title: Establishing Mayo Clinic's Coronavirus Disease 2019 Virtual Clinic: A Preliminary Communication.

text: The coronavirus disease 2019 (COVID-19) pandemic is taking a massive toll on health care systems globally. We developed the COVID-19 virtual clinic (CVC) in conjunction with drive through testing to cope with this situation. There are two arms of the CVC: (1) a screening arm and (2) positive patient arm. Screening is performed over the phone based on the Centers for Disease Control and Prevention screening guideline. Positive patients are followed at regular intervals by video appointments where concerns can be addressed by a provider while also tracking symptom progression. We enrolled 63 positive patients out of 1,153 screened for COVID-19 as of this writing. The CVC continues to address patients' concerns and symptoms in an effort to minimize emergency department and hospital patient volumes, as incidence increases. Drive through testing in conjunction with a virtual clinic allows us to provide high-quality care in an anxious time without consuming excessive personal protective equipment or unnecessarily exposing health care workers. This article could serve as a model to guide other practices to cope with this and future pandemics.


CCR5 antagonism in HIV infection: ways, effects, and side effects.


Covid-19: Important potential side effects of wearing face masks that we should bear in mind.


title: Pandemic swine-origin H1N1 influenza A virus isolates show heterogeneous virulence in macaques.

text: The first influenza pandemic of the new millennium was caused by a newly emerged swine-origin influenza virus (SOIV) (H1N1). This new virus is characterized by a previously unknown constellation of gene segments derived from North American and Eurasian swine lineages and the absence of common markers predictive of human adaptation. Overall, human infections appeared to be mild, but an alarming number of young individuals presented with symptoms atypical for seasonal influenza. The new SOIV also showed a sustained human-to-human transmissibility and higher reproduction ratio than common seasonal viruses, altogether indicating a higher pathogenic potential for this newly emerged virus. To study the virulence of the SOIV, we used a recently established cynomolgus macaque model and compared parameters of clinical disease, virology, host responses, and pathology/histopathology with a current seasonal H1N1 virus. We here show that infection of macaques with two genetically similar but clinically distinct SOIV isolates from the early stage of the pandemic (A/Mexico/4108/2009 and A/Mexico/InDRE4487/2009) resulted in upper and lower respiratory tract infections and clinical disease ranging from mild to severe pneumonia that was clearly advanced over the mild infection caused by A/Kawasaki/UTK-4/2009, a current seasonal strain. Unexpectedly, we observed heterogeneity among the two SOIV isolates in virus replication, host transcriptional and cytokine responses, and disease progression, demonstrating a higher pathogenic potential for A/Mexico/InDRE4487/2009. Differences in virulence may explain more severe disease, as was seen with certain individuals infected with the emerged pandemic influenza virus. Thus, the nonhuman primate model closely mimics influenza in humans.


title: The Effects of Uniquely-Processed Titanium on Balance and Walking Performance in Healthy Older Adults.

text: The increased risk of falls associated with advancing age has increased demand for methods to improve balance and mobility. The primary purpose of the study was to determine whether wearing Aqua Titan-treated stockings could improve balance and walking performance in an older population; secondary was to elucidate the mechanisms. In a randomized, double-blind crossover, 16 healthy older adults (age, 67.9 ± 4.2 years; BMI, 24.8 ± 3.1 kg/m²) performed two 4-day trials composed of baseline measures and fatiguing exercise on Day 1, with recovery measures at 14, 38 and 62 h post-exercise, wearing Aqua Titan and control stockings. Balance, walking performance, triceps surae stretch reflex, ankle range of motion and gastrocnemius muscle microvascular perfusion, blood flow and oxygen consumption were measured at baseline and during recovery. Aqua Titan had no effect on the microvascular parameters, but increased total ankle range of motion at 38 h (2.4°; 95% CI ± 1.8°) and 62 h (2.7°; ±1.7°), contributed to by increases in dorsiflexion and plantar flexion. There was decreasing persistence in the medial-lateral center of pressure movement at 38 h (q = 0, −0.0635 ± 0.0455), compared to control stockings. Aqua Titan garments hold potential for improving balance and mobility in older adults in the days following a bout of fatiguing exercise. The proposed mechanisms associated with enhanced sensory feedback require further exploration.


title: Time-course of upper respiratory tract viral infection and COPD exacerbation.

text: Viral respiratory tract infections have been implicated as the predominant risk factor for acute exacerbations of COPD (AECOPD). We aimed to evaluate, longitudinally, the association between upper respiratory tract infections (URTI) caused by viruses and AECOPD.Detection of 18 viruses was performed in naso- and orοpharyngeal swabs in 450 COPD patients (GOLD 2-4), followed for a mean of 27 months, at stable periods (n=1909), at URTI onset (n=391), 10 days after the URTI (n=356) and at AECOPD (n=177) using a multiplex nucleic acid amplification testing.Evidence of at least one respiratory virus was significantly higher at URTI onset (52.7%), at 10 days following a URTI (15.2%) and at exacerbation (38.4%), compared with the stable period (5.3%, p<0.001). At stable visits rhinovirus accounted for 54.2% of all viral infections, followed by coronavirus (20.5%). None of the viruses could be identified in two consecutive stable visits. Patients with viral infection at URTI onset did not have a higher incidence of exacerbation, compared with patients without viral infection (p=0.993). Τhe incidence of any viral infection at AECOPD was similar between URTI-related AECOPD and non-URTI-related AECOPD (p=0.359). Only 24% of the patients that had a URTI-related AECOPD had the same virus at URTI and AECOPD. Detection of parainfluenza 3 at URTI onset was associated with higher risk of AECOPD (p=0.003). Rhinovirus and coronavirus were the most frequently detected viruses at AECOPD visits accounting for 35.7% and 25.9% of all viral infections, respectively.The prevalence of viral infection at the stable period of COPD is low. The risk of exacerbation following the onset of URTI symptoms depends on the particular virus associated with the event and was significant only for parainfluenza 3.


Author's Response to Letter to Editor on "Characteristics and Outcomes of Middle East Respiratory Syndrome Coronavirus Patients Admitted to an Intensive Care Unit in Jeddah, Saudi Arabia".


Respiratory failure and non-invasive respiratory support during the covid-19 pandemic: an update for re-deployed hospital doctors and primary care physicians.


title: Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target.

text: A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging 2019-nCoV is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Actin protein was also suggested as a host factor that participates in cell entry and pathogenesis of 2019-nCoV; therefore, drugs modulating biological activity of this protein (e.g. ibuprofen) were suggested as potential candidates for treatment of this viral infection. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target.


title: The female continence mechanism measured by high resolution manometry: Urethral bulking versus midurethral sling.

text: AIMS Traditional technology to characterize urethral pressure changes during dynamic conditions is limited by slow response times or artifact-inducing withdrawal maneuvers. The 8F high-resolution manometry (HRM) catheter (ManoScan™ ESO, Covidien) has advantages of fast response times and the ability to measure urethral pressures along the urethral length without withdrawal. Our objective was to determine static and dynamic maximum urethral closure pressures (MUCPs) and resting functional urethral length (FUL) in women using HRM before and after transurethral bulking and compare results to other women who underwent midurethral sling (MUS). METHODS We recorded rest, cough, and strain MUCPs and FUL in 24 women before and after transurethral bulking with polydimethylsiloxane (Macroplastique®) using the HRM catheter and compared these changes to HRM values from 26 women who had the same measures before and after MUS. RESULTS At rest, MUCPs increased minimally after both urethral bulking and MUS (3 vs 0.4 cm H2 O respectively, P = 0.4). Under dynamic conditions there were statistically insignificant small increases in MUCP and these increases were markedly less than after MUS (cough: 1.5 vs 63.8 cm H2 O, P < 0.001 and strain: 11.5 vs 57.7 cm H2 O, P < 0.001). FUL increased by 0.5 cm after transurethral bulking (P = 0.003), and decreased by 0.25 cm after MUS placement (P = 0.012). CONCLUSIONS The mechanism of continence after urethral bulking differs from MUS. While MUS increases dynamic MUCP, bulking may rely on increasing the length of the continence zone.


title: Low reproducibility of randomized clinical trials methodology related to sampling: a systematic methodological review.

text: OBJECTIVES The reporting of sampling methods in Randomized Clinical Trials (RCTs) allows for research quality assessment, determination of sampling bias, and assures the presence of details necessary for reproducibility in future trials. The purpose of this study was to: (1) determine if sampling methodology was reproducible in RCTs related to musculoskeletal physical therapy (MSKPT) interventions to treat non-specific low back pain (NSLBP) and (2) establish if there was a relationship between sample reproducibility and established measures of research quality. METHODS Data were collected through a systematic review by a professional librarian. The identified RCTs were assessed for methodological quality by two blinded individual reviewers. Data analysis was performed by a third, blinded researcher; additional comparisons were made based on Journal Impact Factor and PEDro score. RESULTS Ninety-nine published peer-reviewed RCTs were identified that met inclusion criteria. Only 29% of the articles were judged to be reproducible based on the reported sampling methodology. There were meaningful correlations between two out of ten of the sampling reporting criteria and the judgement made if the sample was reported in significant detail to allow for replication. There was no relationship between sampling reporting criteria, Journal Impact Factors (JIFs), and Physiotherapy Evidence Database (PEDro) scores. DISCUSSION The reporting of sampling methodology needs to be considered to ensure reproducibility and avoid sampling bias. Despite the proliferation of measures of research quality, the overall reporting quality of RCTs continues to be inadequate to allow widespread reproducibility of trials. LEVEL OF EVIDENCE 1a.


title: Consideration of Pannexin 1 channels in COVID-19 pathology and treatment.

text: Pannexin1 (PANX1) is a ubiquitously expressed, channel-forming protein found in a number of tissues thoughout the body (e.g. lung, vasculature, liver, central nervous system, immune system) that is important in many key physiological and immune responses. PANX1 channels passively flux ATP (predominantly), multiple metabolites, and likely other small anions. PANX1 channels regulate inflammation and host responses to several pathogens, including viruses. While there is currently no evidence suggesting novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and PANX1 directly interact, there is an urgent need for therapeutic strategies, especially those targeting the hyper-inflammation and cytokine storm that occurs in severe cases of COVID-19. Here we argue that PANX1, and drugs known to target PANX1 (including the FDA-approved drug probenecid), should be the focus of further investigation in the context of SARS-CoV-2 infection and its associated pathology in COVID-19 patients.


title: The COVID-19 outbreak in Italy: initial implications for organ transplantation programs.

text: The spread of Coronavirus Disease 2019 (COVID-19) has already reached a pandemic dimension within few weeks. Italy has been one of the first countries dealing with the outbreak of COVID-19 and severe measures have been adopted to limit viral transmission. The spread of COVID-19 may have several implications in organ transplant activity that physicians should be aware of. The initial experience gained during the COVID-19 outbreak shows that around 10% of infected patients in Italy need intensive care management to overcome the acute respiratory distress syndrome. Due to the exponential rise of infected patients we are now facing an actual risk of saturation of intensive care unit (ICU) beds. A restriction in the number of ICU beds available for both donors and transplant recipients may unfavorably influence the overall donation activity, and eventually lead to a reduced number of transplants. Preliminary Italian data show that a 25% reduction of procured organs has already occurred during the first 4 weeks of COVID-19 outbreak. This underlines the need to closely monitor what will be further happening in ICUs due to the COVID-19 spread in the attempt to preserve transplant activity, especially in Western countries where deceased donors represent the major organ resource.


