title: Characterization of intestinal Escherichia coli isolated from calves with diarrhea due to rotavirus and coronavirus.

text: PURPOSE To address more information about changes in commensal Escherichia coli during virus intestinal infection, we characterized 30 faecal E. coli isolates from calves (21 to 60 days old) with diarrhea due to rotavirus and coronavirus, which received, before diagnosis, tetracycline, gentamicin and enrofloxacin drugs. METHODOLOGY Clermont's phylogenetic classification; presence of genes for curli, cellulose, fimbriae (F4, F5, F6, F18, F41); and antimicrobial susceptibility were used to characterize the isolates. Disk diffusion technique and PCR were used as methodologies. RESULTS E. coli isolates from calves with diarrhea were phylogenetically classified as B1 (70%, 21/30), B2 (3.33%, 1/30), C (3.33%, 1/30), D (3.33%, 1/30), E (13.33%, 4/30) and unknown (6.7 %; 2/30), whereas E. coli isolates from the control group were classified only as B1 (83.3%, 25/30), E (10 %; 3/30) and unknown (6,7 %; 2/30). E. coli isolates from calves with diarrhea showed a much higher resistance profile with 16 (53.3%) multiresistant isolates. Only isolates (30%-9/30) from diarrheic calves were also positive for fimbriae, specifically 16.7% (5/30) for F5 and 13.3% (4/30) for F18. CONCLUSION To sum up, E. coli isolates from calves with diarrhea showed differences in relation to the control group, confirming changes in commensal E. coli during virus intestinal infection. It can be emphasized that some care should be taken to manage diarrheic calves: the pathological agent must be diagnosed prior to treatment; antibacterial treatment should be with antimicrobials with a different mechanism of action; and finally, treated animals should be maintained separately from others because they can carry micro-organisms with a resistant profile.


title: Analysis of Workflow and Time to Treatment and the Effects on Outcome in Endovascular Treatment of Acute Ischemic Stroke: Results from the SWIFT PRIME Randomized Controlled Trial.

text: Purpose To study the relationship between functional independence and time to reperfusion in the Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial in patients with disabling acute ischemic stroke who underwent endovascular therapy plus intravenous tissue plasminogen activator (tPA) administration versus tPA administration alone and to investigate variables that affect time spent during discrete steps. Materials and Methods Data were analyzed from the SWIFT PRIME trial, a global, multicenter, prospective study in which outcomes were compared in patients treated with intravenous tPA alone or in combination with the Solitaire device (Covidien, Irvine, Calif). Between December 2012 and November 2014, 196 patients were enrolled. The relation between time from (a) symptom onset to reperfusion and (b) imaging to reperfusion and clinical outcome was analyzed, along with patient and health system characteristics that affect discrete steps in patient workflow. Multivariable logistic regression was used to assess relationships between time and outcome; negative binomial regression was used to evaluate effects on workflow. The institutional review board at each site approved the trial. Patients provided written informed consent, or, at select sites, there was an exception from having to acquire explicit informed consent in emergency circumstances. Results In the stent retriever arm of the study, symptom onset to reperfusion time of 150 minutes led to 91% estimated probability of functional independence, which decreased by 10% over the next hour and by 20% with every subsequent hour of delay. Time from arrival at the emergency department to arterial access was 90 minutes (interquartile range, 69-120 minutes), and time to reperfusion was 129 minutes (interquartile range, 108-169 minutes). Patients who initially arrived at a referring facility had longer symptom onset to groin puncture times compared with patients who presented directly to the endovascular-capable center (275 vs 179.5 minutes, P < .001). Conclusion Fast reperfusion leads to improved functional outcome among patients with acute stroke treated with stent retrievers. Detailed attention to workflow with iterative feedback and aggressive time goals may have contributed to efficient workflow environments. (©) RSNA, 2016 Online supplemental material is available for this article.


title: Single-stage nipple-areolar complex reconstruction technique, outcomes, and patient satisfaction.

text: INTRODUCTION Nipple-areolar reconstruction (NAR) is the final phase of breast reconstruction and is associated with increased patient satisfaction. Nipple-areolar reconstruction is typically performed in 2 separate stages, which include nipple reconstruction and tattooing of the nipple-areolar complex (NAC). Previous studies have demonstrated that increased duration of the reconstruction is associated with decreased patient satisfaction. Because a 2-stage reconstruction prolongs the reconstructive process, we introduce a simple and novel method of single-stage NAR (SS NAR), which combines the use of local flaps for nipple reconstruction and medical tattooing of the NAC in 1 session and delivers predictable outcomes with high patient satisfaction. METHODS A retrospective chart review of patients who underwent SS NAR at our institution during the period from September 2010 to May 2012 was performed. Patient demographics, complications, outcomes, and overall patient satisfaction were assessed. A modified questionnaire (Likert scale) was used to assess patient satisfaction of nipple size, color, shape, and projection. RESULTS Twenty-nine SS NARs were performed in 18 patients: 7 unilateral and 11 bilateral. Mean age was 45 years (range, 34-60 years). No major complications were identified. Mean length of follow-up was 10 months (range, 2-22 months). A 17% complication rate was observed: 14% (4/29) had irregular dye uptake of the areola, and 3% (1/29) had dehiscence from silicone guard pressure on the incision. Two patients underwent revisions: one patient underwent additional tattooing, and the other required flap readvancement and implant downsizing secondary to the wound dehiscence. We obtained a 70% survey response rate with 100% of responders who reported that they were "very satisfied" with NAC in each dimension. CONCLUSIONS Our study demonstrates that SS NAR is a safe procedure with reproducible, excellent clinical results and very low complication rates or need for revisions. This method is cost-effective, convenient for the patient, and shortens patient recovery time with high patient satisfaction.


COVID-19, Risk, Fear, and Fall-out.


title: Continual hemodynamic monitoring with a single-use transesophageal echocardiography probe in critically ill patients with shock: a randomized controlled clinical trial.

text: PURPOSE Mortality in circulatory shock is high. Enhanced resolution of shock may improve outcomes. We aim to determine whether adding hemodynamic monitoring with continual transesophageal echocardiography (hTEE) to usual care accelerates resolution of hemodynamic instability. METHODS 550 patients with circulatory shock were randomly assigned to four groups stratified using hTEE (hTEE vs usual care) and assessment frequency (minimum every 4 h vs 8 h). Primary outcome was time to resolution of hemodynamic instability, analyzed as intention-to-treat (ITT) analysis at day 6 and in a predefined secondary analysis at days 3 and 28. RESULTS Of 550 randomized patients, 271 with hTEE and 274 patients with usual care were eligible and included in the ITT analysis. Time to resolution of hemodynamic instability did not differ within the first 6 days [hTEE vs usual care adjusted sub-hazard ratio (SHR) 1.20, 95% confidence interval (CI) 0.98-1.46, p = 0.067]. Time to resolution of hemodynamic instability during the 72 h of hTEE monitoring was shorter in patients with TEE (hTEE vs usual care SHR 1.26, 95% CI 1.02-1.55, p = 0.034). Assessment frequency had no influence. Time to resolution of clinical signs of hypoperfusion, duration of organ support, length of stay and mortality in the intensive care unit and hospital, and mortality at 28 days did not differ between groups. CONCLUSIONS In critically ill patients with shock, hTEE monitoring or hemodynamic assessment frequency did not influence resolution of hemodynamic instability or mortality within the first 6 days. TRIAL REGISTRATION AND STATISTICAL ANALYSIS PLAN ClinicalTrials.gov Identifier: NCT02048566.


title: DNA microarray for detection of gastrointestinal viruses.

text: Gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species, and an additional 5 species were validated using clinical samples. Detection limits of 1 × 10(3) virus particles of Human adenovirus C (HAdV), Human astrovirus (HAstV), and group A Rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased by one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%), and coinfection with more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by Anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), Human enterovirus (HEV) (9.2%), Human parechovirus (1.3%), Sapporo virus (1.3%), and Human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by reverse transcription-PCR (RT-PCR) detection of 5 gastrointestinal viruses. The RT-PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV, and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore, some discrepancies in detection of mixed infections were observed and were addressed by reverse transcription-quantitative PCR (RT-qPCR) of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant virus. The microarray described in this work should help in understanding the etiology of gastroenteritis in humans and animals.


title: Stigma and social participation in Southern India: differences and commonalities among persons affected by leprosy and persons living with HIV/AIDS.

text: Stigma is a common phenomenon worldwide and infectious diseases like HIV/AIDS and leprosy are often associated with high levels of stigma. Several studies have been conducted concerning the effects of stigma and the impact on social participation, but comparative studies are rare. The objective of this study was to identify differences and similarities between HIV/AIDS and leprosy-related stigma. From April till July 2009, 190 questionnaire-based interviews were conducted to assess the levels of internalized stigma (Internalized Stigma of Mental Illness scale), perceived stigma (Explanatory Model Interview Catalogue stigma scale) and social participation (Participation scale) in a cross-sectional sample of people affected by leprosy (PL) and people living with HIV/AIDS (PLHA). Respondents were selected from several hospitals, charity projects and during home visits in Vellore district, Tamil Nadu. Our results showed that both PLHA (n = 95) and leprosy-affected respondents (n = 95) faced a substantial burden of internalized and perceived stigma, with the former reporting a significantly higher level of stigma. As a result, PLHA faced more frequent and also more severe participation restrictions than PL. Especially, restrictions in work-related areas were reported by the majority of the respondents. In conclusion, PLHA faced a significantly higher level of stigma and participation restriction than PL. However, the latter also reported a substantial burden of stigma and participation restrictions. The study suggests that it may be possible to develop joint interventions based on the commonalities found. More research is needed to define these more precisely and to test the effectiveness of such joint interventions in reducing stigma and improving social participation.


title: COVID-19 and human spermatozoa - potential risks for infertility and sexual transmission.

text: The COVID-19 (SARS-CoV-2) virus has created a global pandemic responsible for over 500,000 deaths and untold human and economic suffering. Attention has rightly focused on the respiratory system, because this is where a life-and-death battle is waged between the viral horde and the host's immune system. However, other tissues are also susceptible to viral attack including the kidney, heart and brain. The purpose of this communication is to highlight the evidence that the male reproductive system, particularly spermatozoa, constitute another vulnerable target, raising the possibility that COVID-19 might ultimately induce male infertility and/or facilitate the sexual transmission of this virus, depending on the level of infection.


