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Antibiotics and triazole fungicides coexist in varying concentrations in natural aquatic environments, resulting in complex mixtures. These mixtures can potentially affect aquatic ecosystems. Accurately distinguishing synergistic and antagonistic mixtures and predicting mixture toxicity are crucial for effective mixture risk assessment. We tested the toxicities of 75 binary mixtures of antibiotics and fungicides against Auxenochlorella pyrenoidosa. Both regression and classification models for these mixtures were developed using machine learning models: random forest (RF), k-nearest neighbors (KNN), and kernel k-nearest neighbors (KKNN). The KKNN model emerged as the best regression model with high values of determination coefficient (R2 = 0.977), explained variance in prediction leave-one-out (Q2LOO = 0.894), and explained variance in external prediction (Q2F1 = 0.929, Q2F2 = 0.929, and Q2F3 = 0.923). The RF model, the leading classifier, exhibited high accuracy (accuracy = 1 for the training set and 0.905 for the test set) in distinguishing the synergistic and antagonistic mixtures. These results provide crucial value for the risk assessment of mixtures.
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Organic transistors based on organic semiconductors together with quantum dots (QDs) are attracting more and more interest because both materials have excellent optoelectronic properties and solution processability. Electronics based on nontoxic QDs are highly desired considering the potential health risks but are limited by elevated surface defects, inadequate stability, and diminished luminescent efficiency. Herein, organic synaptic transistors based on environmentally friendly ZnSe/ZnS core/shell QDs with passivating surface defects are developed, exhibiting optically programmable and electrically erasable characteristics. The synaptic transistors feature linear multibit storage capability and wavelength-selective memory function with a retention time above 6000 s. Various neuromorphic applications, including memory enhancement, optical communication, and memory consolidation behaviors, are simulated. Utilizing an established neuromorphic model, accuracies of 92% and 91% are achieved in pattern recognition and complicated electrocardiogram signal processing, respectively. This research highlights the potential of environmentally friendly QDs in neuromorphic applications and health monitoring.
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To develop and validate a machine learning based algorithm to estimate physical activity (PA) intensity using the smartwatch with the capacity to record PA and determine outdoor state. Two groups of participants, including 24 adults (13 males) and 18 children (9 boys), completed a sequential activity trial. During each trial, participants wore a smartwatch, and energy expenditure was measured using indirect calorimetry as gold standard. The support vector machine algorithm and the least squares regression model were applied for the metabolic equivalent (MET) estimation using raw data derived from the smartwatch. Exercise intensity was categorized based on MET values into sedentary activity (SED), light activity (LPA), moderate activity (MPA), and vigorous activity (VPA). The classification accuracy was evaluated using area under the ROC curve (AUC). The METs estimation accuracy were assessed via the mean absolute error (MAE), the correlation coefficient, Bland-Altman plots, and intraclass correlation (ICC). A total of 24 adults aged 21-34 years and 18 children aged 9-13 years participated in the study, yielding 1790 and 1246 data points for adults and children respectively for model building and validation. For adults, the AUC for classifying SED, MVPA, and VPA were 0.96, 0.88, and 0.86, respectively. The MAE between true METs and estimated METs was 0.75 METs. The correlation coefficient and ICC were 0.87 (p < 0.001) and 0.89, respectively. For children, comparable levels of accuracy were demonstrated, with the AUC for SED, MVPA, and VPA being 0.98, 0.89, and 0.85, respectively. The MAE between true METs and estimated METs was 0.80 METs. The correlation coefficient and ICC were 0.79 (p < 0.001) and 0.84, respectively. The developed model successfully estimated PA intensity with high accuracy in both adults and children. The application of this model enables independent investigation of PA intensity, facilitating research in health monitoring and potentially in areas such as myopia prevention and control.
