title: Urban scaling of health outcomes: a protocol for a scoping review.

text: INTRODUCTION With most of the world's population living in urban areas, it is important to understand the health effects of city living. Precise descriptions of the relations of city size and growth with population health metrics have not been systematically described. Describing these relationships can provide clues regarding the factors driving differences in health across cities. OBJECTIVE The goal of this scoping review is to map the existing evidence regarding the scaling properties of health outcomes, with a special emphasis on city size and growth. METHOD AND ANALYSIS We will conduct this scoping review based on a structured search of a combination of keywords for the exposures that aim to capture the population growth and size of cities along with degree of urbanisation, for health-related outcomes regardless of their type (incidence or prevalence of diseases and injuries and mortality). We will search the MEDLINE and Latin American & Caribbean Health Sciences Literature databases from inception for studies in English, Spanish or Portuguese and perform manual searches of references and citations in the included studies. The search will be conducted from April 2019 to September 2019. We will report results using the PRISMA-ScR guidelines. This review aims to inform future research on the role of increasing levels of urbanisation on health outcomes, provide clues into what city level factors may drive patterns of urban health and lead to the design and implementation of policies that promote sustainable growth and improved health. ETHICS AND DISSEMINATION This review will not collect any primary data and will rely on published articles. The findings of this review will be published in a peer-reviewed scientific journal.


2016 AHA/ACC Guideline on the Management of Patients with Lower Extremity Peripheral Artery Disease: Executive Summary.


title: Topical delivery of nonsteroidal anti-inflammatory drugs for osteoarthritis.

text: Osteoarthritis (OA) is one of the most commonly reported chronic pain syndromes experienced in the United States. Treatment guidelines for OA recommend acetaminophen for first-line pharmacotherapy for these patients; however, this strategy is rarely effective as monotherapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the next step in therapy and have accumulated a large body of data to support their efficacy for OA. Unfortunately, this class of agents is not without the potential for significant adverse effects. In an effort to capture the efficacy of NSAIDs while decreasing their side effect burden, many clinicians are turning to the topical administration of these agents. Localized pain and smaller, superficial joints may be especially amenable to the topical administration of NSAIDs. Numerous commercially available topical NSAID formulations have been shown to be efficacious in patients with OA. This review focuses on the topical delivery of NSAIDs for the treatment of OA.


title: Increase of paradoxical excitement response during propofol-induced sedation in hazardous and harmful alcohol drinkers.

text: BACKGROUND Paradoxical excitement response during sedation consists of loss of affective control and abnormal movements. Chronic alcohol abuse has been proposed as a predisposing factor despite lack of supporting evidence. Because alcohol and propofol have a common site of action, we postulated that paradoxical excitement responses during propofol-induced sedation occur more frequently in hazardous and harmful alcohol drinkers than in social or non-drinkers. METHODS One hundred and ninety patients undergoing orthopaedic knee joint surgery were enrolled in this prospective and observational study. Subjects were divided into Group HD (hazardous and harmful drinkers) or Group NHD (no hazardous drinkers) according to the alcohol use disorder identification test (AUDIT). In study 1, propofol infusion was adjusted to achieve the bispectral index at 70-80 using target-controlled infusion. In study 2, the target concentration of propofol was fixed at 0.8 (study 2/Low) or 1.4 μg ml(-1) (study 2/High). Paradoxical excitement responses were categorized by intensity into mild, moderate, or severe. RESULTS The overall incidence of paradoxical excitement response was higher in Group HD than in Group NHD in study 1 (71.4% vs 43.8%; P=0.022) and study 2/High (70.0% vs 34.5%; P=0.006) but not in study 2/Low. The incidence of moderate-to-severe response was significantly higher in Group HD of study 1 (28.6% vs 3.1%; P=0.0005) and study 2/High (23.3% vs 3.4%; P=0.029) with no difference in study 2/Low. Severe excitement response occurred only in Group HD of study 1 and study 2/High. CONCLUSIONS Paradoxical excitement occurred more frequently and severely in hazardous and harmful alcohol drinkers than in social drinkers during propofol-induced moderate-to-deep sedation, but not during light sedation.


title: Alteration of coupling between brain and heart induced by sedation with propofol and midazolam.

text: For a comprehensive understanding of the nervous system, several previous studies have examined the network connections between the brain and the heart in diverse conditions. In this study, we identified coupling between the brain and the heart along the continuum of sedation levels, but not in discrete sedation levels (e. g., wakefulness, conscious sedation, and deep sedation). To identify coupling between the brain and the heart during sedation, we induced several depths of sedation using patient-controlled sedation with propofol and midazolam. We performed electroencephalogram (EEG) spectral analysis and extracted the instantaneous heart rate (HR) from the electrocardiogram (ECG). EEG spectral power dynamics and mean HR were compared along the continuum of sedation levels. We found that EEG sigma power was the parameter most sensitive to changes in the sedation level and was correlated with the mean HR under the effect of sedative agents. Moreover, we calculated the Granger causality (GC) value to quantify brain-heart coupling at each sedation level. Additionally, the GC analysis revealed noticeably different strengths and directions of causality among different sedation levels. In all the sedation levels, GC values from the brain to the heart (GCb→h) were higher than GC values from the heart to the brain (GCh→b). Moreover, the mean GCb→h increased as the sedation became deeper, resulting in higher GCb→h values in deep sedation (1.97 ± 0.18 in propofol, 2.02 ± 0.15 in midazolam) than in pre-sedation (1.71 ± 0.13 in propofol, 1.75 ± 0.11 in midazolam; p < 0.001). These results show that coupling between brain and heart activities becomes stronger as sedation becomes deeper, and that this coupling is more attributable to the brain-heart direction than to the heart-brain direction. These findings provide a better understanding of the relationship between the brain and the heart under specific conditions, namely, different sedation states.


title: Extent and cost of inappropriate use of tumour markers in patients with pulmonary disease: a multicentre retrospective study in Shanghai, China.

text: OBJECTIVES The currently implemented healthcare reform in China requires substantial capital investment. Although overtreatment results in serious waste, inappropriate laboratory use is widespread, and overuse of tumour markers (TMs) has attracted increasing attention. DESIGN Retrospective study. SETTING The respiratory, thoracic surgery and oncology departments of three hospitals in Shanghai from 2014 to 2015. PARTICIPANTS Patients with chronic obstructive pulmonary disease (COPD) and primary bronchogenic lung cancer (PLC). Based on clinical guidelines and physician experience, the criteria of suitability of TM examinations were determined, and the number, cost and proportion of inappropriate TM requests were analysed. RESULTS The area under the receiver operating characteristic curve for carcinoembryonic antigen+cytokeratin fragment 21-1+squamous cell carcinoma antigen+neuron-specific enolase in patients with COPD and PLC was 0.813, in accordance with the cost-effectiveness principle, indicating good clinical and health economics values. In the 2706 patients, 12 496-16 956 (58.27%-79.06%) of TM requests were inappropriate. Furthermore, the involved expense was 650 200-1 014 156 yuan, accounting for 7.69%-12.00% of examination expenses and 1.35%-2.11% of hospitalisation costs. CONCLUSIONS We found that the inappropriate use of TMs was widespread for patients with pulmonary disease. Clinicians should use TMs strictly according to the guidelines to effectively manage laboratory resources and control costs.


Prediction Models - Development, Evaluation, and Clinical Application.


title: Functional analysis of two cavities in flavivirus NS5 polymerase.

text: Flavivirus NS5 protein encodes methyltransferase and RNA-dependent RNA polymerase (RdRp) activities. Structural analysis of flavivirus RdRp domains uncovered two conserved cavities (A and B). Both cavities are located in the thumb subdomains and represent potential targets for development of allosteric inhibitors. In this study, we used dengue virus as a model to analyze the function of the two RdRp cavities. Amino acids from both cavities were subjected to mutagenesis analysis in the context of genome-length RNA and recombinant NS5 protein; residues critical for viral replication were subjected to revertant analysis. For cavity A, we found that only one (Lys-756) of the seven selected amino acids is critical for viral replication. Alanine substitution of Lys-756 did not affect the RdRp activity, suggesting that this residue functions through a nonenzymatic mechanism. For cavity B, all four selected amino acids (Leu-328, Lys-330, Trp-859, and Ile-863) are critical for viral replication. Biochemical and revertant analyses showed that three of the four mutated residues (Leu-328, Trp-859, and Ile-863) function at the step of initiation of RNA synthesis, whereas the fourth residue (Lys-330) functions by interacting with the viral NS3 helicase domain. Collectively, our results have provided direct evidence for the hypothesis that cavity B, but not cavity A, from dengue virus NS5 polymerase could be a target for rational drug design.


title: Injury of the thoracic aorta during laparoscopic esophagectomy.

text: We report an unusual complication of laparoscopic esophagectomy for carcinoma. During posterior transhiatal dissection, massive bleeding occurred from the left side of the supradiaphragmatic thoracic aorta. A small tear was clearly visible and temporary bleeding control by packing and pressure with a grasper through one of the trocars was effective. A median laparotomy was performed and the aorta was sutured using a standard laparoscopic needle holder. The esophagectomy was successfully completed through a right thoracic approach. Injury to the intrathoracic aorta may occur during transhiatal dissection of the lower mediastinum. Use of a laparoscopic needle holder allowed to repair the supradiaphragmatic aorta through a laparotomy without the need of patient repositioning for a transthoracic approach.


title: Percutaneous thermal ablation combined with TACE versus TACE monotherapy in the treatment for liver cancer with hepatic vein tumor thrombus: A retrospective study.

text: PURPOSE To investigate the efficacy of percutaneous thermal ablation combined with transarterial chemoembolization (TACE) versus TACE monotherapy in treating primary liver cancer with hepatic vein tumor thrombus (HVTT), and to identify potential factors of overall survival after combination therapy. MATERIALS AND METHODS Patients with primary liver cancer and HVTT from 2011 to 2016 at our institute were retrospectively identified. They were divided into two groups (group A and group B). Patients in group A underwent TACE with subsequent percutaneous thermal ablation, while patients in group B who were unsuitable for ablation received TACE monotherapy. Characteristics and survival data of the two groups were analyzed and compared. Relevant factors for overall survival (OS) of group A were explored by univariate analysis. RESULTS Twenty-six patients were included and analyzed. The median OS for group A (n = 13) was 18 months, while the 1-, 2- and 3-year survival rates were 58.6%, 46.9% and 46.9%, respectively. The median OS for group B (n = 13) was 6.5 months and the 1-year survival rate was 10.9%. The survival of group A was significantly better than group B (P = 0.02). The following factors were related with overall survival of group A: ablation technique, complete response of tumor and HVTT, Child-pugh grade, pre-operative extrahepatic metastases and lymph node metastases. In group A, patients who achieved complete response had the longest average survival time (42.1 months). CONCLUSION For patients with primary liver cancer and HVTT, percutaneous thermal ablation and TACE present better efficacy than TACE monotherapy. Long-term survival could be achieved in selected patients.


