The aim of this paper is to develop an intelligent event-driven Electrocardiogram (ECG) processing module in order to achieve an efficient solution for diagnosis of the cardiac diseases. The suggested method acquires the signal with an event-driven A/D converter (EDADC). The output of EDADC is passed through the activity selection and interpolation blocks. It allows focusing only on the important signal parts and resampling it uniformly. Later on, the signal is de-noised. The autoregressive (AR) method is used to extract the classifiable features of the de-noised signal. Afterwards, the output is classified by employing different robust classification techniques such as support vector machines (SVMs), K- Nearest Neighbor (KNN) and Artificial Neural Network (ANN). The event-driven feature enables to adapt the system processing load according to the signal temporal variations. This interesting feature of the devised system aptitudes a drastic reduction in its processing activity and therefore in the power consumption as compared to the traditional ones. A comparison of the performance of different classifiers is also made in terms of accuracy. Results show that the proposed system is a potential candidate for an automatic diagnosis of the cardiac diseases.

Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered as expression vector systems for recombinant protein expression and vaccine development. Due to the presence of non-structural genes encoding the replicase complex, a 200,000-fold amplification of viral RNA occurs in the cytoplasm of infected cells providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. The self-replicating RNA viral vectors can be administered as replicon RNA, recombinant viral particles, or layered DNA/RNA replicons. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus and recently coronaviruses, especially SARS-CoV-2 the causative agent of the COVID-19 pandemic. Measles virus and rhabdovirus vector-based SARS-CoV-2 vaccine candidates have been subjected to clinical trials. Moreover, RNA vaccine candidates based on self-amplifying alphaviruses have also been evaluated in clinical settings. Various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been targeted for vaccine development. Robust immune responses and protection have been demonstrated in animal models. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.

The prevalence of overweight/obesity in the adult population in the Philippines has doubled in the past 20 years. Zumba exercise has recently been implemented throughout the Philippines. However, there is scarce information on the effects of Zumba on obesity and Zumba participants’ characteristics in the Philippines. This study described the current practice of Zumba in the Philippines, along with the practitioners’ characteristics, and identified factors associated with Zumba participation. In this observational, cross-sectional study, a structured questionnaire was used to survey 10 Zumba locations in September 2019. Anthropometric measurements of participants were assessed. Respondents included 171 women (88.6%) and 22 men (11.4%), with a mean (±SD) age of 44.1 (± 8.9) years. All respondents answered that Zumba was enjoyable, and some answered “very enjoyable.” Determinants of frequent participation were as follows: being older than the mean age of participants, starting Zumba to enjoy dancing, starting Zumba not to lose weight, shopping mall location, and participation fee required. “To enjoy dance” being a motivation for Zumba practice was identified as a determinant of frequent participation, rather than “to lose weight.” The element of “enjoyable” may strongly influence continuation and frequent participation of Zumba exercise in the Philippines.

As the novel COVID-19 disease spreads around the world, the most affected population are those who suffer from the most common chronic diseases, such as obesity, hypertension, and type 2 diabetes, which are quite associated with the so-called age-related diseases. On the other hand, since the Spanish influenza outbreak, humanity has not experienced an infectious disease that synergizes so quickly with chronic diseases, making it mortal for those individuals with comorbidities. In this context, COVID-19 is challenging for health systems all around the world due to the high prevalence of chronic diseases. Nowadays, we are facing the beginning of a new era in which health infectious and chronic diseases meet. Therefore, epidemiologic and biomedical researchers must work together to solve further contingencies, and politicians should direct science-centered decisions on public health. In the present paper, we make an urgent call to learn from the COVID-19 lessons in order to mitigate the chronic diseases prevalence and to address the influence of the infectious diseases on the aging process; since we are about to begin the Decade of Healthy Aging.

The review analyzes a possible role of autoimmune processes in the pathogenesis of schizophrenia and evolution of concepts on this issue from its origin to present. Risks of autoimmune processes causing schizophrenia are associated with several factors: an impaired functioning of dopaminergic and glutamatergic systems in the brain, kynurenine pathway disorder with overproduction of quinolinic, anthranilic and kynurenic acids (possibly altering both neurons and T-regulators), increased intestinal permeability, as well as food antigens’ effects, stress and infections with various pathogens at different stages of ontogenesis. An increase in the levels of proinflammatory cytokines and chemokines as well as a decrease in the levels of anti-inflammatory ones also may contribute to schizophrenia risks. Schizophrenia often occurs in those patients having various autoimmune diseases and their first-degree relatives. Cases of schizophrenia resulted from autoimmune pathogenesis (including autoimmune encephalitis caused by autoantibodies against various neuronal antigens) are characterized by quite severe cognitive and psychotic symptoms and less favorable prognosis. This severe course may result from the chronic immune damage of the neuronal receptors such as NMDA, GABA, and others and depend on hyperprolactinemia, induced by antipsychotics, but aggravating autoimmune processes [with 2 tables, 4 figures, bibliography: 99 references].

Mastitis is an inflammation of the mammary gland initiated by pathogenic bacteria. In fact, mastitis is the second most important reason for the culling of cows from dairy herds, after infertility. In this review we focus on various forms of mastitis, including subclinical and clinical mastitis. We also stress the importance of the dry-off period as an important time when pathogenic bacteria might start their insult to the mammary gland. An important part of the review is the negative effects of mastitis on milk production and composition, as well as economic consequences for dairy farms. The two most important groups of bacteria that are involved in infection of the udder, Gram-negative and Gram-positive bacteria, are also discussed. Although all cows have both innate and adaptive immunity against most pathogens, some are more susceptible to the disease than others. That’s why we summarize the most important components of innate and adaptive immunity so that the reader understands the specific immune responses of the udder to pathogenic bacteria. One of the most important sections of this review is interrelationship of mastitis with other diseases, especially retained placenta, metritis and endometritis, ketosis, and laminitis. Is mastitis the cause or the consequence of this disease? Finally, the review concludes with treatment and preventive approaches to mastitis.

Background: Rituximab is a monoclonal antibody widely used in the treatment of inflammatory and autoimmune disorders. Despite reports of its effectiveness in the treatment of demyelinating diseases of central nervous system (DDCNS), it is not yet approved for use in these disorders. The aim of this study was to investigate the effectiveness and safety of low dose rituximab in three different subgroups of DDCNS including relapsing-remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS) and neuromyelitis-optica-spectrum disorders (NMOSD).Methods: In a prospective cohort study, we monitored expanded-disability-status-scale (EDSS), relapses (new attacks) and serum-IgG levels to assess effectiveness and drug-adverse-events for safety in patients with RRMS, SPMS and NMOSD. These patients were candidates to receive rituximab according to our common practice protocol. We switched patients to rituximab if there was poor response to first line therapies. We follow a low dose protocol in our center (500 mg twice, two weeks apart, repeating every six months) and these patients treated in a 4-year period were assessed retrospectively for evaluation of our protocol’s safety and effectiveness. Results: 99 patients (42 RRMS, 43 SPMS and 14 NMOSD) received rituximab for a range of 12 to 40 months period. New attacks occurred in 8 RRMS (19%), 10 SPMS (23%) and 1 NMOSD (7%) patients. EDSS decreased in RRMS and NMOSD cases. Serum-IgG levels decremented in SPMS and NMOSD patients. Drug-adverse-events happened in two cases.Conclusion: In this study, low dose rituximab showed substantial effectiveness in preventing disease progression with a considerably good safety profile.

SIRT6 is a NAD+ dependent enzyme and stress response protein that has sparked the curiosity of a plethora of researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in several different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses and so on. Only in recent times however did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles and structure [1]. Even until very recently, SIRT6 was known more for chromatin signaling but being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases namely, diabetes, cancer, neurodegenerative diseases and heart disease has been demonstrated. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies, involving SIRT6, that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest understanding of SIRT6 and how it can alter the course of several life-threatening diseases that cripple today’s society such as processes related to aging, cancer, neurodegenerative diseases, heart disease and diabetes. In addition, SIRT6 has shown to be involved in liver disease, inflammation and bone related issues but more emphasis is given to the former. Lastly, any recent promising pharmacological investigations and study of potential therapeutic targets are also delineated in this review.

This work explores the significance of toothbrushing in maintaining optimal oral health, delving into its benefits, proper techniques, and types of toothbrushes. The primary cause of caries, periodontal diseases, and halitosis is oral biofilm development. One of the most fundamental practices in maintaining oral health is toothbrushing. Studies have confirmed that mechanical procedures for controlling plaque and toothbrushing, in particular, significantly decrease plaque accumulation. The significance of teeth brushing in preventing dental caries has been well-acknowledged for a considerable period. Dentists recommend brushing twice daily for at least two min to ensure thorough cleaning. Unfortunately, precise guidelines from dental associations are often missing. Authors mention that two min of brushing are insufficient for significant plaque removal; plaque removal increases with augmented brushing time, with maximum removal at 180 s. Multiple studies have documented that engaging in the practice of brushing one’s teeth twice a day has a preventive impact. Various toothbrush designs, including both manual and electric options, have been created to improve the elimination of dental biofilm and reduce the accumulation and persistence of bacteria. In conclusion, toothbrushing is a simple yet incredibly important practice for maintaining oral health. The benefits extend beyond just a bright smile, encompassing caries, gum disease, halitosis prevention, and the preservation of tooth enamel. Adhering to proper toothbrushing techniques, selecting the right toothbrush, and understanding the connection between oral health and overall well-being can lead to a healthier life. To foster favorable toothbrushing behaviors among the population, dental practitioners and public health experts must know the factors that influence toothbrushing habits.

Exhaled breath condensate (EBC) sample analysis is an entirely non-invasive novel sample collection method that is fast, easy to perform, and effort-appeared independent. EBC samples can be very useful in identifying the biomarkers of many diseases. This review provides an updated overview of EBC pH disturbances in different disorders as well as physiological levels among healthy individuals since 2012. Our meta-analysis addresses some of the key questions related to sample processing before pH measurement and discusses various methods of condensate standardization that can be employed prior to conducting a pH assay. Given the recent widespread interest in research into the use of EBC to identify biomarkers, it is necessary to establish a pathway leading from analytical methods for biomarker evaluation using EBC pH to clinical applications of this technology. This review fills a gap in the literature and attempts to connect theory to practical analytical approaches to analyzing EBC samples and making critical treatment-related decisions next to the patient's bed.

