Development Of Disease Research Articles

MiHUBx: adigital progress hub for the use of intersectoral clinical data sets using the example of diabetic macular edema

Evidence-based treatment recommendations are helpful in the corresponding discipline-specific treatment but can hardly take data from real-world care into account. In order to make better use of this in everyday clinical practice, including with respect to predictive statements about disease development or treatment success, models with data from treatment must be developed in order to use them for the development of assistive artificial intelligence. The aim of the Use Case1 of the medical informatics hub in Saxony (MiHUBx) is the development of amodel based on treatment and research data for a treatment algorithm supported by biomarkers and also the development of the necessary digital infrastructure. Step by step, the necessary partners in hospitals and practices will be brought together technically or through research questions within Use Case1 "Ophthalmology meets Diabetology", aregional digital progress hub in health, the medical informatics hub in Saxony (MiHUBx) of the nationwide medical informatics initiative (MII). Based on joint studies with diabetologists, robust serological and imaging biomarkers were selected that provide evidence of the development of diabetic macular edema (DME). In the future, these and other scientifically proven prognostic markers will be incorporated into atreatment algorithm that is supported by artificial intelligence (AI). For this purpose, model procedures are being developed together with medical informatics specialists. At the same time, adata integration center (DIZ) was established. In addition to the structured and technical combination of the previously disseminated and partially heterogeneous treatment data, the Use Case1 defines the chances and hurdles for using such real-world data to develop artificial intelligence.

Relationship Between Acute Severe Acute Respiratory Syndrome Coronavirus 2 Viral Clearance and Long Coronavirus 2019 (Long COVID) Symptoms: A Cohort Study.

The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics during acute infection and the development of long coronavirus disease 2019 (COVID-19), or "long COVID," is largely unknown. Between October 2021 and February 2022, 7361 people not known to have COVID-19 self-collected nasal swab samples for SARS-CoV-2 reverse-transcription polymerase chain reaction testing every 24-48 hours for 10-14 days. Participants whose first known SARS-CoV-2 infection was detected were surveyed for long COVID in August 2023. Their slopes of viral clearance were modeled using linear mixed effects models with random slopes and intercepts, and the relative risk (RR) of long COVID based on viral slopes was calculated using a log binomial model, adjusted for age, symptoms, and variant. Sex-based interaction terms were also evaluated for significance. A total of 172 participants were eligible for analyses, and 59 (34.3%) reported long COVID. The risk of long COVID with 3-4 symptoms (adjusted RR, 2.44 [95% confidence interval, .88-6.82]) and ≥5 symptoms (4.97 [1.90-13.0]) increased with each unit increase in slope of viral clearance. While the probability of long COVID increased with slowed viral clearance among women, the same relationship was not observed among men (interaction term: P = .02). Acute SARS-CoV-2 symptoms of abdominal pain (adjusted RR, 5.41 [95% confidence interval, 2.44-12.0]), nausea (3.01 [1.31-6.89]), and body aches (2.58 [1.26-5.30]) were most strongly associated with long COVID. We observed that slower viral clearance rates during acute COVID-19 were associated with increased risk and more symptoms of long COVID . Early viral-host dynamics appear to be mechanistically linked to the development of long COVID.

Preparing for stormy weather: building VA health system resilience for dialysis emergency preparedness in the era of climate change.

Climate change has been implicated as the driver for the increasing number, intensity, duration, and consequences of catastrophic weather events. As a result of extreme weather events, climate change has also been implicated as an important mediator of adverse kidney health outcomes, not only increasing the risk for the development of acute and chronic kidney diseases, but also disrupting the delivery of critical kidney health services. In particular, the delivery of dialysis services during major emergencies remains an ongoing and increasing problem, with a recognized need for improved emergency preparedness and disaster management (EP-DM) strategies to mitigate the increased risk of morbidity and mortality associated with missed dialysis treatment. There are increasing reports detailing the challenges of kidney dialysis care in times of crisis, to include those resulting from both man-made and natural disasters. Optimized management of the high-risk vulnerable dialysis patient population must include both facility-facing comprehensive continuity of operations and emergency response plans, and ongoing patient-facing emergency preparedness education. This review discusses the adverse impact of climate change-related natural disasters on the delivery of dialysis services, and the evolving EP-DM strategies developed and implemented by the Veterans Health Administration (VA) to optimize the care and well being of the vulnerable end stage kidney disease (ESKD) patient population.