title: Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study.

text: IMPORTANCE Left atrial fibrosis is prominent in patients with atrial fibrillation (AF). Extensive atrial tissue fibrosis identified by delayed enhancement magnetic resonance imaging (MRI) has been associated with poor outcomes of AF catheter ablation. OBJECTIVE To characterize the feasibility of atrial tissue fibrosis estimation by delayed enhancement MRI and its association with subsequent AF ablation outcome. DESIGN, SETTING, AND PARTICIPANTS Multicenter, prospective, observational cohort study of patients diagnosed with paroxysmal and persistent AF (undergoing their first catheter ablation) conducted between August 2010 and August 2011 at 15 centers in the United States, Europe, and Australia. Delayed enhancement MRI images were obtained up to 30 days before ablation. MAIN OUTCOMES AND MEASURES Fibrosis quantification was performed at a core laboratory blinded to the participating center, ablation approach, and procedure outcome. Fibrosis blinded to the treating physicians was categorized as stage 1 (<10% of the atrial wall), 2 (≥10%-<20%), 3 (≥20%-<30%), and 4 (≥30%). Patients were followed up for recurrent arrhythmia per current guidelines using electrocardiography or ambulatory monitor recording and results were analyzed at a core laboratory. Cumulative incidence of recurrence was estimated by stage at days 325 and 475 after a 90-day blanking period (standard time allowed for arrhythmias related to ablation-induced inflammation to subside) and the risk of recurrence was estimated (adjusting for 10 demographic and clinical covariates). RESULTS Atrial tissue fibrosis estimation by delayed enhancement MRI was successfully quantified in 272 of 329 enrolled patients (57 patients [17%] were excluded due to poor MRI quality). There were 260 patients who were followed up after the blanking period (mean [SD] age of 59.1 [10.7] years, 31.5% female, 64.6% with paroxysmal AF). For recurrent arrhythmia, the unadjusted overall hazard ratio per 1% increase in left atrial fibrosis was 1.06 (95% CI, 1.03-1.08; P < .001). Estimated unadjusted cumulative incidence of recurrent arrhythmia by day 325 for stage 1 fibrosis was 15.3% (95% CI, 7.6%-29.6%); stage 2, 32.6% (95% CI, 24.3%-42.9%); stage 3, 45.9% (95% CI, 35.5%-57.5%); and stage 4, 51.1% (95% CI, 32.8%-72.2%) and by day 475 was 15.3% (95% CI, 7.6%-29.6%), 35.8% (95% CI, 26.2%-47.6%), 45.9% (95% CI, 35.6%-57.5%), and 69.4% (95% CI, 48.6%-87.7%), respectively. Similar results were obtained after covariate adjustment. The addition of fibrosis to a recurrence prediction model that includes traditional clinical covariates resulted in an improved predictive accuracy with the C statistic increasing from 0.65 to 0.69 (risk difference of 0.05; 95% CI, 0.01-0.09). CONCLUSIONS AND RELEVANCE Among patients with AF undergoing catheter ablation, atrial tissue fibrosis estimated by delayed enhancement MRI was independently associated with likelihood of recurrent arrhythmia. The clinical implications of this association warrant further investigation.


title: Respiratory viruses in healthy infants and infants with cystic fibrosis: a prospective cohort study.

text: RATIONALE Acute viral respiratory tract infections in children with cystic fibrosis (CF) are known causes of disease exacerbation. The role of viral infections during infancy is, however, less known, although early infancy is thought to be a crucial period for CF disease development.We prospectively assessed symptomatic and asymptomatic viral detection in the first year of life in infants with CF and healthy controls. METHODS In a prospective cohort study, we included 31 infants with CF from the Swiss Cystic Fibrosis Infant Lung Development Cohort and 32 unselected, healthy infants from the Basel Bern Infant Lung Development Cohort and followed them throughout the first year of life. Respiratory symptoms were assessed by weekly telephone interviews. Biweekly nasal swabs were analysed for 10 different viruses and two atypical bacteria with real-time seven duplex PCR (CF=561, controls=712). MEASUREMENTS AND RESULTS Infants with CF and healthy controls showed similar numbers of swabs positive for virus (mean 42% vs 44%; OR 0.91, 95% CI 0.66 to 1.26, p=0.6). Virus-positive swabs were less often accompanied by respiratory symptoms in infants with CF (17% vs 23%; OR 0.64, 95% CI 0.43 to 0.95, p=0.026). This finding was pronounced for symptomatic human rhinovirus detection (7% vs 11%; OR 0.52, 95% CI 0.31 to 0.9, p=0.02). CONCLUSIONS Viral detection is not more frequent in infants with CF and respiratory symptoms during viral detection occur even less often than in healthy controls. It is likely an interplay of different factors such as local epithelial properties and immunological mechanisms that contribute to our findings.


title: The evolving practice of hybrid natural orifice transluminal endoscopic surgery (NOTES) for rectal cancer.

text: BACKGROUND Natural orifice transluminal endoscopic surgery (NOTES) has emerged as the area of focus in laparoscopic surgery. Hybrid NOTES (hNOTES) has some potential advantages for treating rectal cancer. METHODS Between May 2013 and November 2013, a total of 20 patients (11 males) who received hNOTES at two institutes participating in the study were documented and reviewed. Surgical outcomes, including complications and pathological outcomes, were analyzed. RESULTS The mean age of patients was 57.8 ± 10.1 years (range 34-78). Eleven patients received preoperative neoadjuvant chemoradiotherapy, with the mean distance between tumor and anal verge being 5.9 ± 1.7 cm (mean 2-8). The mean estimated intraoperative blood loss was 68 ± 106 ml (range 30-500), with one case converted to open procedure due to uncontrolled bleeding. Eight cases underwent simultaneous two-team approach. The mean operative time was 200.8 ± 47.7 min (range 110-285). Circular stapling was performed for 14 cases (70 %) as the anastomosis, and protective stoma performed for 17 cases (85 %). The overall postoperative complication rate was 25 %. Two cases (10 %) develop pelvic abscess due to leakage, which were controlled by medical treatments. The distal and circumferential margins were all free of tumor cells, and the mean distal margin length was 2.4 ± 0.98 cm (range 0.5-4). CONCLUSIONS Hybrid NOTES for rectal cancer is safe and feasible. Rapid experience-building accelerates its evolution, as reflected here by the high stapling rate and the idea of a two-team approach. It has the potential to become an option of treating rectal cancers.


The conundrum of off-label and unlicensed drug usage in neonatology.


title: Phase 2 study of pemetrexed plus carboplatin, or pemetrexed plus cisplatin with concurrent radiation therapy followed by pemetrexed consolidation in patients with favorable-prognosis inoperable stage IIIA/B non-small-cell lung cancer.

text: INTRODUCTION There is no consensus chemotherapy regimen with concurrent radiotherapy (RT) for inoperable stage IIIA/B non-small-cell lung cancer. This trial evaluated pemetrexed with carboplatin (PCb) or cisplatin (PC) with concurrent RT followed by consolidation pemetrexed. METHODS In this open-label, noncomparative phase II trial, patients with inoperable stage IIIA/B non-small-cell lung cancer (initially all histologies, later restricted to nonsquamous) were randomized (1:1) to PCb or PC with concurrent RT (64-68 Gy over days 1-45). Consolidation pemetrexed monotherapy was administered every 21 days for three cycles. Primary endpoint was 2-year overall survival (OS) rate. RESULTS From June 2007 to November 2009, 98 patients were enrolled (PCb: 46; PC: 52). The 2-year OS rate was PCb: 45.4% (95% confidence interval [CI], 29.5-60.0%); PC: 58.4% (95% CI, 42.6-71.3%), and in nonsquamous patients was PCb: 48.0% (95% CI, 29.0-64.8%); PC: 55.8% (95% CI, 38.0-70.3%). Median time to disease progression was PCb: 8.8 months (95% CI, 6.0-12.6 months); PC: 13.1 months (95% CI, 8.3-not evaluable [NE]). Median OS (months) was PCb: 18.7 (95% CI, 12.9-NE); PC: 27.0 (95% CI, 23.2-NE). The objective response rates (ORRs) were PCb: 52.2%; PC: 46.2%. Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. Most patients completed scheduled chemotherapy and RT during induction and consolidation phases. No drug-related deaths were reported during chemoradiotherapy. CONCLUSIONS Because of study design, efficacy comparisons cannot be made. However, both combinations with concurrent RT were active and well tolerated.


Call for infection control to stem MERS.


Pathologists and the coronavirus distraction effect.


title: Learning curve for robotic-assisted laparoscopic rectal cancer surgery.

text: INTRODUCTION One of the main uses of robotic assisted abdominal surgery is the mesorectal excision in patients with rectal cancer. The aim of the present study is to analyse the learning curve for robotic assisted laparoscopic resection of rectal cancer. PATIENTS AND METHODS We included in our study 43 consecutive rectal cancer resections (16 females and 27 males) performed from January 2008 through December 2010. Mean age of patients was 66 ± 9.0 years. Surgical procedures included both abdomino-perineal and anterior resections. We analysed the following parameters: demographic data of the patients included in the study, intra- and postoperative data, time taking to set up the robot for operations (set-up or docking time), operative time, intra- and postoperative complications, conversion rates and pathological specimen features. The learning curve was analysed using cumulative sum (CUSUM) methodology. RESULTS The procedures understudied included seven abdomino-perineal resections and 36 anterior resections. In our series of patients, mean robotic set-up time was 62.9 ± 24.6 min, and the mean operative time was 197.4 ± 44.3 min. Once we applied CUSUM methodology, we obtained two graphs for CUSUM values (operating time and success), both of them showing three well-differentiated phases: phase 1 (the initial 9-11 cases), phase 2 (the middle 12 cases) and phase 3 (the remaining 20-22 cases). Phase 1 represents initial learning; phase 2 plateau represents increased competence in the use of the robotic system, and finally, phase 3 represents the period of highest skill or mastery with a reduction in docking time (p = 0.000), but a slight increase in operative time (p = 0.007). CONCLUSION The CUSUM curve shows three phases in the learning and use of robotic assisted rectal cancer surgery which correspond to the phases of initial learning of the technique, consolidation and higher expertise or mastery. The data obtained suggest that the estimated learning curve for robotic assisted rectal cancer surgery is achieved after 21-23 cases.


