Multifactorial Strategies Research Articles

The Influence of Sports-Related Concussion on Cognition and Landing Biomechanics in Collegiate Athletes.

Injury surveillance data indicate that collegiate athletes are at greater risk for lower extremity (LE) injuries following sports-related concussion (SRC). While the association between SRC and LE injury appears to be clinically relevant up to 1-year post-SRC, little evidence has been provided to determine possible mechanistic rationales. Thus, we aimed to compare collegiate athletes with a history of SRC to matched controls on biomechanical and cognitive performance measures associated with LE injury risk. Athletes with a history of SRC (n = 20) and matched controls (n = 20) performed unanticipated bilateral land-and-cut tasks and cognitive assessments. Group-based analyses (ANOVA) and predictive modeling (C5.0 decision tree algorithm) were used to compare group differences on biomechanical and cognitive measures. Collegiate athletes with a history of SRC demonstrated approximately six degrees less peak knee flexion on both dominant (p = 0.03, d = 0.71) and nondominant (p = 0.02, d = 0.78) limbs during the land-and-cut tasks compared to controls. Verbal Memory, knee flexion, and Go/No Go total score (C5.0 decision tree algorithm) were identified as the strongest indicators of previous SRC injury history. Reduced knee flexion during sport-specific land-and-cut tasks may be a mechanism for increased LE injury risk in athletes with a history of SRC. There appears to be multiple biomechanical and cognitive predictors for identifying previous SRC in collegiate athletes, providing evidence to support a multifactorial SRC management strategy to reduce future injury risk.

Nonsteroidal mineralocorticoid receptor blockers as a new tool for managing cardiorenal risks in type 2 diabetes mellitus

Today, the importance of targeted cardionephroprotection is increasingly increasing as one of the vectors of a multifactorial therapeutic strategy to reduce the risk of development and progression of complications of type 2 diabetes. Pathological hyperactivation of the renin-angiotensin-aldosterone system (RAAS) and mineralocorticoid receptors (MCRs) is considered as one of the mechanisms for the development of cadiorenal syndrome (RCS) in diabetes. Blocking this pathophysiological pathway in patients with CKD and type 2 diabetes can break the vicious circle of mutually aggravating damage to the kidneys and heart. ACE inhibitors and angiotensin receptor blockers (ARBs) are currently the standard of care in patients with CRS due to diabetes. But despite their effectiveness, the residual risk of CKD progression within 4–5 years remains high in almost half of patients with type 2 diabetes, mainly due to multicomponent processes of MCR hyperactivation. This causes a range of pathological reactions affecting the entire body and may contribute to kidney, heart and CD disease in patients with type 2 diabetes by promoting inflammation and fibrosis. Functional and structural changes in the kidneys and heart develop, which leads to the development of metabolic disorders, arterial hypertension, cardiovascular complications and progressive CKD. Pharmacological blockade of aldosterone binding to MCR appears to be an effective additional line for preventing the progression of the pathological cascade of KRS reactions in type 2 diabetes. The recently developed selective non-steroidal MCR antagonist (nsAMPR) finerenone has convincingly demonstrated improved renal and cardiovascular outcomes in patients with CKD and type 2 diabetes. This review covers in detail the role of MCRs in the development of cardiorenal syndrome in type 2 diabetes and CKD, describes the mechanisms of effectiveness of MCR blockade in preventing the progression of cardiorenal syndrome in type 2 diabetes and the difference between non-steroidal MCRs and steroids, and presents the results of RCTs confirming the cardionephroprotective potential of nsAMCRs in CKD and diabetes. type 2, and the place of finerenone as a multifactorial therapeutic strategy for type 2 diabetes in clinical practice.

Reducing falls among residents of retirement homes: A DNP project.

