docid: fqujozki

title: Down-regulation of Myelin Gene Expression in Human Oligodendrocytes by Nitric Oxide: Implications for Demyelination in Multiple Sclerosis.

text: Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system (CNS) with unknown etiology. Several studies have shown that demyelination in MS is caused by proinflammatory mediators and nitric oxide (NO), which is released by perivascular infiltrates and/or activated glial cells. Both endogenous NO released by microglia and astrocytes; and NO generated from exogenous NO donors are known to induce oligodendrocytes death. However, the molecular mechanism of oligodendroglial death is poorly understood. Here we explore the role of NO in modulating the expression of myelin-specific genes that leads to oligodendroglial death. We investigated the effect of NO on the expression of myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), myelin oligodendrocyte glycoprotein (MOG), and proteolipid protein (PLP) in human primary oligodendrocytes. Combination of IFN-γ and bacterial lipopolysaccharide (LPS) or double stranded RNA in the form of polyIC induced the production of NO and decreased the expression of myelin gene in human fetal mixed glial cultures. Either a scavenger of NO (PTIO) or an inhibitor of inducible nitric oxide synthase (L-NIL) abrogated (LPS+IFN-γ)- and polyIC-mediated suppression of myelin genes in human mixed glial cells. The role of NO was further corroborated by the inhibition of myelin gene expression in purified human oligodendroglia by several NO donors including SNP, NOC-7, SIN-1, and SNAP. This study illustrates a novel biological role of NO in down-regulating the expression of myelin genes preceding the death of oligodendrocytes.


title: Keystone Perforator Island Flap for Postmastectomy Defect Resurfacing in Late-stage Breast Cancer Patients.

text: Late-stage breast cancer usually presents with locally advanced disease, with or without metastasis. The primary tumor is typically large with skin infiltration which affects quality of life. Surgical resection will result in an extensive defect which potentially deteriorates patients' quality of life if not properly managed. Keystone perforator island flap (KPIF) is a local advancement flap based on multiple perforators which can be a reliable reconstructive method to close an extensive defect. Methods This is a case series of 11 patients with symptomatic late-stage breast cancers indicated for neoadjuvant chemotherapy and subsequent mastectomy at Dharmais Cancer Hospital. The postmastectomy defect was closed with KPIF and clinical evaluation included flap success rate, percentage of flap necrotic area, and quality of life. There are modifications of the KPIF consisting of the more rounded shape and additional flap movement of the flap's distal lateral ends to the center resembling an "omega" conformation. Results Mean percentage of flap necrosis area was 9.7% and none of the patients needed additional surgery. The patients' quality of life evaluated using Patient-reported Aesthetic European Organization for Research and Treatment of Cancer (EORTC) Quality of Life, Questionnaire-Core 30-questions (QLQ-C30) and Quality of Life, Questionnaire-Breast Cancer-23-questions (QLQ-BR23) was fair, with sufficiently good scores for global health status and functional scale, and minimal symptomatology burden. The lowest score was for fatigue and financial difficulties parameters from QLQ-C30 and sexual functioning and future perspective from QLQ-BR23. Conclusion This is a preliminary study to show that a KPIF could be considered as a method for defect-resurfacing reconstruction after mastectomy.


Cause of systemic lupus erythematosus: a novel self-organized criticality theory of autoimmunity.


Working together to contain and manage COVID-19.


title: Protocols for Developing Novel Chikungunya Virus DNA Vaccines.

text: To date, there have been several million infections by the Chikungunya virus (CHIKV), a mosquito-transmitted emerging pathogen that is considered to be taxonomically an Old World RNA virus. Although original CHIKV outbreaks were restricted to India, East Asian countries, Northern Italy, and France, a recent sharp rise had been identified in 41 countries or territories in the Caribbean, Central America, South America, and North America. A total of 1,012,347 suspected and 22,579 laboratory-confirmed CHIKV cases have been reported from these areas, which signals an increasing risk to the US mainland. Unlike past epidemics that were usually associated with Ae. aegypti transmission, the Caribbean outbreak was associated with Ae. albopictus transmission as the principal mosquito vector. In addition, the substantial increase in the number of deaths during this epidemic, as well as incidence of neurologic disease, suggests that CHIKV may have become more virulent. Currently, there are no licensed vaccines or therapeutics available for CHIKV or its associated disease pathologies. Therefore, development of new vaccines and therapies that could confer immunity and/or treat clinical symptoms of CHIKV is greatly desired. This chapter describes the use of entirely cutting edge technologies/methodologies developed by our group for the development and evaluation of novel DNA vaccines against CHIKV.


title: Panax quinquefolium saponin Optimizes Energy Homeostasis by Modulating AMPK-Activated Metabolic Pathways in Hypoxia-Reperfusion Induced Cardiomyocytes.

text: OBJECTIVE To investigate the effects and underlying mechanisms of Panax quinquefolium saponin (PQS) on energy deficiency in hypoxia-reperfusion (H/R) induced cardiomyocytes. METHODS The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h. Cardiomyocytes recruited from neonatal rat ventricular myocytes (NRVMs) were randomly divided into control, H/R, H/R+compound C (C.C), H/R+PQS, and H/R+C. C+PQS groups. BrdU assay, lactase dehydrogenase (LDH) leakage and early apoptosis rate were evaluated to assess cell damages. Contents of high energy phosphate compounds were conducted to detect the energy production. Protein expression levels of adenosine monophosphate-activated protein kinase a (AMPKα), glucose transporter 4 (GLUT4), phosphate fructose kinase 2 (PFK2), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and acetyl CoA carboxylase 2 (ACC2) in the regulatory pathways were measured by Western blotting. Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters. RESULTS PQS (50 mg/L) pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability, up-regulation of LDH leakage, acceleration of early apoptosis, and reduction of energy production (P<0.05). Compared with the H/R group, up-regulated expression of AMPKα, GLUT4, PFK2, FAT/CD36 and ACC2 were observed, and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group (P<0.05). These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group (P<0.05). CONCLUSION PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders, by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.


title: Immunologic changes during Pandemic (H1N1) 2009, China.

text: We analyzed changes in immunologic values over time for 28 hospitalized patients with pandemic (H1N1) 2009. Levels of interleukin-6, interferon-y, and interleukin-10 increased 1 day after illness onset and then decreased to baseline levels. Levels of virus-specific antibody were undetectable 1 day after illness onset and peaked 36 days later.


title: The nsp1alpha and nsp1 papain-like autoproteinases are essential for porcine reproductive and respiratory syndrome virus RNA synthesis.

text: The two N-terminal cleavage products, nsp1alpha and nsp1beta, of the replicase polyproteins of porcine reproductive and respiratory syndrome virus (PRRSV) each contain a papain-like autoproteinase domain, which have been named PCPalpha and PCPbeta, respectively. To assess their role in the PRRSV life cycle, substitutions and deletions of the presumed catalytic cysteine and histidine residues of PCPalpha and PCPbeta were introduced into a PRRSV infectious cDNA clone. Mutations that inactivated PCPalpha activity completely blocked subgenomic mRNA synthesis, but did not affect genome replication. In contrast, mutants in which PCPbeta activity was blocked proved to be non-viable and no sign of viral RNA synthesis could be detected, indicating that the correct processing of the nsp1beta/nsp2 cleavage site is essential for PRRSV genome replication. In conclusion, the data presented here show that a productive PRRSV life cycle depends on the correct processing of both the nsp1alpha/nsp1beta and nsp1beta/nsp2 junctions.