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Algoritmos , Exercício Físico , Humanos , Masculino , Feminino , Exercício Físico/fisiologia , Criança , Adulto , Adolescente , Adulto Jovem , Metabolismo Energético/fisiologia , Calorimetria Indireta/métodos , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Curva ROCRESUMO
Organic ion-gated transistors (OIGTs) demonstrate commendable performance for versatile neuromorphic systems. However, due to the fragility of organic materials to organic solvents, efficient and reliable all-photolithography methods for scalable manufacturing of high-density OIGT arrays with multimode neuromorphic functions are still missing, especially when all active layers are patterned in high-density. Here, a flexible high-density (9662 devices per cm2) OIGT array with high yield and minimal device-to-device variation is fabricated by a modified all-photolithography method. The unencapsulated flexible array can withstand 1000 times' bending at a radius of 1 mm, and 3 months' storage test in air, without obvious performance degradation. More interesting, the OIGTs can be configured between volatile and nonvolatile modes, suitable for constructing reservoir computing systems to achieve high accuracy in classifying handwritten digits with low training costs. This work proposes a promising design of organic and flexible electronics for affordable neuromorphic systems, encompassing both array and algorithm aspects.
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OBJECTIVE: Tislelizumab may induce immune-related adverse events, especially adverse skin events. Early detection and timely intervention of cutaneous adverse events are crucial to improve patients' quality of life and reduce the disruption of therapeutic regimens. This study aimed to determine the clinical characteristics of cutaneous adverse reactions to tislelizumab and offer a reference for its rational clinical use. METHODS: Case reports of cutaneous adverse reactions induced by tislelizumab were collected from the relevant databases (up to 31 March 2023). Patient age, sex, primary disease, medication use, occurrence of adverse skin conditions, treatment, and outcomes were recorded and descriptively analysed. RESULTS: A total of 13 patients were enrolled, including six males and seven females, aged 55-79 years, with a median age of 75 years and a mean age of 70.92 ± 8.84 years. The original disease was lung carcinoma in none patients, cervical carcinoma in two, and urothelial carcinoma and squamous cell carcinoma in one each. The time from the initiation of medication use to the occurrence of cutaneous adverse reactions ranged from 7 to 177 days. Among the 13 patients, 10 showed improvement after drug withdrawal or symptomatic treatment. Two patients died (one died of disease progression and multiorgan failure, one died of acute coronary syndrome), and one patient's adverse skin reactions persisted without treatment. CONCLUSIONS: Tislelizumab-related cutaneous adverse reactions mostly occur after several days to months of treatment. In clinical practice, evaluation and monitoring should be strengthened. More attention should be paid to erythema and rashes, which may be signs of serious adverse skin reactions. Early detection and intervention can ensure the safe use of drugs and provide greater clinical benefits to patients.
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Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Síndrome de Stevens-Johnson , Neoplasias da Bexiga Urinária , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/epidemiologia , Carcinoma de Células de Transição/complicações , Qualidade de Vida , Neoplasias da Bexiga Urinária/complicaçõesRESUMO
For most organic synaptic transistors based on the charge trapping effect, different atmosphere conditions lead to significantly different device performance. Some devices even lose the synaptic responses under vacuum or inert atmosphere. The stable device performance of these organic synaptic transistors under varied working environments with different humidity and oxygen levels can be a challenge. Herein, a moisture- and oxygen-insensitive organic synaptic device based on the organic semiconductor and photoinitiator molecules is reported. Unlike the widely reported charge trapping effect, the photoinduced free radical is utilized to realize the photosynaptic performance. The resulting synaptic transistor displays typical excitatory postsynaptic current, paired-pulse facilitation, learning, and forgetting behaviors. Furthermore, the device exhibits decent and stable photosynaptic performances under high humidity and vacuum conditions. This type of organic synaptic device also demonstrates high potential in ultraviolet B perception based on its environmental stability and broad ultraviolet detection capability. Finally, the contrast-enhanced capability of the device is successfully validated by the single-layer-perceptron/double-layer network based Modified National Institute of Standards and Technology pattern recognition. This work could have important implications for the development of next-generation environment-stable organic synaptic devices and systems.
