Investigating the impact of inhaled paraquat: A comprehensive evaluation protocol.

This paper provides a complete protocol for studying the effects of inhaled paraquat (PQ), a toxic herbicide that has negative effects systemically and on the lungs. The protocol aims to evaluate the effects of aerosolized PQ exposure on lung and systemic injury in an animal model, which will provide significant information for therapeutic interventions for PQ-induced pulmonary and systemic damage. The protocol involves the following key components: 1. Study groups: By including control, non-treated aerosolized PQ-exposed, and treated PQ-exposed animals with various agent groups in the experiment, lung and systemic injury in each group could be evaluated, and different measured parameters could be compared among groups. 2. PQ exposure: Animals in the PQ-exposed groups are subjected to PQ aerosol inhalation, simulating occupational or accidental exposure in farmers working with this herbicide. 3. Assessment measures: To determine the degree of lung and systemic injury and its physiological effects, several assessments, such as biochemical markers, histopathological analysis, and functional tests, are used. The protocol offers reliable and accurate results by using standardized methods and data collection. The effect of PQ exposure on lung and systemic injury could be evaluated by statistical analysis of the collected data, which also makes it easier to identify possible protective agents or interventions. This comprehensive evaluation protocol provides an essential basis for studying the mechanisms behind PQ-induced lung and systemic injury and assessing the effectiveness of preventative or therapeutic strategies in minimizing its adverse effects.

Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine.

Energy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, cell fate (proliferation, survival, apoptosis, malignant transformation etc.), and, on the other hand, carcinogenesis, tumor development, progression and metastazing versus anti-cancer protection and cure. The orchestrator is the mitochondria who produce, store and invest energy, conduct intracellular and systemically relevant signals decisive for internal and environmental stress adaptation, and coordinate corresponding processes at cellular and organismal levels. Consequently, the quality of mitochondrial health and homeostasis is a reliable target for health risk assessment at the stage of reversible damage to the health followed by cost-effective personalized protection against health-to-disease transition as well as for targeted protection against the disease progression (secondary care of cancer patients against growing primary tumors and metastatic disease). The energy reprogramming of non-small cell lung cancer (NSCLC) attracts particular attention as clinically relevant and instrumental for the paradigm change from reactive medical services to predictive, preventive and personalized medicine (3PM). This article provides a detailed overview towards mechanisms and biological pathways involving metabolic reprogramming (MR) with respect to inhibiting the synthesis of biomolecules and blocking common NSCLC metabolic pathways as anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules to yield mitochondrial substrates for energy homeostasis and nucleotide synthesis. Histone modification and DNA methylation can predict the onset of diseases, and plasma C7 analysis is an efficient medical service potentially resulting in an optimized healthcare economy in corresponding areas. The MEMP scoring provides the guidance for immunotherapy, prognostic assessment, and anti-cancer drug development. Metabolite sensing mechanisms of nutrients and their derivatives are potential MR-related therapy in NSCLC. Moreover, miR-495-3p reprogramming of sphingolipid rheostat by targeting Sphk1, 22/FOXM1 axis regulation, and A2 receptor antagonist are highly promising therapy strategies. TFEB as a biomarker in predicting immune checkpoint blockade and redox-related lncRNA prognostic signature (redox-LPS) are considered reliable predictive approaches. Finally, exemplified in this article metabolic phenotyping is instrumental for innovative population screening, health risk assessment, predictive multi-level diagnostics, targeted prevention, and treatment algorithms tailored to personalized patient profiles-all are essential pillars in the paradigm change from reactive medical services to 3PM approach in overall management of lung cancers. This article highlights the 3PM relevant innovation focused on energy metabolism as the hub to advance NSCLC management benefiting vulnerable subpopulations, affected patients, and healthcare at large. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00357-5.

Systemic health effects of noise exposure.