XMRV and CFS--the sad end of a story.


title: Autoadjustable sutures and modified seldinger technique applied to laparoscopic jejunostomy.

text: This is a simple technique to be applied to those patients requiring an alternative feeding method. This technique has been successfully applied to 25 patients suffering from esophageal carcinoma. The procedure involves laparoscopic approach, suture of the selected intestinal loop to the abdominal wall and jejunostomy using Seldinger technique and autoadjustable sutures. No morbidity or mortality was reported.


title: The use of expanding ports in laparo-endoscopic single-site surgery may cause more pain: a meta-analysis of randomized clinical trials.

text: BACKGROUND Previous meta-analyses on the clinical outcome after laparo-endoscopic single-site surgery (LESS) versus conventional laparoscopic surgery (CLS) have not revealed any major differences in postoperative pain between the two procedures. This meta-analysis aims to evaluate the difference in postoperative pain between the two procedures, focusing on whether LESS was conducted with a non-expanding port (LESSnonex) or a port expanding (LESSex) within the incision. METHOD EMBASE, Medline, PubMed, Science Citation Index Expanded, and Cochrane Central Register of Controlled Trials were searched for randomized clinical trials (RCTs) on LESS versus CLS for general abdominal procedures. Weighted mean difference (WMD) and Odds ratios (OR) were calculated with 95% confidence intervals (CI). RESULTS A total of 29 RCTs with 2999 procedures were included. Pain (VAS 0-10) 6 h after surgery was significantly lower in the group where LESS was conducted with LESSnonex compared to CLS, WMD=-0.72 (- 1.10 to - 0.33). Pain 18-24 h was significantly higher in the group where LESS was conducted with LESSex compared to CLS, WMD = 0.38 (0.01-0.75). Wound-related complications were significantly more frequent in LESSex procedures compared to CLS, OR = 1.94 (1.03-3.63). CONCLUSION The present meta-analysis indirectly indicates that the type of access device that is used for an abdominal LESS procedure may contribute to the development of early postoperative pain as the use of a non-expanding model was associated with a more advantageous outcome. Direct randomized comparison of LESSnonex and LESSex is warranted to confirm if the use of expanding access devices generates more pain and wound complications.


Venous interventions.


title: Airway management considerations in patients with COVID-19.

text: Approximately 12% to 15% of hospitalized patients with COVID-19 infection require invasive ventilation via endotracheal intubation. The key to minimizing risk of disease transmission during this aerosol-generating procedure is careful preparation, which includes having necessary equipment and medications on hand as well as an experienced intubation team who can troubleshoot any unforeseen complications. Personal protective equipment should be donned and doffed in the presence of an assistant (ie, "buddy" system).


title: Cuticular pheromones stimulate hygienic behavior in the honey bee (Apis mellifera).

text: The health of western honey bee (Apis mellifera) colonies is challenged by the parasitic mite Varroa destructor and the numerous harmful pathogens it vectors. Selective breeding for the naturally occurring social immune trait "hygienic behavior" has emerged as one sustainable approach to reducing the mites' impact on honey bees. To expand our understanding of hygienic triggers and improve hygienic selection tools, we tested the hypothesis that the cuticular compounds (Z)-10-tritriacontene and (Z)-6-pentadecene, previously associated with unhealthy honey bee brood and/or brood targeted for hygiene, are triggers of honey bee hygienic behavior independent of brood health. In support of our hypothesis, application of synthetic (Z)-10-tritriacontene and (Z)-6-pentadecene onto brood and brood cell caps significantly increased hygienic behavior compared to application of similarly structured hydrocarbon controls (Z)-16-dotriacontene and (Z)-7-pentadecene. Furthermore, we demonstrate a significant positive correlation between colony-level hygienic responses to (Z)-10-tritriacontene and the traditional freeze-killed brood assay for selection of hygienic honey bee stocks. These results confirm biological activity of (Z)-6-pentadecene and reveal (Z)-10-tritriacontene as a novel hygiene trigger. They also support development of improved tools for honey bee colony monitoring and hygienic selection, and thus may accelerate development of honey bee stocks with greater resistance to Varroa and associated pathogens.


title: Cost-effectiveness of stent-retriever thrombectomy in combination with IV t-PA compared with IV t-PA alone for acute ischemic stroke in the UK.

text: OBJECTIVE To evaluate the cost-effectiveness of neurothrombectomy with a stent retriever (Solitaire * Revascularization Device) in treating acute ischemic stroke patients from the UK healthcare provider perspective. METHODS A Markov model was developed to simulate health outcomes and costs of two therapies over a lifetime time horizon: stent-retriever thrombectomy in combination with intravenous tissue-type plasminogen activator (IV t-PA), and IV t-PA alone. The model incorporated an acute phase (0-90 days) and a rest of life phase (90+ days). Health states were defined by the modified Rankin Scale score. During the rest of life phase, patients remained in the same health state until a recurrent stroke or death. Clinical effectiveness and safety data were taken from the SWIFT PRIME study. Resource use and health state utilities were informed by published data. RESULTS Combined stent-retriever thrombectomy and IV t-PA led to improved quality-of-life and increased life expectancy compared to IV t-PA alone. The higher treatment costs associated with the use of stent-retriever thrombectomy were offset by long-term cost savings due to improved patient health status, leading to overall cost savings of £33 190 per patient and a net benefit of £79 402. Deterministic and probabilistic sensitivity analyses demonstrated that the results were robust to a wide range of parameter inputs. LIMITATIONS The acute and long-term costs resource use data were taken from a study based on a patient population that was older and may have had additional comorbidities than the SWIFT PRIME population, resulting in costs that may not be representative of the cohort within this model. In addition, the estimates may not reflect stroke care today as no current evidence is available; however, the cost estimates were deemed reasonable by clinical opinion. CONCLUSIONS Combined stent-retriever neurothrombectomy and IV t-PA is a cost-effective treatment for acute ischemic stroke compared with IV t-PA alone.


title: Informal carers' experience and outcomes of assistive technology use in dementia care in the community: a systematic review protocol.

text: BACKGROUND Dementia is one of the greatest health and care priorities globally. Caring for persons with dementia is a challenge and often leads to negative psychological, physiological and financial consequences for informal carers (family members or friends). Many informal carers experience moderate to severe levels of burden. Advances in technology have the potential to assist persons with dementia and their carers, through assistive technology (AT) devices such as electronic medication dispensers, robotic devices and motion detectors. However, little is known about informal carers' experience and the impact of these technologies on them. This review aims to investigate the outcomes and experience of carers of persons with dementia, who live at home and use AT. METHOD MEDLINE, Embase, CINAHL, AMED, ALOIS, PsycINFO, Trial registries and OpenGrey databases will be searched for studies of any design that have investigated carer experience and/or outcomes of AT use for persons with dementia living at home. Manual searches from reference lists of relevant papers will also be undertaken. Outcomes of interest are carers' self-reported outcomes (which include perceived burden, quality of life and wellbeing) and carer experiences (such as usefulness, benefits and disadvantages of AT and impact on caregiver/care receiver relationship). Two independent reviewers will screen identified papers with pre-defined eligibility criteria and extract data using a bespoke extraction form. Discrepancies will be resolved in discussion with a third reviewer. A synthesis of eligible studies and summary will be provided. DISCUSSION A systematic review of quantitative, qualitative and mixed methods evidence of informal carers' experience of AT use in dementia in the community will be carried out. It is anticipated that this will highlight (1) investigations on impact of AT use on carers, (2) outcome measures and experience questionnaires that have been used and (3) the types of studies carried out so far on this topic. The results from the review will be presented in a summary matrix of common types (e.g. mobile phones, alarms) and uses (e.g. communication, safety, personal care) of AT in dementia care and also identify AT that is not usually available through government or health system funding. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017082268 .


title: Discovering potent small molecule inhibitors of cyclophilin A using de novo drug design approach.

text: This work describes an integrated approach of de novo drug design, chemical synthesis, and bioassay for quick identification of a series of novel small molecule cyclophilin A (CypA) inhibitors (1-3). The activities of the two most potent CypA inhibitors (3h and 3i) are 2.59 and 1.52 nM, respectively, which are about 16 and 27 times more potent than that of cyclosporin A. This study clearly demonstrates the power of our de novo drug design strategy and the related program LigBuilder 2.0 in drug discovery.


Exemestane with ovarian suppression in premenopausal breast cancer.


title: The short-term recovery of corticomotor responses in elbow flexors.

text: BACKGROUND The recovery of neurophysiological parameters at various time intervals following fatiguing exercise has been investigated previously. However, the repetition of neuromuscular assessments during the recovery period may have interfered with the true corticomotor excitability responses. In this experiment, fatiguing contractions were combined with a single post-fatigue assessment at varying time points. Ten participants undertook 5 bouts of 60-s maximal voluntary contractions (MVC) of the elbow flexors, separated by 20 min. Before and after each 60-s fatiguing exercise (FAT), participants performed a series of 6-s contractions at 100, 75 and 50% of their MVC during which transcranial magnetic, transmastoid electrical and brachial plexus electrical stimuli were used to elicit motor evoked potentials (MEP), cervicomedullary motor evoked potentials (CMEP) and compound muscle action potentials (Mmax) in the biceps brachii muscle, respectively. Post-FAT measurements were randomly performed 0, 15, 30, 60, or 120 s after each FAT. RESULTS MVC force declined to 65.1 ± 13.1% of baseline following FAT and then recovered to 82.7 ± 10.2% after 60 s. The MEP·Mmax-1 ratio recorded at MVC increased to 151.1 ± 45.8% and then returned to baseline within 60 s. The supraspinal excitability (MEP·CMEP-1) measured at MVC increased to 198.2 ± 47.2% and fully recovered after 30 s. The duration of post-MEP silent period recorded at MVC elongated by 23.4 ± 10.6% during FAT (all P < 0.05) but fully recovered after 15 s. CONCLUSIONS The current study represents the first accurate description of the time course and pattern of recovery for supraspinal and spinal excitability and inhibition following a short maximal fatiguing exercise in upper limb.


title: A Hyperbaric Warm Perfusion System Preserves Tissue Composites Ex vivo and Delays the Onset of Acute Rejection.