Epidemiology of Chronic Pulpitis, Dental Caries, and Periapical Disease and Their Possible Risk Factors in an Adult Chinese Population in the Northern Regions of China

Background: Dental diseases and disorders are reported to affect specific ages, genders, and races of patients. Therefore, epidemiological investigations are necessary for understanding dental diseases and disorders. Objectives: This cross-sectional study aims to determine the prevalence and potential risk factors of chronic pulpitis, dental caries, and periapical disease in adults seeking treatment at the Tianjin Stomatological Hospital, Tianjin, a major referral center in the Northern region of China. Methods: A total of 3,245 males and females visited the Department of Adult Dentistry and the Department of Endodontics of the Tianjin Stomatological Hospital, Tianjin, China, for oral health concerns from January 17, 2020, to November 18, 2023. Among these patients, 615 (19%) were receiving treatment for chronic pulpitis, dental caries, and/or periapical diseases at the institute. Demographic parameters and clinical examination results of 496 patients (119 patients were excluded due to missing information) who were being treated for chronic pulpitis (long-term inflammation of the dental pulp), dental caries (a biofilm-mediated, sugar-driven, multifactorial, dynamic disease), and/or periapical disease (inflammation around the tooth root) with varying severity (moderate or severe) were included in the study. Results: Of the 496 patients, 300 (60%) were females, 328 (66%) were aged 60 years or older, and 295 (59%) had issues with mandibular teeth. Among the patients, 250 (50%), 301 (61%), and 151 (30%) were diagnosed with dental caries, chronic pulpitis, and periapical disease(s), respectively. Female gender (P = 0.041), age ≥ 60 years (P = 0.045), and issues with mandibular teeth (P = 0.046) were found to be associated with chronic pulpitis, dental caries, and periapical diseases in the patients. Conclusions: The prevalence of dental diseases and disorders in Han Chinese adults is 19% in the Northern regions of China. Chronic pulpitis and dental caries are the most prevalent dental diseases, while periapical diseases occur less frequently among Han Chinese adults in the Northern regions of China. Females, individuals aged ≥ 60 years, and issues with mandibular teeth are independent risk factors for the development of chronic pulpitis, dental caries, and periapical disease in adult patients in Northern regions of China. Policymakers in China should consider the findings of this study to reduce dental diseases and disorders in Chinese adults, especially in the Northern regions of China.

Interplay between Netrin-1 and Norrin controls arteriovenous zonation of blood–retina barrier integrity

The integrity of the blood-retina barrier (BRB) is crucial for phototransduction and vision, by tightly restricting transport of molecules between the blood and surrounding neuronal cells. Breakdown of the BRB leads to the development of retinal diseases. Here, we show that Netrin-1/Unc5b and Norrin/Lrp5 signaling establish a zonated endothelial cell gene expression program that controls BRB integrity. Using single-cell RNA sequencing (scRNA-seq) of postnatal BRB-competent mouse retina endothelial cells (ECs), we identify >100 BRB genes encoding Wnt signaling components, tight junction proteins, and ion and nutrient transporters. We find that BRB gene expression is zonated across arteries, capillaries, and veins and regulated by opposing gradients of the Netrin-1 receptor Unc5b and Lrp5-β-catenin signaling between retinal arterioles and venules. Mice deficient for Ntn1 or Unc5b display more BRB leakage at the arterial end of the vasculature, while Lrp5 loss of function causes predominantly venular BRB leakage. ScRNA-seq of Ntn1 and Unc5b mutant ECs reveals down-regulated β-catenin signaling and BRB gene expression that is rescued by Ctnnb1 overactivation, along with BRB integrity. Mechanistically, we demonstrate that Netrin-1 and Norrin additively enhance β-catenin transcriptional activity and Lrp5 phosphorylation via the Discs large homologue 1 (Dlg1) scaffolding protein, and endothelial Lrp5-Unc5b function converges in protection of capillary BRB integrity. These findings explain how arteriovenous zonation is established and maintained in the BRB and reveal that BRB gene expression is regulated at the level of endothelial subtypes.

