title: Severe cerebral hypovolemia on perfusion CT and lower body weight are associated with parenchymal haemorrhage after thrombolysis.

text: INTRODUCTION Haemorrhagic transformation of acute ischemic stroke (AIS) and particularly parenchymal haemorrhage (PH) remains a feared complication of intravenous thrombolysis (IVT). We aimed to identify clinical and perfusion CT (PCT) variables which are independently associated with PHs. METHODS In this observational cohort study, based on the Acute Stroke Registry Analysis of Lausanne (ASTRAL) from 2003 to December 2013, we selected patients with AIS involving the middle cerebral artery (MCA) territory who were thrombolysed within 4.5 h of symptoms' onset and who had a good quality baseline PCT at the beginning of IVT. In addition to demographic, clinical, laboratory and non-contrast CT data, volumes of salvageable tissue and ischemic core on PCT, as well as absolute CBF and CBV values within the ischemic regions were compared in patients with and without PH in multivariate analysis. RESULTS Of the 190 included patients, 24 (12.6%) presented a PH (11 had PH1 and 13 had PH2). In multivariate analysis of the clinical and radiological variables, the lowest CBV in the core and lower body weight was both significantly associated with PH (p = 0.009 and p = 0.024, respectively). CONCLUSION In thrombolysed MCA strokes, maximal hypoperfusion severity depicted by lowest CBV values in the core region and lower body weight are independently correlated with PH. This information, if confirmed in other case series, may add to the stratification of revascularisation decisions in patients with a perceived high PH risk.


title: Tracheal Intubation with Aura-i and aScope-2: How to Minimize Apnea Time in an Unpredicted Difficult Airway.

text: The supraglottic airway's usefulness as a dedicated airway is the subject of continuing development. We report the case of an obese patient with unpredicted difficult airway management in which a new "continuous ventilation technique" was used with the Aura-i laryngeal mask and the aScope-2 devices. The aScope-2/Aura-i system implemented airway devices for the management of predictable/unpredictable difficult airway. The original technique required the disconnection of the mount catheter from Aura-i, the introduction of the aScope-2 into the laryngeal mask used as a conduit for video assisted intubation and then towards the trachea, followed by a railroading of the tracheal tube over the aScope-2. This variation in the technique guarantees mechanical ventilation during the entire procedure and could prevent the risk of hypoventilation and/or hypoxia.


Annals On Call - Protecting Health Care Workers From COVID-19.


title: Outpatient management of community-acquired pneumonia.

text: PURPOSE OF REVIEW The first guidelines on community-acquired pneumonia (CAP) were published in 1993, but since then many of the challenges regarding the outpatient management of CAP persist. These include the difficulty in establishing the initial clinical diagnosis, its risk stratification, which will dictate the place of treatment, the empirical choice of antibiotics, the relative scarcity of novel antibiotics and the importance of knowing local microbiological susceptibility patterns. RECENT FINDINGS New molecular biology methods have changed the etiologic perspective of CAP, especially the contribution of virus. Lung ultrasound and biomarkers might aid diagnosis and severity stratification in the outpatient setting. Antibiotic resistance is a growing problem that reinforces the importance of novel antibiotics. And finally, prevention and the use of anti-pneumococcal vaccine are instrumental in reducing the burden of disease. SUMMARY Most of CAP cases are managed in the community; however, most research comes from hospitalized severe patients. New and awaited advances might contribute to aid diagnosis, cause and assessment of patients with CAP in the community. This knowledge might prove decisive in the execution of stewardship programmes that maintain current antibiotics, safeguard future ones and reinforce prevention.


title: Seasonal influenza activity in Hong Kong and its association with meteorological variations.

text: Influenza seasons appear consistently in the temperate regions, but are more variable in tropical/subtropical regions. The determinant for such variation remains poorly understood. This study documented the activity of influenza over a 10-year period in Hong Kong; examining its association with changes in temperature and relative humidity. The two types of influenza exhibited different correlations with meteorological variations. Influenza A showed two seasonal peaks occurring respectively in winter/spring and summer months in most years. Influenza B showed a clear winter/spring peak, but its activity during summer months was more variable. Cold and humid conditions were associated with a higher activity of both influenza A and B. In contrast, hot and humid conditions were associated with a higher activity of influenza A, but were associated with only a moderate, less consistent increase in the activity of influenza B. A trend of increase in the magnitude of summer peaks of influenza A, but not influenza B, was observed. A hypothetical 2 degrees C rise in temperature would decrease the proportion of favorable days for influenza A in December-April from 78% to 57%, but an increase from 58% to 71% in May-November; with a similar effect (from 83% to 62%) for influenza B during December-April, but a modest change (from 17% to 18%) during May-November. The presence of two seasonal peaks of influenza annually emphasizes the need to evaluate the duration of protective immunity offered by vaccination. Further study on the effects of climate change and global warming on the activity of influenza is warranted.


title: Superselective retrograde lymphatic duct embolization for management of postoperative lymphatic leak.

text: Lymphatic leak is a well-documented complication following neck dissection surgeries. When conservative methods fail to control the leak, thoracic duct embolization becomes an option. Transabdominal access is the standard for this procedure; however, it is not always feasible. We discuss a technique of selective lymphatic vessel embolization utilizing retrograde transvenous access.


title: Treatment failure of fetal posterior communicating artery aneurysms with the pipeline embolization device.

text: Aneurysms that involve the internal carotid artery and posterior communicating artery junction and incorporate a fetal posterior cerebral artery are known as fetal posterior communicating artery aneurysms. We report the outcomes of four patients with fetal posterior communicating artery aneurysms who underwent treatment with the pipeline embolization device with or without adjunctive coil embolization. In our study, all four patients failed to achieve aneurysm occlusion at the last follow-up evaluation. Based on our results, we currently do not recommend the use of the flow diverter for the treatment of fetal posterior communicating artery aneurysms.


Lung ultrasound cannot be used to screen for Covid-19 in children.


title: Alternative Aortic Access: Translumbar, Transapical, Subclavian, Conduit, and Transvenous Access to the Aorta.

text: Large-caliber access to the arterial system is more frequently required in the age of thoracic endovascular aneurysm repair, endovascular aneurysm repair, and transaortic valve implantation. Frequently either anatomical or vessel size constraints preclude use of common access points such as the common femoral, radial, and brachial arteries. Alternative approaches include percutaneous access at alternate sites (subclavian, axillary, and carotid), open surgical access to the heart (left ventricular apex), open surgical access to large-caliber vessels (ascending aorta, subclavian, and axillary arteries, retroperitoneal access to the iliac artery or distal aorta), and novel percutaneous approaches (transvenous). Such approaches require additional skill sets, equipment, and, frequently, multidisciplinary teams to ensure safety and success. The techniques and approaches outlined in this article may allow expansion of endovascular treatments to greater patient populations and disease states than previously thought feasible.


title: Complications of liver resection: laparoscopic versus open procedures.

text: BACKGROUND AND OBJECTIVE Minimally invasive surgery for liver resection remains controversial. This study was designed to compare open versus laparoscopic surgical approaches to liver resection. METHODS We performed a single-center retrospective chart review. RESULTS We compared 45 laparoscopic liver resections with 17 open cases having equivalent resections based on anatomy and diagnosis. The overall complication rate was 25.8%. More open resection patients had complications (52.9% vs 15.5%, P < .008). The conversion rate was 11.1%. The mean blood loss was 667.1 ± 1450 mL in open cases versus 47.8 ± 89 mL in laparoscopic cases (P < .0001). Measures of intravenous narcotic use, intensive care unit length of stay, and hospital length of stay all favored the laparoscopic group. Patients were more likely to have complications or morbidity in the open resection group than in the laparoscopic group for both the anterolateral (P < .085) and posterosuperior (P < .002) resection subgroups. CONCLUSION In this series comparing laparoscopic and open liver resections, there were fewer complications, more rapid recovery, and lower morbidity in the laparoscopic group, even for those resections involving the posterosuperior segments of the liver.


title: The evolution of Ebola virus: Insights from the 2013-2016 epidemic.

text: The 2013-2016 epidemic of Ebola virus disease in West Africa was of unprecedented magnitude and changed our perspective on this lethal but sporadically emerging virus. This outbreak also marked the beginning of large-scale real-time molecular epidemiology. Here, we show how evolutionary analyses of Ebola virus genome sequences provided key insights into virus origins, evolution and spread during the epidemic. We provide basic scientists, epidemiologists, medical practitioners and other outbreak responders with an enhanced understanding of the utility and limitations of pathogen genomic sequencing. This will be crucially important in our attempts to track and control future infectious disease outbreaks.


title: Cosmesis and body image after single-port laparoscopic or conventional laparoscopic cholecystectomy: a multicenter double blinded randomised controlled trial (SPOCC-trial).

text: BACKGROUND Emerging attempts have been made to reduce operative trauma and improve cosmetic results of laparoscopic cholecystectomy. There is a trend towards minimizing the number of incisions such as natural transluminal endoscopic surgery (NOTES) and single-port laparoscopic cholecystectomy (SPLC). Many retrospective case series propose excellent cosmesis and reduced pain in SPLC. As the latter has been confirmed in a randomized controlled trial, patient's satisfaction on cosmesis is still controversially debated. METHODS/DESIGN The SPOCC trial is a prospective, multi-center, double blinded, randomized controlled study comparing SPLC with 4-port conventional laparoscopic cholecystectomy (4PLC) in elective surgery. The hypothesis and primary objective is that patients undergoing SPLC will have a better outcome in cosmesis and body image 12 weeks after surgery. This primary endpoint is assessed using a validated 8-item multiple choice type questionnaire on cosmesis and body image. The secondary endpoint has three entities: the quality of life 12 weeks after surgery assessed by the validated Short-Form-36 Health Survey questionnaire, postoperative pain assessed by a visual analogue scale and the use of analgesics. Operative time, surgeon's experience with SPLC and 4PLC, use of additional ports, conversion to 4PLC or open cholecystectomy, length of stay, costs, time of work as well as intra- and postoperative complications are further aspects of the secondary endpoint. Patients are randomly assigned either to SPLC or to 4PLC. Patients as well as treating physicians, nurses and assessors are blinded until the 7th postoperative day. Sample size calculation performed by estimating a difference of cosmesis of 20% (alpha = 0.05 and beta = 0.90, drop out rate of 10%) resulted in a number of 55 randomized patients per arm. DISCUSSION The SPOCC-trial is a prospective, multi-center, double-blind, randomized controlled study to assess cosmesis and body image after SPLC. TRIAL REGISTRATION (clinicaltrial.gov): NCT 01278472.


