Therapeutic Measures Research Articles

Reviewing Expert Attitudes Toward Quaternary Prevention using Traditional Medicine: A Qualitative Study

Introduction: Traditional medicine is based on knowledge, skills, and practices relying on the theories, beliefs, and indigenous experiences of different cultures that has a healthoriented and holistic view. With a holistic and health-oriented approach, quaternary prevention also seeks to prevent harm to the patient.Patient harm can be prevented by using efficient methods of traditional medicine and limiting the use of ineffective and harmful methods. Methods: The quantitative design of the study was conducted using a phenomenological approach among the faculty members of the Faculty of Traditional Medicine of Kerman University of Medical Sciences. Semi-structured interviews were conducted with the participation of 12 individuals selected using purposeful sampling. Content analysis was used to analyze the data. The codes were categorized based on their differences or similarities. Results: Six main themes were identified: prevention, patient benefit, quality of service, patient harm, rules and regulations, and financial burden. 18 sub-themes were extracted. Conclusion: Healthcare providers must protect their patients from the harms and costs of unnecessary diagnostic, therapeutic, and preventative measures. It is likely that adopting effective executive mechanisms, rules, and regulations focusing on the principle of patient benefit can lead to the implementation of a combination of traditional medicine and modern medicine on an extensive scale, aiming to reduce patient harm.

Microfluidic qPCR for detection of 21 common respiratory viruses in children with influenza-like illness.

Multiple respiratory viruses lead to high morbidity and mortality, yet global surveillance platforms focus primarily on seasonal influenza viruses. The COVID-19 pandemic and new RSV vaccines highlight the importance of a broader approach. Upper respiratory tract swabs from children aged 24-59months presenting with influenza-like illness in The Gambia were collected during follow-up of a live-attenuated influenza vaccine randomised controlled trial in 2017-18. A microfluidic quantitative polymerase chain reaction (qPCR) assay was established and used to detect 21 respiratory viruses. 76.6% of samples had one or more viruses detected (n = 121/158). The viruses detected most frequently were rhinovirus (n = 37/158, 23.4%) and adenovirus (n = 34/158, 21.5%), followed by parainfluenza virus 3, influenza B and human metapneumovirus B. A third of positive samples had multiple viruses detected (two n = 31/121, 25.6%; three n = 9/121, 7.4%). Our data demonstrates how microfluidic qPCR is a useful tool for high-throughput, comprehensive detection of multiple respiratory viruses in surveillance platforms. Rapidly changing epidemiology exemplifies the need for new, broader approaches to virus surveillance in low-resource settings to respond to future epidemics and to guide the need for and use of new prevention and therapeutic measures.

EL HÁBITO DE FUMAR Y SU INFLUENCIA EN LA CONSOLIDACIÓN ÓSEA: UNA REVISIÓN INTEGRADORA

Smoking is considered one of the risk factors for various diseases, not only related to the respiratory system but also influencing the physiological processes of various organs and body systems. This article aims to deepen the understanding of the effects of smoking on bone healing by analyzing its molecular, cellular, and clinical bases. This process is subject to possible direct or indirect interferences from chemical substances such as nicotine. It is important to note that, besides conventional cigarettes, there is also indiscriminate use of electronic cigarettes, which, according to an analysis conducted by Pérez and Duarte (2022), have considerably higher nicotine levels than traditional cigarettes. Another study conducted by González et al. (2021) highlights the increasing popularity of these devices among young people, underscoring the importance of preventive measures. According to the National Institute of Traumatology and Orthopedics (INTO), inhaling tobacco smoke increases bone tissue healing time by 60%, thus delaying the body's ability to heal injuries and compromising bone absorption. The clinical repercussions of smoking on the quality and speed of bone recovery after fractures and orthopedic procedures are identified to improve understanding and develop specific clinical strategies and interventions for smoking patients. The specific objectives of this research were to: investigate the molecular and cellular mechanisms of the bone healing process, analyze the effects of smoking on the quality of the formed tissue, evaluate the influence of smoking on the bone healing time in patients after fracture or orthopedic surgery, and finally propose therapeutic strategies and preventive measures to improve bone healing. To this end, a bibliographic search was conducted on articles relevant to the topic using various means. The selection of articles was based on three stages, choosing those that met the inclusion criteria. During the development of this article, it is observed that smoking is an extended and ancestral practice, being a constant and emerging health problem. Additionally, it is considered a modifiable risk factor for decreasing bone density. In conclusion, the need for specific strategies to address complications in bone healing in smoking patients is highlighted.