title: Polybiguanide (PHMB) loaded in PLA scaffolds displaying high hydrophobic, biocompatibility and antibacterial properties.

text: Polyhexamethylenebiguanide hydrochloride (PHMB), a low molecular weight polymer related to chlorohexidine (CHX), is a well-known antibacterial agent. In this study, polylactide (PLA) nanofibers loaded with PHMB were produced by electrospinning to obtain 3D biodegradable scaffolds with antibacterial properties. PLA fibers loaded with CHX were used as control. The electrospun fibers were studied and analyzed by SEM, FTIR, DSC and contact angle measurements. PHMB and CHX release from loaded scaffolds was evaluated, as well as their antibacterial activity and biocompatibility. The results showed that the nanofibers became smoother and their diameter smaller with increasing the amount of loaded PHMB. This feature led to an increase of both surface roughness and hydrophobicity of the scaffold. PHMB release was highly dependent on the hydrophilicity of the medium and differed from that determined for CHX. Lastly, PHMB-loaded PLA scaffolds showed antibacterial properties since they inhibited adhesion and bacterial growth, and exhibited biocompatible characteristics for the adhesion and proliferation of both fibroblast and epithelial cell lines.


title: Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: a multicenter cross-sectional study.

text: OBJECTIVE To clarify the association of clinical and prognostic features with dermatomyositis (DM)-specific autoantibodies (Abs) in adult Japanese patients with DM. DESIGN Retrospective study. SETTING Kanazawa University Graduate School of Medical Science Department of Dermatology and collaborating medical centers. Patients A total of 376 consecutive adult Japanese patients with DM who visited our hospital or collaborating medical centers between 2003 and 2008. MAIN OUTCOME MEASURES Clinical and laboratory characteristics of adult Japanese patients with DM and DM-specific Abs that include Abs against Mi-2, 155/140, and CADM-140. RESULTS In patients with DM, anti-Mi-2, anti-155/140, and anti-CADM-140 were detected in 9 (2%), 25 (7%), and 43 (11%), respectively. These DM-specific Abs were mutually exclusive and were detected in none of 34 patients with polymyositis, 326 with systemic sclerosis, and 97 with systemic lupus erythematosus. Anti-Mi-2 was associated with classical DM without interstitial lung disease or malignancy, whereas anti-155/140 was associated with malignancy. Patients with anti-CADM-140 frequently had clinically amyopathic DM and rapidly progressive interstitial lung disease. Cumulative survival rates were more favorable in patients with anti-Mi-2 compared with those with anti-155/140 or anti-CADM-140 (P < .01 for both comparisons). Nearly all deaths occurred within 1 year after diagnosis in patients with anti-CADM-140. Conclusion Dermatomyositis-specific Abs define clinically distinct subsets and are useful for predicting clinical outcomes in patients with DM.


Simulation applications in emergency medical services.


title: Implementation and strategies to ensure adequate coordination within a Urology Department during the COVID-19 pandemic.

text: PURPOSE to provide an update on the management of a Urology Department during the COVID-19 outbreak, suggesting strategies to optimize assistance to the patients, to implement telemedicine and triage protocols, to define pathways for hospital access, to reduce risk of contagious inside the hospital and to determine the role of residents during the pandemic. MATERIALS AND METHODS In May the 6th 2020 we performed a review of the literature through online search engines (PubMed, Web of Science and Science Direct). We looked at recommendations provided by the EAU and ERUS regarding the management of urological patients during the COVID-19 pandemic. The main aspects of interest were: the definition of deferrable and non-deferrable procedures, Personal Protective Equipment (PPE) and hospital protocols for health care providers, triage, hospitalization and surgery, post-operative care training and residents' activity. A narrative summary of guidelines and current literature for each point of interest was performed. CONCLUSION In the actual Covid-19 scenario, while the number of positive patients globally keep on rising, it is fundamental to embrace a new way to deliver healthcare and to overcome challenges of physical distancing and self-isolation. The use of appropriate PPE, definite pathways to access the hospital, the implementation of telemedicine protocols can represent effective strategies to carry on delivering healthcare.


Single photon emission computed tomography-computed tomography lung perfusion imaging during the COVID-19 pandemic: does nuclear medicine need to reconsider its guidelines?


title: Noninvasive Monitoring of Lesion Size in a Heterologous Mouse Model of Endometriosis.

text: Here, we describe a protocol for the implementation of a heterologous mouse model in which progression of endometriosis can be assessed in real time through noninvasive monitoring of fluorescence emitted by implanted ectopic human endometrial tissue. For this purpose, biopsies of human endometrium are obtained from donor women ongoing oocyte donation. Human endometrial fragments are cultured in the presence of adenoviruses engineered to express cDNA for the reporter fluorescent protein mCherry. Upon visualization, labeled tissues with an optimal rate of fluorescence after infection are subsequently chosen for the implantation in recipient mice. One week prior to the implantation surgery, recipient mice are oophorectomized, and estradiol pellets are placed subcutaneously to sustain the survival and growth of lesions. On the day of surgery mice are anesthetized, and peritoneal cavity accessed through a small (1.5 cm) incision by the linea-alba. Fluorescently labeled implants are tweezed, briefly soaked in glue and attached to the peritoneal layer. Incisions are sutured, and animals left to recover for a couple of days. Fluorescence emitted by endometriotic implants is usually non-invasively monitored every 3 days for 4 weeks with an in vivo imaging system. Variations in the size of endometriotic implants can be estimated in real time by quantification of the mCherry signal and normalization against the initial time-point showing maximal fluorescence intensity. Traditional preclinical rodents of models of endometriosis do not allow non-invasive monitoring of lesion in real time but rather allow evaluation of the effects of drugs assayed at the end point. This protocol allows one to track lesions in real time and is more useful to explore the therapeutic potential of drugs in preclinical models of endometriosis. The main limitation of the model thus generated is that non-invasive monitoring is not possible over long periods of time due to the episomal expression of Ad-virus.


title: A randomized, double-blind study examining the comparative efficacies and safety of inhaled epinephrine and nasal decongestant in hospitalized infants with acute bronchiolitis.

text: Optimal treatment of acute bronchiolitis is currently unclear. In a double-blind study, we found no significant differences between inhaled epinephrine and nasal decongestant in hospitalized infants with acute bronchiolitis regarding length of hospitalization, need for oxygen supplementation, or intravenous fluids and clinical score. Nasal decongestant is as effective as inhaled epinephrine in acute bronchiolitis.


title: [Consideration and suggestions on development of blood transfusion department under the epidemic situation of novel coronavirus pneumonia].

text: 输血一直以来都是临床治疗中必不可少的手段。随着新型冠状病毒肺炎疫情的持续发展，如何做好输血科工作人员的自我防护，如何做好无偿献血志愿者招募工作，如何保障医院正常开展手术，如何保证急救患者的临床用血，如何发挥输血科的相关技术辅助治疗新型冠状病毒肺炎患者，都是目前输血科亟待解决的问题。结合各项政策的发布以及笔者所在医院的输血工作经验，本文对以上问题提出个人建议及思考，希望起到抛砖引玉的作用，以期更好地发挥输血医学特长，为进一步做好预防工作，切实保障血液安全供应做好充分的工作。.


title: A unique pathology associated with pelvic pain and adnexal mass.

text: OBJECTIVE To present a unique case of pelvic pain. DESIGN Case report. SETTING Academic institution. PATIENT(S) Thirty-nine year-old with history of endometriosis presented with pelvic pain and possible adnexal mass. INTERVENTION(S) Imaging results were not consistent and suggested possible adnexal mass and hydrosalpinx in different studies. Physical exam was concerning for a vaginal mass that was felt not to be contiguous with the adnexa. At laparoscopy, a 3 cm pararectal mass was identified immediately lateral to the uterosacral ligament and medial to the ureter. This mass was completely resected laparoscopically. MAIN OUTCOME MEASURE(S) Resolution of pelvic pain. RESULT(S) Pathologic diagnosis was ganglioneuroma. Postoperatively, the patient had resolution of her pelvic pain. CONCLUSION(S) Pelvic ganglioneuromas are a very rare entity but emphasize the importance of a broad differential for pelvic pain.


title: Surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults.

text: BACKGROUND & AIMS Visceral adipose tissue (VAT) is an important risk factor for the metabolic complications associated with obesity. Therefore, a reduction in VAT is considered an important target of obesity therapy. We evaluated whether reducing VAT mass by surgical removal of the omentum improves insulin sensitivity and metabolic function in obese patients. METHODS We conducted a 12-month randomized controlled trial to determine whether reducing VAT by omentectomy in 22 obese subjects increased their improvement following Roux-en-Y gastric bypass (RYGB) surgery in hepatic and skeletal muscle sensitivity to insulin study 1. Improvement was assessed by using the hyperinsulinemic-euglycemic clamp technique. We also performed a 3-month, longitudinal, single-arm study to determine whether laparoscopic omentectomy alone, in 7 obese subjects with type 2 diabetes mellitus (T2DM), improved insulin sensitivity study 2. Improvement was assessed by using the Frequently Sampled Intravenous Glucose Tolerance Test. RESULTS The greater omentum, which weighed 0.82 kg (95% confidence interval: 0.67-0.97), was removed from subjects who had omentectomy in both studies. In study 1, there was an approximate 2-fold increase in muscle insulin sensitivity (relative increase in glucose disposal during insulin infusion) and a 4-fold increase in hepatic insulin sensitivity 12 months after RYGB alone and RYGB plus omentectomy, compared with baseline values (P<.001). There were no significant differences between groups (P>.87) or group x time interactions (P>.36). In study 2, surgery had no effect on insulin sensitivity (P=.844) or use of diabetes medications. CONCLUSIONS These results demonstrate that decreasing VAT through omentectomy, alone or in combination with RYGB surgery, does not improve metabolic function in obese patients.


title: A systematic N-terminal peptide quantitative labeling strategy for differential proteomic analysis.

