title: A prospective randomised trial of LigaSure Small Jaw® versus conventional neck dissection in head and neck cancer patients.

text: OBJECTIVES We compared the differences between LigaSure Small Jaw®-assisted and conventional neck dissection in patients with head and neck cancer. DESIGN Prospective randomised study. SETTING Tertiary referral hospital. PARTICIPANTS Patients scheduled to undergo neck dissection due to head and neck cancer were eligible for this study. The study group was treated using the LigaSure vessel sealing system (Small Jaw®; Covidien, Colorado, USA) for dissection and hemostasis throughout the whole procedures (ClinicalTrials.gov number: NCT02597582). MAIN OUTCOMES MEASURES Operation duration, perioperative blood loss, postoperative drainage amount and postoperative pain status. RESULTS The study group consisted of 21 patients, while the control group had 20 patients. The operation duration was shorter (97.1 versus 116.3 min, P = 0.022) and the average amount of injected analgesics was lower (8.8 versus 17.7 ampules, P = 0.037) in the study group. CONCLUSIONS The assistance of the LigaSure Small Jaw® during functional neck dissection shortened the operation duration and decreased the amount of injected analgesics needed.


title: One-Year Outcomes Following Directional Atherectomy of Infrapopliteal Artery Lesions: Subgroup Results of the Prospective, Multicenter DEFINITIVE LE Trial.

text: PURPOSE To report a subgroup analysis of the prospective, multicenter, single-arm DEFINITIVE LE trial to assess the effectiveness of directional atherectomy for the treatment of infrapopliteal artery lesions at 1 year. METHODS In the DEFINITIVE LE trial, follow-up assessments occurred up to 1 year postprocedure. Of the 800 patients enrolled, 145 subjects with 189 infrapopliteal lesions met the criteria for this analysis. Seventy (48.3%) and 75 (51.7%) patients were suffering critical limb ischemia (CLI) and intermittent claudication, respectively; 68.3% (99/145) had diabetes. The mean lesion length was 58±44 mm (all lesions); 20.2% were occluded. The primary endpoint for patients with claudication was duplex ultrasound-derived primary patency, while for subjects with CLI it was freedom from major amputation of the target limb at 1 year. Endpoints and adverse events were independently assessed. RESULTS Procedure success (≤30% residual stenosis) was achieved in 84% of treated lesions. The 1-year primary patency rate was 84% (claudicants 89.6% and CLI patients 78%, p=0.11), and the freedom from major amputation rate was 97.1% (claudicants 100% and CLI 93.8%, p=0.03). In both claudication and CLI patients, significant improvements in Rutherford category and objective measures of walking distance and quality of life were seen at 1 year in comparison to baseline. CONCLUSION This study demonstrates that directional atherectomy in infrapopliteal arteries results in promising technical and clinical results at 1 year for claudicant as well as CLI patients.


Raf: a key regulatory kinase for transduction of mitogenic and metabolic signals of the probiotic Saccharomyces boulardii.


title: Bisphenol A induces protection through modulation of the immune response against the helminth parasite Taenia crassiceps.

text: AIMS Industrial growth has increased the exposure to endocrine disruptor compounds (EDCs) in all organisms. Bisphenol A (BPA), an EDC, has been demonstrated to be involved in the susceptibility to parasite infections. However, few studies have analyzed this connection in more depth. The aim of this study was to determine if early BPA exposure in female mice affects the systemic immune response and the susceptibility to T. crassiceps infection. METHODS AND RESULTS BALB/cice were exposed to BPA at postnatal day 3. At 6 weeks of age, they were inoculated with T. crassiceps larvae, and 2 weeks later, were euthanized. The number of parasites was quantified. By flow cytometry, in the spleen, the peripheral and mesenteric lymph nodes, the different innate and adaptive immune cell modulation was analyzed, and RT-PCR cytokine expression was also evaluated. BPA induced a reduction of 40% in parasite load. BPA treatment modulated some lineages of the innate immune response and caused slight changes in cells belonging to the adaptive immune response. Additionally, BPA enhanced the type 2 cytokine profile. CONCLUSION Neonatal BPA treatment in female mice affects not only the percentage of different immune cells but also theirex vivo cytokine gene expression., decreasing T. crassiceps cysticercosis susceptibility.


title: 0.2% chlorhexidine acetate as skin disinfectant prevents skin lesions in extremely preterm infants: a preliminary report.

text: OBJECTIVE The skin disinfectant '0.5% chlorhexidine gluconate in 70% alcohol' (0.5% CHG-70% alc) may cause skin lesions in extremely preterm infants (gestational age <26 weeks). In April 2013, 0.2% chlorhexidine gluconate solution in acetate (0.2% CHG-acetate) was introduced as skin disinfectant for extremely preterm infants in our neonatal intensive care units. We aimed to compare the incidence of skin lesions and central line-associated bloodstream infection (CLABSI) among extremely preterm infants when using 0.5% CHG-70% alc and 0.2% CHG-acetate. DESIGN Retrospective pre-post comparison cohort study. PATIENTS All electronic patient records of extremely preterm infants born between January 2011-March 2013 ('0.5% CHG-70% alc' cohort) and April 2013-October 2015 ('0.2% CHG-acetate' cohort) were reviewed. MAIN OUTCOME MEASURES The incidence of skin lesions and CLABSI. Skin lesions were defined as the presence of erythema, blisters, excoriation, oedema or induration. CLABSI was defined according to the definition of the US Centers for Disease Control and Prevention. RESULTS The incidence of skin lesions was 22% (95% CI 11% to 37%) in the '0.5% CHG-70% alc' cohort (n=41) and 5% (95% CI 1% to 15%; p=0.02) in the '0.2% CHG-acetate' cohort (n=41). The incidence of CLABSI was the same in both groups (28%; 95% CI 14% to 46% in '0.5% CHG-70% alc' vs 27%; 95% CI 14% to 44% in '0.2% CHG-acetate'; p=0.98). CONCLUSIONS Using 0.2% CHG-acetate as skin disinfectant in extremely preterm infants resulted in statistically significant reduction of skin lesions, without increasing the risk of CLABSI as compared with 0.5% CHG-70% alc.


title: T helper type 2 bias and type 17 suppression in primary dengue virus infection in infants and young children.

text: BACKGROUND The immune response to dengue virus (DENV) primary infection in infants and young children is not well characterized. In Northern Argentina, >90% of the population was DENV-naïve before the 2009 outbreak, allowing evaluation of age-dependent primary responses to infection. METHODS We conducted a comparative study of the immune response to DENV in 27 infected infants, young children and their mothers. Lymphocyte T helper (Th) 1, Th2, Th17 and inflammatory responses were assayed in blood during the 2009 DENV-1 epidemic. RESULTS The immune response to DENV-1 was significantly biased to Th2 in infected infants and young children, compared to infants with other febrile illnesses (for IL-4 p < 0.001) and to their infected mothers (for IL-4 p < 0.01). In addition, IL-17 suppression was observed in the memory response to DENV-1 in infected infants (p < 0.01 vs placebo). CONCLUSION Age-related differences in the primary response to DENV, characterized by an immature Th2 polarization and Th17 suppression in infants, should be studied further in order to expand our understanding of the mechanism of dengue pathogenesis.


Are emergency surgical patients "collateral victims" of COVID-19 outbreak?


Multidisciplinary practical guidelines for gastrointestinal access for enteral nutrition and decompression from the Society of Interventional Radiology and American Gastroenterological Association (AGA) Institute, with endorsement by Canadian Interventional Radiological Association (CIRA) and Cardio


title: Transferrin receptor binds virus capsid with dynamic motion.

text: Canine parvovirus (CPV) is an important pathogen causing severe diseases in dogs, including acute hemorrhagic enteritis, myocarditis, and cerebellar disease. Cross-species transmission of CPV occurs as a result of mutations on the viral capsid surface that alter the species-specific binding to the host receptor, transferrin receptor type-1 (TfR). The interaction between CPV and TfR has been extensively studied, and previous analyses have suggested that the CPV-TfR complex is asymmetric. To enhance the understanding of the underlying molecular mechanisms, we determined the CPV-TfR interaction using cryo-electron microscopy to solve the icosahedral (3.0-Å resolution) and asymmetric (5.0-Å resolution) complex structures. Structural analyses revealed conformational variations of the TfR molecules relative to the binding site, which translated into dynamic molecular interactions between CPV and TfR. The precise footprint of the receptor on the virus capsid was identified, along with the identity of the amino acid residues in the virus-receptor interface. Our "rock-and-roll" model provides an explanation for previous findings and gives insights into species jumping and the variation in host ranges associated with new pandemics in dogs.


title: The Psychosocial Impact of COVID-19 on health care workers.

text: At the end of 2019, a disease was identified, COVID-19, caused by a new type of easy and fast spreading virus, which led to the beginning of a worldwide pandemic. One of the most exposed groups to the virus and its psychosocial consequences is the healthcare workers, due to their implication in caring for affected people. Health workers are exposed to a fast and unpredictable situation that requires more human resources and materials than usual, however, the lack of means on account to this situation entails an increased probability of suffering different consequences, including the burnout syndrome, to which, generally, this professionals are already vulnerable. In addition, quarantine is added as a measure to prevent the spread of the pandemic, which is another handicap for healthcare workers. Quarantine means these professionals are more likely to suffer the foreseeable psychological consequences in general population, specifically, it has been observed that Post-Traumatic Stress Disorder (PTSD) is more prevalent, because of the stress load of the situation experienced.


title: Improved Deep Learning Network Based in combination with Cost-sensitive Learning for Early Detection of Ovarian Cancer in Color Ultrasound Detecting System.

