Search

Objective: Do-Not-Attempt-Resuscitation orders originated in the early 1960s with the establishment of advanced cardiopulmonary resuscitation. These orders aim to limit therapeutic efforts in cases where it may be futile. The decision not to resuscitate a patient is a process that involves a series of ethical, legal, and clinical considerations. Still, it also requires a process in which priority is given to the patients and their autonomy. The objective of this study was to describe the knowledge and attitudes of physicians working in Chile toward Do-Not-Attempt-Resuscitation orders. Methods: A cross-sectional study was conducted, in which a digital questionnaire was sent to physicians from different regions of Chile. Quantitative variables were analyzed using measures of central tendency and dispersion (e.g., median and interquartile range), while qualitative variables were evaluated using frequencies and percentages. Results: Four hundred and thirty-one physicians completed the survey. 85.4% were familiar with the ethical and legal guidelines for cardiopulmonary resuscitation and the rights and duties of the patient. 39.2% believed that patients should have the final decision Do-Not-Attempt-Resuscitation orders, especially if they themselves requested not to be resuscitated. 87.7% mentioned that the Do-Not-Attempt-Resuscitation orders should be reassessed if the patient’s prognosis improves. In addition, it was found that the decision not to resuscitate was not always discussed with the patient or their family. Conclusions: The study revealed an ethical conflict regarding Do-Not-Attempt-Resuscitation orders and their management by Chilean physicians. Therefore, it is necessary to create recommendations and provide training to guide professionals in this process, which should also involve patients and their families.

Abstract Electronic nicotine delivery systems (ENDS), also commonly known as electronic cigarettes (e-cigs) are considered in most cases as a safer alternative to tobacco smoking and therefore have become extremely popular among all age groups and sex. It is estimated that up to 15% of pregnant women are now using e-cigs in the US which keeps increasing at an alarming rate. Harmful effects of tobacco smoking during pregnancy are well documented for both pregnancy and postnatal health, however limited preclinical and clinical studies exist to evaluate the long-term effects of prenatal e-cig exposure on postnatal health. Therefore, the aim of our study is to evaluate the effect of maternal e-cig use on postnatal blood-brain barrier (BBB) integrity and behavioral outcomes of mice of varying age and sex. In this study, pregnant CD1 mice (E5) were exposed to e‐Cig vapor (2.4% nicotine) until postnatal day (PD) 7. Weight of the offspring was measured at PD0, PD7, PD15, PD30, PD45, PD60 and PD90. The expression of structural elements of the BBB, tight junction proteins (ZO-1, claudin-5, occludin), astrocytes (GFAP), pericytes (PDGFRβ) and the basement membrane (laminin α1, laminin α4), neuron specific marker (NeuN), water channel protein (AQP4) and glucose transporter (GLUT1) were analyzed in both male and female offspring using western blot and immunofluorescence. Estrous cycle was recorded by vaginal cytology method. Long‐term motor and cognitive functions were evaluated using open field test (OFT), novel object recognition test (NORT) and morris water maze test (MWMT) at adolescence (PD 40–45) and adult (PD 90–95) age. In our study, significantly reduced expression of tight junction proteins and astrocyte marker were observed in male and female offspring until PD 90 (P

Abstract Background The short and long-term health effects of JUUL electronic cigarette (e-Cig) are largely unknown and warrant extensive research. We hypothesized that JUUL exposure could cause cerebrovascular toxicities impacting the progression and outcome of ischemic stroke comparable to tobacco smoke (TS) exposure. Methods We exposed male C57 mice to TS/JUUL vapor for 14 days. LCMS/MS was used to measure brain and plasma nicotine and cotinine level. Transient middle cerebral artery occlusion (tMCAO) followed by reperfusion was used to mimic ischemic stroke. Plasma levels of IL-6 and thrombomodulin were assessed by enzyme-linked immunosorbent assay. At the same time, western blotting was used to study blood–brain barrier (BBB) tight junction (TJ) proteins expression and key inflammatory and oxidative stress markers. Results tMCAO upregulated IL-6 and decreased plasma thrombomodulin levels. Post-ischemic brain injury following tMCAO was significantly worsened by JUUL/TS pre-exposure. TJ proteins expression was also downregulated by JUUL/TS pre-exposure after tMCAO. Like TS, exposure to JUUL downregulated the expression of the antioxidant Nrf2. ICAM-1 was upregulated in mice subjected to tMCAO following pre-exposure to TS or JUUL, with a greater effect of TS than JUUL. Conclusions These results suggest that JUUL exposure could negatively impact the cerebrovascular system, although to a lesser extent than TS exposure.