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.

Studies comparing provider and patient views and experiences of self-management within primary healthcare are particularly scarce in disadvantaged settings. In this qualitative study, patient and provider perceptions of self-management were investigated in five socio-economically disadvantaged communities in Stockholm. Twelve individual interviews and three group interviews were conducted. Semi-structured interview guides included questions on perceptions of diabetes diagnosis, diabetes care services available at primary health care centers, patient and provider interactions, and self-management support. Data was analysed using thematic analysis. Two overarching themes were identified. These were characterized by inherent dilemmas representing confusions and conflicts that patients and providers experienced in their daily life or practice respectively: adopting and maintaining new routines through practical and appropriate lifestyle choices (patients); and balancing expectations and pre-conceptions of self-management (providers). Patients found it difficult to tailor information and lifestyle advice to fit their daily life. Healthcare providers recognized that patients were in need of support to change behavior, but saw themselves as inadequately equipped to deal with the different cultural and social aspects of self-management. This study highlights patient and provider dilemmas that influence the interaction and collaboration between patients and providers with respect to communication and uptake of self-management advice.

Abstract Eye health is crucial and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation of patients with natural antioxidants and nutraceuticals. In particular, evidence has been accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin, in particular, has been found to protect foto-receptors thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. On the other hand, CoQ10 has been demonstrated to produce consistent effect in reducing ocular pressure thereby leding to protection in patients undergoing glaucoma. Finally, both grape seed extract rich in anthocyanosides and polynsatured fatty acids (PUFAs) seem to contribute in the prevention of retinal disorders. Thus, combination of nutraceuticals and anti-oxidants may represent the right solution for a multiaction activity in eye protection to be associated to current drug therapies, and this will be of potential interest in early stages of eye disorders.

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.

This systematic review investigates the failure rate and marginal bone loss (MBL) of dental implants placed in Solid-organ transplant (SOT) patients compared to healthy controls. Three databases (PubMed, Web of Sciences and the Cochrane Library) were searched up to June 2020 (PROSPERO CRD42019124896). Case-control and cohort studies reporting data failure rate and marginal bone loss (MBL) of dental implants placed in SOT patients were included. The risk of bias of observational studies was assessed through the Newcastle-Ottawa Scale (NOS). Four case-control studies fulfilled the inclusion criteria, all of low risk of bias. Meta-analyses revealed consistently lower implant failure rate than control populations at patient and implant levels. SOT patients had a significant difference of -18% (p-value <0.001) of MLB towards healthy patients. SOT status poses no serious threat to implant survival. Overall, this group of patients presented lower levels of dental implant failure rate and marginal bone loss compared to otherwise healthy patients. Further intervention trials with wider sample size and longer follow-ups are necessary to confirm these summary results.

Antibiotics are commonly used to treat infectious diseases. However, massive and inappropriate antibiotics usage cause many problems including the emergence and spread of antibiotic-resistant bacteria. To avoid this issue, in modern countries the interest of using probiotics in feed supplementation to promote health and prevent or treat intestinal infectious diseases in companion animals like dogs has been increasing. We evaluate the probiotic potential of Lactobacilli isolated from healthy dogs faeces. The isolated Lactobacilli were first confirmed by 16SrRNA sequencing, then in vitro tests were conducted to assess survival potential of Lactobacilli under simulated gastrointestinal conditions and adhesion ability to gut epithelia, effects on epithelial barrier function, anti-inflammatory activities, effects on defensin peptides (beta-defensin 3) and inhibitory effects on common pathogens. Lactobacilli showed considerable potential to survive in simulated gastrointestinal environmental conditions, low pH, high bile salt concentrations along with good adhesion properties with MODE-K cells. Pathogenic bacterial growth and their adhesion to MODE-K cells was significantly inhibited by Lactobacilli. Real-time PCR analyses further demonstrated that L. acidophilus strain AR1 and AR3 inhibit Salmonella-induced proinflammatory cytokines (IL-6, IL-8, 1ꞵ) production and reinforce expression of tight junction protein (occludin). None of the strain induce mRNA expression of beta-defensin 3 in MODE-K cells. Based on in vitro results the L. acidophilus strain AR1 has potential to be supplemented in canine feed. However, further in vivo studies investigating health-promoting effects are awaited.

There is a strong anticipated future for human pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The transcriptomics analysis revealed that 86% of the genes were expressed at similar levels in hiPS-HEP as in human primary hepatocytes (hphep). Adult characteristics of the hiPS-HEP were confirmed by the presence of important hepatocyte features, e.g. Albumin secretion and expression of major drug metabolizing genes. Normal energy metabolism is crucial for modeling metabolic diseases, and both transcriptomics data and functional assays showed that hiPS-HEP were similar to hphep regarding uptake of glucose, LDL and fatty acids. Importantly, the inflammatory state of the hiPS-HEP was low under standard conditions, but in response to lipid accumulation and ER stress the inflammation marker TNFα was upregulated. Furthermore, hiPS-HEP could be co-cultured with primary hepatic stellate cells both in 2D and in 3D spheroids, paving the way for using these co-cultures for modeling NASH. Taken together, hiPS-HEP have the potential to serve as an in vitro model for metabolic diseases. Furthermore, differently expressed genes identified in this study can serve as targets for future improvements of the hiPS-HEP.

The short study implicates few basic similarities of COVID-19 such as diseases origination, symptoms, diagnosis with other relatable viral diseases viz SARS-CoV, common Flu, pneumonia etc. In the present situation, other viral diseases are frequently chaotic and misled with COVID-19 disease because of few clinical features similarities in signs and symptoms and also due to lack of specific diagnostic test. To avoid unnecessary suspects, quarantines of false positive results and to prevent the spread of COVID-19 diseases, the scientific technical research field are highly encourage to implement an efficient, rapid and sophisticated superior test for early stages of infection detection. It will be significantly convenient for physician, laboratory technicians and most importantly the common population facing a psychological disturbance.

The semi-logarithmic plot of the cumulative number of cases of epidemics resembles the response of a first-order systems for a step load. This similarity was utilized to develop a first order model that can be used for extracting information about the dynamics of infectious disease epidemics. The developed model was validated using COVID-19 data of China. It was also heuristically fitted to other 13 countries. Obtained results indicated that the model can reliably forecasts the number of infected person, epidemic growth speed towards steady-state condition (process time constant, T), and time to reach steady-state condition (4T). The developed model will help public health authorities in developing more effective control strategies of epidemics.

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.

Inflammatory bowel disease (IBD) is a chronic disease mediated by the immune system and characterized by the inflammation of the gastrointestinal tract. One of the possible treatments for this pathology is a change in the type of diet, the enteral nutrition (EN) is one of them. This study is to understand how the use of EN can affect the adult population diagnosed with IBD. We conducted a systematic review, meta-analysis and a meta-regression. On the different databases, (MEDLINE, Scopus, Cochrane, LILACS, Cinhal, WOS) we found 363 registers, the accuracy was 12% (44 registers); After a Full-text review, only 30 research studies were selected for qualitative synthesis and 11 for Meta-analysis and Meta-regression. The variables used were Crohn’s Disease Activity Index (CDAI), C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR). EN has shown to have efficacy for the treatment of Crohn’s Disease and is compatible with other medicines. As for the CDAI or the rates of remission, there were no differences between enteral and parenteral nutrition. Polymeric formulas, have shown better results with respect to the CRP. The long-term treatment could dilute the good CDAI results that are obtained at the start of the EN treatment.

Cardiovascular diseases (CVD) are the leading cause of premature death and disability in humans. Increasing data suggest that CVD is closely related to lipid metabolism and signaling. This study aimed to assess whether circulating lysophospholipids (LPL), lysophosphatidic acids (LPA) and monoacylglycerols (MAG) may be considered as biomarkers of CVD. For this objective, the evolution of the plasma levels of 22 compounds (13 LPL, 6 LPA and 3 MAG) was monitored by liquid chromatography coupled with tandem mass spectrometry (HPLC/MS²) in different rat models of CVD, i.e. angiotensin-II-induced hypertension (HTN), ischemic chronic heart failure (CHF) and sugen/hypoxia(SuHx)-induced pulmonary hypertension (PH). On one hand, there was modest changes on the monitored compounds in HTN (LPA 16:0, 18:1 and 20:4), LPC 16:1) and CHF (LPA 16:0, LPC 18:1 and LPE 16:0 and 18:0) models compared to control rats but these changes were no longer significant after correction for multiple testing. On the other hand, PH was associated with important changes in plasma LPA with a significant increase in the 16:0, 18:1, 18:2, 20:4 and 22:6 species. A deleterious impact of LPA was confirmed on isolated human pulmonary smooth muscle cells with an increase in their proliferation. This study demonstrates that circulating LPA species are increased in rats with PH and may contribute to the pathophysiology of this disease. Additional experiments are needed to assess whether the modulation of LPA signaling in PH may be of interest.

Chronic noncommunicable diseases (CNCDs) have been a major public health concern worldwide, especially diabetes, cardiovascular disease, chronic obstructive pulmonary disease, hypertension, in addition to obesity, which is even more worrying when the subject involves the covid-19 pandemic, because such incidences correlate with the need for intensive care units, including the possibility of death of the patient. Therefore, for countries with the highest numbers of critical cases, it is important to assess the incidence of these diseases to guide the public that most needs guidance on public policies for social isolation.

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.