Helen Salisbury: GPs still have no access to coronavirus testing.


Comparison of Cuff Pressure Increases by Transesophageal Echocardiography: A Simulation Analysis Using a Porcine Pharyngeal Model.


title: Discrimination, Skin Color Satisfaction, and Adjustment among Latinx American Youth.

text: Race-related biases and discrimination and easily observable race-related characteristics, such as skin color, appear to go hand and hand, but it remains unclear how these factors work together to shape youth development. The current study addresses this gap by investigating skin color satisfaction as a mediator between perceptions of discrimination and adjustment. Data are from a cross-sectional sample of Latinx youth (N = 175; Mage = 12.86; 51.4% female; 86.9% US-born) who completed measures of foreigner-based objectification, peer discrimination, adult discrimination, self-esteem, depressive symptoms, and the importance or value attributed to academic success. Evidence of significant indirect effects of skin color satisfaction in the links between foreigner-based objectification and self-esteem as well as academic importance was found. Skin color satisfaction did not mediate links between either peer or adult discrimination and self-esteem, depression, and academic importance. The results provide support that being perceived as a foreigner has negative implications for Latinx youth adjustment through skin color satisfaction. The present study expands understanding of how different forms of differential treatment may affect minoritized youth. Implications and future research ideas are discussed.


title: Open fetal surgery for myelomeningocele - is there the learning curve at reduction mother and fetal morbidity?

text: OBJECTIVES We aimed to show how increased experience of a surgery team in fMMC repair influences maternal and fetal/neonatal outcomes. MATERIAL AND METHODS We compare perinatal results of fMMC repair in our Fetal Surgery Center (FSC) in cohort groups for the early period (2005-2011 year; previous - PFSC, n = 46) and current period (2012-2015 year; current - CFSC, n = 74) to results of the randomized Management of Myelomeningocele Study (MOMS, 78 patients). RESULTS The maternal morbidity due to fMMC repair was low and there was no difference comparing CFSC to PFSC and MOMS. The frequency of iatrogenic preterm labor (iPTL) ≤ 30 weeks of gestation decreased from 34.1% in PFSC to 23.9% in CFSC. Iatrogenic preterm premature rupture of membranes (iPPROM) was a common complication after fMMC repair in all cohorts. The total reduction rate of hindbrain hernation (HH) was similar in CFSC - 90.3% and PFSC - 82.1%. CONCLUSIONS The increasing experience of our surgery team in fMMC repair majorly decreased the risk of iPTL.


title: Partial splenectomy: A case series and systematic review of the literature.

text: Backgrounds/Aims Partial splenectomy (PS) is a surgical option for splenic mass, in order to reduce postoperative complications and preserve the splenic function. Despite this, data in literature is still scarce. The present study aimed to reveal our recent experience and provide a comprehensive overview of the feasibility and complications related to various surgical approaches. Methods Data of patients who underwent PS, between 2014 and 2017 were retrospectively reviewed. Literature was searched for studies reporting all types of PS in adult or adolescent patients. Results Five PS were performed in our department: two (40%) by laparoscopy and three (60%) by laparotomy. Two (40%) postoperative complications were detected, and in one of them, total splenectomy (TS) by laparotomy was finally required. There were no deaths or complications at last follow-up. Twenty studies including 213 patients were identified in the literature search. The rate of conversion from laparoscopic to open surgery was 3% (range, 5-50%) and in 3% of cases (range, 7-10%) PS was converted into total TS and the overall morbidity rate was 8% (range, 5-25%). In comparison to laparotomy, the conversion rate of laparoscopic approach to TS was 3.5% (vs. 1.4%) and a morbidity rate of 9.8% (vs. 4.3%). Conclusions The present review shows that PS is a viable procedure in selected cases. The mini-invasive approach seemed to be feasible despite the presence of higher rate of complications than the open technique. In future, further studies on this topic are needed by involving more patients. Furthermore, it is proposed that the development of robotic surgery could make this approach the new gold-standard technique for spleen-preserving surgery.


COVID-19 Severity Correlates with Weaker T Cell Immunity, Hypercytokinemia and Lung Epithelium Injury.


title: Increase of SARS-CoV 3CL peptidase activity due to macromolecular crowding effects in the milieu composition.

text: The 3C-like peptidase of the severe acute respiratory syndrome virus (SARS-CoV) is strictly required for viral replication, thus being a potential target for the development of antiviral agents. In contrast to monomeric picornavirus 3C peptidases, SARS-CoV 3CLpro exists in equilibrium between the monomer and dimer forms in solution, and only the dimer is proteolytically active in dilute buffer solutions. In this study, the increase of SARS-CoV 3CLpro peptidase activity in presence of kosmotropic salts and crowding agents is described. The activation followed the Hofmeister series of anions, with two orders of magnitude enhancement in the presence of Na₂SO₄, whereas the crowding agents polyethylene glycol and bovine serum albumin increased the hydrolytic rate up to 3 times. Kinetic determinations of the monomer dimer dissociation constant (K(d)) indicated that activation was a result of a more active dimer, without significant changes in K(d) values. The activation was found to be independent of substrate length and was derived from both k(cat) increase and K(m) decrease. The viral peptidase activation described here could be related to the crowded intracellular environment and indicates a further fine-tuning mechanism for biological control, particularly in the microenvironment of the vesicles that are induced in host cells during positive strand RNA virus infection.


title: Improved Detection of Respiratory Pathogens by Use of High-Quality Sputum with TaqMan Array Card Technology.

text: New diagnostic platforms often use nasopharyngeal or oropharyngeal (NP/OP) swabs for pathogen detection for patients hospitalized with community-acquired pneumonia (CAP). We applied multipathogen testing to high-quality sputum specimens to determine if more pathogens can be identified relative to NP/OP swabs. Children (<18 years old) and adults hospitalized with CAP were enrolled over 2.5 years through the Etiology of Pneumonia in the Community (EPIC) study. NP/OP specimens with matching high-quality sputum (defined as ≤10 epithelial cells/low-power field [lpf] and ≥25 white blood cells/lpf or a quality score [q-score] definition of 2+) were tested by TaqMan array card (TAC), a multipathogen real-time PCR detection platform. Among 236 patients with matched specimens, a higher proportion of sputum specimens had ≥1 pathogen detected compared with NP/OP specimens in children (93% versus 68%; P < 0.0001) and adults (88% versus 61%; P < 0.0001); for each pathogen targeted, crossing threshold (CT) values were earlier in sputum. Both bacterial (361 versus 294) and viral detections (245 versus 140) were more common in sputum versus NP/OP specimens, respectively, in both children and adults. When available, high-quality sputum may be useful for testing in hospitalized CAP patients.


Community-based Cancer Care Quality and Expertise in a COVID-19 Era and Beyond.


title: [Liquid chromatography tandem mass spectrometry for therapeutic drug monitoring of voriconazole in heat-inactivated blood samples: its application during COVID-19 pandemic].

text: OBJECTIVE To investigate the effect of heat inactivation (56℃for 30 min) of SARS-CoV-2 on the results of therapeuticdrug monitoring (TDM) of voriconazole by liquid chromatography tandem mass spectrometry (LC-MS/MS). METHODS We collected clinical blood samples from voriconazole-treated patients in heparinized tubes and sterilized the surface of the tubes with 75% ethanol. The whole blood samples were centrifuged to separate the plasma with or without prior heat inactivation, or only the separated plasma was heat inactivated. Heat inactivation of the samples was carried out at 56 ℃ for 30 min followed by protein precipitation with acetonitrile or ethanol. The plasma standard and quality control samples were inactivated in an identical manner and tested with LC-MS/MS along with the treated samples. RESULTS The optimized method showed a high imprecision (with mean intra- and inter-day imprecisions of 3.59% and 2.81%, respectively) and a high accuracy (mean 97.37%) for detecting voriconazole in the inactivated samples at different concentration levels. Sample preparation with acetonitrile or ethanol resulted in a high mean recovery (100.56% or 95.90%) with minimal mean matrix effect (102.85% or 93.62%). The measured voriconazole concentrations in inactivated whole blood, inactivated plasma and the samples without inactivation all showed good linear correlations with correlation coefficients all greater than 0.99. CONCLUSIONS Heat inactivation at 56 ℃ for 30 min combined with ethanol sample preparation only has limited effects to affect LC-MS-based voriconazole concentration measurement in whole blood samples collected in heparinized tubes, and can be used for therapeutic drug monitoring of voriconazole during the ongoing COVID-19 pandemic.


title: Ileal pouch prolapse: prevalence, management, and outcomes.

