title: Protease-mediated entry via the endosome of human coronavirus 229E.

text: Human coronavirus 229E, classified as a group I coronavirus, utilizes human aminopeptidase N (APN) as a receptor; however, its entry mechanism has not yet been fully elucidated. We found that HeLa cells infected with 229E via APN formed syncytia when treated with trypsin or other proteases but not in a low-pH environment, a finding consistent with syncytium formation by severe acute respiratory syndrome coronavirus (SARS-CoV). In addition, trypsin induced cleavage of the 229E S protein. By using infectious viruses and pseudotyped viruses bearing the 229E S protein, we found that its infection was profoundly blocked by lysosomotropic agents as well as by protease inhibitors that also prevented infection with SARS-CoV but not that caused by murine coronavirus mouse hepatitis virus strain JHMV, which enters cells directly from the cell surface. We found that cathepsin L (CPL) inhibitors blocked 229E infection the most remarkably among a variety of protease inhibitors tested. Furthermore, 229E infection was inhibited in CPL knockdown cells by small interfering RNA, compared with what was seen for a normal counterpart producing CPL. However, its inhibition was not so remarkable as that found with SARS-CoV infection, which seems to indicate that while CPL is involved in the fusogenic activation of 229E S protein in endosomal infection, not-yet-identified proteases could also play a part in that activity. We also found 229E virion S protein to be cleaved by CPL. Furthermore, as with SARS-CoV, 229E entered cells directly from the cell surface when cell-attached viruses were treated with trypsin. These findings suggest that 229E takes an endosomal pathway for cell entry and that proteases like CPL are involved in this mode of entry.


title: Laparoscopic right hemihepatic vascular inflow occlusion by lowering of the hilar plate.

text: INTRODUCTION Laparoscopic liver resection under hemihepatic vascular inflow occlusion has advantages over the conventional Pringle's maneuver, especially in patients with cirrhosis. However, laparoscopic hemihepatic vascular inflow occlusion is technically challenging. SUBJECTS AND METHODS From March 2013 to August 2013, 8 consecutive patients who underwent laparoscopic liver resection under right hemivascular inflow occlusion using the lowering of the hilar plate approach. RESULTS There were 3 women and 5 men, with a mean age of 52.6 years (range, 44-73 years). The pathologies were hepatocellular carcinoma (n=3), sarcomatoid liver carcinoma (n=1), hepatic vascular epithelial tumor (n=1), hemangioma (n=2), and colorectal liver metastases (n=1). The types of resection included right hepatectomy (n=3), right anterior sectionectomy (n=1), segments 5 and 6 resection (n=1), and segment 6 resection (n=2). All patients underwent right hemivascular inflow occlusion. The mean operation time was 186.2 minutes (range, 100-280 minutes). The mean time taken to prepare for hemivascular inflow occlusion was 17.8 minutes (range, 15-20 minutes). The mean intraoperative blood loss was 218.8 mL (range, 100-300 mL). The mean duration of vascular control was 25.6 minutes (range, 15-40 minutes). No patients developed postoperative liver failure. There was no postoperative morbidity or mortality. The mean hospital stay was 6 days (range, 5-7 days). CONCLUSIONS Hemihepatic vascular inflow occlusion using the lowering of the hilar plate approach was safe and feasible. It facilitated laparoscopic liver resection by minimizing blood loss during liver parenchymal transection.


title: Two-Port Fetoscopic Repair of Myelomeningocele in Fetal Lambs.

text: OBJECTIVE The aim of this study was to assess the feasibility and the effectiveness of a fetoscopic myelomeningocele (MMC) repair with a running single suture using a 2-port access in the sheep model. METHODS Eighteen fetuses underwent surgical creation of a MMC defect at day 75. Fetuses were then randomized into 3 groups. Four fetuses remained untreated (control group). In the other 14 fetuses, a prenatal repair was performed at day 90: 7 fetuses had an open repair (oMMC), and 7 fetuses had a fetoscopic repair (fMMC) using a single-layer running suture through a 2-port access. Lambs were sacrificed at term, and histological examinations were performed. RESULTS Hindbrain herniation was observed in all live lambs in the control group. A complete closure of the defect was achieved in all the lambs of the fMMC group. A complete healing of the defect and no hindbrain herniation were observed in all live lambs of the oMMC and fMMC groups. The durations of surgeries were not statistically different between the oMMC and the fMMC groups (60 vs. 53 min, p = 0.40), as was the risk of fetal loss (fMMC: 1/7, oMMC: 3/7, p = 0.56). DISCUSSION Fetoscopic repair of MMC can be performed using a single-layer running suture through a 2-port access and may be promising to reduce the risk of premature rupture of membranes.


title: Interferon gamma in autoimmunity: A complicated player on a complex stage.

text: Early views of autoimmune disease cast IFNγ as a prototypic pro-inflammatory factor. It is now clear that IFNγ is capable of both pro- and anti-inflammatory activities with the functional outcome dependent on the physiological and pathological setting examined. Here, the major immune modulatory activities of IFNγ are reviewed and current evidence for the impact of IFNγ on pathology and regulation of several autoimmune diseases and disease models is summarized.


title: The IL-33 Receptor/ST2 acts as a positive regulator of functional mouse bone marrow hematopoietic stem and progenitor cells.

text: There is a paucity of information on a potential role for the IL-33 receptor/ST2 in the regulation of mouse bone marrow (BM) hematopoietic stem (HSC) and progenitor (HPC) cells. Comparing the BM of st2-/- and wild type (WT) control mice using functional assays, it was found that st2-/- BM cells had poorer engrafting capacity than WT BM in a competitive repopulating assay using congenic mice, with no changes in reconstitution of B-, T- and myeloid cells following transplantation. The BM of st2-/- mice also had fewer granulocyte-macrophage, erythroid, and multipotential progenitors than that of WT BM and these st2-/- HPC were in a slow cycling state compared to that of the rapidly cycling HPC of the WT mice. While functional assessment of HSC and HPC demonstrated that ST2 has a positive influence on regulation of HSC, we could not pick up differences in st2-/- compared to WT BM using only phenotypic analysis of HSC and HPC populations prior to transplantation, again demonstrating that phenotypic analysis of HSC and HPC do not always recapitulate the functional assessments of these immature hematopoietic cells.


COVID-19 and the ABO blood group connection.


title: Randomized assessment of rapid endovascular treatment of ischemic stroke.

text: BACKGROUND Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. METHODS We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). RESULTS The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P=0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P=0.75). CONCLUSIONS Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.).


Paying for Medicaid - State Budgets and the Case for Expansion in the Time of Coronavirus.


Changes in Suicide and Resilience-related Google Searches during the Early Stages of the COVID-19 Pandemic.


As the profession soldiers on, all members hear the call to arms.


title: Ultrashort imaging to reperfusion time interval arrests core expansion in endovascular therapy for acute ischemic stroke.

text: BACKGROUND AND PURPOSE The shorter the time interval between the estimation of the ischemic core by imaging and reperfusion, the more likely that core expansion is minimized. We aimed to assess the feasibility of achieving an ultrashort imaging to reperfusion time in routine clinical practice. METHODS The study subjects were a prospective cohort of patients with acute ischemic stroke treated with endovascular therapy in a tertiary center in whom an imaging to reperfusion time of <60 min was achieved. RESULTS Imaging to reperfusion time of <60 min was accomplished in 11 patients. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 11 and the median baseline Alberta Stroke Program Early CT Score (ASPECTS) was 8. The median time interval from imaging to endovascular reperfusion was 47 min. The median ASPECTS score on the 24 h CT scan was also 8 and the median 24 h NIHSS score was 1. Upon discharge, 82% of patients achieved a modified Rankin scale score of ≤ 1. CONCLUSIONS An imaging to endovascular reperfusion time of <60 min is feasible and resulted in minimal core expansion on follow-up imaging in patients with acute ischemic stroke.


title: Broadband near-infrared spectroscopy can detect cyanide-induced cytochrome aa3 inhibition in rats: a proof of concept study.

text: PURPOSE Clinically available near-infrared spectroscopy (NIRS) devices use two to five wavelengths of light to measure the relative amounts of oxyhemoglobin and deoxyhemoglobin in tissue to determine tissue hemoglobin oxygen saturation (StO2). In addition to StO2, broadband NIRS devices (using hundreds of wavelengths of light) may be able to measure the oxidation state of mitochondrial cytochrome aa3 (Cytox) which reflects the subcellular energetic state. We hypothesize that broadband NIRS devices can measure Cytox independent of changes in hemoglobin saturation. METHODS In this prospective non-randomized study, 20 male Sprague-Dawley rats (300 g) were anesthetized with isoflurane, tracheally intubated, and ventilated with 100% O2 containing 2% isoflurane. They were subsequently instrumented with a broadband NIRS device that used a halogen light source coupled to an emitting fibreoptic cable. Three receiving fibreoptic cables were utilized; one analyzed the light source and the other two were directed at the base of the skull. Each receiving fibre was connected to a spectrometer to measure light intensity. Sodium cyanide (NaCN) 5 mg·kg-1 iv was injected in order to produce cytochrome aa3 reduction. Two to three minutes after injection, oxygen was eliminated and 100% nitrogen (i.e., anoxia) was used for ventilation in order to induce a reduction in both cytochrome aa3 and hemoglobin desaturation. Changes in the cytochrome oxidation state and hemoglobin oxygenation were calculated using a broadband algorithm and compared before and after both the NaCN and anoxia interventions. RESULTS The NaCN injection resulted in a decrease in median [interquartile range (IQR)] deoxyhemoglobin (-0.014 [-0.29 to -0.005] arbitrary units [AU]; P < 0.001), an increase in oxyhemoglobin (0.013 [-0.011 to 0.031] AU; P < 0.001), and a reduction in cytochrome aa3 (-0.015 [-0.020 to -0.011] AU; P < 0.001). Anoxia resulted in an increase in median [IQR] deoxyhemoglobin (0.13 [0.11 to 0.18] AU; P < 0.001), a decrease in oxyhemoglobin (-0.17 [-0.22 to -0.15] AU; P < 0.001), and a reduction in cytochrome aa3 (-0.04 [-0.06 to -0.03] AU; P < 0.001). CONCLUSION Broadband NIRS can effectively measure the directionality of changes in both Cytox and StO2 by uncoupling the cytochrome and hemoglobin signals through inhibition of the electron transport chain and anoxia.