title: Evaluation of prognostic indicators using validated canine insulinoma tissue microarrays.

text: Tissue microarray (TMA) technology allows analysis of multiple tumour samples simultaneously on a single slide. The aim of the present study was to develop and assess a TMA containing 32 primary canine insulinomas and 13 insulinoma metastases. The results of histopathological and immunohistochemical analyses of triplicate core biopsies were compared with those of individual tissue sections using weighted κ statistics. Inter-observer agreement of TMA immunohistochemistry scores were assessed for chromogranin A (CgA), insulin, growth hormone (GH), growth hormone receptor (GHR) and Ki67 index, as well as the prognostic utility of clinicopathological, histopathological and immunohistochemical criteria. There was substantial agreement of scores for histopathological parameters (κ = 0.64-0.70) and a substantial to near-perfect agreement for homogenous immunohistochemical parameters (κ = 0.69-1.00). Except for GH, which demonstrated heterogeneous staining, there was good to excellent inter-observer agreement for all other immunohistochemical staining scores (intra-class correlation coefficients: 0.70-1.00). On univariate analysis, the presence of nuclear atypia was significantly predictive of disease-free intervals (DFIs) for canine insulinoma, while tumour size, TNM stage, necrosis and Ki67 index were significant in terms of prognosis, with respect to both DFI and survival time. On multivariate analysis, tumour size and Ki67 index retained predictive power for survival time, as did tumour size for DFI. This study confirms the applicability of TMA technology for evaluation of canine insulinoma.


title: Endovascular treatment of distal middle cerebral artery aneurysms: Report of eight cases and literature review.

text: BACKGROUND Endovascular treatment is an alternative choice for the treatment of distal middle cerebral artery (dMCA) aneurysm, in addition to open surgery; but is still seldom considered. We performed this retrospective study to evaluate the outcome of dMCA in patients. METHODS During a period of 10 years, we were able to identify seven patients with a total of eight dMCA aneurysms that were treated endovascularly. They were five men and two women, with a mean age of 36.1 years. All of the aneurysms, including five infectious and three dissecting ones, were treated for the aneurysm and its parent artery's occlusion, using coils and/or glue. RESULTS The clinical follow-up (9-96 m, mean 36.8 m) showed that they all improved over baseline; except for one patient in whom a mild right hemiparesis remained, after the hematoma evacuation. Angiographic follow-up (7-24 m; mean: 14.6 m) showed that all of them were stable and without the need for recanalization. CONCLUSIONS Our data indicated that endovascular treatment is a safe and effective alternative for the treatment of dMCA aneurysms, and should be considered when treating these aneurysms.


title: Efficacy and toxicity of rectal cancer reirradiation using IMRT for patients who have received prior pelvic radiation therapy.

text: PURPOSE Locally recurrent rectal cancer may cause significant morbidity. Prior reports of rectal cancer reirradiation following local recurrence suggest treatment efficacy, with variable rates of late toxicity. Modern techniques including intensity modulated radiation therapy (IMRT) may improve the therapeutic index. We report outcomes for pelvic reirradiation as treatment for rectal cancer using IMRT. METHODS AND MATERIALS The records of 31 patients undergoing reirradiation for rectal cancer between 2004 and 2013 were reviewed. All patients underwent IMRT using an accelerated hyperfractionation (39 Gy in 1.5-Gy fractions delivered twice daily, n=15) or once-daily fractionation technique (median dose, 30.4 Gy; range, 27-40 Gy in 15-22 fractions; n = 16). The median cumulative dose was 77 Gy (range, 59-113), and the median interval from prior pelvic radiation therapy was 39.8 months (range, 10.1-307.6). Treatment intent was palliative in 20 patients and neoadjuvant or adjuvant in 11 patients. Surgery was generally reserved for patients with an isolated local recurrence. Concurrent chemotherapy was administered for 25/31 patients, most frequently capecitabine (n=11) or continuous infusion 5-fluorouracil (n=10). RESULTS Median follow-up was 11.3 months. The prescribed treatment was completed in 29/31 patients (93.5%). Among 18 patients with symptoms attributable to recurrent disease, successful palliation was achieved in 10/18 (55.6%). The rate of grade 2 and grade 3 acute toxicities was 32.3% and 3.2%, respectively. Local control rates at 1 and 2 years were 61.3% and 47.3%, respectively. Median overall survival was 21.9 months, and 1-year survival was 66.7% for patients who had surgical resection versus 58.7% for those who did not (P = .0802). CONCLUSIONS Rectal cancer reirradiation using IMRT is well-tolerated in the setting of prior pelvic radiation therapy. Given significant risk of local progression, further dose escalation may be warranted for patients with life expectancy exceeding 1 year.


Invited Discussion on: Subfascial Breast Augmentation with Crossed Fascial Sling, Under Tumescent Anesthesia with or Without Sedation and Lower Periareolar Access.


docid: nnlmvrpe

title: Removal of floating inferior vena cava thrombus with the AngioVac device.


title: Association of rhinovirus with exacerbations in young children affected by cystic fibrosis: Preliminary data.

text: Rhinovirus (RV) is a common respiratory viral infection linked to worsening of chronic respiratory diseases including cystic fibrosis (CF) and asthma. RV was tested by RT-PCR in samples (n = 465) collected from the upper (nasal swab, oropharyngeal suction, and sputum) and lower (bronchoalveolar washings) respiratory tract of 110 children with CF. Air samples (n = 52) collected from the operating theatres and outpatient clinics were tested for RV. RV was found in 43% of children <5 years suffering an exacerbation, and 12% of older children (5-17 years). RV particles were detected in the air of clinic rooms. Detection of RV is important in better understanding viral infections in patients with CF.


docid: ohxizwuh

title: Virulent Pseudorabies Virus Infection Induces a Specific and Lethal Systemic Inflammatory Response in Mice.

