title: [Pharmacovigilance study on drug-induced cardiac injury during treatment of COVID-19].

text: Because coronavirus disease 2019(COVID-19) is highly contagious and serious, it has posed a major threat to public health worldwide. The curative effects of integrated traditional Chinese medicine and Western medicine in the treatment of COVID-19 have been widely recognized and confirmed. However, medical workers shall pay attention to drug-induced heart injury in clinical application. Based on the guideline from the Diagnosis and Treatment Plans for COVID-19(trial seventh edition), taking the recommended drugs as examples, by Western medicine, traditional Chinese medicine, Chinese herbal injection and integrated traditional Chinese and Western medicine, the study analyzed the basic characteristics of recommended drugs for cardiac injury by means of literature review and bioinformatics methods, and summarized cardiac adverse reactions, toxicity mechanisms, combined pharmacotherapy, special population and drug monitoring, focusing on the clinical manifestations, toxic components, targets and regulatory mechanisms of drug-induced cardiac injury. The findings suggested being vigilant to drug-induced cardiac injury during the treatment of COVID-19, playing the advantages of clinical pharmacists and clinical Chinese pharmacists, improving the knowledge reserve of pharmacovigilance, strengthening the prescription review, medication notification and medication monitoring, promoting rational drug use and paying attention to special populations and high-risk groups. The study aims to provide suggestions and reference for pharmacovigilance and pharmaceutical care for front-line doctors and pharmacists against COVID-19, in order to avoid the occurrence of drug-induced heart injury for patients with COVID-19.


Do flawed data on caloric intake from NHANES present problems for researchers and policy makers?


Varicose veins.


title: Transanal employment of single access ports is feasible for rectal surgery.

text: OBJECTIVE To evaluate the feasibility of transanal single port surgery in 15 consecutive patients. BACKGROUND The current method of choice for local resection of rectal tumors is transanal endoscopic microsurgery (TEM), a complex and expensive technique. Single access surgery is easy, relatively cheap, and more broadly applied in laparoscopy. Evidence regarding transanal use of single access ports is scarce. METHODS Consecutive patients with a rectal lesion otherwise eligible for TEM were operated using the Single Site Laparoscopic Access System (SSL) and standard laparoscopic instrumentation. Patient, lesion and procedure characteristics, hospitalization length, and peroperative and postoperative complications were recorded. RESULTS Fifteen patients were planned for single port transanal surgery. In 2 patients (13.3%), intrarectal retractor expansion failed, and conversion to conventional TEM was necessary. The remaining 13 patients were successfully operated. Rectal lesions (mean diameter 36 mm, standard deviation ±25 mm, mean distance from the dentate line 6 cm [±4.5]) included adenoma in 7 patients, T1 adenocarcinoma in 1, T2 adenocarcinoma in 3, carcinoid in 1, and fibrosis only in 1 (after prior polypectomy). All patients were operated in lithotomy position. Resections were en bloc, full thickness, and had complete margins. Resection specimens measured 65 (±35) × 52 (±24) mm. Twelve rectal defects were sutured. One peroperative pneumoscrotum occurred. Mean operating time was 57 (±39) minutes. One patient presented with postoperative hemorrhage, treated conservatively (postoperative morbidity rate 7.7%). Mean hospitalization lasted 2.5 days (±2.7). CONCLUSIONS Transanal single port surgery via the SSL is feasible and safe and may become a promising alternative to TEM.


title: TIGR® matrix surgical mesh - a two-year follow-up study and complication analysis in 65 immediate breast reconstructions.

text: In recent years, it has become increasingly popular to use matrices, such as acellular dermal matrices, in implant-based breast reconstruction. To lower the cost and to avoid implanting biological material, the use of synthetic meshes has been proposed. This is the first study examining TIGR® Mesh in a larger series of immediate breast reconstruction. The aims of the study were to examine complications and predictors for complications. All consecutive patients operated on with breast reconstruction with TIGR® Matrix Surgical Mesh and tissue expanders (TEs) or permanent implant between March 2015 and September 2016 in our department were prospectively included. Exclusion criteria were ongoing smoking, BMI (kg/m2) > 30, planned postoperative radiation, and inability to leave informed consent. Fifteen breasts (23%) were affected by complications within 30 d: four (6.2%) major complications and eleven (17%) minor complications. The major complications included two implant losses and one pulmonary embolism (PE). Predictors for a complication were age over 51 years, BMI over 24.5 kg/m2, large resection weight, and the need for a wise pattern excision of skin. Four minor surgical complications occurred after 30 d (minimum follow-up 17 months). There were no implant losses. In addition, minor aesthetic corrections, such as dog-ear resection, were performed in 10 breasts. In conclusion, breast reconstruction with a TE in combination with TIGR® Matrix Surgical Mesh can be performed with a low complication rate.


title: The effects of A1 pulley release after flexor tendon repair in a cadaveric model.

text: BACKGROUND Decreasing rupture rates after flexor tendon repair is accomplished by increasing the strength of the repair and by decreasing the forces across tendons during rehabilitation. The authors sought to determine whether A1 pulley release affects work of flexion after a zone 2 flexor tendon repair. METHODS Four fresh-frozen cadaveric hands were thawed to room temperature. The flexor digitorum profundus and flexor pollicis longus tendons were tested in a tensile testing machine. In hands 1 and 2, work of flexion of uninjured tendons was evaluated through the sequential division of the A1 pulley, starting with either the proximal 50 percent or the distal 50 percent of the pulley. In hands 3 and 4, zone 2 flexor digitorum profundus lacerations were created and repaired using a modified Kessler technique; then, sequential division of the A1 pulley was performed. Force-excursion curves were generated and used to calculate work of flexion. Analysis of variance was performed for multigroup comparisons, and t tests were performed for pairwise comparisons. Values of p < 0.05 were considered statistically significant. RESULTS In uninjured tendons, work of flexion decreased with sequential division of the A1 pulley. After tendon repair, work of flexion increased significantly from baseline in all digits. A1 pulley release after flexor tendon repair produced significant decreases in work of flexion in all digits. CONCLUSIONS A1 pulley release effectively decreases work of flexion after flexor tendon repair. Release performed at the time of tendon repair may decrease the forces across tendons in the postoperative period.


title: Strategies to tackle unrecognized bilateral renal artery occlusion after endovascular aneurysm repair.

text: BACKGROUND Unintentional renal artery occlusion after endovascular aortic aneurysm repair (EVAR) is an uncommon phenomenon. The sequelae from this specific complication are severe; consequently, the topic of renal artery coverage is a pertinent issue. We present a case series of patients undergoing EVAR with unintentional renal artery coverage, review the treatment options available, and suggest a treatment algorithm for this scenario based on the evidence. METHODS AND RESULTS We report four patients who were found to have renal artery occlusion after EVAR detected up to 5 weeks postoperatively. Renal revascularization was achieved using endovascular renal artery stenting in two patients, and open hepato-spleno-renal bypass in the remaining two cases. Treatment strategies used led to symptom resolution and recovery of renal function in all cases. CONCLUSIONS Both open and endovascular techniques may be used as procedures to treat this condition-the choice of procedure is primarily determined by accessibility of the renal orifice.


title: Single incision laparoscopic cholecystectomy: a single center experience.

text: INTRODUCTION Single Incision Laparoscopic Surgery (SILS) is a variation in which trocar scars are hidden in the umbilicus. We sought to determine whether SILS cholecystectomy is a safe alternative to a conventional laparoscopic cholecystectomy. METHODS We retrospectively reviewed our series of 205 SIL cholecystectomies (SILC) performed between May 2008-June 2010. The first 50 cases were done by initially insufflating the abdomen with a veress needle through the umbilicus and then placing 3, 5 mm ports in the umbilicus. The remaining cases were performed using a cut down approach at the umbilicus, followed by placement of a three-trocar SILS port under direct vision. RESULTS Two hundred and five patients (M:F = 48:157) underwent SILC during the study period. Median age was 45 (range = 21-62). Mean BMI range was 35 (range = 21-44). Mean operative time was 60 min (range = 40-120 min) and a follow up period that ranges from 1 to 21 months. Patient pathologies included: Chronic cholecystitis (74%), Acute cholecystitis (17%), Choledocholithiasis (6.8%), Gallstone pancreatitis (2%) and gallbladder polyp (0.5%). An additional port was placed in the umbilicus in 3% of cases. No cases were converted to open. Complications occurred in 4% of cases including: 3 patients with retained stones, 2 patients with post-op wound infection, 2 patients with incisional hernias in the umbilical region and 1patient with a veress injury. CONCLUSION SIL cholecystectomy can be done safely. It offers a better cosmetic result, which may lead to greater patient satisfaction.


title: Seroprevalence of Coxiella burnetii in domesticated and feral cats in eastern Australia.

text: The seroprevalence of Coxiella burnetii (C. burnetii) in cats in eastern Australia is unknown, and the risk of transmission from cats to humans is undetermined. This study aimed to determine the exposure of cats to C. burnetii in four distinct cat subpopulations. An indirect immunofluoresence assay (IFA) and an Enzyme-linked immunosorbent assay (ELISA) used for detection of anti-C. burnetii antibodies in humans were adapted, verified for use on feline serum, and compared. Cat serum samples (n=712) were tested with IFA from four subpopulations [cattery-confined breeding cats, pet cats, feral cats and shelter cats]. The proportions of seropositive cats were; cattery-confined breeding cats (35/376, 9.3%), pets (2/198, 1%), feral cats (0/50), shelter cats (0/88). The significant variables in C. burnetii seropositivity were cattery-confined breeding cat subpopulation and sterilisation status, with infected cats 17.1 (CI 4.2-70.2; P<0.001) times more likely to be cattery-confined breeding cats and 6.00 (CI 2.13-16.89; P<0.001) times more likely to be entire than sterilised. ELISA was used on 143 of 712 sera tested with IFA, and the Cohen's Kappa coefficient of 0.75 indicated 92.2% agreement between the two assays. These results confirm that Australian cats have been exposed to C. burnetii and that a higher seroprevalence of C. burnetii is seen amongst cattery-confined breeding cats. Cat breeders and veterinary personnel involved in feline reproductive procedures may be at higher risk of exposure to C. burnetii.