title: New spectrum of COVID-19 manifestations in children: Kawasaki-like syndrome and hyperinflammatory response.

text: Since late April 2020, data regarding Kawasaki-like syndrome and hyperinflammatory response in children associated with COVID-19 has rapidly emerged. Much remains unknown about the risk factors, pathogenesis, prognosis, and specific therapy for this emerging manifestation of COVID-19 known as Multisystem Inflammatory Syndrome in Children (MIS-C). MIS-C is rare and early recognition is crucial though no standardized treatment guideline have been established. Worldwide collaboration will be important as more cases are recognized going forward.


title: Nanoparticulate delivery systems for antiviral drugs.

text: Nanomedicine opens new therapeutic avenues for attacking viral diseases and for improving treatment success rates. Nanoparticulate-based systems might change the release kinetics of antivirals, increase their bioavailability, improve their efficacy, restrict adverse drug side effects and reduce treatment costs. Moreover, they could permit the delivery of antiviral drugs to specific target sites and viral reservoirs in the body. These features are particularly relevant in viral diseases where high drug doses are needed, drugs are expensive and the success of a therapy is associated with a patient's adherence to the administration protocol. This review presents the current status in the emerging area of nanoparticulate delivery systems in antiviral therapy, providing their definition and description, and highlighting some peculiar features. The paper closes with a discussion on the future challenges that must be addressed before the potential of nanotechnology can be translated into safe and effective antiviral formulations for clinical use.


title: Microarray detection of gene overexpression in primary spontaneous pneumothorax.

text: Primary spontaneous pneumothorax (PSP) often occurs after the rupture of small bullae or subpleural blebs in otherwise normal lungs. The underlying mechanism(s) remain unclear. The aim of this study was to identify genes potentially involved in the development of PSP. Microarray analysis was performed to identify specific gene expression patterns. Expression levels of genes identified to be significantly up- or down-regulated in association with PSP were confirmed by real-time polymerase chain reaction (qRT-PCR) and Western blotting. Immunohistochemistry was performed to identify lung cell types highly expressing these genes. Microarray analysis revealed that expression levels of hypoxia-inducible factor-3 alpha (HIF-3alpha) and caspase-8 were significantly up-regulated in tissue from patients with PSP, whereas interferon-gamma, interleukin (IL)-6, and IL-8 were down-regulated (all P < .05). These genes are related to hypoxia, apoptosis, and inflammation. HIF-3alpha and caspase-8 protein levels were increased in samples from patients with PSP. HIF-3alpha and caspase-8 were localized in mesothelial cells, alveolar type II pneumocytes, and bronchoalveolar epithelial cells in samples from patients with PSP. Our findings, although obviously preliminary given the small sample size, suggest that hypoxia, inflammation, and apoptosis may play important roles in the pathogenesis of PSP.


title: The Expectations and Challenges of Wildlife Disease Research in the Era of Genomics: Forecasting with a Horizon Scan-like Exercise.

text: The outbreak and transmission of disease-causing pathogens are contributing to the unprecedented rate of biodiversity decline. Recent advances in genomics have coalesced into powerful tools to monitor, detect, and reconstruct the role of pathogens impacting wildlife populations. Wildlife researchers are thus uniquely positioned to merge ecological and evolutionary studies with genomic technologies to exploit unprecedented "Big Data" tools in disease research; however, many researchers lack the training and expertise required to use these computationally intensive methodologies. To address this disparity, the inaugural "Genomics of Disease in Wildlife" workshop assembled early to mid-career professionals with expertise across scientific disciplines (e.g., genomics, wildlife biology, veterinary sciences, and conservation management) for training in the application of genomic tools to wildlife disease research. A horizon scanning-like exercise, an activity to identify forthcoming trends and challenges, performed by the workshop participants identified and discussed 5 themes considered to be the most pressing to the application of genomics in wildlife disease research: 1) "Improving communication," 2) "Methodological and analytical advancements," 3) "Translation into practice," 4) "Integrating landscape ecology and genomics," and 5) "Emerging new questions." Wide-ranging solutions from the horizon scan were international in scope, itemized both deficiencies and strengths in wildlife genomic initiatives, promoted the use of genomic technologies to unite wildlife and human disease research, and advocated best practices for optimal use of genomic tools in wildlife disease projects. The results offer a glimpse of the potential revolution in human and wildlife disease research possible through multi-disciplinary collaborations at local, regional, and global scales.


title: Effects of dexmedetomidine vs sufentanil during percutaneous tracheostomy for traumatic brain injury patients: A prospective randomized controlled trial.

text: BACKGROUND Percutaneous tracheostomy, almost associated with cough reflex and hemodynamic fluctuations, is a common procedure for traumatic brain injury (TBI) patients, especially those in neurosurgery intensive care units (NICUs). However, there are currently a lack of effective preventive measures to reduce the risk of secondary brain injury. The aim of this study was to compare the effect of dexmedetomidine (DEX) vs sufentanil during percutaneous tracheostomy in TBI patients. METHODS The 196 TBI patients who underwent percutaneous tracheostomy were randomized divided into 3 groups: group D1 (n = 62, DEX infusion at 0.5 μg·kg for 10 minutes, then adjusted to 0.2-0.7 μg·kg·hour), group D2 (n = 68, DEX infusion at 1 μg·kg for 10 minutes, then adjusted to 0.2-0.7 μg·kg·hour), and group S (n = 66, sufentanil infusion 0.3 μg·kg for 10 minutes, then adjusted to 0.2-0.4 μg·kg·hour). The bispectral index (BIS) of all patients was maintained at 50 to 70 during surgery. Anesthesia onset time, hemodynamic variables, total cumulative dose of DEX/sufentanil, total doses of rescue propofol and fentanyl, time to first dose of rescue propofol and fentanyl, number of intraoperative patient movements and cough reflexes, adverse events, and surgeon satisfaction score were recorded. RESULTS Anesthesia onset time was significantly lower in group D2 than in both other groups (14.35 ± 3.23 vs 12.42 ± 2.12 vs 13.88 ± 3.51 minutes in groups D1, D2, and S, respectively; P < .001). Both heart rate and mean arterial pressure during percutaneous tracheostomy were more stable in group D2. Total doses of rescue propofol and fentanyl were significantly lower in group D2 than in group D1 (P < .001). The time to first dose of rescue propofol and fentanyl were significantly longer in group D2 than in both other groups (P < .001). The number of patient movements and cough reflexes during percutaneous tracheostomy were lower in group D2 than in both other groups (P < .001). The overall incidences of tachycardia and hypertension (which required higher doses of esmolol and urapidil, respectively) were also lower in group D2 than in both other groups (P < .05). Three patients in group S had respiratory depression compared to X in the D1 group and X in the D2 group. The surgeon satisfaction score was significantly higher in group D2 than in both other groups (P < .05). CONCLUSIONS During percutaneous tracheostomy, compared with sufentanil, DEX (1 μg·kg for 10 minutes, then adjusted to 0.2-0.7 μg·kg·hour) can provide the desired attenuation of the hemodynamic response without increased adverse events. Consequently, DEX could be used safely and effectively during percutaneous tracheostomy in TBI patients.


title: 2019-nCoV acute respiratory disease, Australia: Epidemiology Report 1 (Reporting week 26 January - 1 February 2020).

text: This is the first epidemiological report of novel coronavirus (2019-nCoV) acute respiratory disease infections reported in Australia at 19:00 Australian Eastern Daylight Time [AEDT] 1 February 2020. It includes data on Australian cases notified during the week 26 January to 1 February 2020 and in the previous week (19 to 25 January 2020), the international situation and current information on the severity, transmission and spread of the 2019-nCoV infection.


title: T2-hypointense adnexal lesions: an imaging algorithm.

text: T2-weighted sequences are an integral part of magnetic resonance (MR) imaging performed for the characterization of adnexal lesions. A relatively small number of these lesions demonstrate low signal intensity on T2-weighted MR images. In the majority of cases, a specific diagnosis can be made by interpreting the signal intensity of the lesion with respect to certain pathologic correlates, including blood products, smooth muscle, fibrous tissue, and calcification, as well as high lesion cellularity. For example, lesions that are at least as dark as skeletal muscle are almost always benign, whereas those whose T2 signal intensity is higher than that of skeletal muscle constitute a more heterogeneous group composed of benign, borderline, and malignant disease entities. The authors propose a diagnostic algorithm that takes these features into account, as well as the appearances of the lesion with additional pulse sequences, to aid in the correct interpretation of T2-hypointense adnexal lesions. Knowledge of the anatomy, the T1-weighted imaging features, and the enhancement characteristics of adnexal lesions allows accurate characterization of these lesions, resulting in appropriate patient management.


title: Abdominal Visceral Infarction in 3 Patients with COVID-19.

text: A high incidence of thrombotic events has been reported in patients with coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We report 3 clinical cases of patients in Italy with COVID-19 who developed abdominal viscera infarction, demonstrated by computed tomography.