Falls among older adults (OAs) living in retirement homes (RHs) in Canada are a major public health concern due to high morbidity and mortality as well as significant healthcare expenditures. This quality improvement (QI) initiative, conducted for the author's Doctor of Nursing Practice (DNP) project, aimed to decrease fall rates and ED transfers related to falls among OAs in six RHs across the Greater Toronto Area in Ontario, Canada through a multipart intervention with two primary goals. First, the project aimed to facilitate RH NPs' implementation of a comprehensive fall risk assessment and fall prevention strategy in their practice by incorporating the Stopping Elderly Accidents, Deaths & Injuries (STEADI) toolkit into their armamentarium. Second, it sought to enhance the knowledge of the RHs' registered practical nurses (RPNs), personal support workers (PSWs), and unregulated care providers (UCPs) in assessing fall risk and incorporating fall prevention strategies in their daily practice. By improving NP, RPN, PSW, and UCP knowledge and increasing (by 20%) RPN, PSW, and UCP use of fall prevention strategies, this QI initiative successfully reduced fall rates in the RHs by 40.4%, with no falls requiring transfer to the ED, in the postintervention period. The results of this project highlight the need for an interdisciplinary approach to fall risk reduction in RHs that includes implementation of multifactorial intervention strategies as well as effective organizational policies and procedures for maximum impact.

Guarding the gatekeepers: a comprehensive approach to control nosocomial measles.

Despite substantial vaccination progress, persistent measles outbreaks challenge global elimination efforts, particularly within healthcare settings. In this paper, we critically review the factors contributing to measles outbreak and effective control measures for nosocomial transmission of measles. We systematically searched electronic databases for articles up to 17th May, 2023. This was performed by two independent reviewers, with any disagreements resolved by a third reviewer. We also searched governmental and international health agencies for relevant studies. Forty relevant articles were systematically reviewed, revealing key factors fuelling measles outbreak in healthcare settings, including high transmissibility capability; high intensity exposure; delayed care; failure to use protective equipment and implement control measures; vaccine failure; unclear immunisation history and lack of registries; and lacking recommendation on healthcare workers' (HCWs) measles vaccination. To combat these challenges, successful control strategies were identified which include early notification of outbreak and contact tracing; triaging all cases and setting up dedicated isolation unit; strengthening protective equipment use and physical measures; improving case detection; determining immunity status of HCWs; establishing policy for measles vaccination for HCWs; management of exposed personnel; and developing a pre-incident response plan. A coordinated and comprehensive approach is essential to promptly identify and manage measles cases within healthcare settings, necessitating multifactorial strategies tailored to individual settings. These findings provide a valuable foundation for refining strategies to achieve and maintain measles elimination status in healthcare environments.

High molecular/low acetylated chitosans reduce adhesion of Campylobacter jejuni to host cells by blocking JlpA

Infections caused by Campylobacter spp. are a major cause of severe enteritis worldwide. Multifactorial prevention strategies are necessary to reduce the prevalence of Campylobacter. In particular, antiadhesive strategies with specific inhibitors of early host–pathogen interaction are promising approaches to reduce the bacterial load. An in vitro flow cytometric adhesion assay was established to study the influence of carbohydrates on the adhesion of C. jejuni to Caco-2 cells. Chitosans with a high degree of polymerization and low degree of acetylation were identified as potent antiadhesive compounds, exerting significant reduction of C. jejuni adhesion to Caco-2 cells at non-toxic concentrations. Antiadhesive and also anti-invasive effects were verified by confocal laser scanning microscopy. For target identification, C. jejuni adhesins FlpA and JlpA were expressed in Escherichia coli ArcticExpress, and the influence of chitosan on binding to fibronectin and HSP90α, respectively, was investigated. While no effects on FlpA binding were found, a strong inhibition of JlpA-HSP90α binding was observed. To simulate real-life conditions, chicken meat was inoculated with C. jejuni, treated with antiadhesive chitosan, and the bacterial load was quantified. A strong reduction of C. jejuni load was observed. Atomic force microscopy revealed morphological changes of C. jejuni after 2 h of chitosan treatment, indicating disturbance of the cell wall and sacculi formation by electrostatic interaction of positively charged chitosan with the negatively charged cell surface. In conclusion, our data indicate promising antiadhesive and anti-invasive potential of high molecular weight, strongly de-acetylated chitosans for reducing C. jejuni load in livestock and food production.Key points• Antiadhesive effects of chitosan with high DP/low DA against C. jejuni to host cells• Specific targeting of JlpA/Hsp90α interaction by chitosan• Meat treatment with chitosan reduces C. jejuni load

