Fulminant Myocarditis and Venoarterial Extracorporeal Membrane Oxygenation: A Systematic Review.

This systematic review aimed to look at the effectiveness of venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy in treating fulminant myocarditis and evaluating the optimal length of time a patient should be placed on VA-ECMO. Fulminant myocarditis is a potentially life-threatening medical condition most commonly brought on by cardiogenic shock, which often progresses to severe circulatory compromise, requiring the patient to be placed on some form of mechanical circulatory assistance to maintain adequate tissue perfusion. Medical centers have multiple mechanical assistive devices available for treatment at their disposal, but our area of focus was placed on one system in particular: VA-ECMO therapy. Although the technology has been around for more than 30 years, there is limited information on how effective VA-ECMO is regarding the treatment of fulminant myocarditis. Due to the lack of data regarding the treatment administration of VA-ECMO for fulminant myocarditis, standard treatment duration guidelines do not exist, resulting in a wide variation of treatment administrations among medical centers. In regard to short-term outcomes, VA-ECMO has shown to be effective in treating fulminant myocarditis, with a one-year post-hospital survival rate ranging from 57.1% to 78% at discharge. For long-term health and survival, the studies that recorded long-term survival ranged from 65% to 94.1%. However, given the small number of studies that pursue this, more research is needed to prove the efficacy of VA-ECMO for the treatment of fulminant myocarditis.

Trimethylamine-N-oxide and cerebral stroke risk: A review.

Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced by the action of gut microbiota and the hepatic enzyme Flavin Mono­oxygenase 3 (FMO3). TMAO level has a positive correlation with the risk of cardiovascular events, including stroke, and their level is influenced mainly by dietary choice and the action of liver enzyme FMO3. TMAO plays a role in the development of atherosclerosis plaque, which is one of the causative factors of the stroke event. Preclinical and clinical investigations on the TMAO and associated stroke risk, severity, and outcomes are summarised in this review. In addition, mechanisms of TMAO-driven vascular dysfunction are also discussed, such as inflammation, oxidative stress, thrombus and foam cell formation, altered cholesterol and bile acid metabolism, etc. Post-stroke inflammatory cascades involving activation of immune cells, i.e., microglia and astrocytes, result in Blood-brain-barrier (BBB) disruption, allowing TMAO to infiltrate the brain and further aggravate inflammation. This event occurs as a result of the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway through the release of inflammatory cytokines and chemokines that further aggravate the BBB and initiate further recruitment of immune cells in the brain. Thus, it's likely that maintaining TMAO levels and associated gut microbiota could be a promising approach for treating and improving stroke complications.

Bulat-Klarica-Oreskovic Hypothesis: A Comprehensive Review.

Classical theories of cerebrospinal fluid (CSF) production and flow are taught throughout medical education. The idea that CSF is produced and/or filtered by the choroid plexus and flows in one direction throughout the ventricular system has been a largely accepted thesis. However, modern studies have called into question the validity of this hypothesis, suggesting that CSF does not move unidirectionally but rather is driven by microvessel contractions in a to-and-fro manner throughout the cerebrospinal system. Moreover, new insights suggest that in addition to CSF production, the exchange of fluids and proteins between the cortical vasculature and the interstitium may function as the brain's version of a lymphatic system. This comprehensive review provides evidence for a different framework of CSF flow. One that includes perivascular pulsations that push CSF back and forth, allowing exchange between the CSF and interstitium, and with CSF production occurring throughout the cerebrospinal system. These findings could be revolutionary in understanding the pathophysiology of CSF flow and in the treatment of pathologies such as intracranial hypertension, hydrocephalus, Alzheimer's disease, and many others.

Non-alcoholic Fatty Liver Disease and Gallstones: A Systematic Review.

