title: Plasma FGF-19 Levels are Increased in Patients with Post-Bariatric Hypoglycemia.

text: BACKGROUND Hypoglycemia is an increasingly recognized complication of bariatric surgery. Mechanisms contributing to glucose lowering remain incompletely understood. We aimed to identify differentially abundant plasma proteins in patients with post-bariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB), compared to asymptomatic post-RYGB. METHODS Proteomic analysis of blood samples collected after overnight fast and mixed meal challenge in individuals with PBH, asymptomatic RYGB, severe obesity, or overweight recruited from outpatient hypoglycemia or bariatric clinics. RESULTS The top-ranking differentially abundant protein at 120 min after mixed meal was fibroblast growth factor 19 (FGF-19), an intestinally derived hormone regulated by bile acid-FXR signaling; levels were 2.4-fold higher in PBH vs. asymptomatic post-RYGB (mean + SEM, 1094 ± 141 vs. 428 ± 45, P < 0.001, FDR < 0.01). FGF-19 ELISA confirmed 3.5-fold higher concentrations in PBH versus asymptomatic (360 ± 70 vs. 103 ± 18, P = 0.025). To explore potential links between increased FGF-19 and GLP-1, residual samples from other human studies in which GLP-1 was modulated were assayed. FGF-19 levels did not change in response to infusion of GLP-1 and PYY in overweight/obese individuals. Infusion of the GLP-1 receptor antagonist exendin 9-39 in recently operated asymptomatic post-RYGB did not alter FGF-19 levels after mixed meal. By contrast, GLP-1 receptor antagonist infusion yielded a significant increase in FGF-19 levels after oral glucose in individuals with PBH. While plasma bile acids did not differ between PBH and asymptomatic post-RYGB, these data suggest unique interrelationships between GLP-1 and FGF-19 in PBH. CONCLUSIONS Taken together, these data support FGF-19 as a potential contributor to insulin-independent pathways driving postprandial hypoglycemia in PBH.


title: High-flow oxygen therapy and other inhaled therapies in intensive care units.

text: In this Series paper, we review the current evidence for the use of high-flow oxygen therapy, inhaled gases, and aerosols in the care of critically ill patients. The available evidence supports the use of high-flow nasal cannulae for selected patients with acute hypoxaemic respiratory failure. Heliox might prevent intubation or improve gas flow in mechanically ventilated patients with severe asthma. Additionally, it might improve the delivery of aerosolised bronchodilators in obstructive lung disease in general. Inhaled nitric oxide might improve outcomes in a subset of patients with postoperative pulmonary hypertension who had cardiac surgery; however, it has not been shown to provide long-term benefit in patients with acute respiratory distress syndrome (ARDS). Inhaled prostacyclins, similar to inhaled nitric oxide, are not recommended for routine use in patients with ARDS, but can be used to improve oxygenation in patients who are not adequately stabilised with traditional therapies. Aerosolised bronchodilators are useful in mechanically ventilated patients with asthma and chronic obstructive pulmonary disease, but are not recommended for those with ARDS. Use of aerosolised antibiotics for ventilator-associated pneumonia and ventilator-associated tracheobronchitis shows promise, but the delivered dose can be highly variable if proper attention is not paid to the delivery method.


title: The Microbiology of Coronaviruses.

text: The end of 2019 marked the start of coronavirus disease (COVID-19) pandemic from China, which went on to envelope more than 190 countries and territories across the globe. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from a group of betacoronaviruses, is responsible for COVID-19. The virulent factors include the presence of envelope and spike proteins having receptor bonding domains (RBD). Clinical manifestations can range from mild respiratory infections to fatal outcomes. The viability of virus ranges from 3 to 72 hours. Polymerase chain reaction (PCR) is the diagnostic test of choice in this pandemic situation. Due to the absence of specific antivirals and vaccine, adoption of preventive option can help to combat the specific life-threatening outcomes.


title: How we should respond to the Coronavirus SARS-CoV-2 outbreak: A German perspective.

text: BACKGROUND In the early phase of the COVID-19 pandemic Germany missed to set up efficient containment measures. Consequently, the number of cases increased exponentially until a lockdown was implemented to suppress the spread of SARS-CoV-2. Fortunately, Germany has a high capability for coronavirus lab testing and more than 30,000 ICU beds. These capabilities and the lockdown turned out to be an advantage to combat the pandemic and to prevent a health-system overload. AIM The aim was to predict the plateau day of SARS-CoV-2 infections or deaths. RESULTS The effect on the viral spread of the German measures taken and the impact on the peak of new infection cases is shown. By normalizing daily case numbers, the plateau day of the current outbreak in Germany could be calculated to be reached at April 12, 2020 (day 103 of 2020). CONCLUSION Normalized case number curves are helpful to predict the time point at which no further new infections will occur. Upon reaching the plateau day during a lockdown phase, a residual time-period of about 2-3 weeks can be utilized to prepare a safe unlocking period. As can be learned from Asian countries such as South Korea and Taiwan there must be strict rules to keep the risk of infection low. Those include social distancing, face mask wearing in combination with digital contact tracing and serosurveillance studies. Following those rules, a safe dance around the infection curve allows to keep the population at a reduced infection rate.


title: Challenges to and facilitators of occupational epidemiology research in the UK.

text: This study investigated the challenges and facilitators of occupational epidemiology (OE) research in the UK, and evaluated the impact of these challenges. Semi-structured in-depth interviews with leading UK-based OE researchers, and a survey of UK-based OE researchers were conducted. Seven leading researchers were interviewed, and there were 54 survey respondents. Key reported challenges for OE were diminishing resources during recent decades, influenced by social, economic and political drivers, and changing fashions in research policy. Consequently, the community is getting smaller and less influential. These challenges may have negatively affected OE research, causing it to fail to keep pace with recent methodological development and impacting its output of high-quality research. Better communication with, and support from other researchers and relevant policy and funding stakeholders was identified as the main facilitators to OE research. Many diseases were initially discovered in workplaces, as these make exceptionally good study populations to accurately assess exposures. Due to the decline of manufacturing industry, there is a perception that occupational diseases are now a thing of the past. Nevertheless, new occupational exposures remain under-evaluated and the UK has become reliant on overseas epidemiology. This has been exacerbated by the decline in the academic occupational medicine base. Maintaining UK-based OE research is hence necessary for the future development of occupational health services and policies for the UK workforce.


title: Reconfiguring the scope and practice of regional anesthesia in a pandemic: the COVID-19 perspective.

text: The COVID-19 outbreak is on the world. While many countries have imposed general lockdown, emergency services are continuing. Healthcare professionals have been infected with the virulent severe acute respiratory syndrome coronavirus-2 (SARS), which spreads by close contact and aerosols. The anesthesiologist is particularly vulnerable to aerosols while performing intubation and other airway related procedures. Regional anesthesia (RA) minimizes the need for airway manipulation and the risks of cross infection to other patients, and the healthcare personnel. In this context, for prioritizing RA over general anesthesia, wherever possible, a structured algorithmic approach is outlined. The role of percentage saturation of hemoglobin with oxygen (oxygen saturation), blood pressure and early use of point-of-care ultrasound in differential diagnosis and specific management is detailed. The perioperative anesthetic implications of multisystem manifestations of COVID-19, anesthetic management options, the scope of RA and considerations for its safe conduct in operating rooms is described. An outline for safe and rapid training of healthcare personnel, with an Entrustable Professional Activity framework for ascertaining the practice readiness among trained residents for RA in COVID-19, is suggested. These are the authors' experiences gained from the current pandemic and similar SARS, Middle East Respiratory Syndrome and influenza outbreaks in recent past faced by our authors in Singapore, India, Hong Kong and Canada.


title: Impact of abdominal shape on living liver donor outcomes in mini-incision right hepatic lobectomy: Comparison among 3 techniques.

text: Although minimally invasive techniques for living donor hepatectomy have been developed, the surgical feasibility and limitations remain to be elucidated. The risks and outcomes involved need to be better understood prior to their widespread application. The aim of this study was to assess feasibility of minimally invasive donor hepatectomy by reviewing our experience. A total of 99 living donor liver transplantations performed between 2000 and 2016 were retrospectively reviewed. All 99 living liver donors underwent right hepatectomy. The breakdown of the techniques is as follows: the standard technique in 33 patients; the laparoscopic-assisted minilaparotomy technique (hybrid technique group) in 19 patients; and the upper midline incision technique without laparoscopic assistance (minilaparotomy group) in 47 patients. An association between donor operative outcomes and body habitus, such as body mass index (BMI), abdominal truncal depth (approximated by celiac axis [CA] depth ratio), and umbilical circumference (UC) were assessed. Perioperative factors were compared between the standard technique and the minimally invasive technique. The minilaparotomy group had significantly shorter operative time (P = 0.046) and hospital stay (P = 0.005) than the standard technique group. Postoperative complication rates were similar between the 3 groups (P = 0.16). In the minilaparotomy group, greater BMI (P = 0.02), CA depth ratio (P = 0.04), and UC (P = 0.004) were found to be risk factors for postoperative complications. In the minilaparotomy group, CA depth ratio > 0.41, UC > 90 cm, and BMI > 30 kg/m2 were significantly associated with longer operative time and hospital stay. In the standard technique group, none of the body size factors were associated with postoperative outcomes. In conclusion, the minilaparotomy technique is safe and feasible, though technical difficulties may be encountered when performed on donors with larger body habitus. Ongoing efforts are required to ensure living donor safety. Liver Transplantation 24 516-527 2018 AASLD.


title: Endovascular Treatment With or Without Prior Intravenous Alteplase for Acute Ischemic Stroke.

