The stomatognathic system (SS) is a functional unit of the body that depends on the balance of several tissues. It consists of various structures, including the temporomandibular joint. Temporomandibular disorder (TMD...The stomatognathic system (SS) is a functional unit of the body that depends on the balance of several tissues. It consists of various structures, including the temporomandibular joint. Temporomandibular disorder (TMD) can occur due to alterations in the SS. The Fonseca Anamnestic Index (FAI) is a scale used to evaluate and to characterize the TMD Type: no DTM, mild, moderate and severe. The aim is to evaluate the prevalence of signs and symptoms related to TMD in university students of the Parque das Rosas Campus, Universidade Estácio de Sá that practice sports. This investigation was approved (CAAE number 325678413.9.0000.5284). Two hundred eighth students (110 male and 98 female, aged 19 - 35 years) accepted to be in this investigation. All the participants answered a General Questionnaire (GQ) and the FAI. The GQ had questions about the age, sex and the presence of TMD. The FAI was used. A statistical difference (p > 0.05) was not found about the presence of TMD. Among the female, an elevated number of the students with signal or symptoms related to the temporomandibular with statistic significance (p < 0.05) was observed. In the population without TMD, the prevalence of this disorder is higher between male than female. Considering the FAI, among the female students, there is a prevalence of the Mild Type. Considering the evaluation of the type of TMD among the male and female students no difference was found between male and female to the types mild and moderate, however, the prevalence of the severe Type is higher in female than in male with statistical significance. In conclusion, TMD is a relevant clinical condition with an important prevalence among the university students. Moreover, the type of the TMD could be considered due to prevalence of the Type Severe among the women.展开更多
Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central ne...Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.展开更多
Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammat...Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.展开更多
Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articul...Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.展开更多
Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structu...Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structural and metabolic support to neurons but also actively participate in modulating synaptic transmission,neurovascular coupling,and inflammatory responses in the brain.展开更多
The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches.Photoreceptor degeneration,the common endpoint in various retinal diseases,including retinitis pigmento...The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches.Photoreceptor degeneration,the common endpoint in various retinal diseases,including retinitis pigmentosa and age-related macular degeneration,leads to vision loss or blindness.While primary cell death is driven by genetic mutations,oxidative stress,and neuroinflammation,additional mechanisms contribute to disease progression.In retinitis pigmentosa,a multitude of genetic alterations can trigger the degeneration of photoreceptors,while other retinopathies,such as agerelated macular degeneration,are initiated by combinations of environmental factors,such as diet,smoking,and hypertension,with genetic predispositions.Nutraceutical therapies,which blend the principles of nutrition and pharmaceuticals,aim to harness the health benefits of bioactive compounds for therapeutic applications.These compounds generally possess multi-target effects.Polyphenols and flavonoids,secondary plant metabolites abundant in plant-based foods,are known for their antioxidant,neuroprotective,and anti-inflammatory properties.This review focuses on the potential of polyphenols and flavonoids as nutraceuticals to treat neurodegenerative diseases such as retinitis pigmentosa.Furthermore,the importance of developing reliable delivery methods to enhance the bioavailability and therapeutic efficacy of these compounds will be discussed.By combining nutraceuticals with other emerging therapies,such as genetic and cell-based treatments,it is possible to offer a more comprehensive approach to treating retinal degenerative diseases.These advancements could lead to a viable and accessible option,improving the quality of life for patients with retinal diseases.展开更多