Noise, any unwanted sound, is pervasive and impacts large populations worldwide. Investigators suggested that noise exposure not only induces auditory damage but also produces various organ system dysfunctions. Although previous reviews primarily focused on noise-induced cardiovascular and cerebral dysfunctions, this narrow focus has unintentionally led the research community to disregard the importance of other vital organs. Indeed, limited studies revealed that noise exposure impacts other organs including the liver, kidneys, pancreas, lung, and gastrointestinal tract. Therefore, the aim of this review was to examine the effects of noise on both the extensively studied organs, the brain and heart, but also determine noise impact on other vital organs. The goal was to illustrate a comprehensive understanding of the systemic effects of noise. These systemic effects may guide future clinical research and epidemiological endpoints, emphasizing the importance of considering noise exposure history in diagnosing various systemic diseases.

Unusual systemic and nondental effects of maxillary expansion therapy: A comprehensive and updated review of literature.

In dental practice, pediatric patients with a wide range of manifestations of malocclusion viz. crossbite, dental crowding, and skeletal Class III due to transverse discrepancy of the abnormally constricted maxilla or palate are found. However, the dental management of such kind of malocclusion with narrow palate needs a meticulous dental evaluation. Appliances used for treating such malocclusion conditions may include Slow-Maxillary Expansion (SME) or Rapid Maxillary Expansion (RME) orthodontic or orthopedic appliances. Considerable success has been described in the literature using the maxillary/palatal expansion modality. Unusual systemic and nondental effects of expansion appliances therapy have been described in some scientific studies. However, no comprehensive review article has been published describing the nondental and systemic effects of RME/SME therapy in Pediatric Dentistry. Considering the above scenarios, the updated and comprehensive review of the relevant literature is necessary for health professionals. Dental professionals including pediatric dentists and orthodontists need to consider such untoward or unexpected effects of RME/SME treatment modality. Hence, the current comprehensive review article has been written with the aim to meticulously describe the relevant scientific literature about nondental/extraoral and systemic effects of RME/SME appliances.

Inhalation Pharmacodynamics.

Pharmacodynamics (PD) is discussed in relation to inhalation exposure to inhaled pharmaceutical and toxic agents. Clearly PD is closely related to pharmacokinetics, and this relation is illustrated with reference to inhaled insulin. PD can be related to pharmacologic responses, and some examples are cited. However, PD can also be thought of as the improvement or deterioration in lung disease state. Some of the major PD endpoints, including histopathology, pulmonary function, and bronchoalveolar lavage are reviewed. Brief reference is also given to other specialty biomarkers of PD response.

Assessing the Effects of Changing Patterns of Inhaled Corticosteroid Dosing and Adherence with Fluticasone Furoate and Budesonide on Asthma Management.

INTRODUCTION: Pharmacological asthma management focuses on the use of inhaled corticosteroid (ICS)-containing therapies, which reduce airway inflammation and provide bronchoprotection, improving symptom control and reducing exacerbation risk. ICS underuse due to poor adherence is common, leading to poor clinical outcomes including increased risk of mortality. This article reviews efficacy versus systemic activity profiles for various adherence patterns and dosing regimens of fluticasone furoate (FF)-containing and budesonide (BUD)-containing asthma therapies in clinical trials and real-world studies. METHODS: We performed a structured literature review (1 January 2000-3 March 2022) and mathematical modelling analysis of FF-containing and BUD-containing regular daily dosing in patients with mild-to-severe asthma, as-needed BUD/formoterol (FOR) in mild asthma, and BUD/FOR maintenance and reliever therapy (MART) dosing in moderate-to-severe asthma, to assess efficacy (bronchoprotection) and systemic activity (cortisol suppression) profiles of dosing patterns of ICS use in multiple adherence scenarios. RESULTS: A total of 22 manuscripts were included in full-text review and 18 in the model simulations. Focusing on FF-containing or BUD-containing treatments at comparable adherence rates, regular daily FF or FF/vilanterol (VI) dosing provided more prolonged bronchoprotection and fewer systemic effects than daily BUD, daily BUD/FOR, or BUD/FOR MART dosing, especially in low adherence scenarios. In model simulations and the real-world setting, FF/VI generally provided longer bronchoprotection, lower systemic activity, and greater clinical benefits over BUD/FOR as well as consistently higher adherence. CONCLUSION: In this literature review and modelling analysis, FF/VI was found to show clinical advantages on asthma control over BUD/FOR. These findings have implications for helping clinicians select the most suitable inhaled therapy for their patients with asthma.