Pain Management Best Practices During the COVID-19 Pandemic: The Well-being Perspectives of Chronic Pain Fellows.


title: Redesigning Portable Health Clinic Platform as a Remote Healthcare System to Tackle COVID-19 Pandemic Situation in Unreached Communities.

text: Medical staff carry an inordinate risk of infection from patients, and many doctors, nurses, and other healthcare workers are affected by COVID-19 worldwide. The unreached communities with noncommunicable diseases (NCDs) such as chronic cardiovascular, respiratory, endocrine, digestive, or renal diseases became more vulnerable during this pandemic situation. In both cases, Remote Healthcare Systems (RHS) may help minimize the risk of SARS-CoV-2 transmission. This study used the WHO guidelines and Design Science Research (DSR) framework to redesign the Portable Health Clinic (PHC), an RHS, for the containment of the spread of COVID-19 as well as proposed corona logic (C-Logic) for the main symptoms of COVID-19. Using the distributed service platform of PHC, a trained healthcare worker with appropriate testing kits can screen high-risk individuals and can help optimize triage to medical services. PHC with its new triage algorithm (C-Logic) classifies the patients according to whether the patient needs to move to a clinic for a PCR test. Through modified PHC service, we can help people to boost their knowledge, attitude (feelings/beliefs), and self-efficacy to execute preventing measures. Our initial examination of the suitability of the PHC and its associated technologies as a key contributor to public health responses is designed to "flatten the curve", particularly among unreached high-risk NCD populations in developing countries. Theoretically, this study contributes to design science research by introducing a modified healthcare providing model.


title: Multiple nucleic acid binding sites and intrinsic disorder of severe acute respiratory syndrome coronavirus nucleocapsid protein: implications for ribonucleocapsid protein packaging.

text: The nucleocapsid protein (N) of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genomic RNA and is crucial for viability. However, the RNA-binding mechanism is poorly understood. We have shown previously that the N protein contains two structural domains--the N-terminal domain (NTD; residues 45 to 181) and the C-terminal dimerization domain (CTD; residues 248 to 365)--flanked by long stretches of disordered regions accounting for almost half of the entire sequence. Small-angle X-ray scattering data show that the protein is in an extended conformation and that the two structural domains of the SARS-CoV N protein are far apart. Both the NTD and the CTD have been shown to bind RNA. Here we show that all disordered regions are also capable of binding to RNA. Constructs containing multiple RNA-binding regions showed Hill coefficients greater than 1, suggesting that the N protein binds to RNA cooperatively. The effect can be explained by the "coupled-allostery" model, devised to explain the allosteric effect in a multidomain regulatory system. Although the N proteins of different coronaviruses share very low sequence homology, the physicochemical features described above may be conserved across different groups of Coronaviridae. The current results underscore the important roles of multisite nucleic acid binding and intrinsic disorder in N protein function and RNP packaging.


title: New pathways to medicare coverage for innovative PET radiopharmaceuticals: report of a Medical Imaging & Technology Alliance (MITA) workshop.

text: PET and PET/CT have revolutionized the diagnosis, staging, and monitoring of treatment effect or recurrence for a wide range of cancers and shown promise for improving health outcomes for patients with cardiovascular and central nervous system diseases. However, this technology is challenged by insurance coverage policies that hinder patients' access to PET and discourage technologic innovation. Recently, the Medical Imaging & Technology Alliance (MITA), a Washington-based industry association, convened a workshop to consider new pathways for making decisions on Medicare coverage of new PET radiopharmaceuticals and imaging procedures that are currently subject to a national noncoverage decision, or "exclusionary rule." Stakeholders from the government, medical professional societies, academia, patient groups, and industry gathered to brainstorm alternatives to the national noncoverage decision and evaluate their potential to improve access and enhance innovation. Ultimately, MITA, on behalf of the PET community, expects to use the outcomes of the workshop to propose that the Centers for Medicare and Medicaid Services reconsider this current national noncoverage decision for PET and adopt a new framework for coverage.


title: Rehabilitation after COVID-19: an evidence-based approach.

text: After severe COVID-19 disease, many patients will experience a variety of problems with normal functioning and will require rehabilitation services to overcome these problems. The principles of and evidence on rehabilitation will allow an effective response. These include a simple screening process; use of a multi-disciplinary expert team; four evidence-based classes of intervention (exercise, practice, psychosocial support, and education particularly about self-management); and a range of tailored interventions for other problems. The large number of COVID-19 patients needing rehabilitation coupled with the backlog remaining from the crisis will challenge existing services. The principles underpinning vital service reconfigurations needed are discussed.


Covid-19: Exposing frontline NHS staff to dangers by asking them to reuse PPE.


title: Model informed dosing of Hydroxycholoroquine in COVID-19 patients: Learnings from the recent experience, remaining uncertainties and Gaps.

text: AIMS In the absence of a commonly agreed dosing protocol based on pharmacokinetic considerations, the dose and treatment duration for hydroxychloroquine (HCQ) COVID-19 disease currently vary across national guidelines and clinical study protocols. We have used a model-based approach to explore the relative impact of alternative dosing regimens proposed in different dosing protocols for hydroxychloroquine in COVID-19. METHODS We compared different PK exposures using Monte Carlo simulations based on a previously published population pharmacokinetic model in patients with rheumatoid arthritis, externally validated using both independent data in lupus erythematous patients and recent data in French COVID-19 patients. Clinical efficacy and safety information from COVID-19 patients treated with HCQ were used to contextualize and assess the actual clinical value of the model predictions. RESULTS Literature and observed clinical data confirm the variability in clinical responses in COVID-19 when treated with the same fixed doses. Confounding factors were identified that should be taken into account for dose recommendation. For 80% of patients, doses higher than 800mg day on D1 followed by 600mg daily on following days might not be needed for being cured. Limited adverse drug reactions have been reported so far for this dosing regimen, most often confounded by co-medications, comorbidities or underlying COVID-19 disease effects. CONCLUSION Our results were clear indicating the unmet need for characterization of target PK exposures to inform HCQ dosing optimization in COVID-19. Dosing optimization for HCQ in COVID-19 is still an unmet need. Efforts in this sense are a prerequisite for best the benefit/risk balance.


title: Endoleak and in-stent thrombus detection with CT angiography in a thoracic aortic aneurysm phantom at different tube energies using filtered back projection and iterative algorithms.

text: PURPOSE To determine the lower limit of dose reduction with hybrid and fully iterative reconstruction algorithms in detection of endoleaks and in-stent thrombus of thoracic aorta with computed tomographic (CT) angiography by applying protocols with different tube energies and automated tube current modulation. MATERIALS AND METHODS The calcification insert of an anthropomorphic cardiac phantom was replaced with an aortic aneurysm model containing a stent, simulated endoleaks, and an intraluminal thrombus. CT was performed at tube energies of 120, 100, and 80 kVp with incrementally increasing noise indexes (NIs) of 16, 25, 34, 43, 52, 61, and 70 and a 2.5-mm section thickness. NI directly controls radiation exposure; a higher NI allows for greater image noise and decreases radiation. Images were reconstructed with filtered back projection (FBP) and hybrid and fully iterative algorithms. Five radiologists independently analyzed lesion conspicuity to assess sensitivity and specificity. Mean attenuation (in Hounsfield units) and standard deviation were measured in the aorta to calculate signal-to-noise ratio (SNR). Attenuation and SNR of different protocols and algorithms were analyzed with analysis of variance or Welch test depending on data distribution. RESULTS Both sensitivity and specificity were 100% for simulated lesions on images with 2.5-mm section thickness and an NI of 25 (3.45 mGy), 34 (1.83 mGy), or 43 (1.16 mGy) at 120 kVp; an NI of 34 (1.98 mGy), 43 (1.23 mGy), or 61 (0.61 mGy) at 100 kVp; and an NI of 43 (1.46 mGy) or 70 (0.54 mGy) at 80 kVp. SNR values showed similar results. With the fully iterative algorithm, mean attenuation of the aorta decreased significantly in reduced-dose protocols in comparison with control protocols at 100 kVp (311 HU at 16 NI vs 290 HU at 70 NI, P ≤ .0011) and 80 kVp (400 HU at 16 NI vs 369 HU at 70 NI, P ≤ .0007). CONCLUSION Endoleaks and in-stent thrombus of thoracic aorta were detectable to 1.46 mGy (80 kVp) with FBP, 1.23 mGy (100 kVp) with the hybrid algorithm, and 0.54 mGy (80 kVp) with the fully iterative algorithm.


title: Anemia-related hemogram, uterine artery pulsatility index, and blood pressure for the effects of Four-Agents-Decoction (Si Wu Tang) in the treatment of primary dysmenorrhea.

text: OBJECTIVES We previously reported pain intensity as the primary outcome of Four-Agents-Decoction (Si Wu Tang) for treating primary dysmenorrhea. We further explored other effects of this formula in accordance with the theory of Traditional Chinese Medicine on anemia-related hemogram parameters for "nourishing blood" and uterine artery pulsatility index (PI) for "blood stagnation." DESIGN Data were assessed for post-hoc analysis from 76 young women from the Taipei metropolitan area of Taiwan who participated in the randomized double-blind clinical trial. Analysis of variance and t test were used to examine the treatment effect between and within the Four-Agents-Decoction and placebo groups. OUTCOME MEASURES In addition to pain intensity, anemia-related hemogram parameters, uterine artery PI, menstruation characteristics, and blood pressure were compared. RESULTS Compared to placebo, biochemical indicators for anemic status did not change differently after the treatment with Four-Agents-Decoction (Si Wu Tang). The changes in uterine artery PI, menstrual pain intensity, and blood pressure were statistically greater in the active treatment group than in the placebo group. In the 25 women receiving ultrasound examination on the same menstruation day, the directions of the changes in both PI and in visual analog scale (VAS) pain intensity aligned well. The changes in the left PI, right PI, and VAS pain intensity in the Four-Agents-Decoction group were -0.391 +/- 0.861, -0.344 +/- 1.03, and -0.251 +/- 2.02 cm; those in the placebo group were 0.208 +/- 1.10, 0.372 +/- 1.06, and 0.438 +/- 2.98 cm, respectively. Inversely, the changes in blood pressure were 11.4 +/- 10.5 mm Hg for systolic blood pressure and 8.36 +/- 8.65 mm Hg for diastolic pressure for the Four-Agents-Decoction group and 6.36 +/- 8.66 and 2.91 +/- 11.2 mm Hg, respectively, for the placebo group. The directions of the changes did not shift, nor did the values change drastically, after adjusting for the level at screening cycle. CONCLUSIONS The anemia status evaluated in conventional medicine does not readily explain the effect of "nourishing blood" by Four-Agents-Decoction (Si Wu Tang) from this exploratory study. Although we did not find strong statistical significance of treatment effect, the decreased PI and extra blood pressure elevation may indicate an improvement of "blood stagnation" in the Four-Agents-Decoction group. The added information warrants a further larger clinical trial with an increased power to enhance our understanding of the efficacy, the dose-response relationship, and the mode of action of this ancient formula for treating primary dysmenorrhea.