Caring for orthopaedic patients affected by elective surgery suspensions


title: A totally thoracoscopic ablation for persistent atrial fibrillation.

text: We report the case of a 72-year-old female with persistent atrial fibrillation who underwent a totally thoracoscopic ablation. A successful normal sinus conversion was achieved.


title: Innovative Surgical Approaches and Selection Criteria of Large Acne Keloidalis Nuchae Lesions.

text: Background Acne keloidalis nuchae is a debilitating condition mainly affecting the occipital region or nape of the neck. Surgical approaches are limited in aesthetic outcomes. Three innovative surgical approaches based on selection criteria are presented for enhanced and more predictable wound healing and posterior hairline cosmesis. Methods "Bat excision" and secondary intention healing are shown for 2 of 37 representative patients and confined to the area between the occipital protuberance superiorly and posterior hairline inferiorly. Lesions with ≤3 cm vertical width were required to be in the lower one-half portion of this zone. The same procedure was aided by the use of tension sutures for lesions with >3 cm vertical width area within the defined zone. It was also suitable for breaches of the 2 horizontal lines defined above but generally located in the nuchal area. Debridement of premature epithelizing granulation tissue is shown in 2 additional patients. Results Use of these procedures with debridement in selected patients allowed fine control over the hairline shape and resulted in narrower scars. The mean maximum sagittal width of excised lesions was 5.4 cm. Excised lesion width ≥6.5 cm was highly predictive of >2.5 cm wide scar (P = 0.001). Conclusion Innovative procedures based on selection criteria can extend the approach of acne keloidalis nuchae excision with secondary intention healing to better control the final hairline shape and minimize scarring.


title: Metabolomics in neonatal life.

text: Metabolomics (or metabonomics) is based on the systematic study of the complete set of metabolites in a biological sample and is considered the most innovative of the 'omics' sciences. The metabolome is currently regarded as the 'new clinical biochemistry' it is the most predictive phenotype, through consideration of epigenetic differences. Among more than 5000 papers listed in PubMed on this topic in the last three years, less than 60 refer to neonatal life. Aim of this review is to present the clinical applications of metabolomics in neonatology, including results of recent studies performed in experimental models and newborns.


title: Transcultural Nurses' Caring for Pilgrims for the First Time During Hajj Season in Saudi Arabia.

text: The Kingdom of Saudi Arabia invests tremendous governmental resources to support the annual Hajj season, including providing free world-class healthcare for all visiting pilgrims. Nurses from around the Kingdom are encouraged to work at Makkah during this period. These nurses come from different cultural backgrounds and provide care for pilgrims from around the world. The study utlized descriptive phenomenology design. A total of 11 transcultural nurses were interviewed. A thematic analysis was performed to understand the lived experience of the transcultural nurses participating in the Hajj for the first time. Five themes emerged. These included serving with satisfaction; a supportive and fair system; professional and personal values; difference, and difficulties and problems. This is the first study of transcultural nurses' experiences of providing nursing care to pilgrims during the Hajj. The results highlight transcultural nurses' perceptions of the benefits and challenges of providing care during the Hajj and potential strategies to improve preparation and care quality.


title: Worldwide differences in COVID-19-related mortality.

text: Mortality statistics due to COVID-19 worldwide are compared, by adjusting for the size of the population and the stage of the pandemic. Data from the European Centre for Disease Control and Prevention, and Our World in Data websites were used. Analyses are based on number of deaths per one million inhabitants. In order to account for the stage of the pandemic, the baseline date was defined as the day in which the 10th death was reported. The analyses included 78 countries and territories which reported 10 or more deaths by April 9. On day 10, India had 0.06 deaths per million, Belgium had 30.46 and San Marino 618.78. On day 20, India had 0.27 deaths per million, China had 0.71 and Spain 139.62. On day 30, four Asian countries had the lowest mortality figures, whereas eight European countries had the highest ones. In Italy and Spain, mortality on day 40 was greater than 250 per million, whereas in China and South Korea, mortality was below 4 per million. Mortality on day 10 was moderately correlated with life expectancy, but not with population density. Asian countries presented much lower mortality figures as compared to European ones. Life expectancy was found to be correlated with mortality.


title: Generation of plant-derived recombinant DTP subunit vaccine.

text: The current diphtheria-tetanus-pertussis (DTP) pediatric vaccine is produced from the corresponding pathogenic bacteria Corynebacterium diphtheriae, Clostridium tetani and Bordetella pertussis; five injected doses of DTaP (acellular) vaccine are required for every child in the standard US vaccination schedule. Because the vaccine is derived from native live sources, adverse effects are possible and production is complex and costly. To address issues of safety, ease of renewability and expense, we used recombinant technology in an effort to develop a subunit DPT vaccine derived in non-pathogenic plant expression systems. Expression of diphtheria toxin (DT), tetanus fragment-C (TetC) and the non-toxic S1 subunit of pertussis toxin (PTX S1) antigenic proteins in soluble form in low-alkaloid tobacco plants and carrot cell cultures allowed efficient downstream purification to levels suitable for intramuscular injection in BALB/c mice. At working concentrations of 5mug per dose, these preparations induced high levels of antigen-specific IgGs in mouse sera. Our results clearly support the feasibility of producing recombinant pediatric vaccine components in plants.


Novel bulking agent for faecal incontinence (Br J Surg 2011; 98: 1644-1652).


Pandemic SARS-CoV-2 laboratory preparedness in India: An opportunity beyond diagnostics.


Scores of coronavirus vaccines are in competition - how will scientists choose the best?


title: Utility of vital signs, heart rate variability and complexity, and machine learning for identifying the need for lifesaving interventions in trauma patients.

text: To date, no studies have attempted to utilize data from a combination of vital signs, heart rate variability and complexity (HRV, HRC), as well as machine learning (ML), for identifying the need for lifesaving interventions (LSIs) in trauma patients. The objectives of this study were to examine the utility of the above for identifying LSI needs and compare different LSI-associated models, with the hypothesis that an ML model would be superior in performance over multivariate logistic regression models. One hundred four patients transported from the injury scene via helicopter were selected for the study. A wireless vital signs monitor was attached to the patient's arm and used to capture physiologic data, including HRV and HRC. The power of vital sign measurements, HRV, HRC, and Glasgow Coma Scale score (GCS) to identify patients requiring LSIs was estimated using multivariate logistic regression and ML. Receiver operating characteristic (ROC) curves were also obtained. Thirty-two patients underwent 75 LSIs. After logistic regression, ROC curves demonstrated better identification for LSIs using heart rate (HR) and HRC (area under the curve [AUC] of 0.81) than using HR alone (AUC of 0.73). Likewise, ROC curves demonstrated better identification for LSIs using GCS and HRC (AUC of 0.94) than using GCS and HR (AUC of 0.92). Importantly, ROC curves demonstrated that an ML model using HR, GCS, and HRC (AUC of 0.99) had superior performance over multivariate logistic regression models for identifying the need for LSIs in trauma patients. Development of computer decision support systems should utilize vital signs, HRC, and ML in order to achieve more accurate diagnostic capabilities, such as identification of needs for LSIs in trauma patients.


title: COVID-19 Situation and Challenges for Nepal.

text: Nepal is at a high risk of increasing COVID-19 cases through people who recently returned to Nepal from other countries. The health care system of Nepal is fragile, and the country is not having the necessary infrastructure to cope with an increasing number of infections and pandemic situations.


title: [Obesity as a risk factor for complications during acute respiratory infections in children].

text: Obesity has a high prevalence among children. On the other hand, acute respiratory infections especially of viral origin, are an important cause of morbidity and mortality in this age group. During the recent pandemic of influenza A (H1N1) virus, obesity was identified as a novel independent risk factor for severity multiple markers of the disease. We reviewed the evidence associating obesity with a worse course of respiratory diseases in children. Nine out of 40 retrieved articles, were chosen to be reviewed. We concluded that there is evidence suggesting that immunomodulatory effects of obesity could be considered as a novel risk factor. Thus, bearing in mind the drastic rise in obesity prevalence around the world and in Chile, and the latent possibility of new respiratory pandemics caused by viruses, studying the possible effect of obesity aggravating viral respiratory infections will become important.


Cardiac and Pulmonary Transplant Considerations During COVID-19 Pandemic.


title: A revolutionary design change to improve stapler safety.

text: BACKGROUND Postoperative staple line leaks and bleeding are the most common reasons for complications in surgical procedures that involve organ resection, such as sleeve gastrectomy. Increasing the safety of these operations requires improving the instruments (endostaplers or endocutters) used for stapling and sectioning the tissues. METHODS We present a new prototype stapler for marketing in resection surgery, especially designed for the sleeve gastrectomy. RESULTS We suggest that the medical instrument industry creates devices in which the channel along which the knife blade runs is located asymmetrically. This would allow more staples to be placed on the side of the gastric remnant, thus improving the sealing and hemostasis of the suture line and reducing the number of complications for patients as a result. CONCLUSIONS The application of new concepts in medical surgical devices can improve the safety of the procedures in our patients.


title: Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10-year intention-to-treat analysis.

text: In a long-term (10-year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post-LT tumor recurrence, and long-term intention-to-treat, disease-specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand-alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow-up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor-specific waiting list dropout rates, post-LT tumor recurrence, and 10-year post-LT and intention-to-treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post-LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence-free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention-to-treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively. CONCLUSION RFA as a first-line stand-alone bridge therapy to LT achieves excellent long-term overall and tumor-specific survivals, with a low dropout rate from tumor progression despite long wait list times and a sustained low tumor recurrence rate upon post-LT follow-up of up to 10 years. (Hepatology 2017;65:1979-1990).


title: The impact of atrial fibrillation type on the risks of thromboembolic recurrence, mortality and major haemorrhage in patients with previous stroke: A systematic review and meta-analysis of observational studies.

text: Introduction There is conflicting evidence on the impact of atrial fibrillation (AF) type, i.e. non-paroxysmal AF or paroxysmal AF, on thromboembolic recurrence. The consensus of risk equivalence is greatly based on historical evidence, focussing on initial stroke risks. We conducted a systematic review and meta-analysis to describe the impact of AF type on the risk of thromboembolic recurrence, mortality and major haemorrhage in patients with previous stroke. Methods We systematically searched four multidisciplinary databases from inception to December 2018. We selected observational studies investigating clinical outcomes in patients with ischaemic stroke and AF, stratified by AF type. We assessed all included studies for risk of bias using the 'Risk of Bias In Non-randomised Studies - of Exposures' tool. The Comprehensive Meta-Analysis Software was used to calculate odds ratios from crude event rates. Results After reviewing 14,127 citations, we selected 108 studies for full-text screening. We extracted data from a total of 26 studies, reporting outcomes on 23,054 patients. Overall, risk of bias was moderate. The annual incidence rates of thromboembolism in patients with non-paroxysmal AF and paroxysmal AF were 7.1% (95% confidence interval: 4.2-11.7) and 5.2% (95% confidence interval: 3.2-8.2), respectively. The odds ratio for thromboembolism in patients with non-paroxysmal AF versus paroxysmal AF was 1.47 (95% confidence interval: 1.08-1.99, p = 0.013). The annual mortality rates in patients with non-paroxysmal AF and paroxysmal AF were 20.0% (95% confidence interval: 13.2-28.0) and 10.1% (95% confidence interval: 5.4-17.3), respectively, and odds ratio was 1.90 (95% confidence interval: 1.43-2.52, p < 0.001). There was no difference in rates of major haemorrhage, odds ratio = 1.01 (95% confidence interval: 0.61-1.69, p = 0.966). Conclusion In patients with prior stroke, non-paroxysmal AF is associated with significantly higher risk of thromboembolic recurrence and mortality than paroxysmal AF. Although current guidelines make no distinction between non-paroxysmal AF and paroxysmal AF for secondary stroke prevention, future guidance and risk stratification tools may need to consider this differential risk (PROSPERO ID: CRD42019118531).