text: PURPOSE The purpose of this study is to develop a new systematic strategy for differential proteomic analysis. EXPERIMENTAL DESIGN The new systematic strategy was developed by coupling the stable isotope-coded N-terminal acetyl labeling for guanidinated peptides with LTQ-FT MS for accurate data acquisition, and an in-house graphic user interface program called "MS-based acetyl quantification" for automatic data processing. RESULTS The standard peptide mixture test showed that this method is easy and highly effective, with a linear dynamic range from 0.1 to 10 (R(2) value >0.999 and slope error <5%), down to 25 fmol. Moreover, the range of quantitative ratios differing from the target value of 1.0 was statistically determined to be (0.6527, 1.5350) for the 99% confidence level in a fraction of plasma samples. The practicability of this method was further demonstrated in a pilot study on the differential proteomic analysis of cerebrospinal fluid, with the uncovering of 33 dysregulated proteins from different development stages. CONCLUSIONS AND CLINICAL RELEVANCE The outcome of the differential proteomic analysis of plasma protein and cerebrospinal fluid confirmed the whole strategy as a promising alternative for exploration of potential biomarker in complex clinical or biological samples.


title: Uniportal video assisted thoracoscopic lobectomy: primary experience from an Eastern center.

text: BACKGROUND Uniportal video-assisted thoracoscopic surgery (VATS) lobectomy is an emerging technique for the surgical resection of non-small cell lung cancer (NSCLC). Besides its wide debates on safety and efficacy throughout the world, there were few report on uniportal VATS from the Eastern countries. In this article, we summarized our primary experience on uniportal VATS lobectomy in an Eastern center. METHODS From October 2013 till February 2014, 54 consecutive uniportal VATS lobectomy were performed in the Department of Thoracic Surgery, Zhongshan Hospital of Fudan University. Patients' clinical features and operative details were recorded. Post-operatively, the morbidity and mortality were recorded to analyze the safety and efficacy of uniportal VATS lobectomy for NSCLCs. RESULTS Among the 54 planned uniportal VATS lobectomy, there was one conversion to mini-thoracotomy due to lymph node sticking. Extra ports were required in two patients. The uniportal VATS lobectomy was achieved in 51 out of 54 patients (94.4%). The average operation duration was 122.2±37.5 min (90-160 min). The average volume of estimated blood loss during the operation was 88.8±47.1 mL (50-200 mL). The mean chest tube duration and hospital stay were 3.2±1.9 days and 4.6±2.0 days, respectively. There was no postoperative mortality in this study. Two patients suffered from prolonged air leakage (5 and 7 days), and one atrial fibrillation was observed in this cohort. CONCLUSIONS Based on our primary experience, uniportal VATS lobectomy is a safe and effective procedure for the surgical resection of NSCLCs. The surgical refinements and instrumental improvements would facilitate the technique. Further studies based on larger population are required to determine its benefits towards patients with NSCLCs.


title: Effect of desflurane-remifentanil vs. Propofol-remifentanil anesthesia on arterial oxygenation during one-lung ventilation for thoracoscopic surgery: a prospective randomized trial.

text: BACKGROUND One-lung ventilation during thoracic surgery frequently disturbs normal systemic oxygenation. However, the effect of anesthetics on arterial oxygenation during one-lung ventilation has not been well established in human study. In this clinical trial, we investigated whether a difference between desflurane-remifentanil and propofol-remifentanil anesthesia can be observed with regard to oxygenation during one-lung ventilation for thoracoscopic surgery. METHODS Adult patients with lung cancer, scheduled for video-assisted thoracoscopic lobectomy without preoperative oxygen support, were screened and randomized to receive desflurane or propofol, with remifentanil continuous infusion in both groups. Mechanical ventilation was performed with tidal volume of 8 ml/kg and FIO2 0.5 during two-lung ventilation, and 6 ml/kg and 1.0 during one-lung ventilation, both with positive end-expiratory pressure of 5 cmH2O. Arterial blood gas analysis was performed preoperatively, during two-lung ventilation, and after 15, 30, 45, and 60 min of one-lung ventilation. The primary endpoint was PaO2 at 30 min after initiating one-lung ventilation. Statistical analyses included the independent t-test for the primary endpoint and a mixed model with a post-hoc analysis to evaluate the serial changes in values. RESULTS Patients were recruited between July 9 and December 2, 2014. In total, 103 patients were analyzed (n = 52 in desflurane group and n = 51 in propofol group). The primary endpoint, PaO2 at 30 min of one-lung ventilation was lower in the desflurane group than the propofol group (170 ± 72 vs. 202 ± 82 mmHg; p = 0.039). Serial changes in PaO2 during one-lung ventilation showed lower levels during desflurane anesthesia compared with propofol anesthesia (mean difference, 45 mmHg; 95% confidence interval, 16-75 mmHg; p = 0.003). CONCLUSIONS In conclusion, desflurane-remifentanil anesthesia resulted in decreased arterial oxygenation compared with that of propofol-remifentanil anesthesia during one-lung ventilation for thoracoscopic surgery in patients with lung cancer. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02191371 , registered on July 7, 2014.


Classic Spotlight, 2012 and 2013: Articles of Significant Interest Selected from the Journal of Virology Archives by the Editors.


title: Physical therapy interventions for cervicogenic dizziness in a military-aged population: protocol for a systematic review.

text: BACKGROUND Traumatic cervicogenic dizziness is dizziness that is temporally associated with neck pain and injury after other causes of dizziness have been excluded. It can lead to activity limitations and participation restrictions that may include lost duty or work days. The objective of this systematic review is to determine which interventions are most effective in decreasing dizziness or vertigo and neck pain in military-aged adults with traumatic cervicogenic dizziness. METHODS The literature will be systematically searched using the following online databases: MEDLINE, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, CENTRAL, Cochrane Methodology Register), CINAHL, SCOPUS, Web of Science, and J-STAGE. The review will include randomized controlled trials (RCTs), including cluster RCTs and controlled (non-randomized) clinical trials or cluster trials, and observational studies (including prospective and retrospective comparative cohort and case-control or nested case-control studies) and determine the effectiveness of physical therapy interventions for the treatment of traumatic cervicogenic dizziness in military-aged adults. Assessment of methodological quality will be performed by two independent, blinded reviewers using the PEDro scale. The level of evidence will be determined using the GRADE scale. The primary outcome measures will be change in dizziness and neck pain and disability from baseline to the last available follow-up, measured using the Dizziness Handicap Inventory and Neck Disability Index. Other relevant outcome measures will include self-reported change in symptoms, time to return to duty or work, and quality of life. DISCUSSION This systematic review will identify, evaluate, and integrate the evidence on the effectiveness of physical therapy interventions for cervicogenic dizziness in a military-aged population. We anticipate our findings may inform individual treatment and future research. Clinical recommendations generated from this systematic review may inform military physical therapy treatment of individuals with cervicogenic dizziness. SYSTEMATIC REVIEW REGISTRATION In accordance with the guidelines, our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 21 January 2020 (registration number CRD42020150853). In the event of protocol amendments, the date of each amendment will be accompanied by a description of the change and the rationale.


title: Encephalitis and CSF increased level of interferon-α in Kikuchi-Fujimoto disease.

text: Neurological manifestations have been reported in Kikuchi-Fujimoto disease (KFD). Characteristics of brain lesions are not defined. In addition, no biological indexes are known to help clinicians along the diagnosis process. The authors describe encephalitis associated with KFD. Brain MRI, positron emission tomography (PET) scan and a large biological assessment including interferon α (INF-α) level measurement in cerebrospinal fluid (CSF) were performed. A 39-year-old man with chronic headaches developed diplopia, slow ideation and behavioural disturbances. MRI showed brain lesions particularly in the pontine region and internal temporal lobes with enhancement of the perivacular space and the walls of the lateral ventricle. The IFN-α level was increased in the CSF without viral infection. Cervical and mediastinal adenitis were evident as a hypermetabolic focus on a PET scan, and biopsy confirmed the diagnosis of KFD. The encephalitis spontaneously remitted. The authors characterised brain lesions especially related to KFD in association with increased of IFN-α level in the CSF.


Seven days in medicine: 4-10 March 2020.


title: Growth of the conceptus from day 33 to 45 of pregnancy is minimally associated with concurrent hormonal or metabolic status in postpartum dairy cows.

text: A hypothetical explanation for pregnancy loss in postpartum dairy cows is that the metabolic environment of the cow inhibits the growth of the conceptus and places the pregnancy at risk for loss. The objective of the current study, therefore, was to model the association between cow-level metabolic indicators and conceptus growth during early pregnancy (day 33-45 after AI) and to determine if an association (if present) is large enough to cause pregnancy loss. Metabolic indicators included milk production, changes in body weight and body condition score, parity, and concentrations of circulating hormones and metabolites (glucose, non-esterified fatty acids, growth hormone, IGF1, progesterone, and pregnancy-associated glycoproteins). One-hundred cows were enrolled. Cows that became pregnant with single conceptus pregnancies (n=53) weighed more (P<0.007) and had fewer uterine polymorphonuclear neutrophils (uterine health indicator; P<0.051) compared with cows that failed to become pregnant. The embryo and amniotic vesicle were measured by using ultrasound on day 33, 35, 38, 40, 42, and 45 of pregnancy. Most of the cow-level indicators that were included in the model of conceptus growth failed to achieve statistical significance. Day of pregnancy had the largest effect on conceptus growth (size and cross-sectional area of the embryo and amniotic vesicle; P<0.001). There were effects of sex of fetus (male fetuses larger than female), insulin (negative association), and body weigh change (positive association) on embryo length and cross-sectional area but these effects were small when compared with the range in conceptus length or area that we observed. The conclusion was that the capacity of the cow to become pregnant was associated with body weight and uterine health but we failed to find a large association with metabolic status on conceptus growth from day 33 to 45 of pregnancy in lactating dairy cows.


title: Impact of adult weight management interventions on mental health: a systematic review and meta-analysis protocol.

text: INTRODUCTION The effects of interventions targeting weight loss on physical health are well described, yet the evidence for mental health is less clear. It is essential to better understand the impact of weight management interventions on mental health to optimise care and minimise risk of harm. We will assess the effect of behavioural weight management interventions on mental health in adults with overweight and obesity. METHODS AND ANALYSIS The systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. We will include behavioural weight management interventions with a diet and/or physical activity component focusing on weight loss for adults with a body mass index ≥25 kg/m2. Randomised controlled trials (RCTs) and cluster RCTs will be the only eligible study designs. Outcomes of interest will be related to mental health. The following databases were searched from inception to 07 May 2019: MEDLINE, Embase, Cochrane database (CENTRAL), PsycINFO, ASSIA, AMED and CINAHL. The search strategy was based on four concepts: (1) adults, defined as ≥18 years, with overweight/obesity, defined as BMI ≥25kg/m², (2) weight management interventions, (3) mental health outcomes and (4) study design. The search was restricted to English-language published papers, with no other restrictions applied. Two stage screening for eligibility will be completed by two independent reviewers, with two independent reviewers completing data extraction and risk of bias assessment. Data permitting, a random-effects meta-analysis of outcomes, subgroup analyses and meta-regression will be conducted. If not appropriate, narrative synthesis and 'levels of evidence' assessment will be completed. ETHICS AND DISSEMINATION Ethical approval is not required as primary data will not be collected. The completed systematic review will be disseminated in a peer-reviewed journal, at conferences and contribute towards the lead author's PhD thesis. PROSPERO REGISTRATION NUMBER CRD42019131659.