text: Pseudorabies virus (PRV) is an alphaherpesvirus that infects the peripheral nervous system (PNS). The natural host of PRV is the swine, but it can infect most mammals, including cattle, rodents, and dogs. In these nonnatural hosts, PRV always causes a severe acute and lethal neuropathy called the "mad itch," which is uncommon in swine. Thus far, the pathophysiological and immunological processes leading to the development of the neuropathic itch and the death of the animal are unclear. Using a footpad inoculation model, we established that mice inoculated with PRV-Becker (virulent strain) develop a severe pruritus in the foot and become moribund at 82 h postinoculation (hpi). We found necrosis and inflammation with a massive neutrophil infiltration only in the footpad and dorsal root ganglia (DRGs) by hematoxylin and eosin staining. PRV load was detected in the foot, PNS, and central nervous system tissues by quantitative reverse transcription-PCR. Infected mice had elevated plasma levels of proinflammatory cytokines (interleukin-6 [IL-6] and granulocyte colony-stimulating factor [G-CSF]) and chemokines (Gro-1 and monocyte chemoattractant protein 1). Significant IL-6 and G-CSF levels were detected in several tissues at 82 hpi. High plasma levels of C-reactive protein confirmed the acute inflammatory response to PRV-Becker infection. Moreover, mice inoculated with PRV-Bartha (attenuated, live vaccine strain) did not develop pruritus at 82 hpi. PRV-Bartha also replicated in the PNS, and the infection spread further in the brain than PRV-Becker. PRV-Bartha infection did not induce the specific and lethal systemic inflammatory response seen with PRV-Becker. Overall, we demonstrated the importance of inflammation in the clinical outcome of PRV infection in mice and provide new insights into the process of PRV-induced neuroinflammation.IMPORTANCE Pseudorabies virus (PRV) is an alphaherpesvirus related to human pathogens such as herpes simplex virus 1 and varicella-zoster virus (VZV). The natural host of PRV is the swine, but it can infect most mammals. In susceptible animals other than pigs, PRV infection always causes a characteristic lethal pruritus known as the "mad itch." The role of the immune response in the clinical outcome of PRV infection is still poorly understood. Here, we show that a systemic host inflammatory response is responsible for the severe pruritus and acute death of mice infected with virulent PRV-Becker but not mice infected with attenuated strain PRV-Bartha. In addition, we identified IL-6 and G-CSF as two main cytokines that play crucial roles in the regulation of this process. Our findings give new insights into neuroinflammatory diseases and strengthen further the similarities between VZV and PRV infections at the level of innate immunity.


title: Response: D-dimer triage for COVID-19.

text: We thank Dr Al-Najar and colleagues for their letter(1). Our Research Letter(2) from work completed early April 2020 is intended to rapidly communicate our finding of 93% 28-day survival (95% CI, 92-95%) for a normal D-dimer on admission and 98% survival (95% CI, 96-99%) for a normal D-dimer two days later. Because we reported on 749 patients, those estimates had high precision. We chose death as a hard relevant outcome, rather than severity. 100% of patients had gold-standard PCR RNA positivity.


title: Internalized Stigma among Bedouin and Jews with Mental Illness: Comparing Self-Esteem, Hope, and Quality of Life.

text: The aim of this study was to assess the differences in internalized-stigma, self-esteem, hope, and quality of life in individuals with mental illness from two diverse cultures (Bedouins and Jews) and to examine the relationships between self-stigma and self-esteem, hope, and quality of life in participants from both cultures. Two hundred participants with mental illness in Israel were assessed on the Internalized Stigma of Mental Illness (ISMI) scale. The Arab Bedouin participants tended to internalize stigma to a greater extent than the Jewish participants. Overall, there was a significant negative correlation between self-stigma, self-esteem, and hope and between alienation and quality of life in both groups although the correlation was stronger among the Arab Bedouin participants. By contrast, the associations between self-stigma and quality of life were only significant for two of the self-stigma dimensions (alienation and discrimination) among the Jewish participants. These results contribute to a better understanding of the role internalized stigma may play in the life of people with mental illness from diverse cultures. They may help design culturally appropriate intervention programs for people with mental illness.


title: Recent trends in airway management: we are not ready to give up fiberoptic endoscopy.

text: The purpose of this correspondence is to discuss recent findings related to current trends in airway management and to discuss the utilization rates of video laryngoscopes versus traditional techniques in USA, UK, and Canada. To highlight the increased use of video laryngoscopes in difficult airway situations, data on the use of alternative airway devices at our institution collected from 2008 to 2010 are presented alongside the results of previously published surveys collected from 2002 to 2013.


title: Imprints of pandemic lockdown on subsurface water quality in the coastal industrial city of Tuticorin, South India: A revival perspective.

text: Globally, the incidences of environmental improvements owing to seizing the anthropogenic activities during the lockdown have been reported through news articles and photographs, yet a formal scholarly study has been lacking to substantiate the imprints of lockdown. We hereby present the imprints of lockdown on water quality (both chemical and biological) parameters during the nationwide lockdown (COVID-19 epidemic) in India between 25th March to 30th May 2020. The present study describes the changes in chemical and biological water quality parameters based on twenty-two groundwater samples from the coastal industrial city of Tuticorin in Southern India, taken before (10 and 11th February 2020) and during the lockdown (19 and 20th April 2020) periods. The physico-chemical parameters compared are pH, total dissolved solids (TDS) and electrical conductivity (EC), nitrate (NO3), fluoride (F), chromium (Cr), iron (Fe), copper (Cu), zinc (Zn), cadmium (Cd), lead (Pb), arsenic (As), and selenium (Se), and the bacterial parameters are total coliforms, fecal coliforms, E. coli, and fecal streptococci. Among the metals, the significant reductions in Se (42%), As (51%), Fe (60%) and Pb (50%) were noticed probably owing to no or very less wastewater discharges from metal-based industries, seafood-based industries and thermal power plants during the lockdown. Reduction in NO3 (56%), total coliform (52%) and fecal coliforms (48%) indicated less organic sewage from the fishing industries. Contents of Cr, Cu, Zn and Cd, however, remained similar and fluoride did not show any change, probably as they were sourced from rock-water interactions. Similarly, we did not observe alterations in E. coli and fecal streptococci due to no significant change in domestic sewage production during the lockdown. The multivariate analyses aptly illustrated this and the principal component analyses helped to identify the sources that controlled water qualities of the lockdown compared to the pre-lockdown period. Our observation implies that groundwater is definitely under active interaction with surface waters and thus a quick revival could be observed following the seizing of anthropogenic activities.


title: Magnetic Resonance for Noninvasive Detection of Microcirculatory Disease Associated With Allograft Vasculopathy: Intracoronary Measurement Validation.

text: INTRODUCTION AND OBJECTIVES Cardiac allograft vasculopathy affects both epicardial and microcirculatory coronary compartments. Magnetic resonance perfusion imaging has been proposed as a useful tool to assess microcirculation mostly outside the heart transplantation setting. Instantaneous hyperemic diastolic flow velocity-pressure slope, an intracoronary physiology index, has demonstrated a better correlation with microcirculatory remodelling in cardiac allograft vasculopathy than other indices such as coronary flow velocity reserve. To investigate the potential of magnetic resonance perfusion imaging to detect the presence of microcirculatory remodeling in cardiac allograft vasculopathy, we compared magnetic resonance perfusion data with invasive intracoronary physiological indices to study microcirculation in a population of heart transplantation recipients with macrovascular nonobstructive disease demonstrated with intravascular ultrasound. METHODS We studied 8 heart transplantation recipients (mean age, 61 [12] years, 100% male) with epicardial allograft vasculopathy defined by intravascular ultrasound, nonsignificant coronary stenoses and negative visually-assessed wall-motion/perfusion dobutamine stress magnetic resonance. Quantitative stress and rest magnetic resonance perfusion data to build myocardial perfusion reserve index, noninvasively, and 4 invasive intracoronary physiological indices were determined. RESULTS Postprocessed data showed a mean (standard deviation) myocardial perfusion reserve index of 1.22 (0.27), while fractional flow reserve, coronary flow velocity reserve, hyperemic microvascular resistance and instantaneous hyperemic diastolic flow velocity-pressure slope were 0.98 (0.02), cm/s/mmHg, 2.34 (0.55) cm/s/mmHg, 2.00 (0.69) cm/s/mmHg and 0.91 (0.65) cm/s/mmHg, respectively. The myocardial perfusion reserve index correlated strongly only with the instantaneous hyperemic diastolic flow velocity-pressure slope (r=0.75; P=.033). CONCLUSIONS Myocardial perfusion reserve index derived from a comprehensive dobutamine stress magnetic resonance appears to be a reliable technique for noninvasive detection of microcirculatory coronary disease associated with cardiac allograft vasculopathy.