title: Laboratory Assay Evaluation Demystified: A Review of Key Factors Influencing Interpretation of Test Results Using Different Assays for SARS-CoV-2 Infection Diagnosis.

text: Laboratory tests are an integral part of the diagnosis and management of patients; however, these tests are far from perfect. Their imperfections can be due to patient health condition, specimen collection, and/or technological difficulty with performing the assay and/or interpretation. To be useful clinically, testing requires calculation of positive predictive values (PPVs) and negative predictive values (NPVs). During the current global pandemic of COVID-19 (coronavirus disease 2019), multiple assays with unknown clinical sensitivity and specificity have been rapidly developed to aid in the diagnosis of the disease. Due to a lack of surveillance testing, the prevalence of COVID-19 remains unknown. Hence, using this situation as an clinical example, the goal of this article is to clarify the key factors that influence the PPV and NPV yielded by diagnostic testing, By doing so, we hope to offer health-care providers information that will help them better understand the potential implications of utilizing these test results in clinical patient management.


title: Impact of the COVID-19 pandemic on urology residency training in Italy.

text: In the global emergency scenario caused by COVID-19 pandemic, the Urology residents' training might be critically affected. To provide insights on this issue, a 25-items online Survey was sent to all Italian residents one month after the first case of COVID-19 in Italy, to evaluate their routine involvement in "clinical" (on-call duty, outpatient visits, diagnostic procedures) and "surgical" (endoscopic, open and minimally invasive surgery) training activities before and during the COVID-19 period. Overall, 351/577 (60.8%) residents completed the Survey. Before the COVID-19 pandemic, the proportion of residents routinely involved in "clinical" and "surgical" activities ranged from 79.8% to 87.2% and from 49.3% to 73.5%, respectively. In the COVID-19 period, the proportion of residents experiencing a severe reduction (>40%) or complete suppression (>80%) of training exposure ranged between 41.1% and 81.2% for "clinical" activities while between 44.2% and 62.1% for "surgical" activities. This reduction was even more pronounced for residents attending the final year of training. Our study is the first to provide real-life data on how Urology residency training can be impaired during an emergency period. To address this challenge, strategies aiming to increase the use of telemedicine, smart learning programs and tele-mentoring of surgical procedures, are warranted.


Croup in children.


title: Bacterial resistance to antisense peptide phosphorodiamidate morpholino oligomers.

text: Peptide phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA mimics that bind cRNA and inhibit bacterial gene expression. The PPMO (RFF)(3)RXB-AcpP (where R is arginine, F, phenylalanine, X is 6-aminohexanoic acid, B is β-alanine, and AcpP is acyl carrier protein) is complementary to 11 bases of the essential gene acpP (which encodes acyl carrier protein). The MIC of (RFF)(3)RXB-AcpP was 2.5 μM (14 μg/ml) in Escherichia coli W3110. The rate of spontaneous resistance of E. coli to (RFF)(3)RXB-AcpP was 4 × 10(-7) mutations/cell division. A spontaneous (RFF)(3)RXB-AcpP-resistant mutant (PR200.1) was isolated. The MIC of (RFF)(3)RXB-AcpP was 40 μM (224 μg/ml) for PR200.1. The MICs of standard antibiotics for PR200.1 and W3110 were identical. The sequence of acpP was identical in PR200.1 and W3110. PR200.1 was also resistant to other PPMOs conjugated to (RFF)(3)RXB or peptides with a similar composition or pattern of cationic and nonpolar residues. Genomic sequencing of PR200.1 identified a mutation in sbmA, which encodes an active transport protein. In separate experiments, a (RFF)(3)RXB-AcpP-resistant isolate (RR3) was selected from a transposome library, and the insertion was mapped to sbmA. Genetic complementation of PR200.1 or RR3 with sbmA restored susceptibility to (RFF)(3)RXB-AcpP. Deletion of sbmA caused resistance to (RFF)(3)RXB-AcpP. We conclude that resistance to (RFF)(3)RXB-AcpP was linked to the peptide and not the phosphorodiamidate morpholino oligomer, dependent on the composition or repeating pattern of amino acids, and caused by mutations in sbmA. The data further suggest that (RFF)(3)R-XB PPMOs may be transported across the plasma membrane by SbmA.


Operating in a Pandemic: Lessons and Strategies from an Orthopaedic Unit at the Epicenter of COVID-19 in Singapore.


title: The effect of facility characteristics on patient safety, patient experience, and service availability for procedures in non-hospital-affiliated outpatient settings: A systematic review.

text: BACKGROUND Over recent decades, numerous medical procedures have migrated out of hospitals and into freestanding ambulatory surgery centers (ASCs) and physician offices, with possible implications for patient outcomes. In response, states have passed regulations for office-based surgeries, private organizations have established standards for facility accreditation, and professional associations have developed clinical guidelines. While abortions have been performed in office setting for decades, states have also enacted laws requiring that facilities that perform abortions meet specific requirements. The extent to which facility requirements have an impact on patient outcomes-for any procedure-is unclear. METHODS AND FINDINGS We conducted a systematic review to examine the effect of outpatient facility type (ASC vs. office) and specific facility characteristics (e.g., facility accreditation, emergency response protocols, clinician qualifications, physical plant characteristics, other policies) on patient safety, patient experience and service availability in non-hospital-affiliated outpatient settings. To identify relevant research, we searched databases of the published academic literature (PubMed, EMBASE, Web of Science) and websites of governmental and non-governmental organizations. Two investigators reviewed 3049 abstracts and full-text articles against inclusion/exclusion criteria and assessed the quality of 22 identified articles. Most studies were hampered by methodological challenges, with 12 of 22 not meeting minimum quality criteria. Of 10 studies included in the review, most (6) examined the effect of facility type on patient safety. Existing research appears to indicate no difference in patient safety for outpatient procedures performed in ASCs vs. physician offices. Research about specific facility characteristics is insufficient to draw conclusions. CONCLUSIONS More and higher quality research is needed to determine if there is a public health problem to be addressed through facility regulation and, if so, which facility characteristics may result in consistent improvements to patient safety while not adversely affecting patient experience or service availability.


title: The Relationship Between Training Load and Injury in Athletes: A Systematic Review.

text: BACKGROUND The relationship between training load and musculoskeletal injury is a rapidly advancing area of research in need of an updated systematic review. OBJECTIVE This systematic review examined the evidence for the relationship between training load and musculoskeletal injury risk in athlete, military, and first responder (i.e. law enforcement, firefighting, rescue service) populations. METHODS The CINAHL, EMBASE, MEDLINE, SportDISCUS, and SCOPUS databases were searched using a comprehensive strategy. Studies published prior to July 2017 were included if they prospectively examined the relationship between training load and injury risk. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS) and Oxford Centre for Evidence-Based Medicine levels of evidence. A narrative synthesis of findings was conducted. RESULTS A total of 2047 articles were examined for potential inclusion. Forty-six met the inclusion criteria and 11 known to the authors but not found in the search were added, for a total of 57 articles. Overall, 47 studies had at least partially statistically significant results, demonstrating a relationship between training load and injury risk. Included articles were rated as poor (n = 15), fair (n = 6), and good (n = 36) based on NOS score. Articles assessed as 'good' were considered level 2b evidence on the Oxford Centre for Evidence-Based Medicine Model, and articles assessed as 'fair' or 'poor' were considered level 4 evidence. CONCLUSIONS Our results demonstrate that the existence of a relationship between training load and injury continues to be well supported in the literature and is strongest for subjective internal training load. The directionality of this relationship appears to depend on the type and timeframe of load measured.


title: Therapeutic potential of resveratrol against emerging respiratory viral infections.

text: Resveratrol has been widely studied for its therapeutic potential due to its antioxidant, anti-inflammatory and anti-microbial properties. In particular, resveratrol has shown promising antiviral activity against numerous viruses responsible for severe respiratory infections. Amongst these, influenza virus, respiratory syncytial virus and the emerging SARS-cov-2 are known to cause pneumonia, acute respiratory distress syndrome or multi-organ failure, especially, in vulnerable individuals like immunocompromised patients or the elderly, leading to a considerable economic burden worldwide. In this context, resveratrol may have potential value for its anti-inflammatory activity, since most of the severe virus-associated complications are related to the overactivation of the host-immune response, leading to lung damage. Herein, we present an overview of the antiviral activity and potential mechanisms of resveratrol against the respiratory tract viruses considered as a public threat for their rapid transmission and high morbidity and mortality in the general population.


title: In vivo evaluation of putative hematopoietic stem cells derived from human pluripotent stem cells.

text: Efficient derivation and isolation of hematopoietic stem cells (HSCs) from human pluripotent stem cell (hPSC) populations remains a major goal in the field of developmental hematopoiesis. These enticing pluripotent stem cells (comprising both human embryonic stem cells and induced pluripotent stem cells) have been successfully used to generate a wide array of hematopoietic cells in vitro, from primitive hematoendothelial precursors to mature myeloid, erythroid, and lymphoid lineage cells. However, to date, PSC-derived cells have demonstrated only limited potential for long-term multilineage hematopoietic engraftment in vivo - the test by which putative HSCs are defined. Successful generation and characterization of HSCs from hPSCs not only requires an efficient in vitro differentiation system that provides insight into the developmental fate of hPSC-derived cells, but also necessitates an in vivo engraftment model that allows identification of specific mechanisms that hinder or promote hematopoietic engraftment. In this chapter, we will describe a method that utilizes firefly luciferase-expressing hPSCs and bioluminescent imaging to noninvasively track the survival, proliferation, and migration of transplanted hPSC-derived cells. Combined with lineage and functional analyses of engrafted cells, this system is a useful tool to gain insight into the in vivo potential of hematopoietic cells generated from hPSCs.


