto (RP) (N=663) e São Luís (SL) (N=892). A DM durante a gravidez e no segundo ano de vida da criança foi avaliada, respectivamente, através da Escala de Depressão do Centro de Estudos Epidemiológicos-CES-D (≥24) e da Escala de Depressão Pós-natal de Edinburg-EPDS (≥12). O desenvolvimento infantil foi avaliado por meio do teste de triagem da Escala Bayley (BSID-III), quando as crianças tinham entre 12 e 24 meses de idade. Houve associação entre DM no segundo ano de vida da criança e comprometimento na dimensão Comunicação Receptiva do desenvolvimento da linguagem, principalmente quando a análise incluiu depressão durante a gravidez e variáveis sociodemográficas. Tal associação foi encontrada apenas no município com piores indicadores sociodemográficos. Nossos achados corroboraram a influência da DM no segundo ano de vida da criança no neurodesenvolvimento infantil, especificamente na dimensão Comunicação Receptiva do Desenvolvimento da Linguagem em SL. Além disso, os resultados sugeriram um possível papel das variáveisambientais e socioeconômicas nessa associação, chamando a atenção para o monitoramento do pré-natal e programas de intervenção para mães que vivem em contextos socioeconômicos desfavoráveis.

Abstract Background Disease suppressiveness of soils to fungal root pathogens is typically induced in the field by repeated infections of the host plant and concomitant changes in the taxonomic composition and functional traits of the rhizosphere microbiome. Here, we studied this remarkable phenomenon for Bipolaris sorokiniana in two wheat cultivars differing in resistance to this fungal root pathogen. Results The results showed that repeated exposure of the susceptible wheat cultivar to the pathogen led to a significant reduction in disease severity after five successive growth cycles. Surprisingly, the resistant wheat cultivar, initially included as a control, showed the opposite pattern with an increase in disease severity after repeated pathogen exposure. Amplicon analyses revealed that the bacterial families Chitinophagaceae, Anaerolineaceae and Nitrosomonadaceae were associated with disease suppressiveness in the susceptible wheat cultivar; disease suppressiveness in the resistant wheat cultivar was also associated with Chitinophagaceae and a higher abundance of Comamonadaceae. Metagenome analysis led to the selection of 604 Biosynthetic Gene Clusters (BGCs), out of a total of 2,571 identified by AntiSMASH analysis, that were overrepresented when the soil entered the disease suppressive state. These BGCs are involved in the biosynthesis of terpenes, non-ribosomal peptides, polyketides, aryl polyenes and post-translationally modified peptides. Conclusion Combining taxonomic and functional profiling we identified key changes in the rhizosphere microbiome during disease suppression. This illustrates how the host plant relies on the rhizosphere microbiome as the first line of defense to fight soil-borne pathogens. Microbial taxa and functions identified here can be used in novel strategies to control soil-borne fungal pathogens.

Analyzing the impacts of climate change on phytosanitary problems in Brazil is crucial due to the country’s special role in global food security as one of the largest producers of essential commodities. This review focuses on the effects of climate change on plant diseases and discusses its main challenges in light of Brazil’s diverse agricultural landscape. To assess the risk of diseases caused by fungi, bacteria, viruses, oomycetes, nematodes, and spiroplasms, we surveyed 304 pathosystems across 32 crops of economic importance from 2005 to 2022. Results show that diseases caused by fungi account for 79% of the pathosystems evaluated. Predicting the occurrence of diseases in a changing climate is a complex challenge, and the continuity of this work is strategic for Brazil’s agricultural defense. The future risk scenarios analyzed here aim to help guide disease mitigation for cropping systems. Despite substantial progress and ongoing efforts, further research will be needed to effectively prevent economic and environmental damage.