Urban environments are frequently populated by different insect species. Some of them are very beautiful and appealing to the people around them, such as ladybugs and butterflies, while some others are molestants and even dangerous to public health. Mosquitoes often inhabit urban environments by staying close to their hosts (humans, birds, etc.), while phytophagous species such as stinkbugs find hosts among ornamental plants and shelters during the winter around humans. This article describes the early discoveries and distribution of two invasive mosquito species, Aedes albopictus, and Ae. japonicus (Diptera: Culicidae), which were recorded in Serbia in 2009 and 2018, respectively. Both species are important for human health, due to their nuisance behavior and because they are vectors of many viruses. On the other hand, in 2015 and 2008, two invasive stinkbug species, Halyomorpha halys and Nezara viridula (Hemiptera: Pentatomidae) were observed to spread, respectively. Since then, these species have disrupted human population in urban areas, but also damaged a range of crops and ornamental plants. All species have been monitored in the territory of Serbia, and establishment and distribution have been confirmed so far.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts and provides data suggesting that the topical administration of melatonin as eye drops is a real possibility. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

Background: Asthma is a widespread chronic respiratory disease that poses a significant public health challenge. The current study investigated the associations between air pollution and asthma severity among individuals residing near the Sohar industrial port (SIP) in Oman. Despite the presence of multiple major industrial complexes in Oman, limited knowledge regarding their impact on respiratory health is accredited. Hence, the primary objective of this study is to offer valuable insights into the respiratory health consequences of industrial air pollution in Al Batinah North. Methods: The state health clinics' records for patient visits related to asthma were collected for the timeframe spanning 2014 to 2022. Exposure was defined as the distance from SIP, Majan Industerial Area (MIA) and Sohar Industerial Zone (SIZ) to determine high, intermediate, and low exposure zones (12 km, respectively). Exposure effect modifications by age, gender, and smoking status were also examined. Results: The conducted cross-sectional study of 410 patients (46.1% males and 53.9% females) living in over 17 areas around SIP revealed that 73.2% of asthmatics were under 50 years old, with severity significantly associated with closeness to the port. Risk ratios were estimated to be (RR:2.42; CI95%: 1.01–5.78), (RR:1.91; CI95%: 1.01–3.6), and (RR:1.68; CI95%: 0.92–3.09) for SIP, MIP and SIZ areas, respectively, compared to the control area. Falaj Al Qabail (6.4 km) and Majees (6 km) had the highest number of asthma patients (N. 69 and N. 72), and highest percentages of severe asthma cases among these patients (28% and 24%) with significant risk ratios (RR:2.97; CI95%: 1.19–7.45 and RR:2.55; CI95%: 1.00–6.48), correspondingly. Moreover, severe asthma prevalence peaked in the 25-50 age group (RR:2.05; CI95%: 1.26–3.33), and this linkage between asthma and age was much more pronounced in males than females. Smoking and exposure to certain contaminant (dust and smoke) increased also the risk of severe asthma symptoms, but their effects were less important in the high risk zone, suggesting much more important risk factor. A neural network model accurately predicted asthma risk (94.8% accuracy), with proximity to Sohar Industrial Port as the most influential predictor. Conclusion: The study highlights the High asthma burden near Sohar Industrial Port, linked to port proximity and smoking and wind direction as major risk factors. These findings inform vital public health policies to reduce air pollution and improve respiratory health in the region, prompting national policy review.

Opossums, native to the Americas, are unique marsupials with over 100 species. The Common Opossum and Virginia Opossum are notable species. They are nocturnal, omnivorous, and adapt to various habitats. Their reproduction involves a short gestation and marsupial pouch development. Despite their ecological benefits like seed dispersal and insect control, their proximity to human habitats exposes them to pathogens, posing public health risks. These include protozoa, helminths, and arthropods that can spread zoonotic parasites and vector-borne diseases. The marsupial immune system, including opossums, is complex, rivaling eutherian mammals. Key immune genes were identified in the grey short-tailed opossum genome. CD1 protein and VpreB surrogate light chain were also found. Marsupials are proposed as ideal models for studying developmental immunology. A West Indian opossum (Didelphis marsupialis) was found and examined. Blood tests revealed abnormalities, including a low white blood cell count and signs of anemia. The results contribute to understanding the species’ health and adaptability in the wild.

This review article focuses on the role of Artificial Intelligence (AI) in transforming healthcare in Africa, specifically in combatting infectious diseases, neglected tropical diseases (NTDs), and antimicrobial resistance. We provide a comprehensive overview of the significance of AI in the healthcare industry, highlighting its urgency and importance in addressing these specific health challenges in Africa. We begin by discussing the role of AI in infectious disease surveillance and outbreak detection. We explore how AI technology can be employed for real-time tracking and prediction of outbreaks, providing examples of successful AI applications in infectious disease surveillance within the African context.Next, we examine the potential of AI-enabled diagnosis and treatment for faster and more accurate diagnoses of infectious diseases and NTDs. We highlight specific examples of AI applications in diagnosing and treating these diseases in Africa, showcasing the potential of AI to improve clinical outcomes and save lives.Furthermore, we focus on how AI-driven drug discovery and development can expedite the search for new treatments for infectious diseases and combat antimicrobial resistance. We present examples of AI applications in drug discovery within the African context, illustrating the potential for AI to revolutionize the development of effective therapeutics.In addition, we delve into how AI-powered public health interventions can enhance the design and implementation of targeted interventions. We explore how AI can optimize resource allocation and facilitate data-driven decision-making processes, providing examples of AI applications in public health in Africa.Finally, we address the challenges and limitations of implementing AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. We discuss potential barriers and ethical concerns surrounding AI applications in healthcare, aiming to encourage informed and responsible utilization of AI technologies.Overall, this review emphasizes the importance and potential of AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. It positions AI as a catalyst for revolutionizing healthcare in the region, leading to more effective disease surveillance, diagnosis, treatment, drug discovery, and public health interventions.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

Pregnancy is a complex biological process which is associated with significant metabolic and hemodynamic changes of the maternal body which allow a normal fetal growth. The inability to adapt to these changes can affect the cardiovascular health. During pregnancy, women may experience mood swings, anxiety and emotional ambivalence. These symptoms can lead to stress and have a negative impact on the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women in order to manage these cases properly. The current narrative review explores and summarizes the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. Understanding the physiological adaptations that the body undergoes throughout pregnancy is crucial for educating and supporting individuals as well as healthcare professionals. This enables them to recognize any risk factors or pathological conditions that may exacerbate pregnant women's health. In order to reduce maternal morbidity and mortality from cardiovascular disease, a psychological and cardiovascular risk factor screening that is done either before or during pregnancy may be able to identify situations that call for particular medical and/or psychological therapies.

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop of new, disease-modifying drugs to treat AD and PD, thereby decreasing the social and economic burdens linked to these NDs.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

Our aim was to determine the secondary antibody deficiency profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%; chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG <400 mg/dL in 60.0%, IgA <40 mg/dL in 55.0%, and CD19 <20 cells/mm³ in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 1.9% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (P=0.0001). Most patients progressed to hypo-γ-globulinemia and secondary antibody deficiency after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases, therefore monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement

Pigmented corn is a gramineae food of great biological, cultural and nutritional importance for many Latin American countries, with more than 250 breeds in the American continent. It confers a large number of health benefits due to its diverse and abundant bioactive compounds. In this narrative review we decided to organize the information on the nutrients, bioactive compounds and phytochemicals present in pigmented corn, as well as their effects on human health. Phenolic compounds and anthocyanins are some of the most studied and representative compounds in these grasses, with a wide range of health properties, mainly the reduction of prooxidant molecules. Carotenoids are a group of molecules belonging to the terpenic compounds, present in a large number of pigmented corn breeds, mainly the yellow ones, whose biological activity incorporates a wide spectrum. Bioactive peptides can be found in abundance in corn, having very diverse biological effects that include analgesic, opioid, antihypertensive, etc. activity. Other compounds with biological activity found in pigmented corn are resistant starches, some fatty acids, phytosterols, policosanols, phospholipids, ferulic acid and phlobaphenes, as well as a great variety of vitamins, elements, and fibers. This review aims to disseminate and integrate the existing knowledge on compounds with biological activity in pigmented corn, in order to promote their research, interest and use by scientists, nutrition professionals, physicians, industries and the general population.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

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.’

The study of rare diseases is important not only for the individuals affected but also for the advancement of medical knowledge and a deeper understanding of human biology and genetics. The wide repertoire of structural information now available from reliable and accurate prediction methods provides the opportunity to investigate the molecular origins of most of the rare diseases reviewed in the Orpha.net database. Thus, it has been possible to analyze the topology of the missense mutations found in the 2,535 proteins involved in Mendelian rare diseases (MRD), which form the database for our structural bioinformatics study. The amino acid substitutions responsible for MRD show different mutation site distributions at different three-dimensional protein depths. We then predicted the depth-dependent effects of mutations for the 20,248 pathogenic variants that are present in our database. The results of this structural bioinformatics investigation are relevant, as they provide additional clues to mitigate the damage caused by MRD.

Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins and decrease levels of toxic proteins. ASOs are being developed for the treatment of several diseases, including motor neuron diseases (MNDs), a group of neurodegenerative disorders characterised by the loss of motor neurons, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MND, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.

Calcium (Ca2+) ions act as second messenger, regulating several cell functions. Mitochondria are critical organelles for the regulation of intracellular Ca2+. Mitochondrial calcium (mtCa2+) uptake is ensured by the presence in the inner mitochondrial membrane (IMM) of the mitochondrial calcium uniporter (MCU) complex, a macromolecular structure composed of pore-forming and regulatory subunits. MtCa2+ uptake plays a crucial role in the regulation of oxidative metabolism and cell death. Many evidences demonstrate that dysregulation of mtCa2+ homeostasis can have serious pathological outcomes. In this review, we briefly discuss the molecular structure and the function of the MCU complex and then we focus our attention on human diseases in which a dysfunction in mtCa2+ has been showed.