text: With the development of theories and technologies in medical imaging, most of the tumors can be detected in the early stage. However, the nature of ovarian cysts lacks accurate judgement, leading to that many patients with benign nodules still need Fine Needle Aspiration (FNA) biopsies or surgeries, increasing the physical pain and mental pressure of patients as well as unnecessary medical health care costs. Therefore, we present an image diagnosis system for classifying the ovarian cysts in color ultrasound images, which novelly applies the image features fused by both high-level features from deep learning network and low-level features from texture descriptor. Firstly, the ultrasound images are enhanced to improve the quality of training data set and the rotation invariant uniform local binary pattern (ULBP) features are extracted from each of the images as the low-level texture features. Then the high-level deep features extracted by the fine-tuned GoogLeNet neural network and the low-level ULBP features are normalized and cascaded as one fusion feature that can represent both the semantic context and the texture patterns distributed in the image. Finally, the fusion features are input to the Cost-sensitive Random Forest classifier to classify the images into "malignant" and "benign". The high-level features extracted by the deep neural network from the medical ultrasound image can reflect the visual features of the lesion region, while the low-level texture features can describe the edges, direction and distribution of intensities. Experimental results indicate that the combination of the two types of features can describe the differences between the lesion regions and other regions, and the differences between lesions regions of malignant and benign ovarian cysts.


title: Theory-based explanation as intervention.

text: Cogent explanations are an indispensable means of providing new information and an essential component of effective education. Beyond this, we argue that there is tremendous untapped potential in using explanations to motivate behavior change. In this article we focus on health interventions. We review four case studies that used carefully tailored explanations to address gaps and misconceptions in people's intuitive theories, providing participants with a conceptual framework for understanding how and why some recommended behavior is an effective way of achieving a health goal. These case studies targeted a variety of health-promoting behaviors: (1) children washing their hands to prevent viral epidemics; (2) parents vaccinating their children to stem the resurgence of infectious diseases; (3) adults completing the full course of an antibiotic prescription to reduce antibiotic resistance; and (4) children eating a variety of healthy foods to improve unhealthy diets. Simply telling people to engage in these behaviors has been largely ineffective-if anything, concern about these issues is mounting. But in each case, teaching participants coherent explanatory frameworks for understanding health recommendations has shown great promise, with such theory-based explanations outperforming state-of-the-art interventions from national health authorities. We contrast theory-based explanations both with simply listing facts, information, and advice and with providing a full-blown educational curriculum, and argue for providing the minimum amount of information required to understand the causal link between a target behavior and a health outcome. We argue that such theory-based explanations lend people the motivation and confidence to act on their new understanding.


title: Structural Basis of the SARS-CoV-2/SARS-CoV Receptor Binding and Small-Molecule Blockers as Potential Therapeutics.

text: Over the past two decades, deadly coronaviruses have caused major challenges to public health, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2, 2019) pandemic. The path for virus invasion into humans and other hosts is mediated by "host-pathogen" interactions, specifically, virus-receptor binding. An in-depth understanding of the virus-receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and/or small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus-receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June, 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RdRp, against human coronaviruses, including SARS-CoV-2. This article has been accepted for publication on June 23, 2020. Changes may still occur before final publication. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


title: Augmented autologous pericranium duraplasty in 100 posterior fossa surgeries--a retrospective case series.

text: BACKGROUND Primary closure of the dura in posterior fossa (p-fossa) surgeries is technically difficult and usually requires the use of a dural substitute. A variety of substitutes are currently available and data suggest that autologous materials are preferred in comparison with nonautologous substitutes. OBJECTIVE To report our experience using locally harvested autologous pericranium as a dural substitute in patients who underwent p-fossa surgeries. METHODS Retrospective analysis of patients who had undergone p-fossa craniotomies between 2005 and 2011. All patients received locally harvested autologous pericranium for duraplasty augmented with a dural sealant. Data were reviewed for complications including: surgical site infection, meningitis, cerebrospinal fluid leak, the radiographic formation of a pseudomeningocele, and any new neurological symptoms related to the incision or repair. RESULTS One hundred patients were identified. Indications for surgery included tumor, vascular lesions, or hemorrhage requiring surgical intervention, symptomatic Chiari I malformation, microvascular decompression for trigeminal neuralgia, and trauma requiring surgical decompression. The complication rate was 1% with 1 patient developing an nonsteroidal anti-inflammatory drug-induced aseptic meningitis and graft dehiscence requiring surgical revision. CONCLUSION Autologous pericranium with dural sealant augmentation is an effective way to repair the durotomy in p-fossa surgeries. To the best of our knowledge, this is currently the largest study using this technique in the adult neurosurgical literature. Our results report a much lower rate of complications in comparison with other duraplasty studies.


title: Construct validity of an inanimate training model for laparoscopic appendectomy.

text: BACKGROUND AND OBJECTIVE The use of training models in laparoscopic surgery allows the surgical team to practice procedures in a safe environment. The aim of this study was to determine the capability of an inanimate laparoscopic appendectomy model to discriminate between different levels of surgical experience (construct validity). METHODS The performance of 3 groups with different levels of expertise in laparoscopic surgery--experts (Group A), intermediates (Group B), and novices (Group C)--was evaluated. The groups were instructed of the task to perform in the model using a video tutorial. Procedures were recorded in a digital format for later analysis using the Global Operative Assessment of Laparoscopic Skills (GOALS) score; procedure time was registered. The data were analyzed using the analysis of variance test. RESULTS Twelve subjects were evaluated, 4 in each group, using the GOALS score and time required to finish the task. Higher scores were observed in the expert group, followed by the intermediate and novice groups, with statistically significant difference. Regarding procedure time, a significant difference was also found between the groups, with the experts having the shorter time. The proposed model is able to discriminate among individuals with different levels of expertise, indicating that the abilities that the model evaluates are relevant in the surgeon's performance. CONCLUSIONS Construct validity for the inanimate full-task laparoscopic appendectomy training model was demonstrated. Therefore, it is a useful tool in the development and evaluation of the resident in training.


title: COVID-19, Australia: Epidemiology Report 10 (Reporting week to 23:59 AEST 5 April 2020).

text: Confirmed cases in Australia notified up to 5 April 2020: Notifications = 5,805; Deaths = 33. Notifications in Australia remain predominantly among people with recent overseas travel, with some locally-acquired cases being detected. Most locally-acquired cases are able to be linked back to a confirmed case, with a small portion unable to be epidemiologically link. The distribution of overseas-acquired cases to locally acquired cases varies by jurisdiction. Early indications are that reduction in international travel, domestic movement, social distancing measures and public health action are slowing the spread of the disease. Internationally, cases continue to increase, with high rates of increase observed in the European region and the United States of America. The epidemiology differs from country to country depending not only on the disease, but also on differences in case detection, testing and implemented public health measures.


Errors in Text, Figure, and End Matter.


title: Laparoscopy-assisted total gastrectomy: a simplified approach.

text: Laparoscopy-assisted total gastrectomy (LATG), esophagojejunostomy is an effective but difficult procedure to perform. We describe a simple modification that substantially facilitates insertion of the anvil into the esophagus and avoids oral injuries and complications. After mobilization of the stomach and esophagus, a semicircumferential esophagotomy is made at the anterior esophageal wall. An OrVil anvil (Orvil, Covidien, Norwalk, CT, USA) is delivered laparoscopically and secured with a POLYSORB (Covidien) suture to the esophagus. The suture is advanced anteriorly so that the center rod penetrates the esophageal wall. The esophagus is transected with the stapler at this point. A circular-stapled esophagojejunostomy is then performed using the hemidouble stapling technique. Laparoscopy-assisted total gastrectomies were performed for 40 patients with gastric cancers (T1N0M0). All procedures were completed laparoscopically without any complications. The time required to place the anvil averaged 5 min compared with 9 min reported by others. There were no major complications or mortality in this series. The major advantage of this technique is that circular stapling is much easier than linear stapling, allowing surgeons without advanced surgical skills in LATG to perform the procedure effectively and safely.


title: Spatio-temporal variation and risk assessment of hydrochemical indices in a large diversion project of the Yellow River, northern China, from 2008 to 2017.

text: Large-scale, inter-basin water diversion projects have been developed to relieve water scarcity crisis and water pollution problems. Environmental status and ecosystem impacts are largely unknown for the Wanjiazhai Yellow River Diversion Project (YRDP-WJZ), a water body critical in northern China. In the current study, twelve hydrochemical indices (including Mn, Cu, Zn, Hg, Pb, NH3-N, COD-Mn, DO, BOD5, COD, TP, and TN) were collected from 2008 to 2017 based on multiple analytical approaches to understand environmental status and ecological risks. Human health risk and threats to aquatic organisms from heavy metals were assessed. Heavy metals have no regular spatial distribution. Biochemical parameters and nutrients pollute seriously in midstream and downstream, respectively. Hydrochemical indices suggested high levels of pollution in the midstream section. Water quality improved downstream of the Fenhe Reservoir, but total nitrogen and total phosphorus in the downstream section increased in recent years. The Canadian Council of Ministers of the Environment Water Quality Index (CWQI) suggested midstream water quality was poor in general, and 80% of annual calculations had a marginal grade. For aquatic organisms, ecological risks of Cu and Zn were high. For local residents, drinking water was generally safe, but continued monitoring is critical due to ongoing threats to water quality in these areas.


title: Surgery with curative intent for stage IV gastric cancer: Is it a reality of illusion?

text: Gastric cancer with metastases outside of the regional lymph nodes is deemed oncologically unresectable. Nevertheless, some metastatic lesions are technically resectable by applying established surgical techniques such as para-aortic lymphadenectomy and hepatectomy. At the time of compilation of the Japanese gastric cancer treatment guidelines version 4, systematic reviews were conducted to see whether it is feasible to make any recommendation to dissect both the primary and metastatic lesions with intent to cure, possibly as part of multimodality treatment. Long-term survivors were found among carefully selected groups of patients both in prospective and retrospective studies. In addition, there is a growing list of publications reporting encouraging outcomes of gastrectomy conducted after exceptionally good response to chemotherapy, usually among patients who underwent R0 resection. This type of surgery is often referred to as conversion surgery. It is sometimes difficult to define a clear borderline between curative surgery scheduled after neoadjuvant chemotherapy and the conversion surgery. This review summarizes what we knew after the literature reviews conducted at the time of compiling the Japanese guidelines and in addition reflects some new findings obtained thereafter through clinical trials and retrospective studies. Metastases were divided into three categories based on the major metastatic pathways: lymphatic, hematogenous, and peritoneal. In each of these categories, there were findings that could provide hope for patients with metastatic disease. These findings implied that the surgical technique that we already use could become more useful upon further developments in antineoplastic agents and drug delivery.


