title: Mapping evidence on access to healthcare information by women of reproductive age in low-and-middle-income countries: scoping review protocol.

text: BACKGROUND Research shows that there are inadequate interventions in resource-limited settings that could enable women of reproductive age to access and use health services in those settings. The main objective of this scoping review is to map the evidence on access to healthcare information by women of reproductive age in LMICs. METHOD AND ANALYSIS The primary search will include Google Scholar, Science Direct, PubMed, EBSCOhost (Academic search complete, CINAHL with full text, MEDLINE with full text, MEDLINE), Emerald, Embase, CDSR, PsycINFO, published and peer review journals, organisational projects, conference papers, reference list, grey literature sources, as well as reports related to this objective will be included in the study. Identified keywords will be used to search articles from the studies. The articles and abstracts will be screened by two independent reviewers (JS and TPMT). Inclusion and exclusion criteria will be considered to guide the screening. A thematic content analysis will be used to present the narrative account of the reviews, using NVivo computer software (version 11). DISCUSSIONS The scoping review will focus on women of reproductive age in LMICs. We anticipate finding relevant literature on the interventions aimed at accessing health care services in LMICs. The study findings will help reveal research gaps to guide future research. SCOPING REVIEW REGISTRATION Not registered with PROSPERO (not needed). PROTOCOL AND REGISTRATION This scoping review was not registered.


title: Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E.

text: The tocotrienol vitamin E has potent antioxidant property, however absorption is low due to high lipid solubility. A self emulsifying preparation of tocotrienol rich vitamin E (SF-TRE) had been reported to increase their bioavailability. This randomized, placebo controlled, blinded end point clinical study aimed to determine the effects of 50, 100 and 200 mg daily of SF-TRE and placebo for two months on arterial compliance and vitamin E blood levels. Assessment of arterial compliance by carotid femoral pulse wave velocity (PWV) and augmentation index (AI), plasma vitamin E, serum total cholesterol and low density lipoprotein cholesterol were taken before and after 2 months' treatment in 36 healthy males. Un-supplemented tocotrienol levels were low, after treatment, all SF-TRE treated groups had significantly higher plasma alpha, delta and delta tocotrienol concentrations compared to placebo. Augmentation index change from baseline to end of treatment for groups placebo, 50, 100, and 200 mg were 2.22+/-1.54, -6.59+/-2.84, -8.72+/-3.77, and -6.27+/-2.67% respectively (p=0.049, 0.049, and 0.047 respectively). Groups 100 and 200 mg showed significant improvement after treatment with pulse wave velocity reductions of 0.77 m/s and 0.65 m/s respectively (p=0.007 and p=0.002). There was no effect of SF-TRE on serum lipids. We conclude that there was a trend towards improvement in arterial compliance with 2 months' of SF-TRE.


title: Polyanalgesic Consensus Conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel.

text: INTRODUCTION The use of intrathecal (IT) infusion of analgesic medications to treat patients with chronic refractory pain has increased since its inception in the 1980s, and the need for clinical research in IT therapy is ongoing. The Polyanalgesic Consensus Conference (PACC) panel of experts convened in 2000, 2003, and 2007 to make recommendations on the rational use of IT analgesics based on preclinical and clinical literature and clinical experiences. METHODS The PACC panel convened again in 2011 to update the standard of care for IT therapies to reflect current knowledge gleaned from literature and clinical experience. A thorough literature search was performed, and information from this search was provided to panel members. Analysis of published literature was coupled with the clinical experience of panel members to form recommendations regarding the use of IT analgesics to treat chronic pain. RESULTS After a review of literature published from 2007 to 2011 and discussions of clinical experience, the panel created updated algorithms for the rational use of IT medications for the treatment of neuropathic pain and nociceptive pain. CONCLUSIONS The advent of new algorithmic tracks for neuropathic and nociceptive pain is an important step in improving patient care. The panel encourages continued research and development, including the development of new drugs, devices, and safety recommendations to improve the care of patients with chronic pain.


docid: vzxmnqws

title: A preliminary systematic review and meta-analysis of randomized-controlled trials of cognitive remediation therapy for anorexia nervosa.

text: Cognitive remediation therapy (CRT) for anorexia nervosa (AN) was developed as an adjuvant treatment to target set-shifting and central coherence inefficiencies important in AN and to ultimately improve clinical outcomes of those with AN. The primary aim of this preliminary systematic review and meta-analysis was to determine the effect of CRT for AN relative to control treatments in randomized-controlled trials (RCTs) on neuropsychological inefficiencies at end-of-treatment. Secondary aims were to assess the effect of CRT for AN on dropout, eating-disorder-related, and other psychological outcomes at end-of-treatment. Systematic review and meta-analytic procedures were conducted in accordance with PRISMA Guidelines. RCTs evaluating CRT for AN compared to a control treatment were identified via ProQuest, PsycINFO, PubMed, and SCOPUS. Seven RCTs and one quasi-RCT of CRT for AN were included. RCT quality ratings ranged from fair (n = 3) to good (n = 4). Random-effects meta-analysis was conducted using Hedge's g. Study heterogeneity was assessed using I2 and publication bias was assessed with Begg's adjusted-rank correlation and the trim-and-fill method. CRT was not associated with improvement in central coherence compared to control treatments at end-of-treatment (g = 0.25, 95% CI = -0.35, 0.85, k = 3). Set-shifting outcomes were mixed due to heterogeneity of set-shifting measures across studies. CRT may prevent dropout; yet, more studies are needed to draw conclusions. CRT did not confer advantage over control treatments for eating-disorder-related and other psychological outcomes at end-of-treatment. Future RCTs of CRT for AN should use precise measures to assess constructs (particularly for set shifting), increase sample size, and implement longitudinal follow-up. (Word Count: 247 words).


Covid-19: Risk of second wave is very real, say researchers.


title: COVID-19: a defining moment for clinical pharmacology?

text: COVID-19 is overshadowing society across the world and it will redefine many aspects of how we live and work in the future. In a crisis, people are rightly looking for solutions from their leaders and experts and their response and actions will define them for years to come. COVID-19 may also be such a defining moment for clinical pharmacology in terms of its role in drug development and therapy. Though most drug development takes years from discovery to approval, for the COVID-19 pandemic, drug development is on a fundamentally different timeline.


docid: mmtoabww

title: Phosphate and nitrate uptake dynamics in Palmaria palmata (Rhodophyceae): ecological and physiological aspects of nutrient availability.

text: Uptake dynamics of dissolved inorganic phosphate (DIP) and dissolved inorganic nitrate (DIN) in young Palmaria palmata (n=49), cultivated in a range of DIP concentrations (0.0-6.0 µmol · L-1 ) and non-limiting DIN concentration (50 µmol · L-1 ) under fully controlled laboratory conditions, were quantified in a 'pulse-and-chase' approach over 5 weeks. Two different uptake rates were specified: (1) surge uptake (VS ) after starvation and (2) maintenance uptake with filled nutrient pools (VM ). VS for DIP of 1.57±0.29 µmol · cm-2 · d-1 and DIN of 15.6±4.3 µmol · cm-2 · d-1 , as well as VM for DIP of 0.57±0.22 µmol · cm-2 · d-1 and DIN of 5.6±2.1 µmol · cm-2 · d-1 were calculated. In addition, an absolute size of the internal storage capacity (ISC) for DIP of 22 µmol · cm2 and DIN of 222 µmol · cm2 was determined. A DIP to DIN uptake ratio of 1:10 under VM showed a weekly rhythmic uptake pattern, highlighted by a high correlation between DIP and DIN uptake (R=0.943). VS for DIN did not occur under DIP depletion, but uptake rates increased with increasing DIP availability. Hence, DIP availability limited access to DIN, which was also reflected by total dissolvable protein concentrations in sporophytes, which ranged from 10.2±2.5% to 24.6±8.0% dry weight depending on DIP availability. Similarly, total dissolvable carbohydrate concentration ranged from 22.1±3.6% to 54.3±12.3% dry weight. The data presented in this study opens further insight into ecological and physiological aspects of nutrient availability in P. palmata and allows for an optimization in cultivation.


Stenting in acute stroke: counterpoint.


Impending Shortages of Kidney Replacement Therapy for COVID-19 Patients.


What COVID-19 outbreak in Iran teaches us about virtual medical education.


docid: aexvjbxa

title: Bariatric surgery to treat severely obese patients with type 2 diabetes: A consensus statement.


Partha Kar: Covid-19 and ethnicity-why are all our angels white?


title: F-18-fluorodeoxyglucose positron emission tomography combined with CT in critically ill patients with suspected infection.

text: PURPOSE To assess the value of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with CT in critically ill patients suspected of having an infection. METHODS FDG-PET CT scans requested for evaluation of a suspected infection or inflammatory process in critically ill, mechanically ventilated patients were analyzed (blinded for the final clinical diagnosis) and compared with clinical follow-up. RESULTS Thirty-five FDG-PET/CT scans performed in 33 ICU patients (28 adults and 5 children), median age 58 years (range 1 month-72 years), were analyzed. Twenty-one FDG-PET/CT scans were true positive. Three FDG-PET/CT scans were considered false positive, in one case leading to additional diagnostic procedures (specificity 79%). Additionally, 11 true negatives were found (sensitivity 100%), leading to an overall accuracy of 91%. CONCLUSIONS FDG-PET/CT scanning is of additional value in the evaluation of suspected infection in critically ill patients in whom conventional diagnostics did not lead to a diagnosis. Apart from the high accuracy, in this study it appeared that, in addition to conventional diagnostic techniques that were routinely performed, a normal FDG-PET/CT ruled out important infections requiring prolonged antibiotic therapy or drainage. Since sensitivity is lower in highly metabolic active tissues (e.g., endocarditis, meningitis), the FDG-PET/CT scan is not suited to detect infections in these tissues.


title: Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force.

text: The COVID-19 pandemic has raised a host of ethical challenges, but key among these has been the possibility that health care systems might need to ration scarce critical care resources. Rationing policies for pandemics differ by institution, health system, and applicable law. Most seem to agree that a patient's ability to benefit from treatment and to survive are first-order considerations. However, there is debate about what clinical measures should be used to make that determination and about other factors that might be ethically appropriate to consider. In this paper, we discuss resource allocation and several related ethical challenges to the healthcare system and society, including how to define benefit, how to handle informed consent, the special needs of pediatric patients, how to engage communities in these difficult decisions, and how to mitigate concerns of discrimination and the effects of structural inequities.


