Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer’s Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease.

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The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment

Alzheimer's disease (AD), considered the most common type of dementia, is characterized by a progressive loss of memory, visuospatial, language and complex cognitive abilities. In addition, patients often show comorbid depression and aggressiveness. Aging is the major factor contributing to AD; however, the initial cause that triggers the disease is yet unknown. Scientific evidence demonstrates that AD, especially the late onset of AD, is not the result of a single event, but rather it appears because of a combination of risk elements with the lack of protective ones. A major risk factor underlying the disease is neuroinflammation, which can be activated by different situations, including chronic pathogenic infections, prolonged stress and metabolic syndrome. Consequently, many therapeutic strategies against AD have been designed to reduce neuro-inflammation, with very promising results improving cognitive function in preclinical models of the disease. The literature is massive; thus, in this review we will revise the translational evidence of these early strategies focusing in anti-diabetic and anti-inflammatory molecules and discuss their therapeutic application in humans. Furthermore, we review the preclinical and clinical data of nutraceutical application against AD symptoms. Finally, we introduce new players underlying neuroinflammation in AD: the activity of the endocannabinoid system and the intestinal microbiota as neuroprotectors. This review highlights the importance of a broad multimodal approach to treat successfully the neuroinflammation underlying AD.

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Can We Treat Neuroinflammation in Alzheimer's Disease?

Alzheimer’s disease (AD) is the most common cause of dementia Epidemiological studies show the association between AD and type 2 diabetes (T2DM), although the mechanisms are not fully understood Dietary habits and lifestyle, that are risk factors in both diseases, strongly modulate gut microbiota composition Also, the brain-gut axis plays a relevant role in AD, diabetes and inflammation, through products of bacterial metabolism, like short-chain fatty acids We provide a comprehensive review of current literature on the relation between dysbiosis, altered inflammatory cytokines profile and microglia in preclinical models of AD, T2DM and models that reproduce both diseases as commonly observed in the clinic Increased proinflammatory cytokines, such as IL-1β and TNF-α, are widely detected Microbiome analysis shows alterations in Actinobacteria, Bacteroidetes or Firmicutes phyla, among others Altered α- and β-diversity is observed in mice depending on genotype, gender and age; therefore, alterations in bacteria taxa highly depend on the models and approaches We also review the use of pre- and probiotic supplements, that by favoring a healthy microbiome ameliorate AD and T2DM pathologies Whereas extensive studies have been carried out, further research would be necessary to fully understand the relation between diet, microbiome and inflammation in AD and T2DM

https://www.mdpi.com/2218-273X/11/2/262/pdf

Alzheimer's Disease and Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models.

The potential to treat neurodegenerative diseases (NDs) of the major bioactive compound of green tea, epigallocatechin-3-gallate (EGCG), is well documented. Numerous findings now suggest that EGCG targets protein misfolding and aggregation, a common cause and pathological mechanism in many NDs. Several studies have shown that EGCG interacts with misfolded proteins such as amyloid beta-peptide (Aβ), linked to Alzheimer’s disease (AD), and α-synuclein, linked to Parkinson’s disease (PD). To date, NDs constitute a serious public health problem, causing a financial burden for health care systems worldwide. Although current treatments provide symptomatic relief, they do not stop or even slow the progression of these devastating disorders. Therefore, there is an urgent need to develop effective drugs for these incurable ailments. It is expected that targeting protein misfolding can serve as a therapeutic strategy for many NDs since protein misfolding is a common cause of neurodegeneration. In this context, EGCG may offer great potential opportunities in drug discovery for NDs. Therefore, this review critically discusses the role of EGCG in NDs drug discovery and provides updated information on the scientific evidence that EGCG can potentially be used to treat many of these fatal brain disorders.

https://www.mdpi.com/2218-273X/11/5/767/pdf

Green Tea Epigallocatechin-3-gallate (EGCG) Targeting Protein Misfolding in Drug Discovery for Neurodegenerative Diseases.

Human lifestyle and dietary behaviors contribute to disease onset and progression. Neurodegenerative diseases (NDDs), considered multifactorial disorders, have been associated with changes in the gut microbiome. NDDs display pathologies that alter brain functions with a tendency to worsen over time. NDDs are a worldwide health problem; in the US alone, 12 million Americans will suffer from NDDs by 2030. While etiology may vary, the gut microbiome serves as a key element underlying NDD development and prognosis. In particular, an inflammation-associated microbiome plagues NDDs. Conversely, sequestration of this inflammatory microbiome by a correction in the dysbiotic state of the gut may render therapeutic effects on NDDs. To this end, treatment with short-chain fatty acid-producing bacteria, the main metabolites responsible for maintaining gut homeostasis, ameliorates the inflammatory microbiome. This intimate pathological link between the gut and NDDs suggests that the gut-brain axis (GBA) acts as an underexplored area for developing therapies for NDDs. Traditionally, the classification of NDDs depends on their clinical presentation, mostly manifesting as extrapyramidal and pyramidal movement disorders, with neuropathological evaluation at autopsy as the gold standard for diagnosis. In this review, we highlight the evolving notion that GBA stands as an equally sensitive pathological marker of NDDs, particularly in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and chronic stroke. Additionally, GBA represents a potent therapeutic target for treating NDDs.

