Greater Burden Research Articles

THE ROLE OF SEMAPHORINS IN CANCERS WITH SPECIAL FOCUS ON UROLOGICAL MALIGNANCIES

Introduction: Semaphorins are multi-function extracellular proteins with signaling properties involved in many processes in the human body. Surprisingly, in carcinogenesis, they may function as promoting or suppressing agents or both at the same time. Semaphorins in the field of urological cancers have been insufficiently studied so far, mainly in prostate cancer. They seem promising markers in urological cancers diagnostics and possibly treatment. This matter is the more worthy of interest since urological cancers are a great medical and economic burden. The review briefly discusses the current state of knowledge about semaphorins in cancers, mainly in urology. Conclusions: The most investigated cancer was prostate, whereas there is not enough information about semaphorins in bladder cancer and renal cell carcinoma. Apparently, semaphorin 5B exerts a negative influence on renal cell carcinoma, and semaphorins 3A and 4D on bladder cancer. In case of prostate cancer, semaphorins 3B, 3C, 4F are considered to promote neoplasm development. On the other hand, semaphorins 3A and 3E are considered beneficial.

Prevalence, Antibiotics Susceptibility Profile of <i>Listeria Monocytogenes</i>, and Its Associated Risk Factors Among Pregnant Women Attending Millennium Health Center

<i>Background</i>: <i>Listeria monocytogenes</i> is a facultative intracellular pathogen that causes serious invasive infections in pregnant women, resulting in disseminated fetal infections, abortions, and still-births. Although it causes a greater burden on pregnant women and their infants, the case in Ethiopia is overlooked, and there is a scarcity of data on <i>L. monocytogenes,</i> particularly in the southern parts of Ethiopia. Therefore, this study aimed to determine the prevalence and, antibiotics susceptibility of <i>L. monocytogenes</i> and its associated risk factors among pregnant women attending the Millennium Health Center, Hawassa, Ethiopia. <i>Method</i>: A cross-sectional study was conducted on 203 pregnant women between May 30 and July 30, 2022. Socio-demographic data and 5 ml venous blood samples were collected from pregnant women using structured questionnaire. Data were analyzed using SPSS version 25. Bivariate logistic regression was carried out then variables with <i>p</i><0.25 were further analyzed by multivariate logistic regressions, <i>p</i>-values <0.05 were accepted as statistically significant. <i>Results</i>: The overall prevalence of <i>L. monocytogenes</i> among pregnant women was found to be 11/203 (5.42%; 95% CI=2.88-9.38). <i>L. monocytogenes</i> was resistant to benzyl penicillin (90.91%) and meropenem (81.82%), but susceptible to ampicillin (90.91%). Raw meat (AOR=6.99; 95% CI=1.39-35.14), <i>p</i>=0.018), uncooked vegetables (AOR=6.62; 95% CI=1.04-42.30), <i>p</i>=0.046), unpasteurized milk (AOR=7.56; 95% CI=1.33-42.97), <i>p</i>=0.023) and fever (AOR=14.65; 95% CI=3.15-68.15), <i>p</i>=0.001) were significantly associated with <i>L. monocytogenes</i> infection. <i>Conclusion</i>: <i>L. monocytogenes</i> was resistant to benzyl penicillin, meropenem, erythromycin, and sulfamethoxazole but susceptible to ampicillin. Raw meat, uncooked vegetables, unpasteurized milk, and fever were significantly associated with <i>L. monocytogenes</i>.