docid: isotemlf

title: Development of a magnetic capture hybridization real-time PCR assay for detection of tumorigenic Agrobacterium vitis in grapevines.

text: Agrobacterium vitis, the causal agent of grape crown gall, can have severe economic effects on grape production. The bacterium survives systemically in vines and, therefore, is disseminated in propagation material. We developed an assay for use in indexing programs that is efficient and sensitive for detecting A. vitis in grape tissue. Initially, real-time polymerase chain reaction (PCR) primers specific for diverse tumorigenic strains of A. vitis were developed using the virD2 gene sequence. To overcome the effects of PCR inhibitors present in plant tissue, DNA extraction methods that included magnetic capture hybridization (MCH), immunomagnetic separation (IMS), and extraction with the Mo Bio Powerfood kit were compared. The assays incorporating MCH or IMS followed by real-time PCR were 10,000-fold more sensitive than direct real-time PCR when tested using boiled bacterial cell suspensions, with detection thresholds of 10(1) CFU/ml compared with 10(5) CFU/ml. DNA extraction with the Powerfood DNA extraction kit was 10-fold more sensitive than direct real-time PCR, with a detection threshold of 10(4) CFU/ml. All three assays were able to detect A. vitis in healthy-appearing grapevine cuttings taken from infected vines.


title: Remote community-based public health nursing during a disaster: an ethnographic case study in Japan.

text: BACKGROUND The Great East Japan Earthquake that occurred on March 11, 2011 generated a tsunami that directly struck Japan. Public health nurses (PHNs) played important roles in this disaster response and community recovery. This research identified a PHN's experience in an affected area. METHODS An ethnographic case study approach was used to obtain in-depth information regarding the experiences of one PHN, using semi-structured interviews, participant observation, and statistical documents. RESULTS Six themes were identified and explored, including that the PHN undertook overwhelming responsibilities to protect the local residents, made several autonomous decisions, and had a strong sense of mission. These were based on the relationship-building that occurred with the local residents due to the geographical characteristics and her own preparations. CONCLUSIONS The findings encourage PHNs to participate in simulations of disasters in preparation for major catastrophes and establish good collaborative efforts with residents by being a part of the community.


title: Accelerated care versus standard care among patients with hip fracture: the HIP ATTACK pilot trial.

text: BACKGROUND A hip fracture causes bleeding, pain and immobility, and initiates inflammatory, hypercoagulable, catabolic and stress states. Accelerated surgery may improve outcomes by reducing the duration of these states and immobility. We undertook a pilot trial to determine the feasibility of a trial comparing accelerated care (i.e., rapid medical clearance and surgery) and standard care among patients with a hip fracture. METHODS Patients aged 45 years or older who, during weekday, daytime working hours, received a diagnosis of a hip fracture requiring surgery were randomly assigned to receive accelerated or standard care. Our feasibility outcomes included the proportion of eligible patients randomly assigned, completeness of follow-up and timelines of accelerated surgery. The main clinical outcome, assessed by data collectors and adjudicators who were unaware of study group allocations, was a major perioperative complication (i.e., a composite of death, preoperative myocardial infarction, myocardial injury after noncardiac surgery, pulmonary embolism, pneumonia, stroke, and life-threatening or major bleeding) within 30 days of randomization. RESULTS Of patients eligible for inclusion, 80% consented and were randomly assigned to groups (30 to accelerated care and 30 to standard care) at 2 centres in Canada and 1 centre in India. All patients completed 30-day follow-up. The median time from diagnosis to surgery was 6.0 hours in the accelerated care group and 24.2 hours in the standard care group (p < 0.001). A major perioperative complication occurred in 9 (30%) of the patients in the accelerated care group and 14 (47%) of the patients in the standard care group (hazard ratio 0.60, 95% confidence interval 0.26-1.39). INTERPRETATION These results show the feasibility of a trial comparing accelerated and standard care among patients with hip fracture and support a definitive trial. TRIAL REGISTRATION ClinicalTrials.gov, no. NCT01344343.


title: Well-Defined Star-Shaped Polyglutamates with Improved Pharmacokinetic Profiles As Excellent Candidates for Biomedical Applications.

text: There is a need to develop new and innovative polymer carriers to be used as drug delivery systems and/or imaging agents owing to the fact that there is no universal polymeric system that can be used in the treatment of all diseases. Additionally, limitations with existing systems, such as a lack of biodegradability and biocompatibility, inevitably lead to side effects and poor patient compliance. New polymer therapeutics based on amino acids are excellent candidates for drug delivery, as they do not suffer from these limitations. This article reports on a simple yet powerful methodology for the synthesis of 3-arm star-shaped polyglutamic acid with well-defined structures, precise molecular weights (MW), and low polydispersity (Đ = <1.3). These were synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCA) in a divergent method from novel multifunctional initiators. Herein, their exhaustive physicochemical characterization is presented. Furthermore, preliminary in vitro evaluation in selected cell models, and exhaustive in vivo biodistribution and pharmacokinetics, highlighted the advantages of these branched systems when compared with their linear counterparts in terms of cell uptake enhancement and prolonged plasma half-life.


title: Nephroprotective effects of enalapril after [177Lu]-DOTATATE therapy using serial renal scintigraphies in a murine model of radiation-induced nephropathy.

text: BACKGROUND Radiation-induced nephropathy is still dose limiting in radionuclide therapy of neuroendocrine tumors. We investigated the nephroprotective potential of the angiotensine converting enzyme inhibiting drug enalpril after [177Lu]-DOTATATE therapy in a murine model of radiation-induced nephropathy by renal scintigraphy. At first, the appropriate therapy activity to induce nephropathy was identified. Baseline scintigraphy (n = 12) entailed 12-min dynamic acquisitions after injection of 25 MBq [99mTc]-MAG3, which was followed by radionuclide therapy at four escalating activities of [177Lu]-DOTATATE: group (Gp) 1: 10 MBq; Gp 2: 20 MBq; Gp 3: 40 MBq; Gp 4: 65 MBq. Follow-up [99mTc]-MAG3 scintigraphy was carried out at days 9, 23, 44, and 65. The treatment activity for the intervention arm was selected on the basis of histological examination and declining renal function. In the second part, daily administration by gavage of 10 mg/kg/d enalapril or water (control group) was initiated on the day of radionuclide therapy. Follow-up scintigraphy was carried out at days 9, 23, 44, 65, and 86. We also created a non-therapy control group to detect therapy-independent changes of renal function over time. For all scintigraphies, mean renogram curves were analyzed and the "fractional uptake rate" (FUR; %I.D./min ± SEM) of the tracer by the kidneys was calculated as an index of renal clearance. RESULTS At day 65 of follow-up, no significant change in the FUR relative to baseline (11.0 ± 0.3) was evident in radionuclide therapy groups 1 (11.2 ± 0.5) and 2 (10.1 ± 0.6), but FUR was significantly reduced in groups 3 (8.93 ± 0.6, p < 0.05) and 4 (6.0 ± 0.8, p < 0.01); we chose 40 MBq [177Lu]-DOTATATE (Gp 3) for the intervention study. Here, at the last day of follow-up (day 86), FUR was unaltered in enalapril-treated mice (11.8 ± 0.5) relative to the baseline group (12.4 ± 0.3) and non-therapy group (11.9 ± 0.8), whereas FUR in the control group had undergone a significant decline (9.3 ± 0.5; p < 0.01). Histological examination revealed prevention of kidney damage by enalapril treatment. CONCLUSIONS Treatment with enalapril is effective for nephroprotection during radionuclide therapy with [177Lu]-DOTATATE in mice. Although these results are only limitedly transferable to human studies, enalapril might serve as a promising drug in the mitigation of nephropathy following treatment with [177Lu]-DOTATATE.