An analytical model of a floating heaving box integrated with a vertical flexible porous membrane placed right next to the box applications to wave energy extraction and breakwater systems is developed under the reduc...An analytical model of a floating heaving box integrated with a vertical flexible porous membrane placed right next to the box applications to wave energy extraction and breakwater systems is developed under the reduced wave equation.The theoretical solutions for the heave radiating potential to the assigned physical model in the corresponding zones are attained by using the separation of variables approach along with the Fourier expansion.Applying the matching eigenfunction expansion technique and orthogonal conditions,the unknown coefficients that are involved in the radiated potentials are determined.The attained radiation potential allows the computation of hydrodynamic coefficients of the heaving buoy,Power Take-Off damping,and wave quantities.The accuracy of the analytical solution for the hydrodynamic coefficients is demonstrated for different oblique angles with varying numbers of terms in the series solution.The current analytical analysis findings are confirmed by existing published numerical boundary element method simulations.Several numerical results of the hydrodynamic coefficients,power capture,power take-off optimal damping,and transmission coefficients for numerous structural and physical aspects are conducted.It has been noted that the ideal power take-off damping increases as the angle of incidence rises,and the analysis suggests that the ability to capture waves is more effective in shallower waters compared to deeper ones.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
Neurodegenerative diseases affect millions of people worldwide,with Alzheimer’s disease(AD)being the leading cause of dementia.It is estimated that more than 50 million people live with this condition,which is expect...Neurodegenerative diseases affect millions of people worldwide,with Alzheimer’s disease(AD)being the leading cause of dementia.It is estimated that more than 50 million people live with this condition,which is expected to triple by 2050,driven mainly by the aging of the global population(GBD 2019 Dementia Forecasting Collaborators,2022).展开更多
Eucalyptus staigeriana essential oil(EsEO)has well-known anthelmintic activity in small ruminants.However,its volatility limits its therapeutic action.The aim of this study was to develop a water-in-oil sodium alginat...Eucalyptus staigeriana essential oil(EsEO)has well-known anthelmintic activity in small ruminants.However,its volatility limits its therapeutic action.The aim of this study was to develop a water-in-oil sodium alginatebased nanoemulsion with an effective in vitro effect on the eggs and larvae of Haemonchus contortus,a gastrointestinal parasite of sheep and goats.Four oil-in-water sodium alginate-based emulsions were prepared using a high-energy method with different proportions of Tween 80,EsEO,and sodium alginate(ALG)4%.The physical-chemical characterization included stability,particle size,zeta potential and infrared spectra.The effects of the emulsions were evaluated against H.contortus via the egg hatching test(EHT)and larval development test(LDT).The results showed that the emulsions were stable over 7 days,nanometer scale particles(218.8 to 371.5 nm)predominating and with negative zeta potentials(−28.9 to−46.9 mV).All four emulsions were more effective than EsEO in the EHT,with 50%effective concentrations(EC50)of 0.088 to 0.15 mg/mL for the emulsions and 0.308 mg/mL for EsEO.However,in the LDT,the emulsions and essential oil had similar effects,with EC50 values of 3.91 to 4.60 mg/mL for the emulsions and 4.17 mg/mL for EsEO.Emulsion 2,with low Tween 80/EsEO and ALG/EsEO ratios,was considered better overall in terms of physical,chemical and anthelmintic assessment and is a promising candidate for further in vivo assays against adult H.contortus.展开更多
Mortality prediction in respiratory health is challenging,especially when using large-scale clinical datasets composed primarily of categorical variables.Traditional digital twin(DT)frameworks often rely on longi-tudi...Mortality prediction in respiratory health is challenging,especially when using large-scale clinical datasets composed primarily of categorical variables.Traditional digital twin(DT)frameworks often rely on longi-tudinal or sensor-based data,which are not always available in public health contexts.In this article,we propose a novel proto-DT framework for mortality prediction in respiratory health using a large-scale categorical biomedical dataset.This dataset contains 415,711 severe acute respiratory infection cases from the Brazilian Unified Health System,including both COVID-19 and non-COVID-19 patients.Four classification models—extreme gradient boosting(XGBoost),logistic regression,random forest,and a deep neural network(DNN)—are trained using cost-sensitive learning to address class imbalance.The models are evaluated using accuracy,precision,recall,F1-score,and area under the curve(AUC)related to the receiver operating characteristic(ROC).The framework supports simulated interventions by modifying selected inputs and recalculating predicted mortality.Additionally,we incorporate multiple correspondence analysis and K-means clustering to explore model sensitivity.A Python library has been developed to ensure reproducibility.All models achieve AUC-ROC values near or above 0.85.XGBoost yields the highest accuracy(0.84),while the DNN achieves the highest recall(0.81).Scenario-based simulations reveal how key clinical factors,such as intensive care unit admission and oxygen support,affect predicted outcomes.The proposed proto-DT framework demonstrates the feasibility of mortality prediction and intervention simulation using categorical data alone.This framework provides a foundation for data-driven explainable DTs in public health,even in the absence of time-series data.展开更多