Prediction of 12-month recurrence of pancreatic cancer using machine learning and prognostic factors.

Pancreatic cancer is lethal and prevalent among other cancer types. The recurrence of this tumor is high, especially in patients who did not receive adjuvant therapies. Early prediction of PC recurrence has a significant role in enhancing patients' prognosis and survival. So far, machine learning techniques have given us insight into favorable performance efficiency in various medical domains. So, this study aims to establish a prediction model based on machine learning to achieve better prediction on this topic. In this retrospective research, we used data from 585 PC patient cases from January 2019 to November 2023 from three clinical centers in Tehran City. Ten chosen ensemble and non-ensemble algorithms were used to establish prediction models on this topic. Random forest and support vector machine with an AU-ROC of approximately 0.9 obtained more performance efficiency regarding PC recurrence. Lymph node metastasis, tumor size, tumor grade, radiotherapy, and chemotherapy were the best factors influencing PC recurrence. Random forest and support vector machine algorithms demonstrated high-performance ability and clinical usability to improve doctors' decisions in achieving different therapeutic and diagnostic measures.

Major considerations of maxillary/mandible osteonecrosis caused by bisphosphonates in the dental implant scenario: a systematic review

Introduction: The literature has shown that several patients with a history of bisphosphonate treatment appear to be at risk for medication-related osteonecrosis of the jaw (MRONJ) osteonecrosis of the jaw. Objective: It was analyzing the use of BP associated with dentistry. Because it is a possible alternative for the reduction of loss and increase in bone density, as well as for the possibility of osteonecrosis, which requires therapeutic and preventive measures in the involvement of invasive practices such as dental implants. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from April to June 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: 85 articles were founded, and 54 articles were evaluated and 30 were included in this systematic review. Considering the Cochrane tool for risk of bias, the global assessment resulted in 24 studies with a high risk of bias and 18 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2 =81.9% >50%. It was concluded that osteoporosis is a metabolic condition that affects alveolar bone density, but does not present problems for the installation of osseointegrated implants, as long as there is sufficient bone mass in the region where the tooth will be implanted. It suggests to the dental surgeons the knowledge of the diagnosis so that it makes a careful evaluation, directing the professional to observe the quality of the bone through routine image examinations. Further, alendronate sodium is used to decrease bone resorption, the drug should be considered as an adjunctive therapeutic agent for the treatment of osteoporosis.

Acupuncture for patients with Alzheimer's disease: An evidence map of randomized controlled trials, systematic reviews, and meta-analysis.

Background: Acupuncture is an effective complementary treatment for Alzheimer's disease (AD). This review aims to summarize the available evidence provided by randomized controlled trials (RCTs) and systematic reviews (SRs) or meta-analyses (MAs) on the effect of acupuncture on AD. Objective: To systematically summarize and combine clinical research evidence on AD distribution. Methods: We conducted a comprehensive search of various databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Data, Chinese BioMedical Literature Database (CBM) and Chonqing VIP (CQVIP), from their inception to September 2023. Relevant literature about acupuncture for AD was included, and the characteristics of the evidence map were presented through charts and textual analyses. Results: In total, 117 RCTs and 17 SRs or MAs were included. The results were divided into three categories: basic characteristics of the included literature, clinical characteristics and quality assessment of the included RCTs, and clinical characteristics and quality assessment of the included SRs and MAs. Conclusions: Acupuncture as a therapeutic measure for AD has some advantages in improving cognition and quality of life; thus, it is imperative to conduct multi-center, large-scale RCTs to enhance the evidence supporting the use of acupuncture in AD. This is the first evidence map exploring acupuncture treatment for AD, providing insights into the current clinical research landscape on acupuncture treatment for AD. Furthermore, the findings of this study highlight research gaps in this field and serve as a valuable reference for guiding the planning and selection of topics for future research.

Burden of post-acute COVID-19 sequelae in healthcare workers and its course over a 30-month period-results from a prospective multicentre cohort.