Systemic Effects of Prenatal Carotenoid Supplementation in the Mother and her Child: The Lutein and Zeaxanthin in Pregnancy (L-ZIP) Randomized Trial -Report Number 1.

BACKGROUND: Adding carotenoids, particularly lutein (L) and zeaxanthin (Z), to prenatal micronutrient formulations has been promoted to enhance infant visual and neural development and to maintain maternal health. Although these claims are biologically plausible, they are not yet supported by a compelling prospective trial. OBJECTIVE: We investigated the effect of prenatal carotenoid supplementation on biomarkers of maternal and infant systemic carotenoid status. METHODS: We randomly assigned 47 first trimester pregnant subjects by 1:1 allocation to receive standard-of-care prenatal vitamins plus a 10 mg L and 2 mg Z softgel (the Carotenoid group) or standard-of-care prenatal vitamins with a placebo softgel (the Control group) for 6-8 mo. Maternal carotenoid concentrations in the serum and skin at the end of each trimester and postpartum were measured with HPLC and resonance Raman spectroscopy, respectively. Infants' systemic carotenoid status was assessed using similar techniques but optimized for infants. Repeated measures and paired t-tests were determined, and a P value < 0.05 was considered statistically significant. RESULTS: After supplementation, there was a statistically significant increase in maternal serum L + Z concentrations, serum total carotenoid concentrations, and skin carotenoid status (P < 0.001 for all) in the Carotenoid group relative to the Control group at all study time points. Similarly, infants whose mothers were in the Carotenoid group had a significant 5-fold increase in cord blood L + Z concentrations, over a 3-fold increase in cord blood total carotenoids, and a 38% increase in skin carotenoids compared with the Control group (P < 0.0001 for all). In addition, there was a strong positive, statistically significant correlation between postpartum maternal and infant systemic carotenoid status (P < 0.0001). CONCLUSION: Prenatal carotenoid supplementation significantly increased maternal and infant systemic (skin and serum) carotenoid status, which may benefit pregnant women and their infants' health. This trial was registered at clinicaltrials.gov as NCT03750968.

Safety of purified Vero cell rabies vaccine manufactured in Pakistan: a comparative analysis of intradermal and intramuscular routes.

BACKGROUND: Rabies vaccines are conventionally given via the intramuscular (IM) route; however, switching the route of administration from IM to intradermal (ID) without affecting efficacy can be advantageous in terms of cost, dosing, and time. Hence, it is indispensable to evaluate its safety along different routes. This study was carried out to ascertain the frequency of adverse drug events (ADEs) and associated factors, as well as to compare safety based on the IM and ID routes. METHODS: A prospective observational study was carried out on 184 individuals with rabies exposure. The vaccination schedules for post-exposure prophylaxis (PEP) included 0.2 milliliter (mL) of purified Vero cell rabies vaccine (PVRV) administered ID at two different sites with 0.1 mL each on days 0, 3, and 7 in first group (3-dose regimen ID) and 0.5 mL administered IM on days 0, 3, 7, 14, and 28 in the second group (5-dose regimen IM). The safety of the vaccines was determined by reviewing ADEs during physical examinations and follow-up. ADEs were characterized by local and systemic effects. RESULTS: Of the total, 99 (53.80%) patients reported ADEs. Those who reported local and systemic ADEs were 80 (43.48%) and 59 (32.06%), respectively, while simultaneous occurrence was reported in 40 (40.40%) patients. The most frequent local ADE (76; 41.30%) reported was pain, followed by erythema (18; 9.78%). Additionally, fever had the highest proportion (25; 13.59%) for systemic effects, followed by headache (15; 8.15%). The patients reported with ADEs by the IM and ID routes were comparable (p >.05). Similarly, both local and systemic effects were also comparable (p >.05). CONCLUSION: Half of the study participants reported ADEs. Almost similar proportions of local and systemic effects were observed. Likewise, the ADEs recorded were comparable for both routes. PVRV carries very low safety concerns with either route for administration.

Air Pollutant impacts on the brain and neuroendocrine system with implications for peripheral organs: a perspective.

