title: Using a simple apparatus to measure direct and diffuse photosynthetically active radiation at remote locations.

text: Plant canopy interception of photosynthetically active radiation (PAR) drives carbon dioxide (CO2), water and energy cycling in the soil-plant-atmosphere system. Quantifying intercepted PAR requires accurate measurements of total incident PAR above canopies and direct beam and diffuse PAR components. While some regional data sets include these data, e.g. from Atmospheric Radiation Measurement (ARM) Program sites, they are not often applicable to local research sites because of the variable nature (spatial and temporal) of environmental variables that influence incoming PAR. Currently available instrumentation that measures diffuse and direct beam radiation separately can be cost prohibitive and require frequent adjustments. Alternatively, generalized empirical relationships that relate atmospheric variables and radiation components can be used but require assumptions that increase the potential for error. Our goal here was to construct and test a cheaper, highly portable instrument alternative that could be used at remote field sites to measure total, diffuse and direct beam PAR for extended time periods without supervision. The apparatus tested here uses a fabricated, solar powered rotating shadowband and other commercially available parts to collect continuous hourly PAR data. Measurements of total incident PAR had nearly a one-to-one relationship with total incident radiation measurements taken at the same research site by an unobstructed point quantum sensor. Additionally, measurements of diffuse PAR compared favorably with modeled estimates from previously published data, but displayed significant differences that were attributed to the important influence of rapidly changing local environmental conditions. The cost of the system is about 50% less than comparable commercially available systems that require periodic, but not continual adjustments. Overall, the data produced using this apparatus indicates that this instrumentation has the potential to support ecological research via a relatively inexpensive method to collect continuous measurements of total, direct beam and diffuse PAR in remote locations.


title: A strategy to simultaneously eradicate the natural reservoirs of rabies and Ebola virus.

text: The efficacy of a recombinant live-attenuated or chemically inactivated bivalent vaccine against rabies virus (RABV) and Ebola virus (EBOV) infection was evaluated in a lethal mouse model of infection. The vaccines were derived from the live-attenuated Street Alabama Dufferin B19 RABV platform already approved for veterinary use, where intramuscular, intranasal and intraperitoneal administration of the recombinant vaccines were avirulent in adult mice. Significant levels of serum RABV- and EBOV-specific antibodies were observed postvaccination, with levels that correlated with protection in vaccinated mice post-RABV or -EBOV challenge. These results justify further studies in guinea pigs and nonhuman primates, and highlight a promising strategy to eradicate the natural reservoirs of RABV and EBOV.


title: A Novel Mobile Phone Application for Pulse Pressure Variation Monitoring Based on Feature Extraction Technology: A Method Comparison Study in a Simulated Environment.

text: BACKGROUND Pulse pressure variation (PPV) can be used to assess fluid status in the operating room. This measurement, however, is time consuming when done manually and unreliable through visual assessment. Moreover, its continuous monitoring requires the use of expensive devices. Capstesia™ is a novel Android™/iOS™ application, which calculates PPV from a digital picture of the arterial pressure waveform obtained from any monitor. The application identifies the peaks and troughs of the arterial curve, determines maximum and minimum pulse pressures, and computes PPV. In this study, we compared the accuracy of PPV generated with the smartphone application Capstesia (PPVapp) against the reference method that is the manual determination of PPV (PPVman). METHODS The Capstesia application was loaded onto a Samsung Galaxy S4 phone. A physiologic simulator including PPV was used to display arterial waveforms on a computer screen. Data were obtained with different sweep speeds (6 and 12 mm/s) and randomly generated PPV values (from 2% to 24%), pulse pressure (30, 45, and 60 mm Hg), heart rates (60-80 bpm), and respiratory rates (10-15 breaths/min) on the simulator. Each metric was recorded 5 times at an arterial height scale X1 (PPV5appX1) and 5 times at an arterial height scale X3 (PPV5appX3). Reproducibility of PPVapp and PPVman was determined from the 5 pictures of the same hemodynamic profile. The effect of sweep speed, arterial waveform scale (X1 or X3), and number of images captured was assessed by a Bland-Altman analysis. The measurement error (ME) was calculated for each pair of data. A receiver operating characteristic curve analysis determined the ability of PPVapp to discriminate a PPVman > 13%. RESULTS Four hundred eight pairs of PPVapp and PPVman were analyzed. The reproducibility of PPVapp and PPVman was 10% (interquartile range, 7%-14%) and 6% (interquartile range, 3%-10%), respectively, allowing a threshold ME of 12%. The overall mean bias for PPVappX1 was 1.1% within limits of -1.4% (95% confidence interval [CI], -1.7 to -1.1) to +3.5% (95% CI, +3.2 to +3.8). Averaging 5 values of PPVappX1 with a sweep speed of 12 mm/s resulted in the smallest bias (+0.6%) and the best limits of agreement (±1.3%). ME of PPVapp was <12% whenever 3, 4, or 5 pictures were taken to average PPVapp. The best predictive value for PPVapp to detect a PPVman > 13% was obtained for PPVappX1 by averaging 5 pictures showing a PPVapp threshold of 13.5% (95% CI, 12.9-15.2) and a receiver operating characteristic curve area of 0.989 (95% CI, 0.963-0.998) with a sensitivity of 97% and a specificity of 94%. CONCLUSIONS Our findings show that the Capstesia PPV calculation is a dependable substitute for standard manual PPV determination in a highly controlled environment (simulator study). Further studies are warranted to validate this mobile feature extraction technology to predict fluid responsiveness in real conditions.


title: COVID-19 Hits Cancer Research Funding.

text: As the COVID-19 pandemic stretches on, investigators are becoming increasingly concerned about longer-term effects on grants and funding for cancer research. Institutions and philanthropic organizations are especially likely to be hit hard by the economic crisis, with effects that will be particularly acute for early-career investigators.


title: Single-incision laparoscopic surgery for gallstone ileus: An alternative surgical procedure.

text: INTRODUCTION Gallstone ileus (GI) results from the passage of a stone through a cholecystoenteric fistula, subsequently causing a bowel obstruction. The ideal treatment procedure for GI remains controversial. PRESENTATION OF CASE A 63-year-old female was admitted to our hospital following persistent nausea and vomiting for 7 days. Computed tomography revealed a partially calcified 4-cm circular object in the jejunum, and the proximal intestine was dilated, with concomitant pneumobilia. Based on the preoperative diagnosis of GI, enterotomy with stone extraction by single-incision laparoscopic surgery (SILS) was performed. The patient's postoperative course was uneventful, and the cholecystoduodenal fistula closed spontaneously 4 months after the surgery. DISCUSSION Recent studies have reported that enterotomy with stone extraction alone is associated with better outcomes than with more invasive techniques. This case also suggests that enterotomy with stone extraction alone and careful postoperative follow-up is feasible for the management of GI. Although the use of laparoscopy in the management of GI has been described previously, laparoscopic surgery has not been widely performed, and SILS is not generally performed. When only this less demanding procedure is required, laparoscopic surgery, including SILS, can be a viable option. CONCLUSION SILS can be an alternative surgical procedure for the management of GI.


title: Effects of moderate and severe arterial hypotension on intracerebral perfusion and brain tissue oxygenation in piglets.

text: BACKGROUND Hypotension is common in anaesthetised children, and its impact on cerebral oxygenation is unknown. The goal of the present study was to investigate the effects of moderate systemic arterial hypotension (mHT) and severe hypotension (sHT) on cerebral perfusion and brain tissue oxygenation in piglets. METHODS Twenty-seven anaesthetised piglets were randomly allocated to a control group, mHT group, or sHT group. Cerebral monitoring comprised a tissue oxygen partial pressure ( [Formula: see text] ) and laser Doppler (LD) perfusion probe advanced into the brain tissue, and a near-infrared spectroscopy sensor placed over the skin measuring regional oxygen saturation (rSO2). Arterial hypotension was induced by blood withdrawal and i.v. nitroprusside infusion [target MAP: 35-38 (mHT) and 27-30 (sHT) mm Hg]. Data were analysed at baseline, and every 20 min during and after treatment. RESULTS Compared with control, [Formula: see text] decreased equally with mHT and sHT [mean (SD) after 60 min: control: 17.1 (6.4); mHT: 6.4 (3.6); sHT: 7.2 (4.3) mm Hg]. No differences between groups were detected for rSO2 and LD during treatment. However, in the sHT group, rSO2 increased after restoring normotension [from 49.3 (9.5) to 58.9 (8.9)% Post60]. sHT was associated with an increase in blood lactate [from 1.5 (0.4) to 2.4 (0.9) mmol L-1], and a decrease in bicarbonate [28 (2.4) to 25.8 (2.6) mmol L-1] and base excess [4.7 (1.9) to 2.0 (2.7) mmol L-1] between baseline and 60 min after the start of the experiment. CONCLUSIONS Induction of mHT and sHT by hypovolaemia and nitroprusside infusion caused alterations in brain tissue oxygenation in a piglet model, but without detectable changes in brain tissue perfusion and regional oxygen saturation.


title: Concurrent transperitoneal repair for incidentally detected inguinal hernias during robotically assisted radical prostatectomy.

text: OBJECTIVE To report our experience with concurrent intraperitoneal inguinal herniorrhaphy using prosthetic mesh during robotically assisted radical prostatectomy (RARP) for incidentally discovered inguinal hernias. METHODS We performed a retrospective review of 1118 consecutive RARPs performed by one surgeon between July 2005 and July 2011. Cases that included concurrent hernia repair were compared with a group of patients matched 1:1 for age, body mass index, and year of surgery, who underwent RARP alone (controls). RESULTS A total of 91 patients underwent 113 concurrent inguinal hernia repairs during RARP. Twenty-two patients (24%) underwent bilateral repair. Of the 69 patients undergoing unilateral repair, 41 (45%) underwent left-sided repair, and 29 (31%) underwent right-sided repair. Thirty-five (38%) patients had previous inguinal hernia repair. Body mass index of cases and controls were 27.5 ± 3.4 and 27.8 ± 3.1 kg/m(2), respectively. Mean operative time in cases was 185 ± 28 minutes vs 168 ± 31 minutes in controls (P <.001). Estimated blood loss was 170 ± 61 mL for cases vs 194 ± 82 mL for controls (P = .03). No differences were observed in length of stay or prevalence of postoperative complications. There was 1 hernia recurrence, which necessitated repeat repair 1 year after surgery. No mesh infections or other complications related to hernia repairs were observed. CONCLUSION Inguinal hernias are a common intraoperative finding during RARP. Concurrent repair appears safe and effective with only a slight increase in operative time, and no increase in morbidity.