The United Nations Sustainable Development Goal(SDG) 2 aims to achieve Zero Hunger by 2030.However,global hunger and food insecurity have continued to rise at an alarming rate(UN 2023).Subtropical regions are home to ...The United Nations Sustainable Development Goal(SDG) 2 aims to achieve Zero Hunger by 2030.However,global hunger and food insecurity have continued to rise at an alarming rate(UN 2023).Subtropical regions are home to more than 30% of the world's population,predominantly in developing countries where per capita farmland and food supply are only 40% of those in developed nations(FAO 2018).Meeting the Zero Hunger target amid ongoing population growth in these regions requires a substantial increase in agricultural production while minimizing soil degradation and adverse ecological impacts.This challenge is shared by many countries across South Asia,Africa,and Central and South America.展开更多
For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language defi...For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.展开更多
This study examines the methods to plan the development of offshore oilfields over the years,which are used to support the decision-making on the development of offshore oilfields.About 100 papers are analysed and cat...This study examines the methods to plan the development of offshore oilfields over the years,which are used to support the decision-making on the development of offshore oilfields.About 100 papers are analysed and categorised into different groups of main early-stage decisions.The present study stands in contrast to the contributions of the operations research and system engineering review articles,on the one hand,and the petroleum engineering review articles,on the other.This is because it does not focus on one methodological approach,nor does it limit the literature analysis by offshore oilfield characteristics.Consequently,the present analysis may offer valuable insights,for instance,by identifying environmental planning decisions as a recent yet highly significant concern that is currently being imposed on decision-making process.Thus,it is evident that the incorporation of safety criteria within the technical-economic decision-making process for the design of production systems would be a crucial requirement at development phase.展开更多
Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understoo...Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understood,in particular the influence on the hydrodynamic forces and moments of the distance of the foil to the free surface.Considering this,the present paper documents an experimental investigation in which forces and torque produced,under uniform flow,by a full-scale state-of-the-art hydrofoil(suitable both for kitesurf and windsurf)were measured.A range of velocities,angles of attack,and submergences were tested,leading to Froude numbers based on submergence with maximum values around five,a typical range in actual sailing conditions.From these tests,formulae for the hydrodynamic coefficients have been proposed.They can be used for developing Velocity Prediction Programs(VPP)for this kind of craft,a necessary tool to plan racing configurations and to analyze their racing performance.With the aim of making the experimental data useful for benchmarking numerical models and for future research on related topics such as foil ventilation and transition to turbulence,the specimen’s 3D file is provided as supplementary material to this paper.展开更多
Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemot...Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.展开更多
In this paper,we propose a new privacy-aware transmission scheduling algorithm for 6G ad hoc networks.This system enables end nodes to select the optimum time and scheme to transmit private data safely.In 6G dynamic h...In this paper,we propose a new privacy-aware transmission scheduling algorithm for 6G ad hoc networks.This system enables end nodes to select the optimum time and scheme to transmit private data safely.In 6G dynamic heterogeneous infrastructures,unstable links and non-uniform hardware capabilities create critical issues regarding security and privacy.Traditional protocols are often too computationally heavy to allow 6G services to achieve their expected Quality-of-Service(QoS).As the transport network is built of ad hoc nodes,there is no guarantee about their trustworthiness or behavior,and transversal functionalities are delegated to the extreme nodes.However,while security can be guaranteed in extreme-to-extreme solutions,privacy cannot,as all intermediate nodes still have to handle the data packets they are transporting.Besides,traditional schemes for private anonymous ad hoc communications are vulnerable against modern intelligent attacks based on learning models.The proposed scheme fulfills this gap.Findings show the probability of a successful intelligent attack reduces by up to 65%compared to ad hoc networks with no privacy protection strategy when used the proposed technology.While congestion probability can remain below 0.001%,as required in 6G services.展开更多
Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kines...Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.展开更多