Prosthesis Infolding Incidence and Short-Term Outcomes in Transcatheter Aortic Valve Implantation Using Evolut Self-Expandable Device: A Multicenter Study

Transcatheter aortic valve implantation (TAVI) is an established treatment strategy in aortic valve disease. Infolding, as a nonuniform expansion of the prosthesis leading to introflection of part of the device circumference, is a complication specific to self-expandable prostheses. The aim of the study is to determine incidence, predictors, treatment strategy, and outcomes of infolding during Medtronic Evolut TAVI (Minneapolis, MN, US). Between January 2018 and March 2022, all patients treated with Evolut TAVI were included in a multicenter observational retrospective study. According to the occurrence of infolding, the enrolled cohort was divided into 2 groups; periprocedural characteristics and 30-day outcomes were compared. A total of 1,470 patients were included; 23 infolding cases (1.6%) were detected. Preprocedural imaging showed larger aortic anatomy and greater calcium burden in the infolding group. Infolding occurred mostly with Evolut Pro+ and size 34 mm and was diagnosed before full prosthesis release in 78.3%. The rate of moderate-to-severe paravalvular regurgitation was higher in the infolding group (21.7% vs 1.9%, p <0.001). Short-term follow-up showed greater all-cause and cardiovascular mortality (respectively, 4.3% vs 0.7% and 4.3% vs 0.6%, p <0.05) and higher rate of pacemaker implantation (33.3% vs 15.7%, p = 0.042) in case of infolding. High right cusp calcium score and resheathing maneuvers were independent predictors of infolding. In conclusion, prosthesis infolding is a TAVI complication burdened by worse cardiovascular outcomes. Prompt intraprocedural infolding diagnosis is pivotal, especially in case of great native valve calcium burden and resheathing maneuvers, to safely overcome this complication by prosthesis recapture or postdilation.

Toward understanding the role of genomic repeat elements in neurodegenerative diseases.

Neurodegenerative diseases cause great medical and economic burdens for both patients and society; however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

Oral health in children and adolescents with special healthcare needs in South Africa: A narrative review

Children and adolescents with special healthcare needs (CWSHCN) may experience disproportionately poorer general and oral health than healthy children.1-3 They are more at risk of common conditions such as dental caries and gingivitis resulting from poor oral health.4 They comprise of children and youth “with or at risk of chronic physical, developmental, behavioral or emotional conditions”,5 including, inter alia, intellectual disability (ID), cerebral palsy (CP), learning disability (LD), autism spectrum disorder (ASD), hearing impairment (HI), Down Syndrome (DS), physical disabilities (PD), visual impairments (VI) and epilepsy (EP). Globally, the prevalence of disabilities is increasing, even in developing countries such as South Africa (SA), resulting in a greater burden on healthcare systems.6

Burdens and resources of Austrian clinical psychologists: results of a qualitative study two years into the COVID-19 pandemic

BackgroundThe COVID-19 pandemic increased the mental health burden in the general population, enhancing the demands placed on mental healthcare professionals.MethodsThis study aimed to assess the burdens and resources of clinical psychologists that emerged since the beginning of the pandemic. N = 172 Austrian clinical psychologists participated in a cross-sectional online survey between April and May 2022. The burdens and the sources of support that emerged during the pandemic were analyzed using qualitative content analysis.ResultsMental health-related issues were identified as the greatest burden, followed by work-related themes and restrictions imposed by the government to combat the spreading of the virus. The most important resources mentioned by the clinical psychologists were social contacts and recreational activities. Practising mindfulness and focusing on inner processes and work-related aspects were further important resources mentioned.ConclusionOverall, it seems that clinical psychologists have a high awareness of mental health-related problems related to the pandemic and use adaptive coping strategies to deal with them.

Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study.

Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher's exact test was used for comparison of categorical variables. A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Global, regional, and national burden of pancreatitis in older adults, 1990–2019: A systematic analysis for the global burden of disease study 2019