text: Background It is unclear whether intravenous thrombolysis ( IVT ) with alteplase before endovascular treatment ( EVT ) is beneficial for patients with acute ischemic stroke caused by a large vessel occlusion. We compared clinical and procedural outcomes, safety, and workflow between patients treated with both IVT and EVT and those treated with EVT alone in routine clinical practice. Methods and Results Using multivariable regression, we evaluated the association of IVT + EVT with 90-day functional outcome (modified Rankin Scale), mortality, reperfusion, first-pass effect, and symptomatic intracranial hemorrhage in the MR CLEAN (Multicenter Randomised Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) Registry. Of 1485 patients, 1161 (78%) were treated with IVT + EVT , and 324 (22%) with EVT alone. Patients treated with IVT + EVT had atrial fibrillation less often (16% versus 44%) and had better pre-stroke modified Rankin Scale scores (pre-stroke modified Rankin Scale 0: 73% versus 52%) than those treated with EVT alone. Procedure time was shorter in the IVT + EVT group (median 62 versus 68 minutes). Nontransferred IVT + EVT patients had longer door-to-groin-puncture times (median 105 versus 94 minutes). IVT + EVT was associated with better functional outcome (adjusted common odds ratio 1.47; 95% CI : 1.10-1.96) and lower mortality (adjusted odds ratio 0.58; 95% CI : 0.40-0.82). Successful reperfusion, first-pass effect, and symptomatic intracranial hemorrhage did not differ between groups. Conclusions In this observational study, patients treated with IVT + EVT had better clinical outcomes than patients who received EVT alone. This finding may demonstrate a true benefit of IVT before EVT , but its interpretation is hampered by the possibility of residual confounding and selection bias. Randomized trials are required to properly assess the effect of IVT before EVT .


title: Early versus delayed removal of indwelling catheters in patients after elective cesarean section: a prospective randomized trial.

text: PURPOSE We conducted a prospective randomized controlled trial to compare postoperative urinary catheter removal 2 versus 12 h after elective cesarean section in terms of irritative symptoms, first void time, incidence of urinary tract infection, postoperative mobilization time, and hospitalization time. METHODS A total of 134 women admitted to Duzce University Hospital for primary or recurrent elective cesarean section were randomized into two groups. A total of 62 women were enrolled in the early group, with indwelling catheter removal 2 h after cesarean section; 74 women were enrolled in the delayed group, with catheter removal 12 h after the cesarean section. The groups were prospectively compared in terms of irritative urinary symptoms, bacteriuria, hematuria, length of hospital stay, and mobilization time. RESULTS Urinary frequency (p = .04), microscopic hematuria incidence (p = .04), postoperative mobilization time (p = .01), and length of hospital stay (p = .009) were significantly lower in the early group than in the delayed group. There were no significant differences in terms of bacteruria, urinary retention, dysuria, and first postoperative voiding time. CONCLUSIONS Early removal of urinary catheters after elective cesarean section is associated with reduced mobilization time and hospital stay.


title: Modified Anesthesia Protocol for Electroconvulsive Therapy Permits Reduction in Aerosol-Generating Bag-Mask Ventilation during the COVID-19 Pandemic.

text: INTRODUCTION Electroconvulsive therapy (ECT) is a critical procedure in psychiatric treatment, but as typically delivered involves the use of bag-mask ventilation (BMV), which during the COVID-19 pandemic exposes patients and treatment staff to potentially infectious aerosols. OBJECTIVE To demonstrate the utility of a modified anesthesia protocol for ECT utilizing preoxygenation by facemask and withholding the use of BMV for only those patients who desaturate during the apneic period. METHODS This chart review study analyzes patients who were treated with ECT using both the traditional and modified anesthesia protocols. RESULTS A total of 106 patients were analyzed, of whom 51 (48.1%) required BMV using the new protocol. Of clinical factors, only patient BMI was significantly associated with the requirement for BMV. Mean seizure duration reduced from 52.0 ± 22.4 to 46.6 ± 17.1 s, but seizure duration was adequate in all cases. No acute physical, respiratory, or psychiatric complications occurred during treatment. CONCLUSIONS A modified anesthesia protocol reduces the use of BMV by more than 50%, while retaining adequate seizure duration.


Will the pandemic permanently alter scientific publishing?


title: Hysterectomy and ovarian cystectomy using natural orifice transluminal endoscopic surgery: An initial experience at Tzu Chi General Hospital.

text: Objectives The objective of this study is to report our initial experience with patients undergoing transvaginal natural orifice transluminal endoscopic surgery (NOTES). Materials and Methods From September 2016 to December 2016, patients who were not virgins and did not have pelvic inflammation or obliteration of the cul-de-sac who underwent NOTES hysterectomy or ovarian cystectomy (OC) were included in the study. Results Transvaginal NOTES was performed smoothly in six patients, two patients (mean age 35 years, mean body mass index [BMI] 25) received an OC and four patients (mean age 49 years, mean BMI 27) underwent a hysterectomy. One patient with a hysterectomy received concurrent adhesiolysis. The mean surgical times were 74 and 75 min and blood loss was 50 and 87.5 ml in the OC and hysterectomy groups, respectively. One patient with a hysterectomy had a postoperative fever with 38°C last for 2 days. Pain scores were 0 at 48 h postoperatively in both groups. Conclusion Transvaginal NOTES is a feasible and safe technique for hysterectomy and OC in our patients and those in previous reports. This procedure was minimally invasive with no scars on the abdomen as well as little pain.


title: Ki 67 is an independent predictive biomarker of cancer specific and local recurrence-free survival after lung tumor ablation.

text: BACKGROUND The objective of this work was to evaluate the feasibility of histopathological analysis of tissue extracted on multitined electrodes and assess whether tissue characteristics can be used as biomarkers of oncologic outcomes after lung tumor radiofrequency (RF) ablation. METHODS Treatment-related data regarding RF ablation of lung malignancies at our institution was collected using a Health Insurance Portability and Accountability Act-compliant ablation database. Institutional review board waiver was obtained for this study. Immunohistochemical analysis of tissue extracted from the electrodes after lung tumor RF ablation was performed for proliferation (Ki-67) and apoptosis (caspase-3). Patient, tumor demographics, and ablation parameters were recorded. Local tumor progression-free survival (LPFS), disease-specific survival (DSS), and overall survival (OS) were assessed using Kaplan-Meier methodology. Multivariate analysis determined factors affecting these oncological outcomes. RESULTS A total of 47 lung tumors in 42 patients were ablated; 30 specimens were classified as coagulation necrosis (CN) and 17 as Ki-67-positive (+) tumor cells (viable). Tumor sizes were similar in the CN and Ki-67+ groups (P = 0.32). Median LPFS was 10 versus 16 months for Ki-67+ and CN groups, and 1-year LPFS was 34 and 75 %, respectively (P = 0.003). Median OS was 20 and 46 months (P = 0.12), and median DSS was 20 and 68 months (P = 0.01) for the Ki-67 + and CN groups, respectively. Identification of Ki-67+ tumor cells more than tripled the risk of death from cancer [hazard ratio (HR) = 3.65; 95 % confidence interval (95 % CI), 1.34-9.95; P = 0.01] and tripled the risk of local tumor progression (LTP) (HR = 3.01; 95 % CI, 1.39-6.49; P = 0.005). CONCLUSIONS Ki-67+ tumor cells on the electrode after pulmonary tumor RF ablation is an independent predictor of LTP, shorter LPFS, and DSS.


title: Video-assisted thoracoscopic thymectomy using 5-mm ports and carbon dioxide insufflation.

text: The continuous development and refinement of minimally invasive approaches to thymectomy over the last two decades has potential benefits for patients in terms of better cosmesis, less postoperative pain, shorter length of stay, earlier return to daily activities, less bleeding and fewer complications overall with similar outcomes regarding survival, recurrence of thymoma and complete remission (CR) for myasthenia gravis patients. A variety of different approaches have been described previously. This is a detailed description of video-assisted thoracoscopic thymectomy using three 5 mm ports, carbon dioxide (CO2) insufflation and bipolar electrocoagulation (LigaSure).


title: Transcutaneous immunization: an overview of advantages, disease targets, vaccines, and delivery technologies.

text: Skin is an immunologically active tissue composed of specialized cells and agents that capture and process antigens to confer immune protection. Transcutaneous immunization takes advantage of the skin immune network by inducing a protective immune response against topically applied antigens. This mode of vaccination presents a novel and attractive approach for needle-free immunization that is safe, noninvasive, and overcomes many of the limitations associated with needle-based administrations. In this review we will discuss the developments in the field of transcutaneous immunization in the past decade with special emphasis on disease targets and vaccine delivery technologies. We will also briefly discuss the challenges that need to be overcome to translate early laboratory successes in transcutaneous immunization into the development of effective clinical prophylactics.


COVID-19: a danger and an opportunity for the future of general practice.


Year in review 2010: tuberculosis, pleural diseases, respiratory infections.


Lung Ultrasound in COVID-19 Patients - More Shadows Than Information - Letter to the Editor on the Article "W. LU et al. Ultraschall in Med. 2020 Apr 15".


title: Vessel sealing versus suture ligation for canine ovarian pedicle haemostasis: a randomised clinical trial.

text: Vessel sealing (VS) is well established in laparoscopic ovariectomy (OVE) in dogs. The objectives of this study were to evaluate the efficacy of ovarian pedicle haemostasis by VS using a commercially available VS tool in open OVE and compare it with suture ligation (SL). A prospective, randomised clinical trial including 20 female dogs was designed. Open OVE was performed via a standard mid-line celiotomy by a single surgeon using a standardised protocol. At random, the right ovarian pedicle was sealed (VS) or ligated (SL) whereas the left pedicle was treated by the alternative technique. Surgical times for procedural stages and intra-operative complications were recorded and statistically evaluated. Total surgical time was 29.28±11.13 minutes (range 12.50-62.13 minutes) and time from identification to removal of the ovary was significantly less when sealing (VS 2.22±0.58 minutes) than when ligating (SL 4.10±1.13 minutes P=0.0001). Intra-operative complications were rare for both techniques (failure of the electrode of the VS device (n=3); ovarian pedicle haemorrhage due to ligature slippage (n=1)). The results of the current study indicate that ovarian pedicle haemostasis achieved by VS is significantly faster than by placement of ligatures without appearing to compromise safety.


title: A single herpesvirus protein can mediate vesicle formation in the nuclear envelope.

text: Herpesviruses assemble capsids in the nucleus and egress by unconventional vesicle-mediated trafficking through the nuclear envelope. Capsids bud at the inner nuclear membrane into the nuclear envelope lumen. The resulting intralumenal vesicles fuse with the outer nuclear membrane, delivering the capsids to the cytoplasm. Two viral proteins are required for vesicle formation, the tail-anchored pUL34 and its soluble interactor, pUL31. Whether cellular proteins are involved is unclear. Using giant unilamellar vesicles, we show that pUL31 and pUL34 are sufficient for membrane budding and scission. pUL34 function can be bypassed by membrane tethering of pUL31, demonstrating that pUL34 is required for pUL31 membrane recruitment but not for membrane remodeling. pUL31 can inwardly deform membranes by oligomerizing on their inner surface to form buds that constrict to vesicles. Therefore, a single viral protein can mediate all events necessary for membrane budding and abscission.


docid: crohccdm

title: Second-Trimester Miscarriage in a Pregnant Woman With SARS-CoV-2 Infection.