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AIMS: Retinal age derived from fundus images has been verified as a novel ageing biomarker. We aim to explore the association between retinal age gap (retinal age minus chronological age) and incident diabetic retinopathy (DR). METHODS: Retinal age prediction was performed by a deep learning model, trained and validated based on 19,200 fundus images of 11,052 disease-free participants. Retinal age gaps were determined for 2311 patients with diabetes who had no history of diabetic retinopathy at baseline. DR events were ascertained by data linkage to hospital admissions. Cox proportional hazards regression models were performed to evaluate the association between retinal age gaps and incident DR. RESULTS: During the median follow-up period of 11.0 (interquartile range: 10.8-11.1) years, 183 of 2311 participants with diabetes developed incident DR. Each additional year of the retinal age gap was associated with a 7% increase in the risk of incident DR (hazard ratio [HR] = 1.07, 95% confidence interval [CI] 1.02-1.12, P = 0.004), after adjusting for confounding factors. Participants with retinal age gaps in the fourth quartile had a significantly higher DR risk compared to participants with retinal age gaps in the lowest quartile (HR = 2.88, 95% CI 1.61-5.15, P < 0.001). CONCLUSIONS: We found that higher retinal age gap was associated with an increased risk of incident DR. As an easy and non-invasive biomarker, the retinal age gap may serve as an informative tool to facilitate the individualized risk assessment and personalized screening protocol for DR.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Fatores de Risco , Diabetes Mellitus Tipo 2/complicações , Estudos Prospectivos , RetinaRESUMO
PURPOSE: To investigate the effectiveness and cutoffs of axial length/corneal radius (AL/CR) ratio for myopia detection in children by age. METHODS: Totally, 21 kindergartens and schools were enrolled. Non-cycloplegic autorefraction (NCAR), axial length (AL), horizontal and vertical meridian of corneal radius (CR1, CR2), and cycloplegic autorefraction were measured. Receiver operating characteristic (ROC) curve was used to obtain the effectiveness and cutoff for myopia detection. RESULTS: Finally, 7803 participants aged 3-18 years with mean AL/CR ratio of 2.99 ± 0.16 were included. Area under the ROC curve (AUC) of AL/CR ratio for myopia detection (0.958 for AL/CR1, 0.956 for AL/CR2, 0.961 for AL/CR) was significantly larger than that of AL (0.919, all P < 0.001), while AUCs of the three were similar with different cutoffs (> 2.98, > 3.05, and > 3.02). When divided by age, the ROC curves of AL/CR ratio in 3- to 5-year-olds showed no significance or low accuracy (AUCs ≤ 0.823) in both genders. In ≥ 6-year-olds, the accuracies were promising (AUCs ≥ 0.883, all P < 0.001), the cutoffs basically increased with age (from > 2.93 in 6-year-olds to > 3.07 in 18-year-olds among girls, and from > 2.96 in 6-year-olds to > 3.07 in 18-year-olds among boys). In addition, boys presented slightly larger cutoffs than girls in all ages except for 16 and 18 years old. For children aged 3-5 years, AL/CR ratio or AL combined with NCAR increased AUC to > 0.900. CONCLUSION: AL/CR ratio provided the best prediction of myopia with age-dependent cutoff values for all but preschool children, and the cutoffs of boys were slightly larger than those of girls. For preschool children, AL/CR ratio or AL combined with NCAR is recommended to achieve satisfactory accuracy. AL/CR ratio calculated by two meridians showed similar predictive power but with different cutoffs.
