Novelties on Neuroinflammation in Alzheimer's Disease-Focus on Gut and Oral Microbiota Involvement.

Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through the microbiota-gut-brain axis, including in Alzheimer's disease (AD). This review aims to provide a comprehensive synthesis of recent findings on the involvement of gut and oral microbiota in the neuroinflammatory processes associated with AD, emphasizing novel insights and therapeutic implications. This review reveals that dysbiosis in AD patients' gut and oral microbiota is linked to heightened peripheral and central inflammatory responses. Specific bacterial taxa, such as Bacteroides and Firmicutes in the gut, as well as Porphyromonas gingivalis in the oral cavity, are notably altered in AD, leading to significant changes in microglial activation and cytokine production. Gut microbiota alterations are associated with increased intestinal permeability, facilitating the translocation of endotoxins like lipopolysaccharides (LPS) into the bloodstream and exacerbating neuroinflammation by activating the brain's toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and amyloid peptides, can cross the blood-brain barrier and modulate neuroinflammatory responses. While microbial amyloids may contribute to amyloid-beta aggregation in the brain, certain SCFAs like butyrate exhibit anti-inflammatory properties, suggesting a potential therapeutic avenue to mitigate neuroinflammation. This review not only highlights the critical role of microbiota in AD pathology but also offers a ray of hope by suggesting that modulating gut and oral microbiota could represent a novel therapeutic strategy for reducing neuroinflammation and slowing disease progression.

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.

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.

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.

Modulated Neuroprotection in Unresponsive Wakefulness Syndrome after Severe Traumatic Brain Injury.

BACKGROUND: We aimed to assess the effects of modulated neuroprotection with intermittent administration in patients with unresponsive wakefulness syndrome (UWS) after severe traumatic brain injury (TBI). METHODS: Retrospective analysis of 60 patients divided into two groups, with and without neuroprotective treatment with Actovegin, Cerebrolysin, pyritinol, L-phosphothreonine, L-glutamine, hydroxocobalamin, alpha-lipoic acid, carotene, DL-α-tocopherol, ascorbic acid, thiamine, pyridoxine, cyanocobalamin, Q 10 coenzyme, and L-carnitine alongside standard treatment. MAIN OUTCOME MEASURES: Glasgow Coma Scale (GCS) after TBI, Extended Glasgow Coma Scale (GOS E), Disability Rankin Scale (DRS), Functional Independence Measurement (FIM), and Montreal Cognitive Assessment (MOCA), all assessed at 1, 3, 6, 12, and 24 months after TBI. RESULTS: Patients receiving neuroprotective treatment recovered more rapidly from UWS than controls (p = 0.007) passing through a state of minimal consciousness and gradually progressing until the final evaluation (p = 0.000), towards a high cognitive level MOCA = 22 ± 6 points, upper moderate disability GOS-E = 6 ± 1, DRS = 6 ± 4, and an assisted gait, FIM =101 ± 25. The improvement in cognitive and physical functioning was strongly correlated with lower UWS duration (-0.8532) and higher GCS score (0.9803). CONCLUSION: Modulated long-term neuroprotection may be the therapeutic key for patients to overcome UWS after severe TBI.

Radial Extracorporeal Shockwave Therapy versus Ultrasound Therapy in Adult Patients with Idiopathic Scoliosis.

BACKGROUND: This study aimed to compare the effectiveness of radial extracorporeal shockwave and ultrasound therapies in adult patients with idiopathic scoliosis in terms of pain, disability, and quality of life. METHODS: Forty-eight patients with idiopathic scoliosis were randomly divided into three groups of 16: shockwave, ultrasound, and control. The patients were evaluated at admission (day one) and at discharge (day 14) for pain, by using the visual analogue scale; for disability, by using the Oswestry disability index; and for the quality of life, with short form-36. RESULTS: Radial extracorporeal shockwave therapy was more effective than ultrasound in reducing pain (p = 0.004) and increasing quality of life, bringing extra vitality (p = 0.003) and emotional comfort (p = 0.007) to the patient. Both shockwave therapy (p = 0.001) and ultrasound therapy (p = 0.003) were effective in reducing pain. In terms of disability, both treatments had similar effects (p = 0.439). CONCLUSION: Radial shockwave was significantly more effective than ultrasound in reducing pain and increasing the quality of life, bringing additional vitality and emotional comfort to the patient with idiopathic scoliosis. In terms of disability, both treatments had similar effects when associated with kinesitherapy.

Mobile Mechatronic/Robotic Orthotic Devices to Assist-Rehabilitate Neuromotor Impairments in the Upper Limb: A Systematic and Synthetic Review.

This paper overviews the state-of-the-art in upper limb robot-supported approaches, focusing on advancements in the related mechatronic devices for the patients' rehabilitation and/or assistance. Dedicated to the technical, comprehensively methodological and global effectiveness and improvement in this inter-disciplinary field of research, it includes information beyond the therapy administrated in clinical settings-but with no diminished safety requirements. Our systematic review, based on PRISMA guidelines, searched articles published between January 2001 and November 2017 from the following databases: Cochrane, Medline/PubMed, PMC, Elsevier, PEDro, and ISI Web of Knowledge/Science. Then we have applied a new innovative PEDro-inspired technique to classify the relevant articles. The article focuses on the main indications, current technologies, categories of intervention and outcome assessment modalities. It includes also, in tabular form, the main characteristics of the most relevant mobile (wearable and/or portable) mechatronic/robotic orthoses/exoskeletons prototype devices used to assist-rehabilitate neuromotor impairments in the upper limb.

Evolution of traumatic spinal cord injury in patients with ankylosing spondylitis, in a Romanian rehabilitation clinic.

The ankylosing spondylitis (AS) is a systemic, multi-factorial, chronic rheumatic disease. Patients are highly susceptible to vertebral fractures with or without spinal cord injury (AS-SCI), even after a minor trauma. The study is a retrospective descriptive survey of post-acute, traumatic AS-SCI patients, transferred from the neurosurgical department and admitted in a Romanian Neurorehabilitation Clinic, during 2010-2014. There were 11 males associating AS-SCI (0.90% of all consecutive SCI admitted cases), with an average age of 54.6 years (median 56, limits 42-73 years). The average duration between the medically diagnosed AS and the actual associated spinal fracture(-s) moment was 21.4 years (median 23; limits 10-34 years). Low-energy trauma was incriminated in 54.5% cases. The spinal level of fracture was: cervical (four cases), thoracic (three), lumbar (four), assessed at admission as: American Spinal Injury Association (ASIA) Impairment Scale (AIS) A (four subjects), C (five) and D (two). By the time of discharge, neither patient has neurologically deteriorated; five patients (45.5%) improved of at least grade 1 (AIS). The overall complications were mainly infections: symptomatic urinary tract infections (seven patients; 63.6%), pulmonary (three subjects; 27.3%) and spondylodiscitis (one case; 9%). The average follow-up period was 15.3 months (median 12; limits 1-48 months) after discharge; three subjects gained functional improvement to AIS-E. The clinical profile (different risk factors, mechanisms, types and levels of spinal fractures, additional encephalic and/or cord lesions, co-morbidities), different post-surgical and/or general complications acquired during admission in our rehabilitation ward, served us for future prevention strategies and a better therapeutic management.