text: BACKGROUND Ischemia-reperfusion injury (IRI) precipitates acute rejection of vascularized composite allografts (VCA). Hyperbaric preservation of tissues ex vivo, between harvest and revascularization, may reduce IRI and mitigate acute rejection of VCA. METHODS A porcine heterotopic musculocutaneous gracilis flap model was used. In phase 1, control autografts (n = 5) were infused with University of Wisconsin Solution (UWS) and stored at 4°C for 3 hours. Intervention autografts (n = 5) were placed in a hyperbaric oxygen organ preservation system for 5 hours and infused with hyperoxygenated UWS at 20°C and 3 atm. Grafts were replanted into the animals' necks. In phase 2, similarly treated control (n = 8) and intervention grafts (n = 8) were allotransplanted into the necks of animals separated by a typed and standardized genetic mismatch. No systemic immunosuppression was given. Systemic markers of IRI, and clinical and histopathological assessments of necrosis and rejection were performed. RESULTS Autotransplanted tissue composites preserved in the hyperbaric chamber showed histopathological evidence of less muscle necrosis at 3 hours (p = 0.05). Despite a longer period of ischemia, no evidence was found of a difference in systemic markers of IRI following revascularization in these groups. Allotransplanted tissues supported ex vivo within the hyperbaric perfusion device experienced acute rejection significantly later than corresponding controls. CONCLUSION Hyperbaric warm perfusion preserves musculocutaneous tissue composites ex vivo for longer than standard cold preservation in this model. This translates into a delay in acute rejection of allotransplanted tissue composites.


title: Expectoration of the staple line: a delayed complication after previous lobectomy.

text: In the literature, bronchopleural fistula after thoracic surgery is usually reported in the perioperative setting; however, the incidence of delayed fistula still remains unknown. We herein report a case of a 54-year old man who was referred to the Emergency Department for dyspnoea and productive cough with expectoration of a whitish 'suture-like' tissue. Two months before, the patient underwent an uneventful right lower lobectomy for squamous-cell lung cancer. A computed tomography scan revealed a para-mediastinal localized pneumothorax (measuring 6 cm in the major axis) starting from a right lower bronchus interruption associated with a middle lobe consolidation. The patient was consequently admitted for respiratory monitoring and underwent a fibre-optic bronchoscopy to assess bronchial integrity: the right lower bronchus was completely dehiscent and connected to an empty pleural closed pouch, with no inflammatory signs or sputum-like effusion. After the procedure, the clinical course was unremarkable with gradual improvement of clinical conditions: in particular, the cough disappeared and no sign of fever, leucocytosis or respiratory failure was observed. Thus, after a multidisciplinary meeting, the patient was discharged 7 days after admission and re-evaluated monthly. Six months after diagnosis, the patient was symptom-free with complete closure of the fistula on radiological imaging.


title: Efficient trans-encapsidation of hepatitis C virus RNAs into infectious virus-like particles.

text: Recently, complete replication of hepatitis C virus (HCV) in tissue culture was established using the JFH1 isolate. To analyze determinants of HCV genome packaging and virion assembly, we developed a system that supports particle production based on trans-packaging of subgenomic viral RNAs. Using JFH1 helper viruses, we show that subgenomic JFH1 replicons lacking the entire core to NS2 coding region are efficiently encapsidated into infectious virus-like particles. Similarly, chimeric helper viruses with heterologous structural proteins trans-package subgenomic JFH1 replicons. Like authentic cell culture-produced HCV (HCVcc) particles, these trans-complemented HCV particles (HCV(TCP)) penetrate target cells in a CD81 receptor-dependent fashion. Since HCV(TCP) production was limited by competition between the helper and subgenomic RNA and to avoid contamination of HCV(TCP) stocks with helper viruses, we created HCV packaging cells. These cells encapsidate various HCV replicons with high efficiency, reaching infectivity titers up to 10(6) tissue culture infectious doses 50 per milliliter. The produced particles display a buoyant density comparable to HCVcc particles and can be propagated in the packaging cell line but support only a single-round infection in naïve cells. Together, this work demonstrates that subgenomic HCV replicons are assembly competent, thus excluding cis-acting RNA elements in the core-to-NS2 genomic region essential for RNA packaging. The experimental system described here should be helpful to decipher the mechanisms of HCV assembly and to identify RNA elements and viral proteins involved in particle formation. Similar to other vector systems of plus-strand RNA viruses, HCV(TCP) may prove valuable for gene delivery or vaccination approaches.


Recanalization of a Challenging Chronic Total Occlusion of the Superficial Femoral Artery through the Profunda Femoris Using a Pure Retrograde Technique.


title: Severe acute respiratory syndrome coronavirus triggers apoptosis via protein kinase R but is resistant to its antiviral activity.

text: In this study, infection of 293/ACE2 cells with severe acute respiratory syndrome coronavirus (SARS-CoV) activated several apoptosis-associated events, namely, cleavage of caspase-3, caspase-8, and poly(ADP-ribose) polymerase 1 (PARP), and chromatin condensation and the phosphorylation and hence inactivation of the eukaryotic translation initiation factor 2alpha (eIF2alpha). In addition, two of the three cellular eIF2alpha kinases known to be virus induced, protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), were activated by SARS-CoV. The third kinase, general control nonderepressible-2 kinase (GCN2), was not activated, but late in infection the level of GCN2 protein was significantly reduced. Reverse transcription-PCR analyses revealed that the reduction of GCN2 protein was not due to decreased transcription or stability of GCN2 mRNA. The specific reduction of PKR protein expression by antisense peptide-conjugated phosphorodiamidate morpholino oligomers strongly reduced cleavage of PARP in infected cells. Surprisingly, the knockdown of PKR neither enhanced SARS-CoV replication nor abrogated SARS-CoV-induced eIF2alpha phosphorylation. Pretreatment of cells with beta interferon prior to SARS-CoV infection led to a significant decrease in PERK activation, eIF2alpha phosphorylation, and SARS-CoV replication. The various effects of beta interferon treatment were found to function independently on the expression of PKR. Our results show that SARS-CoV infection activates PKR and PERK, leading to sustained eIF2alpha phosphorylation. However, virus replication was not impaired by these events, suggesting that SARS-CoV possesses a mechanism to overcome the inhibitory effects of phosphorylated eIF2alpha on viral mRNA translation. Furthermore, our data suggest that viral activation of PKR can lead to apoptosis via a pathway that is independent of eIF2alpha phosphorylation.


title: [Bioinformatics analysis on molecular mechanism of ribavirin and interferon-α in treating MERS-CoV].

text: OBJECTIVE To study the molecular mechanism of ribavirin and interferon-α in the treatment of Middle East Respiratory Syndrome (MERS) by bio-informatic methods. METHODS MERS-CoV-related microarray data was searched from Array Express database and analyzed by Agilent GeneSpring GX software. Target genes of ribavirin and interferon-α were acquired from Comparative Toxicogenomics Database (CTD). PANTHER TOOL and DAVID platform were used for the analysis of GO and Pathway. RESULTS One set of MERS-CoV related microarray data and 27 target genes of ribavirin and interferon-α were acquired from the online databases. Data on Genes from microarray were divided into two time-related gene clusters by using the Unsupervised Hierarchical Clustering. Data from the GO analysis indicated that the target genes of ribavirin and interferon-α as well as the genes from the microarray were mainly enriched in 10 biological processes, including cellular process, metabolic process, immune system process and biological regulation, et al. Data on drug target genes, first and second cluster of microarray would involve 9, 3 and 23 signaling pathways respectively, and only the former two showed 7 common pathways, which were related to pathogen recognition, cytokine release and autoimmune response. CONCLUSION Ribavirin in combination with interferon-α might have therapeutic effects on MERS patients through several signaling pathways. Genes in the second cluster might serve as target genes to be used for screening of new drugs in treating the MERS-CoV infection.


title: Airborne Transmission of Highly Pathogenic Influenza Virus during Processing of Infected Poultry.

text: Exposure to infected poultry is a suspected cause of avian influenza (H5N1) virus infections in humans. We detected infectious droplets and aerosols during laboratory-simulated processing of asymptomatic chickens infected with human- (clades 1 and 2.2.1) and avian- (clades 1.1, 2.2, and 2.1) origin H5N1 viruses. We detected fewer airborne infectious particles in simulated processing of infected ducks. Influenza virus-naive chickens and ferrets exposed to the air space in which virus-infected chickens were processed became infected and died, suggesting that the slaughter of infected chickens is an efficient source of airborne virus that can infect birds and mammals. We did not detect consistent infections in ducks and ferrets exposed to the air space in which virus-infected ducks were processed. Our results support the hypothesis that airborne transmission of HPAI viruses can occur among poultry and from poultry to humans during home or live-poultry market slaughter of infected poultry.


title: Burst-suppression ratio underestimates absolute duration of electroencephalogram suppression compared with visual analysis of intraoperative electroencephalogram.

text: Background Machine-generated indices based on quantitative electroencephalography (EEG), such as the patient state index (PSI™) and burst-suppression ratio (BSR), are increasingly being used to monitor intraoperative depth of anaesthesia in the endeavour to improve postoperative neurological outcomes, such as postoperative delirium (POD). However, the accuracy of the BSR compared with direct visualization of the EEG trace with regard to the prediction of POD has not been evaluated previously. Methods Forty-one consecutive patients undergoing non-cardiac, non-intracranial surgery with general anaesthesia wore a SedLine ® monitor during surgery and were assessed after surgery for the presence of delirium with the Confusion Assessment Method. The intraoperative EEG was scanned for absolute minutes of EEG suppression and correlated with the incidence of POD. The BSR and PSI™ were compared between patients with and without POD. Results Visual analysis of the EEG by neurologists and the SedLine ® -generated BSR provided a significantly different distribution of estimated minutes of EEG suppression ( P =0.037). The Sedline ® system markedly underestimated the amount of EEG suppression. The number of minutes of suppression assessed by visual analysis of the EEG was significantly associated with POD ( P =0.039), whereas the minutes based on the BSR generated by SedLine ® were not associated with POD ( P =0.275). Conclusions Our findings suggest that SedLine ® (machine)-generated indices might underestimate the minutes of EEG suppression, thereby reducing the sensitivity for detecting patients at risk for POD. Thus, the monitoring of machine-generated BSR and PSI™ might benefit from the addition of a visual tracing of the EEG to achieve a more accurate and real-time guidance of anaesthesia depth monitoring and the ultimate goal, to reduce the risk of POD.


COVID-19 - Considerations and Implications for Surgical Learners.


title: Peripapillary hyperreflective ovoid mass-like structures (PHOMS): OCTA may reveal new findings.

text: PURPOSE Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are novel and not well characterized findings occurring in several disorders of the optic nerve. The aim of this study is to present two cases of tilted disc syndrome (TDS) and one case with optic disc drusen undergoing a multimodal imaging approach. METHODS In this case series, a qualitative evaluation of the OCTA findings in regions with PHOMS was performed. RESULTS Structural OCT revealed the presence of PHOMS. OCTA identified the presence of a vascular complex within this hyperreflective structure. CONCLUSIONS Assuming that PHOMS are thought to correspond to herniating nerve fibers or be secondary to axoplasmic stasis, this vascular complex may represent a displacement of the deeper vessels deputed at the irroration of the optic nerve into the retina or, alternatively, might be secondary to an increase in vascular endothelial growth factor (VEGF) levels and a subsequent development of neovessels.