title: HYPERKALEMIA IN TWO JAGUARS ( PANTHERA ONCA) ANESTHETIZED WITH DEXMEDETOMIDINE, KETAMINE, AND ISOFLURANE.

text: Two jaguars were anesthetized with dexmedetomidine, ketamine, and isoflurane. Arterial blood samples analyzed shortly after darting revealed no abnormalities. Samples analyzed 2 and 1.5 hr after darting revealed moderate hyperkalemia in both animals (6.8 and 6.2 mEq/L, respectively). Shortly after hyperkalemia was recognized, one jaguar developed electrocardiographic abnormalities (sinoventricular rhythm and widened QRS complexes), and a few minutes later, suffered cardiopulmonary arrest. Resuscitation with chest compressions, intermittent positive-pressure ventilation, and epinephrine was successful, and autonomous breathing and circulation resumed within a few minutes. Anesthesia-related hyperkalemia has been reported in a variety of large felids but has not been reported previously in jaguars. In all reports, α-2 adrenergic agonists were used as part of the immobilization protocol. Due to the presumptively high incidence and mortality caused by this complication, frequent monitoring of electrolyte concentrations and prompt treatment of hyperkalemia is recommended when anesthetizing large felids, including jaguars.


title: Single incision thoracoscopic left lower lobe superior segmentectomy for non-small cell lung cancer.

text: Lobectomy with mediastinal node dissection has been standard treatment for non-small cell lung cancer (NSCLC). Nowadays, video-assisted thoracoscopic surgery (VATS) is gaining acceptance as an alternative treatment option, given the quality-of-life benefits that it confers. For the VATS procedure, most surgeons create two or three ports with a utility incision of 3 to 5 cm. However, with acquired skill and instrumentation advances, single-incision thoracoscopic surgery has emerged over time. Here, we report the case of an 86-year-old female with NSCLC treated by single-incision segmentectomy.


title: Prevention of venous thromboembolism: consensus, controversies, and challenges.

text: The last 50 years have witnessed a multitude of publications evaluating the efficacy, safety and cost effectiveness of many different thromboprophylaxis interventions. There is widespread consensus that thromboprophylaxis safely reduces morbidity and mortality. More than 25 evidence-based guidelines, published since 1986, also recommend routine thromboprophylaxis in the majority of hospitalized patients. As a result, thromboprophylaxis is recognized as a key safety priority for hospitals. Some of the remaining areas of controversy that will be discussed in this paper include the role of individual risk assessments to determine thrombosis risk and prophylaxis, replacement of low-dose heparin by low-molecular-weight heparin (LMWH), the optimal duration of prophylaxis, the role of combined thromboprophylaxis modalities, the safety of anticoagulant prophylaxis with regional analgesia, the use of LMWHs in chronic renal insufficiency, and the emerging role of new oral anticoagulants as thromboprophylactic agents. Despite the overwhelming evidence supporting thromboprophylaxis, rates of thromboprophylaxis use remain far from optimal. Successful implementation strategies to bridge this knowledge:care gap are the most important current challenges in this area. These strategies must be multifaceted, utilizing local, systems-based approaches as well as legislation and incentives that reinforce best practices.


title: Novel bat adenoviruses with an extremely large E3 gene.

text: Bats carry diverse RNA viruses, some of which are responsible for human diseases. Compared to bat-borne RNA viruses, relatively little information is known regarding bat-borne DNA viruses. In this study, we isolated and characterized three novel bat adenoviruses (BtAdV WIV9-11) from Rhinolophus sinicus. Their genomes, which are highly similar to each other but distinct from those of previously sequenced adenoviruses (AdVs), are 37 545, 37 566 and 38 073 bp in size, respectively. An unusually large E3 gene was identified in their genomes. Phylogenetic and taxonomic analyses suggested that these isolates represent a distinct species of the genus Mastadenovirus. Cell susceptibility assays revealed a broad cell tropism for these isolates, indicating that they have a potentially wide host range. Our results expand the understanding of genetic diversity of bat AdVs.


title: Gamma interferon signaling in oligodendrocytes is critical for protection from neurotropic coronavirus infection.

text: Neurotropic coronavirus induces acute encephalomyelitis and demyelination in mice. Infection of BALB/c (H-2(d)) mice expressing a dominant negative gamma interferon (IFN-gamma) receptor specifically in oligodendrocytes was examined to determine the influence of IFN-gamma signaling on pathogenesis. Inhibition of IFN-gamma signaling in oligodendrocytes increased viral load, infection of oligodendrocytes, oligodendrocyte loss, demyelination, and axonal damage resulting in increased mortality. IFN-gamma levels and the inflammatory response were not altered, although the level of tumor necrosis factor (TNF) mRNA was increased. These data indicate that IFN-gamma signaling by oligodendroglia reduces viral replication but affects both demyelination and tissue destruction in a host-specific manner.


Viruses and lower respiratory tract infections: does more mean worse?


Cirrhotic patients in icu with gastro-intestinal bleeding managed according to recent guidelines display altered brain hemoglobin oxygen's saturation assessed by near infrared spectroscopy.


title: Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: A Promising Medication for Chronic Obstructive Pulmonary Disease?

text: Chronic obstructive pulmonary disease (COPD) is a complex disorder that primarily affects the lungs and is characterized not only by local pulmonary, but also by systemic inflammation which promotes the development of extrapulmonary and cardiovascular co-morbidities. Angiotensin converting enzyme (ACE) inhibitors and ARBs (angiotensin receptor blockers) are widely used drugs in the treatment of cardiovascular diseases, with growing evidence suggesting potential benefits in COPD patients. The purpose of this review is to describe the correlation of renin-angiotensin system (RAS) with COPD pathophysiology and to present the latest data regarding the potential role of RAS blockers in COPD.


title: Endovascular Therapy for Ruptured Cerebral Aneurysms in the Elderly: Poor Accessibility of the Guiding Catheter and Use of Local Anesthesia as the Predictors of Procedure-Related Rupture.

text: BACKGROUND Endovascular therapy is favored for ruptured intracranial aneurysms in the elderly. However, poor accessibility to the aneurysm through the parent artery and use of local anesthesia in this age group may predispose to intraprocedural complications. OBJECTIVE To evaluate whether age-related poor access to the ruptured target aneurysm and use of local anesthesia are associated with increased incidence of procedure-related rupture during endovascular embolization. METHODS A total of 117 patients with 117 ruptured aneurysms underwent endovascular embolization at a single institution. Correlation of increasing age with poor accessibility of the guiding catheter was analyzed. In addition, the distance from the aneurysm to the guiding catheter was investigated to identify an association with incidence of procedure-related rupture. Correlation of local anesthesia with procedure-related rupture was also evaluated in the multivariable analysis. RESULTS Increasing age was significantly associated with poor accessibility of the guiding catheter (P = .001, Mann-Whitney U test). Procedure-related rupture occurred in 9 of 117 aneurysms (7.7%). Longer distance between distal aneurysms and low-positioned guiding catheters carried a higher risk of procedure-related rupture than a shorter distance between proximal aneurysms and high-positioned guiding catheters (odds ratio, 19.3; 95% confidence interval, 1.84-201; P = .01, multivariable analysis). Use of local anesthesia was also a significant risk factor of procedure-related rupture by multivariable analysis. CONCLUSION Increasing age was correlated with poor accessibility of the guiding catheter in endovascular embolization of ruptured intracranial aneurysms. Distally located aneurysms treated through a low-positioned guiding catheter and use of local anesthesia increased the risk of procedure-related rupture.


title: Nasal and pulmonary vaccine delivery using particulate carriers.

text: INTRODUCTION Many human pathogens cause respiratory illness by colonizing and invading the respiratory mucosal surfaces. Preventing infection at local sites via mucosally active vaccines is a promising and rational approach for vaccine development. However, stimulating mucosal immunity is often challenging. Particulate adjuvants that can specifically target mucosal immune cells offer a promising opportunity to stimulate local immunity at the nasal and/or pulmonary mucosal surfaces. AREAS COVERED This review analyzes the common causes of respiratory infections, the challenges in the induction of mucosal and systemic responses and current pulmonary and nasal mucosal vaccination strategies. The ability of various particulate adjuvant formulations, including lipid-based particles, polymers and other particulate systems, to be effectively utilized for mucosal vaccine delivery is discussed. EXPERT OPINION Induction of antibody and cell-mediated mucosal immunity that can effectively combat respiratory pathogens remains a challenge. Particulate delivery systems can be developed to target mucosal immune cells and effectively present antigen to evoke a rapid and long-term local immunity in the respiratory mucosa. In particular, particulate delivery systems offer the versatility of being formulated with multiple adjuvants and antigenic cargo, and can be tailored to effectively prime immune responses across the mucosal barrier. The opportunity for rational design of novel subunit particulate vaccines is emerging.


title: Oncolytic viruses: a new class of immunotherapy drugs.

text: This corrects the article DOI: 10.1038/nrd4663.


title: The Vertical Array Reconstruction Technique in Pylorus-Preserving Pancreatoduodenectomy.

text: BACKGROUND/AIMS We describe a new reconstruction method of duodenojejunal anastomosis, the "vertical array reconstruction" (VAR) technique, following pylorus-preserving pancreatoduodenectomy (PPPD). METHODS The VAR technique aligns the stomach, duodenum, and jejunal loop vertically along the body's longitudinal axis. It was performed in 120 consecutive patients (between June 2008 and October 2015) who underwent PPPD. We evaluated the incidence of delayed gastric emptying (DGE). RESULTS The incidence of DGE was 1.7% (n = 2). The proposed clinical grading classified these 2 cases of DGE as grade B. There was no DGE related to pancreatic fistula. The median duration to starting a solid diet was 3 days (range 3-5 days). The median operative time was 450 min (range 391-550 min). CONCLUSION The VAR technique allows the upper digestive tract to be aligned linearly and can minimize the risk of DGE after PPPD.


