Topical Cellular/Tissue and Molecular Aspects Regarding Nonpharmacological Interventions in Alzheimer's Disease-A Systematic Review.

One of the most complex and challenging developments at the beginning of the third millennium is the alarming increase in demographic aging, mainly-but not exclusively-affecting developed countries. This reality results in one of the harsh medical, social, and economic consequences: the continuously increasing number of people with dementia, including Alzheimer's disease (AD), which accounts for up to 80% of all such types of pathology. Its large and progressive disabling potential, which eventually leads to death, therefore represents an important public health matter, especially because there is no known cure for this disease. Consequently, periodic reappraisals of different therapeutic possibilities are necessary. For this purpose, we conducted this systematic literature review investigating nonpharmacological interventions for AD, including their currently known cellular and molecular action bases. This endeavor was based on the PRISMA method, by which we selected 116 eligible articles published during the last year. Because of the unfortunate lack of effective treatments for AD, it is necessary to enhance efforts toward identifying and improving various therapeutic and rehabilitative approaches, as well as related prophylactic measures.

Epidemiology of Injuries in Professional and Amateur Football Men (Part II).

Background (1): Men's football is a physically demanding contact sport that involves intermittent bouts of sprinting, jogging, walking, jumping and changes of direction. The physical demands of the game vary by level of play (amateur club, sub-elite and open club or international), but injury rates at all levels of the men's football game remain the highest of all sports. Objective: The aim of this study is to conduct a systematic review of data from the epidemiological literature regarding the profile, severity and mechanisms of injuries and the frequency of recurrent injuries in professional and amateur football players. Methods (2): A systematic review, according to PRISMA guidelines, was performed up to June 2023 in the databases of PubMed, Web of Science, Google academic, Google scholar and the Diva portal. Twenty-seven studies that reported data on the type, severity, recurrence and mechanisms of injury in professional and amateur men's football were selected and analyzed. Two reviewers independently audited data and assessed the study quality using the additional and adapted version of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and the Newcastle Ottawa Scale (NOS) to assess risk of bias for the quality of external validity. Results (3): In professional male football players, the mean prevalence of muscle/tendon injuries was 39.78%, followed by joint and ligament injuries-21.13%, contusions-17.86%, and fractures-3.27%, and for amateur football players, the prevalence's were 44.56% (muscle/tendon injuries), 27.62% (joint and ligament injuries), 15.0% (contusions) and 3.05% (fracture), respectively. The frequency of traumatic injuries was higher in amateur football players (76.88%) compared to professional football players (64.16%), the situation being reversed in the case of overuse injuries: 27.62% in professional football players and 21.13% in amateur football players. Most contact injuries were found in professional footballers (50.70%), with non-contact injuries predominating in amateur footballers (54.04%). The analysis of the severity of injuries showed that moderate injuries dominated in the two categories of footballers; the severe injuries in amateur footballers exceeded the severe injuries recorded in professional footballers by 9.60%. Recurrence proportions showed an inverse relationship with the level of play, being higher in amateur footballers (16.66%) compared to professional footballers (15.25%). Conclusions (4): Football-related injuries have a significant impact on professional and amateur football players and their short- and long-term health status. Knowing the frequency of severe diagnoses, such as strains, tears and cramps of the thigh muscles, ankle ligament sprains and hip/groin muscle strain requires the establishment of adequate programs to prevent them, especially in amateur football players, who are more prone to serious injuries.

Mechanistic Intimate Insights into the Role of Hydrogen Sulfide in Alzheimer's Disease: A Recent Systematic Review.

In the rapidly evolving field of Alzheimer's Disease (AD) research, the intricate role of Hydrogen Sulfide (H2S) has garnered critical attention for its diverse involvement in both pathological substrates and prospective therapeutic paradigms. While conventional pathophysiological models of AD have primarily emphasized the significance of amyloid-beta (Aß) deposition and tau protein hyperphosphorylation, this targeted systematic review meticulously aggregates and rigorously appraises seminal contributions from the past year elucidating the complex mechanisms of H2S in AD pathogenesis. Current scholarly literature accentuates H2S's dual role, delineating its regulatory functions in critical cellular processes-such as neurotransmission, inflammation, and oxidative stress homeostasis-while concurrently highlighting its disruptive impact on quintessential AD biomarkers. Moreover, this review illuminates the nuanced mechanistic intimate interactions of H2S in cerebrovascular and cardiovascular pathology associated with AD, thereby exploring avant-garde therapeutic modalities, including sulfurous mineral water inhalations and mud therapy. By emphasizing the potential for therapeutic modulation of H2S via both donors and inhibitors, this review accentuates the imperative for future research endeavors to deepen our understanding, thereby potentially advancing novel diagnostic and therapeutic strategies in AD.