text: AIM The study aim is to review the prevalence, management, and outcomes for patients diagnosed with ileal pouch prolapse after restorative proctocolectomy. MATERIALS AND METHODS Patients were identified retrospectively from a prospectively maintained pouch database. Parameters analyzed included presenting symptoms, indications for pouch surgery, type of ileal pouch-anal anastomosis, treatment modalities, and outcomes. RESULTS Of 3,176 patients who underwent ileal pouch surgery, 11 were diagnosed with pouch prolapse (0.3%). Seven had full-thickness prolapse and four mucosal prolapse. Six were male, and five were female. Indication for index surgery was ulcerative colitis (nine patients), familial adenomatous polyposis (one patient), and colonic inertia (one patient). Median age at pouch prolapse was 34 years. Median time from index surgery to prolapse diagnosis was 2 years. Two patients with mucosal prolapse responded to conservative management; two required mucosal excisions. An abdominal approach was successful in four out of seven patients with full thickness prolapse. The three failures subsequently underwent continent ileostomy formation and prompted us to add biological mesh to future pouchpexy repairs. CONCLUSIONS Pouch prolapse is rare, and there are no obvious predisposing factors. Mucosal prolapse may be treated by stool bulking or a local perineal procedure. Full thickness prolapse requires definitive surgery and is associated with risk of pouch loss.


title: Abuse-deterrent opioids: an update on current approaches and considerations.

text: OBJECTIVE Abuse and misuse of prescription opioids is a significant public health concern. This review examines the strategies used to confer abuse-deterrent properties on opioid abuse-deterrent formulations (ADFs), the characteristics and supporting data for each of the available ADFs, and the role of opioid ADFs as part of a comprehensive opioid risk management plan. METHODS A PubMed search was performed for articles published within the last 10 years using the search terms "abuse deterrent opioids". Articles were limited to clinical studies and reviews focusing on United States (US) Food and Drug Administration (FDA)-approved opioid ADFs in the US. RESULTS There are currently nine extended-release and one immediate-release opioid pain medications with US FDA-approved ADF labelling. All use either physical and chemical barriers or agonist/antagonist combinations to deter manipulation and abuse. Evidence is mounting that introduction of opioid ADFs has been associated with decreased rates of abuse and diversion of opioids in the US. CONCLUSIONS Although not sufficient by themselves to prevent prescription opioid abuse and misuse, opioid ADFs are an important component of a healthcare provider's comprehensive opioid risk management plan (along with utilization of prescription drug monitoring programs, clinical assessment tools, urine tests, co-prescribing of naloxone to patients at risk of an overdose, access to non-pharmacological treatments and addiction/mental health resources, among others). Adoption of opioid ADFs should be considered as part of an overall public health opioid risk management plan involving all stakeholders to balance legitimate safe and effective use of opioids against misuse and abuse.


title: Retention of laryngoscopy skills in medical students: a randomised, cross-over study of the Macintosh, A.P. Advance(™) , C-MAC(®) and Airtraq(®) laryngoscopes.

text: In addition to being effective and easy to learn how to use, the ideal laryngoscope should be associated with minimal reduction in skill performance during gaps in practice over time. We compared the time taken to intubate the trachea of a manikin by novice medical students immediately after training, and then after 1 month, with no intervening practice. We designed a two-period, four-group, randomised, cross-over trial to compare the Macintosh, Venner(™) A.P. Advance(™) with difficult airway blade, C-MAC(®) with D-Blade and Airtraq(®) with wireless video-viewer. A bougie was used to aid intubation with the Macintosh and the C-MAC. After training, there was no significant difference in median (IQR [range]) intubation time using the videolaryngoscopes compared with the Macintosh, which took 30 (26.5-35 [12-118])s. One month later, the intubation time was longer using the C-MAC (41 (29.5-52 [20-119])s; p = 0.002) and A.P. Advance (40 (28.5-57.5 [21-107])s; p = 0.0003)m compared with the Macintosh (27 (21-29 [16-90])s); there was no difference using the Airtraq (27 (20.5-32.5 [15-94])s; p = 0.258) compared with the Macintosh. While skill acquisition after a brief period of learning and practice was equal for each laryngoscope, performance levels differed after 1 month without practice. In particular, the consistency of performance using the C-MAC and A.P. Advance was worse compared with the Macintosh and the Airtraq. While the clinical significance of this is doubtful, we believe that reliable and consistent performance at laryngoscopy is desirable; for the devices that we tested, this requires regular practice.


title: "Ramping up telemedicine in pediatric urology- Tips for using a new modality".

text: The COVID pandemic has incited the rapid implementation of telehealth services. Through telemedicine, pediatric urologists can counsel children and their families about genitourinary tract conditions, while adhering to social distancing requirements and keeping families safe at home. With the accelerated use of telemedicine, it is crucial to maintain standards of providing high-quality and secure urologic care. Clinicians must practice effective virtual communication or 'webside' manner. While research may not be a priority, collecting data on telemedicine efforts will be critical in bringing about both payer-based and legislative reforms to encourage and enable wider telemedicine use in the post-COVID world.


title: Delayed Radical Prostatectomy is Not Associated with Adverse Oncological Outcomes: Implications for Men Experiencing Surgical Delay Due to the COVID-19 Pandemic.

text: PURPOSE The 2019 Novel Coronavirus (COVID-19) pandemic has forced many healthcare organizations to divert efforts and resources to emergent patient care, delaying many elective oncological surgeries. We investigated an association between delay in radical prostatectomy (RP) and oncological outcome. MATERIALS AND METHODS This is a retrospective review of men with intermediate and high-risk prostate cancer (PC) in the National Cancer Database (NCDB) underdoing radical prostatectomy from 2010-2016. Immediate RP was defined as RP within 3-months of diagnosis, while delayed RP was analyzed in 3-month intervals up to 12-months. Multivariable logistic regression models were fit to test for associations between levels of delayed RP and outcomes of interest (adverse pathology, upgrading on RP, node positive disease, and post-RP secondary treatments) compared with men undergoing immediate RP. RESULTS We identified 128,062 men with intermediate- and high-risk PC treated with RP. After adjustment, we did not appreciate a significant difference in odds of adverse pathology, upgrading, node positive disease, or post-RP secondary treatments between men treated with immediate RP and any level of delay up to 12 months. Subgroup analysis of men with Grade group 4 and 5 PC did not demonstrate an association between delayed RP and worse oncological outcomes. CONCLUSIONS In the NCDB, delayed RP was not associated with early adverse oncological outcomes at RP. These results may provide reassurance to patients and urologists balancing care in the current pandemic.


title: In the Aftermath.

text: After the initial surge of COVID-19, it's time for nurses to look inward and ahead.


title: Laparoendoscopic single-site nephroureterectomy with bladder cuff excision for upper urinary tract transitional-cell carcinoma: technical details based on oncologic principles.

text: PURPOSE To describe our technical details of laparoendoscopic single-site (LESS) nephroureterectomy with bladder cuff excision for the management of upper urinary tract transitional-cell carcinoma (TCC) based on oncologic principles. PATIENTS AND METHODS Two patients underwent LESS nephroureterectomy for upper urinary tract TCC. In both cases, we used a homemade single-port device that consisted of a wound retractor and a surgical glove. Using the flexible laparoscopic instruments, nephrectomy was performed using procedures similar to those of conventional laparoscopic nephrectomy. Bladder cuff excision was performed laparoscopically using the same procedure with open technique. RESULTS All procedures were completed successfully without conversion to conventional laparoscopic or open surgery and without additional extraumbilical trocars or incisions. LESS nephreoureterectomy with bladder cuff excision was performed in 385 and 285 minutes with estimated blood loss of 100 and 350 mL, respectively. Both patients were discharged on postoperative day 3 without perioperative complications. CONCLUSIONS LESS nephroureterectomy with bladder cuff excision for upper urinary tract TCC is a minimally invasive technique that may reproduce the open surgical technique and adhere to oncologic principles.


title: The Covidien LigaSure Maryland Jaw Device.

text: Since its invention nearly 20 years ago, the Covidien LigaSure device along with its ForceTriad generator has dominated the Electrothermal Bipolar Vessel Sealing market. The LigaSure was used for surgical procedures, both open and laparoscopic. The purpose of this review is to provide evidence of the safety and utility of the LigaSure device compared to more traditional means of hemostasis and its ultrasonic competitor, particularly in laparoscopic applications. We will provide evidence related to electrothermal bipolar vessel sealing in general and look specifically at Covidien's newest product, the LigaSure Maryland Jaw Device.


title: Dead body management amidst global pandemic of Covid-19.

text: Covid-19 has reached almost all the nations in the world. More and more people are dying from it and in some countries, even the army has been called upon to help dispose of the dead as there is a shortage of coffins, and undertakers are overwhelmed. Therefore, it is essential to have measures in place to contain the spread of infection while handling dead bodies. In view of this, different guidelines and protocols have been proposed bearing in mind the limited information we have about the virus. This review article sets them out for better reference.


title: A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.

text: First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most recently, the United States. Human-to-human transmission has been documented, with nosocomial transmission appearing to be an important route of infection. The recent increase in cases of MERS in the Middle East coupled with the lack of approved antiviral therapies or vaccines to treat or prevent this infection are causes for concern. We report on the development of a synthetic DNA vaccine against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein induced potent cellular immunity and antigen-specific neutralizing antibodies in mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge, all of the monkeys in the control-vaccinated group developed characteristic disease, including pneumonia. Vaccinated macaques were protected and failed to demonstrate any clinical or radiographic signs of pneumonia. These studies demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge, indicating that this strategy may have value as a possible vaccine modality against this emerging pathogen.


title: Role of RNA interference (RNAi) in dengue virus replication and identification of NS4B as an RNAi suppressor.

text: RNA interference (RNAi) is an important antiviral defense response in plants and invertebrates; however, evidences for its contribution to mammalian antiviral defense are few. In the present study, we demonstrate the anti-dengue virus role of RNAi in mammalian cells. Dengue virus infection of Huh 7 cells decreased the mRNA levels of host RNAi factors, namely, Dicer, Drosha, Ago1, and Ago2, and in corollary, silencing of these genes in virus-infected cells enhanced dengue virus replication. In addition, we observed downregulation of many known human microRNAs (miRNAs) in response to viral infection. Using reversion-of-silencing assays, we further showed that NS4B of all four dengue virus serotypes is a potent RNAi suppressor. We generated a series of deletion mutants and demonstrated that NS4B mediates RNAi suppression via its middle and C-terminal domains, namely, transmembrane domain 3 (TMD3) and TMD5. Importantly, the NS4B N-terminal region, including the signal sequence 2K, which has been implicated in interferon (IFN)-antagonistic properties, was not involved in mediating RNAi suppressor activity. Site-directed mutagenesis of conserved residues revealed that a Phe-to-Ala (F112A) mutation in the TMD3 region resulted in a significant reduction of the RNAi suppression activity. The green fluorescent protein (GFP)-small interfering RNA (siRNA) biogenesis of the GFP-silenced line was considerably reduced by wild-type NS4B, while the F112A mutant abrogated this reduction. These results were further confirmed by in vitro dicer assays. Together, our results suggest the involvement of miRNA/RNAi pathways in dengue virus establishment and that dengue virus NS4B protein plays an important role in the modulation of the host RNAi/miRNA pathway to favor dengue virus replication.