title: Totally laparoscopic caudate lobe resection: technical aspects and literature review.

text: The particular anatomic location of the hepatic caudate lobe between the hilar plate and inferior vena cava means that it is still considered unsuitable for laparoscopic measures and a difficult site even for conventional surgery. Here we describe the first case to be reported in the literature of caudate lobe resection for a single metastasis from breast adenocarcinoma that was completed using an exclusively laparoscopic procedure and a simplified scheme involving the placement of 4 trocars, without any need for conversion or the Pringle maneuver. The patient was 31 years old with a history of radical right mastectomy and chemotherapy. The patient's postoperative course was uneventful and she was discharged 4 days after the surgery. Twelve months on, she is currently alive and disease free.


title: Comparison of combined nose-throat swabs with nasopharyngeal aspirates for detection of pandemic influenza A/H1N1 2009 virus by real-time reverse transcriptase PCR.

text: Data assessing the diagnostic accuracies of use of different respiratory samples for the detection of the novel influenza A/H1N1 2009 virus by molecular methods are lacking. The objective of this study was to compare the sensitivity of combined nose and throat swabs (CNTS) with that of nasopharyngeal aspirates (NPA). This was a prospective study of adults and children with suspected influenza. Real-time reverse transcriptase PCR testing was used for the virological diagnosis. Of the 2,473 patients included, 264 with paired CNTS and NPA were randomly selected. Novel influenza A/H1N1 virus was identified in at least one sample for 115 (43.6%) patients, the majority of them young adults. In 109 patients (94.8%) the virus was identified in the CNTS, and in 98 (85.2%) it was identified in the NPA (P = 0.02). In 93 patients (80.1%), the virus was identified in both specimens. Spearman's rho correlation coefficient between the two methods was 0.82 (P < 0.001). There were no significant differences in accuracy between the specimens when patients were stratified according to demographic or clinical characteristics except in the case of women, in whom the sensitivity of CNTS was higher (P = 0.01). The combination of CNTS and NPA had a significantly higher sensitivity in identifying the virus than did each method alone (P = 0.02 for the comparison of the combination of both sampling methods with CNTS, and P < 0.001 for the comparison with NPA). We conclude that in patients with the novel influenza A/H1N1 virus, the diagnostic yield of CNTS is higher than that of NPA. The combination of both sampling methods increases the likelihood of diagnosing the virus.


Ambitious rhetoric and appalling reality: the UK government's response to covid-19.


title: Randomised clinical trial: the 5-HT4 agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy.

text: BACKGROUND A substantial proportion of patients with gastro-oesophageal reflux disease (GERD) have only a partial response to proton pump inhibitor (PPI) therapy. Prokinetic drugs may improve reflux symptoms by enhancing oesophageal motility and gastric emptying. AIM To evaluate the effect of revexepride, a novel prokinetic 5-hydroxytryptamine type 4 (5-HT4 ) receptor agonist, compared with placebo, in patients with GERD who have a partial response to PPIs. METHODS A phase 2b, double-blind, parallel-group study was conducted, in which patients were randomised to one of three revexepride treatment groups (0.1, 0.5 and 2.0 mg three times daily) or placebo (1:1:1:1 ratio). Daily e-diary data captured patients' symptoms over an 8-week treatment period. The primary efficacy outcome was the weekly percentage of regurgitation-free days in the second half of the study (weeks 5-8). RESULTS In total, 480 patients were randomised and 477 received treatment (mean age 47.9 years; 61% women). The mean percentage of regurgitation-free days increased from baseline (range, 15.0-18.8%) to week 8 (62.3-70.5%) in all four study arms; however, there were no statistically significant differences in this change between placebo and the three treatment arms. No dose-dependent relationship in treatment effect was observed for any of the study endpoints. The incidence of treatment-emergent adverse events (TEAEs) was revexepride dose-dependent. Only one serious TEAE occurred and none resulted in death. CONCLUSIONS Revexepride was no more effective than placebo in controlling regurgitation in patients with GERD symptoms partially responsive to PPIs. Revexepride was well tolerated. ClinicalTrials.gov Identifier: NCT01472939.


title: Comparison of motor diagnoses by Chicago Classification versions 2.0 and 3.0 on esophageal high-resolution manometry.

text: BACKGROUND The Chicago Classification (CC) uses high-resolution manometry (HRM) software tools to designate esophageal motor diagnoses. We evaluated changes in diagnostic designations between two CC versions, and determined motor patterns not identified by either version. METHODS In this observational cohort study of consecutive patients undergoing esophageal HRM over a 6-year period, proportions meeting CC 2.0 and 3.0 criteria were segregated into esophageal outflow obstruction, hypermotility, and hypomotility disorders. Contraction wave abnormalities (CWA), and 'normal' cohorts were recorded. Symptom burden was characterized using dominant symptom intensity and global symptom severity. Motor diagnoses, presenting symptoms, and symptom burden were compared between CC 2.0 and 3.0, and in cohorts not meeting CC diagnoses. KEY RESULTS Of 2569 eligible studies, 49.9% met CC 2.0 criteria, but only 40.3% met CC 3.0 criteria (P<.0001). Between CC 2.0 and 3.0, 82.8% of diagnoses were concordant. Discordance resulted from decreasing proportions of hypermotility (4.4%) and hypomotility (9.0%) disorders, and increase in 'normal' designations (13.0%); esophageal outflow obstruction showed the least variation between CC versions. Symptom burden was higher with CC 3.0 diagnoses (P≤.005) but not with CC 2.0 diagnoses (P≥.1). Within 'normal' cohorts for both CC versions, CWA were associated with higher likelihood of esophageal symptoms, especially dysphagia, regurgitation, and heartburn, compared to truly normal studies (P≤.02 for each comparison). CONCLUSIONS AND INFERENCES Despite lower sensitivity, CC 3.0 identifies esophageal motor disorders with higher symptom burden compared to CC 2.0. CWA, which are associated with both transit and perceptive symptoms, are not well identified by either version.


title: Asymptomatic SARS-CoV-2 Infection in Nursing Homes, Barcelona, Spain, April 2020.

text: During the coronavirus disease pandemic in Spain, from April 10-24, 2020, a total of 5,869 persons were screened for severe acute respiratory syndrome coronavirus 2 at nursing homes. Among residents, 768 (23.9%) tested positive; among staff, 403 (15.2%). Of those testing positive, 69.7% of residents and 55.8% of staff were asymptomatic.


title: A Multicenter Collaboration to Assess the Safety of Laparoscopic Ventral Rectopexy.

text: BACKGROUND Concerns have been raised regarding the potential risk of mesh complications after laparoscopic ventral rectopexy. OBJECTIVE This study aimed to determine the risk of mesh and nonmesh morbidity after laparoscopic ventral rectopexy and to compare the safety of synthetic meshes with biological grafts. DESIGN This was a retrospective review. SETTINGS The study used data collated from prospective pelvic floor databases in 5 centers (3 in the United Kingdom, 1 in Australia, and 1 in Italy). PATIENTS All of the patients undergoing laparoscopic ventral rectopexy over a 14-year period (1999-2013) at these centers were included in the study. MAIN OUTCOME MEASURES The primary outcome was mesh morbidity, classified as vaginal erosion, rectal erosion, rectovaginal fistula, or perineal erosion. Secondary outcomes were nonmesh morbidity. RESULTS A total of 2203 patients underwent surgery; 1764 (80.1%) used synthetic mesh and 439 (19.9%) used biological grafts. There were 2 postoperative deaths (0.1%). Forty-five patients (2.0%) had mesh erosion, including 20 vaginal, 17 rectal, 7 rectovaginal fistula, and 1 perineal. Twenty-three patients (51.1%) required treatment for minor erosion morbidity (local excision of stitch/exposed mesh), and 18 patients (40.0%) were treated for major erosion morbidity (12 laparoscopic mesh removal, 3 mesh removal plus colostomy, and 3 anterior resection). Erosion occurred in 2.4% of synthetic meshes and 0.7% of biological meshes. The median time to erosion was 23 months. Nonmesh complications occurred in 11.1% of patients. LIMITATIONS This was a retrospective study including patients with minimal follow-up. The study was unable to determine whether patients will develop future erosions, currently have asymptomatic erosions, or have been treated in other institutions for erosions. CONCLUSIONS Laparoscopic ventral rectopexy is a safe operation. Mesh erosion rates are 2% and occasionally require resectional surgery that might be reduced by the use of biological graft. An international ventral mesh registry is recommended to monitor mesh problems and to assess whether type of mesh has any impact on functional outcomes or the need for revisional surgery for nonerosion problems.


title: Pancreatic pseudocystgastrostomy with a peroral, flexible stapler: human natural orifice transluminal endoscopic surgery anastomoses in 2 patients (with videos).

text: BACKGROUND Complex, symptomatic pancreatic pseudocysts often must be surgically drained. Natural orifice surgery is an emerging field in which surgical procedures are performed by using an endoluminal approach through an existing body orifice. PATIENTS AND SETTING Two patients at our institution, an academic, tertiary care center. DESIGN Two patients who underwent a standard, stapled, surgical cystgastrostomy for drainage of a complex, infected pseudocyst by using a flexible stapling device are described. These procedures were performed under endoscopic observation and guidance, all transorally, without the need for laparotomy or laparoscopy. RESULTS Both patients had a technically successful outcome, and both did well after surgery, with only mild chest pain and throat discomfort in one, and no adverse sequelae at all in the other patient. Both patients had complete resolution of their complex, debris-filled pseudocysts at 6 weeks when examined by endoscopy and at 3 months when examined by CT. CONCLUSIONS An entirely endoscopic, peroral, stapled pseudocystgastrostomy is feasible and can lead to an excellent outcome. For properly selected patients, this may be an alternative to more traditional types of surgical cystgastrostomy.