docid: arpafmee

title: Impact of fixed implant supported prostheses in edentulous patients: protocol for a systematic review.

text: INTRODUCTION Edentulism is a debilitating and irreversible condition described as the 'final marker of disease burden for oral health'. Therapy with dental implants is being used on a large scale to replace missing teeth and to rehabilitate edentulous patients with overdentures and implant supported fixed dentures as a method of solving the problem of instability and lack of retention associated with conventional removable prostheses. Fixed implant supported prostheses are an alternative for implant rehabilitation treatment that allow patients to have new fixed teeth. They can be indicated in partial or total edentulous patients, and they can replace single teeth, or teeth and supporting tissues (hybrid prosthesis). They overcome the limitations of conventional dentures, increasing stability and retention, providing functional and psychological advantages for the patients. METHODS AND ANALYSIS We will electronically search for randomised controlled trials evaluating the effects of fixed implant supported prostheses in edentulous patients in the following databases: Pubmed/MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. We will also try to obtain literature screening references of included studies, searching for trial protocols in the WHO International Clinical Trials Registry Platform, reviewing International Team for Implantology conference proceedings and searching for non-published studies through Open Gray. Two researchers will independently undertake selection of studies, data extraction and assessment of the quality of the included studies. Data synthesis and subgroup analyses will be performed using special Review Manager software. Data will be combined in a meta-analysis using a random effects model. RESULTS The results will be presented as risk ratios for dichotomous data, and as mean difference or standardised mean difference for continuous data. ETHICS AND DISSEMINATION No ethics approval is considered necessary. The results of this study will be disseminated via peer reviewed publications and social networks. TRIAL REGISTRATION NUMBER CRD42015022086.


docid: ghasrwqc

title: [Asymptomatic and pre-symptomatic cases of COVID-19 contribution to spreading the epidemic and need for targeted control strategies].

text: The asymptomatic carrier state of COVID-19 has become a topic of concern for preventing a possible epidemic rebound. This review describes and defines the COVID-19 asymptomatic carrier state and outlines methods for identifying counting and reporting these cases. The author elaborates that the asymptomatic carrier state can be further divided into asymptomatic infection and pre-symptomatic infection after extended follow-up based on the nature of disease progression. The author presents the limited available data about infectiousness of asymptomatic and pre-symptomatic cases and their possible contributions to the overall epidemic of COVID-19 observed so far in China. Challenges of a possible second epidemic wave of COVID-19 caused by asymptomatic and pre-symptomatic cases are discussed and suggestions for control strategies and scientific research are provided.


title: Impact of stroke mechanism in acute basilar occlusion with reperfusion therapy.

text: Objective We aimed to evaluate the impact of underlying mechanism of basilar artery (BA) occlusion on the outcomes after endovascular therapy (EVT) for reperfusion and the outcome factors associated with each mechanism, and to identify radiologic parameters enabling to distinguish the underlying mechanism. Methods From a registry database, 194 consecutive patients with acute BA occlusion who underwent EVT were analyzed. Stroke mechanism, classified into in situ atherosclerotic thrombosis (ISAT) and embolism, clot sign location profiles in pre-angiography magnetic resonance image (MRI), parameters of angiography and EVT, and reperfusion were assessed. Poor outcome was defined as a modified Rankin-Scale score at 90 days of 3-6. Results The mean age was 68.8±11.8 years (range 21-92 years) and seventy-eight (40.2%) were female patients. 102 (52.6%) patients were classified into an embolism mechanism and 92 (47.4%) into an ISAT mechanism. Overall, ISAT mechanism compared with embolism was significantly associated with poor outcomes (P = 0.002), along with the NIHSS scores, reperfusion status, and collateral status. In the embolism group, reperfusion (P = 0.001), NIHSS scores (P < 0.001), and onset-to-treatment time (P = 0.030) were significant outcome factors. However, in the ISAT group, baseline collateral status (P = 0.001) and NIHSS scores (P < 0.001) were significant outcome factors. A clot sign at the distal BA segment on pre-angiography MRI was strongly associated with embolism mechanism (P < 0.001). Interpretation Stroke mechanism has a major influence on outcomes, and outcome predictors differ according to the underlying mechanism in acute BA occlusion with EVT. Clot sign profile on pre-angiography MRI might be useful to determine the underlying mechanism.


title: Delayed prophylaxis with unfractionated heparin increases the risk of venous thromboembolic events in patients with moderate to severe traumatic brain injury: a retrospective analysis.

text: BACKGROUND Venous thromboembolism (VTE) is a recognized complication in patients with traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Currently, no standard exists for optimal timing or a pharmacological agent for VTE prophylaxis (pharmacological thromboprophylaxis - PTP) in patients with TBI. PTP is often delayed out of fear of causing extension of intracranial hemorrhage (ICH). The purpose of this study was to report the frequency of VTE and ICH progression after initiation of PTP with a continuous infusion of unfractionated heparin in patients with moderate to severe TBI, and to identify risk factors associated with development of VTE. METHODS In this single-center retrospective study, patients with moderate to severe TBI admitted to the ICU of a Swiss Level I Trauma Center over a three-year period were analyzed. RESULTS In 23 (13%) of the 177 patients included in the study a VTE episode occurred during the hospital stay. ICH progression after initiation of PTP occurred in 7 (4%) patients. In a multivariable logistic regression model, only the timing of initiation of PTP was identified as an independent predictor of VTE. CONCLUSIONS In this study population, the risk of developing VTE increased with the delay of initiation of a pharmacological VTE prophylaxis, while ICH progression after initiation of PTP was a rare event.


title: Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial.

text: BACKGROUND Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. METHODS For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. FINDINGS Between March 3, 2008, and March 31, 2014, we randomly assigned 1108 patients to receive a sliding hip screw (n=557) or cancellous screws (n=551). Reoperations within 24 months did not differ by type of surgical fixation in those included in the primary analysis: 107 (20%) of 542 patients in the sliding hip screw group versus 117 (22%) of 537 patients in the cancellous screws group (hazard ratio [HR] 0·83, 95% CI 0·63-1·09; p=0·18). Avascular necrosis was more common in the sliding hip screw group than in the cancellous screws group (50 patients [9%] vs 28 patients [5%]; HR 1·91, 1·06-3·44; p=0·0319). However, no significant difference was found between the number of medically related adverse events between groups (p=0·82; appendix); these events included pulmonary embolism (two patients [<1%] vs four [1%] patients; p=0·41) and sepsis (seven [1%] vs six [1%]; p=0·79). INTERPRETATION In terms of reoperation rates the sliding hip screw shows no advantage, but some groups of patients (smokers and those with displaced or base of neck fractures) might do better with a sliding hip screw than with cancellous screws. FUNDING National Institutes of Health, Canadian Institutes of Health Research, Stichting NutsOhra, Netherlands Organisation for Health Research and Development, Physicians' Services Incorporated.


title: Middle East Respiratory Syndrome Coronavirus and Severe Acute Respiratory Syndrome Coronavirus.

text: Emerging infectious diseases continue to be of a significant importance worldwide with the potential to cause major outbreaks and global pandemics. In 2002, the world had witnessed the appearance of the severe acute respiratory syndrome coronavirus in China which disappeared abruptly within 6 months. About a decade later, a new and emerging novel coronavirus named the Middle East respiratory syndrome coronavirus (MERS-CoV) was described in a patient from Saudi Arabia. These two coronaviruses shared multiple similarities in the epidemiology, clinical presentations, and posed challenges in its prevention and management. Seven years since its discovery, MERS-CoV continues to be a lethal zoonotic pathogen capable of causing severe pneumonia with high case fatality rates and the ability to cause large health care-associated outbreaks.


title: Comparison of the Diagnostic Yield of EUS Needles for Liver Biopsy: Ex Vivo Study.

text: BACKGROUND AND AIMS EUS-guided liver biopsy is an emerging method of liver tissue acquisition which is safe and had been shown to produce excellent histological yield. There is limited data comparing the diagnostic yield of different FNA needles. We aimed to compare the diagnostic performance of four commercially available 19-gauge FNA needles. METHODS Four FNA needles and one percutaneous needle were used to perform liver biopsies on two human cadaveric livers: Cook Echotip Procore™, Olympus EZ Shot 2™, Boston Scientific Expect Slimline™, Covidien SharkCore™, and an 18-gauge percutaneous needle (TruCore™, Argon Medical Devices). Each needle obtained biopsies by three, six, and nine complete back-and-forth motions of the needle ("throw") with a fanning technique. The combined lengths of specimen fragments and the total number of complete portal tracts (CPT) were measured by a blinded pathologist. One-way analysis of variance (ANOVA) and Bonferroni correction were used for statistical analysis. RESULTS A total of 52 liver biopsies were performed. The Covidien SharkCore needle had significantly greater number of CPT compared to other FNA needles. The number of "throws" did not impact the number of CPT significantly. There was no statistically significant difference in mean total specimen length between each FNA needle type. CONCLUSION The Covidien SharkCore needle produced superior histological specimen by capturing more CPT, possibly due to its unique needle design.


title: Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a WHO priority pathogen for which vaccines are urgently needed. Using an immune-focusing approach, we created self-assembling particles multivalently displaying critical regions of the MERS-CoV spike protein ─fusion peptide, heptad repeat 2, and receptor binding domain (RBD) ─ and tested their immunogenicity and protective capacity in rabbits. Using a "plug-and-display" SpyTag/SpyCatcher system, we coupled RBD to lumazine synthase (LS) particles producing multimeric RBD-presenting particles (RBD-LS). RBD-LS vaccination induced antibody responses of high magnitude and quality (avidity, MERS-CoV neutralizing capacity, and mucosal immunity) with cross-clade neutralization. The antibody responses were associated with blocking viral replication and upper and lower respiratory tract protection against MERS-CoV infection in rabbits. This arrayed multivalent presentation of the viral RBD using the antigen-SpyTag/LS-SpyCatcher is a promising MERS-CoV vaccine candidate and this platform may be applied for the rapid development of vaccines against other emerging viruses such as SARS-CoV-2.


docid: wlhdkpbk

title: Achilles tendon vibration-induced changes in plantar flexor corticospinal excitability.