Nanotechnology for microglial targeting and inhibition of neuroinflammation underlying Alzheimer’s pathology

BackgroundAlzheimer's disease (AD) is considered to have a multifactorial etiology. The hallmark of AD is progressive neurodegeneration, which is characterized by the deepening loss of memory and a high mortality rate in the elderly. The neurodegeneration in AD is believed to be exacerbated following the intercoupled cascades of extracellular amyloid beta (Aβ) plaques, uncontrolled microglial activation, and neuroinflammation. Current therapies for AD are mostly designed to target the symptoms, with limited ability to address the mechanistic triggers for the disease. In this study, we report a novel nanotechnology based on microglial scavenger receptor (SR)-targeting amphiphilic nanoparticles (NPs) for the convergent alleviation of fibril Aβ (fAβ) burden, microglial modulation, and neuroprotection.MethodsWe designed a nanotechnology approach to regulate the SR-mediated intracellular fAβ trafficking within microglia. We synthesized SR-targeting sugar-based amphiphilic macromolecules (AM) and used them as a bioactive shell to fabricate serum-stable AM–NPs via flash nanoprecipitation. Using electron microscopy, in vitro approaches, ELISA, and confocal microscopy, we investigated the effect of AM–NPs on Aβ fibrilization, fAβ-mediated microglial inflammation, and neurotoxicity in BV2 microglia and SH-SY5Y neuroblastoma cell lines.ResultsAM–NPs interrupted Aβ fibrilization, attenuated fAβ microglial internalization via targeting the fAβ-specific SRs, arrested the fAβ-mediated microglial activation and pro-inflammatory response, and accelerated lysosomal degradation of intracellular fAβ. Moreover, AM–NPs counteracted the microglial-mediated neurotoxicity after exposure to fAβ.ConclusionsThe AM–NP nanotechnology presents a multifactorial strategy to target pathological Aβ aggregation and arrest the fAβ-mediated pathological progression in microglia and neurons.Graphical

Study of Impact of Lifestyle Modification on Diabetes and Prediabetes in an Urban Population

Diabetes mellitus has emerged as a prevalent noncommunicable disease worldwide. It ranks among the top causes of mortality in high-income countries and has reached epidemic proportions in newly developing nations.1 Continuous medical care and monitoring is required in Diabetes mellitus along with multi-factorial risk reduction strategies along associated with glycemic control. Due to population aging, growth, urbanization, a lack of physical exercise, and a high incidence of obesity, there are more persons with DM. Lifestyle factors include eating patterns, exercise routines, alcohol consumption, and smoking. An improvement in these parameters would lead to better adherence to hypoglycemic medications. An epidemiological study on diabetes and prediabetes in an urban area with reference to lifestyle modification. An interventional community-based study was conducted in an urban setup. Personal interviews using a semi-structured, pretested questionnaire were the main technique of data gathering. Detailed information has been taken on the demographic and socio-economic characteristics at both the individual and household levels. All responders provided their willingly given consent. Every second household was visited by systematic random sampling procedure to select 400 respondents. Finally, analysis was carried out on 346 respondents. All respondents were questioned using structured a pretested, questionnaire after taking informed consent. Significant difference was observed with positive family history of diabetes, obesity, physical activities in male, high calorie intake, stress, chewable tobacco and blood pressure level with diabetes and pre-diabetes. Compared to responders with normal level of blood glucose, pre diabetics and diabetics individual showed more positive family histories. Compared to responders with normal blood glucose levels, pre-diabetics and diabetics were more likely to be overweight. With regard to personal habits of the respondents, smoking was associated with more than 1-fold increase risk of obtaining serum glucose level >110 mg/dl as compared to non-smokers.The current research was an attempt to examine the effect of intervention with reference to life style modification. From the study, it is evident that overall awareness about diabetes has been found low and no awareness has been found about pre-diabetes. The present study also demonstrated that education is the fundamental tool to make the population aware of their health issues. Awareness about pre-diabetes and diabetes, which can make them beneficial for community and nation and so, they can play an innovative role for prevention of diabetes.