Introduction: Despite the prevalence of the perception that electronic cigarettes (e-cig) are a safer alternative to tobacco smoke, growing concern about their potential toxic impact warrants adequate investigation focusing on special populations like maternal and pediatric groups. This study evaluated the consequences of maternal e-cig use on neonatal neuroinflammation, oxidative stress, and mitochondrial function in primary cultured neurons and postnatal day (PD) 7 and 90 brain.Methodology: Pregnant CD1 mice were exposed to e‐cig vapor (2.4% nicotine) from gestational day 5 (E5) till PD7, and the primary neurons were isolated from pups at E16/17. Cellular total reactive oxygen species (ROS) and mitochondrial superoxide were measured in primary neurons using CM-H2DCFDA and Mitosox red, respectively. Mitochondrial function was assessed by Seahorse XF Cell Mitostress analysis. The level of pro-inflammatory cytokines was measured in primary neurons and PD7 and PD90 brains by RT-PCR and immunobead assay. Western blot analysis evaluated the expression of antioxidative markers (SOD-2, HO-1, NRF2, NQO1) and that of the proinflammatory modulator NF-κB.Results: Significantly higher level of total cellular ROS (p < 0.05) and mitochondrial superoxide (p < 0.01) was observed in prenatally e-cig-exposed primary neurons. We also observed significantly reduced antioxidative marker expression and increased proinflammatory modulator and cytokines expression in primary neurons and PD7 (p < 0.05) but not in PD90 postnatal brain.Conclusion: Our findings suggest that prenatal e-cig exposure induces postnatal neuroinflammation by promoting oxidative stress (OS), increasing cytokines’ levels, and disrupting mitochondrial function. These damaging events can alter the fetal brain’s immune functions, making such offspring more vulnerable to brain insults.

Background: In medicine, social networks contribute to the professional training because it is a way to improve the knowledge and skills of students, residents and specialists; additionally, these networks allow the dissemination of evidence. However, Latin American surgeons' influence within this social network is not highlighted. In this study, using the hashtags #SoMe4Surgery and #SoMe4IQLatAm, the participation of Latin American surgeons in Twitter is established. Study Design: This is a prospective cross-sectional study of the academic tweets published in the period between October 13 and October 19, 2020, on Twitter by the academic accounts @Cirbosque and @MISIRG1 who are users of the social network Twitter in Latin America who participate in the network with the hashtags #SoMe4Surgery and #SoMe4IQLatAm with academic use. Results: A total of 56 tweets and 665 retweets were analyzed. Male sex presents greater interaction, as well as Mondays and Tuesdays week days. Geolocation was recorded as 37.1% in Latin America and 17.6% in Europe. #SoMe4Surgery was mentioned in 31 tweets and generated 211,700 impressions and 25,557 interactions, and #SoMe4IQLatam was mentioned in 25 tweets and achieved 57,585 impressions and 21,901 interactions. A growth of the participation rate of 6.5% in @Cirbosque and 10.5% in @ MISIRG1 was estimated for 2021. Conclusion: The use of social networks, particularly Twitter, in the surgeon community has proven to be a valuable tool during the last decade. The tweet that needs to be shared among more surgeons should be linked to the hashtag #SoMe4IQLatAm and #SoMe4Surgery and Twitter surgeon leaders mentions.

