Revolutionizing Ischemic Stroke Diagnosis and Treatment: The Promising Role of Neurovascular Unit-Derived Extracellular Vesicles.

Ischemic stroke is a fatal and disabling disease worldwide and imposes a significant burden on society. At present, biological markers that can be conveniently measured in body fluids are lacking for the diagnosis of ischemic stroke, and there are no effective treatment methods to improve neurological function after ischemic stroke. Therefore, new ways of diagnosing and treating ischemic stroke are urgently needed. The neurovascular unit, composed of neurons, astrocytes, microglia, and other components, plays a crucial role in the onset and progression of ischemic stroke. Extracellular vesicles are nanoscale lipid bilayer vesicles secreted by various cells. The key role of extracellular vesicles, which can be released by cells in the neurovascular unit and serve as significant facilitators of cellular communication, in ischemic stroke has been extensively documented in recent literature. Here, we highlight the role of neurovascular unit-derived extracellular vesicles in the diagnosis and treatment of ischemic stroke, the current status of extracellular vesicle engineering for ischemic stroke treatment, and the problems encountered in the clinical translation of extracellular vesicle therapies. Extracellular vesicles derived from the neurovascular unit could provide an important contribution to diagnostic and therapeutic tools in the future, and more studies in this area should be carried out.

Exosomes as biomarkers and therapeutic measures for ischemic stroke.

Ischemic stroke (IS) is the leading cause of long-term disability in the world and characterized by high morbidity, recurrence, complications, and mortality. Due to the lack of early diagnostic indicators, limited therapeutic measures and inadequate prognostic indicators, the diagnosis and treatment of IS remains a particular challenge at present. It has recently been reported that exosomes (EXOs) play a significant role in the pathogenesis and treatment of IS. The purpose of this paper is to probe the role of EXOs in diagnostic biomarkers and therapeutic measures for IS and to provide innovative ideas for improving the prognosis of IS.

Research progress in the risk factors and screening assessment of dysphagia in the elderly.

With the aging of the population, the incidence of dysphagia has gradually increased and become a major clinical and public health issue. Early screening of dysphagia in high-risk populations is crucial to identify the risk factors of dysphagia and carry out effective interventions and health management in advance. In this study, the current epidemiology, hazards, risk factors, preventive, and therapeutic measures of dysphagia were comprehensively reviewed, and a literature review of screening instruments commonly used globally was conducted, focusing on their intended populations, main indicators, descriptions, and characteristics. According to analysis and research in the current study, previous studies of dysphagia were predominantly conducted in inpatients, and there are few investigations and screenings on the incidence and influencing factors of dysphagia in the community-dwelling elderly and of dysphagia developing in the natural aging process. Moreover, there are no unified, simple, economical, practical, safe, and easy-to-administer screening tools and evaluation standards for dysphagia in the elderly. It is imperative to focus on dysphagia in the community-dwelling elderly, develop unified screening and assessment tools, and establish an early warning model of risks and a dietary structure model for dysphagia in the community-dwelling elderly.

Integrated review of the nexus between toxic elements in the environment and human health.

Emerging pollutants in the environment due to economic development have become a global challenge for environmental and human health management. Potentially toxic elements (PTEs), a major group of pollutants, have been detected in soil, air, water and food crops. Humans are exposed to PTEs through soil ingestion, consumption of water, uptake of food crop products originating from polluted fields, breathing of dust and fumes, and direct contact of the skin with contaminated soil and water. The dose absorbed by humans, the exposure route and the duration (i.e., acute or chronic) determine the toxicity of PTEs. Poisoning by PTEs can lead to excessive damage to health as a consequence of oxidative stress produced by the formation of free radicals and, as a consequence, to various disorders. The toxicity of certain organs includes neurotoxicity, nephrotoxicity, hepatotoxicity, skin toxicity, and cardiovascular toxicity. In the treatment of PTE toxicity, synthetic chelating agents and symptomatic supportive procedures have been conventionally used. In addition, there are new insights concerning natural products which may be a powerful option to treat several adverse consequences. Health policy implications need to include monitoring air, water, soil, food products, and individuals at risk, as well as environmental manipulation of soil, water, and sewage. The overall goal of this review is to present an integrated view of human exposure, risk assessment, clinical effects, as well as therapy, including new treatment options, related to highly toxic PTEs.

Research progress on treatment measures for pediatric acute lung injury / 中国小儿急救医学

Pediatric acute lung injury(ALI)is a common disease in pediatric intensive care unit with a high fatality rate.Because the etiology of ALI is complex, the exact pathogenesis of ALI is not clear.At present, it is known that the important factors leading to the incidence of ALI in children are oxidative stress and dysregulation of inflammatory response.Progressive hypoxemia and respiratory distress are the main clinical manifestations of ALI.Respiratory support and drug control are the common treatment measures.In recent years, stem cell and molecular targeted therapy as new treatment pathways of ALI, have achieved certain achievements in the research, and are expected to become new treatment methods of ALI in chidren.