Epidemiology of Injuries in Men's Professional and Amateur Football (Part I).

Background (1): Football is the most popular sport among men, associated with a certain risk of injury, which leads to short- and long-term health consequences. While the injury profile of professional footballers is known, little is known about the injury profile of amateur footballers; amateur football is a major and diverse area, the development of which should be a priority for football associations around the world and UEFA. The aim of this study was to perform a systematic review of epidemiological literature data on injuries in professional and amateur football players belonging to certain leagues. Methods (2): A systematic review according to the PRISMA guidelines was performed until June 2023 in the databases PubMed, Web of Science, Google Academic, Google Scholar, and Diva portal. Forty-six studies reporting injury incidence in professional and amateur men's football were selected and analyzed. Two reviewers independently extracted data and assessed study quality using an adapted version of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and the Newcastle Ottawa Scale (NOS) to assess risk of bias for the quality of external validity. Results (3): The overall incidence of injuries in professional male football players was 7.75 ± 2.28, 95% confidence interval, injuries/1000 h of exposure and that of amateur football players was 7.98 ± 2.95, 95% confidence interval, injuries/1000 h of exposure. The incidence of match injuries (30.64 ± 10.28, 95% confidence interval, injuries/1000 exposure hours) was 7.71 times higher than the training injury incidence rate (3.97 ± 1.35, 95% confidence interval, injuries/1000 h) in professional football players and 5.45 times higher in amateurs (17.56 ± 6.15 vs. 3.22 ± 1.4, 95% confidence interval, injuries/1000 h). Aggregate lower extremity injuries had the highest prevalence in both categories of footballers, being 83.32 ± 4.85% in professional footballers and 80.4 ± 7.04% in amateur footballers: thigh, ankle, and knee injuries predominated. Conclusions (4): Professional and amateur football players are at substantial risk of injury, especially during matches that require the highest level of performance. Injury rates have implications for players, coaches, and sports medicine practitioners. Therefore, information on football injuries can help develop personalized injury risk mitigation strategies that could make football safer for both categories of football players. The current findings have implications for the management, monitoring, and design of training, competition, injury prevention, especially severe injury, and education programs for amateur football players.

Hydrogen Sulfide: An Emerging Regulator of Oxidative Stress and Cellular Homeostasis-A Comprehensive One-Year Review.

Hydrogen sulfide (H2S), traditionally recognized as a toxic gas, has emerged as a critical regulator in many biological processes, including oxidative stress and cellular homeostasis. This review presents an exhaustive overview of the current understanding of H2S and its multifaceted role in mammalian cellular functioning and oxidative stress management. We delve into the biological sources and function of H2S, mechanisms underlying oxidative stress and cellular homeostasis, and the intricate relationships between these processes. We explore evidence from recent experimental and clinical studies, unraveling the intricate biochemical and molecular mechanisms dictating H2S's roles in modulating oxidative stress responses and maintaining cellular homeostasis. The clinical implications and therapeutic potential of H2S in conditions characterized by oxidative stress dysregulation and disrupted homeostasis are discussed, highlighting the emerging significance of H2S in health and disease. Finally, this review underscores current challenges, controversies, and future directions in the field, emphasizing the need for further research to harness H2S's potential as a therapeutic agent for diseases associated with oxidative stress and homeostatic imbalance. Through this review, we aim to emphasize H2S's pivotal role in cellular function, encouraging further exploration into this burgeoning area of research.

The Role of Hydrogen Sulfide (H2S) in Epigenetic Regulation of Neurodegenerative Diseases: A Systematic Review.

This review explores the emerging role of hydrogen sulfide (H2S) in modulating epigenetic mechanisms involved in neurodegenerative diseases. Accumulating evidence has begun to elucidate the multifaceted ways in which H2S influences the epigenetic landscape and, subsequently, the progression of various neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's disease. H2S can modulate key components of the epigenetic machinery, such as DNA methylation, histone modifications, and non-coding RNAs, impacting gene expression and cellular functions relevant to neuronal survival, inflammation, and synaptic plasticity. We synthesize recent research that positions H2S as an essential player within this intricate network, with the potential to open new therapeutic avenues for these currently incurable conditions. Despite significant progress, there remains a considerable gap in our understanding of the precise molecular mechanisms and the potential therapeutic implications of modulating H2S levels or its downstream targets. We conclude by identifying future directions for research aimed at exploiting the therapeutic potential of H2S in neurodegenerative diseases.