Covid-19: GPs call for appraisals and CQC inspections to be suspended.


docid: eltwyvmp

title: Percutaneous radiofrequency lung ablation combined with transbronchial saline injection: an experimental study in swine.

text: To evaluate the efficacy of radiofrequency lung ablation with transbronchial saline injection. The bilateral lungs of eight living swine were used. A 13-gauge bone biopsy needle was inserted percutaneously into the lung, and 1 ml of muscle paste was injected to create a tumor mimic. In total, 21 nodules were ablated. In the saline injection group (group A), radiofrequency ablation (RFA) was performed for 11 nodules after transbronchial saline injection under balloon occlusion with a 2-cm active single internally cooled electrode. In the control group (group B), conventional RFA was performed for 10 nodules as a control. The infused saline liquid showed a wedge-shaped and homogeneous distribution surrounding a tumor mimic. All 21 RFAs were successfully completed. The total ablation time was significantly longer (13.4 +/- 2.8 min vs. 8.9 +/- 3.5 min; P = 0.0061) and the tissue impedance was significantly lower in group A compared with group B (73.1 +/- 8.8 Omega vs. 100.6 +/- 16.6 Omega; P = 0.0002). The temperature of the ablated area was not significantly different (69.4 +/- 9.1 degrees C vs. 66.0 +/- 7.9 degrees C; P = 0.4038). There was no significant difference of tumor mimic volume (769 +/- 343 mm(3) vs. 625 +/- 191 mm(3); P = 0.2783). The volume of the coagulated area was significantly larger in group A than in group B (3886 +/- 1247 mm(3) vs. 2375 +/- 1395 mm(3); P = 0.0221). Percutaneous radiofrequency lung ablation combined with transbronchial saline injection can create an extended area of ablation.


title: The New World arenavirus Tacaribe virus induces caspase-dependent apoptosis in infected cells.

text: The Arenaviridae is a diverse and growing family of viruses that already includes more than 25 distinct species. While some of these viruses have a significant impact on public health, others appear to be non-pathogenic. At present little is known about the host cell responses to infection with different arenaviruses, particularly those found in the New World; however, apoptosis is known to play an important role in controlling infection of many viruses. Here we show that infection with Tacaribe virus (TCRV), which is widely considered the prototype for non-pathogenic arenaviruses, leads to stronger induction of apoptosis than does infection with its human-pathogenic relative Junín virus. TCRV-induced apoptosis occurred in several cell types during late stages of infection and was shown to be caspase-dependent, involving the activation of caspases 3, 7, 8 and 9. Further, UV-inactivated TCRV did not induce apoptosis, indicating that the activation of this process is dependent on active viral replication/transcription. Interestingly, when apoptosis was inhibited, growth of TCRV was not enhanced, indicating that apoptosis does not have a direct negative effect on TCRV infection in vitro. Taken together, our data identify and characterize an important virus-host cell interaction of the prototypic, non-pathogenic arenavirus TCRV, which provides important insight into the growing field of arenavirus research aimed at better understanding the diversity in responses to different arenavirus infections and their functional consequences.


title: A relationship between acute respiratory illnesses and weather.

text: Weekly data from 7 years (2004-2010) of primary-care counts of acute respiratory illnesses (ARIs) and local weather readings were used to adjust a multivariate time-series vector error correction model with covariates (VECMX). Weather variables were included through a partial least squares index that consisted of weekly minimum temperature (coefficient = - 0·26), weekly median of relative humidity (coefficient = 0·22) and weekly accumulated rainfall (coefficient = 0·5). The VECMX long-term test reported significance for trend (0·01, P = 0·00) and weather index (1·69, P = 0·00). Short-term relationship was influenced by seasonality. The model accounted for 76% of the variability in the series (adj. R 2 = 0·76), and the co-integration diagnostics confirmed its appropriateness. The procedure is easily reproducible by researchers in all climates, can be used to identify relevant weather fluctuations affecting the incidence of ARIs, and could help clarify the influence of contact rates on the spread of these diseases.


docid: hzxndtji

title: Validity evidence for a new portable, lower-cost platform for the fundamentals of endoscopic surgery skills test.

text: BACKGROUND The fundamentals of endoscopic surgery (FES) examination measures the knowledge and skills required to perform safe flexible endoscopy. A potential limitation of the FES skills test is the size and cost of the simulator on which it was developed (GI Mentor II virtual reality endoscopy simulator; Simbionix LTD, Israel). A more compact and lower-cost alternative (GI Mentor Express) was developed to address this issue. The purpose of this study was to obtain evidence for the validity of scores obtained on the Express platform, so that it can be used for testing. STUDY DESIGN General surgery residents at various levels of training and practicing endoscopists at five institutions participated. Each completed the five FES tasks on both simulator platforms in random order, with 3-14 days between tests. Scores were calculated using the same standardized computer-generated algorithm and compared using Pearson's correlation coefficient. RESULTS There were 58 participants (mean age 32; 76% male) with a broad range of endoscopic experience. The mean (95% confidence interval) FES scores were 72 (67:77) on the GI Mentor II and 66 (60:71) on the Express. The correlation between scores on the two platforms was 0.86 (0.77:0.91; p < 0.0001). CONCLUSION There is a high correlation between FES manual skills scores measured on the original platform and the new Express, providing evidence to support the use of the GI Mentor Express for FES testing.


The Neglected Dimension of Global Security--A Framework for Countering Infectious-Disease Crises.