COVID-19 and Perinatal Psychiatry.


docid: hnbxfbeo

title: Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset.

text: BACKGROUND Timely diagnosis of SARS-CoV-2 infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value of the antibody test to RNA test need to be demonstrated. METHOD Serial sera of 80 patients with PCR-confirmed COVID-19 were collected at the First Affiliated Hospital of Zhejiang University, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described. RESULTS The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post exposure (d.p.e) or 9, 10 and 12 days post onset (d.p.o), respectively. The antibody levels increased rapidly beginning at 6 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7 d.p.o), Ab showed the highest sensitivity (64.1%) compared to IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3% 2 weeks later, respectively. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays. CONCLUSIONS A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patients.


title: [Psychological status and sleep quality of nursing interns during the outbreak of COVID-19].

text: OBJECTIVE To investigate the psychological status and sleep quality of nursing interns in collective isolation during the outbreak of coronavirus disease 2019 (COVID-19) and provide evidence for adequate interventions. METHODS We surveyed a total of 95 nursing interns who were isolated collectively in a general teaching hospital in Guangzhou using a self-designed questionnaire, which consisted of a basic information form, self-rating anxiety scale (SAS), self-rating depression scale (SDS) and Pittsburgh Sleep Quality Index (PSQI). Descriptive analysis, single factor analysis and correlation analysis were used to analyze the current status of the interns' psychology and sleep quality, the potential factors affecting their psychology and sleep quality, and the correlation between their psychological status and sleep quality. RESULTS The surveyed interns had SAS, SDS and PSQI score of 37.79±6.59, 43.98±9.74 and 5.20±3.14, respectively, which were significant higher than the national norms in China (P < 0.05). Correlation analysis indicated that both anxiety and depression were positively correlated with the sleep quality score (r=0.508 and 0.546, respectively). Univariate analysis showed that the major factors affecting the psychological status and sleep quality of the interns during collective isolation included recent contact with persons from the affected area before isolation and the onset of fever during the isolation. CONCLUSIONS These interns showed relatively high levels of anxiety and depression during the collective isolation to affect their sleep quality, and interventions should be timely administered to improve their mental health and sleep quality.


Going viral with kindness.


title: Models predicting survival to guide treatment decision-making in newly diagnosed primary non-metastatic prostate cancer: a systematic review.

text: OBJECTIVES Men diagnosed with non-metastatic prostate cancer require standardised and robust long-term prognostic information to help them decide on management. Most currently-used tools use short-term and surrogate outcomes. We explored the evidence base in the literature on available pre-treatment, prognostic models built around long-term survival and assess the accuracy, generalisability and clinical availability of these models. DESIGN Systematic literature review, pre-specified and registered on PROSPERO (CRD42018086394). DATA SOURCES MEDLINE, Embase and The Cochrane Library were searched from January 2000 through February 2018, using previously-tested search terms. ELIGIBILITY CRITERIA Inclusion required a multivariable model prognostic model for non-metastatic prostate cancer, using long-term survival data (defined as ≥5 years), which was not treatment-specific and usable at the point of diagnosis. DATA EXTRACTION AND SYNTHESIS Title, abstract and full-text screening were sequentially performed by three reviewers. Data extraction was performed for items in the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies checklist. Individual studies were assessed using the new Prediction model Risk Of Bias ASsessment Tool. RESULTS Database searches yielded 6581 studies after deduplication. Twelve studies were included in the final review. Nine were model development studies using data from over 231 888 men. However, only six of the nine studies included any conservatively managed cases and only three of the nine included treatment as a predictor variable. Every included study had at least one parameter for which there was high risk of bias, with failure to report accuracy, and inadequate reporting of missing data common failings. Three external validation studies were included, reporting two available models: The University of California San Francisco (UCSF) Cancer of the Prostate Risk Assessment score and the Cambridge Prognostic Groups. Neither included treatment effect, and both had potential flaws in design, but represent the most robust and usable prognostic models currently available. CONCLUSION Few long-term prognostic models exist to inform decision-making at diagnosis of non-metastatic prostate cancer. Improved models are required to inform management and avoid undertreatment and overtreatment of non-metastatic prostate cancer.


title: SARS-CoV-2-specific antibody detection in healthcare workers in Germany with direct contact to COVID-19 patients

text: BACKGROUND: The novel coronavirus SARS-CoV-2 is associated with a severe respiratory manifestation, COVID-19, and presents a challenge for healthcare systems worldwide. Healthcare workers are a vulnerable cohort for SARS-CoV-2 infection due to frequent and close contact to patients with COVID-19. STUDY DESIGN: Serum samples from 316 healthcare workers of the University Hospital Essen, Germany were tested for SARS-CoV-2-IgG antibodies. A questionnaire was used to collect demographic and clinical data. Healthcare workers were grouped depending on the frequency of contact to COVID-19 patients in high-risk-group (n = 244) with daily contact to known or suspected SARS-CoV-2 positive patients, intermediated-risk-group (n = 37) with daily contact to patients without known or suspected SARS-CoV-2 infection at admission and low-risk-group (n = 35) without patient contact. RESULTS: In 5 of 316 (1.6%) healthcare workers SARS-CoV-2-IgG antibodies could be detected. The seroprevalence was higher in the intermediate-risk-group vs. high-risk-group vs. 2/37 (5.4%) vs. (3/244 (1.2%), p = 0.13). Four of the five subject were tested negative for SARS-CoV-2 via PCR. One (20%) subject was not tested via PCR since he was asymptomatic. CONCLUSION: The overall seroprevalence of SARS-CoV-2 in healthcare workers of a tertiary hospital in Germany is low (1.6%). The data indicate that the local hygiene standard might be effective.


title: Laparo-endoscopic single-site left transperitoneal adrenalectomy.

text: A 53-yr-old woman presented with abdominal pain. Ultrasonography, computed tomography, and an endocrinologic work-up revealed a 4-cm nonfunctional left adrenal mass. A TriPort laparoscopic adrenalectomy was performed. The TriPort was inserted through a 3-cm subcostal incision. Using 5-mm instruments, a left adrenalectomy was performed. The specimen was dissected (harmonic scalpel) and extracted through a 10-mm bag. A TriPort adrenalectomy was successfully completed in 240 min (blood loss: 20 ml). The postoperative period was uneventful (discharge within 3 d). In our opinion, the TriPort adrenalectomy is feasible and safe, with favourable perioperative and short-term outcomes and a delighted patient at the 8-mo follow-up.


China coronavirus: cases surge as official admits human to human transmission.


title: The role of psychosocial working conditions on burnout and its core component emotional exhaustion - a systematic review.

text: AIMS To analyze the association between psychosocial working conditions and burnout and its core component emotional exhaustion, a systematic literature review was undertaken including cohort studies, case-control studies, and randomized controlled trials. METHODS The literature search in Medline and PsycInfo was based on a defined search string and strict exclusion and inclusion criteria. Evaluation of the 5,599 initially identified search hits by two independent reviewers and a detailed quality assessment resulted in six methodologically adequate cohort studies considering the relationship between psychosocial working conditions and burnout (one study) as well as the burnout core component emotional exhaustion (five studies). RESULTS The results of our systematic review point to a relationship between psychosocial working conditions and the development of emotional exhaustion/burnout. Particularly high job demands seem to play a role in the development of emotional exhaustion. However, strong intercorrelations between workplace factors, as a matter of principle, make the identification of a single psychosocial workplace factor (being associated with an especially high or low risk of burnout) difficult. CONCLUSIONS Multidimensional approaches including reduction of work demands, enhancement of decision latitude and improving the social climate might be promising for preventing burnout and emotional exhaustion. However, methodologically adequate intervention studies are urgently needed to prove the effectiveness of workplace interventions.


title: Mitochondrial bioenergy alterations in avian HD11 macrophages infected with infectious bronchitis virus.

text: To establish an association between mitochondrial dysfunction and apoptosis following infectious bronchitis virus (IBV) infection, HD11 avian macrophage cells were infected with the Massachusetts 41 (M41) strain. Our results show that the M41 strain of IBV induced cytopathic effects followed by the release of new viral particles. Elevated numbers of apoptotic cells were observed at 24, 48 and 72 h post-infection (p.i.). Viral infection was associated with mitochondrial membrane depolarization and reactive oxygen species (ROS) production at all of the examined timepoints p.i. In summary, IBV M41 replication in infected HD11 macrophages seems to induce mitochondrial bioenergy failure, acting as a respiratory chain uncoupler, without compromising viral replication.


title: Association of red blood cell transfusion and postoperative outcomes after endovascular aortic repair.