Air pollutants are being increasingly linked to extrapulmonary multi-organ effects. Specifically, recent studies associate air pollutants with brain disorders including psychiatric conditions, neuroinflammation and chronic diseases. Current evidence of the linkages between neuropsychiatric conditions and chronic peripheral immune and metabolic diseases provides insights on the potential role of the neuroendocrine system in mediating neural and systemic effects of inhaled pollutants (reactive particulates and gases). Autonomically-driven stress responses, involving sympathetic-adrenal-medullary and hypothalamus-pituitary-adrenal axes regulate cellular physiological processes through adrenal-derived hormones and diverse receptor systems. Recent experimental evidence demonstrates the contribution of the very stress system responding to non-chemical stressors, in mediating systemic and neural effects of reactive air pollutants. The assessment of how respiratory encounter of air pollutants induce lung and peripheral responses through brain and neuroendocrine system, and how the impairment of these stress pathways could be linked to chronic diseases will improve understanding of the causes of individual variations in susceptibility and the contribution of habituation/learning and resiliency. This review highlights effects of air pollution in the respiratory tract that impact the brain and neuroendocrine system, including the role of autonomic sensory nervous system in triggering neural stress response, the likely contribution of translocated nano particles or metal components, and biological mediators released systemically in causing effects remote to the respiratory tract. The perspective on the use of systems approaches that incorporate multiple chemical and non-chemical stressors, including environmental, physiological and psychosocial, with the assessment of interactive neural mechanisms and peripheral networks are emphasized.

Immune System Activation in Patients with Metastatic Renal Cell Carcinoma Induced by the Systemic Abscopal Effects of Radiation Therapy.

INTRODUCTION: Renal cell carcinoma (RCC) is characterized by large histopathologic heterogeneity and classified with multiple histological subtypes. Radiation therapy has long played a key role in the management of both local and metastatic RCC. An out-of-field tumor regression (abscopal response) effect of radiation therapy has gained significant importance in the treatment of different tumor types including RCC. In this study, we provide a detailed overview of the current state of knowledge and clinical experience of radiation therapy-induced abscopal effects in patients with advanced RCC. METHODS: The PRISMA guidelines were followed to identify the published articles for the study. Using electronic databases such as MEDLINE via PubMed and Google Scholar, a systematic literature review was performed to find published clinical evidence for radiation therapy-induced abscopal effects in patients with advanced RCC. The clinical data of radiation therapy-induced abscopal effects were reviewed, and the outcomes have been summarized. RESULTS: In this study, we evaluated peer-reviewed published reports to find clinical evidence for the abscopal effect following radiation therapy in patients with advanced RCC. The clinical data on the systemic abscopal effects of radiation therapy were reviewed, and the outcomes were summarized. Our literature search indicated that the evidence for abscopal effects of radiation therapy in advanced RCC yielded over 20 case reports. The evidence indicates that abscopal effects of local radiation therapy may occur in RCC through tumor cell destruction with the subsequent release of tumor antigens that systemically stimulate the immune system of the host to activate the body's immune effector cells and produce distant nontarget antitumor effects. The activation of the immune system by local radiation therapy forms the basis to combine immunotherapy to boost its abscopal effects. CONCLUSIONS: Collectively, these findings suggest that radiation therapy can induce systemic abscopal effects through immune system activation, and thus, the addition of immunotherapeutic agents increases the potential to boost the systemic abscopal responses in patients with advanced cancers including RCC.

The Effect of Subglottic Steroid injection on Blood Glucose in a Cohort of Patients With Subglottic Stenosis.

OBJECTIVE: The objective of this work was to assess the effect of a single intralesional subglottic steroid injection on fasting blood glucose over 7 days in a cohort of patients with subglottic stenosis. METHODS: A prospective cohort study of patients undergoing intralesional steroid injections at a tertiary academic center. Patients had baseline bloodwork performed, including fasting blood glucose (FBG), and hemoglobin A1C levels. Demographic data and risk factors were collected. Fasting capillary glucose (FCG) was measured using a capillary glucometer and performed by patients daily from days 0 to 7 after a single injection of Triamcinolone into the subglottic airway. Data were analyzed using descriptive and comparative statistics. RESULTS: Eleven patients were enrolled, and 10 completed data collection over 7 days. All were female, with a mean age of 52.6 years (SD 17.5). Two patients were diabetic (non-insulin dependent). There was a statistically significant increase in FCG on day 1 post-injection (mean = 122.4 mg/dl compared to 100.7 mg/dl) that normalized for all patients within 24-72 h. The mean increase in FCG was 21.5% (SD 22.5%) of the initial value for the cohort. The diabetic group had statistically significant higher glucose values on day 1 compared to the non-diabetic group (146.5 mg/dl compared to 117.0 mg/dl). CONCLUSION: A single subglottic steroid injection appears to cause a transient increase in FCG 1 day post injection, which resolves after 24-72 h and can be more pronounced in diabetic patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1590-1594, 2023.