Flavonoids are polyphenolic phytochemical compounds found in many plants, fruits, vegetables, and leaves. They have a multitude of medicinal applications due to their anti-inflammatory, anti-oxidative, anti-viral, and anti-carcinogenic properties. Furthermore, they also have neuroprotective and cardioprotective effects. Their biological properties depend on the chemical structure of flavonoids, their mechanism of action, and their bioavailability. The flavonoid’s beneficial effects have been proven for a variety of diseases. In the last few years, it is demonstrated that flavonoids’ effects are mediated by inhibiting the NF-κB (Nuclear Factor-κB) pathway. In this review, we have summarized the effects of some flavonoids on the most common diseases such as cancer, cardiovascular, and neurodegenerative human diseases. In particular, here we collected all recent studies describing plant-derived flavonoids’ protective and prevention role, by specifically focusing their action on the NF-κB signaling pathway.

Succinic semialdehyde dehydrogenase (SSADH) is a mitochondrial enzyme involved in the catabolism of the neurotransmitter γ-amino butyric acid. Pathogenic variants in the gene encoding this enzyme cause SSADH deficiency, a developmental disease manifesting as hypotonia, autism and epilepsy. SSADH deficiency patients usually have family-specific gene variants. Here, we describe a family exhibiting four different SSADH variants, Val90Ala, Cys93Phe, and His180Tyr/Asn255Asp (a double variant). We provide a structural and functional characterization of these variants and show that Cys93Phe and Asn255Asp are pathogenic variants that affect the stability of the SSADH protein. Due to impairment of the cofactor NAD+ binding, these variants show a highly reduced enzyme activity. However, Val90Ala and His180Tyr exhibit normal activity and expression. The His180Tyr/Asn255Asp variant exhibits a highly reduced activity as a recombinant species, is inactive and shows a very low expression in eukaryotic cells. A treatment with substances that support protein folding by either increasing chaperone protein expression or by chemical means was not capable of increasing the expression of the pathogenic variants of the SSADH deficiency patient. However, stabilization of the folding of pathogenic SSADH variants by other substances may provide a treatment option for this disease.

This experiment was carried out to determine the overall prevalence of pigeon diseases and especially emphasized on prevalence of parasitic diseases in study areas. During this study 45 farms were selected which have >20 pair of pigeon for commercial and >10 pair pigeon for traditional farm in the three study area namely Rajshahi, Natore and Pabna district of Bangladesh. The data were collected from different farm within the study area through a questionnaire and interview schedule with the farm owners. During one year of study period a total Out of 3677 pigeon, positive case in cage of external parasites were 722 and internal parasite positives 114 from 263 fecal sample. The overall prevalence of gastrointestinal and external parasites in pigeon at northern Bangladesh is obtained. The infestation of lice Columbaecula columbae and fly Pseudolynchia canariensis were observed 18.08% and 1.55% respectively. The present study found two species of ectoparasites lice and fly. Diversity of ectoparasite in birds infestation may be depend on many factors, which may include home range, behavior, size and roosting habit of the host. The overall prevalence of gastrointestinal parasites in pigeon are founded that 43.34% in research area. Specific incidence was 22.81% in Ascariasis, 18.63% in Capilariasis and 1.90% in Raillietina parasite in pigeon. Ascaridia colombae is one of the most common (22.81%) helminth species in pigeons in this study. The effect of breed of pigeon observed in present studies the highest in indigenous (63.47%) and lowest exotic (36%) prevalence of gastrointestinal parasite was observed. The specific percentages of Ascariasis, Capilariasis and Raillatina gastrointestinal parasites of pigeon were found 20% & 31.74%; 14% & 30.15% and 2% & 1.58% in exotic & indigenous breed, respectively. In the present study, there is a relation between the occurrence of gastrointestinal parasitic infections with the age of the pigeons which showed that high prevalence in adults (50%) and compare to young (22.22%). but it was statistically significant (P>0.05). In relation with farming system the gastrointestinal parasitic incidence of pigeon was observed in modern and tradition farming system, the highest incidence was 71.16% in traditional & lowest 31.14% in modern farming. When observed specifically in Ascariasis, Capillariasis & Raillietina were 16.39% & 37.41%; 13.11% & 31.25% and 1.63% & 2.5% in modern & traditional, respectively. The effect of regions on the prevalence of gastrointestinal parasites in pigeon was observed in Pabna (68.32%), Natore (57.84%) and Rajshahi (33.33%). The specific percentages of Ascariasis, Capilariasis and Raillatina gastrointestinal parasites of pigeon were 18.18%, 33.33% & 26.31%; 14.54%, 33.33% & 23.38% and 0.606%, 1.66% & 7.89% in Rajshahi, Pabna and Natore, respectively.

The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is a suitable environment that provides various kinds of biological niches such as teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome plays an important role in triggering, development, and progression of oral and systemic diseases. Currently, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology, and is overwhelmingly promising compared to the previous era. It has been found that patients with oral diseases and systemic diseases have variations in the oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that oral microbiome plays in influencing oral and systemic diseases, and updates the knowledge related to the oral microbiome over the past 30 years. A wide range of updates was provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and help develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics.

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45–70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: &lt; 400 mg, 400–800 mg, and &gt;800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. &gt;10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the &gt;10 postmenopausal years subgroup, daily calcium intake &gt;800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11–0.64), stroke (OR, 0.06; 95% CI, 0.01–0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11–0.64). Our findings suggest that a dietary calcium intake of &gt;800 mg/day decreases the risk of CVD events in women who have been menopausal for &gt;10 years.

Background: When we talk about zoonoses, it is undeniable that we have a human and animal population that has been isolated in studies over time. Besides human and animal health, zoonoses also impact the economy and society. Therefore, the integration of the analysis in this area is essential to optimize resources in public health decisions. We have new challenges in public health that we need to overcome in a more comprehensive method such as One Health. For better measures in public health, the dual burden of zoonoses seems a logical way to determine the integral impact of such diseases in society and thus take better measures to prevent and reduce the impact of these diseases. Methods: We follow the guidelines for “Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). We search human and animal zoonoses on Embase, Ovid Medline, Scopus, Web of Science, and Google Scholar, from an unrestricted period until November 2021. For the search, we consider the Disability Adjusted Life Years (DALYs) for the human zoonotic burden and the animal zoonotic burden in monetary terms. A librarian collaborates to optimize the search string for the databases, and two reviewers screen eligible articles (first by title, then by abstracts, and finally, by full-text assessment.) For the analysis, we aim to convert the burden of zoonoses of all selected studies into the zoonotic Disability Adjusted Life Years (zDALYs) – including the human and animal components. Discussion: The study results will provide information on published studies that have accounted for the dual burden of zoonoses (both human and animal health aspects.) In addition, the synthesis of the available literature will address the knowledge gap in this area in order to know to what extent it is possible to convert the burden of human zoonoses to the animal burden of zoonoses and integrate them into a more comprehensive approach (dual burden of zoonoses.)

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.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary &amp; safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

Abstract: Peptide pools composed of short amino acid sequences have proven to be versatile tools in various research areas and clinical applications. They are powerful tools for epitope mapping, immunotherapy, and vaccine development. Their importance lies in their ability to map complex protein structures, enabling a comprehensive understanding of immune responses and facilitating the identification of potential therapeutic agents. The application of peptide pools also extends to the field of personalized medicine, offering tailored solutions for diseases such as cancer and infectious diseases. Peptide pools are complex mixtures of immunostimulatory antigens primarily intended for T-cell stimulation. They are commercially available in many different compositions and variants. However, unlike other reagents that consist of only one or a few compounds, peptide pools are highly complex products with limited stability. This makes their quality control a major challenge. Quantitative peptide analysis usually requires sophisticated methods, in most cases isotope-labeled standards and reference materials. None of these are routinely available for these products. Synthesis and purification of all labeled peptides might be required. Usually, this approach would be prohibitively laborious and expensive. Therefore, an approach is needed to provide a practical and feasible method for quality control of peptide pools. With insufficient quality control, the use of such products could lead to incorrect experimental results, which would worsen the well-known reproducibility crisis in the biomedical sciences. Here we propose the use of ultra-high performance liquid chromatography (UHPLC) with two detectors, a standard UV detector (at 214 nm) for quantitative analysis and a high-resolution mass spectrometer (HRMS) for identity confirmation. To be cost-efficient and fast, quantification and identification are performed in one chromatographic run. An optimized protocol is shown, and different peak integration methods are compared and discussed. This work was performed using a peptide pool known as CEF, which consists of 32 peptides derived from cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza virus, ranging from 8 to 12 amino acids in length.

Study of micro-RNA regulatory networks (known as miRNA’s or miR’s), during development and in known pathologies have been the basis of study over the past decades. Herein, we recapitulate these findings in order to highlight the best underlying mechanisms found to date. We also seek to elucidate how miRNA dysregulation can be associated with many cardiovascular diseases. Furthermore, we discuss miR regulation mechanism during in early development in vivo and invitro. Since many of the miR’s are precursors to transcriptional regulation, we relate back to their molecular control as we can then look together at the fundamental disease they might be exacerbating by this dysregulation.