text: BACKGROUND Several studies have documented worse postoperative outcomes in patients who received red blood cell (RBC) transfusion perioperatively during cardiac surgery or in critical care settings. These findings were attributed to activation of the inflammatory response with the release of cytokines and immune suppression. The aim of this study was to evaluate the association of RBC transfusion on the day of surgery and postoperative outcomes following endovascular aortic repair (EVAR). METHODS A total of 510 patients who underwent EVAR from April 2005 to March 2007 were considered for analysis. The exposure of interest was whether or not patients receive RBC transfusion on the day of surgery. The primary outcome was a composite in-hospital morbidity/mortality outcome. The authors assessed the association between RBC transfusion and our composite outcome using logistic regression after adjusting for the available potential confounders using propensity score matching. RESULTS Propensity scores were estimated for 418 out of the 510 patients; 92 patients were not included because of missing data. Propensity matching resulted in 42 successfully matched pairs. Median (quartiles) propensity score was 0.46 (0.28, 0.66) for the matched patients with transfusion and 0.46 (0.29, 0.61) for the matched patients without transfusion (P = .75, Wilcoxon rank sum test). Results of the multivariable model developed after propensity score matching suggest that RBC transfusion was not significantly associated with experiencing a postoperative complication; estimated odds ratio (95% confidence interval) of 2.7 (0.8, 9.0), P = .11. CONCLUSION In this study, RBC transfusion was not independently associated with an increased incidence of in-hospital morbidity and mortality after EVAR.


title: Virus-induced inflammasome activation is suppressed by prostaglandin D2/DP1 signaling.

text: Prostaglandin D2 (PGD2), an eicosanoid with both pro- and anti-inflammatory properties, is the most abundantly expressed prostaglandin in the brain. Here we show that PGD2 signaling through the D-prostanoid receptor 1 (DP1) receptor is necessary for optimal microglia/macrophage activation and IFN expression after infection with a neurotropic coronavirus. Genome-wide expression analyses indicated that PGD2/DP1 signaling is required for up-regulation of a putative inflammasome inhibitor, PYDC3, in CD11b+ cells in the CNS of infected mice. Our results also demonstrated that, in addition to PGD2/DP1 signaling, type 1 IFN (IFN-I) signaling is required for PYDC3 expression. In the absence of Pydc3 up-regulation, IL-1β expression and, subsequently, mortality were increased in infected DP1-/- mice. Notably, survival was enhanced by IL1 receptor blockade, indicating that the effects of the absence of DP1 signaling on clinical outcomes were mediated, at least in part, by inflammasomes. Using bone marrow-derived macrophages in vitro, we confirmed that PYDC3 expression is dependent upon DP1 signaling and that IFN priming is critical for PYDC3 up-regulation. In addition, Pydc3 silencing or overexpression augmented or diminished IL-1β secretion, respectively. Furthermore, DP1 signaling in human macrophages also resulted in the up-regulation of a putative functional analog, POP3, suggesting that PGD2 similarly modulates inflammasomes in human cells. These findings demonstrate a previously undescribed role for prostaglandin signaling in preventing excessive inflammasome activation and, together with previously published results, suggest that eicosanoids and inflammasomes are reciprocally regulated.


title: Prospective evaluation of vesicourethral anastomosis outcomes in robotic radical prostatectomy during early experience in a university hospital.

text: PURPOSE Robotic assisted radical prostatectomy (RARP) presents challenges for the surgeon, especially during the initial learning curve. We aimed to evaluate early and mid-term functional outcomes and complications related to vesicourethral anastomosis (VUA), in patients who underwent RARP, during the initial experience in an academic hospital. We also assessed possible predictors of postoperative incontinence and compared these results with the literature. MATERIALS AND METHODS We prospectively collected data from consecutive patients that underwent RARP. Patients with at least 6 months of follow-up were included in the analysis for the following outcomes: time to complete VUA, continence and complications related to anastomosis. Nerve-sparing status, age, BMI, EBL, pathological tumor staging, and prostate size were evaluated as possible factors predicting early and midterm continence. Results were compared with current literature. RESULTS Data from 60 patients was assessed. Mean time to complete VUA was 34 minutes, and console time was 247 minutes. Continence in 6 months was 90%. Incidence of urinary leakage was 3.3%, no patients developed bladder neck contracture or postoperative urinary retention. On multivariate analysis, age and pathological staging was associated to 3-month continence status. CONCLUSION Our data show that, during early experience with RARP in a public university hospital, it is possible to achieve good results regarding continence and other outcomes related to VUA. We also found that age and pathological staging was associated to early continence status.


title: Comparison Between Stable Line Reinforcement by Barbed Suture and Non-reinforcement in Sleeve Gastrectomy: a Randomized Prospective Controlled Study.

text: INTRODUCTION Laparoscopic sleeve gastrectomy (LSG) is now a popular bariatric procedure worldwide with rising prevalence over the last decade. Staple line leak and bleeding are the most dangerous complications of LSG. Staple line reinforcement (SLR) by oversewing the staple line was suggested to reduce the incidence of leak and bleeding. We designed a randomized controlled prospective study to investigate the value of SLR by invaginating the whole staple line using unidirectional absorbable 3/0 V-Loc 180 sutures (Covidien, Mansfield, MA, USA) to no SLR in LSG. PATIENTS AND METHODS Nine hundred and twenty patients undergoing LSG between March 2016 and March 2017 were included in the study; they were prospectively randomized into two groups: A and B, each of 460 patients. In group A, the entire staple line was invaginated with continuous seromuscular suturing using 3/0 V-Loc 180 suture (Covidien, Mansfield, MA, USA), and in group B, no reinforcement was done. The patients were selected according to National Institute of Health (NIH) guidelines. All procedures were performed by the same team of experienced bariatric surgeons. Patients were followed up for 6 weeks after surgery for occurrence of complications. RESULTS The two groups were matched considering the demographic data. Operative time was significantly longer in group A (P = 0.001), with mean operative time in group A was 69 min, while that in Group B was 50.8 min. Leak occurred in eight cases (1.7%) in group B and none (0%) in group A; leak was significantly lower in group A (P = 0.008). Bleeding occurred in two patients (0.4%) in group A and in seven (1.5%) in group B (P = 0.178), with no statistically significant difference between both groups as regards bleeding. CONCLUSION Comparing SLR by invaginating the whole staple line using unidirectional absorbable 3/0 V-Loc 180 sutures (Covidien, Mansfield, MA, USA) to no SLR in a relatively large cohort of patients undergoing LSG, in a randomized controlled prospective study, has proved statistically significant value for SLR by invaginating sutures.


title: Endoscopic therapies for Barrett's neoplasia.

text: The standard of care for treatment of Barrett's esophagus (BE) with early esophageal neoplasia, including high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC), has undergone a revolution over the past several years. With the introduction and popularization of endoscopic ablative technologies, along with the refinement of endoscopic mucosal resection (EMR) techniques, the majority of cases of early neoplasia in the setting of BE now are managed by endoscopic approaches. As a result, many patients who previously would have been referred for esophagectomy now may be spared from this major surgical procedure with its inherent morbidity, potential for mortality, and negative impact on long-term gastrointestinal function. The esophageal surgeon must be knowledgeable about the indications for such endoscopic therapies, as well as their limitations and potential pitfalls, so as to apply them in the appropriate clinical scenarios.


title: A randomized trial comparing Tai Chi with and without cognitive-behavioral intervention (CBI) to reduce fear of falling in community-dwelling elderly people.

text: The aim of this randomized trial was to compare the effects of Tai Chi with and without CBI on a primary outcome of reducing the fear of falling, and on secondary outcomes including encouraging better social engagement, improving self-perceived personal wellbeing, and achieving better mobility among elderly people with fear of falling. One hundred and twenty-two community-dwelling elderly people aged ≥ 65 were randomly assigned to either a Tai Chi or a Tai Chi plus CBI group. Participants' level of fear of falling, physical mobility, self-perceived personal wellbeing and social participation were compared before and after completing the 8-week intervention and then at a 2-month follow-up. The findings showed that Tai Chi both with and without CBI had a similar effect on reducing elderly people's fear of falling, but only Tai Chi plus CBI had a positive effect on participants' self-perceived personal wellbeing. Tai Chi both with and without CBI had no effect on participants' self-perceived social participation and mobility. Apart from a slight improvement in participants' self-perceived personal wellbeing, other outcome effects were similar for Tai Chi with and without CBI. This finding raises a question about the additive effects of combined intervention over Tai Chi alone in reducing elderly people's fear of falling. In view of the higher demand for resources and manpower to implement a combined intervention, further study is still required to confirm the potential additional benefits of this combined intervention prior to recommending it to community services.


title: Keeping people with epilepsy safe during the Covid-19 pandemic.

text: OBJECTIVES To provide information on the impact of the COVID-19 pandemic on people with epilepsy and provide consensus recommendations on how to provide the best possible care for people with epilepsy while avoiding visits to urgent care facilities and hospitalizations during the Novel Coronavirus pandemic. METHODS The authors developed consensus statements in 2 sections. The first was "How should we/clinicians modify our clinical care pathway for people with epilepsy during the COVID-19 pandemic?" The second was "What general advice should we give to people with epilepsy during this crisis? Authors individually scored statements on a scale of -10 (strongly disagree) to +10 (strongly agree). 5/11 recommendations for physicians and 3/5 recommendations for individuals/families were rated by all authors as 7 or above (strongly agree) on the first round of rating. Subsequently, a tele-conference was held where statements for which there was a lack of strong consensus were revised. RESULTS After revision, all consensus recommendations received a score of 7 or above. The recommendations focus on administration of as much care as possible at home to keep people with epilepsy out of health care facilities, where they are likely to encounter COVID-19 (including strategies for rescue therapy), as well as minimization of risk of seizure exacerbation through adherence, and through ensuring a regular supply of medication. We also provide helpful links to additional helpful information for people with epilepsy and health providers. CONCLUSION These recommendation may help healthcare professionals provide optimal care to people with epilepsy during the coronavirus pandemic.


title: Reduce Driveline Trauma Through Stabilization and Exit Site Management: 30 Days Feasibility Results from the Multicenter RESIST Study.