Proper treatment of infectious air could potentially mitigate the spread of airborne viruses such as porcine reproductive and respiratory syndrome virus (PRRSV). The objective of this research is to test the effectiveness of ultraviolet (UV) in inactivating aerosolized PRRSV, specifically, four UV lamps, UV-A (365 nm, both fluorescent and LED-based), "excimer" UV-C (222 nm), and germicidal UV-C (254 nm), were tested. The two UV-C lamps effectively irradiated fast-moving PRRSV aerosols with short treatment times (<2 s). One-stage and two-stage UV inactivation models estimated the UV doses needed for target percentage (%) reductions on PRRSV titer. UV-C (254 nm) dose needed for 3-log (99.9%) reduction was 0.521 and 0.0943 mJ/cm2, respectively, based on one-stage and two-stage models. An order of magnitude lower UV-C (222 nm) doses were needed for a 3-log reduction, i.e., 0.0882 and 0.048 mJ/cm2, based on one-stage and two-stage models, respectively. However, the cost of 222-nm excimer lamps is still economically prohibitive for scaling-up trials. The UV-A (365 nm) lamps could not reduce PRRSV titers for tested doses up to 4.11 mJ/cm2. Pilot-scale or farm-scale testing of UV-C on PRRSV aerosols simulating barn ventilation rates are recommended based on its effectiveness and reasonable costs comparable to HEPA filtration.

Three decades have now passed since the first papers linking climate change to issues in human disease and healthcare. One of the most active topics in this area has been the implication of climate change events, particularly temperature and humidity fluctuations, in the northward spread of vector-borne viruses from more tropical regions into Europe and North America. However, some detailed studies of one such emerging disease, tick-borne encephalitis virus (TBEv), have called the connection into question, concentrating the debate on the investigation of precise mechanisms for the spread of viral disease. More recently, firmer statistical correlations have been made between climate variables, the presence of insect vectors and the prevalence of viral disease, particularly for West Nile Virus (WNV). These insights suggest avenues for mechanistic confirmation of the involvement of climate change in other diseases where the connection remains conjectural.

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.

Porcine reproductive and respiratory syndrome virus (PRRSV) infections cause significant economic losses to swine producers every year. Aerosols containing infectious PRRSV are an important route of transmission, and proper treatment of air could mitigate the airborne spread of the virus within and between barns. Previous bioaerosol studies focused on the microbiology of PRRSV aerosols; thus, the current study addressed the engineering aspects of virus aerosolization and collection. Specific objectives were to (1) build and test a virus aerosolization system, (2) achieve a uniform and repeatable aerosol generation and collection throughout all replicates, (3) identify and minimize sources of variation, (4) verify that the collection system (impingers) performed similarly. The system for virus aerosolization was built and tested (Obj. 1). The uniform airflow distribution was confirmed using a physical tracer (<12% relative standard deviation) for all treatments and sound engineering control of flow rates (Obj. 2). Theoretical uncertainty analyses and mass balance calculations showed <3% loss of air mass flow rate between the inlet and outlet (Obj. 3). A comparison of TCID₅₀ values among impinger fluids showed no statistical difference between any two of the three trials (p-value = 0.148, 0.357, 0.846) (Obj. 4). These results showed that the readiness of the system for research on virus aerosolization and treatment (e.g., by ultraviolet light), as well as its potential use for research on other types of airborne pathogens and their mitigation on a laboratory scale.

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce retinal detachment to perform the subretinal placement of the transplanted cell; and (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

Oxidative phosphorylation (OxPhos) is the basic function of mitochondria although the land-scape of mitochondrial functions is continuously growing to include more aspects of cellular homeostasis. Thanks to the application of -omics technologies to the study of the OxPhos system, novel features emerge from the cataloging of novel proteins as mitochondrial thus adding de-tails to the mitochondrial proteome and defining novel metabolic cellular interrelations, espe-cially in the human brain. We focussed on the diversity of bioenergetics demand and different aspects of mitochondrial structure, functions, and dysfunction in the brain. Definition as ‘mitoexome’, ‘mitoproteome’ and ‘mitointeractome’ have entered the field of ‘mitochondrial medicine’. In this context, we reviewed several genetic defects that hamper the last step of aerobic metabolism mostly involving the nervous tissue as one of the most prominent energy-dependent tissues and, as consequence, as a primary target of mitochondrial dysfunction. The dual genetic determination of the OxPhos complexes is one of the reasons for the complexity of the geno-type-phenotype correlation when facing human diseases associated with mitochondria defects; clinically, are characterized by extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. Finally, we briefly discuss the fu-ture directions of the multi-omics study of human brain disorders.

A 62-year-old male was diagnosed with B-CLL and treated with Fludarabine-containing regimen which maintained the disease in partial response. Nine years after diagnosis, a rapidly growing systemic lymphadenopathy was observed, and a biopsy specimen revealed the presence of typical Hodgkin/Reed–Sternberg (HRS) cells, surrounded by T-lymphocytes and CLL cells. Sequencing analysis of the germline CDR3 region of the IGH gene showed that the HRS cells were clonally unrelated to the preexisting CLL cells and the HRS cells were composed of five different clones, leading to the molecular diagnosis of de novo lymphocyte-rich classic Hodgkin LPDs with SLL. Because the initial treatment was neither effective for classic Hodgkin LPDs nor for SLL, Bendamustine, Rituximab (BR) was started and complete remission was achieved, which has continued for more than one year so far. BR may be a good therapeutic option for both entities without causing hematological toxicity.

Background: Gastrointestinal parasitic infections are one of the global health concerns in developing countries like Bangladesh. Among them, Cryptosporidium spp. plays an essential role in causing diarrhea, malnutrition, and poor cognitive function, especially in children. The study was conducted to identify the frequency of cryptosporidium cases and other parasitic agents. Methods: A Cross-sectional observational study was conducted among 219 hospitalized children with diarrhea. The conventional microscopic technique was applied for parasitic detection. A particular staining procedure was performed to identify oocysts of Cryptosporidium spp. And PCR was conducted to determine the SSU rRNA and gp60 gene of Cryptosporidium. Results: Cyst of Giardia, ova of Ascaris lumbricoides (AL), Trichuris trichiura (TT), AL, and TT were identified in 2.3%, 1.4%, 0.5%, and 0.9% samples by wet mount preparation. The distribution of Cryptosporidium spp. was 1.4% and 4.1%, which was detected by the staining method and nested PCR. Factors independently associated with Cryptosporidium infection are unsafe water, lack of regular hand washing, and insufficiency of exclusive breastfeeding. Conclusions: This is the first report to detect the frequency of Cryptosporidium and other intestinal parasites and associated factors in Chattogram city of Bangladesh.

Repetitive nature of the ribosomal DNA (rDNA) gene makes the sequencing of hundreds copies of mammalian 45S rDNA (about 45-kb per copy) extremely difficult and its assembly is often excluded. Increasing evidence shows that 45S rDNA variations (copy number or single nucleotide), structural ribosomal RNA (rRNA) transcript variants, and non-structural rRNA transcripts (sense and anti-sense long noncoding rRNAs that include promoter rRNAs, and rRNA-derived fragments) play essential roles in mammalian development and diseases. Complete pictures of the hundreds copies of 45S rDNA and their rRNA transcripts require further innovation in sequencing techniques that include bioinformatics. The advancements in mammalian rDNA and rRNA sequencings and the discoveries of novel functions of the rDNA variants and rRNA transcripts are discussed here.

Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

Specific aquaporins (AQP), called peroxyporins, play a relevant role in controlling H2O2 permeability and ensure reactive oxygen species wasting during oxidative stress. Another target involved in oxidative stress is the Sigma1 Receptor (S1R), since its activation is triggered by oxidative or endoplasmic reticulum stress. Herein we evaluated the effect of S1R modulators on AQP-dependent water permeability in the presence and in the absence of oxidative stress. Applying stopped-flow light scattering and fluorescent probe methods, water and hydrogen peroxide permeability in Hela cells have been studied. Results evidenced that S1R agonists can restore water permeability in heat-stressed cells and the co-administration with a S1R antagonist totally counteracted the ability to restore the water permeability. All compounds except one were able to counteract the oxidative stress of HeLa cells specifically knocked down for S1R. Taken together, our results support the hypothesis that the investigated compounds act as dual aquaporin and Sigma1 receptor (DAS) modulators. The finding that small molecules can modulate both AQP and S1R opens a new direction toward the identification of innovative drugs able to regulate cell survival during oxidative stress in pathologic conditions, like cancer and degenerative diseases.

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.

The makeup of human microbiota has been linked to a number of autoimmune disorders. Recent developments in whole metagenome sequencing and 16S rRNA sequencing technology have considerably aided research into the microbiome and its relationship to disease. Due to the inherent high dimensionality and complexity of data generated by high-throughput platforms, conventional bioinformatics techniques could only provide an inadequate explanation for the most relevant changes and seldom provide correct predictions. Machine learning, on the other hand, is a subset of artificial intelligence applications that enable the untangling of high-dimensional systems and intricate knots in correlation by learning complex patterns and improving automatically from training data without being explicitly programmed. Machine learning is increasingly being utilized to research the influence of microbes on the onset of illness and other clinical features since computer power has increased dramatically in the last few decades. In this review paper, we focused on emerging methodological approaches of supervised machine learning algorithms for identification of autoimmune disorders utilizing metagenomics data, as well as the potential benefits and limitations of machine learning models in clinical applications.

In March 2020 the World Health Organization declared the “pandemic state” due to COVID-19 imposing strict confinement of the world population. People were forced to spend more time at home, changing some daily routines, including social interactions, the possibility to perform sports, and diet habits. These changes could exert a greater impact on patients suffering from chronic diseases, such as endocrine patients. This study aimed to assess the effects of Covid-19 induced quarantine on daily habits in a group of patients with endocrine disorders, focusing on food consumption, eating, and sleep habits during the confinement. Eighty-five endocrine patients were enrolled. A structured interview was administered investigating: socio-demographic information, general medical conditions and habits adopted during the quarantine. All patients underwent the Spielberger State Anxiety Inventory (STAI-Y1) to assess state anxiety. Subjects had mainly a sedentary lifestyle. We found a significant increase in the number of cigarettes in smokers, an increase of meals consumed during the confinement and a high rate of sleep disorder occurrence, especially insomnia. The changes of daily habits were, probably, due to the alterations of routine, that determined more bore and inactivity during the day.