Circulating Levels of Low-Density Granulocytes and Cell-Free DNA as Predictors of Cardiovascular Disease and Bone Deterioration in SLE Patients.

The present work evaluates the predictive value of low-density granulocytes (LDGs) for the development of cardiovascular disease (CVD) and/or bone deterioration (BD) in a 6-year prospective study in systemic lupus erythematosus (SLE). Considering the high SLE-LDG capacity to form neutrophil extracellular traps (NETs), circulating levels of total cell-free DNA (cirDNA) and relative amounts of mitochondrial and nuclear DNA (mtDNA and nDNA, respectively) were tested as LDG-associated biomarkers to identify SLE patients at risk of CVD and BD. The frequency of total blood LDGs, as well as the CD16negCD14neg (nLDG) and CD16posCD14low (pLDG) subsets, was quantified by flow cytometry in 33 controls and 144 SLE patients. Total cirDNA and relative amounts of mitochondrial (mtDNA) and nuclear (nDNA) cell-free DNA were measured by fluorometry or qPCR in plasma from a subgroup of 117 patients and 23 controls at enrolment. Our findings showed increased blood levels of SLE-nLDGs at enrolment associated with prospective CVD development (pCVD) and the presence of BD, thus revealing LDG expansion as a predictor of both comorbidities in SLE progression. The amounts of the different types of circulating DNA analyzed were increased in patients, especially those presenting with traditional CV risk factors or subclinical atheromatosis. Similar to nLDGs, the nDNA concentration could predict the development of pCVD in SLE, supporting the quantification of cirDNA levels as a surrogate marker of LDGs in clinical practice.

A newly developed oral infection mouse model of shigellosis for immunogenicity and protective efficacy studies of a candidate vaccine.

Shigella infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl3) plus desferrioxamine intraperitoneally followed by oral infection with virulent Shigella flexneri 2a resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing Shigella invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against Shigella, indicating that the model is suitable for testing of vaccine candidates. To protect both Shigella and Salmonella, a chimeric recombinant vaccine (rIpaB-T2544) was developed by fusing IpaB with Salmonella outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with Shigella (S. flexneri 2a, Shigella dysenteriae, and Shigella sonnei) using our present mouse model and Salmonella (Salmonella Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral Shigella infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against Shigella.

Features of molecular phenotype and ultrastructure of smooth muscle cells in ascending aorta in premature born rats

Preterm birth can contribute to the development of diseases of circulatory system in adulthood due to the incompleteness of the morphogenesis of the blood vessels wall. Smooth muscle cells are the leading cell population in the middle shell of the aortic wall and are plastic in nature, i. e. they are able to change their phenotype depending on the conditions of their environment. The presence of synthetically active smooth muscle cells in the aortic wall of an adult individual is a predictor of the formation of a wide range of cardiovascular diseases. The aim of our study is to identify the morphofunctional features of molecular phenotype and ultrastructure of smooth muscle cells of ascending aorta wall in rats born 12 and 24 hours prematurely. The paper presents the results of immunohistochemical and morphometric, as well as ultrastructural analysis of ascending aorta wall in Wistar rats born 12 and 24 hours prematurely. It has been shown that preterm birth leads to a later change in the phenotype of smooth muscle cells from synthetic to contractile, which can negatively affect the morphofunctional state of the cardiovascular system.