This review focuses on the emerging evidence for the association between estimated cardiorespiratory fitness (eCRF) and metabolic risk factors. Given the challenges associated with directly measuring cardiorespiratory fitness (CRF) in large populations, eCRF presents a practical alternative for predicting metabolic health risks. A literature search identified six relevant cohort studies from 2021 to 2024 that investigated the association of eCRF with hypertension, hyperglycemia, dyslipidemia, and obesity. The review findings highlight a consistent inverse relationship between higher eCRF and lower incidence of metabolic risks in line with CRF cohort studies. This review highlights the importance of low eCRF as a primordial indicator for metabolic risks and underscores the need for broader application. Future research directions should include exploring eCRF's predictive accuracy across diverse populations and health outcomes and testing its real-world applicability in healthcare and public health settings.

This review delves into using natural antimicrobials in the dairy industry and examines various sources of these compounds, including microbial, plant, and animal sources. It highlights dairy products' most commonly used natural antimicrobials, such as nisin, lysozyme, lactoferrin, chitosan, and essential oils. It discusses the mechanisms by which they inhibit microbial growth and improve the shelf life of dairy products. Moreover, the review explores encapsulation technology as a promising approach for increasing the viability of natural antimicrobials. It discusses how encapsulation technology can protect these compounds from environmental factors that can reduce their effectiveness, such as pH, temperature, and oxygen exposure. The review also highlights the different materials that can be used for encapsulation, such as alginate, chitosan, and starch, and discusses their properties and suitability for encapsulating different natural antimicrobials. Finally, the review examines the benefits and challenges of using natural antimicrobials in dairy products. While natural antimicrobials offer several advantages, including improved safety, quality, and sensory properties of dairy products, it's crucial to be aware of the challenges associated with their use, such as potential allergenicity, regulatory requirements, and consumer perception. The review concludes by emphasizing the need for further research to identify and develop effective and safe natural antimicrobials for the dairy industry to ensure the quality and safety of dairy products for consumers.

The diagnosis and treatment of autoimmune diseases are major challenges. Their signs, symptoms, and their clinical severity change throughout the course of the disease. The available treatments for these conditions do not result in complete remission, and their long-term use generates several side effects. The main challenges in this field are the development of more sensitive diagnostic tools, and effective treatments. Studies in patients and animal models reported alterations in monocyte phenotype, activation, and function. These cells play an essential role in the pathogenesis of chronic inflammatory states and have become a target for extracorporeal monitoring and specific intervention. Nanoparticles (NPs) are ultrafine particles that can be used as contrast agents in diagnostic imaging techniques to detect specific cells in inflammatory infiltrates in tissues that are not easily accessible by biopsy. In addition, NPs can be designed to deliver drugs to a cell population or tissue. This review describes several experimental pieces of evidence demonstrating that monocytes and macrophages can specifically uptake various types of NPs, thus becoming detectable in vivo by magnetic resonance imaging and susceptible to be modulated by therapeutic agents. Hence, nanoparticles targeting mononuclear phagocytes represent promising tools for diagnosing and treatment.

This brief commentary challenges the use of the term "energy deficiency" in nutrition and metabolism, providing a critical examination of its scientific and philosophical aspects. It emphasizes the need to consider rare diseases associated with actual energy deficiency, which extend beyond the scope of everyday tiredness or fatigue. By analyzing energy balance and its complexities, this critique underscores the oversimplification associated with the term and its potential for misleading implications. It highlights the dynamic nature of energy metabolism and the intricate mechanisms involved in maintaining energy equilibrium, including the impact of rare genetic and physiological abnormalities. In addition to the discussion on energy balance, this commentary explores the manifestation of rare diseases that disrupt energy production, utilization, or hormonal regulation. Conditions such as mitochondrial diseases, glycogen storage diseases, adrenal insufficiency, and Prader-Willi syndrome are examined, shedding light on their profound impact on individuals' energy levels and overall health. The distinct time courses, underlying mechanisms, and clinical implications of protein deficiency, energy deficiency, and vitamin C deficiency are also compared, further emphasizing the complexity of energy metabolism and its relationship with various nutrient deficiencies. To foster a more comprehensive understanding of energy metabolism and enhance clarity in communication within the field, the commentary proposes the adoption of alternative terminology, such as "energy flux," to capture the multifaceted nature of energy balance more accurately. By reevaluating the terminology employed, researchers and healthcare professionals can better convey the intricate dynamics of energy metabolism and address the unique challenges faced by individuals with rare diseases causing actual energy deficiency. In conclusion, this commentary serves as a thought-provoking exploration of the concept of energy deficiency in nutrition and metabolism. It highlights the limitations of the term in capturing the complexities of energy balance, particularly in the context of rare diseases. By broadening the discussion to include these rare conditions, it encourages a more comprehensive understanding of energy metabolism and calls for precise and nuanced terminology to facilitate effective communication and advancements in the field.

Laws and regulations make powerful contribution in addressing multitudes of public health concerns. We examined the Public Health Act (PHA) in Malawi to understand its relevance to the ever-growing and changing threats posed by infectious and non-infectious diseases. The current Public Health Act of Malawi came into effect in 1948 to protect and preserve public health. The Act has undergone several amendments, the last one being in 1975. It draws much of its inspiration and standards from the 19th century British laws on insanitary housing, poor ventilation, and drainage. Such laws are silent on emerging major public health concerns including non-communicable diseases (NCDs) such as cardiovascular diseases and diabetes as well as road traffic injuries. This makes the Act outdated and ill equipped to address the 21st century public health concerns. Although supplementary legislation such as the HIV/AIDS Act and Mental Treatment Act have recently been enacted, they are yet to be consolidated into the Public Health Act. Consequently, existing policies and strategic plans that are meant to address gaps in public health and ensure coordinated effort lack support of laws and regulations. The Act also places great emphasis on mandatory vaccinations, quarantine and isolation against smallpox, a disease that has long been eradicated. Furthermore, although the Public Health Act outlines powers, duties and penalties, it fails to reinforce acceptable behaviour due to the insignificant penalties for noncompliance. There is a need for immediate and prompt revision and restructuring of the Public Health Act based on scientific evidence. Such laws require adequate consultation and interaction with key experts and stakeholders from a wide range of disciplines.

The ongoing global pandemic caused by coronavirus disease 2019 (COVID-19) has once again demonstrated the significance of the Coronaviridae family in causing human disease outbreaks. As SARS-CoV-2 was first detected in December 2019, information on its tropism, host range, and clinical presentation in animals is limited. Given the limited information, data from other coronaviruses may be useful to inform scientific inquiry, risk assessment and decision-making. We review the endemic and emerging alpha- and betacoronavirus infections of wildlife, livestock, and companion animals, and provide information on the receptor usage, known hosts, and clinical signs associated with each host for 15 coronaviruses discovered in people and animals. This information can be used to guide implementation of a One Health approach that involves human health, animal health, environmental, and other relevant partners in developing strategies for preparedness, response, and control to current and future coronavirus disease threats.

During the COVID-19 pandemic, individuals with symptoms other than cough or fever have refrained from seeking medical advice. However, a delay in treatment might lead to serious consequences. At the same time, digital health initiatives have emerged to overcome this bottleneck of healthcare. Herein, we report the results of a multi-center initiative using a combination of patient history and artificial intelligence (AI) to identify individuals with rare neuromuscular diseases. First, a questionnaire with 46 items was developed by interviewing patients with muscular dystrophies, amyotrophic lateral sclerosis, Morbus Pompe, neuropathies, and myasthenia gravis. Second, patients with proven neurological diseases answered the questionnaire. Third, a combination of classifiers (artificial neural network, support vector, and random forest) was trained and, finally, the system was challenged with new questionnaires. Users with an abnormal questionnaire pattern received a unique code for data privacy and contact details for a neurologist for further advice. The neurologists confirmed or refuted the AI-based diagnosis. The questionnaire was accessed 3122 times, leading to 853 unique codes. Only for a few patients the computer-based diagnoses and the confirmed final diagnoses were reported to us. However, for these few patients, the genetic testing and high CK levels finally ended their long-lasting diagnostic odyssey.

With the term neuroinflammation has defined the typical inflammatory response of the brain closely related to the onset of many neurological diseases. Neuroinflammation is well known, but its mechanisms and pathways are not entirely comprehended. Currently, some progress has been achieved through many efforts and research. Consequently, new cellular and molecular mecha-nisms, diverse from conventional ones, are emerging. In listing some of those that will be the sub-ject of our description and discussion, essential are the important role of peripheral and infiltrated monocytes and clonotypic cells, alterations in gut/brain axis, dysregulation of the apelinergic sys-tem, as well as changes in the endothelial glycocalyx of blood-brain barrier, variation in expres-sion of some genes and levels of the encoding molecules by microRNAs (miRNAs), or other epige-netic factors and distinctive transcriptional factors, as well as the role of autophagy, ferroptosis, sex differences and modifications in the circadian cycle. Such mentioned mechanisms can add significant pieces in understanding the complex etiological puzzle of neuroinflammation. In addi-tion, they could represent biomarkers and targets of neurodegenerative diseases, in increase in our old populations.

The stability of the gut barrier is very important for keeping the gut healthy and stopping dangerous substances from getting into the bloodstream. Several diseases, including cancer, have been linked to the gut barrier being broken. Live bacteria called probiotics that are good for the host have been shown to have the ability to improve the gut barrier and lower the risk of cancer in the gastrointestinal system. This review looks at how probiotics affect the health of the gut barrier and what that might mean for preventing cancer. Researchers have found that probiotics strengthen the connections between intestine cells, encourage the production of protective mucins, and change the make-up and balance of the gut bacteria. These processes help keep the gut barrier strong and stop harmful chemicals from getting into the bloodstream. Probiotics may help lower the chance of cancer by reducing inflammation throughout the body and protecting the GI tract from harmful substances. But more study is needed to fully understand the benefits of different probiotic strains, the best amounts to take, and how they affect the health of the gut barrier. Understanding how probiotics, the health of the gut barrier, and the risk of cancer all work together can help us come up with new ways to avoid and treat cancer.