Non-alcoholic fatty liver disease (NAFLD) is steatosis of the liver that resembles alcohol-induced liver injury but is a metabolic disorder. Most patients are obese with increased triglyceride levels due to increased intake of fatty food, which can cause excess fat to build up in the liver. At the same time, continuous ingestion of fatty foods can lead to gallstones (GS) due to the overproduction of cholesterol. NAFLD and GS have been seen to coincide, and there might be a relationship between them. This systematic review analyzes the incidence of NAFLD and GS to determine a bidirectional relationship. A comprehensive literature review was done using ProQuest, PubMed, and ScienceDirect, and included only experimental studies and meta-analyses. The search included the keywords 'gallstones and non-alcoholic fatty liver disease' and 'cholelithiasis and non-alcoholic fatty liver disease'. Our initial search included 10,665 articles and was narrowed down to 19 through extensive inclusion and exclusion criteria. There is a bidirectional relationship between the incidence of NAFLD and GS, where an increase in either can lead to an increase in the other. Both NAFLD and GS share similar risk factors leading to the development of each disease. On average, there's an increase in the prevalence of gallstones in NAFLD patients, and patients with GS were also more likely to have NAFLD. There was a prevalence of NAFLD in those with asymptomatic gallstones as well, indicating that the risk factors are crucial in the development of both. As a result, some research is determining whether an evaluation of the liver should be routine during cholecystectomy due to the increased risk of developing NAFLD.

Colostrum and Preterm Babies: A Systematic Review.

Colostrum from mothers is rich in immunomodulating bio-factors such as immunoglobulins (IgA), lactoferrin, and oligosaccharides and supports gut microbial and inflammatory processes. The support in these processes may provide some relief for infants who are born pre-term. Pre-term infants are more likely to develop necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and ventilator-acquired/associated pneumonia (VAP). Due to the components of colostrum, there may be incentives towards early administration for preterm infants. An extensive literature review was done using ProQuest, ScienceDirect, and PubMed. Only meta-analyses and experimental studies were used. The search included the keywords 'colostrum and preterm' and 'colostrum and necrotizing enterocolitis'. The initial search generated 13,543 articles and was narrowed to 25 articles through comprehensive inclusion and exclusion criteria. There were significantly higher levels of Lactobacillus and Bifidobacterium in pre-term infants given colostrum and a decrease in Moraxellaceae and Staphylococcaceae. Salivary secretory IgA increased following oral colostrum administration in pre-term infants along with downregulation of interleukin (IL)-1b and IL-8. It was also observed that tumor necrosis factor (TNF)-a, and interferon-gamma (IFN-g) were significantly higher in the control group. There was no significant difference in the incidence of LOS, NEC, or VAP between pre-term infants receiving colostrum and those who did not. Secondary outcomes such as time to full enteral feeding were improved in pre-term infants receiving oral colostrum in addition to reduced hospital stays. Lastly, there was no difference in mortality between pre-term infants that received colostrum compared to those who did not.

Polyphenols, Autophagy and Neurodegenerative Diseases: A Review.

Polyphenols are secondary metabolites from plant origin and are shown to possess a wide range of therapeutic benefits. They are also reported as regulators of autophagy, inflammation and neurodegeneration. The autophagy pathway is vital in degrading outdated organelles, proteins and other cellular wastes. The dysregulation of autophagy causes proteinopathies, mitochondrial dysfunction and neuroinflammation thereby contributing to neurodegeneration. Evidence reveals that polyphenols improve autophagy by clearing misfolded proteins in the neurons, suppress neuroinflammation and oxidative stress and also protect from neurodegeneration. This review is an attempt to summarize the mechanism of action of polyphenols in modulating autophagy and their involvement in pathways such as mTOR, AMPK, SIRT-1 and ERK. It is evident that polyphenols cause an increase in the levels of autophagic proteins such as beclin-1, microtubule-associated protein light chain (LC3 I and II), sirtuin 1 (SIRT1), etc. Although it is apparent that polyphenols regulate autophagy, the exact interaction of polyphenols with autophagy markers is not known. These data require further research and will be beneficial in supporting polyphenol supplementation as a potential alternative treatment for regulating autophagy in neurodegenerative diseases.

Anticoagulants and Dementia: A Systematic Review.