Objective To determine whether frailty is a risk factor for hospitalization and mortality in older adults enrolled in the "Chronic Heart Failure Program" at a hospital in Lima, Peru, between 2018–2021.Metho...Objective To determine whether frailty is a risk factor for hospitalization and mortality in older adults enrolled in the "Chronic Heart Failure Program" at a hospital in Lima, Peru, between 2018–2021.Methods This was an ambispective cohort study. A total of 85 older adults participating in the Chronic Heart Failure Program at Guillermo Almenara National Hospital were included. Each had an initial frailty assessment, forming two cohorts: frail and non-frail older adults. Medical records were reviewed, and patients were followed for one year to track events of interest(hospitalization and mortality). Overall survival and risk factors for hospitalization and death were determined.Results During follow-up, 15.3% of the older adults died, and frailty was identified in 58.8% of the patients. Overall survival using the Kaplan-Meier method was 96.5% at 3 months after entering the Chronic Heart Failure Program;92.9% at 6 months;and85.9% at one year. Multivariate analysis using Poisson regression found that frailty was not a risk factor for hospitalization(a RR =0.92;95% CI: 0.42–2.03). Survival analysis using the Cox proportional hazards model showed that frailty was also not a risk factor for mortality after one year of follow-up(a HR = 1.32;95% CI: 0.27–6.53).Conclusions Our research does not confirm frailty as a risk factor for hospitalization or mortality in older adults enrolled in the“Chronic Heart Failure Program” after one year of follow-up.展开更多
Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders...Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.展开更多
文摘The stomatognathic system (SS) is a functional unit of the body that depends on the balance of several tissues. It consists of various structures, including the temporomandibular joint. Temporomandibular disorder (TMD) can occur due to alterations in the SS. The Fonseca Anamnestic Index (FAI) is a scale used to evaluate and to characterize the TMD Type: no DTM, mild, moderate and severe. The aim is to evaluate the prevalence of signs and symptoms related to TMD in university students of the Parque das Rosas Campus, Universidade Estácio de Sá that practice sports. This investigation was approved (CAAE number 325678413.9.0000.5284). Two hundred eighth students (110 male and 98 female, aged 19 - 35 years) accepted to be in this investigation. All the participants answered a General Questionnaire (GQ) and the FAI. The GQ had questions about the age, sex and the presence of TMD. The FAI was used. A statistical difference (p > 0.05) was not found about the presence of TMD. Among the female, an elevated number of the students with signal or symptoms related to the temporomandibular with statistic significance (p < 0.05) was observed. In the population without TMD, the prevalence of this disorder is higher between male than female. Considering the FAI, among the female students, there is a prevalence of the Mild Type. Considering the evaluation of the type of TMD among the male and female students no difference was found between male and female to the types mild and moderate, however, the prevalence of the severe Type is higher in female than in male with statistical significance. In conclusion, TMD is a relevant clinical condition with an important prevalence among the university students. Moreover, the type of the TMD could be considered due to prevalence of the Type Severe among the women.
基金supported by funds from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brasil(CNPq)(312286/2023-6,307201/2023-6,and Instituto Nacional Saude Cerebral INSC,No.406020/2022-1)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior(CAPES)Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro-FAPERJ(E-26/010.002260/2019,E-26/010.001652/2019,E-26/010.101036/2018,E-26/202.774/2018,E-26/210.240/2020,E-26/211.138/2021,26/210.823/2021,E-26/211.325/2021,E-26/210.779/2021,E-26/201.086/2022,E-26/210.312/2022,E-26/203.262/2023,E-26/200.195/2023)(to LEBS)。
文摘Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.
基金supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil(CAPES)[Finance Code 001](to MGS)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)fellowship[research grants 309840/2022-8]。
文摘Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.
文摘Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.
文摘Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structural and metabolic support to neurons but also actively participate in modulating synaptic transmission,neurovascular coupling,and inflammatory responses in the brain.
基金Fundação de AmparoàPesquisa do Estado de São Paulo(FAPESP,Brazil,#2020/11667-0)and Universidade Federal do ABC(UFABC,Brazil)were recipients of fellowships from FAPESP:THLV(#2021/11969-9 and#2024/00828-3),GBS(#2021/14227-3),and GMB(#2024/10858-7)+1 种基金recipients of fellowships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES,Brazil):MIM(Finance Code 001,#88887.597402/2021-00)recipients of fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,Brazil.):GKD(#145164/2024-1),and DRA(#308819/2022-5).