text: Daily Achilles tendon vibration has been shown to increase muscle force, likely via corticospinal neural adaptations. The aim of the present study was to determine the extent by which corticospinal excitability is influenced during direct Achilles tendon vibration. Motor-evoked potentials (MEPs) were elicited in the soleus (SOL), gastrocnemius medialis (GM) and tibialis anterior (TA) by transcranial magnetic stimulation of the motor cortical area of the leg with and without Achilles tendon vibration at various frequencies (50, 80 and 110 Hz). Contralateral homologues were also investigated. SOL and GM MEP amplitude significantly increased by 226 ± 188 and 66 ± 39%, respectively, during Achilles tendon vibration, without any difference between the tested frequencies. No MEP changes were reported for TA or contralateral homologues. Increased SOL and GM MEP amplitude suggests increased vibration-induced corticospinal excitability independent of vibration frequency.


title: COVID-19 crisis in Jordan: Response, scenarios, strategies, and recommendations.

text: UNSTRUCTURED As of 12th April 2020, a total of 389 cases of COVID-19 were confirmed in Jordan. To control this imminent threat, Jordan has enforced public health infection prevention and control measures, called for social distancing, seized all forms of inbound and outbound movement/ international travel, and enacted the Defence Law that transferred the authority to Minister of Defence to work and formulate orders according to the situation. In an effort to support the government in anticipating the requirements of the health system in the upcoming period, an in-depth reflection and examination of different scenarios of the disease spread were developed. This viewpoint suggested different strategies and measures for case detection and contact tracing, clinical management of cases, public health system functioning, and civil society organizations contribution. It is necessary to accelerate containment of the disease to protect the economy and to maintain the continuity of some activities to mitigate the subsequent social, economic and financial impacts. This requires finding a coping mechanism for a period that may be prolonged until laboratories develop a vaccine. In specific, it is strongly recommended to promote community health awareness towards public health prevention and control measures, increase the efficiency and comprehensiveness of the epidemiological investigation/ active and passive surveillance, and employ technology and digital health solutions to track cases and contacts. It is also recommended to increase and expand resources of intensive care units including respirators, increase the capacity and the number of trained health staff in the area of public health and epidemiology, ensure continued provision of essential public health programs and mobilize the resources of non-governmental sector and donors to provide services for refugees and vulnerable populations.


title: Round Ligament Technique and Use of a Vessel-sealing Device to Facilitate Complete Salpingectomy at the Time of Vaginal Hysterectomy.

text: Prophylactic salpingectomy at the time of hysterectomy has been recommended for women at average risk for ovarian cancer. Vaginal hysterectomy is considered the preferred approach to a benign hysterectomy, and adnexectomy should not be considered a contraindication to this approach. This paper with accompanying video describes and demonstrates the round ligament technique and use of a vessel-sealing device to facilitate removal of the entire fallopian tube at the time of vaginal hysterectomy.


Covid-19: Doctors are told not to perform CPR on patients in cardiac arrest.


title: The problem of medical-psychiatric illness in the homeless and its occurrence in the midst of a viral pandemic: A commentary.

text: This article has the purpose of examining the problem of getting help for the medical-psychiatric-substance use group of "homeless" people on the streets of our cities, who refuse treatment. The problem has gradually worsened since closure of state hospitals and subsequent lack of community resources. It has been stalemated, in part, by advocates, who argue for personal autonomy and freedom rather than involuntary diagnosis and treatment over the life of these people. It has reached a crisis situation secondary to such potential patients being imprisoned and/or sick with COVID-19 being potential health and legal threats. We review A) the nature of the problem, B) the current social-legal availability of treatment and long-term management (or lack of one) in the context of societal rejection of these potential patients, and C) suggest what might be done, locally and nationally. Mandating scientifically-based medical orders to citizens regardless of personal freedom - are now being implemented to manage the COVID-19 pandemic. We argue for creating a similar med-psych short- and long-term system as a new approach to help this group. They are now mostly being ignored "to die on the streets."


title: Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging.

text: Low-cost and high-resolution on-chip microscopes are vital for reducing cost and improving efficiency for modern biomedicine and bioscience. Despite the needs, the conventional microscope design has proven difficult to miniaturize. Here, we report the implementation and application of two high-resolution (approximately 0.9 microm for the first and approximately 0.8 microm for the second), lensless, and fully on-chip microscopes based on the optofluidic microscopy (OFM) method. These systems abandon the conventional microscope design, which requires expensive lenses and large space to magnify images, and instead utilizes microfluidic flow to deliver specimens across array(s) of micrometer-size apertures defined on a metal-coated CMOS sensor to generate direct projection images. The first system utilizes a gravity-driven microfluidic flow for sample scanning and is suited for imaging elongate objects, such as Caenorhabditis elegans; and the second system employs an electrokinetic drive for flow control and is suited for imaging cells and other spherical/ellipsoidal objects. As a demonstration of the OFM for bioscience research, we show that the prototypes can be used to perform automated phenotype characterization of different Caenorhabditis elegans mutant strains, and to image spores and single cellular entities. The optofluidic microscope design, readily fabricable with existing semiconductor and microfluidic technologies, offers low-cost and highly compact imaging solutions. More functionalities, such as on-chip phase and fluorescence imaging, can also be readily adapted into OFM systems. We anticipate that the OFM can significantly address a range of biomedical and bioscience needs, and engender new microscope applications.


title: Transgenic T-cell receptor immunotherapy for cancer: building on clinical success.

text: With the advent of immunotherapy as a realistic and promising option for cancer treatment, adoptive cellular therapies are gaining significant interest in the clinic. Whilst the recent successes of chimeric antigen receptor T-cell therapies for haematological malignancies are widely known, they have yet to show great success in solid cancers. However, immune cells transduced with T-cell receptors have been shown to traffic to and exert anti-cancer effects on solid tumour cells with some great successes. In this review, we explore the field of transgenic T-cell receptor immunotherapy, highlighting some of the key clinical trials which have paved the way for this type of cellular immunotherapy. Some trials have shown amazing clinical results, including long-term remissions and minimal toxicity, and can be looked at as an exemplar for this adoptive cell therapy. There have also been key trials where unexpected, fatal, off-tumour toxicity has occurred, and these trials have also been instrumental in shaping safer clinical trials, particularly regarding preclinical testing. In addition to previous trials, we analysed the current clinical trial space for T-cell receptor T-cell therapy, showing which trials are dominating in the clinic and which targets are being prioritised by researchers around the world. By looking at both past and current trials, we have been able to identify key drivers in developing transgenic T-cell receptor immunotherapy for the future.


Research in Extracorporeal Life Support: A Call to Action.


title: Hantaan virus nucleocapsid protein binds to importin alpha proteins and inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappa B.

text: Hantaviruses such as Hantaan virus (HTNV) and Andes virus cause two human diseases, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, respectively. For both, disease pathogenesis is thought to be immunologically mediated and there have been numerous reports of patients with elevated levels of proinflammatory and inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), in their sera. Multiple viruses have developed evasion strategies to circumvent the host cell inflammatory process, with one of the most prevalent being the disruption of nuclear factor kappa B (NF-kappaB) activation. We hypothesized that hantaviruses might also moderate host inflammation by interfering with this pathway. We report here that the nucleocapsid (N) protein of HTNV was able to inhibit TNF-alpha-induced activation of NF-kappaB, as measured by a reporter assay, and the activation of endogenous p65, an NF-kappaB subunit. Surprisingly, there was no defect in the degradation of the inhibitor of NF-kappaB (IkappaB) protein, nor was there any alteration in the level of p65 expression in HTNV N-expressing cells. However, immunofluorescence antibody staining demonstrated that cells expressing HTNV N protein and a green fluorescent protein-p65 fusion had limited p65 nuclear translocation. Furthermore, we were able to detect an interaction between HTNV N protein and importin alpha, a nuclear import molecule responsible for shuttling NF-kappaB to the nucleus. Collectively, our data suggest that HTNV N protein can sequester NF-kappaB in the cytoplasm, thus inhibiting NF-kappaB activity. These findings, which were obtained using cells transfected with cDNA representing the HTNV N gene, were confirmed using HTNV-infected cells.


Is the conclusion available? Letter to the Editor concerning the study of Prof. Jin titled "Clinical features and outcomes of pregnant women suspected of coronavirus disease 2019".


title: What Is the Impact of High-Resolution Manometry in the Functional Diagnostic Workup of Gastroesophageal Reflux Disease?

text: International guidelines agree that high-resolution esophageal manometry (HRM) is an integral part of the diagnostic evaluation of patients with refractory reflux symptoms and should be performed before antireflux surgery. Its most important goal is to explore differential diagnoses, in particular major esophageal motility disturbances, that may be responsible for symptoms. HRM additionally provides insights into all relevant pathomechanisms of gastroesophageal reflux disease (GERD): It can reveal important information on the morphology and function of the esophagogastric junction (EGJ), the presence of a hiatus hernia, transient lower esophageal sphincter relaxations, and dysmotility of the esophageal body. To obtain this information, a 3-step hierarchical system has been proposed for the algorithmic characterization of esophageal motor function. The first step is to investigate the morphology and contractility of the EGJ, the second to monitor esophageal body motor patterns in response to water swallows, and the third to determine the contraction reserve in patients with abnormal esophageal motor function using provocation tests. Observations made with HRM can not only explain the cause of symptoms in GERD patients but may also have the potential to direct specific treatment.