Many patients diagnosed with atrial fibrillation (AF) develop dementia. Most AF patients are also prescribed some antithrombotic medication to reduce the incidence of stroke, as clots can form within the left atrium. Some research has found that, excluding patients who have experienced strokes, anticoagulants may serve as protective agents against dementia in AF. This systematic review aims to analyze the incidence of dementia in patients who were prescribed anticoagulants. A comprehensive literature review was conducted using the databases PubMed, ProQuest, and ScienceDirect. Only experimental studies and meta-analyses were chosen. The search included the keywords "dementia and anticoagulant" and "cognitive decline and anticoagulants". Our initial search generated 53,306 articles, which were narrowed down to 29 by applying strict inclusion and exclusion algorithms. There was a decreased risk of dementia in patients who had been prescribed oral anticoagulants (OACs) in general, but only studies investigating direct oral anticoagulants OACs (DOACs) suggested that they were protective against dementia. Vitamin K antagonist (VKA) anticoagulants showed conflicting results, with some studies indicating they might increase the risk for dementia, while others suggested that they are protective against it. Warfarin, a specific VKA, was mainly shown to reduce the risk of dementia but was not as effective as DOACs or other OACs. Lastly, it was found that antiplatelet therapy may increase the risk of dementia in AF patients.

Peripheral Arterial Disease: A Narrative Review.

Peripheral arterial disease (PAD) describes the partial or complete occlusion of blood flow in the distal arteries of the body. A decreased arterial patency may occur due to a reduction in the elasticity or diameter of the vessel. The goal of interventions is to decrease incidence and reduce complications by identifying and minimizing the primary causes. This paper discusses PAD affecting the aortoiliac, common femoral, and femoropopliteal arteries. In a significant portion of the population, PAD may lack usual symptoms such as limb pain, claudication, and diminished pulses. Imaging techniques become crucial to ensuring timely diagnosis, monitoring treatment effectiveness, and preventing recurrence. Duplex ultrasound (DUS) is a cheap and non-invasive preliminary technique to detect atherosclerotic plaques and grade arterial stenosis. Magnetic resonance angiography (MRA) provides the added advantage of minimizing artifacts. Digital subtraction angiography (DSA) remains the gold standard for grading the degree of stenosis but is only employed second-line to DUS or MRA due to the high dose of nephrotoxic contrast. Computed tomography angiography (CTA) is able to overcome the anatomical limitations of DUS and MRA and proves to be a suitable alternative to DSA in patients with renal disease. Preventative measures involve monitoring blood pressure, cholesterol levels, and tobacco usage. First-line treatment options include endovascular procedures as well as surgical interventions in cases of significant arterial involvement. Endovascular treatments involve the use of balloon angioplasty, drug-coated balloons, and drug-coated stents, to name a few, that serve as minimally invasive techniques to manage PAD. Surgical procedures, although more complex, are considered gold-standard treatment options for long and intricate lesions. Endovascular methods are generally preferred over surgical options as the complication risk is severely reduced and the rates of reintervention are comparable to surgical options.

Inferior Vena Cava Filters and Complications: A Systematic Review.

Inferior vena cava (IVC) filters have been used since the 1960s to treat patients with acute risk of pulmonary embolism (PE) to prevent migration of thrombus by trapping it within the filter. Traditional usage has been in patients with contraindication to anticoagulation that carry a significant mortality risk. In this systematic review, we sought to evaluate complications associated with placement of inferior vena cava filters based on published data from the past 20 years. A search was performed on October 6th, 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews, using three databases (ProQuest, PubMed and ScienceDirect) for articles published between the dates of February 1, 2002 and October 1, 2022. Results were filtered to include full-text, clinical studies, and randomized trials written in English pertaining to keywords "IVC filter AND complications", "Inferior Vena Cava Filter AND complications", "IVC filter AND thrombosis" and "Inferior Vena Cava Filter AND thrombosis". Articles identified by the three databases were pooled and further screened for relevance based on inclusion and exclusion criteria. Initial search results yielded 33,265 hits from all three databases combined. Screening criteria were applied, with 7721 results remaining. After further manual screening, including removal of duplicate hits, a total of 117 articles were selected for review. While there are no consensus guidelines for best practice, there is compelling evidence that IVC filters can provide significant protection against PE with minimal complications if the treatment window is appropriate. Increase in the variety of filter models has led to broader availability, but skepticism remains about their efficacy and safety, with ongoing controversy surrounding appropriate indications. Further research is needed to establish clear guidelines on appropriate indications for IVC placement and to determine time course of complications versus benefits for indwelling filters.

Improving Access to Child and Adolescent Weight Loss Surgery: A Review of Updated National and International Practice Guidelines.