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Miopia , Refração Ocular , Pré-Escolar , Humanos , Masculino , Feminino , Adolescente , Criança , Testes Visuais , Rádio (Anatomia) , Miopia/diagnóstico , Córnea , MidriáticosRESUMO
Pain perception nociceptors (PPN), an important type of sensory neuron, are capable of sending out alarm signals when the human body is exposed to destructive stimuli. Simulating the human ability to perceive the external environment and spontaneously avoid injury is a critical function of neural sensing of artificial intelligence devices. The demand for developing artificial PPN has subsequently increased. However, due to the application scenarios of bionic electronic devices such as human skin, electronic prostheses, and robot bodies, where a certain degree of surface deformation constantly occurs, the ideal artificial PPN should have the stretchability to adapt to real scenarios. Here, an organic semiconductor nanofiber artificial pain perception nociceptor (NAPPN) based on a pre-stretching strategy is demonstrated to achieve key pain aspects such as threshold, sensitization, and desensitization. Remarkably, while stretching up to 50%, the synaptic behaviors and injury warning ability of NAPPN can be retained. To verify the wearability of the device, NAPPN was attached to a curved human finger joint, on which PPN behaviors were successfully mimicked. This provides a promising strategy for realizing neural sensing function on either deformed or mobile electronic devices.
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Inteligência Artificial , Nociceptores , Humanos , Células Receptoras Sensoriais , Eletrônica , Percepção da DorRESUMO
Organic optoelectronic synaptic devices that can reliably operate in high-temperature environments (i.e., beyond 121°C) or remain stable after high-temperature treatments have significant potential in biomedical electronics and bionic robotic engineering. However, it is challenging to acquire this type of organic devices considering the thermal instability of conventional organic materials and the degradation of photoresponse mechanisms at high temperatures. Here, high-temperature synaptic phototransistors (HTSPs) based on thermally stable semiconductor polymer blends as the photosensitive layer are developed, successfully simulating fundamental optical-modulated synaptic characteristics at a wide operating temperature range from room temperature to 220°C. Robust optoelectronic performance can be observed in HTSPs even after experiencing 750 h of the double 85 testing due to the enhanced operational reliability. Using HTSPs, Morse-code optical decoding scheme and the visual object recognition capability are also verified at elevated temperatures. Furthermore, flexible HTSPs are fabricated, demonstrating an ultralow power consumption of 12.3 aJ per synaptic event at a low operating voltage of -0.05 mV. Overall, the conundrum of achieving reliable optical-modulated neuromorphic applications while balancing low power consumption can be effectively addressed. This research opens up a simple but effective avenue for the development of high-temperature and energy-efficient wearable optoelectronic devices in neuromorphic computing applications.
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Background: Thousands of research studies concerning genome-wide association studies (GWAS) in Alzheimer's disease (AD) have been published in the last decades. However, a comprehensive understanding of the current research status and future development trends of GWAS in AD have not been clearly shown. In this study, we tried to gain a systematic overview of GWAS in AD by bibliometric and visualization analysis. Methods: The literature search terms are: ("genome-wide analysis" or "genome-wide association study" or "whole-genome analysis") AND ("Alzheimer's Disease" or "Alzheimer Disease"). Relevant publications were extracted from the Web of Science Core Collection (WoSCC) database. Collected data were further analyzed using VOSviewer, CiteSpace and R package Bibliometrix. The countries, institutions, authors and scholar collaborations were investigated. The co-citation analysis of publications was visualized. In addition, research hotspots and fronts were examined. Results: A total of 1,350 publications with 59,818 citations were identified. The number of publications and citations presented a significant rising trend since 2013. The United States was the leading country with an overwhelming number of publications (775) and citations (42,237). The University of Washington and Harvard University were the most prolific institutions with 101 publications each. Bennett DA was the most influential researcher with the highest local H-index. Neurobiology of Aging was the journal with the highest number of publications. Aß, tau, immunity, microglia and DNA methylation were research hotspots. Disease and causal variants were research fronts. Conclusion: The most frequently studied AD pathogenesis and research hotspots are (1) Aß and tau, (2) immunity and microglia, with TREM2 as a potential immunotherapy target, and (3) DNA methylation. The research fronts are (1) looking for genetic similarities between AD and other neurological diseases and syndromes, and (2) searching for causal variants of AD. These hotspots suggest noteworthy directions for future studies on AD pathogenesis and genetics, in which basic research regarding immunity is promising for clinical conversion. The current under-researched directions are (1) GWAS in AD biomarkers based on large sample sizes, (2) studies of causal variants of AD, and (3) GWAS in AD based on non-European populations, which need to be strengthened in the future.