Exploring the Potential Benefits of Natural Calcium-Rich Mineral Waters for Health and Wellness: A Systematic Review.

This systematic review investigates the potential health and wellness benefits of natural calcium-rich mineral waters. It emphasizes the importance of dietary calcium sourced from natural mineral waters in promoting bone health, maintaining cardiovascular function, aiding in weight management, and enhancing overall well-being. The review process involved the comprehensive analysis of peer-reviewed articles, clinical trials, and experimental studies published within the last decade. Findings reveal that consuming calcium-rich mineral water can contribute significantly to daily calcium intake, particularly for those with lactose intolerance or individuals adhering to plant-based diets. The unique bioavailability of calcium from such waters also appears to enhance absorption, thus potentially offering an advantage over other calcium sources. The potential benefits extend to the cardiovascular system, with some studies indicating a reduction in blood pressure and the prevalence of cardiovascular diseases. Emerging evidence suggests that calcium-rich mineral water might have a role in body weight management, though further research is needed. The review identifies several areas requiring additional research, such as the potential interaction between calcium-rich mineral water and other dietary components, the effects on populations with specific health conditions, and the long-term effects of consumption. In conclusion, natural calcium-rich mineral waters show promise as a readily accessible and bioavailable sources of dietary calcium, potentially beneficial for a broad range of individuals. However, further investigation is required to fully understand its range of health impacts and define optimal intake levels.

PRISMA Systematic Literature Review, including with Meta-Analysis vs. Chatbot/GPT (AI) regarding Current Scientific Data on the Main Effects of the Calf Blood Deproteinized Hemoderivative Medicine (Actovegin) in Ischemic Stroke.

BACKGROUND: Stroke is a significant public health problem and a leading cause of death and long-term disability worldwide. Several treatments for ischemic stroke have been developed, but these treatments have limited effectiveness. One potential treatment for this condition is Actovegin®/AODEJIN, a calf blood deproteinized hemodialysate/ultrafiltrate that has been shown to have pleiotropic/multifactorial and possibly multimodal effects. The actual actions of this medicine are thought to be mediated by its ability to reduce oxidative stress, inflammation, and apoptosis and to enhance neuronal survival and plasticity. METHODS: To obtain the most up-to-date information on the effects of Actovegin®/AODEJIN in ischemic stroke, we systematically reviewed the literature published in the last two years. This review builds upon our previous systematic literature review published in 2020, which used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method to search for and select related articles over almost two decades, between 1 January 2001 and 31 December 2019. Additionally, we compared the results of our PRISMA search (human intelligence-based) with those obtained from an interrogation of a GPT-based chatbot (ChatGPT) in order to ensure comprehensive coverage of potentially relevant studies. RESULTS: Our updated review found limited new evidence on the use of Actovegin®/AODEJIN in ischemic stroke, although the number of articles on this subject consistently increased compared to that from our initial systematic literature review. Specifically, we found five articles up to 2020 and eight more until December 2022. While these studies suggest that Actovegin®/AODEJIN may have neuroprotective effects in ischemic stroke, further clinical trials are needed to confirm these findings. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. DISCUSSION: Our funnel analysis showed no evidence of publication bias, suggesting that the limited number of studies identified was not due to publication bias but rather due to a lack of research in this area. However, there are limitations when using ChatGPT, particularly in distinguishing between truth and falsehood and determining the appropriateness of interpolation. Nevertheless, AI can provide valuable support in conducting PRISMA-type systematic literature reviews, including meta-analyses. CONCLUSIONS: The limited number of studies identified in our review highlights the need for additional research in this area, especially as no available therapeutic agents are capable of curing central nervous system lesions. Any contribution, including that of Actovegin (with consideration of a positive balance between benefits and risks), is worthy of further study and periodic reappraisal. The evolving advancements in AI may play a role in the near future.

Hydrogen Sulfide and Oxygen Homeostasis in Atherosclerosis: A Systematic Review from Molecular Biology to Therapeutic Perspectives.