title: COVID-19 pandemic: mental health and beyond - The Indian perspective.

text: India is a de facto continent in the garb of a country. COVID-19 is an unprecedented global pandemic spanning continents. Being the second most populous country in the world, experts regard how India deals with the outbreak will have enormous impact on the world's ability to deal with it. The country has been in lockdown since 25th March 2020 until the current time of early May 2020, and despite several challenges there has been early success. The major conflict now is the health benefits weighed up against the deleterious social and economic consequences of prolonged lockdown i.e. life versus livelihood. This unprecedented calamity could potentially cause or exacerbate various psychiatric disorders. It is recognised that lifestyle changes and limited screen time may help reduce mental health difficulties. Considering the physical barriers to consultation, development of telemedicine services is needed. This pandemic, like other previous pandemics, will pass and until this happens we must remain extremely vigilant.


title: The COVID-19 pandemic and international federation of medical students' association exchanges: thousands of students deprived of their clinical and research exchanges.

text: The repercussions of the COVID-19 pandemic for medical students are enormous and not limited to the interruption of courses in medical schools and/or hospital training rotations, the introduction of teaching exclusively online, postponement of examinations, and of the new academic year, but extend beyond that. The mobility of students within the framework of the International Federation of Medical Students' Associations (IFMSA) is also strongly affected by the unexpected interruption of this program and the deprivation of thousands of students worldwide of this fine opportunity for training, exchange and sharing. The International Federation of Medical Students' Associations (IFMSA) was founded in 1951 and currently maintains 135 National Member Organizations (NMOs) from 125 countries, representing a network of 1.3 million medical students around the globe. Moroccan students, members of IFMSA like students from other countries, are also concerned. Clinical and research exchanges, carried out under the auspices of the IFMSA, allow all the students to discover the health care and medical education systems of another country in a different sociocultural environment. To maintain student motivation and deal with the repercussions of cancelled exchanges, IFMSA could propose online training programs, adapted to student needs during this period of confinement and deconfinement from June to September 2020.


Feasibility and Preliminary Results of Effectiveness of Social Media-based Intervention on the Psychological Well-being of Suspected COVID-19 Cases during Quarantine.


title: Identification of a novel higher molecular weight isoform of USP7/HAUSP that interacts with the Herpes simplex virus type-1 immediate early protein ICP0.

text: The Herpes simplex virus type-1 (HSV-1) regulatory protein ICP0, a RING-finger E3 ubiquitin ligase, stimulates the onset of viral lytic replication and the reactivation of quiescent viral genomes from latency. Like many ubiquitin ligases ICP0 induces its own ubiquitination, a process that can lead to its proteasome-dependent degradation. ICP0 counteracts this activity by recruiting the cellular ubiquitin-specific protease USP7/HAUSP. Here we show that ICP0 can also interact with a previously unidentified isoform of USP7 (termed here USP7(beta)). This isoform is not a predominantly ubiquitinated, SUMO-modified, or phosphorylated species of USP7 but is constitutively expressed in a number of different cell types. Like USP7, USP7(beta) binds specifically to an electrophilic ubiquitin probe, indicating that it contains an accessible catalytic core with potential ubiquitin-protease activity. The interaction formed between ICP0 and USP7(beta) requires ICP0 to have an intact USP7-binding domain and results in its susceptibility to ICP0-mediated degradation during HSV-1 infection.


Adverse Consequences of Rushing a SARS-CoV-2 Vaccine: Implications for Public Trust.


title: Impact of Hemoglobin A1c Levels on Residual Platelet Reactivity and Outcomes After Insertion of Coronary Drug-Eluting Stents (from the ADAPT-DES Study).

text: An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether HbA1c levels are associated with high platelet reactivity (HPR) in patients loaded with clopidogrel and aspirin, thereby constituting an argument for intensified antiplatelet therapy in patients with poor glycemic control. In the prospective, multicenter Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c <6.5% (n = 551, 48.12%), 6.5% to 8.5% (n = 423, 36.9%), and >8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208 and aspirin reaction units >550, respectively. HPR on clopidogrel was frequent (48.3%), whereas HPR on aspirin was not (3.9%). Patients with HbA1c >8.5% were younger, more likely non-Caucasian, had a greater body mass index, and more insulin-treated diabetes and acute coronary syndromes. Proportions of PRU >208 (42.5%, 50.2%, and 62.3%, p <0.001) and rates of definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models that included PRU, high HbA1c levels (>8.5) remained associated with ST (hazard ratio 3.92, 95% CI 1.29 to 12.66, p = 0.02) and cardiac death (hazard ratio 4.24, 95% CI 1.41 to 12.70) but not bleeding at 2-year follow-up. There was no association between aspirin reaction units >550 and HbA1c levels. In conclusion, in this large-scale study, HbA1c and HPR were positively associated, but the clinical effect on adverse outcome was driven by poor glycemic control, which predicted ST and cardiac death after PCI regardless of PRU levels, warranting efforts to improve glycemic control after DES implantation in patients with diabetes mellitus.


title: Effect of the application of a bundle of three measures (intraperitoneal lavage with antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin ointment application on the skin staples) on the surgical site infection after elective laparoscopic colorectal cancer surgery.

text: BACKGROUND Surgical site infection (SSI) prevention bundles include the simultaneous use of different measures, which individually have demonstrated an effect on prevention of SSI. The implementation of bundles can yield superior results to the implementation of individual measures. The aim of this study was to address the effect of the application of a bundle including intraperitoneal lavage with antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin ointment application on the skin staples, on the surgical site infection after elective laparoscopic colorectal cancer surgery. METHODS A prospective, randomized study was performed, including patients with diagnosis of colorectal neoplasms and plans to undergo an elective laparoscopic surgery. The patients were randomized into two groups: those patients following standard bundles (Group 1) and those ones following the experimental bundle with three additional measures, added to the standard bundle. Incisional and organ space SSI were investigated. The study was assessor-blinded. RESULTS A total of 198 patients were included in the study, 99 in each group. The incisional SSI rate was 16% in Group 1 and 2% in Group 2 [p = 0.007; RR = 5.6; CI 95% (1.4-17.8)]. The organ-space SSI rate was 4% in Group 1 and 0% in Group 2 [p = 0.039; RR = 1.7; CI 95% (1.1-11.6)]. Median hospital stay was 5.5 days in Group 1 and 4 days in Group 2 (p = 0.028). CONCLUSIONS The addition of intraperitoneal lavage with antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin ointment application on the skin staples, to a standard bundle of SSI prevention, reduces the incisional and organ-space SSI and consequently the hospital stay, after elective laparoscopic colorectal cancer surgery (ClinicalTrials.gov Identifier: NCT03081962).


title: Role of preoperative endoscopic clipping in laparoscopic distal gastrectomy for early gastric cancer.

text: In this study, we evaluate the usefulness of preoperative endoscopic clipping for early gastric cancer (EGC) localization in laparoscopic distal gastrectomy.We retrospectively screened all consecutive patients who underwent laparoscopic distal gastrectomy for EGC by 1 surgeon at Chungnam National University Hospital between January 2014 and December 2016. Patients who underwent combined surgery and patients who had tumors at the lower third of the stomach were excluded. Endoscopic clipping was performed prior to surgery by specialized endoscopists. During the operation, endoscopic metal clips were found using surgical devices, and laparoscopic vessel clips were attached on the presumed site; thereafter, intraoperative radiographs were obtained for confirmation.We analyzed a total of 196 patients; of them, 101 were classified into the clipping group (CG) and 95 into the non clipping group (NCG). The 2 groups were comparable regarding their demographic characteristics. The CG showed less additional resection (2 of 101 patients [2.0%] vs 9 of 95 patients [9.4%], P = .021) and better outcomes in terms of the operation time (P = .000), duration of hospital stay (P = .036), and postoperative atelectasis (P = .001) than the NCG.Preoperative endoscopic clipping was helpful in determining the exact resection margin in laparoscopic distal gastrectomy for EGC.


title: Single-port access transaxillary totally endoscopic thyroidectomy: a new approach for minimally invasive thyroid operation.

text: PURPOSE Various techniques for minimally invasive thyroid surgery have been described over the last decade. As interest in single-port access laparoscopic surgery (SPA™) continues to grow, the authors present their technique and short-term outcomes for single-port access transaxillary totally endoscopic thyroidectomy in the management of benign thyroid tumors in a series of 4 patients. PATIENTS AND METHODS Four consecutive patients from a prospectively maintained endoscopic thyroidectomy database were analyzed under an institutional review board-approved protocol. Clinical characteristics and short-term outcomes were reviewed. RESULTS All the patients were young women with no prior neck surgery. A single-port totally endoscopic thyroidectomy was performed for thyroid adenoma in 2 cases and for nodular goiter in 2 cases. Retraction, exposure, and extraction were possible in all cases. The average operating room time was 92.5 minutes. Postoperative pain scores on postoperative day 1 were all 1/10. No patient experienced complications. The median hospital stay was 1.75 days. The mean specimen size was 2.7 cm × 2.375 cm × 2.625 cm. The patients were uniformly pleased with the cosmetic results of the operation. CONCLUSIONS Single-port access transaxillary totally endoscopic partial thyroidectomy appears to be safe and feasible. This technique may provide both an attractive way to reduce injury to the anterior neck tissue and a method for ideal cosmetic effect.


title: Health Risk Information Engagement and Amplification on Social Media.

text: Emerging pandemics call for unique health communication and education strategies in which public health agencies need to satisfy the public's information needs about possible risks while preventing risk exaggeration and dramatization. As a route to providing a framework for understanding public information behaviors in response to an emerging pandemic, this study examined the characteristics of communicative behaviors of social media audiences in response to Ebola outbreak news. Grounded in the social amplification of risks framework, this study adds to an understanding of information behaviors of online audiences by showing empirical differences in audience engagement with online health information. The data were collected from the Centers for Disease Control and Prevention (CDC) Facebook channel. The final data set included 809 CDC posts and 35,916 audience comments. The analysis identified the differences in audience information behaviors in response to an emerging pandemic, Ebola, and health promotion posts. While the CDC had fewer posts on Ebola than health promotion topics, the former received more attention from active page users. Furthermore, audience members who actively engaged with Ebola news had a small overlap with those who engaged with non-Ebola information during the same period. Overall, this study demonstrated that information behavior and audience engagement is topic dependent. Furthermore, audiences who commented on news about an emerging pandemic were homogenous and varied in their degree of information amplification.