What makes people talk about Ebola on social media? A retrospective analysis of Twitter use.


Aortic root thrombosis after transhiatal esophagectomy: a case report.


title: Acute Otitis Media and Other Complications of Viral Respiratory Infection.

text: BACKGROUND Viral upper and lower respiratory tract infections (URI, LRI) are common in infants. We determined the prevalence of viral URI and its complications, including acute otitis media (AOM) and LRI, and assessed the effect of bacterial-viral interactions, and genetic and environmental risks on AOM development. METHODS Healthy infants were enrolled from near birth and followed to the first episode of AOM up to 12 months of age. Nasopharyngeal specimens were collected at monthly intervals (months 1-6, 9) and during viral URI episodes for bacterial culture and viral polymerase chain reaction studies. Subjects were followed closely for AOM development. RESULTS A total of 367 infants were followed for 286 child-years; 887 URI (305 infants) and 180 AOM episodes (143 infants) were documented. Prevalence of URI, LRI, and AOM in the first year was 3.2, 0.25, and 0.67 per child-year, respectively. Cumulative AOM incidence by ages 3, 6, and 12 months was 6%, 23%, and 46%. Infants with and without AOM had 4.7 and 2.3 URI episodes per child-year, respectively (P < .002). Pathogenic bacterial colonization rates by month were significantly higher in infants with AOM (P < .005). Breastfeeding reduced both URI and AOM risks (P < .05). Significant bacterial-viral interactions occurred with Moraxella catarrhalis and a variety of respiratory viruses and altered URI and AOM risks. CONCLUSIONS Almost half of infants experienced AOM by age 1. Important AOM risk factors included frequent viral URI, pathogenic bacterial colonization, and lack of breastfeeding. Bacterial-viral interactions may play a significant role in AOM pathogenesis and deserve further investigation.


title: Shorter circular staple is height associated with lower anastomotic stricture rate in laparoscopic gastric bypass.

text: BACKGROUND Anastomotic stenosis, leak, and hemorrhage are common stapler-related complications of laparoscopic Roux-en-Y gastric bypass. In May 2007, we transitioned from a 25-mm diameter, 4.8-mm-height circular stapler to a 25-mm, 3.5-mm-height circular stapler. We hypothesized that the staple height would be associated with a decreased incidence of perioperative complications. METHODS The records of 360 consecutive patients who had undergone laparoscopic Roux-en-Y gastric bypass from May 1, 2006 to March 31, 2008 were retrospectively abstracted. The National Surgical Quality Improvement Project and Michigan Bariatric Surgery Collaborative databases were used to collect the patient demographics and track complications of laparoscopic Roux-en-Y gastric bypass. Data were collected on the rates of anastomotic stenosis requiring dilation of the gastrojejunostomy, anastomotic leak, hemorrhage requiring transfusion, and wound infection. Patients with a 4.8-mm staple height gastrojejunostomy were compared with those with a 3.5-mm staple height gastrojejunostomy for differences in complications. RESULTS The groups were similar with respect to age, gender, body mass index, hypertension, hyperlipidemia, diabetes, sleep apnea, and surgery duration. In the 4.8- and 3.5-mm staple height groups, 15% and 6.1% required gastrojejunal dilation, respectively (P = .01). A trend was seen toward a decrease in postoperative hemorrhage (5% versus 2.8%) with the shorter staple height. No anastomotic leaks occurred, and the incidence of wound infection (1.7% versus 2.2%) was similar between the 2 groups. CONCLUSION In the present study, the use of a 25-mm, 3.5-mm staple height circular stapler was associated with a decreased rate of anastomotic stenosis.


Comments on contaminants in thallous (201Tl) chloride.


title: Multiple sclerosis: molecular mechanisms and therapeutic opportunities.

text: The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy.


title: Architectural and ultrastructural features of tessellated calcified cartilage in modern and extinct chondrichthyan fishes.

text: Tessellated calcified cartilage (TCC) is a distinctive kind of biomineralized perichondral tissue found in many modern and extinct chondrichthyans (sharks, rays, chimaeroids and their extinct allies). Customarily, this feature has been treated somewhat superficially in phylogenetic analyses, often as a single 'defining' character of a chondrichthyan clade. TCC is actually a complex hard tissue with numerous distinctive attributes, but its utility as a character complex for phylogenetic analysis has not yet been optimized. In this paper, we attempt to improve this situation by presenting new terminology for certain aspects of tesseral architecture, including single-monolayered, multiple-monolayered, polylayered and voussoir tesserae; new histological data, including thin sections of TCC in several Paleozoic taxa; and new proposals for ways in which various characters and states (many of which are defined here for the first time) could be applied in future phylogenetic analyses of chondrichthyan fishes. We conclude that many, but not all of the unique attributes of modern TCC were evolved by the Early Devonian (ca 400 MY). The globular calcified cartilage reported in Silurian sinacanthids, and the so-called 'sub-tessellated' perichondral biomineralization (with irregular and ill-defined geometries of a layer or layers of calcified cartilage blocks) of certain extinct 'acanthodians' (e.g., Climatius, Ischnacanthus, Cheiracanthus) could represent evolutionary precursors of TCC, which seems to characterize only part of the chondrichthyan total group. We hypothesize that heavily biomineralized 'layer-cake' TCC in certain Paleozoic chondrichthyans perhaps served a dual physiological role, as a phosphate sink and in providing increased skeletal density in very large (7+ m) Devonian-Permian marine sharks such as ctenacanths, and as an adaptation to calcium-deficient environments among Permo-Carboniferous non-marine sharks such as xenacanths. By contrast, the equivalent tissue in modern elasmobranchs probably serves only to reinforce regions of cartilage (mostly in the jaws) subjected to high loading. We also note that much of the variation observed in tesseral architecture (including localized remodeling), ultrastructure and histology in modern and extinct chondrichthyans is confined to the perichondrally-facing cap zone (where Type-1 collagen matrix predominates in modern TCC), whereas the main body of the tessera (where Type-2 collagen matrix predominates) exhibits comparatively little evidence of remodeling and histological or structural variation. This article is protected by copyright. All rights reserved.


title: Genetic diversity of Toona sinensis Roem in China revealed by ISSR and SRAP markers.

text: Toona sinensis Roem has an important value as a type of traditional vegetable and Chinese medicinal herb, and is also a valuable source of wood in China. In this study, we used the inter-simple sequence repeat (ISSR) and sequence-related amplified polymorphism (SRAP) markers to assess the level and pattern of genetic diversity in five domesticated T. sinensis populations in China. Our results indicated a relatively low level of genetic diversity both at species (Hs = 0.1662, 0.2098, respectively) and population levels (Hs = 0.0978, 0.1145, respectively). Molecular variance analyses revealed a relatively high degree of differentiation among populations (GST = 0.3901, 0.4498), and low levels of gene flow (Nm = 0.7816 and 0.6116). We divided the five populations into two groups by cluster analysis: group one consists of populations collected from the south part of China (e.g., Yuxi, Yunan Province and Zuanjiang, Chongqing Municipality), and group two contains those cultivated in north part of China (e.g., Hengshui, Hebei Province, Jinan and Rizhao, Shandong Province). The correlation of genetic relationships among populations fits well with their geographical distribution (Mantel test; r = 0.7236 and 0.6789, respectively). Asexual propagation, limited gene flow and geographic isolation are most likely the key factors associated with the observed genetic structure of T. sinensis grown in China. The present study indicated that both ISSR and SRAP markers were effective and reliable for assessing the degree of T. sinensis genetic variations.


title: Anti-infective Natural Products from Cyanobacteria.

text: Cyanobacteria are a promising yet underexplored source for novel natural products with potent biological activities. While predominantly cytotoxic compounds have been isolated from cyanobacteria in the past, there are also a significant number of compounds known that possess anti-infective activities. As the need for novel anti-infective lead compounds is high, this manuscript aims at giving a concise overview on the current knowledge about anti-infective secondary metabolites isolated from cyanobacteria. Antibacterial, antifungal, antiviral, antiprotozoal, and molluscicidal activities are discussed. Covering up to February 2015.


title: Metabolism and biological activity of α-tocopherol derived from vitamin E-enriched transgenic maize in broilers.

text: BACKGROUND The aim of this study was to investigate the metabolism of α-tocopherol derived from vitamin E-enriched transgenic maize (VER) and its effects on antioxidant and immune functions in broilers aged 1 to 42 days. A total of 360 1-day-old male broilers were randomly divided into three groups containing six replicates with 20 broilers per replicate. The negative control (NC) group and the positive control (PC) group were given non-GM maize and non-GM maize plus exogenous vitamin E (VE), respectively, and the VER group was given VER replacing the non-GM maize given to the NC group. Between days 1 and 21 and days 22 and 42, VE levels were 4.38 and 4.63 mg kg-1 in the NC group, and 14.11 and 14.91 mg kg-1 in the PC and VER group, respectively. RESULTS The results showed that α-tocopherol from both VER and additives increased α-tocopherol transfer protein and cytochrome P450 concentrations. Additionally, serum α-tocopherol and α-tocopherylquinone levels of broilers in the PC and VER groups were significantly higher than those in the NC group (P < 0.05). Compared with the NC group, broilers in both groups that received α-tocopherol had reduced NF-κB p65 concentrations, significantly decreased serum prostaglandin E2 , IL-6, malondialdehyde, and hydrogen peroxide levels (P < 0.05), and significantly increased glutathione, glutathione peroxidase, and total antioxidant capacity (P < 0.05). CONCLUSION In summary, both VER and non-GM maize fortified with exogenous VE showed similar effects on broilers, indicating that the α-tocopherol in VER has sufficient biological activity. This article is protected by copyright. All rights reserved.


title: The enterovirus protease inhibitor rupintrivir exerts cross-genotypic anti-norovirus activity and clears cells from the norovirus replicon.