BackgroundTo describe the past, present and future burden of pancreatitis in older adults, and to explore cross-national inequalities across socio-demographic index (SDI). MethodsData on pancreatitis in older adults, including mortality and disability-adjusted life years (DALYs) rates, were collected from the Global Burden of Disease (GBD) 2019 study. Temporal trends were measured using joinpoint analyses and predicted using a Bayesian age-period-cohort model. Additionally, the unequal distribution of the burden of pancreatitis in older adults was quantified. ResultsFrom 1990 to 2019, the number of deaths and DALYs due to pancreatitis in older adults has been increasing annually. However, in most regions of the world, age-standardized death rates (ASDR) and age-standardized DALYs rates have been declining. The burden of pancreatitis in older adults was highest in low SDI region, primarily affecting the population aged 65–74, with a greater burden on males than females. Furthermore, from 1990 to 2019, absolute and relative cross-national inequalities in pancreatitis among older adults have remained largely unchanged. It is projected that in the next 11 years, the number of deaths in older adults due to pancreatitis will continue to increase, but the ASDR is expected to decline. ConclusionOver the past 30 years, the ASDR and age-standardized DALYs rate of pancreatitis in older adults have shown a decline globally, but the absolute burden continues to increase. Cross-national health inequalities persist. Therefore, it is necessary to develop targeted intervention measures and enhance awareness among this vulnerable population regarding the risk factors associated with pancreatitis.

Efficient privacy-preserving Gaussian process via secure multi-party computation

Gaussian processes (GPs), known for their flexibility as non-parametric models, have been widely used in practice involving sensitive data (e.g., healthcare, finance) from multiple sources. With the challenge of data isolation and the need for high-performance models, how to jointly develop privacy-preserving GP for multiple parties has emerged as a crucial topic. In this paper, we propose a new privacy-preserving GP algorithm, namely PP-GP, which employs secret sharing (SS) techniques. Specifically, we introduce a new SS-based exponentiation operation (PP-Exp) through confusion correction and an SS-based matrix inversion operation (PP-MI) based on Cholesky decomposition. However, the advantages of the GP come with a great computational burden and space cost. To further enhance the efficiency, we propose an efficient split learning framework for privacy-preserving GP, named Split-GP, which demonstrably improves performance on large-scale data. We leave the private data-related and SMPC-hostile computations (i.e., random features) on data holders, and delegate the rest of SMPC-friendly computations (i.e., low-rank approximation, model construction, and prediction) to semi-honest servers. The resulting algorithm significantly reduces computational and communication costs compared to PP-GP, making it well-suited for application to large-scale datasets. We provide a theoretical analysis in terms of the correctness and security of the proposed SS-based operations. Extensive experiments show that our methods can achieve competitive performance and efficiency under the premise of preserving privacy.

Changing trends in the global, regional, and national burden of iodine deficiency among adolescents and young adults: population-based study.

Globally, the iodine deficiency burden among adolescents has substantially decreased since 1990; however, low-SDI countries still bear a great burden. Implementation measures and monitoring systems should be strengthened to reduce the iodine deficiency burden, especially among adolescents. • Iodine deficiency can cause severe or irreversible developmental disorders, particularly in adolescents and young adults. • Universal Salt Iodization was implemented for ensuring appropriate iodine intake. • We found substantial declines in the prevalence rates of iodine deficiency among adolescents during the past three decades. Globally, the disability-adjusted life-year rate of iodine deficiency among adolescents decreased from 56.17 in 1990 to 35.38 in 2019. • Iodine deficiency among adolescents in low- sociodemographic index countries still bear a great burden.

The Predictive Value of Neutrophil Extracellular Trap-Related Risk Score in Prognosis and Immune Microenvironment of Colorectal Cancer Patients.

Colorectal cancer (CRC) has brought great healthy burden for patients. Neutrophil extracellular traps (NETs) have been explored in several tumors, while it remains largely unclear in CRC. CRC-related data were downloaded from Cancer Genome Atlas and Gene Expression Omnibus databases. Then, a NET risk score was built after univariate Cox and LASSO Cox regression analysis. Prognostic value was evaluated via survival analysis, stratification analysis, and ROC analysis. The functional enrichment analysis was conducted basing on bulk and scRNA-seq data. The immune landscape difference was analyzed using CIBERSORT, XCell, and MCPcounter portals. NET risk score was built for CRC patients, basing on G0S2, HIST1H2BC, CRISPLD2, and IL17A. In TCGA-CRC and validation datasets, regardless of age or gender, high-risk CRC patients had significantly worse prognosis, besides higher NET risk score was mainly found in samples with MSI-H and advanced T, N, and M stages. Employing multiple databases, we noticed that M0 and M2 Macrophages infiltrated the most in high-risk CRC patients, besides M2 Macrophages and neutrophils showed positive correlation with NET risk score. A novel reliable prognostic NET risk score was developed for CRC patients, and high-risk patients had unfavorable prognosis with advanced disease status.