Should aspirin be used for prophylaxis of COVID-19-induced coagulopathy?


title: Safety and efficacy of 1020 consecutive laparoscopic sleeve gastrectomies performed as a primary treatment modality for morbid obesity. A single-center experience from the metabolic and bariatric surgical accreditation quality and improvement program.

text: BACKGROUND LSG is widely accepted as a definitive treatment for obesity. Due to lack of large series with long-term follow-up, disagreement remains regarding its safety and efficacy. We present a series of 1020 consecutive LSGs performed with long-term follow-up. METHODS A retrospective review of a prospectively collected database was conducted on patients who underwent LSG from January 2005 to February 2014. Data included weight, height, BMI, ideal body weight, comorbid conditions, intraoperative complications, mean length of hospital stay (LOS), early (<30 days) readmission, early and late (>30 days) postoperative complications, and percentage of excess weight loss (%EWL). RESULTS Of the 1020 patients, 66.6 % (n = 679) were female, with a mean age of 38.4 ± 16.5 years. Mean BMI at the time of first visit was 43.4 ± 5.8 kg/m(2). The most common comorbid conditions identified were diabetes mellitus (89.4 %), sleep apnea (86.4 %), hypertension (80.3 %), and hyperlipidemia (70 %). Over the entire follow-up period, 57 % of diabetic patients experienced significant improvement or remission. There was no mortality in this series. Early postoperative complications within 30 days of surgery included leak in 0.1 % (n = 1), stricture in 0.1 % (n = 1), emesis in 23 % (n = 234), dehydration in 19 % (n = 194), prolonged ileus in 18 % (183), and self-limited bleeding in 3 % (n = 30). Mean LOS was of 3.4 ± 2.1 days, with a 3.8 % overall rate of early readmissions. Long-term morbidity was found in 3.9 % of patients (n = 40) and included stricture in 0.49 % (n = 5) and GERD in 6 % (n = 61). The overall 30-day mortality rate was 0 %. Mean %EWL at 3 months to 1, 3, 5, and 8 years was 72 ± 16.8, 86 ± 22.3, 63 ± 19, 61 ± 11, and 52 ± 9.2, respectively. CONCLUSIONS This study confirms that LSG is safe and has very low rates of early and long-term complications when compared to other well-established procedures. Additionally, LSG that appears results in significant improvement of obesity-related comorbid conditions.


title: Temporary Emergency Guidance to US Stroke Centers During the COVID-19 Pandemic.

text: During this unprecedented time of extraordinary stress on the US healthcare system, the AHA/ASA Stroke Council-as individuals in our localities and together as an entity at the national level-acknowledge the mounting concern regarding optimal stroke care during the COVID-19 pandemic among vascular neurologists and those clinicians who care for patients with stroke. We therefore seek to provide guidance for the care of stroke patients in the midst of the crisis. Ordinarily, national recommendations go through a rigorous process of development, refinement, peer review, and thoughtful promulgation. None of that is possible at this time, yet we believe there is a substantial need for a broad policy statement that reflects both the commonality of the pandemic across the US and the individual variability necessary at local sites. We issue this temporary statement as an interim stopgap opinion, pending a more thorough and considered process.


title: The Facial Action Coding System for Characterization of Human Affective Response to Consumer Product-Based Stimuli: A Systematic Review.

text: To characterize human emotions, researchers have increasingly utilized Automatic Facial Expression Analysis (AFEA), which automates the Facial Action Coding System (FACS) and translates the facial muscular positioning into the basic universal emotions. There is broad interest in the application of FACS for assessing consumer expressions as an indication of emotions to consumer product-stimuli. However, the translation of FACS to characterization of emotions is elusive in the literature. The aim of this systematic review is to give an overview of how FACS has been used to investigate human emotional behavior to consumer product-based stimuli. The search was limited to studies published in English after 1978, conducted on humans, using FACS or its action units to investigate affect, where emotional response is elicited by consumer product-based stimuli evoking at least one of the five senses. The search resulted in an initial total of 1,935 records, of which 55 studies were extracted and categorized based on the outcomes of interest including (i) method of FACS implementation; (ii) purpose of study; (iii) consumer product-based stimuli used; and (iv) measures of affect validation. Most studies implemented FACS manually (73%) to develop products and/or software (20%) and used consumer product-based stimuli that had known and/or defined capacity to evoke a particular affective response, such as films and/or movie clips (20%); minimal attention was paid to consumer products with low levels of emotional competence or with unknown affective impact. The vast majority of studies (53%) did not validate FACS-determined affect and, of the validation measures that were used, most tended to be discontinuous in nature and only captured affect as it holistically related to an experience. This review illuminated some inconsistencies in how FACS is carried out as well as how emotional response is inferred from facial muscle activation. This may prompt researchers to consider measuring the total consumer experience by employing a variety of methodologies in addition to FACS and its emotion-based interpretation guide. Such strategies may better conceptualize consumers' experience with products of low, unknown, and/or undefined capacity to evoke an affective response such as product prototypes, line extensions, etc.


Can cross-handed approach improve maneuver in transumbilical laparoscopic surgery?


title: An alignment-free method to find similarity among protein sequences via the general form of Chou's pseudo amino acid composition.

text: In this paper, we propose a method to create the 60-dimensional feature vector for protein sequences via the general form of pseudo amino acid composition. The construction of the feature vector is based on the contents of amino acids, total distance of each amino acid from the first amino acid in the protein sequence and the distribution of 20 amino acids. The obtained cosine distance metric (also called the similarity matrix) is used to construct the phylogenetic tree by the neighbour joining method. In order to show the applicability of our approach, we tested it on three proteins: 1) ND5 protein sequences from nine species, 2) ND6 protein sequences from eight species, and 3) 50 coronavirus spike proteins. The results are in agreement with known history and the output from the multiple sequence alignment program ClustalW, which is widely used. We have also compared our phylogenetic results with six other recently proposed alignment-free methods. These comparisons show that our proposed method gives a more consistent biological relationship than the others. In addition, the time complexity is linear and space required is less as compared with other alignment-free methods that use graphical representation. It should be noted that the multiple sequence alignment method has exponential time complexity.


title: Monitoring of brain and systemic oxygenation in neurocritical care patients.

text: Maintenance of adequate oxygenation is a mainstay of intensive care, however, recommendations on the safety, accuracy, and the potential clinical utility of invasive and non-invasive tools to monitor brain and systemic oxygenation in neurocritical care are lacking. A literature search was conducted for English language articles describing bedside brain and systemic oxygen monitoring in neurocritical care patients from 1980 to August 2013. Imaging techniques e.g., PET are not considered. A total of 281 studies were included, the majority described patients with traumatic brain injury (TBI). All tools for oxygen monitoring are safe. Parenchymal brain oxygen (PbtO2) monitoring is accurate to detect brain hypoxia, and it is recommended to titrate individual targets of cerebral perfusion pressure (CPP), ventilator parameters (PaCO2, PaO2), and transfusion, and to manage intracranial hypertension, in combination with ICP monitoring. SjvO2 is less accurate than PbtO2. Given limited data, NIRS is not recommended at present for adult patients who require neurocritical care. Systemic monitoring of oxygen (PaO2, SaO2, SpO2) and CO2 (PaCO2, end-tidal CO2) is recommended in patients who require neurocritical care.


title: Randomized controlled trial of barbed polyglyconate versus polyglactin suture for robot-assisted laparoscopic prostatectomy anastomosis: technique and outcomes.

text: BACKGROUND Transperitoneal robot-assisted laparoscopic prostatectomy (RALP) urethrovesical anastomosis is a critical step. Although the prevalence of urine leaks ranges from 4.5% to 7.5% at high-volume RALP centers, urine leaks prolong catheterization and may lead to ileus, peritonitis, and require intervention. Barbed polyglyconate sutures maintain running suture line tension and may be advantageous in RALP anastomosis for reducing this complication. OBJECTIVE To compare barbed polyglyconate and polyglactin 910 (Vicryl, Ethicon, Somerville, NJ, USA) running sutures for RALP anastomosis. DESIGN, SETTING, AND PARTICIPANTS This was a prospective, randomized, controlled, single-surgeon study comparing RALP anastomosis using either barbed polyglyconate (n = 45) or polyglactin 910 (n = 36) sutures. SURGICAL PROCEDURE RALP anastomosis using either barbed polyglyconate or polyglactin 910 sutures was studied. MEASUREMENTS Operative time, cost differential, perioperative complications, and cystogram contrast extravasation by anastomosis suture type were measured. RESULTS AND LIMITATIONS Although baseline characteristics and overall operative times were similar, barbed polyglyconate sutures were associated with shorter mean anastomosis times of 9.7 min versus 9.8 min (p = 0.014). In addition, anastomosis with barbed polyglyconate rather than polyglactin 910 sutures was associated with more frequent cystogram extravasation 8 d postoperatively (20.0% vs 2.8%; p = 0.019), longer mean catheterization times (11.1 d vs 8.3 d; p = 0.048), and greater suture costs per case ($51.52 vs $8.44; p < 0.001). After 8 of 29 (27.6%) barbed polyglyconate anastomosis sites demonstrated postoperative day 8 cystogram extravasation, we modified our technique to avoid overtightening, reducing cystogram extravasation to 1 (6.3%) of 16 subsequent barbed polyglyconate anastomosis sites. Potential limitations include small sample size and the single-surgeon study design. CONCLUSIONS Compared to traditional sutures, barbed polyglyconate is more costly and requires technical modification to avoid overtightening, delayed healing, and longer catheterization time following RALP.


title: Recovery of renal function after long-term dialysis and resolution of cardiomyopathy in a patient with aHUS receiving eculizumab.

text: We present the case of a 18-month-old girl with renal and cardiac manifestations of atypical haemolytic uraemic syndrome (aHUS), and a novel complement factor H mutation. Transient haematological remission was achieved with intensive plasmapheresis, but cardiac function deteriorated and renal function was not restored. Initiation of eculizumab after 6 months of dialysis significantly improved organ function. At 43 months after presentation, haematological values had normalised and cardiac function had improved. Dialysis was discontinued after 10 months (the longest reported time in a patient with aHUS) and the estimated glomerular filtration rate had recovered to 70 mL/min/1.73 m(2). In conclusion, treatment of aHUS with eculizumab, even after long-term dialysis, can significantly improve renal function. Discontinuation of dialysis and resolution of cardiac function has implications on the potential recovery and treatment choice of such patients. Earlier initiation of eculizumab, however, might have prevented the irreversible renal sclerosis and cardiac dysfunction.