As healthcare workers (HCW) have been disproportionally affected by COVID-19, its post-acute sequelae (PASC) in HCW can impact healthcare systems. We assessed the burden and course of PASC in HCW over a 30-month period. In a prospective multicentre HCW cohort in Switzerland, PASC surveys were conducted in 03/2021, 09/2021, 06/2022, 04/2023, and 10/2023. Stratified by viral variant at first infection, the prevalence of PASC symptoms, self-experienced PASC and the Post-COVID Functional Status (PCFS) were analysed cross-sectionally in 10/2023, self-perceived success of therapeutic measures used was assessed. The evolution of PASC symptoms and PCFS in Wild-type and non-Wild-type infected HCW compared to uninfected controls was analysed longitudinally across all surveys. In cross-sectional analysis, 1704 HCW (median age 47years, 82.2% female) were included. Thereof, 30.7% reported ≥ 1 PASC symptom in 10/2023, with 115 (6.7%) stating to have or have had PASC. Both were most common after Wild-type infection compared to other variants. Overall, 17/115 (15%) indicated relevant/severe restrictions in their daily activities and of 85 (74%) that tried ≥ 1 measure against their symptoms, 69 (81%) reported having benefitted. Longitudinal analysis (n = 653) showed a significantly higher proportion of Wild-type infected HCW to report PASC symptoms compared to controls in 03/2021 (+ 21%, 95% CI 4-39), with decreasing trend (+ 7%, 95%CI -10-25 in 10/2023). This effect was not evident for non-Wild-type infected HCW. Over a 30month period, overall PASC burden in our HCW cohort decreased, although 1% still experience relevant restrictions in their daily life; Wild-type infected individuals show the highest disease burden.

Molecular-Genetic Determinants of Chronic Heart Failure Associated with Type 2 Diabetes and Osteoporosis

This article presents the results of a study on the molecular-genetic factors influencing the development of chronic heart failure (CHF) comorbid with type 2 diabetes mellitus (T2DM) and osteoporosis in postmenopausal women. Polymorphic variants of the IL-1β, eNOS, and angiotensinogen genes were found to be associated with an increased risk of CHF in the presence of T2DM. Alleles and genotypes that can serve as predictors of disease progression were identified. Based on the obtained data, strategies for a personalized approach to the diagnosis and secondary prevention of CHF are proposed. The results emphasize the importance of genetic analysis for improving the prediction of cardiovascular complications and planning therapeutic measures.

Height below 154 cm is a risk factor for pulmonary edema in twin pregnancy: An observational study.

In recent years, twin pregnancies have become increasingly common. The aim of our study was to analyze the exposure to risk factors for postpartum pulmonary edema in twin pregnancies. We get all our data from the "DATADRYAD" database, which is available directly. We used a variety of statistical methods, including multivariate logistic regression analysis and smoothed curve fitting. The aim was to critically assess the relationship between height and the occurrence of postpartum pulmonary edema in pregnant women with twin pregnancies. Among pregnant women whose height was <154 cm, the risk of postpartum development of pulmonary edema gradually decreased with increasing height (OR = 0.65, P = .0104). There was no relationship between maternal height and postpartum development of pulmonary edema among pregnant women with height higher than 154 cm (P = .9142). Pregnant women who were taller than 154 cm had a 76% lower risk of developing pulmonary edema postpartum compared to pregnant women whose height was lower than 154 cm (P = .0005). Our study suggests that pregnant women with twin pregnancies whose height is <154 cm are more likely to suffer from postpartum pulmonary edema. Therefore, healthcare professionals and caregivers should pay closer attention to twin pregnancies with heights below 154 cm, be alert to the occurrence of pulmonary edema, and take preventive and therapeutic measures as early as possible. This will help prevent the development of pulmonary edema.

Fasting-Mimicking Diet Prevents Pancreatic Carcinogenesis via Gut Microbiota and Metabolites.