Is Biologic Treatment of Hidradenitis Suppurativa During the COVID-19 Pandemic Different from Psoriasis Biologic Treatment?


title: Computational studies of drug repurposing and synergism of lopinavir, oseltamivir and ritonavir binding with SARS-CoV-2 Protease against COVID-19.

text: A novel coronavirus (SARS-CoV-2) has caused a major outbreak in humans all over the world, and it is the latest pandemic in the series of other infectious diseases. The concept of drug repurposing has been used successfully for many years for known diseases. Considering the emergency and urgency, drug repurposing concept is being explored for coronavirus disease (COVID-19) as well. Recently, the combination of three known drugs, lopinavir, oseltamivir and ritonavir has been proposed to control the virulence to a great extent in COVID-19 affected patients within 48 hours. Hence, we tried to understand the effect of synergism of these drugs against the SARS-CoV-2 protease using sequential docking studies. As a result, combination of three drugs showed a better binding energy than that of individual drugs. Further, the complex was subjected to molecular dynamics simulations to get insights into the stability of the complex, considering the simultaneous interactions between three drugs and the protein. The protein complexed with three drugs remained stable during the simulations. Hence, these drugs can be explored further for drug repurposing against the successful inhibition of COVID-19.


Human metapneumovirus and human coronavirus NL63.


title: Emergencies after endoscopic procedures.

text: Endoscopy adverse events (AEs), or complications, are a rising concern on the quality of endoscopic care, given the technical advances and the crescent complexity of therapeutic procedures, over the entire gastrointestinal and bilio-pancreatic tract. In a small percentage, not established, there can be real emergency conditions, as perforation, severe bleeding, embolization or infection. Distinct variables interfere in its occurrence, although, the awareness of the operator for their potential, early recognition, and local organized facilities for immediate handling, makes all the difference in the subsequent outcome. This review outlines general AEs' frequencies, important predisposing factors and putative prophylactic measures for specific procedures (from conventional endoscopy to endoscopic cholangio-pancreatography and ultrasonography), with comprehensive approaches to the management of emergent bleeding and perforation.


title: Comparison of two- and three-dimensional display for performance of laparoscopic total gastrectomy for gastric cancer.

text: PURPOSE Introduction of three-dimensional (3D) display might remove technical obstacles of laparoscopic surgery and improve laparoscopic skills. We analyzed the effect of 3D technology on operative performance during laparoscopic total gastrectomy (LTG) for gastric cancer and assessed its advantages over two-dimensional (2D) laparoscopy. METHODS This study included 30 consecutive surgeries of LTG with esophagojejunostomy by the overlap method performed (3D group, n = 15, 2D group, n = 15). The surgical outcomes were compared between the 3D and 2D groups. Further, we compared the performance time, the frequency of bleeding requiring hemostasis, and the frequency of remaking the surgical view by the assistant's forceps in each laparoscopic scene between the 3D and 2D groups. RESULTS All surgeries were completed without any complications. The total time of pure laparoscopic scenes was shorter in the 3D than 2D group (154.2 vs. 182.7 min, P = 0.026), and total blood loss was almost the same (10 vs. 20 g, P = 0.195). The operative time during lymphadenectomy in scenes 6 and 7 were significantly shorter in the 3D than the 2D group (scene 6, 13.5 vs. 17.5 min, P = 0.003, and scene 7, 12.4 vs. 18.4, P = 0.025) and esophagojejunostomy (30.3 vs. 39.4 min, P = 0.008). The frequency of tissue exposure by the assistant was significantly less in the 3D group than the 2D group in scenes 6 and 7 (scene 6, n = 3.0 vs. 4.0, P = 0.006, and scene 7, n = 3.0 vs. 4.0, P = 0.017). CONCLUSIONS 3D display is useful due to improvement of surgical skill during difficult situations such as lymphadenectomy around the celiac artery, which requires handling in the tangential view, and reconstruction using the suturing technique in a narrow space.


title: Prisons: Amplifiers of the COVID-19 Pandemic Hiding in Plain Sight.

text: On February 29, 2020, nearly half of incident cases (233 of 565) of COVID-19 reported in Wuhan, China, were from the city's prison system. A separate prison outbreak, 450 miles away, in Shendong, China, was traced to officials who had visited Wuhan and infected seven prison guards and 200 inmates.1 Modern prisons have faced infectious outbreaks but none at the scale of COVID-19's. On March 26, 2020, the United States reported its first death of an incarcerated patient, in Georgia, and New York City jails reported an infection rate seven times higher than in the rest of the city, a current US epicenter of COVID-19. (Am J Public Health. Published online ahead of print May 14, 2020: e1-e3. doi:10.2105/AJPH.2020.305713).


Covid-19 global pandemic: options for management of gynecologic cancers. The experience in surgical management of ovarian cancer in the second highest affected Italian region.


title: COMPARISON OF RADIOFREQUENCY ABLATION AND CURETTAGE IN OSTEOID OSTEOMA IN CHILDREN.

text: Objective Osteoid osteoma, which is observed in the adolescent and young adult population as benign bone tumors, appears as a single nidus with a diameter < 2 cm and is treated with open surgery. However, technological advances in medicine have made it possible to apply less invasive procedures in surgery. Methods Between 2006-2014, 24 patients < 18 years of age were treated for osteoid osteoma. Patient demographic data, surgical data, complications, and recurrences were noted. Results Twenty-four patients (mean age, 11 [2-18] years) were treated and followed up for a mean 3.58 (range, 1-9) years. Mean patient age in the curettage group was 12.1 (range, 3-18) years. Mean operation length was 69.5 (range, 60-120) minutes. Mean hospital stay was 1.3 (range, 0-2) days. Mean patient age in the radiofrequency ablation (RFA) group was 10.7 (range, 2-17) years. Five patients were female and 8 were male. Mean operation length was 49.6 (range, 20-90) minutes. Mean hospital stay was 0.3 (range, 0-1) days. Mean follow-up time was 1.76 (range, 1-4) years. Mean operation length, hospital stay, and follow-up were significantly shorter in the RFA group. Conclusions Considering reduced costs due to shorter hospitalization periods and the ability to reach anatomically difficult locations, percutaneous procedures are likely to replace the conventional open approach. Level of evidence: II, retrospective study.


title: Coronavirus infection induces DNA replication stress partly through interaction of its nonstructural protein 13 with the p125 subunit of DNA polymerase δ.

text: Perturbation of cell cycle regulation is a characteristic feature of infection by many DNA and RNA viruses, including Coronavirus infectious bronchitis virus (IBV). IBV infection was shown to induce cell cycle arrest at both S and G(2)/M phases for the enhancement of viral replication and progeny production. However, the underlying mechanisms are not well explored. In this study we show that activation of cellular DNA damage response is one of the mechanisms exploited by Coronavirus to induce cell cycle arrest. An ATR-dependent cellular DNA damage response was shown to be activated by IBV infection. Suppression of the ATR kinase activity by chemical inhibitors and siRNA-mediated knockdown of ATR reduced the IBV-induced ATR signaling and inhibited the replication of IBV. Furthermore, yeast two-hybrid screens and subsequent biochemical and functional studies demonstrated that interaction between Coronavirus nsp13 and DNA polymerase δ induced DNA replication stress in IBV-infected cells. These findings indicate that the ATR signaling activated by IBV replication contributes to the IBV-induced S-phase arrest and is required for efficient IBV replication and progeny production.


title: Single-incision laparoscopic surgery increases the risk of unintentional thermal injury from the monopolar "Bovie" instrument in comparison with traditional laparoscopy.

text: BACKGROUND Single-incision laparoscopic surgery (SILS) places multiple instruments in close, parallel proximity, an orientation that may have implications in the production of stray current from the monopolar "Bovie" instrument. The purpose of this study was to compare the energy transferred during SILS compared to traditional four-port laparoscopic surgery (TRD). METHOD In a laparoscopic simulator, instruments were inserted via SILS or TRD setup. The monopolar generator delivered energy to a laparoscopic L-hook instrument for 5-s activations on 30-Watts coag mode. The primary outcome (stray current) was quantified by measuring the heat of liver tissue held adjacent to the non-electrically active 10-mm telescope tip and Maryland grasper in both the SILS and TRD setups. To control for the potential confounder of stray energy coupling via wires outside the surgical field, the camera cord and active electrode wires were oriented parallel or completely separated. RESULTS SILS and TRD setups create similar amounts of stray current as measured by increased tissue temperature at the non-electrically active telescope tip (41 ± 12 vs. 39 ± 10 °C; p = 0.71). Stray current was greater in SILS compared to TRD at the tip of the non-electrically active Maryland forceps (38 ± 9 vs. 20 ± 10 °C; p < 0.01). Separation of the active electrode and camera cords did not change the amount of stray energy in the SILS orientation for either telescope (39 ± 10 °C bundled vs. 36 ± 10 °C separated; p = 0.40) or grasper (38 ± 9 °C bundled vs. 34 ± 11 °C separated; p = 0.19) but did in the TRD orientation (41 ± 12 bundled vs. 24 ± 10 separated; p < 0.01). When SILS was compared to TRD with the cords separated, SILS increased stray energy at both the telescope tip and grasper tip (36 ± 10 vs. 24 ± 10 °C; p < 0.01 and 34 ± 11 vs. 17 ± 8 °C; p < 0.01). CONCLUSION SILS increases stray energy transfer nearly twice as much as TRD with the use of the monopolar instrument. Strategies to mitigate the amount of stray energy in the TRD setup such as separation of the active electrode and camera cords are not effective in the SILS setup. These practical findings should enhance surgeons using the SILS approach of increased stray energy that could result in injury.


title: How could metabolomics change pediatric health?