Differences in Well-Being at School Between Young Students With and Without a Refugee Background.

Students with a refugee background are a vulnerable group in education. Adverse experiences and unsafe circumstances that they encounter prior, during and after their flight can place a great burden on their mental health and psychological well-being. Little is known about the psychological well-being of young refugee students in kindergarten and early years of primary school. The current study examined the psychological well-being of 4- to 8-year-old students with a refugee background residing in the Netherlands (n = 136), compared to Dutch peers without a refugee background (n = 406). Primary school teachers completed three questionnaires which assessed multiple indicators of their students' psychological well-being: Strengths and Difficulties Questionnaire (SDQ), Social-Emotional Questionnaire (SEV) and Risk and Protective factors Trauma Observation School Situations (RaPTOSS). In line with the hypothesis, results showed overall lower psychological well-being among refugee students compared to non-refugee students. Teachers observed more total difficulties in socio-emotional functioning, anxious and mood disturbing behavior, ADHD symptoms, problematic social behavior and post-traumatic stress symptoms (small effects), and less developed trauma protective factors and prosocial behavior (medium effects) among students with a refugee background compared to their non-refugee peers. However, the findings also demonstrated that half of the refugee students did not have any scores that fall in the clinical range of the psychological and behavioral problems assessed. The results underline the need to promote protective factors such as positive self-image, self-regulation skills, safety and relations in the classroom and prosocial behavior among students with a refugee background.

Comparison of geographical and individual deprivation index to assess the risk of Sars-CoV-2 infection and disease severity: a retrospective cohort study

BackgroundIt has been shown that COVID-19 affects people at socioeconomic disadvantage more strongly. Previous studies investigating the association between geographical deprivation and COVID-19 outcomes in Italy reported no differences in case-hospitalisation and case-fatality. The objective of this research was to compare the usefulness of the geographic and individual deprivation index (DI) in assessing the associations between individuals' deprivation and risk of Sars-CoV-2 infection and disease severity in the Apulia region from February to December 2020.MethodsThis was a retrospective cohort study. Participants included individuals tested for SARS-CoV-2 infection during the study period. The individual DI was calculated employing polychoric principal component analysis on four census variables. Multilevel logistic models were used to test associations between COVID-19 outcomes and individual DI, geographical DI, and their interaction.ResultsIn the study period, 139,807 individuals were tested for COVID-19 and 56,475 (43.5%) tested positive. Among those positive, 7902 (14.0%) have been hospitalised and 2215 (4.2%) died. During the first epidemic wave, according the analysis done with the individual DI, there was a significant inversely proportional trend between the DI and the risk of testing positive. No associations were found between COVID-19 outcomes and geographic DI. During the second wave, associations were found between COVID-19 outcomes and individual DI. No associations were found between the geographic DI and the risk of hospitalisation and death. During both waves, there were no association between COVID-19 outcomes and the interaction between individual and geographical DI.ConclusionsEvidence from this study shows that COVID-19 pandemic has been experienced unequally with a greater burden among the most disadvantaged communities. The results of this study remind us to be cautious about using geographical DI as a proxy of individual social disadvantage because may lead to inaccurate assessments. The geographical DI is often used due to a lack of individual data. However, on the determinants of health and health inequalities, monitoring has to have a central focus. Health inequalities monitoring provides evidence on who is being left behind and informs equity-oriented policies, programmes and practices. Future research and data collection should focus on improving surveillance systems by integrating individual measures of inequalities into national health information systems.