Ischemic stroke of unclear aetiology: a case-by-case analysis and call for a multi-professional predictive, preventive and personalised approach.

Due to the reactive medical approach applied to disease management, stroke has reached an epidemic scale worldwide. In 2019, the global stroke prevalence was 101.5 million people, wherefrom 77.2 million (about 76%) suffered from ischemic stroke; 20.7 and 8.4 million suffered from intracerebral and subarachnoid haemorrhage, respectively. Globally in the year 2019 - 3.3, 2.9 and 0.4 million individuals died of ischemic stroke, intracerebral and subarachnoid haemorrhage, respectively. During the last three decades, the absolute number of cases increased substantially. The current prevalence of stroke is 110 million patients worldwide with more than 60% below the age of 70 years. Prognoses by the World Stroke Organisation are pessimistic: globally, it is predicted that 1 in 4 adults over the age of 25 will suffer stroke in their lifetime. Although age is the best known contributing factor, over 16% of all strokes occur in teenagers and young adults aged 15-49 years and the incidence trend in this population is increasing. The corresponding socio-economic burden of stroke, which is the leading cause of disability, is enormous. Global costs of stroke are estimated at 721 billion US dollars, which is 0.66% of the global GDP. Clinically manifested strokes are only the "tip of the iceberg": it is estimated that the total number of stroke patients is about 14 times greater than the currently applied reactive medical approach is capable to identify and manage. Specifically, lacunar stroke (LS), which is characteristic for silent brain infarction, represents up to 30% of all ischemic strokes. Silent LS, which is diagnosed mainly by routine health check-up and autopsy in individuals without stroke history, has a reported prevalence of silent brain infarction up to 55% in the investigated populations. To this end, silent brain infarction is an independent predictor of ischemic stroke. Further, small vessel disease and silent lacunar brain infarction are considered strong contributors to cognitive impairments, dementia, depression and suicide, amongst others in the general population. In sub-populations such as diabetes mellitus type 2, proliferative diabetic retinopathy is an independent predictor of ischemic stroke. According to various statistical sources, cryptogenic strokes account for 15 to 40% of the entire stroke incidence. The question to consider here is, whether a cryptogenic stroke is fully referable to unidentifiable aetiology or rather to underestimated risks. Considering the latter, translational research might be of great clinical utility to realise innovative predictive and preventive approaches, potentially benefiting high risk individuals and society at large. In this position paper, the consortium has combined multi-professional expertise to provide clear statements towards the paradigm change from reactive to predictive, preventive and personalised medicine in stroke management, the crucial elements of which are:Consolidation of multi-disciplinary expertise including family medicine, predictive and in-depth diagnostics followed by the targeted primary and secondary (e.g. treated cancer) prevention of silent brain infarctionApplication of the health risk assessment focused on sub-optimal health conditions to effectively prevent health-to-disease transitionApplication of AI in medicine, machine learning and treatment algorithms tailored to robust biomarker patternsApplication of innovative screening programmes which adequately consider the needs of young populations.

Predicted COVID-19 molecular effects on endometrium reveal key dysregulated genes and functions.

