: Chronic liver diseases stimulate a degree of hepatocyte injury. This previously mentioned modifications, alters the known liver architecture and finally ends in cirrhosis. The management of this liver pathology, is centred on the treatment of the causes and complications. Liver transplantation can be required in some cases. The aim of this article is to identify the best available evidences analyzing liver samples, normall and pathological.Were made permanent preparations and used two colors. Hematoxylin–Eosin and also Goldner Szekely trichrome stains stain for observation at optical microscope with x10 and x40 lens magnification. Samples liver collected during necropsy, from healthy patients and from patients diagnosed with cirrhosis. Normal liver with hepatocytes, Kiernann space, connective septa, observations using lens x10 and samples colored with Goldner Szekely trichrome stains. Beside, for comparisions, ill liver images, classic stain H&E. Our contribution in the written text, is related to the impact of physical, psychological and physiological factors.

Cerebrovascular diseases represent a significant mortality rate worldwide and constitute a major public health and economic challenge. Many African countries such as Cape Verde are going through an epidemiological transition from communicable to non-communicable diseases, demographic and socioeconomic changes and facing an increase in cerebrocardiovascular diseases associated with increased cardiovascular risk. The present study aimed to identify the prevalence of risk factors that predispose to cardiovascular diseases in adult individuals residing on the island of Santiago. Cross-sectional population-based study with individuals over 18 years of age, of both sexes. Data collection took place in October and November 2021, in all municipalities on the island of Santiago. Individuals with Cape Verdean nationality who stayed abroad for more than one year and who arrived on the island of Santiago less than 30 days ago and individuals with any type of disability that could prevent them from participating in the study were excluded from the study. The sample size was calculated based on the projection of the population of the island of Santiago for the year 2021, according to the appropriate epidemiological model. Sociodemographic data were obtained through the application of a questionnaire containing age, sex, race, weight, height, risk factors (presence of diabetes, dyslipidemia, heredity, physical activity, smoking habits, history of cerebrovascular events, control of weight and blood pressure). RESULTS: Study sample is predominantly female (54.8%), the age group with the largest number was 18-27 years (21%); 42.2% with BMI ≥ 25 kg/m2; 65.1% sedentary; Smoking 7.3% and alcoholism 14.4%; 6.5% with diagnosed heart disease; 19.9% with close family members with cardiac pathology; 2.7% had a stroke, 0.1% had a transient ischemic attack; 0.5% acute myocardial infarction; 23.5% had the periodic habit of assessing blood pressure; 32.6% hypertensive; 4.5% with diabetics. CONCLUSIONS: The study showed that there is a high prevalence of cerebrovascular risk factors on Santiago Island, especially in females. Smoking and alcoholism showed a relationship with males. BMI, physical inactivity, diabetes and dyslipidemia were shown to be related to sex. Hypertension and Diabetes revealed a significant relationship with age group. Alcoholism, smoking, hypercholesterolemia and hypertriglyceridemia maintained a significant relationship with the municipalities.

Chronic liver diseases stimulate a degree of hepatocyte injury. This previously mentioned modifications, alters the known liver architecture and finally ends in cirrhosis. Liver pathology as cirrhosis develops after a long period of pathological alterations. The management of this liver pathology, is centred on the treatment of the causes and complications. Liver transplantation can be required in some cases. The aim of this article is to identify the best available evidences analyzing liver samples, normall and pathological. Normal liver with hepatocytes, Kiernann space, connective septa, observations using lens x10 and samples colored with Goldner Szekely trichrome stains. Beside, for comparisions, ill liver images, classic stain H&E. Inflammation is a great point that results in replacement of the healthy liver parenchyma with fibrotic tissue and regenerative nodules. In addition, progressive portal hypertension, systemic inflammation, and liver failure drive cirrhosis outcomes. All this previously mentioned factors, area great impact on the health-related quality of life of adult patients with liver cirrhosis. The management of this liver pathology, is centred on the treatment of the causes and complications. Liver transplantation can be required in some cases.

Tobacco use is bad for your health in many ways, not just your lungs. It affects many other parts of your body, including your nervous system. This abstract looks at the link between smoking and the nervous system and shows how smoking affects the nerve system in specific ways. There are a lot of different diseases and risks that can come from smoking. By weakening blood vessels and making it easier for blood clots to form, smoking makes the chance of having a stroke much higher. Using tobacco is also linked to a drop in brain function and memory problems, as well as a higher chance of neurodegenerative diseases like Alzheimer's disease and dementia. Also, people who smoke have a higher chance of getting multiple sclerosis, which is a long-term autoimmune disease that affects the central nervous system. It can also cause peripheral neuropathy, which can damage nerves and cause tingling, pain, and stiffness in the limbs. Nicotine, the substance that makes tobacco addicting, changes the brain's reward circuits. This makes it hard to stop smoking because it leads to addiction. In addition to these effects on the body, smoking also has effects on the mind. It makes mood disorders like sadness and anxiety more likely, making the symptoms worse and hurting general health. Understanding the effects of smoking on the brain is important for improving overall health and getting people to stop smoking. Public health efforts, education, and targeted interventions are needed to make people aware of these risks and help them make choices about smoking that are based on accurate information. By looking at how smoking affects the brain, we can try to make people's lives better and protect their and their communities' well-being.

The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. It implies the extraction and analysis of non-solid biological tissues (serum, plasma, saliva, urine and cerebrospinal fluid) without undergoing invasive procedures to determine disease prognosis. Liquid biopsy can be used for the screening of several components such as extracellular vesicles, microRNAs, cell-free DNA, cell-free mitochondrial and nuclear DNA, circulating tumor cells, circulating tumor DNA, transfer RNA and circular DNA or RNA derived from body fluids. Its application includes early disease diagnosis, surveillance of disease activity, and treatment response monitoring, with growing evidence for validating this methodology in cancer, liver disease, and central nervous system (CNS) disorders. This review will provide an overview of mentioned liquid biopsy components, which could serve as valuable biomarkers for the evaluation of complex neurological conditions, including Alzheimer’s disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, traumatic brain injury, CNS tumors, and neuroinfectious diseases. Furthermore, this review highlights the future directions and potential limitations associated with liquid biopsy.

Biomarkers play key roles in diagnosis, risk assessment, treatment and supervision of car-diovascular diseases (CVD). Optical biosensors and assays are valuable analytical tools answering the need for fast and reliable measurements of biomarkers levels. This review presents a survey of recent literature with a focus on the past 5 years. The data indicates continuing trends towards multiplexed, simpler, cheaper, faster and innovative sensing while newer tendencies concern minimizing the sample volume or using alternative sam-pling matrices such as saliva, for less invasive assays. The use of enzyme mimicking activity of nanomaterials gained ground in comparison to their more traditional roles as signaling probe, immobilization support for biomolecules or for signal amplification. The growing use of aptamers as replacements for antibodies prompted emerging applications of DNA am-plification and editing techniques. Optical biosensors and assays were tested with larger sets of clinical samples and compared with the current standard methods. The ambitious goals on the horizon for CVD testing include the discovery and determination of relevant biomarkers with the help of artificial intelligence, more stable specific recognition elements for biomarkers and fast, cheap readers and disposable tests to facilitate rapid testing at home. As the field is progressing at an impressive pace the opportunities for biosensors in the optical sensing of CVD biomarkers remain significant.

Tree members of the genus Acacia have benefits that are obvious for enhancing soil fertility in farming, forestry and agroforestry in regions with nutrient-poor soils, and for restoring degraded ecosystems and lands. Nevertheless, the species of the genus Acacia have got the potential to bring about significant adverse impacts on biodiversity or ecosystem functioning when it gets invasive. The ecology of the species in nearly all areas of its created range remains poorly understood. Here we have compiled the information regarding the importance, cultivation and the production of important species of genus Acacia. We hope this information will be useful to get awareness about the crucial trees in the genus Acacia.

Mucosal vaccines can target specific mucosal surfaces, such as the respiratory, genital, or intestinal mucosa. Conventional systemic immunization, such as intramuscular injections, do not provide mucosal immunity, including IgA, nor do they prevent pathogens from entering the mucous membranes. Nasal immunization protects mucosal membranes, but nasal antigen presentation appears to entail adjuvant to stimulate immunogenicity. Current treatments for mucosal diseases such as inflammatory bowel disease (IBD) and allergic dermatitis only aimed to temporarily relieve symptoms. Moreover, these treatments not only have drug resistance or side effects, but the disease can recur, leading to switching to other treatments. Therefore, there is a need to develop safe and effective treatments that provide better long-term outcomes to reduce the risk of recurrence. Regulatory T (Treg) cells have been used to suppress inflammation. To find advances in mucosal treatment, we investigated the therapeutic effects of intranasal pep27 mutant immunization. Here, a new method of Treg induction through intranasal immunization without adjuvant has been developed to potentially overcome allergies and mucosal inflammation of the lung-gut axis in animal models. The implementation of the pep27 mutant for these therapies should be preceded by studies of Treg resilience through clinical translational studies of dietary changes.

Prototypical functions of the chemokine receptor CCR6 include immune regulation by manoeuvring cell chemotaxis and selective delimiting of the pro-inflammatory TH17 and regulatory Treg subsets during chronic or acute systemic inflammation. Inhibition of CCR6 is proposed to attenuate disease symptoms and promote recuperation of multiple inflammatory and autoimmune disorders. Prescription medicines with pharmacodynamics involving the inhibition of the chemokine axis CCR6-CCL20 is very limited. Developing such therapeutics is still at an early experimental stage which has mostly utilized pre-clinical models and neutralizing mono or polyclonal antibodies against either partner, CCR6 or CCL20. Other methods have been constitutive use of small molecules as peptide inhibitors or small interfering ribonucleic acid (siRNA) to interfere with transcription at the nuclear level. We in our review aim at introducing the wide array of potential CCR6-CCL20 inhibitors that have been tried to date in the research field with accent on attendant immune-modulator capacity and which are immensely promising compounds as forerunners of future curatives. 16 different tractable inhibitors of the CCR6-CCL20 duo have been identified to possess high medicinal potential to the drug developers worldwide to treat autoimmune and inflammatory diseases. A multitude of antibody preparations are already available in the current pharmaceutical market as patented treatment for diseases in which the CCR6-CCL20 axis is operative, yet must be used only as supplements with existing routinely prescribed medication as they collectively produce adverse side effects. Novel inhibitors are needed to evaluate this invaluable therapeutic target which holds much promise in the research and development of complaisant remedies for inflammatory diseases.

Leishmaniasis is one of the Neglected tropical diseases. Studies show that the poor knowledge about epidemiological aspects of Leishmaniasis within communities causes the collapse of existing disease control programs. Therefore, the present study focuses on a detailed survey of the existing awareness among the threatened population in the Medawachchiya PHI Area in the Anuradhapura District, Sri Lanka aiming to assist the health staff to organize community-based vector control programs effectively in the future. Assessment of the awareness of the two hundred and seventy households (n=270) residents from ten GNDs was carried out by using a structured questionnaire. Among 143 females and 134 males, only 75.1% have knowledge about the disease. 5.8%(n=16) of the participants know only about the vector and 28.9% (n=80) know their control methods. The study shows a shortage of a considerable amount of awareness about the disease among the studied population The study found that age and education levels had significant impacts on knowledge, attitudes, and practices. However, factors like gender, marital status, occupation, income, and expenses did not show significant correlations. The present study suggests the huge scope for community-related vector control methods for greater achievements in vector control methods by implementing a continuous educational program.

This commentary is focused on radioactive contaminations in the Urals, where the consequences were more severe in the long term than those after the Chernobyl accident. The difference is that the latter was a technogenic catastrophe, but the former - a radioactive contamination tolerated since 70 years with several accidents in between. In earlier publications of Russian researchers no cancer frequency elevation was reported after exposures below 0.5 Sv or generally in the populations exposed to low doses. Later on, the same scientists started to claim similar relative risks for cancer and other diseases among exposed people in the Urals and in atomic bomb survivors from Hiroshima and Nagasaki. Apparently, an unofficial directive has been behind this ideological shift noticed around the year 2005. Trimming of statistics has been not unusual in the former Soviet Union. Potential motives included fostering radiophobia, stirring anti-nuclear protests in other countries and strangulation of nuclear energy aimed at the boosting of fossil fuel prices. Recent publications claiming cardiovascular risks after low-dose low-rate exposures and recommending more stringent standards of radiological protection are discussed here in some detail. Such recommendations for dose rates compatible with the natural radiation background are obviously nonsensical.

This article presents a systematic mapping study dedicated to conduct a literature review on machine learning and IoT applied in the identification of diseases through heart sounds. This research was conducted between January 2010 and July 2021, considering IEEE Xplore, PubMed Central, ACM Digital Library, JMIR- Journal of Medical Internet Research, Springer Library, and Science Direct. The initial search resulted in 4,372 papers, and after applying the inclusion and exclusion criteria, 58 papers were selected for full reading to answer the research questions. The main results are: of the 58 articles selected, 46 (79.31%) mention heart rate observation methods with wearable sensors and digital stethoscopes, and 34 (58.62%) mention care with machine learning algorithms. The analysis of the studies based on the bibliometric network generated by the VOSviewer showed in 13 studies (22.41%) a trend related to the use of intelligent services in the prediction of diagnoses related to cardiovascular disorders.

This article discusses the application of thermal quality control methods for plant tissues. The purpose of the work is to determine the optimal parameters of thermal impact on a spherical-shaped plant control object, ensuring the detection of surface and subsurface defects. The authors of the work proposed mathematical models of the temperature field for a spherical body with defects and a flat sample when exposed to the thermal influence of a pulsed source. As a result of the use of mathematical models, the thermophysical characteristics of plant tissues of varying degrees of disease damage were obtained, which made it possible to simulate the temperature field of the control object and obtain an image of classified tissues. The developed recommendations made it possible to select the optimal parameters of the thermal effect on the test object.