Comprehensive evaluation on performance and local impact in energy, environment, and economy of different rural clean heating modes: A case study in Northeastern China

To improve the atmospheric environment, the clean heating projects such as “coal-to-electricity” and “coal-to-gas” have been implemented in China, while leading to significantly increase in heating costs for rural residents and the supply pressure of fossil fuels in some rural areas. As the local renewable energy, biomass briquette can be used for rural heating. However, the local resource feasibility for the biomass heating has not been paid enough attention to, besides, the performance and potential local impacts of different heating modes has not been comprehensively estimated. Based on multiple attribute decision-making, this paper proposes an evaluation system by integrating the performance comparison and local impact in energy, environment, and economy, especially including an assessment on local biomass resource feasibility. The clean heating modes of biomass, electricity, and gas are evaluated along with the current coal heating mode in Harbin and Qiqihar as case studies. Results show that in the case regions, the biomass mode has sufficient resources and achieves significant comprehensive benefits, with the relative proximity nearly twice that of the coal mode. All the three clean heating modes can achieve environmental benefits. Due to the best economic feasibility, the biomass mode is suitable for the current rural economic level, with the cost intensity of 0.01 yuan/MJ, and the ratio of heating cost to disposable income less than 1%. The electric mode hardly produces comprehensive benefits because of the high cost. The gas mode is the least recommended due to significant energy demand and great economic burden.

Micro- and Macrovascular Complications of Type 2 Diabetes in Southern Iran

Objectives: Type 2 diabetes mellitus (T2DM) is one of the most common diseases worldwide, imposing a great burden on the community by its complications. This study evaluates micro-and macrovascular complications of T2DM and the associated factors in the south of Iran. Methods: This cross-sectional study was conducted on T2DM patients referred to the Diabetes Clinic of Shahid Mohammadi Hospital in Bandar Abbas City, Iran, in 2018. Patients’ age, sex, marital status, smoking status, diabetes medications, cardiovascular disease, and duration of T2DM were recorded. Weight, height, and blood pressure were measured and body mass index was calculated for every participant. Also, all patients were evaluated regarding diabetes complications, including retinopathy, nephropathy, and neuropathy. Serum fasting plasma glucose (FPG), lipid profile, glycated hemoglobin, creatinine levels as well as urinary albumin were also measured in the patients. Results: Of the 263 T2DM patients included in the current study with a mean age of 55.32±13.09 years, 109 (41.4%) were male. The most common T2DM complications were chronic kidney disease (CKD) (49.8%) and nephropathy (36.5%), followed by neuropathy (30.8%), retinopathy (19%) and ischemic heart disease (8.7%). Elevated systolic blood pressure was significantly correlated with the presence of all complications. Patients with ischemic heart disease, CKD, neuropathy, and retinopathy were significantly older than subjects without such complications. Diabetes was significantly more prolonged in patients with ischemic heart disease and CKD. Elevated FPG was only correlated with CKD (P=0.019) and nephropathy (P=0.003), while increased glycated hemoglobin and decreased high-density lipoprotein were significantly associated with retinopathy (P=0.050 and P=0.001, respectively). Moreover, a significant relationship was observed between elevated urinary albumin with retinopathy and neuropathy. Discussion: Diabetic kidney disease was the most common complication of T2DM in the current study. Increased systolic blood pressure is the most important risk factor for the development of diabetic complications.