COVID-19—A Guide to Rapid Implementation of Telehealth Services: A Playbook for the Pediatric Gastroenterologist


Coronavirus Disease 2019, Prothrombotic Factors, and Venous Thromboembolism.


Mini-incision technique for repair of inguinal hernias: an alternative to laparoscopy?


title: An Innovative Ergometer to Measure Neuromuscular Fatigue Immediately after Cycling.

text: PURPOSE When assessing neuromuscular fatigue (NMF) from dynamic exercise using large muscle mass (e.g., cycling), most studies have delayed measurement for 1 to 3 min after task failure. This study aimed to determine the reliability of an innovative cycling ergometer permitting the start of fatigue measurement within 1 s after cycling. METHODS Twelve subjects participated in two experimental sessions. Knee-extensor NMF was assessed by electrical nerve and transcranial magnetic stimulation with both a traditional chair setup (PRE- and POST-Chair, 2 min postexercise) and the new cycling ergometer (PRE, every 3 min during incremental exercise and POST-Bike, at task failure). RESULTS The reduction in maximal voluntary contraction force POST-Bike (63% ± 12% PRE; P < 0.001) was not different between sessions and there was excellent reliability at PRE-Bike (intraclass correlation coefficient [ICC], 0.97; coefficients of variation [CV], 3.2%) and POST-Bike. Twitch (Tw) and high-frequency paired-pulse (Db100) forces decreased to 53% ± 14% and 62% ± 9% PRE, respectively (P < 0.001). Both were reliable at PRE-Bike (Tw: ICC, 0.97; CV, 5.2%; Db100: ICC, 0.90; CV, 7.3%) and POST-Bike (Tw: ICC, 0.88; CV, 11.9; Db100: ICC, 0.62; CV, 9.0%). Voluntary activation did not change during the cycling protocol (P > 0.05). Vastus lateralis and rectus femoris M-wave and motor-evoked potential areas showed fair to excellent reliability (ICC, 0.45-0.88). The reduction in maximal voluntary contraction and Db100 was greater on the cycling ergometer than the isometric chair. CONCLUSIONS The innovative cycling ergometer is a reliable tool to assess NMF during and immediately postexercise. This will allow fatigue etiology during dynamic exercise with large muscle mass to be revisited in various populations and environmental conditions.


title: Laparoscopic intersphincteric resection with a SILS port for very low rectal cancer: a case report.

text: Since intersphincteric resection (ISR) for rectal cancer was established in the 1990 s, this technique has been applied to very low rectal cancer. This procedure requires advanced techniques for anorectal surgery. However, it is indicated only for early lesions and should be as minimally invasive as possible. We describe a minimally invasive ISR with a single-incision laparoscopic surgery (SILS) port. Our case involves a 59-year-old man with hemorrhage from the rectum. Pathologic examination of the transanally resected specimen revealed that the tumor had invaded into the deeper submucosa. To minimize surgical incisions, a SILS port was utilized in place of a 10- and a 5-mm trocar. The SILS port was inserted through a 2.5 cm transverse incision in the right lower abdomen, where a diverting stoma would be created. Two flexible or straight forceps introduced through this port afforded an easier dissection of the rectum to the levator ani muscle, and transanal dissection of the internal sphincter was performed in the standard manner to connect with the abdominal dissection. The only postoperative incision other than a stoma and surgical drain was one 10-mm incision above the umbilicus. Our technique of ISR with the SILS port is a useful clinical application of minimally invasive surgery.


title: Towards cardiopulmonary resuscitation without vasoactive drugs.

text: PURPOSE OF REVIEW Whereas there is clear evidence for improved survival with cardiopulmonary resuscitation (CPR) and defibrillation during cardiac arrest management, there is today lacking evidence that any of the recommended and used drugs lead to any long-term benefit for the patients. In this review, we try to discuss our current view on why advanced life support (ALS) today can be performed without the use of drugs, and instead gain all focus on improving the tasks we know improve survival: CPR and defibrillation. RECENT FINDINGS Previous and recent cardiac arrest drug studies have been reviewed. These are mostly consisting of retrospective register data, some experimental data and a few new randomized trials. The alternative drug-free ALS concept is also discussed with relevant studies. SUMMARY There is currently no evidence to support any specific drugs during cardiac arrest. Good-quality CPR, early defibrillation and goal-directed postresuscitation care is more important. Healthcare systems should not prioritize implementation of unproven drugs before good quality of care can be documented. More drug studies are indeed required, and future research needs to incorporate better diagnostic tools to test more specific and tailored therapies that account for underlying causes and individual responsiveness.


title: [Feasibility analysis on acupuncture therapy for the treatment of Corona Virus Disease 2019 and the exploration on the application scheme].

text: The situation of Corona Virus Disease 2019 (COVID-19) is still severe at present. In order to better fight against the epidemic and give full play to the advantages of traditional Chinese medicine, we explored the feasibility of acupuncture therapy in the intervention of COVID-19 through analyzing the relevant literature in both ancient and modern time. Additionally, we analyzed the intervention scheme of acupuncture for COVID-19 developed by China Association of Acupuncture and Moxibustion and supplemented the protocol of the intervention with auricular acupuncture. It was proposed that the advantages of acupuncture and moxibustion should be fully displayed while Chinese herbal medications have been applied in the treatment of COVID-19. During treatment, acupuncture physicians should be rationally allocated to a certain proportion so as to adequately utilize comprehensive therapeutic approaches and guarantee people's safety to the greatest extent. Eventually, the clinical therapeutic effect may be improved, the national resources be economized on and the COVID-19 epidemic be conquered early.


title: Design and Construction of Chimeric VP8-S2 Antigen for Bovine Rotavirus and Bovine Coronavirus.

text: PURPOSE Bovine Rotavirus and Bovine Coronavirus are the most important causes of diarrhea in newborn calves and in some other species such as pigs and sheep. Rotavirus VP8 subunit is the major determinant of the viral infectivity and neutralization. Spike glycoprotein of coronavirus is responsible for induction of neutralizing antibody response. METHODS In the present study, several prediction programs were used to predict B and T-cells epitopes, secondary and tertiary structures, antigenicity ability and enzymatic degradation sites. Finally, a chimeric antigen was designed using computational techniques. The chimeric VP8-S2 antigen was constructed. It was cloned and sub-cloned into pGH and pET32a(+) expression vector. The recombinant pET32a(+)-VP8-S2 vector was transferred into E.oli BL21CodonPlus (DE3) as expression host. The recombinant VP8-S2 protein was purified by Ni-NTA chromatography column. RESULTS The results of colony PCR, enzyme digestion and sequencing showed that the VP8-S2 chimeric antigen has been successfully cloned and sub-cloned into pGH and pET32a(+).The results showed that E.coli was able to express VP8-S2 protein appropriately. This protein was expressed by induction of IPTG at concentration of 1mM and it was confirmed by Ni-NTA column, dot-blotting analysis and SDS-PAGE electrophoresis. CONCLUSION The results of this study showed that E.coli can be used as an appropriate host to produce the recombinant VP8-S2 protein. This recombinant protein may be suitable to investigate to produce immunoglobulin, recombinant vaccine and diagnostic kit in future studies after it passes biological activity tests in vivo in animal model and or other suitable procedure.


title: Surveillance and early warning systems of infectious disease in China: From 2012 to 2014.

text: Appropriate surveillance and early warning of infectious diseases have very useful roles in disease control and prevention. In 2004, China established the National Notifiable Infectious Disease Surveillance System and the Public Health Emergency Event Surveillance System to report disease surveillance and events on the basis of data sources from the National Notifiable Infectious Disease Surveillance System, China Infectious Disease Automated-alert and Response System in this country. This study provided a descriptive summary and a data analysis, from 2012 to 2014, of these 3 key surveillance and early warning systems of infectious disease in China with the intent to provide suggestions for system improvement and perfection.