Given the remarkable progress in global health and overall quality of life, the significant rise in life expectancy has become intertwined with the surging occurrence of neurodegenerative disorders (ND). This emerging trend is poised to pose a substantial challenge to the fields of medicine and public health in the years ahead. In this context, Alzheimer's disease (AD) is regarded as a ND that causes recent memory loss, motor impairment and cognitive deficits. AD is the most common cause of dementia in the elderly and its development is linked to multifactorial interac-tions between the environment, genetics, aging and lifestyle. The pathological hallmarks in AD are the accumulation of beta amyloid (A) peptide, the hyperphosphorylation of tau protein, neuro-toxic events and impaired glucose metabolism. Due to pharmacological limitations and in view of the prevailing glycemic hypometabolism, the ketogenic diet (KD) emerges as a promising non-pharmacological possibility for managing AD, an approach that has already demonstrated efficacy in addressing other disorders, notably epilepsy. KD consists of a food regimen in which carbohydrate intake is discouraged at the expense of increased lipid consumption, inducing met-abolic ketosis, whereby the main source of energy becomes ketone bodies, instead of glucose. Thus, under these dietary conditions, neuronal death through lack of energy would be decreased, inasmuch as the metabolism of lipids is not impaired in AD. In this way, the clinical picture of patients with AD would potentially improve, through the slowing down of symptoms and delaying the progression of the disease. Hence, this review aims to explore the rationale behind utilizing the KD in AD treatment while emphasizing the metabolic interplay between KD and the improvement of AD indicators, drawing insights from both pre-clinical and clinical investigations.

There is a need for a modified Global Physical Activity Questionnaire (GPAQ) to estimate physical activity levels more accurately in populations. We aimed to develop a modified GPAQ and examine its construct validity among adults in Kerala state, India. We incorporated locality-specific, metabolic equivalent task (MET)-based activities into the original GPAQ and administered this modified GPAQ among randomly selected 451 individuals (age ≥20 years) residing in the Trivandrum district of Kerala. Construct validity was assessed using Generalized Linear Models by examining the association of total moderate-to-vigorous physical activity (MVPA) MET-minutes per week estimated by the modified GPAQ with clinical measures. The mean age of participants was 45.4 (SD: 14.1) years and 52.6% were female. Increasing total MVPA MET-minutes per week was associated with decreasing weight (β=-0.011 kg, 95% CI: -0.020, -0.002), waist circumference (β=-0.013 cm, 95% CI: -0.023, -0.004), and systolic blood pressure (β=-0.009 mmHg, 95% CI: -0.015, -0.002), independent of age, sex, education, occupation, current smoking, current alcohol use, and fruit and vegetable intake. The validity coefficients and associations between total MVPA MET-minutes per week and theoretical constructs of physical activity were in agreement with those predicted, providing evidence of construct validity for the modified GPAQ.

The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally for the first time in order to integrate neurodegeneration within the energetics of the cancer acid-base conceptual frame. At all levels of study, molecular, biochemical, metabolic and clinical, the intimate nature of both processes appears to be opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranged original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) becomes an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Also within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth.

Cardiovascular diseases (CVD´s) continue as the primary cause of death worldwide. During the past couple of years, and with the surge of the COVID-19 pandemic, deaths linked to CVD´s were -slightly overshadowed by those deaths related to COVID-19, albeit during the highest peaks of the pandemic. The present study derived form understanding the correlation between both diseases, from the standpoint of patients already diagnosed with CVD´s (n = 41883) and what comorbidities had the highest influence on overall patient death (n = 3637). Obesity, hypertension, and diabetes are all linked to worsening the outcome of COVID-19 positive patients, hence they were considered when looking at the overview of all CVD positive patients. Our finding showed that 1697 deaths were related to diabetes (p < 0.001), 987 deaths were related to obesity (p < 0.001), and lastly 2499 deaths were attributed to hypertension (p < 0.001) individually. Using logistic regression modeling, we found diabetes (OR: 1.744, p < 0.001) and hypertension (OR: 2.179, p < 0.001) had a high impact on patient deaths. Hence, having a CVD diagnosis, with hypertension and/or diabetes seems to increase the likely-hood of complication leading to death in COVID-19 positive patients.

Endothelial cells are the crucial inner lining of blood vessels, pivotal in vascular homeostasis and integrity. However, these cells are perpetually subjected to a myriad of mechanical, chemical, and biological stresses that can compromise their plasma membranes. A sophisticated repair system involving key molecules, such as calcium, annexins, dysferlin, and MG53, is essential for maintaining endothelial viability. These components orchestrate complex mechanisms, including exocytosis and endocytosis, to repair membrane disruptions. Dysfunctions in this repair machinery, often exacerbated by aging, are linked to endothelial cell death, subsequently contributing to the onset of atherosclerosis and the progression of cardiovascular diseases (CVD) and stroke, major causes of mortality in the United States. Thus, identifying the core machinery for endothelial cell membrane repair is critically important for understanding the pathogenesis of CVD and stroke and developing novel therapeutic strategies for combating CVD and stroke. This review summarizes the recent advances in understanding the mechanisms of endothelial cell membrane repair. The future directions of this research area are also highlighted.

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spirals down to immune cell activation and chronic state of low‐level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback-loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

Background. A strong association between Activities of Daily Living (ADL)/Instrumental Activities of Daily Living (IADL) disability, chronic disease, and depressive symptoms among different racial/ethnic groups of older adults has been well established. However, whether this relationship remains true among refugee populations such as Vietnamese in the United States has not yet been investigated. Methods. Using linear regressions, we tested the relationships between ADL/IADL disability, common chronic diseases, and depressive symptoms among 208 Vietnamese-origin older adults from the two convenience samples in 2017 and 2018 (≥65 years) from the Vietnamese Aging and Care Survey (VACS) in the Houston, Texas area. Results. Study participants (N=208) were 56.2% female of average 75.4 years old with low education and low socioeconomic status. Most self-rated their health as fair/poor (80%). Regression analyses showed significant associations between liver disease and total ADL/IADL difficulties with higher depressive symptoms. Conclusions. Older Vietnamese with more ADL/IADL disability and liver disease reported higher depressive symptoms. Complications from chronic conditions and pain might limit activities and impact older Vietnamese psychologically. Healthcare professionals can connect older Vietnamese with culturally and linguistically relevant adult daycare centers to provide them with social and exercise opportunities.

The multitarget therapeutic strategy, as opposed to the more traditional ‘one disease-one tar-get-one drug’, may hold promise in treating multifactorial neurodegenerative syndromes, such as Alzheimer’s disease (AD) and related dementias. Recently, combining a photopharmacology approach with the multitarget-directed ligand (MTDL) design strategy, we disclosed a novel donepezil-like compound, namely 2-(4-((diethylamino)methyl)benzylidene)-5-methoxy- 2,3-dihydro-1H-inden-1-one (1a), which in the E diastereomeric form (and about tenfold less in the UV-B photo-induced isomer Z) showed the best activity as dual inhibitor of the AD-related targets acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). Herein, we investigated further photoisomerizable 2-benzylideneindan-1-one analogs 1b-h with the unconjugated tertiary amino moiety bearing alkyls of different bulkiness and lipophilicity. For each compound the thermal stable E diastereoisomer, along with the E/Z mixture as produced by UV-B light irradia-tion in the photostationary state (PSS, 75% Z), was investigated for the inhibition of human ChEs and MAOs. The pure E-diastereoisomer of the N-benzyl(ethyl)amino analog 1h achieved low nanomolar AChE and high nanomolar MAO-B inhibition potencies (IC50s 39 and 355 nM, re-spectively), whereas photoisomerization to the Z isomer (75% Z in the PSS mixture) resulted in a decrease (about 30%) of AChE inhibitory potency, and not in the MAO-B one. Molecular docking studies were performed to rationalize the different E/Z diastereoselectivity of 1h toward the two target enzymes.

China is not only short of fresh water resources per capita, but also faces a serious problem of water pollution in recent years, with 190 million people suffering from excessive levels of harmful substances in their drinking water. Such as arsenic poisoning and fluorosis and other endemic water diseases high incidence. As a series of water pollution prevention plan of action by the Chinese government announced that, this paper uses the modified Undesirable Dynamic Network model empirical analysis of China's 31 provincial administrative region economic growth, wastewater treatment, and water disease control efficiency between 2013 and 2017. The results show that the efficiency of water pollution disease in all four regions of China and the total efficiency in the three regions of east, west and central China all show a decreasing trend, and the efficiency scores and rankings of all provinces and cities within the region fluctuate greatly. The eastern region with the most developed economy has the best overall performance, with higher efficiency in Water consumption and Water disease control. However, the efficiency of wastewater treatment in northeast China is stable and better. Given the high level of economic development in China and the results of the above mentioned efficiency in water pollution and water diseases, improving the efficiency and quality of wastewater treatment in China is regarded as an important factor in achieving the strategic goal of green growth.

Although significant efforts have been made to combat the spread of vector-borne diseases (VBDs), they still account for more than 17% of all infectious diseases. According to the World Health Organization (WHO), there were 216 million estimated cases in 2016, which is a 9.3% decrease from the estimated cases reported one decade earlier. It is known that the built environment, through features such as openings, can propagate the spread of malaria. There have been some significant efforts directed at addressing this risk. This notwithstanding, there are some knowledge gaps that have resulted in a missed opportunity for synergistically tackling the problem of vectors through leveraging design decisions made by built environment professionals. This work assesses the extent to which design decisions in the built environment can have a positive impact on the efforts directed at mitigating the risk of malaria based on selected cases from East Africa. Secondary data derived from relevant urban health journals as well as repositories curated by leading health agencies such as WHO were synthesized and analyzed using a web of causation approach. The outcome of the analysis is a schema of primary and secondary source (risk) factors. The use of the web of causation approach revealed the existing factor-to-factor interactions that could have a reinforcing effect. This information was used to identify the critical linkages and interdependencies across different factors. The outcome of the analysis was mapped against risk factors that can be linked to decisions made during the six primary phases of the construction life cycle: preliminary phase, conceptual design, detailed design, construction, facilities management, and end of life/disuse. The findings of the research have established that 1) there is, in fact, a built environment–related opportunity that can be leveraged to advance the impact of malaria mitigation effort; 2) cross-disciplinary synergies are critical to managing the interdependencies and complexity of malaria risk factors that have a reinforcing effect; and 3) a knowledge-management framework that serves as a decision support tool would be valuable for sharing data under a push-and-pull mechanism, in which data shared in real time can address the timeliness of mitigating the spread of malaria at the earliest stages for the greatest impact. Based on the findings, a conceptual architecture for a decision support framework has been proposed. This will be developed into a knowledge-management platform in subsequent efforts.

Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date Alzheimer's and Parkinson's disease are the most common NDs. The risk of developing NDs increases dra-matically with age, and genetic and environmental factors can be crucial in their progression. The main feature of NDs is the abnormal presence of specific proteins that can lead to neuronal death, proteotoxic stress, and alteration of catabolic systems, which are major players in the processes of neurodegeneration and neuroinflammation. Despite research efforts to date, the therapies cur-rently in use for the treatment of NDs provide marginal therapeutic benefit, so the focus is now being direct toward the search of natural products that could be a valuable aid in combating these diseases, including the natural compound Andrographis paniculata (Ap) and especially its main constituent Andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap is capable to modulate neuroinflammatory and neurodegenerative responses, determining a reduction in inflammatory markers and oxidative stress in various NDs. Therefore, in this review we will focus on the molecular mechanisms through which Ap and Andro are able to modulate the processes of neurodegeneration and neuroinflammation that are major causes of neuronal death and cognitive decline.

Obesity is related to the establishment of chronic inflammation and metabolic diseases, but it can be positively influenced by the regular practice of physical activity. The study aimed to compare the anthropometric, metabolic, and inflammatory parameters of physically active Military Police Officers (MPOs) with those who are less physically active. Sixty male MPOs, low activity (n=28) and physically active (n=32) participated. The following parameters were measured: plasma cytokine levels, C-reactive protein (CRP) levels, circulating glucose triglyceride (TAG) and high-density lipoprotein cholesterol (HDL-C) levels, and plasma glutamic oxalacetate transaminase (GOT), glutamic-pyruvate transaminase (GPT), and gamma-glutamyl transferase (GGT) activities. The physically active group presented lower body fat and reduced TAG and IL-8 levels compared to the low activity group. Moreover, a negative correlation between SPE and SBP, DBP, BPM was detected for the physically active group (p<0.05) but not in the low activity group. Furthermore, the physically active group's work time (WT) values were not correlated with the important metabolic markers SBP, DBP, BPM, GLU, TAG (p>0.05) but could be in the low activity group (p<0.05). These findings highlight the fundamental protective role of physical activity in controlling body composition, subclinical inflammation, and cardiovascular risk in MPOs.

The importance of diet and the gut-brain axis for brain health and cognitive function is increasingly acknowledged. Dietary interventions are tested for their potential to prevent and/or treat brain disorders. Intermittent fasting (IF), the abstinence or strong limitation of calories for 12 to 48 hours, alternated with periods of regular food intake, has shown promising results on neurobiological health in animal models. In this review article, we discuss the potential benefits of IF on cognitive function and the possible effects on the prevention and progress of brain-related disorders in animals and humans. We do so by summarizing the effects of IF which - through metabolic, cellular and circadian mechanisms - lead to anatomical and functional changes in the brain. Our review shows that there is no clear evidence of a positive short-term effect of IF on cognition in healthy subjects. Clinical studies show benefits of IF for epilepsy, Alzheimer’s disease and multiple sclerosis on disease symptoms and progress. Findings from animal studies show mechanisms by which Parkinson’s disease, ischaemic stroke, autism spectrum disorder and mood- and anxiety disorders could benefit from IF. Future research should disentangle whether positive effects of IF hold true regardless of age or the presence of obesity. Also, variations in fasting patterns, total caloric intake and intake of specific nutrients may be relevant components of IF success. Longitudinal studies and Randomized Clinical Trials (RCTs) will provide a window into the long-term effects of IF on the development and progress of brain-related diseases.