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BACKGROUND: Most cancer patients suffer from the pain of chemotherapy-induced nausea and vomiting (CINV). This meta-analysis was performed to evaluate the efficacy and safety of a regimen consisting of aprepitant, dexamethasone, and 5-HT3 receptor antagonists in the prevention and treatment of CINV. METHODS: A systematic literature search was conducted across multiple databases, including PubMed, EMbase, Cochrane Library, MEDLINE, CENTRAL, HEED, CNKI, Wanfang, and VIP, to identify randomized controlled trials (RCTs) investigating the use of triple therapy (aprepitant, 5-HT3 receptor antagonist, and dexamethasone) to prevent and treat CINV. Meta-analysis was performed using RevMan 5.4 and Stata17 software, employing either a fixed-effect or random-effect model based on statistical heterogeneity. RESULTS: A meta-analysis of 23 randomized controlled trials (RCTs) involving 7956 patients was conducted. Efficacy: Results showed significantly improved complete responses (CRs) for CINV in the test group versus the control group in the overall, acute, and delayed phases. Furthermore, in the test group, substantial alleviation of nausea symptoms was observed in the delayed and overall phases but not in the acute phase. Safety: There was no statistically significant difference in the incidence of febrile neutropenia, diarrhea, anorexia, and headache between the 2 groups. The incidence of fatigue and hiccups in the test group was higher than that in the control group; however, the incidence of constipation was significantly lower. CONCLUSIONS: Aprepitant-containing triple therapy is highly effective in the prevention and treatment of CINV, with reliable medication safety.
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Antieméticos , Antineoplásicos , Humanos , Aprepitanto/uso terapêutico , Antieméticos/uso terapêutico , Receptores 5-HT3 de Serotonina/uso terapêutico , Morfolinas/uso terapêutico , Antineoplásicos/efeitos adversos , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/prevenção & controle , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Dexametasona/uso terapêuticoRESUMO
Increasing attention has been paid to organic electronics emulating the characteristics and functions of the peripheral nervous system (PNS) and central nervous system (CNS) in living organisms, which has important implications for exploring electronics from the underlying architecture to emulate biological sensory synapses/neurons and develop brain-like chips. However, the vast majority of current research has been limited to biomimetic electronics that implement the functionality of a single PNS or CNS. Here, we develop solution-processed optoelectronic synaptic transistors (OSTs) that simultaneously simulate the visual nociceptor perception functions of the PNS as well as the memorizing and computing functions of the CNS, where CsPbCl3 quantum dots (QDs) and organic semiconductor serve as the photoactive layer and channel layer, respectively. Benefiting from the distinctive absorption characteristic of CsPbCl3 QDs, the OSTs illustrate decent ultraviolet light selectivity, which can be utilized to mimic visual nociceptor behavior triggered by ultraviolet irradiation for pain perception. Furthermore, the OSTs successfully achieve 1000 conductance states, which also confirms the outstanding conductivity regulation ability of the OSTs and their potential in pattern recognition based on artificial neural networks. This work provides a pathway for the development of future artificial vision and neuromorphic computing using OSTs based on solution-processable organic semiconductors and QDs.