An Epidemiological Study on Diabetes and Pre-Diabetes in an Urban Area with Reference to Lifestyle Modification

Diabetes mellitus (DM) is one of the most common non-communicable diseases (NCDs) globally. It is the fourth or fifth leading cause of death in most high-income countries and there is substantial evidence that it is an epidemic in newly industrialized and many economically developing countries. Diabetes mellitus is a chronic illness requiring continuous medical care with multifactorial risk reduction strategies beyond glycemic control. Ongoing patient self-management education and support are critical to preventing acute complications and reducing the risk of long-term complications. Genetic factors are responsible for at least some of this. However, as evidenced by the increased incidence of diabetes mellitus in urban populations, the fast epidemiological shift linked to food pattern alterations and decreased physical activity is the main cause of the diabetes mellitus epidemic. Due to population aging, growth, urbanization, a lack of physical exercise, and a high incidence of obesity, there are more persons with DM. Lifestyle factors include eating patterns, exercise routines, alcohol consumption, and smoking. An improvement in these parameters would lead to better adherence to hypoglycemic medications. An epidemiological study on diabetes and pre-diabetes in an urban area with reference to lifestyle modification. A community-based intervention study. It was conducted in an urban area. Personal interviews using a semi-structured, pretested questionnaire were the main technique of data gathering. Detailed information has been taken on the demographic and socio-economic characteristics at both the individual and household levels. All responders provided their willingly given consent. Every second household was visited by systematic random sampling procedure to select 400 respondents. Due to non-response, inaccuracy and/or unreliability of information 50 Cases were not included in the analysis. Four more instances of diabetes were also removed from the research. Finally, analysis was carried out on 346 respondents. All respondents were questioned using a pretested, semi-structured questionnaire after giving their informed consent. Significant difference was observed with positive family history of diabetes, obesity, physical activities in male, high calorie intake, stress, chewable tobacco and blood pressure level with pre-diabetes and diabetes. Compared to responders with normal blood glucose levels, pre-diabetics and diabetics showed more positive family histories. Compared to responders with normal blood glucose levels, pre-diabetics and diabetics were more likely to be overweight. With regard to personal habits of the respondents, smoking was associated with more than 1-fold increase risk of obtaining serum glucose level >110 mg/dl as compared to nonsmokers. The current research was an attempt to examine the effect of intervention with reference to life style modification. From the study, it is evident that overall awareness about diabetes has been found low and no awareness has been found about pre-diabetes. The present study also demonstrated that education is the fundamental tool to make the population aware of their health issues. Awareness about pre-diabetes and diabetes, which can make them beneficial for community and nation and so, they can play an innovative role for prevention of diabetes.

Effectiveness of a breastfeeding promotion intervention model based on Society ecosystems Theory for maternal women: a study protocol of randomized controlled trial

BackgroundBreastfeeding is recognized internationally as the most scientific and effective way to feed infants and young children. According to the World Health Organization in 2022, the exclusive breastfeeding rate within 6 months is 34.1% in China, which is still far from the goal of “more than 60% exclusive breastfeeding rate of infants within 6 months” by 2030 required by China’s State Council. It is necessary to promote breastfeeding and provide maternal breastfeeding guidance to increase exclusive breastfeeding. Factors influencing breastfeeding can be explained by the society ecosystems theory, distributed in macro, mezzo and micro systems. The interventions focused on breastfeeding promotion are mainly carried out in the health systems and services, home and family environment, community environment, work environment, policy environment or a combination of these facilities. But there is sparse research on integrating resources in the macro, mezzo and micro systems of maternal breastfeeding processes to promote breastfeeding behavior. A randomized controlled trial will test the effect of a breastfeeding promotion intervention model based on the society ecosystems theory versus usual prenatal and postnatal care on maternal and infant health and the exclusive breastfeeding rate at 6 months.Methods/designThe study is a single-blind, parallel design, randomized controlled trial with an intervention group (n = 109) and a control group (n = 109) that compares the effect of a breastfeeding promotion intervention model based on the society ecosystems theory with usual prenatal and postnatal care. The intervention covers macro- (policy, culture), mezzo- (family-hospital-community) and micro- (biological, psychological and social) systems of the maternal breastfeeding process. Infant feeding patterns, neonatal morbidity and physical and mental health of antenatal and postpartum women will be collected at baseline (28 to 35 weeks of gestation), 1-, 4-, and 6-month postpartum.DiscussionThis is a multifaceted, multifactorial, and multi-environmental breastfeeding promotion strategy to help mothers and their families learn breastfeeding knowledge and skills. The study provides a new modality for adding breastfeeding interventions to prenatal and postnatal care for healthcare providers in the hospital and the community.Trial registration: Chinese Clinical Trial Registry at www.chictr.org.cn, ChiCTR2300075795.