A call for the appropriate application of clinical pharmacological principles in the search for safe and efficacious COVID-19 (SARS-COV-2) treatments.


title: Characterization of a model of systemic inflammation in humans in vivo elicited by continuous infusion of endotoxin.

text: Investigating the systemic inflammatory response in patients with critical illness such as sepsis, trauma and burns is complicated due to uncertainties about the onset, duration and severity of the insult. Therefore, in vivo models of inflammation are essential to study the pathophysiology and to evaluate immunomodulatory therapies. Intravenous bolus administration of endotoxin to healthy volunteers is a well-established model of a short-lived systemic inflammatory response, characterized by increased plasma cytokine levels, flu-like symptoms and fever. In contrast, patients suffering from systemic inflammation are often exposed to inflammatory stimuli for an extended period of time. Therefore, continuous infusion of endotoxin may better reflect the kinetics of the inflammatory response encountered in these patients. Herein, we characterize a novel model of systemic inflammation elicited by a bolus infusion of 1 ng/kg, followed by a 3hr continuous infusion of 1 ng/kg/h of endotoxin in healthy volunteers, and compared it with models of bolus administrations of 1 and 2 ng/kg of endotoxin. The novel model was well-tolerated and resulted in a more pronounced increase in plasma cytokine levels with different kinetics and more prolonged symptoms and fever compared with the bolus-only models. Therefore, the continuous endotoxin infusion model provides novel insights into kinetics of the inflammatory response during continuous inflammatory stimuli and accommodates a larger time window to evaluate immunomodulating therapies.


Electrical Impedance Tomography for Positive End-expiratory Pressure Titration in COVID-19 Related ARDS.


title: Antiviral agents derived from novel 1-adamantyl singlet nitrenes.

text: BACKGROUND Amantadine constitutes an interesting, diamond crystal lattice-shaped, antivirally active amine with an inhibitory effect on influenza A viruses causing common 'flu' in humans. Unfortunately, amantadine forfeited most of its therapeutic potential because of resistance development in recent influenza A virus isolates. The antiviral efficacy of amantadine congeners can be chemically modified, resulting in re-constitution, improvement and/or extension of antiviral activities mediated by amino-adamantyls. METHODS Newly synthesized compounds were evaluated towards HIV type-1 (HIV-1) replication in primary human lymphocytes. One N-phenacyl amantadine derivative was investigated for inhibiting the in vitro replication of respiratory viruses (influenza A viruses, influenza B virus, human parainfluenza virus type 3 and severe acute respiratory syndrome coronavirus). RESULTS Two ketone-stabilized 1-adamantyl singlet nitrenes were discovered serendipitously. To our best knowledge these are the first persistently stable nitrenes to be reported. Their structure was proved by determining the X-ray single crystal structure of one hydrolytic elaboration product. This salt adduct revealed an incommensurately modulated crystal structure, which was solved by extensive computational refinement. We could show that ketone-stabilized 1-adamantyl singlet nitrenes are versatile synthons for the synthesis of antiviral drug candidates. An amantadine-folate conjugate was inhibitory on HIV-1 replication in primary human lymphocytes, and one N-phenacyl amantadine derivative was inhibitory towards low pathogenic avian influenza A virus (H5N1) replication in vitro. CONCLUSIONS These results indicate that the aromatic-aliphatic ketone-stabilized 1-adamantyl singlet nitrenes, beyond being of fundamental interest in organic chemistry, represent versatile synthons for the synthesis of new amantadine-related potentially antiviral drugs.


title: Simultaneous thoraco-laparoscopic repair of giant hiatal hernias: an alternative approach.

text: Laparoscopic repair of giant hiatal hernias with intrathoracic displacement of organs is recommended to relieve troublesome symptoms in patients. During this procedure, incomplete excision of the hernia sac from the mediastinum and omission of creating a 'non-tension-free position' of the cardio-esophageal junction into the abdominal cavity are associated with hiatal hernia recurrence. Giant hiatal hernias therefore often require a thoracotomy or thoracoscopy, to free dense adhesions higher up the chest. These procedures may increase the risk of perioperative morbidity due to lengthy operating times. We developed an operation procedure for giant hiatal hernia repair containing all the benefits of minimal invasive surgery, with overview of both thoracic and abdominal herniated structures. Three patients with a giant hiatal hernia were treated by a simultaneous thoraco-laparoscopic approach, which proved to be technically feasible and safe. Simultaneous thoraco-laparoscopic hernia repair can be considered a reasonable treatment option in selected cases such as type IV hernias, hernia recurrence or traumatic diaphragmatic herniation.


title: Platycladus orientalis leaves: a systemic review on botany, phytochemistry and pharmacology.

text: Platycladus orientalis leaves (Cebaiye) have been used for thousands of years as traditional Chinese medicine (TCM). According to the theory of TCM, they are categorized as a blood-cooling and hematostatic herb. In clinical practice, they were usually prescribed with heat-clearing herbs to reinforce the efficacy of hemostasis. The review provides the up-to-date information from 1980 to present that is available on the botany, processing research, phytochemistry, pharmacology and toxicology of the leaves. The information is collected from scientific journals, books, theses and reports via library and electronic search (Google Scholar, Pubmed and CNKI). Through literature reports, we can find that the leaves show a wide spectrum of pharmacological activities, such as anti-inflammatory, antioxidant, antimicrobial, disinsection, anticancer, diuretic, hair growth-promoting, neuroprotective and antifibrotic activities. Diterpene and flavonoids would be active constituents in P. orientalis leaves. Many studies have provided evidence for various traditional uses. However, there is a great need for additional studies to elucidate the mechanism of blood-cooling and hematostatic activity of the leaves. Therefore, the present review on the botany, traditional uses, phytochemistry and toxicity has provided preliminary information for further studies of this herb.


title: Targeting cardiovascular inflammation: next steps in clinical translation.

text: Systemic vascular inflammation plays multiple maladaptive roles which contribute to the progression and destabilization of atherosclerotic cardiovascular disease (ASCVD). These roles include: (i) driving atheroprogression in the clinically stable phase of disease; (ii) inciting atheroma destabilization and precipitating acute coronary syndromes (ACS); and (iii) responding to cardiomyocyte necrosis in myocardial infarction (MI). Despite an evolving understanding of these biologic processes, successful clinical translation into effective therapies has proven challenging. Realizing the promise of targeting inflammation in the prevention and treatment of ASCVD will likely require more individualized approaches, as the degree of inflammation differs among cardiovascular patients. A large body of evidence has accumulated supporting the use of high-sensitivity C-reactive protein (hsCRP) as a clinical measure of inflammation. Appreciating the mechanistic diversity of ACS triggers and the kinetics of hsCRP in MI may resolve purported inconsistencies from prior observational studies. Future clinical trial designs incorporating hsCRP may hold promise to enable individualized approaches. The aim of this Clinical Review is to summarize the current understanding of how inflammation contributes to ASCVD progression, destabilization, and adverse clinical outcomes. We offer forward-looking perspective on what next steps may enable successful clinical translation into effective therapeutic approaches-enabling targeting the right patients with the right therapy at the right time-on the road to more individualized ASCVD care.


title: Medical Students' Perceptions and an Anatomy Teacher's Personal Experience Using an e-Learning Platform for Tutorials During the Covid-19 Crisis.

text: The Covid-19 crisis has caused devastation around the world, where face-to-face (F2F) teaching in universities has been abandoned and anatomy education courses shifted to the virtual mode (Evans et al., 2020; Ravi et al., 2020). In fact, e-learning platforms have become increasingly popular in teaching practices in tertiary institutions, in particular health professional education (Lewis et al., 2014), and mainly ascribed to observed learning benefits through verbal, visual, and auditory stimulations (Selim, 2007; Jelonek, 2015). E-learning is a way of teaching supported by digital technologies as underlined by the definition that e-learning is "the use of new multimedia technologies and the internet to improve the quality of learning by facilitating access to resources and services, as well as remote exchange and collaboration" (Alonso et al., 2005).


title: Pulmonary infectious complications after hematopoietic stem cell transplantation: a practical guide to clinicians.

text: PURPOSE OF REVIEW The current review highlights the most relevant articles on lung infections following hematopoietic stem cell transplantation (HCT) published over the last year. Between 30 and 50% of HCT recipients will develop pulmonary infiltrates. These pulmonary complications may be infectious (caused by virus, bacteria, fungi, or protozoa) or noninfectious (e.g., fluid overload, heart failure, transfusion reactions like transfusion associated lung injury and transfusion-associated circulatory overload, drug reactions, engraftment syndrome, idiopathic pneumonia syndrome, diffuse alveolar hemorrhage, cryptogenic organizing pneumonia, and bronchiolitis obliterans syndrome). RECENT FINDINGS New data on the yield of bronchoscopy and bronchoalveolar lavage (BAL), the prevalence and clinical manifestations of respiratory viruses and the usefulness of molecular techniques for diagnosis have been published. In addition, guidelines or meta-analyses on the management of neutropenic fever, serological diagnosis of fungal infections and diagnosis and management of Pneumocystis and aspergillosis have been published. SUMMARY Respiratory viruses are important pathogens after HCT. PCR in the BAL is becoming the diagnostic modality of choice for a variety of infections. The best approach for the empirical management of pulmonary infiltrates following HCT remains to be defined.


title: Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial.

text: Purpose The efficacy of neoadjuvant chemoradiotherapy (NCRT) plus surgery for locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. In this trial, we compared the survival and safety of NCRT plus surgery with surgery alone in patients with locally advanced ESCC. Patients and Methods From June 2007 to December 2014, 451 patients with potentially resectable thoracic ESCC, clinically staged as T1-4N1M0/T4N0M0, were randomly allocated to NCRT plus surgery (group CRT; n = 224) and surgery alone (group S; n = 227). In group CRT, patients received vinorelbine 25 mg/m2 intravenously (IV) on days 1 and 8 and cisplatin 75 mg/m2 IV day 1, or 25 mg/m2 IV on days 1 to 4 every 3 weeks for two cycles, with a total concurrent radiation dose of 40.0 Gy administered in 20 fractions of 2.0 Gy on 5 days per week. In both groups, patients underwent McKeown or Ivor Lewis esophagectomy. The primary end point was overall survival. Results The pathologic complete response rate was 43.2% in group CRT. Compared with group S, group CRT had a higher R0 resection rate (98.4% v 91.2%; P = .002), a better median overall survival (100.1 months v 66.5 months; hazard ratio, 0.71; 95% CI, 0.53 to 0.96; P = .025), and a prolonged disease-free survival (100.1 months v 41.7 months; hazard ratio, 0.58; 95% CI, 0.43 to 0.78; P < .001). Leukopenia (48.9%) and neutropenia (45.7%) were the most common grade 3 or 4 adverse events during chemoradiotherapy. Incidences of postoperative complications were similar between groups, with the exception of arrhythmia (group CRT: 13% v group S: 4.0%; P = .001). Peritreatment mortality was 2.2% in group CRT versus 0.4% in group S ( P = .212). Conclusion This trial shows that NCRT plus surgery improves survival over surgery alone among patients with locally advanced ESCC, with acceptable and manageable adverse events.