Atherosclerosis is a complex pathological condition marked by the accumulation of lipids in the arterial wall, leading to the development of plaques that can eventually rupture and cause thrombotic events. In recent years, hydrogen sulfide (H2S) has emerged as a key mediator of cardiovascular homeostasis, with potential therapeutic applications in atherosclerosis. This systematic review highlights the importance of understanding the complex interplay between H2S, oxygen homeostasis, and atherosclerosis and suggests that targeting H2S signaling pathways may offer new avenues for treating and preventing this condition. Oxygen homeostasis is a critical aspect of cardiovascular health, and disruption of this balance can contribute to the development and progression of atherosclerosis. Recent studies have demonstrated that H2S plays an important role in maintaining oxygen homeostasis by regulating the function of oxygen-sensing enzymes and transcription factors in vascular cells. H2S has been shown to modulate endothelial nitric oxide synthase (eNOS) activity, which plays a key role in regulating vascular tone and oxygen delivery to tissues. The comprehensive analysis of the current understanding of H2S in atherosclerosis can pave the way for future research and the development of new therapeutic strategies for this debilitating condition. PROSPERO ID: 417150.

Molecular Aspects of Hypoxic Stress Effects in Chronic Ethanol Exposure of Neuronal Cells.

Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury (hypoxic stress induced by treatment with deferoxamine or cobalt chloride) in chronic ethanol-consuming patients (ethanol-exposed neural cultures (SK-N-SH)) in order to explain the clinical paradigm of better outcomes for spinal cord injury chronic ethanol-consuming patients. The results show that long-term ethanol exposure has a cytotoxic effect, inducing apoptosis. At 24 h after the induction of hypoxic stress (by deferoxamine or cobalt chloride treatments), reduced ROS in long-term ethanol-exposed SK-N-SH cells was observed, which might be due to an adaptation to stressful conditions. In addition, the HIF-1α protein level was increased after hypoxic treatment of long-term ethanol-exposed cells, inducing fluctuations in its target metabolic enzymes proportionally with treatment intensity. The wound healing assay demonstrated that the cells recovered after stress conditions, showing that the ethanol-exposed cells that passed the acute step had the same proliferation profile as the cells unexposed to ethanol. Deferoxamine-treated cells displayed higher proliferative activity than the control cells in the proliferation-migration assay, emphasizing the neuroprotective effect. Cells have overcome the critical point of the alcohol-induced traumatic impact and adapted to ethanol (a chronic phenomenon), sustaining the regeneration process. However, further experiments are needed to ensure recovery efficiency is more effective in chronic ethanol exposure.

Lithium Biological Action Mechanisms after Ischemic Stroke.

Lithium is a source of great scientific interest because although it has such a simple structure, relatively easy-to-analyze chemistry, and well-established physical properties, the plethora of effects on biological systems-which influence numerous cellular and molecular processes through not entirely explained mechanisms of action-generate a mystery that modern science is still trying to decipher. Lithium has multiple effects on neurotransmitter-mediated receptor signaling, ion transport, signaling cascades, hormonal regulation, circadian rhythm, and gene expression. The biochemical mechanisms of lithium action appear to be multifactorial and interrelated with the functioning of several enzymes, hormones, vitamins, and growth and transformation factors. The widespread and chaotic marketing of lithium salts in potions and mineral waters, always at inadequate concentrations for various diseases, has contributed to the general disillusionment with empirical medical hypotheses about the therapeutic role of lithium. Lithium salts were first used therapeutically in 1850 to relieve the symptoms of gout, rheumatism, and kidney stones. In 1949, Cade was credited with discovering the sedative effect of lithium salts in the state of manic agitation, but frequent cases of intoxication accompanied the therapy. In the 1960s, lithium was shown to prevent manic and also depressive recurrences. This prophylactic effect was first demonstrated in an open-label study using the "mirror" method and was later (after 1970) confirmed by several placebo-controlled double-blind studies. Lithium prophylaxis was similarly effective in bipolar and also unipolar patients. In 1967, the therapeutic value of lithemia was determined, included in the range of 0.5-1.5 mEq/L. Recently, new therapeutic perspectives on lithium are connected with improved neurological outcomes after ischemic stroke. The effects of lithium on the development and maintenance of neuroprotection can be divided into two categories: short-term effects and long-term effects. Unfortunately, the existing studies do not fully explain the lithium biological action mechanisms after ischemic stroke.

Topical Reappraisal of Molecular Pharmacological Approaches to Endothelial Dysfunction in Diabetes Mellitus Angiopathy.