Genomic search for COVID-19 severity clues.


title: The appropriate use of neurostimulation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain. Neuromodulation Appropriateness Consensus Committee.

text: INTRODUCTION The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes. METHODS The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks. RESULTS The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician. CONCLUSIONS The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly.


title: The Effects of Primary Care-Based Parenting Interventions on Parenting and Child Behavioral Outcomes: A Systematic Review.

text: Behavioral parenting interventions can enhance positive parenting practice, which is crucial in preventing maltreatment and promoting child well-being. Primary care has been increasingly recognized as an underutilized platform to widely disseminate evidence-based parenting interventions, given parents' ongoing access to primary care without stigma and the perceptions toward health-care providers as a trustworthy source of information about positive parenting. This study sought to explore the effects of primary care-based parenting interventions on parenting practice and child behavioral outcomes while examining the types of and the theories of change underlying these interventions. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Randomized controlled trials or quasi-experimental studies of interventions targeting caregivers of children aged between 1 and 17 were included in the review. Information sources included electronic databases, relevant government and private organizational websites, and expert consultations. The final sample included 17 studies focusing on 10 interventions. Positive results were found in knowledge gain, locus of control, monitoring, parent-child interactions, and negative discipline. Child behavior outcomes were inconsistent as most studies reported nonsignificant changes while one study reported significant intervention effects on various externalizing behaviors. A limited number of studies described the process of adapting, installing, and implementing the interventions in primary care. Future studies should examine the types, dosages, and delivery formats that are most suitable and sustainable in the context of primary care to maximize its utility in promoting child well-being while preventing maltreatment through integrated behavioral parenting interventions.


title: Use of intraoperative ablation as an adjunct to surgical resection in the treatment of recurrent colorectal liver metastases.

text: OBJECTIVE To evaluate the role of intraoperative ablation as an adjunct to resection in patients with recurrent colorectal liver metastases (rCLM). METHODS All patients undergoing curative-intent reoperative surgery for rCLM from 1992 to 2009 at a tertiary cancer center were included. Overall survival (OS) and recurrence-free survival (RFS) were compared between patients treated with resection alone or in combination with ablation. RESULTS A total of 112 reoperative hepatectomies were performed, of which 16 were combined with ablation. The proportion of patients treated with resection and ablation increased from 0% to 41%. Patients undergoing resection and ablation had a greater tumor burden (median, 4 vs. 1, p < 0.0001) and higher baseline clinical risk scores (median, 3 vs. 2, p = 0.065) than patients undergoing resection alone. Patients undergoing resection and ablation had lower intraoperative blood loss than patients undergoing resection alone (344 vs. 877 ml, p = 0.018). Five-year OS from the time of surgery was 48.6%. In multivariable analysis, there was no significant difference in OS or RFS based on the treatment modality. CONCLUSION In patients with rCLM, the use of intraoperative ablation can extend the limits of surgical resection in patients with disease that might otherwise not be amenable to complete resection.


title: Decline in Child Vaccination Coverage During the COVID-19 Pandemic - Michigan Care Improvement Registry, May 2016-May 2020.

text: On March 13, 2020, the United States declared a national state of emergency to control the pandemic spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). Public health response measures to mitigate the pandemic have centered on social distancing and quarantine policies, including shelter-in-place and stay-at-home orders. Michigan implemented a stay-at-home order on March 23, 2020, to facilitate social distancing (2). Such strategies might result in decreased accessibility to routine immunization services, leaving children at risk for vaccine-preventable diseases and their complications (3). To evaluate whether vaccination coverage has changed during the pandemic, data from the Michigan Care Improvement Registry (the state's immunization information system) (MCIR) were analyzed. Changes in vaccine doses administered to children and the effects of those changes on up-to-date status were examined for vaccinations recommended at milestone ages corresponding to the end of an Advisory Committee on Immunization Practices (ACIP) recommendation period for one or more vaccines (4).


title: Interferon-γ promotes double-stranded RNA-induced TLR3-dependent apoptosis via upregulation of transcription factor Runx3 in airway epithelial cells.

text: Viral respiratory tract infections are the most common illness in humans. Infection of the respiratory viruses results in accumulation of viral replicative double-stranded RNA (dsRNA), which is one of the important components of infecting viruses for the induction of lung epithelial cell apoptosis and innate immune response, including the production of interferon (IFN). In the present study, we have investigated the regulation of dsRNA-induced airway epithelial cell apoptosis by IFN. We found that transcription factor Runx3 was strongly induced by type-II IFNγ, slightly by type-III IFNλ, but essentially not by type-I IFNα in airway epithelial cells. IFNγ-induced expression of Runx3 was predominantly mediated by JAK-STAT1 pathway and partially by NF-κB pathway. Interestingly, Runx3 can be synergistically induced by IFNγ with a synthetic analog of viral dsRNA polyinosinic-polycytidylic acid [poly(I:C)] or tumor necrosis factor-α (TNFα) through both JAK-STAT1 and NF-κB pathways. We further found that dsRNA poly(I:C)-induced apoptosis of airway epithelial cells was mediated by dsRNA receptor toll-like receptor 3 (TLR3) and was markedly augmented by IFNγ through the enhanced expression of TLR3 and subsequent activation of both extrinsic and intrinsic apoptosis pathways. Last, we demonstrated that upregulation of Runx3 by IFNγ promoted TLR3 expression, thus amplifying the dsRNA-induced apoptosis in airway epithelial cells. These novel findings indicate that IFNγ promotes dsRNA-induced TLR3-dependent apoptosis via upregulation of transcription factor Runx3 in airway epithelial cells. Findings from our study may provide new insights into the regulation of airway epithelial cell apoptosis by IFNγ during viral respiratory tract infection.


title: Hospital pharmacist experience in a multidisciplinary team in special care settings.

text: The COVID-19 pandemic is placing huge strain on health systems and professionals. Emergency departments and their pharmacy services have been the first to face this challenge before any other pharmacy units. This article provides a description of the experience of two public hospitals located in the Autonomous Community of Madrid, Spain. Team working and reciprocal trust have made it possible to meet the unprecedented demand for health services and has facilitated rapid decision making. Strategies have been developed to guarantee the availability, distribution and safe use of medications. Other strategies have included favoring communication within Emergency Departments pharmacy services, and between these services and Emergency Departments during the pandemic. Multidisciplinary cooperation and information sharing have traditionally formed the base for efficient and quality work, along with solid technologies that guarantee a safe use of medications. The crucial role of information and communication technologies during the pandemic may give rise to a new model of pharmaceutical care, which should not replace face-to- face Emergency Department pharmacist support and advice. Promoting the re- humanization of healthcare and pharmacy services is essential. An adequate technical training and the development of abilities such as flexibility, planning and coordination skills, and an assertive communication and management of emotions will be key to the successful management of unimaginable settings in the future.


COVID-19-Leitfaden für die Priorisierung von Operationen bei malignen thorakalen Erkrankungen


title: The role of echocardiography in SARS-CoV-2 pandemic: a compromise among appropriateness, safety and clinical impact.

text: SARS-CoV-2 infection, responsible for COVID-19, can determine cardiac events, which require a quick diagnosis and management, and should not be overlooked due to the presence of COVID-19 infection. In some cases, cardiovascular symptoms can also be the first and only manifestation of SARS-CoV-2 infection. In patients with COVID-19, the full cardiovascular disease diagnostic algorithm can be hindered by logistic restrain mainly derived from the difficulty of transporting patients in critical conditions to Radiology or Hemodynamics wards. The echocardiography in SARS-CoV-2 pandemic can help for differential diagnosis of cardiac events, which can be related or unrelated by the infection and can likely impact on short-term prognosis. Indeed, transthoracic echocardiography plays a key role in the screen for CV complications of COVID-19 infection: it must be focused cardiac ultrasound study (FoCUS) performed at bedside. All transthoracic, transesophageal and stress echocardiograms in patients in which test results are unlikely to change the management strategy should be postponed.


title: Human ocular-derived virus-specific CD4+ T cells control varicella zoster virus replication in human retinal pigment epithelial cells.

text: PURPOSE Varicella zoster virus (VZV)-induced retinitis is characterized by the presence of virus-infected cells in the retinal layer and the ocular infiltration of VZV-specific T cells. Herein, the susceptibility of human retinal pigment epithelial (RPE) cells to VZV infection and the ability of virus-specific CD4(+) T cells to control VZV infection in RPE cells in vitro is addressed. METHODS Human primary RPE cell cultures (n=2) were infected with a VZV strain expressing green fluorescent protein. The infection and viability of infected RPE cells was monitored by flow cytometry or by a fluorescent imager on RPE monolayers. RPE cells, pretreated with or without interferon-gamma (IFN-gamma), were infected with VZV and subsequently cultured with VZV-specific CD4(+) T-cell clones (TCCs; n=3) recognizing disparate VZV proteins presented by different HLA class II alleles. IFN-gamma production and cytotoxicity of the TCCs in response to VZV-infected RPE cells was determined by flow cytometry. RESULTS Human RPE cells are permissive to a productive VZV infection. VZV-infected RPE cells presented the cognate antigen to the CD4(+) TCCs only if the RPE cells were pretreated with IFN-gamma and expressed the appropriate HLA class II allele. VZV-specific TCCs inhibited productive VZV infection in RPE cells, which was in part attributed to TCC-mediated killing of the VZV-infected RPE cells. CONCLUSIONS The results presented suggest that RPE cells may play a role as retina-resident antigen-presenting cells in the intraocular, VZV-specific, T cell-mediated inflammatory response of VZV-induced uveitis.


title: Functional analyses of the three simian hemorrhagic fever virus nonstructural protein 1 papain-like proteases.

text: UNLABELLED The N-terminal region of simian hemorrhagic fever virus (SHFV) nonstructural polyprotein 1a is predicted to encode three papain-like proteases (PLP1α, PLP1β, and PLP1γ). Catalytic residues and cleavage sites for each of the SHFV PLP1s were predicted by alignment of the SHFV PLP1 region sequences with each other as well as with those of other arteriviruses, and the predicted catalytic residues were shown to be proximal by homology modeling of the SHFV nsp1s on porcine respiratory and reproductive syndrome virus (PRRSV) nsp1 crystal structures. The functionality of the predicted catalytic Cys residues and cleavage sites was tested by analysis of the autoproteolytic products generated in in vitro transcription/translation reactions done with wild-type or mutant SHFV nsp1 constructs. Cleavage sites were also analyzed by mass spectroscopy analysis of selected immunoprecipitated cleavage products. The data showed that each of the three SHFV PLP1s is an active protease. Cys63 was identified as the catalytic Cys of SHFV PLP1α and is adjacent to an Ala instead of the canonical Tyr observed in other arterivirus PLP1s. SHFV PLP1γ is able to cleave at both downstream and upstream nsp1 junction sites. Although intermediate precursor polyproteins as well as alternative products generated by each of the SHFV PLP1s cleaving at sites within the N-terminal region of nsp1β were produced in the in vitro reactions, Western blotting of SHFV-infected, MA104 cell lysates with SHFV nsp1 protein-specific antibodies detected only the three mature nsp1 proteins. IMPORTANCE SHFV is unique among arteriviruses in having three N-terminal papain-like protease 1 (PLP1) domains. Other arteriviruses encode one or two active PLP1s. This is the first functional study of the SHFV PLP1s. Analysis of the products of in vitro autoprocessing of an N-terminal SHFV nonstructural 1a polypeptide fragment showed that each of the three SHFV PLP1s is active, and the predicted catalytic Cys residues and cleavage sites for each PLP1 were confirmed by testing mutant constructs. Several unique features of the SHFV PLP1s were discovered. The SHFV PLP1α catalytic Cys63 is unique among arterivirus PLP1s in being adjacent to an Ala instead of a Trp. Other arterivirus PLP1s cleave only in cis at a single downstream site, but SHFV PLP1γ can cleave at both the downstream nsp1γ-nsp2 and upstream nsp1β-nsp1γ junctions. The three mature nsp1 proteins were produced both in the in vitro reactions and in infected cells.