title: Impact of nonpharmacological interventions on COVID-19 transmission dynamics in India.

text: Background As of May 4, 2020, India has reported 42,836 confirmed cases and 1,389 deaths from COVID-19. India's multipronged response included nonpharmacological interventions (NPIs) like intensive case-based surveillance, expanding testing capacity, social distancing, health promotion, and progressive travel restrictions leading to a complete halt of international and domestic movements (lockdown). Objectives We studied the impact of NPI on transmission dynamics of COVID-19 epidemic in India and estimated the minimum level of herd immunity required to halt it. Methods We plotted time distribution, estimated basic (R0) and time-dependent effective (Rt) reproduction numbers using software R, and calculated doubling time, the growth rate for confirmed cases from January 30 to May 4, 2020. Herd immunity was estimated using the latest Rtvalue. Results Time distribution showed a propagated epidemic with subexponential growth. Average growth rate, 21% in the beginning, reduced to 6% after an extended lockdown (May 3). Based on early transmission dynamics, R0was 2.38 (95% confidence interval [CI] =1.79-3.07). Early, unmitigated Rt= 2.51 (95% CI = 2.05-3.14) (March 15) reduced to 1.28 (95% CI = 1.22-1.32) and was 1.83 (95% CI = 1.71-1.93) at the end of lockdown Phase 1 (April 14) and 2 (May 3), respectively. Similarly, average early doubling time (4.3 days) (standard deviation [SD] = 1.86) increased to 5.4 days (SD = 1.03) and 10.9 days (SD = 2.19). Estimated minimum 621 million recoveries are required to halt COVID-19 spread if Rtremains below 2. Conclusion India's early response, especially stringent lockdown, has slowed COVID-19 epidemic. Increased testing, intensive case-based surveillance and containment efforts, modulated movement restrictions while protecting the vulnerable population, and continuous monitoring of transmission dynamics should be a way forward in the absence of effective treatment, vaccine, and undetermined postinfection immunity.


title: Vedolizumab for Inflammatory Bowel Disease: two year results of the ICC Registry, a nationwide prospective observational cohort study.

text: Prospective data of vedolizumab treatment for inflammatory bowel disease (IBD) patients beyond one year of treatment is scarce but needed for clinical decision making. We prospectively enrolled 310 IBD (191 Crohn's disease CD, 119 ulcerative colitis, UC) patients with a follow-up period of 104 weeks (IQR: 103-104) in a nationwide registry. The corticosteroid-free clinical remission rate (Harvey Bradshaw Index ≤4, short clinical colitis activity index ≤2) at week 52 and 104 was 28% and 19% for CD and 27% and 28% for UC, respectively. 59% maintained corticosteroid-free clinical remission between week 52 and 104. Vedolizumab with concomitant immunosuppression showed comparable effectiveness outcomes compared to vedolizumab monotherapy (week 104: 21% vs. 23%, p=0.77), while 8 out of 13 severe infections occurred in patients treated with concomitant immunosuppression. To conclude, the clinical effect was 19% for CD and 28% for UC after 2 years of follow-up regardless of concomitant immunosuppression.


title: Modes of mechanical ventilation vary between hospitals and intensive care units within a university healthcare system: a retrospective observational study.

text: OBJECTIVE As evidence-based guidance to aid clinicians with mechanical ventilation mode selection is scant, we sought to characterize the epidemiology thereof within a university healthcare system and hypothesized that nonconforming approaches could be readily identified. We conducted an exploratory retrospective observational database study of routinely recorded mechanical ventilation parameters between January 1, 2010 and December 31, 2016 from 12 intensive care units. Mode epoch count proportions were examined using Chi squared and Fisher exact tests as appropriate on an inter-unit basis with outlier detection for two test cases via post hoc pairwise analyses of a binomial regression model. RESULTS Final analysis included 559,734 mode epoch values. Significant heterogeneity was demonstrated between individual units (P < 0.05 for all comparisons). One unit demonstrated heightened utilization of high-frequency oscillatory ventilation, and three units demonstrated frequent synchronized intermittent mandatory ventilation utilization. Assist control ventilation was the most commonly recorded mode (51%), followed by adaptive support ventilation (23.1%). Volume-controlled modes were about twice as common as pressure-controlled modes (64.4% versus 35.6%). Our methodology provides a means by which to characterize the epidemiology of mechanical ventilation approaches and identify nonconforming practices. The observed variability warrants further clinical study about contributors and the impact on relevant outcomes.


title: [The influence of the menstrual cycle on acute and persistent pain after laparoscopic cholecystectomy].

text: BACKGROUND AND OBJECTIVES Fluctuations of female sex hormones during menstrual cycle influence pain perception. Endogenous pain inhibition is impaired in follicular phase of menstrual cycle. We tested the primary hypothesis that the women having surgery during their follicular phase have more acute pain and require higher opioids than those in the luteal phase, and secondarily we tested that women who have surgery during their follicular phase have more incisional pain at 3 month postoperatively. METHODS 127 adult females having laparoscopic cholecystectomy were randomized to have surgery during the luteal or follicular phase of their menstrual cycle. Standardized anesthesia and pain management regimen was given to all patients. Pain and analgesic consumption were evaluated in post-anesthesia care unit and every 4h in the first 24h. Adverse effects were questioned every 4h. Time to oral intake and ambulation were recorded. Post-surgical pain, hospital anxiety, depression scale, SF-12 questionnaire were evaluated at 1 and 3 month visits. RESULTS There was no difference in acute pain scores and analgesic consumption through the 24h period, Visual Analog Scale at 24h was 1.5±1.5cm for follicular group 1.4±1.7cm for luteal group (p=0.57). Persistent postoperative pain was significantly more common one and at three month, with an incidence was 33% and 32% in the patients at follicular phase versus 16% and 12% at luteal phase, respectively. The Visual Analog Scale at one and at three month was 1.6±0.7cm and 1.8±0.8cm for follicular group and 2.7±1.3cm and 2.9±1.7cm in the luteal group (p=0.02), respectively. There were no significant differences between the groups with respect to anxiety and depression, SF-12 scores at either time. Nausea was more common in follicular-phase group (p=0.01) and oral feeding time was shorter in follicular phase (5.9±0.9h) than in luteal phase (6.8±1.9h, p=0.02). CONCLUSIONS Although persistent postoperative pain was significantly more common one and three months after surgery the magnitude of the pain was low. Our results do not support scheduling operations to target particular phases of the menstrual cycle.


title: Enhancing immunity through autophagy.

text: Next to the proteasome, autophagy is the main catabolic pathway for the degradation of cytoplasmic constituents. The immune system uses it both as an effector mechanism to clear intracellular pathogens and as a mechanism to monitor its products for evidence of pathogen invasion and cellular transformation. Because autophagy delivers intracellular material for lysosomal degradation, its products are primarily loaded onto MHC class II molecules and are able to stimulate CD4+ T cells. This process might shape the self-tolerance of the CD4+ T cell repertoire and stimulate CD4+ T cell responses against pathogens and tumors. Beyond antigen processing, autophagy's role in cell survival is to assist the clonal expansion of B and T cells for efficient adaptive immune responses. These immune-enhancing functions make autophagy an attractive target for therapeutic manipulation in human disease.


title: Acellular fetal bovine dermal matrix for treatment of chronic ulcerations of the midfoot associated with Charcot neuroarthropathy.

text: BACKGROUND Gross deformity of the foot in Charcot neuroarthropathy can lead to collapse and subsequent ulceration, infection, amputation, or premature death. This study evaluated healing of midfoot ulcerations of Charcot neuroarthropathy using PriMatrix, a novel acellular fetal bovine dermal matrix. METHODS In this retrospective analysis, 20 patients with ulcerations of the midfoot associated with Charcot neuroarthropathy were treated with either PriMatrix in addition to standard wound care (PriMatrix group,n = 12) or standard wound care alone (control group, n = 8). All patients had chronic, nonhealing foot ulcerations of at least 2250 mm(3) for a minimum of 30 days duration. All foot ulcerations were full thickness with subcutaneous involvement. Ankle brachial index ≥0.90 and/or transcutaneous oximetry (TcPo(2)) ≥40 mm Hg at the periulcer site was necessary for inclusion. Patients were excluded if they had acute or chronic osteomyelitis of the foot. RESULTS Demography, risk factors, baseline severity of Charcot neuroarthropathy, and wound volume (control 4078 mm(3), PriMatrix 3737.5 mm(3), P = nonsignificant) were similar between treatment groups. Mean time to healing in the PriMatrix group (116 days, 95% CI = 109-123) was significantly shorter than in the control group (180 days, 95% confidence interval [CI] = 171-188); P < .0001. A significantly faster rate of healing was observed with PriMatrix (87.9 mm(3)/wk, 95% CI = 115.2% to 60.6%) compared with control (59.0 mm(3)/wk, 95% CI = 72.8% to 45.3%); P < .0001). CONCLUSIONS The significantly faster rate of healing and steeper slope of volume reduction in the PriMatrix group warrants further investigation into its effects on healing of neuropathic ulcerations and potential limb salvage.


title: A nationwide web-based automated system for outbreak early detection and rapid response in China.

text: Timely reporting, effective analyses and rapid distribution of surveillance data can assist in detecting the aberration of disease occurrence and further facilitate a timely response. In China, a new nationwide web-based automated system for outbreak detection and rapid response was developed in 2008. The China Infectious Disease Automated-alert and Response System (CIDARS) was developed by the Chinese Center for Disease Control and Prevention based on the surveillance data from the existing electronic National Notifiable Infectious Diseases Reporting Information System (NIDRIS) started in 2004. NIDRIS greatly improved the timeliness and completeness of data reporting with real-time reporting information via the Internet. CIDARS further facilitates the data analysis, aberration detection, signal dissemination, signal response and information communication needed by public health departments across the country. In CIDARS, three aberration detection methods are used to detect the unusual occurrence of 28 notifiable infectious diseases at the county level and transmit information either in real time or on a daily basis. The Internet, computers and mobile phones are used to accomplish rapid signal generation and dissemination, timely reporting and reviewing of the signal response results. CIDARS has been used nationwide since 2008; all Centers for Disease Control and Prevention (CDC) in China at the county, prefecture, provincial and national levels are involved in the system. It assists with early outbreak detection at the local level and prompts reporting of unusual disease occurrences or potential outbreaks to CDCs throughout the country.


title: Pressure-controlled versus volume-controlled ventilation during one-lung ventilation in elderly patients with poor pulmonary function.