Alzheimer's disease (AD) remains a significant challenge in the field of neurodegenerative disor-ders, even nearly a century after its discovery, due to the elusive nature of its causes. The develop-ment of drugs that target multiple aspects of the disease has emerged as a promising strategy to address the complexities of AD and related conditions. The immune system's role, particularly in AD, has gained considerable interest, with nanobodies representing a new frontier in biomedical research. Advances in targeting antibodies against amyloid-β (Aβ) and using messenger RNA for genetic translation have revolutionized the production of antibodies and drug development, open-ing new possibilities for treatment. Despite these advancements, conventional treatments for AD, such as Cognex, Exelon, Razadyne, and Aricept, often have limited long-term effectiveness, under-scoring the need for innovative solutions. This necessity has led to the incorporating of advanced technologies like artificial intelligence and machine learning into the drug discovery process for neurodegenerative diseases. These technologies help identify therapeutic targets and optimize lead compounds, offering a more effective approach to addressing the challenges of AD and similar conditions.

This mini-review examines the complex relationship between the gut microbiota and human health, with a special focus on its role in conditions such as inflammatory bowel disease (IBD) and cardiovascular disease (CVD). It explores how dietary patterns can affect the composition of the gut microbiota, thus contributing to the development of various diseases. The gut microbiota is crucial in the production of metabolites such as trimethylamine N-oxide (TMAO), which play a significant role in the development of both IBD and CVD. High levels of TMAO and other metabolites, such as phenylacetylglutamine, have been linked to an increased risk of CVD. The review highlights the potential of dietary interventions and therapies designed to modulate the gut microbiota in reducing these risks. Following a Mediterranean diet may offer cardiovascular protection, emphasizing the need for further research into the molecular mechanisms of diet-related changes in the microbiota.

Complex diseases are prevalent medical conditions which are characterized by strong inter-patient differences in symptom profiles, disease trajectory and treatment response. The challenges in understanding and managing these diseases are due to their complex pathophysiology, comprising of a combination of genetic and environmental factors. The traditional model of disease assumes a clear distinction between health and disease, as well as between different diagnoses, but recent findings with regards to diseasomes and network pleiotrophy suggest that this dogma is not useful in understanding complex diseases. This paper presents a novel model, in which the individual disease burden is determined as a function of molecular, physiological and pathological factors simultaneously: disease(symptoms(traits(genes AND environment))). From this a high-dimensional space is defined which includes all individual disease burdens, ranging from healthy (i.e. low disease burden) to multi-morbidity (i.e. high disease burden), termed the disease landscape. This model provides a novel way to conceptualize human physiology and pathophysiology in the context of complex diseases and may present a useful concept to simultaneously address the strong interindividual heterogeneity of diagnose cohorts as well as the lack of clear distinction between diagnoses and health and disease, thus facilitating the progression towards personalized medicine.

The COVID-19 pandemic caused by SARS-COV-2 has infected over 500,000 people causing over 25,000 deaths in the last 10 weeks. A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 (ACE2). Recent studies have reported that patients with hypertension and diabetes treated with ACE inhibitors or angiotensin receptor blockers might be at a higher risk of COVID-19 infection as these drugs have been reported to increase ACE2 expression. This has raised the need to systematically investigate the effect of different drugs including antihypertensives on modulating ACE2 expression. Here, we analyzed a publicly available CMAP dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules. We show that only one subclass of antihypertensives drugs - ACE inhibitors, are significantly enriched for drugs up-regulating ACE2 expression. Studying the effects of the 672 clinically approved drugs in CMAP, we chart the drug categories that affect ACE2 expression. Specifically, we find that panobinostat (an HDAC inhibitor) confers the highest up-regulation of ACE2 expression while isotretinoin (a vitamin A derivative) is its strongest down-regulator. Our results provide initial candidates guiding further in vitro and in vivo studies aimed at assessing drug effects on ACE2 expression.

Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient or absent activity of the enzyme alfa-galactosidase A. This defect enzyme leads to accumulation of glycolipids, primarily globotriaosylceramide (Gb3), in the vascular endothelium of several organs, including the skin, kidneys, nervous system, and heart. The characteristic early clinical features of Fabry disease include acroparaesthesia, angiokeratoma, heat intolerance, hypohidrosis, cornea verticillata and gastrointestinal symptoms. Later complications occur with the disease progression and include progressive renal failure, hypertrofic cardiomyopathy, cerebrovascular disease and reduced life expectancy. Anderson Fabry disease is therefore a disabling and systemic disease which requires a timely diagnosis. The purpose of our study is to define sweat glands morphological abnormalities in children and adolescents with Fabry disease with minimal symptoms and in patients affected by variants of Fabry disease in which biopsy is essential, to establish a baseline morphological diagnosis of the disease before to undergo to kidney or endomyocardial biopsy or when the classical approach is not possible because of some complications, with minimal discomfort for patients.

Background and Objectives: Trichomonas tenax is a protozoan, participating in the human oral microflora. It is considered as a potential paradontopathogen. This microorganism is also reported in the respiratory tract. We aimed to analyze the available literature about the prevalence of Trichomonas tenax in the population affected by periodontal disease. Materials and Methods: Тhe searching with keywords: ,,Trichomonas tenax” and “periodontal diseases’’ in Scopus, PubMed and ScienceDirect databases was able to identify several systematic reviews and original articles until July 2023. All studies with suffering from periodontal disease people, mentioned year of publication, country, specified detection methods, total number of tested samples as well as the percentage of those infected with Trichomonas tenax were included. Irrelevant articles were excluded. Results: We found 137 studies, but only 64 studies about distribution of Trichomonas tenax in patients with gum disease underwent qualitative analysis. The highest number of studies have been conducted in Iran, Poland and Iraq. Different methods have been used to detect the unicellular organism, each with different specificity and sensitivity. Conclusions: Interest in Trichomonas tenax has grown considerably since 2000. Because of its association with periodontal disease, Trichomonas tenax role in the inflammatory process shouldn’t be overlooked.

The use of smartphones, coupled with different sensors, makes it an attractive solution for measuring different physical and physiological features, allowing for the monitoring of various parameters and even identifying some diseases. The BITalino device allows the use of different sensors, including Electroencephalography (EEG) and Electrocardiography (ECG) sensors, to study different health parameters. With these devices, the acquisition of signals is straightforward, and it is possible to connect them using a Bluetooth connection. With the acquired data, it is possible to measure parameters such as calculating the QRS complex and its variation with ECG data to control the individual's heartbeat. Similarly, by using the EEG sensor one could analyze the individual's brain activity and frequency. The purpose of this paper is to present a method for recognition of the diseases related to ECG and EEG data, with sensors available in off-the-shelf mobile devices and sensors connected to a BITalino device. The data were collected during the elderly's experiences, performing the Timed-Up and Go test, and the different diseases found in the sample in the study. The data were analyzed, and the following features were extracted from the ECG, including heart rate, heart rate variability, the average QRS interval, the average R-R interval, and the average R-S interval, and the EEG, including frequency and variability. Finally, the diseases are correlated with different parameters, proving that there are relations between the individuals and the different health conditions.

Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated to IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and of weak evidence. This review summarizes the current knowledge on the complex interactions among diet, microbiome and epigenetics in IBD. Whereas over-abundance of calories and some macronutrients increases gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, D, folic acid and beta-carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, anti-inflammatory dietary patterns as a complex intervention approach have become popular over the recent years. Hence, exclusive enteral nutrition in pediatric Crohn’s disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet and most recently the Mediterranean diet have shown strong anti-inflammatory properties and provide a promise for improving disease symptoms. Definitely, more work is required to evaluate the role of individual food compounds and complex nutritional interventions with potential to decrease inflammation as means for prevention and management of IBD.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

Knowledge on the health of banana trees is critical for farmers to profit from banana cultivation. Fusarium wilt and banana blood diseases (BDB), two significant diseases infecting banana trees, are caused by Fusarium oxysporum and Ralstonia syzygii, respectively. They have successfully caused a decline in crop yield as they destroy the trees, starting sequentially from the pseudostem to the fruits. The entire distribution of BDB and Fusarium on a plantation can be understood using advanced geospatial information obtained from multispectral aerial photographs taken using an unmanned aerial vehicle (UAV), combined with the reliable data field of infected trees. Vegetation and soil indices derived from a multispectral aerial photograph, such as normalized difference vegetation index, modified chlorophyll absorption ratio index, normalized difference water index (NDWI) and soil pH, may have to be relied on to explain the precise location of these two diseases. In this study, a random forest algorithm was used to handle a large dataset consisting of two models: the banana diseases multispectral model and the banana diseases spectral model. The results show that the soil indices, soil pH and NDWI are the most important variables for predicting the spatial distribution of these two diseases. Simultaneously, the plantation area affected by BDB is more extensive than that affected by Fusarium, if the variation of planted banana cultivars is not considered.

Asthma is the most prevalent cause of chronic respiratory diseases. Herein, we evaluate asthma burden in Mexico based on results from the Global Burden of Disease (GBD 2019) study 2019. Using data from the GBD 2019, we estimated asthma prevalence, incidence, mortality, and disability-adjusted lived years (DALYs) counts and crude and age-standardized rates per 100,000 people with a 95% uncertainty interval (UI) by sex and age at the national and subnational levels in Mexico from 1990 to 2019. At the national level, asthma affected 3.35 million (95% UI, 2.59-4.37) people, with 606.0 thousand (433.0-811.1) new incident cases and 1,655 (3-1,931) deaths during 2019. Asthma caused a slightly higher burden in females and affected mainly age groups between 1 and 14 years of age. The burden of asthma gradually decreased from 1990 to 2010. However, during the last decade (2010-2019), prevalence increased by 8.2%, as did incidence by 11.3%, whereas mortality and DALYs decreased by 23.3 and 1.6%, respectively. Finally, the burden of asthma displayed a heterogeneous pattern of disease at the subnational level. In conclusion, asthma causes a significant health loss in Mexico that differentially affects the population distributed among the states of the country, thus causing health disparities that should be addressed to provide sustainable asthma diagnosis and control to reduce its burden, especially at early stages of life.