The COVID-19 pandemonium continues: (Withdrawal of published clinical studies in Lancet and N Engl J Med, 2020).


docid: srjuefoj

title: Antidepressant effects on emotional temperament: toward a biobehavioral research paradigm for major depressive disorder.

text: BACKGROUND Given the limited efficacy of current pharmacotherapy for major depressive disorder (MDD) and the historical decline in antidepressant development, there is increasing clinical urgency to develop more effective treatments. OBJECTIVES To synthesize findings from clinical psychology and affective neuroscience related to the construct of emotional temperament; to examine the effects of antidepressants on the temperament dimensions of positive (PA) and negative affectivity (NA); and to propose a biobehavioral research paradigm for the treatment of MDD. METHODS We begin with an introduction to PA and NA, which emphasizes their construct development, historical context, and relevance to psychopathology. We then review studies of antidepressant effects on PA and NA, and explore two related hypotheses: (1) Cause-correction: The antidepressant response may fundamentally occur through changes in emotional temperament, with subsequent spread to syndrome or symptom changes; (2) preferential effects: Antidepressants with different mechanisms of action may have preferential effects on PA or NA. RESULTS Preliminary findings appear to support the cause-correction hypothesis; there is insufficient clinical evidence to support the preferential effects hypothesis. CONCLUSIONS PA and NA are biologically based temperament dimensions, which modulate emotional, motivational, and behavioral responses to positive and negative incentives. They can be altered by antidepressants, and may independently contribute to depression improvement. In addition, the distinct biobehavioral features of PA and NA suggest that combined pharmacological and cognitive-behavioral treatments targeting these dimensions may have specific, and perhaps, synergistic antidepressant effects.


title: Ventilation control for airborne transmission of human exhaled bio-aerosols in buildings.

text: The emergence of respiratory diseases, i.e., severe acute respiratory syndrome (SARS) epidemic in 2003, H1N1 influenza epidemic in 2011 and Middle East respiratory syndrome (MERS) outbreak, reiterated the significance of ventilation in buildings. The role of ventilation in removing exhaled airborne bio-aerosols and preventing cross infections has been multidisciplinary extensively studied after the SARS outbreak in 2003. The characteristics of droplet-borne, short-range airborne and long-range airborne transmission of infectious diseases were identified. Increasing ventilation rate can effectively reduce the risk of long-range airborne transmission, while it may be of little useful in preventing the droplet-borne transmission. To maintain the airflow direction from clean cubicles to dirty cubicles is an effective way to prevent the cross infection between cubicles, which is widely used in hospital isolation rooms. Field measurements showed that wrong air flow direction was due to poor construction quality or maintenance. The impacts of different airflow patterns on removing large droplets and fine droplet nuclei were discussed. Some new concepts in general ventilation systems and local personalized equipment were also introduced. This review updates current knowledge of the airborne transmission of pathogens and the improvement of ventilation efficiency concerning the infection prevention.


title: Mechanical ventilation.

text: Over the past several years, there has been an introduction of numerous modes of mechanical ventilation, each with their own advantages and limitations. This article reviews the common modes of mechanical ventilation, new technologies, and specific ventilator strategies that have been shown to be beneficial. In addition, it reviews the steps that should be taken when troubleshooting a ventilator.


title: Nasal secretion concentrations of IL-5, IL-6, and IL-10 in children with and without upper respiratory tract viruses.

text: OBJECTIVE To determine if levels of interleukin (IL) 5, IL-6, and IL-10 or their ratios in nasal secretion are diagnostic of viral upper respiratory tract infections (vURTIs) and coldlike illnesses (CLIs) in children. DESIGN Longitudinal study of children for vURTIs, CLIs, and concentrations and ratios of nasal cytokines. SETTING Outpatient assessments of children. PARTICIPANTS A total of 224 children, aged 1 to 9 years. MAIN OUTCOME MEASURES Concentrations of IL-5, IL-6, and IL-10 in nasal secretions, vURTIs diagnosed by polymerase chain reaction (PCR) detection of upper respiratory tract viruses, and concurrent CLIs diagnosed by parents. RESULTS Of 1269 secretion samples, 552 (43.5%) were collected during a vURTI (PCR findings positive for an assayed virus [PCR(+)]). A concurrent CLI was diagnosed for 34% of the PCR(+) samples and for 18% of the samples found to be negative by PCR analysis (PCR(-)). Cytokine concentrations and ratios were highly variable and skewed to the lower values. The significance of the cytokine concentrations and ratios as discriminators of groups defined by the presence or absence of virus and of subgroups defined by the presence or absence of a CLI was evaluated using receiver operating characteristic curves. All measures were significant discriminators of the PCR(+) vs PCR(-) groups, and most were significant discriminators of the paired CLI subgroups. The concentration of IL-6 and the IL-5/IL-6 ratio were the best discriminators across all groups and subgroups. However, the sensitivities and specificities of those discriminators at the best cutoff values were on the order of 0.7 for the most extreme pairwise comparison (PCR(+)CLI(+) vs PCR(-)CLI(-)) and lower for the other comparison groups. CONCLUSION The low sensitivities and specificities for cytokine-based assignment of specimens to the paired groups and subgroups limit their usefulness for diagnosis of infection or illness.


title: Architectures and Mechanical Properties of Drugs and Complexes of Surface-Active Compounds at Air-Water and Oil-Water Interfaces.

text: BACKGROUND Drugs can represent a multitude of compounds from proteins and peptides, such as growth hormones and insulin and on to simple organic molecules such as flurbiprofen, ibuprofen and lidocaine. Given the chemical nature of these compounds two features are always present. A portion or portions of the molecule that has little affinity for apolar surfaces and media and on the contrary a series of part or one large part that has considerable affinity for hydrophilic, polar or charged media and surfaces. A series of techniques are routinely used to probe the molecular interactions that can arise between components, such as the drug, a range of surface- active excipients and flavor compounds, for example terpenoids and the solvent or dispersion medium. RESULTS Fifty-eight papers were included in the review, a large number (16) being of theoretical nature and an equally large number (14) directly pertaining to medicine and pharmacy; alongside experimental data and phenomenological modelling. The review therefore simultaneously represents an amalgam of review article and research paper with routinely used or established (10) and well-reported methodologies (also included in the citations within the review). Experimental data included from various sources as diverse as foam micro-conductivity, interferometric measurements of surface adsorbates and laser fluorescence spectroscopy (FRAP) are used to indicate the complexity and utility of foams and surface soft matter structures for a range of purposes but specifically, here for encapsulation and incorporation of therapeutics actives (pharmaceutical molecules, vaccines and excipients used in medicaments). Techniques such as interfacial tensiometry, interfacial rheology (viscosity, elasticity and visco-elasticity) and nanoparticle particle size (hydrodynamic diameter) and charge measurements (zeta potential), in addition to atomic force and scanning electron microscopy have proven to be very useful in understanding how such elemental components combine, link or replace one another (competitive displacement). They have also proven to be both beneficial and worthwhile in the sense of quantifying the unseen actions and interplay of adsorbed molecules and the macroscopic effects, such as froth formation, creaming or sedimentation that can occur as a result of these interactions. CONCLUSION The disclosures and evaluations presented in this review confirm the importance of a theoretical understanding of a complex model of the molecular interactions, network and present a framework for the understanding of really very complex physical forms. Future therapeutic developers rely on an understanding of such complexity to garner a route to a more successful administration and formulation of a new generation of therapeutic delivery systems for use in medicine.


title: Deep sequencing: becoming a critical tool in clinical virology.

text: Population (Sanger) sequencing has been the standard method in basic and clinical DNA sequencing for almost 40 years; however, next-generation (deep) sequencing methodologies are now revolutionizing the field of genomics, and clinical virology is no exception. Deep sequencing is highly efficient, producing an enormous amount of information at low cost in a relatively short period of time. High-throughput sequencing techniques have enabled significant contributions to multiples areas in virology, including virus discovery and metagenomics (viromes), molecular epidemiology, pathogenesis, and studies of how viruses to escape the host immune system and antiviral pressures. In addition, new and more affordable deep sequencing-based assays are now being implemented in clinical laboratories. Here, we review the use of the current deep sequencing platforms in virology, focusing on three of the most studied viruses: human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus.


docid: othldzfh

title: AlloDerm with split-thickness skin graft for coverage of the forearm free flap donor site.

text: OBJECTIVE Major causes of donor site morbidity after free flap harvest are lack of split-thickness skin graft (STSG) take and tendon exposure. Long-term cosmesis remains poor. AlloDerm has shown cosmetically better donor site healing, albeit prolonged healing. We sought to evaluate the use of STSG with AlloDerm compared with STSG alone. STUDY DESIGN Case series with chart review. SETTING Academic tertiary care medical center. METHODS AND SUBJECTS Institutional review board-approved study. Microvascular database queried from 2002 to 2012. Subjects with forearm free flaps and either AlloDerm + STSG or STSG alone for donor site reconstruction were included. Morbidity outcomes were compared. RESULTS Eighty patients (50 male, 30 female) received AlloDerm + STSG at the donor site. Major and minor donor site complications were 15.0% and 18.8% in the AlloDerm + STSG group compared with 10.2% and 16.9% in the STSG-only group (P = .30 and P = .72), respectively. Complete STSG loss (5.0% vs 3.0%, P = .48), tendon exposure (5.0% vs 5.4%, P = 1.0), functional impairment (2.5% vs 1.8%, P = .66), infection (8.8% vs 9.6%, P = 1.0), hematoma/seroma (5.0% vs 3.6%, P = .73), and paresthesia (1.3% vs 3.6%, P = .43) were not significant. No patients required a second STSG after loss in the AlloDerm + STSG group compared with 60% (P = .17). Cosmetic results were superior in the AlloDerm + STSG group as rated by the surgeon (3.5 vs 2.6, P = .03) and patients (3.7 vs 2.9, P = .05) on a scale of 1 to 5. CONCLUSION Our results suggest that the use of AlloDerm with STSG can provide thicker coverage of the forearm defect, with minimal donor site morbidity and superior cosmetic results compared with STSG alone.


title: Intraprocedural Thrombus Fragmentation During Interventional Stroke Treatment: A Comparison of Direct Thrombus Aspiration and Stent Retriever Thrombectomy.

text: PURPOSE The aim of this study was to compare the rates of intraprocedural thrombus fragmentation between the exclusive thrombus aspiration technique (ADAPT) and the use of stent retrievers. MATERIALS AND METHODS Cases with successful recanalization of the primary occlusion site (POS) with either of the techniques were analyzed (n = 36 ADAPT, n = 61 stent retriever). The primary endpoint was the evaluation of intraprocedural thrombus fragmentation before applying additional maneuvers to enhance reperfusion success. Grading was performed using the modified thrombolysis in cerebral infarction (mTICI) perfusion scale grade with the implementation of an additional TICI 2c grade. Secondary endpoints were procedural complications and clinical data. RESULTS After opening of the POS, 83.3% successful reperfusions were reached using the ADAPT technique and 88.5% using stent retrievers (p = 0.47). Subarachnoid hemorrhages (SAH) appeared only when using stent retrievers (16.4 vs. 0%, p = 0.010). The number of maneuvers was significantly higher (median 2 vs. 1, p = 0.006), and procedural time was longer in the stent retriever group (median 30 vs. 13 min, p < 0.0001). There was no significant difference between both techniques with regard to the occurrence of embolizations to new territories (2.8 vs. 8.2%, p = 0.28). CONCLUSION When retrieving of the primary thrombus is possible, ADAPT results in comparable reperfusion grades as do stent retrievers. This suggests that comparable distraction forces act on the thrombus and that both techniques possess a comparable risk of periprocedural thrombus fragmentation. SAH exclusively occurred after using stent retrievers, which may further promote ADAPT as safe and fast initial front-line approach.