文摘The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches.Photoreceptor degeneration,the common endpoint in various retinal diseases,including retinitis pigmentosa and age-related macular degeneration,leads to vision loss or blindness.While primary cell death is driven by genetic mutations,oxidative stress,and neuroinflammation,additional mechanisms contribute to disease progression.In retinitis pigmentosa,a multitude of genetic alterations can trigger the degeneration of photoreceptors,while other retinopathies,such as agerelated macular degeneration,are initiated by combinations of environmental factors,such as diet,smoking,and hypertension,with genetic predispositions.Nutraceutical therapies,which blend the principles of nutrition and pharmaceuticals,aim to harness the health benefits of bioactive compounds for therapeutic applications.These compounds generally possess multi-target effects.Polyphenols and flavonoids,secondary plant metabolites abundant in plant-based foods,are known for their antioxidant,neuroprotective,and anti-inflammatory properties.This review focuses on the potential of polyphenols and flavonoids as nutraceuticals to treat neurodegenerative diseases such as retinitis pigmentosa.Furthermore,the importance of developing reliable delivery methods to enhance the bioavailability and therapeutic efficacy of these compounds will be discussed.By combining nutraceuticals with other emerging therapies,such as genetic and cell-based treatments,it is possible to offer a more comprehensive approach to treating retinal degenerative diseases.These advancements could lead to a viable and accessible option,improving the quality of life for patients with retinal diseases.
基金Open access funding provided by FCT|FCCN(b-on)the Strategic Research Plan of the Centre for Marine Technology and Ocean Engineering(CENTEC),which is financed by the Portuguese Foundation for Science and Technology(Fundação para a Ciência e Tecnologia-FCT)under contract UIDB/UIDP/00134/2020.
文摘An analytical model of a floating heaving box integrated with a vertical flexible porous membrane placed right next to the box applications to wave energy extraction and breakwater systems is developed under the reduced wave equation.The theoretical solutions for the heave radiating potential to the assigned physical model in the corresponding zones are attained by using the separation of variables approach along with the Fourier expansion.Applying the matching eigenfunction expansion technique and orthogonal conditions,the unknown coefficients that are involved in the radiated potentials are determined.The attained radiation potential allows the computation of hydrodynamic coefficients of the heaving buoy,Power Take-Off damping,and wave quantities.The accuracy of the analytical solution for the hydrodynamic coefficients is demonstrated for different oblique angles with varying numbers of terms in the series solution.The current analytical analysis findings are confirmed by existing published numerical boundary element method simulations.Several numerical results of the hydrodynamic coefficients,power capture,power take-off optimal damping,and transmission coefficients for numerous structural and physical aspects are conducted.It has been noted that the ideal power take-off damping increases as the angle of incidence rises,and the analysis suggests that the ability to capture waves is more effective in shallower waters compared to deeper ones.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
基金funded by the São Paulo Research Foundation (FAPESPgrant No. 2022/02327-6)supported by the FAPESP scholarship (2021/00270-4 and 2024/05491-7)
文摘Neurodegenerative diseases affect millions of people worldwide,with Alzheimer’s disease(AD)being the leading cause of dementia.It is estimated that more than 50 million people live with this condition,which is expected to triple by 2050,driven mainly by the aging of the global population(GBD 2019 Dementia Forecasting Collaborators,2022).
基金supported by Conselho Nacional de Desenvolvimento Cientifico eTecnologico(CNPq)(grant No.142165/2018-2)Mr.Araujo-Filho had a doctoral scholarship and Dr.Bevilaqua has a research fellowship(grant No.305911/2019-8)from CNPq.
文摘Eucalyptus staigeriana essential oil(EsEO)has well-known anthelmintic activity in small ruminants.However,its volatility limits its therapeutic action.The aim of this study was to develop a water-in-oil sodium alginatebased nanoemulsion with an effective in vitro effect on the eggs and larvae of Haemonchus contortus,a gastrointestinal parasite of sheep and goats.Four oil-in-water sodium alginate-based emulsions were prepared using a high-energy method with different proportions of Tween 80,EsEO,and sodium alginate(ALG)4%.The physical-chemical characterization included stability,particle size,zeta potential and infrared spectra.The effects of the emulsions were evaluated against H.contortus via the egg hatching test(EHT)and larval development test(LDT).The results showed that the emulsions were stable over 7 days,nanometer scale particles(218.8 to 371.5 nm)predominating and with negative zeta potentials(−28.9 to−46.9 mV).All four emulsions were more effective than EsEO in the EHT,with 50%effective concentrations(EC50)of 0.088 to 0.15 mg/mL for the emulsions and 0.308 mg/mL for EsEO.However,in the LDT,the emulsions and essential oil had similar effects,with EC50 values of 3.91 to 4.60 mg/mL for the emulsions and 4.17 mg/mL for EsEO.Emulsion 2,with low Tween 80/EsEO and ALG/EsEO ratios,was considered better overall in terms of physical,chemical and anthelmintic assessment and is a promising candidate for further in vivo assays against adult H.contortus.