Inside Central Nervous System (CNS) appears neurons and glia cells. There are more glial cells than neurons and have more functions than neurons. Glia name represents different kind of cells, ones from neural origin (astrocytes, radial glia, and oligodendroglia), and others from blood monocytes (microglia). During ontogeny, neurons appear first (rat fetal 15th) and after astrocytes (rat fetal 21th) indicating a bigger importance function in the CNS. Also, during the phylogeny, reptiles have less astrocytes compared to neurons and in humans, astrocytes are double in number than neurons. This data, perhaps means that astrocytes are more special cells and work in memory and learning? Astrocytes have an important role in different mechanisms protecting CNS across the production of antioxidant and anti-inflammatory proteins, cleaning extracellular medium and helping neurons to communicate with each other correctly. Inflammatory mediators production are important to prevent changes in normal physiology. But, excessive or continue production leads to many diseases, such as Alzheimer's disease (AD), Sclerosis Lateral Amyotrophic (ELA), Multiple sclerosis (MS), and neurodevelopment diseases, like Bipolar disorder, Schizophrenia, and Autism's symptomatology. Different drugs and thecniques can reverse oxidative stress and/or inflammatory excess. This review is intended to serve as an approximation to the field.

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer's disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, prion dis-ease, or brain tumors. Diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theranostic applications to meet these needs. This review covers pioneer studies to apply aptamers, which show promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.

According to the recent data, nitric oxide (NO) is a chemical messenger that mediates functions such as vasodilation and neurotransmission, it also possesses antimicrobial and antitumoral activities. Nitric oxide has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. We searched for full-text English publications in Pubmed and SNPedia databases using keywords and combined word searches (nitric oxide, single nucleotide variants, single nucleotide polymorphisms, genes) over the past 15 years. In addition, earlier publications of historical interest were included in the review. In our review, we have sum up all NOS1, NOS2, NOS3, and NOS1AP single nucleotide variants (SNVs) involved in the development of mental disorders and neurological diseases/conditions. The results of studies we have discussed in this review are contradictory, that might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. However, the contribution of genetic and environmental factors has been understudied, that makes this issue increasing for researchers as the understanding of these mechanisms can support a search for new approaches to pathogenetic and disease-modifying treatment.

Chronic diseases are still known as incurable diseases, and we suspect that the medical research model is unfit for characterizing chronic diseases. In this study, we examined accuracy and reliability required for characterizing chronic diseases, reviewed implied presumptions in clinical trials and assumptions used in statistical analysis, examined sources of variances normally encountered in clinical trials, and conducted numeric simulations by using hypothetical data for several theoretical and hypothetical models. We found that the sources of variances attributable to personal differences in clinical trials can distort hypothesis test outcomes, that clinical trials introduce too many errors and too much inaccuracies that tend to hide weak and slow effects of treatments, and that the means of treatments used in statistical analysis have little or no relevance to specific patients. We further found that a large number of uncontrolled co-causal or interfering factors normally seen in human subjects can greatly enlarge the means and the variances of the experimental errors, and the use of high rejection criteria (e.g., low p values) further raises the chances of failing to find treatment effects. As a whole, we concluded that the research model using clinical trials is wrong on multiple grounds, under any of our realistic theoretical and hypothetical models, and that misuse of statistical analysis is most probably responsible for failure to identify treatment effects for chronic diseases and to detect harmful effects of toxic substances in the environment. We proposed alternative experimental models involving the use of single-person or mini optimization trials for studying low-risk weak treatments.

This study applies a cluster analysis to identify typical physical activity (PA) and sedentary behaviour (SB) patterns in people with chronic obstructive pulmonary disease (COPD) before starting pulmonary rehabilitation (PR). We implemented an observational design which assessed baseline data on objectively measured PA and SB from the STAR (Stay Active after Rehabilitation) study. 355 persons wore a accelerometer (Actigraph wGT3X) for seven days before the start of their PR. Sociodemographic and disease-related parameters were assessed at the start of PR. We applied cluster analysis and compared groups applying univariate variance analyses. Data was available for 326 persons (31.6% women; age ø = 58 yr.). Cluster analysis revealed four movement clusters with distinct PA and SB patterns: sedentary non-movers (28.5%), sedentary occasional movers (41.7%), sedentary movers (19.6%), and sedentary exercisers (10.1%). The four clusters showed very different levels of moderate PA before rehabilitation (Ø daily minutes: 9; 28; 38; 70). Notably, all four clusters displayed considerably long average sitting time per day (Ø daily minutes: 644; 561; 490; 446). The groups differed significantly in disease-related parameters of GOLD severity, FEV1, CAT, and 6-Min-Walk-Test. In addition to PA promotion, PR programs should consider the reduction of sitting time as a valuable goal.

Epidemiological studies indicate that skipping breakfast as a universal behavior, may have adverse effects on cardiovascular diseases [CVDs}and metabolic diseases. However, eating breakfast regularly, may increase satiety, thereby reducing overeating later in the day which prevents weight gain. Recent studies indicate that skipping breakfast increases the risk of obesity, metabolic syndrome, hypertension, hypercholesterolemia, type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and cardiovascular mortality as well as all-cause mortality. However, many studies also reported that regular taking of breakfast decreases the risk of CVDs and T2DM and all-cause mortality. Previous studies reported that heavy breakfast, in particular eating western diet may increase circadian rhythm of CVDs and sudden cardiac death. It seems that those who do not eat breakfast, they tend to eat refined and sweetened products, possibly, more in the night resulting in to greater risk of CVDs and T2DM. Breakfast skipping and eating in the night, may be associated with circadian misalignment in the central and peripheral clocks, leading to oxidative stress and inflammation. Increased systemic inflammation damages the adipocytes, beta cells of pancreas, endothelial cells and smooth muscle cells as well as neurons, which may produce dysfunction in these cells resulting in to related diseases. The beneficial effects of breakfast, may also be, at least in part, due to nutrient dense foods rather than time of eating. Eating regular breakfast, in particular rich in Indo-Mediterranean foods; vegetables, whole grains, fruits, spices and nuts may be protective against circadian increase in oxidative stress in the morning, resulting in to significant decline in the risk of CVDs and T2DM.

The progressive impairment analysis in gait from neurological diseases patients such as Hereditary Ataxias (HA) has been carried out using gait data collected with movement sensors. This research is focused on finding the minimum amount required of gait features to recognize efficiently and less intrusive way, HA patients based on data collected with iPhone movement sensors placed on the ankles from 14 HA patients and 14 healthy people. A twofold proposal is made , first a local minimum prominent peak criterion to find out the starting point of each stride, to get 10-stride window about which 56 spatial-temporal features are derived; second a search strategy based on Hill Climbing algorithm to reduce the number of gait features and sensors. The main results were the findings that with two gait patterns a 96% of classification accuracy was achieved by using K-Nearest Neighbors (KNN) and Multi-Layer Perceptron (MLP) algorithms, but in addition, MLP only right ankle sensor patterns were required which also allows to reduce the intrusion.

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.

World Health Organization (WHO) has announced the monkeypox (MPX) epidemic a global public health emergency due to its re-emergence, remarkable increase in the number of MPX cases worldwide, and its potential spread. This paper introduces the symptoms, complications, and features of MPX; its transmission, diagnosis and testing, vaccines and treatment; MPX and sexually transmitted diseases, especially the human immunodeficiency virus (HIV); possible natural hosts or reservoirs of the monkeypox virus (MPXV). A useful tool for MPX and surgical safety recommendations are presented. The challenges in fighting the MPX epidemic, One Health strategy, and future research are discussed.

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.

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [ nuclear factor-κB (NF-кB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.

There is a lack of knowledge concerning the effects of ambient heat exposure on morbidity in Northern Europe. Therefore, this study aimed to evaluate the relationships of daily summer-time temperature and heatwaves with cardiorespiratory hospital admissions in the Helsinki metropolitan area, Finland. Methods: Time-series models adjusted for potential confounders such as air pollution were used to investigate the associations of daily temperature and heatwaves with cause-specific cardiorespiratory hospital admissions, during summer months of 2001-2017. Daily number of hospitalizations was obtained from the national hospital discharge register, weather information from the Finnish Meteorological Institute. Results: Increased daily temperature was associated with decreased risk of total respiratory hospital admissions and asthma. Heatwave days were associated with 20.5% (95% CI: 6.9, 35.9) increased risk of pneumonia admissions and during long or intense heatwaves also with total respiratory admissions in the oldest age group (≥ 75 years). There were also suggestive positive associations between heatwave days and admissions due to myocardial infarction and cerebrovascular diseases. In contrast, risk of arrhythmia admissions was decreased 20.8% (95% CI: 8.0, 31.8) during heatwaves. Conclusions: Heatwaves, rather than single hot days, are a health threat affecting the morbidity even in a Northern climate.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

The COVID-19 pandemic and increased rates of documented Emerging Infectious Diseases (EIDs) in human populations over the last century have drawn attention on understanding pathogens spill over to humans and their zoonotic origin. In this paper we argue that we need to change the thinking about the fundamental cause of zoonoses. Our premise is that deforestation is the primary cause of EIDs events and that, to prevent future pandemics, it needs to be addressed without further delays. Therefore, we review recent trends of proximate and underlying determinants of deforestation, forest degradation and related biodiversity losses while seeking to clarify their links to the determinants of EIDs events. Acknowledging the magnitude of the challenge, we propose responses to stop global deforestation from a trans-disciplinary, intersectoral perspective led by indigenous people. While we envisage that stopping deforestation is the most important approach with long term direct and indirect effects on human, animal and plants health, providing climate changes mitigation and preventing otherwise difficult to predict EID events, we argue that such an initiative may usefully be complemented by reducing contacts between humans and wildlife animals and regulating rather than banning markets where wild animals are sold alive.Finally, we discuss transformative changes to improve planetary-wide forests preservation, soil, plants, animal, and human protection, together with a further understanding of EIDs transmission dynamics, public health veterinary and human disease surveillance, for improved global collective preparedness and action for the management of zoonotic EIDs.