title: Tailored use of transradial access for above-the-knee angioplasty.

text: PURPOSE To report the results and complications of a single-center experience of above-the-knee angioplasty via transradial access (TRA). METHODS In a prospective study, 110 consecutive patients (88 men; mean age 72 years, range 37-90) referred for critical limb ischemia (26, 24%) or claudication were eligible for lower limb angioplasty via TRA (patients with TASC D lesions of the superficial femoral artery and below-the-knee lesions were excluded). RESULTS The majority of patients (84, 76%) were treated via a left TRA. A total of 170 lesions were addressed, of which 38 (22%) were occlusions; 113 stents were positioned in 82 patients. The overall technical success rate was 91%, with a 63% success rate in occlusions and a 98% success rate in stenoses; by location, the success rates were 91% in suprainguinal lesions and 90% in infrainguinal lesions. No hemorrhagic or local complications requiring surgery were observed. At 1-month follow-up, 101 patients had a downward shift of at least one category in the Rutherford classification of symptoms (clinical success rate 92%); 18 (16%) patients had occlusion of their access radial artery, but none had symptoms or discomfort. CONCLUSION The present study demonstrates that TRA is a safe and effective approach for lower extremity arterial revascularization, at least for interventionists with longstanding experience in TRA and in selected anatomical subsets.


title: Long-term analysis of surgical correction of the senile upper lip.

text: OBJECTIVE A quantitative comparison of immediate and long-term results of surgical correction of the senile upper lip using lip advancement and lip lift. METHODS Retrospective review of 30 patients who underwent senile upper lip repair, including lip advancement or lip lift. Digital image analysis was used to standardize each patient's preoperative and postoperative photographs for accurate, objective comparison. RESULTS Lip lift and lip advancement achieve significant improvement in the appearance of the senile upper lip (P < .001). This improvement is sustained during many years (mean, 5 y; P < .001). Using repeated measures analysis of variance, no significant difference was found in the operative group compared with the control group when examining age-related change. CONCLUSION Lip advancement and lip lift can restore the senile upper lip to a more youthful and natural appearance with sustained long-term benefits.


title: Laparoendoscopic single-site surgery for benign urologic disease with a homemade single port device: design and tips for beginners.

text: PURPOSE A single surgeon skilled in conventional laparoscopic surgery used laparoendoscopic single-site surgery (LESS) to treat benign urological diseases. This study reports our surgical results and introduces a simple technique with tips based on our experience. MATERIALS AND METHODS LESS surgery was performed on 116 patients by use of a homemade single-port device composed of an Alexis wound retractor and a powder-free surgical glove. Cases were 44 varicocelectomies (including 8 bilateral cases), 38 renal cyst marsupializations (including 3 bilateral cases), 26 ureterolithotomies (with 1 concomitant ureterolithotomy and contralateral renal cyst marsupialization), 4 prostatic enucleations, and 4 bladder rupture repairs. The mean patient age was 44.43±16.46 years (range, 11 to 76 years), and the male-to-female ratio was 87:29. RESULTS In one ureterolithotomy case, LESS was converted to conventional laparoscopic surgery. The mean operative time was 87.03±45.03 minutes, the estimated blood loss was 61.90 ml (range, 0 to 2,000 ml), and the mean hospital stay was 3.03±2.12 days. Two patients underwent single-port transvesical enucleation of the prostate (STEP) requiring patient-controlled anesthesia. No patients developed major complications, and all patients were satisfied, with 75.86% expressing a high degree of satisfaction. CONCLUSIONS We report successful treatment outcomes for LESS in 116 cases of benign urological disease. Our findings suggest that LESS can replace conventional laparoscopy.


The results of the recent thrombectomy trials may influence stroke care delivery: are you ready?


docid: gbdbyjhn

title: Development of chimpanzee adenoviruses as vaccine vectors: challenges and successes emerging from clinical trials.

text: Replication-defective chimpanzee adenovirus vectors are emerging as a promising new class of genetic vaccine carriers. Chimpanzee adenovirus vectors have now reached the clinical stage and appear to be endowed with all the properties needed for human vaccine development, including high quality and magnitude of the immune response induced against the encoded antigens, good safety and ease of manufacturing on a large-scale basis. Here the authors review the recent findings of this novel class of adenovirus vectors and compare their properties to other clinical stage vaccine vectors derived from poxvirus, alphavirus and human adenovirus.


docid: pgwjnzgu

title: Identifying Core Competencies of Infection Control Nurse Specialists in Hong Kong.

text: PURPOSE To confirm a core competency scale for Hong Kong infection control nurses at the advanced nursing practice level from the core competency items proposed in a previous phase of this study. This would serve as the foundation of competency assurance in Hong Kong hospitals. DESIGN A cross-sectional survey design was used. SETTING All public and private hospitals in Hong Kong. SUBJECTS All infection control nurses in hospitals of Hong Kong. METHODS The 83-item proposed core competency list established in an earlier study was transformed into a questionnaire and sent to 112 infection control nurses in 48 hospitals in Hong Kong. They were asked to rate the importance of each infection prevention and control item using Likert-style response categories. Data were analyzed using the Rasch model. RESULTS The response rate of 81.25% was achieved. Seven items were removed from the proposed core competency list, leaving a scale of 76 items that fit the measurement requirements of the unidimensional Rasch model. CONCLUSIONS Essential core competency items of advanced practice for infection control nurses in Hong Kong were identified based on the measurement criteria of the Rasch model. Several items of the scale that reflect local Hong Kong contextual characteristics are distinguished from the overseas standards. IMPLICATIONS This local-specific competency list could serve as the foundation for education and for certification of infection control nurse specialists in Hong Kong. Rasch measurement is an appropriate analytical tool for identifying core competencies of advanced practice nurses in other specialties and in other locations in a manner that incorporates practitioner judgment and expertise.


title: Early reperfusion rates with IV tPA are determined by CTA clot characteristics.

text: BACKGROUND AND PURPOSE An ability to predict early reperfusion with IV tPA in patients with acute ischemic stroke and intracranial clots can help clinicians decide if additional intra-arterial therapy is needed or not. We explored the association between novel clot characteristics on baseline CTA and early reperfusion with IV tPA in patients with acute ischemic stroke by using classification and regression tree analysis. MATERIALS AND METHODS Data are from patients with acute ischemic stroke and proximal anterior circulation occlusions from the Calgary CTA data base (2003-2012) and the Keimyung Stroke Registry (2005-2009). Patients receiving IV tPA followed by intra-arterial therapy were included. Clot location, length, residual flow within the clot, ratio of contrast Hounsfield units pre- and postclot, and the M1 segment origin to the proximal clot interface distance were assessed on baseline CTA. Early reperfusion (TICI 2a and above) with IV tPA was assessed on the first angiogram. RESULTS Two hundred twenty-eight patients (50.4% men; median age, 69 years; median baseline NIHSS score, 17) fulfilled the inclusion criteria. Median symptom onset to IV tPA time was 120 minutes (interquartile range = 70 minutes); median IV tPA to first angiography time was 70.5 minutes (interquartile range = 62 minutes). Patients with residual flow within the clot were 5 times more likely to reperfuse than those without it. Patients with residual flow and a shorter clot length (≤15 mm) were most likely to reperfuse (70.6%). Patients with clots in the M1 MCA without residual flow reperfused more if clots were distal and had a clot interface ratio in Hounsfield units of <2 (36.8%). Patients with proximal M1 clots without residual flow reperfused 8% of the time. Carotid-T/-L occlusions rarely reperfused (1.7%). Interrater reliability for these clot characteristics was good. CONCLUSIONS Our study shows that clot characteristics on CTA help physicians estimate a range of early reperfusion rates with IV tPA.


title: Bioterrorism: a laboratory who does it?

text: In October 2001, the first disseminated biological warfare attack was perpetrated on American soil. Initially, a few clinical microbiology laboratories were testing specimens from acutely ill patients and also being asked to test nasal swabs from the potentially exposed. Soon after, a significant number of clinical microbiology and public health laboratories received similar requests to test the worried well or evaluate potentially contaminated mail or environmental materials, sometimes from their own break rooms. The role of the clinical and public health microbiology laboratory in response to a select agent event or act of bioterrorism is reviewed.


title: Intubation-related tracheal ischemic lesions: incidence, risk factors, and outcome.

text: PURPOSE To determine incidence, risk factors and outcome of tracheal ischemic lesions related to intubation. METHODS Planned post hoc analysis using patients from a previous randomized controlled study. Fiberoptic tracheoscopy was performed during the 24 h following extubation. In patients with >2 ischemic lesions, ulcer or tracheal rupture, fiberoptic tracheoscopy was repeated 2 weeks after the last extubation. Tracheal ischemic lesions were predefined based on a quantitative score. RESULTS Ninety-six adult patients were included in this study. Eighty (83 %) patients had at least one tracheal ischemic lesion. Thirty-seven (38 %) patients had a tracheal ischemia score > median score (5; IQ 1, 7). The most common tracheal ischemic lesion was ischemia (68 %), followed by hyperemia (54 %), ulcer (10 %), and tracheal rupture (1 %). Univariate analysis identified duration of neuromuscular-blocking agent use, overinflation of tracheal cuff (>30 cmH2O), percentage of P cuff determination >30 cmH2O, duration of assist-control ventilation, and plateau pressure as risk factors for having a tracheal ischemia score >5. Duration of assist-control mechanical ventilation was the only factor independently associated with tracheal ischemia score >5 [OR (95 % CI) 1.10 per hour (1.02-1.20)]. A fiberoptic tracheoscopy was performed 2 weeks after extubation in 22 patients. This examination was normal in all patients, except the one with tracheal rupture who had marked improvement. CONCLUSION Tracheal ischemic lesions are common in intubated, critically ill patients. Duration of assist-control mechanical ventilation through a tracheal tube is the only independent risk factor. These lesions healed in the majority of patients 2 weeks after extubation.