title: Requirements and standards facilitating quality improvement for reporting systems in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

text: To develop standards for high quality in gastrointestinal (GI) endoscopy, the European Society of Gastrointestinal Endoscopy (ESGE) has established the ESGE Quality Improvement Committee. A prerequisite for quality assurance and improvement for all GI endoscopy procedures is state-of-the-art integrated digital reporting systems for standardized documentation of the procedures. The current paper describes the ESGE's viewpoints on the requirements for high-quality endoscopy reporting systems in GI endoscopy. Recommendations 1 Endoscopy reporting systems must be electronic. 2 Endoscopy reporting systems should be integrated into hospitals' patient record systems. 3 Endoscopy reporting systems should include patient identifiers to facilitate data linkage to other data sources. 4 Endoscopy reporting systems shall restrict the use of free-text entry to a minimum, and be based mainly on structured data entry. 5 Separate entry of data for quality or research purposes is discouraged. Automatic data transfer for quality and research purposes must be facilitated. 6 Double entry of data by the endoscopist or associate personnel is discouraged. Available data from outside sources (administrative or medical) must be made available automatically. 7 Endoscopy reporting systems shall facilitate the inclusion of information on histopathology of detected lesions, patient satisfaction, adverse events, and surveillance recommendations. 8 Endoscopy reporting systems must facilitate easy data retrieval at any time in a universally compatible format. 9 Endoscopy reporting systems must include data fields for key performance indicators as defined by quality improvement committees. 10 Endoscopy reporting systems must facilitate changes in indicators and data entry fields as required by professional organizations.


title: Laparoscopic repair of a late-presenting Bochdalek diaphragmatic hernia with acute gastric volvulus.

text: An otherwise healthy 17-year-old boy presented to the paediatric emergency department with acute severe epigastric pain. An admission abdominal radiograph demonstrated gastric dilation, associated with an elevated left hemidiaphragm. Subsequent barium contrast imaging confirmed the diagnosis of organoaxial acute gastric volvulus (AGV). Emergent exploratory laparoscopy revealed AGV with migration of the stomach, spleen, pancreatic tail, splenic flexure, left kidney and adrenal through a left-sided Bochdalek diaphragmatic hernia. Following careful mobilisation of the displaced structures, a mesh closure of the diaphragmatic defect was performed. The patient's postoperative chest radiograph was unremarkable, and he was discharged on the sixth postoperative day after an uneventful recovery. At 2 months the patient was well and asymptomatic, with normal barium contrast imaging results.


title: Receptivity to mandatory influenza vaccination policies for healthcare workers among registered nurses working on inpatient units.

text: A survey that included questions about preferred methods of influenza prevention was completed by 513 registered nurses working on inpatient units. Vaccination was the preferred influenza prevention method among 83.0% of respondents. Of 506 respondents, 283 (56.0%) stated that mandatory influenza vaccination was appropriate for healthcare workers, and 394 (59.4%) of 512 RNs reported that they would support a policy requiring annual influenza vaccination for healthcare workers that allowed for informed declination.


title: Respiratory syncytial virus in the Western Pacific Region: a systematic review and meta-analysis.

text: Background Respiratory syncytial virus (RSV) is the leading cause of viral pneumonia and bronchiolitis, especially in younger children. The burden of RSV infection in adults, particularly in the older age group, is increasingly recognised. However, RSV disease burden and molecular epidemiology in the World Health Organization (WHO) Western Pacific Region (WPR) has not been reviewed systematically. The aim of this systematic review is to investigate the epidemiological aspects of RSV (incidence, prevalence, seasonality and hospitalisation status) and the associated molecular data in the WPRO countries. Methods A systematic search was conducted in international literature databases (MEDLINE, EMBASE, Scopus and Web of Science) to identify RSV-related publications from January 2000 to October 2017 in the WPR countries. Results A total of 196 studies from 15 WPR countries were included. The positivity rate for RSV among respiratory tract infection patients was 16.73% (95% confidence interval (CI) = 15.12%-18.4%). The RSV-positive cases were mostly found in hospitalised compared with outpatients (18.28% vs 11.54%, P < 0.001), and children compared with adults (20.72% vs 1.87%, P < 0.001). The seasonality of RSV in the WPR countries follows the latitude, with the peak of RSV season occurring in the winter in temperate countries, and during the rainy season in tropical countries. The molecular epidemiology pattern of RSV in WPR countries was similar to the global pattern, with NA1 (RSV A) and BA (RSV B) being the predominant genotypes. Conclusions The available data on RSV are limited in several countries within the WPR, with most data focusing on children and hospitalised patients. Further studies and surveillance, incorporating laboratory testing, are needed to determine the burden of RSV infection in the WPR countries.


Mental health and psychological impact of COVID-19: Potential high-risk factors among different groups.


title: Hijacking DNA methyltransferase transition state analogues to produce chemical scaffolds for PRMT inhibitors.

text: DNA, RNA and histone methylation is implicated in various human diseases such as cancer or viral infections, playing a major role in cell process regulation, especially in modulation of gene expression. Here we developed a convergent synthetic pathway starting from a protected bromomethylcytosine derivative to synthesize transition state analogues of the DNA methyltransferases. This approach led to seven 5-methylcytosine-adenosine compounds that were, surprisingly, inactive against hDNMT1, hDNMT3Acat, TRDMT1 and other RNA human and viral methyltransferases. Interestingly, compound 4 and its derivative 2 showed an inhibitory activity against PRMT4 in the micromolar range. Crystal structures showed that compound 4 binds to the PRMT4 active site, displacing strongly the S-adenosyl-l-methionine cofactor, occupying its binding site, and interacting with the arginine substrate site through the cytosine moiety that probes the space filled by a substrate peptide methylation intermediate. Furthermore, the binding of the compounds induces important structural switches. These findings open new routes for the conception of new potent PRMT4 inhibitors based on the 5-methylcytosine-adenosine scaffold.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.


title: The 24-h progression of menstrual pain in women with primary dysmenorrhea when given diclofenac potassium: a randomized, double-blinded, placebo-controlled crossover study.

text: PURPOSE Primary dysmenorrhea, which refers to painful, spasmodic cramping in the lower abdomen just before/or during menstruation, is the most common gynecological complaint in women of reproductive age. Non-steroidal anti-inflammatory drugs have been prescribed as the first-line therapy for pain relief from dysmenorrhea. We aimed to investigate the efficacy of the daily recommended dose (150 mg) of diclofenac potassium, administered at set intervals across the first 24 h of menstruation, in treating severe menstrual pain in 24 women with severe primary dysmenorrhea. METHODS In a randomized, placebo-controlled, double-blind cross-over study, women rated their menstrual pain intensity on a 100-mm visual analog scale across set time intervals over a 24-h period. RESULTS Menstrual pain intensity was significantly reduced after taking the first capsule of diclofenac, and remained consistently lower (P < 0.0001), compared with initial pain intensity, in the morning (before treatment), throughout the day, evening, and into the next morning. Also, women rated their pain intensity as significantly lower (P < 0.001) at each time point across the 24-h time interval of the cycle when receiving diclofenac compared with the cycle when they received placebo. No woman required rescue medication when taking diclofenac potassium compared with six women taking rescue medications during the placebo trial. When taking only placebo, women rated their menstrual pain intensity as persistently severe across the first 24 h of menstruation. CONCLUSION These results show that the recommended daily dose of diclofenac potassium, in three 50 mg doses across the day and evening, offers effective menstrual pain relief across 24 h, compared with placebo, in women with severe primary dysmenorrhea.


title: Exercise and well-being during COVID 19 - Time to boost your immunity.

text: INTRODUCTION The COVID-19 pandemic is causing devastating global morbidity and mortality. Worldwide measures are taken to prevent human to human transmission and improve general health. Public lifestyle and health are affected by social distancing and isolation. A strong host immune response to the novel coronavirus is a key factor, for protection against infection and avoiding reaching severe stages of the disease. AREAS COVERED Pathophysiology and the human immune response of similar coronaviruses have been previously described. The novel coronavirus has distinct clinical stages related to the immune response. Exercise improves host innate immunity and affords protection to viral infections. Exercise also mitigates the negative effects of isolation including stress, anxiety and sedentarism, all of which further reduces immunity and increases non-communicable disease risk. EXPERT OPINION Improving host immunity and mitigating the negative effects of isolation via physical activity is strongly justified. Exercise should be done in moderate intensities and volumes during the current pandemic, which is a nutritionally, psychologically, socially challenging environment in the presence of a virulent viral organism. Proactively creating innovative health promotion models with technology and government involvement with best available evidence should be encouraged to reduce physical inactivity during the current COVID-19 pandemic and after.


title: Intravenous contrast medium administration and scan timing at CT: considerations and approaches.

text: The continuing advances in computed tomographic (CT) technology in the past decades have provided ongoing opportunities to improve CT image quality and clinical practice and discover new clinical CT imaging applications. New CT technology, however, has introduced new challenges in clinical radiology practice. One of the challenges is with intravenous contrast medium administration and scan timing. In this article, contrast medium pharmacokinetics and patient, contrast medium, and CT scanning factors associated with contrast enhancement and scan timing are presented and discussed. Published data from clinical studies of contrast medium and physiology are reviewed and interpreted. Computer simulation data are analyzed to provide an in-depth analysis of various factors associated with contrast enhancement and scan timing. On the basis of basic principles and analysis of the factors, clinical considerations and modifications to protocol design that are necessary to optimize contrast enhancement for common clinical CT applications are proposed.


title: Impact of SAMMPRIS on the future of intracranial atherosclerotic disease management: polling results from the ICAD symposium at the International Stroke Conference.