text: The percutaneous lead management kit (PLMK) was developed for the HeartMate 2 (HM2) left ventricular assist device (LVAD) to reduce trauma at the exit site and to maintain a clean environment. REduce Driveline Trauma through StabIlization and Exit Site ManagemenT (RESIST) was a multicenter, prospective, nonrandomized study designed to evaluate the feasibility of the PLMK for managing the HM2 driveline exit site. Fifty patients were enrolled at five sites at a median of 495 days post-HM2 implant; 92% (46 of 50) of patients used the PLMK for a minimum of 30 days. At 30 days, more patients found the PLMK to be extremely comfortable (80% vs. 37%, p < 0.001) and extremely effective at stabilizing the driveline (82% vs. 40%, p < 0.001) compared with each center's standard of care. Frequency of dressing changes was 6-7 days or higher for 85% of the patients with PLMK. Three patients developed driveline infection while on PLMK (6%, 0.15 events per patient year), and 35 patients continued to use the PLMK after 6 months. The PLMK is easy to use, increases patient comfort, and increases driveline stability with a dressing change frequency of 6-7 days.


title: The oncogene ERG: a key factor in prostate cancer.

text: ETS-related gene (ERG) is a member of the E-26 transformation-specific (ETS) family of transcription factors with roles in development that include vasculogenesis, angiogenesis, haematopoiesis and bone development. ERG's oncogenic potential is well known because of its involvement in Ewing's sarcoma and leukaemia. However, in the past decade ERG has become highly associated with prostate cancer development, particularly as a result of a gene fusion with the promoter region of the androgen-induced TMPRRSS2 gene. We review ERG's structure and function, and its role in prostate cancer. We discuss potential new therapies that are based on targeting ERG.


title: Cerebrovascular events in COVID-19 patients.

text: Neurological manifestations in patients with COVID-19 are more frequently being reported. Cerebrovascular events have been reported in around 3% of patients. In this review we summarize the published literature on cerebrovascular events in patients with COVID-19 as available on the PubMed database. So far, 3 studies have reported cerebrovascular events. Cerebrovascular events were identified on screening patients with decreased consciousness or in the presence of focal neurological deficits. These events were common in elderly, critically ill patients and in patients with prior cardio-cerebrovascular comorbidities. The diagnosis of cerebrovascular events was confirmed with computed tomography of the brain in most studies reporting neurological events. Multiple pathological mechanisms have been postulated regarding the process of neurological and vascular injury among which cytokine storm is shown to correlate with mortality. Patients with severe illness are found to have a higher cardio- cerebrovascular comorbidity. With an increasing number of cases and future prospective studies, the exact mechanism by which these cerebrovascular events occur and attribute to the poor outcome will be better understood.


title: National and international policies to mitigate disease threats.

text: To devise and implement effective health policy, we must define the problem, choose the tools, craft the policy, build consensus, set goals and deadlines, raise funds and take action. Success or failure depends on the perception of risk, the strength of the underlying science, the efficacy of the technology, ownership and intellectual property, the conflict between individual and public health, the choice of weaker (guidelines) and stronger (law) policy instruments, the level of public interest, political opportunity, institutional inertia, mechanisms for enforcement and who foots the bill. All these things considered, this paper is a brief policy-making guide by example, illustrating some achievements and disappointments with reference to cholera, drug-resistant tuberculosis, HIV/AIDS and rabies.


title: Facial Plastic and Reconstructive Surgery During the COVID-19 Pandemic: Implications in Craniomaxillofacial Trauma and Head and Neck Reconstruction.

text: BACKGROUND The global COVID-19 pandemic has had a profound impact on facial plastic and reconstructive surgery. Our review serves as a safety resource based on the current literature and is aimed at providing best-practice recommendations. Specifically, this article is focused on considerations in the management of craniomaxillofacial trauma as well as reconstructive procedures after head and neck oncologic resection. METHODS Relevant clinical data were obtained from peer-reviewed journal articles, task force recommendations, and published guidelines from multiple medical organizations utilizing data sources including PubMed, Google Scholar, MEDLINE, and Google search queries. Relevant publications were utilized to develop practice guidelines and recommendations. CONCLUSIONS The global COVID-19 pandemic has placed a significant strain on health care resources with resultant impacts on patient care. Surgeons operating in the head and neck are particularly at risk of occupational COVID-19 exposure during diagnostic and therapeutic procedures and must therefore be cognizant of protocols in place to mitigate exposure risk and optimize patient care.


title: Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide.

text: Numerous materials have been developed to try and harness the antimicrobial properties of nitric oxide (NO). However, the short half-life and reactivity of NO have made precise, tunable delivery difficult. As such, conventional methodologies have generally relied on donors that spontaneously release NO at different rates, and delivery profiles have largely been constrained to decaying dynamics. In recent years, the possibility of finely controlling NO release, for instance with light, has become achievable and this raises the question of how delivery dynamics influence therapeutic potential. Here we investigated this relationship using Escherichia coli as a model organism and an approach that incorporated both experimentation and mathematical modeling. We found that the best performing delivery mode was dependent on the NO payload, and developed a mathematical model to quantitatively dissect those observations. Those analyses suggested that the duration of respiratory inhibition was a major determinant of NO-induced growth inhibition. Inspired by this, we constructed a delivery schedule that leveraged that insight to extend the antimicrobial activity of NO far beyond what was achievable by traditional delivery dynamics. Collectively, these data and analyses suggest that the delivery dynamics of NO have a considerable impact on its ability to achieve and maintain bacteriostasis.


title: The Exponentially Increasing Rate of Patients Infected with COVID-19 in Iran.

text: BACKGROUND Coronavirus, the cause of severe acute respiratory syndrome (COVID-19), is rapidly spreading around the world. Since the number of corona positive patients is increasing sharply in Iran, this study aimed to forecast the number of newly infected patients in the coming days in Iran. METHODS The data used in this study were obtained from daily reports of the Iranian Ministry of Health and the datasets provided by the Johns Hopkins University including the number of new infected cases from February 19, 2020 to March 21, 2020. The autoregressive integrated moving average (ARIMA) model was applied to predict the number of patients during the next thirty days. RESULTS The ARIMA model forecasted an exponential increase in the number of newly detected patients. The result of this study also show that if the spreading pattern continues the same as before, the number of daily new cases would be 3574 by April 20. CONCLUSION Since this disease is highly contagious, health politicians need to make decisions to prevent its spread; otherwise, even the most advanced and capable health care systems would face problems for treating all infected patients and a substantial number of deaths will become inevitable.


title: Intraprocedural Safety and Technical Success of the MVP Micro Vascular Plug for Embolization of Pulmonary Arteriovenous Malformations.

text: This case series describes early experience, intraprocedural safety, and technical success of the MVP Micro Vascular Plug (MVP; Covidien, Irvine, California) for embolization of 20 pulmonary arteriovenous malformations (PAVMs) using 23 plugs in seven patients with hereditary hemorrhagic telangiectasia. There was no device migration, and all devices were successfully detached electrolytically. Immediate cessation of flow through the feeding artery was achieved in 21 of 23 (91%) deployments. There was one minor complication. This series demonstrates the MVP to be safe and technically successful in the treatment of PAVMs.


docid: oielratx

title: Obesity a Risk Factor for Severe COVID-19 Infection: Multiple Potential Mechanisms.


title: Process for developing evidence-informed practice recommendations: venous leg ulcer example.

text: PURPOSE To provide the wound care practitioner with an overview of the search process for venous leg ulcer clinical practice guidelines and appraisal of their quality applying the Appraisal of Guideline Research and Evaluation (AGREE) Instrument. TARGET AUDIENCE This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES After reading this article and taking this test, the reader should be able to: 1. Describe the process used to identify and review current wound care guidelines. 2. Describe how the AGREE Instrument evaluates the methodological quality of practice guidelines.


Will COVID-19 pandemic-associated lockdown increase myopia in Indian children?


title: Flexor tendon healing within the tendon sheath using bioabsorbable poly-L/D-lactide 96/4 suture. A histological in vivo study with rabbits.

text: The bioabsorbable poly-L/D-lactide (PLDLA) 96/4 suture has good biomechanical and knot properties, and sufficient tensile strength half-life for flexor tendon repair. In the present study, the biocompatibility of PLDLA suture was compared with that of coated braided polyester suture in the rabbit flexor digitorum profundus tendon repaired within the tendon sheath. Postoperative unrestricted active mobilization was allowed. The tendons were studied histologically after 1-, 3-, 6-, 12-, 26-, and 52-week follow-ups. No differences were found in the biocompatibility between the suture materials, with only scattered multinuclear giant cells near the sutures in both groups from 6 weeks onwards. At 52 weeks, most of the PLDLA material was absorbed and the histological structure of the tendon appeared normal, whereas in the polyester repairs the suture knots filled the repair site, causing bulking of the tendon surface, and the collagen alignment appeared disoriented. The results suggest that the PLDLA 96/4 is a suitable suture material for flexor tendon repair.


title: Rapid construction of sigmoid bladder augmentation using absorbable staples: long-term results and comparison to standard colocystoplasty in children with neurogenic bladder.

text: OBJECTIVE Absorbable staples facilitate detubularization and reconfiguration of the bowel when performing augmentation colocystoplasty. We compared the outcomes of stapled sigmoid augmentation with standard sutured colocystoplasty. MATERIALS AND METHODS Between 2003 and 2011, 108 children underwent bladder augmentation at our institution. Colocystoplasty was used in 30 patients (27.8%). Medical charts of children who underwent stapled (n = 8) or sutured (n = 22) sigmoid augmentation were compared with regard to patient demographics and surgical complications, including anastomotic leak and urolithiasis. RESULTS Eight children with underwent stapled sigmoid colocystoplasty. Average age at surgery was 8 years (range 4-17 years). Time to detubularize and refashion the bowel segment prior to augmentation was consistently under 5 min. Average length of follow-up was 44 months (range 12-80 months). One patient experienced anastomotic leak. Two of eight children (25%) in the stapled anastomosis cohort developed bladder stones. Twenty-two patients underwent standard sigmoid augmentation during the same time period (average age 8.2 years; range 4-16 years). One of 22 (4.5%) experienced anastomotic leak. Seven of 22 (31.8%) developed cystolithiasis. CONCLUSIONS Complications from stapled sigmoid anastomosis are similar to those from standard colocystoplasty. Use of absorbable staples decreases operating time by avoiding bowel spatulation and suturing, and should be considered in pediatric patients undergoing colocystoplasty.