title: Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells.

text: Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases.


title: Haemorrhagic Transformation after Ischaemic Stroke in Patients Taking Non-vitamin K Antagonist Oral Anticoagulants.

text: BACKGROUND AND PURPOSE To evaluate the frequency and outcome of haemorrhagic transformation (HT) after ischaemic stroke in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). METHODS Patients with stroke on treatment with a NOAC were prospectively enrolled in this multicentre observational study between February 2012 and 2015. Brain imaging at admission and follow-up imaging until day 7 were reviewed for HT. Functional outcome was assessed by the modified Rankin scale (mRS) before the index event, at discharge, and at 3-months. RESULTS 231 patients without recanalisation therapy (no-RT), and 32 patients with RT were eligible for analysis. Any HT was present at admission in 9/231 no-RT patients (3.9%, 95% CI 2.0 to 7.3) and in none of the patients with RT. In patients with follow-up imaging (no-RT, n=129, and RT, n=32), HT was present in 14.0% (no-RT; 95% CI, 8.9 to 21.1), and 40.6% (RT, 95% CI, 25.5 to 57.8), respectively. After adjustment for stroke severity, this difference between the no-RT and RT groups became non-significant. Symptomatic ICH was observed in 1 patient per group. HT was not associated with unfavourable outcome (mRS 3-6) at 3-months in multivariable analysis. Resumption of OAC after stroke was delayed in patients with HT compared to those without (15 d [IQR, 5-26] vs. 1 d [0-4], P<0.001). CONCLUSIONS The frequency and severity of HT after stroke on NOAC appears similar to previous reports for vitamin K antagonists and no anticoagulation. Whether asymptomatic HT should delay resumption of preventive anticoagulation requires further investigation.


title: Impact of transapical aortic cannulation for acute type A aortic dissection.

text: OBJECTIVE Early and mid-term result of transapical aortic (TAA) cannulation technique was evaluated compared with femoral artery (FA) cannulation in Acute Type A Aortic Dissection(AAAD). METHODS From January 2000 to October 2013, 80 consecutive patients with AAAD were underwent the ascending aortic replacement at Nagasaki Kouseikai Hospital. These patients were divided into two groups according to the cannulation site, FA cannulation (n = 34) and TAA cannulation (n = 46). Early and mid-term outcomes were compared between two groups. RESULT Preoperative patient characteristics were almost comparable between groups. The time from skin incision to starting cardiopulmonary bypass (CPB) was significantly shorter in the TAA group (45 ± 16 vs 23 ± 5.1 min; P <0.001). There were no significant differences in post-operative cerebral infarction in two groups (17% versus 11%; P = NS). The operative mortality rate was 8.8% in FA group and 4.3% in TAA group (P = NS). During follow up (mean, 6.8 years), survival at 3 years and 5 years was 77.4% and 71.9% in TAA group and 76.3% and 73.8% in FA group, respectively. CONCLUSION The postoperative morbidity and mortality between the two groups were almost the same. TAA cannulation for acute Type A aortic dissection is faster, easy and safe with acceptable early and mid-term outcome.


title: Bovine Respiratory Disease Treatment Failure: Impact and Potential Causes.

text: Bovine respiratory disease (BRD) is often attributed to complex interactions between the host, pathogen, and the environment. Likewise, many BRD treatment failures result from interactions between the host, pathogen, environment, drug, and drug administrator. Investigating and addressing the underlying causes of BRD treatment failures can improve clinical outcomes and animal welfare of future cases, improve morale of employees, reduce direct costs of dealing with BRD treatment failures, refine antimicrobial prescribing practices, and advance antimicrobial stewardship. This article discusses these interactions and provides guidance to veterinary practitioners on evaluating the success of treatment protocols.


docid: qflhtlbu

title: Complete genome sequence of a Chinese virulent porcine epidemic diarrhea virus strain.

text: CH/S is a virulent porcine epidemic diarrhea virus (PEDV) strain and is used as the virulent strain to evaluate the protection rates of vaccines against PEDV infection in China. Here, we report the complete genome sequence of strain CH/S, which may aid in understanding the molecular characteristics of this strain.


title: The etiology of community-acquired pneumonia among children under 5 years of age in mainland China, 2001-2015: A systematic review.

text: BACKGROUND The aim of this systematic review was to examine the etiology of community-acquired pneumonia (CAP) among Chinese children younger than 5 y and provide evidence for further cost-effectiveness analyses for vaccine development, diagnostic strategies and empirical treatments. METHODS The literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data were obtained by searching PubMed, Embase, Web-of Science, and the Chinese databases Wanfang Data and China National Knowledge Infrastructure. All CAP etiological studies on children under 5 y of age from China published in Chinese and English between the years of 2001 and 2015 were included. A total of 48 studies were included in the final review, comprising 100 151 hospitalized children with CAP episodes. Heterogeneity and the percentage of variation between studies was analyzed based on Q statistic and I2 indices, respectively. Random effect models were used to calculate the weighted average rate in all analyses. RESULTS The most frequently detected bacterial agents were Klebsiella pneumoniae (5.4%), Streptococcus pneumoniae (5.2%), Escherichia coli (5.2%), Staphylococcus aureus (3.9%), Haemophilus influenza (3.6%) and Haemophilus parainfluenzae (3.3%). The most frequently detected viruses were human rhinovirus (20.3%, in just 2 studies), respiratory syncytial virus (RSV, 17.3%), human bocavirus (9.9%), parainfluenza virus (5.8%), human metapneumovirus (3.9%) and influenza (3.5%). Mycoplasma pneumoniae and Chlamydophila pneumoniae were identified in 9.5% and 2.9%, respectively, of children under 5 y of age with CAP. CONCLUSION This article provides the most comprehensive analysis to date of the factors contributing to CAP in children under 5 y of age. S. pneumoniae, H. influenzae and influenza were the most common vaccine-preventable diseases in children. Corresponding, vaccines should be introduced into Chinese immunization programs, and further economic evaluations should be conducted. RSV is common in Chinese children and preventative measures could have a substantial impact on public health. These data also have major implications for diagnostic strategies and empirical treatments.


title: Polyanalgesic Consensus Conference--2012: consensus on diagnosis, detection, and treatment of catheter-tip granulomas (inflammatory masses).

text: INTRODUCTION Continuous intrathecal infusion of drugs to treat chronic pain and spasticity has become a standard part of the algorithm of care. The use of opioids has been associated with noninfectious inflammatory masses at the tip of the intrathecal catheter, which can result in neurologic complications. METHODS The Polyanalgesic Consensus Conference is a meeting of a group of well-published and experienced practitioners; the purpose of the meeting is to update the standard of care for intrathecal therapies to reflect current knowledge gleaned from literature and clinical experience. An exhaustive literature search was performed, and information from this search was provided to panel members. Analysis of the published literature was coupled with the clinical experience of panel participants to form recommendations regarding intrathecal inflammatory masses or granulomas. RESULTS The panel has made recommendations for the prevention, diagnosis, and management of intrathecal granulomas. CONCLUSION The use of chronic infusions of intrathecal opioids is associated with the formation of inflammatory masses at the intrathecal catheter tip in a small minority of treated patients. Nonetheless, the appearance of these space-occupying lesions can lead to devastating neurologic sequelae. The prevention, early detection, and successful treatment of intraspinal granulomas are important considerations when offering intrathecal drug therapy to patients with chronic intractable pain.


title: Interplay between innate immunity and negative-strand RNA viruses: towards a rational model.

text: The discovery of a new class of cytosolic receptors recognizing viral RNA, called the RIG-like receptors (RLRs), has revolutionized our understanding of the interplay between viruses and host cells. A tremendous amount of work has been accumulating to decipher the RNA moieties required for an RLR agonist, the signal transduction pathway leading to activation of the innate immunity orchestrated by type I interferon (IFN), the cellular and viral regulators of this pathway, and the viral inhibitors of the innate immune response. Previous reviews have focused on the RLR signaling pathway and on the negative regulation of the interferon response by viral proteins. The focus of this review is to put this knowledge in the context of the virus replication cycle within a cell. Likewise, there has been an expansion of knowledge about the role of innate immunity in the pathophysiology of viral infection. As a consequence, some discrepancies have arisen between the current models of cell-intrinsic innate immunity and current knowledge of virus biology. This holds particularly true for the nonsegmented negative-strand viruses (Mononegavirales), which paradoxically have been largely used to build presently available models. The aim of this review is to bridge the gap between the virology and innate immunity to favor the rational building of a relevant model(s) describing the interplay between Mononegavirales and the innate immune system.


title: Ictal apnea linked to contralateral spread of temporal lobe seizures: Intracranial EEG recordings in refractory temporal lobe epilepsy.

text: PURPOSE Respiratory mechanisms are implicated in sudden unexpected death in epilepsy (SUDEP). We previously demonstrated a high incidence of ictal hypoxemia in temporal lobe seizures. We now report on the temporal relationship between ictal apnea and seizure onset and spread in patients undergoing video-EEG (electroencephalography) telemetry (VET) with intracranial electrodes. METHODS Ten patients with medically refractory temporal lobe epilepsy (TLE) undergoing VET were studied. Data from synchronously recorded digital pulse oximetry (SaO(2)), end-tidal CO(2) (ETCO(2)), nasal airflow, abdominal excursions, and electrocardiography were obtained. RESULTS Sixty-one seizures were captured. SaO(2) in the ictal/postictal period was available for 52 seizures, apnea onset times for 27 seizures, and ETCO(2) for 16 seizures. Apneas occurred only when seizures spread to the contralateral temporal lobe. The mean delay to apnea onset was significantly shorter after contralateral seizure spread (2.87 s) than after seizure onset (58.4 s); p < 0.001. The mean SaO(2) nadir with partial seizures or partial seizures prior to secondary generalization was 89.4 +/- 8.6% (91.5, 69-100). Following generalized convulsions the mean oxygen saturation nadir was 75.8 +/- 10.6% (78.5, 58-90). ETCO(2) elevations occurred with each ictal desaturation below 85%. CONCLUSIONS There is a close temporal relationship between spread of seizures to the contralateral hemisphere and the onset of seizure-associated apnea. Apnea onsets are more tightly linked to time of contralateral spread than to time of seizure onset. Patients with TLE in whom there is evidence of contralateral seizure spread may be at higher risk for ictal-related respiratory dysfunction than those in whom seizures remain unilateral.