Abstract: The objective of this meta-analysis was to evaluate the factors associated with mortality of elderly Italians diagnosed with the new coronavirus who resided in institutions or who were hospitalized as a result of the disease. Methods: A systematic review following the recommenda-tions of The Joanna Briggs Institute (JBI), where the PEO strategy was utilized - Population, Exposure and Outcome. P, being the elderly over 65 years old. E, the SARS-CoV_2 pandemic. O, mortality. The NCBI / PubMed, LILACS, EMBASE and CINAHL databases were used until July 31, 2020.; Results: Five Italian studies were included in the meta-analysis, with the number of elderly people varying between 18 and 1591 patients. The main morbidities presented by the elderly in the studies were: dementia, diabetes, chronic kidney disease and hypertension. Conclusions: The factors as-sociated with the mortality of elderly Italian people diagnosed with SARS-CoV-2 who lived in in-stitutions or who were hospitalized because of the disease were evaluated. It was found that de-mentia, diabetes, chronic kidney disease and hypertension are the main the main diagnosed dis-eases for mortality in elderly people with Covid-19.

Objective: The purpose of the present study was to analyze the management of dental extractions in patients affected by coagulation disorders in order to prevent bleeding intraoperative and postoperative complications. Subjects and Methods: This study included 17 patients with a diagnosis of a coagulation disorder, who had been subjected to a single or multiple dental extraction. Recombinant activated Factor VII was administered in those patients who were affected by a deficit of factor VII ranged between 10,5% and 21%. The other patients were treated locally with tranexamic acid. Results: A total of 50 teeth were extracted, 7 by surgical extraction and 43 by simple extraction. Of the 17 patients included 9 of them suffering from factor VII deficiency, 5 from factor V deficiency, 1 from Glanzmann's thrombasthenia and 2 from Haemophilia A. Pretreatment with recombinant activated factor VII was performed on a total of 8 patients with factor VII deficiency; the remaining 9 patients underwent tranexamic acid treatment. 1 hemorragic postoperative complication was observed. Conclusions: Surgical and no surgical extractions appear to be a safe procedure for patients affected by coagulation disorders when appropriate prophylaxis is adopted.

Diagnostics is believed to drive about 70% of medical interventions, but this may not be true for all demographics. With more than 30% of the African population living in extreme poverty ($1.9 per day - 2022); and healthcare costs competing unfavorably against unbridled access to antibiotics and herbal concoctions, especially in Sub-Saharan Africa, how do you convince such a people to choose diagnostics first? More importantly, how do you design a medical device targeted at meeting the diagnostic needs of this demographic? In developing diagnostic devices for such a market, what is worth sacrificing? How dire is the need for advanced technologies in devices developed for such a demographic? These are questions that remain unaddressed by the technological breakthroughs and current research in medical device development, especially for infectious disease diagnostics. The objective of this paper is to underscore critical concerns which must be considered in the bid to successfully design medical diagnostic devices for Africa and perhaps, other limited-resource settings. It is also written as a suggestive guidance document for researchers whose interest is in the development of infectious disease diagnostic platforms for rural Africa and similar limited-resource environments.

Aims Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3- dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) has been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. Main methods SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. Key findings No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. Significance The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

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.

Introduction. COVID-19 is a pathology caused by the SARS-CoV2 virus. The World Health Organization has reported more than 94 million cases and two million deaths worldwide. Objective: To describe the seroprevalence, spatial distribution, and clinical and sociodemographic variables of SARS-CoV2 in a community of the Colombian Amazon region. Methods. In December 2020, a cross-sectional observational study was carried out in a population located in the Colombian Amazon in the municipality of Mitú. Sociodemographic and clinical data were taken. Besides, 590 blood samples were taken, and an antibody detection was carried out with an ELISA and a recombinant protein N antigen of SARS-CoV2. Results. A seroprevalence of 57.6% was observed. The highest proportion of the infection is located in inter-municipal transport zones. The bivariate analysis did not show differences in the SARS-CoV2 infection rate concerning the variables sex, age-range, and the presence of comorbidities (P> 0.05). The bivariate and multivariate analysis showed that being symptomatic and presenting neurological manifestations of the upper respiratory tract are clinical variables associated with SARS-CoV2 infection (P <0.05). One of the causes of this virus's high spread in this community could be that 53.3% of the people were asymptomatic. Conclusions. Our data showed a high burden and transmission of SARS-CoV-2 in this indigenous community. This could be linked to cultural behaviors and the high infection rate in asymptomatic patients.

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.

The Golgi apparatus (GA) dysfunctions in Parkinson’s Disease (PD), neurodevelopmental disorders (NDDs), cancer, and organelle structural biology (OSB) can provide insights into therapeutic targets, gene therapy, and drug design. Primary defects and fragmentation within the GA are implicated in a wide range of neurodegenerative diseases. GA defects typically result in mislocation of proteins, accumulation of undegraded proteins, and impaired glycosylation of proteins. Inhibition of vesicular trafficking by α-synuclein (aSyn) may affect the dopamine-producing neurons and neuromodulators. GA regulates apoptosis during pathological mechanisms of neurological diseases and could provide new avenues in treatments through translation research. PD patients bearing the hereditary E46K disease mutation manifest the clinical picture of parkinsonism. How do we provide high resolution nanoimages of the GA during disease to capture dysfunction? Could we visualize the aSyn traffic jam between vesicles in the organelles ER and GA? OSB is emerging as a field as more technology advances and is more accessible. Structural studies of the GA will advance the field of neurological disease forward with an in depth understanding of dysfunction, fragmentation, and defects. Discoveries of the GA in PD, NDDs, and cancer would break new ground and provide translational medicine data of these diseases. Future research could be visualizing high angle annular dark field-STEM (HAADF-STEM) tomograms, cryogenic electron tomography (cryo-ET), multiplex correlative light and electron microscopy (cryo-CLEM), nanobody-assisted tissue immunostaining for volumetric EM (NATIVE) and using soft X-ray tomography (SXT) and computational reconstruction of the GA.

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.

An evaluation of emerging issues in One Health (OH) in Sub-Saharan Africa was undertaken to map the existing OH initiatives in Sub-Saharan African (SSA) countries. Desk review, expert opinions survey, limited interviews and wider consultations with selected OH stakeholders were conducted. The strengths, weaknesses, opportunities and threats to OH initiatives were identified. OH influence, interest and impacts were evaluated. One Health is transiting from multidisciplinary to transdisciplinary concepts and OH viewpoint should move from ‘proxy for zoonoses’, to include issues of climate change, nutrition and food safety, social sciences, geography, policy and planning, economics, welfare and well-being, antimicrobial resistance (AMR), vector-borne diseases, toxicosis and pesticides issues. While the identified major strengths should be boosted, the weaknesses should be addressed.OH Networks in SSA were spatially and temporally spread across SSA and stakeholders were classified as key, latent, marginal and OH defenders. Imbalance in stakeholders’ representation led to hesitation in buying-in from stakeholders who are outside the main networks. Theory of change, monitoring and evaluation frameworks, and tools to standardized evaluation of OH policies is needed for sustained future of OH and the future OH engagement should be outputs and outcomes-driven and not activity-driven.National roadmap for OH implementation and institutionalization is necessary and proofs of concepts in OH should be verified and scaled-up. Dependence on external funding is unsustainable and must be addressed. Necessary policy and legal instrument to support OH nationally and sub-nationally should be implemented taking cognizance of contemporary issues like urbanization, endemic poverty and other emerging issues. Utilizing current technologies and OH approach to address ongoing pandemic of COVID-19 and other emerging diseases is desirable. Finally, OH implementation should be anticipatory and not reactive to significantly benefit budgeting and contain disease outbreaks in animal sources before the risk of spillover to human can be envisaged.

Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they caused requires the sampling of body fluids (blood, lymph, peritoneal fluid, cerebrospinal fluid, etc.) or organ biopsies (bone marrow, spleen, etc.), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, Google. The information of each selected article (n=333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on Human African Trypanosomiasis and a the absence on animal Trypanosomiasis. Among the collected data high heterogeneity in terms of the I² statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigen for leishmaniasis and Chagas disease. Data on conjunctival swab can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristle showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristle for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here we report that among eighteen representatives of the multifunctional S100 protein family only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent Kd values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1-0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatic analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect efficacy of anti-TNF treatment in various diseases.

BACKGROUND Krukenberg tumor is a rare metastatic tumor of the ovary with characteristic histopathological features known as signet-ring cells. It usually presents in women around 45 years of age, however, we present an uncommon case in a 38-year-old pregnant woman. We report this case because of the unusual findings, the uncommon presentation in this younger age bracket, its diagnostic challenge, and poor prognosis. CASE PRESENTATION We describe an unusual case of a young woman with a history of painful vaginal bleeding at 13 weeks of pregnancy and treated for abruptio placentae. In her routine prenatal visit at week 20 of pregnancy, she was found to have a uterine fundus greater than her gestational age and referred to the hospital to discard polyhydramnios. At her admission a pelvic ultrasound was performed with normal findings of a 25 weeks pregnancy, also showing bilateral enlarged ovaries with heterogeneous echogenicity. The MRI showed a left tumoral lesion with dimensions of 22.1 x 13.6 x 16.3 cm, with lobulated regular contours with displacement of peripheral structures and mild compression of the bladder, the left ureter, and the inferior vena cava. The lesion was heterogeneous with irregular borders. The patient was programmed for a cesarean section; during the operation, the abdominal cavity showed bilateral tumors compatible with MRI findings, the ovarian tumors were sent to pathology and the results showed poorly differentiated mucinous adenocarcinoma (WHO III) with extensive signet-ring cells, an indicative of Krukenberg tumor. CONCLUSION: The case presented is rare due to its presentation in a pregnant woman without identifiable risk factors for gastric cancer. The incidental finding suggests the pregnancy masked the clinical presentation of gastric cancer, and the rapid deterioration of the patient is consistent with the aggressiveness described in the literature. The limited descriptions of this neoplasm in our country and the torpid evolution of this case highlight the importance of further studies of this cancer in Mexico.