text: In the last years, 'omics' technologies, and especially metabolomics, emerged as expanding scientific disciplines and promising technologies in the characterization of several pathophysiological processes.In detail, metabolomics, able to detect in a dynamic way the whole set of molecules of low molecular weight in cells, tissues, organs, and biological fluids, can provide a detailed phenotypic portray, representing a metabolic "snapshot."Thanks to its numerous strength points, metabolomics could become a fundamental tool in human health, allowing the exact evaluation of individual metabolic responses to pathophysiological stimuli including drugs, environmental changes, lifestyle, a great number of diseases and other epigenetics factors.Moreover, if current metabolomics data will be confirmed on larger samples, such technology could become useful in the early diagnosis of diseases, maybe even before the clinical onset, allowing a clinical monitoring of disease progression and helping in performing the best therapeutic approach, potentially predicting the therapy response and avoiding overtreatments. Moreover, the application of metabolomics in nutrition could provide significant information on the best nutrition regimen, optimal infantile growth and even in the characterization and improvement of commercial products' composition.These are only some of the fields in which metabolomics was applied, in the perspective of a precision-based, personalized care of human health.In this review, we discuss the available literature on such topic and provide some evidence regarding clinical application of metabolomics in heart diseases, auditory disturbance, nephrouropathies, adult and pediatric cancer, obstetrics, perinatal conditions like asphyxia, neonatal nutrition, neonatal sepsis and even some neuropsychiatric disorders, including autism.Our research group has been interested in metabolomics since several years, performing a wide spectrum of experimental and clinical studies, including the first metabolomics analysis of human breast milk. In the future, it is reasonable to predict that the current knowledge could be applied in daily clinical practice, and that sensible metabolomics biomarkers could be easily detected through cheap and accurate sticks, evaluating biofluids at the patient's bed, improving diagnosis, management and prognosis of sick patients and allowing a personalized medicine. A dream? May be I am a dreamer, but I am not the only one.


Covid-19: Keep essential malaria services going during pandemic, urges WHO.


title: Possible causes for decreased susceptibility of children to coronavirus.

text: IMPACT The possible reason about non-susceptibility of children to coronavirus may lie in different angiotensin-converting enzyme (ACE) activity and immunity of children.The first possible reason is about ACE activity. A research revealed that children had higher ACE activities. The next possible reason is about immunity.Some adjuvant drug such as thymosin may provide benefit help for 2019-nCoV patients.


Diagnostic utility of bronchoscopy in adults with acute myeloid leukemia and other high-grade myeloid neoplasms.


title: Critically ill pregnant patient with COVID-19 and neonatal death within two hours of birth.

text: While most pregnant women with coronavirus disease 2019 (COVID-19) appear to experience a milder clinical course [1,2], the present report describes a critical case of COVID-19 in a pregnant woman. We discuss the identification, diagnosis, disease progression, and treatment outcome in a 31-year-old pregnant woman admitted to Xiaolan People's Hospital of Zhongshan at 35+2 weeks of pregnancy with no known comorbidity or history of chronic illness. Onset of symptoms in the patient began with a sore throat and dry cough for 4 days, followed by fever and dyspnea for half a day.


title: Percutaneous endoscopic gastrostomy in children: Is early feeding safe?

text: BACKGROUND Percutaneous endoscopic gastrostomy (PEG) is the preferred method to provide nutritional support for patients with normal gastrointestinal function but cannot be fed orally for a variety of reasons. Owing to safety concerns, the first feeding after PEG tube placement is generally delayed. Early feeding may be an option; however, childhood studies regarding early feeding after the PEG procedure are highly insufficient. METHODS A prospective randomized controlled study was conducted to compare early (4th hour) and late (12th hour) feeding after the PEG procedure. The PEG process was performed with the standard pull technique. Prophylactic antimicrobial drugs were not used. Complications such as gastric residue after feeding, vomiting, fever, systemic signs of infection, and duration of hospital stay were recorded. Tube feeding training was given to parents during their stay in the hospital in both groups. In the first and third days following PEG, the patients were visited by an experienced nurse in their homes and evaluated in terms of potential complications. RESULTS The study was completed with a total of 69 patients: 35 in the early feeding group and 34 in the late feeding group. The demographic characteristics of the groups were similar. Vomiting was rare and detected as similar in both groups (early feeding group 8.5% [3/35], late feeding group 8.8% [3/34], P = 1.00). Rarely, minor gastric residue was observed in both groups (early feeding group 11.4%, late feeding group 8.8% [P = 1.00]). The amount of gastric residue in the early feeding group was a maximum of 13.2 mL, whereas the late feeding group had a maximum of 14.3 mL. The average duration of stay in the hospital for the early and late feeding groups was calculated as 6.7 ± 0.64 and 28.3 ± 3.74 hours, respectively (P < 0.001). Leakage from gastrostomy fistulas, peritonitis, and aspiration were not observed in any patients. CONCLUSIONS The feeding at the fourth hour after PEG placement was safe and well tolerated by patients and shortened the duration of the hospital stay. The use of prophylactic antibiotics seems to be unnecessary before the procedure.


title: Non-invasive estimation of jugular venous oxygen saturation: a comparison between near infrared spectroscopy and transcutaneous venous oximetry.

text: The ability of practitioners to assess the adequacy of global oxygen delivery is dependent on an accurate measurement of central venous saturation. Traditional techniques require the placement of invasive central venous access devices. This study aimed to compare two non-invasive technologies for the estimation of regional venous saturation (reflectance plethysmography and near infrared spectroscopy [NIRS]), using venous blood gas analysis as gold standard. Forty patients undergoing cardiac surgery were recruited in two groups. In the first group a reflectance pulse oximeter probe was placed on the skin overlying the internal jugular vein. In the second group, a Somanetics INVOS oximeter patch was placed on the skin overlying the internal jugular vein and overlying the ipsilateral cerebral hemisphere. Central venous catheters were placed in all patients. Oxygen saturation estimates from both groups were compared with measured saturation from venous blood. Twenty patients participated in each group.Data were analyzed by the limits of agreement technique suggested by Bland and Altman and by linear regression analysis. In the reflectance plethysmography group, the mean bias was 4.27% and the limits of agreement were 58.3 to -49.8% (r(2) = 0.00, p = 0.98). In the NIRS group the mean biases were 10.8% and 2.0% for the sensors attached over the cerebral hemisphere and over the internal jugular vein, respectively, and the limits of agreement were 33.1 to -11.4 and 19.5 to -15.5% (r(2) = 0.22, 0.28;p = 0.04, 0.03) for the cerebral hemisphere and internal jugular sites, respectively. While transcutaneous regional oximetry and NIRS have both been used to estimate venous and tissue oxygen saturation non-invasively, the correlation between estimates of ScvO(2) and SxvO(2) were statistically significant for near infrared spectroscopy, but not for transcutaneous regional oximetry. Placement of cerebral oximetry patches directly over the internal jugular vein (as opposed to on the forehead) appeared to approximate internal jugular venous saturation better (lower mean bias and tighter limits of agreement), which suggests this modality may with refinement offer the practitioner additional clinically useful information regarding global cerebral oxygen supply and demand matching.


title: COVID-19 and the Rohingya Refugees in Bangladesh: The Challenges and Recommendations.

text: The current situation of global pandemic COVID-19 can put the 1.1 million Rohingya refugees, living in Bangladesh, in a substantially vulnerable position. A poor, overcrowded living condition, limited access to safe drinking water and health services, and a restricted communication system have substantially increased the risk of rapid spread of COVID-19 in these refugee camps. As COVID-19 infection has already been reported in Bangladesh, this infection will inevitably proliferate among this segregated and neglected community. Thus, in this short report, we describe the current challenges Rohingya refugee camps are facing and suggest possible prevention measures to avoid COVID-19 in these vulnerable areas.


Covid-19: Call for a rapid forward looking review of the UK's preparedness for a second wave-an open letter to the leaders of all UK political parties.


title: Development of an equine coronavirus-specific enzyme-linked immunosorbent assay to determine serologic responses in naturally infected horses.

text: Equine coronavirus (EqCoV) infection has been documented in most reports through quantitative qPCR analysis of feces and viral genome sequencing. Although qPCR is used to detect antigen during the acute disease phase, there is no equine-specific antibody test available to study EqCoV seroprevalence in various horse populations. We developed an enzyme-linked immunosorbent assay (ELISA) targeting antibodies to the spike (S) protein of EqCoV and validated its use, using acute and convalescent sera from 83 adult horses involved in 6 outbreaks. The EqCoV S protein-based ELISA was able to reliably detect antibodies to EqCoV in naturally infected horses. The greatest seroconversion rate was observed in horses with clinical signs compatible with EqCoV infection and EqCoV qPCR detection in feces. The EqCoV S protein-based ELISA could be used effectively for seroepidemiologic studies in order to better characterize the overall infection rate of EqCoV in various horse populations.


title: Evaluation of bispectral index monitoring efficacy in endoscopic patients who underwent retrograde cholangiopancreatography and received sedoanalgesia.

text: Introduction Bispectral index (BIS) monitoring provides an objective, non-invasive measurement of the level of consciousness in a sedated patient. Aim In this prospective study, we aimed to investigate the hypothesis that risk of respiratory depression could be reduced and the desired level of sedation with minimal doses of propofol could be achieved by using BIS monitoring in endoscopic retrograde cholangiopancreatography (ERCP) procedures. Material and methods Sixty patients in the ASA 1-2 category, who were scheduled for an ERCP with sedation, were randomly divided into two groups. The procedure was performed, and sedation was administered so that the patient's Ramsay Sedation Score (RSS) would be 4-5 in the first group (group 1) and the patient's BIS value would be 65-75 in the second group (group 2). Cardiopulmonary complications, the total duration of the procedure, and the total amount of propofol administered were recorded. Results The mean SpO2 measurements at the third minute, fifth minute, and 10th minute were higher in the BIS group (p < 0.001) (p < 0.05). The mean number of respirations during the third, fifth, 10th, and 15th minute of sedation was significantly higher in the RSS group than in the BIS group (p < 0.05). There was no difference between the groups in terms of recovery time, total propofol amount, and additional doses of bolus propofol. Conclusions BIS monitoring during sedation with propofol for ERCP did not reduce total propofol use, but it may be an efficient guide for the timing of additional dose administration, which could reduce the risk of respiratory depression, and it could be used safely as an objective method in the follow-up of level of sedation.


title: Comparison of various scores for predicting success of chronic total occlusion percutaneous coronary intervention.