title: Protocol for the SAFEST review: the Shock-Absorbing Flooring Effectiveness SysTematic review including older adults and staff in hospitals and care homes.

text: INTRODUCTION Falls in hospitals and care homes are a major issue of international concern. Inpatient falls are the most commonly reported safety incident in the UK's National Health Service (NHS), costing the NHS £630 million a year. Injurious falls are particularly life-limiting and costly. There is a growing body of evidence on shock-absorbing flooring for fall-related injury prevention; however, no systematic review exists to inform practice. METHODS AND ANALYSIS We will systematically identify, appraise and summarise studies investigating the clinical and cost-effectiveness, and experiences of shock-absorbing flooring in hospitals and care homes. Our search will build on an extensive search conducted by a scoping review (inception to May 2016). We will search electronic databases (AgeLine, CINAHL, MEDLINE, NHS Economic Evaluation Database, Scopus and Web of Science; May 2016-present), trial registries and grey literature. We will conduct backward and forward citation searches of included studies, and liaise with study researchers. We will evaluate the influence of floors on fall-related injuries, falls and staff work-related injuries through randomised and non-randomised studies, consider economic and qualitative evidence, and implementation factors. We will consider risk of bias, assess heterogeneity and explore potential effect modifiers via subgroup analyses and sensitivity analyses. Where appropriate we will combine studies through meta-analysis. We will use the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach to evaluate the quality of evidence and present the results using summary of findings tables, and adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. ETHICS AND DISSEMINATION We will follow the ethical principles of systematic review conduct, by attending to publication ethics, transparency and rigour. Our dissemination plan includes peer-reviewed publication, presentations, press release, stakeholder symposium, patient video and targeted knowledge-to-action reports. This review will inform decision-making around falls management in care settings and identify important directions for future research. PROSPERO REGISTRATION NUMBER CRD42019118834.


title: Translational medicine policy issues in infectious disease.

text: The European Academies Science Advisory Council has published a series of reports on infectious disease policy issues, analyzing priorities for building the science base as part of public health strategy. Among current challenges facing the European Union are the needs to tackle antibiotic resistance, promote vaccine innovation, prepare for the emergence of novel zoonoses, and integrate research approaches to human and animal health. The scientific community must help public policy-makers to address the organization, balance, and sustainability of research funding and infrastructure; encourage the creation of a more supportive regulatory environment for translational medicine; and evaluate new models for public-private partnership to facilitate innovation.


Covid-19: Trump declares intention to "re-open economy" within weeks against experts' advice.


Third-quarter biotech job picture.


title: Re-evaluating the Utility of Stress Ulcer Prophylaxis in the Critically Ill Patient: A Clinical Scenario-Based Meta-Analysis.

text: STUDY OBJECTIVE Because recent studies have challenged the efficacy of stress ulcer prophylaxis (SUP) in the critically ill patient, our objective was to evaluate the efficacy of SUP with proton pump inhibitors (PPIs) or histamine2 -receptor antagonists (H2 RAs) against placebo, control, no therapy, or enteral nutrition alone in critically ill adults. DESIGN Meta-analysis with trial sequential analysis (TSA) of 34 randomized controlled trials. PATIENTS A total of 3220 critically ill adults who received PPIs or H2 RAs versus placebo, control, no therapy, or enteral nutrition. MEASUREMENTS AND MAIN RESULTS A systematic review was performed using a random effects meta-analysis with TSA according to a predefined protocol. Randomized controlled trials comparing PPIs or H2 RAs with either placebo, control, no therapy, or enteral nutrition alone were identified through a comprehensive search of the literature. Two blinded reviewers independently assessed studies for inclusion, risk of bias, and extracted data using Cochrane Collaborative methodology. The predefined primary outcomes were clinically important, overt, and any (clinically important plus overt) gastrointestinal bleeding. Secondary outcomes included pneumonia, Clostridium difficile-associated diarrhea (CDAD), and mortality. Subgroup analyses were conducted for the primary outcome by PPI or H2 RA use, intensive care unit (ICU) subtype, studies published after early goal-directed therapy (EGDT), the presence of risk factors for stress ulceration, and enteral nutrition use. Of the 34 trials included, 33 were judged as high risk of bias and 1 was judged as low risk. Use of SUP significantly reduced clinically important bleeding (risk ratio [RR] 0.53, 95% confidence interval [CI] 0.37-0.76, p<0.001; I2 = 0%), overt bleeding (RR 0.55, 95% CI 0.39-0.76, p=0.0003; I2 = 53%), and any bleeding (RR 0.54, 95% CI 0.41-0.71, p<0.00001; I2 = 58%). TSA confirmed these findings. No significant differences in pneumonia, CDAD, or mortality were noted. Subgroup analyses revealed significant reductions in clinically important bleeding with SUP in neurosurgical patients (RR 0.37, p<0.05) but not in surgery/trauma or medical ICU patients with risk factors. SUP provided no benefit in studies published after EGDT. SUP significantly reduced clinically important bleeding regardless of the use of enteral nutrition (p<0.05). CONCLUSION This meta-analysis demonstrated that SUP use was associated with significant reductions in bleeding but not mortality. SUP should not be abandoned until large randomized trials demonstrate the futility of this intervention.


docid: iilyeoxb

title: COVID-19 Curbside Consults at www.CCJM.org.


Pandemic research: UK must coordinate.


title: ESBL-Producing and Macrolide-Resistant Shigella sonnei Infections among Men Who Have Sex with Men, England, 2015.

text: In England in 2015, Shigella sonnei isolates from men who have sex with men produced extended-spectrum β-lactamases and exhibited macrolide resistance. Whole-genome sequencing showed a close relationship among the isolates, which harbored a plasmid that was previously identified in a shigellosis outbreak among this population but has acquired a mobile element.


title: Effect of heliox on end-tidal CO2 measurement in healthy adults.

text: BACKGROUND Therapeutic gases and other modalities delivered by inhalation may affect the accuracy of capnographic measurements in 2 ways. First is the specificity of the measurement of CO2 within the device, and second is the dilution effect of supplemental gases in the ambient air during CO2 sampling by the device. Our goal was to determine if variables such as inhaled gas composition, gas flows delivered via non-rebreather mask, and mouth open or closed affect measurements of end-tidal CO2 pressure (PETCO2) measured with the Capnostream 20 capnograph. METHODS We measured PETCO2 and breathing frequency by capnography in 20 adult normal subjects, with coaching to maintain respiratory frequency between 10 and 20 breaths/min. SpO2 was monitored to detect hypoxemia. A 6 min wash-out period occurred between each 6 min level of testing. RESULTS A mixed models analysis revealed that the mean ± SD PETCO2 for all subjects and flows while breathing heliox (37 ± 5 mm Hg) was not different (P = .50) from the value while breathing room air (36 ± 5 mm Hg). Repeated measurements with given subjects over 6 min periods of breathing spontaneously 0 L/min, with 10 L/min, and with 15 L/min of either air or heliox showed no difference in PETCO2 related to flow: P = .97 for 0 L/min vs 10 L/min, P = .87 for 0 L/min vs. 15 L/min. CONCLUSIONS In normal subjects, PETCO2 measurements with the Capnostream 20 were not affected by heliox or gas flow at 10 or 15 L/min through a non-rebreathing mask.


title: A newly developed tracheal tube offering 'pressurised sealing' outperforms currently available tubes in preventing cuff leakage: A benchtop study.

text: BACKGROUND No currently used tracheal tube offers full protection against aspiration of oropharyngeal secretions into the lower airways. OBJECTIVE We developed a tracheal tube equipped with two polyvinylchloride (PVC) cuffs with a supplementary port opening between the cuffs through which a continuous positive pressure of 5 cmH2O is provided [double-cuffed PVC (PVCdc)]. We compared this PVCdc with four different cuff types (cylindrical PVC, conical PVC, cylindrical polyurethane and conical polyurethane). DESIGN A comparison study using an in-vitro benchtop model of an artificial rigid trachea. INTERVENTIONS Tracheal tubes were placed in the artificial trachea. Both cuffs were kept inflated at 25 cmH2O. Total 3 ml dyed water was placed above the cuff and leakage recorded under static and dynamic [5 cmH2O positive end-expiratory pressure (PEEP) alone or positive pressure ventilation plus 5 cmH2O PEEP] conditions. At the end of the dynamic experiments, PEEP was zeroed (PEEP alone) or the tracheal tubes were disconnected from the ventilator (positive pressure ventilation plus PEEP). RESULTS In the static model, leakage flows [medians (range)] were 9.8 (6.2 to 20) for the cylindrical PVC, 1.3 (0.2 to 3.8) for the conical PVC, 0.03 (0.007 to 0.1) for the cylindrical polyurethane, 0.04 (0.003 to 0.2) for the conical polyurethane and 0.0 (0.0 to 0.0) ml min for the PVCdc cuff (P < 0.001, PVCdc vs. all other cuffs). In the dynamic setting, no leakage was detected for up to 60 min with any of the cuffs studied. Loss of PEEP or tracheal tube disconnection resulted in dye inflow alongside all cuffs except for the PVCdc (P < 0.001, PVCdc vs. all other cuffs). CONCLUSION A 'pressure seal' incorporated in a double-cuffed tracheal tube prevented fluid passage into the lower airways. Clinically, this may translate into absence of inflow of bacteriologically contaminated secretions into the lungs and thus a lower incidence of ventilator-associated infection.


title: Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease.

text: Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and that has now been declared a global pandemic by the World Health Organization. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In this context, this study aimed to evaluate in silico the molecular interactions of drugs with therapeutic indications for treatment of COVID-19 (Azithromycin, Baricitinib and Hydroxychloroquine) and drugs with similar structures (Chloroquine, Quinacrine and Ruxolitinib) in docking models from the SARS-CoV-2 main protease (M-pro) protein. The results showed that all inhibitors bound to the same enzyme site, more specifically in domain III of the SARS-CoV-2 main protease. Therefore, this study allows proposing the use of baricitinib and quinacrine, in combination with azithromycin; however, these computer simulations are just an initial step for conceiving new projects for the development of antiviral molecules.