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Gut–Brain Axis as a Pathological and Therapeutic Target for Neurodegenerative Disorders

Alzheimer's disease (AD) is a complex multifactorial disease involving chronic neuroinflammation and neurodegeneration. It has been recently recognized that gut microbiota interacts with the brain, and it is termed as microbiota-gut-brain axis. Modulation of this axis has been recently reported to affect the pathogenesis of neurodegenerative diseases, such as AD. Gut microbiota has a pivotal role in regulating multiple neuro-chemical pathways through the highly interconnected gut-brain axis. Recent emerging evidences have highlighted that the intestinal microflora takes part in bidirectional communication between the gut and the brain. Due to this, the researchers have suggested that human gut microflora may even act as the "second brain" and may be responsible for neurodegenerative disorders like Alzheimer's disease. Dysbiosis of gut microbiota can induce increased intestinal permeability and systemic inflammation. This may lead to the development of AD pathologies and cognitive impairment via the neural, immune, endocrine, and metabolic pathways. Thus, the modulation of gut microbiota through personalized diet, oral bacteriotherapy may lead to alteration of gut microbiota their products including amyloid protein. It has been demonstrated that modulation of the gut microbiota induces beneficial effects on neuronal pathways consequently leading to delay the progression of Alzheimer's disease. Thus, this approach may provide a novel therapeutic option for treatment of AD.

Emerging role of gut microbiota in modulation of neuroinflammation and neurodegeneration with emphasis on Alzheimer's disease.

Coronavirus disease 2019 (COVID-19) a pandemic is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The virus belongs to the Coronaviridae family and the key reservoir of the virus are bats. Since the outbreak of this disease across the globe, millions of people have been affected, resulting in mild to severe illness and significant mortality. COVID-19 is primarily transmitted from person to person through droplet infection, contact, or feco-oral routes. The host, environmental, and viral risk factors all play a role in COVID-19. The infection can manifest as a mild illness including upper respiratory infections and non-severe pneumonia, or as a severe pneumonia involving ARDS, multiple organ failure, and death. Symptoms of COVID-19 include fever, cough, fatigue, dyspnea, anorexia, productive sputum, myalgia, sore throat, nausea, dizziness, diarrhea, headache, vomiting, abdominal pain, loss of taste and smell. Management includes primary care, community care and acute care. In this article, we present a brief overview of the epidemiology, etiopathogenesis and general symptoms of SARS-CoV-2, as well as current understanding of pulmonary rehabilitation procedures routinely recommended to treat patients post COVID-19.

Pulmonary rehabilitation post COVID-19

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968687

Impact of the COVID-19 pandemic on people with disabilities and implications for health services research

Objective: Cut throat injuries pose a great therapeutic challenge due to the multiple vital structures that are vulnerable to injuries in a small, confined unprotected area. In this study, we describe the site and depth of the injury, etiology, management, and prognosis.
Methods: This was a retrospective study of 18 laryngotracheal trauma patients treated at the department of ENT in MDM hospital between April 2017 and January 2020. 
Results: Out of 176 cases of penetrating neck injury, 18 patients presented with a breach in the laryngotracheal framework. Male: female ratio was 17:1. The peak age of incidence is in the 2nd and 4th decade of life. Accidental cut throat injury was the most common mode of injury (83%), followed by homicidal (11%) and then suicidal (5%). Endotracheal intubation (where possible) or emergency tracheostomy was done to secure the airway in all the cases, followed by surgical debridement and laryngeal/hypopharynx repair. Post-operative endoscopy is useful to identify complications. Wound dehiscence was the most common complication.
Conclusion: Cut throat injuries are one of the common ENT surgical emergency. Timely intervention is paramount, because it may otherwise cause death of the patient. Securing the airway, control of hemorrhage, and fluid and blood replacement is the mainstay to prevent complications such as shock, sepsis, laryngeal stenosis, or fistula formation.

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Laryngotracheal trauma management and associated morbidity and mortality: 4-year experience at a tertiary care center

Endothelial damage, astrogliosis, microgliosis, and neuronal degeneration are the most common events after spinal cord injury (SCI). Studies highlighted that studying the spatiotemporal profile of these events might provide a deeper understanding of the pathophysiology of SCI. For imaging of these events, available conventional techniques such as 2-dimensional histology and immunohistochemistry (IHC) are well established and frequently used to visualize and detect the altered expression of the protein of interest involved in these events. However, the technique requires the physical sectioning of the tissue, and results are also open to misinterpretation. Currently, researchers are focusing more attention toward the advanced tools for imaging the spinal cord's various physiological and pathological parameters. The tools include two-photon imaging, light sheet fluorescence microscopy, in vivo imaging system with fluorescent probes, and in vivo chemical and fluorescent protein-expressing viral-tracers. These techniques outperform the limitations associated with conventional techniques in various aspects, such as optical sectioning of tissue, 3D reconstructed imaging, and imaging of particular planes of interest. In addition to this, these techniques are minimally invasive and less time-consuming. In this review, we will discuss the various advanced imaging methodologies that will evolve in the future to explore the fundamental mechanisms after SCI.

Divya Goyal

Papers

Emerging role of gut microbiota in modulation of neuroinflammation and neurodegeneration with emphasis on Alzheimer's disease.

Pulmonary rehabilitation post COVID-19

Impact of the COVID-19 pandemic on people with disabilities and implications for health services research

Laryngotracheal trauma management and associated morbidity and mortality: 4-year experience at a tertiary care center

In Vivo and 3D Imaging Technique(s) for Spatiotemporal Mapping of Pathological Events in Experimental Model(s) of Spinal Cord Injury.