Diabetes mellitus (DM) is a frequent medical problem, affecting more than 4% of the population in most countries. In the context of diabetes, the vascular endothelium can play a crucial pathophysiological role. If a healthy endothelium-which is a dynamic endocrine organ with autocrine and paracrine activity-regulates vascular tone and permeability and assures a proper balance between coagulation and fibrinolysis, and vasodilation and vasoconstriction, then, in contrast, a dysfunctional endothelium has received increasing attention as a potential contributor to the pathogenesis of vascular disease in diabetes. Hyperglycemia is indicated to be the major causative factor in the development of endothelial dysfunction. Furthermore, many shreds of evidence suggest that the progression of insulin resistance in type 2 diabetes is parallel to the advancement of endothelial dysfunction in atherosclerosis. To present the state-of-the-art data regarding endothelial dysfunction in diabetic micro- and macroangiopathy, we constructed this literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We interrogated five medical databases: Elsevier, PubMed, PMC, PEDro, and ISI Web of Science.

Main Cations and Cellular Biology of Traumatic Spinal Cord Injury.

Traumatic spinal cord injury is a life-changing condition with a significant socio-economic impact on patients, their relatives, their caregivers, and even the community. Despite considerable medical advances, there is still a lack of options for the effective treatment of these patients. The major complexity and significant disabling potential of the pathophysiology that spinal cord trauma triggers are the main factors that have led to incremental scientific research on this topic, including trying to describe the molecular and cellular mechanisms that regulate spinal cord repair and regeneration. Scientists have identified various practical approaches to promote cell growth and survival, remyelination, and neuroplasticity in this part of the central nervous system. This review focuses on specific detailed aspects of the involvement of cations in the cell biology of such pathology and on the possibility of repairing damaged spinal cord tissue. In this context, the cellular biology of sodium, potassium, lithium, calcium, and magnesium is essential for understanding the related pathophysiology and also the possibilities to counteract the harmful effects of traumatic events. Lithium, sodium, potassium-monovalent cations-and calcium and magnesium-bivalent cations-can influence many protein-protein interactions, gene transcription, ion channel functions, cellular energy processes-phosphorylation, oxidation-inflammation, etc. For data systematization and synthesis, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) methodology, trying to make, as far as possible, some order in seeing the "big forest" instead of "trees". Although we would have expected a large number of articles to address the topic, we were still surprised to find only 51 unique articles after removing duplicates from the 207 articles initially identified. Our article integrates data on many biochemical processes influenced by cations at the molecular level to understand the real possibilities of therapeutic intervention-which must maintain a very narrow balance in cell ion concentrations. Multimolecular, multi-cellular: neuronal cells, glial cells, non-neuronal cells, but also multi-ionic interactions play an important role in the balance between neuro-degenerative pathophysiological processes and the development of effective neuroprotective strategies. This article emphasizes the need for studying cation dynamics as an important future direction.

Recent Advances in Molecular Research on Hydrogen Sulfide (H2S) Role in Diabetes Mellitus (DM)-A Systematic Review.

Abundant experimental data suggest that hydrogen sulfide (H2S) is related to the pathophysiology of Diabetes Mellitus (DM). Multiple molecular mechanisms, including receptors, membrane ion channels, signalingmolecules, enzymes, and transcription factors, are known to be responsible for the H2S biological actions; however, H2S is not fully documented as a gaseous signaling molecule interfering with DM and vascular-linked pathology. In recent decades, multiple approaches regarding therapeutic exploitation of H2S have been identified, either based on H2S exogenous apport or on its modulated endogenous biosynthesis. This paper aims to synthesize and systematize, as comprehensively as possible, the recent literature-related data regarding the therapeutic/rehabilitative role of H2S in DM. This review was conducted following the "Preferred reporting items for systematic reviews and meta-analyses" (PRISMA) methodology, interrogating five international medically renowned databases by specific keyword combinations/"syntaxes" used contextually, over the last five years (2017-2021). The respective search/filtered and selection methodology we applied has identified, in the first step, 212 articles. After deploying the next specific quest steps, 51 unique published papers qualified for minute analysis resulted. To these bibliographic resources obtained through the PRISMA methodology, in order to have the best available information coverage, we added 86 papers that were freely found by a direct internet search. Finally, we selected for a connected meta-analysis eight relevant reports that included 1237 human subjects elicited from clinical trial registration platforms. Numerous H2S releasing/stimulating compounds have been produced, some being used in experimental models. However, very few of them were further advanced in clinical studies, indicating that the development of H2S as a therapeutic agent is still at the beginning.

Parkinson's Disease and SARS-CoV-2 Infection: Particularities of Molecular and Cellular Mechanisms Regarding Pathogenesis and Treatment.