The sustainable development goals(SDG) of the UNO would be difficult to achieve without prevention of metabolic diseases and other non-communicable diseases (NCDs). Western diet and lifestyle, which are major risk factors of NCDs, are known to cause oxidative stress and decrease in production of molecular hydrogen in the intestines which leads to a decline in endogenous antioxidant status in the body, leading to increase in systemic inflammation. Many experts consider molecular hydrogen as a potential nutrient, which may be administered as gas in the body. There are gaps in the knowledge about the role molecular hydrogen plays, in the treatment of metabolic diseases and other NCDs This review aims to discuss the role of hydrogen in the pathogenesis and prevention of NCDs. Molecular hydrogen (H2) has been studied extensively as a therapeutic gas, with an estimated 2000 publications to date, exploring its potential therapeutic use in 170 disease models across every organ in the mammalian body. Hydrogen therapy can be administered through several methods, such as H2 inhalation, dissolving H2 gas in water to make hydrogen-rich water (HRW) for oral consumption or topical application, or hydrogen-rich saline. The exact mechanism of action of molecular hydrogen is not known but it is in itself a potential antioxidant that can also inhibit hydroxyl and nitrosyl radicals in the cells and tissues. Hydrogen is known to cause a marked decline in oxidative stress, and inflammation that are crucial in the pathogenesis of NCDs. Hydrogen therapy has been found protective against NCDs, including, metabolic diseases, cardiovascular diseases (CVDs), neurodegenerative diseases, chronic kidney disease, cancer and chronic lung diseases.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

Ticks drive a wide diversity of pathogens to a great variety of hosts, including humans. We conducted a tick surveillance study in northwestern Spain between 2014 and 2019. Ticks were removed from people and were identified. Tick numbers, species, development stages, evolution over time, seasonal and geographical distribution, and epidemiological characteristics of people bitten by ticks were studied. We collected ticks from 8143 people. Nymphs of Ixodes ricinus were the most frequently collected. Rhipicephalus bursa, Rhipicephalus sanguineus sensu lato (s.l), Hyalomma marginatum, Hyalomma lusitanicum, Dermacentor marginatus, Dermacentor reticulatus and Haemaphysalis punctata were also found, with adults as the main stage. Hyalomma spp. and R. bursa have been progressively increasing over time. Although bites occurred throughout the year, the highest number of incidents were reported from April to July. The distribution patterns of the tick species were different between the north and the south of the region, which was related to cases detected in humans of the pathogens they carried. Adult men were more likely to be bitten by ticks than women. Ticks were most frequently removed from adults from the lower limbs, while for children they were mainly attached to the head. Epidemiological surveillance is essential given the increase in tick populations in recent years, mainly of species potentially carrying pathogens causing emerging diseases in Spain, such as the Crimean Congo Hemorraghic Fever (CCFH).

A case report of the diagnosis of Long Term Sequelae of West Nile Neuroinvasive Disease in a patient with 9 years history. Empirical data of symptoms and test reports has been presented and based on the available data likely pathogenesis of the disease has been discussed. The empirical data has been compared to the published literature to reach a highly confident diagnosis.

Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of inflammatory bowel disease (IBD) including Crohn’s disease. Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation. This review focuses on the role of UPR in the pathogenesis in IBD from an immunologic perspective. The roles of macrophage and mesenchymal cells in the UPR from in vitro and in vivo animal models are discussed. The links between ER stress and other signaling pathways such as senescence and autophagy are introduced. Recent advances in the understanding of the epigenetic regulation of UPR signaling are also updated here. The future directions of development of the UPR research and therapeutic strategies to manipulate ER stress levels are also reviewed.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering.’

Vitamin D plays an important role in maintaining healthy mineralized skeleton. It is also consid-ered an immunomodulatory agent that regulate the innate and adaptive immune systems. Multi-ple observational studies have demonstrated the association between low level of serum 25-hydroxyvitamin D [25(OH)D] and presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies and oste-oarthritis (OA). Nevertheless, the specific benefits of vitamin D supplement for treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for improvement of disease ac-tivity of RA, SLE and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently from others since inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain serum 25(OH)D level at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis and fracture, and possibly 40 – 60 ng/mL (100 – 150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

Probiotics are namely yeast and bacteria which are regarded as dietary supplements and food. Many probiotics are being commonly used now, the most frequently used, lactic acid bacteria are called Lactobacillus and Bifidobacterium. Many of the diseases associated with GIT are related to microbiota found in GIT, an imbalance of which causes gastrointestinal diseases. Probiotics, in light of scientific literature, are thought to play an important role in relieving symptoms of many diseases associated with GIT, i.e. beneficially regulating the microbiota composition. In the present review, we aimed to highlight the main considerations for main probiotic formulations to date. This study reviews the role of different probiotic formulations introduced so far in treating GI diseases in cohort ageing ≤18 years. We searched PubMed and Clinicaltrials.gov without any restrictions. This study comprises the descriptive and comparative analysis between Single-organism and Composite probiotics. These GI diseases include NEC, FAP, AGE, Acute Diarrhea, Ulcerative Colitis and etc. The results have been categorized according to title and outcomes. The positive outcomes emphasize the drug’s effectiveness in improving health and the negative outcome elaborates on the adverse effects the drug may have shown. Conclusively, discussed practices will assist in reducing GI disorders and strengthening the gut. Further insight into the various gut microbes and microbiomes with specific demographic is recommended.

Heat shock proteins (Hsps) are highly conserved molecules that are constitutively expressed and upregulated in response to physiological stress conditions. These immunogenic chaperones can have essential functions in fungi, particularly in dimorphic pathogens. Histoplasma capsulatum and Paracoccidioides species are dimorphic fungi that are the causative agents of histoplasmosis and paracoccidioidomycosis, respectively, which are systemic mycoses with significant rates of morbidity and mortality. Current treatment consists of long-term antifungal agents, and there is an urgent need for new therapeutic approaches with higher efficacy, lower toxicity, better biodistribution and improved selectivity. We engineered an immunoglobulin G1 (IgG1) isotype chimeric mouse-human monoclonal antibody, titled ch-MAb 4E12, from the parental IgG2a MAb 4E12, a monoclonal antibody to H. capsulatum Hsp60 that is protective in experimental histoplasmosis and paracoccidioidomycosis models elicited by H. capsulatum var. capsulatum and Paracoccidioides lutzii, respectively. The ch-MAb 4E12 increased phagolysosomal fusion and enhanced the yeasts uptake by PMA differentiated human THP1 macrophage cells in vitro. At low concentrations, the chimeric antibody significantly reduced the pulmonary and splenic fungal burden compared to an irrelevant antibody or no treatment. These results are the first to show that a chimeric mouse-human antibody can modify infection caused by dimorphic fungi.

Background: Nutritional rickets is still considered as a global health problem especially in low-resource countries and immigrant societies of developed countries. Generalized skeletal deformities including angular knee deformities as genu varum and genu valgum are prominent features of nutritional rickets. Angular knee deformities can cause gait difficulties. However, the true remodelling potential of the healed knee deformities is largely unknown to the pediatric and orthopedic community. Aims: The primary objective of this study protocol is to investigate the natural history of disease in regard to the remodelling potential of angular knee deformities in children and adolescents with healed nutritional rickets. And determine the potential patient- and deformity-related factors that are associated with a favorable deformity remodelling as age and sex of patients and type, severity, laterality of deformities etc. Methods: This will be a prospective observational analytical cohort natural history of disease study. A minimum of at least 140 knees with healed nutritional rickets and angular knee deformities will be observed at regular three-monthly intervals over a period of at least one year. We will report two outcome variables namely; clinical and radiological tibio-femoral angle. And independent patient and deformity-related variables as age, sex, deformity type, severity and laterality. Inferential statistics namely bivariate and multivariate analysis will be employed accordingly to identify the relation between outcome variables and the different independent variables. Ethics and dissemination: This protocol study has been approved by the institutional research ethics committee. Results will be presented at conferences and submitted to relevant international and society publications. Authors will also communicate the results to their scholarly networks and post them on scholarly networking sites. Conclusions: This study has the potential for improving the decision-making process as to which patients deserve conservative treatment and which deserve surgical deformity correction. Results are expected to have an impact on the clinical practice of pediatricians, orthopedic surgeons and family physicians alike.

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.

The rising incidence of complex illnesses and their costs have revolutionized basic research, patient management, and societal needs. Between 70 to 90% of the risk of developing a disease is due to the air we breathe, the water we drink, and the surroundings in which we work and live. Visibly polluted, infectious or not, the fact remains that we are more than ever exposed to environmental risks. Air pollution is the fourth most prevalent deadly risk factor worldwide and by far the leading risk factor for hundreds of diseases, including respiratory infections, inflammatory illness, and cancer. Thus, an unhealthy environment can be considered as a pandemic, affecting 280 million people and claiming 12 million deaths every year. Although critical for identifying of the people at risk, the causal environment components (pollutants and/or the microbiome), and the affected physiological mechanisms are not well understood. Herein, we consider the dysregulation of macroautophagy (hereafter referred to as ‘autophagy’), as the mechanism at the heart of an immediate response to environmental stress. We discuss the missing link between the autophagy gene variations, and the exposome in the susceptibility, prognosis, and management of complex diseases when embracing personalized medicine.

Foliar fungal diseases in tomatoes include early blight (Alternaria linariae), Septoria leaf spot (Septoria lycopersici), and late blight (Phytophthora infestans) which is oomycetes. These are one of the significant production constraints in tomatoes. We describe the etiology, host range, distribution, symptoms, and disease cycle to understand the biology followed by management practices emphasizing the resistance breeding approach for these diseases. In crop improvement efforts, we provide an analytical review, including conventional and molecular methods for improving this disease resistance. Modern breeding tools, including genomics, genetic transformation, and genome editing, can be used to improve these traits. There is a good possibility of using these tools in the future to improve these traits.