Musculoskeletal and Psychological Rehabilitation.

Although it has long been believed that stress has a detrimental effect on health and the risk of disease, little research has been done on the precise mechanisms by which this happens. The literature produced by past workers suggests many possibly intersecting mechanistic pathways that might be useful for future fundamental and clinical study. Exercise has been thoroughly researched as a non-pharmacologic strategy to increase bone mass. Many evidence-based treatment recommendations for patients suffering from osteoporosis-related fractures, potential courses of care, and rehabilitation concur that multidisciplinary therapy would be the most beneficial. Older and recent articles about musculoskeletal and psychological rehabilitation in the management of osteoporosis published in prominent and reputed journals are reviewed. Important and interesting information from some of the cross-references is also included. Opinions and impressions from the experience of treating osteoporosis are added while describing various aspects of psychological and physical rehabilitation. The recent evidence, reviewed here, also indicates the possibility of cross-effects between osteoporosis and psychological issues. A multi-factorial and personalised strategy should be explored for improved outcomes in patients under psychological stress, particularly those at increased risk of osteoporosis development. Reviewing current publications, the objectives of rehabilitation are evolving based on the disease's stage. For example, during the initial stage of a vertebral body collapse, the patient is treated with bracing, physical therapy, education, local and systemic analgesics, and a brief period of bed rest. The need to mobilise the patient carefully and safely along with a mix of medical care, dietary supplements, rehabilitation, and instructions to facilitate daily living activities, are endorsed to manage post-fracture osteoporosis. This chapter is not to make treatment advice, but rather to outline potential connections between psychological stress and low bone density and to emphasise potential multi-system consequences of pharmaceutical therapies. The goal is to enhance activities of daily living, which will increase safety, minimise falls, and maintain bone mass. Osteoporosis and fragility fractures can be prevented and managed with regular medical check-ups, daily exercise and yoga, a healthy diet, fall prevention measures,recreational groupactivities, supportive medications, control ofcomorbidities, use of assistivedevices, and customised rehabilitation programmes.

Analysis of Multifactor Fundamentals Stock Selection Based on Backtesting

In recent years, quantitative finance has become a major trend for investing which brings stable returns with controllable risks. Among various different quantitative strategies, multifactorial stock selection strategy based on fundamental data (e.g., financial statements, macro- and micro-economy data) is one of the widely investigated strategies. On this basis, this study chooses Chinese listed company to verify the feasibility and effectiveness of the stock selection strategy. To be specific, the Ricequant platform is utilized to realize the backtesting as well as data retrieving in order to estimate and evaluate the performances of the strategies. According to the analysis, several indicators show great ability to gain extra returns compared with systematic risks and market performances. In other words, the feasibility of explicability of the quantitative strategy based on multifactorial model is verified in Chinese market. Overall, these results shed light on guiding further exploration of fundamental analysis of different underlying assets based on multifactorial analysis.