Objective: To explore sex differences in cardiovascular disease (CVD) related risk factors such as diabetes, hypertension, and demographic, anthropometric, biochemical, clinical, and nutritional differences among 40-60 years old Pakistani CVD patients.Design: This was a cross-sectional, descriptive study.Setting: The present study was conducted at the Mayo/King Edward Medical University (K.E.M.U) Hospital Cardiology Department (CCU-I & CCU-II), Lahore, from February 2020 to June 2020. A self-administered questionnaire was used for data collection.Participants: A random sample of 300 cardiac patients was included in the study. Patient records, food frequency questionnaire and 24-hour dietary recall was used to solicit information about demographic, anthropometric, biochemical, and clinical measurements; dietary intake parameters; and CVD risk factors such as hypercholesterolemia, hypertension, diabetes, and smoking. Results: Men CVD patients had higher BMI (33.43 kg/m² vs. 28.69 kg/m²) and higher prevalence of hypertension (81.1% vs. 59%), hypercholesterolemia (82.4% vs. 54.5%) and smoked more cigarettes (72.6% vs. 9%) as compared to women while there was higher prevalence of diabetes among women as compared to men (59% vs. 29.4%). There were 85% women vs. 80% men consuming white bread, while half of the men reported using meat daily, as compared to only 16.6% women. There were 51.5% women and 17% men who reported consuming fruits and vegetables daily. There were 40% men and 16% women who reported consuming soft drinks. Conclusion: The study showed significant sex differences in the nutritional status and risk factors of patients with CVD.

Patients with sAID are a population at high risk of severe COVID outcomes but evidence on the efficacy of SARS-CoV-2 vaccination in this group of patients is scarce. To investigate the efficacy of SARS-CoV-2 vaccination in patients with systemic autoinflammatory diseases (sAID) receiving interleukin-1 inhibition is important. Vaccination responses from 100 sAID patients most of whom were treated with IL-1inhibitors (N=96) and 100 healthy controls (HC) were ana-lyzed. After 2nd SARS-CoV-2 vaccination, sAID patients showed similar anti-SARS-CoV-2 anti-body responses (mean (SD): 6.7 (2.7)) compared to HC (5.7 (2.4)) as well as similar neutralizing antibodies (85.1 ±22.9% vs. 82.5 ±19.7%). Anti-SARS-CoV-2 antibody responses and neutralizing antibodies were similar in sAID patients after SARS-CoV-2 infection and double vaccination. Furthermore, while antibodies increased after 1st and 2nd vaccination in sAID patients they did not further increase after 3rd and 4th vaccination. No difference was found in antibody responses between anakinra and anti-IL-1 antibody treatments and also the additional use of colchicine or other drugs did not impair vaccination responses. Primary and booster SARS-CoV-2 vaccination lead to protective antibody responses in sAID patients, which are at the same level of vaccination responses in HC and in sAID patients after SARS-CoV-2 infection. Immunomodulatory treatments used in sAID do not seem to affect antibody responses to the SARS-CoV-2 vaccine.

Myeloperoxidase (MPO) belong to the family of heme containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kD) is the product of MPO gene located on long arm of chromosome 17. The primary gene product undergoes several modifications like removal of introns and signal peptide and leads to the formation of enzymatically inactive glycosylated apoproMPO which complexes with chaperons, producing active proMPO by the insertion of heme moiety. The active enzyme is a homodimer of heavy and light chain protomers. This enzyme is released into extracellular fluid after oxidative stress and different inflammatory responses. MPO is the only type of peroxidase using H2O2 to oxidize several halides and pseudohalides to form different hypohalous acids. So the antibacterial activities of MPO involve the production of reactive oxygen and reactive nitrogen species. Controlled MPO release at the site of infection is of prime importance for its efficient activities. Any uncontrolled degranulation exaggerates the inflammation that can also lead to tissue damage even in absence of inflammation. Several types of tissue injuries and pathogenesis of several other major chronic diseases like rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes and cancer have been reported to be linked with myeloperoxidase derived oxidants. So the enhanced level of MPO activity is one of the best diagnostic tool of inflammatory and oxidative stress biomarkers among these commonly occurring diseases.

Aging is a major risk factor for the higher incidence and prevalence of chronic conditions, such as cancer, cardiovascular and metabolic diseases, and neurodegenerative diseases. Closely linked with the onset of all these age-related diseases is immunosenescence, a condition defined as progressive reconfiguration of the immune functions leading to an increased susceptibility to infectious diseases, poorer response to vaccination, increased prevalence of cancer, rheumatoid arthritis, and other chronic diseases characterized by a pro-inflammatory state named inflammaging. Given that immunosenescence frames age-related diseases, it is natural to ask how these illnesses are related under the context of innate and adaptative components of the immune system. Knowledge processing by Formal Concept Analysis (FCA) of age-related diseases framed in an immunosenescence multivalued context shows that a hierarchy among these diseases emerges with a subconcept-superconcept nested structure, with two clusters, first made of metabolic diseases, cancer, and cardiovascular diseases. Second metabolic and neurodegenerative diseases and rheumatoid arthritis. Metabolic diseases seem to be a pivot illness and they must be a primary target given their global incidence and prevalence and their cost-effective treatments like regular physical activity, weight loss, healthy diet, stopping smoking, and reducing or managing stress. Another implication of the ontological analysis of age-related diseases is about the nature of immunosenescence, suggesting that initial symptoms of age-related diseases are mainly related to innate immune mechanisms, and developing of severe symptoms of age-related diseases like cancer, cardiovascular or neurodegenerative diseases depends on the activation of acquired immunity processes.

Ulcerative colitis has a significant impact on the quality of life for the patients, and can substantially increase the risk of colon cancer in patients suffering long-term. Conventional treatments provide only modest relief paired with a high risk of side effects, while complementary and alternative medicines can offer safe and effective options. Over the past decade, we have shown that American ginseng has anti-oxidant and anti-inflammatory properties that can suppress mouse colitis and prevent colitis associated colon cancer. With the goal of isolating a single active compound, we further fractionated the hexane fraction, and found the most abundant molecule in this fraction was the polyacetylene, Panaxynol. After isolating and characterizing Panaxynol, we tested the efficacy of Panaxynol in the treatment and prevention of colitis in mice and studied the mechanism of action. We demonstrate here that Panaxynol effectively treats colitis in a Dextran Sulfate Sodium mouse model by targeting macrophages for DNA damage and apoptosis. Positive outcomes from this study could take American ginseng one-step further towards becoming a conventional drug for the treatment of colitis, and possibility exploring other autoimmune diseases associated with macrophage dysfunction.

Antibiotic therapy is a cornerstone of modern medicine, yet the development of antibiotic re-sistance threatens to render these therapies ineffective. The gut microbiota, a complex ecosystem of microorganisms residing in the gastrointestinal tract, plays a critical role in modulating anti-biotic efficacy and resistance. This review delves into the intricate relationship between gut mi-crobiota, antibiotic therapy, and resistance, and discusses the potential applications of gut mi-crobiota research in guiding personalized antibiotic therapy and resistance mitigation strategies. Recent advancements in metagenomics, metatranscriptomics, and metabolomics have demon-strated the potential for tailored antibiotic regimens that minimize collateral damage to com-mensal bacteria and reduce the risk of resistance. Adjuvant therapies such as probiotics, prebi-otics, and synbiotics have shown promise in restoring gut microbial balance and mitigating the adverse effects of antibiotic therapy. We address the challenges associated with this emerging field including the need for standardized methodologies, ethical considerations, and interdisci-plinary collaboration. With continued interdisciplinary collaboration and the implementation of standardized methodologies, gut microbiota research can contribute to the global fight against antibiotic resistance and improve patient outcomes.

Annually, millions of people worldwide are affected by skin diseases, and current therapeutic approaches have limited efficacy. Advances in the treatment of exosomes have led to the development of new therapeutic methods that hold promising potential for improving the treatment options for skin diseases. The aim of this study is to produce pharmaceutical and cosmetic compounds based on exosomes for the treatment of skin conditions such as eczema, pigmentation disorders, skin sagging and aging, cellular skin regeneration, increased skin moisture, and prevention of skin shedding, among others. This study examines the effects of exosomes derived from plants, humans, medicinal algae, and fungi to treat skin diseases. Spectrophotometric analysis reveals the presence of nucleic acids and proteins in exosome samples, indicating their cargo composition. TEM micrographs demonstrate that the exosome isolation process preserves the integrity of the membrane and the crucial spherical structure for their functionality. DLS analysis confirms that isolated exosomes have a size similar to typical exosome dimensions. MTT assays indicate concentration-dependent cytotoxic effects of exosomes on skin cells, with a calculated IC50 representing a significant decrease in cell viability. Real-time PCR shows higher gene expression levels of collagen I and collagen III, indicating the potential of exosomes to enhance collagen synthesis. Tyrosinase enzyme expression analysis demonstrates the influence of exosome treatments on pathways related to melanin production. The use of exosomes derived from various sources provides a promising platform for developing new drugs in the treatment of skin diseases. Additionally, exosomes can be utilized in the treatment of autoimmune diseases and cancer, transforming them into a hopeful field of research. Plant-derived exosomes are environmentally friendly and can serve as the next generation of drug delivery systems for treating various diseases.

Cardiovascular disease is the number one cause of death in the world and Quoting from WHO, around 31% of deaths in the world are caused by cardiovascular diseases and more than 75% of deaths occur in developing countries. The results of patients with cardiovascular disease produce many medical records that can be used for further patient management. This study aims to develop a method of data mining by grouping patients with cardiovascular disease to determine the level of patient complications in the two clusters. The method applied is principal component analysis (PCA) which aims to reduce the dimensions of the large data available and the techniques of data mining in the form of cluster analysis which implements the K-Medoids algorithm. The results of data reduction with PCA resulted in five new components with a cumulative proportion variance of 0.8311. The five new components are implemented for cluster formation using the K-Medoids algorithm which results in the form of two clusters with a silhouette coefficient of 0.35. Combination of techniques of Data reduction by PCA and the application of the K-Medoids clustering algorithm are new ways for grouping data of patients with cardiovascular disease based on the level of patient complications in each cluster of data generated.

Humanity is currently facing several global problems, such as global warming, air pollution, water pollution, deforestation, desertification and land degradation, which are connected to the consequences of negative human activity. One of the possible and effective institutional tools for environmental protection is the environmental education of the general population. It is a relatively well-known and used environmental protection policy tool that governments of all developed countries have in their instrument mix. This qualitative analysis assigned itself the task of investigating whether the ability of environmental education can be affected by certain neuropsychological diseases in addition to thinking about the psychology of environmental education at large. In order to fulfill this main task, the authors asked themselves the following research questions: 1st - Is pedagogical psychology identical and also applicable in the case of environmental education? And 2nd - What effect do some neuropsychological disorders have on the ability of environmental education? Based on the study, analysis, selection and comparison of current professional scientific works obtained from the research activities of current researches on this topic, it is possible to accept the premise that the psychology of environmental education is basically the same as the general psychology of education and that neuropsychological diseases do indeed affect the ability of environmental education similarly to scholarly education.

The World Health Organization has highlighted the substantial impact of viral hepatitis on individuals, healthcare systems, and economies worldwide. This study's objective is to monitor disease notifications to assess their trend. Data were analyzed from infectious disease notifications detected in the Marche Region (Italy) and entered on the Nuovo Sistema Informativo Sanitario portal between 01/01/2012 and 31/12/2021. In this period there were 399 confirmed reports, of which 47,9% were for hepatitis A, 26,8% for B, 7% for C, 18,3% for E; 67.4% were male and the average age was 43.5 years old. The year with the highest peak was 2017, with 18% of reports, while the year with the lowest number was 2020 followed by 2021, with 3.8% and 4.5% respectively. Effective surveillance systems are key to combating the spread of hepatitis and reducing its impact, although they have been affected by the Sars-CoV-2 pandemic, with many cases remaining undetected.

Bioactive compounds are the food constituents, providing beneficial health effects to functional foods and nutraceuticals. These compounds have antioxidants activity including anti-inflammatory, antifungal, and have additional preventative actions. Since these compounds are important constituents enhancing function of the foods, therefore, these constituents are necessary to be incorporated under the umbrella of functional foods. Functional foods provides health benefits though bioactive compounds, as these compounds target mechanisms that manage, prevent, and/or treat chronic or acute diseases. The bioactive compounds are quite essential for functional foods that are crucial for optimal health, thereby leading to the inclusion of these compounds in the most recent definition of functional foods. Some experts have defined that bioactive compounds are the chemical components that contributes and regulates in biological mechanisms. These bioactive compounds are more accurately defined by Dr. Martirosyan and Pisarski as the “primary and secondary metabolites of nutritive and non-nutritive natural components generating health benefits by preventing or managing chronic disease or its symptoms”. These compounds have potential antioxidant and anti-inflammatory activity, which provide benefits to health. Although they are a small proportion of a food source, these compounds can also trigger the mechanisms that will alter and can improve human health. Certain bioactive compounds present in foods are extremely beneficial, but if consumed in excess, they can cause toxicity. Therefore, each bioactive compound must be fully evaluated in order to establish a beneficial and a toxic threshold amount.