Analysis on mental-insanity and cessation-of-dangerousness examinations in three Brazilian custodial institutions: a retrospective cross-sectional study

ABSTRACT BACKGROUND: In Brazil, the right to healthcare and the incorporation of best scientific evidence in public health are universally guaranteed by law. However, the treatment offered to patients with mental disorders in custodial hospitals in this country has not been rigorously evaluated. OBJECTIVES: To analyze the psychiatric diagnoses and treatments implemented in three Brazilian custodial institutions. DESIGN AND SETTING: This was a retrospective, cross-sectional and descriptive study on patients held in custody in three Brazilian institutions, as judicially-determined safety measures due to their mental disorders, and the tools used in diagnoses and treatments. These institutions are in Rio de Janeiro and the Federal District. METHODS: The data from medical and judicial records that were made available were assessed regarding the diagnoses that were made and the instruments that were used. RESULTS: None of these inpatients were evaluated using validated tools, and only a few medical records presented clear descriptions of the cases. No patient with substance involvement had undergone laboratory toxicological assays. It was not possible to verify the adequacy of treatments because the procedures were inadequately described in the records. CONCLUSIONS: No standardized protocols or instruments for diagnosing mental health disorders or assessing use of psychoactive substances had been applied among the inpatients at these custodial institutions in Rio de Janeiro and the Federal District. The treatments that were prescribed to these inpatients consisted mainly of drugs.

Emerging role of transcription factor EB in mitochondrial quality control.

Mitochondria are energy producers that play a vital role in cell survival. Mitochondrial dysfunction is involved in many diseases, including metabolic syndrome, neurodegenerative disorders, cardiomyopathies, cancer, obesity, and diabetic kidney disease, and challenges still remain in terms of treatments for these diseases. Mitochondrial quality control (MQC), which is defined as the maintenance of the quantity, morphology, and function of mitochondria, plays a pivotal role in maintaining cellular metabolic homeostasis and cell survival. Recently, growing evidence suggests that the transcription factor EB (TFEB) plays a pivotal role in MQC. Here, we systemically investigate the potential role and mechanisms of TFEB in MQC, which include the activation of mitophagy, regulation of mitochondrial biogenesis, reactive oxygen species (ROS) clearance, and the balance of mitochondria fission-fusion cycle. Importantly, we further discuss the therapeutic measures and effects aimed at TFEB on mitochondrial dysfunction-related diseases. Taken together, targeting TFEB to regulate MQC may represent an appealing therapeutic strategy for mitochondrial dysfunction related-diseases.

Conflicting Priorities Between Risk Management and Treatment of Schizophrenia in Swiss Forensic Services-A Case Report.

The Swiss Criminal Code provides measures for mentally-ill offenders focusing on their need for treatment. This may lead to the deprivation of the patient's liberty up to several years. Under certain circumstances the mentally-ill offender can be sentenced to an indefinite incarceration. This case presentation we will describe a forensic psychiatric patient diagnosed with schizophrenia who was ordered an indefinite incarceration in Switzerland after he had been sentenced to 8 years of imprisonment for a deliberate killing. Initial presentation of symptomatology included formal thought disorders and negative symptoms such as affective flattening and alogia. Due to a scarcity of adequate treatment sites in the 90s and lack of scope for risk assessment and management, the patient could only be treated within highly regiment prison environments in the past. There, the patient's treatment concept primarily focused on short-term psychiatric care instead of providing an adequate treatment plan that would have been essential for the patient's improvement of chronic symptoms. This case description aims to present some of the fundamental issues observed in the forensic mental health system, where strong efforts are made to balance risk management and the treatment of severe mental health disorders. We will put the patient's own course of treatment and his progress within the penal system into context with ethical challenges in the forensic and correctional services and will provide potential recommendations for future research in the field of forensic psychiatry.

Impact on mortality of adherence to evidence-based interventions in patients with catheter-related bloodstream infection due to methicillin-sensitive Staphylococcus aureus.

BACKGROUND: Recent studies have demonstrated improved survival when the management of Staphylococcus aureus bloodstream infection (BSI) is compliant with evidence-based therapeutic interventions. Whether this effect extends to low-risk sources, such as catheter-related BSI, remains unclear. METHODS: We retrospectively included 225 episodes of methicillin-sensitive S. aureus catheter-related BSI diagnosed in our centre during two non-consecutive periods: 2002-2004 (first period (101 episodes)) and 2009-2013 (second period (124 episodes)). We evaluated the adherence (percentage of compliance = (no. of interventions performed/no. of interventions recommended) × 100) to the following bundle: early catheter removal (≤72 hours), early initiation of appropriate antibiotic therapy, adequate sampling of follow-up blood cultures, transthoracic echocardiography (TTE) during hospitalization and adequate duration of therapy. RESULTS: Patients in the second period had a higher burden of comorbidities and more severe underlying conditions. All-cause 30-day mortality was 9.3%, with a significant difference between the first and second periods (13.9% versus 5.6%; p value = .035). Bundle adherence was significantly higher in the second period, particularly for follow-up blood cultures (26.7% versus 48.4%; p value = .001), performance of TTE (45.5% versus 84.7%; p value < .001) and appropriate duration of therapy (34.7% versus 50.0%; p value = .022). Bundle adherence ≥ 55% was associated with lower 30-day mortality (hazard ratio: 0.31; 95% confidence interval: 0.13-0.76). This effect remained significant across propensity score-based models adjusted for septic shock, study period and underlying conditions. CONCLUSIONS: There was a survival benefit in adhering to a bundle of evidence-based interventions in the specific setting of catheter-related BSI due to methicillin-sensitive S. aureus.