Covid-19: Patients who are improving could have treatment withdrawn if others could benefit more.


title: Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

text: OBJECTIVES The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. METHODS A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). RESULTS The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. CONCLUSIONS Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.


title: Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods.

text: BACKGROUND Hypothermia is being used with increasing frequency to prevent or mitigate various types of neurologic injury. In addition, symptomatic fever control is becoming an increasingly accepted goal of therapy in patients with neurocritical illness. However, effectively controlling fever and inducing hypothermia poses special challenges to the intensive care unit team and others involved in the care of critically ill patients. OBJECTIVE To discuss practical aspects and pitfalls of therapeutic temperature management in critically ill patients, and to review the currently available cooling methods. DESIGN Review article. INTERVENTIONS None. MAIN RESULTS Cooling can be divided into three distinct phases: induction, maintenance, and rewarming. Each has its own risks and management problems. A number of cooling devices that have reached the market in recent years enable reliable maintenance and slow and controlled rewarming. In the induction phase, rapid cooling rates can be achieved by combining cold fluid infusion (1500-3000 mL 4 degrees C saline or Ringer's lactate) with an invasive or surface cooling device. Rapid induction decreases the risks and consequences of short-term side effects, such as shivering and metabolic disorders. Cardiovascular effects include bradycardia and a rise in blood pressure. Hypothermia's effect on myocardial contractility is variable (depending on heart rate and filling pressure); in most patients myocardial contractility will increase, although mild diastolic dysfunction can develop in some patients. A risk of clinically significant arrhythmias occurs only if core temperature decreases below 30 degrees C. The most important long-term side effects of hypothermia are infections (usually of the respiratory tract or wounds) and bedsores. CONCLUSIONS Temperature management and hypothermia induction are gaining importance in critical care medicine. Intensive care unit physicians, critical care nurses, and others (emergency physicians, neurologists, and cardiologists) should be familiar with the physiologic effects, current indications, techniques, complications and practical issues of temperature management, and induced hypothermia. In experienced hands the technique is safe and highly effective.


title: Identification and differentiation of human schistosomes by polymerase chain reaction.

text: Recent increasing number of travelers, immigrants and foreign workers from schistosomiasis endemic area has thus resulted in the importation of schistosomiasis to non-endemic countries. To avoid ova-induced pathogenicity, sensitive and specific diagnostic means at an early stage of infection are therefore crucial. In this study, we developed polymerase chain reaction (PCR) primers specific for human schistosome species. The PCR products were obtained in a species-specific manner (479 bp, Schistosoma mansoni; 365 bp, S. haematobium; 614 bp, S. japonicum; 303 bp, S. mekongi) and were detectable from 0.01 pg of total worm DNA (S. haematobium, S. japonicum, S. mekongi). The primer sets were also available for multiplex use. Although some difficulties were experienced in amplifying the parasite DNA from the infected animals, schistosome DNA could be detected from one day post infection. The PCR method described herein will therefore be beneficial to detect human schistosomiasis, after some improvements in this method.


Redefining physicians' role in assisted dying.


title: Hiatal hernia repair with the use of biologic meshes: a literature review.

text: During the past few years, biologic meshes, primarily evolved for routine and complex cases of abdominal wall reconstruction, have been evaluated in clinical cases and experimental models. Although there is published experience on the use of small intestine submucosa and human cadaveric dermis in hiatal hernia repair with encouraging results, porcine dermal collagen (PDC) matrix has not been subject of study to date in this patient population. A systematic review of the literature was conducted, aiming at evaluating the biomechanical characteristics of cross-linked PDC in comparison to synthetic and biologic meshes. Evidence shows that cross-linked PDC is superior to synthetic meshes in terms of incorporation, adhesion formation, and mesh fibrosis; their biodynamic and biotechnical characteristics do not seem to be superior to other bioprosthetic materials according to current data. The clinical and experimental results of cross-linked PDC implants justify their pilot clinical evaluation in hiatal hernia patients.


title: Temporal relationship between environmental influenza A and Epstein-Barr viral infections and high multiple sclerosis relapse occurrence.

text: BACKGROUND Multiple sclerosis (MS) relapses have been associated with viral and bacterial infection epidemics in MS patients who have not used interferon. OBJECTIVES We studied whether environmental viral infections in the general population can be associated with increased MS relapse occurrence using retrospective data from 1986 to 1995 when interferons were not yet available. METHODS Logistic regression modelling was used to compare retrospectively the monthly relapse occurrence from 407 MS patients in Turku University hospital archives and data on ten different specifically diagnosed viral infection epidemics in the general population of Southwestern Finland from 1986 to 1995. The outcome was the odds ratio (OR) of very high relapse occurrence versus low relapse occurrence, or moderate versus low relapse occurrence. RESULTS After a peak in diagnosed influenza A cases in the general population, the MS relapse occurrence was 6.5 times more likely to be very high (95% CI 1.8-24.0) and 7.1 times more likely to be moderately high (95% CI 1.5-33.2). An increase in MS relapse counts also followed Epstein-Barr virus (EBV) infections (OR 4.4, 95% CI 1.3-15.1), but we found no significant association with adenovirus infections and MS relapses. The MS relapse occurrence was lowest in the summer months July-August (Chi-square test, p<0.01). CONCLUSIONS Our findings suggest that influenza A and EBV viral infections in the general population are associated with a higher occurrence of exacerbations in MS patients, and thus environmental infection data should be included in epidemiological models on MS relapses.


title: [Critical illness polyneuropathy and myopathy as neurological complications of sepsis].

text: Intensive care unit acquired weakness (ICUAW) is a frequent and severe complication of intensive care management. Within ICUAW critical illness polyneuropathy (CIP) and myopathy (CIM) can be differentiated. The major symptom of ICUAW is progressive quadriparesis, which makes weaning from the respirator more difficult, can appear early after admission to an ICU and can often be detected several months after discharge from the ICU. The pathophysiology of ICUAW is multifactorial and complex. Potential therapeutic approaches are the early and sufficient therapy of mulitorgan dysfunction, optimal control of glucose levels as well as early and intensive physiotherapy. This review article discusses the data on incidence, pathophysiology, diagnostic approaches and prognosis of ICUAW.


title: Expression and prognostic significance of pyruvate dehydrogenase kinase 1 in bladder urothelial carcinoma.

text: Muscular infiltrating bladder urothelial carcinoma (MIBC) is a highly malignant disease with a poor prognosis. Radical cystectomy is the standard treatment. However, due to surgery and postoperative complications, the quality of life of patients is seriously affected. Therefore, it is increasingly important to find prognostic markers and new therapeutic targets for MIBC. Here, we investigated the expression of PDK1, a key regulator of glucose metabolism, in bladder urothelial carcinoma (BLCA) and its effect on prognosis. The expression pattern of PDK1 was examined by bioinformatics analysis and immunohistochemistry. A total of 101 cases of BLCA were selected for tissue microarrays (TMAs) that contained both tumour and paired normal tissues. We demonstrated that PDK1 expression was correlated with tumour grade and Ki67expression in our TMA cohort (all p values < 0.05). Kaplan-Meier survival analysis showed that patients with MIBC with high PDK1 expression had a worse prognosis than patients with low PDK1 expression (p = 0.016). Multifactor risk analysis showed that increased PDK1 expression was an independent prognostic factor affecting the overall survival of MIBC patients. GSEA showed that the mTOR pathway, HIF pathway, glycolysis, PI3K/AKT/mTOR signalling, etc. were differentially enriched in the PDK1 high expression phenotype. Hence, PDK1 may be a prognostic and therapeutic target for MIBC.


title: Cytokines in Chronic Rhinosinusitis. Role in Eosinophilia and Aspirin-exacerbated Respiratory Disease.

text: RATIONALE The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear. OBJECTIVES To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues. METHODS Expression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay. MEASUREMENTS AND MAIN RESULTS CRSwNP NP had increased levels of type 2 mediators, including IL-5 (P < 0.001), IL-13 (P < 0.001), eotaxin-2 (P < 0.001), and monocyte chemoattractant protein (MCP)-4 (P < 0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-γ messenger RNA or protein was low and not different among the chronic rhinosinusitis subtypes examined. Compared with CRSwNP, AERD NP had elevated protein levels of eosinophil cationic protein (ECP) (P < 0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < 0.01), and MCP-1 (P = 0.01), as well as decreased gene expression of tissue plasminogen activator (tPA) (P = 0.02). Despite the higher eosinophilia in AERD, there was no associated increase in type 2 mediator protein levels observed. CONCLUSIONS CRSwNP was characterized by a predominant type 2 inflammatory environment, whereas CRSsNP did not reflect a classic type 1 milieu, as has been suggested previously. AERD can be distinguished from CRSwNP by elevated ECP levels, but this enhanced eosinophilia is not associated with elevations in traditional type 2 inflammatory mediators associated with eosinophil proliferation and recruitment. However, other factors, including GM-CSF, MCP-1, and tPA, may be important contributors to AERD pathogenesis.


title: Community-Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs.