text: OBJECTIVE THE AIM WAS TO INVESTIGATE THE EFFECTS OF TWO DIFFERENT VENTILATORY STRATEGIES: Pressure-controlled ventilation (PCV) versus volume-controlled ventilation (VCV) in elderly patients with poor pulmonary function during one-lung ventilation (OLV). PATIENTS AND METHODS The patients were enrolled into the study having poor pulmonary function (forced expiratory volume in 1 s <1.5 L) and undergoing radical resection of pulmonary carcinoma requiring at least 2 h of OLV. Patients were respectively allocated to VCV group and PCV group. The intraoperative data, arterial, and mixed venous blood gases were obtained at baseline, 20, 40, 60, 80, 100 and 120 min after OLV and end of surgery. The postoperative data had been recorded and arterial gas measurements were performed at 6, 12 and 24 h after surgery in Intensive Care Unit. RESULTS Comparison of the VCV group and PCV group, PaO2 and P(A-a)O2 were higher and dead space to tidal volume was lower in the PCV group (P < 0.05) after the point of OLV +60, Ppeak was higher in the VCV group (P < 0.05). There were significant advantages in PCV groups with regard to the PaO2 of three points in postoperation, the duration of postoperative ventilation duration, intensive care duration of stay and the days stay in hospital after surgery. CONCLUSIONS The use of PCV compared with VCV during OLV in elderly patients with poor pulmonary function has significant advantages of intraoperative and postoperative oxygenation and it might be a factor, which can beneficial to postoperative recovery.


title: Vav1 downmodulates Akt in different breast cancer subtypes: a new promising chance to improve breast cancer outcome.

text: Targeting different members of the Akt pathways is a promising therapeutic chance in solid tumors including breast cancer. The variable expression levels of Akt isoforms with opposite effects on tumor growth and metastasis, however, make it difficult to select the inhibitors to be used for specific breast tumor subtypes. Using in vitro and in vivo models, we demonstrated here that Vav1, ectopically expressed in invasive breast tumors derived cells, downmodulates Akt acting at expression and/or activation levels depending on tumor subtype. The decreased p-Akt1 (Ser473) levels are a common effect of Vav1 upmodulation, suggesting that, in breast tumor-derived cells and independently of their phenotype, Vav1 interferes with signaling pathways ended to specifically recruit Akt1. Only in ER-negative cell lines, the silencing of Vav1 induced the expression but not the activation of Akt2. A retrospective analysis of early invasive breast tumors allowed to establish the prognostic significance of the p-Akt/Vav1 relationship. In particular, low Vav1 levels negatively influence the follow-up of patients with low p-Akt in their primary tumors and subjected to adjuvant chemotherapy. As the use of specific or pan Akt inhibitors may not be sufficient or may even be detrimental, increasing the levels of Vav1 could be a new approach to improve breast cancer outcomes. This might be particularly relevant for tumors with a triple-negative phenotype, for which target-based therapies are not currently available.


Paediatric care in the time of COVID-19 in countries with under-resourced healthcare systems.


title: Quarterly intrinsic disorder digest (January-February-March, 2014).

text: This is the 5th issue of the Digested Disorder series that represents a reader's digest of the scientific literature on intrinsically disordered proteins. We continue to use only 2 criteria for inclusion of a paper to this digest: The publication date (a paper should be published within the covered time frame) and the topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the first quarter of 2014; i.e., during the period of January, February, and March of 2014. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included papers a short description is given on its major findings.


title: Assessment of dyssynchrony by gated myocardial perfusion imaging does not improve patient management.

text: Clinical trials have demonstrated improved outcomes with cardiac resynchronization therapy in patients with heart failure and electrical evidence of dyssynchrony. There has been intense effort at developing imaging markers of dyssynchrony with the aim of improved risk stratification. However, these efforts have not been fruitful to date. This article discusses mechanisms of cardiac dyssynchrony, reviews clinical data supporting resynchronization therapy, and addresses the lack of convincing evidence to support the use of noninvasive imaging measures of dyssynchrony in improving patient management.


title: Comparison of a reusable with a disposable vessel-sealing device in a sheep model: efficacy and costs.

text: OBJECTIVE To compare the efficacy of the new reusable vessel-sealing device MarSeal (KLS Martin, Tuttlingen, Germany) with the conventional standard disposable LigaSure device (Covidien-Valleylab, Boulder, CO) in an in vivo animal model. DESIGN Prospective animal study. SETTING Center of Experimental Surgery at a university hospital. ANIMALS Thirteen sheep. INTERVENTION(S) The carotid and femoral arteries were dissected bilaterally and sealed randomly with MarSeal unilaterally and consecutively with LigaSure contralaterally in vivo. Afterward the burst pressure was determined for each artery. MAIN OUTCOME MEASURE(S) Sealing time, failure rate, and burst pressure. RESULT(S) The mean diameter of all arteries sealed did not differ significantly between the two groups (MarSeal 5.40 mm vs. LigaSure 5.35 mm). The mean sealing time was significantly shorter with use of the reusable device (MarSeal 5.2 seconds vs. LigaSure 9.1 seconds). We did not find a significant difference in sealing failure rates between the groups (MarSeal 7.0% vs. LigaSure 9.1%). In addition, analysis of mean burst pressure did not reveal a significant difference between the different devices (MarSeal 429 mm Hg vs. LigaSure 484 mm Hg). There was no significant difference with respect to lateral thermal damage (MarSeal 0.91 cm vs. LigaSure 0.93 cm). CONCLUSION(S) In our in vivo animal study, the new reusable MarSeal device appears to be equivalently effective for vessel sealing when compared with the conventional disposable LigaSure device.


title: Cutting edge: influence of Tmevpg1, a long intergenic noncoding RNA, on the expression of Ifng by Th1 cells.

text: The majority of the genome is noncoding and was thought to be nonfunctional. However, it is now appreciated that transcriptional control of protein coding genes resides within these noncoding regions. Thousands of genes encoding long intergenic noncoding RNAs (lincRNAs) have been recently identified throughout the genome, which positively or negatively regulate transcription of neighboring target genes. Both TMEVPG1 and its mouse ortholog encode lincRNAs and are positioned near the IFN-γ gene (IFNG). In this study, we show that transcription of both mouse and human TMEVPG1 genes is Th1 selective and dependent on Stat4 and T-bet, transcription factors that drive the Th1 differentiation program. Ifng expression is partially restored in Stat4-/-Tbx21-/- cells through coexpression of T-bet and Tmevpg1, and Tmevpg1 expression contributes to, but alone is not sufficient to, drive Th1-dependent Ifng expression. Our results suggest that TMEVPG1 belongs to the general class of lincRNAs that positively regulate gene transcription.


title: Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium.

text: RATIONALE Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19), a predominantly respiratory illness. The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. OBJECTIVES The objective was to gain insight into the expression of ACE2 in the human airway epithelium. METHODS Airway epithelium sampled by fiberoptic bronchoscopy of trachea, large airway epi-thelium (LAE) and small airway epithelium (SAE) of nonsmokers and smokers was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarray, RNA-seq and 10x single cell transcriptome analysis, with associated examination of ACE2-related miRNA. MEASUREMENTS AND MAIN RESULTS (1) ACE2 is expressed similarly in the trachea and LAE with lower expression in the SAE; (2) in the SAE, ACE2 is expressed in basal, intermediate, club, mu-cus and ciliated cells; (3) ACE2 is up-regulated in the SAE by smoking, significantly in males; (4) levels of miR-1246 expression could play a role in ACE2 up-regulation in the SAE of smokers; and (5) ACE2 is expressed in airway epithelium differentiated in vitro on air-liquid interface cultures from primary airway basal stem/progenitor cells; this can be replicated using LAE and SAE immortalized basal cell lines derived from healthy nonsmokers. CONCLUSIONS ACE2, the gene encoding the receptor for SARS-CoV-2, is expressed in the human airway epithelium, with variations in expression relevant to the biology of initial steps in SARS-CoV-2 infection. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).


title: Application of a laparoscopic technique for vasectomy in standing horses.

text: This report describes a technique for standing laparoscopic vasectomy in stallions through a prospective descriptive study. A preliminary study was carried out with two experimental intact male horses and subsequently the procedure was performed in two clinical cases. These horse owners want to keep their animals in the most possible natural way, preserving its stallion behaviour in a herd without generating offspring. The horses were sedated and restrained in stocks and laparoscopic vasectomy was performed using three portal sites in both paralumbar fossae recording surgical times. A 4-cm segment of each ductus deferens (DD) was occluded with laparoscopic vessel sealing devices and subsequently excised. Semen collection was performed using an artificial vagina before the laparoscopic procedure and at 15 and 60 days postoperatively. Sexual behaviour and spermiogram were analysed. Two months after vasectomy, control laparoscopy was performed in experimental horses to assess the surgical site. Bilateral vasectomy could be performed without intraoperative complications in a mean surgical time of 20 min per DD. Success of the procedure was confirmed in all cases by azoospermic ejaculates 60 days after vasectomy. This is the first time that the technique for laparoscopic vasectomy is described in horses.


title: Natural History and Management of Blunt Traumatic Pseudoaneurysms of the Internal Carotid Artery: The Harborview Algorithm Based Off a 10-Year Experience.

text: OBJECTIVE To define the natural history of, and treatment strategy for, blunt traumatic internal carotid artery (ICA) pseudoaneurysms. BACKGROUND The natural history and management of traumatic ICA pseudoaneurysms is controversial. METHODS We retrospectively identified all traumatic ICA pseudoaneurysms diagnosed on head/neck computed tomographic angiography at a high-volume trauma center over a 10-year period. Radiographic and clinical data were recorded, and a treatment algorithm was derived. RESULTS Forty-three pseudoaneurysms were diagnosed in 39 patients. All patients were treated with daily aspirin unless contraindicated, and 82% underwent daily transcranial Doppler ultrasonography with embolic monitoring. A rate of 8 or more emboli per hour was predictive of embolic stroke (P = 0.0076). Acute ischemic or embolic stroke was seen in 7 patients (16%) with an overall mortality in this subpopulation of 42% (n = 3). Four patients (9%) underwent acute surgical treatment (parent vessel sacrifice and/or arterial bypass) for ongoing ischemia. Long-term radiographic and clinical follow-up was obtained for 36 surviving patients (mean = 8 months; range: 1 week-5 years), all of whom were maintained on daily aspirin. No delayed ischemic or embolic events were reported. For ICA pseudoaneurysms treated with aspirin and observation alone, 9 (28%) increased in size, 17 (53%) decreased or stabilized, and 6 (19%) resolved. Enlargement of 5 mm or more in maximal diameter underwent delayed endovascular treatment with a 100% obliteration rate and no complications. CONCLUSIONS Traumatic ICA pseudoaneurysms are safely treated with daily aspirin, embolic monitoring, and radiographic surveillance. Acute stroke or hemorrhage, or delayed radiographic progression, are indications for endovascular or surgical treatment.