文摘Mortality prediction in respiratory health is challenging,especially when using large-scale clinical datasets composed primarily of categorical variables.Traditional digital twin(DT)frameworks often rely on longi-tudinal or sensor-based data,which are not always available in public health contexts.In this article,we propose a novel proto-DT framework for mortality prediction in respiratory health using a large-scale categorical biomedical dataset.This dataset contains 415,711 severe acute respiratory infection cases from the Brazilian Unified Health System,including both COVID-19 and non-COVID-19 patients.Four classification models—extreme gradient boosting(XGBoost),logistic regression,random forest,and a deep neural network(DNN)—are trained using cost-sensitive learning to address class imbalance.The models are evaluated using accuracy,precision,recall,F1-score,and area under the curve(AUC)related to the receiver operating characteristic(ROC).The framework supports simulated interventions by modifying selected inputs and recalculating predicted mortality.Additionally,we incorporate multiple correspondence analysis and K-means clustering to explore model sensitivity.A Python library has been developed to ensure reproducibility.All models achieve AUC-ROC values near or above 0.85.XGBoost yields the highest accuracy(0.84),while the DNN achieves the highest recall(0.81).Scenario-based simulations reveal how key clinical factors,such as intensive care unit admission and oxygen support,affect predicted outcomes.The proposed proto-DT framework demonstrates the feasibility of mortality prediction and intervention simulation using categorical data alone.This framework provides a foundation for data-driven explainable DTs in public health,even in the absence of time-series data.
文摘The United Nations Sustainable Development Goal(SDG) 2 aims to achieve Zero Hunger by 2030.However,global hunger and food insecurity have continued to rise at an alarming rate(UN 2023).Subtropical regions are home to more than 30% of the world's population,predominantly in developing countries where per capita farmland and food supply are only 40% of those in developed nations(FAO 2018).Meeting the Zero Hunger target amid ongoing population growth in these regions requires a substantial increase in agricultural production while minimizing soil degradation and adverse ecological impacts.This challenge is shared by many countries across South Asia,Africa,and Central and South America.
文摘For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.
基金the Strategic Research Plan of the Centre for Marine Technology and Ocean Engineering(CENTEC),which is financed by the Portuguese Foundation for Science and Technology(Fundação para a Ciência e a Tecnologia FCT)under contract UIDB/UIDP/00134/2020.
文摘This study examines the methods to plan the development of offshore oilfields over the years,which are used to support the decision-making on the development of offshore oilfields.About 100 papers are analysed and categorised into different groups of main early-stage decisions.The present study stands in contrast to the contributions of the operations research and system engineering review articles,on the one hand,and the petroleum engineering review articles,on the other.This is because it does not focus on one methodological approach,nor does it limit the literature analysis by offshore oilfield characteristics.Consequently,the present analysis may offer valuable insights,for instance,by identifying environmental planning decisions as a recent yet highly significant concern that is currently being imposed on decision-making process.Thus,it is evident that the incorporation of safety criteria within the technical-economic decision-making process for the design of production systems would be a crucial requirement at development phase.
文摘Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understood,in particular the influence on the hydrodynamic forces and moments of the distance of the foil to the free surface.Considering this,the present paper documents an experimental investigation in which forces and torque produced,under uniform flow,by a full-scale state-of-the-art hydrofoil(suitable both for kitesurf and windsurf)were measured.A range of velocities,angles of attack,and submergences were tested,leading to Froude numbers based on submergence with maximum values around five,a typical range in actual sailing conditions.From these tests,formulae for the hydrodynamic coefficients have been proposed.They can be used for developing Velocity Prediction Programs(VPP)for this kind of craft,a necessary tool to plan racing configurations and to analyze their racing performance.With the aim of making the experimental data useful for benchmarking numerical models and for future research on related topics such as foil ventilation and transition to turbulence,the specimen’s 3D file is provided as supplementary material to this paper.