The incidence of pancreatic cancer has been increasing globally in recent years and dietary is a well-defined factor contributing to its carcinogenesis. In this study, we showed that in a cerulein-induced KC (Pdx1-cre; LSL-Kras G12D/+) mouse model, a fasting-mimicking diet (FMD)─comprising fasting for 3 days followed by 4 days of refeeding, repeated over three 1-week cycles─significantly retards the progression of pancreatic carcinogenesis. FMD treatment altered gut microbiota, notably boosting butyrate-producing bacteria and elevating butyric acid levels in pancreatic tissues. Furthermore, lysine pan-crotonylation (pan-Kcr) expression was markedly upregulated in pancreatic intraepithelial neoplasia (PanIN) tissues from FMD-treated mice. Treatment of normal pancreatic duct and pancreatic cancer cells with sodium butyrate also upregulated pan-Kcr expression while reducing cell proliferation. Our findings reveal the pivotal role of dietary factors in the carcinogenesis of the pancreas and support further clinical studies of FMD as an antineoplastic therapeutic measure.

Epigenomic biomarkers of cardiometabolic disease: How far are we from daily practice?

Determining whether someone has cardiometabolic disease (CMD), especially in the early stages, can be complicated. Risk stratification ordinarily depends on an extended process relying on medical history that typically considers blood pressure, cholesterol, smoking and diabetes status. Physicians have long relied on these key patient characteristics to assess CMD risk. However, these widely used clinical assessments are often identified later in life and by definition, in those individuals with progressed disease. This is partly because the onset of CMD naturally occurs in adulthood, however, the underlying processes can occur much earlier in life, even in the absence of obvious symptoms. For one thing, the pathways towards pathology may exist for years before symptom onset. Thus, among other things, there are opportunities to provide doctors with better insights into future disease prediction especially in younger adults with diabetes. The rapid rise in CMD together with the increased rates of obesity and diabetes in this population only emphasises the importance of predictive molecular biomarkers. One notable aspect is that traditional risk scores, such as those based on cholesterol measurements, are frequently found to be within normal ranges in younger populations. At the same time, given the significant overlap in risk factors for cardiovascular disease (CVD) and diabetes, the unmet clinical need is for early biomarkers of CMD that may help improve risk assessment in younger adults. This editorial highlights advances in the use of polygenic risk scores and emerging utility of genetic biomarkers to define intermediate CMD phenotypes discussing new classification criteria involving DNA methylation of genes to improve risk assessment. CMD is the number one cause of mortality and accounts for 31% of all global deaths. CMD is also multifactorial, comprising cardiovascular disease (CVD) and diabetes that have significant overlap in risk factors and disease biology. Diabetes is arguably the strongest risk factor for CVD development. Accounting for almost 90% of diabetes cases worldwide, type 2 diabetes (T2D) affects about 527 million people. The global economic burden is estimated at 1.3 trillion USD annually and is close to 1.8% of global GDP [1]. Despite the progress in preventive and therapeutic measures of CVD, the increasing CMD rates only underscore the important need of molecular biomarkers for early detection [2]. Determining whether someone has CMD usually involves an extended diagnostic process that has become essential for risk stratification and disease prevention [3]. While the onset of CMD typically occurs in adulthood, disease development commences much earlier, and this has scientists questioning whether molecular biomarkers could improve current prognostic risk scores. Predicting which people with T2D are most likely to develop CVD remains a significant challenge despite the recent advances in genetic mapping.Graphical abstract

English

Introduction: Addressing the health problems of prison inmates is a major challenge for public administrations, which are responsible for guaranteeing the necessary services to deal with them. It is therefore essential to know which are the chronic pathologies that affect them most frequently, what impact they have on the oral cavity and what type of treatments are required. The aim of this study is to shed further light on these questions. Material and method: Articles in PubMed on chronic and oral pathologies and treatment needs were reviewed. Results: The most prevalent chronic pathologies are heart disease, chronic respiratory disease, diabetes and cancer. Anxiety and depression are also highly prevalent among the prison population, along with the consumption of tobacco, alcohol and drugs of abuse. They are responsible for the appearance of caries and periodontal diseases, the treatment of which should be carried out in the prison environment. Conclusions: The level of dental care among the prison population is very low. Therefore, it is necessary to implement preventive and therapeutic measures among inmates to improve their oral health and, consequently, their general health.