title: Components separation technique combined with a double-mesh repair for large midline incisional hernia repair.

text: BACKGROUND The surgical treatment of large midline incisional hernias remains a challenge. The aim of this report is to present the results of a new technique for large midline incisional hernia repair which combines the components-separation technique with a double-prosthetic-mesh repair. METHODS The records of all consecutive patients who received a double-mesh combined with the components-separation technique for ventral hernia repair were reviewed. The clinical, surgical, and follow-up data were analyzed. RESULTS Nine patients [3 women, 6 men; median age = 62 years (range = 26-77)] were included in the study. Median transverse defect size was 20 cm (range = 15-25). The median duration of hospital stay was 8 days (range = 5-17). Postoperative complications occurred in 66% (6/9). Follow-up [median = 13 months (range = 3-49)] showed no recurrent hernias, but one patient had a small hernia after a relaparotomy for colon carcinoma recurrence. The overall occurrence of wound infections was 44% (4/9). There was no mortality. CONCLUSION The components-separation technique in combination with a double-mesh has shown a low recurrence rate in the short-term follow-up. However, there is a considerable occurrence of postoperative wound infections. Long-term results of the hernia recurrence rate have to be awaited.


title: Population proteomics: investigation of protein diversity in human populations.

text: Outlined in this review is the concept of population proteomics, its aspects, enabling approaches, and significance in understanding proteins' roles in physiological processes and diseases. Population proteomics addresses the need for individual assessment of proteins across large populations to delineate the existence of structural variations, determine their frequency, and explore the association of the modifications with specific diseases. Besides the basic concepts and underlying reasons for such protein diversity studies, also reviewed here are the results of two fundamental studies that investigated human plasma protein diversity across the healthy population in the United States. Such studies of protein diversity are needed to map all the post-expression protein modifications and determine the wild-type protein profiles, similar to the human diversity studies at the genome level that have helped redefine the "normal" human genome.


title: A validation method for near-infrared spectroscopy based tissue oximeters for cerebral and somatic tissue oxygen saturation measurements.

text: We describe the validation methodology for the NIRS based FORE-SIGHT ELITE® (CAS Medical Systems, Inc., Branford, CT, USA) tissue oximeter for cerebral and somatic tissue oxygen saturation (StO2) measurements for adult subjects submitted to the United States Food and Drug Administration (FDA) to obtain clearance for clinical use. This validation methodology evolved from a history of NIRS validations in the literature and FDA recommended use of Deming regression and bootstrapping statistical validation methods. For cerebral validation, forehead cerebral StO2 measurements were compared to a weighted 70:30 reference (REF CXB) of co-oximeter internal jugular venous and arterial blood saturation of healthy adult subjects during a controlled hypoxia sequence, with a sensor placed on the forehead. For somatic validation, somatic StO2 measurements were compared to a weighted 70:30 reference (REF CXS) of co-oximetry central venous and arterial saturation values following a similar protocol, with sensors place on the flank, quadriceps muscle, and calf muscle. With informed consent, 25 subjects successfully completed the cerebral validation study. The bias and precision (1 SD) of cerebral StO2 compared to REF CXB was -0.14 ± 3.07%. With informed consent, 24 subjects successfully completed the somatic validation study. The bias and precision of somatic StO2 compared to REF CXS was 0.04 ± 4.22% from the average of flank, quadriceps, and calf StO2 measurements to best represent the global whole body REF CXS. The NIRS validation methods presented potentially provide a reliable means to test NIRS monitors and qualify them for clinical use.


Intermittent Mandatory Ventilation Will Live Forever.


title: Stereotactic MR-Guided Online Adaptive Radiation Therapy (SMART) for Ultracentral Thorax Malignancies: Results of a Phase 1 Trial.

text: Purpose Stereotactic body radiation therapy (SBRT) is an effective treatment for oligometastatic or unresectable primary malignancies, although target proximity to organs at risk (OARs) within the ultracentral thorax (UCT) limits safe delivery of an ablative dose. Stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) may improve the therapeutic ratio using reoptimization to account for daily variation in target and OAR anatomy. This study assessed the feasibility of UCT SMART and characterized dosimetric and clinical outcomes in patients treated for UCT lesions on a prospective phase 1 trial. Methods and Materials Five patients with oligometastatic (n = 4) or unresectable primary (n = 1) UCT malignancies underwent SMART. Initial plans prescribed 50 Gy in 5 fractions with goal 95% planning target volume (PTV) coverage by 95% of prescription, subject to strict OAR constraints. Daily real-time online adaptive plans were created as needed to preserve hard OAR constraints, escalate PTV dose, or both, based on daily setup MR image set anatomy. Treatment times, patient outcomes, and dosimetric comparisons were prospectively recorded. Results All initial and daily adaptive plans met strict OAR constraints based on simulation and daily setup MR imaging anatomy, respectively. Four of the 5 patients received ≥1 adapted fraction. Ten of the 25 total delivered fractions were adapted. A total of 30% of plan adaptations were performed to improve PTV coverage; 70% were for reversal of ≥1 OAR violation. Local control by Response Evaluation Criteria in Solid Tumors was 100% at 3 and 6 months. No grade ≥3 acute (within 6 months of radiation completion) treatment-related toxicities were identified. Conclusions SMART may allow PTV coverage improvement and/or OAR sparing compared with nonadaptive SBRT and may widen the therapeutic index of UCT SBRT. In this small prospective cohort, we found that SMART was clinically deliverable to 100% of patients, although treatment delivery times surpassed our predefined, timing-based feasibility endpoint. This technique is well tolerated, offering excellent local control with no identified acute grade ≥3 toxicity.


title: Optimizing Medication Management During the COVID-19 Pandemic: It Takes a Village.

text: Coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has particularly affected nursing homes and long-term care facilities. To support frontline health care professionals caring for older adults, the current article provides guidance on strategies to optimize medication management within nursing homes and long-term care facilities. In addition, the article reviews two medications that have been granted U.S. Food and Drug Administration emergency use authorization for treatment of COVID-19: hydroxychloroquine and remdesivir. Finally, this article highlights resources and strategies for improving communication among an interprofessional team during the ongoing pandemic, as well as education on COVID-19. Although the COVID-19 pandemic has had many negative implications, it has also brought to attention opportunities to improve the delivery of care and increase the importance of working as an interprofessional team ("village") during these challenging times. [Journal of Gerontological Nursing, 46(7), 3-8.].


title: Transumbilical single-port laparoscopic-assisted vaginal hysterectomy via 12-mm trocar incision site.

text: BACKGROUND Single-port laparoscopic-assisted vaginal hysterectomy (S-LAVH) uses only one transumbilical incision site and has better cosmetic result than conventional multiport LAVH. This study aimed to evaluate our initial experience with S-LAVH compared with the more conventional three-port LAVH in women with benign uterine diseases. METHODS Between April 2009 and April 2010, S-LAVH was attempted on 183 patients with benign uterine diseases through a transumbilical incision for a 12-mm trocar, and conventional LAVH was performed on 275 patients by the same surgeon. The medical records of patients were reviewed. The age, body mass index, operative time, blood loss, and uterine weight on pathologic report were compared. RESULTS Two of 183 patients in the S-LAVH group were converted to two- or three-port surgery, compared with none in the conventional group. Data analysis was done for 181 patients in the S-LAVH group and 275 patients in the conventional LAVH group. No major complications, including ureteral or bladder injuries, occurred in any of the patients. No statistically significant differences were found in mean age, mean body mass index, mean operative time, mean anesthesia time, mean estimated blood loss, or mean postoperative days to passage of flatus, but the mean uterine weights on the pathologic reports were significantly reduced in the S-LAVH group. CONCLUSION S-LAVH could be a feasible alternative method for removal of the uterus with a better cosmetic outcome resulting from single wound in selected patients. For patients with large-sized uterus, more surgical experience and improvement in instruments suitable for S-LAVH are needed.


Several neonates reported positive for COVID-19.


title: Confirmed dioestrus in pseudopregnant mice using vaginal exfoliative cytology improves embryo transfer implantation rate.

text: Embryo transfer is a commonly performed surgical technique. In mice, protocols typically specify pairing recipient females with vasectomized males to induce a receptive uterine environment for embryo implantation. However, this induced receptive state is not always maintained until implantation occurs. The use of a well-characterized correlation between oestrous state and exfoliative vaginal cytology was therefore evaluated to assess uterine receptivity immediately before embryo transfer. Eight- to 12-week-old virgin female CD1 mice (n = 22) were paired overnight with vasectomized males and successfully mated, indicated by the presence of a vaginal plug. These dams underwent embryo transfer 3 days later with embryos obtained from superovulated 4-week-old F1 (C57BL/6 × CBA) females. Non-invasive vaginal lavage was conducted immediately before transfer. Dams were killed 6 days after transfer and the uterus collected for histological analysis. Embryo implantation rate in mice was 96% when cytological analysis of the lavage samples signified dioestrus (n = 6), whereas the implantation rate was <15% (n = 16) when cytology signified other stages of oestrous. This simple, quick, non-invasive measure of receptivity was accurate and easily adopted and, when applied prospectively, will avoid unnecessary surgery and subsequent culling of non-suitable recipients, while maximizing the implantation potential of each recipient female.


title: Pneumatically driven surgical instrument capable of estimating translational force and grasping force.

text: BACKGROUND In robot-assisted minimally invasive surgery, feedback as well as sensing of translational and grasping forces allows surgeons to manipulate the robots using an appropriate force. However, there have been limited reports on single instruments capable of sensing both forces (translational force and grasping force), with the exception of instruments with electronic sensors. METHODS In this study, a pneumatically driven surgical instrument capable of estimating both translational and grasping forces is developed. Our estimation method is based on the dynamics and pneumatic pressure changes of the instrument. For each force estimation, we applied a joint mechanism consisting of disks and a flexible backbone and constructed pneumatic driving systems, kinematic models, dynamic models, controller, and force estimator. RESULTS We confirmed experimentally that the mean absolute error between the measured forces and the estimated translational and grasping forces is 0.2 N or less for any condition. From these results, it is seen that the mechanical interference between the joint actuation mechanism and grasper actuation mechanism is negligibly small. CONCLUSIONS A method for estimating both forces was proposed, and experimental results confirmed the effectiveness of the method.