The rise of childhood obesity is a growing concern due to its negative impact on health. Metabolic bariatric surgery (MBS) has gained popularity as an effective and adequate intervention for children and adolescent patients living with severe obesity. Nonetheless, access to MBS for this population is still limited. The objective of this paper is to conduct a comprehensive review of the latest national and international practice guidelines and improve access to MBS for children and adolescents. The paper focuses on the recommendations from the 2023 American Academy of Pediatrics (AAP) and 2022 guidelines from the American Society for Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). Recently updated guidelines from the ASMBS and IFSO aim to improve access to MBS for children and adolescents and recommend patient selection, preoperative evaluation, and postoperative care. While lifestyle changes, medication, and behavioral therapy are commonly prescribed, they often fail to achieve permanent weight loss and its maintenance. Weight-loss surgeries like sleeve gastrectomy (SG) and gastric bypass (RYGB) show promising results in managing severe obesity in adolescents. SG has become the preferred method for treating severe obesity in adolescents, surpassing RYGB. Weight stigma is also explored in this review, revealing its negative effects on individuals who are overweight and underweight. Furthermore, telehealth is identified as an increasingly valuable tool for managing pediatric obesity, as it can improve access to care, particularly for those in remote areas where physicians trained to treat childhood obesity and the shortage of bariatric surgeons experienced in treating younger adolescents and pediatricians with advanced training are major obstacles.

Necrotizing Fasciitis Secondary to Mycotic Femoral Aneurysm: A Narrative Review of Diagnosis and Management Strategies.

This comprehensive literature review aims to investigate the pathophysiology, clinical manifestations, diagnostic tools, and treatment options for necrotizing fasciitis secondary to mycotic femoral aneurysm, a rare and potentially lethal infectious disease, particularly focusing on any changes throughout the years for an update of the current literature. The pathophysiology of necrotizing fasciitis and mycotic femoral aneurysms is a complex and multifaceted process that typically involves bacterial infections as a common precursor to the onset of these conditions. This can potentially lead to the formation of an aneurysm. As the infection progresses, it can spread from the aneurysm to surrounding soft tissues, resulting in significant tissue damage, obstructed blood circulation, and ultimately culminating in cell death and necrosis. Clinical manifestations of these conditions are diverse and encompass a range of symptoms, such as fever, localized pain, inflammation, skin changes, and other indicators. It is worth noting that skin color can influence the presentation of these conditions, and in patients with diverse skin tones, certain symptoms may be less noticeable due to a lack of visible discoloration. Imaging, laboratory findings, and clinical presentation are important components of the diagnosis of mycotic aneurysms. CT scans are a reliable tool for identifying specific features of infected femoral aneurysms, and elevated inflammatory laboratory results can also suggest a mycotic aneurysm. In the case of necrotizing fasciitis, clinicians should maintain a high level of suspicion as this condition is rare but life-threatening. Clinicians will need to view the big picture when an infection may be caused by necrotizing fasciitis, considering CT imaging, blood work, and clinical presentation of the patient without delaying surgical intervention. By incorporating the diagnostic tools and treatment options outlined in this review, healthcare professionals can improve patient outcomes and reduce the burden of this rare and potentially lethal infectious disease.

Effect of Cannabis on Memory Consolidation, Learning and Retrieval and Its Current Legal Status in India: A Review.

Cannabis is one of the oldest crops grown, traditionally held religious attachments in various cultures for its medicinal use much before its introduction to Western medicine. Multiple preclinical and clinical investigations have explored the beneficial effects of cannabis in various neurocognitive and neurodegenerative diseases affecting the cognitive domains. Tetrahydrocannabinol (THC), the major psychoactive component, is responsible for cognition-related deficits, while cannabidiol (CBD), a non-psychoactive phytocannabinoid, has been shown to elicit neuroprotective activity. In the present integrative review, the authors focus on the effects of cannabis on the different cognitive domains, including learning, consolidation, and retrieval. The present study is the first attempt in which significant focus has been imparted on all three aspects of cognition, thus linking to its usage. Furthermore, the investigators have also depicted the current legal position of cannabis in India and the requirement for reforms.

Role of Endogenous Lipopolysaccharides in Neurological Disorders.