The first report of rhinosinusitis by Rhizopus delemar in a patient with severe COVID-19 in Iran: a case report

BackgroundMucormycosis is a severe and fatal fungal infection in patients with coronavirus disease 2019 caused by Mucorales. Here we present a case of a 63-year-old man with coronavirus disease 2019 infection, along with rhinosinusitis mucormycosis caused by Rhizopus delemar.Case presentationA 63-year-old Iranian man suffering from a coronavirus disease 2019 infection with symptoms of cough, shortness of breath, and generalized body pain. On the basis of the clinical manifestations, such as headache, a history of black nasal discharge, nasal hypoesthesia, facial swelling, numbness, nasal obstruction, presence of necrotic lesions on the nasal passages on physical examination, and abnormal computed tomography scans of paranasal sinuses, the patient underwent surgical debridement. Direct microscopy of specimens obtained from the paranasal sinuses, and subsequent isolation and identification, revealed a rhinosinusitis mucormycosis caused by R. delemar. Despite therapeutic measures, such as sinus debridement surgery and antifungal therapy with amphotericin B injection (50 mg/day), the patient died after 35 days of hospitalization.ConclusionIn this report, we present the first documented case of human infection with R. delemar in a patient with coronavirus disease 2019 infection, who also exhibited rhinosinusitis mucormycosis. R. delemar appears to be an emerging agent of rhinosinusitis mucormycosis in this region. Furthermore, prompt diagnosis and the exploration of alternative antifungal treatments, beyond amphotericin B, may be crucial for effectively managing patients with R. delemar infections.

Antiviral Susceptibility of Swine-Origin Influenza A Viruses Isolated from Humans, United States.

Since 2013, a total of 167 human infections with swine-origin (variant) influenza A viruses of A(H1N1)v, A(H1N2)v, and A(H3N2)v subtypes have been reported in the United States. Analysis of 147 genome sequences revealed that nearly all had S31N substitution, an M2 channel blocker-resistance marker, whereas neuraminidase inhibitor-resistance markers were not found. Two viruses had a polymerase acidic substitution (I38M or E199G) associated with decreased susceptibility to baloxavir, an inhibitor of viral cap-dependent endonuclease (CEN). Using phenotypic assays, we established subtype-specific susceptibility baselines for neuraminidase and CEN inhibitors. When compared with either baseline or CEN-sequence-matched controls, only the I38M substitution decreased baloxavir susceptibility, by 27-fold. Human monoclonal antibodies FI6v3 and CR9114 targeting the hemagglutinin's stem showed variable (0.03 to >10 µg/mL) neutralizing activity toward variant viruses, even within the same clade. Methodology and interpretation of laboratory data described in this study provide information for risk assessment and decision-making on therapeutic control measures.

Chemical Probes Review: Choosing the Right Path Towards Pharmacological Targets in Drug Discovery, Challenges and Future Perspectives.

Chemical probes are essential for academic research and target validation for disease identification. They facilitate drug discovery, target function investigation, and translation studies. A chemical probe provides starting material that can accelerate therapeutic values and safety measures for identifying any biological target in drug discovery. Essential read outs depend on their versatility in biochemical testing, proving the hypothesis, selectivity, specificity, affinity towards the target site, and valuable in new therapeutic approaches. Disease management will depend upon chemical probes as a primitive tool to ascertain the physicochemical stability for in vivo and in vitro studies useful for clinical trials and industrial application in the future. For cancer research, bacterial infection, and neurodegenerative disorders, chemical probes are integrated circuits which are on pipeline for the drug discovery process Furthermore, pharmacological modulators incorporate activators, crosslinkers, degraders, and inhibitors. Reports accessed depend on their structural, mechanical, biochemical, and pharmacological characterization in drug discovery research. The perspective for designing any chemical probes concludes with the utilization of drug discovery and identification of the potential target. It focuses mainly on evidence-based studies and produces promising results in successfully delivering novel therapeutics to treat cancers and other disorders at the target site. Moreover, natural product pharmacophores like rapamycin, cephalosporin, and α-lactamase are utilized for drug discovery. Chemical probes revolutionize computational-based study design depending on identifying novel targets within the database framework. Chemical probes are the clinical answers for drug development and goforward tools in solving other riddles for scientists and researchers working in this industries.