COVID-19 exerts systemic effects that can compromise various organs and systems. Although retrospective and in silico studies and prospective preliminary analysis have assessed the possibility of direct infection of the endometrium, there is a lack of in-depth and prospective studies on the impact of systemic disease on key endometrial genes and functions across the menstrual cycle and window of implantation. Gene expression data have been obtained from (i) healthy secretory endometrium collected from 42 women without endometrial pathologies and (ii) nasopharyngeal swabs from 231 women with COVID-19 and 30 negative controls. To predict how COVID-19-related gene expression changes impact key endometrial genes and functions, an in silico model was developed by integrating the endometrial and COVID-19 datasets in an affected mid-secretory endometrium gene co-expression network. An endometrial validation set comprising 16 women (8 confirmed to have COVID-19 and 8 negative test controls) was prospectively collected to validate the expression of key genes. We predicted that five genes important for embryo implantation were affected by COVID-19 (downregulation of COBL, GPX3 and SOCS3, and upregulation of DOCK2 and SLC2A3). We experimentally validated these genes in COVID-19 patients using endometrial biopsies during the secretory phase of the menstrual cycle. The results generally support the in silico model predictions, suggesting that the transcriptomic landscape changes mediated by COVID-19 affect endometrial receptivity genes and key processes necessary for fertility, such as immune system function, protection against oxidative damage and development vital for embryo implantation and early development.

Pre-pregnancy check-up of maternal vascular status and associated phenotype is crucial for the health of mother and offspring.

Abstract: Cardiovascular disease remains the leading cause of disease burden globally with far-reaching consequences including enormous socio-economic burden to healthcare and society at large. Cardiovascular health is decisive for reproductive function, healthy pregnancy and postpartum. During pregnancy, maternal cardiovascular system is exposed to highly increased haemodynamic stress that significantly impacts health status of the mother and offspring. Resulting from sub-optimal maternal health conditions overlooked in pre-pregnancy time, progressive abnormalities can be expected during pregnancy and postpartum. Contextually, there are two main concepts to follow in the framework of predictive, preventive and personalised medicine, namely to develop:1. advanced screening of sub-optimal health conditions in young populations to predict and prevent individual health risks prior to planned pregnancies2. in-depth companion diagnostics during pregnancy to predict and prevent long-lasting postpartum health risks of the mother and offspring.Data collected in the current study demonstrate group-specific complications to health of the mother and offspring and clinical relevance of the related phenotyping in pre-pregnant mothers. Diagnostic approach proposed in this study revealed its great clinical utility demonstrating important synergies between cardiovascular maladaptation and connective tissue dysfunction. Co-diagnosed pre-pregnancy low BMI of the mother, connective tissue dysfunction, increased stiffness of peripheral vessels and decreased blood pressure are considered a highly specific maternal phenotype useful for innovative screening programmes in young populations to predict and prevent severe risks to health of the mother and offspring. This crucial discovery brings together systemic effects characteristic, for example, for individuals with Flammer syndrome predisposed to the phenotype-specific primary vascular dysregulation, pregnancy-associated risks, normal tension glaucoma, ischemic stroke at young age, impaired wound healing and associated disorders. Proposed maternal phenotyping is crucial to predict and effectively protect both the mother and offspring against health-to-disease transition. Pre-pregnancy check-up focused on sub-optimal health and utilising here described phenotypes is pivotal for advanced health policy. Plain English abstract: Cardiovascular health is decisive for reproductive function and healthy pregnancy. During pregnancy, maternal cardiovascular system may demonstrate health-to-disease transition relevant for the affected mother and offspring. Overlooked in pre-pregnancy time, progressive abnormalities can be expected during pregnancy and lifelong. Here we co-diagnosed maternal pre-pregnancy low bodyweight with systemic effects which may increase risks of pregnancy, eye and heart disorders and ischemic stroke at young age, amongst others. Innovative screening  programmes focused on sub-optimal health in young populations to predict and to mitigate individual health risks prior to pregnancy is an essential innovation for health policy proposed.

Toxicity of micro(nano)plastics with different size and surface charge on human nasal epithelial cells and rats via intranasal exposure.