Abstract Background Knowledge of the entry receptors responsible for SARS-CoV-2 is key to understand the neural transmission and pathogenesis of COVID-19 characterized by a neuroinflammatory scenario. Understanding the brain distribution of angiotensin converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, remains mixed. Smoking has been shown as a risk factor for COVID-19 severity and it is not clear how smoking exacerbates the neural pathogenesis in smokers. Methods Immunohistochemistry, real-time PCR and western blot assays were used to systemically examine the spatial-, cell type- and isoform-specific expression of ACE2 in mouse brain and primary cultured brain cells. Experimental smoking exposure was conducted to evaluate the effect of smoking on brain expression. Results We observed ubiquitous expression of ACE2 but uneven brain distribution, with high expression in the cerebral microvasculature, medulla oblongata, hypothalamus, subventricular zones, and meninges around medulla oblongata and hypothalamus. Co-staining with cell type-specific markers demonstrates ACE2 is primarily expressed in astrocytes around the microvasculature, medulla oblongata, hypothalamus, ventricular and subventricular zones of cerebral ventricles, and subependymal zones in rhinoceles and rostral migratory streams, radial glial cells in the lateral ventricular zones, tanycytes in the third ventricle, epithelial cells and stroma in the cerebral choroid plexus, as well as cerebral pericytes, but rarely detected in neurons and cerebral endothelial cells. ACE2 expression in astrocytes is further confirmed in primary cultured cells. Furthermore, isoform-specific analysis shows astrocyte ACE2 has the peptidase domain responsible for SARS-CoV-2 entry, indicating astrocytes are indeed vulnerable to SARS-CoV-2 infection. Finally, our data show experimental tobacco smoking and electronic nicotine vaping exposure increase proinflammatory and/or immunomodulatory cytokine IL-1a, IL-6 and IL-5 without significantly affecting ACE2 expression in the brain, suggesting smoking may pre-condition a neuroinflammatory state in the brain. Conclusions The present study demonstrates a spatial- and cell type-specific expression of ACE2 in the brain, which might help to understand the acute and lasting post-infection neuropsychological manifestations in COVID-19 patients. Our data highlights a potential role of astrocyte ACE2 in the neural transmission and pathogenesis of COVID-19. This also suggests a pre-conditioned neuroinflammatory and immunocompromised scenario might attribute to exacerbated COVID-19 severity in the smokers.

Abstract This study reports on performance enhancement of a Cu2ZnSnS4 solar cell introducing Sb2S3 as hole transport layer (HTL) along WS2 as buffer layer. We have investigated photovoltaic (PV) characteristics by utilizing SCAPS‐1D. A comparative analysis on PV performances between conventional CZTS/CdS and proposed Ni/Sb2S3/CZTS/WS2/FTO/Al solar cells is presented. It is revealed that “spike like” band structure at the CZTS/WS2 interface having smaller conduction band offset makes it potential alternative to commonly used CdS buffer. This report also evaluates that the Sb2S3 as an HTL inserted at the rear of CZTS enhances performances by reducing carrier recombination at back interface with appropriate band alignment. The impacts of thickness, carrier concentration of different layers, and bulk defect density in CZTS as well as the interface defects on cell outputs are analyzed. The influences of temperature, work function, and cell resistances are also examined. Optimum absorber thickness of 1.0 μm along doping density of 1017 cm−3 is selected. A maximum efficiency of 30.63% is achieved for the optimized CZTS cell. Therefore, these results suggest that Sb2S3 as HTL and WS2 as buffer layer can be employed effectively to develop highly efficient and low‐cost CZTS solar cells.

This commentary discusses the effect of misuse of intravenous sedation regimens in lowering the systemic blood pressure in mechanically ventilated neurosurgical patients in the intensive care unit.