Effect of Environmental Factors and Date of Sowing on Disease Development

Understanding the effect of environmental factors and sowing dates on disease development is crucial for optimizing crop health, improving yield, and devising effective, timely disease management strategies in agriculture. The current investigation, which was conducted During 2021 in the laboratory of the Department of Plant Pathology, Naini Agricultural Institute, and Sam Higginbottom University of Agriculture Technology and Sciences. To investigate the impact of environment and date of sowing on development of disease Maydis leaf blight of maize. During Kharif 2021 and 2022, for all four sowing dates, the disease progression of maydis leaf blight on maize variety CML-186 was monitored at weekly intervals beginning at 45 DAS of crop. It can be concluded that the crop stage showed the highest disease incidence at 45, 80, and 87 DAS; consequently, this stage tends to exhibit the most susceptible reaction during Kharif 2021. The crop stage with the highest disease incidence during Kharif 2022 was at 45, 52, and 80 DAS; as a result, this stage typically exhibits the most susceptible response. During Kharif 2021 and 2022, for all four sowing dates, the AUDPC of maydis leaf blight on maize variety CML-186 was noted at weekly intervals beginning at 45 DAS of crop.

The Influence of Genetic Polymorphisms in Cytochrome P450 (CYP1A1 and 2D6) Gene on the Susceptibility to Philadelphia Negative Chronic Myeloid Leukemia in Sudanese Patients

The most frequent type of leukemia in Africa is chronic myeloid leukemia (CML). The genetic background of the rarer Philadelphia chromosome (Ph) Ph-ve (BCR-ABL-ve) subform of CML is largely unknown in African patients. Therefore, in this study, we aimed to investigate the role of CYP1A1 and 2D6 SNPs in the pathogenesis of Ph-ve CML in the Sudanese population. A total of 126 patients were selected for analysis. DNA was isolated from Ph-ve CML patients and a control group for PCR-RFLP analysis of SNPs CYP1A1*2C and CYP2D6*4. The CYP1A1 gene significantly expressed the GG variant genotype (p < 0.05) in 23.1% of the Ph-ve CML patients and 8% of the control group. In contrast, the CYP2D6 GA genotype was strongly associated with a reduced risk of developing Ph-ve CML (p < 0.005) with a frequency of 50% in Ph-ve patients and 93% in the control group. CYP1A1 GG polymorphism was prevalent among patients with Ph-ve CML, suggesting its role in disease development. CYP2D6 GA (IM) polymorphism was uncommon among patients, compared with the control group, possibly indicating a protective role of the polymorphisms from Ph-ve CML. This study demonstrates an association between key metabolic SNPs and Ph-ve CML and highlights the role that altered xenobiotic metabolism may play in the development of several human leukemias.

Curcumin: Epigenetic Modulation and Tumor Immunity in Antitumor Therapy.

Curcumin is the main ingredient of the Chinese herbal turmeric rhizome, used to treat tumors, diabetes, inflammation, neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, and liver diseases. The antitumor effects of curcumin have received even more attention. One of the main mechanisms of antitumor effects includes inhibition of tumor invasion and migration, induction of tumor cell apoptosis, and inhibition of various cell signaling pathways. It has been found that the antitumor biological activity of curcumin in the body is associated with epigenetic mechanisms. That also implies that curcumin may act as a potential epigenetic modulator to influence the development of tumor diseases. The immune system plays an essential role in the development of tumorigenesis. Tumor immunotherapy is currently one of the most promising research directions in the field of tumor therapy. Curcumin has been found to have significant regulatory effects on tumor immunity and is expected to be a novel adjuvant for tumor immunity. This paper summarizes the antitumor effects of curcumin from four aspects: molecular and epigenetic mechanisms of curcumin against a tumor, mechanisms of curcumin modulation of tumor immunotherapy, reversal of chemotherapy resistance, and novel drug delivery system of curcumin, which provide new directions for the development of new antitumor drugs.

Factores de riesgo de obesidad y sobrepeso en infantes: estudio basado en la ENDI

Excess weight (overweight and obesity) in infants represents a growing public health challenge globally, with significant implications for the development of non-communicable chronic diseases. In this context, the present study aimed to investigate factors associated with overweight and obesity in infants aged 2 to 5 years in Ecuador during the period between 2022 and 2023. For this purpose, a cross-sectional study was conducted, using data from the National Survey of Child Malnutrition, evaluating 13,539 children aged 2 to 5 years. Socioeconomic and demographic data were collected using previously validated structured questionnaires. Regarding the results, associated factors were identified through bivariate and multivariate logistic regression. The prevalence of overweight and obesity was 5.5%, being more prevalent in boys (6.4%). Furthermore, it was determined that belonging to the white and mixed-race ethnicity predisposes the individual to develop overweight/obesity; likewise, it was established that being a girl, being poor due to unmet basic needs, presenting malnutrition, and anemia are "protective" factors against excess weight.