Emerging infectious disease threats require rapid response tools to inform diagnostics, treatment, and outbreak control. RNA-based metagenomics offers this; however, most approaches are time-consuming and laborious. Here, we present a simple and fast protocol – the RAPIDprep assay – with the aim to provide cause agnostic laboratory diagnosis of infection within 24 hours of sample collection by sequencing ribosomal RNA-depleted total RNA. The method is based on the synthesis and amplification of double-stranded cDNA followed by short-read sequencing with minimal handling and clean-up steps to improve processing time. The approach was optimized and applied to a range of clinical respiratory samples to demonstrate diagnostic and quantitative performance. Our results showed robust depletion of both human and microbial rRNA, and library amplification across different sample types, qualities and extraction kits using a single protocol without input nucleic acid quantification or quality assessment. Furthermore, we demonstrate the genomic yield of both known and undiagnosed pathogens with complete genomes recovered in most cases to inform molecular epidemiological investigations and vaccine design. The RAPIDprep assay is a simple and effective tool, and representative of an important shift towards integration of modern genomic techniques to infectious disease investigations.

Ethnomedicine refers to the use of medicinal plants by a society, ethnic group or tribe for health benefits and for the prevention, treatment, and cure of different ailments. The healthy relationship between plants and humans has been continuing since the start of human civilization. The present study aims to document the medicinal information about plants used by ethnic people in different wards of Suryabinyak Municipality, Bhaktapur district, to conserve and utilize the traditional knowledge. Ethnomedicinal data were collected by a Rapid Rural Appraisal (RRA) method such as door to door surveys, direct observation. Individual interviews, field visits, and a questionnaire survey with the guidance of key informants. The present study has documented 107 medicinal plant species under 60 families which are used for prevention and treatment of 39 different diseases like Jaundice, diarrhea, dysentery, and cancer and 46 distinct health benefits like cough, cold, anti-bleeding, stomachache, diarrhea, fever, blood pressure, fracture, toothache, etc. Suryabinayak Municipality has a rich diversity in culture, ethnic groups, and medicinal plants, along with a wide geographic and climatic condition. However, with modernization, urbanization, deforestation, and increasing residential areas, the occurrence and use of medicinal plants have been diminished. Thus, documentation of this research is vital for further pharmaceutical research and enhancement and preservation of traditional knowledge of local people living in Suryabinayak Municipality and Nepal.

Healthy houses is a problem on developing countries. This study mainly focus on urban areas and the health effect of poor water and sanitation, floor, inadequate heating, poor food storage and overcrowding. This research has used qualitative method with questionnaires has spread to a hundred and six homes about characteristics of healthy home. The questionnaires have spread to Pondok village and Bukit Kerman village, Kerinci District, Jambi Province, Indonesia. Result showed 90% houses too dense and 10 no dense, 98% houses on this area are unhealthy houses and 10% healthy houses. Unhealthy houses that affected diseases such as 20% diaarhea, 29% other diseases, 13% ARI, 10% malaria 15% skin and 12% no diseases. We recommended to make a public health policy to reducing unhealthy houses on this area.

Interstitial lung diseases (ILDs) constitute a group of more than 200 disorders, being idiopathic pulmonary fibrosis (IPF) one of the most frequent. Telomere length (TL) shortening causes loss of function of the lung parenchyma. However, little is known about its role as prognostic factor in ILD patients. With the aim of investigating the role of TL and telomerase activity in the prognosis of patients affected by ILDs, we analysed lung tissue samples from 61 patients. We measured relative TL and telomerase activity by conventional procedures. Both clinical and molecular parameters were associated with overall survival by the Kaplan-Meier method. Patients with IPF had poorer prognosis than patients with other ILDs (p = 0.034). When patients were classified according to TL, those with shortened telomeres reported lower overall survival (p = 0.085); differences reached statistical significance after excluding ILD patients who developed cancer (p = 0.021). In a Cox regression analysis, TL behaved as a risk-modifying variable for death associated with rheumatological disorders (RD) co-occurrence (p = 0.029). Also, in patients without cancer, ferritin was significantly increased in cases with RD and IPF co-occurrence (p = 0.032). In relation to telomerase activity, no significant differences were detected. In conclusion, TL in lung tissue emerges as a prognostic factor in ILD patients, Specifically, in cases with RD and IPF co-occurrence, TL can be considered as a risk-modifying variable for death.

Systemic sclerosis (also known as scleroderma) is a chronic fibrosing autoimmune disease with both skin and multisystem organ involvement. Scleroderma has the highest mortality among all rheumatic diseases. The pathophysiology mechanism of systemic sclerosis is a progressive self-amplifying process, which implicates the widespread microvascular damage, followed by a dysregulation of innate and adaptive immunity and inflammation, and diffuse fibrosis of the skin and visceral organs. Fibrosis of internal organs is a hint for systemic sclerosis, moreover associated with interstitial lung disease (SSc-ILD) is a complex process. We report a case of a 56 years old female, diagnosed with Systemic Sclerosis 16 years ago. The systemic and clinical manifestations, respiratory functional tests, radiological aspects and specific therapy were discussed.

In this study, we report the antibacterial mechanisms of action of uniform silver nanoparticles (AgNPs) and decorated activated carbon nanocomposite (CAC-AgNPs) obtained using a green synthesis approach. The nanomaterials were characterized by ultraviolet-visible (UV-vis) absorption spectra and Fourier transform infrared (FTIR) spectra. The antibacterial activity of the as-prepared nanomaterials was evaluated against an array of bacterial strains by microdilution method, whereas their cytotoxicity profile was evaluated on Vero cells (human mammalian cells). The antibacterial mechanistic studies of active nanomaterials were carried out through bacterial growth kinetics, nucleic acid leakage test, and catalase inhibition assay. A silver nanocomposite was successfully fabricated from Croton macrostachyus-based activated carbon. The as-prepared nanomaterials exhibited antibacterial activity against an array of bacterial strains (minimum inhibitory concentration (MIC) range: 62.5 to 500 µg/mL), the most susceptible being Escherichia coli and Staphylococcus aureus. Cytotoxicity studies of the nanomaterials on Vero cells revealed that the nanocomposite (median cytotoxic concentration (CC50): 213.6 µg/mL) was less toxic than the nanoparticles (CC50 value: 164.75 µg/mL) counterpart. Antibacterial mechanistic studies unveiled that the nanomaterials induced (i) bacteriostatic activity vis-à-vis E. coli and S. aureus and (ii) inhibition of catalase in these bacteria. This novel contribution on the antibacterial mechanisms of action of silver nanocomposite from C. macrostachyus-based activated carbon might contribute to the understanding of antibacterial action of these biomaterials. Nevertheless, more chemistry and in vivo experiments, as well as in depth antibacterial mechanistic studies are warranted for the successful utilization of these antibacterial biomaterials.

We report the first correction by Prime editing of a mutation in the RYR1 gene, paving the way to gene therapies for RYR1-related myopathies. The RYR1 gene codes for a calcium channel named Ryanodine receptor 1, which is expressed in skeletal muscle fibers. The failure of this channel causes muscle weakness in patients, which degenerates into motor disabilities. Currently, there are no effective treatments for these diseases, which are mainly caused by point mutations. Prime editing allows the modification of precise nucleotides in the DNA. Our results showed a 59% correction rate of the T4709M mutation in the RYR1 gene in human myoblasts by RNA delivery of the Prime editing components. It is to be noted that the T4709M is recessive, and thus, persons having a heterozygous mutation are healthy. These results are the first demonstration that it is possible to correct mutations in the RYR1 gene.

Since their discovery in 1993, numerous microRNAs (miRNAs) have been identified in humans and other eukaryotic organisms, and their role as key regulators of gene expression is still being elucidated. It is now known that miRNAs not only play a central role in the processes that ensure normal development and physiology, but they are often dysregulated in various diseases. In this review, we present an overview of the role of miRNAs in normal renal development and physiology, in maladaptive renal repair after injury, and in the pathogenesis of renal parenchymal diseases. In addition, we describe methods used for their detection and their potential as therapeutic targets. Continued research on renal miRNAs will undoubtedly improve our understanding of diseases affecting the kidneys and may also lead to new therapeutic agents.

Deforestation and associated changing landscapes are major components of environmental changes, with important implications for ecosystem functioning and biodiversity conservation. Tropical forests are hot spots of biodiversity and provide multiple goods and ecosystem services which benefit people in many ways Forest also play an important role in health-related legends, myths, and fairy tales from all over the world, and are important sources of new potential emerging microbial threats to human. Although plausibly numerous abundant microbial forms with a forest origin may exist, our systematic literature review shows that forest-derived infection studies are relatively unexplored, and both taxonomically and geographically biased. Since biodiversity has been associated with emergence of novel infectious diseases at macro-scale, we describe the main biogeographical patterns in the emerging infection-biodiversity-forest loss nexus. Then, we illustrate four fine-scale case studies to decipher the underlying processes of increased infection risk in changing forest clearing landscapes. Finally, we identify scientific challenges and regional management measures required to mitigate these important new emerging threats.

Obesity is one of the factors leading to the development of atherosclerosis. This metabolic disorder is associated with an increased production of reactive oxygen species, which affect the oxidative stress level. The aim of this study was to evaluate oxidative/antioxidative status and to investigate the correlation between redox markers and anthropometric parameters and body composition in adult patients after myocardial infarction and in individuals without a cardiovascular event in the past. Descriptive data on socio-demographic, clinical, and anthropometric features and blood samples were collected and categorized into two equal groups: after myocardial infarction (study group (SG), n = 80) and without a cardiovascular event (control group (CG), n = 80). The oxidative/antioxidative status was assessed in plasma on the basis of total oxidative/capacitive status (PerOx), total antioxidative status/capacity (ImAnOx), and oxidized low-density lipoprotein (oxLDL). OxLDL was significantly higher in the CG group compared to the SG group (p = 0.02). No significant differences were found with regard to PerOx and ImAnOx values between the studied groups. Significant positive correlation between PerOx and percentage of adipose tissue (FM [%]) and body adiposity index (BAI) was found in the two studied groups. ImAnOx significantly positively correlated with VAI in SG and FM% in CG. OxLDL negatively correlated with body mass index and waist to hip circumference ratio in CG. The total oxidative/antioxidative status is related to the amount of adipose tissue and the BAI of the subjects. It was observed that it correlates more frequently with the visceral distribution of body fat.

Background: We aimed to assess the association between DII and PD and the mediation effect of DII in the association of PD with systemic inflammation. Using the National Health and Nutrition Examination Survey (NHANES) 2009-2010, 2011-2012 and 2013-2014, participants that received periodontal exam and provided dietary recall data were included. The inflammatory potential of diet was calculated via DII. Periodontitis was defined according to the 2012 case definition. The clinical outcomes of interest were mean periodontal probing (PPD), mean clinical attachment loss (CAL) and thresholds of PPD and CAL. White blood cells (WBC), segmented neutrophils and C-reactive protein (CRP) were used as proxies for systemic inflammation. The periodontal measures were regressed across DII values using adjusted multivariate linear regression. Adjusted mediation analysis appraised the influence of DII in the association of periodontitis and systemic inflammation. 10,178 participants were included. DII was significantly correlated with mean PPD, mean CAL, thresholds of PPD and CAL, WBC, segmented neutrophils and DII (p&lt;0.01). A linear regression logistic adjusted for multiple confounding variables confirmed the association between DII and mean PPD (B = 0.02, Standard Error [SE]: 0.02, p&lt;0.001) and CAL (B = -0.02, SE: 0.01, p&lt;0.001). The association of mean PPD and mean CAL with both white blood cells and segmented neutrophils were mediated by DII (from 2.1 to 3.5%, p&lt;0.001). In the 2009-2010 subset, the association of mean CAL with serum CRP was mediated by DII (52.0%, p&lt;0.01). In conclusion, inflammatory diet and PD may be associated. Also, the inflammatory diet significantly mediated the association of leukocyte counts and systemic inflammation with periodontitis.

Asthma is a significant public health concern. This study identified the provinces with the highest morbidity and mortality rates due to asthma among the working-age population (15-69 years) in the Republic of Ecuador. The secondary objective was to explain the possible differences attribut-able to occupational exposure. This nationwide ecological and exploratory study was conducted in 24 provinces between 2016 and 2019. Government databases were used as sources of infor-mation. Standardized rates were calculated for codes the J45 and J46. The hospitalization mor-bidity rate for asthma decreased from 6.51 to 5.76 cases per 100,000 working-age population, and the mortality rate has consistently been low and stable from 0.14 to 0.15 deaths per 100,000 working-age population. Geographic differences between the provinces were evident. The risk of hospitalization and death due to asthma was higher in the Pacific coast (five provinces) and the Andean region (two provinces). The high rates observed in provinces with greater agricultural and industrial development could be the main determinants of national heterogeneity and could act as occupational risk factors. The contribution of occupational hazards in each province should be examined in depth through ad hoc studies. These findings provide valuable information for creating public policies aimed at promoting and safeguarding the respiratory health of the popu-lation, particularly that of workers.