text: Potent and safe inhibitors of norovirus replication are needed for the treatment and prophylaxis of norovirus infections. We here report that the in vitro anti-norovirus activity of the protease inhibitor rupintrivir is extended to murine noroviruses and that rupintrivir clears human cells from their Norwalk replicon after only two passages of antiviral pressure. In addition, we demonstrate that rupintrivir inhibits the human norovirus (genogroup II [GII]) protease and further explain the inhibitory effect of the molecule by means of molecular modeling on the basis of the crystal structure of the Norwalk virus protease. The combination of rupintrivir with the RNA-dependent RNA polymerase inhibitors 2'-C-methylcytidine and favipiravir (T-705) resulted in a merely additive antiviral effect. The fact that rupintrivir is active against noroviruses belonging to genogroup I (Norwalk virus), genogroup V (murine norovirus), and the recombinant 3C-like protease of a GII norovirus suggests that the drug exerts cross-genotypic anti-norovirus activity and will thus most likely be effective against the clinically relevant human norovirus strains. The design of antiviral molecules targeting the norovirus protease could be a valuable approach for the treatment and/or prophylaxis of norovirus infections.


title: Corticospinal Excitability to the Biceps Brachii is Not Different When Arm Cycling at a Self-Selected or Fixed Cadence.

text: BACKGROUND The present study compared corticospinal excitability to the biceps brachii muscle during arm cycling at a self-selected and a fixed cadence (SSC and FC, respectively). We hypothesized that corticospinal excitability would not be different between the two conditions. METHODS The SSC was initially performed and the cycling cadence was recorded every 5 s for one minute. The average cadence of the SSC cycling trial was then used as a target for the FC of cycling that the participants were instructed to maintain. The motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation (TMS) of the motor cortex were recorded from the biceps brachii during each trial of SSC and FC arm cycling. RESULTS Corticospinal excitability, as assessed via normalized MEP amplitudes (MEPs were made relative to a maximal compound muscle action potential), was not different between groups. CONCLUSIONS Focusing on maintaining a fixed cadence during arm cycling does not influence corticospinal excitability, as assessed via TMS-evoked MEPs.


title: Robotic Compartment-Based Radical Surgery in Early-Stage Cervical Cancer.

text: A radical hysterectomy with pelvic lymphadenectomy is the recommended treatment option in patients with early-stage cervical cancer. Although various classifications were developed in order to define the resection margins of this operation, no clear standardization could be achieved both in the nomenclature and in the extent of the surgery. Total mesometrial resection (TMMR) is a novel procedure which aims to remove all components of the compartment formed by Müllerian duct in which female reproductive organs develop. TMMR differs from the conventional radical hysterectomy techniques in that its surgical philosophy, terminology, and partly resection borders are different. In this paper, a TMMR with therapeutic pelvic lymphadenectomy operation that we performed for the first time with robot-assisted laparoscopic (robotic) approach in an early-stage cervical cancer patient was presented. This procedure has already been described in open surgery by Michael Höckel and translated to the robotic surgery by Rainer Kimmig. Our report is the second paper, to our knowledge, to present the initial experience regarding robotic TMMR in the English literature.


title: Impacts of rapid recanalization and collateral circulation on clinical outcome after intraarterial thrombolysis.

text: BACKGROUND AND PURPOSE Rapid recanalization might improve clinical outcomes after intraarterial thrombolysis (IAT) for acute ischemic stroke patients with collateral circulation. We determined whether rapid recanalization and collateral circulation affect clinical outcomes after IAT. METHODS We retrospectively evaluated the clinical and radiological data of 134 consecutive patients who underwent IAT for intracranial artery occlusion. The interval from symptom onset to recanalization after IAT (onset-to-recanalization time) as an estimate of the probability of good clinical outcome (modified Rankin scale 0-2) was calculated in patients with collateral circulation in the ischemic hemisphere, which was rated poor (0/1 American Society of Interventional and Therapeutic Neuroradiology criteria) or good (2-4). Changes in National Institute of Health Stroke Scale (NHISS) score before and after IAT and modified Rankins scale scores 3 months after discharge were compared with respect to onset-to-recanalization time. RESULTS In patients with good collateral circulation, the estimated onset-to-recanalization time for a 0.5 probability of a good clinical outcome was 347 minutes; with poor collateral circulation, it was 172 minutes for a 0.2 probability of good clinical outcome. Outcome analyses according to onset-to-recanalization time showed patients recanalized <6 hours had lower NHISS scores (<4.5, 4.5-6, >6 hours of onset-to-recanalization time, and non-recanalization: 5.1, 6.9, 11.9, and 19.8, respectively) at discharge and higher percentages of good clinical outcome (69%, 66.7%, 21.9%, and 0%, respectively) 3 months after IAT. CONCLUSIONS The time window to expect a high probability of a good clinical outcome after IAT is highly dependent on the collateral circulation.


title: Sustained availability of 99mTc: possible paths forward.

text: The availability of (99m)Tc for single-photon imaging in diagnostic nuclear medicine is crucial, and current availability is based on the (99)Mo/(99m)Tc generator fabricated from fission-based molybdenum (F (99)Mo) produced using high enriched uranium (HEU) targets. Because of risks related to nuclear material proliferation, the use of HEU targets is being phased out and alternative strategies for production of both (99)Mo and (99m)Tc are being evaluated intensely. There are evidently no plans for replacement of the limited number of reactors that have primarily provided most of the (99)Mo. The uninterrupted, dependable availability of (99m)Tc is a crucial issue. For these reasons, new options being pursued include both reactor- and accelerator-based strategies to sustain the continued availability of (99m)Tc without the use of HEU. In this paper, the scientific and economic issues for transitioning from HEU to non-HEU are also discussed. In addition, the comparative advantages, disadvantages, technical challenges, present status, future prospects, security concerns, economic viability, and regulatory obstacles are reviewed. The international actions in progress toward evolving possible alternative strategies to produce (99)Mo or (99m)Tc are analyzed as well. The breadth of technologies and new strategies under development to provide (99)Mo and (99m)Tc reflects both the broad interest in and the importance of the pivotal role of (99m)Tc in diagnostic nuclear medicine.


PET and SPECT Imaging in the SARS-CoV-2 Pandemic.


title: Prophylactic platelet transfusions prior to surgery for people with a low platelet count.

text: This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the clinical effectiveness and safety of prophylactic platelet transfusions prior to surgery for people with a low platelet count or platelet dysfunction (inherited or acquired).


title: Comparison of the Luminex xTAG respiratory viral panel with xTAG respiratory viral panel fast for diagnosis of respiratory virus infections.

text: Nucleic acid tests are sensitive and specific and provide a rapid diagnosis, making them invaluable for patient and outbreak management. Multiplex PCR assays have additional advantages in providing an economical and comprehensive panel for many common respiratory viruses. Previous reports have shown the utility of the xTAG respiratory viral panel (RVP) assay manufactured by Luminex Molecular Diagnostics for this purpose. A newer generation of this kit, released in Canada in early 2010, is designed to simplify the procedure and reduce the turnaround time by about 24 h. The assay methodology and targets included in this version of the kit are different; consequently, the objective of this study was to compare the detection of a panel of respiratory viral targets using the older Luminex xTAG RVP (RVP Classic) assay with that using the newer xTAG RVP Fast assay. This study included 334 respiratory specimens that had been characterized for a variety of respiratory viral targets; all samples were tested by both versions of the RVP assay in parallel. Overall, the RVP Classic assay was more sensitive than the RVP Fast assay (88.6% and 77.5% sensitivities, respectively) for all the viral targets combined. Targets not detected by the RVP Fast assay included primarily influenza B virus, parainfluenza virus type 2, and human coronavirus 229E. A small number of samples positive for influenza A virus, respiratory syncytial virus B, human metapneumovirus, and parainfluenza virus type 1 were not detected by the RVP Classic assay and in general had low viral loads.


title: Fully robotic total pancreatectomy: technical aspects and outcomes.

text: Robotic total pancreatectomy (RTP) is a novel surgical approach currently performed by a select group of skilled surgeons. As robotic approaches to pancreatic surgery increase worldwide, rates of RTP are expected to increase. However, the standard technique is still evolving and several technical problems still require evaluation. Here, we describe our approach in a stepwise fashion and discuss solutions to overcome technical difficulties.


title: Efficacy of introducing a checklist to reduce central venous line associated bloodstream infections in the ICU caring for adult patients.

text: BACKGROUND Central line-associated bloodstream infections (CLABSI) are a major source of sepsis in modern intensive care medicine. Some years ago bundle interventions have been introduced to reduce CLABSI. The use of checklists may be an additional tool to improve the effect of these bundles even in highly specialized institutions. In this study we investigate if the introduction of a checklist reduces the frequency of CLABSI. METHODS During the study period from October 2011 to September 2012, we investigated the effect of implementing a checklist for the placement of central venous lines (CVL). Patients were allocated either to the checklist group or to the control group, roughly in a 1:2 ratio. The frequency of CLABSI was compared between the two groups. RESULTS During the study period 4416 CVL were inserted; 1518 in the checklist group and 2898 in the control group. The use of the checklist during CVL placement resulted in a lower CLABSI frequency. The incidence in the checklist group was 3.8 per 1000 catheter days as compared to 5.9 per 1000 catheter days in the control group (IRR = 0.57; p = 0.001). The use of the checklist also reduced the frequency of catheter colonisation significantly, 36.3 per 1000 catheter days in the checklist group vs 21.2 per 1000 catheter days in the control group, respectively (IRR = 0.58; p < 0.001). CONCLUSION The introduction of a checklist to improve the adherence to hygiene standards while placement of central venous lines reduced the frequency of infections significantly.


title: Mutational analysis of the functional sites in porcine reproductive and respiratory syndrome virus non-structural protein 10.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) is prevalent throughout the world and has caused major economic losses to the pig industry. Arterivirus non-structural protein 10 (nsp10) is a superfamily 1 helicase participating in multiple processes of virus replication. PRRSV nsp10, however, has not yet been well characterized. In this study, a series of nsp10 mutants were constructed and analysed for functional sites of different enzymic activities. We found that nsp10 could bind both ssDNA and dsDNA, and this binding activity could be inactivated by mutations at Cys25 and His32. These two mutations also abolished unwinding activity without affecting ATPase activity. In addition, substitution of Ala227 by Ser eliminated helicase activity, whilst substitution by Val enhanced unwinding activity. Taken together, our results showed that Cys25 and His32 in PRRSV nsp10 were critical for nucleic acid binding and unwinding, and that Ala227 played an important role in helicase activity.