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.

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.

Neurodegenerative diseases, including Alzheimer's, Huntington's, Parkinson’s, and Amyotrophic Lateral Sclerosis, involve neuron degeneration linked to the misfolding of amyloidogenic proteins, resulting in β-sheet-enriched aggregates. This phenomenon disrupts the normal folding of proteins critical for cellular function. Genetic mutations, proteolytic cleavage, oxidative stress, and aging contribute to misfolding. Parkinson's disease (PD) is closely tied to alpha-synuclein (αS) misfolding, with A53T mutation and Lewy bodies (LB) in PD brains pivotal to understanding the disease mechanism. Other synuclein homologues (βS, γS) further contribute to synucleinopathies. Mutants (A30P, A53T, E46K, H50Q, and G51D) underscore αS&#39;s role in PD development. This concise review focuses on molecular and pathological aspects of neurodegenerative diseases, emphasizing αS in PD. The integration of genetic, structural, and mechanistic insights highlights the disorders. complexity, paving the way for future therapeutic strategies targeting protein misfolding and aggregation.

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence show that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.

Cold atmospheric plasma (CAP) has emerged as a promising therapeutic technology, distinguished by its safety, efficiency, and minimal side effects. With increasing applications in dermatology, CAP demonstrates antimicrobial efficacy against bacteria, viruses, and fungi, supports tissue proliferation and wound healing, and hinders the growth and migration of tumor cells. This review encompasses the concept, physical characteristics, and current research applications of CAP in dermatology. CAP, a gas cloud produced by ionizing gases, operates at room temperature, ensuring safety and efficacy in dermatological use. Its effects are mediated through active components like reactive oxygen and nitrogen species (RONS) and ultraviolet radiation. The extensive research covered in this paper explores CAP's applications in skin infections, immune-related diseases, and tumor diseases. As a biologically suitable technology, cold atmospheric pressure plasma finds widespread use in medicine, including medical device sterilization, dentistry, oncology, and dermatology. The direct and indirect forms of CAP applications, including plasma-activated liquids, complement each other. CAP holds promise as a dermatological treatment technique, but further exploration and research are needed. This article briefly explores CAP's diverse applications and potential utility within dermatology. The objective is to enhance the progress of plasma medicine by furnishing a concise overview of the applications of this groundbreaking technology in dermatological contexts.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) linked with coronavirus disease 2019 (COVID-19) poses a serious threat to public health worldwide. Firstly, the SARS-CoV-2 was reported in Wuhan, Hubei Province, China in December 2019. Initially, the major proportion of virus-infected cases (i.e. about 99%) was reported in China and now it is being reported in other counties as well. Humans begin to be infected within their communities and transmittance of the viral epidemic increased rapidly due to lack of understanding of its transmission routes and precautionary measures. The existence of SARS-CoV-2 in China threatened the population greatly due to the high incidence of fatal respiratory infections. Current investigations speculated that this virus transferred into a human from viral-infected bats. However, the process of interspecies viral transmission is an important scientific question to be addressed. Due to the continuous increase in the patients infected with COVID-19 associated pneumonia, the World Health Organization (WHO) has included this viral epidemic to the priority list of diseases. Therefore, accelerated research developments are required to control the spread of this outbreak, as it is declared as a public health emergency by WHO especially in the absence of efficacious drugs and vaccines. Our review encompasses the recent status of disease severity in China, a particular replication mechanism of SARS-CoV-2 and potential risks and precautionary measures required to avoid contact with this fatal viral infection.

Plant-based alternative medicine is normally grounded on empiric cultural perception, as the main objective, these practices intent to either maintain good health or to provide a route to turn-the-tide on a specific disease or ailment. Amongst the thousands of plants that have been used and studied, Neem (Azadirachta indica) seems to have a very interesting tale to tell, since its properties to ward-off certain diseases have overtime, and in a rigorous way, been proven. The preceding concise review is a collection of some of the most relevant studies today, not only focusing on the health benefits obtained by its use, but digging into the molecular mechanisms of how the properties come about. In particular, we take a look over antioxidant properties and how these mediate and mitigate important molecules such as IL-6 and TNF-, leading the way in reducing systematic damage by oxidative stress. Further, we relate this oxidative reduction to other systemic diseases such as cancer and diabetes, as these are currently becoming the most rampant killers. As of yet not all is known about the different ways of extracting or the total composition of an extract, as these may be from different parts of the plant. Therefore, we also allude to an important cautionary view where toxicological effects and conflicting outcomes arise. Overall, presented results show a great potential for the different extracts of Neem as their antioxidant activity can be taken advantage off, and potentially used in modern medicine.

With a mild Mediterranean-type climate, Corsica is endemic for canine vector-borne diseases (CVBDs) such as dirofilariosis (a mosquitoes borne-diseases: MBDs), leishmaniosis and ehrlichiosis. The aim of this present study was to evaluate a monthly multi-modal prophylactic strategy (MMP) against CVBDs occurring in Corsica. The study was conducted as a comparative field trial in which eighty dogs allocated into two groups were included: (i) Group 1 consisted of 25 dogs under the MMP [per-os administration of 1.5 tablet of milbemycine oxime-praziquantel and a topical line-on application of a 3.6 mL solution of dinotefuran-permethrin-pyriproxyfen] and (ii) Group 2 under various real-life prophylactic treatment (RLP) based on the use of ectoparasiticide products [different formulations: deltamethrin, fluralaner, fipronil] and/or macrocyclic lactones based-products [milbemycin oxime/praziquantel, milbemycin oxime, moxidectin] during the period ranging from June to October 2017. All animals were followed for one year and had blood drawn at day 0, followed by follow-up at 6 and 12 months. Samples were screened for filariosis using molecular tools as well as for leishmaniosis and ehrlichiosis using indirect immunofluorescence assay (IFA). At the end of the study, no new cases of CVBDs were recorded within Group 1. In Group 2, the cumulative incidence of CVBDs was 20.0% (n= 11; p= 0.015) including dirofilarioses due to Dirofilaria immitis and/or D. repens, with 16.4% (n= 9; p=0.027). Ehrlichiosis was 5.5% (n= 3; p=0.241). No new cases of leishmaniosis were detected in Group 2. The data illustrated that, unlike the RLP treatment which failed to protect at least 20% of dogs, the MMP based on the concurrent administration of milbemycine oxime-praziquantel and dinotefuran-permethrin-pyriproxyfen is efficient to protect dogs against CVBDs in a high-risk area.

Maternal obesity and gestational diabetes predispose to metabolic disturbances in the next generation. Moreover, the lactation phase also stands as critical for metabolic programming. Nevertheless, the precise mechanisms originating these changes remain unclear. Here we investigate the consequences of maternal diet lipid-rich diet during gestation and lactation, and its impact on metabolism and behavior in the offspring. Two experimental groups of Wistar female rats were used: a control group (NC) that fed a standard diet during gestation and lactation periods and an overnutrition group that fed a high-fat diet (HF, 60% lipid-rich) during the same phases. Offspring were analyzed at postnatal days 21, 28, and 2 months-old (PD21, PD28, PD60) for metabolic profile (weight, fasting glycemia insulin sensitivity, glucose tolerance) and euthanized for brain collection to evaluate by western blot markers of synaptic dynamics, metabolism and inflammation in the hypothalamus, hippocampus and prefrontal cortex. At 2 months-old, behavioral tests for anxiety, stress, cognition, and food habits were conducted. We observe that female offspring born from HF mothers exhibited increased weight gain and decreased glucose tolerance that attenuates with age. In offspring males, weight gain increased at P21 and worsened with age, while glucose tolerance remained unchanged. Offspring of HF mothers exhibited elevated levels of anxiety and stress during behavioral tests, displaying decreased predisposition for curiosity compared to the NC group. In addition, offspring from mothers with HF showed increased food consumption and a lower tendency towards food-related aggression. We conclude that exposure to HF diet during pregnancy and lactation induces dysmetabolism in the offspring accompanied by heightened stress and anxiety. There was sexual dimorphism in metabolic traits but not behavioral phenotypes.

We hypothesized that reticuloruminal temperature and pH, as well as cow activity, can be used as biomarkers for the early diagnosis of clinical mastitis in dairy cows. Therefore, we aimed to detect the relationship between reticuloruminal temperature and pH, cow activity, and clinical mastitis in dairy cows. We randomly selected cows with clinical mastitis and clinical healthy cows (HG) out of 600 milking cows. We recorded the following parameters during the experiment: reticulorumen tem-perature (RR temp.), reticulorumen pH (RR pH), and cow activity. We used smaXtec boluses (smaXtec animal care technology®, Graz, Austria). In this investigation, reticulorumen data ob-tained seven days before diagnosis were compared to HG data from the same time period. CM cows were observed on the same days as the healthy cows. The healthy group’s RR pH was 7.32% higher than that of cows with CM. Reticulorumen temperature was also 1.25% higher in the CM group than in the control group. The healthy group had a higher average value for walking activity and was 17.37% higher than the CM group. The data of reticulorumen pH changes during 24 h showed that during the day, the pH changed from 5.53 to 5.83 in the CM group. By contrast, pH changed from 6.05 to 6.31 in the control group. The lowest reticulorumen pH in the CM group was detected on the third day before diagnosis. It was 15.76% lower than the highest reticulorumen pH detected on the sixth day before diagnosis. The lowest reticulorumen pH in CM cows was detected at 0 and 1 days before diagnosis. It was 1.45% lower than the highest reticulorumen pH detected on the second day before diagnosis. The lowest walking activity in the CM group was detected 0 days before diagnosis, 50.60% lower than on the fifth day before diagnosis. The lowest walking activity was detected 0 days before diagnosis, 39.57% lower than on the seventh day before diagnosis. In this study, we found that reticuloruminal temperature, reticuloruminal pH, and cow ac-tivity could be used as biomarkers for the early diagnosis of clinical mastitis in dairy cows.