Clostridiodes difficile in COVID-19 Patients, Detroit, Michigan, USA, March-April 2020.


title: COVID-19 and Cities: from Urban Health strategies to the pandemic challenge. A Decalogue of Public Health opportunities.

text: BACKGROUND AND AIM OF THE WORK The ongoing pandemic of COVID-19, which nowadays has exceeded 2.5 million notified infections in the world and about 200,000 deaths, is a strong reminder that urbanization has changed the way that people and communities live, work, and interact, and it's necessary to make resilient the systems and local capacities to prevent the spread of infectious diseases. How we can re-design the concept of Public Health in relation to the built environment and the contemporary cities? METHODS According to the previous statements and scenario, aim of this paper is to integrate the Urban Health strategic objectives, focusing the possible responses, both immediate and medium-long term, to the current environmental, social, and economic aspects of the "period" of physical distancing. Results. Immediate Actions are 01. program the flexibility of city schedules; 02. plan a smart and sustainable mobility network; 03. define a neighborhood services' plan; 04. develop a digitization of the urban context, promoting the smart communities; 05. re-think the accessibility to the places of culture and tourism. Medium-long term Actions are 06. design the indoor flexibility of domestic living spaces; 07. re-think building typologies, fostering the presence of semi-private or collective spaces; 08. renovate the basic care services' network; 09. integrate the existing environmental emergency plans, with those related to the health emergencies; 10. improve stakeholders' awareness of the factors affecting Public Health in the cities. CONCLUSIONS The Decalogue of Public Health opportunities may provide a useful basis for Designers (Architects and Urban Planners), Policy Makers, Public Health experts and Local Health Agencies, in promoting actions and policies aimed to transform our cities in healthier and Salutogenic living environments. (www.actabiomedica.it).


title: EFFECTS OF LIVE-TRAPPING AND ISOFLURANE ANESTHESIA ON FREE-RANGING AMERICAN MARTENS (MARTES AMERICANA).

text: Seventy-two free-ranging American martens ( Martes americana ) in Michigan, US were immobilized using isoflurane from 2011 to 2015. In total, 129 anesthetic procedures were performed with no mortalities. Hypothermia and hyperthermia were the most common anesthetic complications, and the mean rectal temperatures were significantly higher during summer than in winter. Dental abnormalities were common; the majority of abnormal findings were broken or discolored teeth attributed to previous dental trauma and were not trap-induced. Blood (n=72) was analyzed from 53 martens for venous blood gas, lactate, hematocrit, and/or selected serum biochemistry analytes. Lactate concentration was measured by two different devices (VetScan i-STAT 1 and Lactate Plus) and compared for clinical agreement for 26 samples. Both methods for lactate measurement provided statistically similar results. Using domestic feline reference ranges, the acid-base status and relative arterial oxygen saturation of anesthetized martens in this study were normal as determined by blood pH and pulse oximetry, respectively. Serum biochemistry parameters, multiple environmental parameters, and marten-specific attributes were evaluated for their influence on lactate in American martens using linear regression and an information-theoretic approach with model averaging. Blood urea nitrogen was in all of the top models and was positively related to lactate (β=0.02, 95% confidence interval: 0.00-0.04). Initial body temperature, ambient temperature, and time from trap discovery until immobilization of martens were informative predictors for lactate level. Recommendations for the live-trapping and isoflurane anesthesia of free-ranging martens include using caution during warmer summer months, minimizing disturbance prior to induction, monitoring lactate in addition to vital rates, and being prepared to prevent or treat both hypothermia and hyperthermia during any time of year.


title: Thermal ablation techniques: a curative treatment of bone metastases in selected patients?

text: INTRODUCTION Thermal ablation techniques (radiofrequency-ablation/cryotherapy) can be indicated with a curative intent. The success rate and prognostic factors for complete treatment were analysed. MATERIAL/METHODS The medical records of all patients who had undergone curatively intended thermal ablation of bone metastases between September 2001 and February 2012 were retrospectively analysed. The goal was to achieve complete treatment of all bone metastases in patients with oligometastatic disease (group 1) or only of bone metastases that could potentially lead to skeletal-related events in patients with a long life expectancy (group 2). We report the rate of complete treatment according to patient characteristics, primary tumour site, bone metastasis characteristics, radiofrequency ablation/cryotherapy and the treatment group (group 1/group 2). RESULTS Eighty-nine consecutive patients had undergone curatively intended thermal ablation of 122 bone metastases. The median follow-up was 22.8 months [IQR = 12.2-44.4]. In the intent-to-treat analysis, the 1-year complete treatment rate was 67% (95%CI: 50%-76%). In the multivariate analysis the favourable prognostic factors for complete local treatment were oligometastatic status (p = 0.02), metachronous (p = 0.004) and small-sized (p = 0.001) bone metastases, without cortical bone erosion (p = 0.01) or neurological structures in the vicinity (p = 0.002). CONCLUSION Thermal ablation should be included in the therapeutic arsenal for the cure of bone metastases. KEY POINTS • Thermal ablation techniques are currently performed to palliate pain caused by bone metastases. • In selected patients, thermal ablation can also be indicated with a curative intent. • Oligometastatic and/or metachronous diseases are good prognostic factors for local success. • Small-size (<2 cm) bone metastases and no cortical erosion are good prognostic factors.


title: A review of open source ventilators for COVID-19 and future pandemics.

text: Coronavirus Disease 2019 (COVID-19) threatens to overwhelm our medical infrastructure at the regional level causing spikes in mortality rates because of shortages of critical equipment, like ventilators. Fortunately, with the recent development and widespread deployment of small-scale manufacturing technologies like RepRap-class 3-D printers and open source microcontrollers, mass distributed manufacturing of ventilators has the potential to overcome medical supply shortages. In this study, after providing a background on ventilators, the academic literature is reviewed to find the existing and already openly-published, vetted designs for ventilators systems. These articles are analyzed to determine if the designs are open source both in spirit (license) as well as practical details (e.g. possessing accessible design source files, bill of materials, assembly instructions, wiring diagrams, firmware and software as well as operation and calibration instructions). Next, the existing Internet and gray literature are reviewed for open source ventilator projects and designs. The results of this review found that the tested and peer-reviewed systems lacked complete documentation and the open systems that were documented were either at the very early stages of design (sometimes without even a prototype) and were essentially only basically tested (if at all). With the considerably larger motivation of an ongoing pandemic, it is assumed these projects will garner greater attention and resources to make significant progress to reach a functional and easily-replicated system. There is a large amount of future work needed to move open source ventilators up to the level considered scientific-grade equipment, and even further work needed to reach medical-grade hardware. Future work is needed to achieve the potential of this approach by developing policies, updating regulations, and securing funding mechanisms for the development and testing of open source ventilators for both the current COVID19 pandemic as well as for future pandemics and for everyday use in low-resource settings.


title: Serotonin Receptor Agonist 5-Nonyloxytryptamine Alters the Kinetics of Reovirus Cell Entry.

text: UNLABELLED Mammalian orthoreoviruses (reoviruses) are nonenveloped double-stranded RNA viruses that infect most mammalian species, including humans. Reovirus binds to cell surface glycans, junctional adhesion molecule A (JAM-A), and the Nogo-1 receptor (depending on the cell type) and enters cells by receptor-mediated endocytosis. Within the endocytic compartment, reovirus undergoes stepwise disassembly, which is followed by release of the transcriptionally active viral core into the cytoplasm. In a small-molecule screen to identify host mediators of reovirus infection, we found that treatment of cells with 5-nonyloxytryptamine (5-NT), a prototype serotonin receptor agonist, diminished reovirus cytotoxicity. 5-NT also blocked reovirus infection. In contrast, treatment of cells with methiothepin mesylate, a serotonin antagonist, enhanced infection by reovirus. 5-NT did not alter cell surface expression of JAM-A or attachment of reovirus to cells. However, 5-NT altered the distribution of early endosomes with a concomitant impairment of reovirus transit to late endosomes and a delay in reovirus disassembly. Consistent with an inhibition of viral disassembly, 5-NT treatment did not alter infection by in vitro-generated infectious subvirion particles, which bind to JAM-A but bypass a requirement for proteolytic uncoating in endosomes to infect cells. We also found that treatment of cells with 5-NT decreased the infectivity of alphavirus chikungunya virus and coronavirus mouse hepatitis virus. These data suggest that serotonin receptor signaling influences cellular activities that regulate entry of diverse virus families and provides a new, potentially broad-spectrum target for antiviral drug development. IMPORTANCE Identification of well-characterized small molecules that modulate viral infection can accelerate development of antiviral therapeutics while also providing new tools to increase our understanding of the cellular processes that underlie virus-mediated cell injury. We conducted a small-molecule screen to identify compounds capable of inhibiting cytotoxicity caused by reovirus, a prototype double-stranded RNA virus. We found that 5-nonyloxytryptamine (5-NT) impairs reovirus infection by altering viral transport during cell entry. Remarkably, 5-NT also inhibits infection by an alphavirus and a coronavirus. The antiviral properties of 5-NT suggest that serotonin receptor signaling is an important regulator of infection by diverse virus families and illuminate a potential new drug target.


title: Prosthetic bypass for restenosis after endarterectomy or stenting of the carotid artery.