Background: After the outbreak of a novel coronavirus (i.e. SARS COV2) in China and its diffusion around the world, great attentions was reserved to the increased incidence of venous thromboembolism in these patients. A specific antiviral action of heparins toward SARS COV2 has been reported in vitro such as a well know action of heparins to prevent VTE in inpatients with infective disease has already been reported since several years. Yet, because fondaparinux represent the pharmacological antithrombotic active sequence of all heparins and because its clinical indication o prevent VTE in inpatients is similar to heprains, we realized a retrospective analysis in inpatients with SARS COV2 on the incidence of VTE during pharmacological prophylaxis with enoxaparin or fondaparinux. This retrospective analysis was named FONDENOXAVID. Methods: We conducted a retrospective cohort study that used patients with SARS COV2 during the Italian outbreak from February 18, 2020 to April 30, 2020. Our aim was to compare the clinical characteristics, prophylactic treatment and outcomes in inpatients positive to SARS COV2 at risk to develop venous thromboembolism, in particular venous thrombosis with or without pulmonary embolism, during in-hospital primary thromboprophylaxis with enoxaparin (40 mg or 60 mg once daily) or fondaparinux (2.5 mg once daily). Statistical analysis was conducted with using MatLab R2016B and eventually ad hoc functions. Results: There were not significative differences in clinical characteristics between patients that used enoxaparin or fondaparinux as thromboprpophylaxis for SARS COV2. The cumulative incidence of thrombotic events was not different in patients that used enoxaparin or fondaparinux as thromboprpophylaxis. No differences were found also in d-dimer and fibrinogen levels test at the admission and after 3 weeks as markers of prolonged inflammation due to SARS COV2. Discussion: The increased incidence of VTE in vivo has been reported in several studies although prophylaxis with low molecular weight heparin was conducted in some of them. The clinical indication to prevent VTE was similar for heparins and fondaparinux. In our results a non-inferiority to prevent VTE was recorded when inpatients with SARS COV2 were treated with prophylactic doses of enoxaparin or fondaparinux according to international guidelines. The incidence of VTE in this retrospective analysis showed that Fondaparinux at fixed doses of 2.5 mg daily was not inferior to enoxaparin (4000 UI daily). Our results testify that fondaparinux and enoxaparin showed the same efficacy to reduce the incidence of VTE in inpatients with SARS COV2.

Conservation agriculture (CA) could be very effective for agricultural sustainability under Mediterranean environments, where farmers rely on short rotation based on durum wheat. In this work we investigated the effect of different combination of tillage treatments and crop sequence (conventional tillage and wheat monocropping, CT-WW; conventional tillage, and wheat following faba-bean, CT-WF; zero tillage and wheat monocropping, ZT-WW; zero tillage and wheat following faba-bean, ZT-WF) on yield, grain quality traits as well as on diseases incidence and severity in durum wheat (var. Saragolla). The results of a two-years of data of a long-term experiment (7-year experiment; split-plot design) are discussed. The CA approach (ZT+WF), which induced always the highest grain yields (6.1 t ha-1 and 3.3 t ha-1 in 2016 and 2017) thanks to an increased number of spikes m-2 (296 vs 269 and 303 vs 287 spikes m-2 in 2016 and 2017, respectively) as well as to a more pronounced ear length, demonstrated significant positive influences in terms of grain quality. It promoted grain protein accumulation (12.1% for ZT+WF versus 11.4% for ZT+WW and 12.4% for ZT+WF versus 10.6% for ZT+WW in 2016 and 2017), improved gluten quality (in terms of SDS sedimentation test) and colour of the grain. The abundance of crop residues determined a higher incidence and severity of Zymoseptoria tritici leaf symptoms under CA system; nevertheless the late appearance of infection was the main reason of not affecting yield and quality traits. The presence of faba-bean (WF) in the rotation significantly reduced leaf symptoms of Z. tritici.

Background: COVID-19 was initially identified as a respiratory system disorder, but it has been discovered to interact with and influence the cardiovascular system. COVID-19-associated cardiovascular (CV) complications are common, resulting in high acute phase mortality and a large number of morbidities in the chronic phase, thus severely impacting patients' quality of life and health outcomes. Nevertheless, clinical, cellular, and molecular biological factors underlying the pathophysiology of cardiovascular complications associated with COVID-19 are poorly understood. Objective: This review investigates putative underlying clinical factors as well as cellular and molecular biological mechanisms by which COVID-19 leads to acute CV complications, including state-of-the-art genomic sequencing-based findings, assessing the long-term CV consequences of COVID-19, and aiming to shed light on developing strategies for differential diagnosis, risk prognostic stratification, prevention, and clinical management of CV sequlea in COVID-19 patients. Methods: For this purpose, a through review of literature and published data was carried out from first report of COVID-19 till October 2023 to find out a comprehensive account of clinical, cellular and molecular genetic factors underlying COVID-19-associated cardiovascular diseases. Results: We found that the relationship between COVID-19 and CV risk is complex and multifaceted. In addition to acute COVID-19 detertriuos effects, COVID-19 survivors may experience long-term CV effects. We provide a detailed account of the involvement of a large number of genomic alterations, microRNAs, and novel viral as well as host proteins in CVDs associated with COVID-19, which has helped identify some novel drug targets to treat COVID-19-related cardiovascular complications. Conclusions: The relationship between COVID-19 and CV risk is complex and multifaceted. While COVID-19 primarily affects the respiratory system, it can also significantly affect CV health. as compared to classical cardiovascular diseases, there are new clinical, cellular and molecular biological factors in CVDs related to COVID-19, that need specific diagnostic assays, prognostic stratification and treatment modules. Therefore, specail care is must taken to treat cardiovascular diseases associated with COVID-19.

Much evidence reveals an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these, the most important is the Trimethylamine N-Oxide (TMAO), which is responsible through various mechanisms for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with HF, and the possible strategies to influence its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and new therapeutic target of HF.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

Temporomandibular joint disorders (TMD) are characterized by their multifactorial etiology and pathogenesis. A 3-year prospective study was conducted in a Portuguese TMD department to study the prevalence of different TMD signs and symptoms and their association with risk factors and comorbidities. Five hundred ninety-five patients were included using an online database: EUROTMJ. Most patients were female (80.50 %), with a mean age of 38.20±15.73 years. The main complaints were temporomandibular joint (TMJ) clicking (13.26%), pain (12.49%), and masticatory muscle tension (12.15%). The main clinical findings were myalgia (74%), TMJ clicking (60-62%) and arthralgia (31-36%). Risk factors such as clenching (60%) and bruxism (30%) were positively associated with TMJ pain and myalgia. Orthodontic treatment (20%) and wisdom tooth removal (19%) were positively associated with TMJ clicking, while jaw trauma (6%) tracheal intubation (4%) and orthognathic surgery (1%) were positively associated with TMJ crepitus, limited man-dibular range of motion and TMJ pain, respectively. 42.88% of TMD patients had other associated chronic diseases, most of them were mental behavioral or neurodevelopmental disorders (33.76%), namely, anxiety (20%) and depression (13%). The authors also observed a positively association of mental disorders with the degree of TMJ pain and myalgia. Online database seems to be a relevant scientific instrument for healthcare providers who treat TMD. The authors expect that EUROTMJ database can serve as a milestone for other TMD departments.

KV channel-interacting proteins (KChIPs) belong to a family of Ca2+-binding EF-hand proteins that are able to bind to the N-terminus of the KV4 channel α-subunits. As the auxiliary subunit, KChIPs are critically involved in regulating the amplitude and gating properties of KV4 channels by modulating their cell surface trafficking, voltage-dependent activation, inactivation kinetics, and recovery rate from inactivation. IKs, ICa,L, and INa can also be regulated by KChIPs. KChIPs are predominantly expressed in the brain and heart, where they contribute to the maintenance of the excitability of neurons and cardiomyocytes by modulating the KV4 currents. Interestingly, all KChIPs can act as transcription factors to control the expression of genes involved in pain, memory, and circadian regulation. Altered expression of KChIPs has been implicated in the pathogenesis of many diseases, such as arrhythmia, heart failure, Alzheimer's disease, etc. In this review, we summarize the research progress of KChIPs in their structural properties, physiological functions, and pathological roles in disease progression, and provide an overview of the therapeutic potential of KChIPs as pharmacological targets for associated disorders.

Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease, char-acterized by the progressive death of motor neurons, leading to paralysis and death. It is a rare disease distinguished by high patient-to-patient heterogeneity, making its study arduous and complex. Extracellular vesicles (EVs) emerged as an important player in ALS development. Thus, ALS phenotype-expressing cells can spread their abnormal bioactive cargos through the secretion of EVs, even at far distant tissues. Importantly, due to their nature and composition, EVs’ formation and cargo can be exploited for the better comprehension of this elusive disease and identification of novel biomarkers, as well as for potential therapeutic applications, such as those based on stem cell-derived exosomes. This review highlights the recent advances in the identification of the role of EVs in ALS etiopathology and how EVs can be promising new approaches for therapeutic strategies.

In the last years evidence has emerged that neurodegenerative diseases (NDs) are strongly associated with the microbiome composition in the gut. Parkinson’s disease (PD) is the most intensively studied neurodegenerative disease in this context. In this review, we performed a systematic evaluation of published literature comparing changes in colonic microbiome in PD to the ones observed in other NDs including Alzheimer’s Disease (AD), Multiple system atrophy (MSA), Multiple sclerosis (MS), Neuromyelitis optica (NMO) and Amyotrophic lateral sclerosis (ALS). To warrant comparability of different studies, only human case-control studies were included. Several studies showed an increase of Lactobacillus, Bifidobacterium, Verrucomicrobiaceae and Akkermansia in PD. A decrease in PD was observed of Faecalibacterium spp., Coprococcus spp., Blautia spp., Prevotella spp. and Prevotellaceae. On low taxonomic resolution, like phylum level, the changes are not disease specific and inconsistent. However, on higher taxonomic resolution like genus or species level, a minor overlap was observed between PD and MSA, both alpha synucleinopathies. We show that a methodical standardization of sample collection and analysis is necessary for ensuring the reproducibility and comparability of data. We also provide the evidence, that assessing the microbiota composition at high taxonomic resolution, reveals changes in relative abundance, that may be specific or characteristic for one disease, or a disease-group and might evolve discriminative power. The interactions between bacterial species and strains and moreover the co-abundances must be more deeply investigated before assumptions of the effects of specific bacteria on the host can be made with certainty.

Severe combined immunodeficiency (SCID) is a primary inherited immunodeficiency that could be fatal, usually due to opportunistic infections caused by bacteria, viruses, fungi, and protozoa if left untreated. Opportunistic infections are the most common presentation of SCID these include viral, fungal, or intracellular bacteria, and infection should prompt immunological investigation. This review aimed to provide a comprehensive approach to the microrganisms associated with severe combined immunodeficiency (SCID) and its management. The authors described SCID as a syndrome and summarized the different microorganisms that affect children and how they are managed.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to cause 2019-coronavirus disease (COVID-19) pandemic is a zoonotic coronavirus and crosses species to infect human populations, where an efficient transmission of virus occurs human-to-human. Nationwide lockdown is being adopted to stop public transport, keep people at their homes and out of their work, and maintain social distancing. In turn, large geographic areas in the world (including China, Italy, Spain, and USA) has been almost halted. This temporary halt is significantly slashing down the air pollution (air pollutants and warming gases) in most cities across the world. This paper: (i) introduces both COVID-19 and air pollution; (ii) overviews the relation of air pollution with respiratory/lung diseases; (iii) compiles and highlights major data appeared in media and journals reporting lowering of air pollution in major cities those have been highly impacted by the COVID-19; and also (iv) lists the way forward in the present context. Because COVID-19 is an ongoing pandemic and currently far from over, strong conclusions could not be drawn with very limited data at present. The temporary slashed down global air pollution as a result of COVID-19 restrictions are expected to stimulate the researchers, policy makers and governments for the judicious use of resources; thereby minimise the global emissions, and maintain their economies once the pandemic eases. On the other, lifting of the nationwide lockdown and eventual normalisation of the temporarily halted sectors may also reverse the currently COVID-19 pandemic-led significantly slashed down global air pollution that could make the future respiratory health crisis grimmer.

Vaccination is an important method of immunological preventive care required for health management of all animal including fish. More particularly, immunization is important in in-land fisheries for the management of diseases in fish brood stocks and healthy seed production. According to the latest statistics in 2020, 90.3 million tonnes of captured fish production was achieved from the aquaculture sector. Out of the above, 78.8 million tonnes from marine and 11.5 million tonnes from inland waters aquaculture sectors. About 4% decline in fish production was achieved in 2020 than 2018 from inland fisheries sectors. On the other hand, the digestive protein content, healthy fats and nutritional values of fish products are comparitively more affordable as compared to other meat sources. In 2014, about 10% aquatic cultured animals were lost (costing &gt; 10 billion $ global annual loss) due to infectious diseases. Therefore, vaccination in fish especially in brood stocks is one of the most important approaches to stop such losses in the fisheries sector. Fish vaccines consist of either whole killed pathogens, subunit of a protein, a recombinant protein, DNA vaccines or live attenuated vaccines. Challenges existing are adaption of vaccination in fisheries sector, route of administration, use of effective adjuvants and most importantly lack of effective results. Use of autogenous vaccines, vaccination via intramuscular, intraperitoneal or oral routes, and most importantly adding vaccines in feed using top dressing methods or as a constituent in fish feed are now in emerging. These method shall lower the risk of using antibiotics in cultured water which in turn will reduce the environmental contamination.

RNA transcripts play a crucial role as witnesses of gene expression health. Identifying disruptive short sequences in RNA transcription and regulation is essential for potentially treating diseases. Let’s delve into the mathematical intricacies of these sequences. We’ve previously devised a mathematical approach for defining a “healthy” sequence (10.14218/GE.2023.00079). This sequence is characterized by having at most four distinct nucleotides (denoted as nt≤4). It serves as the generator of a group denoted as fp. The desired properties of this sequence are as follows: fp should be close to a free group of rank nt−1, it must be aperiodic, fp should not have isolated singularities within its SL2(C) character variety (specifically within the corresponding Groebner basis). Now, let’s explore the concept of singularities. There are cubic surfaces associated with the character variety of a four-punctured sphere denoted as S24. When we encounter these singularities, we find ourselves dealing with some algebraic solutions of a dynamical second-order differential (and transcendental) equation known as the Painlevé VI equation (10.3390/dynamics4010001). In certain cases, S24 degenerates, in the sense that two punctures collapse, resulting in a “wild” dynamics governed by the Painlevé equations of an index lower than VI. In our paper, we provide examples of these fascinating mathematical structures within the context of miRNAs. Specifically, we find a clear relationship between decorated character varieties of Painlevé equations and the character variety calculated from the seed of oncomirs. These findings should find applications in cancer research.