Simulation has shown good results in medical scenarios in which the patient's problem can be solved by following protocols previously established in clinical practice guidelines. Therefore, the implementation of simulation programs in neurocritical care improves the outcomes of patients at clinical centers because a properly trained professional will be able to provide the most effective care in the shortest time possible, safeguarding the patient's life. Some learning and simulation models that can be included in medical education to improve neurocritical vascular care include task trainers, full-body mannequins, standardized patients, and computer-based simulation. Specifically, medical simulation in academic training programs in health sciences has a great impact on the development of specific skills, which could potentially reduce medical-legal and economic issues, improve care, and result in the management of clinical events. Simulation is established as an essential educational tool, allowing the instruction of knowledge from an interactive perspective and offering a broader vision when it comes to medical practice. The objective of this article is to present evidence related to the usefulness and impact of medical simulation in neurovascular critical care education.

Our lab previously established that metformin, a first-line type two diabetes treatment, activates the Nrf2 pathway and improves post-stroke recovery. Metformin’s brain permeability value and potential interaction with blood–brain barrier (BBB) uptake and efflux transporters are currently unknown. Metformin has been shown to be a substrate of organic cationic transporters (Octs) in the liver and kidneys. Brain endothelial cells at the BBB have been shown to express Octs; thus, we hypothesize that metformin uses Octs for its transport across the BBB. We used a co-culture model of brain endothelial cells and primary astrocytes as an in vitro BBB model to conduct permeability studies during normoxia and hypoxia using oxygen–glucose deprivation (OGD) conditions. Metformin was quantified using a highly sensitive LC-MS/MS method. We further checked Octs protein expression using Western blot analysis. Lastly, we completed a plasma glycoprotein (P-GP) efflux assay. Our results showed that metformin is a highly permeable molecule, uses Oct1 for its transport, and does not interact with P-GP. During OGD, we found alterations in Oct1 expression and increased permeability for metformin. Additionally, we showed that selective transport is a key determinant of metformin’s permeability during OGD, thus, providing a novel target for improving ischemic drug delivery.

Abstract The blood–brain barrier (BBB) is a fundamental component of the central nervous system. Its functional and structural integrity is vital in maintaining the homeostasis of the brain microenvironment. On the other hand, the BBB is also a major hindering obstacle for the delivery of effective therapies to treat disorders of the Central Nervous System (CNS). Over time, various model systems have been established to simulate the complexities of the BBB. The development of realistic in vitro BBB models that accurately mimic the physiological characteristics of the brain microcapillaries in situ is of fundamental importance not only in CNS drug discovery but also in translational research. Successful modeling of the Neurovascular Unit (NVU) would provide an invaluable tool that would aid in dissecting out the pathological factors, mechanisms of action, and corresponding targets prodromal to the onset of CNS disorders. The field of BBB in vitro modeling has seen many fundamental changes in the last few years with the introduction of novel tools and methods to improve existing models and enable new ones. The development of CNS organoids, organ-on-chip, spheroids, 3D printed microfluidics, and other innovative technologies have the potential to advance the field of BBB and NVU modeling. Therefore, in this review, summarize the advances and progress in the design and application of functional in vitro BBB platforms with a focus on rapidly advancing technologies.

The occlusion of a cerebral artery by a thrombus accounts for about 80% of strokes. Reperfusion can save hypoperfused brain tissue from early cerebral blood flow restoration (CBF), thus limiting neurological impairment. The most successful treatments for stroke care have proven to be reperfusion techniques. One of the key drawbacks of these treatment methods is that early ischemic brain tissue reperfusion can lead to adverse effects, including blood-brain barrier breakdown, which can lead to cerebral oedema, haemorrhage of the brain, or both. Haemorrhages are especially devastating after reperfusion and are associated with exceptionally high morbidity and mortality. Fear of haemorrhage-related reperfusion greatly restricts the use of stroke therapies. Reperfusion injury, a mechanism that further damages brain cells, the ischemic arterial wall, and the microvasculature, is due to the deleterious effects of early restoration of cerebral blood flow following stroke. It seems clear that the brain will benefit from therapies to restore CBF to an ischemic region. The brain's reliance on normal CBF levels is underlined by the sensitivity of the brain to relatively short ischaemic cycles. Experimental and clinical data, however, suggests that tissue damage can be aggravated by organ reperfusion. [1] Studies have failed to prove that infarct size is increased by reperfusion. Reperfusion can aggravate the formation of oedema and lead to abnormal blood flow patterns and microvascular lesions within the reperfused areas.