title: Hand-Assisted Laparoscopic Approach in Colon Surgery.

text: BACKGROUND This study sought to compare outcomes of patients who underwent hand-assisted laparoscopic (HAL) colectomy with open and laparoscopic colectomy (LP). STUDY DESIGN The NSQIP databases were used to examine the clinical data of patients who underwent elective colectomy during 2012-2013. Multivariate regression analysis was performed to compare the three surgical approaches. RESULTS We sampled a total of 21,090 patients who underwent colectomy. Of these, 7480 (35.5 %) had open colectomy (OC), 8751 (41.5 %) had a laparoscopic colectomy, 2860 (13.6 %) had a HAL colectomy, and 1999 (9.5 %) had an open procedure converted from LC or HAL. Multivariate regression analysis revealed HAL colectomy had a similar mortality (AOR 0.53, P = 0.07) and a lower morbidity (AOR 0.37, P < 0.01) compared to OC. LC had lower mortality (AOR 0.58, P = 0.02) and morbidity (AOR 0.43, P < 0.01) compared to OC. Mortality of patients who underwent HAL was not significantly different from LC (AOR 0.90, P = 0.79); however, morbidity of such patients was significantly higher than for patients who underwent LC (AOR 1.29, P < 0.01). CONCLUSIONS HAL colectomy is a safe approach with significant advantages compared to open colectomy. Although the morbidity of patients who underwent HAL is higher than patients who underwent LC, the morbidity rate is still lower than OC.


Response to: Meticulous surgical technique cannot be replaced by cholangiography.


title: How to Defend COVID-19 in Taiwan? Talk about People's Disease Awareness, Attitudes, Behaviors and the Impact of Physical and Mental Health.

text: This study explored awareness, attitudes, and behavior in relation to Coronavirus Disease 2019 (COVID-19) prevention among Taiwanese citizens and their physical and mental health statuses. Through collection of 2132 questionnaire responses in field research, the present researchers analyzed the data using descriptive statistics and various approaches. In conclusion, the public's high level of willingness to share information, sufficient knowledge of and consensus on epidemic prevention between individuals and families, strict compliance with relevant regulations, effective preventive measures, and adequate public facilities have contributed to control of COVID-19. However, vigilance and awareness of the pandemic in some individuals, epidemic-prevention campaigns, and community-based preventive measures were insufficient. Some citizens subsequently suffered from headaches, anxiety, and mood instability. Furthermore, demographic variables (place of residence, sex, age, and occupation) and physical and mental health status produced various effects on citizens' awareness, attitude, and behavior regarding epidemic prevention as well as the perceived effect of COVID-19 on physical and mental health.


title: Augmented genetic decoding: global, local and temporal alterations of decoding processes and codon meaning.

text: The non-universality of the genetic code is now widely appreciated. Codes differ between organisms, and certain genes are known to alter the decoding rules in a site-specific manner. Recently discovered examples of decoding plasticity are particularly spectacular. These examples include organisms and organelles with disruptions of triplet continuity during the translation of many genes, viruses that alter the entire genetic code of their hosts and organisms that adjust their genetic code in response to changing environments. In this Review, we outline various modes of alternative genetic decoding and expand existing terminology to accommodate recently discovered manifestations of this seemingly sophisticated phenomenon.


title: The effect of extended post-discharge chemical thromboprophylaxis on venous thromboembolism rates after bariatric surgery: a prospective comparison trial.

text: BACKGROUND The effect of extended post-discharge thromboprophylaxis (ETP) on venous thromboembolism (VTE) rates following bariatric surgery (BS) is unknown. METHODS 308 consecutive patients who underwent BS between 2003 and 2007 and who had > 1 month of follow-up were included. In-hospital-only VTE prophylaxis (group A), or extended 10-day ETP (group B) was used in 132 and 176 patients, respectively. All patients underwent bilateral lower extremity venous Doppler studies (BLEVDS) prior to discharge. Primary endpoint was the incidence of VTE within 30 days postoperatively. VTE was defined as a clinically evident deep vein thrombosis or pulmonary embolism documented by positive BLEVDS, or computed chest tomography. The primary safety endpoint was bleeding associated with > or = 2 g/dL decrease in hemoglobin compared with baseline, transfusion or reoperation. RESULTS The incidence of VTE was 1.9% (6/308); 66.6% (4/6) of cases occurred after cessation of thromboprophylaxis. There were no deaths in either group. With the exception of percentage open surgical approach (A: 3% versus B: 0%, p = 0.03), percentage conversions (A: 0 versus B: 3.8%, p = 0.01), and hospital stay (A: 3 versus B: 2.2 days, p < 0.0001), the two groups were comparable in relation to age, sex, body mass index, percentage revision surgery, operative time, and history of VTE. VTE rate was significantly higher in group A (A: 4.5% versus B: 0%, p = 0.006). Although morbidity was higher in group A (A: 12.1% versus B: 1.1%, p < 0.0001), no VTE event occurred in patients who had other complications. The incidence of significant bleeding was lower in group B (A: 5.3% versus B: 0.56%, p = 0.02). CONCLUSIONS ETP is safe and effective in reducing the incidence of VTE as compared with in-hospital thromboprophylaxis only.


title: Minimally invasive approaches for gastric cancer-Japanese experiences.

text: Since development of laparoscopy-assisted distal gastrectomy with lymph node dissection in 1991 in Japan, laparoscopic gastrectomy (LAG) is improving and evolving. Recently, advanced LAG techniques including D2 lymph node dissection or anastomosis after total gastrectomy have been developed. Retrospective and prospective multicenter studies have been conducted for early and non-early gastric cancers to establish high-quality evidence. This review summarizes the current trends of minimally invasive approaches for gastric cancer based on current Japanese experiences.


title: Short-interval intracortical inhibition: Comparison between conventional and threshold-tracking techniques.

text: BACKGROUND Short-interval intracortical inhibition (SICI) is conventionally measured as the relative amplitude reduction of motor evoked potentials (MEPs) by subthreshold conditioning stimuli. In threshold-tracking SICI (T-SICI), stimulus intensity is instead adjusted repeatedly to maintain a constant MEP and inhibition is measured as the relative threshold increase. T-SICI is emerging as a useful diagnostic test, but its relationship to conventional amplitude SICI (A-SICI) is unclear. OBJECTIVE To compare T-SICI and its reliability with conventional A-SICI measurements. METHODS In twelve healthy volunteers (6 men, median age 30 years), conventional and T-SICI were recorded at conditioning stimuli (CS) of 50-80% resting motor threshold (RMT) and interstimulus interval of 2.5 ms. Measurements were repeated on the same day and at least a week later by a single operator. RESULTS Across the CS range, mean group T-SICI showed a strong linear relationship to the mean group values measured by conventional technique (y = 29.7-0.3x, R2 = 0.99), but there was considerable interindividual variability. At CS 60-80% RMT, T-SICI had excellent intraday (intraclass correlation coefficient, ICC, 0.81-0.92) and adequate-to-excellent interday (ICC 0.61-0.88) reproducibility. Conventional SICI took longer to complete (median of 5.8 vs 3.8 min, p < 0.001) and tended to have poorer reproducibility (ICC 0.17-0.42 intraday, 0.37-0.51 interday). With T-SICI, smaller sample sizes were calculated for equally powered interventional studies. CONCLUSION The close relationship between conventional and T-SICI suggests that both techniques reflect similar cortical inhibitory mechanisms. Threshold-tracking measurements of SICI may be able to improve reproducibility, to shorten acquisition time and to reduce sample sizes for interventional studies compared with the conventional technique.


title: An algorithm for correcting systematic energy deficits in the atom probe mass spectra of insulating samples.

text: Improvements in the mass resolution of a mass spectrometer directly correlate to improvements in peak identification and quantification. Here, we describe a post-processing technique developed to increase the quality of mass spectra of strongly insulating samples in laser-pulsed atom probe microscopy. The technique leverages the self-similarity of atom probe mass spectra collected at different times during an experimental run to correct for electrostatic artifacts that present as systematic energy deficits. We demonstrate the method on fused silica (SiO2) and neodymium-doped ceria (CeO2) samples which highlight the improvements that can be made to the mass spectrum of strongly insulating samples.


title: The heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a host factor required for dengue virus and Junín virus multiplication.

text: Heterogeneous nuclear ribonucleoproteins (hnRNPs) are cellular factors involved in the replication of several viruses. In this study we analyzed the expression and intracellular localization of hnRNP A2 and hnRNP K in cell cultures infected with two viruses that cause human hemorrhagic fevers: dengue virus type 2 (DENV-2) and Junín virus (JUNV). We determined that DENV-2 promoted the cytoplasmic translocation of hnRNP K and to a lesser extent of hnRNP A2, meanwhile, JUNV infection induced an increase in hnRNP K cytoplasmic localization whereas hnRNP A2 remained mainly in the nucleus of infected cells. Both hnRNP K and hnRNP A2 were localized predominantly in the nucleus of JUNV persistently-infected cells even after superinfection with JUNV indicating that persistent infection does not alter nucleo-cytoplasmic transport of these hnRNPs. Total levels of hnRNP K expression were unaffected by DENV-2 or JUNV infection. In addition we determined, using small interfering RNAs, that hnRNP K knockout inhibits DENV-2 and JUNV multiplication. Our results indicate that DENV-2 and JUNV induce hnRNP K cytoplasmic translocation to favor viral multiplication.


title: Exponentially Decelerated Contrast Media Injection Rate Combined With a Novel Patient-Specific Contrast Formula Reduces Contrast Volume Administration and Radiation Dose During Computed Tomography Pulmonary Angiography.