Lipopolysaccharide (LPS) is a cell-wall immunostimulatory endotoxin component of Gram-negative bacteria. A growing body of evidence reveals that alterations in the bacterial composition of the intestinal microbiota (gut dysbiosis) disrupt host immune homeostasis and the intestinal barrier function. Microbial dysbiosis leads to a proinflammatory milieu and systemic endotoxemia, which contribute to the development of neurodegenerative diseases and metabolic disorders. Two important pathophysiological hallmarks of neurodegenerative diseases (NDDs) are oxidative/nitrative stress and inflammation, which can be initiated by elevated intestinal permeability, with increased abundance of pathobionts. These changes lead to excessive release of LPS and other bacterial products into blood, which in turn induce chronic systemic inflammation, which damages the blood-brain barrier (BBB). An impaired BBB allows the translocation of potentially harmful bacterial products, including LPS, and activated neutrophils/leucocytes into the brain, which results in neuroinflammation and apoptosis. Chronic neuroinflammation causes neuronal damage and synaptic loss, leading to memory impairment. LPS-induced inflammation causes inappropriate activation of microglia, astrocytes, and dendritic cells. Consequently, these alterations negatively affect mitochondrial function and lead to increases in oxidative/nitrative stress and neuronal senescence. These cellular changes in the brain give rise to specific clinical symptoms, such as impairment of locomotor function, muscle weakness, paralysis, learning deficits, and dementia. This review summarizes the contributing role of LPS in the development of neuroinflammation and neuronal cell death in various neurodegenerative diseases.

Vertebral Artery Stenosis: A Narrative Review.

Vertebral artery stenosis (VAS) is the cause of approximately 20% of ischemic strokes in the posterior circulation. There are several causes of vertebral artery stenosis, including atherosclerosis, calcification, dissections, fibromuscular dysplasia, giant cell arteritis, neurofibromatosis type 1, and bony compressions. The most common cause of VAS is atherosclerosis which is derived from the macrophage-induced oxidation of low-density lipoproteins (LDLs), alongside the accumulation of cholesterol. Calcification of the vertebral artery occurs when there is excess calcium and phosphate deposition in the vessel. Dissection of the vertebral artery can lead to the formation of a hematoma causing stenosis of the vertebral artery. Fibromuscular dysplasia can result in stenosis due to the deposition of collagen fibers in the tunica media, intima, or adventitia. Giant cell arteritis, an autoimmune disorder, causes inflammation of the internal elastic membrane resulting in eventual stenosis of the artery. Neurofibromatosis type 1, an autosomal dominant disorder, results in the stenosis of the vertebral artery due to the altered function of neurofibromin. Mechanical compression of the vertebral artery by bone can also cause stenosis of the vertebral artery. Digital subtraction angiography (DSA) is considered the current gold standard in diagnosing vertebral artery stenosis; however, its associated morbidity and mortality have led to increased use of non-invasive techniques such as duplex ultrasonography (DUS), computed tomography angiography (CTA), and magnetic resonance angiography (MRA). Currently, asymptomatic and symptomatic vertebral artery stenoses are treated by risk factor modification and medical treatment. However, it is recommended that surgical (endarterectomy, reconstruction, and decompression) and endovascular (balloon coronary, bare-metal, and drug-eluting stents) treatments are also used for symptomatic vertebral artery stenosis.

An Overview of Parkinson's Disease: Curcumin as a Possible Alternative Treatment.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain and basal ganglia, followed by dopamine deficiency in the brain. Dopamine plays a crucial role in motor coordination, memory, and cognition; its decrease in PD leads to dyskinesia, cognitive deficits, and depression. In addition, the formation of alpha-synuclein protein aggregates (Lewy bodies) causes further damage to the CNS. Current treatment options include dopamine precursors, inhibitors of dopamine metabolism, upregulation of autophagy, adenosine A2A antagonists, and surgical intervention as a last resort. A challenge arises from a progressive decrease in treatment efficacy as the disease progresses and this necessitates exploration of adjunctive treatments. Epidemiological studies suggest that the prevalence of PD varies between ethnic groups of Caucasians, Asians, and African Americans. Notably, the prevalence of PD is lower in countries of Southeastern Asia including India. The differences in the diet of various ethnic groups may suggest an origin for this difference in the prevalence of PD. One staple ingredient in traditional Asian cuisine is turmeric. Curcuma longa, popularly known as turmeric, is an orange tuberous rhizome that has been used for centuries in traditional Indian cuisine and traditional medicine. Turmeric contains curcumin, a potent antioxidant that scavenges reactive oxygen species and chelates toxic metals. Curcumin has been proposed to be a neuroprotective agent due to its potent antioxidative properties. Though preliminary studies in animal model systems have suggested a protective effect of curcumin on dopaminergic neurons, the direct benefits of curcumin on the progress of PD remains poorly understood. In this review, we explore the promising use of curcumin as an adjunct to conventional PD treatments in order to enhance treatment and improve outcomes.