INTRODUCTION Urethral injury is an uncommon surgical complication of penile prosthesis (PP) surgery. Conventional dogma requires abortion of the procedure if the adjacent corporal body is involved or delayed implantation to avert device infection associated with urinary extravasation. Besides the setback of the aborted surgery, this management approach also presents the possible difficulty of encountering corporal fibrosis at the time of reoperation. AIM We report an approach using primary urethral repair and temporary suprapubic cystostomy for the management of incidental urethral injuries in a cohort of patients allowing for successful completion of unaborted PP implantation. MATERIALS AND METHODS We performed a retrospective analysis of all patients receiving PPs from 1990 to 2014 in which incidental urethral injuries were repaired and PP implantation was completed with suprapubic cystostomy (suprapubic tube [SPT] insertion). After allowing for urethral healing and urinary diversion via SPT for 4-8 weeks, the PP was activated. MAIN OUTCOME MEASURES Successful management was determined by the absence of perioperative complications within 6 months of implantation. RESULTS We identified four cases, all receiving inflatable PPs, managed with temporary suprapubic cystostomy. These patients sustained urethral injuries during corporal dissection (one patient), corporal dilation (one patient), and penile straightening (two patients). All patients were managed safely and successfully. CONCLUSION Primary urethral repair followed by temporary suprapubic cystostomy offers a surgical approach to complete PP implantation successfully in patients who sustain urethral injury complications, particularly for complex PP surgeries. Anele UA, Le BV, and Burnett AL. Suprapubic cystostomy for the management of urethral injuries during penile prosthesis implantation.


title: Effects of barbed suture during robot-assisted radical prostatectomy on postoperative tissue damage and longitudinal changes in lower urinary tract outcome.

text: OBJECTIVE To compare the postoperative tissue damage and longitudinal changes in functional and patient-reported outcomes after vesicourethral anastomosis with barbed suture and nonbarbed suture in robot-assisted laparoscopic radical prostatectomy (RARP). MATERIALS AND METHODS This was a prospective cohort study involving 88 consecutive patients who underwent RARP. These patients were categorized into the barbed suture group (n = 50) and the nonbarbed suture group (n = 38). Urethral and periurethral damages determined by magnetic resonance imaging at nine months after RARP were compared using generalized linear models. The International Prostate Symptom Score (IPSS), quality of life (QOL) index, uroflowmetry, and the 1-h pad test were measured at baseline and at 1, 3, 6, 9, and 12 months after RARP. The findings were analyzed using mixed-effects models. Confounding was adjusted for using propensity score covariate adjustment. RESULTS The likelihood of having Grade 2/3 urethral and periurethral damages was greater in the barbed suture group than in the nonbarbed suture group (adjusted risk ratios: 2.98 and 3.85, respectively). IPSS, QOL index, and urinary leakage transiently increased at one month after RARP in both groups. QOL index was higher in the barbed suture group than in the nonbarbed suture group at 1, 9, and 12 months (P = 0.023, P = 0.025, and P = 0.011, respectively). The barbed suture group had significantly more cases of urinary incontinence than the nonbarbed suture group at 3 months (P = 0.041). Other outcomes were comparable between the two groups at all time points. CONCLUSIONS This cohort study showed that, after RARP, barbed sutures during VUA induced more severe tissue damage as determined by MRI and greater transient aggravation of QOL and continence function than nonbarbed sutures. The present findings suggest that using nonbarbed sutures during VUA may facilitate earlier acquisition of urinary QOL and urinary continence.


title: Radiofrequency ablation of osteoid osteoma: Aiming for excellent outcomes in an Australasian context.

text: INTRODUCTION To report a series of patients with osteoid osteoma treated by radiofrequency ablation in whom no complications or recurrences occurred. METHODS Over a 13-year period, 32 consecutive patients with osteoid osteoma were treated by radiofrequency ablation in an Australasian teaching centre. RESULTS All patients had resolution of symptoms with no complication or recurrence. CONCLUSIONS This series is further evidence for the use of radiofrequency ablation as the primary treatment for osteoid osteoma.


Hospital staff take the knee in Boston.


title: Laparoscopy-assisted resection of an undiagnosed liver tumor and ascending colon cancer via mini median laparotomy: report of a case.

text: We describe how we resected a hepatic angiomyolipoma and ascending colon cancer synchronously via laparoscopic left lateral segmentectomy and laparoscopic right colectomy, respectively. The patient was a 72-year-old man, admitted to our hospital after a liver tumor and ascending colon cancer were detected during a general health check. Computed tomography (CT) showed a hypervascular liver tumor mimicking hepatocellular carcinoma, 2 cm in diameter, in segment 3 of the liver. The ascending colon cancer was diagnosed as T2N0M0, Stage I. The left lateral liver and right colon were mobilized laparoscopically and hepatic transaction, followed by resection and anastomosis of the colon, were performed extracorporeally through the same 7-cm upper median incision. This type of laparoscopy-assisted combined resection is useful to obtain a pathological diagnosis of the liver tumor and to remove the entire tumor in a minimally invasive and cosmetic manner.


title: Sustainable health promotion for the seniors during COVID-19 outbreak: a lesson from Tokyo.

text: The COVID-19 pandemic is novel corona virus infection outbreak that has gone global in 2020. Current prevention policies consist of hand hygiene and social distancing. Emergencies overloaded health services and shocked the logistics chains in many countries, especially Italy and China. Having more than a quarter of its population being elderly, Japan is at high risk for COVID-19 induced morbidity and mortality. This situation cancelled schedules of all routine group exercise activities for the seniors in Japan. While the outbreak is ongoing, staying at home is safe. However, successive days of being house-ridden and limited movement can lead to excessive physical inactivity. Some elderly who are not moving much can lose a significant amount of muscle strength, flexibility and aerobic capacity. It can accelerate the frailty and dependency of the seniors, and subsequently, claiming of care and health services. Moreover, existing and new evidences showed that physical activity can promote antiviral immunity. An alternative to usual group exercise activities is crucial to keep seniors active without affecting social distancing. While staying at home for long, functional exercises maintaining basic level of physical activity and movements are urgently required to be introduced to the seniors in Tokyo and around the world to prevent functional decline. Home exercise is a practical option. Therefore, we made a home-version of the functional training exercise video with different sets of 10-minutes exercise for 7 days a week. This breakthrough alternative may sustain health promotion for the elderly persons to preserve their active aging and maintain optimal health.


title: Guaiphenesin-ketamine-xylazine infusion to maintain anesthesia in mules undergoing field castration.

text: BACKGROUND In order to determine whether a combination of guaiphenesin, ketamine and xylazine can induce safe and satisfactory anaesthesia in mules undergoing field castration, eight healthy adult intact male mules were employed. They were premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of xylazine (0.3 mg/kg IV) was administered in case of inadequate depth of sedation. Anaesthesia was induced with IV thiopental (6 mg/kg). The quality of sedation and induction was recorded. Anaesthesia was maintained with an infusion of guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and haemoglobin oxygen saturation (SpO2) were measured every 5 min. The data were analysed with simple one-way analysis of variance (ANOVA). A P value < 0.05 was considered statistically significant. Time of anesthesia, time of surgery and time of recovery were recorded. RESULTS Only one mule required an additional dose of xylazine to achieve a satisfactory depth of sedation. Thiopental at the dose of 6 mg/kg IV resulted in smooth induction and lateral recumbency in all animals. GKX provided adequate anaesthesia to perform castration in all mules. Muscle relaxation was deemed adequate and physiological variables remained stable and within references values during the anaesthesia and did not change in response to surgical stimulation. Time (mean ± standard deviation) from the end of the infusion to sternal recumbency and time from sternal recumbency to standing were 27.7 ± 4.6 and 30.1 ± 7.7 min, respectively. CONCLUSIONS The combination of xylazine, thiopental and GKX provides satisfactory short-term anaesthesia in mules undergoing field castration.


title: Interstitial engraftment of adipose-derived stem cells into an acellular dermal matrix results in improved inward angiogenesis and tissue incorporation.

text: Acellular dermal matrices (ADM) are commonly used in reconstructive procedures and rely on host cell invasion to become incorporated into host tissues. We investigated different approaches to adipose-derived stem cells (ASCs) engraftment into ADM to enhance this process. Lewis rat adipose-derived stem cells were isolated and grafted (3.0 × 10(5) cells) to porcine ADM disks (1.5 mm thick × 6 mm diameter) using either passive onlay or interstitial injection seeding techniques. Following incubation, seeding efficiency and seeded cell viability were measured in vitro. In addition, Eighteen Lewis rats underwent subcutaneous placement of ADM disk either as control or seeded with PKH67 labeled ASCs. ADM disks were seeded with ASCs using either onlay or injection techniques. On day 7 and or 14, ADM disks were harvested and analyzed for host cell infiltration. Onlay and injection techniques resulted in unique seeding patterns; however cell seeding efficiency and cell viability were similar. In-vivo studies showed significantly increased host cell infiltration towards the ASCs foci following injection seeding in comparison to control group (p < 0.05). Moreover, regional endothelial cell invasion was significantly greater in ASCs injected grafts in comparison to onlay seeding (p < 0.05). ADM can successfully be engrafted with ASCs. Interstitial engraftment of ASCs into ADM via injection enhances regional infiltration of host cells and angiogenesis, whereas onlay seeding showed relatively broad and superficial cell infiltration. These findings may be applied to improve the incorporation of avascular engineered constructs.


title: Antipsychotic reduction and/or cessation and antipsychotics as specific treatments for tardive dyskinesia.