Meticulous surgical technique cannot be replaced by cholangiography.


title: A broadband acoustic stimulus is more likely than a pure tone to elicit a startle reflex and prepared movements.

text: A loud acoustic stimulus that elicits a startle reflex has long been used to study the neurophysiology of cortical and subcortical neural circuits. More recent investigations have shown that startle can act as an early trigger for prepared actions, suggesting a brainstem role in the preparation and initiation of actions. However, in order to attribute any startle-triggered voluntary responses to activation in subcortical structures it is necessary to measure a startle-related activity in these structures. The current study investigated the most effective stimulus for eliciting a detectible startle reflex. While more intense stimuli are more likely to elicit a startle reflex, the current study examined whether broadband noise is more likely than a pure tone to produce a startle at various intensities above 100 dB. Participants performed a button release reaction time task in response to either a 1 kHz tone or a broadband noise pulse with intensities ranging from 82 to 124 dB. Reaction time and EMG from the wrist extensors and the sternocleidomastoid (SCM) were measured. Results showed that startle-related SCM EMG was elicited more frequently by broadband noise compared to pure tones. The higher proportion of startle reflexes observed in SCM was associated with a higher incidence of the voluntary task being triggered early. A higher incidence of startle following broadband noise is attributed to the activation of a larger proportion of the basilar membrane; thus, a lower intensity broadband noise stimulus may be used to elicit startle reflex at a similar rate as a higher intensity pure tone.


title: Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial.

text: INTRODUCTION Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and/or low dose inotropic therapy. The mechanisms underlying this benefit remain uncertain. The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery. METHODS Randomised, controlled, single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery. For eight hours after surgery, intra-venous fluid therapy was guided by measurements of central venous pressure (CVP group), or stroke volume (SV group). In a third group stroke volume guided fluid therapy was combined with dopexamine (0.5 mcg/kg/min) (SV & DPX group). RESULTS 135 patients were recruited (n = 45 per group). In the SV & DPX group, increased global oxygen delivery was associated with improved sublingual (P < 0.05) and cutaneous microvascular flow (P < 0.005) (sublingual microscopy and laser Doppler flowmetry). Microvascular flow remained constant in the SV group but deteriorated in the CVP group (P < 0.05). Cutaneous tissue oxygen partial pressure (PtO2) (Clark electrode) improved only in the SV & DPX group (P < 0.001). There were no differences in serum inflammatory markers. There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group (CVP group ten patients (22%); pooled SV and SV & DPX groups seven patients (8%); P = 0.03) (post hoc analysis). CONCLUSIONS Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery, microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery. These observations may explain improved clinical outcomes associated with this treatment in previous trials. TRIAL REGISTRATION NUMBER ISRCTN 94850719.


title: SARS-CoV-2 infection in children in Parma.

text: not available.


title: A Clinical Study of Noninvasive Assessment of Lung Lesions in Patients with Coronavirus Disease-19 (COVID-19) by Bedside Ultrasound.

text: PURPOSE This study was conducted to explore the clinical value of noninvasive assessment of bedside ultrasound in the diagnosis of lung lesions of Coronavirus Disease-19. METHODS In this retrospective study, 30 patients with Coronavirus Disease-19 admitted to our hospital from January 18 to February 5, 2020, were selected as the research subjects. All cases were examined by lung ultrasound and CT. Lung lesions were reviewed by blinded observers, with imaging scores being used to analyze the ultrasound findings of lung lesions in patients with Coronavirus Disease-19 and with chest CT being used as the reference standard. The clinical value of ultrasound in the noninvasive assessment of lung lesions was evaluated. RESULTS Lung ultrasound signs in patients with Coronavirus Disease-19 were mainly manifested as interstitial pulmonary edema (90.0 %, 27/30) and pulmonary consolidations (20.0 %, 6/30). The lung lesions were mainly distributed in the subpleural and peripheral pulmonary zones. The lower lobe and the dorsal region had a greater tendency to be involved. There was moderate agreement (Kappa = 0.529) between the noninvasive assessment of bedside ultrasound for lung lesions in patients with Coronavirus Disease-19 and CT. The ultrasound scores to evaluate mild, moderate and severe lung lesions exhibited sensitivity of 68.8 % (11/16), 77.8 % (7/9), 100.0 % (2/2), specificity of 85.7 % (12/14), 76.2 % (16/21), 92.9 % (26/28), and diagnostic accuracy of 76.7 % (23/30), 76.7 % (23/30), 93.3 % (28/30), respectively. The follow-up dynamic ultrasound examination showed that the condition of all patients worsened gradually, with the ultrasound scores of lung lesions increasing to varying degrees. CONCLUSION Though the diagnostic efficacy of bedside ultrasound is relatively low for mild to moderate patients, it is high for severe patients. Bedside ultrasound has important clinical significance for noninvasive assessment and dynamic observation of lung lesions in patients with Coronavirus Disease-19, which is worth further consideration.


title: Modelling of the Sedative Effects of Propofol in Patients undergoing Spinal Anaesthesia: A Pharmacodynamic Analysis.

text: Sedation can increase patient comfort during spinal anaesthesia. Understanding the relationship between the propofol effect-site concentration (Ce) and patient sedation level could help clinicians achieve the desired sedation level with minimal side effects. We aimed to model the relationship between the propofol Ce and adequate and deep sedation and also incorporate covariates. Thirty patients scheduled for orthopaedic surgery received spinal anaesthesia with 0.5% bupivacaine. Propofol was administered via an effect-site target-controlled infusion device using the Schnider pharmacokinetic model. The pharmacodynamic models for both adequate sedation [Observer's Assessment of Alertness/Sedation (OAA/S) scores of 3-4] and deep sedation (OAA/S scores of 1-2) were developed using nonlinear mixed-effects modelling. Increments in the propofol Ce were associated with increased depths of sedation. In the basic model, the estimated population Ce50 values for adequate and deep sedation were 0.94 and 1.52 μg/ml, respectively. The inclusion of the patient's age and sensory block level for adequate sedation and of age for deep sedation as covariates significantly improved the basic model by decreasing the objective function's minimum value from 10696.72 to 10677.92 (p = 0.0003). The simulated Ce50 values for adequate sedation in 20-year-old patients with a T12 sensory level and in 80-year-old patients with a T4 level were 1.63 and 0.53 μg/ml, respectively. Both age and sensory block level should be considered for adequate sedation, and the propofol concentration should be reduced for elderly patients with a high spinal block to avoid unnecessarily deep levels of sedation.


More on Covid-19 in Immune-Mediated Inflammatory Diseases.


docid: ehfksgcy

title: Percutaneous Image-Guided Ablation in the Treatment of Osseous Metastases from Non-small Cell Lung Cancer.

text: INTRODUCTION Percutaneous image-guided ablation is an emerging minimally invasive therapy for patients with metastatic bone disease for whom radiation therapy is ineffective or contraindicated. The purpose of this study was to examine the safety and efficacy of percutaneous ablation in achieving pain palliation and local tumor control of osseous metastases from non-small cell lung cancer (NSCLC). METHODS A retrospective review was performed of 76 musculoskeletal metastases in 45 patients treated with percutaneous ablation. 63% (48/76) were treated with radiofrequency ablation (RFA), 35% (27/76) with cryoablation, and 1.3% (1/76) with microwave ablation (MWA). In 70% (53/76) of cases, associated cementoplasty was performed. Primary outcomes measured were pre- and post-procedure pain scores 4 weeks after treatment and local tumor control at 3-, 6-, and 12-month follow-up. RESULTS Mean age of the cohort was 63.6 ± 9.5 years. Median tumor diameter was 3.60 cm (range 1.0-10.0 cm). Mean and median pain scores before treatment were 7.5 ± 2.3 and 8.0, respectively. Post-procedure, patients reported significantly decreased pain scores at 4 weeks (mean, 3.7 ± 3.5; median, 3.0; p < 0.00001). Radiographic local tumor control rates were 83% (35/42) at 3 months, 77% (23/30) at 6 months, and 68% (17/25) at 12 months after treatment. The overall complication rate was 2.6% (2/76). CONCLUSION Percutaneous tumor ablation is a well-tolerated, minimally invasive procedure associated with improving pain palliation and achieving local tumor control of osseous metastases from NSCLC. LEVEL OF EVIDENCE Level 4, case series.