title: Two-stage goal-directed therapy protocol for non-donor open hepatectomy: an interventional before-after study.

text: PURPOSE Hemodynamic management during low central venous pressure (L-CVP)-assisted hepatectomy involves fluid restriction during resection and fluid resuscitation after resection. Recently, high stroke volume variation (SVV) has been reported as an alternative to L-CVP for reducing blood loss during a hepatectomy. The current study evaluated the impact of a newly implemented SVV-based goal-directed therapy (GDT) protocol on blood loss during hepatectomy. METHODS We conducted a before-after comparative study, which included L-CVP-assisted hepatectomy cases (control group) and GDT-assisted hepatectomy cases (intervention group). The GDT protocol included SVV, cardiac index, and mean arterial pressure as hemodynamic parameters. The target SVV ranges were ≥ 13% and ≤ 12% before and after the resection, respectively. The primary endpoint was the proportion of patients whose blood loss was < 400 mL (median of our hepatectomy cases) in the GDT group, and it was compared to a predefined threshold of 50%. We also investigated factors associated with blood loss using multiple regression analysis. RESULTS We included 66 patients in the control group and 50 in the GDT group. In the GDT group, the median blood loss was 220 mL and 36 patients (72%) lost < 400 mL blood. This was significantly greater than 50% (P < 0.001). Post-resection GDT-guided fluid optimization reduced positive intraoperative fluid balance compared to that achieved by the conventional fluid therapy used in the control. Multiple regression analysis showed that GDT application, epidural anesthesia, operative time, and hydroxyethyl-starch infusion volume were associated with blood loss. CONCLUSION Compared to conventional management, SVV-guided GDT may reduce blood loss during hepatectomies.


title: Effects of dietary vitamin A content on antibody responses of feedlot calves inoculated intramuscularly with an inactivated bovine coronavirus vaccine.

text: OBJECTIVE To investigate effects of low dietary vitamin A content on antibody responses in feedlot calves inoculated with an inactivated bovine coronavirus (BCoV) vaccine. ANIMALS 40 feedlot calves. PROCEDURES Calves were fed diets containing high (3,300 U/kg) or low (1,100 U/kg) amounts of vitamin A beginning on the day of arrival at a feedlot (day 0) and continuing daily until the end of the study (day 140). Serum retinol concentrations were evaluated in blood samples obtained throughout the study. Calves were inoculated IM with an inactivated BCoV vaccine on days 112 and 126. Blood samples obtained on days 112 and 140 were used for assessment of BCoV-specific serum IgG1, IgG2, IgM, and IgA titers via an ELISA. RESULTS The low vitamin A diet reduced serum retinol concentrations between days 112 and 140. After the BCoV inoculation and booster injections, predominantly serum IgG1 antibodies were induced in calves fed the high vitamin A diet; however, IgG1 titers were compromised at day 140 in calves fed the low vitamin A diet. Other isotype antibodies specific for BCoV were not affected by the low vitamin A diet. CONCLUSIONS AND CLINICAL RELEVANCE Dietary vitamin A restriction increases marbling in feedlot cattle; however, its effect on antibody responses to vaccines is unknown. A low vitamin A diet compromised the serum IgG1 responses against inactivated BCoV vaccine, which suggested suppressed T-helper 2-associated antibody (IgG1) responses. Thus, low vitamin A diets may compromise the effectiveness of viral vaccines and render calves more susceptible to infectious disease.


title: Computed Tomographic Perfusion Selection and Clinical Outcomes After Endovascular Therapy in Large Vessel Occlusion Stroke.

text: BACKGROUND AND PURPOSE Different imaging paradigms have been used to select patients for endovascular therapy in stroke. We sought to determine whether computed tomographic perfusion (CTP) selection improves endovascular therapy outcomes compared with noncontrast computed tomography alone. METHODS Review of a prospectively collected registry of anterior circulation stroke patients undergoing stent-retriever thrombectomy at a tertiary care center between September 2010 and March 2016. Patients undergoing CTP were compared with those with noncontrast computed tomography alone. The primary outcome was the shift in the 90-day modified Rankin scale (mRS). RESULTS A total of 602 patients were included. CTP-selected patients (n=365, 61%) were younger (P=0.02) and had fewer comorbidities. CTP selection (n=365, 61%) was associated with a favorable 90-day mRS shift (adjusted odds ratio [aOR]=1.49; 95% confidence interval [CI], 1.06-2.09; P=0.02), higher rates of good outcomes (90-day mRS score 0-2: 52.9% versus 40.4%; P=0.005), modified Thrombolysis in Cerebral Infarction-3 reperfusion (54.8% versus 40.1%; P<0.001), smaller final infarct volumes (24.7 mL [9.8-63.1 mL] versus 34.6 mL [13.1-88 mL]; P=0.017), and lower mortality (16.6% versus 26.8%; P=0.005). When matched on age, National Institutes of Health Stroke Scale (NIHSS) score, and glucose (n=424), CTP remained associated with a favorable 90-day mRS shift (P=0.016), lower mortality (P=0.02), and higher rates of reperfusion (P<0.001). CTP better predicted functional outcomes in patients presenting after 6 hours (as assessed by comparison of logistic regression models: Akaike information criterion: 199.35 versus 287.49 and Bayesian information criterion: 196.71 versus 283.27) and those with an Alberta Stroke Program Early Computed Tomography Score ≤7 (Akaike information criterion: 216.69 versus 334.96 and Bayesian information criterion: 213.6 versus 329.94). CONCLUSIONS CTP selection is associated with a favorable mRS shift in patients undergoing stent-retriever thrombectomy. Future prospective studies are warranted.


Emergence of novel influenza a H1N1 virus as a pandemic agent.


David Oliver: Covid-19-recriminations and political point scoring must wait.


docid: jdpwahhp

title: Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery.

text: Background Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design Nonprespecified subgroup analysis of a multicenter factorial trial. Computerized Internet randomization was done between 2010 and 2013. Patients, clinicians, data collectors, and outcome adjudicators were blinded to treatment assignment. (ClinicalTrials.gov: NCT01082874). Setting 135 centers in 23 countries. Patients Adults aged 45 years or older who had or were at risk for atherosclerotic disease and were having noncardiac surgery. Exclusions were placement of a bare-metal stent within 6 weeks, placement of a drug-eluting stent within 1 year, or receipt of nonstudy aspirin within 72 hours before surgery. Intervention Aspirin therapy (overall trial, n = 4998; subgroup, n = 234) or placebo (overall trial, n = 5012; subgroup, n = 236) initiated within 4 hours before surgery and continued throughout the perioperative period. Of the 470 subgroup patients, 99.9% completed follow-up. Measurements The 30-day primary outcome was death or nonfatal myocardial infarction; bleeding was a secondary outcome. Results In patients with prior PCI, aspirin reduced the risk for the primary outcome (absolute risk reduction, 5.5% [95% CI, 0.4% to 10.5%]; hazard ratio [HR], 0.50 [CI, 0.26 to 0.95]; P for interaction = 0.036) and for myocardial infarction (absolute risk reduction, 5.9% [CI, 1.0% to 10.8%]; HR, 0.44 [CI, 0.22 to 0.87]; P for interaction = 0.021). The effect on the composite of major and life-threatening bleeding in patients with prior PCI was uncertain (absolute risk increase, 1.3% [CI, -2.6% to 5.2%]). In the overall population, aspirin increased the risk for major bleeding (absolute risk increase, 0.8% [CI, 0.1% to 1.6%]; HR, 1.22 [CI, 1.01 to 1.48]; P for interaction = 0.50). Limitation Nonprespecified subgroup analysis with small sample. Conclusion Perioperative aspirin may be more likely to benefit rather than harm patients with prior PCI. Primary Funding Source Canadian Institutes of Health Research.


title: Immune system cells in healthy ferrets: an immunohistochemical study.

text: The ferret has emerged as an excellent animal model to characterize several physiologic and pathologic conditions. The distribution and characterization of different types of immune system cells were studied in healthy ferret tissues. Eight primary antibodies were tested for immunohistochemistry in formalin-fixed tissues: anti-CD3, anti-CD79α, anti-CD20, anti-HLA-DR, anti-lysozyme, anti-CD163, anti-SWC3, and anti-Mac387. The anti-CD3 antibody labeled T cells mainly in interfollicular and paracortical areas of lymph nodes, cortex and thymic medulla, and periarteriolar lymphoid sheaths in the spleen. The anti-CD79α and anti-CD20 antibodies immunolabeled B cells located in lymphoid follicles at lymph nodes, spleen, and Peyer patches. The CD79α and CD20 antibodies also labeled cells with nonlymphoid morphology in atypical B-cell locations. The anti-HLA-DR antibody labeled macrophages, some populations of B and T lymphocytes, and different populations of dendritic cells in lymph nodes, Peyer patches, spleen, and thymus. The anti-lysozyme antibody immunolabeled macrophages in the liver, lymph nodes, spleen, and thymus. The Mac-387, CD163, and SWC3 antibodies did not show any positive reaction in formalin-fixed or frozen tissues. To elucidate the origin of the uncommon CD79α/CD20 positive cells, a double immunohistochemistry was carried out using the anti-HLA-DR + the anti-CD79α, the anti-HLA-DR + the anti-CD20, and the anti-lysozyme + the anti-CD79α antibodies. Double labeling was mainly observed when the anti-HLA-DR + the anti-CD79α antibodies were combined. The immunohistologic characterization and distribution of these immune system cells in healthy ferret tissues should be of value in future comparative studies of diseases in ferrets.


title: Off-label use of atypical antipsychotics: cause for concern?