Subclavian Artery Calcification: A Narrative Review.

Subclavian artery calcification (SAC) affects 2% of the population and presents a serious risk of developing into subclavian steal syndrome (SSS). Risk factors for plaque formation of the subclavian artery include diabetes, hypertension, and smoking. While SAC generally presents as asymptomatic, symptoms in severe cases may include numbness, pain at rest, and ischemic gangrene. Patients with severe SSS are at high risk of developing neurological symptoms as a result of vertebrobasilar insufficiency affecting posterior cerebral perfusion. On physical examination, SSS is preliminarily diagnosed from bilateral inter-arm systolic blood pressure discrepancy (>10 mmHg), which can be further confirmed with vascular imaging. Duplex ultrasound (DUS) is a cost-effective and non-invasive baseline technique for visualizing luminal stenosis and quantifying peak systolic velocity (PSV). Computed tomography angiography (CTA) provides high-quality, fast, three-dimensional (3D) imaging at the cost of introducing nephrotoxic contrast agents. Magnetic resonance angiography (MRA) is the safest 3D imaging modality, without the use of X-rays and contrast agents, that is useful in assessing plaque characteristics and degree of stenosis. DUS-assisted digital subtraction angiography (DSA) remains the gold standard for grading the degree of stenosis in the subclavian artery and determining the distance between the puncture site and lesion, which can be carried out in a combined procedure with endovascular management strategies. The fundamental treatment options are surgical and endovascular intervention. Endovascular treatment options include percutaneous transluminal angiography (PTA) for recanalization of the stenosed vessel and permanent balloon stenting to prevent collapse after PTA. Overall, the benefits of endovascular management encompass faster recovery, lower stenosis recurrence rate, and lower incidence of complications, making it the treatment of choice in low-risk patients. Surgical interventions, although more complex, are considered gold-standard treatment options.

Obstructive Sleep Apnea as a Risk Factor for Venous Thromboembolism: A Systematic Review.

Obstructive sleep apnea (OSA), is a prevalent condition characterized by repeated episodes of pharyngeal airway obstruction resulting in hypopnea and apnea episodes during sleep leading to nightly awakenings. OSA is a major contributor to the healthcare burden worldwide due to its high cardiovascular morbidity and mortality. There is growing evidence to support a pathophysiological link between OSA and venous thromboembolism (VTE). The pro-inflammatory state along with intermittent hypoxia that is invoked in OSA is associated with blood hypercoagulability, venous stasis, and endothelial dysfunction leading to deep vein thrombosis (DVT) and pulmonary embolism (PE). In this systematic review, we aim to analyze and assess the available literature on OSA and VTE (or DVT/PE) to determine whether OSA is an independent risk factor for VTE.

Analysis of Psilocybin-Assisted Therapy in Medicine: A Narrative Review.

Psilocybin-containing mushrooms have been consumed by various cultures in many different parts of the world for thousands of years. Psilocybin, a classic psychedelic, contains unique psychoactive properties and has been incorporated into religious ceremonies and investigated for its medicinal value. In the mid-20th century, psilocybin, along with most other classic psychedelics (5HT-2A agonists), was classified as a Schedule I substance, bringing a halt to research on its medicinal utility. The resurgence of clinical trials involving psilocybin in the 21st century has produced promising results concerning the treatment of addiction, depression, and end-of-life mood disorders. Results from these trials have shown significant reductions in depression and anxiety when compared with a placebo, and one trial found no significant difference when compared to a routinely prescribed selective serotonin reuptake inhibitor (SSRI). Studies conducted with patients with advanced-stage cancer have demonstrated that psilocybin may also be beneficial at reducing depression and anxiety associated with psychological crises due to a terminal diagnosis. Psilocybin therapy in the treatment of addiction, which is notoriously difficult to treat, has shown encouraging results. Due to its low toxicity and low risk of overuse, psilocybin has the potential to have a significant influence in the field of addiction medicine. Psilocybin addiction research has been primarily focused on nicotine and alcohol and, in a few small, open-label trials, has shown superiority over traditional therapies. Psilocybin has a relatively unique and incompletely understood mechanism of action, which allows it to be given at several isolated periods. This infrequent dosing regimen has been shown to produce durable effects with minimal toxicity. This review analyzes the potential of psilocybin in the treatment of addiction, depression, and end-of-life mood disorders. In addition, it will discuss the difficulties involved with conducting scientific research on psychedelic compounds, adverse effects, and the therapeutic measures that are necessary to accompany the safe and effective administration of these psychoactive chemicals.