Micro (nano)plastics (MNPs) have become emerging environmental contaminants, yet their toxicity and systemic effects via intranasal exposure remain unclear. This study investigated the in vitro toxicity of thirteen polystyrene MNPs with different surface functionalization (carboxylic (C-PS), amino (A-PS), and bare (PS)) and sizes (20-2000 nm) on human nasal epithelial cells (HNEpCs) at 10-1250 µg/mL as well as their in vivo toxicity to rats via intranasal administration at 125 µg/mL. The in vitro study showed that PS20, PS50, A-PS50, PS500, and A-PS500 significantly inhibited cell viability, which was dependent on particle concentration. A-PS induced higher cytotoxicity than C-PS and PS, and most MNPs inhibited cell proliferation after 24-h. Flow cytometry analysis suggested that PS induced cell apoptosis, while A-PS caused cell necrosis. MNPs were phagocytosed by HNEpCs and entered nucleus. The in vivo study showed that MNPs inhibited dietary behaviors of rats. Histological analysis indicated that PS20, PS200, and A-PS50 thinned out nasal mucosa. Immunohistochemical analysis revealed that exposure to PS20, PS200, and A-PS50 enhanced expression of transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8). Systemic effects including hepatocyte cytoplasmic vacuolation and renal tubule dilatation were observed. The results suggested that nasal inhalation of MNPs may disturb energy metabolism and damage upper respiratory tract, liver, and kidneys.

Health promotion through structured oral hygiene and good tooth alignment.

Aim: Periodontal diseases and caries are two of the most common forms of chronic degenerative diseases, with consequences not only for the oral cavity manifesting as tooth loss, orofacial pain and xerostomia, but also with effects on the cardiovascular system and, in the elderly, on the pneumonia rate. This can be prevented or controlled by structured oral hygiene. Method: Based on a systematic literature search in PubMed, the possibilities for ensuring structured oral hygiene are analyzed. Results and conclusion: Limiting the consumption of sugary meals and beverages, regular removal of food debris - supplemented by sugar-free chewing gum if desired - and preventing plaque formation by brushing with fluoridated toothpastes, using dental floss and interdental brushes after meals, serve to prevent or control gingivitis, periodontitis and caries. In the long term, the development of periodontitis-associated cardiovascular diseases and, in the elderly, the risk of pneumonia can probably be reduced. Antiseptic rinsing of the oral cavity is an important supplement to prevent periodontitis, especially in cases of limited ability to perform mechanical biofilm removal, but also for the prevention of respiratory infections. Proper functional tooth alignment is important for optimal mechanical cleaning to prevent plaque accumulation. If correction of misaligned teeth is possible with the use of removable aligners instead of fixed orthodontic appliances, these are to be preferred because of the better accessibility for mechanical hygiene measures.

Mitochondrial health quality control: measurements and interpretation in the framework of predictive, preventive, and personalized medicine.

Mitochondria are the "gatekeeper" in a wide range of cellular functions, signaling events, cell homeostasis, proliferation, and apoptosis. Consequently, mitochondrial injury is linked to systemic effects compromising multi-organ functionality. Although mitochondrial stress is common for many pathomechanisms, individual outcomes differ significantly comprising a spectrum of associated pathologies and their severity grade. Consequently, a highly ambitious task in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM/3PM) is to distinguish between individual disease predisposition and progression under circumstances, resulting in compromised mitochondrial health followed by mitigating measures tailored to the individualized patient profile. For the successful implementation of PPPM concepts, robust parameters are essential to quantify mitochondrial health sustainability. The current article analyses added value of Mitochondrial Health Index (MHI) and Bioenergetic Health Index (BHI) as potential systems to quantify mitochondrial health relevant for the disease development and its severity grade. Based on the pathomechanisms related to the compromised mitochondrial health and in the context of primary, secondary, and tertiary care, a broad spectrum of conditions can significantly benefit from robust quantification systems using MHI/BHI as a prototype to be further improved. Following health conditions can benefit from that: planned pregnancies (improved outcomes for mother and offspring health), suboptimal health conditions with reversible health damage, suboptimal life-style patterns and metabolic syndrome(s) predisposition, multi-factorial stress conditions, genotoxic environment, ischemic stroke of unclear aetiology, phenotypic predisposition to aggressive cancer subtypes, pathologies associated with premature aging and neuro/degeneration, acute infectious diseases such as COVID-19 pandemics, among others.

Circulating cell free DNA and citrullinated histone H3 as useful biomarkers of NETosis in endometrial cancer.