text: BACKGROUND Various scoring systems have been developed to predict the technical outcome and procedural efficiency of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS We examined the predictive capacity of 3 CTO PCI scores (Clinical and Lesion-related [CL], Multicenter CTO registry in Japan [J-CTO] and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention [PROGRESS CTO] scores) in 664 CTO PCIs performed between 2012 and 2016 at 13 US centers. RESULTS Technical success was 88% and the retrograde approach was utilized in 41%. Mean CL, J-CTO and PROGRESS CTO scores were 3.9±1.9, 2.6±1.2 and 1.4±1.0, respectively. All scores were inversely associated with technical success (p<0.001 for all) and had moderate discriminatory capacity (area under the curve 0.691 for the CL score, 0.682 for the J-CTO score and 0.647 for the PROGRESS CTO score [p=non-significant for pairwise comparisons]). The difference in technical success between the minimum and maximum CL score strata was the highest (32%, vs. 15% for J-CTO and 18% for PROGRESS CTO scores). All scores tended to perform better in antegrade-only procedures and correlated significantly with procedure time and fluoroscopy dose; the CL score also correlated significantly with contrast utilization. CONCLUSIONS CL, J-CTO and PROGRESS CTO scores perform moderately in predicting technical outcome of CTO PCI, with better performance for antegrade-only procedures. All scores correlate with procedure time and fluoroscopy dose, and the CL score also correlates with contrast utilization.


title: Single Incision Laparoscopic Colorectal Surgery Using Conventional Laparoscopic Instruments: Initial Experience with 44 Cases.

text: BACKGROUND We aimed to retrospectively investigate the short-term outcome, technical feasibility, and safety of single incision transumbilical laparoscopic colorectal surgery (SITULCS) using conventional laparoscopic surgical instruments. METHODS From April 2009 to July 2012, 44 patients with colorectal tumors underwent SITULCS at our department by using conventional laparoscopic instruments. The operations included right hemicolectomy (n = 8), sigmoidectomy (n = 5), total colectomy (n = 4), anterior resection of rectal cancer (n = 23), and abdominoperineal resection of rectal cancer (n = 4). We accessed the intraperitoneal lesions by three trocars through a single triangle-shaped umbilical incision using conventional instruments. RESULTS We successfully completed SITULCS without specially designed instruments. No patient was converted to multiport laparoscopic surgery or open surgery. Only one case developed intraoperative bleeding and one postoperative adhesive intestinal obstruction. CONCLUSION Our experience shows that SITULCS using conventional instruments is feasible, safe, and convenient.


title: Paclitaxel-eluting stents for the treatment of femoropopliteal arterial stenoses: focus on the Zilver PTX drug-eluting peripheral stent.

text: Restenosis is one of the major limitations of the percutaneous treatment of peripheral artery disease, leading to the need for repeat interventions, limb loss and increased cost of therapy. The current standard of percutaneous treatment of stenotic lesions in the femoropopliteal arterial segment includes balloon angioplasty and bare-metal stenting. Recently, research in the field adapting the coronary arterial bed treatment model led to the inclusion of antimitotic drugs in the form of drug-eluting stents to combat neointimal proliferation and reduce the burden of restenosis. Randomized trial and registry data emerged indicating improved long-term outcomes with drug-eluting stents in peripheral arteries, lending the way to more widespread adaptation of this modality in the management of patients with peripheral artery disease.


title: [COVID-19 - More Lung Pocus and Sparing Use of Stethoscope, Chest X-Ray and Lung CT].

text: COVID-19 - More Lung Pocus and Sparing Use of Stethoscope, Chest X-Ray and Lung CT Abstract. For an optimal management of COVID-19 (Coronary Virus Disease) we depend on a fast and reliable diagnosis and severity assessment. The gold standard so far is RT-PCR (reverse transcriptase polmerase chain reaction) from the nasopharyngeal smear. Current tests have a sensitivity of 60-90 %. As a consequence, we must expect 10-40 % false negative results. In addition to oxygen saturation for severity classification, stethoscope, chest X-ray and lung computer tomography are routinely used. However, the standard methods stethoscope and chest X-ray are unreliable. Moreover, all three diagnostic examination techniques expose physicians, support staff and subsequent patients to an additional risk of exposure. In view of the contagiousness of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus), lung point-of-care ultrasound (Lu-PoCUS) is a still underutilized valuable alternative, especially when using pocket devices. In this review the current value and role of stethoscope, pulsoxymetry, chest x ray, lung computer tomography and lung point-of-care ultrasound will be determined based on the available literature.


title: Structural elucidation of in vivo metabolites of isobavachalcone in rat by LC-ESI-MS(n) and LC-NMR.

text: Isobavachalcone (IBC) is a prenylated chalcone and belongs to the class of flavonoids, which is an active component isolated from Psoralea corylifolia L. IBC showed a range of significant pharmacological activities, including antibacterial, anticancer, anti-reverse transcriptase and antioxidant actions. In this research, the mass spectral fragmentation pattern of IBC was investigated to predict the in vivo metabolites, and five phase I metabolites and ten phase II metabolites of IBC in rat bile were elucidated and identified after oral administration using novel LC-ESI-MS(n) and LC-NMR method. The molecular structures of these metabolites were proposed on the basis of the characteristics of their precursor ions, product ions, MS/MS fragment behaviors and chromatographic retention time. The phase I metabolites were mainly biotransformed via the hydroxylation, reduction, cyclization and oxidative cleavage reactions. The phase II metabolites were mainly identified as the glucuronide conjugates and sulfated conjugates. All these findings were reported for the first time and would contribute to a further understanding of the in vivo intermediate processes and metabolic mechanism of isobavachalcone and its analogs.


Ensuring Uptake of Vaccines against SARS-CoV-2.


title: Diffusion Tensor Imaging Detects Occult Cerebellar Injury in Severe Neonatal Hypoxic-Ischemic Encephalopathy.

text: BACKGROUND Despite the benefits of whole-body hypothermia therapy, many infants with hypoxic-ischemic encephalopathy (HIE) die or have significant long-term neurodevelopmental impairment. Prospectively identifying neonates at risk of poor outcome is essential but not straightforward. The cerebellum is not classically considered to be a brain region vulnerable to hypoxic-ischemic insults; recent literature suggests, however, that the cerebellum may be involved in neonatal HIE. In this study, we aimed to assess the microstructural integrity of cerebellar and linked supratentorial structures in neonates with HIE compared to neurologically healthy neonatal controls. METHODS In this prospective cohort study, we performed a quantitative diffusion tensor imaging (DTI) analysis of the structural pathways of connectivity, which may be affected in neonatal cerebellar injury by measuring fractional anisotropy (FA) and mean diffusivity (MD) within the superior, middle, and inferior cerebellar peduncles, dentate nuclei, and thalami. All magnetic resonance imaging (MRI) studies were grouped into 4 categories of severity based on a qualitative evaluation of conventional and advanced MRI sequences. Multivariable linear regression analysis of cerebellar scalars of patients and controls was performed, controlling for gestational age, age at the time of MRI, and HIE severity. Spearman rank correlation was performed to correlate DTI scalars of the cerebellum and thalami. RESULTS Fifty-seven (23 females, 40%) neonates with HIE and 12 (6 females, 50%) neonatal controls were included. There were 8 patients (14%) in HIE severity groups 3 and 4 (injury of the basal ganglia/thalamus and/or cortex). Based on a qualitative analysis of conventional and DTI images, no patients had evidence of cerebellar injury. No significant differences between patients and controls were found in the FA and MD scalars. However, FA values of the middle cerebellar peduncles (0.294 vs. 0.380, p < 0.001) and MD values of the superior cerebellar peduncles (0.920 vs. 1.007 × 10-3 mm/s2, p = 0.001) were significantly lower in patients with evidence of moderate or severe injury on MRI (categories 3 and 4) than in controls. In patients, cerebellar DTI scalars correlated positively with DTI scalars within the thalami. CONCLUSION Our results suggest that infants with moderate-to-severe HIE may have occult injury of cerebellar white-matter tracts, which is not detectable by the qualitative analysis of neuroimaging data alone. Cerebellar DTI scalars correlate with thalamic measures, highlighting that cerebellar injury is unlikely to occur in isolation and may reflect the severity of HIE. The impact of concomitant cerebellar injury in HIE on long-term neurodevelopmental outcome warrants further study.


title: Children and the COVID-19 pandemic.

text: As a result of the COVID-19 pandemic, many school districts have closed for the remainder of the academic year. These closures are unfortunate because, for many students, schools are their only source of trauma-informed care and supports. When schools reopen, they must develop a comprehensive plan to address the potential mental health needs of their students. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Prioritizing Physician Mental Health as COVID-19 Marches On.


title: Hand-assisted laparoscopic repair of a grade IV rectal tear in a postparturient mare.

text: CASE DESCRIPTION An 8-year-old multiparous Thoroughbred broodmare was admitted for evaluation of a rectal tear sustained during parturition. CLINICAL FINDINGS On initial evaluation, the mare had mild signs of abdominal discomfort. A full-thickness rectal tear located 30 cm cranial to the anus and extending approximately 15 cm longitudinally along the surface of the small colon between the 4 and 6 o'clock positions, when viewed from behind, was diagnosed on examination per rectum. TREATMENT AND OUTCOME Laparoscopic evaluation of the abdomen was performed to assess the tear and extent of peritoneal contamination. A hand-assisted repair via a flank incision was performed. The tear was closed in a single-layer, simple continuous pattern with size-0 polydioxanone with a handheld needle holder. Subsequently, a ventral midline celiotomy was performed, and intestinal contents were evacuated via a pelvic flexure enterotomy and a typhlotomy. Following surgery, the mare was managed with IV fluid therapy, partial parenteral nutrition, antimicrobials, and NSAIDs for 5 to 7 days before being gradually reintroduced to a complete pelleted feed and alfalfa hay. Prior to discharge, examination per rectum revealed no stricture formation associated with repair. The mare was discharged from the hospital and performed successfully as a broodmare, with the delivery of a live foal 1 year after surgery. CLINICAL RELEVANCE Successful repair with an excellent outcome was achieved in this mare. Hand-assisted laparoscopic repair should be considered as a possible treatment option in horses with grade IV rectal tears.


title: Comparison of hematology, plasma biochemistry, and blood gas variables between 2 venipuncture sites in Southern Stingrays (Dasyatis americana).

text: BACKGROUND The Southern Stingray (Dasyatis americana) is a batoid elasmobranch frequently exhibited in zoological institutions. Blood is commonly collected from the caudal hemal arch at the tail base in stingrays for the purpose of health assessment and clinical pathology tests. An alternative site that allows a dorsal or ventral approach without necessitating puncture of a cartilaginous structure has been identified between the cartilaginous pectoral fin rays (ceratotrichia). OBJECTIVES The purpose of the study was to compare CBC, plasma biochemistry analytes, and blood gas variables between blood samples collected from the caudal and pectoral fin vasculature sites of the Southern Stingray. METHODS Fifteen captive Southern Stingrays (10 females, 5 males) from 4 zoo and aquarium facilities were sampled. Lithium heparinized blood samples were collected from the caudal and pectoral venipuncture sites of each animal. Values from estimated total and differential leukocyte counts, plasma biochemistry analytes, and blood gas variables were compared. RESULTS There were no statistically significant differences between venipuncture sites for the measured analytes except for CK activity, which was statistically significantly higher in the pectoral site samples. Levels of agreement between sites were good or moderate for 22 analytes and poor for ALT, AST, CK, pO2 , lactate, monocytes, and eosinophils. CONCLUSIONS The good agreement between sampling sites for the majority of the measured analytes and the lack of differences that would alter clinical interpretation support the use of the pectoral site as an alternative to the traditional caudal fin venipuncture site in Southern Stingrays.