text: Licensed indications for medicines were designed to regulate the claims that can be made about a medicine by a pharmaceutical company. Off-label prescribing (i.e. prescribing a drug for an indication outside of that for which it is licensed) is legal and an integral part of medical practice. In psychiatry, off-label prescribing is common and gives clinicians scope to treat patients who are refractory to standard therapy or where there is no licensed medication for an indication. However, efficacy or safety of such off-label use may not be established. There is a growing list of licensed indications for atypical antipsychotics (AAP) beyond schizophrenia and bipolar affective disorder, and also more evidence for other indications where pharmaceutical companies have not obtained a license. Pharmaceutical companies have promoted AAPs for off-label indications to increase sales and consequently have been fined by the US FDA for this. Since the 1990s, AAP use has expanded considerably, for example, the off-label use of quetiapine alone accounted for an estimated 17% of the AAP spend in New Zealand in 2010. There are a number of potential problems with the expanded use of AAPs outside of schizophrenia and related psychoses. A larger population will be exposed to their adverse effects, which include weight gain, type 2 diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. There are also concerns with the abuse of these agents, in particular quetiapine. Given that an increasing percentage of the population is being treated with these agents, off-label prescribing of AAPs is a cause for concern; they have a propensity to cause significant side effects and their efficacy and long-term safety for most off-label indications remains largely unknown, and therefore the risks and benefits of their use should be carefully weighed up prior to prescribing these agents off-label.


title: The different tests for the diagnosis of COVID-19 - A review in Brazil so far.

text: SARS-CoV-2 is a novel virus from the coronavirus family that emerged in the end of December 2019 in Wuhan, China. The virus is now widespread and causing the current pandemic of COVID-19, a highly pathogenic viral pneumonia, commonly presented with fever and cough, which frequently lead to lower respiratory tract disease with poor clinical outcomes associated with older age and underlying health conditions. Supportive care for patients is typically the standard protocol because no specific effective antiviral therapies have been identified so far. The current outbreak is challenging governments and health authorities all over the world. In here we present a comparison among the current diagnostic tools and kits being used to test Brazilian population.


title: Safety and Efficacy of New-Generation Drug-Eluting Stents in Women Undergoing Complex Percutaneous Coronary Artery Revascularization: From the WIN-DES Collaborative Patient-Level Pooled Analysis.

text: OBJECTIVES The purpose of this study was to investigate the safety and efficacy of new-generation drug-eluting stents (DES) versus early-generation DES in women undergoing complex percutaneous coronary intervention (CPCI). BACKGROUND Whether the benefits of new-generation DES are preserved in women undergoing complex percutaneous revascularization is unknown. METHODS We pooled patient-level data from women enrolled in 26 randomized trials of DES. Study population was categorized according to the presence or absence of CPCI, which was defined as the composite of total stent length >30 mm, ≥2 stents implanted, ≥2 lesions treated, or bifurcation lesion as target vessel. The primary endpoint was major adverse cardiovascular events (MACE) defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. RESULTS Of 10,241 women included in the pooled database, 4,629 (45%) underwent CPCI. Compared with non-CPCI, women who underwent CPCI had a higher 3-year risk of MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.45 to 1.83; p < 0.0001). In women who underwent CPCI, use of new-generation DES was associated with significantly lower 3-year risk of MACE (adjusted HR: 0.81; 95% CI: 0.68 to 0.96), target lesion revascularization (adjusted HR: 0.74; 95% CI: 0.57 to 0.95), and definite or probable stent thrombosis (ST) (adjusted HR: 0.50; 95% CI: 0.30 to 0.83). The benefit of new-generation DES on efficacy and safety outcomes was uniform between CPCI and non-CPCI groups, without evidence of interaction. By landmark analysis, new-generation DES were associated with low rates (≤0.4%) of very-late ST irrespective of procedural complexity. CONCLUSIONS Women undergoing CPCI remain at higher risk of adverse events. The long-term ischemic benefits of new-generation DES platforms are uniform among complex and non-complex percutaneous revascularization procedures in women.


title: Detection of African swine fever, classical swine fever, and foot-and-mouth disease viruses in swine oral fluids by multiplex reverse transcription real-time polymerase chain reaction.

text: African swine fever (ASF), classical swine fever (CSF), and foot-and-mouth disease (FMD) are highly contagious animal diseases of significant economic importance. Pigs infected with ASF and CSF viruses (ASFV and CSFV) develop clinical signs that may be indistinguishable from other diseases. Likewise, various causes of vesicular disease can mimic clinical signs caused by the FMD virus (FMDV). Early detection is critical to limiting the impact and spread of these disease outbreaks, and the ability to perform herd-level surveillance for all 3 diseases rapidly and cost effectively using a single diagnostic sample and test is highly desirable. This study assessed the feasibility of simultaneous ASFV, CSFV, and FMDV detection by multiplex reverse transcription real-time polymerase chain reaction (mRT-qPCR) in swine oral fluids collected through the use of chewing ropes. Animal groups were experimentally infected independently with each virus, observed for clinical signs, and oral fluids collected and tested throughout the course of infection. All animal groups chewed on the ropes readily before and after onset of clinical signs and before onset of lameness or serious clinical signs. ASFV was detected as early as 3 days postinoculation (dpi), 2-3 days before onset of clinical disease; CSFV was detected at 5 dpi, coincident with onset of clinical disease; and FMDV was detected as early as 1 dpi, 1 day before the onset of clinical disease. Equivalent results were observed in 4 independent studies and demonstrate the feasibility of oral fluids and mRT-qPCR for surveillance of ASF, CSF, and FMD in swine populations.


title: Tocilizumab treatment for Cytokine Release Syndrome in hospitalized COVID-19 patients: survival and clinical outcomes.

text: BACKGROUND Tocilizumab, an interleukin-6 receptor antagonist (IL-6Ra), can treat cytokine release syndrome (CRS) with observed improvements in COVID-19 case series. RESEARCH QUESTION Can tocilizumab benefit hospitalized COVID-19 patients? STUDY DESIGN and Methods: An observational study of consecutive COVID-19 patients hospitalized from 03.10-31.20 and followed through 04.21.20 was conducted by chart review. Patients were treated with tocilizumab using an algorithm that targeted CRS. Survival and mechanical ventilation (MV) outcomes were reported for 14 days and stratified by disease severity designated at admission (severe, ≥3L supplemental oxygen to maintain oxygen saturation >93%). For tocilizumab-treated patients, a pre/post analyses of clinical response, biomarkers and safety outcomes was assessed. Post-hoc survival analyses were conducted for race/ethnicity. RESULTS Among 239 patients, median age was 64 years; 36% and 19% were Black and Hispanic, respectively. Hospital census increased exponentially, yet MV census did not. Severe disease was associated with lower survival (78% vs 93%; p<0.001), greater proportion requiring MV (44% vs 5%; p<0.001) and longer median MV days (5.5 vs 1.0; p=0.003). Tocilizumab-treated patients (N=153, 64%) involved 90% of severe patients; 44% of non-severe patients received it for evolving CRS. Tocilizumab-treated patients with severe disease had higher admission hsCRP levels (120 vs 71mg/L; p<0.001), received tocilizumab sooner (2 vs 3 days; p<0.001), but survival was similar to non-severe patients (83% vs 91%; p=0.11). For tocilizumab-treated patients requiring MV, survival was 75% (95%CI=64%-89%). After tocilizumab, few adverse events occurred, oxygenation and inflammatory biomarkers (e.g., hsCRP, IL-6) improved; however, D-dimer and sIL2R levels increased significantly. Survival in Blacks and Hispanics, after controlling for age, was significantly higher than in whites (log-rank p=0.002). INTERPRETATION A treatment algorithm that included tocilizumab to target CRS may influence mechanical ventilation and survival outcomes. In tocilizumab-treated patients, oxygenation and inflammatory biomarkers improve with higher than expected survival. Randomized trials must confirm these findings.


docid: xkzvzonj

title: [Coronavirus, emerging viruses].

text: Coronavirus is a large family of viruses that infect mammals and birds. Coronaviruses are known to cross barrier species and infect new ones. In the past twenty years, we witnessed the emergence of three different coronaviruses, the latest one being the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for the COVID-19 (covid disease 19) pandemic. Coronaviruses are enveloped virus with a long positive sense RNA genome. Like all viruses, they hijack the cellular machinery to replicate and produce new virions. There is no approved vaccine or specific antiviral molecule against coronaviruses but with the urgency to treat COVID-19, several candidate therapies are currently investigated.


title: Comparison of laparoscopic sleeve gastrectomy leak rates in four staple-line reinforcement options: a systematic review.

text: OBJECTIVE The study compared laparoscopic sleeve gastrectomy (LSG) staple-line leak rates of 4 prevalent surgical options: no reinforcement, oversewing, nonabsorbable bovine pericardial strips (BPS), and absorbable polymer membrane (APM). BACKGROUND LSG is a multipurpose bariatric/metabolic procedure with effectiveness proven through the intermediate term. Staple-line leak is a severe complication of LSG for which no definitive method of prevention has been identified. METHODS The systematic review study design was employed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement screening guidelines. Inclusion criteria centered on variables potentially relevant to LSG leak: leak rate, age, gender, calibrating bougie size, distance between pylorus and gastric transection line, overall complication rate, and mortality. Analysis of variance models were used to explore differences in select demographic and surgical technique variables characterizing each reinforcement group. An omnibus χ(2) test followed by independent Fisher's exact tests were used to compare leak rates. RESULTS There were 659 articles identified; 41 duplicates removed. Of 618 remaining articles, 324 did not meet inclusion criteria. Of the 294 remaining articles, 206 were eliminated (kin studies, those not reporting staple-line or leak incidence, those reporting discontinued products). There were 88 papers included in the analysis. Statistically significant differences were found between groups across demographic and surgical variables studied (p<0.001). There were 191 leaks in 8,920 patients; overall leak rate 2.1%. Leak rates ranged from 1.09% (APM) to 3.3% (BPS); APM leak rate was significantly lower than other groups (p< 0.05). CONCLUSION Systematic review of 88 included studies representing 8,920 patients found that the leak rate in LSG was significantly lower using APM staple-line reinforcement than oversewing, BPS reinforcement, or no reinforcement.


Internal thoracic artery harvesting with a LigaSure device.