In this study, a hole transport layer (HTL)-free perovskite solar cell (PSC) structure with CH3NH3SnI3 as an active layer and TiO2 as an electron transport layer (ETL) has been proposed for the first time. The solar cell capacitance simulator in one dimension program has been carried out to design the proposed HTL-free CH3NH3SnI3-based PSC and simulate its performance. The output parameters of the proposed PSC, such as open circuit voltage (Voc), short-circuit current density (Jsc), fill factor (FF), power conversion efficiency, and quantum efficiency, are evaluated by varying the physical parameters of various layers. The thermal stability of the proposed cell has also been analyzed. The thicknesses of the ETL and the absorber are optimized to be 0.05 and 1.0 µm, respectively. A conversion efficiency of 26.33% along with Voc of 0.98 V, Jsc of 31.93 mA/cm2, and an FF of 84.34% is obtained for the proposed HTL-free CH3NH3SnI3-based PSC. These simulation results would be helpful in fabricating highly efficient and inexpensive PSCs.

Proper regulation of energy metabolism in the brain is crucial for maintaining brain activity in physiological and different pathophysiological conditions. Ischemic stroke has a complex pathophysiology which includes perturbations in the brain energy metabolism processes which can contribute to worsening of brain injury and stroke outcome. Smoking and diabetes are common risk factors and comorbid conditions for ischemic stroke which have also been associated with disruptions in brain energy metabolism. Simultaneous presence of these conditions may further alter energy metabolism in the brain leading to a poor clinical prognosis after an ischemic stroke event. In this review, we discuss the possible effects of smoking and/or diabetes on brain glucose utilization and mitochondrial energy metabolism which, when present concurrently, may exacerbate energy metabolism in the ischemic brain. More research is needed to investigate brain glucose utilization and mitochondrial oxidative metabolism in ischemic stroke in the presence of smoking and/or diabetes, which would provide further insights on the pathophysiology of these comorbid conditions and facilitate the development of therapeutic interventions.

BackgroundGlobally, studies have shown conflicting results regarding the association of blood groups with SARS CoV-2 infection.ObjectiveTo observe the association between ABO blood groups and the presentation and outcomes of confirmed COVID-19 cases.Design, setting, and participantsThis was a prospective cohort study of patients with mild-to-moderately severe COVID-19 infections who presented in the COVID-19 unit of Dhaka Medical College Hospital and were enrolled between 01 June and 25 August, 2020. Patients were followed up for at least 30 days after disease onset. We grouped participants with A-positive and A-negative blood groups into group I and participants with other blood groups into group II.ResultsThe cohort included 438 patients; 52 patients were lost to follow-up, five died, and 381 completed the study. The prevalence of blood group A [144 (32.9%)] was significantly higher among COVID-19 patients than in the general population (p < 0.001). The presenting age [mean (SD)] of group I [42.1 (14.5)] was higher than that of group II [38.8 (12.4), p = 0.014]. Sex (p = 0.23) and co-morbidity (hypertension, p = 0.34; diabetes, p = 0.13) did not differ between the patients in groups I and II. No differences were observed regarding important presenting symptoms, including fever (p = 0.72), cough (p = 0.69), and respiratory distress (p = 0.09). There was no significant difference in the median duration of symptoms in the two group (12 days), and conversion to the next level of severity was observed in 26 (20.6%) and 36 patients (13.8%) in group I and II, respectively. However, persistent positivity of RT-PCR at 14 days of initial positivity was more frequent among the patients in group I [24 (19%)] than among those in group II [29 (11.1%)].ConclusionsThe prevalence of blood group A was higher among COVID-19 patients. Although ABO blood groups were not associated with the presentation or recovery period of COVID-19, patients with blood group A had delayed seroconversion.