text: OBJECTIVE The objective of this study was to evaluate the results of prosthetic carotid bypass (PCB) with polytetrafluoroethylene (PTFE) grafts as an alternative to carotid endarterectomy (CEA) in treatment of restenosis after CEA or carotid artery stenting (CAS). METHODS From January 2000 to December 2014, 66 patients (57 men and 9 women; mean age, 71 years) presenting with recurrent carotid artery stenosis ≥70% (North American Symptomatic Carotid Endarterectomy Trial [NASCET] criteria) were enrolled in a prospective study in three centers. The study was approved by an Institutional Review Board. Informed consent was obtained from all patients. During the same period, a total of 4321 CEAs were completed in the three centers. In these 66 patients, the primary treatment of the initial carotid artery stenosis was CEA in 57 patients (86%) and CAS in nine patients (14%). The median delay between primary and redo revascularization was 32 months. Carotid restenosis was symptomatic in 38 patients (58%) with transient ischemic attack (n = 20) or stroke (n = 18). In this series, all patients received statins; 28 patients (42%) received dual antiplatelet therapy, and 38 patients (58%) received single antiplatelet therapy. All PCBs were performed under general anesthesia. No shunt was used in this series. Nasal intubation to improve distal control of the internal carotid artery was performed in 33 patients (50%), including those with intrastent restenosis. A PTFE graft of 6 or 7 mm in diameter was used in 6 and 60 patients, respectively. Distal anastomosis was end to end in 22 patients and end to side with a clip distal to the atherosclerotic lesions in 44 patients. Completion angiography was performed in all cases. The patients were discharged under statin and antiplatelet treatment. After discharge, all of the patients underwent clinical and Doppler ultrasound follow-up every 6 months. Median length of follow-up was 5 years. RESULTS No patient died, sustained a stroke, or presented with a cervical hematoma during the postoperative period. One transient facial nerve palsy and two transient recurrent nerve palsies occurred. Two late strokes in relation to two PCB occlusions occurred at 2 years and 4 years; no other graft stenosis or infection was observed. At 5 years, overall actuarial survival was 81% ± 7%, and the actuarial stroke-free rate was 93% ± 2%. There were no fatal strokes. CONCLUSIONS PCB with PTFE grafts is a safe and durable alternative to CEA in patients with carotid restenosis after CEA or CAS in situations in which CEA is deemed either hazardous or inadvisable.


title: Emerging viral diseases: confronting threats with new technologies.

text: Emerging viral diseases pose ongoing health threats, particularly in an era of globalization; however, new biomedical research technologies such as genome sequencing and structure-based vaccine and drug design have improved our ability to respond to viral threats.


title: Gastrointestinal failure in the ICU.

text: PURPOSE OF REVIEW The current review summarizes different aspects of assessment of gastrointestinal function and provides a practical approach to management of adult patients with gastrointestinal dysfunction in the ICU. RECENT FINDINGS Different ways to define gastrointestinal failure have been used in the past. Recently, the term 'acute gastrointestinal injury (AGI)' has been proposed to specifically describe gastrointestinal dysfunction as a part of multiple organ dysfunction syndrome. Possible pathophysiological mechanisms and different aspects in assessment of gastrointestinal function in adult ICU patients are presented. Currently, there is no single marker that could reliably describe gastrointestinal dysfunction. Therefore, monitoring and management is still based on complex assessment of different gastrointestinal symptoms and feeding intolerance, even though this approach includes a large amount of subjectivity. The possible role of biomarkers (citrulline, enterohormones, etc.) and additional parameters like intra-abdominal pressure remains to be clarified. SUMMARY Defining gastrointestinal failure remains challenging but broad consensus needs to be reached and disseminated soon to allow conduct of interventional studies. A systematic approach to management of gastrointestinal problems is recommended.


title: COVID-19: A Matter of Planetary, not Only National Health.

text: The COVID-19 pandemic highlights the multidimensional and inseparable connection between human health and environmental systems. COVID-19, similar to other emerging zoonotic diseases, has had a devastating impact on our planet. In this perspective, we argue that as humans continue to globalize and encroach on our surrounding natural systems, societies must adopt a "planetary health lens" to prepare and adapt to these emerging infectious diseases. This piece further explores other critical components of a planetary health approach to societal response, such as the seasonality of disease patterns, the impact of climate change on infectious disease, and the built environment, which can increase population vulnerabilities to pandemics. To address planetary health threats that cross international borders, such as COVID-19, societies must practice interdependence sovereignty and direct resources to organizations that facilitate shared global governance, and thus can enable us to adapt and ultimately build a more resilient world.


Call to action for the cardiovascular side of COVID-19.


title: Should enteral nutrition be started in the first week of critical illness?

text: PURPOSE OF REVIEW To review the mechanistic evidence for early enteral nutrition in critically ill patients within the first week of ICU admission. RECENT FINDINGS There is a lack of recent large randomized controlled trials showing clinically important outcome benefits related to early enteral nutrition. Most supporting studies are based on the animal models, and explore mechanisms of benefit related to gut immunity and oxidative stress. In addition, the impact of nutrient deprivation on the microbiome recently shown in a human trial is compelling. Large randomized controlled clinical trials have emerged in the last 2 years, however, comparing minimal enteral nutrition therapy and enteral nutrition versus parenteral nutrition. They call into question the low quality of clinical evidence and the widespread support for early enteral nutrition as a primary recommendation. As a result, the questions of whether or not enteral nutrition should be initiated in the first week versus standard of care or parenteral nutrition and how clinicians justify this recommendation are raised. SUMMARY Despite the wide range of quality in the current clinical outcomes evidence, early enteral nutrition within the first week of ICU admission, delivered to the appropriate patient, promotes gut-mediated immunity, lowers metabolic response to stress, maintains microbial diversity, and improves clinical outcomes versus standard of care or parenteral nutrition therapy.


Type 2 diabetes as a major risk factor for COVID-19 severity: a meta-analysis.


title: Hypertrophic adenoid is a major infection site of human bocavirus 1.

text: Human bocavirus 1 (HBoV1) is associated with respiratory infections worldwide, mainly in children. Similar to other parvoviruses, it is believed that HBoV1 can persist for long periods of time in humans, probably through maintaining concatemers of the virus single-stranded DNA genome in the nuclei of infected cells. Recently, HBoV-1 was detected in high rates in adenoid and palatine tonsils samples from patients with chronic adenotonsillar diseases, but nothing is known about the virus replication levels in those tissues. A 3-year prospective hospital-based study was conducted to detect and quantify HBoV1 DNA and mRNAs in samples of the adenoids (AD), palatine tonsils (PT), nasopharyngeal secretions (NPS), and peripheral blood (PB) from patients undergoing tonsillectomy for tonsillar hypertrophy or recurrent tonsillitis. HBoV1 was detected in 25.3% of the AD samples, while the rates of detection in the PT, NPS, and PB samples were 7.2%, 10.5%, and 1.7%, respectively. The viral loads were higher in AD samples, and 27.3% of the patients with HBoV had mRNA detectable in this tissue. High viral loads and detectable mRNA in the AD were associated with HBoV1 detection in the other sample sites. The adenoids are an important site of HBoV1 replication and persistence in children with tonsillar hypertrophy. The adenoids contain high HBoV1 loads and are frequently positive for HBoV mRNA, and this is associated with the detection of HBoV1 in secretions.


title: Influence of an impedance threshold valve on ventilation with supraglottic airway devices during cardiopulmonary resuscitation in a manikin.

text: AIM This study investigates if a n impedance threshold valve (ITV) might improve survival after cardiac arrest by increasing vital organ blood flow. The combination of ITV and supraglottic airway devices (SADs) has not been previously studied. This simulation study in a manikin aimed at analysing differences in ventilation with different SADs without and with an ITV. METHODS In a resuscitation manikin, cardiopulmonary resuscitation (CPR) was performed with interrupted (30:2) and continuous chest compressions using facemask, tracheal tube and 10 SADs (six different laryngeal masks, LT-D, LTS-D, Combitube((R)) and Easy Tube((R))). Ventilation was performed with and without an ITV. A total of 550 CPR cycles of 3-min duration were performed with chest compressions and ventilation standardised by use of a mechanical thumper device and an emergency ventilator. RESULTS Sufficient ventilation was possible with all devices tested. For ventilation during continuous chest compressions, there were significantly reduced tidal volumes for all airway devices with ITV use. By contrast, during interrupted chest compressions, no differences in tidal volumes with the ITV occurred in the majority of devices. The maximum reduction of tidal volume for any device was 7.8% of the volume reached without the ITV. CONCLUSION Based on the findings of this manikin trial, the use of an ITV for ventilation during CPR is possible in combination with supraglottic airway devices. Merging these two strategies warrants further clinical evaluation to judge the relevance of tidal volume reduction found in this trial.


title: Antibiotic therapy in elderly patients with acute exacerbation of chronic bronchitis.

text: Chronic bronchitis (CB) is a critical component of chronic obstructive pulmonary disease (COPD). Emphysema, reversible airway disease and bronchiectasis also contribute to COPD. Elderly patients are at increased risk for COPD and its components - emphysema, CB and bronchiectasis. In addition, older patients are at increased risk for resistant organisms during episodes of acute exacerbation of CB (AECB). These organisms include the more common bacteria implicated in AECB, such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae, and less common nonenteric, Gram-negative organisms such as Pseudomonas aeruginosa. Risk-stratified antibiotic treatment guidelines for AECB appear to be useful, although they have not been prospectively validated for the general CB population, and especially not in the elderly CB population. Many of the AECB treatment guidelines that are stratified based on risk factors have recommended that the oral respiratory fluoroquinolone antibiotics (gemifloxacin, levofloxacin and moxifloxacin) play a second-line but pivotal role, particularly in patients who have failed initial antibiotic treatment for simple CB or as initial treatment for complicated CB.


title: Cytokine responses in porcine respiratory coronavirus-infected pigs treated with corticosteroids as a model for severe acute respiratory syndrome.