文摘Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.
基金funding from the European Commission by the Ruralities project(grant agreement no.101060876).
文摘In this paper,we propose a new privacy-aware transmission scheduling algorithm for 6G ad hoc networks.This system enables end nodes to select the optimum time and scheme to transmit private data safely.In 6G dynamic heterogeneous infrastructures,unstable links and non-uniform hardware capabilities create critical issues regarding security and privacy.Traditional protocols are often too computationally heavy to allow 6G services to achieve their expected Quality-of-Service(QoS).As the transport network is built of ad hoc nodes,there is no guarantee about their trustworthiness or behavior,and transversal functionalities are delegated to the extreme nodes.However,while security can be guaranteed in extreme-to-extreme solutions,privacy cannot,as all intermediate nodes still have to handle the data packets they are transporting.Besides,traditional schemes for private anonymous ad hoc communications are vulnerable against modern intelligent attacks based on learning models.The proposed scheme fulfills this gap.Findings show the probability of a successful intelligent attack reduces by up to 65%compared to ad hoc networks with no privacy protection strategy when used the proposed technology.While congestion probability can remain below 0.001%,as required in 6G services.
基金supported by the Portuguese Foundation for Science and Technology(FCT),Centro 2020 and Portugol2020 and the EU FEDER program,via the project GoBack to SIV(PTDC/CVT-CVT/32261/2017,CENTRO-01-0145-FEDER-032261)the doctoral grants of PDC(SFRH/BD/139974/2018)and BMS(2020.06525.BD and DOI 10.54499/2020.06525.BD)+5 种基金the post-doctoral grant to JPF(SFRH/BPD/113359/2015-program-contract described in paragraphs 4,5,6 of art.23 of Law no.100157/2016,of August 29,as amended by Law no.57/2017 of July 2019),the project PTDC/MED-NEU/1677/2021 to JBRthe Institute of Biomedicine iBiMED(UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020,UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020)its LiM Bioimaging Facility-a PPBI node(POCI-01-0145-FEDER-022122)supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University(HHU)Düsseldorf,of the Biologisch-Medizinisches Forschungszentrum(BMFZ)of HHUfinanced by the Spanish"Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica,Ministerio de Economia y Competitividad(Instituto de Salud CarlosⅢ)",co-financed by the European Union(FEDER program),(grant FIS P/20/00318 and FIS P23/00337 to VC)grant CPP2021-009070 to VC by the"Proyectos de colaboracion publico-privada,Plan de Investigacion Cientifica,Tecnica y de inovacion 2021-2023,Ministerio de Ciencia e Innovacion,Union Europea,Agencia Estatal de Investigacion,Espana"。
文摘Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.
文摘Objective To determine whether frailty is a risk factor for hospitalization and mortality in older adults enrolled in the "Chronic Heart Failure Program" at a hospital in Lima, Peru, between 2018–2021.Methods This was an ambispective cohort study. A total of 85 older adults participating in the Chronic Heart Failure Program at Guillermo Almenara National Hospital were included. Each had an initial frailty assessment, forming two cohorts: frail and non-frail older adults. Medical records were reviewed, and patients were followed for one year to track events of interest(hospitalization and mortality). Overall survival and risk factors for hospitalization and death were determined.Results During follow-up, 15.3% of the older adults died, and frailty was identified in 58.8% of the patients. Overall survival using the Kaplan-Meier method was 96.5% at 3 months after entering the Chronic Heart Failure Program;92.9% at 6 months;and85.9% at one year. Multivariate analysis using Poisson regression found that frailty was not a risk factor for hospitalization(a RR =0.92;95% CI: 0.42–2.03). Survival analysis using the Cox proportional hazards model showed that frailty was also not a risk factor for mortality after one year of follow-up(a HR = 1.32;95% CI: 0.27–6.53).Conclusions Our research does not confirm frailty as a risk factor for hospitalization or mortality in older adults enrolled in the“Chronic Heart Failure Program” after one year of follow-up.
基金supported by the NIA/NIH(1K01AG060040).Studies performed by JN were funded by the NICHD/NIH(5R00HD096117)Microscopy Core Facility supported,in part,with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
文摘Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.