ASSOCIATION OF SERUM URIC ACID WITH DIABETES MELLITUS TYPE-2: A NARRATIVE REVIEW

Diabetes mellitus type 2 (T2DM) is a disease which imposes a great burden on the health resources of the emerging and developing world. It is a global pandemic which leads to chronic complications. Serum uric acid (SUA) is a biomarker that could be of value in detection of early complications and better prognosis in diabetic patients. SUA serves both as a causal factor and disease progression marker in DM, having a causal relationship with diabetic complications. This narrative review aims to determine the association between SUA and T2DM. Research articles from the year 2005 to 2023 were selected for this review. Literature search was conducted from PubMed and Google Scholar which resulted in short listing of 15 articles. It also reflects upon the diabetic complications associated with Hyperuricemia (HUA) and focuses on the health implications of HUA in T2DM patients. SUA and T2DM were negatively associated in 8 research studies and positively associated in 6 studies in which one revealed a partial association, one was prevalent in the female gender only, and one was negatively associated in uncontrolled DM. Another study was associated with both hypouricemia and HUA. Pak J Physiol 2024;20(1):52-7

Anthelmintic screening of Bangladeshi medicinal plants and related phytochemicals using in vitro and in silico methods: An ethnobotanical perspective

Ethnopharmacological relevanceInfections caused by parasitic worms or helminth continue to pose a great burden on human and animal health, particularly in underdeveloped tropical and subtropical countries where they are endemic. Current anthelmintic drugs present serious limitations and the emergence of drug resistance has made it increasingly challenging to combat such infections (helminthiases). In Bangladesh, medicinal plants are often used by indigenous communities for the treatment of helminthiases. Knowledge on such plants along with screening for their anthelmintic activity has the potential to lead to the discovery of phytochemicals that could serve as novel molecular scaffolds for the development of new anthelminthic drugs. Aim of the studyThe purpose of this study was i) to conduct an ethnobotanical survey to gather data on Bangladeshi medicinal plants used in the treatment of helminthiases, ii) to test plants with the highest use values for their in vitro anthelmintic activity, and iii) to carry out in silico screening on phytochemicals present in the most active plant extract to investigate their ability to disrupt β-tubulin function in helminths. MethodsThe ethnobotanical survey was conducted across three sub-districts of Bangladesh, namely Mathbaria, Phultala and Khan Jahan Ali. The in vitro screening for anthelmintic activity was performed in a motility test using adult Haemonchus contortus worms. Virtual screening using PyRx was performed on the phytochemicals reported from the most active plant, exploring their interactions with the colchicine binding site of the β-tubulin protein target (PDB ID: 1SA0). ResultsThe survey respondents reported a total of 32 plants for treating helminthiases. Based on their use values, the most popular choices were Ananas comosus (L.) Merr., Azadirachta indica A.Juss., Carica papaya L., Citrus maxima (Burm.) Merr., Curcuma longa L., Momordica charantia L., Nigella sativa L. and Syzygium cumini (L.) Skeels. In vitro anthelmintic testing revealed that A. indica leaves and bark had the highest activity with LC50 values of 16 mg/mL in both cases. Other plant extracts also exhibited good anthelmintic activity with LC50 values ranging from 16 to 52 mg/mL, while the value for albendazole (positive control) was 8.39 mg/mL. The limonoids nimbolide and 28-deoxonimbolide showed a binding affinity of −8.9 kcal/mol, and satisfied all drug-likeness parameters. The control ligand N-deacetyl-N-(2-mercaptoacetyl)colchicine had a binding affinity of −6.9 kcal/mol. ConclusionFurther in silico and in vitro studies are warranted on the identified limonoids to confirm the potential of these derivatives as novel drug templates for helminthiases. The current study supports the need for an ethnobotanical survey-based approach to discover novel drug templates for helminthiases.

Synergistic interaction between hyperlipidemia and obesity as a risk factor for stress urinary incontinence in Americans