text: BACKGROUND Since the 1950s antipsychotic medication has been extensively used to treat people with chronic mental illnesses such as schizophrenia. These drugs, however, have also been associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. Various strategies have been examined to reduce a person's cumulative exposure to antipsychotics. These strategies include dose reduction, intermittent dosing strategies such as drug holidays, and antipsychotic cessation. OBJECTIVES To determine whether a reduction or cessation of antipsychotic drugs is associated with a reduction in TD for people with schizophrenia (or other chronic mental illnesses) who have existing TD. Our secondary objective was to determine whether the use of specific antipsychotics for similar groups of people could be a treatment for TD that was already established. SEARCH METHODS We updated previous searches of Cochrane Schizophrenia's study-based Register of Trials including the registers of clinical trials (16 July 2015 and 26 April 2017). We searched references of all identified studies for further trial citations. We also contacted authors of trials for additional information. SELECTION CRITERIA We included reports if they assessed people with schizophrenia or other chronic mental illnesses who had established antipsychotic-induced TD, and had been randomly allocated to (a) antipsychotic maintenance versus antipsychotic cessation (placebo or no intervention), (b) antipsychotic maintenance versus antipsychotic reduction (including intermittent strategies), (c) specific antipsychotics for the treatment of TD versus placebo or no intervention, and (d) specific antipsychotics versus other antipsychotics or versus any other drugs for the treatment of TD. DATA COLLECTION AND ANALYSIS We independently extracted data from these trials and estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who dropped out had no improvement. MAIN RESULTS We included 13 RCTs with 711 participants; eight of these studies were newly included in this 2017 update. One trial is ongoing.There was low-quality evidence of a clear difference on no clinically important improvement in TD favouring switch to risperidone compared with antipsychotic cessation (with placebo) (1 RCT, 42 people, RR 0.45 CI 0.23 to 0.89, low-quality evidence). Because evidence was of very low quality for antipsychotic dose reduction versus antipsychotic maintenance (2 RCTs, 17 people, RR 0.42 95% CI 0.17 to 1.04, very low-quality evidence), and for switch to a new antipsychotic versus switch to another new antipsychotic (5 comparisons, 5 RCTs, 140 people, no meta-analysis, effects for all comparisons equivocal), we are uncertain about these effects. There was low-quality evidence of a significant difference on extrapyramidal symptoms: use of antiparkinsonism medication favouring switch to quetiapine compared with switch to haloperidol (1 RCT, 45 people, RR 0.45 CI 0.21 to 0.96, low-quality evidence). There was no evidence of a difference for switch to risperidone or haloperidol compared with antipsychotic cessation (with placebo) (RR 1 RCT, 48 people, RR 2.08 95% CI 0.74 to 5.86, low-quality evidence) and switch to risperidone compared with switch to haloperidol (RR 1 RCT, 37 people, RR 0.68 95% CI 0.34 to 1.35, very low-quality evidence).Trials also reported on secondary outcomes such as other TD symptom outcomes, other adverse events outcomes, mental state, and leaving the study early, but the quality of the evidence for all these outcomes was very low due mainly to small sample sizes, very wide 95% CIs, and risk of bias. No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, outcomes that we designated as being important to patients. AUTHORS' CONCLUSIONS Limited data from small studies using antipsychotic reduction or specific antipsychotic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches. There is a need for larger trials of a longer duration to fully investigate this area.


title: Empowering patients in decision making in radiation oncology - can we do better?

text: The decision as to whether or not a patient should receive radiation therapy as part of their cancer treatment is based on evidence-based practice and on recommended international consensus treatment guidelines. However, the merit of involving the patients' individual preferences and values in the treatment decision is frequently overlooked. Here, we review the current literature pertaining to shared decision making in the field of radiation oncology, including discussion of the patient's perception of radiation therapy as a treatment option and patient involvement in clinical trials. The merit of decision aids during the shared decision making process in radiation oncology is considered, as are patient preferences for active or passive involvement in decisions about their treatment. Clarity of terminology, a better understanding of effective strategies and increased resources will be needed to ensure shared decision making in radiation oncology becomes a reality.


Opening Hospitals to More Patients During the COVID-19 Pandemic-Making It Safe and Making It Feel Safe.


title: An Unusual Cause of Acute Heart Failure: A Case Report of Iliocaval Venous Stent Migration.

text: Stent migration is an uncommon complication of endovascular stenting procedures. It could cause serious cardiovascular complications. In this article, we describe an interesting case of acute heart failure as a result of stent embolization from the left common iliac vein into the right ventricle and how it was identified and managed.


title: Intraoperative bispectral index monitoring and time to extubation after cardiac surgery: secondary analysis of a randomized controlled trial.

text: BACKGROUND Fast track recovery is a care process goal after cardiac surgery. Intraoperative anesthetic depth may impact recovery, but the impact of brain monitoring on time to extubation and intensive care unit (ICU) length of stay after cardiac surgery has not been extensively studied. Our goal was to determine if BIS-guided anesthesia improves time to extubation compared to MAC-guided anesthesia in a cardiac surgery population. METHODS In this secondary outcome analysis of a randomized controlled study, we analyzed 294 patients undergoing elective coronary bypass grafting, valve replacements, and bypass plus valve replacements at a single tertiary referral center between February 1, 2009 and April 30, 2010. We analyzed cardiac surgery patients that had been randomized to BIS-guided anesthesia alerts (n = 131) or MAC-guided anesthesia alerts (n = 163). The primary outcome measure was time to extubation in the BIS-guided and anesthetic concentration-guided groups. Secondary outcomes were length of stay in the ICU and total postoperative hospital length of stay. RESULTS Valid extubation time data were available for 247 of 294 patients. The median [IQR] time to extubation was 307 [215 to 771] minutes in the BIS group and 323 [196 to 730] minutes in the anesthetic concentration group (p = 0.61). The median [IQR] ICU length of stay was 54 [29 to 97] hours versus 70 [44 to 99] hours (p = 0.11). In terms of postoperative hospital length of stay, there was no difference between the groups with median [IQR] times of 6 [5-8] days (p = 0.69) in each group. CONCLUSIONS The use of intraoperative BIS monitoring during cardiac surgery did not change time to extubation, ICU length of stay or hospital length of stay. Data regarding BIS monitoring and recovery in an exclusively cardiac surgery population are consistent with recent effectiveness studies in the general surgical population. TRIAL REGISTRATION ClinicalTrials.gov number NCT00689091.


Rammya Mathew: Innovation during the pandemic.


The Use of Disposable Gloves by General Public During COVID-19 Increases the Risk of Cross-Contamination.


title: Diaphragm electromyography results at different high flow nasal cannula flow rates.

text: Heated, humidified, high-flow nasal cannula (HHHFNC) is increasingly being used, but there is a paucity of evidence as to the optimum flow rates in prematurely born infants. We have determined the impact of three flow rates on the work of breathing (WOB) assessed by transcutaneous diaphragm electromyography (EMG) amplitude in infants with respiratory distress or bronchopulmonary dysplasia (BPD). Flow rates of 4, 6 and 8 L/min were delivered in random order. The mean amplitude of the EMG trace and mean area under the EMG curve (AEMGC) were calculated and the occurrence of bradycardias and desaturations recorded. Eighteen infants were studied with a median gestational age of 27.8 (range 23.9-33.5) weeks and postnatal age of 54 (range 3-122) days. The median flow rate prior to the study was 5 (range 3-8) L/min and the fraction of inspired oxygen (FiO2) was 0.29 (range 0.21-0.50). There were no significant differences between the mean amplitude of the diaphragm EMG and the AEGMC and the number of bradycardias or desaturations between the three flow rates.Conclusions: In infants with respiratory distress or BPD, there was no advantage of using high (8 L/min) compared with lower flow rates (4 or 6 L/min) during support by HHHFNC. What is known: • Humidified high flow nasal cannulae (HHHFNC) is increasingly being used as a non-invasive form of respiratory support for prematurely born infants. • There is a paucity of evidence regarding the optimum flow rate with 1 to 8 L/min being used. What is new: • We have assessed the work of breathing using the amplitude of the electromyogram of the diaphragm at three HHHFNC flow rates in infants with respiratory distress or BPD. • No significant differences were found in the EMG amplitude results or the numbers of bradycardias or desaturations at 4, 6 and 8 L/min.


title: Using country-level variables to classify countries according to the number of confirmed COVID-19 cases: An unsupervised machine learning approach.

text: Background: The COVID-19 pandemic has attracted the attention of researchers and clinicians whom have provided evidence about risk factors and clinical outcomes. Research on the COVID-19 pandemic benefiting from open-access data and machine learning algorithms is still scarce yet can produce relevant and pragmatic information. With country-level pre-COVID-19-pandemic variables, we aimed to cluster countries in groups with shared profiles of the COVID-19 pandemic. Methods: Unsupervised machine learning algorithms (k-means) were used to define data-driven clusters of countries; the algorithm was informed by disease prevalence estimates, metrics of air pollution, socio-economic status and health system coverage. Using the one-way ANOVA test, we compared the clusters in terms of number of confirmed COVID-19 cases, number of deaths, case fatality rate and order in which the country reported the first case. Results: The model to define the clusters was developed with 155 countries. The model with three principal component analysis parameters and five or six clusters showed the best ability to group countries in relevant sets. There was strong evidence that the model with five or six clusters could stratify countries according to the number of confirmed COVID-19 cases (p<0.001). However, the model could not stratify countries in terms of number of deaths or case fatality rate. Conclusions: A simple data-driven approach using available global information before the COVID-19 pandemic, seemed able to classify countries in terms of the number of confirmed COVID-19 cases. The model was not able to stratify countries based on COVID-19 mortality data.