Is clinical effectiveness in the eye of the beholder during the COVID-19 pandemic?


title: Membrane Cholesterol Modulates Oligomeric Status and Peptide-membrane Interaction of Severe Acute Respiratory Syndrome Coronavirus Fusion Peptide.

text: The N-terminal fusion peptide (residues 770-788) of S2 glycoprotein of the severe acute respiratory syndrome corona virus (SARS-CoV), exposed upon receptor binding, is crucial for virus entry into the host cell. The fusion peptide alters the membrane organization and dynamics of the host membrane to facilitate membrane fusion. Generally, the effect of fusion peptide on the membrane is sensitive to the lipid composition of target membranes. In this present work, we have utilized steady state and time-resolved fluorescence spectroscopy in tandem with circular dichroism spectroscopy to elucidate the binding, oligomeric status, secondary structure of the fusion peptide and its impact on the depth-dependent membrane organization and dynamics. We have used depth-dependent fluorescence probes, 1,6-diphenyl-1,3,5-hexatriene (DPH) and its trimethylammonium derivative (TMA-DPH), to evaluate the effect of the peptide-binding along the bilayer normal. We have exploited the energy transfer efficiency of tryptophan between TMA-DPH and DPH to determine the relative location of the solitary tryptophan present in the membrane-bound fusion peptide. We have further evaluated the effect of membrane cholesterol on the binding and organization of the peptide and the impact of peptide binding on the depth-dependent physical properties of the membrane at various cholesterol concentrations. Our results clearly demonstrate that the membrane cholesterol alters the oligomeric status of the membrane-bound peptide and the effect of peptide-binding on the depth-dependent membrane organization and dynamics. The role of cholesterol is important as the eukaryotic host cells contain good amount of cholesterol that might be important for the entry of pathogenic viruses.


title: Cerebral oxygenation and processed EEG response to clamping and shunting during carotid endarterectomy under general anesthesia.

text: Clamping and shunting during carotid endarterectomy (CEA) surgery causes changes in cerebral blood flow. The purpose of this study was to assess and compare, side by side, the cerebral oxygenation (rSO2) and processed electroencephalogram (EEG) response bilaterally to carotid artery clamping and shunting in patients undergoing CEA under general anesthesia. With institutional approval and written informed consent, patients undergoing CEA under general anesthesia and routine carotid artery shunting were recorded bilaterally, simultaneously and continuously with an rSO2 and processed EEG monitor. The response of the monitors during carotid artery clamping and shunting were assessed and compared between monitors and bilaterally within each monitor. Sixty-nine patients were included in the study. At clamping the surgical-side and contralateral-side rSO2 dropped significantly below the baseline incision value (-17.6 and -9.4% respectively). After shunting, the contralateral-side rSO2 returned to baseline while the surgical-side rSO2 remained significantly below baseline (-9.0%) until the shunt was removed following surgery. At clamping the surgical-side and contralateral-side processed EEG also dropped below baseline (-19.9 and -20.6% respectively). However, following shunt activation, the processed EEG returned bilaterally to baseline. During the course of this research, we found the rSO2 monitor to be clinically more robust (4.4% failure rate) than the processed EEG monitor (20.0% failure rate). There was no correlation between the rSO2 or processed EEG changes that occurred immediately after clamping and the degree of surgical side stenosis measured pre-operatively. Both rSO2 and processed EEG respond to clamping and shunting during CEA. Cerebral oximetry discriminates between the surgical and contralateral side during surgery. The rSO2 monitor is more reliable in the real-world clinical setting. Future studies should focus on developing algorithms based on these monitors that can predict clamping-induced cerebral ischemia during CEA in order to decide whether carotid artery shunting is worth the associated risks. From the practical point of view, the rSO2 monitor may be the better monitor for this purpose.


title: Delayed fatigue in finger flexion forces through transcutaneous nerve stimulation.

text: OBJECTIVE Weakness of the hand is a major impairment which limits independent living. Neuromuscular electrical stimulation (NMES) is a common approach to help restore muscle strength. Traditional NMES directly over the muscle often leads to a rapid onset of muscle fatigue. In this study, we investigated the force sustainability of finger flexor muscles using a transcutaneous nerve stimulation approach. APPROACH Finger flexion forces and high-density electromyogram (HD EMG) signals were obtained while electrical stimulation was applied to the ulnar and median nerve bundles through a stimulation grid on the proximal arm segment. Stimulation was also applied to the finger flexor muscle belly targeting the motor point, serving as a control condition. The force produced from the two stimulation approaches were initially matched, and muscle fatigue was subsequently induced with 5 min of continuous stimulation. The rate of decay of the force and EMG amplitude were quantified, and the spatial distribution of the muscle activation during the sustained contraction was also evaluated. MAIN RESULTS The proximal nerve stimulation approach induced a slower decay in both force and EMG, compared with the stimulation at the motor point. The spatial distribution of the elicited muscle activation showed that the proximal nerve stimulation led to a distributed activation across the intrinsic and extrinsic finger flexor muscles and also activated a wider area within the extrinsic muscle. SIGNIFICANCE Our findings demonstrated that the stimulation of the proximal nerve bundles can elicit sustained force output and delayed decrease in the rate of force decline. This is potentially due to a spatially distributed activation of the muscle fibers, compared with the traditional motor point stimulation. Future development of our nerve stimulation approach may enable prolonged usage during rehabilitation or assistance for better functional outcomes.


title: Identification of Novel Linear Epitopes Located in the Infectious Bronchitis Virus Spike S2 Region.

text: We identified novel linear epitopes on the infectious bronchitis virus (IBV) spike S2 region. The conformational structure of the IBV spike protein was predicted from a homologous protein, human coronavirus NL63 spike. Although the obtained structure was incomplete, most of the IBV spike protein structure was predicted; the N-terminus of the S1 region could not be predicted due to its variability. In the model, the region located in the proximity of the fusion peptide appeared to be well conserved, and we evaluated the antigenicity of these domains, which are involved in the membrane fusion machinery. Western blotting revealed that IBV TM86 spike residues 686-723 were antigenic. Epitope mapping analysis using synthesized peptides revealed that IBV TM86 spike 669-685 (SNFSTGAFNISLLLTPP), 686-697 (SNPRGRSFIEDL), and 692-703 (SFIEDLLFTSVE) residues were major linear epitopes; two identified epitopes (686-697 and 692-703) were covered by the fusion peptide, and the other epitope (669-685) was adjacent to the fusion peptide. Although the identified epitopes are identically located as the neutralizing epitope in severe acute respiratory syndrome coronavirus, the recombinant protein that includes those epitopes could not elicit neutralizing antibodies against IBV. This is the first report describing IBV spike S2 epitopes located in the proximity of the fusion peptide, and it is suggested that the spike fusion machinery of IBV may differ from that of severe acute respiratory syndrome coronavirus, or, alternatively, IBV may have another mechanism to penetrate the cell membrane.


title: Code Blue During the COVID-19 Pandemic.

text: The surging COVID-19 pandemic has raised ethical and moral dilemmas that Western nations with first-rate medical care facilities rarely confront-how to best allocate standard life-saving medical resources when escalating demand outstrips supply. Sadly, these quandaries are familiar challenges in resource-poor countries. What makes this pandemic notable is that the scope and number of reported cases have been primarily in First World nations, raising questions in some settings about the use of emergency treatments like resuscitation care for in-hospital cardiac arrest (IHCA). This perspective reviews the debate around these ethical and moral dilemmas more broadly but focuses specifically on IHCA and the response of the medical community.


Bats and Viruses: A New Frontier of Emerging Infectious DiseasesBats and Viruses: A New Frontier of Emerging Infectious Diseases. By L.-F. Wang and C. Cowled (editors). John Wiley and Sons, Inc., Hoboken, New Jersey, USA. 2015. 384 pp. ISBN 978-1-118-81873-2. US $150 hardback.


Mortality Data in the Kingdom of Tonga: A Review of Changing Trends over the Ten Years since 1996.