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Background and purpose: In recent years, synaptic plasticity disorders have been identified as one of the key pathogenic factors and the early pathological characteristics of Alzheimer's disease (AD). In this study, we tried to use bibliometric analysis to gain a systematic understanding about synaptic plasticity in Alzheimer's disease. Methods: We extracted relevant publications from the Web of Science Core Collection (WoSCC) on August 29th, 2022. Then, we used CiteSpace, VOSviewer and other online bibliometric platforms to further analyze the obtained data. Results: A total of 2,348 published articles and reviews about synaptic plasticity in AD from 2002 to 2022 were identified. During the past two decades, the overall trends of the numbers and citations of manuscripts were on the rise. The United States was the leading country with the largest number of publications which showed its crucial role in this field. The collaboration network analysis showed that the United States and China had the most frequent collaboration. In addition, Harvard University was the institution with the greatest number of publications and cited times. Among all authors, Selkoe DJ was the most influential author with the greatest cited times. The journal of Alzheimer's disease published the maximum number of documents in the field of synaptic plasticity in AD within 20 years. Furthermore, the results of keywords burst detection showed that the hot topics have shifted from the synaptic transmission, precursor protein and plaque formation to neuroinflammation, microglia and alpha synuclein. Conclusion: This study analyzed 2,348 publications with 82,025 references covering the topic of synaptic plasticity in AD and presented the research trends. The results indicated that neuroinflammation, microglia and alpha synuclein were the current research hotspots, which implied the potential clinical applications to AD.
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BACKGROUND: Conflicting evidence exists on the association between ageing and obesity. Retinal age derived from fundus images has been validated as a novel biomarker of ageing. In this study, we aim to investigate the association between different anthropometric phenotypes based on body mass index (BMI) and waist circumference (WC) and the retinal age gap (retinal age minus chronological age). METHODS: A total of 35,550 participants with BMI, WC and qualified retinal imaging data available were included to investigate the association between anthropometric groups and retinal ageing. Participants were stratified into 7 different body composition groups based on BMI and WC (Normal-weight/Normal WC, Overweight/Normal WC, Mild obesity/Normal WC, Normal-weight/High WC, Overweight/High WC, Mild obesity/High WC, and Severe obesity/High WC). Linear regression and logistic regression models were fitted to investigate the association between the seven anthropometric groups and retinal age gap as continuous and categorical outcomes, respectively. RESULTS: A total of 35,550 participants (55.6% females) with a mean age 56.8 ± 8.04 years were included in the study. Individuals in the Overweight/High WC, Mild obesity/High WC and Severe obesity/High WC groups were associated with an increase in the retinal age gap, compared with those in the Normal Weight/Normal WC group (ß = 0.264, 95% CI: 0.105-0.424, P =0.001; ß = 0.226, 95% CI: 0.082-0.371, P = 0.002; ß = 0.273, 95% CI: 0.081-0.465, P = 0.005; respectively) in fully adjusted models. Similar findings were noted in the association between the anthropometric groups and retinal ageing process as a categorical outcome. CONCLUSION: A significant positive association exists between central obesity and accelerated ageing indexed by retinal age gaps, highlighting the significance of maintaining a healthy body shape.