text: The effectiveness and potential immunosuppressive effects of anti-inflammatory glucocorticoids in the lungs of severe acute respiratory syndrome (SARS) patients are undefined. We treated porcine respiratory coronavirus (PRCV)-infected conventional pigs with the corticosteroid dexamethasone (DEX) as a model for SARS. Innate and Th1 cytokines in bronchoalveolar lavage (BAL) and serum were elevated in PRCV-infected pigs compared to controls, but were decreased after DEX treatment in the PRCV-infected, DEX-treated (PRCV/DEX) pigs. Although decreased in BAL, Th2 cytokine levels were higher in serum after DEX treatment. Levels of the proinflammatory cytokine interleukin-6 in BAL and serum were decreased in PRCV/DEX pigs early but increased later compared to those in phosphate-buffered saline-treated, PRCV-infected pigs, corresponding to a similar trend for lung lesions. PRCV infection increased T-cell frequencies in BAL, but DEX treatment of PRCV-infected pigs reduced frequencies of T cells; interestingly B and SWC3a(+) (monocytes/macrophages/granulocytes) cell frequencies were increased. DEX reduced numbers of PRCV-stimulated Th1 gamma interferon-secreting cells in spleen, tracheobroncheolar lymph nodes, and blood. Our findings suggest that future glucocorticoid treatment of SARS patients should be reconsidered in the context of potential local immunosuppression of immune responses in lung and systemic Th1 cytokine-biased suppression.


title: Detection of human bocavirus from fecal samples of Hungarian children with acute gastroenteritis.

text: OBJECTIVES Human bocavirus (HBoV), a newly identified member of the Parvoviridae family is associated with respiratory tract and gastroenteric infections, mostly of young children. HBoV infections show a seasonal distribution with the peak in temperate areas being in the winter months. METHODS In our study, 35 throat swabs from children under 5 years with acute respiratory symptoms and 61 stool samples from children (<5 years) with acute gastroenteritis were collected in the period of October 2007-March 2008. A HBoV-specific polymerase chain reaction for detection of the virus, and sequence analysis for identification of virus variants were performed. RESULTS Although respiratory samples were all negative, 3.3% of stool samples (2/61) proved to be positive for HBoV. The virus carrier children were 3 and 5 years old. The ratio of HBoV positive samples is similar to international results (2.1-5.5%). CONCLUSIONS According to the result of sequence analysis of HBoV, the occurrence of genotype 2 of HBoV in Hungary is confirmed.


title: Intermittent pneumatic compression is a cost-effective method of orthopedic postsurgical venous thromboembolism prophylaxis.

text: Background Venous thromboembolism (VTE) is a major complication after lower-limb arthroplasty that increases costs and reduces patient's quality of life. Using anticoagulants for 10-35 days following arthroplasty is the standard prophylaxis, but its cost-effectiveness after accounting for bleeding complications remains unproven. Methods A comprehensive, clinical model of VTE was created using the incidences, clinical effects (including bleeding), and costs of VTE and prophylaxis from randomized controlled trials, meta-analyses, and large observational studies. Over 50 years, the total health care costs and clinical impact of three prophylaxis strategies, that are as follows, were compared: low-molecular-weight heparin (LMWH) alone, intermittent pneumatic compression (IPC), and IPC with LMWH (IPC+LMWH). The cost per VTE event that was avoided and cost per quality-adjusted life year (QALY) gained in both the US and Australian health care settings were calculated. Results For every 2,000 patients, the expected number of VTE and major bleeding events with LMWH were 151 and 6 in the USA and 160 and 46 in Australia, resulting in a mean of 11.3 and 9.1 QALYs per patient, respectively. IPC reduced the expected VTE events by 11 and 8 in the USA and Australia, respectively, compared to using LMWH alone. IPC reduced major bleeding events compared to LMWH, preventing 1 event in the US and 7 in Australia. IPC+LMWH only reduced VTE events. Neither intervention substantially impacted QALYs but both increased QALYs versus LMWH. IPC was cost-effective followed by IPC+LMWH. Conclusion IPC and IPC+LMWH are cost-effective versus LMWH after lower-limb arthroplasty in the USA and Australia. The choice between IPC and IPC+LMWH depends on expected bleeding risks.


Lidia Fonseca.


title: Peptide inhibitors of viral assembly: a novel route to broad-spectrum antivirals.

text: We investigated the potential of small peptide segments to function as broad-spectrum antiviral drug leads. We extracted the α-helical peptide segments that share common secondary-structure environments in the capsid protein-protein interfaces of three unrelated virus classes (PRD1-like, HK97-like, and BTV-like) that encompass different levels of pathogenicity to humans, animals, and plants. The potential for the binding of these peptides to the individual capsid proteins was then investigated using blind docking simulations. Most of the extracted α-helical peptides were found to interact favorably with one or more of the protein-protein interfaces within the capsid in all three classes of virus. Moreover, binding of these peptides to the interface regions was found to block one or more of the putative "hot spot" regions on the protein interface, thereby providing the potential to disrupt virus capsid assembly via competitive interaction with other capsid proteins. In particular, binding of the GDFNALSN peptide was found to block interface "hot spot" regions in most of the viruses, providing a potential lead for broad-spectrum antiviral drug therapy.


title: Upregulation of vascular endothelial growth factor (VEGF) in the retinas of transgenic mice overexpressing interleukin-1beta (IL-1beta) in the lens and mice undergoing retinal degeneration.

text: IL-1beta is a pro-inflammatory agent associated with angiogenesis and increased vascular permeability. To determine whether IL-1beta elicits these responses through an upregulation of VEGF, transgenic mice that overexpress IL-1beta in the lens were evaluated at various time points for the localization of VEGF, the location and extent of blood-retinal barrier (BRB) breakdown, and the origin and extent of neovascularization (NV). In homozygous and heterozygous transgenic mice, but not controls, intense VEGF immunoreactivity was scattered throughout the retina at postnatal days 5-7 (P5-7), just after the onset of inflammatory cell infiltration. VEGF staining in the retina remained widespread, but weak from P9-15. Beginning at P15, the intensity of VEGF immunoreactivity achieved a second peak, which it maintained through adulthood. This peak coincided with significant retinal destruction due to massive inflammation. The onset of BRB breakdown coincided with the upregulation of VEGF (P5-7) and widespread BRB breakdown was demonstrated from about P9. From P9-12, aggregates of cells positive for Griffonia simplicifolia isolectin-B4, a marker for vascular endothelial cells, formed on the retinal surface. These cells migrated into the retina at P12-15 with the more superficial cells forming a network of vessels and the deeper cells remaining in small clusters, thus demonstrating that NV occurs much later than BRB breakdown. Non-transgenic FVB/N mice, which undergo retinal degeneration beginning at about P9, also demonstrate the latter peak of VEGF upregulation and the accompanying BRB breakdown, but not the early upregulation. VEGF immunostaining of transgenic and non-transgenic mouse retinas was eliminated by pre-incubation of the VEGF antibodies with VEGF peptide. The data suggest that the early peak of VEGF upregulation (P5-7) and its accompanying BRB breakdown is due to IL-1beta expression and is likely to be dependent on inflammatory cell infiltration. The latter peak appears to be related to retinal destruction.


title: COVID-19 pandemic. What should PRM specialists do? A clinician's perspective.

text: BACKGROUND COVID-19 pandemic is rapidly spreading all over the world, creating the risk for an healthcare collapse. While acute care and intensive care units are the main pillars of the early response to the disease, rehabilitative medicine should play an important part in allowing COVID-19 survivors to reduce disability and optimize the function of acute hospital setting. AIM To share the experience and the international perspective of different rehabilitation centers, treating COVID-19 survivors. DESIGN Not applicable. POPULATION COVID-19 survivors. METHODS A group of Physical Medicine & Rehabilitation specialists from eleven different countries in Europe and North America have shared their clinical experience in dealing with COVID-19 survivors and how they have managed the re-organization of rehabilitation services. RESULTS In our experience the most important sequelae of severe and critical forms of COVID-19 are: 1) respiratory; 2) cognitive, central and peipheral nervous system; 3) deconditioning; 4) critical illness related myopathy and neuropathy; 5) dysphagia; 6) joint stiffness and pain; 7) psychiatric. CONCLUSIONS We analyze all these consequences and propose some practical treatment options, based on current evidence and clinical experience, as well as several suggestions for management of rehabilitation services and patients with suspected or confirmed infection by SARS-CoV-2. CLINICAL REHABILITATION IMPACT COVID-19 survivors have some specific rehabilitation needs. Experience from other centers may help colleagues in organizing their services and providing better care to their patients.


Nursing Home Social Work During COVID-19.


title: Differences in Clinical Characteristics of Covid-19 in Hispanic/Latino Population.

text: The Centers for Disease Control and Prevention (CDC) suggest several possible symptoms associated with coronavirus disease 2019 (COVID-19), including cough, shortness of breath (SOB), fever, chills, muscle pain, sore throats, new loss of taste or smell, nausea, vomiting, or diarrhea. ("Centers for Disease Control and Prevention. Symptoms of Coronavirus.,") The clinical characteristics from the study by Yu et al. published in Transboundary and Emerging Diseases and other Chinese studies were different from those we observe in the United States.


title: Blood pressure variability and leukoaraiosis in acute ischemic stroke.

text: Higher blood pressure, blood pressure variability, and leukoaraiosis are risk factors for early adverse events and poor functional outcome after ischemic stroke, but prior studies differed on whether leukoaraiosis was associated with blood pressure variability, including in ischemic stroke. In the Third International Stroke Trial, blood pressure was measured in the acute phase of ischemic stroke immediately prior to randomization, and at 0.5, 1, and 24 h after randomization. Masked neuroradiologists rated index infarct, leukoaraiosis, and atrophy on CT using validated methods. We characterized blood pressure variation by coefficient of variance and three other standard methods. We measured associations between blood pressure, blood pressure variability, and leukoaraiosis using generalized estimating equations, adjusting for age, and a number of covariates related to treatment and stroke type/severity. Among 3017 patients, mean (±SD) systolic and diastolic blood pressure decreased from 155(±24)/82(±15) mmHg pre-randomization to 146(±23)/78(±14) mmHg 24 h later ( P < 0.005). Mean within-subject coefficient of variance was 0.09 ± 0.05 for systolic and 0.11 ± 0.06 for diastolic blood pressure. Patients with most leukoaraiosis were older and had higher blood pressure than those with least ( P < 0.0001). Although statistically significant in simple pairwise comparisons, no measures of blood pressure variability were associated with leukoaraiosis when adjusting for confounding variables ( P > 0.05), e.g. age. Our results suggest that blood pressure variability is not a potential mechanism to explain the association between leukoaraiosis and poor outcome after acute stroke.