text: CLINICAL RELEVANCE Matching contrast injection timing with vessel dynamics significantly improves vessel opacification and reduces contrast dose in the assessment of pulmonary embolism during computed tomography (CT) pulmonary angiography. PURPOSE The aim of this study was to investigate opacification of the pulmonary vasculature (PV) during CT pulmonary angiography using a patient-specific contrast formula (PSCF) and exponentially decelerated contrast media (EDCM) injection rate. MATERIALS AND METHODS Institutional review board approved this retrospective study. Computed tomography pulmonary angiography was performed on 200 patients with suspected pulmonary embolism using a 64-channel CT scanner. Patient demographics were equally distributed. Patients were randomly assigned to 2 equal protocol groups: protocol A used a PSCF, and protocol B involved the use of a PSCF combined with EDCM. The mean cross-sectional opacification profile of 8 central and 11 peripheral PVs were measured for each patient, and arteriovenous contrast ratio was calculated. Protocols were compared using Mann-Whitney U nonparametric statistics. Jackknife alternative free-response receiver operating characteristic analyses were used to assess diagnostic efficacy. Interobserver variations were investigated using kappa methods. RESULTS A number of pulmonary arteries demonstrated increases in opacification (P < 0.02) for protocol B compared with A, whereas opacification in all veins was reduced in protocol B (P < 0.03). Subsequently, increased arteriovenous contrast ratio in protocol B compared with A was observed at all anatomic locations (P < 0.0002). An increase in jackknife alternative free-response receiver operating characteristic figure of merit (P < 0.0002) and interobserver variation was observed with protocol B compared with protocol A (κ = 0.3-0.73). Mean contrast volume was reduced in protocol B (29 [4] mL) compared with protocol A (33 [9] mL). Mean effective radiation dose in protocol B (1.2 [0.4] mSv) was reduced by 14% compared with protocol A (1.4 [0.6] mSv). CONCLUSIONS Significant improvements in visualization of the PV can be achieved with a low contrast volume using an EDCM and PSCF. The reduced risk of cancer induction is highlighted.


title: Advances in Antiviral Therapies Targeting Toll-like Receptors.

text: INTRODUCTION Organisms have evolved a rapid and non-specific way to defend themselves via Toll-like receptors (TLRs), which recognize specific signatures present on invading microbes and viruses. Once detected, these receptors flood the cell with cytokines and IFNs that not only help to eradicate the invading viruses but also activate the adaptive immune response. Owing to difficulties in viral detection, a whole class of TLRs is dedicated to sensing viral nucleic acids, while other TLRs detect viral coat proteins and aid in establishing antiviral immunity. To protect humans better, TLRs and their downstream mediators can be used as potential drug targets, which can be either activated or inhibited, to counter viral infections. AREAS COVERED The current review focuses on TLR-targeting investigational drugs developed to treat viral diseases and virus-induced complications. EXPERT OPINION TLRs are a good choice for eradicating viral infections because they can fine-tune the immune response. However, TLRs should be exploited carefully, as there have been instances where their activation has led to unwanted responses in terms of both immune and viral activation. Therefore, more focus should be placed on novel drugs that can induce significant and long-term immunity, while concomitantly alleviating side effects.


title: Pandemic influenza A (H1N1) virus infection and avian influenza A (H5N1) virus infection: a comparative analysis.

text: The 2009 H1N1 and H5N1 influenza viruses are newly (re-) emerged influenza A viruses (2009 A(H1N1) and A(H5N1), respectively) that have recently posed tremendous health threats in many regions worldwide. With the 2009 outbreak of H1N1 influenza A, the world witnessed the first influenza pandemic of the 21st century. The disease has rapidly spread across the entire globe, and has resulted in hundreds of thousands of cases with confirmed infection. Although characterized by high transmissibility, the virulence and fatality of the 2009 A(H1N1) influenza virus have thus far remained relatively low. The reverse holds true for A(H5N1) influenza; at a fatality rate that exceeds 60%, it is known to cause severe damage to the human respiratory system, but is not presently capable of efficient transmission from human to human. Apart from the clear differences between the two types of influenza, there are some significant similarities that warrant attention. In particular, the more severe and fatal 2009 A(H1N1) influenza cases have shown symptoms similar to those reported in cases of A(H5N1) influenza. Histopathological findings for these cases, to the extent available, also appear to have similarities for both diseases in terms of damage and severity. Here we review important recent publications in this area, and we discuss some of the key commonalities and contrasts between the two influenza A types in terms of their biology, origins, clinical features, pathology and pathogenesis, and receptors and transmissibility.


title: Randomized Clinical Trial of Epidural Compared with Conventional Analgesia after Minimally Invasive Colorectal Surgery.

text: BACKGROUND The effectiveness of thoracic epidural analgesia (EA) vs conventional IV analgesia (IA) after minimally invasive surgery is still unproven. We designed a randomized controlled trial comparing EA with IA after minimally invasive colorectal surgery. STUDY DESIGN A total of 87 patients who underwent minimally invasive colorectal procedures at a single institution between 2011 and 2014 were enrolled. Eight patients were excluded and 38 were randomized to EA and 41 to IA. Pain was assessed with the Visual Analogue Scale and quality of life with the Overall Benefit of Analgesia Score daily until discharge. RESULTS Mean age was 57 ± 14 years, 43% of patients were female, and mean BMI was 28.6 ± 6 kg/m2. The 2 groups were similar in demographic characteristics and distribution of diagnoses and procedures. Epidural analgesia had a higher incidence of hypotensive systolic blood pressure (<90 mmHg) episodes (9 vs 2; p < 0.05) and a trend toward longer Foley catheter duration (3 ± 2 days vs 2 ± 4 days; p > 0.05). Epidural and IA had equivalent mean lengths of stay (4 ± 3 days vs 4 ± 3 days), daily Visual Analogue Scale scores (2.4 ± 2.0 vs 3.0 ± 2.0), and Overall Benefit of Analgesia Scores (3.2 ± 2.0 vs 3.2 ± 2.0), and similar time to start oral diet (2.8 ± 2 days vs 2.2 ± 1 days). Epidural analgesia patients used a higher total dose of narcotics (147.5 ± 192.0 mg vs 98.1 ± 112.0 mg; p > 0.05). Epidural and IV analgesia had equivalent total hospital charges ($144,991 ± $67,636 vs $141,339 ± $75,579; p > 0.05). CONCLUSIONS This study indicates that EA has no added clinical benefit in patients undergoing minimally invasive colorectal surgery. A trend toward higher total narcotics use and complications with EA was demonstrated.


title: Involvement of CD8+ T cell-mediated immune responses in LcrV DNA vaccine induced protection against lethal Yersinia pestis challenge.

text: Yersinia pestis (Y. pestis) is the causative pathogen of plague, a highly fatal disease for which an effective vaccine, especially against mucosal transmission, is still not available. Like many bacterial infections, antigen-specific antibody responses have been traditionally considered critical, if not solely responsible, for vaccine-induced protection against Y. pestis. Studies in recent years have suggested the importance of T cell immune responses against Y. pestis infection but information is still limited about the details of Y. pestis antigen-specific T cell immune responses. In current report, studies are conducted to identify the presence of CD8+ T cell epitopes in LcrV protein, the leading antigen of plague vaccine development. Furthermore, depletion of CD8+ T cells in LcrV DNA vaccinated Balb/C mice led to reduced protection against lethal intranasal challenge of Y. pestis. These findings establish that an LcrV DNA vaccine is able to elicit CD8+ T cell immune responses against specific epitopes of this key plague antigen and that a CD8+ T cell immune response is involved in LcrV DNA vaccine-elicited protection. Future studies in plague vaccine development will need to examine if the presence of detectable T cell immune responses, in particular CD8+ T-cell immune responses, will enhance the protection against Y. pestis in higher animal species or humans.


The place of new haemostatic techniques in thyroid surgery.


title: How Will COVID-19 Affect Long-Term Care?

text: We hope to be ready for the next COVID-like crisis, but what if the next crisis is something completely different?


Learning together to safely intubate patients with COVID-19.


title: TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein.

text: The type II transmembrane serine proteases TMPRSS2 and HAT can cleave and activate the spike protein (S) of the severe acute respiratory syndrome coronavirus (SARS-CoV) for membrane fusion. In addition, these proteases cleave the viral receptor, the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), and it was proposed that ACE2 cleavage augments viral infectivity. However, no mechanistic insights into this process were obtained and the relevance of ACE2 cleavage for SARS-CoV S protein (SARS-S) activation has not been determined. Here, we show that arginine and lysine residues within ACE2 amino acids 697 to 716 are essential for cleavage by TMPRSS2 and HAT and that ACE2 processing is required for augmentation of SARS-S-driven entry by these proteases. In contrast, ACE2 cleavage was dispensable for activation of the viral S protein. Expression of TMPRSS2 increased cellular uptake of soluble SARS-S, suggesting that protease-dependent augmentation of viral entry might be due to increased uptake of virions into target cells. Finally, TMPRSS2 was found to compete with the metalloprotease ADAM17 for ACE2 processing, but only cleavage by TMPRSS2 resulted in augmented SARS-S-driven entry. Collectively, our results in conjunction with those of previous studies indicate that TMPRSS2 and potentially related proteases promote SARS-CoV entry by two separate mechanisms: ACE2 cleavage, which might promote viral uptake, and SARS-S cleavage, which activates the S protein for membrane fusion. These observations have interesting implications for the development of novel therapeutics. In addition, they should spur efforts to determine whether receptor cleavage promotes entry of other coronaviruses, which use peptidases as entry receptors.


title: The Endoloop technique for the primary closure of direct inguinal hernia defect during the endoscopic totally extraperitoneal approach.