text: OBJECTIVE There are few data regarding the effect of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial results on the management of intracranial atherosclerotic disease (ICAD). We sought to understand the impact of the SAMMPRIS trial on current ICAD clinical practices and future trial design. METHODS During the ICAD symposium at the 2012 International Stroke Conference, electronic data were collected regarding attendees' clinical management of ICAD and opinions on the feasibility of future trials post-SAMMPRIS. RESULTS 217 attendees from different specialties, including neurologists (57%), neurointerventionalists (9%) and neurosurgeons (5%), participated in the session. The majority of respondents (77%) indicated that the results of SAMMPRIS have impacted their consideration for intracranial stenting. Post-SAMMPRIS, 84% selected 'SAMMPRIS-style' medical management for the treatment of ICAD. For patients with ICAD who failed aggressive medical therapy, 82% would consider an alternative approach to continuing medical therapy (30% considered clinical trial enrollment, 28% suggested angioplasty and stenting and 24% angioplasty). The majority of participants (85%) were willing to randomize patients with symptomatic ICAD in future trials. For the next ICAD trial, 29% indicated that angioplasty alone should be compared with aggressive medical therapy. CONCLUSIONS Our polling results suggest that the SAMMPRIS trial has had an impact on the current treatment of ICAD. Treatment of patients who failed medical therapy varied widely from aggressive medical therapy to balloon angioplasty, stenting or enrollment in future clinical trials. The willingness to continue clinical trials and randomize patients supports the need for future ICAD studies.


title: Thigh-length versus below-knee stockings for deep venous thrombosis prophylaxis after stroke: a randomized trial.

text: BACKGROUND Graduated compression stockings are widely used for deep venous thrombosis (DVT) prophylaxis. Although below-knee stockings are used more often than thigh-length stockings, no reliable evidence indicates that they are as effective as thigh-length stockings. OBJECTIVE To compare the effectiveness of thigh-length stockings with that of below-knee stockings for preventing proximal DVT in immobile, hospitalized patients with stroke. DESIGN Parallel-group trial with centralized randomization (minimization within centers) to ensure allocation concealment. The ultrasonographers who looked for DVT were blinded, but the patients and caregivers were not. (Controlled-trials.com registration number: ISRCTN28163533) SETTING 112 hospitals in 9 countries. PATIENTS 3114 immobile patients hospitalized with acute stroke between January 2002 and May 2009. INTERVENTION 1552 patients received thigh-length stockings and 1562 patients received below-knee stockings to wear while they were in the hospital. MEASUREMENTS Ultrasonographers performed compression duplex ultrasonography in 1406 patients (96% of survivors) in each treatment group between 7 and 10 days after enrollment. They performed a second scan in 643 patients in the thigh-length stockings group and 639 in the below-knee stockings group at about 25 to 30 days. The primary outcome was symptomatic or asymptomatic DVT in the popliteal or femoral veins, detected on either scan. RESULTS Patients were retained in their assigned group for all analyses. The primary outcome occurred in 98 patients (6.3%) who received thigh-length stockings and 138 (8.8%) who received below-knee stockings (absolute difference, 2.5 percentage points [95% CI, 0.7 to 4.4 percentage points]; P = 0.008), an odds reduction of 31% (CI, 9% to 47%). Seventy-five percent of patients in both groups wore the stockings for 30 days or until they were discharged, died, or regained mobility. Skin breaks occurred in 61 patients who received thigh-length stockings (3.9%) and 45 (2.9%) who received below-knee stockings. LIMITATION Blinding was incomplete, 2 scans were not obtained for all enrolled patients, and the trial was stopped before the target accrual was reached. CONCLUSION Proximal DVT occurs more often in patients with stroke who wear below-knee stockings than in those who wear thigh-length stockings. PRIMARY FUNDING SOURCE Medical Research Council of the United Kingdom, Chief Scientist Office of the Scottish Government, and Chest Heart and Stroke Scotland.


title: Thrombus composition in acute ischemic stroke: a histopathological study of thrombus extracted by endovascular retrieval.

text: BACKGROUND AND PURPOSE The composition of occlusive thrombus in acute ischemic stroke may affect treatment success. Neuroimaging characteristics may correlate with thrombus composition. In this study we aimed to investigate the relationship between the hyperdense artery sign (HAS) on imaging and thrombus composition. MATERIALS AND METHODS Acute ischemic stroke patients who underwent endovascular thrombus retrieval from 2010-2012 were prospectively recruited. One blinded pathologist prepared the histology sections of retrieved thrombi whereby staining with haematoxylin and eosin and CD34 immunostain were performed. Histology sections were categorised into 4 phases of thrombus formation: red blood cell (RBC) dominant, RBC proportion equal to fibrin, fibrin dominant and organised fibrin. Computed tomography (CT) brain scans were assessed for HAS. Fisher's exact test was performed to identify an association between HAS and thrombus composition. RESULTS Forty patients were included. The mean age was 65.6±12.9 years and 67.5% were male. Atrial fibrillation was detected in 19 (47.5%) patients, diabetes mellitus in 6 (15.0%), hypercholesterolaemia in 11 (27.5%), hypertension in 20 (50.0%) and previous stroke or transient ischemic attack in 8 (20.0%) patients. Of the retrieved thrombi, 11 (27.5%) were RBC dominant, 11 (27.5%) RBC proportion was equal to fibrin, 7 (17.5%) fibrin dominant and 11 (27.5%) organised fibrin pathology. HAS was present in 29 (72.5%) patients and was significantly associated with thrombus early phase pathology (P<0.05). CONCLUSION HAS was significantly associated with early phase thrombus composition. This may enable the prediction of thrombus composition and allow for targeted selection of therapeutic modality.


title: Identification of an HLA-DPB1*0501 restricted Melan-A/MART-1 epitope recognized by CD4+ T lymphocytes: prevalence for immunotherapy in Asian populations.

text: CD4 T lymphocytes play a central role in orchestrating an efficient antitumor immune response. Much effort has been devoted in the identification of major histocompatibility complex class II eptiopes from different tumor-associated antigens. Melan-A/MART-1 is expressed specifically in normal melanocytes and tumor cells of 75% to 100% of melanoma patients. Melan-A/MART-1 is considered as an attractive target for cancer immunotherapy. In the past, several human leukocyte antigen (HLA) class II restricted epitopes have been identified and characterized, including Melan-A/MART-11-20 (HLA-DR11 restricted), Melan-A/MART-125-36 (HLA-DQ6 and HLA-DR3 restricted), Melan-A/MART-127-40 (HLA-DR1 restricted), Melan-A/MART-151-73 (HLA-DR4 restricted), Melan-A/MART-191-110 (HLA-DR52 restricted), and Melan-A/MART-1100-111 (HLA-DR1 restricted). Owing to the infrequent expression of the above HLA class II alleles in Asian populations, immunotherapy using these defined Melan-A/MART-1 peptides could potentially only benefit a very small percentage of Asian melanoma patients. In this study, we established several CD4 T-cell clones by in vitro stimulation of peripheral blood mononuclear cells from a healthy donor by a peptide pool of 28 to 30 amino acid long peptides spanning the entire Melan-A/MART-1 protein. These CD4 T-cell clones recognized a peptide that is embedded within Melan-A/MART-121-50, in a HLA-DPB1*0501 restricted manner. Finally, we demonstrated that this epitope is naturally processed and presented by dendritic cells. HLA-DPB1*0501 is frequently expressed in Asian population (44.9% to 73.1%). Therefore, this epitope could provide a new tool and could significantly increase the percentage of melanoma patients that can benefit from cancer immunotherapy.


title: Flow Diverters for Treatment of 160 Ophthalmic Segment Aneurysms: Evaluation of Safety and Efficacy in a Multicenter Cohort.

text: BACKGROUND Treatment of ophthalmic segment aneurysms (OSA) remains challenging. Flow diverter stents (FDS) have evolved as a promising endovascular treatment option for aneurysms of the internal carotid artery and are associated with high occlusion rates and a favorable morbidity and mortality profile. OBJECTIVE To determine safety and efficacy of FDS for OSA in a large, multicenter cohort. METHODS A retrospective analysis of prospectively maintained databases of 127 consecutive patients harboring 160 OSA treated with FDS was performed. Aneurysms were classified based on location and morphology. Follow-up with digital subtraction angiography (DSA) was performed 6 to 18 months after treatment. RESULTS Follow-up DSA was available for 101 (63.1%) aneurysms with a mean follow-up of 18 months. Complete occlusion was observed in 90 aneurysms (89.1%), near-complete occlusion (>95%) in 3 (3%), and incomplete occlusion (<95%) in 8 aneurysms (7.9%). One aneurysm was retreated with another FDS (0.9%). No risk factors for incomplete occlusion were identified. The OA was occluded at the latest follow-up in 6 cases (7.1%). Permanent morbidity occurred in 4 patients (3.1%), and there was no mortality related to the FDS procedure. CONCLUSION Treatment of OSA with FDS was found to be safe and effective. The retreatment rate was extremely low and aneurysms that occluded did not reanalyze.


title: COVID-19 , School Closings and Weight Gain.

text: We found the publication on "COVID-19 Related School Closings and Risk of Weight Gain Among Children" to be interesting.1 Rundle et al. noted that "we anticipate that the COVID-19 pandemic will likely double out-of-school time this year for many children in the U.S. and will exacerbate the risk factors for weight gain associated with summer recess."1 In fact, there are several factors relating to nutritional status of the children. We would like to share observations from Thailand, the second country in the timeline of COVID-19.2 In Thailand, school aged children in rural areas where COVID-19 disease outbreak exists are usually underweight.3 Thus, school closing means the children have to live with poor parents adding to economic problems of the family.


title: Acute disseminated encephalomyelitis in children: a single institution experience of 28 patients.

text: The aim of this study is to describe the clinical, laboratory, and neuroimaging features, treatment and outcome of acute disseminated encephalomyelitis (ADEM) in Taiwanese children to compare with two series from United States of America and Japan. We retrospectively reviewed the medical records and magnetic resonance images of 28 children, 23 boys and 5 girls, with ADEM between January 2001 and December 2009. Their mean age at disease onset was 6 years 9 months. Twenty four children experienced a prodromal illness. There was no special seasonal distribution in our patients. They presented mostly with impaired consciousness and headache. Cerebrospinal fluid samples of 21 patients were analyzed and none showed intrathecal oligoclonal bands. Magnetic resonance imaging showed variable findings: lesions with abnormal signal changes frequently found in the subcortical white matter of frontal and parietal lobes. No patient showed cortical gray matter involvement. We also found a high rate of deep gray matter involvement including thalami and basal ganglia. Treating with steroids was usually associated with a rapid recovery and both intravenous high dose methylprednisolone and dexamethasone had the same effect. All patients survived. Twenty three patients recovered completely with only mild sequelae in the remaining five children.