Accumulating data suggest that chronic neuroinflammation-mediated neurodegeneration is a significant contributing factor for progressive neuronal and glial cell death in age-related neurodegenerative pathology. Furthermore, it could be encountered as long-term consequences in some viral infections, including post-COVID-19 Parkinsonism-related chronic sequelae. The current systematic review is focused on a recent question aroused during the pandemic's successive waves: are there post-SARS-CoV-2 immune-mediated reactions responsible for promoting neurodegeneration? Does the host's dysregulated immune counter-offensive contribute to the pathogenesis of neurodegenerative diseases, emerging as Parkinson's disease, in a complex interrelation between genetic and epigenetic risk factors? A synthetic and systematic literature review was accomplished based on the "Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses" (PRISMA) methodology, including registration on the specific online platform: International prospective register of systematic reviews-PROSPERO, no. 312183. Initially, 1894 articles were detected. After fulfilling the five steps of the selection methodology, 104 papers were selected for this synthetic review. Documentation was enhanced with a supplementary 47 bibliographic resources identified in the literature within a non-standardized search connected to the subject. As a final step of the PRISMA method, we have fulfilled a Population-Intervention-Comparison-Outcome-Time (PICOT)/Population-Intervention-Comparison-Outcome-Study type (PICOS)-based metanalysis of clinical trials identified as connected to our search, targeting the outcomes of rehabilitative kinesitherapeutic interventions compared to clinical approaches lacking such kind of treatment. Accordingly, we identified 10 clinical trials related to our article. The multi/interdisciplinary conventional therapy of Parkinson's disease and non-conventional multitarget approach to an integrative treatment was briefly analyzed. This article synthesizes the current findings on the pathogenic interference between the dysregulated complex mechanisms involved in aging, neuroinflammation, and neurodegeneration, focusing on Parkinson's disease and the acute and chronic repercussions of COVID-19. Time will tell whether COVID-19 neuroinflammatory events could trigger long-term neurodegenerative effects and contribute to the worsening and/or explosion of new cases of PD. The extent of the interrelated neuropathogenic phenomenon remains obscure, so further clinical observations and prospective longitudinal cohort studies are needed.

Considerations about Hypoxic Changes in Neuraxis Tissue Injuries and Recovery.

Hypoxia represents the temporary or longer-term decrease or deprivation of oxygen in organs, tissues, and cells after oxygen supply drops or its excessive consumption. Hypoxia can be (para)-physiological-adaptive-or pathological. Thereby, the mechanisms of hypoxia have many implications, such as in adaptive processes of normal cells, but to the survival of neoplastic ones, too. Ischemia differs from hypoxia as it means a transient or permanent interruption or reduction of the blood supply in a given region or tissue and consequently a poor provision with oxygen and energetic substratum-inflammation and oxidative stress damages generating factors. Considering the implications of hypoxia on nerve tissue cells that go through different ischemic processes, in this paper, we will detail the molecular mechanisms by which such structures feel and adapt to hypoxia. We will present the hypoxic mechanisms and changes in the CNS. Also, we aimed to evaluate acute, subacute, and chronic central nervous hypoxic-ischemic changes, hoping to understand better and systematize some neuro-muscular recovery methods necessary to regain individual independence. To establish the link between CNS hypoxia, ischemic-lesional mechanisms, and neuro-motor and related recovery, we performed a systematic literature review following the" Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA") filtering method by interrogating five international medical renown databases, using, contextually, specific keywords combinations/"syntaxes", with supplementation of the afferent documentation through an amount of freely discovered, also contributive, bibliographic resources. As a result, 45 papers were eligible according to the PRISMA-inspired selection approach, thus covering information on both: intimate/molecular path-physiological specific mechanisms and, respectively, consequent clinical conditions. Such a systematic process is meant to help us construct an article structure skeleton giving a primary objective input about the assembly of the literature background to be approached, summarised, and synthesized. The afferent contextual search (by keywords combination/syntaxes) we have fulfilled considerably reduced the number of obtained articles. We consider this systematic literature review is warranted as hypoxia's mechanisms have opened new perspectives for understanding ischemic changes in the CNS neuraxis tissue/cells, starting at the intracellular level and continuing with experimental research to recover the consequent clinical-functional deficits better.

Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke.