Is regulation preventing the development of therapeutics that may prevent future coronavirus pandemics?


Repurposing a Pediatric ICU for Adults.


title: Low sensitivity of a-defensin (Synovasure) test for intra-operative exclusion of prosthetic joint infection.

text: Background and purpose - The Synovasure lateral flow test was developed as a rapid test for the detection or exclusion of periprosthetic joint infection (PJI). 3 studies have reported promising results on its diagnostic value in total joint revision surgery. We aimed to assess the sensitivity and specificity of the Synovasure test to exclude infection in patients undergoing revision surgery for suspected early aseptic loosening of a total hip or knee arthroplasty. Patients and methods - In a prospective study design, 37 patients who underwent revision surgery for suspected early aseptic loosening (< 3 years after primary arthroplasty) were included. The Synovasure test was used intraoperatively to confirm the aseptic nature of the loosening and 6 tissue cultures were obtained in all cases. Exclusion criteria were patients with a preoperatively confirmed PJI, acute revisions (< 90 days after primary arthroplasty) and cases with malpositioning, wear, or instability of the prosthesis. Results - 5 of the 37 patients were diagnosed with a PJI based on the intraoperative tissue cultures. In only 1 out of these 5 cases this was confirmed by the intraoperative Synovasure test. No tests were falsely positive. Interpretation - In this case series the Synovasure lateral flow test had a low sensitivity to exclude PJI in patients with suspected aseptic loosening. The role of the Synovasure lateral flow test in the intraoperative exclusion of PJI during revision surgery for suspected early aseptic loosening appears to be more limited than previously indicated.


Coronavirus disease 2019 pandemic: Do not forget patients with severe mental illness.


title: Synthetically derived bat influenza A-like viruses reveal a cell type- but not species-specific tropism.

text: Two novel influenza A-like viral genome sequences have recently been identified in Central and South American fruit bats and provisionally designated "HL17NL10" and "HL18NL11." All efforts to isolate infectious virus from bats or to generate these viruses by reverse genetics have failed to date. Recombinant vesicular stomatitis virus (VSV) encoding the hemagglutinin-like envelope glycoproteins HL17 or HL18 in place of the VSV glycoprotein were generated to identify cell lines that are susceptible to bat influenza A-like virus entry. More than 30 cell lines derived from various species were screened but only a few cell lines were found to be susceptible, including Madin-Darby canine kidney type II (MDCK II) cells. The identification of cell lines susceptible to VSV chimeras allowed us to recover recombinant HL17NL10 and HL18NL11 viruses from synthetic DNA. Both influenza A-like viruses established a productive infection in MDCK II cells; however, HL18NL11 replicated more efficiently than HL17NL10 in this cell line. Unlike conventional influenza A viruses, bat influenza A-like viruses started the infection preferentially at the basolateral membrane of polarized MDCK II cells; however, similar to conventional influenza A viruses, bat influenza A-like viruses were released primarily from the apical site. The ability of HL18NL11 or HL17NL10 viruses to infect canine and human cells might reflect a zoonotic potential of these recently identified bat viruses.


title: Time, distance, shielding and ALARA; drawing similarities between measures for radiation protection and Coronavirus disease pandemic response.

text: The practice of radiation oncology requires stringent adherence to specific steps and principles designed to minimize exposure of an individual to unnecessary doses of radiation. The basic principles of such measures to reduce the risk of exposure and limit the doses of irradiation follow the "as low as reasonably achievable " or ALARA principle by using the concepts of time, distance and shielding. Potential exposures in radiation oncology are controlled through combination of optimal design and installation of radiation delivery equipment with well-defined standard operating procedures (SOPs). In the modern era of viral pandemics, similar principles can also be applied toward prevention of viral transmission and protection of populations at risk. In the ongoing COVID-19 pandemic, the probability of an individual getting infected is dependent on the viral load that an individual is exposed to in public spaces over a period of time. All prevention and control measures are based on preventing any such exposure to the virus, that can be achieved through limiting space for movement of the virus, using barriers and increasing distance to vulnerable surfaces, and limiting the duration of exposure. Apart from adhering to the laid-down provisions of a lock-down, preventive measures recommended for the general public include maintaining hand-hygiene, social distancing, and using facemasks to break the chain of transmission. Appropriate triage and customization of treatment protocols can help curtail hospital visits and time-spent by cancer patients during pandemic times, thereby reducing their risk of exposure as well as allowing efficient utilization of resources. The outbreak of the contagious COVID-19 pandemic threatens to disrupt healthcare systems globally with its unprecedented challenges. However, despite all the difficulties and hardships, it has also enabled new ways of learning and communication, which are likely to persist even in the post-COVID world.


title: Seroprevalence of Middle East Respiratory Syndrome Corona Virus in dromedaries and their traders in upper Egypt.

text: INTRODUCTION Camel trade in Egypt depends mainly on importation. Seemingly healthy imported camels are responsible for the ingress of serious diseases into Egypt. A striking example of this concerning public health globally is the Middle East respiratory coronavirus (MERS-CoV) which causes case fatalities of over 34%. Here, we determined the seroepidemiological situation of the MERS-CoV in imported camels and their traders in Upper Egypt. METHODOLOGY Sera of sixty-three dromedaries and twenty-eight camel traders were recruited (January 2015-December 2016). The age, gender, and sampling locality of each sampled camel and human were obtained. Semi-quantitative anti-MERS-CoV IgG ELISAs which utilize the purified spike protein domain S1 antigen of MERS coronavirus (MERS-CoV S1) were used to detect specific IgG antibodies against the virus. RESULTS The data showed that 58.73% of imported camels and 25% of traders had antibodies specific to MERS-CoV. Interestingly, like seroreactive camels, all seropositive humans were apparently healthy without any history of developing severe respiratory disease in the 14 days prior to sampling. Having specific antibodies among the examined camel sera was significantly different (P < 0.0001) in relation to various sampling localities, gender and age groups. In contrast, the seropositivity rate of MERS-CoV IgG in humans did not differ significantly by any of the studied factors. CONCLUSIONS The current study provides the first serological evidence of occupational exposure of humans to MERS-CoV in Africa. Additionally, it reports that imported camels could be implicated in introducing MERS-CoV into Egypt. Accordingly, application of strict control measures to camel importation is a priority.


title: The Tensile Strength of Full-Thickness Skin: A Laboratory Study Prior to Its Use as Reinforcement in Parastomal Hernia Repair.

text: Purpose: Parastomal hernia is a common complication of an enterostoma. Current methods of repair have high recurrence rates and are associated with severe complications. Autologous full-thickness skin as reinforcement may reduce the recurrence and complication rates. This study aims to investigates the tensile strength of full-thickness skin; information that is essential if we are to proceed with clinical trials on humans. Methods: Full-thickness skin samples from 12 donors were tested for tensile strength, as well as the load tolerated by a suture through the skin. Strips of skin were cut out and stretched until breaking point. Sutures were made through skin samples and traction applied until either the tissue or the suture gave way. All done while recording the forces applied using a dynamometer. Identical tests were carried out on commercially available synthetic and biologic graft material for comparison. Results: The full-thickness skin strips had a median tensile strength of 604 N/cm. This tensile strength was significantly higher than that of the compared materials evaluated in this study. In full-thickness skin, the suture, or tissue endured a median force of 67 N before giving way, which was as high as, or higher than similar sutures through the compared materials. Conclusions: The tensile strength of full-thickness skin vastly exceeds the physiological forces affecting the abdominal wall, and sutures through skin endure high loads before giving way. The tensile strength of a full-thickness skin graft and the strength of sutures through this material will not limit its use for reinforcement in parastomal hernia repair.


title: Laparoendoscopic single site nephrectomy with the SPIDER surgical system: engineering advancements tested in a porcine model.

text: UNLABELLED Abstract Background and Purpose: The Single Port Instrument Delivery Extended Reach (SPIDER) surgical system was developed for true continuous instrument triangulation during laparoendoscopic single site (LESS) surgery. We present our initial preclinical experience with the SPIDER surgical system during renal surgery. MATERIAL AND METHODS Bilateral laparoscopic nephrectomies were performed in a live adult porcine animal model using the SPIDER device. A standard surgical approach was used via direct video guidance. RESULTS The procedure was successfully performed without surgical error or complication. The SPIDER system proved easy to use with only a minimal learning curve. Intracorporeal surgical knots were tied without difficulty using this single site system. CONCLUSIONS Our initial experience with the SPIDER surgical system during renal surgery is promising. SPIDER allows for true single port instrument triangulation offering a superior operative experience to currently available LESS surgical systems.


title: Giant Intracranial Aneurysms: Surgical Treatment and Analysis of Risk Factors.

text: OBJECTIVE To study clinical outcome of giant intracranial aneurysms (diameter ≥25 mm) treated with different surgical modalities and to analyze factors affecting prognosis. METHODS A retrospective analysis was performed of 204 consecutive patients with giant intracranial aneurysms who underwent surgical treatment in our department from 1995 to 2008. Clinical outcome was evaluated with the Glasgow Outcome Scale. RESULTS Surgical modalities included direct aneurysm neck clipping in 102 patients (50.0%), parent artery reconstruction in 51 patients (25.0%), proximal artery ligation in 23 patients (11.3%; 4 patients combined with revascularization), trapping in 26 patients (12.7%), and wrapping in 2 patients (1.0%). Follow-up data were available for 181 patients (88.7%), with a mean follow-up period of 62 months (range, 12-164 months). A good outcome (Glasgow Outcome Scale score 5) was observed in 114 patients (63.0%), and a poor outcome (Glasgow Outcome Scale score 1-4) was observed in 67 patients (37.0%). Independent factors that affected prognosis were age and location of aneurysm. Older age (≥50 years) and location of aneurysm in posterior circulation were associated with poor outcome. In 85 patients with preoperative subarachnoid hemorrhage, patients with a higher Hunt and Hess grade (≥3) had a worse outcome compared with patients with a low Hunt and Hess grade (1 or 2). Surgical modalities and other factors were not significantly associated with clinical outcome. CONCLUSIONS Giant intracranial aneurysms are effectively treated with craniotomy and surgical treatment. Older age, aneurysm location in posterior circulation, and higher Hunt and Hess grade are risk factors affecting prognosis.