Video consultations in UK primary care in response to the COVID-19 pandemic.


title: Influence of the postoperative inflammatory response on cognitive decline in elderly patients undergoing on-pump cardiac surgery: a controlled, prospective observational study.

text: BACKGROUND The role of non-infective inflammatory response (IR) in the aetiology of postoperative cognitive dysfunction (POCD) is still controversial. The aim of this controlled, prospective observational study was to assess the possible relationship between the grade of IR, defined by procalcitonin (PCT) changes, and development of POCD related to cardiac surgery. METHODS Forty-two patients, who were ≥ 60 years of age and scheduled for elective cardiac surgery, were separated into the low inflammatory (LIR) and high inflammatory (HIR) response groups based on their PCT levels measured on the first postoperative day. A matched normative control group of 32 subjects was recruited from primary care practice. The PCT and C-reactive protein (CRP) levels were monitored daily during the first five postoperative days. The cognitive function and mood state were preoperatively tested with a set of five neurocognitive tests and two mood inventories and at the seventh postoperative day. The Reliable Change Index modified for practice (RCIp) using data from normative controls was applied to determine the significant decline in test performance. RESULTS The LIR (n = 20) and HIR (n = 22) groups differed significantly in the PCT (p < 0.001) but not in the CRP time courses. The incidence of POCD at the first postoperative week was 35.7% in the cohort. The LIR and HIR groups did not vary in the RCIp Z scores of neurocognitive tests and frequencies of POCD (7 vs 8 cases, respectively, p > 0.05). Additionally, there was no difference in the mood states, anxiety levels and perioperative parameters known to influence the development of POCD. CONCLUSIONS In this study, the magnitude of the non-infective inflammatory response generated by on-pump cardiac surgery did not influence the development of POCD in the early postoperative period in elderly patients.


title: Is Repeat PTA of a Failing Hemodialysis Fistula Durable?

text: Purpose. Our objective was to evaluate the outcome of percutaneous transluminal angioplasty (PTA) and particularly rePTA in a failing arteriovenous fistula (AV-fistula). Are multiple redilations worthwhile? Patients and Methods. All 159 stenoses of AV fistulas that were treated with PTA, with or without stenting, during 2008 and 2009, were included. Occluded fistulas that were dilated after successful thrombolysis were also included. Median age was 68 (interquartile range 61.5-78.5) years and 75% were male. Results. Seventy-nine (50%) of the primary PTAs required no further reintervention. The primary patency was 61% at 6 months and 42% at 12 months. Eighty (50%) of the stenoses needed at least one reintervention. Primary assisted patency (defined as patency after subsequent reinterventions) was 89% at 6 months and 85% at 12 months. The durability of repeated PTAs was similar to the durability of the primary PTA. However, an early primary PTA carried a higher risk for subsequent reinterventions. Successful dialysis was achieved after 98% of treatments. Nine percent of the stenoses eventually required surgical revision and 13% of the fistulas failed permanently. Conclusion. The present study suggests that most failing AV-fistulas can be salvaged endovascularly. Repeated PTA seems similarly durable as the primary PTA.


title: Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection.

text: Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV pathogenesis. We have shown that STAT1 plays an important role in the severity of SARS-CoV pathogenesis and that it is independent of the role of STAT1 in interferon signaling. Mice lacking STAT1 have greater weight loss, severe lung pathology with pre-pulmonary-fibrosis-like lesions, and an altered immune response following infection with SARS-CoV. We hypothesized that STAT1 plays a role in the polarization of the immune response, specifically in macrophages, resulting in a worsened outcome. To test this, we created bone marrow chimeras and cell-type-specific knockouts of STAT1 to identify which cell type(s) is critical to protection from severe lung disease after SARS-CoV infection. Bone marrow chimera experiments demonstrated that hematopoietic cells are responsible for the pathogenesis in STAT1(-/-) mice, and because of an induction of alternatively activated (AA) macrophages after infection, we hypothesized that the AA macrophages were critical for disease severity. Mice with STAT1 in either monocytes and macrophages (LysM/STAT1) or ciliated lung epithelial cells (FoxJ1/STAT1) deleted were created. Following infection, LysM/STAT1 mice display severe lung pathology, while FoxJ1/STAT1 mice display normal lung pathology. We hypothesized that AA macrophages were responsible for this STAT1-dependent pathology and therefore created STAT1/STAT6(-/-) double-knockout mice. STAT6 is essential for the development of AA macrophages. Infection of the double-knockout mice displayed a lack of lung disease and prefibrotic lesions, suggesting that AA macrophage production may be the cause of STAT1-dependent lung disease. We propose that the control of AA macrophages by STAT1 is critical to regulating immune pathologies and for protection from long-term progression to fibrotic lung disease in a mouse model of SARS-CoV infection.


title: Gamma Irradiation as an Effective Method for Inactivation of Emerging Viral Pathogens.

text: Gamma irradiation using a cobalt-60 source is a commonly used method for the inactivation of infectious specimens to be handled safely in subsequent laboratory procedures. Here, we determined irradiation doses to safely inactivate liquid proteinaceous specimens harboring different emerging/reemerging viral pathogens known to cause neglected tropical and other diseases of regional or global public health importance. By using a representative arenavirus, bunyavirus, coronavirus, filovirus, flavivirus, orthomyxovirus, and paramyxovirus, we found that these enveloped viruses differed in their susceptibility to irradiation treatment with adsorbed doses for inactivation of a target dose of 1 × 106 50% tissue culture infectious dose (TCID50)/mL ranging from 1 to 5 MRads. This finding seemed generally inversely correlated with genome size. Our data may help to guide other facilities in testing and verifying safe inactivation procedures.


Pertinence of Telehealth in a Rush Conversion to Virtual Allergy Practice during the COVID-19 Outbreak.


title: Pharmacophore-based virtual screening: a review of recent applications.

text: IMPORTANCE OF THE FIELD In research relating to the development of new drugs, hit identification and validations are critical for successful optimization of candidates. To achieve rapid identification of new lead compounds, high-throughput screening assays have been employed in many pharmaceutical companies and laboratories. However, their success depends on the assay system relevant to in vivo conditions and they are physically limited by the repertoire of compounds. As an alternative or complementary approach to high-throughput screening assays, virtual screening is an efficient method to identify drug candidates in silico from large chemical compound databases. Its usefulness has been verified by current applications that successfully retrieved hit and lead identifications against various disease targets. However, for better application, the scoring functions for distinguishing possible active and inactive compounds must beimproved. AREAS COVERED IN THIS REVIEW In this review, we provide an overview of pharmacophore-based virtual screening methods with a special focus on their successful application towards finding hits against various diseasetargets. WHAT THE READER WILL GAIN Readers will rapidly gain insight into the recent successful applications of pharmacophore-based virtual screening. They will acknowledge that this technique is a powerful and cost-effective alternative to high-throughput assays. TAKE HOME MESSAGE Although there are many hurdles yet to be resolved, virtual screening techniques will emerge as essential infrastructure and as a prerequisite for developing new lead compounds with therapeuticapplications.


title: Specificities of human CD4+ T cell responses to an inactivated flavivirus vaccine and infection: correlation with structure and epitope prediction.

text: Tick-borne encephalitis (TBE) virus is endemic in large parts of Europe and Central and Eastern Asia and causes more than 10,000 annual cases of neurological disease in humans. It is closely related to the mosquito-borne yellow fever, dengue, Japanese encephalitis, and West Nile viruses, and vaccination with an inactivated whole-virus vaccine can effectively prevent clinical disease. Neutralizing antibodies are directed to the viral envelope protein (E) and an accepted correlate of immunity. However, data on the specificities of CD4(+) T cells that recognize epitopes in the viral structural proteins and thus can provide direct help to the B cells producing E-specific antibodies are lacking. We therefore conducted a study on the CD4(+) T cell response against the virion proteins in vaccinated people in comparison to TBE patients. The data obtained with overlapping peptides in interleukin-2 (IL-2) enzyme-linked immunosorbent spot (ELISpot) assays were analyzed in relation to the three-dimensional structures of the capsid (C) and E proteins as well as to epitope predictions based on major histocompatibility complex (MHC) class II peptide affinities. In the C protein, peptides corresponding to two out of four alpha helices dominated the response in both vaccinees and patients, whereas in the E protein concordance of immunodominance was restricted to peptides of a single domain (domain III). Epitope predictions were much better for C than for E and were especially erroneous for the transmembrane regions. Our data provide evidence for a strong impact of protein structural features that influence peptide processing, contributing to the discrepancies observed between experimentally determined and computer-predicted CD4(+) T cell epitopes. Importance: Tick-borne encephalitis virus is endemic in large parts of Europe and Asia and causes more than 10,000 annual cases of neurological disease in humans. It is closely related to yellow fever, dengue, Japanese encephalitis, and West Nile viruses, and vaccination with an inactivated vaccine can effectively prevent disease. Both vaccination and natural infection induce the formation of antibodies to a viral surface protein that neutralize the infectivity of the virus and mediate protection. B lymphocytes synthesizing these antibodies require help from other lymphocytes (helper T cells) which recognize small peptides derived from proteins contained in the viral particle. Which of these peptides dominate immune responses to vaccination and infection, however, was unknown. In our study we demonstrate which parts of the proteins contribute most strongly to the helper T cell response, highlight specific weaknesses of currently available approaches for their prediction, and demonstrate similarities and differences between vaccination and infection.


Outbreak Column 13: Nosocomial Staphylococcus aureus outbreaks (part 2 - guidelines).


title: Natural-like products as potential SARS-CoV-2 Mpro inhibitors: in-silico drug discovery.

text: In December 2019, a COVID-19 epidemic was discovered in Wuhan, China, and since has disseminated around the world impacting human health for millions. Herein, in-silico drug discovery approaches have been utilized to identify potential natural products (NPs) as Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) inhibitors. The MolPort database that contains over 100,000 NPs was screened and filtered using molecular docking techniques. Based on calculated docking scores, the top 5,000 NPs/natural-like products (NLPs) were selected and subjected to molecular dynamics (MD) simulations followed by molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. Combined 50 ns MD simulations and MM-GBSA calculations revealed nine potent NLPs with binding affinities (ΔGbinding ) > -48.0 kcal/mol. Interestingly, among the identified NLPs, four bis([1,3]dioxolo)pyran-5-carboxamide derivatives showed ΔGbinding > -56.0 kcal/mol, forming essential short hydrogen bonds with HIS163 and GLY143 amino acids via dioxolane oxygen atoms. Structural and energetic analyses over 50 ns MD simulation demonstrated NLP-Mpro complex stability. Drug-likeness predictions revealed the prospects of the identified NLPs as potential drug candidates. The findings are expected to provide a novel contribution to the field of COVID-19 drug discovery. Communicated by Ramaswamy H. Sarma.


title: National Differences in Remission of Type 2 Diabetes Mellitus After Roux-en-Y Gastric Bypass Surgery-Subgroup Analysis of 2-Year Results of the Diabetes Surgery Study Comparing Taiwanese with Americans with Mild Obesity (BMI 30-35 kg/m2).