BACKGROUND: Cancer mortality is mainly caused by organ failure and thrombotic events. It has been demonstrated that NETosis, a chromatin release mechanism implemented by neutrophils, may contribute to these lethal systemic effects. Our aim was to investigate NETosis biomarkers in endometrial cancer (EC). METHODS: The experiments were conducted on 21 healthy subjects (HS) with no gynecological conditions, and on 63 EC patients. To assess the presence of NETosis features, IHC and IF was performed using antibodies against citrullinated histone H3 (citH3), neutrophil elastase (NE) and histone 2B. Serum levels of cell free DNA (cfDNA), cell free mitochondrial DNA (cfmtDNA) and citH3 were measured by qPCR using one microliter of deactivated serum, and by ELISA assay respectively. Fragmentation pattern of serum cfDNA was analyzed using the Agilent 2100 Bioanalyzer and High Sensitivity DNA Chips. Receiver operating characteristic (ROC) analysis was used to identify a cut off for cfDNA and cfmtDNA values able to discriminate between ECs and HSs. Correlation analysis and multiple correspondence analysis (MCA) between cfDNA, mtcfDNA, citH3 and blood parameters were used to identify the potential association among serum parameters in EC grades. RESULTS: We demonstrated the presence of NETosis features in tissues from all EC grades. Serum cfDNA and cfmtDNA levels discriminate ECs from HSs and a direct correlation between citH3 and cfDNA content and an inverse correlation between cfmtDNA and citH3 in EC sera was observed, not detectable in HSs. MCA indicates cfDNA, cfmtDNA and citH3 as features associated to G1 and G2 grades. A correlation between increased levels of cfDNA, citH3 and inflammation features was found. Finally, serum nucleosomal cfDNA fragmentation pattern varies in EC sera and correlates with increased levels of cfDNA, citH3, lymphocytes and fibrinogen. CONCLUSION: Our data highlight the occurrence of NETosis in EC and indicate serum cfDNA and citH3 as noninvasive biomarkers of tumor-induced systemic effects in endometrial cancer.

Extension and Severity of Self-Reported Side Effects of Seven COVID-19 Vaccines in Mexican Population.

A few studies examined the comparative side effects of Coronavirus Disease-19 (COVID-19) vaccines. We compared the extension and severity of self-reported side effects of seven COVID-19 vaccines [BNT162b2 (Pfizer-BioNTech), ChAdOx1 (AstraZeneca), mRNA-1273 (Moderna), CoronaVac (Sinovac Life Sciences), Gam-COVID-Vac (Gamaleya's Sputnik V), Ad5-nCoV (CanSinoBIO), and Ad26.CoV2.S (Johnson & Johnson/Janssen)] in the Mexican population. We also evaluated the association of type of vaccine, sex, age, comorbidity, and history of allergies to the extent and severity of side effects. This was a cross-sectional study carried out online between August 12 and September 3, 2021 in Mexico. The first inclusion criterion was to receive a COVID-19 vaccine and the second, being at least 18 years old. The survey link was distributed via multiple social media platforms. We questioned about the type of vaccine and symptoms based on short-term side effects reported in the literature. Side effect extension was classified as local, systemic, or both. We asked about the need to take medicine, stop activities/miss work, or seek medical attention. Then, a severity index was constructed based on responses. Descriptive and stepwise multivariate logistic ordinal regression analyses were used to calculate odds ratio (OR) and 95% CI for each outcome adjusted by potential confounders. The mean age was 38.9 ± 11.0 years (n = 4,024). Prevalence of at least one side effect varied between vaccines and by a number of doses. At dose 1, ChAdOx1 was the vaccine with the highest rate of at least one side effect (85%) followed by Gam-COVID-Vac (80%). Both were associated to greater extension (adjusted OR 2.53, 95% CI 2.16, 2.96 and adjusted OR 2.41, 95% CI 1.76, 3.29, respectively) and severity of side effects (adjusted OR 4.32, 95% CI 3.73, 5.00 and adjusted OR 3.00, 95% CI 2.28, 3.94, respectively). Young age (<50 years), female sex, comorbidity, and history of allergies were associated with greater extension and severity, independent of the type of vaccine and potential confounders. At dose 2, mRNA-1273 was the vaccine with the highest rate of side effects (88%) and the only vaccine associated to greater extension (adjusted OR 2.88, 95% CI 1.59, 5.21) and severity of symptoms (adjusted OR 3.14, 95% CI 1.82, 5.43). Continuous studies are necessary to acknowledge more post-vaccine symptoms in different populations.