Electron Tomography as a Tool to Study SARS-CoV-2 Morphology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel betacoronavirus, is the causative agent of COVID-19, which has caused economic and social disruption worldwide. To date, many drugs and vaccines have been developed for the treatment and prevention of COVID-19 and have effectively controlled the global epidemic of SARS-CoV-2. However, SARS-CoV-2 is highly mutable, leading to the emergence of new variants that may counteract current therapeutic measures. Electron microscopy (EM) is a valuable technique for obtaining ultrastructural information about the intracellular process of virus replication. In particular, EM allows us to visualize the morphological and subcellular changes during virion formation, which would provide a promising avenue for the development of antiviral agents effective against new SARS-CoV-2 variants. In this review, we present our recent findings using transmission electron microscopy (TEM) combined with electron tomography (ET) to reveal the morphologically distinct types of SARS-CoV-2 particles, demonstrating that TEM and ET are valuable tools for visually understanding the maturation status of SARS-CoV-2 in infected cells. This review also discusses the application of EM analysis to the evaluation of genetically engineered RNA viruses.

The place of pasireotide in precision treatment of patients with acromegaly

Due to the syndromal nature of acromegaly, the effectiveness of its treatment depends on the consideration of age, clinical and pathomorphological features of the disease, which determine the logistics of the selection of personalized therapeutic measures. The disadvantage of the used empirical pharmacotherapy scheme with the help of the ‘trial and error’ method is the formal prescription of drugs without taking into account the peculiarities of the morphofunctional status of the supervised GH-secreting tumors and the targeting of drugs. The lack of differentiated approach to acromegaly treatment is accompanied by a high percentage of therapeutic failures, and also deliberately deprives a significant proportion of patients of the opportunity to achieve timely and safe control of the disease and improve the quality of life. The review presents a comparative analysis of modern drugs used in acromegaly with a focus on the clinical efficacy of the second-generation somatostatin receptor ligand – pasireotide. The mechanism of action and pharmacotherapeutic possibilities of pasireotide LAR are considered. The therapeutic niche for this drug is patients with the presence of sparsely granulated somatotrophic tumor (SGST), characterized by aggressive course, tendency to recurrence and refractoriness to therapy with first-generation somatostatin receptor ligands.Implementation of a precision approach using clinical, morphological, radiological and functional predictors allows not only to identify the specific morphotype of somatotrophic tumor, but also to predict the efficacy of the planned treatment. A table of multidirectional biomarkers of long-term sensitivity of tumor cells to first- and second-generation somatostatin receptor ligands is presented. When SGST, large size of the residual tumor and poor expression of the 2nd subtype of somatostatin receptors are detected, pasireotide LAR can be used as a 1st-line treatment, in both mono- and combination therapy with pegvisomant. Special caution is required when treating patients with diabetes mellitus or predisposition to its development. The paper discusses in detail the measures aimed at prevention, dynamic control and correction of pasireotide-associated hyperglycemia.

Quantifying the impact of disease severity changes on the burden of blindness: A global decomposition analysis.

Despite the significant impact of blindness on the affected individuals' quality of life, its burden has not been assessed according to temporal cause-specific changes in severity, impeding our ability to evaluate the impact of blindness on population health accurately. Therefore, we aimed to comprehensively quantify the changes in cause-specific blindness burden according to changes in disease severity for 18 causes of blindness. For this cross-sectional population-based study, we derived data on prevalence, disability-adjusted life-years (DALYs), and population size between 1990 and 2019 from the Global Burden of Disease 2019 study. Using the decomposition method, we attributed changes in total DALYs to population growth, population ageing, and changes in prevalence rate and disease severity between 1990 and each subsequent year globally, regionally, nationally, and by sex, cause, and sociodemographic index (SDI). The absolute and relative contributions to the variation in blindness-related DALYs between 1990 and each year from 1991 to 2019 then served as a measure of changes in disease severity. Changes in disease severity from 1990 to 2019 were associated with 15 165.11 DALYs in men and 20 639.32 DALYs in women. We observed disease severity increases in most countries/territories, with attributable DALY proportions ranging from -0.07% to 1.30% in men and from -0.06% to 1.73% in women. Notably, both attributable proportions and DALYs were greater in women than men. The largest increases in attributable DALYs were observed for cataracts, refraction disorders, and glaucoma globally; age-related macular degeneration in high-SDI countries; and trachoma and retinopathy of prematurity in lower-SDI countries. Growth in the burden of cause-specific blindness due to increased disease severity reflects the lag of healthy vision life behind increasing life expectancy, necessitating the implementation of preventive and long-term therapeutic measures focussed on improving visual outcomes.