text: SUMMARYPatients undergoing solid-organ transplantation (SOT) or allogeneic hematopoietic cell transplantation (HCT) are at increased risk for infectious complications. Community-acquired respiratory viruses (CARVs) pose a particular challenge due to the frequent exposure pre-, peri-, and posttransplantation. Although influenza A and B viruses have a top priority regarding prevention and treatment, recent molecular diagnostic tests detecting an array of other CARVs in real time have dramatically expanded our knowledge about the epidemiology, diversity, and impact of CARV infections in the general population and in allogeneic HCT and SOT patients. These data have demonstrated that non-influenza CARVs independently contribute to morbidity and mortality of transplant patients. However, effective vaccination and antiviral treatment is only emerging for non-influenza CARVs, placing emphasis on infection control and supportive measures. Here, we review the current knowledge about CARVs in SOT and allogeneic HCT patients to better define the magnitude of this unmet clinical need and to discuss some of the lessons learned from human influenza virus, respiratory syncytial virus, parainfluenzavirus, rhinovirus, coronavirus, adenovirus, and bocavirus regarding diagnosis, prevention, and treatment.


title: Agonist and antagonist recognition by RIG-I, a cytoplasmic innate immunity receptor.

text: Cytoplasmic RNA receptors are important in the detection of and response to viral infections. We analyzed ligand recognition by the retinoic acid-inducible protein I (RIG-I) protein in biochemical assays and in transiently transfected cells and characterized the requirements for both single- and double-stranded RNA agonists for RIG-I activation of signaling. RIG-I mutants such as K270A and T409A/S411A that were defective in signaling with triphosphorylated single-stranded RNAs were perfectly capable of signaling with dsRNAs. Furthermore, phosphorothioated oligodeoxynucleotides were found to antagonize RIG-I signaling. Both agonists and antagonist bind purified RIG-I protein and a truncated RIG-I protein that lacked the signaling domain. The agonists were necessary to activate RIG-I ATPase activity in vitro, whereas antagonist inhibited ATPase activity. Differential scanning fluorometry showed that RIG-I bound to agonists, and antagonists have different denaturation properties, suggesting a difference in protein conformations. Last, single particle reconstruction was used to generate three-dimensional models of the RIG-I dimers in complex with an agonist and an antagonist. The two complexes exhibited dramatically different structures.


title: Treatment of Insulinomas by Laparoscopic Radiofrequency Ablation: Case Reports and Literature Review.

text: Despite its rarity, insulinoma is the most common type of pancreatic endocrine neoplasm, with an occurrence of 1 to 5 per million per year in the population. Surgical resection or enucleation is the first line of curative treatment choice for insulinoma. Eight patients with symptomatic insulinomas treated by radiofrequency ablation have been described since 2009. In the past two years, we treated two patients with symptomatic insulinomas (one in the pancreatic tail and the other in the pancreatic neck) successfully using laparoscopic radiofrequency ablation. Both patients achieved complete elimination without any significant complications. Our study suggests laparoscopic radiofrequency ablation could be developed as a safe and effective alternative treatment to surgery for the patients with insulinomas who refuse or are not eligible for surgery.


docid: obdqkbtw

title: Banxia Xiexin Decoction () Treats Diabetic Gastroparesis through PLC-IP3-Ca2+/NO-cGMP-PKG Signal Pathway.

text: OBJECTIVE To test the effect of Banxia Xiexin Decoction (, BXD) on the contraction and relaxation of gastric smooth muscle (SM) in diabetic gastroparesis (DGP) model rats, and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro. METHODS Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table: control group, model group, high-, medium- and low-dose BXD groups (9.2, 4.6 and 1.8 g/(kg·d), respectively), and domperidone group (10 mg/(kg·d)), 10 rats per group. DGP model was established initially by a single intraperitoneal injection of streptozotocin (STZ), and was confirmed by recording gastric emptying, intestinal transport velocity and gastric myoelectric activity of rats after 2 months. Each group was treated with a corresponding drug for 4 weeks. The mRNA and protein expressions of phospholipase C (PLC), inositol triphosphate (IP3), neuronal nitric oxide synthase (nNOS), and cyclic guanosine monophosphate (cGMP) dependent protein kinase G (PKG) were detected by reverse transcription-polymerase chain reaction and Western blot, respectively, while nitric oxide (NO) and cGMP expressions were detected by enzyme-linked immunosorbent assay. Gastric tissues were obtained from rats for primary cell culture preparation. Gastric SM cells were treated with 0.8 µmol/L of STZ or STZ plus 1,000, 500 and 200 µg/mL of BXD or STZ plus 2.5 µmol/mL of domperidone for 24, 48, 72 or 96 h, respectively. The length of gastric SM cells and intracellular Ca2+ concentration ([Ca2+]i) before and after BXD treatment was measured. RESULTS Compared with the model group, high- and medium-dose BXD and domperidone significantly increased the expressions of PLC, IP3, NO, nNOS, cGMP and PKG in rat's gastric tissue (P<0.01). Gastric SM cells treated with BXD showed a time- and dose-dependent increase in cell viability (P<0.01). The treatment with high- and medium-dose BXD and domperidone inhibited the increase in gastric SM cells length and increased [Ca2+]i compared with the model cells (P<0.01). CONCLUSIONS Treatment with high- and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats. The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP3-Ca2+/NO-cGMP-PKG signal pathway.


title: Inhibition of Cytosolic Phospholipase A2α Impairs an Early Step of Coronavirus Replication in Cell Culture.

text: Coronavirus replication is associated with intracellular membrane rearrangements in infected cells, resulting in the formation of double-membrane vesicles (DMVs) and other membranous structures that are referred to as replicative organelles (ROs). The latter provide a structural scaffold for viral replication/transcription complexes (RTCs) and help to sequester RTC components from recognition by cellular factors involved in antiviral host responses. There is increasing evidence that plus-strand RNA (+RNA) virus replication, including RO formation and virion morphogenesis, affects cellular lipid metabolism and critically depends on enzymes involved in lipid synthesis and processing. Here, we investigated the role of cytosolic phospholipase A2α (cPLA2α) in coronavirus replication using a low-molecular-weight nonpeptidic inhibitor, pyrrolidine-2 (Py-2). The inhibition of cPLA2α activity, which produces lysophospholipids (LPLs) by cleaving at the sn-2 position of phospholipids, had profound effects on viral RNA and protein accumulation in human coronavirus 229E-infected Huh-7 cells. Transmission electron microscopy revealed that DMV formation in infected cells was significantly reduced in the presence of the inhibitor. Furthermore, we found that (i) viral RTCs colocalized with LPL-containing membranes, (ii) cellular LPL concentrations were increased in coronavirus-infected cells, and (iii) this increase was diminished in the presence of the cPLA2α inhibitor Py-2. Py-2 also displayed antiviral activities against other viruses representing the Coronaviridae and Togaviridae families, while members of the Picornaviridae were not affected. Taken together, the study provides evidence that cPLA2α activity is critically involved in the replication of various +RNA virus families and may thus represent a candidate target for broad-spectrum antiviral drug development.IMPORTANCE Examples of highly conserved RNA virus proteins that qualify as drug targets for broad-spectrum antivirals remain scarce, resulting in increased efforts to identify and specifically inhibit cellular functions that are essential for the replication of RNA viruses belonging to different genera and families. The present study supports and extends previous conclusions that enzymes involved in cellular lipid metabolism may be tractable targets for broad-spectrum antivirals. We obtained evidence to show that a cellular phospholipase, cPLA2α, which releases fatty acid from the sn-2 position of membrane-associated glycerophospholipids, is critically involved in coronavirus replication, most likely by producing lysophospholipids that are required to form the specialized membrane compartments in which viral RNA synthesis takes place. The importance of this enzyme in coronavirus replication and DMV formation is supported by several lines of evidence, including confocal and electron microscopy, viral replication, and lipidomics studies of coronavirus-infected cells treated with a highly specific cPLA2α inhibitor.


title: Effectiveness of an Eight-Week Web-Based Mindfulness Virtual Community Intervention for University Students on Symptoms of Stress, Anxiety, and Depression: A Randomized Controlled Trial.

text: BACKGROUND A student mental health crisis is increasingly acknowledged and will only intensify with the COVID-19 crisis. Given accessibility of methods with demonstrated efficacy in reducing depression and anxiety (e.g., mindfulness meditation and cognitive behavioural therapy [CBT]) and limitations imposed by geographic obstructions and localized expertise, web-based alternatives have become vehicles for scaled-up delivery of benefits at modest cost. Mindfulness Virtual Community (MVC), a web-based program informed by cognitive behavioral therapy (CBT) constructs and featuring online videos, discussion forums, and videoconferencing was developed to target depression, anxiety, and experiences of excess stress among university students. OBJECTIVE Assessment of an eight-week web-based mindfulness and cognitive behavioural therapy (CBT) program in reducing symptoms of depression, anxiety, and stress (primary outcomes) and increasing mindfulness (secondary outcome) within a randomized controlled trial (RCT) with undergraduate students at a large Canadian university. METHODS An RCT was designed to assess undergraduate students (n = 160) who were randomly allocated to a web-based guided mindfulness-CBT condition (n = 80) or to a waitlist control condition (WLC) (n = 80). The eight-week intervention consisted of a web-based platform consisting of (1) 12 video-based modules with psycho-education on students' preidentified life challenges and applied mindfulness practice; (2) anonymous peer-to-peer discussion forums; and (3) anonymous, group-based, professionally guided 20-minute live videoconferences. The outcomes (depression, anxiety, stress, and mindfulness) were measured via online survey at baseline and at eight weeks post-intervention using the Patient Health Questionniare-9 (PHQ9), the Beck Anxiety Inventory (BAI), the Perceived Stress Scale (PSS), and the Five Facets Mindfulness Questionnaire Short Form (FFMQ-SF). Analyses employed generalized estimation equation (GEE) methods with AR(1) covariance structures and were adjusted for possible covariates (gender, age, country of birth, ethnicity, English as first language, paid work, unpaid work, relationship status, physical exercise, self-rated health, and access to private mental health counselling). RESULTS Of the 159 students who provided T1 data, 32 were males and 125 were females with a mean age of 22.55 years. Participants in the MVC (n = 79) and WLC (n = 80) groups were similar in sociodemographic characteristics at T1 with the exception of gender and weekly hours of unpaid volunteer work. At post-intervention follow-up, per the adjusted comparisons, there were statistically significant between-group reductions in depression scores (β = -2.21, P = .01) and anxiety scores (β = -4.82, P = .006) and a significant increase in mindfulness scores (β = 4.84, P = .02) compared to WLC. There were no statistically significant differences in perceived stress for MVC (β = .64, P = .48) compared to WLC. CONCLUSIONS With MVC intervention, there were significantly reduced depression and anxiety symptoms but no significant effect on perceived stress. Online mindfulness interventions can be effective in addressing common mental health conditions among post-secondary populations on a large scale, simultaneously reducing the current burden on traditional counselling services. CLINICALTRIAL https://doi.org/10.1186/ISRCTN12249616.