Letter to the editor:Defensive Medicine and the Neurosurgeon: Rules for Success in Pandemics.


title: Coronaviruses resistant to a 3C-like protease inhibitor are attenuated for replication and pathogenesis, revealing a low genetic barrier but high fitness cost of resistance.

text: Viral protease inhibitors are remarkably effective at blocking the replication of viruses such as human immunodeficiency virus and hepatitis C virus, but they inevitably lead to the selection of inhibitor-resistant mutants, which may contribute to ongoing disease. Protease inhibitors blocking the replication of coronavirus (CoV), including the causative agents of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), provide a promising foundation for the development of anticoronaviral therapeutics. However, the selection and consequences of inhibitor-resistant CoVs are unknown. In this study, we exploited the model coronavirus, mouse hepatitis virus (MHV), to investigate the genotype and phenotype of MHV quasispecies selected for resistance to a broad-spectrum CoV 3C-like protease (3CLpro) inhibitor. Clonal sequencing identified single or double mutations within the 3CLpro coding sequence of inhibitor-resistant virus. Using reverse genetics to generate isogenic viruses with mutant 3CLpros, we found that viruses encoding double-mutant 3CLpros are fully resistant to the inhibitor and exhibit a significant delay in proteolytic processing of the viral replicase polyprotein. The inhibitor-resistant viruses also exhibited postponed and reduced production of infectious virus particles. Biochemical analysis verified double-mutant 3CLpro enzyme as impaired for protease activity and exhibiting reduced sensitivity to the inhibitor and revealed a delayed kinetics of inhibitor hydrolysis and activity restoration. Furthermore, the inhibitor-resistant virus was shown to be highly attenuated in mice. Our study provides the first insight into the pathogenicity and mechanism of 3CLpro inhibitor-resistant CoV mutants, revealing a low genetic barrier but high fitness cost of resistance. Importance: RNA viruses are infamous for their ability to evolve in response to selective pressure, such as the presence of antiviral drugs. For coronaviruses such as the causative agent of Middle East respiratory syndrome (MERS), protease inhibitors have been developed and shown to block virus replication, but the consequences of selection of inhibitor-resistant mutants have not been studied. Here, we report the low genetic barrier and relatively high deleterious consequences of CoV resistance to a 3CLpro protease inhibitor in a coronavirus model system, mouse hepatitis virus (MHV). We found that although mutations that confer resistance arise quickly, the resistant viruses replicate slowly and do not cause lethal disease in mice. Overall, our study provides the first analysis of the low barrier but high cost of resistance to a CoV 3CLpro inhibitor, which will facilitate the further development of protease inhibitors as anti-coronavirus therapeutics.


Turning to Faith and Technology During the Coronavirus Disease 2019 Crisis.


title: Intrasaccular flow-disruption treatment of intracranial aneurysms: preliminary results of a multicenter clinical study.

text: BACKGROUND AND PURPOSE The endovascular treatment of intracranial aneurysms with unfavorable anatomy (large aneurysms, wide-neck) is frequently challenging and is also associated with a high incidence of significant recurrences. The WEB, an intrasaccular flow disrupter, was designed for use in this type of aneurysm. We report our early experience with this device in this multicenter study. MATERIALS AND METHODS Twenty patients with 21 aneurysms were treated by using the WEB in 3 European centers. The ability to successfully deploy the WEB, immediate posttreatment angiographic results, adverse events, clinical outcome, and angiographic follow-up results were recorded. RESULTS Aneurysm location was the ICA (4/21, 19.1%), MCA (8/21, 38.1%), AcomA (5/21, 23.8%), and BA (4/21, 19.1%). No treatment failures were reported. Treatment was performed exclusively with the WEB in 16/21 (76.2%) patients. Additional treatment (coiling and/or stent placement) was used in 5/21 (23.8%) patients. One patient (4.8%) experienced transient clinical worsening (mRS 1 at 1 month, mRS 0 at 3 months) related to a thromboembolic event. Inadvertent detachment of the WEB was observed, and the WEB was retrieved in 1 patient, without adverse effects. In the short-term follow-up (2-8 months), adequate occlusion (total occlusion or neck remnant) was observed in 80.0% of aneurysms. CONCLUSIONS Intrasaccular flow disruption is a new endovascular approach for aneurysm treatment. In our preliminary experience, this treatment was feasible and mostly used in bifurcation aneurysms (MCA, BA, ICA) with unfavorable anatomy. Further studies are needed to precisely evaluate the indications, safety, and efficacy of this new technique.


Covid-19: Staff at Nightingale Hospital in London get wellbeing area courtesy of John Lewis.


title: Contribution of redox status to hepatitis C virus E2 envelope protein function and antigenicity.

text: Disulfide bonding contributes to the function and antigenicity of many viral envelope glycoproteins. We assessed here its significance for the hepatitis C virus E2 envelope protein and a counterpart deleted for hypervariable region-1 (HVR1). All 18 cysteine residues of the antigens were involved in disulfides. Chemical reduction of up to half of these disulfides was compatible with anti-E2 monoclonal antibody reaction, CD81 receptor binding, and viral entry, whereas complete reduction abrogated these properties. The addition of 5,5'-dithiobis-2-nitrobenzoic acid had no effect on viral entry. Thus, E2 function is only weakly dependent on its redox status, and cell entry does not require redox catalysts, in contrast to a number of enveloped viruses. Because E2 is a major neutralizing antibody target, we examined the effect of disulfide bonding on E2 antigenicity. We show that reduction of three disulfides, as well as deletion of HVR1, improved antibody binding for half of the patient sera tested, whereas it had no effect on the remainder. Small scale immunization of mice with reduced E2 antigens greatly improved serum reactivity with reduced forms of E2 when compared with immunization using native E2, whereas deletion of HVR1 only marginally affected the ability of the serum to bind the redox intermediates. Immunization with reduced E2 also showed an improved neutralizing antibody response, suggesting that potential epitopes are masked on the disulfide-bonded antigen and that mild reduction may increase the breadth of the antibody response. Although E2 function is surprisingly independent of its redox status, its disulfide bonds mask antigenic domains. E2 redox manipulation may contribute to improved vaccine design.


title: New frontiers in venous sinus stenting: Illustrative cases.

text: Idiopathic intracranial hypertension (IIH) occurs rarely, with severe patients recalcitrant to pharmacologic management often requiring cerebrospinal fluid diversion. We report two patients with variant IIH successfully treated with venous sinus stenting: 1) A 65-year-old man with severe vision loss, papilledema, and cognitive decline treated with four telescoped stents across a long, severely stenotic transverse-sigmoid system, and 2) a 58-year-old woman with headaches, vision loss, and papilledema secondary to a jugular paraganglioma causing severe jugular bulb stenosis that required contralateral venous sinus stenting. At 3-month and 1-month follow-up, respectively, ophthalmologic examinations showed vision improvement. The first patient also had improved cognition, and the second patient also had improved headaches.


title: Effect of nitrous oxide on bispectral index values at equi-minimum alveolar concentrations of sevoflurane and desflurane.

text: BACKGROUND AND AIMS Bispectral index (BIS) values may be anaesthetic agent-specific, depending on their ability to suppress the electroencephalogram (EEG) signals. We carried out a prospective, randomised clinical trial to study the effect of nitrous oxide (N2O) on the BIS values at an equi-minimum alveolar concentration (MAC) of sevoflurane and desflurane. METHODS Sixty adult patients undergoing spine surgery were randomised into two groups; Group S (sevoflurane; n = 30) and Group D (desflurane; n = 30) for the maintenance of anaesthesia in oxygen and air or oxygen and N2O mixture (FiO2-0.4) (Stage 1). BIS and fraction of inspired and end-tidal concentration of agents were noted at 1.0 MAC. In Stage 2, air or N2O was discontinued and the other carrier gas was introduced. At steady state of this carrier gas, values were again noted as in Stage 1. Statistical analysis was performed using two-way analysis of variance followed by Bonferroni correction, and Student's t-test for paired data. P<0.05 was considered statistically significant. RESULTS With air-oxygen as the carrier gas, sevoflurane and desflurane resulted in comparable BIS values (P = 0.44). With addition of 60% N2O, there was a significant increase in BIS values at 1.0 MAC for both the agents. Furthermore, higher BIS values were observed with sevoflurane compared to desflurane (P = 0.01). CONCLUSION Sevoflurane and desflurane at equi-MAC concentration exert similar effect on BIS values when used with air-oxygen. N2O results in higher BIS values; this effect is more pronounced in combination with sevoflurane.


title: COVID-19 pandemic: what consequences for cardiac rehabilitation?

text: The ongoing COVID-19 pandemic spreading all around the world has stressed over its capabilities and determined profound changes in the health systems in all countries and has caused hundreds of thousand deaths. Health professionals have been called to a tremendous effort to deal with this emergency, often contaminating or succumbing themselves to the disease.


title: Bat severe acute respiratory syndrome-like coronavirus ORF3b homologues display different interferon antagonist activities.

text: The ORF3b protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has a nuclear localization signal (NLS) at its C terminus and antagonizes interferon (IFN) function by modulating the activity of IFN regulatory factor 3 (IRF3). SARS-like coronaviruses (SL-CoVs) found in bats share an identical genome organization and high sequence identity for most of their gene products. In this study, ORF3b homologues were identified from three bat SL-CoV strains. These ORF3b homologues were C-terminally truncated and lacked the C-terminal NLS of SARS-CoV. IFN antagonist activities analysis demonstrated that one SL-CoV ORF3b still possessed IFN antagonist and IRF3-modulating activities. These results indicate that different ORF3b proteins display different IFN antagonist activities and this function is independent of the protein's nuclear localization, suggesting a potential link between bat SL-CoV ORF3b function and viral pathogenesis.


Exposure to ionising radiation in the clinical workplace: What do medical students know?


'Medications should be prescribed by doctors, not the president': leading Brazilian scientist discusses the pandemic.


title: Expecting the unexpected: Echo laboratory preparedness in the time of COVID-19.

text: COVID-19 poses a unique set of challenges to the healthcare system due to its rapid spread, intensive resource utilization, and relatively high morbidity and mortality. Healthcare workers are at especially high risk of exposure given the viruses spread through close contact. Reported cardiac complications of COVID-19 include myocarditis, acute coronary syndrome, cardiomyopathy, pericardial effusion, arrhythmia, and shock. Thus, echocardiography is integral in the timely diagnosis and clinical management of COVID-19 patients. Rush University Medical Center has been at the forefront of the COVID-19 response in Illinois with high numbers of cases reported in Chicago and surrounding areas. The echocardiography laboratory at Rush University Medical Center (RUMC) proactively took numerous steps to balance the imaging needs of a busy, nearly 700-bed academic medical center while maintaining safety.


title: A ruptured aneurysm in the vasa corona at the craniocervical junction with dysgenesis of the posterior inferior cerebellar artery.

text: This paper reports the case of a ruptured aneurysm in the vasa corona at the craniocervical junction with dysgenesis of the posterior inferior cerebellar artery (PICA). Dysgenesis of the proximal PICA in the present case caused the development of a pial anastomosis in the vasa corona, resulting in the formation of an aneurysm because of increased haemodynamic stress at the vasa corona. The aneurysm was successfully treated with transarterial coil embolization. The clinical entity in the present case is extremely rare and it is important to consider an aberrant vascular anomaly as the cause of an isolated spinal aneurysm.