text: BACKGROUND The purpose of this study is to compare effects of different nations on Roux-en-Y gastric bypass (RYGB) vs. intensive medical management (IMM) in achieving remission of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS Between April 2008 and December 2011, this randomized, controlled clinical trial was conducted at four teaching hospitals in the United States and Taiwan involving 71 participants with mild obesity (BMI 30-35 kg/m2). Thirty-six of 71 participants were randomly assigned to the RYGB group, and the others were in IMM group. Partial or complete remission of T2DM was defined as blood HbA1c < 6.5 % (48 mmol/mol) or <6 % (42 mmol/mol) without any antihyperglycemic medication for at least 1-year duration, respectively. RESULTS At baseline, Taiwanese participants had a lower BMI, younger age, and shorter duration of T2DM than American participants. At 24 months, weight loss was greater in the RYGB group in both populations than in the IMM group. No IMM participant of either population had partial or complete remission of T2DM. In the RYGB group, a substantial proportion of the subjects achieved complete or partial remission (57 % in Taiwanese and 27 % in American participants, P = 0.08). Logistic regression revealed stimulated C-peptide (Odds ratio 2.22, P = 0.02) but not nationality as a significant predictor of diabetes remission. CONCLUSION Adding RYGB to lifestyle and medical management was associated with a greater likelihood of remission of T2DM in both Taiwanese and American subjects with mild obesity with type 2 diabetes. Residual beta-cell function at baseline appears to be the major factor predicting remission of T2DM. Trial registry number: clinicaltrials.gov Identifier: NCT00641251.


title: Rapid simultaneous detection of enterovirus and parechovirus RNAs in clinical samples by one-step real-time reverse transcription-PCR assay.

text: Enteroviruses (EVs) are recognized as the major etiological agent in meningitis in children and young adults. The use of molecular techniques, such as PCR, has substantially improved the sensitivity of enterovirus detection compared to that of virus culture methods. PCR-based methods also can detect a much wider range of EV variants, including those within species A, as well as human parechoviruses (HPeVs) that often grow poorly in vitro and which previously have been underdiagnosed by traditional methods. To exploit these developments, we developed a real-time one-step reverse transcription-PCR (RT-PCR) for the rapid and sensitive detection of EV and HPeV in clinical specimens. Two commercially available RT-PCR kits were used (method I, Platinum one-step kit; method II, Express qPCR one-step kit) with primers and probes targeting the EV and HPeV 5'-untranslated regions (5'UTR). Amplification dynamics (threshold cycle [C(T)]values and efficiencies) of absolutely quantified full-length RNA transcripts representative of EV species A to D and HPeV were similar, demonstrating the effectiveness of both assays across the range of currently described human EV and HPeV variants. Probit analysis of multiple endpoint replicates demonstrated comparable sensitivities of the assays for EV and HPeV (method I, approximately 10 copies per reaction for both targets; method II, 20 copies per reaction). C(T) values were highly reproducible on repeat testing of positive controls within assays and between assay runs. Considering the sample turnaround time of less than 3 h, the multiplexed one-step RT-PCR method provides rapid diagnostic testing for EV and HPeV in cases of suspected central nervous system infections in a clinically relevant time frame.


title: Summary of Notifiable Infectious Diseases and Conditions - United States, 2014.

text: The Summary of Notifiable Infectious Diseases and Conditions-United States, 2014 (hereafter referred to as the summary) contains the official statistics, in tabular and graphic form, for the reported occurrence of nationally notifiable infectious diseases and conditions in the United States for 2014. Unless otherwise noted, data are final totals for 2014 reported as of June 30, 2015. These statistics are collected and compiled from reports sent by U.S. state and territory, New York City, and District of Columbia health departments to the National Notifiable Diseases Surveillance System (NNDSS), which is operated by CDC in collaboration with the Council of State and Territorial Epidemiologists (CSTE). This summary is available at http://www.cdc.gov/mmwr/mmwr_nd/index.html. This site also includes summary publications from previous years.


title: A war of attrition against antibiotic resistance: Current strategies try to keep antibiotic resistance at bay and further encourage research to produce genuinely novel antibacterials.

text: To fight antibiotic resistance, novel drugs are urgently needed. Regulatory agencies are addressing the economic problems and offer new incentives for developing new antibiotics.


title: Safety and efficacy of the Derivo Embolization Device for the treatment of unruptured intracranial aneurysms: a multicentric study.

text: BACKGROUND The Derivo Embolization Device (DED) is a novel flow diverter stent that provides increased x-ray visibility, an improved delivery system, and potentially reduced thrombogenicity. The objective of this study was to evaluate the early safety and efficacy of the second-generation DED. METHODS We retrospectively analyzed all patients with unruptured intracranial aneurysms (UIAs) treated with the DED between November 2015 and December 2017 in three German tertiary care centers. Procedural details, complications, and morbidity within 30 days after treatment, as well as the aneurysm occlusion rates after 6 months (O'Kelly-Marotta scale, OKM), were evaluated. RESULTS Implantation of the DED was attempted in 42 patients with 42 aneurysms. All procedures were technically successful. Multiple DEDs were used in three aneurysms (7.2%) and adjunctive coiling in 11 (26.2%). Procedure-related complications occurred in four cases (9.5%) including three thromboembolic events and one aneurysm perforation. The morbidity rate was 2.4% and there was no mortality. One patient suffered an ischemic stroke with persistent aphasia at 30-day follow-up due to a thromboembolic infarct (modified Rankin Scale score 1). Among 33 patients (78.6%) available for angiographic follow-up, complete (OKM D) and favorable (OKM C+D) aneurysm occlusion was obtained in 72.7% (24/33) and 87.9% (29/33), respectively. CONCLUSIONS Endovascular treatment of UIAs with the DED is associated with high procedural safety and adequate occlusion rates. Examinations at 1- and 2-year follow-up will provide data on the long-term safety and angiographic outcomes of this device.


A Cheap, Simple Test That Predicts Complications: What's Not to Like?: Commentary on an article by Noam Shohat, MD, et al.: "Serum Fructosamine: A Simple and Inexpensive Test for Assessing Preoperative Glycemic Control".


Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group.


Clinical features and outcomes of coronavirus disease 2019 (COVID-19) patients with chronic Hepatitis B virus infection.


title: Conserved High Free Energy Sites in Human Coronavirus Spike Glycoprotein Backbones.

text: Methods previously developed by the author are applied to uncover several sites of interest in the spike glycoproteins of all known human coronaviruses (hCoVs), including SARS-CoV-2 that causes COVID-19. The sites comprise three-dimensional neighborhoods of peptides characterized by four key properties: (1) they pinpoint regions of high free energy in the backbone whose obstruction might interrupt function; (2) by their very definition, they occur rarely in the universe of all gene-encoded proteins that could obviate host response to compounds designed for their interference; (3) they are common to all seven hCoV spikes, possibly retaining activity in light of inevitable viral mutation; and (4) they are exposed in the molecular surface of the glycoprotein. These peptides in SARS-CoV-2 are given by the triples of residues (131, 117, 134), (203, 227, 228), and (1058, 730, 731) in its spike.


title: Cost-efficiency of laparoscopic versus open colon surgery in a tertiary care center.

text: BACKGROUND Real-world cost analysis of elective laparoscopic versus open colon resection in a tertiary Canadian teaching hospital was performed to evaluate the financial impact of minimally invasive surgery with the appointment of an experienced laparoscopic surgeon in a single-payer system. METHODS A retrospective review of elective laparoscopic and open segmental colectomies (2005-2010) was performed. Combined cases and procedures performed for inpatients were excluded to minimize cost variation. The hospital case-costing system was used to calculate the hourly cost of operating room time and the daily hospital ward stay. The cost of disposable equipment was calculated manually. A cost-minimization analysis was performed from the hospital perspective, which excludes physician payment. Cases were analyzed on an intention-to-treat basis. RESULTS For this study, 470 right-side colectomies (322 open and 148 laparoscopic) and 266 left-side colectomies (181 open and 85 laparoscopic) were found to match the inclusion criteria. The operating room time was longer for the laparoscopic procedures than for the open procedures: 203.4 versus 173.4 min (P = 0.1) for right and extended right hemicolectomy (RC) and 287.4 versus 173.4 min (P = 0.009) for left and sigmoid colectomy (LC). This resulted in higher operating room costs: $4,094.10 versus $3312.11 for RC and $5,784.88 versus $4,582.55 for LC. The median hospital stay for an index admission was shorter for both sides: 5 days versus 8 days (P = 0.01) for RC and 4 days versus 6 days (P = 0.04). This resulted in lower ward costs: $4,556.07 versus $6,632.82 for RC and $3,297.24 versus $5,949.09 for LC. The cost of care per index admission after laparoscopic versus open resection was $10,097.93 versus $10,444.69 for RC and $11,067.72 versus. $11,146.56 for LC. The introduction of laparoscopic surgery has saved our institution $58,021.43 over 5 years. CONCLUSION The reasons for observed differences in operating room time and length of hospital stay were uncontrolled and may be multifactorial. However, the results demonstrate that adopting a laparoscopic approach for elective colon surgery resulted in progressive financial savings.


title: Managing an obstetrics and gynaecology department in time of COVID pandemic: safety and efficacy first at Foch hospital.

text: Obstetrics and Gynecology department in France were not ready for the outbreak of the COVID pandemic, but ingenuity and dedication of personnel allowed to perform safely and avoid nocomial transmission of COVID.


title: Chemical modifications of antisense morpholino oligomers enhance their efficacy against Ebola virus infection.

text: Phosphorodiamidate morpholino oligomers (PMOs) are uncharged nucleic acid-like molecules designed to inactivate the expression of specific genes via the antisense-based steric hindrance of mRNA translation. PMOs have been successful at knocking out viral gene expression and replication in the case of acute viral infections in animal models and have been well tolerated in human clinical trials. We propose that antisense PMOs represent a promising class of therapeutic agents that may be useful for combating filoviral infections. We have previously shown that mice treated with a PMO whose sequence is complementary to a region spanning the start codon of VP24 mRNA were protected against lethal Ebola virus challenge. In the present study, we report on the abilities of two additional VP24-specific PMOs to reduce the cell-free translation of a VP24 reporter, to inhibit the in vitro replication of Ebola virus, and to protect mice against lethal challenge when the PMOs are delivered prior to infection. Additionally, structure-activity relationship evaluations were conducted to assess the enhancement of antiviral efficacy associated with PMO chemical modifications that included conjugation with peptides of various lengths and compositions, positioning of conjugated peptides to either the 5' or the 3' terminus, and the conferring of charge modifications by the addition of piperazine moieties. Conjugation with arginine-rich peptides greatly enhanced the antiviral efficacy of VP24-specific PMOs in infected cells and mice during lethal Ebola virus challenge.