COVID-19, guests and crews of cruise: observation on Thai citizens.


title: Correction: Viruses Utilize Cellular Cues in Distinct Combination to Undergo Systematic Priming and Uncoating.

text: [This corrects the article DOI: 10.1371/journal.ppat.1005467.].


title: Hepatitis C virus induces CD81 and claudin-1 endocytosis.

text: Hepatitis C virus (HCV) leads to progressive liver disease and hepatocellular carcinoma. Current treatments are only partially effective, and new therapies targeting viral and host pathways are required. Virus entry into a host cell provides a conserved target for therapeutic intervention. Tetraspanin CD81, scavenger receptor class B member I, and the tight-junction proteins claudin-1 and occludin have been identified as essential entry receptors. Limited information is available on the role of receptor trafficking in HCV entry. We demonstrate here that anti-CD81 antibodies inhibit HCV infection at late times after virus internalization, suggesting a role for intracellular CD81 in HCV infection. Several tetraspanins have been reported to internalize via motifs in their C-terminal cytoplasmic domains; however, CD81 lacks such motifs, leading several laboratories to suggest a limited role for CD81 endocytosis in HCV entry. We demonstrate CD81 internalization via a clathrin- and dynamin-dependent process, independent of its cytoplasmic domain, suggesting a role for associated partner proteins in regulating CD81 trafficking. Live cell imaging demonstrates CD81 and claudin-1 coendocytosis and fusion with Rab5 expressing endosomes, supporting a role for this receptor complex in HCV internalization. Receptor-specific antibodies and HCV particles increase CD81 and claudin-1 endocytosis, supporting a model wherein HCV stimulates receptor trafficking to promote particle internalization.


title: Totally robotic low anterior resection with total mesorectal excision and splenic flexure mobilization.

text: Some limitations of conventional laparoscopy have been overcome by the enhanced dexterity of the robotic da Vinci system, and its use in gastrointestinal procedures is evolving. However, difficulties accessing multiple quadrants of the abdomen with the first robotic system led to a rather slow introduction of the da Vinci into the field of abdominal surgery compared with its success with urologic and cardiac procedures. The new da Vinci S HD system offers improved range of motion that allows for easier access to a wider surgical field. The authors developed a new "one-step" setup to perform a low anterior resection with total mesorectal excision and splenic flexure mobilization for rectal cancer using a completely robotic approach. This technical report describes all the major aspects for successful performance of this complex minimally invasive procedure.


title: [Health protection guideline of conference designated hotel during COVID-19 outbreak].

text: This guideline stipulates the management requirements, personal protection and comprehensive security of conference designated hotels. It is applicable to the unified standard prevention and control of conference designated hotels during COVID-19 outbreak.


title: T-cell intracellular antigens in health and disease.

text: T-cell intracellular antigen 1 (TIA1) and TIA1-related/like protein (TIAR/TIAL1) are 2 proteins discovered in 1991 as components of cytotoxic T lymphocyte granules. They act in the nucleus as regulators of transcription and pre-mRNA splicing. In the cytoplasm, TIA1 and TIAR regulate and/or modulate the location, stability and/or translation of mRNAs. As knowledge of the different genes regulated by these proteins and the cellular/biological programs in which they are involved increases, it is evident that these antigens are key players in human physiology and pathology. This review will discuss the latest developments in the field, with physiopathological relevance, that point to novel roles for these regulators in the molecular and cell biology of higher eukaryotes.


title: Miniature in vivo robot for laparoendoscopic single-site surgery.

text: BACKGROUND The aim of this study was to develop a multidexterous robot capable of generating the required forces and speeds to perform surgical tasks intra-abdominally. Current laparoscopic surgical robots are expensive, bulky, and fundamentally constrained by a small entry incision. A new approach to minimally invasive surgery places the robot completely within the patient. Miniature in vivo robots may allow surgeons to overcome current laparoscopic constraints such as dexterity, orientation, and visualization. METHODS A collaborative research group from the Department of Surgery at the University of Nebraska Medical Center and the College of Engineering at the University of Nebraska-Lincoln designed and built a surgical robot prototype capable of performing specific surgical tasks within the peritoneal cavity. RESULTS The basic robotic design consists of two arms each connected to a central body. Each arm has three degrees of freedom and rotational shoulder and elbow joints. This combination allows a surgeon to grasp, manipulate, cauterize, and perform intracorporeal suturing. The robot's workspace is a hollow hemisphere with an inner radius of 75 mm and an outer radius of 205 mm. Its versatility was demonstrated in four procedures performed in a porcine model: cholecystectomy, partial colectomy, abdominal exploration, and intracorporeal suturing. CONCLUSIONS Miniature in vivo robots have the potential to address the limitations of using articulated instrumentation to perform advanced laparoscopic surgical procedures. Once inserted into the peritoneal cavity, the robot provides a stable platform for visualization with sufficient dexterity and speed to perform surgical tasks from multiple orientations and workspaces.


title: Discovery of High Affinity Receptors for Dityrosine through Inverse Virtual Screening and Docking and Molecular Dynamics.

text: Dityrosine is the product of oxidation that has been linked to a number of serious pathological conditions. Evidence indicates that high amounts of dityrosine exist in oxidized milk powders and some milk related foodstuffs, further reducing the nutritional value of oxidized proteins. Therefore, we hypothesize that some receptors related to special diseases would be targets for dityrosine. However, the mechanisms of the interaction of dityrosine with probable targets are still unknown. In the present work, an inverse virtual screening approach was performed to screen possible novel targets for dityrosine. Molecular docking studies were performed on a panel of targets extracted from the potential drug target database (PDTD) to optimize and validate the screening results. Firstly, two different conformations cis- and trans- were found for dityrosine during minimization. Moreover, Tubulin (αT) (-11.0 kcal/mol) was identified as a target for cis-dityrosine (CDT), targets including αT (-11.2 kcal/mol) and thyroid hormone receptor beta-1 (-10.7 kcal/mol) presented high binding affinities for trans-dityrosine (TDT). Furthermore, in order to provide binding complexes with higher precision, the three docked systems were further refined by performing thermo dynamic simulations. A series of techniques for searching for the most stable binding pose and the calculation of binding free energy are elaborately provided in this work. The major interactions between these targets and dityrosine were hydrophobic, electrostatic and hydrogen bonding. The application of inverse virtual screening method may facilitate the prediction of unknown targets for known ligands, and direct future experimental assays.


title: Interventions to Improve Mental Health, Well-Being, Physical Health, and Lifestyle Behaviors in Physicians and Nurses: A Systematic Review.

text: OBJECTIVE This systematic review focused on randomized controlled trials (RCTs) with physicians and nurses that tested interventions designed to improve their mental health, well-being, physical health, and lifestyle behaviors. DATA SOURCE A systematic search of electronic databases from 2008 to May 2018 included PubMed, CINAHL, PsycINFO, SPORTDiscus, and the Cochrane Library. STUDY INCLUSION AND EXCLUSION CRITERIA Inclusion criteria included an RCT design, samples of physicians and/or nurses, and publication year 2008 or later with outcomes targeting mental health, well-being/resiliency, healthy lifestyle behaviors, and/or physical health. Exclusion criteria included studies with a focus on burnout without measures of mood, resiliency, mindfulness, or stress; primary focus on an area other than health promotion; and non-English papers. DATA EXTRACTION Quantitative and qualitative data were extracted from each study by 2 independent researchers using a standardized template created in Covidence. DATA SYNTHESIS Although meta-analytic pooling across all studies was desired, a wide array of outcome measures made quantitative pooling unsuitable. Therefore, effect sizes were calculated and a mini meta-analysis was completed. RESULTS Twenty-nine studies (N = 2708 participants) met the inclusion criteria. Results indicated that mindfulness and cognitive-behavioral therapy-based interventions are effective in reducing stress, anxiety, and depression. Brief interventions that incorporate deep breathing and gratitude may be beneficial. Visual triggers, pedometers, and health coaching with texting increased physical activity. CONCLUSION Healthcare systems must promote the health and well-being of physicians and nurses with evidence-based interventions to improve population health and enhance the quality and safety of the care that is delivered.


title: Cerebral blood volume lesion extent predicts functional outcome in patients with vertebral and basilar artery occlusion.

text: Background CT perfusion may improve diagnostic accuracy in posterior circulation stroke. The posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) on Computed Tomography Angiography source images (CTA-SI) predicts functional outcome in patients with basilar artery occlusion. Aims We assessed the prognostic value of pc-ASPECTS on CT perfusion in patients with vertebral and basilar artery occlusion (VBAO) in comparison with CTA-SI. Methods Whole-brain CT perfusion from consecutive stroke patients with VBAO at four stroke centers was retrospectively analyzed. pc-ASPECTS - a 10-point score assessing hypoattenuation on CTA-SI - was calculated from CT perfusion parameters as focally reduced cerebral blood flow or cerebral blood volume, focally increased time to peak of the deconvolved tissue residue function (Tmax) or mean transit time. Two investigators independently reviewed the images. Reliability was assessed with intraclass correlation coefficient. Good outcome was defined as modified Rankin scale ≤3 at three months. Results We included 60 patients with VBAO. After assessment of four CT perfusion maps simultaneously, area-under-ROC curve (AROC) was 0.83 (95%CI 0.72-0.93) for cerebral blood volume, 0.76 (95%CI 0.64-0.89) for cerebral blood flow, 0.77 (95%CI 0.64-0.89) for Tmax, 0.70 (95%CI 0.56-0.84) for mean transit time versus area-under-ROC curve 0.64 (95%CI 0.50-0.79) for CTA-SI. Cerebral blood volume had greater accuracy compared with CTA-SI for poor outcome (p = 0.04). In logistic regression analysis, cerebral blood volume pc-ASPECTS≤8 was independently associated with poor outcome (OR 9.3 95%CI 2.2-41; p = 0.003, adjusted for age and clinical severity). Inter-rater agreement was substantial for cerebral blood volume pc-ASPECTS (intraclass correlation coefficient 0.82 95%CI 0.71-0.90 versus 0.67 for CTA-SI 95%CI 0.43-0.81). Conclusions Cerebral blood volume pc-ASPECTS may identify VBAO patients at higher risk of disability.


Pulmonary mucormycosis: what is the best strategy for therapy?


Healthcare virtualization amid COVID-19 pandemic: an emerging new normal.