title: Long-term survival in six cats with mediastinal cysts.

text: CASE SERIES SUMMARY Mediastinal cysts were diagnosed as incidental findings in six cats evaluated for non-thoracic disease, including staging for historic bladder leiomyosarcoma, flea dermatitis and hairballs, and hyperthyroidism. Radiographically, the cysts appeared as soft tissue opacities cranial to the heart. Ultrasound revealed the masses to be thin-walled, single lumen, anechoic fluid-filled structures. One cat also had thoracic and abdominal CT performed for cancer staging; the CT revealed a well-defined, fluid-attenuating mass without peripheral contrast enhancement in the cranial mediastinum. Fine-needle aspiration confirmed acellular fluid consistent with a cyst in five cases; in one case the cyst ruptured during aspiration and no fluid was obtained. Post-aspiration, all masses were no longer visible with ultrasound or radiographs. No treatment was recommended for the cysts. Long-term follow-up (2-9 years post-diagnosis) was available in all six cats. The cysts recurred in five cats yet was never associated with clinical signs. RELEVANCE AND NOVEL INFORMATION Mediastinal cysts are an important benign differential for cranial mediastinal masses in cats. Treatment for the cysts does not appear to be indicated. This series also includes the first CT description of this clinical entity.


title: A Systematic Review of HIV Interventions for Young Women in Sub-Saharan Africa.

text: Adolescent girls and young women (AGYW) ages (15-24 years old) in Southern and Eastern Africa account for nearly 30% of all new HIV infections. We conducted a systematic review of studies examining the effectiveness of behavioral, structural, and combined (behavioral + structural) interventions on HIV incidence and risky sexual behaviors among AGYW. Following PRISMA guidelines, we searched PubMed, CINAHL, Web of Science, and Global Health. Twenty-two studies met inclusion criteria conducted in Eastern and Southern Africa and comprised behavioral, structural, or combined (behavioral and structural) interventions. All findings are based on 22 studies. HIV incidence was significantly reduced by one structural intervention. All three types of interventions improved condom use among AGYW. Evidence suggests that structural interventions can reduce HIV incidence, while behavioral and combined interventions require further investigation.


title: Molecular analysis of bacterial contamination on stethoscopes in an intensive care unit.

text: BACKGROUND Culture-based studies, which focus on individual organisms, have implicated stethoscopes as potential vectors of nosocomial bacterial transmission. However, the full bacterial communities that contaminate in-use stethoscopes have not been investigated. METHODS We used bacterial 16S rRNA gene deep-sequencing, analysis, and quantification to profile entire bacterial populations on stethoscopes in use in an intensive care unit (ICU), including practitioner stethoscopes, individual-use patient-room stethoscopes, and clean unused individual-use stethoscopes. Two additional sets of practitioner stethoscopes were sampled before and after cleaning using standardized or practitioner-preferred methods. RESULTS Bacterial contamination levels were highest on practitioner stethoscopes, followed by patient-room stethoscopes, whereas clean stethoscopes were indistinguishable from background controls. Bacterial communities on stethoscopes were complex, and community analysis by weighted UniFrac showed that physician and patient-room stethoscopes were indistinguishable and significantly different from clean stethoscopes and background controls. Genera relevant to healthcare-associated infections (HAIs) were common on practitioner stethoscopes, among which Staphylococcus was ubiquitous and had the highest relative abundance (6.8%-14% of contaminating bacterial sequences). Other HAI-related genera were also widespread although lower in abundance. Cleaning of practitioner stethoscopes resulted in a significant reduction in bacterial contamination levels, but these levels reached those of clean stethoscopes in only a few cases with either standardized or practitioner-preferred methods, and bacterial community composition did not significantly change. CONCLUSIONS Stethoscopes used in an ICU carry bacterial DNA reflecting complex microbial communities that include nosocomially important taxa. Commonly used cleaning practices reduce contamination but are only partially successful at modifying or eliminating these communities.


title: Carotid artery bursting pressure and seal time after multiple uses of a vessel sealing device.

text: OBJECTIVE To determine any loss of function of a single-use bipolar vessel sealing device after repeated sterilization and use on canine carotid arteries. STUDY DESIGN Ex vivo; randomized block design (dog). SAMPLE POPULATION Carotid artery segments (n = 90) from 15 canine cadavers. METHODS Six 10-mm LigaSure Atlas 20 cm devices (Covidien Inc, Minneapolis, Minnesota) were used to seal canine carotid artery segments in one cadaver, then resterilized using ethylene oxide and reused in a second cadaver, and so on, for a total of 15 uses/15 cadavers per LigaSure. Sealing times and bursting pressures of each carotid artery segment after each use were recorded. Charring and sticking at each seal location was qualitatively assessed. RESULTS Mean (SD) sealing time for all segments was 5.3 (1.4) seconds, ranging from 2.7 to 9.5 seconds. There was no significant change in sealing time for successive uses (P = .117). The mean (SD) bursting pressure for all segments was 1041.3 (316.7) mm Hg, ranging from 355 to 1555 mm Hg. There was no change in bursting pressure across uses (P = .57). Moderate sticking and charring occurred at each time point but was not subjectively different throughout the study. CONCLUSION The LigaSure Atlas vessel sealing device can be used and resterilized with ethylene oxide up to 15 times with no change in sealing time or bursting pressure of the seal.


title: Pediatric Forearm Fractures Are Effectively Immobilized With a Sugar-Tong Splint Following Closed Reduction.

text: INTRODUCTION Following closed reduction and initial casting of pediatric forearm fractures, loss of reduction (LOR) occurs in ∼5% to 75% of fractures. Sugar-tong splinting has been shown to maintain acceptable reduction in pediatric distal radius fractures while potentially avoiding issues associated with circumferential casting. We hypothesized that the sugar-tong splint would be an acceptable method for initial immobilization to prevent LOR in distal, mid-shaft, and proximal pediatric forearm fractures. METHODS This is an IRB-approved, retrospective study. Inclusion criteria included pediatric patients age 4 to 16 years old, open growth plates, with a displaced forearm fracture (radius, ulna, or both bone) that underwent closed reduction. The clinical protocol involved closed reduction and application of a sugar-tong splint by an orthopaedic resident under conscious sedation in the emergency room. Clinical follow-up occurred at 1, 2, 4, and 6-week intervals with a long-arm cast overwrap applied at the initial clinic visit. Primary outcome was radiographic LOR which was defined as a change of >10 degrees of angulation on anterior posterior/lateral projections from initial postreduction radiograph or previous follow-up radiograph. The secondary outcome was the need for further intervention. RESULTS Sixty-four (38%) patients demonstrated radiographic LOR with 90% of LORs occurring in the first 2 weeks. LOR was significantly more common in distal radius fractures [48/110 (44%)] than with either proximal [2/14 (14%), P=0.04] or mid-shaft radius fractures [7/41 (17%), P=0.004]. There was no difference in LOR by location for ulna fractures [proximal=2/13 (15%), middle=4/38 (11%), distal=20/77 (26%), P>0.08]. There was no difference in radial LOR in patients with isolated radius fractures compared with both bone forearm fracture (17/40 vs. 40/125, P=0.22), or ulnar LOR between isolated ulna and both bone forearm fracture (0/3 vs. 26/125, P>0.99). CONCLUSION The sugar-tong splint is effective at maintaining reduction of pediatric forearm fractures similar to published rates for casting. While effective at all levels of the forearm, the sugar-tong splint performed best in proximal and mid-shaft forearm fractures. LEVEL OF EVIDENCE Level IV.


title: Cryo-electron tomography of porcine reproductive and respiratory syndrome virus: organization of the nucleocapsid.

text: Porcine reproductive and respiratory virus (PRRSV) is an enveloped positive-sense RNA virus of the family Arteriviridae that causes severe and persistent disease in pigs worldwide. The PRRSV virion consists of a lipid envelope that contains several envelope proteins surrounding a nucleocapsid core that encapsidates the RNA genome. To provide a better understanding of the structure and assembly of PRRSV, we have carried out cryo-electron microscopy and tomographic reconstruction of virions grown in MARC-145 cells. The virions are pleomorphic, round to egg-shaped particles with an average diameter of 58 nm. The particles display a smooth outer surface with only a few protruding features, presumably corresponding to the envelope protein complexes. The virions contain a double-layered, hollow core with an average diameter of 39 nm, which is separated from the envelope by a 2-3 nm gap. Analysis of the three-dimensional structure suggests that the core is composed of a double-layered chain of nucleocapsid proteins bundled into a hollow ball.


title: Stilbene-based Natural Compounds as Promising Drug Candidates against COVID-19.

text: The pandemic coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a great threat to public health. Currently, no potent medicine is available to treat COVID-19. Quest for new drugs especially from natural plant sources is an area of immense potential. The current study aimed to repurpose stilbenoid analogs, reported for some other biological activities, against SARS-CoV-2 spike protein and human ACE2 receptor complex for their affinity and stability using molecular dynamics simulation and binding free energy analysis based on molecular docking. Four compounds in total were probed for their binding affinity using molecular docking. All of the compounds showed good affinity (> -7 kcal/mol). However, fifty nanoseconds molecular dynamic simulation in aqueous solution revealed highly stable bound conformation of resveratrol to the viral protein: ACE2 receptor complex. Net free energy of binding using MM-PBSA also affirmed the stability of the resveratrol-protein complex. Based on the results, we report that stilbene based compounds in general and resveratrol, in particular, can be promising anti-COVID-19 drug candidates acting through disruption of the spike protein. Our findings in this study are promising and call for further in vitro and in vivo testing of stiblenoids, especially resveratrol against the COVID-19.


title: Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial.

text: BACKGROUND Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. METHODS Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase-myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. RESULTS We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] -0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI -0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). INTERPRETATION Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. TRIAL REGISTRATION ClinicalTrials.gov, no. NCT01071265.


title: Analysis of ACE2 Genetic Variability among Populations Highlights a Possible Link with COVID-19-Related Neurological Complications.

text: Angiotensin-converting enzyme 2 (ACE2) has been recognized as the entry receptor of the novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Structural and sequence variants in ACE2 gene may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection and the COVID-19-related phenotype. The present study investigated the genetic variability of ACE2 in terms of single nucleotide variants (SNVs), copy number variations (CNVs), and expression quantitative loci (eQTLs) in a cohort of 268 individuals representative of the general Italian population. The analysis identified five SNVs (rs35803318, rs41303171, rs774469453, rs773676270, and rs2285666) in the Italian cohort. Of them, rs35803318 and rs2285666 displayed a significant different frequency distribution in the Italian population with respect to worldwide population. The eQTLs analysis located in and targeting ACE2 revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link between ACE2 genetic variability and the neurological complications in patients with COVID-19. Further research is needed to clarify the possible relationship between ACE2 expression and the susceptibility to neurological complications in patients with COVID-19. In fact, patients at higher risk of neurological involvement may need different monitoring and treatment strategies in order to prevent severe, permanent brain injury.