History in a Crisis - Lessons for Covid-19.


title: Nursing Informatics and School Nursing: Specialists Wanted.

text: Hospitals and healthcare systems have nursing informaticists who contribute to quality patient care and safety by managing data and facilitating the use of technology. Schools typically do not employ nurses specifically in positions labeled as nursing informaticists, though the role is critical in the schools. This article highlights the subspecialty of nursing informatics within the school nurse role. Three school nurses will share their use of nursing informatics skills to optimize student health.


Delivering immunotherapy with bacteria.


title: Semi-prone video-assisted thoracoscopy for the treatment of large infracarinal traction diverticula.

text: BACKGROUND Large middle-third esophageal diverticula are rare. Thoracotomy has been proposed as mainstay of treatment; however, minimally invasive resection through lateral or prone position thoracoscopy has been described. METHODS The technical aspects of the novel semi-prone minimally invasive thoracoscopy (spVATS) in the management of large (> 5 cm) infracarinal traction diverticula are described. Operative outcomes, pre- and postoperative symptoms (Eckardt score) and quality of life (Short-Form 36) are analyzed. RESULTS Four symptomatic patients underwent spVATS for traction midesophageal diverticula. The median age was 59 years and 75% were males. The median diverticulum size was 7.0 cm (range 5.5-8). The median preoperative Eckardt score was 8.4 (range 5-10), and the overall incidence of respiratory symptoms was 50%. Esophageal manometry was performed in three patients with no evidence of underlying motility disorders. The median operative time was 149 min (range 125-175). No intraoperative complications or open conversions occurred. Postoperative morbidity and mortality were 25% and 0%, respectively. The median hospital length of stay was 7.5 days (range 6-10). The median postoperative follow-up was 22 months (range 5-35). At the last follow-up, there was a significant improvement of patients' symptoms (p = 0.024) and quality of life (p < 0.05) with complete resolution of respiratory symptoms. CONCLUSION In summary, spVATS seems a valuable approach to treat large midesophageal traction diverticula in centers experienced with minimally invasive esophageal surgery. Further studies are needed to validate the advantages and promising outcomes of the spVATS providing more robust evidence on the treatment of this rare clinical entity.


Tertiary lymphoid structures target the antitumor immune response to lung cancer.


title: Public health significance of neuroticism.

text: The personality trait of neuroticism refers to relatively stable tendencies to respond with negative emotions to threat, frustration, or loss. Individuals in the population vary markedly on this trait, ranging from frequent and intense emotional reactions to minor challenges to little emotional reaction even in the face of significant difficulties. Although not widely appreciated, there is growing evidence that neuroticism is a psychological trait of profound public health significance. Neuroticism is a robust correlate and predictor of many different mental and physical disorders, comorbidity among them, and the frequency of mental and general health service use. Indeed, neuroticism apparently is a predictor of the quality and longevity of our lives. Achieving a full understanding of the nature and origins of neuroticism, and the mechanisms through which neuroticism is linked to mental and physical disorders, should be a top priority for research. Knowing why neuroticism predicts such a wide variety of seemingly diverse outcomes should lead to improved understanding of commonalities among those outcomes and improved strategies for preventing them.


title: Tabletop exercise to prepare institutions of higher education for an outbreak of COVID-19.

text: Complete Table Top Exercise Manual.


docid: qjyihlcg

title: Significance of the Extent of Intestinal Resection on the Outcome of a Short-bowel Syndrome in a Porcine Model.

text: AIM OF THE STUDY Insufficient data are available to determine the most suitable extent of intestinal resection required to induce short-bowel syndrome (SBS) in pigs. This study aimed to compare the three main SBS-models published. METHODS A 75%, 90%, or 100% mid-intestinal resection was performed in groups of n = 5 pigs each. Clinical (body weight, stool consistency) and biochemical (serum eletrolytes, citrulline, albumin, prealbumin, and transferrin) parameters were determined daily, functional (D-xylose resorption) and histological (intestinal villus length) parameters were determined after 2 weeks. A t-test and ANOVA were used for statistical analysis. RESULTS Only in the 100% group, we observed a persistent weight loss (13.6 ± 3.8%) and diarrhea, as well as a decrease in prealbumin-levels (41%) and transferrin levels (33%). Serum electrolytes remained stable in all groups during the observation period. Citrulline stabilized at different levels (100% group 13.9 ± 1.0 μmol/L; 90% group 18.8 ± 1.0 μmol/L; 75% group 26.3 ± 1.4 μmol/L; all p < .05). D-xylose resorption was lowest in the 100%, followed by 90% and 75% group (100% group 32.8 ± 4.9 mg/L; 90% group 50.0 ± 19.6 mg/L; 75% group 57.8 ± 8.8 mg/L; p = .393). Intestinal villus length decreased in all groups (100% group 11.0%; 90% group 14.0%; 75% group 19.1%). CONCLUSIONS 75% intestinal resection is less suitable as an SBS model, as animals tend to recover remarkably. The 90% model is suitable for longer-term studies, as animals might survive longer due to partial compensation. Due to severe nutritional, biochemical, and physiological derangements, the 100% model can only be used for acute experiments and those immediately followed by small bowel transplantation.


Endoscopic ultrasound-guided fine needle biopsy through the interstices of a colonic stent for the diagnosis of metastatic breast cancer using a forward-viewing linear echoendoscope.


title: Evaluating Efficacy of Antimicrobial and Antifouling Materials for Urinary Tract Medical Devices: Challenges and Recommendations.

text: In Europe, the mean incidence of urinary tract infections in intensive care units is 1.1 per 1000 patient-days. Of these cases, catheter-associated urinary tract infections (CAUTI) account for 98%. In total, CAUTI in hospitals is estimated to give additional health-care costs of £1-2.5 billion in the United Kingdom alone. This is in sharp contrast to the low cost of urinary catheters and emphasizes the need for innovative products that reduce the incidence rate of CAUTI. Ureteral stents and other urinary-tract devices suffer similar problems. Antimicrobial strategies are being developed, however, the evaluation of their efficacy is very challenging. This review aims to provide considerations and recommendations covering all relevant aspects of antimicrobial material testing, including surface characterization, biocompatibility, cytotoxicity, in vitro and in vivo tests, microbial strain selection, and hydrodynamic conditions, all in the perspective of complying to the complex pathology of device-associated urinary tract infection. The recommendations should be on the basis of standard assays to be developed which would enable comparisons of results obtained in different research labs both in industry and in academia, as well as provide industry and academia with tools to assess the antimicrobial properties for urinary tract devices in a reliable way.


title: Multiple Genomic Events Altering Hominin SIGLEC Biology and Innate Immunity Predated the Common Ancestor of Humans and Archaic Hominins.

text: Human-specific pseudogenization of the CMAH gene eliminated the mammalian sialic acid (Sia) Neu5Gc (generating an excess of its precursor Neu5Ac), thus changing ubiquitous cell surface "self-associated molecular patterns" (SAMPs) that modulate innate immunity via engagement of CD33-related-Siglec receptors. The Alu-fusion-mediated loss-of-function of CMAH fixed ∼2-3 million years ago (Mya), possibly contributing to the origins of the genus Homo. The mutation likely altered human SAMPs, triggering multiple events, including emergence of human-adapted pathogens with strong preference for Neu5Ac recognition and/or presenting Neu5Ac-containing molecular mimics of human glycans, which can suppress immune responses via CD33-related-Siglec engagement. Human-specific alterations reported in some genes encoding Sia-sensing proteins suggested a "hotspot" in hominin evolution. The availability of more hominid genomes including those of two extinct hominins now allows full reanalysis and evolutionary timing. Functional changes occur in 8/13 members of the human genomic cluster encoding CD33-related-Siglecs, all predating the human common ancestor. Comparisons with great ape genomes indicate that these changes are unique to hominins. We found no evidence for strong selection after the Human-Neanderthal/Denisovan common ancestor, and these extinct hominin genomes include almost all major changes found in humans, indicating that these changes in hominin sialobiology predate the Neanderthal-human divergence ∼0.6Mya. Multiple changes in this genomic cluster may also explain human-specific expression of CD33rSiglecs in unexpected locations such as amnion, placental trophoblast, pancreatic islets, ovarian fibroblasts, microglia, NK cells and epithelia. Taken together, our data suggest that innate immune interactions with pathogens markedly altered hominin Siglec biology between 0.6-2 Mya, potentially affecting human evolution.


Pflegeforschung zu COVID-19: Aus den Versäumnissen der Vergangenheit für die Zukunft lernen.


title: Secondary research uses of residual newborn screening dried bloodspots: a scoping review.

text: PURPOSE Residual newborn screening dried bloodspots (DBS) are a valuable resource for research but the extent, type, and nature of uses are unknown. The objective of this research was to systematically review the published literature about secondary research uses of residual DBS using a scoping review protocol. METHODS A total of 654 publications meeting the inclusion criteria with a 94% interrater reliability were identified. A coding template was created with input from expert advisory board to summarize the data. Electronic literature search of Ovid MEDLINE, Embase (via Embase.com), CINAHL (EBSCO),and Science and Social Sciences Citation Indices (via Web of Science) was conducted. RESULTS A large proportion of the secondary research with DBS was conducted within the United States (30%). The number of published studies utilizing DBS are increasing each year, primarily with observational or case-control designs. Only a small number of studies reported whether or not consent was obtained and if the DBS were identifiable or not. CONCLUSION Outcomes of this research indicate that residual DBS are well utilized worldwide for research addressing individual and public health issues. Future analyses will summarize outcomes of disease-specific research and provide evidence of the use of residual DBS in research on health outcomes.


title: Lectin Affinity Plasmapheresis for Middle East Respiratory Syndrome-Coronavirus and Marburg Virus Glycoprotein Elimination.

text: BACKGROUND/AIMS Middle East respiratory syndrome coronavirus (MERS-CoV) and Marburg virus (MARV) are among the World Health Organization's top 8 emerging pathogens. Both zoonoses share nonspecific early symptoms, a high lethality rate, and a reduced number of specific treatment options. Therefore, we evaluated extracorporeal virus and glycoprotein (GP) elimination by lectin affinity plasmapheresis (LAP). METHODS For both MERS-CoV (pseudovirus) as well as MARV (GPs), 4 LAP devices (Mini Hemopurifiers, Aethlon Medical, San Diego, CA, USA) and 4 negative controls were tested. Samples were collected every 30 min and analyzed for reduction in virus infectivity by a flow cytometry-based infectivity assay (MERS-CoV) and in soluble GP content (MARV) by an immunoassay. RESULTS The experiments show a time-dependent clearance of MERS-CoV of up to 80% within 3 h (pseudovirus). Up to 70% of MARV-soluble GPs were eliminated at the same time. Substantial saturation of the binding resins was detected within the first treatment hour. CONCLUSION MERS-CoV (pseudovirus) and MARV soluble GPs are eliminated by LAP in vitro. Considering the high lethality and missing established treatment options, LAP should be evaluated in vivo. Especially early initiation, continuous therapy, and timed cartridge exchanges could be of importance.