We are experiencing an unprecedented urbanization process that alongside with physical, social and economic developments is having a significant impact on population’s health. Due to higher apprehensions of pollution, violence and poverty, our modern cities no longer ensure a good quality of life so they become unhealthy environments. This study aims to measure the socio-environmental and hematologic profile of residents of Santo André’s landfill – “Bairro Espírito Santo” by using the contextualization of the studied area. The research method is Observational type and from Retrospective cohort and by convenience sampling in Santo André in the Greater ABC region. The study determined a socio environmental profile and the hematologic diseases screening related to a close location to the landfill. The disease manifests itself within a broad spectrum of symptoms that causes changes in blood count parameters. The full blood counts analysis was performed, indicating that the blood counts of residents living near the landfill led to positive hematological changes and diseases like Leukopenia, Anemia, Neutropenia and lymphocytosis were the most common changes. However it is considered that the proof of the relation of cause- effect to environmental exposures that may trigger chronic manifestations in humans requires specific studies that are often complicated.

The plague caused by the Yersinia pestis bacterium is primarily a flea-transmitted zoonosis of rodents that can also be conveyed to humans and other mammals. In this work, we analyzed the spatial and temporal distribution of rodents’ populations during active and quiescent periods of the plague in the municipality of Exu, northeastern Brazil. The geospatial analyses had shown that all rodent species occurred through the whole territory of the municipality with different hotspots for the risk of occurrence of the different species. Important fluctuation in the rodent populations was observed with a reduction in the wild rodent fauna following the end of a plague epidemic period, mostly represented by Necromys lasiurus and increase of the commensally species Rattus rattus. A higher abundance of rats might lead to an increased exposure of humans populations, favoring spillovers of plague and other rodent-borne diseases. Our analysis contributed to further highlight the role of the wild rodent species as the amplifier hosts and of the commensally rats (Rattus rattus) as the preserver hosts on the quiescent period on that transmission infection area.

Over the last 20 years, begomoviruses have emerged as devastating pathogens, limiting the production of different crops worldwide. Weather conditions increase vector populations, with negative effects on crop production. In this work we evaluated the relationship between the in-cidence of begomovirus and climatic conditions before and during the crop cycle. Soybean and bean fields from the northwest (NW) of Argentina were monitored for 14 years and classified as moderate (≤50%) and severe (> 50%) according to the relative incidence. Two hundred bio-meteorological variables were constructed, summarizing meteorological data in 10-day peri-ods from June to March of each crop year. The studied variables included temperature, precipi-tation, relative humidity, wind (speed and direction), pressure, cloudiness and visibility. For bean, high maximum winter temperatures, low spring humidity and precipitation 10 days before planting correlated with severe incidence. In soybeans, high late winter and pre-planting tem-peratures, and low spring precipitations were found to be good predictors of high incidence of begomovirus presence. The results suggest that temperature and pre-sowing precipitations can be used to predict incidence status [predictive accuracy: 82% (bean) and 75% (soybean)]. Thus, these variables can be incorporated in early warning systems for crop management deci-sion-making to reduce the virus impact on bean and soybean crops.

Amyloids result from the aggregation of several unrelated proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they are rich in intermolecular β-sheets and are the causative agents of several diseases, both neurodegenerative and systemic. It is believed that the most toxic species are small aggregates, referred to as oligomers, rather than the final fibrillar assemblies. Their mechanisms of toxicity are mostly mediated by aberrant interactions with the cell membranes, with resulting derangement of membrane-related functions. Much effort is being put in the search for natural antiamyloid agents, and/or in the development of synthetic molecules. Actually, it is well documented that the prevention of amyloid aggregation results in several cytoprotective effects. Here, we portray the state of the art in the field. Several natural compounds are effective antiamyloid agents, notably tetracyclines and polyphenols. They are generally non-specific, as documented by their partially overlapping mechanisms, and the capability to interfere with the aggregation of several unrelated proteins. Among rationally designed molecules, we mention the prominent examples of β-breakers peptides, whole antibodies and fragments thereof, and the special case of drugs contrasting transthyretin aggregation. In this framework, we stress the pivotal role of the computational approaches. When combined with biophysical methods, in several cases they have helped clarify in detail the protein/drug modes of interaction, which make it plausible that more effective drugs will be developed in the future.

The COVID-19 pandemic has highlighted the vitalness of telehealth in our medical world, where considering a restructuring of healthcare services has become paramount. In fact, telemedicine has recently earned a valuable place in many specialties; and its implications in cardiology and cardiovascular medicine were among the leading interests. In this letter, we gathered previous evidence supporting the merit of telemedicine in the fields of cardiology and cardiovascular medicine—medical branches in which patients require meticulous care and continuous monitoring—as well as protrusions of concerns about the uncertainty regarding the efficacy of telemedicine’s future implications and technologies. In sum, in the context of this still on-going pandemic, medical institutions must strive to improve telehealth technologies and implement solid future research directions in this growing field—to be able to persevere in meeting the needs of the patients. As long as no conclusive evidence exists regarding the fields where telemedicine is most worthwhile, healthcare systems will always keep the dread of wasting resources on developing ineffective programs. We conclude that telemedicine has been attributed a considerable attention in managing cardiac and cardiovascular conditions; nevertheless, further studies with solid designs are still needed to confirm its validity and utility in those specialties.

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.

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).

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.

Lycopene is a compound of colored origin that shows strong antioxidant activity. The ability to neutralize free radicals by lycopene is the basis of its pro-health effect, including the ability to inhibit the development of many civilization diseases. Therefore, this study focuses on the importance of the antioxidant effect of lycopene in inhibiting the development of such diseases as cardiovascular diseases, diseases of the etiology of etiology, diseases within the nervous system.

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.

Although genome-wide association studies (GWAS) have identified several hundred loci associated with autoimmune diseases, their mechanistic insights are still poorly understood. The human genome is more complex than common single nucleotide polymorphisms (SNPs) that are interrogated by GWAS arrays. Some structural variants such as insertions-deletions, copy number variations, and minisatellites that are not very well tagged by SNPs cannot be fully explored by GWAS. Therefore, it is possible that some of these loci may have large effects on autoimmune disease risk. In addition, other layers of regulations such as gene-gene interactions, epigenetic-determinants, gene and environmental interactions also contribute to the heritability of autoimmune diseases. This review focuses on discussing why studying these elements may allow us to gain a more comprehensive understanding of the aetiology of complex autoimmune traits.

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.

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.

Thalassemia is one of the most prevalent genetic disorders worldwide which has been previously found to have an association with several physiological and organ complications. Several studies found both its positive and inverse correlation with glomerular filtration rate (GFR). Therefore, in this meta-analysis, we tried to assess the accurate correlation of thalassemia with GFR. We searched in Google Scholar, PubMed, and ScienceDirect, and from the initial 96 articles we finally could include 15 studies. The quality and publication bias assessment confirmed that all the studies were of high to moderate quality with no publication bias. The main outcome of the mean difference (MD) was -6.45, 95%CI: -18.50, 5.60 (P<0.00001), which indicated a negative correlation of GFR with thalassemia. The sensitivity analyses found one study as a slight outlier and reanalyzing the data excluding that study MD was achieved as -13.90, 95%CI: -24.22, -3.59 (P<0.00001) which even strongly supports our main outcome. Our result determined that the GFR is generally higher in healthy people as compared to thalassemia patients.

(1) Background: Prevention of acute cardiovascular events in patients with cardiovascular diseases (CVDs) requires promoting health-protective behaviors (e.g., physical activity) and preventing health-compromising behaviors (sitting). Digital health interventions provide much potential. Based on multiple behavioral change theory, an intervention (reCardial app) was evaluated, and the following hypotheses were tested: H1: Health behaviors (physical activity, sitting) and disease self-management (self-care maintenance, self-care confidence) are closely interrelated. H2: Change in health behaviors and disease self-management indicators over time is more pronounced in reCardial app-users. H3: In the intervention group, changes in systolic and diastolic blood pressure indicate a positive trajectory. (2) Methods: A study with the design of a randomized controlled trial over 12 weeks was conducted. 40 CVD-patients were randomized equally to the Intervention Group (35% women; Mage=60.6years) and Control Group (45% women; Mage=61.5years). (3) Results: Findings support H1 with significant correlations between health behaviors (r=0.45-0.63**), and disease self-management (r=-0.32-0.54**), H2 with Eta²=0.21 (not statistically significant) and H3 partially with d=0.101 for systolic blood pressure but not regarding diastolic blood pressure. (4) Conclusions: Replications are needed with larger samples and more objective measures. The app can help prevent and manage CVD by means of promoting health-protective behaviors and preventing health-compromising behaviors. Taking different behaviors into account can increase intervention effects and with that support of users.

The accumulation of loss of function mutations in the uricase gene well explains the high urate levels in hominoids (apes and humans) compared to other mammals. The loss of human uricase activity may have allowed humans to survive environmental stressors, evolution bottlenecks, and life-threatening pathogens. While high urate levels may contribute to developing cardiometabolic disorders such as hypertension and insulin resistance, low urate levels may increase the risk for neurodegenerative diseases. The double-edged sword effect of uric acid has resurrected a growing interest in the antioxidant role of urate and the role of the uricase gene in modulating the risk of obesity. Characterizing both the effect of uric acid levels and the uricase gene in different animal models may provide new insights into the potential therapeutic benefits of uric acid and novel uricase-based therapy.