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Obesidade Mórbida , Sobrepeso , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Obesidade Abdominal/epidemiologia , Bancos de Espécimes Biológicos , Obesidade/epidemiologia , Índice de Massa Corporal , Circunferência da Cintura , Reino Unido/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVE: To investigate associations between different glycemic status and biological age indexed by retinal age gap. METHODS: A total of 28,919 participants from the UK Biobank study with available glycemic status and qualified retinal imaging data were included in the present analysis. Glycemic status included type 2 diabetes mellitus (T2D) disease status and glycemic indicators of plasma glycated hemoglobin (HbA1c) and glucose. Retinal age gap was defined as the difference between the retina-predicted age and chronological age. Linear regression models estimated the association of different glycemic status with retinal age gap. RESULTS: Prediabetes and T2D was significantly associated with higher retinal age gaps compared to normoglycemia (regression coefficient [ß] = 0.25, 95% confidence interval [CI]: 0.11-0.40, P = 0.001; ß = 1.06, 95% CI: 0.83-1.29, P < 0.001; respectively). Multi-variable linear regressions further found an increase of HbA1c was independently associated with higher retinal age gaps among all subjects or subjects without T2D. Significant positive associations were noted across the increasing HbA1c and glucose groups with retinal age gaps compared to the normal level group. These findings remained significant after excluding diabetic retinopathy. CONCLUSIONS: Dysglycemia was significantly associated with accelerated ageing indexed by retinal age gaps, highlighting the importance of maintaining glycemic status.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas , Glicemia/análise , Bancos de Espécimes Biológicos , Glucose , Retina , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: To evaluate the correlation between cognitive signatures and the risk of diabetic vascular complications and mortality, based on a multicountry prospective study. METHODS: The participants comprised 27,773 diabetics from the UK Biobank (UKB) and 1307 diabetics from the Guangzhou Diabetic Eye Study (GDES) cohort. The exposures were brain volume and cognitive screening tests for UKB participants, whilst the global cognitive score (GCS) measuring orientation to time and attention, episodic memory, and visuospatial abilities were determined for GDES participants. The outcomes for the UKB group were mortality, as well as macrovascular (myocardial infarction [MI] and stroke), microvascular (end-stage renal disease [ESRD], and diabetic retinopathy [DR]) events. The outcomes for the GDES group were retinal and renal microvascular damage. RESULTS: In the UKB group, a 1-SD reduction in brain gray matter volume was associated with 34%-77% higher risks of incident MI, ESRD, and DR. The presence of impaired memory was associated with 18%-73% higher risk of mortality and ESRD; impaired reaction was associated with 1.2-1.7-fold higher risks of mortality, stroke, ESRD, and DR. In the GDES group, the lowest GCS tertile exhibited 1.4-2.2-fold higher risk of developing referable DR and a twofold faster decline in renal function and retinal capillary density compared with the highest tertile. Restricting data analysis to individuals aged less than 65 years produced consistent results. CONCLUSION: Cognitive decline significantly elevates the risk of diabetic vascular complications and is correlated with retinal and renal microcirculation damage. Cognitive screening tests are strongly recommended as routine tools for management of diabetes.
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Diabetes Mellitus Tipo 2 , Angiopatias Diabéticas , Retinopatia Diabética , Falência Renal Crônica , Acidente Vascular Cerebral , Humanos , Estudos de Coortes , Estudos Prospectivos , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/complicações , Angiopatias Diabéticas/etiologia , Cognição , Falência Renal Crônica/complicações , Acidente Vascular Cerebral/complicações , Encéfalo , Fatores de Risco , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
BACKGROUND: Our previous studies indicated that anesthesia and surgery could aggravate cognitive impairment of 5XFAD transgenic (Tg) mice, and this aggravation was associated with tau hyperphosphorylation. We previously identified that GNA13 (the gene encoding Gα13) was a hub gene with tau hyperphosphorylation. OBJECTIVE: This study aims to further investigate the mechanism that whether the Gα13-mediated signaling pathway acts as an instigator to regulate cofilin activation and autophagy impairment in this process. METHODS: 5XFAD Tg mice and their littermate (LM) mice were randomly allocated into four groups: LM Control group, LM Anesthesia/Surgery group, AD Control group, and AD Anesthesia/Surgery group. For mice in the Anesthesia/Surgery groups, abdominal surgery was performed under 1.4% isoflurane anesthesia followed by sustaining anesthetic inhalation for up to 2âh. RESULTS: Compared with the AD Control group, protein levels of Gα13, ROCK2, LPAR5, and p-tau/tau46 ratio were increased, while p-cofilin/cofilin protein expression ratio was decreased in the AD Anesthesia/Surgery group. However, the differences in these protein levels were not significant among LM groups. CONCLUSION: This study demonstrated that anesthesia and surgery might exacerbate p-tau accumulation in 5XFAD Tg mice but not in LM mice. And this might be closely related to cofilin activation via Gα13-mediated signaling cascade.