title: Fundamental differences between the nucleic acid chaperone activities of HIV-1 nucleocapsid protein and Gag or Gag-derived proteins: biological implications.

text: The HIV-1 Gag polyprotein precursor has multiple domains including nucleocapsid (NC). Although mature NC and NC embedded in Gag are nucleic acid chaperones (proteins that remodel nucleic acid structure), few studies include detailed analysis of the chaperone activity of partially processed Gag proteins and comparison with NC and Gag. Here we address this issue by using a reconstituted minus-strand transfer system. NC and NC-containing Gag proteins exhibited annealing and duplex destabilizing activities required for strand transfer. Surprisingly, unlike NC, with increasing concentrations, Gag proteins drastically inhibited the DNA elongation step. This result is consistent with "nucleic acid-driven multimerization" of Gag and the reported slow dissociation of Gag from bound nucleic acid, which prevent reverse transcriptase from traversing the template ("roadblock" mechanism). Our findings illustrate one reason why NC (and not Gag) has evolved as a critical cofactor in reverse transcription, a paradigm that might also extend to other retrovirus systems.


title: SARS coronavirus nucleocapsid protein monoclonal antibodies developed using a prokaryotic expressed protein.

text: Immunological detection of viruses and their components using monoclonal antibodies (MAbs) is a powerful diagnostic method. Here we report a detailed method for the establishment of MAbs against severe acute respiratory syndrome coronavirus (SARS-CoV). To express and purify the nucleocapsid protein (N protein) of SARS-CoV and generate MAbs against the N protein, gene encoding N protein was separated into two parts according to the prediction of epitopes and cloned into pET32a(+), respectively. Expression of the target proteins were induced by M isopropyl-β-thio-D-galactopyranoside (IPTG) and purified by a single-step affinity chromatography on a Ni-NTA column. BALB/c mice were immunized with the purified recombinant proteins to prepare MAbs by hybridoma technique. The reactivity and specificity of the MAbs were analyzed by ELISA and Western blot analysis. Seven MAbs against N1 and two MAbs against N2 were obtained. In the present study, recombinant SARS-CoV N protein was expressed and purified and nine specific MAbs against SARS-CoV N protein were obtained successfully. This panel of anti-N MAbs may be used as a tool for rapid and specific diagnosis of SARS-CoV.


title: Analytic Vaccinology: Antibody-Driven Design of a Human Cytomegalovirus Subunit Vaccine.

text: Identification of the most relevant protective antigens has represented a considerable obstacle for the development of subunit vaccines against viral infections, including human cytomegalovirus (HCMV) infection. This chapter describes the method of analytic vaccinology, centered on the clonal analysis of human B cell response to HCMV, which represents an essential tool for assessing the impact of individual viral antigens in the antiviral antibody response. By providing key information on the immunogenicity and protective properties of the antibodies elicited by viral proteins, the analytic vaccinology method guides the selection of the most appropriate vaccine candidates. Here we discuss methodologies for the generation of human monoclonal antibodies from B cells of immune donors, antibody screening in in vitro assays of antigen binding and virus neutralization, and strategies of animal immunization useful for the preclinical evaluation of selected viral antigens. The approach of analytic vaccinology could be universally applied to the characterization of B-cell immune response against any virus of interest and ultimately used for vaccine development.


title: Danish national clinical guidelines for surgical and nonsurgical treatment of patients with lumbar spinal stenosis.

text: PURPOSE To summarize the recommendations from the national clinical guideline published by the Danish Health Authority regarding surgical and nonsurgical interventions in treatment of lumbar spinal stenosis in patients above the age of 65 years. METHODS A multidisciplinary working group formulated recommendations based on the GRADE approach. RESULTS Seven of the recommendations were based on randomized controlled trials and three on professional consensus. The guideline recommends surgical decompression for symptomatic lumbar spinal stenosis. Supervised exercise and postsurgical supervised exercise are recommended due to the general beneficial effects of training on general health, even though there was no evidence on an effect on neurogenic pain. The guideline does not recommend manual therapy, paracetamol, NSAIDs, opioids, neurogenic pain medication, muscle relaxants, and decompression combined with instrumented fusion as there was no evidence of the beneficial effect. CONCLUSION The recommendations are based on low to very low quality of evidence or professional consensus as well as patient preferences and positive or harmful effects of the intervention. The true treatment effect may therefore be different from the estimated effects, which is why the results should be interpreted with caution. The working group recommends intensified research in relation to all aspects of management of lumbar spinal stenosis. These slides can be retrieved under Electronic Supplementary Material.


Psychoanalysis and the pandemic: Editor's Introduction.


title: In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium.

text: The goal of this method is to introduce a transgene into the endothelium of isolated segments of both rabbit common carotid arteries. The method achieves focal endothelial-selective transgenesis, thereby allowing an investigator to determine the biological roles of endothelial-expressed transgenes and to quantify the in vivo transcriptional activity of DNA sequences in large artery endothelial cells. The method uses surgical isolation of rabbit common carotid arteries and an arteriotomy to deliver a transgene-expressing viral vector into the arterial lumen. A short incubation period of the vector in the lumen, with subsequent aspiration of the lumen contents, is sufficient to achieve efficient and durable expression of the transgene in the endothelium, with no detectable transduction or expression outside of the isolated arterial segment. The method allows assessment of the biological activities of transgene products both in normal arteries and in models of human vascular disease, while avoiding systemic effects that could be caused either by targeting gene delivery to other sites (e.g. the liver) or by the alternative approach of delivering genetic constructs to the endothelium by germ line transgenesis. Application of the method is limited by the need for a skilled surgeon and anesthetist, a well-equipped operating room, the costs of purchasing and housing rabbits, and the need for expertise in gene-transfer vector construction and use. Results obtained with this method include: transgene-related alterations in arterial structure, cellularity, extracellular matrix, or vasomotor function; increases or reductions in arterial inflammation; alterations in vascular cell apoptosis; and progression, retardation, or regression of diseases such as intimal hyperplasia or atherosclerosis. The method also allows measurement of the ability of native and synthetic DNA regulatory sequences to alter transgene expression in endothelial cells, providing results that include: levels of transgene mRNA, levels of transgene protein, and levels of transgene enzymatic activity.


title: mRNA display design of fibronectin-based intrabodies that detect and inhibit severe acute respiratory syndrome coronavirus nucleocapsid protein.

text: The nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) coronavirus plays important roles in both viral replication and modulation of host cell processes. New ligands that target the N protein may thus provide tools to track the protein inside cells, detect interaction hot spots on the protein surface, and discover sites that could be used to develop new anti-SARS therapies. Using mRNA display selection and directed evolution, we designed novel antibody-like protein affinity reagents that target SARS N protein with high affinity and selectivity. Our libraries were based on an 88-residue variant of the 10th fibronectin type III domain from human fibronectin (10Fn3). This selection resulted in eight independent 10Fn3 intrabodies, two that require the N-terminal domain for binding and six that recognize the C terminus, one with Kd=1.7 nM. 10Fn3 intrabodies are well expressed in mammalian cells and are relocalized by N in SARS-infected cells. Seven of the selected intrabodies tested do not perturb cellular function when expressed singly in vivo and inhibit virus replication from 11- to 5900-fold when expressed in cells prior to infection. Targeting two sites on SARS-N simultaneously using two distinct 10Fn3s results in synergistic inhibition of virus replication.


title: Lifestyle interventions to maternal weight loss after birth: a systematic review.

text: BACKGROUND Over the past decades, there has been an increase in overweight and obesity in women of childbearing age, as well as the general population. Overweight and obesity are related to a later, increased risk of type 2 diabetes and cardiovascular diseases. Increasing weight between pregnancies has a negative impact on the development of the fetus in a subsequent pregnancy. It is also related to long-term obesity and overweight for the woman. Accordingly, weight control in women of the childbearing age is important for both women and their offspring. Information and communication technology (ICT) has become an integrated part of many peoples' lives, and it has the potential to prevent disease. In this systematic review, we summarize the evidence from randomized controlled trials to compare effects of different ICT-based interventions to support postpartum women to achieve weight loss. METHODS A systematic search was performed in PubMed, Embase, PsycInfo, CINAHL, Web of Science, Scopus, and Cochrane, searching on terms, such as postpartum, weight loss, telemedicine, and randomized controlled trials. Two independent researchers undertook study selection and data extraction. Results were reported narratively. The systematic review only included studies that were randomized controlled trials. RESULTS Eight studies were included in the systematic review. All of them were characterized by applying one or more ICT components to assist postpartum women in weight control, and had weight loss as an outcome measure. A significant difference was found in weight loss between control group and intervention group in the majority of the studies. However, five of the studies had a relatively short follow-up period (40 days to 16 weeks), six of the studies had a relatively small sample size (18 to 66 women), and half of the studies indicated challenges with adherence to the interventions over time. CONCLUSION ICT-based interventions can support postpartum women to achieve a healthy lifestyle and weight control. Future studies should focus on larger sample sizes, longer follow-up periods, and adherence to the interventions. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42018080731.