Explorative Study on Isolation and Characterization of a Microviridae G4 Bacteriophage, EMCL318, against Multi-Drug-resistant Escherichia coli 15-318.

Bacteriophages screened and isolated from sewage water samples exhibited antibacterial activities against multi-drug-resistant Escherichia coli strains. Five different water samples from Canadian habitats such as Kamloops Wastewater Treatment Center, Domtar, the Pacific Ocean, Bisaro Anima Cave, and alkali ponds, were used in this study. Four Enterobacteriaceae strains including one non-resistant and three clinical multi-drug Escherichia coli strains (E. coli 15-102, E. coli 15-124, and E. coli 15-318) were selected as target bacteria to screen for the bacteriophages from these collected water samples. Seeded agar assay technique was implemented for the screening. It was found that only sewage water sample exhibited a significant number of plaques count with the E. coli 15-318 (1.82 × 10² plaques/plate) cells in comparison to E. coli non-resistant strain K12 (8 plaques/plate). The phage did not produce plaques in the E. coli 15-124 and E. coli 15-102 strains. The bacteriophage, designated EMCL318, was isolated, purified, characterized, and identified to belong to the G4 species of the Family Microviridae, GenBank accession number MG563770. This is an explorative study conducted in order to reveal the viruses as alternative potentials to fight against emerging and existing multi-drug-resistant infectious diseases.

Topical Discoveries on Multi-Target Approach to Manage Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is recognized as progressive multifaceted and multi-factorial neurodegenerative disorder which causes dementia among elderly people. Although, researchers in this field have put considerable efforts for the investigation of novel and appropriate therapeutic measures towards the cure of AD, unfortunately, no effective prevention therapy for this disease is available till date. In fact, various aspects involved in the onset and progression of AD are still disputed or uncovered. However, to achieve definite and direct cure of AD, researcher's attention has been drawn towards exploration of new therapeutics targets. In this review, we have discussed the current progress of various aspects of pathophysiological mechanisms behind AD, together with recent investigational therapeutic approaches and present tools with an emphasis on Multi Target Directed Drugs approach. METHOD: We have scrutinized numerous peer-reviewed research articles to assemble and discuss significant research findings and success achieved in the last decade pertinent to the application of Multi-Target Directed Drugs in the treatment of AD. RESULTS: The main emphasis of the review was to understand the various aspects of pathophysiological mechanisms involved in AD, along with the recent developments on potential AD targets and application of Multi-Target Directed Drugs approach against AD. In addition, a brief overview of major drawbacks of conventional anti-AD drugs has also been included. We found that several strategies including in silico approach could be used for multi-target drug designing against AD. However, various synthetic/natural compounds and nano-formulations have the ability to be developed as multi-target drugs for AD. CONCLUSION: The present review comprises imperative information regarding AD pathology and disease process along with recent researches going on to develop treatment strategies against AD. Thus, this review might be helpful for physician, neurologist and scientist in understanding the diverse roots of AD for designing primary cure skills and scaffold of pharmacological treatment to manage AD.

Treatment of inflammatory internal root resorption with biodentine: a case report

Internal root resorption has been described as a resorptive defect of the internal aspect of the root following necrosis of odontoblasts as a result of chronic inflammation and bacterial invasion of the pulp tissue. Successful treatment outcome depends on early diagnosis, removal of the cause, proper treatment of the resorbed root. The present case report demonstrates the use of biodentine for the management of internal resorption.he aim of this study was to evaluate the efficacy of different lengths of time of passive ultrasonic irrigation (PUI) in removing calcium hydroxide (CH) paste from root canal, using scanning electron microscopy and energy dispersive spectrometry (SEM/EDS).

Trust: need for an improved communication between the public world and the pharmaceutical companies.

In the industrialized world, the negative image that many people (including politicians) have of pharmaceutical companies not only makes the life for those working in this field more difficult, in a sense it is a road block. Without an improvement in communication between the public world and the pharmaceutical industry, one can foresee this industry steadily becoming a more difficult environment to work in. There is a clear need for knowing more about all the work done inside these companies before a new drug is approved (it is not all about marketing...). That society has no understanding of the ever-increasing costs of new drugs is also related to this lack of understanding of how tricky and cumbersome the process is to take a new idea for treating a certain disease to production of a marketed drug. With a relatively small investment of money, but with an investment of much good will, brain power, and trust, it should be possible to bring all relevant parties together and make a change.