Adverse childhood experiences are known to program children for disrupted biological cycles, premature aging, microbiome dysbiosis, immune-inflammatory misregulation, and chronic disease multimorbidity. To date, the microbiome has not been a major focus of deprogramming efforts despite its emerging role in every aspect of ACE-related dysbiosis and dysfunction. This article examines: 1) the utility of incorporating microorganism-based, anti-aging approaches to combat ACE-programmed chronic diseases (also known as noncommunicable diseases and conditions, NCDs) and 2) microbiome regulation of core systems biology cycles that affect NCD comorbid risk. In this review microbiota influence over three key cyclic rhythms (circadian cycles, the sleep cycle, and the lifespan/longevity cycle) as well as tissue inflammation and oxidative stress are discussed as an opportunity to deprogram ACE-driven chronic disorders. Microbiota, particularly those in the gut, have been shown to affect host-microbe interactions regulating the circadian clock, sleep quality, as well as immune function/senescence and regulation of tissue inflammation. The microimmunosome is one of several systems biology targets of gut microbiota regulation. Furthermore, correcting misregulated inflammation and increased oxidative stress is key to protecting telomere length and lifespan/longevity and extending what has become known as the healthspan. This review article concludes that to reverse the tragedy of ACE-programmed NCDs and premature aging, managing the human holobiont microbiome should become a routine part of healthcare and preventative medicine across the life course.

Systemic autoimmune diseases (SAIDs) such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA) are fully related to the unregulated innate and adaptive immune systems involved in their pathogenesis. They have similar pathogenic characteristics including the interferon signature, loss of tolerance to self-nuclear antigens, and enhanced tissue damage like necrosis and fibrosis. Glucocorticoids and immunosuppressants, which have limited specificity and are prone to tolerance, are used as the first-line therapy. A plethora of novel immunotherapies have been developed including monoclonal and bispecific antibodies, and other biological agents to target cellular and soluble factors involved in disease pathogenesis such as B cells, co-stimulatory molecules, cytokines or their receptors, and signalling molecules. Many of these have shown encouraging results in clinical trials. CAR-T cell therapy is considered the most promising technique for curing autoimmune diseases, with recent successes in the treatment of SLE and SSc.

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.

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.

Anthocyanins are among the best-known phenolic compounds and possess remarkable biological activities, including antioxidant, anti-inflammatory, anticancer, and antidiabetic effects. Despite their therapeutic benefits, they are not widely used as health-promoting agents due to their insta-bility, low absorption, and thus, low bioavailability and rapid metabolism in the human body. Recent research suggests that the application of nanotechnology could increase their solubility and/or bioavailability, and thus, their biological potential. Therefore, in this review, we decided to provide, for the first time, a comprehensive overview of in vitro and in vivo studies on nanocarriers used as delivery systems of anthocyanins, and their aglycones, i.e., anthocyanidins alone or com-bined with conventional drugs to the treatment or management of chronic diseases.

Brucellosis infection induces fever, chills, sweats, headache, myalgia, arthralgia, anorexia, fa-tigue, and mood disorders. In mice, it causes a rise in IL-6, TNF-, and IFN-; and reduces sero-tonin and dopamine levels in hippocampus. There is loss in muscle strength and equilibrium and increased anxiety and hopelessness. Imipramine (ImiP) is a tricyclic antidepressant that increases the capacity of macrophages to destroy intracellular microorganisms in vivo. The effect of ImiP was evaluated in Balb/c mice infected with Brucella abortus 2308. Serum levels were determined in IFN-, IL-6, TNF-, IL-12, MCP-1, and IL-10 by FACS; the bacterial count in the spleen, by CFU; the serotonin concentration in the hippocampus, by HPLC; and strength, equilibrium, and mood by behavioral tests. Our results showed that infected vs. control mice had a significant rise in lev-els of IFN-, IL-6, TNF-, and IL-12 with a low IFN-/IL-6 ratio, elevated bacterial-counts, alter-ations in serotonin concentration at hippocampus, and decreased muscular strength, equilibrium, and mood. Infected mice treated with ImiP vs. infected mice showed: 1) improved mood; 2) in-creased hippocampal serotonin availability, splenic dendritic cells, and macrophage phagocytic activity; and 3) upturn inflammation and reduced CFU ability. Our results support that ImiP fa-vors positive outcomes in subjects handling Brucella infections likely by improving psychoim-mune resilience.

Bacteriophages are viruses obligately infecting bacteria. They constitute the most numerous categories of biological forms populating our biosphere and are highly diverse and capable of infecting almost all bacteria. Phages make use of their host cell molecular machinery to express their own genes as they lack the ability to independently reproduce themselves. The inimitable characteristics of bacteriophages have enabled them to become propitious tools in biotechnology and genetic engineering. Phages show no tropism for mammalian cells but however, can be easily modified to present targeting ligands on their surface as coat protein fusions without any negative impacts on phage structure. These displayed ligands thereupon guide the recognition, interaction, and internalization of the phage into cells wherein efficiency of transfection is directly influenced by the copy number of the ligands used for targeting. Engineered phages are more efficacious for transgene delivery and gene expression in cancer cells when compared to other non-viral gene transfer strategies and are therefore being employed in developing cancer vaccines. The high level of stability as well as resistance of bacteriophages to various environmental conditions have enabled the development of virus-like particles (VLPs) capable of successful deliverance of several therapeutic drug cargos into tumors by selective targeting. Phage display technology has been used in therapy of Alzheimer’s disease and drug delivery into the brain. Exogenous peptides fused into the coat protein of phages enables the display of these peptides on the phage surface to generate combinatorial phage that facilitates their rapid separation using their ability to bind to a specific molecular target. Phage therapy has been shown to be safe in clinical settings when compared to antibiotics as it shows no adverse anaphylaxis nor adverse effects such as the emergence of multi-drug resistant bacteria. This review provides intriguing details of the use of natural and engineered phages in the therapy of diseases such as cancer, bacterial infections, bovine mastitis and dementia in addition to the use of CRISPR-Cas9 technology in generating genetically engineered phages. Further, the use of phage display technology in generating monoclonal antibodies against various human diseases is elucidated.

Neurodegenerative protein conformational diseases are characterized by misfolding and aggregation of metastable proteins encoded within the host genome. The host is also home to thousands of proteins encoded within exogenous genomes harbored by bacteria, fungi, and viruses. Yet, their contributions to host protein-folding homeostasis, or proteostasis, remain elusive. Recent studies, including our previous work, suggest that bacterial products contribute to toxic aggregation of endogenous host proteins. We refer to these products as bacteria-derived protein aggregates (BDPAs). Furthermore, antibiotics were recently associated with increased risk for neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis  possibly by virtue of altering the composition of the human gut microbiota. Other studies have shown a negative correlation between disease progression and antibiotic administration, supporting their protective effect against neurodegenerative diseases. These contradicting studies emphasize the complexity of the human gut microbiota, the gut-brain axis, and the effect of antibiotics. Here, we further our understanding of bacteria’s effect on host protein folding using the model Caenorhabditis elegans. We employed genetic and chemical methods to demonstrate that the proteotoxic effect of bacteria on host protein folding correlates with the presence of BDPAs. Furthermore, the abundance and proteotoxicity of BDPAs are influenced by gentamicin, an aminoglycoside antibiotic that induces protein misfolding, and by butyrate, a short-chain fatty acid that we previously found to affect host protein aggregation and the associated toxicity. Collectively, these results increase our understanding of host-bacteria interactions in the context of protein conformational diseases.

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).

Endocytosis in mammalian cells is a fundamental cellular machinery that regulates vital physiological processes, such as the absorption of metabolites, release of neurotransmitters, hormonal secretion, cellular defense, and delivery of biomolecules across the plasma membrane. A remarkable characteristic of the endocytic machinery is the sequential assembly of the complex proteins at the plasma membrane followed by transportation of various cargo molecules to different cellular compartments. In all eukaryotic cells, functional characterization of endocytic pathways is based on dynamics of the protein complex modules. To coordinate the assembly and functions of the numerous parts of the endocytic machinery, the endocytic proteins interact significantly within and between the modules. Clathrin dependent and independent endocytosis, caveolar pathway and receptor mediated endocytosis have been attributed in a greater variety of physiological and pathophysiological roles such as, autophagy, metabolism, cell division, apoptosis, cellular defense, and intestinal permeabilization. Notably, any defect or alteration in the endocytic machinery results in the development of pathological consequences associated with human diseases such as cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. In this review, an in-depth endeavor has made to illustrate the process of endocytosis, and associated mechanisms describing pathological manifestation associated with dysregulated endocytosis machinery.