title: Ioflupane 123I (DAT scan) SPECT identifies dopamine receptor dysfunction early in the disease course in progressive apraxia of speech.

text: OBJECTIVE To describe 123I-FP-CIT (DAT scan) SPECT findings in progressive apraxia of speech (PAOS) patients and to compare those findings with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). BACKGROUND PAOS is a neurodegenerative syndrome in which patients present with apraxia of speech, a motor speech disorder affecting programming and planning of speech. Patients with PAOS predictably develop Parkinsonism. DAT scan is a neuroimaging tool that assesses the integrity of presynaptic dopamine transporters in striatum and is usually abnormal in PSP and CBS. METHODS As part of an NIH-funded grant, we performed a DAT scan on 17 PAOS patients early in the disease course. DaTQUANT software was used to quantify uptake in the left and right caudate and anterior/posterior putamen, with striatum to background ratios (SBRs). The PAOS cohort was compared to 15 PSP and 8 CBS patients. RESULTS Five PAOS patients (29%) showed abnormalities in at least one striatal region on DAT scan. When the five PAOS patients with abnormal DAT were compared to the PSP and CBS patients, the only difference observed was lower uptake in the posterior putamen in PSP (p = 0.03). There were no differences is putamen/caudate ratio or in symmetry of uptake, across all groups. There was also no difference in MDS-UPDRS-III scores between PAOS patients with and without abnormal DAT scans (p = 0.56). CONCLUSIONS Abnormal DAT scan is observed early in the disease course in approximately 30% of PAOS patients, with striatal abnormalities similar to those in PSP and CBS.


title: Notes From the Field: Vape Shop Business Operations Compliance in the Wake of COVID-19.

text: The novel 2019 Coronavirus Disease (COVID-19) pandemic has led to the closing of all but essential businesses in California. However, several nonessential businesses have remained open in Southern California despite the mandated "stay at home" order issued by the governor. As part of an ongoing vape shop project involving 88 participating shops, this study investigated the number of vape shops that remained open amidst the coronavirus outbreak and related mandates. Examination of shop social media websites and telephone calls to shops revealed that 61.4% (n = 54) have remained open, particularly within Korean/Asian and Hispanic/Latino ethnic locations (32 of the 54 shops). Importantly, walk-in service was much higher within Hispanic/Latino locations compared to African American, Korean/Asian, or non-Hispanic White neighborhoods (p = 0.03). It is not known if shops that stayed open were in direct violation of the order, didn't know all the details of the order, or found a loophole in the order and believed that they were an essential business. Better communication between the vape shop industry and public health officials during this pandemic is needed.


title: Robotic-assisted vesicovaginal fistula repair using an extravesical approach without interposition grafting.

text: BACKGROUND Post-hysterectomy vesicovaginal fistula (VVF) is rare. In addition to conventional abdominal and vaginal approaches, robotic-assisted VVF repairs have recently been described. We present a case of an extravesical, robotic-assisted VVF repair, without placement of an interposition graft performed in a Canadian teaching center. CASE A 51-year-old woman presented with urinary incontinence 5 days after laparoscopic hysterectomy. Computed tomography cystogram, cystoscopy, and methylene blue dye test, confirmed a VVF above the bladder trigone. The patient underwent a robotic-assisted VVF repair 3 months after presentation, without complication. An abdominal, extravesical approach was used. Operative time was 116 min and repeat CT cystogram showed no evidence of persistent. CONCLUSION We have demonstrated that a VVF repair, using a robotic-assisted, extravesical approach without interposition graft placement, can be safe, less invasive and have a successful outcome at 1 year of follow-up.


title: Predictive value of the respiratory exchange ratio for the occurrence of postoperative complications in laparoscopic surgery: a prospective and observational study.

text: Indirect measurement of the respiratory exchange ratio (RER) has been shown to predict the occurrence of postoperative complications after major open non-cardiac surgery. Our main objective was to demonstrate the ability of the RER, indirectly measured by the anaesthesia respirator, to predict the occurrence of postoperative complications following laparoscopic surgery. We performed an observational, prospective and monocentric study. Haemodynamic and respiratory parameters were collected at several timepoints to calculate the RER by a non-volumetric method: RER = (FetCO2-FiCO2)/(FiO2-FetO2). Fifty patients were prospectively included. Nine patients (18%) had at least one postoperative complication. The mean RER was significantly higher for the subgroup of patients with complications than the subgroup without (1.04 ± 0.27 vs 0.88 ± 0.13, p < 0.05). The RER could predict the occurrence of post-operative complications with an area under the ROC curve of 0.73 (95% CI 0.59-0.85, p = 0.021). The best cut off was 0.98, with a sensitivity of 56% and a specificity of 88%. One hour after insufflation, the FiO2-FetO2 difference was significantly lower and the RER was significantly higher in the complications subgroup than in the subgroup without complications (4.4/- 1.6% vs 5.8/- 1.2%, p = 0.001 and 0.95 [0.85-1.04] vs 0.83 [0.75-0.92], p = 0.04, respectively). The RER measured during laparoscopic surgery can predict the occurrence of postoperative complications.Trial registration The objectives and procedures of the study was registered at Clinicaltrials.gov (NCT03751579); date: November 23, 2018.


title: Complex thoracoscopic pulmonary resections for the treatment of lung cancer-a review.

text: Minimally invasive surgery is increasingly being used in cancer resections. Benefits attributed to minimally invasive surgery include improved functional and oncological outcomes. In keeping with this trend, thoracoscopic lung resections are gaining acceptance amongst thoracic oncologic surgeons. As surgeons become more comfortable with these approaches, more complex resections are being performed through these techniques. This review article summarizes the current state of the art with respect to complex thoracoscopic resections.


docid: hvmzxpeg

title: Angiotensin-converting enzyme 2 (ACE2) from raccoon dog can serve as an efficient receptor for the spike protein of severe acute respiratory syndrome coronavirus.

text: Raccoon dog is one of the suspected intermediate hosts of severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, the angiotensin-converting enzyme 2 (ACE2) gene of raccoon dog (rdACE2) was cloned and sequenced. The amino acid sequence of rdACE2 has identities of 99.3, 89.2, 83.9 and 80.4 % to ACE2 proteins from dog, masked palm civet (pcACE2), human (huACE2) and bat, respectively. There are six amino acid changes in rdACE2 compared with huACE2, and four changes compared with pcACE2, within the 18 residues of ACE2 known to make direct contact with the SARS-CoV S protein. A HeLa cell line stably expressing rdACE2 was established; Western blot analyses and an enzyme-activity assay indicated that the cell line expressed ACE2 at a similar level to two previously established cell lines that express ACE2 from human and masked palm civet, respectively. Human immunodeficiency virus-backboned pseudoviruses expressing spike proteins derived from human SARS-CoV or SARS-CoV-like viruses of masked palm civets and raccoon dogs were tested for their entry efficiency into these cell lines. The results showed that rdACE2 is a more efficient receptor for human SARS-CoV, but not for SARS-CoV-like viruses of masked palm civets and raccoon dogs, than huACE2 or pcACE2. This study provides useful data to elucidate the role of raccoon dog in SARS outbreaks.