title: Attitudes of patients and care providers toward a surgical site marking policy.

text: BACKGROUND In the fall of 2005, the University Health Network in Toronto, Canada, initiated a policy requiring the surgeon-or his or her delegate-to sign the incision site for all operations. Little is known about what health care providers and patients think about official surgical site marking policy. METHOD Twenty-one patients and health care providers were interviewed, and the authors conducted field observations of surgeons while they marked their patients. The data were analyzed using grounded theory methods. FINDINGS Surgical site marking was perceived to be a safety precaution for operations involving multiple sides and structures but not for cases where there is no uncertainty about the intended operative site. Participants believed that marking could also facilitate error if the wrong side was marked. Site marking was perceived to have the effect of ensuring that the surgeon meets with the patient prior to the operation on the day of surgery. Concerns were raised with respect to who should mark patients and marking surgical sites for genital surgery or other private body sites. CONCLUSIONS For operations that involve multiple possible surgical sites, site marking should be carried out by individuals who are knowledgeable about the patient and the proposed procedure. For operations in which there is no uncertainty about the intended site, interventions other than site marking could be implemented to ensure patient-surgeon interactions on the day of surgery. Surgical site marking procedures should respect patient dignity and privacy.


title: Targets of caspase-6 activity in human neurons and Alzheimer disease.

text: Caspase-6 activation occurs early in Alzheimer disease and sometimes precedes the clinical manifestation of the disease in aged individuals. The active Caspase-6 is localized in neuritic plaques, in neuropil threads, and in neurofibrillary tangles containing neurons that are not morphologically apoptotic in nature. To investigate the potential consequences of the activation of Caspase-6 in neurons, we conducted a proteomics analysis of Caspase-6-mediated cleavage of human neuronal proteins. Proteins from the cytosolic and membrane subcellular compartments were treated with recombinant active Caspase-6 and compared with undigested proteins by two-dimensional gel electrophoresis. LC/MS/MS analyses of the proteins that were cleaved identified 24 different potential protein substrates. Of these, 40% were cytoskeleton or cytoskeleton-associated proteins. We focused on the cytoskeleton proteins because these are critical for neuronal structure and function. Caspase-6 cleavage of alpha-Tubulin, alpha-Actinin-4, Spinophilin, and Drebrin was confirmed. At least one Caspase-6 cleavage site was identified for Drebrin, Spinophilin, and alpha-Tubulin. A neoepitope antiserum to alpha-Tubulin cleaved by Caspase-6 immunostained neurons, neurofibrillary tangles, neuropil threads, and neuritic plaques in Alzheimer disease and co-localized with active Caspase-6. These results imply that the early and neuritic activation of Caspase-6 in Alzheimer disease could disrupt the cytoskeleton network of neurons, resulting in impaired neuronal structure and function in the absence of cell death. This study provides novel insights into the pathophysiology of Alzheimer disease.


title: Monitoring and delivery of sedation.

text: Sedation for medical procedures is provided in a variety of clinical settings by medical personnel with differing levels of education and training. Although generally a safe practice, there is a degree of morbidity and mortality associated with sedation practice. Monitoring standards continue to be refined by professional societies with the goal of improving care. The depth of sedation should be monitored with clinical criteria. Processed electroencephalographic monitors currently do not contribute significantly to sedation care. Monitoring ventilation using pulse oximetry should be abandoned for more direct methods, such as capnography-transcutaneous carbon dioxide, respiratory acoustical and thoracic impedance monitoring could also play a role. Propofol has become widely utilized for sedation, although there are concerns about its margin of safety and synergistic interactions with other agents. Dexmedetomidine and propofol/ketamine also have utility. Patient-controlled sedation pumps and target-controlled infusion devices have been developed to improve patient care and satisfaction. A computer-assisted propofol sedation device to be used by non-anaesthesiologists has been approved in the USA by the Food and Drug Administration. More computer-assisted sedation delivery devices are likely to be developed, but their clinical utility is unclear.


Is capnography mandatory during sedation for endoscopy?


title: Factors Associated With Recurrent Ischemic Stroke in the Medical Group of the SAMMPRIS Trial.

text: IMPORTANCE The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial showed that aggressive medical therapy was more effective than stenting for preventing stroke in patients with symptomatic intracranial stenosis. However, 15% of patients in the medical group still experienced a primary end point during a median follow-up of 32.7 months. OBJECTIVE To determine baseline features that were associated with a high rate of a primary end point in the medical arm of the SAMMPRIS Trial. DESIGN, SETTING, AND PARTICIPANTS A post hoc analysis of patients in the medical arm only of the SAMMPRIS trial. Enrollment occurred between October 2008 and April 2013 and included 227 patients randomized to medical management alone. Baseline demographic features, vascular risk factors, qualifying event, brain imaging, and angiographic features were analyzed. Bivariate and multivariable proportional hazard regression modeling was performed to relate baseline features to the time until a primary end point. The post hoc analysis was conducted from November 2014 to June 2015. INTERVENTIONS The SAMMPRIS Trial compared stenting with aggressive medical management in patients with a stroke or transient ischemic attack attributed to 70% to 99% stenosis of a major intracranial artery. MAIN OUTCOMES AND MEASURES The primary outcome was any of the following: stroke or death within 30 days of enrollment, ischemic stroke in the territory of the symptomatic intracranial artery beyond 30 days after enrollment, or any stroke or death within 30 days after stenting a patient in the medical group during follow-up. RESULTS A total of 227 patients were included in the study, 82 of whom were female, and the mean (SD) age was 59.5 (11.8) years. Being female (hazard ratio [HR], 1.9; 95% CI, 0.96-3.7), having diabetes mellitus (HR, 1.8; 95% CI, 0.9-3.5), not taking a statin at enrollment (HR, 2.6; 95% CI, 1.2-5.7), stroke as the qualifying event (HR, 2.5; 95% CI, 1.03-6.0), Rankin grade of 1 or greater (HR, 2.3; 95% CI, 0.9-5.5), old infarct in the territory of the stenotic artery (HR, 2.6; 95% CI, 1.3-5.1), and greater than 80% stenosis (HR, 1.9; 95% CI, 0.9-3.7) were associated (P < .10) with higher risk on bivariate analysis. Factors that were significantly associated with a primary end point on multivariable analyses were old infarct in the territory (HR, 2.6; 95% CI, 1.3-5.3; P = .006), stroke as the qualifying event (HR, 3.0; 95% CI, 1.1-7.7; P = .03), and no statin use at enrollment (HR, 2.4; 95% CI, 1.1-5.2; P = .03). CONCLUSIONS AND RELEVANCE Old infarct in the territory of the stenosis, new stroke presentation, and absence of statin use at enrollment were independently associated with high rates of the primary end point in the medical group in the SAMMPRIS Trial. These features may be useful for selecting high-risk patients for future clinical trials evaluating alternative therapies for intracranial stenosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00576693.


The equity of remote-access open-book examinations during Covid-19 and beyond: Medical students' perspective.


title: Performance of biological mesh materials in abdominal wall reconstruction: study protocol for a randomised controlled trial.

text: INTRODUCTION Abdominal wall hernias are a common source of morbidity and mortality. The use of biological mesh has become an important adjunct in successful abdominal wall reconstruction. There are a variety of biological mesh products available; however, there is limited evidence supporting the use of one type over another. This study aims to compare the performance (eg, the rate of hernia recurrence) of either a crosslinked biological mesh product or a non-crosslinked product in patients undergoing abdominal wall reconstruction. METHODS AND ANALYSIS This is a single-centre, dual arm randomised controlled trial. Patients requiring abdominal wall reconstruction will be assessed for eligibility. Eligible patients will then undergo an informed consent process following by randomisation to either (1) crosslinked porcine dermis mesh (Permacol); or (2) non-crosslinked porcine dermis mesh (Strattice). These groups will be compared for the rate of hernia recurrence at 1 and 2 years as well as the rate of postoperative complications (eg, surgical site infections). ETHICS AND DISSEMINATION This study has been approved by the institution's research ethics board and registered with clinicaltrials.gov. All eligible participants will provide informed consent prior to randomization. The results of this study may help guide the choice of biologic mesh for this population. The results of this study will be published in peer-reviewed journals as well as national and international conferences. TRIAL REGISTRATION NUMBER NCT02703662.


title: Norovirus recombinants: recurrent in the field, recalcitrant in the lab - a scoping review of recombination and recombinant types of noroviruses.

text: Noroviruses are recognized as the major global cause of sporadic and epidemic non-bacterial gastroenteritis in humans. Molecular mechanisms driving norovirus evolution are the accumulation of point mutations and recombination. Intragenotypic recombination has long been postulated to be a driving force of GII.4 noroviruses, the predominant genotype circulating in humans for over two decades. Increasingly, emergence and re-emergence of different intragenotype recombinants have been reported. The number and types of norovirus recombinants remained undefined until the 2007 Journal of General Virology research article 'Norovirus recombination' reported an assembly of 20 hitherto unclassified intergenotypic norovirus recombinant types. In the intervening decade, a host of novel recombinants has been analysed. New recombination breakpoints have been described, in vitro and in vivo studies supplement in silico analyses, and advances have been made in analysing factors driving norovirus recombination. This work presents a timely overview of these data and focuses on important aspects of norovirus recombination and its role in norovirus molecular evolution. An overview of intergenogroup, intergenotype, intragenotype and 'obligatory' norovirus recombinants as detected via in silico methods in the field is provided, enlarging the scope of intergenotypic recombinant types to 80 in total, and notably including three intergenogroup recombinants. A recap of advances made studying norovirus recombination in the laboratory is given. Putative drivers and constraints of norovirus recombination are discussed and the potential link between recombination and norovirus zoonosis risk is examined.