title: [Partial Nephrectomy in cT1 Renal Tumours: Conventional Laparoscopic Partial Nephrectomy Compared with LESS Partial Nephrectomy in SITUS Technique].

text: BACKGROUND Partial nephrectomy is the treatment of choice for clinical stage 1 renal tumours. Open partial nephrectomy is the standard operative technique. The use of minimally-invasive strategies such as laparoscopic, robot-assisted partial nephrectomy or laparoendoscopic single site (LESS) partial nephrectomy has increased in recent years. PATIENTS/MATERIAL AND METHODS In this retrospective study, patients undergoing laparoscopic partial nephrectomy between December 2008 and November 2013 were evaluated. All patients presented with renal lesions suspicious for malignancy. Operations were performed as conventional laparoscopic transperitoneal partial nephrectomies (cLPN) or LESS partial nephrectomies (LESS-PN) in SITUS technique (single incision transumbilical surgery). The aim of the study was to compare perioperative outcome parameters such as duration of surgery, time of ischaemia, complications, need for transfusion, conversion rates, changes in renal function and duration of hospital stay in both groups. RESULTS A total of 85 laparoscopic partial nephrectomies were performed in this study (72 cLPN and 13 LESS-PN). The average tumour size was 2.68±1.47 cm (cLPN) vs. 2.46±1.11 cm (LESS-PN). The mean duration of surgery was 175.17±50.026 min (cLPN) and 185.77±35.991 min (LESS-PN). 45 (62.5%) operations (cLPN) vs. 10 (76.9%) (LESS-PN) were performed in zero-ischaemia technique. There were no significant differences in perioperative outcome parameters between both groups. Postoperative complication rates (Clavien-Dindo≥3) were 11.1% (cLPN) vs. 7.7% (LESS-PN). CONCLUSIONS LESS partial nephrectomy in SITUS technique is an attractive alternative to conventional laparoscopic and open partial nephrectomy.


title: Recent progress in laparoscopic liver resection.

text: Laparoscopic liver resection has been performed in a limited number of centers, but worldwide the adoption and worldwide progress of the procedure have been slow since the 1990s, mainly because of the difficulty of controlling the hemorrhage during dissection of the hepatic parenchyma. In the late 2000s, technological innovations, improvement in surgical technique, and surgeons' accumulation of experience have led to more rapid progress of laparoscopic liver resection. Now, laparoscopic liver resection is able to be done by several approaches, for all locations of the tumors, for several diseases, with several types of resection, not only for tumors but for liver transplantation, with equivalent or better results compared with open surgery. Laparoscopic liver resection has been a standard procedure for left lateral sectionectomy or peripheral resection of the anterior liver, and other types of laparoscopic liver resection are expected to be standard in the near future.


title: Isolation and molecular characterization of porcine epidemic diarrhea viruses collected in Japan in 2014.

text: Porcine epidemic diarrhea virus (PEDV) is the etiological agent of porcine epidemic diarrhea (PED), which is threatening the swine industry all over the world. In Japan, although there were no reported PED cases from 2007 to 2012, a large-scale PED outbreak started in 2013, causing severe economic losses. Although several PEDV studies have been conducted in Japan, more PEDV isolates and sequence information are needed to understand the molecular biology and epidemiology of PEDV. Here, we isolated seven Japanese PEDV strains from intestinal tissue samples collected in 2014 and determined the spike gene sequences of 13 Japanese PEDV strains, including the above seven isolates. Phylogenetic analysis shows that all of the strains are genetically distinct from classical Japanese PEDV strains isolated prior to 2013 and can be classified into two different genotypes: 12 strains belong to the North American clade composed of recent highly pathogenic PEDV strains, and the remaining one strain belongs to the so-called insertion deletion (INDEL) clade. These data suggest multiple PEDV invasions from abroad to Japan. Notably, compared to classical Japanese strains, all of the recent Japanese strains have two amino acid substitutions in a known neutralizing epitope. In addition, one of the strains acquired an additional mutation in another neutralizing epitope that is highly conserved among PEDVs, including the classical and recent isolates. Our isolates and findings will be useful for future investigations aimed at understanding, controlling, and preventing PED.


title: A genetic score can identify men at high risk for prostate cancer among men with prostate-specific antigen of 1-3 ng/ml.

text: BACKGROUND The diagnostic performance of a genetic score based on single nucleotide polymorphisms (SNPs) is unknown in the prostate-specific antigen (PSA) range of 1-3 ng/ml. A substantial proportion of men in this PSA span have prostate cancer (PCa), but biomarkers to determine who should undergo a prostate biopsy are lacking. OBJECTIVE To evaluate whether a genetic risk score identifies men in the PSA range of 1-3 ng/ml who are at higher risk for PCa. DESIGN, SETTING, AND PARTICIPANTS Men aged 50-69 yr with PSA 1-3 ng/ml and without a previous prostate biopsy were selected from the STHLM2 cohort. Of 2696 men, 49 SNPs were genotyped, and a polygenic risk score was calculated. Of these men, 860 were invited according to risk score, and 172 underwent biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The risk of PCa was assessed using univariate and multivariate logistic regression analysis. RESULTS AND LIMITATIONS PCa was diagnosed in 47 of 172 participants (27%), with Gleason sum 6 in 36 of 47 men (77%) and Gleason sum ≥7 in 10 of 47 men (21%); one man had intraductal cancer. The genetic score was a significant predictor of a positive biopsy (p=0.028), even after adjusting for PSA, ratio of free to total PSA, prostate volume, age, and family history. There was an increase in the odds ratio of 1.60 (95% confidence interval, 1.05-2.45) with increasing genetic risk score. The absolute risk difference of positive biopsy was 19 percentage points, comparing the high and low genetic risk group (37% vs 18%). CONCLUSIONS A risk score based on SNPs predicts biopsy outcome in previously unbiopsied men with PSA 1-3 ng/ml. Introducing a genetic-based risk stratification tool can increase the proportion of men being classified in line with their true risk of PCa.


title: Prevention of influenza at Hajj: applications for mass gatherings.

text: Outbreaks of infectious diseases that spread via respiratory route, e.g. influenza, are common amongst Hajj congregation in Mecca, Saudi Arabia. The Saudi Arabian authority successfully organized the Hajj 2009 amidst fear of pandemic influenza. While severe influenza A(H1N1)pdm09 was rare, the true burden of pandemic influenza at Hajj that year remains speculative. In this article we review the latest evidence on influenza control and discuss our experience of influenza and its prevention at Hajj and possible application to other mass gatherings. Depending on study design the attack rate of seasonal influenza at Hajj has ranged from 6% in polymerase chain reaction or culture confirmed studies to 38% in serological surveillance. No significant effect of influenza vaccine or the use of personal protective measures against influenza has been established from observational studies, although the uptake of the vaccine and adherence to face masks and hand hygiene has been low. In all, there is a relatively poor evidence base for control of influenza. Until better evidence is obtained, vaccination coupled with rapid antiviral treatment of symptomatic individuals remains the mainstay of prevention at Hajj and other mass gatherings. Hajj pilgrimage provides a unique opportunity to test the effectiveness of various preventive measures that require a large sample size, such as testing the efficacy of plain surgical masks against laboratory-confirmed influenza. After successful completion of a pilot trial conducted among Australian pilgrims at the 2011 Hajj, a large multinational cluster randomized controlled trial is being planned. This will require effective international collaboration.


The role of the environment and its pollution in the prevalence of COVID-19.


title: Reviewing clinical guideline development tools: features and characteristics.

text: BACKGROUND To improve consistency and streamline development and publication of clinical guidelines (GL), there is a need for appropriate software support. We have found few specific tools for the actual authoring and maintaining of GLs, and correspondingly few analyses or reviews of GL development tool functionality. In order to assist GL developers in selecting and evaluating tools, this study tries to address the perceived gap by pursuing four goals: 1) identifying available tools, 2) reviewing a representative group of tools and their supported functionalities, 3) uncovering themes of features that the studied tools support, and 4) compare the selected tools with respect to the themes. METHODS We conducted a literature search using PubMed and Google Scholar in order to find GL development tools (GDT). We also explored tools and Content Management Systems (CMS) used in representative organisations and international communities that develop and maintain GLs. By reading a selected representative group of five GL tool manuals, exploring tools hands-on, we uncovered 8 themes of features. All found tools were compared according to these themes in order to identify the level of functionality they offer to support the GL development and publishing process. In order to limit the scope, tools for designing computer-interpretable/executable GL are excluded. RESULTS After finding 1552 published papers, contacting 7 organizations and international communities, we identified a total of 19 unique tools, of which 5 tools were selected as representative in this paper. We uncovered a total of 8 themes of features according to the identified functionalities that each tool provides. Four features were common among tools: Collaborative authoring process support, user access control, GL repository management, electronic publishing. We found that the GRADE methodology was supported by three of the reviewed tools, while only two tools support annotating GL with MeSH terms. We also identified that monitoring progress, reference management, Managing versions (version control), and Change control (tracking) were often the missing features. CONCLUSION The results can promote sector discussion and eventual agreement on important tool functionality. It may aid tool and GL developers towards more efficient, and effective, GL authoring.