Urinary incontinence is a common disease among middle-aged and elderly women, which not only affects the physical and mental health of patients, but also brings a great medical burden to society. Obesity is a known risk factor for urinary incontinence and is the most common secondary cause of hyperlipidemia. Most obese patients also suffer from hyperlipidemia in the clinic. However, few studies have explored the role of hyperlipidemia in women with urinary incontinence. Using data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES), we aimed to evaluated the independent associations of high body mass index and hyperlipidemia with urinary incontinence in Americans by conducting a weighted multivariate logistic regression model. Additive interactions were also assessed using the relative excess risk due to interaction (RERI), attributed proportion of interaction (AP) and synergy index (S). This study demonstrated that hyperlipidemia was associated with a higher risk of stress urinary incontinence among women with obesity (OR = 1.52, 95% CI = 1.03–2.25), and there was a significant synergistic effect of hyperlipidemia and obesity on stress urinary incontinence(adjusted RERI: 3.75, 95% CI 0.30–7.20; adjusted AP: 0.67, 95% CI 0.54–0.80; adjusted S: 5.49, 95% CI 4.15–7.27). Moreover, fasting serum triglyceride lipids were the most relevant blood lipid indicator for the risk of stress urinary incontinence, especially among obese women younger than 50 years old, which contributes to the development of more refined lipid control protocols for patients with urinary incontinence in different age groups.

Nanomedicines against Chagas disease: a critical review.

Chagas disease (CD) is the most important endemic parasitosis in South America and represents a great socioeconomic burden for the chronically ill and their families. The only currently available treatment against CD is based on the oral administration of benznidazole, an agent, developed in 1971, of controversial effectiveness on chronically ill patients and toxic to adults. So far, conventional pharmacological approaches have failed to offer more effective and less toxic alternatives to benznidazole. Nanomedicines reduce toxicity and increase the effectiveness of current oncological therapies. Could nanomedicines improve the treatment of the neglected CD? This question will be addressed in this review, first by critically discussing selected reports on the performance of benznidazole and other molecules formulated as nanomedicines in in vitro and in vivo CD models. Taking into consideration the developmental barriers for nanomedicines and the degree of current technical preclinical efforts, a prospect of developing nanomedicines against CD will be provided. Not surprisingly, we conclude that structurally simpler formulations with minimal production cost, such as oral nanocrystals and/or parenteral nano-immunostimulants, have the highest chances of making it to the market to treat CD. Nonetheless, substantive political and economic decisions, key to facing technological challenges, are still required regarding a realistic use of nanomedicines effective against CD.

Rapid intervention team strategy improves intervention quality for patients undergoing hemodialysis with arteriovenous shunt dysfunction or failure.

Vascular access dysfunction is a great burden for hemodialysis patients. Early intervention of a dysfunctional arteriovenous shunt is associated with higher technical success and may improve midterm patency. This trial aimed to estimate the feasibility of a new system, the "rapid intervention team" (RIT) strategy. We recruited hemodialysis patients who visited our hospital because of arteriovenous shunt dysfunction or failure to undergo an RIT strategy from September 1, 2019 to December 31, 2022. In addition, we included a control group comprising patients who underwent percutaneous intervention for arteriovenous shunt dysfunction or failure before this strategy was implemented from February 1, 2017 to December 31, 2022. Case number, time to intervention, all-cause mortality, cumulative survival rate, and number of patients who required temporary dialysis catheter insertion and recreation were compared between the two groups. The primary endpoints were double-lumen insertion, a composite outcome involving permanent catheter insertion, and the need for recreation. The secondary endpoint was all-cause mortality. We enrolled 1054 patients, including 544 (51.6%) and 510 (48.4%) in the RIT and control groups, respectively. Even with the coronavirus disease of 2019 (COVID-19) pandemic, the number of cases significantly increased after the implementation of the RIT strategy (from 216 in 2019 to 828 in 2022, p for trend <0.001). The RIT group had a shortened time to intervention ( p for trend <0.001). The implementation of the RIT strategy was significantly associated with a reduced risk of insertion of a temporary double-lumen catheter and recreation of vascular access (1% vs 6% and 1% vs 28%, respectively; both p < 0.01). The cumulative survival rate was not significantly different between the RIT and control groups ( p = 0.16). The implementation of the RIT strategy improves the quantity and quality of percutaneous transluminal intervention for arteriovenous shunt dysfunction or failure in patients undergoing hemodialysis.