Covid-19: should the public wear face masks?


Risk of disease transmission with bone allograft.


title: Orf Virus VIR Antagonizes p53-Mediated Antiviral Effects to Facilitate Viral Replication.

text: As a zoonotic disease, ovine contagious pustular dermatitis (Orf) is a serious threat to sheep as well as humans. Orf virus (ORFV) interferon resistance protein (VIR) is the principal virulence protein that encodes a dsRNA-binding protein to inhibit host antiviral response. p53 is one of the key proteins of the host antiviral innate immunity. It not only enhances type I interferon secretion but also induces apoptosis in infected cells, and plays a crucial role in the immune response against various viral infections. However, it remains to be elucidated what role p53 plays in ORFV replication and whether ORFV's own protein VIR regulates p53 expression to promote self-replication. In this study, we showed that p53 has an antiviral effect on ORFV and can inhibit ORFV replication. In addition, ORFV nonstructural protein VIR interacts with p53 and degrades p53, which inhibits p53-mediated positive regulation of downstream antiviral genes. This study provides new insight into the immune evasion mediated by ORFV and identifies VIR as an antagonistic factor for ORFV to evade the antiviral response.


The increasing impact of Chinese innovative drug research on the global stage with a focus on drug discovery.


Our Medical and Social Responsibility in Addressing the Opioid Epidemic.


title: The impact of laparoscopic anti-reflux surgery in patients with Barrett's esophagus.

text: BACKGROUND Barrett's esophagus (BE) is a major risk factor for esophageal adenocarcinoma. It is believed that BE is caused by chronic gastro-esophageal reflux disease (GERD). Laparoscopic anti-reflux surgery (LARS) restores the competency of the cardia and may thereby change the natural course of BE. We studied the impact of LARS on the histological profile of BE and on the control of GERD. METHODS We identified all patients with BE who underwent LARS from 1994 to 2007 and contacted them to assess post-operative GERD symptoms via questionnaire. Endoscopy findings, histology, 24 hour pH monitoring, and manometry were also collected using our prospectively maintained database. Histological regression was defined as either loss of dysplasia or disappearance of BE. RESULTS Two hundred and fifteen patients met the initial inclusion criteria; in 82 of them histology from post-operative endoscopy was available for review. Endoscopy was performed a median of 8 years (range, 1-16 years) after surgery. Regression of BE occurred in 18 (22%) patients while in 6 (7%) BE progressed to dysplasia or cancer. Thirty-six (43%) patients underwent pre- and post-operative manometry. The median lower esophageal sphincter pressure increased from 9 to 17 mmHg in these patients. Thirty-four (41%) patients underwent pre- and post-operative pH studies. The median DeMeester score decreased from 54 to 9. Sixty-seven (82%) of 82 patients completed the post-operative questionnaire; 86% of these patients reported improvement in heartburn and regurgitation. CONCLUSIONS LARS was associated with both physiologic and symptomatic control of GERD in patients with BE. LARS resulted in regression of BE in 22% of patients and progression in 7%. Thus, continued surveillance of Barrett's is needed after LARS.


title: A multicenter, simulation-based skills training collaborative using shared GI Mentor II systems: results from the Texas Association of Surgical Skills Laboratories (TASSL) flexible endoscopy curriculum.

text: BACKGROUND The Texas Association of Surgical Skills Laboratories (TASSL) is a nonprofit consortium of surgical skills training centers for the accredited surgery residency programs in Texas. A training and research collaborative was forged between TASSL members and Simbionix (Cleveland, OH, USA) to assess the feasibility and efficacy of a multicenter, simulation- and Web-based flexible endoscopy training curriculum using shared GI Mentor II systems. METHODS Two GI Mentor II flexible endoscopy simulators were provided for the study, and four institutions, namely, the University of Texas Health Science Center-San Antonio (UTHSCSA), Texas A & M University (TAMU), Methodist Hospital (MHD), and Brooke Army Medical Center (BAMC), agreed to share them. One additional site, University of Texas Southwestern (UTSW), already owned a device and participated during the study period. Postgraduate years (PGYs) 1 to 4 subjects completed pre- and posttraining questionnaires and one pre- and posttraining trial of Colonoscopy Case Module 1. EndoBubble 1 and 2 tasks with predefined, expert-derived levels were used for training. Pre- and posttesting performance data were recorded on the simulator and by the Global Assessment of Gastrointestinal Endoscopic Skills (GAGES). All study materials were available through the TASSL Web site. Pre- and posttest comparisons were made by paired t-test. RESULTS The curriculum was completed successfully by 41 participants from four institutions. The mean number of trials to proficiency was 13 ± 10 for EndoBubble 1 and 23 ± 16 for EndoBubble 2. Significant improvements from pre- to posttraining were seen in cecal intubation time (229 ± 97 vs. 150 ± 57 s; p < 0.001), total time (454 ± 147 vs. 320 ± 115 s; p < 0.001), screening efficiency (85% ± 12% vs. 91% ± 5%; p < 0.002), GAGES scores (15 vs. 19; p < 0.001), subjects' endoscopy self-rating scores (1.5 ± 1.0 vs. 2.7 ± 0.6; range, 0-4; p < 0.001), and comfort level with flexible endoscopy skills (3.4 ± 3.0 vs. 7.2 ± 1.2; range, 0-8; p < 0.001). CONCLUSIONS The feasibility of sharing educational and training resources among institutions was demonstrated. Likewise, the concept of "mobile simulation" appears to be useful and effective, with three of the four institutions involved successfully in implementing the training curriculum during a fixed period. Additionally, subjects who completed the training demonstrated both subjective and objective improvements in flexible endoscopy skills.


title: The value of radiography in the follow-up of extremity fractures: a systematic review.

text: BACKGROUND The added value of routine radiography in the follow-up of extremity fractures is unclear. The aim of this systematic review was to create an overview of radiography use in extremity fracture care and the consequences of these radiographs for the treatment of patients with these fractures. MATERIALS AND METHODS Studies were included if they reported on the use of radiography in the follow-up of extremity fractures and on its influence on treatment strategy, clinical outcome, or complications. A comprehensive search of electronic databases (i.e., PubMed, Embase, and Cochrane) was performed to identify relevant studies. Methodological quality was assessed with the Newcastle-Ottawa scale for cohort studies. Level of evidence was assessed using GRADE. The search, quality appraisal, and data extraction were performed independently by two researchers. RESULTS Eleven studies were included. All studies were retrospective cohorts. Of these, only two used a comparative design. Two of the included studies described fractures of both the upper and lower extremities, four studies concerned fractures of the lower extremity only, and five studies focused on fractures of the upper extremity. Pooling of data was not performed because of clinical heterogeneity. Eight studies reported on a change in treatment strategy related to radiography. Percentages ranged from 0 to 2.6%. The overall results indicated that radiographs in the follow-up of extremity fractures seldom alter treatment strategy, that the vast majority of follow-up radiographs are obtained without a clinical indication and that detection of a complication on a radiograph, in the absence of clinical symptoms, is unlikely. All included studies were regarded of a 'very low' level using GRADE. CONCLUSIONS Based on current literature, the added value of routine radiography in the follow-up of extremity fractures seems limited. Results, however, should be interpreted with care, considering that available evidence is of a low level.


Responding to emerging diseases: reducing the risks through understanding the mechanisms of emergence.


title: Comparison of Surgical Outcomes Between Resection and Enucleation in Robot-Assisted Laparoscopic Partial Nephrectomy for Renal Tumors According to the Surface-Intermediate-Base Margin Score: A Propensity Score-Matched Study.

text: OBJECTIVE To compare the surgical outcomes between resection and enucleation in robot-assisted laparoscopic partial nephrectomy (RAPN) based on the Surface-Intermediate-Base margin score (SIB score). PATIENTS AND METHODS This study included 282 patients who underwent RAPN between 2014 and 2016. SIB score was macroscopically evaluated immediately after the surgery. We divided the patients into the following two groups: enucleation (SIB score, 1-2) and resection (SIB score, 3-5). To minimize selection bias between the two surgical methods, patient variables were adjusted by 1:1 propensity score matching. RESULTS Of the 282 patients, 48 were assigned to the enucleation group and 234 to the resection group. After matching, 45 patients were included in each group. The mean preoperative estimated glomerular filtration rate (eGFR) was 70 mL/min/1.73 m2. The mean tumor size was 32-33 mm. The decrease in eGFR (5.6 vs 12%, p = 0.0365) and total perioperative complication (16% vs 38%, p = 0.0171) were significantly lower in the enucleation group than in the resection group. Estimated blood loss was higher in the enucleation group than in the resection group (129 cc vs 117 cc, p = 0.0088), despite a similar transfusion rate. The postoperative length of hospital stay was shorter in the enucleation group than in the resection group (4.1 vs 5.0 days, p = 0.0288). Operation time and surgical margin status were not significantly different between groups. CONCLUSIONS In carefully selected patients, enucleation was associated with more favorable surgical outcomes in the cohort than resection, including improved renal function and a lower complication rate.


title: Infection of human alveolar macrophages by human coronavirus strain 229E.

text: Human coronavirus strain 229E (HCoV-229E) commonly causes upper respiratory tract infections. However, lower respiratory tract infections can occur in some individuals, indicating that cells in the distal lung are susceptible to HCoV-229E. This study determined the virus susceptibility of primary cultures of human alveolar epithelial cells and alveolar macrophages (AMs). Fluorescent antibody staining indicated that HCoV-229E could readily infect AMs, but no evidence was found for infection in differentiated alveolar epithelial type II cells and only a very low level of infection in type II cells transitioning to the type I-like cell phenotype. However, a human bronchial epithelial cell line (16HBE) was readily infected. The innate immune response of AMs to HCoV-229E infection was evaluated for cytokine production and interferon (IFN) gene expression. AMs secreted significant amounts of tumour necrosis factor alpha (TNF-α), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and macrophage inflammatory protein 1β (MIP-1β/CCL4) in response to HCoV-229E infection, but these cells exhibited no detectable increase in IFN-β or interleukin-29 in mRNA levels. AMs from smokers had reduced secretion of TNF-α compared with non-smokers in response to HCoV-229E infection. Surfactant protein A (SP-A) and SP-D are part of the innate immune system in the distal lung. Both surfactant proteins bound to HCoV-229E, and pre-treatment of HCoV-229E with SP-A or SP-D inhibited infection of 16HBE cells. In contrast, there was a modest reduction in infection in AMs by SP-A, but not by SP-D. In summary, AMs are an important target for HCoV-229E, and they can mount a pro-inflammatory innate immune response to infection.