According to the eminent scholar, philosopher, and physician Avicenna, "the doctor has three tools: the word, the plant, the knife." The plant kingdom is recognized as humanity's earliest and most ancient healing source, employed for the management and prevention of illnesses. Tracing back through history, the most ancient documented proof of plants' utilization in medicine dates back to a Sumerian clay slab discovered in Nagpur roughly 5000 years ago. This artifact included a compilation of twelve medicinal recipes that involved over 250 diverse plant species. Sumerian healers extracted powders and infusions from plant roots and stems, while also crediting healing properties to pears and figs. Additionally, they utilized dried and ground young shoots of willow and plum trees, pine and fir needles as a component in compresses and poultices. Often, powders from animal and mineral sources were blended with those extracted from dried and crushed plants. Notably, in addition to water, wine and beer served as solvents. Thus, at least 80 centuries ago, people utilized the most uncomplicated medicinal plant-based preparations for treatment [1]. The "Pen T'Sao," an ancient Chinese text on roots and herbs, authored by Emperor Shen Nung approximately 2500 BC, contains descriptions of 900 medicaments (comprising dried components of medicinal plants). Several of these substances are still in use today, including Rhei rhisoma, camphor, Theae folium, Podophyllum, great yellow gentian, ginseng, datura, cinnamon bark, and ephedra [2]. Regarding Kazakh folk medicine, an area that has yet to be fully explicated and substantiated, it can be stated that the traditional medicinal knowledge of the Kazakh people transcends the mere treatment of ailments and rests on robust theoretical underpinnings. Oteiboydak Tleukabyluly (1388-1478), an astute healer and prominent figure in Kazakh folk medicine during the 15th century, comprehensively explicated the secrets of the healing art in his medical and ethnographic work "Medical Narrative," which he composed between 1466 and 1473 at the behest of az-Zhanibek Khan, who held him in high esteem as a great healer. This medical encyclopedia delineates the functions of various organs of the human body and provides a catalogue of the primary diseases associated with them. Furthermore, it includes a meticulous description of the methods used in traditional medicine at present, such as setting bones, listening to the pulse, and incantations. Through practical experimentation and experimentation conducted in the steppe laboratory, the healer formulated a total of 1,108 different medicinal compounds, of which 858 were derived from medicinal plants, 318 were extracted from animal organs, and roughly 60 were sourced from metals. The moniker "Teacher without a teacher" was bestowed on Oteiboydak Tleukabylov, who discovered methods for treating 1,050 different diseases [3]. At present, the employment of phytotherapy has gained widespread acceptance on a global scale. According to the World Health Organization's (WHO) global review of national policies concerning traditional, complementary, and alternative medicine, as well as the regulation of herbal medicines, there is an evident growth in the European and Asian market for herbal medicines [4]. Kazakhstan boasts a natural flora of over 6,000 plant species [5]. The exact number of medicinal plant species present in Kazakhstan remains uncertain, as the list continues to expand annually. More than 150 plant species have been employed in both official and folk medicine for various ailments. This review focuses on a selection of medicinal plants growing within the territory of the Republic of Kazakhstan that have traditionally been used to alleviate skin diseases. In conducting this study (2010-2023), emphasis was placed on the plants' phytochemical composition, with a particular focus on the principal components responsible for their therapeutic effects against inflammatory skin conditions such as dermatitis, atopic dermatitis, and eczema.

Purpose: Determine the internal consistency and reproducibility test-retest of the Barrier Scale for Cardiac Rehabilitation (BSCR) in Colombian population. Methods: 190 patients (67% men, average age = 65 ± 12 years) completed the scale in two moments, with an average of eight days between applications. Cronbach's Alpha and Intraclass Correlation (ICC) coefficients were calculated. Results: The internal consistency of the Colombian version of the BSCR was good (Cronbach's alpha = 0.85). The ICC of the instrument was 0.69 (95% CI 0.61-0.76), 0.78 (95% CI 0.71-0.84) when used in the interview type, and 0.47 (95% CI 0, 21-0.67) when it was self-completing. Conclusions: The EBRC has an acceptable reliability in the Colombian population, however, its reproducibility decreases when it is self-directed. Identifying barriers using this scale will allow developing strategies to increase participation and adherence to cardiac rehabilitation programs focused on the real needs of patients.

Chronic diseases are characterised by cell’s autophagy and proteins disarrangement resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypo-haemoglobinaemia couses worse prognosis independentely of the principal disease. Currently, the cornerstone of therapy of anaemia is iron supplementation, with or without erythropoietin for the stimulation of hematopoiesis. However, treatment strategies should incorporate the addition of heme, the principal biochemical constituent of haemoglobin. Heme synthesis follows a complex biochemical pathway. The limiting step of heme synthesis is D-ALA availability which, for its synthesis, requires Glycine and Succinil-CoA. Consequently, treatment of anaemia should not be based only on iron availability, but also on the availability of the molecules fundamental for heme synthesis. Therefore, an adequate clinical therapeutic strategy should integrate the standard iron infusion and the supply of essential amino acids and vitamins involved in the heme synthesis. We report preliminary data in selected elderly anaemic patients with congestive heart failure (CHF) and catabolic disarrangement, who, in addition to standard iron therapy, received personalized therapy with essential-AAs and vitamins involved in the maintenance of heme. Notably, such individualized therapy resulted in a significant increase in the serum concentration of haemoglobin after 30 days of treatment compared to standard iron therapy.

The article is devoted to the problem of autoimmune diseases provocation by coronavirus infection and the role of molecular mimicry in this phenomenon. SARS-CoV-2 can disguise its proteins as human ones in order to avoid immune attack. A bioinformatics analysis of the probable pentapeptide sharing between human autoantigens of endocrinocytes and SARS-CoV-2 spike protein, membrane protein and nucleocapsid protein was performed. Antigen mimicry between S-proteins of all other known human Coronaviruses and typical target autoantigens of endocrinocytes was also explored. Six human-identical regions were found in the SARS-CoV-2 membrane and nucleocapsid proteins, all of them in their immunodominant epitopes. All shared epitopes belong to antigens of endocrine cells commonly targeted during autoimmune endocrinopathies. Moreover, samples of the pituitary, adrenal and thyroid from patients who died from coronovirus infection (COVID-19) were studied morphologically using histochemical methods. A high frequency of SARS-CoV-2 caused inflammation of the studied endocrine organs was found in patients who died from severe COVID-19. At the same time, the abundant expression of virus antigens by the cells of the adenohypophysis was combined with the complete absence of its expression by the cells of the neurohypophysis. SARS-CoV-2 infected cells apparently perished by non-apoptotic pathway. The foci of lesions in endocrine organs contained abundant lymphocytic infiltrates which may witness for the impact of autoimmune processes. The facts revealed emphasize the need of endocrinological diagnostic alertness of a physician while observing patients with post-vaccination and post-COVID-19 health disorders. [3 figures, 6 tables, bibliography: 45 references].

Periodontal diseases and Thalassemia Major (TM), which are two chronic inflammatory diseases, are associated with increased levels of proinflammatory cytokines in bio-fluids. Interleukin (IL)-6 and IL-8 have been identified as potent proinflammatory biomarkers in periodontal diseases as well as in patients with β-thalassemia (TM-β). This suggests that patients with TM-β and gingival inflammation have two chronic inflammatory conditions, each of which may affect the other. The objective of this pioneer research was to evaluate the effect of oral hygiene maintenance and care on serum levels of IL-6 and IL-8. 31 participants selected after screening and were given Non-surgical periodontal therapy(NSPT). IL-6 and IL-8 were evaluated by enzyme linked immunohistochemistry assay (ELISA) at baseline and compared at 6 weeks after NSPT. Statistical analysis was done with SPSS v23. The comparison from the baseline to 6-weeks follow-up for both IL-6 and IL-8 was done using Wilcoxon Signed rank test. The descriptive statistics are represented as median and inter quartile range (IQR). Highly significant improvement (p-&lt;0.000) was found for IL-6 and IL-8 when compared at 6 weeks from baseline. Results provide a gateway to new modality in lowering systemic burden of the disease, thereby reducing morbidity, via local measures or oral care.

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.

Malassezia are lipid-dependent basidiomycetous yeast of the normal skin microbiome, although Malassezia DNA has been recently detected in other body sites and has been associated with cer-tain chronic human diseases. This new perspective raises many questions. Are these yeasts truly present in the investigated body site or were they contaminated by other body sites, adjacent or not? Does this DNA contamination come from living or dead yeast? If these yeasts are alive, do they belong to the resident mycobiota or are they transient colonizers which are not permanently established within these niches? And, finally, are these yeasts associated with certain chronic diseases or not? In an attempt to shed light on this knowledge gap, we critically re-viewed the 31 published studies focusing on the association of Malassezia spp. with chronic human diseases, including psoriasis, atopic dermatitis (AD), chronic rhinosinusitis (CRS), asthma, cystic fibrosis (CF), HIV infection, inflammatory bowel disease (IBD), colorectal cancer (CRC), and neurodegenerative diseases.

Non-alcoholic fatty liver disease (NAFLD) continues to rise and has become the most common cause of chronic liver disease among all ages and ethnicities. Metabolic disorders such as obesity and insulin resistance are closely associated with sarcopenia and NAFLD. Sarcopenic obesity is a clinical disorder characterized by the simultaneous loss of skeletal muscle and gain of adipose tissue. It is associated with worse outcomes in individuals with NAFLD. It is projected that NAFLD and sarcopenia will rise as the prevalence of obesity continues to increase at an unparallel rate. Recently, sarcopenia and sarcopenic obesity have gained considerable interest, but we still lack a well-defined definition and a management approach. Therefore, it is imperative to continue shining the light on this topic and better understand the underlying mechanism as well as treatment options. In this review article, we aimed to address the pathophysiology, impact, and outcomes of sarcopenic obesity on NAFLD.

Background: Membranous glomerulonephritis (MGN) is one of the most common causes of nephrotic syndrome in non-diabetic adults, accounting for up to one-third of biopsy diagnostics in some regions. A watchful waiting strategy has been adopted to accurately assess the success of MGN. In this study, we predict prognostic risk factors for primary MGN patients for effective intervention and prognosis. Materials and Methods: This is a retrospective study design involving 125 biopsy-proven MGN subjects on follow-up from January 2012 to October 2019 in Hospital Serdang and Hospital Kuala Lumpur, Malaysia. Result and Conclusion: After the median follow-up of 36 (15.0-57.0) months, 26 (20.8%) consisting of 17 (13.6%) primary MGN and 9 (7.2%) secondary MGN subjects achieved complete remission while 17 (13.6%) and 10 (8.0%) of primary and secondary MGN subjects respectively achieved spontaneous remission. Subjects with nephrotic range proteinuria have 2.917 odds more at risk of primary MGN while subjects with hypertension have 2.417 odds risk of primary MGN compared to those with no hypertension at presentation. Multiple logistic regression models retained only factors directly associated with MGN with only nephrotic range proteinuria associated with primary MGN. Those with nephrotic range proteinuria were 3.04 times the odds of primary MGN when compared with those without nephrotic syndrome (95% C. I = 1.089, 8.472). The nephrotic syndrome could be used to determine the prognosis in patients with primary MGN especially those at risk of end-stage kidney disease.

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.