BACKGROUND: Cerebral circulation delivers the blood flow to the brain through a dedicated network of sanguine vessels. A healthy human brain can regulate cerebral blood flow (CBF) according to any physiological or pathological challenges. The brain is protected by its self-regulatory mechanisms, which are dependent on neuronal and support cellular populations, including endothelial ones, as well as metabolic, and even myogenic factors. OBJECTIVES: Accumulating data suggest that "non-pharmacological" approaches might provide new opportunities for stroke therapy, such as electro-/acupuncture, hyperbaric oxygen therapy, hypothermia/cooling, photobiomodulation, therapeutic gases, transcranial direct current stimulations, or transcranial magnetic stimulations. We reviewed the recent data on the mechanisms and clinical implications of these non-pharmaceutical treatments. METHODS: To present the state-of-the-art for currently available non-invasive, non-pharmacological-related interventions in acute ischemic stroke, we accomplished this synthetic and systematic literature review based on the Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses (PRISMA). RESULTS: The initial number of obtained articles was 313. After fulfilling the five steps in the filtering/selection methodology, 54 fully eligible papers were selected for synthetic review. We enhanced our documentation with other bibliographic resources connected to our subject, identified in the literature within a non-standardized search, to fill the knowledge gaps. Fifteen clinical trials were also identified. DISCUSSION: Non-invasive, non-pharmacological therapeutic/rehabilitative interventions for acute ischemic stroke are mainly holistic therapies. Therefore, most of them are not yet routinely used in clinical practice, despite some possible beneficial effects, which have yet to be supplementarily proven in more related studies. Moreover, few of the identified clinical trials are already completed and most do not have final results. CONCLUSIONS: This review synthesizes the current findings on acute ischemic stroke therapeutic/rehabilitative interventions, described as non-invasive and non-pharmacological.

Translation of the Fugl-Meyer assessment into Romanian: Transcultural and semantic-linguistic adaptations and clinical validation.

Purpose: The Fugl-Meyer Assessment (FMA) scale, which is widely used and highly recommended, is an appropriate tool for evaluating poststroke sensorimotor and other possible somatic deficits. It is also well-suited for capturing a dynamic rehabilitation process. The aim of this study was to first translate the entire sensorimotor FMA scale into Romanian using the transcultural and semantic-linguistic adaptations of its official afferent protocols and to then validate it using the preliminary clinical evaluation of inter- and intra-rater reliability and relevant concurrent validity. Methods: Through three main steps, we completed a standardized procedure for translating FMA's official afferent evaluation protocols into Romanian and their transcultural and semantic-linguistic adaptation for both the upper and lower extremities. For relevant clinical validation, we evaluated 10 patients after a stroke two times: on days 1 and 2. All patients were evaluated simultaneously by two kinesi-physiotherapists (generically referred to as KFT1 and KFT2) over the course of 2 consecutive days, taking turns in the roles of an examiner and observer, and vice versa (inter-rater). Two scores were therefore obtained and compared for the same patient, i.e., being afferent to an inter-rater assay by comparing the assessment outcomes obtained by the two kinesi-physiotherapists, in between, and respectively, to the intra-rater assay: based on the evaluations of the same kinesi-physiotherapist, in two consecutive days, using a rank-based method (Svensson) for statistical analysis. We also compared our final Romanian version of FMA's official protocols for concurrent validity (Spearman's rank correlation statistical method) to both of the widely available assessment instruments: the Barthel Index (BI) and the modified Rankin scale (mRS). Results: Svensson's method confirmed overall good inter- and intra-rater results for the main parts of the final Romanian version of FMA's evaluation protocols, regarding the percentage of agreement (≥80% on average) and for disagreement: relative position [RP; values outside the interval of (-0.1, 0.1) in only two measurements out of the 56 comparisons we did], relative concentration [RC; values outside the interval of (-0.1, 0.1) in only nine measurements out of the same 56 comparisons done], and relative rank variation [RV; all values within an interval of (0, 0.1) in only five measurements out of the 56 comparisons done]. High correlation values were obtained between the final Romanian version of FMA's evaluation protocols and the BI (ρ = 0.9167; p = 0.0002) for FMA-upper extremity (FMA-UE) total A-D (motor function) with ρ = 0.6319 and for FMA-lower extremity (FMA-LE) total E-F (motor function) with p = 0.0499, and close to the limit, with the mRS (ρ = -0.5937; p = 0.0704) for FMA-UE total A-D (motor function) and (ρ = -0.6615; p = 0.0372) for FMA-LE total E-F (motor function). Conclusions: The final Romanian version of FMA's official evaluation protocols showed good preliminary reliability and validity, which could be thus recommended for use and expected to help improve the standardization of this assessment scale for patients after a stroke in Romania. Furthermore, this endeavor could be added to similar international translation and cross-cultural adaptations, thereby facilitating a more appropriate comparison of the evaluation and outcomes in the management of stroke worldwide.