Cell aggregation mediated by ACE2 deletion in Candida auris modulates fungal colonization and host immune responses in the skin.

Candida auris is an emerging multi-drug-resistant fungal pathogen that colonizes the skin and causes invasive infections in hospitalized patients. Multi-cellular aggregative phenotype is widely reported in the C. auris isolates, but its role in skin colonization and host immune response is not yet known. In this study, we generated aggregative phenotype by deleting the ACE2 gene in C. auris and determined the fungal colonization and host immune response using an intradermal mouse model of C. auris skin infection. Our results indicate that mice infected with ace2Δ strain had significantly lower fungal load after 3 and 14 days post-infections compared to the non-aggregative wild-type and the ACE2 reintegrated strain. The colonization of ace2Δ is associated with increased recruitment of CD11b+ Ly6G+ neutrophils and decreased accumulation of CD11b+ Ly6 Chi inflammatory monocytes and CD11b+ MHCII+ CD64+ macrophages. Furthermore, Th17 cells and type 3 innate lymphoid cells (ILCs) were significantly increased in the skin tissue of ace2Δ infected mice. Our findings suggest that aggregative phenotype mediated by ACE2 deletion in C. auris induces potent neutrophil and IL-17-mediated immune response and reduces fungal colonization in the skin.IMPORTANCEC. auris is a rapidly emerging fungal pathogen that can colonize hospitalized patients, especially in skin tissue, and cause invasive infections. C. auris isolates exhibit morphological heterogeneity, and the multicellular aggregative phenotype of C. auris is reported frequently in clinical settings. Understanding the role of fungal morphotypes in colonization, persistence, and immune response in the skin microenvironment will have potential applications in clinical diagnosis and novel preventive and therapeutic measures. Here, we utilized the murine model of intradermal infection and determined that the aggregative phenotype of C. auris as the result of ACE2 gene deletion elicits potential innate and adaptive immune responses in mice. These observations will help explain the differences in the skin colonization and immune responses of the aggregative morphotype of C. auris and open the door to developing novel antifungal therapeutics.

Association between asthma and depression: results from the NHANES 2005-2018 and Mendelian randomization analysis.

Asthma is a common respiratory disease that is believed to be associated with mental disorders. This study aims to assess the correlation and causal relationship between asthma and depression by combining observational and Mendelian randomization (MR) approaches. We collected relevant data from the National Health and Nutrition Examination Survey (NHANES) and employed multivariable logistic regression to evaluate the correlation between asthma and depression. Additionally, a two-sample MR analysis was conducted using inverse variance-weighted (IVW) method, along with multiple sensitivity analyses. The observational study included a total of 23 648 participants, and the results showed that asthma patients had an increased risk of developing depression compared to non-asthma individuals (OR 1.26; 95% CI 1.04-1.57; P < 0.01). The IVW-MR results from two datasets indicated a potential causal relationship between asthma and depression (EBI dataset: OR 1.141; 95% CI 1.051-1.239; P = 0.01; UKB dataset: OR 1.009; 95% CI 1.005-1.013; P < 0.01). These findings suggest that asthma may be a risk factor for the onset of depression, increasing the risk of developing depression. There is a significant correlation and potential causal relationship between asthma and depression, with asthma being a risk factor for the onset of depression. These findings warrant further research for validation and exploration of preventive and therapeutic measures for depression in asthma patients. Key messages What is already known on this topic-There are some potential associations between asthma and depression based on observational studies, but the results of observational studies are often biased. This study aims to further explore the relationship between asthma and depression through a combination of observational studies and Mendelian randomization (MR) analysis. What this study adds-The observational study results from the National Health and Nutrition Examination Survey database and MR analysis are consistent, indicating that after adjusting for multiple covariates and confounding factors, asthma increases the risk of depression and is a risk factor for depression, with similar results obtained at the genetic level. How this study might affect research, practice or policy-Asthma patients not only need active medication treatment, but also need timely psychological attention, and psychological treatment is more important to a certain extent.