text: INTRODUCTION Seroma is a frequent complication of endoscopic totally extraperitoneal (TEP) mesh repair of direct inguinal hernia that may cause discomfort and anxiety. Its volume is proportional to the size of the preperitoneal dead space created after the reduction of the hernia. Attempts to reduce its incidence have included tacking the transversalis fascia (TF) to the pubic ramus or closed suction drainage of the preperitoneal space. Both of these techniques are not without problems. The aim of this study was to evaluate the efficiency of a new alternate technique that must be safe and easily reproducible, using a widely available and inexpensive pre-tied suture loop (Endoloop(®) Ligature) for plication of the weakened TF. METHODS This is a prospective study of consecutive patients diagnosed with inguinal hernia during a 33-month period and eligible for endoscopic TEP repair. A single surgeon performed all operations. Each of the M2 or M3 direct defects, according to the European Hernia Society (EHS), were systematically closed prior to the introduction of the prosthetic mesh and as follows: grasping and inversion of the attenuated TF at its apex, using a laparoscopic forceps and plication of the TF by placing a tight Endoloop of Polydioxanone (PDS) at its base. All meshes were secured with fibrin sealant only. Patients were reviewed in the clinic 2 and 6 weeks after the operation. Further follow-up was scheduled if it was deemed necessary. The primary post-operative outcome parameter was seroma formation; secondary outcome parameters included groin pain, surgical complications, and recurrence. RESULTS Two hundred and fifty hernia repairs were prospectively recorded during this period. All procedures were carried out endoscopically. Seventy-nine patients with 94 direct inguinal hernias were selected in a sequential manner. There were 75 males and four females, with a median age of 57 years. Of those, 55 were combined with an indirect inguinal defect. In total, Endoloops of PDS were used to close the weakened TF in 76 cases (30 M3, 44 M2, and two M1). Only one patient (1.3%) complained of a residual seroma formation, which was still clinically present at 3 months post-operatively, but was not symptomatic. There were only two minor post-operative complications, which occurred in the same patient and were not related to the Endoloop technique. Finally, no patient complained of chronic groin pain and there was no hernia recurrence after a median follow-up of 18 months. CONCLUSIONS The primary closure of direct inguinal hernia defects with a pre-tied suture loop during endoscopic TEP repair is safe, efficient, and very reliable for the prevention of post-operative seroma formation, without increasing the risk of developing chronic groin pain or hernia recurrence. This technique should be the preferred method over stapling of the TF or the insertion of a closed suction drainage device in such a situation.


title: Percutaneous Image-Guided Thermal Ablation for Multifocal Renal Cell Carcinoma: 10-Year Experience at a Single Center.

text: OBJECTIVE The objective of our study was to assess the technical success, safety, and oncologic and renal function outcomes of CT-guided percutaneous thermal ablation for synchronous multiple renal masses in a single session. MATERIALS AND METHODS A retrospective analysis of 23 patients (16 men and 7 women; median age, 70 years) with biopsy-proven multifocal renal cell carcinoma (RCC) masses treated with radiofrequency ablation (RFA), cryoablation, or microwave ablation (MWA) was performed. Preablation, postablation, and follow-up serum blood urea nitrogen, creatinine, and estimated glomerular filtration rate (GFR) levels were recorded to evaluate the stability of renal function. Technical success, complications, treatment response, oncologic outcome, and overall survival were assessed. RESULTS Biopsy-proven RCCs were treated in 23 patients. Median tumor size was 2.3 cm (range, 1.0-4.0 cm). The mean RENAL (radius, exophytic vs endophytic properties, nearness of tumor to the collecting system or sinus, anterior vs posterior, location relative to polar lines) nephrometry score was 6.3 (range, 4.0-10.0); mean PADUA (preoperative aspects and dimensions used for anatomical) score, 7.8 (range, 6.0-11.0); and mean centrality index (C-index), 3.1 (range, 0.7-6.8). The mean ablation time was 23 minutes (range, 3-24 minutes). Technical success was achieved for 100% of tumors. Of the 49 complications, nine (18%) were classified as Clavien-Dindo grade I complications. Complete response was achieved in 41 of the 49 (84%) tumors. Local progression-free, RCC-specific disease-free, and overall survival rates during the imaging follow-up time (mean, 3.1 years; range, 0.1-9.6 years) were 96% (22/23), 100% (23/23), and 91% (21/23), respectively. CONCLUSION CT-guided percutaneous thermal ablation is a safe, effective, and durable treatment intervention for multifocal renal masses.


title: Introduction to the Theme "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology".

text: Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.


The view of Barrett's esophagus from across the pond.


title: The usefulness of endotracheal tube twisting in facilitating tube delivery to glottis opening during GlideScope intubation in infants: randomized trial.

text: Despite an excellent view of the glottis, technical difficulties with endotracheal tube delivery remains in GlideScope intubation. We evaluated whether a spiral-shape twisted tube can facilitate placement of the tracheal tube tip at the center of glottis opening compared to conventional tube for GlideScope intubation in infants. Eighty-six infants were randomly placed in either the conventional tube group (group C) or the twist tube group (group T). In group T, the shaft of the tube was manually twisted into a loose spiral shape. The primary outcome was the initial center location of the tube tip at the glottis opening, and the secondary outcome was total tube handling time. The initial center location rate of the tube tip at the glottis opening was significantly higher in group T than in group C (88% [38/43] vs. 47% [20/43], P < 0.001). In addition, total tube handling time (sec) was significantly shorter in group T than in group C (15.4 ± 4.7 vs. 18.2 ± 5.3, P = 0.012). In this study, the spiral shape twist tube successfully improved the rate of initial center location of the tube tip at glottis opening and facilitated tube delivery in GlideScope intubation in infants.


title: CT portography with gastric variceal volume measurements in the evaluation of endoscopic therapeutic efficacy of tissue adhesive injection into gastric varices: a pilot study.

text: BACKGROUND N-butyl-2-cyanoacrylate (NBCA) injection is used for treating gastric varices (GV). Determining the degree of obliteration of GV is not readily evident at endoscopy. AIMS The aim of this study was to evaluate CT portography with gastric variceal volume calculations to assess endoscopic therapeutic efficacy of NBCA injection. METHODS The study design is a retrospective series pilot study. The setting is a single, tertiary care academic medical center. Ten patients underwent esophagogastroduodenoscopy (EGD) with NBCA injection of GV and had biphasic CT scans performed before and after injection therapy. Based on portal venous images, 3D reconstruction and semi-automated volume calculations of GV were performed. Pre and post injection GV volume calculations were compared. RESULTS The mean pre-procedure GV volume was 89.84 cm3. Eight patients had significant improvement in GV volume from pre-treatment versus post-treatment (95.65 cm3 vs. 49.65 cm3, P-value 0.04). Pre-procedure GV volume was not significantly different in patients treated for active hemorrhage versus no hemorrhage (101.66 cm3 vs. 72.11 cm3, P-value 0.33). Two patients had a subsequent GV hemorrhage after NBCA injection. The mean residual GV volume in these patients versus those that did not re-bleed was significantly more (127.77 cm3 vs. 38.00 cm3, P-value 0.005). CONCLUSIONS CT portography with measurement of GV volume is a potentially useful tool in determining the therapeutic efficacy NBCA injection of GV. Patients with higher residual GV volumes are at increased risk of hemorrhage and may benefit from repeat injection to reach ideal GV volumes.


title: Penaeus monodon is protected against gill-associated virus by muscle injection but not oral delivery of bacterially expressed dsRNAs.

text: Gill-associated virus (GAV) is a nidovirus that commonly infects Penaeus monodon (black tiger shrimp) in eastern Australia, causing morbidity and mortalities in the acute stage of disease. Here we explored the possibility of inhibiting GAV replication and disease using double-stranded (ds)RNAs expressed in bacteria and delivered either orally or by muscle injection. To enhance potential RNA interference (RNAi) responses, 5 long dsRNAs were used that targeted open reading frame 1a/1b (ORF1a/b) gene regions and thus only the genomic length RNA. To examine oral delivery, P. monodon were fed pellets incorporating a pool of formalin-fixed bacteria containing the 5 GAV-specific dsRNAs before being injected with a minimal lethal GAV dose. Feeding with the pellets continued post-challenge but did not reduce mortality accumulation and elevation in GAV loads. In contrast, muscle injection of the dsRNAs purified from bacteria was highly effective at slowing GAV replication and protecting shrimp against acute disease and mortalities. In synergy with these data, dsRNA targeted to P. monodon beta-actin mRNA caused 100% mortality following injection, whilst its oral delivery caused no mortality. Findings confirm that injected dsRNA can mount effective RNAi responses in P. monodon to endogenous shrimp mRNA and exogenous viral RNAs, but when delivered orally in bacteria as a feed component, the same dsRNAs are ineffective. The efficacy of the RNAi response against GAV provided by injection of dsRNAs targeted to multiple genome sites suggests that this strategy might have general applicability in enhancing protection against other shrimp single-stranded (ss)RNA viruses, particularly in hatcheries or breeding programs where injection-based delivery systems are practical.


Multiple drug resistant organisms in healthcare: the failure of contact precautions.


title: Ventilator-associated pneumonia: current status and future recommendations.

text: OBJECTIVE Ventilator-associated pneumonia (VAP) is a common hazardous complication in ICU patients. The aim of the current review is to give an update on the current status and future recommendations for VAP prevention. METHODS This article gives an updated review of the current literature on VAP. The first part briefly reviews pathogenesis and epidemiology while the second includes an in-depth review of evidence-based practice guidelines (EBPG) and new technologies developed for prevention of VAP. RESULTS VAP remains a frequent and costly complication of critical illness with a pooled relative risk of 9-27% and mortality of 25-50%. Strikingly, VAP adds an estimated cost of more than $40,000 to a typical hospital admission. An important aetiological mechanism of VAP is gross or micro-aspiration of oropharyngeal organisms around the cuff of the endotracheal tube (ETT) into the distal bronchi. Prevention of VAP is preferable. Preventative measures can be divided into two main groups: the implemen- tation of EBPGs and use of device-based technologies. EBPGs have been authored jointly by the American Thoracic Society and the Infectious Diseases Society of America. The Canadian Critical Care Trials group also published VAP Guidelines in 2008. Their recommendations are detailed in this review. The current device-based technologies include drainage of subglottic secretions, silver coated ETTs aiming to influence the internal bio-layer of the ETT, better sealing of the lower airways with ultrathin cuffs and loops for optimal cuff pressure control. CONCLUSIONS EBPG consensus includes: elevation of the head of the bed, use of daily "sedation vacations" and decontamination of the oropharynx. Technological solutions should aim to use the most comprehensive combination of subglottic suction of secretions, optimization of ETT cuff pressure and ultrathin cuffs. VAP is a type of hospital-acquired pneumonia that develops more than 48 h after endotracheal intubation. Its incidence is estimated to be 9-27%, with a mortality of 25-50% [Am J Respir Crit Care Med 171:388-416 (2005), Am J Med 85:499-506 (1988), Chest 122:2115-2121 (2002), Intensive Care Med 35:9-29 (2009)]. The most important target in VAP handling is its prevention. The aim of this article is to review the pathogenesis, epidemiology and the different strategies/technologies for prevention of VAP.