Correlations of the triglyceride−glucose index and modified indices with arterial stiffness in overweight or obese adults

BackgroundInsulin resistance (IR) contributes substantially to the development of cardiovascular disease (CVD) and metabolic disorders, particularly obesity. The homeostatic model assessment of IR is a prevalent IR indicator, but insulin measurement is quite impractical for widely use. Given its convenience and accessibility, the triglyceride−glucose (TyG) index, along with modified indices such as the triglyceride−glucose−waist circumference (TyG−WC) and triglyceride−glucose−waist−height ratio (TyG−WHtR), are gaining recognition as practical tools for assessing IR. This study aimed to investigate the specific correlation between the TyG index and its modified indices with arterial stiffness in an overweight or obese population and to explore novel, self-defined modified TyG indices for identifying individuals at elevated risk for such conditions.MethodsThis retrospective study included 1,143 overweight or obese individuals from 2021 to 2023. Medical data, including brachial-ankle pulse wave velocity (baPWV), were collected. Two novel modified TyG indices, TyG-1h and TyG-2h, were defined by substituting the fasting glucose level in the TyG formula with 1-hour and 2-hour post-load plasma glucose levels, respectively. Multivariate logistic regression analyses were conducted to identify parameters that demonstrated a statistically significant correlation with arterial stiffness, defined as a baPWV threshold of ≥ 1400 cm/s. Additionally, restricted cubic spline (RCS) modelling was employed to further explore these relationships in a visually interpretable manner. To evaluate and compare the diagnostic accuracy of the conventional TyG index and its novel modified versions, receiver operating characteristic (ROC) curve analyses were performed.ResultsOur findings revealed that individuals with arterial stiffness presented significantly elevated TyG index and all its modified versions (P< 0.05). By utilizing a binary logistic regression model and adjusting for potential confounders, we determined that all TyG-related parameters independently correlated with an increased risk of developing arterial stiffness. Moreover, TyG-WHtR displayed the best correlation (OR 3.071, 95% CI 1.496-6.303) when stratified by quartiles, followed by TyG-1h (OR 2.298, 95% CI 1.248-4.234) and TyG-2h (OR 2.115, 95% CI 1.175-3.807). ROC curves suggested that TyG-1h and TyG-2h demonstrated superior diagnostic performance compared to TyG, with AUCs of 0.685, 0.679 and 0.673, respectively.ConclusionsThe modified TyG indices exhibited strong effectiveness in identifying arterial stiffness in Chinese overweight or obese individuals.

A study of stressful life events in patients with first-episode acute coronary syndrome (ACS)—a hospital-based case–control study

BackgroundThere is considerable evidence in the literature highlighting the impact of psychological factors on the development of coronary heart disease. In India, there's a rising incidence of traumatic life events alongside coronary heart disease, yet the connection between them remains relatively understudied. Therefore, this study aims to investigate stressful life events among patients experiencing their first episode of acute coronary syndrome (ACS) and compare this with controls.ResultsThe mean number of stressful life events (SLEs) observed was 5.07 ± 2.04 in cases and 4.35 ± 1.88 in controls, with a p-value of < 0.05. Cases had a significantly higher prevalence of medical and psychiatric morbidity than controls, with rates of 89.3% compared to 69.6% for medical issues, and 56.7% versus 24.0% for psychiatric conditions, respectively. Univariate analyses revealed a significant difference between cases and controls in the types of stressors experienced, with cases showing higher odds ratios (OR) for specific events such as Fire or Explosion (OR = 4.5), Transportation accident (OR = 3.4), and Captivity (OR = 2.3). Additionally, bivariate analyses indicated that presence of a comorbid medical illness had an OR of 5.95. At the same time, specific life events like Exposure to fire or explosion (OR = 3.35) and Transportation accidents (OR = 3.08) were more likely to occur in cases. Overall, there were significant differences in the prevalence and pattern of various types of SLEs between cases and controls.ConclusionThe higher number of SLEs observed in cases compared to controls underscores their potential role in cardiac risk. While transportation accidents and fires/explosions demonstrated robust associations with ACS, the variable significance across different types of SLEs suggests a complex relationship between stressor type and cardiac outcomes. These findings highlight the need for prospective studies with larger sample sizes and further research to ascertain and quantify the role of stressful events and the risk of a cardiac event.