Cerebral ischemia, which is a leading cause of disability and mortality worldwide, sets off a chain of molecular and cellular pathologies that are associated with some central nervous system (CNS) disorders, mainly including ischemic stroke, Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy and other CNS diseases. In recent times, despite significant advancements in the treatment of the pathological processes underlying various neurological illnesses, effective therapeutic approaches specifically targeted at minimizing the damage of such diseases remain absent. Remarkably, ischemia causes severe damage to cells in Ischemia-associated CNS Diseases. Cerebral ischemia initiates oxygen and glucose deprivation, which subsequently promotes mitochondrial dysfunction, including MPTP opening, mitophagy dysfunction, and excessive mitochondrial fission, triggering various forms of cell death, such as autophagy, apoptosis, as well as ferroptosis. Ferroptosis, a novel type of regulated cell death (RCD), is characterized by iron-dependent accumulation of lethal reactive oxygen species and lipid peroxidation. Mitochondrial dysfunction and ferroptosis both play critical roles in the pathogenic progression of Ischemia-associated CNS Diseases. In recent years, growing evidence has indicated that mitochondrial dysfunction interplays with ferroptosis to aggravate cerebral ischemia injury. However, the potential connections between mitochondrial dysfunction and ferroptosis in Cerebral Ischemia have not yet been clarified. Thus, we analyze the underlying mechanism between mitochondrial dysfunction and ferroptosis in Ischemia-associated CNS Diseases. We also discovered that GSH depletion and GPX4 inactivation cause lipoxygenase activation and calcium influx following cerebral ischemia injury, resulting in MPTP opening and mitochondrial dysfunction. Additionally, dysfunction in mitochondrial electron transport and an imbalanced fusion-to-fission ratio can lead to the accumulation of reactive oxygen species and iron overload, which further contribute to the occurrence of ferroptosis. This creates a vicious cycle that continuously worsens cerebral ischemia injury. In this study, our focus is on exploring the interplay between mitochondrial dysfunction and ferroptosis, which may offer new insights into potential therapeutic approaches for the treatment of Ischemia-associated CNS Diseases.

The suitability of an animal model to study human diseases heavily relies on the similarity between the two species at the genetic, epigenetic, gene expression and metabolic levels. However, consistent data from different animal models at each level to evaluate this suitability is lacking. With the availability of genome sequences for many mammalian species it is now possible to compare animal models based on the genomic similarities. Here, we compare the coding sequences (CDS) of five mammalian models that include rhesus macaque, marmoset, pig, mouse and rat with those from human. We identified 10,316 conserved CDS across the five organisms and human based on the sequence similarity. Mapping the human disease-associated single nucleotide polymorphisms (SNPs) from these conserved CDS in each species has identified species-specific association with various human diseases. While associations for a disease such as colon cancer were prevalent in multiple model species, pig showed the highest number (117 diseases) of model-specific human disease associations. Based on the percentage of disease-associated SNP-containing genes, marmoset models are well suited to study many human ailments including behavioral and gastrointestinal diseases. Comparison of gene expression levels of the conserved CDS from colon, heart, kidney, lung, skeletal muscle, and spleen tissues in these models showed correlations with human expression levels in a tissue-specific manner. In the gastrointestinal tissues (colon, spleen), the pig showed the highest correlation while mouse displayed a better correlation in the heart and kidney. This study demonstrated genomic as well as tissue-specific expression-based similarity evaluation of five animal models against human that could help investigators select a suitable animal model to study their targeted disease.

Parasitic diseases continue represent a threat on a global scale, particularly among the poorest countries in the world. This is particularly because of the absence of vaccines, and in some cases, resistance against available drugs, currently being used for their treatment. In this review emphasis is laid on natural products and scaffolds from African medicinal plants (AMPs) for lead drug discovery and possible further development of drugs for the treatment of parasitic diseases. In the discussion, emphasis has been laid on alkaloids, terpenoids, quinones, flavonoids and narrower compound classes of compounds with micromolar range activities against Schistosoma, Trypanosoma and Leishmania species. Suggestions for future drug development from African medicinal plants have also been provided.

Ticks are one of the most dominant forced ectoparasites of vertebrates, belonging to the arthropods, which transmit pathogens such as bacteria, viruses, and parasites to humans and animals in Iran and worldwide. Given that, sex ratio factors can affect the epidemiology of vector-borne diseases, this study aimed to identify and determine the ticks' sex ratio and host type (camels, sheep, cattle, dogs, chickens, and pigeons) in different areas of Tehran province. This descriptive cross-sectional study took samples from different animal body parts in four seasons from 20 villages in 2019, in which 685 hard ticks and 121 soft ticks were caught from 1623 studied livestock and poultry. Regarding sex segregation among all caught ticks, 42.01% were male, and 57.99% were female. It is noteworthy that in both mountain and plain environments, R. sanguineus species of hard ticks had the most elevated sex ratio. Most ticks were collected from sheep hosts with 60.04% and the lowest from cattle hosts with 0.62% in tick infestation.

Several studies have already demonstrated the relationship between the loss of natural habitats and the incidence of diseases caused by vectors, such as dengue, which is an acute fever disease, considered a serious public health problem. The aim of the present study was to analyze the relationship between land use changes between 2009 and 2019 and the occurrence of dengue fever in 2015 and 2019 by municipality, using the state of Minas Gerais as a case study. For this, secondary data obtained from openly available sources were used. Natural vegetation cover data were obtained from the MAPBiomas platform and dengue occurrence data from the Ministry of Health, in addition to socioeconomic indicators from the Brazilian Institute for Geography and Statistics. Between 2015 and 2019, 1,255,731 cases of dengue were recorded throughout the state of Minas Gerais, ranging from 0 to 227 per thousand inhabitants between municipalities. The occurrence of dengue was distributed throughout all regions of Minas Gerais, affected by climatic and socioeconomic aspects. In general, municipalities with net loss of natural vegetation, predominantly located in the Cerrado biome, had the highest number of dengue cases in the studied period. Despite the significant positive relationship between these two variables, three of the eight socioeconomic parameters analyzed also affected the occurrence of dengue: population density, human development index (both positively) and Gini inequality index (negatively). These results indicate that, contrary to expectations, municipalities with better social conditions had more dengue cases. Our study indicates that natural vegetation is, directly or indirectly, involved in the ecosystem service of dengue control, despite the occurrence of this disease being affected by multiple factors that interact in a complex way. Thus, policies towards reducing deforestation must be complemented by a continuous investment in public health policies and reduction of social inequalities to efficiently control dengue fever.

Background: Particulate matter and urban air pollution affect the human body and can lead to death. Epidemiological studies should consider the exposure to pollutants and the diverse responses of individuals depending on their sensitivity to the pollutants. Methods: In this study, air pollution measurements were obtained hourly at measuring stations operated by the national and local governments to increase the reliability of the measured values. A β-ray absorption method was used to analyze the measurements of fine dust and determine the particulate matter content. Results: The air pollution data were log-converted to enable the comparison of data from different time periods. The comparison was made, focusing on the period of Seoul's fine dust policy. As a result, the cancer incidence rate also decreased after the policy. The data on individual characteristics were obtained from a survey of Seoul citizens conducted from 2015 to 2016 and using indicators such as the quality of life and social trust of Seoul citizens. Concludions: The survey on the living environment and residence indicated that 80% of the heads of households were men. Women had a greater dissatisfaction than men with the residential, economic, and social environments. The survey questions on well-being were related to the internal and external environment such as air pollution, noise, and fine dust.

The human body supports the growth of a wide array of microbial communities in various niches, such as the oral cavity, gastro-intestinal and urogenital tracts and on the surface of the skin. These host associated microbial communities include yet-un-cultivable bacteria and are influenced by various factors. Together, these communities of bacteria are referred to as the human microbiome. Human oral microbiome consists of both symbionts and pathobionts. Deviation from symbiosis among the bacterial community leads to “dysbiosis”—a state of community disturbance. Dysbiosis occurs due to many confounding factors that predispose to a shift in the composition and relative abundance of microbial communities. Dysbiotic communities have been a major cause for many microbiomes related systemic infections. Such dysbiosis is directed by certain important pathogens called the “keystone pathogens” that could modulate community microbiome variations. One such persistent infection is oral infection, mainly periodontitis, where a wide array of causal organisms has been implied to systemic infections such as cardio vascular disease, diabetes mellitus, rheumatoid arthritis and Alzheimer’s disease. The keystone pathogens co-occur with many yet-cultivable bacteria and their interactions lead to dysbiosis. This has been the focus of recent research. While immune evasion is one of the major modes that lead to dysbiosis, new processes and new virulence factors of bacteria have been shown to be involved in this important process of that determine disease or health state. This review focuses on such dysbiotic communities, their interactions and their virulence factors that predispose the host to other systemic implications.

Inflammatory allergic and nonallergic respiratory pathologies often co-exist. The root cause is not clear. This paper demonstrates that it is ascribable to protons (H⁺) released into cells by exogenous and endogenous acids. The hypothesis of acids as the common cause stems from two considerations: a) it has long been known that exogenous acids present in air pollutants can induce the irritation of epithelial surfaces, particularly the airways, inflammation and bronchospasm; b) according to recent articles, endogenous acids, generated in cells by phospholipases, play a key role in the biochemical mechanisms of initiation and progression of allergic responses. Therefore, the intracellular acidification and consequent Ca²⁺ increase, induced by protons generated by either acid pollutants or endogenous phospholipases, may be the causal mechanism of the multimorbidity of these diseases, and environmental acidity may contribute to their spread.

Argulus is an ectoparasite that frequently infects goldfish, with severe effects and a high death rate. The use of plant extracts has been widely reported to have antiparasitic activities, including one of the solasodine compounds in sour eggplant extracts. This research evaluated the antiparasitic activities of Compositions A (Solanum ferox and Zingiber zerumbet extract at 400 and 200 ppm, respectively), B (SFE and Boesenbergia pandurata at 900 ppm), and C (single Solanum ferox at 400 ppm). The research stages comprised 1) isolation and analysis of solasodine content in sour eggplant extracts and its extract composition, 2) in vitro antiparasitic activities on Argulus sp. at doses of 50 and 100 ppm with a testing time of 60–240 minutes, and 3) in vivo antiparasitic activities on Argulus sp. on goldfish at a dose of 100 ppm and observation for 2–12 hours of medication. The results showed that sour eggplant extracts had a solasodine concentration of 7.151 mg/L, whereas the derivative compositions A, B, and C were 656, 485, and 295 ppm, respectively. The in vitro testing demonstrated that composition A was effective for killing approximately 80–100% of Argulus, whereas compositions B and C killed 80–90% and 60–70%, respectively. Viewed from the effectiveness for killing parasites, the result was excellent (above 50%). The in vivo medication test was continued using three extract compositions at a dose of 100 ppm. Compositions A, B, and C were found to be capable of releasing 81.33, 75.67, and 71.00 arguli, respectively, per fish. We concluded that the single SFE extract and a concoction with BPE and ZZE had reasonable antiparasitic activity, whereas the concoction of SFE and ZZE killed more Argulus parasites at a higher rate.

Acute myocardial infarction (AMI), which is characterized by severe and fatal arrhythmias resultant from cardiac ischemia/reperfusion (CIR), is the leading cause of morbidity and mortality in the world. Considering that epiisopiloturin (EPI), an imidazole alkaloid found in the leaves of Pilocarpus microphyllus produded anti-inflammatory and antioxidant effects in an animal model of peritonitis, paw edema and peritonitis in mice, we decided to investigate the potential cardioprotective activity of EPI in animal model of CIR. Then, adult rats submitted to CIR pretreated with EPI 10 mg/kg (EPI10+CIR group) or 15 mg/kg (EPI15+CIR group) were compared to control animals submitted to CIR treated with saline solution 0.9% (CIR group). To evaluate the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) induced by CIR in these rats, the ECG analysis was performed. Serum levels of cardiac damage markers, total creatine kinase (CK) and CK-MB, were measured. The results showed that the AVB incidence was reduced from 80% to 30%, and LET incidence was reduced from 70% to 20%, compared to CIR group. Serum levels of LDH, total CK and, CK-MB was similar in all groups studied. These results indicate that the treatment with EPI (15 mg/kg, IV) before CIR was effective to produce cardioprotective effects. Thus, the use of EPI could be a promisse strategy to reduce the incidence of severe and fatal arrhythmias associated with AMI.

The modern diet, which consists of food produced with high level of industrial processing, is associated with an increased risk of the development of lifestyle diseases. Current nutritional science is, however, focused on chemical composition of food, and not on the type and degree of processing used during the food production. Here, we take a fresh perspective on the relationship between the extent and type of food processing, and evaluate its impact on consumer health. We argue that the preference for consumption of minimally processed foods, and restriction of ultra-processed foods should be an essential part of a healthy lifestyle, disease prevention, and even treatment. We also present a simple, user-friendly consumer guide, which is intended to be used as a practical, ready-to-go identifier of ultra-processed foods.