Employee thoughts on influenza vaccine: here we go again.


title: Effect of a real-time radiation monitoring device on operator radiation exposure during cardiac catheterization: the radiation reduction during cardiac catheterization using real-time monitoring study.

text: BACKGROUND The Radiation Reduction During Cardiac Catheterization Using Real-Time Monitoring study sought to examine the effect of a radiation detection device that provides real-time operator dose reporting through auditory feedback (Bleeper Sv; Vertec Scientific Ltd; Berkshire, UK) on patient dose and operator exposure during cardiac catheterization. METHODS AND RESULTS Between January 2012 and May 2014, 505 patients undergoing coronary angiography, percutaneous coronary intervention, or both were randomized to use (n=253) or no use (n=252) of the Bleeper Sv radiation monitor. Operator radiation exposure was measured in both groups using a second, silent radiation exposure monitoring device. Mean patient age was 65±8 years, most patients (99%) were men, and 30% had prior coronary artery bypass graft surgery. Baseline clinical characteristics were similar in the 2 study groups. Radial access was used in 18% and chronic total occlusion percutaneous coronary intervention constituted 7% of the total procedures. Median procedure time was 17 (12-27) minutes for diagnostic angiography, 42 (28-70) minutes for percutaneous coronary intervention, and 27 (14-51) minutes in the overall study population, with similar distribution between the study groups. First (9 [4-17] versus 14 [7-25] μSv; P<0.001) and second (5 [2-10] versus 7 [4-14] μSv; P<0.001) operator radiation exposure was significantly lower in the Bleeper Sv group. Use of the device did not result in a significant reduction in patient radiation dose. The effect of the Bleeper Sv device on operator radiation exposure was consistent among various study subgroups. CONCLUSIONS Use of a real-time radiation monitoring device that provides auditory feedback can significantly reduce operator radiation exposure during cardiac catheterization. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01510353.


title: Efficacy of laparoendoscopic single-site biopsy for diagnosis of retroperitoneal tumor of unknown origin.

text: BACKGROUND AND PURPOSE When percutaneous image-guided biopsies are not possible for retroperitoneal tumor of unknown origin (RTUO), surgical tissue diagnosis becomes necessary. Laparotomy and laparoscopic surgery are current standard treatments; however, the laparoendoscopic single-site (LESS) approach offers many potential benefits. We describe our technique for LESS biopsy of RTUO. PATIENTS AND METHODS Five patients underwent LESS biopsy for diagnosis of RTUO. A multichannel port was inserted into the peritoneal or retroperitoneal space through a 3-cm skin incision, which adequately exposed the retroperitoneal tumor. The specimen was grasped and isolated circumferentially from the surrounding tissue. RESULTS LESS surgery was performed successfully without any complications such as open conversion. Mean operative time was 183 min and estimated blood loss was negligible. The diagnoses were IgG4-related retroperitoneal fibrosis (n = 4) and lymphoma (n = 1). Sufficient specimens were safely obtained not only for pathological diagnosis but also for further examinations such as immunophenotyping or DNA analysis. Convalescence was satisfactory. All patients were treated appropriately according to the resulting diagnosis. CONCLUSIONS LESS biopsy for RTUO is a safe and effective alternative to open surgical and standard laparoscopic biopsies. Further studies of clinical experiences are needed to confirm the benefits of this new technique.


title: An experimentally successful new sphincter-conserving treatment for anal fistula.

text: PURPOSE A new sphincter-conserving treatment was evaluated in a porcine model. METHODS A total of 36 fistulas were created by procedures that have been published previously. At fistula induction a skin biopsy was taken from which to culture fibroblasts. Four weeks after induction, when fistulas were well established, the fistula tracks were cored out. Collagen paste modified from Permacol injection (Covidien, Mansfield, MA) was then used as a solitary infill material in 11 tracks, cultured autologous fibroblasts being added to this in a further 18 tracks. The track was cored out in seven controls, but these tracks were not treated with infill material. All of the internal and external openings were closed. Anorectal excision was then carried out under terminal anesthesia at 2 to 12 weeks. Histologic examination of individual tracks was performed by an experienced pathologist. RESULTS In this quadruped all of the infilled tracks healed, autologous fibroblasts having the best tissue integration, but only two of seven control tracks healed. CONCLUSIONS Removal of the fistula track followed by injection of collagen healed all of the cases. The addition of autologous fibroblasts improved the histologic appearance of the tracks. A pilot study in human fistula patients is in progress.


title: Morbidity associated with laparoscopic repair of suprapubic hernias.

text: BACKGROUND Laparoscopic suprapubic hernia repair (LSHR) is frequently a technically difficult procedure. This is often due to extensive adhesions from multiple previous operations, the necessary wide pelvic dissection, and adequate mesh coverage with transfascial suture fixation. The aim of the current study was to document the complications and morbidity associated with the repair of suprapubic hernias. METHODS A retrospective review of patients with complex suprapubic ventral hernias undergoing laparoscopic repair between 2003 and 2007 at 2 university-based practices by 1 surgeon at each facility was conducted. The operative techniques were similar and included dissection into the space of Retzius to mobilize the dome of the bladder, intraperitoneal onlay of mesh using a barrier mesh, careful tack fixation to the pubic bone and Cooper's ligaments, and extensive transfascial suture fixation of the mesh. RESULTS A total of 47 patients were reviewed, 29 women and 18 men, with a mean age of 54 years. Patients averaged 3.5 previous abdominal surgeries (SD +/-2.3) and had a mean body mass index (BMI) of 35.1 (SD +/-7.5). Previous ventral hernia repairs had been performed in 57% of patients. Average defect size was 139.8 cm(2) (SD +/-126) and average mesh size was 453.8 (SD +/-329.0), with an average hernia-to-mesh ratio of 3.2. Median length of stay was 3 days with a mean follow-up of 2.6 months (SD +/-3.1). There were 18 complications (38%): symptomatic seroma (n = 4), prolonged ileus (n = 2), chronic pain (n = 2), postoperative urinary retention (n = 2), enterotomy (n = 1), intraoperative bladder injury (n = 1), postoperative urinary tract infection (n = 1), mesh infection (n = 1), rapid ventricular rate (n = 1), small bowel obstruction (n = 1), pulmonary embolism (n = 1), and pneumonia (n = 1). One patient required conversion to open ventral hernia repair, no injury was identified. Recurrence occurred in 3 patients (6.3%). The mechanisms of recurrence included reherniation at the level of the pubic tubercle, a lateral mesh recurrence in a patient with a high BMI and small abdominal excursion, and in a pregnant patient who developed a fixation suture hernia. CONCLUSIONS Laparoscopic suprapubic hernia repair is safe and effective with a relatively low recurrence rate, considering the complexity of the repair.


title: Montelukast Does not Maintain Symptom Remission After Topical Steroid Therapy for Eosinophilic Esophagitis.

text: BACKGROUND & AIMS Montelukast, a cysteinyl leukotriene type-1 receptor blocker, has been shown in small retrospective studies to reduce symptoms in patients with eosinophilic esophagitis (EoE). We performed a randomized, placebo-controlled, double-blind trial to determine whether montelukast maintains symptomatic remission induced by topical steroid therapy in patients with EoE. METHODS We performed a prospective study of adult patients with EoE (solid-food dysphagia and a peak esophageal eosinophil count of >20 cells/high-powered field) enrolled at the Mayo Clinic in Rochester, Minnesota, from April 2008 through February 2015. All patients had been treated previously for at least 6 weeks with a topical steroid until their symptoms were in remission. Steroids were discontinued and patients then were assigned randomly to groups given montelukast (20 mg/day, n = 20) or placebo (n = 21) for 26 weeks (groups were matched for age, sex, history of allergic disease, reflux symptoms, and endoscopic findings of EoE). Study participants were assessed via a structured telephone interview at weeks 2, 4, 8, 12, 16, 20, and 24. Remission was defined as the absence of solid-food dysphagia. RESULTS Based on an intention-to-treat analysis, after 26 weeks, 40.0% of subjects in the montelukast group and 23.8% in the placebo group were in remission. The odds ratio for remission in the montelukast group was 0.48 (95% confidence interval, 0.10-2.16) (P = .33). No side effects were reported from either group. CONCLUSIONS In a randomized controlled trial of the ability of montelukast to maintain remission in patients in remission from EoE after steroid therapy, we found montelukast to be well tolerated; 40% of patients remained in remission, but this proportion did not differ significantly from that of the placebo group. ClinicalTrials.gov no: NCT00511316.


title: Influence of Device Choice on the Effect of Intra-Arterial Treatment for Acute Ischemic Stroke in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands).

text: BACKGROUND AND PURPOSE Intra-arterial treatment by means of retrievable stents has been proven safe and effective. In MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the choice of the type of thrombectomy device was left to the discretion of the interventionist. The aim of this study was to explore the differences in functional outcome, neurological recovery, reperfusion, extent of infarction, and adverse events according to stent type and make. METHODS The primary outcome was functional outcome at 90 days, assessed with the modified Rankin Scale (mRS). Neuroimaging outcomes included occlusion on computed tomographic angiography at 24 hours, infarct volume at 5 to 7 days, and modified thrombolysis in cerebral infarction scores. Safety outcomes included death within 90 days and any symptomatic intracerebral hemorrhage. We analyzed possible interactions between stent type and treatment with multiple regression models. Treatment effects were adjusted for patient age, stroke severity, and collateral score. RESULTS Of the 500 patients included in the trial, 233 were allocated to intervention. Of these, 124 (53%) were first treated with Trevo (adjusted common odds ratio for shift on the mRS [acOR, 1.98; 95% confidence interval, 1.30-2.92]), 31 (13%) with Solitaire (acOR, 1.90; 95% confidence interval, 0.97-3.73), 40 (17%) with other retrievable stents or mechanical devices (acOR, 0.96; 95% confidence interval, 0.51-3.93], and 38 (16%) could not be treated. There was no interaction between device and treatment effect on functional outcome and all other secondary and safety outcomes. CONCLUSIONS We found no evidence for a differential effect of thrombectomy for acute ischemic stroke by type of stent. CLINICAL TRIAL REGISTRATION URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758.