INVOLVEMENT OF HLA-DRB1*11 AND HLA-DRB1*12 ALLELES IN THE OCCURRENCE OF DENGUE FEVER IN BURKINA FASO

Introduction: Dengue has become the world's most common arbovirosis. In some individuals, genetic factors can increase the risk of developing severe dengue fever. Human leukocyte antigen (HLA) genes are one of the most extensively studied gene groups in human disease. The present study investigated HLA DRB1*11 and HLA DRB1*12 polymorphisms in dengue cases and their susceptibilities in the development of dengue in a population in Ouagadougou, Burkina Faso. Methodology: This was a case-control study involving 56 patients with clinically and biologically confirmed dengue fever and 65 others who had never been in contact with DENV, for a total of 121 individuals. A blood sample was taken from each study participant. After extraction of genomic DNA using the salting-out technique, characterisation of carriage of the HLA-DRB1*11 and 1*12 alleles was carried out using multiplex polymerase chain reaction (PCR). The χ² test, odds ratio (OR), and confidence interval (CI) were calculated using SPSS software to estimate associations and assess the level of risk. Results: Allele frequencies in the general population were 64.4% and 62.8% for HLA DRB1*11 and HLA DRB1*12, respectively. The HLA-DRB1*12 allele was present in 28.9% of cases and 33.9% of controls. The HLA-DRB1*11 allele was present in 32.2% of both cases and controls. In this study, no direct association was found between the presence of the HLA-DRB1*11 and HLA-DRB1*12 alleles and the surveillance of dengue infection. Furthermore, the absence of the HLA-DRB1*11 allele was associated with protection against the development of severe disease (OR = 0.03; 95% CI [0.11 - 0.80]; and p = 0.01). Conclusion: No risk of developing severe dengue fever was found in individuals carrying the HLA-DRB1*11 and HLA-DRB 1*12 alleles. However, further study of other HLA alleles involved in the development of severe dengue may provide more information.

Sustainable integration of artificial intelligence and machine learning approaches within the African infectious disease vaccine research and development ecosystem

Artificial Intelligence and Machine Learning (AI/ML) techniques, including reverse vaccinology and predictive models, have already been applied for developing vaccine candidates for COVID-19, HIV, and Hepatitis, streamlining the vaccine development lifecycle from discovery to deployment. The application of AI and ML technologies for improving heath interventions, including drug discovery and clinical development, are expanding across Africa, particularly in South Africa, Kenya, and Nigeria. Further initiatives are required however to expand AI/ML capabilities across the continent to ensure the development of a sustainable ecosystem including enhancing the requisite knowledge base, fostering collaboration between stakeholders, ensuring robust regulatory and ethical frameworks and investment in requisite infrastructure.

BODIPY‐Based Small‐Molecule Photoacoustic Probes for Biomedical Imaging

Advances in bioimaging technologies capable of visualizing physiological and pathological processes are of great significance for revealing diseases development and promoting clinical diagnosis and treatment. Photoacoustic (PA) imaging, utilizing small‐molecule probes, offers a promising approach for achieving high‐spatiotemporal‐imaging of dynamic biological process. The development of near‐infrared absorbing dyes has significantly contributed to the research of small‐molecule PA probes, particularly boron‐dipyrromethene derivatives (BODIPYs) known for their simple synthesis, tunable NIR photophysical properties and superior PA imaging abilities. This review highlights recent advances in biomedical applications of BODIPY‐based PA probes, including the design strategies, spectral characteristics, response mechanisms and applications for imaging biomarkers such as reactive oxygen/nitrogen species, gaseous signaling molecules and metal ions. The insights provided in this review are expected to guide future studies on small‐molecule PA probes for bioimaging and biosensing.