In the world, migraine is one of the most common cause of disability in adults. To date, there is no a single cause for this disorder, but rather a set of physio-pathogenic triggers, in combination with a genetic predisposition. Among factors related to the migraine onset, a crucial role seems to be played by gut dysbiosis. In fact, it has been demonstrated how the intestine is able to modulate the central nervous system activities, through the gut-brain axis, and how gut dysbiosis can influence neurological pathologies, including migraine attacks. In this contest, in addition to migraine conventional pharmacological treatments, attention has been paid to an adjuvant therapeutic strategy based on different nutritional approaches and lifestyle changes able to positively modulate the gut microbiota composition. In fact, the restoration of the balance between the different gut bacterial species, the reconstruction of the gut barrier integrity and the control of the release of gut-derived inflammatory neuropeptides, obtained through specific nutritional patterns and lifestyle changes, represent a possible beneficial additive therapy for many migraine subtypes. Herein, this review explores the bi-directional correlation between migraine and the main chronic non-communicable diseases, like diabetes mellitus, arterial hypertension, obesity, cancer and chronic kidney diseases, whose link is represented by gut dysbiosis.

Cardiovascular diseases (CVD) account for about 17.3 million annual deaths worldwide. 85% of these deaths occurred as a result of myocardial infarction (MI) and stroke. Chronic heart diseases, such as arterial hypertension (AH), coronary heart disease, various cerebrovascular diseases, dilated and hypertrophic cardiomyopathies are widespread, with a fairly high incidence of mortality and disability. Most of these diseases are characterized by cardiac arrhythmias, conduction and contractility disorders. Additionally, interruption of the electrical activity of the heart, the appearance of extensive ectopic foci and heart failure are all symptoms of a number of severe hereditary diseases. The molecular mechanisms leading to the development of CVD are associated with impaired permeability and excitability of cell membranes and mainly caused by dysfunction of cardiac Ca2+ channels. Acquired channelopathies are caused by metabolic disorders, increased tone of the sympathetic nervous system, age-related changes that lead to deterioration of coronary blood flow and hemodynamics. Currently known channelopathies, such as the long or short QT syndromes, Brugada and Lenegre syndromes, catecholaminergic polymorphic ventricular tachycardia, etc., are congenital and genetic disorders caused by mutations of genes "responsible" for the conductive properties of certain channel-forming proteins, including pore-forming subunits of Ca2+ channels. Over the past 50 years, more than 100 varieties of ion channels have been found in the cardiovascular system cells. The relationship between the activity of these channels and cardiac pathology, as well as the general cellular biological function, has been intensively studied on several cell types and experimental animal models in vivo и in situ. In this review, we discuss the origin of Ca2+ channelopathies and the role of Ca2+ channels of various types: L- R-, T-types voltage-gated calcium channels, RyR2, non-selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, transient receptor potential (TRPC, TRPM7, TRPA1) channels in the development of cardio-vascular pathology.

Genetic disorders are preeminent determinants of infant mortality. The inherited pediatric-onset genetic disorders have consequential stress on child growth and development: several congenital, complex and rare disorders with indistinguishable clinical symptoms where diagnosis always remains a challenging task. Traditional diagnosis methods include biochemical tests followed by chromosomal microarray and sequencing of a single gene or panel of genes. These methods had several limitations, but with the advent of whole-exome sequencing (WES), genetic testing has become cost-effective and transformative. Exome sequencing has been known for its effectiveness, which appropriately elucidates and distinguishes the heterogeneous disorders to avoid misdiagnosis and decode the underlying genetic alterations. WES has led to discovering genes and genomic variants in a broad spectrum of diseases, including autism, epilepsy, congenital heart diseases, neurodevelopmental diseases, cancer, nephrotic disorders, neural tube defects and fetal structural anomalies. WES is significant in producing immense genomic biomarkers that can be made as appropriate pharmacogenomic targets for drug therapy. In this article, we analyze the recent exploration of WES technology to revolutionize not only the process of genetic variation and disease detection but also the convention of preventative and targeted drug discovery.

The intricate relationship between Gray-Level Co-occurrence Matrix (GLCM) metrics and machine learning model performance underscores the need for rigorous dataset evaluation and selection protocols to ensure the reliability and generalizability of classification outcomes. This study involved a thorough examination of selected publicly available plant diseases datasets, with an emphasis on how well they performed as measured by GLCM metrics. After first classifying the datasets according to their GLCM metrics, dataset_2 (D2) and dataset_5 (D5) were found, respectively, to be the best-performing dataset in all GLCM analyses. The same datasets were then used to train deep learning models, and their classification performances were assessed. A noteworthy association was observed between the results of training deep learning models and the performance ratings derived from GLCM studies. More specifically, dataset_2 (D2) performed best in both GLCM analysis and deep learning model performance, indicating a strong correlation between the accuracy of classification and the textural qualities that GLCM captured. In the context of plant disease identification, in particular, these results highlight the significance of clearly defined dataset selection criteria in deep learning applications. Scholars can improve the accuracy and dependability of deep learning models for diagnosing plant diseases by giving preference to datasets with favorable GLCM metrics. The research also emphasizes the importance of texture features being taken into account in addition to conventional image features, highlighting the necessity of transparency and rigor in dataset selection procedures.

Abstract: Delayed initiation of effective antifibrotic therapy in patients with interstitial lung diseases (ILD) may influence the progression and outcome of the disease. This study analyzes the differences in the journey of patients with ILD in the Brazilian and Mexican health systems. An evaluative study was conducted in reference centers for interstitial lung diseases in Brazil and Mexico with a panel of four specialists. The patient's journey in both countries begins when the patient seeks medical care after observing a chronic respiratory symptom. In both countries, due to diagnostic complexity, these patients arrive at ILD referral centers at an advanced stage of the disease. Once diagnosis is established, the treatment onset differs between Mexico and Brazil. Antifibrotic drugs are not yet available by SUS in Brazil, and the purchase is unfeasible for most of the population, which forces specialists to only offer support to patients until the treatment can get the drug. In Mexico, antifibrotics have been available in health sectors since 2018. Brazil and Mexico have several similarities regarding the initial journey of the patient due to diagnosis difficulties, but the outcome tends to be different due to a difference in access to treatment with antifibrotics. For this reason, advancing health policies that ensure proper treatment for patients with ILD is crucial for the sustainability and reliability of the health system.

Elevated immunoglobulin E (IgE) levels are commonly associated with allergies. However, high IgE levels are also found in several other infectious and non-infectious disorders. Elevated IgE levels typically suggest allergies, eczema, or recurrent skin infections. Very high IgE levels are uncommon in patients with active eczema but typically reflect a monogenic atopic condition or inborn immune defects with an atopic phenotype. The aim of our research is to identify if the possible cause of high IgE levels is also dependent on external factors, age, or associated recurrent pathologies such as infections. To answer this question, we performed a one-year retrospective study that included 200 hospitalized children who had at least two viral or bacterial infections in the six months preceding hospitalization. Measurements of IgE and allergen panels (respiratory and digestive) using blood samples revealed that individuals who tested positive for the body’s synthesis of hyperimmunoglobulin E were not observably allergic to any potential allergens despite having higher total serum IgE. According to the results, there was a strong correlation between elevated IgE serum levels and a history of infectious diseases among the patients.

The studies regarding macrophage lncRNAs described in this review can help provide valuable information for developing treatments for various pathological conditions involving macrophages. Over the past century, molecular biology's focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. Long noncoding RNAs (lncRNAs), which are over 200 bases long but do not code for proteins, play roles in gene expression regulation and signal transduction by inducing epigenetic changes or interacting with various proteins and RNAs. These interactions exhibit a range of functions in various cell types including macrophages. Notably, some macrophage lncRNAs influence the activation of NF-κB, a crucial transcription factor governing immune and inflammatory responses. Macrophage NF-κB is instrumental in the progression of various pathological conditions including sepsis, atherosclerosis, cancer, autoimmune disorders, and hypersensitivity. It orchestrates gene expression related to immune responses, inflammation, cell survival, and proliferation. Consequently, its malfunction is a key contributor to the onset and development of these diseases. This review summarizes the role of lncRNAs that regulate NF-κB in macrophage activation and inflammation, especially focusing on their implications in human diseases and their potential as therapeutic targets

According to the World Health Organization, cardiovascular disease (CVD) is the leading cause of death among women worldwide, yet its magnitude is often underestimated. Biological and gender differences affect health, diagnosis, and healthcare in numerous ways. The lack of sex and gender awareness in health research and healthcare is an ongoing issue and affects not only research, but also treatment and outcomes. The importance of recognising the impact of both sex and gender on health and of knowing the differences between the two in healthcare is beginning to gain ground. There is more appreciation of the role that biological differences (sex) and sociocultural power structures (gender) have, and both sex and gender affect health behaviour, the development of diseases, their diagnosis, management, and long-term effects of an illness. An important issue is the knowledge and awareness of women about vascular diseases. The risk of cardiovascular events is drastically underestimated by women themselves, as well as by those around them. The purpose of this review is to draw attention to improving the medical care and treatment of women with vascular diseases.

During a multi-detector computed tomography (MDCT) examination, it is crucial to efficiently organize, store, and transmit medical images in DICOM standard, which requires significant hardware resources and memory. Our project processed large amounts of DICOM images by classifying them based on cross-section views that may carry important information about a possible diagnosis. We ensured that images were retained and saved in PNG format to optimize hardware resources while preserving patient confidentiality. Furthermore, we have developed a graphical, user-friendly interface that allows physicians to visualize specific regions of interest in a patient's brain where changes may indicate disease. Our proposed method enables quick classification of medical images into predefined classes of confirmed diseases of brain parenchyma, contributing to swift decision-making for further diagnosis for more precisely evaluating and characterizing brain changes, and it can lead to the rapid application of adequate therapy, which may result in better outcomes.

CLIPPERS which stand for Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a chronic inflammatory disorder of the central nervous system. The aetiology of CLIPPERS remains unclear, although its pathogenesis shows immune-mediated processes. The diagnosis of CLIPPERS is challenging without a specific biomarker hence, it is important to consider if both the clinical and radiological features are consistent with the diagnosis, or rather any other disease that mimics CLIPPERS. The Authors present a case of a 40-year-old Female patient diagnosed with CLIPPERS syndrome in India. Differential diagnosis, clinical and MRI characteristics of CLIPPERS syndrome, and treatment approaches are discussed.

Nutraceuticals comprise dietary supplements, functional foods, medicinal foods, and pharmaceuticals. However, to date all these concepts are interpreted in different ways with the rapid increasing knowledge on nutrition, medicine, and plant biotechnology changing the concepts about food, health and agriculture. What matters are the bioactive elements conveyed by foodstuffs as nutrients or non-nutrients, which interfere with human metabolism and have impact on health, aging and well-being. Food, not nutrients, is the fundamental unit in nutrition and edible mushrooms, are fungi that supply unique biological compounds, different from plant or animal origin, which significantly impact on health status. Their influence on medicinal interventions has been known and studied for many years. The role on neurodegenerative disorders has been recently investigated and their significance on many other diseases has been well demonstrated. On this note it is synthesized the more recent knowledge of some edible mushrooms and preparations on Ménière’s disease, a lifelong condition it can develop at any age, but most commonly appearing between 40 and 60 years of age.

cGAS is a cytosolic DNA sensor that activates innate immune responses through production of the second messenger 2’3’-cGAMP, which activates the adaptor STING. cGAS senses dsDNA in a length-dependent but sequence-independent manner, and it cannot discriminate self-DNA from foreign DNA. In normal physiological conditions, cellular DNA is sequestered in the nucleus by nuclear envelope and in mitochondria by mitochondrial membrane. When self-DNA leaks into the cytosol during cellular stress, or during mitosis, the cGAS can be exposed to self-DNA and be activated. Recently, many studies have investigated how cGAS keeps inactive and avoids to be aberrantly activated by self-DNA. Thus, the aim of this narrative review is to summarize the mechanisms by which cGAS avoids to sense self-DNA under normal physiological conditions.

With an increasing aging population worldwide, the concept of multimorbidity has attracted growing interest over recent years, especially in frailty, which leads to progressive multisystem decline and increased adverse clinical outcomes. The relative contribution of multiple disorders to overall frailty index in older populations has not been established so far. This study aimed to assess the association between the Vulnerable Elders Survey-13 (VES-13) score, which is acknowledged to be one of the most widely used measures of frailty, and the most common ac-companying diseases among hospitalized adults aged 60 years old and more. 2860 participants with an average age of 83 years were included in this study. Multiple logistic regression with adjustment for age and nutritional status was used to assess the independent impact of every particular disease on vulnerability. Diabetes mellitus type 2, coronary artery disease, atrial fibrillation, heart failure, chronic kidney disease, osteoarthritis, fractures, eyes disorders, depression, dementia, pres-sure ulcers, and urinary incontinence were associated with higher scores of VES-13. Hospital admission of older subjects with those conditions should primarily draw attention to the risk of functional decline and while qualifying older patients for further treatment, particularly in surgery and oncology. At the same time, lipid disorders, gastrointestinal diseases, higher body mass index and albumins level were related to lower risk of being vulnerable, what may be attributed to younger age and better nu-tritional status of those patients.

Dengue virus (DENV) is a member of the Flaviviridae family and is responsible for the most common mosquito-borne human disease. Currently, there are no available antiviral drugs to treat DENV infections. However, certain flavonoids, including baicalein and baicalin, have demon-strated significant anti-DENV effects in vitro. This study aimed to assess the bioavailability of baicalein and its metabolite, baicalin, in the blood serum of Albino Wistar rats using the LC/MS/MS method. The in vitro activity of sera obtained from rats administered baicalein was evaluated for its anti-DENV properties using quantitative RT-PCR and the Foci Forming Reduction Assay (FFRA). The results obtained through LC/MS/MS analysis indicated that the bioavailability of baicalin in rat blood serum reached 44.20 µg/ml one hour after oral administration of baicalein. Furthermore, the sera collected from rats given baicalein exhibited a significant 78.26% inhibition of DENV-2 replication when tested against Dengue-2 using both quantitative RT-PCR and FFRA. These findings suggest that baicalein and baicalin hold promise as potential therapeutic candidates for further investigation in the development of treatments against DENV infections.