title: Reviewing the anaerobic digestion and co-digestion process of food waste from the perspectives on biogas production performance and environmental impacts.

text: In this paper, factors that affect biogas production in the anaerobic digestion (AD) and anaerobic co-digestion (coAD) processes of food waste are reviewed with the aim to improve biogas production performance. These factors include the composition of substrates in food waste coAD as well as pre-treatment methods and anaerobic reactor system designs in both food waste AD and coAD. Due to the characteristics of the substrates used, the biogas production performance varies as different effects are exhibited on nutrient balance, inhibitory substance dilution, and trace metal element supplement. Various types of pre-treatment methods such as mechanical, chemical, thermal, and biological methods are discussed to improve the rate-limiting hydrolytic step in the digestion processes. The operation parameters of a reactor system are also reviewed with consideration of the characteristics of the substrates. Since the environmental awareness and concerns for waste management systems have been increasing, this paper also addresses possible environmental impacts of AD and coAD in food waste treatment and recommends feasible methods to reduce the impacts. In addition, uncertainties in the life cycle assessment (LCA) studies are also discussed.


title: Accuracy of delivered airway pressure and work of breathing estimation during proportional assist ventilation: a bench study.

text: BACKGROUND Proportional assist ventilation+ (PAV+) delivers airway pressure (P aw) in proportion to patient effort (P mus) by using the equation of motion of the respiratory system. PAV+ calculates automatically respiratory mechanics (elastance and resistance); the work of breathing (WOB) is estimated by the ventilator. The accuracy of P mus estimation and hence accuracy of the delivered P aw and WOB calculation have not been assessed. This study aimed at assessing the accuracy of delivered P aw and calculated WOB by PAV+ and examining the factors influencing this accuracy. METHODS Using an active lung model with different respiratory mechanics, we compared (1) the actual delivered P aw by the ventilator to the theoretical P aw as defined by the equation of motion and (2) the WOB value displayed by the ventilator to the WOB measured from a Campbell diagram. RESULTS Irrespective of respiratory mechanics and gain, the ventilator provided a P aw approximately 25 % lower than expected. This underassistance was greatest at the beginning of the inspiration. Intrinsic PEEP (PEEPi), associated with an increase in trigger delay, was a major factor affecting PAV+ accuracy. The absolute value of total WOB displayed by the ventilator was underestimated, but the changes in WOB were accurately detected by the ventilator. CONCLUSION The assistance provided by PAV+ well follows P mus but with a constant underassistance. This is associated with an underestimation by the ventilator of the WOB. PEEPi can be a major factor contributing to PAV+ inaccuracy. Clinical recommendations should include using a high trigger sensitivity and a careful PEEP titration.


title: Fluctuations in Spinal Cord Perfusion During Adult Spinal Deformity Correction Identify Neurologic Changes: Proof of Concept.

text: INTRODUCTION Adult spinal deformity (ASD) surgery carries the risk of spinal cord injury. Spinal cord ischemia is often implicated in the pathogenesis but has not been directly investigated. Here we present our index case as a proof of concept for a study evaluating the role of spinal cord perfusion (SCP) changes in ASD correction. METHODS ASD surgery was performed in the usual fashion with the addition of 1) SCP monitoring, using laser Doppler probe fixated to the dura at the level of the pedicle subtraction osteotomy (PSO) and 2) intrathecal pressure monitoring, using a lumbar drain. Somatosensory evoked potential (SSEP) and motor evoked potential (MEP) were monitored throughout the case. RESULTS An 84-year-old male with kyphoscoliosis and progressive myelopathy causing diminished motor and sensory function was treated with T4 PSO and long segment reconstruction. At baseline, SSEP signals were detectable in all 4 extremities, MEP signals were present in the right foot only, intrathecal pressure was 4 mm Hg, and mean SCP was 21.2 perfusion units. The osteotomy was performed and reduced in 2 steps. After the first step of reduction, MEP signals appeared in the left leg and increased in amplitude in the right leg, and SCP simultaneously increased to 205.6. Further reduction led to MEP signal loss in both legs and decrease in SCP to 39.2. With partial reversal of the reduction, MEP signals returned in both legs and SCP improved to 76.0. Final reduction maneuvers were then performed in a delayed fashion before closure, with stable MEP signals and a final SCP of 42.9. SSEP signals, vital signs, and intrathecal pressure were stable throughout the case. Postoperatively the patient was neurologically stable. CONCLUSIONS The present case provides the first direct evidence that fluctuations in SCP may contribute to neurologic changes during ASD surgery. Further investigation is under way to further elucidate the underlying mechanisms, with the ultimate goal of developing targeted strategies for spinal cord protection during these high-risk cases.


Climate change. What drives climate flip-flops?


title: Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial 'in hibernation', ready for rapid activation.

text: BACKGROUND There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in influenza found an association with increased mortality but there were important concerns regarding the risks of bias. OBJECTIVES To (1) evaluate whether or not low-dose corticosteroids given as an adjunct to standard treatment is beneficial in patients who are hospitalised with severe pandemic influenza and (2) develop an 'off-the-shelf' clinical trial that is ready to be activated in a future pandemic. DESIGN Multicentre, pragmatic, blinded, randomised placebo-controlled trial. SETTING Thirty to 40 hospitals in the UK. PARTICIPANTS Adults (≥ 16 years) admitted to hospital with an influenza-like illness during a pandemic. INTERVENTION Five-day course of dexamethasone (Dexsol®, Rosemont Pharmaceuticals Ltd) 6 mg daily, started within 24 hours of admission. MAIN OUTCOME MEASURE Admission to Intensive Care Unit, or death, within 30 days of admission to hospital. RESULTS This trial has not yet been activated. It is currently set up with full ethics and regulatory approvals in place, ready for rapid activation at the onset of the next pandemic. Hurdles to setting up a pandemic trial include planning for pandemic-level pressures on UK NHS resources and co-enrolment of patients to multiple pandemic studies, ensuring adequate geographical distribution of participating sites, maintaining long-term low-level engagement with site investigators, addressing future trial-specific training needs of local investigators and resilience planning in trial management. Identified threats to trial delivery include changes to research capabilities or policies during the hibernation phase, lack of staff resources during a pandemic and the influence of media at the time of a pandemic. A mismatch in the approach to informed consent required by current regulations to that preferred by patients and the public was identified. CONCLUSIONS This study demonstrates that advance set-up of a trial to be conducted during a pandemic, with full regulatory approvals in place, is possible. Regular review during the hibernation phase will be required. This study serves as a model for the development of other 'off-the-shelf' trials as part of preparedness planning for public health emergencies. TRIAL REGISTRATION Current Controlled Trials ISRCTN72331452. European Union Drug Regulating Authorities Clinical Trials number: 2013-001051-12. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 16. See the NIHR Journals Library website for further project information.


title: Brief interventions for cannabis use in emerging adults: protocol for a systematic review, meta-analysis, and evidence map.

text: BACKGROUND Rates of cannabis use are highest during emerging adulthood (age 18-25), with the prevalence of near daily and daily increasing among this age group. Emerging adults are clinically challenging in terms of harmful cannabis use due to perceptions of high rates of peer use, social acceptance, and low risk of harm. Brief interventions to increase awareness and promote motivation to change are therefore particularly important for this age group. There is existing evidence on the effectiveness of brief interventions for alcohol in emerging adults, but it is not clear if comparable evidence is present for cannabis. The objective of this systematic review is to summarize and critically appraise the existing literature of brief interventions for cannabis use both narratively, to describe the content and delivery of existing interventions, and meta-analytically, to determine the aggregated efficacy of these interventions on cannabis use and other outcomes (e.g., other substance use, mental health, help-seeking behaviors, and academic and occupational outcomes). METHODS A systematic search of randomized controlled trials, quasi-experimental trials, and pre-post designs will be conducted in the following electronic databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO. Ongoing trials will be identified using the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov , and Current Controlled Trials. Unpublished trials will be identified using Proquest Dissertations, OpenGrey, Google Scholar, and brief interventions on the Substance Abuse and Mental Health Services Administration webpage. Two authors will independently screen and extract data from articles using a predetermined screening and extraction forms (which will include risk of bias assessments). Calibration exercises will be performed prior to full screening and extraction. Disagreements will be resolved through discussion or consultation with a third reviewer. All studies will be reported narratively, and if appropriate, we will perform random effects meta-analyses with subgroup analyses and meta-regression. DISCUSSION Results of this review are expected to provide guidance on the content, delivery methods, and effectiveness of brief interventions for cannabis use to assist post-secondary institutions in identifying brief intervention strategies to implement prior to or in response to legalization. SYSTEMATIC REVIEW REGISTRATION CRD42018085412.


Corrections regarding endotherapy for Barrett's esophagus.