Beyond the VA Crisis--Becoming a High-Performance Network.


title: Immunogenicity of a multi-epitope DNA vaccine against hantavirus.

text: Hemorrhagic fever with renal syndrome (HFRS) is a severe epidemic disease caused by hantaviruses including Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava virus (DOBV) and Puumala virus. Three of the four HFRS hantaviruses, HTNV, SEOV, and PUUV are found in China. Currently, there is no effective strategy available to reduce infection risk. In this study, we constructed a multi-epitope chimeric DNA vaccine that encodes expressing 25 glycoprotein epitopes from SEOV, HTNV and PUUV (designated as SHP chimeric gene). Vaccination of BALb/c mice with SHP multi-epitope chimeric DNA vaccine led to a dramatic augmentation of humoral and cellular responses. The SHP vaccine DNA was detected in many organs but not for more than 60 d. There was no risk of mutation due to integration. Thus, the SHP multi-epitope chimeric DNA vaccine is a potential effective and safe DNA vaccine against infection by SEOV, HTNV, and PUUV.


title: Long-term follow-up of endoscopic totally extraperitoneal direct inguinal hernia repair using the Endoloop technique.

text: INTRODUCTION The pre-tied suture Endoloop™ technique for plication of the weakened transversalis fascia is efficient in post-operative seroma prevention, after laparoscopic/endoscopic direct inguinal hernia repair. No studies have evaluated long-term tolerability of this new technique in regards to chronic pain and hernia recurrence. METHODS Prospective longitudinal evaluation study of consecutive patients treated with Endoloop™ for M2 or M3 direct defects, during endoscopic totally extraperitoneal approach. Meshes were secured with fibrin sealant only. All patients had a minimum 2.8 years (median 5.9 years) follow-up. First outcome was chronic groin/testicular pain; secondary outcome parameters included hernia recurrence and Quality of Life (QoL). Patients were assessed by phone interview using the validated Carolinas Comfort Scale (CCS), questioned regarding recurrence and asked to present for clinical review as needed. RESULTS 112 patients (median age 57 years) with 141 direct hernia defects were included during the study period of 2008-2014. An Endoloop™ was used on 127 occasions-79 M2 and 48 M3 direct hernias. One patient had an early recurrence requiring an open repair and was therefore excluded. Thirty-three of the remaining one hundred and eleven patients (29.7%) were lost to long-term follow-up. According to their CCS range, 70 patients (88.6%) were very satisfied with their results, 8 (10.1%) were satisfied, and only one patient (1.3%) who reported chronic groin pain was unsatisfied. There was no reported long-term hernia recurrence. CONCLUSION The PDS Endoloop™ technique for closure of direct inguinal hernia defects is well tolerated with low risk of hernia recurrence, chronic pain, and excellent QoL. This reliability persists to long-term follow-up.


title: Use of a recombinant cysteine proteinase from Leishmania (Leishmania) infantum chagasi for the Immunotherapy of canine visceral Leishmaniasis.

text: BACKGROUND A recombinant cysteine proteinase from Leishmania (Leishmania) infantum chagasi (rLdccys1) was previously shown to induce protective immune responses against murine and canine visceral leishmaniasis. These findings encouraged us to use rLdccys1 in the immunotherapy of naturally infected dogs from Teresina, Piauí, a region of high incidence of visceral leishmaniasis in Brazil. METHODOLOGY/PRINCIPAL FINDINGS Thirty naturally infected mongrel dogs displaying clinical signs of visceral leishmaniasis were randomly divided in three groups: one group received three doses of rLdccys1 in combination with the adjuvant Propionibacterium acnes at one month interval between each dose; a second group received three doses of P. acnes alone; a third group received saline. The main findings were: 1) dogs that received rLdccys1 with P. acnes did not display increase of the following clinical signs: weight loss, alopecia, onychogryphosis, cachexia, anorexia, apathy, skin lesions, hyperkeratosis, ocular secretion, and enlarged lymph nodes; they also exhibited a significant reduction in the spleen parasite load in comparison to the control dogs; 2) rLdccys1-treated dogs exhibited a significant delayed type cutaneous hypersensitivity elicited by the recombinant antigen, as well as high IgG2 serum titers and low IgG1 serum titers; sera from rLdccys1-treated dogs also contained high IFN-γ and low IL-10 concentrations; 3) control dogs exhibited all of the clinical signs of visceral leishmaniasis and had low serum IgG2 and IFN-γ levels and high concentrations of IgG1 and IL-10; 4) all of the dogs treated with rLdccys1 were alive 12 months after treatment, whereas dogs which received either saline or P. acnes alone died within 3 to 7 months. CONCLUSIONS/SIGNIFICANCE These findings illustrate the potential use of rLdccys1 as an additional tool for the immunotherapy of canine visceral leishmaniasis and support further studies designed to improve the efficacy of this recombinant antigen for the treatment of this neglected disease.


title: Time-Series Analysis of Laboratory Values in the Context of Long-Term Hospitalized Patient Mortality.

text: OBJECTIVES Long-term hospitalized patients have a higher risk of adverse outcomes and mortality rate. These patients often rapidly deteriorate, leading to death. We aim to evaluate end-of-life laboratory values time trends among deceased long-term inpatients. METHODS Time-stamped laboratory data for adult inpatients who had died in the hospital were extracted. The data were normalized and time-series analysis was performed. The patients were also clustered based on the laboratory result trends. RESULTS Laboratory results from 257 patients were evaluated. Significant time trends were observed: serum urea nitrogen, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and potassium increased while platelets and albumin decreased. Most patients showed significant shifts in at least four major laboratory indices within the last week of life. CONCLUSIONS In the last week of life in chronically hospitalized patients, an alteration of the physiologic state of the patient occurs that manifests as subtle changes in metabolite levels compared with the patient's baseline.


title: Single-incision laparoscopic pyloromyotomy: initial experience.

text: BACKGROUND Laparoscopic pyloromyotomy has become the standard treatment for hypertrophic pyloric stenosis. Single-incision laparoscopic surgery is an emerging operative approach that utilizes the umbilical scar to hide the surgical incision. OBJECTIVE To describe our initial experience with single-incision laparoscopic pyloromyotomy in 15 infants. MATERIALS AND METHODS Laparoscopic pyloromyotomy was performed through a single skin incision in the umbilicus, using a 4-mm 30 degrees endoscope and a 5-mm trocar. The 3-mm working instruments were inserted directly into the abdomen via separate lateral fascial stab incisions. All patients were prospectively evaluated. RESULTS The procedure was performed in 15 infants (13 male) with mean age of 45 +/- 16 days and mean weight of 4.04 +/- 0.5 kg. All procedures were completed laparoscopically, and one case was converted to a conventional triangulated laparoscopic work configuration after a mucosal perforation was noted. The perforation was repaired laparoscopically. On average, operating time was 29.8 +/- 13.6 min, and postoperative length of stay was 1.5 +/- 0.8 days. All patients were discharged home on full feeds. Follow-up was scheduled 2-3 weeks after discharge, and no postoperative complications were noted in any of the patients. CONCLUSIONS Single-incision laparoscopic pyloromyotomy is a safe and feasible procedure with good postoperative results and excellent cosmesis. The main challenge is the spatial orientation of the instruments and endoscope in a small working space. This can be overcome by a more longitudinally oriented working axis than used in the conventional angulated laparoscopic configuration.


title: Endovascular iliocaval reconstruction for the treatment of iliocaval thrombosis: From imaging to intervention.

text: Thrombosis of the inferior vena cava and iliac veins, known as iliocaval thrombosis, is a common cause of significant morbidity. Patients with chronic iliocaval obstruction often present with life-limiting occlusive symptoms secondary to recurrent lower extremity deep venous thrombosis, swelling, pain, venous stasis ulcers, or phlegmasia. Endovascular iliocaval reconstruction is a technically successful procedure that results in favorable clinical outcomes and stent patency rates with few complications and is often able to relieve debilitating symptoms in affected patients. This review presents an approach to endovascular iliocaval stent reconstruction in patients suffering from chronic iliocaval thrombosis, including background, patient selection, timing of intervention, procedural steps, technical considerations, patient follow-up, and a brief review of outcomes. Schematic illustrations and clinical cases outlining iliocaval stent reconstruction and crossing chronic venous occlusions have been provided.


title: Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications.

text: Post-translational modifications (PTMs) to the tails of the core histone proteins are critically involved in epigenetic regulation. Hypoxia affects histone modifications by altering the activities of histone-modifying enzymes and the levels of hypoxia-inducible factor (HIF) isoforms. Synthetic hypoxia mimetics promote a similar response, but how accurately the hypoxia mimetics replicate the effects of limited oxygen availability on the levels of histone PTMs is uncertain. Here we report studies on the profiling of the global changes to PTMs on intact histones in response to hypoxia/hypoxia-related stresses using liquid chromatography-mass spectrometry (LC-MS). We demonstrate that intact protein LC-MS profiling is a relatively simple and robust method for investigating potential effects of drugs on histone modifications. The results provide insights into the profiles of PTMs associated with hypoxia and inform on the extent to which hypoxia and hypoxia mimetics cause similar changes to histones. These findings imply chemically-induced hypoxia does not completely replicate the substantial effects of physiological hypoxia on histone PTMs, highlighting that caution should be used in interpreting data from their use.


Infectious Disease Mortality Trends in the United States, 1980-2014.