Kinases play an important role in regulating various intracellular signaling pathways that control cell proliferation, differentiation, survival and other cellular processes and their deregulation causes more than 400 diseases. Consequently, macrocyclization can be considered a noteworthy approach to develop new therapeutic agents for human diseases. Macrocyclization has emerged as an effective drug discovery strategy over the past decade to improve target selectivity and potency of small molecules. Small compounds with linear structures upon macrocyclization can lead to changes in their physicochemical and biological properties by firmly reducing conformational flexibility. A number of distinct protein kinases exhibit similar binding sites. Comparison of protein binding site provides crucial insights for the drug discovery and development. Binding site similarities are helpful to understand polypharmacology, identifying potential off-targets and repurposing of known drugs. In this review, we focused on comparing binding sites of those kinases for which macrocyclic inhibitors are available/studied so far. Furthermore, we calculated the volume of binding site pocket for each targeted kinase and then compared it with the binding site pocket of the kinase for which only acyclic inhibitors were designed till date. Our review and analysis of several explored kinases might be useful to target new protein kinases for macrocyclic drug discovery.

Oxidative stress (OS) is a condition in which there is an excess of reactive oxygen species (ROS) in the body, which can lead to cell and tissue damage. This occurs when there is an overproduction of ROS or when the body's antioxidant defense systems are overwhelmed. Quercetin is part of a group of compounds called flavonoids. It is found in high concentrations of vegetables, fruits, and other foods. Over the past decade, a growing number of studies have highlighted the therapeutic potential of flavonoids to modulate neuronal function and prevent age-related neurodegeneration. Therefore, quercetin has been shown to have antioxidant, anticancer, and anti-inflammatory properties, both in vitro and in vivo. Due to its antioxidant character, quercetin alleviates oxidative stress, thus improving cognitive function, reducing the risk of neurodegenerative diseases. On the other hand, quercetin can also help support the body's natural antioxidant defense systems, thus being a potentially practical supplement for managing oxidative stress. This review focuses on experimental studies supporting the neuroprotective effects of quercetin in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD) and epilepsy.

Mucopolysaccharidoses (MPSs) are rare inherited lysosomal storage diseases (LSDs) caused by deficient activity in one of the enzymes responsible for glycosaminoglycans lysosomal degradation. MPS II is caused by pathogenic mutations in the IDS gene, leading to deficient activity of the enzyme iduronate-2-sulfatase, which causes dermatan and heparan sulfate storage in the lysosomes. MPS VI has dermatan sulfate lysosomal storage, owing to a deficiency of arylsulfatase B, due to pathogenic mutations in the ARSB gene. Alterations in the immune system of MPSs mouse models have been described but the data is still scarce concerning MPSs patients. Herein, we study different leukocyte populations in MPS II and VI disease patients. MPS VI, but not MPS II patients, have a decrease percentage of Natural Killer (NK) cells and monocytes when compared with controls. No alterations were identified in the percentage of T, invariant NKT and B cells in both groups of MPS disease patients. However, we uncovered alterations in the naïve versus memory status of both helper and cytotoxic T cells in MPS VI disease patients compared to control group. Indeed, MPS VI disease patients have a higher frequency of naïve T cells and consequently lower frequency of memory T cells than control subjects. Altogether, these results reveal MPS VI disease-specific alterations in some leukocyte populations, suggesting that the type of substrate accumulated and/or enzyme deficient in the lysosome may have a particular effect on the normal cellular composition of the immune system.

Agent-based models (ABMs) are computational models for simulating the actions and interactions of autonomous agents in time and space. These models allow users to simulate the complex interactions between individual agents and the landscapes they inhabit and are increasingly used in epidemiology to understand complex phenomena and make predictions. However, as the complexity of the simulated systems increases, notably when disease control interventions are considered, model flexibility and processing speed can become limiting. Here we introduce SamPy, an open-source Python library for stochastic agent-based modeling of epidemics. SamPy is a modular toolkit for model development, providing adaptable modules that capture host movement, disease dynamics, and disease control interventions. Memory optimization and design provide high computational efficiency allowing modelling of large, spatially-explicit populations of agents over extensive geographical areas. In this article, we demonstrate the high flexibility and processing speed of this new library. The version of SamPy considered in this paper is available at https://github.com/sampy-project/sampy-paper .

Tungiasis is a neglected parasitic skin disease caused by the permanent penetration of the female sand flea (Tunga penetrans) in the skin of the host, mainly the lower extremities.This gradually, it can lead to severe limb deformities.To date it is a health issue mainly in sub-Saharan Africa, the Caribbean, Latin and South America. It occurs mainly in poor rural populations and a major problem for children and the elderly. In diurnal zones, the incidence can reach over 73%. Over the past 20 years, studies in endemic areas on tungiasis have clarified to some extent the scientific community's knowledge for some problems of the disease. In this review, the current data on epidemiology, risk factors and prevention options are examinedof Tungiasis, as well as the expected steps of the international medical community to combat the disease.

Tungiasis is a neglected parasitic skin disease caused by the permanent penetration of the female sand flea (Tunga penetrans) in the skin of the host, mainly the lower extremities.This gradually, it can lead to severe limb deformities.To date it is a health issue mainly in sub-Saharan Africa, the Caribbean, Latin and South America. It occurs mainly in poor rural populations and a major problem for children and the elderly. In diurnal zones, the incidence can reach over 73%. Over the past 20 years, studies in endemic areas on tungiasis have clarified to some extent the scientific community's knowledge for some problems of the disease. In this review, the current data on epidemiology, risk factors and prevention options are examinedof Tungiasis, as well as the expected steps of the international medical community to combat the disease.

Intramammary infections (mastitis) of dairy cows, along with other periparturient diseases, have become problematic within the dairy industry as they lead to loss of milk production. The main objective of this study was to determine whether elevated somatic cell counts (SCC) in cows prior to drying off are related to the incidence of other periparturient diseases. Additionally, we de-termined whether milk composition and milk yield are affected by a high SCC prior to drying off. Somatic cell counts of milk samples were determined prior to dry off (n = 140) and were used to classify cows in the study as high (>200,000 cells/mL) or low (<200,000 cells/mL) SCC. The com-position of milk was analyzed before drying off and at 1 and 2 weeks after calving. The results showed that an elevated SCC before drying off was related to the incidence of ketosis. Cows with a high SCC at drying off also showed an increased likelihood of retained placenta, metritis, and lameness postpartum; however, it was not statistically significant. Milk lactose was lower in cows with high SCC, while protein content was lower after parturition. Milk production was lower for cows with pre-drying elevated SCC, particularly for cows with retained placenta, keto-sis, and mastitis. In conclusion, cows with pre-drying elevated SCC were more likely to develop disease after parturition and produce less milk and with lower lactose and protein content.

AMF (Arbuscular Mychorhizal Fungi) are very well known due to their importance in promoting growth and developments of plants especially vegetables. These fungi can be grown easily, stored and multiplied with simple means, also the application of these fungi is generally on the layer of the soil or near the roots in the inner layers of the soils. The growth of the amf fungi is very easy and they are highly adjustable to any soil and environmental conditions. In this review our main focus is on the use of amf for production of vegetables and also the effect of amf against insects and pests. The amf is known to reduce several symptoms caused by different insect pests and also plant diseases thereby promoting healthy growth of the plants. Also use of this amf will increase the uptake of nutrient from the soils through symbiotic relationships between plants and fungi. The uptake of important minerals which are drawn from deeper layers of soils is observed with the help pf amf. This study reveals the benefits of the use of amf under severe disease and pest incidences thereby known as an alternate for harmful chemical pesticides and fungicides.

Objective: To determine the association of edentulism with different chronic diseases in Mexicans aged 60 years and over. Material and Methods: A cross-sectional study was carried out using data from the World Health Survey for Mexico, which had a probabilistic, multi-stage and cluster sampling. The results of the self-report of chronic diseases (diabetes, arthritis, depression, angina pectoris, asthma and schizophrenia) and of edentulism were analyzed. Dental data were available for 20 of the 32 States of the Mexican Republic. Statistical analysis was performed in Stata 14.0 using the svy module for complex samples. Results: In total, 4213 subjects were included, representing a population of 7,576,057 individuals. The mean age was 70.13 ± 7.82 years (limits 60 to 98). Women represented 56.2%. The chronic diseases analyzed were presented as follows: diabetes 15.0% (N = 1,132,693); arthritis 13.2% (N = 1,001,667); depression 5.5% (N = 414,912); angina pectoris 4.5% (344,315); asthma 3.6% (N = 269,287); and schizophrenia 2.2% (N = 16,988). The prevalence of edentulism was 26.3%, which represents 1,993,463 people aged 60 years and over with this characteristic. For the presence of angina in women aged 60 to 69 years (p &lt;0.05) and depression in men aged 70 years and over (p &lt;0.0001), a higher prevalence of edentulism was observed. Conclusions: In general, there was no observation of association between edentulism was observed on the different chronic diseases included in the study. In the stratified analysis, only in women aged 60 to 69 years, for angina, and in men aged 70 and over, for depression, were associated.

Telomeres are crucial structures that preserve genome stability. Their progressive erosion over rounds of DNA duplication determines senescence of cells and organisms. In a classic view, telomere biology impinges on intracellular signaling pathways regulating DNA damage repair and cell cycle arrest, but new roles of telomeric proteins and transcripts emerge from recent literature. Telomere biology diseases are human disorders associated to telomere attrition. This review wants to overview the recent findings in the field of telomere’s metabolism and to deepen molecular mechanisms of inherited and acquired telomeropathies, explaining new critical connections between telomeric factors and disease pathogenesis

Societal changes have had effects on deaths from all causes in Russia. Up until now, deaths from all causes have been well researched, although several inconsistencies persist on the contributions of researchers. This study assessed research output, trends and topics that shaped deaths from all causes studies in Russia. Using bibliometric and topic modelling approaches, deaths from all causes in Russia published from 1914 to date was analysed using data on publications, citations, journals, keywords co-occurrence, year of publication, institutional affiliations, and country of origin from Scopus. Overall results indicate a steady growth of publications in Russia was documented after 1985. The h-index of some top 10 authors did not surpass single digits. A network visualisation map showed that ‘Russia’, ‘male’, ‘mortality’ and ‘human’ were the most commonly encountered vital terms. Of the ten most prolific authors, McKee M, Shkolnikov VM, Bobak M, Samorodskaya IV and Andreev E were the first five. Although the top 10 journals researching on death causes in Russia were Russian, these journals were not included in the most cited journals. The most prolific institutions studying deaths in Russia included; Tehran University of Medical Sciences, London School of Hygiene and Tropical Medicine, University College London, Max Planck Institute for Demographic Research and National Research University-Higher School of Economics. Findings suggest that deaths from all causes research attention in Russia increased in recent years, but the number of publications and research related engagements (e.g., networking and/ collaboration) does not match-up to other countries (e.g., UK, US, Germany). This research lag calls for more collaborative research between public health disciplines and networking among researchers (i.e., both national and international).

In India the first case of coronavirus disease 2019 (COVID-19) reported on 30 January 2020, and thereafter cases were increasing daily after the last week of Feb. 2020. COVID-19 identified as family member of coronaviridae where previously Middle East Respiratory Syndrome MERS and Severe Acute Respiratory Syndrome SARS belongs to same family. The COVID-19 attacks on respiratory system signing fever, cough and breath shortness, in severe cases may cause pneumonia, SARS or some time death. The aim of this study work is to develop model which predicts the epidemic peak for COVID-19 in India by using the real-time data from 30 Jan to 10 May 2020. There are uncertainties while identifying the population information due to the incomplete and inaccurate data, we initiate the most popular model for epidemic prediction i.e Susceptible, Exposed, Infectious, & Recovered SEIR initially the compartmental model for the prediction. Based on the solution of the state estimation problem for polynomial system with Poisson noise, we estimate that the epidemic peak may reach the early-middle July 2020, initializing recovered R0 to 0 and Infected I0 to 1. The outcomes of the model will help epidemiologist to isolate the source of the disease geospatially and analyze the death. Also government authorities will be able to target their interventions for rapidly checking the spread of the epidemic.

In late February 2020, Coronavirus disease-2019 (COVID-19) has aggressively spread around many bordering provinces of the three most productive regions of northern Italy (Lombardy, Veneto and Emilia Romagna). The first outbreak exploded in the municipality of Codogno (Lombardy). The province of Ferrara (Emilia Romagna) has been indicated as an anomaly due to the lower number of confirmed cases (1·065 cases per 1000 population). We argue that the spread of the virus throughout Emilia Romagna has a possible explanation in the geographical location of most of its provinces along the Via Emilia, an ancient Roman road that runs throughout the region, which we consider as a proxy for citizens’ movement, number of contacts, and social interactions. In order to test this hypothesis, we used a non-linear multiple regression analysis on aggregate province data to investigate the association between the rates of confirmed cases and the distance from the Via Emilia. The results indicate that the infection rate decreases proportionally to the distance from Via Emilia (-14% every 10 km, p<0·001). Further studies are needed, but Ferrara’s “peculiarity” might have a geographical/behavioral explanation, due to its isolation from the regional main connection routes, which are still revolving around a road built by the ancient Romans 2,000 years ago.