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.

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.

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with a distinct set of facial features, growth limitations, and limb anomalies. Its clinical spectrum is broad and presents significant challenges in pediatric diagnosis and management. The variable presentation of the disorder, due to cohesin complex mutations, requires extensive research to refine care and improve outcomes. This article provides a case series review of pediatric CdLS patients, alongside a comprehensive literature review, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. It also discusses the evolution of diagnostic and therapeutic techniques, with an emphasis on innovations in genetic testing, including the detection of mosaicism and novel genetic variations. The aim is to synthesise case studies with current research to advance our understanding of CdLS and the effectiveness of management strategies in pediatric healthcare. This work highlights the need for an integrated, evidence-based approach to diagnosis and treatment, and aims to fill existing research gaps and advocate for holistic care protocols and tailored treatment plans for CdLS patients, ultimately improving their quality of life.

Cardiovascular diseases (CVDs) a leading cause of mortality worldwide. Therefore, there is in-creasing interest in dietary interventions to reduce risk factors associated with these conditions. Cherries and berries are rich sources of bioactive compounds and have attracted attention for their potential cardiovascular benefits. This review summarizes the current research on the effects of cherries and berries consumption on cardiovascular health, including in vivo studies and clinical trials. These red fruits are rich in phenolic compounds, such as anthocyanins and flavonoids, which have multiple bioactive properties. These properties include antioxidant, anti-inflammatory, and vasodilatory effects. Studies suggest that regular consumption of these fruits may reducing in-flammation and oxidative stress, leading to lower blood pressure, improved lipid profiles, and enhanced endothelial function. However, interpreting findings and establishing optimal dosages is challenge due to the variability in fruit composition, processing methods, and study design. Despite these limitations, the evidence highlights the potential of cherries and berries as components of preventive strategies against CVD. Further research is needed to maximize their health benefits and improve clinical practice.

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.

Emerging infectious disease threats are becoming more frequent due to various social, political and geographical pressures including increased human-animal contact, global trade, transportation and changing climate conditions. As a result, the threat that emerging agents can be spread by blood contact or transfusion of blood products also becomes increasingly problematic. Blood transfusion is essential in treating patients with anemia, blood loss, and other medical conditions. However, these lifesaving components can become a vector for spreading diseases, particularly to vulnerable populations. New methods have been implemented on a global basis for prevention of transfusion transmission via plasma, platelet, and whole blood products. Implementing proactive pathogen reduction methods can significantly reduce the likelihood of disease transmission via blood transfusion, even for newly emerging agents whose transmissibility and susceptibility are still being evaluated as they emerge. In this review, we consider the Mirasol PRT system for blood safety which is based on a photochemical method involving Riboflavin and UV light. We provide examples of how emerging threats such as Ebola, SARS-CoV-2, Hepatitis E, monkeypox and other agents have been evaluated in real time regarding effectiveness of this method for reducing the likelihood of disease transmission via transfusion. Keywords: transfusion; blood; pathogen reduction; emerging infectious diseases.

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.

The ATP synthase is a mitochondrial complex embedded in the inner mitochondrial membrane. The enzyme is under the double genetic control of the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Fatal human diseases have been associated with defects in ATP synthase (Complex V) activity linked to mtDNA or nDNA pathogenetic variants in genes encoding structural subunits or assembly factors. Mitochondrial post-translational modifications of key amino acids, reduced/increased subunit expression, or protein to protein ATP synthase interaction, are also some of the mechanisms involved in the age-related disease pathway. All the major neurodegenerative diseases: Parkinson’s, Alzheimer’s and motor neuron diseases such as Amyotrophic Lateral Sclerosis highlight an impaired ATP generation in a mechanism involving the permeability transition pore that triggers a cellular homeostasis failure responsible for different forms of regulated cell death. In this review, we will explore ATP synthase assembly and function in physiological and pathological conditions by referring to the recent cryo-EM studies and by exploring human diseases models.

Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases; divided into poor and normal responders) were enrolled along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet function (PRU), PON1 abundance by western blotting, and PON1 activity by enzymatic assays were measured. PON1 genotyping and computational haplotype phasing were performed for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p&gt; 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 6.79 µU/mL) when compared to controls (22.66 8.30 µU/mL and 22.21 9.66 µU/mL; p= 0.004). PON1 activity among carriers of the most prevalent PON1 haplotype (AA|AA) was significantly lower than in wild-types (7.90 µU/mL vs 22.03 µU/mL; p= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.

Data on immunogenicity, immune response persistency, and safety of COVID-19 boosters in patients with comorbidities are limited. Therefore, we aimed to evaluate and compare three different boosters in individuals who received two doses of the BBIBP-CorV vaccine including underlying diseases and healthy cases as control. One hundred forty subjects including 63 ones with at least one of three underlying diseases (UD) (including obesity, hypertension, and diabetes mellitus) and 77 healthy ones (HC) who had received a booster dose (either PastoCovac Plus or PastoCovac or BBIBP-CorV) were enrolled. The presence of SARS-CoV-2 antibodies was assessed before the booster injection and 28, 60, 90, and 180 days after it. Moreover, the adverse events (AEs) were recorded on days 7 and 21 post-booster shot for evaluating safety outcomes. Significantly increased titers of anti-spike, anti-RBD, and neutralizing antibodies were observed in both UD and HC groups 28 days after the booster dose, although the titer rise of anti-spike IgG and anti-RBD IgG was insignificantly inferior in the UD group compared to the HC group. All antibodies’ titers declined, with no significant differences between the two groups over time. Notably, all specific antibodies persisted up to 180 days; particularly the neutralizing antibody in both groups. Furthermore, no significant difference in antibody levels was observed between each UD subgroup and the HC group, except for neutralizing antibodies in the hypertension sub-group. PastoCovac Plus and PastoCovac boosters induced higher antibodies’ fold rise in UD individuals than BBIBP-CorV booster recipients. Safety outcomes did not show any serious AEs after the booster injection. The overall incidence of AEs post the booster injection was higher in the UD group than the HC group. Furthermore, the highest systemic AEs rate was reported in the UD group receiving the BBIBP-CorV booster. In conclusion, administration of COVID-19 boosters can equally induce robust and persistent humoral immune responses in individuals with or without UD primarily vaccinated with 2-doses of the BBIBP-CorV. Protein-based boosters with higher antibodies' fold rise and lower AEs in individuals with comorbidities might be considered a better choice for these individuals.

As the world's population ages and the resulting health problems become more serious, medical and health policies in developed countries are focused on how to prevent and treat the diseases of the aging population and how to maintain their quality of life. Typical age-related diseases include deafness, cataracts, osteoarthritis, chronic obstructive pulmonary disease, diabetes mellitus, and dementia. Although the mechanisms by which these diseases develop differ, they are all caused by the accumulation of molecular and cellular damage over time. In addition, age-related diseases can cause a decline in physical and mental functions and the ability to perform activities of daily living, as well as the loss of roles in society and a sense of fulfillment in life. Therefore, there is a need for treatment and measures to accurately grasp and maintain their quality of life.

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.

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.

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.

Many neurodegenerative diseases are characterised by impairment of protein quality control mechanisms in neuronal cells. Ineffective clearance of misfolded proteins by the proteasome, autophagy pathways and exocytosis leads to accumulation of toxic protein oligomers and aggregates in neurons. Toxic protein species affect various cellular functions resulting in the development of a spectrum of different neurodegenerative proteinopathies, including Huntington’s disease (HD). Playing an integral role in proteostasis, dysfunction of the ubiquitylation system in HD is progressive and multi-faceted with numerous biochemical pathways affected, in particular the ubiquitin proteasome system and autophagy routes for protein aggregate degradation. Unravelling the molecular mechanisms involved in HD pathogenesis of proteostasis provides insight in disease progression in HD as well as possible therapeutic avenues. Recent developments of potential therapeutics are discussed in this review.

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.

Of the roughly 20,000 canonical human protein sequences, as of September 15, 2020, 6,937 proteins have had their full or partial, medium- to high-resolution structures determined by x-ray crystallography or other methods. Which of these proteins dominate the Protein Data Bank (the PDB) and why? In this paper, we list the 273 top human protein structures based on the number of their PDB entries. This set of proteins accounts for more than 40% of all available human PDB entries and represent past trends as well as current status for protein structural biology. We briefly discuss the relationship which some of the prominent protein structures have with protein research as a whole and mention their relevance to human diseases. The top-10 soluble and membrane proteins are all well-known (most of their first structures being deposited more than 30 years ago). Overall, there is no dramatic change in recent trends in the PDB. Remarkably, the number of structure depositions has grown nearly exponentially over the last 10 or more years (with a doubling time of 7 yrs for proteins from all organisms). Growth in human protein structures is slightly faster (at 5.9 yrs, while E.Coli and Mouse+Rat protein structures accumulate more slowly, Zebrafish protein structures are growing most, at a doubling every 3.7 years, albeit starting from only approx. 100 structure entries in 2010). The information may be informative to senior scientists but also inspire researchers who are new to protein science, providing the year 2020 snap-shot for the state of protein structural biology.