Glucagon in health and diabetes

Abstract For decades all attention focused on the hormone insulin as a key player in diabetes and the role of glucagon was less studied or understood. We now know that both these pancreatic hormones play a critical role in maintaining glucose homeostasis in the body and the secretion of one controls the secretion of the other in an inverse relationship as described by the bihormonal theory of Unger. Glucagon, secreted by the α-cells of the islets of pancreas is a key hormone that has a “hyperglycemic” effect and is secreted in response to low plasma glucose concentration. Besides hypoglycemia, glucagon release is also stimulated by prolonged fasting or starvation, exercise as well as consumption of protein-rich meals. It is regulated by several key endocrine and paracrine mechanisms and the autonomic system in response to various stimuli including nutrient intake through various complex neurohormonal factors. It primarily increases endogenous hepatic glucose production, stimulates lipid and protein catabolism, and plays a key role in appetite regulation and increasing energy expenditure. Therefore, glucagon functions as a counter-regulatory hormone to insulin stimulating hepatic glycogenolysis, gluconeogenesis, fatty acid oxidation, and ketogenesis. With mounting evidence, there has been a paradigm shift in the management of diabetes following the advent of new agents that address different pathophysiological mechanisms contributing to worsening hyperglycemia. Targeting the alpha-cell defect and consequent glucagon hypersecretion has therefore emerged as an important therapeutic strategy in type 2 diabetes mellitus (T2DM) management as well as body weight management. The currently available medications, including glucagon-like peptide 1 (GLP-1) receptor agonists, DPP-4 inhibitors, and amylin mimics (pramlintide), essentially focus on lowering glucagon levels and correcting this critical pathophysiological component in the multifactorial T2DM management strategies.

Enhancing the Heterologous Expression of a Thermophilic Endoglucanase and Its Cost-Effective Production in Pichia pastoris Using Multiple Strategies.

Although Pichia pastoris was successfully used for heterologous gene expression for more than twenty years, many factors influencing protein expression remain unclear. Here, we optimized the expression of a thermophilic endoglucanase from Thermothielavioides terrestris (TtCel45A) for cost-effective production in Pichia pastoris. To achieve this, we established a multifactorial regulation strategy that involved selecting a genome-editing system, utilizing neutral loci, incorporating multiple copies of the heterologous expression cassette, and optimizing high-density fermentation for the co-production of single-cell protein (SCP). Notably, even though all neutral sites were used, there was still a slight difference in the enzymatic activity of heterologously expressed TtCel45A. Interestingly, the optimal gene copy number for the chromosomal expression of TtCel45A was found to be three, indicating limitations in translational capacity, post-translational processing, and secretion, ultimately impacting protein yields in P. pastoris. We suggest that multiple parameters might influence a kinetic competition between protein elongation and mRNA degradation. During high-density fermentation, the highest protein concentration and endoglucanase activity of TtCel45A with three copies reached 15.8 g/L and 9640 IU/mL, respectively. At the same time, the remaining SCP of P. pastoris exhibited a crude protein and amino acid content of up to 59.32% and 46.98%, respectively. These findings suggested that SCP from P. pastoris holds great promise as a sustainable and cost-effective alternative for meeting the global protein demand, while also enabling the production of thermophilic TtCel45A in a single industrial process.

Identification of Confusing Medicine Proprietary Names: Toward Safe Medicine Use-A Cross-Sectional Study in Sri Lanka.

Look-alike sound-alike (LASA) medications have similar pronunciation (phonetic) and/or manifestation (orthographic), which could create confusion among users and challenge the safe use of medicines. The availability of foreign products in local markets aggravates the situation. This study was designed to examine the registered medicine proprietary names in Sri Lanka to discern the presence of similar medicine names in the industry. A cross-sectional study was conducted on the registered drug proprietary names in Sri Lanka. Using the RAND and RANK functions in Microsoft® excel® 365, a random sample of 385 proprietary names was selected. Two evaluators independently evaluated each proprietary name in the sample against the other registered proprietary names following a stepwise text filtering method. After each filter, the resulting proprietary names were manually examined for identical, similar-looking, and similar-sounding proprietary names to the name under evaluation. The observations were matched, categorized, and collated into ten groups. Among the 385 names evaluated, 138 (35.84%) proprietary names had no similarity to existing other registered proprietary names. The rest of the names (n = 247, 64.15%) were found to be either identical (n = 03 pairs), look-alike (n = 91 pairs), or sound-alike (n = 80 pairs) to the registered proprietary names. The findings revealed the presence of equal and similar proprietary names in the system. A multifactorial strategy led by the National Medicine Regulatory Authority (NMRA) is recommended to minimize the confusing names entering the system. Primarily the NMRA's call for action should include adequate industry guidance with specific guidelines, a significant pre-submission assessment process, and denying approval of LASA proprietary names.