The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders.

Mounting evidence shows that the complex gut microbial ecosystem in the human gastrointestinal (GI) tract regulates the physiology of the central nervous system (CNS) via microbiota and the gut-brain (MGB) axis. The GI microbial ecosystem communicates with the brain through the neuroendocrine, immune, and autonomic nervous systems. Recent studies have bolstered the involvement of dysfunctional MGB axis signaling in the pathophysiology of several neurodegenerative, neurodevelopmental, and neuropsychiatric disorders (NPDs). Several investigations on the dynamic microbial system and genetic-environmental interactions with the gut microbiota (GM) have shown that changes in the composition, diversity and/or functions of gut microbes (termed "gut dysbiosis" (GD)) affect neuropsychiatric health by inducing alterations in the signaling pathways of the MGB axis. Interestingly, both preclinical and clinical evidence shows a positive correlation between GD and the pathogenesis and progression of NPDs. Long-term GD leads to overstimulation of hypothalamic-pituitary-adrenal (HPA) axis and the neuroimmune system, along with altered neurotransmitter levels, resulting in dysfunctional signal transduction, inflammation, increased oxidative stress (OS), mitochondrial dysfunction, and neuronal death. Further studies on the MGB axis have highlighted the significance of GM in the development of brain regions specific to stress-related behaviors, including depression and anxiety, and the immune system in the early life. GD-mediated deregulation of the MGB axis imbalances host homeostasis significantly by disrupting the integrity of the intestinal and blood-brain barrier (BBB), mucus secretion, and gut immune and brain immune functions. This review collates evidence on the potential interaction between GD and NPDs from preclinical and clinical data. Additionally, we summarize the use of non-therapeutic modulators such as pro-, pre-, syn- and post-biotics, and specific diets or fecal microbiota transplantation (FMT), which are promising targets for the management of NPDs.

Current Trends in the Duration of Anticoagulant Therapy for Venous Thromboembolism: A Systematic Review.

Anticoagulation therapy is the first line and drug of choice for both the treatment and prophylaxis of venous thromboembolism (deep vein thrombosis and/or pulmonary embolism). Anticoagulation drugs, ranging from different preparations of heparin, warfarin, and newer direct oral drugs such as rivaroxaban and dabigatran, work mainly by inhibiting important factors and enzymes in the coagulation cascade by preventing fibrin formation, platelet aggregation, and clot assembly. With recurrent thrombosis and embolisms being a feared complication for many physicians treating such cases, anticoagulation is often extended beyond the initial three- to six-month acute phase after an incident of venous thromboembolism. For some groups of patients, anticoagulation needs to be offered indefinitely to decrease the risk of a recurrent thrombosis. However, this concomitantly increases obvious and dangerous adverse effects such as increased risk of hemorrhage, as the ability to clot is hindered. This tradeoff between recurrent venous thromboembolism and bleeding is what underscores the controversy of the clinical question: for how long should anticoagulation be administered for venous thromboembolism? This review analyzes the use of anticoagulants in different types of venous thromboembolism and remarks on current consensus and trends on the length of anticoagulation treatment. We are doing so while acknowledging that venous thromboembolism management is an active area of research that is rapidly evolving. A literature search was performed looking at recent studies on anticoagulant administration for the treatment of venous thromboembolism with a focus on varying durations and patient populations. Factors that affect clinical decisions of duration are also elucidated. The most clinically relevant anticoagulants were discussed and their effects on the risk of recurrent thrombosis and embolism, and the risk of bleeding in relation to other drugs were analyzed. Ultimately, this article discussed patterns of anticoagulant treatments duration and which patient groups are likely to benefit the most from certain durations, shedding light on the ambiguity in how physicians should approach administering anticoagulation therapy over time for a broad range of presentations of venous thromboembolism.