COVID-19 and Diabetes: Could Diabetes Technology Research Help Pave the Way for Remote Healthcare?


title: Interventions improving health professionals' practice for addressing patients' weight management behaviours: systematic review of reviews.

text: Health professionals require education and training to implement obesity management guidelines and ultimately impact on the health outcomes experienced by their patients. Therefore, a systematic review of systematic reviews that evaluated interventions designed to change the practice of health professionals when addressing diet and physical activity with their patients was conducted. MEDLINE Complete; Cochrane database of systematic reviews; PsycINFO; CINAHL Complete; Global Health; Embase; INFORMIT: Health Subset; Health System Evidence and RX for change were searched in March 2019, with no date or language limits. Identified references underwent screening, full-text analyses and data extraction in duplicate. The search identified 15 230 references. Five systematic reviews that provided a narrative syntheses of a combined 38 studies were included. Health professional participants generally reported being satisfied with the training interventions. Heterogeneity between and within included reviews, non-controlled designs of individual studies and low quality of evidence at an individual study level and review level made it difficult to draw firm conclusions regarding what interventions are most effective in changing health professionals' knowledge, skills, self-efficacy, attitudes and practice. However, similar gaps in the literature were identified across included reviews. Key areas that could be addressed in future interventions including organization and system-level barriers to providing advice, health professionals' attitudes and motivation and weight stigma have been highlighted. Health professionals and patients could be more involved in the planning and development of interventions that work towards improving diet and physical activity advice and support provided in healthcare.


title: Identification and genetic characterization of a novel picornavirus from chickens.

text: A novel picornavirus from commercial broiler chickens (Gallus gallus domesticus) has been identified and genetically characterized. The viral genome consists of a single-stranded, positive-sense RNA genome of >9243 nt excluding the poly(A) tail and as such represents one of the largest picornavirus genomes reported to date. The virus genome is GC-rich with a G+C content of 54.5 %. The genomic organization is similar to other picornaviruses: 5' UTR-L-VP0-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3' UTR. The partially characterized 5' UTR of >373 nt appears to possess a type II internal ribosomal entry site (IRES), which is also found in members of the genera Aphthovirus and Cardiovirus. This IRES exhibits significant sequence similarity to turkey 'gallivirus A'. The 3' UTR of 278 nt contains the conserved 48 nt 'barbell-like' structure identified in 'passerivirus', 'gallivirus', Avihepatovirus and some Kobuvirus genus members. A predicted large open reading frame (ORF) of 8592 nt encodes a potential polyprotein precursor of 2864 amino acids. In addition, the virus contains a predicted large L protein of 462 amino acids. Pairwise sequence comparisons, along with phylogenetic analysis revealed the highest percentage identity to 'Passerivirus A' (formerly called turdivirus 1), forming a monophyletic group across the P1, P2 and P3 regions, with <40, <40 and <50 % amino acid identity respectively. Reduced identity was observed against 'gallivirus A' and members of the Kobuvirus genus. Quantitative PCR analysis estimated a range of 4×10(5) to 5×10(8) viral genome copies g(-1) in 22 (73 %) of 30 PCR-positive faeces. Based on sequence and phylogenetic analysis, we propose that this virus is the first member of a potential novel genus within the family Picornaviridae. Further studies are required to investigate the pathogenic potential of this virus within the avian host.


title: Laparoscopic ovariectomy in dogs: comparison between single portal and two-portal access.

text: OBJECTIVE To compare surgical times and perioperative complication rates of single portal access and 2-portal laparoscopic ovariectomy (LapOVE) in dogs using a bipolar vessel sealer/divider device, and to evaluate the performance of novice laparoscopists for right ovariectomy. STUDY DESIGN Controlled clinical trial. ANIMALS Female dogs (n=42). METHODS Dogs were divided into groups: 1=single portal and 2=2 portal. LapOVE was performed using a 5 mm vessel sealer/divider device and a 10 mm operating laparoscope (Group 1) or a 5 mm laparoscope (Group 2). Dog characteristics (weight, body condition score, ovarian ligament fat score), operative time, and perioperative complication rate were compared between groups. Right ovariectomy duration was evaluated for 2 novice laparoscopists. RESULTS No significant difference was found in mean total surgical time between group 1 (21.07 min/s) and group 2 (19.06 min/s). Factors significantly affecting times included body condition scores, ovarian ligament fat score, ovarian bleeding, and surgeon expertise. Minor complications (bleeding from ovaries or after splenic trauma) occurred and were similar in both groups. Bleeding was correlated to body condition score and ovarian ligament fat score. Interindividual differences were found among surgeons for right ovariectomy time. CONCLUSIONS Single portal access LapOVE using vessel sealer/divider device is feasible, safe, and does not significantly increase total surgical time in comparison with 2-portal approach. Laparoscopic skills may play a role in ability to perform single portal LapOVE. CLINICAL RELEVANCE LapOVE can be performed using single portal access.


title: Liver Ablation: Best Practice.

text: Tumor ablation in the liver has evolved to become a well-accepted tool in the management of increasing complex oncologic patients. At present, percutaneous ablation is considered first-line therapy for very early and early hepatocellular carcinoma and second-line therapy for colorectal carcinoma liver metastasis. Because thermal ablation is a treatment option for other primary and secondary liver tumors, an understanding of the underlying tumor biology is important when weighing the potential benefits of ablation. This article reviews ablation modalities, indications, patient selection, and imaging surveillance, and emphasizes technique-specific considerations for the performance of percutaneous ablation.


title: ASPECTS, Large Vessel Occlusion, and Time of Symptom Onset: Estimation of Eligibility for Endovascular Therapy.

text: BACKGROUND Understanding how many patients are eligible for endovascular therapy can help develop more effective stroke systems of care. OBJECTIVE To determine the proportion of patients eligible for endovascular therapy. METHODS In this single center retrospective cohort study, we identified patients with acute ischemic stroke from large vessel occlusion (LVO) from January 2014 to December 2015. Selection criteria including LVO location, Alberta stroke program early computed tomography score (ASPECTS) range, hospital arrival time, and the use of intravenous thrombolysis were applied to calculate proportions of patients eligible for endovascular therapy. RESULTS Of 989 patients with acute ischemic stroke, LVO was identified in 224 (23%) cases. Eighty-four percent of patients admitted within 6 h, 75% of patients admitted within 6 to 12 h, and 77% of patients with M1 and internal carotid artery occlusions admitted within 12 to 24 h had favorable ASPECTS for thrombectomy, defined as ASPECTS ≥ 6. Severity of NIHSS (National Institutes of Health Stroke Scale) was predictive of favorable ASPECTS (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.04-0.74; P = .014 for NIHSS > 10 and OR 0.30, 95% CI 0.12-0.80; P = .014 for NIHSS > 20), whereas time of hospital arrival was not (OR 1.73, 95% CI 0.76-4.03; P = .26). Using all class I, Level of Evidence A American Heart Association guidelines criteria, 4% of patients with acute ischemic stroke were eligible for endovascular therapy. Up to 20% of patients were eligible for endovascular therapy with less restrictive criteria (Class IIb; Level of Evidence C). CONCLUSION Depending on the sets of selection criteria, between 4% (the most restrictive criteria) and 20% (the least restrictive criteria) of patients with LVO are potentially eligible for endovascular therapy.


Oceanography. New satellite radar could find 100,000 underwater mountains.


title: Mitochondria and Microbiota dysfunction in COVID-19 pathogenesis.

text: The COVID-19 pandemic caused by the coronavirus (SARS-CoV-2) has taken the world by surprise into a major crisis of overwhelming morbidity and mortality. This highly infectious disease is associated with respiratory failure unusual in other coronavirus infections. Mounting evidence link the accelerated progression of the disease in COVID-19 patients to the hyper-inflammatory state termed as the "cytokine storm" involving major systemic perturbations. These include iron dysregulation manifested as hyperferritinemia associated with disease severity. Iron dysregulation induces reactive oxygen species (ROS) production and promotes oxidative stress. The mitochondria are the hub of cellular oxidative homeostasis. In addition, the mitochondria may circulate "cell-free" in non-nucleated platelets, in extracellular vesicles and mitochondrial DNA is found in the extracellular space. The heightened inflammatory/oxidative state may lead to mitochondrial dysfunction leading to platelet damage and apoptosis. The interaction of dysfunctional platelets with coagulation cascades aggravates clotting events and thrombus formation. Furthermore, mitochondrial oxidative stress may contribute to microbiota dysbiosis, altering coagulation pathways and fueling the inflammatory/oxidative response leading to the vicious cycle of events. Here, we discuss various cellular and systemic incidents caused by SARS-CoV-2 that may critically impact intra and extracellular mitochondrial function, and contribute to the progression and severity of the disease. It is crucial to understand how these key modulators impact COVID-19 pathogenesis in the quest to identify novel therapeutic targets that may reduce fatal outcomes of the disease.


title: Environmental degradation and health risks in Beijing, China.

text: As China's capital city, Beijing is experiencing unprecedented environmental degradation accompanied by complex interactions between urbanization and global environmental change, which places human health at risk on a large spatial and temporal scale. For sustainable development that supports environmental and human health in Beijing and during the upcoming "green" Olympic games in 2008, experts and political leaders must acknowledge the urgent health risks from environmental changes related to urbanization. A range of urban health hazards and associated health risks in Beijing result from a variety of factors including heat islands, air pollution, water crisis, soil pollution, infectious diseases, and urban consumerism; in addition, some hazardous health conditions are associated with inequality in living and working conditions. The authors suggest 2 main areas for policy action and research direction: (1) the need to get full-scale information related to environmental monitoring data and health data (and then to provide new methodological approaches and techniques to implement interventions) and (2) the need for effective cooperation among different sectors.