CD11b deficiency attenuates the ischemia/reperfusion-induced AKI-to-CKD process by regulatingmacrophage polarization.

Severe acute kidney injury (AKI) is a risk factor for the future development of chronic kidney disease (CKD), and macrophages are an essential cell group implicated in injury, repair, and fibrosis during this progress. However, the underlying mechanism of how macrophages participate in the development of the disease is largely unclear. CD11b (Integrin αM) is highly expressed in monocytes/macrophages and has been verified to mediate broad functions. We found that CD11b-knockout mice were protected from the ischemia/reperfusion-induced AKI-to-CKD process. Additionally, renal macrophages from the kidneys of CD11b-deficient mice presented an M2-like, anti-inflammatory phenotype. We demonstrated both invitro and invivo that enhanced alternative activation in CD11b-knockout macrophages is regulated by the interleukin (IL)-4/signal transducer and activator of transcription (STAT) 6 axis, which is mediated by the inactivation of the Src-family kinase (SFK) member Lyn. Importantly, the therapeutical administration of CD11b-neutralizing antibody can effectively prevent AKI-to-CKD progress. Thus, our study verifies that CD11b plays a critical role in limiting the alternative activation of macrophages and may be a potential therapeutic target during the AKI-to-CKD process.

Differential Expression Analyses on Human Aortic Tissue Reveal Novel Genes and Pathways Associated With Abdominal Aortic Aneurysm Onset and Progression.

Abdominal aortic aneurysms (AAAs) are focal dilatations of the abdominal aorta that expand progressively, increasing their risk of rupture. Rupture of an AAA is associated with high mortality rates, but the mechanisms underlying the initiation, expansion, and rupture of AAAs are not yet fully understood. We aimed to characterize the pathophysiology of AAAs and identify new genes associated with AAA initiation and progression. This study used RNA sequencing data on 140 samples, becoming the largest RNA sequencing data set for differential expression studies of AAAs. We performed differential expression analyses and analyses of differential splicing between dilated and nondilated aortic tissue samples, and between AAAs of different diameters. We identified 3002 differentially expressed genes between AAAs and controls that were independent of ischemic time, 1425 of which were new. Additionally, 8 genes (EXTL3, ZFR, DUSP8, DISP1, USP33, VPS37C, ZNF784, RFX1) were differentially expressed between AAAs of varying diameters and between AAAs and control samples. Finally, 7 genes (SPP1, FHL1, GNAS, MORF4L2, HMGN1, ARL1, RNASE4) with differential splicing patterns were also differentially expressed genes between AAAs and controls, suggesting that splicing differences in these genes may contribute to the observed expression changes and disease development. This study identifies new genes and splicing patterns associated with AAAs and validates previous relevant pathways on AAAs. These findings contribute to the understanding of the complex mechanisms underlying AAAs and may provide potential targets to limit AAA progression and mortality risk.

The Frenkel method for assessing balance in the elderly

Background: Aging comprises a gradual process of physical, biochemical and psychological deterioration, with alterations in balance, gait, increased risk of falls and the development of secondary diseases to this event. Considering the proposed context, the interest arises to research the Frenkel method and determine the effect on the balance of the elderly of the Association of Telecommunications Retirees of Guayas. A guide of therapeutic exercises to reduce the risk of falls in this population is designed. Methods: In this way, the present research is a descriptive observational type due to the characteristics of the population, based on a longitudinal study because measurements were carried out at two different times. That is, before and after the intervention. In addition to a quantitative approach for the analysis, data collection was used. The study was applied to 30 older adults, who met the inclusion criteria, as well as the exclusion criteria. Results: A considerable improvement of 4.9% in balance, 5.9% in gait and 40% low risk of falls was evidenced. Conclusions: Considering the findings and results of the study, it is concluded that the execution of the Frenkel Method improves balance and gait in older adults. It also reduces the risk of falls, thus avoiding future complications, promoting active and healthy aging.