Production, purification, and characterization of cold-active lipase from the psychrotroph Pseudomonas sp. A6

Cold-active lipases are presently employed extensively in the detergent, chemical intermediate, fine chemical, food, and pharmaceutical industries. Seven cold-adaptive bacteria were isolated from the Mediterranean Sea near Alexandria, Egypt, and tested for their ability to produce cold-active lipase, with the highest activity at 10 °C. The most potent isolate was Pseudomonas sp. A6. To determine the most important variables, the bacterium was exposed to a necessary medium component and environmental factor screening using a single factor-at-a-time approach, followed by a multifactorial Plackett-Burman design strategy. After purification and characterization, the optimal activity levels for the cold-active lipase were figured out. Inoculation of Pseudomonas A6 under near optimum conditions using medium consisting of (g/L) peptone 7.14; soybean oil 7.5% (v/v); K2HPO4, 0.4; MgSO4, 0.1; glucose 2; pH 8; and temperature 10 °C led to a maximum lipase activity anticipated to be 23.36 U/mL. Purified lipase showed the best activity and thermal stability at a pH of 8 and a temperature of 10 °C. The Pseudomonas A6 lipase tolerated the monovalent ions, while greater valence ions did not.

Breaking down silos: the multifaceted nature of obesity and the future of weight management.

The continued global increase in the prevalence of obesity prompted a meeting at the Royal Society of London investigating causal mechanisms of the disease, 'Causes of obesity: theories, conjectures, and evidence' in October 2022. Evidence presented indicates areas of obesity science where there have been advancements, including an increased understanding of biological and physiological processes of weight gain and maintenance, yet it is clear there is still debate on the relative contribution of plausible causes of the modern obesity epidemic. Consensus was reached that obesity is not a reflection of diminished willpower, but rather the confluence of multiple, complex factors. As such, addressing obesity requires multifactorial prevention and treatment strategies. The accumulated evidence suggests that a continued focus primarily on individual-level contributors will be suboptimal in promoting weight management at the population level. Here, we consider individual biological and physiological processes within the broader context of sociodemographic and sociocultural exposures as well as environmental changes to optimize research priorities and public health efforts. This requires a consideration of a systems-level approach that efficiently addresses both systemic and group-specific environmental determinants, including psychosocial factors, that often serve as a barrier to otherwise efficacious prevention and treatment options. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Abstract 5171: TP-6379, an investigational TGFBR1 inhibitor, shown to remodel the tumor microenvironment and enhance anti-tumorigenic immunological responses in syngeneic mouse models of cancer