title: Extracorporeal Life Support Organization Coronavirus Disease 2019 Interim Guidelines: A Consensus Document from an International Group of Interdisciplinary Extracorporeal Membrane Oxygenation Providers

text: The Extracorporeal Life Support Organization (ELSO) Coronavirus Disease 2019 (COVID-19) Guidelines have been developed to assist existing extracorporeal membrane oxygenation (ECMO) centers to prepare and plan provision of ECMO during the ongoing pandemic. The recommendations have been put together by a team of interdisciplinary ECMO providers from around the world. Recommendations are based on available evidence, existing best practice guidelines, ethical principles, and expert opinion. This is a living document and will be regularly updated when new information becomes available. ELSO is not liable for the accuracy or completeness of the information in this document. These guidelines are not meant to replace sound clinical judgment or specialist consultation but rather to strengthen provision and clinical management of ECMO specifically, in the context of the COVID-19 pandemic.


title: China's heath care system and avian influenza preparedness.

text: The severe acute respiratory syndrome crisis exposed serious deficiencies in China's public health system and willingness to report outbreaks of threats to public health. Consequently, China may be one of the weak links in global preparedness for avian influenza. China's rural health care system has been weakened by 20 years of privatization and fiscal decentralization. China plays a huge role in the global poultry industry, with a poultry population of 14 billion birds, 70%-80% of which are reared in backyard conditions. Although surveillance has been strengthened, obstacles to the timely reporting of disease outbreaks still exist. The weakened health care system prevents many sick people from seeking care at a health care facility, where reporting would originate. Inadequate compensation to farmers for culled birds leads to nonreporting, and local officials may be complicit if they suspect that reporting might lead to economic losses for their communities. At the local level, China's crisis-management ability and multisectoral coordination are weak. The poor quality of infection control in many rural facilities is a serious and well-documented problem. However, traditions of community political mobilization suggest that the potential for providing rural citizens with public health information is possible when mandated from the central government. Addressing these issues now and working on capacity issues, authority structures, accountability, and local reporting and control structures will benefit the control of a potential avian influenza outbreak, as well as inevitable outbreaks of other emerging infectious diseases in China's Pearl River Delta or in other densely populated locations of animal husbandry in China.


title: Dynamics of coronavirus replication-transcription complexes.

text: Coronaviruses induce in infected cells the formation of double-membrane vesicles (DMVs) in which the replication-transcription complexes (RTCs) are anchored. To study the dynamics of these coronavirus replicative structures, we generated recombinant murine hepatitis coronaviruses that express tagged versions of the nonstructural protein nsp2. We demonstrated by using immunofluorescence assays and electron microscopy that this protein is recruited to the DMV-anchored RTCs, for which its C terminus is essential. Live-cell imaging of infected cells demonstrated that small nsp2-positive structures move through the cytoplasm in a microtubule-dependent manner. In contrast, large fluorescent structures are rather immobile. Microtubule-mediated transport of DMVs, however, is not required for efficient replication. Biochemical analyses indicated that the nsp2 protein is associated with the cytoplasmic side of the DMVs. Yet, no recovery of fluorescence was observed when (part of) the nsp2-positive foci were bleached. This result was confirmed by the observation that preexisting RTCs did not exchange fluorescence after fusion of cells expressing either a green or a red fluorescent nsp2. Apparently, nsp2, once recruited to the RTCs, is not exchanged with nsp2 present in the cytoplasm or at other DMVs. Our data show a remarkable resemblance to results obtained recently by others with hepatitis C virus. The observations point to intriguing and as yet unrecognized similarities between the RTC dynamics of different plus-strand RNA viruses.


Platelets in Coronavirus Disease 2019.


title: Physical activity participation and the risk of chronic diseases among South Asian adults: a systematic review and meta-analysis.

text: South Asia specific reviews on the role of physical activity (PA) domains on chronic disease prevention are lacking. This study aimed to systematically review published literature to identify the association between PA domains and chronic diseases and to provide summary estimates of the strength of association. Nine electronic databases were searched using the predefined inclusion criteria which included population (South Asian adults 40 years or older), exposure (PA or sedentary behaviour) and outcome (type 2 diabetes mellitus, breast cancer, colorectal cancer, coronary heart disease, stroke, vascular disease and musculoskeletal diseases and their markers). A random-effects meta-analysis was carried out for cardiometabolic outcomes whereas narrative synthesis was completed for other outcome variables. Inactive or less active South Asian adults were at 31% higher risk of being hypertensive. Likewise, the risk of cardiometabolic outcomes was 1.34 times higher among inactive adults. Household PA was found to have a protective effect on breast cancer risk. Total and leisure time PA had a protective effect on osteoporosis among males and females respectively. Contemporary studies with a longitudinal design, representative samples, valid and reliable assessment of different domains are needed to establish the role of PA in chronic disease prevention in the region.


title: Clinical teaching unit design: a realist systematic review protocol of evidence-based practices for clinical education and health service delivery.

text: INTRODUCTION The clinical teaching unit (CTU) has emerged as a near-ubiquitous model of clinical education across Canadian and international medical schools since it was first proposed over 50 years ago. However, while healthcare has changed dramatically over this period, the CTU model has remained largely unchanged. We thus aimed to systematically review principles of CTU design that contribute to improved outcomes in clinical education and health service delivery. METHODS AND ANALYSIS We will perform a realist systematic review in accordance with the Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) II protocol for realist reviews. Databases, including MEDLINE, Embase, Cochrane Database of Systematic Reviews and Cumulative Index of Nursing and Allied Health Literature (CINAHL), were searched to find primary research articles published from 1993 to 2019 involving CTUs or other teaching wards, and outcomes related to either trainee education or health service delivery. Two reviewers will independently screen studies in a two-stage process. Retrieved titles and/or abstracts of studies will be screened in the first stage, with full texts reviewed in the second stage. Selected articles meeting inclusion criteria will undergo data abstraction using a standardised, pre-piloted form for assessment of study quality and knowledge synthesis. ETHICS AND DISSEMINATION This review will generate higher quality evidence on the design of CTUs as a model for both clinical education and health service delivery. In addition, further knowledge translation efforts may be necessary to ensure that known best practices in CTU design become common practice.


title: Functional and physiological outcomes from an exercise-based dysphagia therapy: a pilot investigation of the McNeill Dysphagia Therapy Program.

text: OBJECTIVE To investigate functional and physiological changes in swallowing performance of adults with chronic dysphagia after an exercise-based dysphagia therapy. DESIGN Intervention study: before-after trial with 3-month follow-up evaluation. SETTING Outpatient clinic within a tertiary care academic health science center. PARTICIPANTS Adults (N=9) with chronic (>12 mo) dysphagia after unsuccessful prior therapies. Subjects were identified from among patients referred to an outpatient dysphagia clinic. Subjects had dysphagia secondary to prior treatment for head/neck cancer or from neurologic injury. All subjects demonstrated clinical and fluoroscopic evidence of oropharyngeal dysphagia. No subject withdrew during the course of this study. INTERVENTIONS All subjects completed 3 weeks of an intensive, exercise-based dysphagia therapy. Therapy was conducted daily for 1h/d, with additional activities completed by subjects each night between therapy sessions. MAIN OUTCOME MEASURES Primary outcomes were clinical and functional change in swallowing performance with maintenance at 3 months after intervention. Secondary, exploratory outcomes included physiological change in swallow performance measured by hyolaryngeal elevation, lingual-palatal and pharyngeal manometric pressure, and surface electromyographic amplitude. RESULTS Clinical and functional swallowing performances improved significantly and were maintained at the 3-month follow-up examination. Subject perspective (visual analog scale) on functional swallowing also improved. Four of 7 subjects who were initially feeding tube dependent progressed to total oral intake after 3 weeks of intervention. Physiological indices demonstrated increased swallowing effort after intervention. CONCLUSIONS Significant clinical and functional improvement in swallowing performance followed a time-limited (3 wk) exercise-based intervention in a sample of subjects with chronic dysphagia. Physiological changes after therapy implicate improved neuromuscular functioning within the swallow mechanism.


title: A high-voltage bipolar transconductance amplifier for electrotactile stimulation.

text: This paper describes a high-performance transconductance amplifier specifically designed for electrotactile (electrocutaneous) stimulation. It enables voltages up to +/-600 V to be produced at the output that will allow the psychophysiological performance associated with stimulation of the fingertip using various stimulation waveforms to be studied more thoroughly. The design has a transconductance of up to 20 mA/V, an 8.8-Momega output resistance, and can provide output currents up to +/-20 mA. A complete schematic diagram is presented along with a discussion of theory of operation and safety issues as well as performance and derating plots from the implemented design.


title: Treatment of distal biceps tendon rupture: why, when, how? Analysis of literature and our experience.

text: INTRODUCTION The rupture of the distal biceps tendon is a relatively uncommon lesion. Even if conservative treatment may be an option in low demanding patients, young and active subjects may benefit from an early surgical reinsertion. Many techniques and fixation devices have been described, but in the literature, there are no clinical evidences that show the superiority of any of these. In this article, we report an analysis of the "state of the art" and our case series of surgical reinsertion with the double approach transosseous technique. MATERIALS AND METHODS Between 2003 and 2013, 26 patients underwent surgical reinsertion, either for acute or for chronic lesions of distal biceps tendon. We evaluated 21 acute cases treated with double approach using DASH and SECEC Elbow Scores. The mean follow-up was 22 months. Range of motion, supination and flexion strength were also recorded. RESULTS Mean final ROM was 6-132° in F/E and 89-0-87° in P/S; flexion and supination strength were 96 and 88 % compared to the opposite side. The main complications were two cases of heterotopic ossifications: one asymptomatic fracture of the proximal radius and one temporary neurapraxia of the radial nerve. CONCLUSIONS Analysing the literature and our outcomes, we underline the importance of timing for surgery, in young and compliant patients, with a valid rehabilitation protocol for excellent results. The choice of surgical technique remains controversial, and we believe that the double approach transosseous reinsertion is a safe, costless and relatively non-invasive technique, offering satisfactory results when performed early.


Imaging clinic operations in the times of COVID-19: Strategies, Precautions and Experiences.