Whose coronavirus strategy worked best? Scientists hunt most effective policies.


Pandemic Emergency Financing Facility: struggling to deliver on its innovative promise.


Covid-19: BMA calls for rapid testing and appropriate protective equipment for doctors.


title: Hemodialysis Vascular Access Care during the COVID-19 Pandemic.

text: Dialysis patients are more vulnerable and susceptible to the severe coronavirus disease 2019 (COVID-19) infection due to multiple comorbidities. Since Taiwan has the highest incidence and prevalence of treated end-stage kidney disease worldwide, it is crucial to act in advance to prevent a potential disaster. In the face of the COVID-19 pandemic, we implement proactive infection control measures to prevent it from spreading without sacrificing the dialysis care quality. In this article, we focused on hemodialysis vascular access (HVA) care in particular. As a life-line of hemodialysis (HD) patients, HVA care has a profound impact on the patient's quality of dialysis and life. Specifically, in our facility, the working and office areas of the HD units are separated to reduce cross-infection. All elective procedures for HVA are postponed, and operating rooms equipped with a negative-pressure anteroom are used for the suspected or confirmed COVID-19 patients. Herein, we share how we modified our HVA care policy not only to prevent our patients from COVID-19 infection but also to maintain the quality of HVA care.


title: Nationwide Survey of Infectious Bronchitis Virus on Layer Farms in Japan During 2015.

text: After accumulating data through a nationwide survey, we characterized the recent prevalences and geographic distributions of various genotypes of infectious bronchitis virus (IBV) on layer farms in Japan. Reverse transcription PCR analysis of fecal samples revealed the presence of the IBV nucleoprotein (N) gene on approximately 30% of the farms surveyed. N-gene detection rates were higher in the Chugoku and Kyushu regions than in the remaining surveyed regions. Phylogenetic analysis of S1 gene sequences revealed that JP-I, JP-II, JP-III, and Massachusetts genotypes were particularly prevalent, with JP-I isolated throughout the country. Additionally, JP-II was the genotype detected most frequently in Chugoku, and JP-III was the most frequent in Kyushu. Unlike the previous results obtained in 1998 through 2003, the European-prevalent 4/91 genotype was no longer circulating in Japan. Moreover, the number of prefectures where multiple genotypes were detected simultaneously increased during that time.


title: Temperature of gas delivered from ventilators.

text: BACKGROUND Although heated humidifiers (HHs) are the most efficient humidifying device for mechanical ventilation, some HHs do not provide sufficient humidification when the inlet temperature to the water chamber is high. Because portable and home-care ventilators use turbines, blowers, pistons, or compressors to inhale in ambient air, they may have higher gas temperature than ventilators with piping systems. We carried out a bench study to investigate the temperature of gas delivered from portable and home-care ventilators, including the effects of distance from ventilator outlet, fraction of inspiratory oxygen (FIO2), and minute volume (MV). METHODS We evaluated five ventilators equipped with turbine, blower, piston, or compressor system. Ambient air temperature was adjusted to 24°C ± 0.5°C, and ventilation was set at FIO2 0.21, 0.6, and 1.0, at MV 5 and 10 L/min. We analyzed gas temperature at 0, 40, 80, and 120 cm from ventilator outlet and altered ventilator settings. RESULTS While temperature varied according to ventilators, the outlet gas temperature of ventilators became stable after, at the most, 5 h. Gas temperature was 34.3°C ± 3.9°C at the ventilator outlet, 29.5°C ± 2.2°C after 40 cm, 25.4°C ± 1.2°C after 80 cm and 25.1°C ± 1.2°C after 120 cm (P < 0.01). FIO2 and MV did not affect gas temperature. CONCLUSION Gas delivered from portable and home-care ventilator was not too hot to induce heated humidifier malfunctioning. Gas soon declined when passing through the limb.


title: [Pregnant women with new coronavirus infection: a clinical characteristics and placental pathological analysis of three cases].

text: Objective: To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy, and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection. Methods: The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology collected by February 4th, 2020 and retrospectively studied. Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR. Results: Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section. All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia. Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV. One premature infant was transferred to Department of Neonatology due to low birth weight. By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment). There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas. One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction. No pathological change of villitis and chorioamnionitis was observed in our observation of three cases. All samples from three placentas were negative for the nucleic acid of 2019-nCoV. Conclusions: The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation. Pathological study suggests that there are no morphological changes related to infection in the three placentas. Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy.


title: Relationship between dietary intake and behaviors with oxytocin: a systematic review of studies in adults.

text: Context Oxytocin plays an important hormonal role in the regulation of feeding and energy intake. Objective The aims of this review were to 1) determine the effects of dietary intake/behaviors on endogenous oxytocin and 2) examine the effect of exogenous oxytocin on dietary intake/behaviors. Data sources Published studies up to December 2016 were identified through searches of 5 electronic databases. Data extraction Eligible studies included those in adults that included a measure related to an individual's diet and a measure of oxytocin and the relationship between the 2 outcomes. Results Twenty-six studies (n = 912 participants; 77% female) were included. The most common dietary outcomes assessed were alcohol, caffeine, calcium, sodium, fat, and calorie intake. It was found that endogenous oxytocin (n = 13) in nonclinical samples did not change significantly (P > 0.05) through altered diet or behaviors (neutral effect); in contrast, significant (P < 0.05) differences (increases and decreases) were identified in clinical samples. Exogenous oxytocin studies (n = 13) found reduced indices of food intake (positive effect) in clinical and nonclinical samples. Conclusions Overall, few studies included comprehensive investigation of dietary intakes through the use of validated assessment tools. Dietary intake and behaviors appear to have some influence on oxytocin, with more pronounced effects found with exogenously administered oxytocin.


title: Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

text: The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.


title: [The impact of viruses in lower respiratory tract infections of the adult. Part II: acute bronchitis, acute exacerbated COPD, pneumonia, and influenza].

text: In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections affect the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series described frequent viral pathogens, pathogenesis of viral LRTI, and diagnostic procedures. In this 2 (nd) part the aetiological role of viruses in the most frequent forms of LRTI will be highlighted, and the third and last part will provide an overview of therapeutic and preventive options.


title: ERK Is a Critical Regulator of JC Polyomavirus Infection.

text: The human JC polyomavirus (JCPyV) infects the majority of the population worldwide and presents as an asymptomatic, persistent infection in the kidneys. In individuals who are immunocompromised, JCPyV can become reactivated and cause a lytic infection in the central nervous system resulting in the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). Infection is initiated by interactions between the capsid protein viral protein 1 (VP1) and the α2,6-linked sialic acid on lactoseries tetrasaccharide c (LSTc), while JCPyV internalization is facilitated by 5-hydroxytryptamine 2 receptors (5-HT2Rs). The mechanisms by which the serotonin receptors mediate virus entry and the signaling cascades required to drive viral infection remain poorly understood. JCPyV was previously shown to induce phosphorylation of extracellular signal-regulated kinase (ERK), a downstream target of the mitogen-activated protein kinase (MAPK) pathway, upon virus entry. However, it remained unclear whether ERK activation was required for JCPyV infection. Both ERK-specific small interfering RNA (siRNA) and ERK inhibitor treatments resulted in significantly diminished JCPyV infection in both kidney and glial cells yet had no effect on the infectivity of the polyomavirus simian virus 40 (SV40). Experiments characterizing the role of ERK during steps in the viral life cycle indicate that ERK activation is required for viral transcription, as demonstrated by a significant reduction in production of large T antigen (TAg), a key viral protein associated with the initiation of viral transcription and viral replication. These findings delineate the role of the MAPK-ERK signaling pathway in JCPyV infection, elucidating how the virus reprograms the host cell to promote viral pathogenesis.IMPORTANCE Viral infection is dependent upon host cell factors, including the activation of cellular signaling pathways. These interactions between viruses and host cells are necessary for infection and play an important role in viral disease outcomes. The focus of this study was to determine how the human JC polyomavirus (JCPyV), a virus that resides in the kidney of the majority of the population and can cause the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML) in the brains of immunosuppressed individuals, usurps a cellular signaling pathway to promote its own infectious life cycle. We demonstrated that the activation of extracellular signal-regulated kinase (ERK), a component of the mitogen-activated protein kinase (MAPK) pathway, promotes JCPyV transcription, which is required for viral infection. Our findings demonstrate that the MAPK-ERK signaling pathway is a key determinant of JCPyV infection, elucidating new information regarding the signal reprogramming of host cells by a pathogenic virus.


title: Early experience with single-incision laparoscopic Nissen fundoplication for gastroesophageal reflux disease in patients with mental retardation via a gastrostomy site incision: report of five cases.

text: Single-incision laparoscopic fundoplication for gastroesophageal reflux disease is not widespread because of its technical difficulty. On the other hand, patients with gastroesophageal reflux frequently also have mental retardation and eating disorders. We have been performing single-incision laparoscopic fundoplication via a gastrostomy site incision since October 2009 for these patients. The treated patients were 4 males and 1 female. A small skin incision was made on the gastrostomy site and a SILS port was placed. Under pneumoperitoneum, a single-incision laparoscopic Nissen fundoplication and gastrostomy were performed with a flexible scope, conventional instruments, and high-dexterity instruments. The pneumoperitoneal time was 115-180 min and blood loss was 1-15 ml. There were no intra- or postoperative complications. The hospital stay was under 8 days for all patients. Using this procedure, the incidence of postoperative intestinal obstruction was very low. The results indicate this procedure can be used as a standard operation for these patients in the future.