Abstract Transforming growth factor-β (TGF-β) receptors regulate SMAD signal transduction and a wide-range of biological processes including, wound healing, angiogenesis, immune modulation, epithelial-mesenchymal transition, cell differentiation, apoptosis, growth, and motility. In transformed cells, TGF-β signaling is frequently exploited to reshape the architecture of the tumor microenvironment (TME) and establish a fibrotic barrier that insulates the tumor from surrounding normal tissue. As a result, immunological threats to the tumor are restricted, as is the anti-tumorigenic potential of immunotherapeutic interventions. Clinically, TGF-β hyperactivity is associated with immunotherapy resistance and poor outcome in a variety of malignancies. We hypothesize that TP-6379, an investigational small molecule inhibitor of TGFBR1, may remodel the TME to expand the access of tumor-seeking lymphocytes to tumor tissue. Herein we describe several anti-tumorigenic effects of TP-6379 observed in multiple mouse models of cancer both as a single agent, and in combination with immunotherapy. In an EMT6 syngeneic mouse model of triple-negative breast cancer (TNBC), we observed that tumor phospho-SMAD2/3 (pSMAD2/3) levels quickly declined post-TP-6379-treatment and were suppressed by 74% after 8 hours. Preclinical data showed TP-6379 plasma levels inversely correlated with pSMAD2/3 suppression. TP-6379 alone was observed to inhibit tumor growth in EMT6 and 4T1 TNBC models, an activity that was enhanced when augmented by immunotherapy. In a Cloudman S91 syngeneic melanoma mouse model, there was a clear subset of mice that responded to combination treatment. Histological analyses of TNBCs and responsive melanomas showed that TP-6379 treatment conferred a loss of induration of tumors, increased vascularization, and increased infiltration of CD45+ leukocytes (including CD8+ T cells), particularly when combined with immunotherapy. High-throughput analyses of tumors uncovered an array of MHC class I and II factors that were observed elevated subject to TP-6379 treatment, an activity that was oftentimes enhanced when combined with immunotherapy. Collectively, these data suggest that TP-6379 may improve immune cell access to tumor tissue via TME remodeling and normalization of vascular networks. Thus, TP-6379 treatment may present a unique and multifactorial anti-tumor strategy, 1) as a single agent to improve anti-tumorigenic immunological responses, and 2) as a combination treatment to boost immunotherapeutic activity. Citation Format: David A. Kircher, Tetyana V. Forostyan, Richard E. Heinz, Curtis A. Allred, Sal Sommakia, Yuta Matsumura, Adam Siddiqui, Jason M. Foulks, Steven L. Warner. TP-6379, an investigational TGFBR1 inhibitor, shown to remodel the tumor microenvironment and enhance anti-tumorigenic immunological responses in syngeneic mouse models of cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5171.

Prevalence of cognitive frailty among older adults in China: a systematic review and meta-analysis

ObjectiveThis study aimed to investigate the prevalence of cognitive frailty among older adults in China.DesignSystematic review and meta-analysis.MethodsWe searched the Cochrane Library, PubMed, Web of Science, Embase, China National Knowledge...

Double or triple combination therapy in systemic arterial hypertension: to whom, when and with what?

La hipertensión arterial sistémica (HAS) es el principal factor de riesgo para muerte prematura en el mundo y en México.1 Se estima que existen 15.2 millones de mexicanos con diagnóstico de HAS, de los cuales 7.48 millones son derechohabientes del IMSS (evaluación de los riesgos financieros considerados en el Programa de Administración de Riesgos Institucionales, ENSANUT, 2018).2

Lifestyle modification and medication use among diabetes mellitus patients attending Jimma University Medical Center, Jimma zone, south west Ethiopia

Diabetes, a non-communicable metabolic disease, causes multiple complications and deaths worldwide. It is a complex, chronic disease that requires continuous medical care with multifactorial risk reduction strategies beyond glycemic control. Ongoing patient education and self-management support are critical for preventing acute complications and reducing the risk of long-term complications. There is ample evidence that healthy lifestyle choices, such as a healthy diet, moderate weight loss, and regular exercise, can maintain normal blood sugar levels and minimize diabetes-related complications. In addition, this lifestyle change has a major impact on controlling hyperglycemia and can help to maintain normal blood sugar levels. This study aimed to assess lifestyle modification and medication use in patients with diabetes mellitus at Jimma University Medical Center. Hospital-based prospective cross-sectional study was conducted from April 1 to September 30, 2021 among DM patients who have follow-up at diabetic clinic of Jimma University Medical Center. Consecutive sampling was used until the required sample size was achieved. Data were checked for completeness, then entered into Epidata version 4.2 software and exported to SPSS version 21.0. Pearson’s chi-square test was performed to determine the association between KAP and independent factors. Variables with a p value < 0.05 were considered significant. A total of 190 participants took part in this study with a response rate of 100%. In this study, 69 (36.3%) participants had good knowledge, 82 (43.2%) moderate knowledge and 39 (20.5%) poor knowledge, 153 (85.8%) had positive attitudes, 141 (74.2%) had good practice. Marital status, Occupational status and educational status were significantly associated with knowledge and attitude towards LSM and medication use. Marital status was the only variable that remained significantly associated with knowledge, attitude and practice towards LSM and medication use. The result of this study showed that more than 20% of the participants had poor knowledge, attitude, and practice towards medication use and LSM. Marital status was the only variable which remained to be significantly associated with KAP towards LSM and medication use.