Haemosporidians are a group of vector-borne parasites belonging to the order Haemosporida. They infect avian hosts and require blood-sucking insects (Diptera) for their transmission. The occurrence and diversity of haemosporidian parasites are shaped primarily by the specificity of the parasite and the susceptibility of the host/vector. In this study, the presence and distribution of haemosporidians in blood samples from birds in urbanized and natural habitats were estimated using microscopic and molecular approaches. Birds in urbanized habitats were infected with four different species of Plasmodium: Plasmodium relictum, P. vaughani, P. matutinum, P. circumflexum, two different species of Haemoproteus: Haemoproteus majoris, H. parabelopolskyi, and Leucocytozoon sp. The species, H. attenuatus, H. concavocentralis, H. minutus, H. pallidus, H. noctue and H. tartakovskyi were additionally identified in birds in natural habitats. Typically, juvenile birds are essential markers of parasite species transmitted in the study area. The juveniles in the urbanized habitats carried the P. relictum, P. vaughani, P. circumflexum, H. parabelopolskyi, H. majoris, and Leucocytozoon species. The most abundant parasite was H. parabelopolskyi, which was found in both types of habitats. The prevalence of the Haemoproteus/Plasmodium species by nested PCR in birds in natural habitats (in totally 43.80%; 53/121) was significantly higher than that in birds in urbanized habitats (in totally 21.94%; 43/196) (p < 0.05), even in spring. There was no statistically significant difference between habitat types in overall infection rate of Leucocytozoon sp. (p > 0.05; 10/121 vs. 19/196), neither overall nor in the spring.

Induced pluripotent stem cells (iPSC) are derived from reprogrammed adult somatic cells. These adult cells are manipulated in vitro to express genes and factors essential for acquiring and maintaining embryonic stem cell (ESC) properties. This technology is widely applied in many fields, and there has been much attention to developing iPSC-based disease models to validate drug discovery platforms and study pathophysiological molecular processes underlying disease onset. Especially in neurological diseases, there is a great need for iPSC-based technological research, as these cells can be obtained from each patient and carry the individual’s bulk of genetic mutations and properties. Moreover, iPSC can differentiate into multiple cell types. These are essential characteristics since the study of neurological diseases is affected by limited access to injured sites, in vitro models composed of various cell types, the complexity of reproducing the brain’s anatomy, ethical issues, and the fact that post-mortem cell culture is challenging. Neurodegenerative diseases enormously impact global health due to their high incidence, symptoms severity, and usually lack of effective therapies. Recently, analyses using disease-specific iPSC-based models confirmed their efficacy for testing multiple drugs. This review summarizes the advances in iPSC technology used in disease modeling and drug testing with a primary focus on neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases.

Background and Objectives: The COVID-19 pandemic influenced the management of patients with immune mediated rheumatic and musculoskeletal diseases (imRMDs) in various ways. The goal of our systematic review was to determine the influence of the first period of the COVID-19 pandemic on the management of imRMDs. Materials and Methods: Systematic literature search of PubMed, Cochrane and Embase databases, including studies with adult patients on the influence of the COVID-19 pandemic on management of imRMDs. There were no restrictions regarding to study-design except for systematic reviews and case reports that were excluded as well as articles on the disease outcomes in case of SARS-CoV-2 infection. Two reviewers screened the studies for inclusion, and, in case of disagreement, consensus was reached after discussion. Results: A total of 5969 potentially relevant studies were found, and, after title, abstract and full-text screening, 35 studies were included with data from 182’746 patients and 2018 rheumatologists. Non-availability of drugs, e.g., hydroxychloroquine and tocilizuab, was frequent (16–69% of patients). Further, medication non-adherence was reported among patients with different RMDs and between different drugs in 4–46% of patients. Changes to preexisting medication were reported in up to 33% of patients (e.g. reducing dose of steroids or cessation of biological disease-modifying antirheumatic drugs). Physical in-office consultations and laboratory testing decreased and as a consequence newly implemented remote consultations increased greatly with an increase of up to 80%. Conclusion: The COVID-19 pandemic influenced the management of imRMDs, especially at the beginning. Influences were wide-ranging, affecting availability of pharmacies, adherence to medication or medication changes, doctor visits and laboratory testing. New systems of care were set up, including virtual clinics and video consultations. These new forms of health care delivery should be spread and implemented worldwide to routine clinical practice to be ready for future pandemics.

Despite needs for new therapies and improvements in existing approaches in cardiovascular, pulmonary, endocrine, and renal disease, investment in these areas is lagging relative to other specialties. This article summarizes a meeting of key stakeholders of U.S. Food and Drug Administration (FDA) officials, representatives from academia, national organizations, and patients and caregivers. The purpose was to identify and discuss high-priority issues, establish areas of common interest, and explore opportunities for collaboration. During the meeting (September 2016), the construct of a “multimorbidity continuum” emerged, in which chronic diseases are understood as their effects on the whole rather than individual organ systems. Cross-disciplinary priorities included: 1) the need to generate greater high-quality evidence at lower cost; 2) the imperative to develop and implement patient-centered approaches to clinical investigations; 3) the importance of trial participation in under-represented populations, particularly with comorbid conditions, and 4) the need for progress in tobacco regulation. Representatives from each therapeutic area reported on their consensus priorities, and FDA representatives discussed the agency’s role in facilitating broader approaches to therapeutic development and evaluation of disease as linked across organ systems rather than in isolation, and emphasized the importance of patient engagement, collaboration and communication across stakeholders.

Receptor-interacting protein kinase 1 (RIPK1) plays a crucial role in controlling inflammation and cell death. Its function is tightly controlled through post-translational modifications, enabling its dynamic switch between promoting cell survival and triggering cell death. Phosphorylation of RIPK1 at various sites serves as a critical mechanism for regulating its activity, exerting either activating or inhibitory effects. Perturbations in RIPK1 phosphorylation status have profound implications for the development of severe inflammatory diseases in humans. This review explores the intricate regulation of RIPK1 phosphorylation and dephosphorylation and highlights the potential of targeting RIPK1 phosphorylation as a promising therapeutic strategy for mitigating human diseases.

Background: Garlic primarily reproduces through vegetative propagation using seed cloves due to infrequent sexual reproduction by true seeds. Growers encounter challenges with pathogens due to the larger size and vegetative nature of seed cloves, as well as the storage conditions conducive to fungal growth. Some Phyto-pathogenic fungi, previously unrecognized as garlic infections, can remain latent within bulb tissues long after harvest. Although outwardly healthy, these infected bulbs may develop rot under specific conditions. Aim of Review: Planting diseased seed cloves can contaminate field soil, with some fungal and bacterial infections persisting for extended periods. The substantial size of seed cloves makes complete eradication of deeply ingrained infections difficult, despite the use of systemic fungicides during pre-planting and post-harvest phases. Additionally, viruses, resistant to fungicides, persist in vegetative material. They are prevalent in much of the garlic used for planting and their host vectors are difficult to eliminate. To address these challenges, tissue culture techniques are increasingly employed to produce disease-free planting stock. Key Scientific Concepts of Review: This review delves into crucial scientific aspects related to garlic propagation and health. Garlic primarily reproduces through vegetative propagation using seed cloves, facing challenges due to their large size and susceptibility to fungal infections. Some fungal pathogens, recently identified as garlic threats, remain dormant within bulbs long after harvest, potentially causing rot under specific conditions. Planting infected seed cloves can introduce pathogens into the soil, where they may persist. Deeply ingrained infections can be challenging to eradicate due to the size of seed cloves. Additionally, viruses persist in garlic seeds and spread through their carrier vectors, unaffected by fungicides. To address these issues, tissue culture techniques offer a promising approach to produce disease-free garlic planting material. This review explores these concepts, emphasizing the importance of producing disease-free garlic seeds and strategies for mitigation.

Emerging infectious diseases (EIDs) continue to be a problem all across the world, but in certain areas the threat is greater than in others. The detection of new diseases will aid in the focus of surveillance efforts. Specifically, identifying a "patient zero" is critical step to help limit further transmission. In fact, several factors have been found to contribute to emerging infectious diseases emergence and transmission. Antigenic drift is an important factor that affects vaccine effectiveness and it is important for scientists and healthcare providers alike to understand how this process works in order to ensure that people receive effective vaccinations against infectious diseases. However, recent advances in biotechnology, immunology and artificial intelligence have enabled us to make progress in diagnosis, treatment, prevention and control of infectious diseases. The fight against infectious diseases will always be ongoing, but the advancement of bioscience offers a promising outlook for the near future. In the last two decades, several high impact zoonotic disease outbreaks have been linked to bat-borne viruses. These include SARS coronavirus, Hendra virus and Nipah virus. In addition, it has been suspected that ebolaviruses and MERS coronavirus are also linked to bats. It is being increasingly accepted that bats are potential reservoirs of a large number of known and unknown viruses, many of which could spillover into animal and human populations. In this article, we discuss the potential risk factors that contribute in emerging infectious diseases. Also, we discuss the management of disease prevention and control.

The emergence of the COVID-19 outbreak has caused a pandemic situation in over 210 countries. Controlling the spread of this disease has proven difficult despite several resources employed. Millions of hospitalization and deaths have been observed, and thousands of cases daily with many measures in place. Due to the complex nature of COVID-19, we proposed a system of time-fractional equations to understand the transmission of the disease better. Nonlocality involved in the model has made fractional differential equations appropriate for modeling the behavior. However, solving these types of models is computationally demanding. Our proposed generalized compartmental COVID-19 model incorporates effective contact rate, transition rate (from exposed quarantine and recovered to susceptible and infected quarantined individuals), quarantine rate, disease-induced death rate, natural death rate, natural recovery rate, recovery rate of quarantine infected for a holistic study of the coronavirus disease. A detailed analysis of the proposed model is carried out, including the existence and uniqueness of solutions, local and global stability analysis of the disease-free equilibrium analysis, and sensitivity analysis. Furthermore, numerical solutions of the proposed model are obtained with the generalized Adam-Bashforth-Moulton method developed for the fractional order model. Our analysis and solutions profile show that each of these incorporated parameters is very important in controlling the spread of COVID-19, especially quarantining exposed and infected individuals and the effective contact rate. Based on the results with different fractional order, we observe that there seems to be a third or even fourth wave of the spike in cases of COVID-19, which is what is happening right now in many countries.