European Federation for Colposcopy (EFC) and European Society of Gynaecological Oncology (ESGO) joint considerations about human papillomavirus (HPV) vaccination, screening programs, colposcopy, and surgery during and after the COVID-19 pandemic.


docid: nwtjhajl

title: Murine Hepatitis Virus nsp14 Exoribonuclease Activity Is Required for Resistance to Innate Immunity.

text: Coronaviruses (CoVs) are positive-sense RNA viruses that infect numerous mammalian and avian species and are capable of causing severe and lethal disease in humans. CoVs encode several innate immune antagonists that counteract the host innate immune response to facilitate efficient viral replication. CoV nonstructural protein 14 (nsp14) encodes 3'-to-5' exoribonuclease activity (ExoN), which performs a proofreading function and is required for high-fidelity replication. Outside of the order Nidovirales, arenaviruses are the only RNA viruses that encode an ExoN, which functions to degrade double-stranded RNA (dsRNA) replication intermediates. In this study, we tested the hypothesis that CoV ExoN also functions to antagonize the innate immune response. We demonstrate that viruses lacking ExoN activity [ExoN(-)] are sensitive to cellular pretreatment with interferon beta (IFN-β) in a dose-dependent manner. In addition, ExoN(-) virus replication was attenuated in wild-type bone marrow-derived macrophages (BMMs) and partially restored in interferon alpha/beta receptor-deficient (IFNAR-/-) BMMs. ExoN(-) virus replication did not result in IFN-β gene expression, and in the presence of an IFN-β-mediated antiviral state, ExoN(-) viral RNA levels were not substantially reduced relative to those of untreated samples. However, ExoN(-) virus generated from IFN-β-pretreated cells had reduced specific infectivity and decreased relative fitness, suggesting that ExoN(-) virus generated during an antiviral state is less viable to establish a subsequent infection. Overall, our data suggest murine hepatitis virus (MHV) ExoN activity is required for resistance to the innate immune response, and antiviral mechanisms affecting the viral RNA sequence and/or an RNA modification act on viruses lacking ExoN activity.IMPORTANCE CoVs encode multiple antagonists that prevent or disrupt an efficient innate immune response. Additionally, no specific antiviral therapies or vaccines currently exist for human CoV infections. Therefore, the study of CoV innate immune antagonists is essential for understanding how CoVs overcome host defenses and to maximize potential therapeutic interventions. Here, we sought to determine the contributions of nsp14 ExoN activity in the induction of and resistance to the innate immune response. We show that viruses lacking nsp14 ExoN activity are more sensitive than wild-type MHV to restriction by exogenous IFN-β and that viruses produced in the presence of an antiviral state are less capable of establishing a subsequent viral infection. Our results support the hypothesis that murine hepatitis virus ExoN activity is required for resistance to the innate immune response.


title: Toward nephrogenesis in the pig kidney: the composite tubulo-glomerular nodule.

text: BACKGROUND Significant differences regarding nephrogenesis and its completion among different animal species have been reported. Since many informations on clinical conditions (i.e. asphyxia, drugs) are extrapolated from piglets, this study aimed at analyzing nephrogenesis in piglets, in order to compare it with existing data on nephrogenesis in humans. METHODS Six male newborn piglets were subjected to euthanasia and their kidneys were harvested. Necropsy revealed no injury and no underlying pathology in any of the animals used in the experiment. RESULTS The analysis of the renal cortex evidenced in all the animals studied the presence of active nephrogenesis. The sequence of events identified during porcine nephrogenesis was characterized by the appearance, in the metanephric mesenchyme, of nodules undergoing mesenchymal-epithelial transition originating a specific picture that we named the tubulo-glomerular nodule. This peculiar developmental structure gives rise to the precursor of tubular and glomerular structures, till the extrusion of developing glomeruli that progressively migrate toward the mid and deep cortex. CONCLUSIONS Nephrogenesis in pig is characterized by a peculiar morphological event, with marked differences compared with humans. These informations should be taken into account when the experimental data in piglets are extrapolated to humans, especially for clinical purposes.


title: Randomized trials of endovascular therapy for stroke--impact on stroke care.

text: Five trials that investigated the efficacy of modern endovascular therapies for stroke--MR CLEAN, ESCAPE, SWIFT PRIME, EXTEND IA and REVASCAT--have been published within the past year, changing the landscape of acute stroke management. The trials used a variety of imaging modalities and combinations of treatment approaches, including the mandatory use of intravenous thrombolysis before the initiation of endovascular therapy. All five trials provided strong evidence to support the use of thrombectomy that is initiated within 6 h of stroke onset, prompting worldwide changes in the guidelines for management of acute stroke by endovascular treatment. The benefits of endovascular therapy were observed irrespective of a patient's age, their NIH Stroke Scale score, or whether they received intravenous thrombolysis. In this article, we review the main findings of these recent trials, focusing on key aspects of their designs, and discuss their impact on the future management of patients with acute stroke that results from large-vessel occlusion. We discuss the values of noncontrast CT ASPECTS, perfusion imaging and angiography for selecting patients to receive endovascular interventions. We also consider the role of thrombectomy beyond 6 h after stroke onset, and in patients with posterior circulation strokes.


docid: wwcpfrqf

title: COVID-19 as an occupational disease?


Covid-19 infection in Crohn's disease under treatment with adalimumab.


title: Synthesis and absolute configuration of novel N,O-psiconucleosides using (R)-N-phenylpantolactam as a resolution agent.

text: A series of novel N,O-psiconucleosides has been prepared in both enantiomeric forms by resolution of an advanced racemic synthetic intermediate using (R)-N-phenylpantolactam as a chiral resolution agent. The absolute configuration of all of these compounds has been unequivocally established by chemical correlation with the novel (R)- or (S)-1-methyl-5-phenylpyrrolidine-2,3-dione, prepared from the known (R)- and (S)-1-methyl-5-phenylpyrrolidin-2-one, respectively.


docid: eamctnik

title: A chemotype that inhibits three unrelated pathogenic targets: the botulinum neurotoxin serotype A light chain, P. falciparum malaria, and the Ebola filovirus.

text: A 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure-activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinoline-based antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum and, in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting β-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities.


Covid-19: medical schools given powers to graduate final year students early to help NHS.


docid: rlpqojjp

title: Covid-19: Medical conferences around the world are cancelled after US cases are linked to Massachusetts meeting.


title: Membrane-shaping host reticulon proteins play crucial roles in viral RNA replication compartment formation and function.

text: Positive-strand RNA viruses replicate their genomes on membranes with virus-induced rearrangements such as single- or double-membrane vesicles, but the mechanisms of such rearrangements, including the role of host proteins, are poorly understood. Brome mosaic virus (BMV) RNA synthesis occurs in ≈70 nm, negatively curved endoplasmic reticulum (ER) membrane invaginations induced by multifunctional BMV protein 1a. We show that BMV RNA replication is inhibited 80-90% by deleting the reticulon homology proteins (RHPs), a family of membrane-shaping proteins that normally induce and stabilize positively curved peripheral ER membrane tubules. In RHP-depleted cells, 1a localized normally to perinuclear ER membranes and recruited the BMV 2a(pol) polymerase. However, 1a failed to induce ER replication compartments or to recruit viral RNA templates. Partial RHP depletion allowed formation of functional replication vesicles but reduced their diameter by 30-50%. RHPs coimmunoprecipitated with 1a and 1a expression redirected >50% of RHPs from peripheral ER tubules to the interior of BMV-induced RNA replication compartments on perinuclear ER. Moreover, RHP-GFP fusions retained 1a interaction but shifted 1a-induced membrane rearrangements from normal vesicles to double membrane layers, a phenotype also induced by excess 1a-interacting 2a(pol). Thus, RHPs interact with 1a, are incorporated into RNA replication compartments, and are required for multiple 1a functions in replication compartment formation and function. The results suggest possible RHP roles in the bodies and necks of replication vesicles.


title: The impact of postoperative complications on the recovery of elderly surgical patients.

text: BACKGROUND While the negative impact of postoperative complications on hospital costs, survival, and cancer recurrence is well known, few studies have quantified the impact of postoperative complications on patient-centered outcomes such as functional status. The objective of this study was to estimate the impact of postoperative complications on recovery of functional status after elective abdominal surgery in elderly patients. METHODS Elderly patients (70 years and older) undergoing elective abdominal surgery, with a planned length of stay >1 day, were prospectively enrolled between July 2012 and December 2014. The primary outcome was time to recovery to the preoperative functional status measured by the short physical performance battery (SPPB) preoperatively and at 1 week, 1, 3, and 6 months after surgery. The comprehensive complication index was calculated to grade the severity and number of postoperative complications. A Weibull survival model with interval censoring was performed, controlling for age, sex, body mass index (BMI), comorbidities (Charlson comorbidity index-CCI), frailty, presence of cancer, nutritional status, wound class, preoperative functional status, and surgical approach. RESULTS Hundred and forty-nine patients (79 men and 70 women) were included in the analysis. Mean age was 77.7 ± 4.9 years, mean BMI was 27.2 ± 5.5 kg/m(2), and the median CCI was 3 (IQR 2-6). The mean preoperative SPPB score was 9.62 ± 2.33. A total of 52 patients (34.9 %) experienced one or more postoperative complications, including four mortalities, and a total of 72 complications. The mean comprehensive complication index score for these patients was 25.7 ± 23.8. In the presence of all other variables included in the model, a higher comprehensive complication index score was found to significantly decrease the hazard of recovery (HR 0.96, CI 0.94-0.98, p value = 0.0004) and hence increase the time to recovery. CONCLUSION Following elective abdominal surgery, elderly patients who experience a greater number and more severe postoperative complications take longer to return to their preoperative functional status.


title: Protection of forensic scene investigation and postmortem examination during the epidemic period of COVID-19.

text: Abstract


title: ACE2/ANG-(1-7)/Mas pathway in the brain: the axis of good.

text: The last decade has seen the discovery of several new components of the renin-angiotensin system (RAS). Among them, angiotensin converting enzyme-2 (ACE2) and the Mas receptor have forced a reevaluation of the original cascade and led to the emergence of a new arm of the RAS: the ACE2/ANG-(1-7)/Mas axis. Accordingly, the new system is now seen as a balance between a provasoconstrictor, profibrotic, progrowth axis (ACE/ANG-II/AT(1) receptor) and a provasodilatory, antifibrotic, antigrowth arm (ACE2/ANG-(1-7)/Mas receptor). Already, this simplistic vision is evolving and new components are branching out upstream [ANG-(1-12) and (pro)renin receptor] and downstream (angiotensin-IV and other angiotensin peptides) of the classical cascade. In this review, we will summarize the role of the ACE2/ANG-(1-7)/Mas receptor, focusing on the central nervous system with respect to cardiovascular diseases such as hypertension, chronic heart failure, and stroke, as well as neurological diseases. In addition, we will discuss the new pharmacological (antagonists, agonists, activators) and genomic (knockout and transgenic animals) tools that are currently available. Finally, we will review the latest data regarding the various signaling pathways downstream of the Mas receptor.