Non-invasive, non-pharmacological/bio-technological interventions towards neurorestoration upshot after ischemic stroke, in adults-systematic, synthetic, literature review.

Considering its marked life-threatening and (not seldom: severe and/or permanent) disabling, potential, plus the overall medico-psycho-socio-economic tough burden it represents for the affected persons, their families and the community, the cerebrovascular accident (CVA)-including with the, by far more frequent, ischemic type-is subject to considerable scientific research efforts that aim (if possible) at eliminating the stroke induced lesions, and consist, as well, in ambitious-but still poorly transferable into medical practice-goals such as brain neuroregeneration and/or repair, within related corollary/upshot of neurorestoration. We have conducted, in this respect, a systematic and synthetic literature review, following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" concept. Accordingly, we have interrogated five internationally renowned medical data bases: Elsevier, NCBI/PubMed, NCBI/PMC, PEDro, and ISI Web of Knowledge/Science (the last one to check whether the initially identified articles are published in ISI indexed journals), based on a large (details in the body text) number of most appropriate, to our knowledge, key word combinations/"syntaxes"-used contextually-and subsequently fulfilling the related, on five steps, filtering/selection methodology. We have thereby selected 114 fully eligible (of which contributive: 83-see further) papers; at the same time, additionally, we have enhanced our documentation-basically, but not exclusively, for the introductive part of this work (see further)-with bibliographic resources, overall connected to our subject, identified in the literature within a non-standardized search. It appears that the opportunity window for morph-functional recovery after stroke is larger than previously thought, actually being considered that brain neurorestoration/repair could occur, and therefore be expected, in later stages than in earlier ones, although, in this context, the number of cases possibly benefitting (for instance after physical and/or cognitive rehabilitation-including with magnetic or direct current transcranial stimulation) is quite small and with more or less conflicting, related outcomes, in the literature. Moreover, applying especially high intense, solicitating, rehabilitation interventions, in early stages post (including ischemic) stroke could even worsen the functional evolution. Accordingly, for clarifications and validation of more unitary points of view, continuing and boosting research efforts in this complex, interdisciplinary domain, is necessary. Until finding (if ever) effective modalities to cure the lesions of the central nervous system (CNS)-including post ischemic stroke-it is reasonable and recommendable-based on rigorous methodologies-the avail of combined ways: physiatric, pharmacologic, possibly also bio-technologic. On a different note, but however connected to our subject: periodic related systematic, synthetic literature reviews reappraisals are warranted and welcome.

The Effect of Nano-Epigallocatechin-Gallate on Oxidative Stress and Matrix Metalloproteinases in Experimental Diabetes Mellitus.

BACKGROUND: The antioxidant properties of epigallocatechin-gallate (EGCG), a green tea compound, have been already studied in various diseases. Improving the bioavailability of EGCG by nanoformulation may contribute to a more effective treatment of diabetes mellitus (DM) metabolic consequences and vascular complications. The aim of this study was to test the comparative effect of liposomal EGCG with EGCG solution in experimental DM induced by streptozotocin (STZ) in rats. METHOD: 28 Wistar-Bratislava rats were randomly divided into four groups (7 animals/group): group 1-control group, with intraperitoneal (i.p.) administration of 1 mL saline solution (C); group 2-STZ administration by i.p. route (60 mg/100 g body weight, bw) (STZ); group 3-STZ administration as before + i.p. administration of EGCG solution (EGCG), 2.5 mg/100 g b.w. as pretreatment; group 4-STZ administration as before + i.p. administration of liposomal EGCG, 2.5 mg/100 g b.w. (L-EGCG). The comparative effects of EGCG and L-EGCG were studied on: (i) oxidative stress parameters such as malondialdehyde (MDA), indirect nitric oxide (NOx) synthesis, and total oxidative status (TOS); (ii) antioxidant status assessed by total antioxidant capacity of plasma (TAC), thiols, and catalase; (iii) matrix-metalloproteinase-2 (MMP-2) and -9 (MMP-9). RESULTS: L-EGCG has a better efficiency regarding the improvement of oxidative stress parameters (highly statistically significant with p-values < 0.001 for MDA, NOx, and TOS) and for antioxidant capacity of plasma (highly significant p < 0.001 for thiols and significant for catalase and TAC with p < 0.05). MMP-2 and -9 were also significantly reduced in the L-EGCG-treated group compared with the EGCG group (p < 0.001). CONCLUSIONS: the liposomal nanoformulation of EGCG may serve as an adjuvant therapy in DM due to its unique modulatory effect on oxidative stress/antioxidant biomarkers and MMP-2 and -9.