Apart from being used as a medicine, cannabis or marijuana is the most widely abused recreational drug all over the world. The legalization and decriminalization of cannabis in Canada and various states of USA may be the underlying reason of the widespread popularity of it among young population. Various studies have reported about the relationship between cannabis use and different detrimental effects like cardiovascular, cerebrovascular, and neurological complications among different age groups. Specifically, the young population is getting adversely affected by this, harmful yet, readily accessible recreational drug. Although the mechanism behind cannabis mediated neurological and cerebrovascular complications has not been elucidated yet, the results of these studies have confirmed the association of these diseases with cannabis. Given the lack of comprehensive study relating these harmful complications with cannabis use, the aim of this narrative literature review article is to evaluate and summarize current studies on cannabis consumption and cerebrovascular/neurological diseases along with the leading toxicological mechanisms.

The blood-brain barrier (BBB) is a fundamental component of the central nervous system (CNS). Its functional and structural integrity is vital to maintain the homeostasis of the brain microenvironment by controlling the passage of substances and regulating the trafficking of immune cells between the blood and the brain. The BBB is primarily composed of highly specialized microvascular endothelial cells. These cells’ special features and physiological properties are acquired and maintained through the concerted effort of hemodynamic and cellular cues from the surrounding environment. This complex multicellular system, comprising endothelial cells, astrocytes, pericytes, and neurons, is known as the neurovascular unit (NVU). The BBB strictly controls the transport of nutrients and metabolites into brain parenchyma through a tightly regulated transport system while limiting the access of potentially harmful substances via efflux transcytosis and metabolic mechanisms. Not surprisingly, a disruption of the BBB has been associated with the onset and/or progression of major neurological disorders. Although the association between disease and BBB disruption is clear, its nature is not always evident, specifically with regard to whether an impaired BBB function results from the pathological condition or whether the BBB damage is the primary pathogenic factor prodromal to the onset of the disease. In either case, repairing the barrier could be a viable option for treating and/or reducing the effects of CNS disorders. In this review, we describe the fundamental structure and function of the BBB in both healthy and altered/diseased conditions. Additionally, we provide an overview of the potential therapeutic targets that could be leveraged to restore the integrity of the BBB concomitant to the treatment of these brain disorders.

The recently discovered novel coronavirus, SARS-CoV-2 (COVID-19 virus), has brought the whole world to standstill with critical challenges, affecting both health and economic sectors worldwide. Although initially, this pandemic was associated with causing severe pulmonary and respiratory disorders, recent case studies reported the association of cerebrovascular-neurological dysfunction in COVID-19 patients, which is also life-threatening. Several SARS-CoV-2 positive case studies have been reported where there are mild or no symptoms of this virus. However, a selection of patients are suffering from large artery ischemic strokes. Although the pathophysiology of the SARS-CoV-2 virus affecting the cerebrovascular system has not been elucidated yet, researchers have identified several pathogenic mechanisms, including a role for the ACE2 receptor. Therefore, it is extremely crucial to identify the risk factors related to the progression and adverse outcome of cerebrovascular-neurological dysfunction in COVID-19 patients. Since many articles have reported the effect of smoking (tobacco and cannabis) and vaping in cerebrovascular and neurological systems, and considering that smokers are more prone to viral and bacterial infection compared to non-smokers, it is high time to explore the probable correlation of smoking in COVID-19 patients. Herein, we have reviewed the possible role of smoking and vaping on cerebrovascular and neurological dysfunction in COVID-19 patients, along with potential pathogenic mechanisms associated with it.

Recent studies on vaccine delivery systems are exploring the possibility of replacing liquid vaccines with solid dose vaccines due to the many advantages that solid dose vaccines can offer. These include the prospect of a needle-free vaccine delivery system leading to better patient compliance, cold chain storage, less-trained vaccinators and fewer chances for needle stick injury hazards. Some studies also indicate that vaccines in a solid dosage form can result in a higher level of immunogenicity compared to the liquid form, thus providing a dose-sparing effect. This review outlines the different approaches in solid vaccine delivery using various routes of administration including, oral, pulmonary, intranasal, buccal, sublingual, and transdermal routes. The various techniques and their current advancements will provide a knowledge base for future work to be carried out in this arena.