title: Effects of intrauterine exposure to 2,3',4,4',5-pentachlorobiphenyl on the reproductive system and sperm epigenetic imprinting of male offspring.

text: Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3',4,4',5-pentachlorobiphenyl (PCB118) is one of the most important dioxin-like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant mice were exposed to 0, 20 and 100 μg/kg/day of PCB118 during the stage of fetal primordial germ cell migration. Compared with the control group, we found morphological alterations of the seminiferous tubules and a higher sperm deformity rate in the male offspring in the treatment groups. Furthermore, the methylation patterns in the treatment groups of the imprinted genes H19 and Gtl2 in the sperm were altered in the male offspring. We also characterized the disturbance of the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3a, Dnmt3b, Dnmt3l, and Uhrf1. The results indicated that intrauterine exposure to low doses of PCB118 could significantly damage the reproductive health of the male offspring. Therefore, attention should be paid to the adverse effects of PCB118 exposure during pregnancy on the reproductive system of male offspring.


title: Spectral representation of reduced protein models.

text: We consider a spectrum-like two-dimensional graphical representation of proteins based on a reduced protein model in which 20 amino acids are grouped into five classes. This particular grouping of amino acids was suggested by Riddle and co-workers in 1997. The graphical representation is based on depicting sequentially the amino acids on five horizontal lines at equal separations. One-letter codes, B, O, U, X and Y, to which numerical values 1 to 5 have been assigned, are suggested as labels for the fictional amino acids that represent all the amino acids within each group. The approach is illustrated on ND6 proteins of eight species having from 168 to 175 amino acids. While visual inspection of the novel spectral graphical representations of proteins may reveal local similarities and dissimilarities of protein sequences, arithmetic manipulations of spectra offer an elegant route to graphic visualization of the degree of similarity for selected pairs of proteins.


title: Tensile Comparison of Polydioxanone, Polyglyconate, and Barbed Glycolide-Trimethylene Carbonate Suture in Canine Cadaveric Tensor Fascia Lata.

text: OBJECTIVE To compare the mode of failure, load at yield, ultimate load to failure and stiffness of non-barbed polydioxanone, non-barbed polyglyconate and barbed glycolide-trimethylene carbonate (GTC) suture in canine cadaveric fascia. STUDY DESIGN Ex vivo biomechanical study. SAMPLE POPULATION 18 fascia lata specimens from 9 canine cadavers. METHODS 6 fascia lata specimens were sutured with polydioxanone, 6 with polyglyconate, and 6 with barbed GTC suture. Load at yield, stiffness, ultimate load to failure were measured using tensile strength testing. Statistical analysis was used to compare outcomes between suture materials. The mode of failure was recorded and described. RESULTS The load at yield and ultimate load to failure were significantly greater for polydioxanone than barbed GTC (P=.045 and P=.016, respectively). The load at yield and ultimate load to failure was not significantly different between polydioxanone and polyglyconate (P=.687 and P=.586, respectively). The load at yield and the ultimate load to failure was not significantly different between polyglyconate and barbed GTC (P=.194 and P=.109, respectively). Stiffness was not different between constructs (P=.103). Polydioxanone and polyglyconate failed by suture breakage and suture pullout. Barbed GTC failed by suture slippage and suture breakage. CONCLUSION Our results showed that under the conditions of this study, 4-0 monofilament polydioxanone had a greater load at yield and load to failure than similarly sized, barbed copolymer suture in the fascia lata. This finding may help direct suture choice for fascial closure.


title: Single shot ultrasound-guided thoracic paravertebral block for opioid-free radical mastectomy: a prospective observational study.

text: Background General anesthesia (GA) is the most commonly used anesthesiological technique for radical mastectomy operations and can be associated with loco-regional anesthesia techniques. The aim of our study, carried out on 51 patients, was to assess the effectiveness of thoracic paravertebral block (TPVB) associated with GA, or as a sole anesthesiological technique for postoperative pain control and for the reduction of intra and postoperative opioids consumption. Materials and methods Fifty-one patients with neoplastic breast disease and elected as candidates for radical mastectomy were included in the study. The primary outcomes for this study were intra and postoperative opioid consumption and postoperative pain intensity. In 37 patients, TPVB was associated with GA while in 14 patients it was used as the sole anesthesiological technique. Data are reported as mean with standard deviation median with interquartile range, number, and percentage, depending on the underlying distribution. Results We did not use intra or postoperative opioids for any patient and the Numeric Rate Scale, assessed at time 0, at the end of the surgery, and 2, 6, 12, and 24 hrs after surgery, was >3 in seven patients only. Conclusions This study aims to show how TPVB can be used to carry out radical mastectomy procedures so that intra and postoperative opioids use can be avoided. In our study, TPVB was used in total mastectomy procedures in association with GA or as the sole anesthesiological technique, without the intra and postoperative use of opioids and with a significant reduction of local anesthetic dosages compared to those reported in the existing literature.


title: Substrate-induced control of product formation by protein arginine methyltransferase 1.

text: Protein arginine methyltransferases (PRMTs) aid in the regulation of many biological processes. Accurate control of PRMT activity includes recognition of specific arginyl groups within targeted proteins and the generation of the correct level of methylation, none of which are fully understood. The predominant PRMT in vivo, PRMT1, has wide substrate specificity and is capable of both mono- and dimethylation, which can induce distinct biological outputs. What regulates the specific methylation pattern of PRMT1 in vivo is unclear. We report that PRMT1 methylates a multisite peptide substrate in a nonstochastic manner, with less C-terminal preference, consistent with the methylation patterns observed in vivo. With a single targeted arginine, PRMT1 catalyzed the dimethylation in a semiprocessive manner. The degree of processivity is regulated by substrate sequences. Our results identify a novel substrate-induced mechanism for modulating PRMT1 product specificity. Considering the numerous physiological PRMT1 substrates, as well as the distinct biological outputs of mono- and dimethylation products, such fine-tuned regulation would significantly contribute to the accurate product specificity of PRMT1 in vivo and the proper transmission of biochemical information.


title: Five-year survival following radiofrequency ablation of small, solitary, hepatic colorectal metastases.

text: PURPOSE Radiofrequency (RF) ablation is an increasingly accepted treatment for nonsurgical candidates with a limited number of colorectal hepatic metastases. RF ablation is most effective in tumors smaller than 4.0 cm. This report describes 5-year survival in patients with single tumors with a maximum diameter of 4 cm. MATERIALS AND METHODS Forty of 291 patients (14%; 24 men, 16 women; mean age, 67 years; age range, 34-86 y) with no or treated extrahepatic disease were identified who were not candidates for resection and who had a minimum follow-up of 6 months. Sixteen had undergone hepatic resection and two had undergone lung resection and lung ablation. Thirty-two (80%) received chemotherapy. Thirty-five were treated under general anesthesia and five under conscious sedation. Our standard ablation protocol used internally water-cooled electrodes introduced percutaneously with ultrasonography and computed tomography guidance and monitoring. Follow-up data were obtained from primary care physicians or oncologists. RESULTS Mean tumor diameter was 2.3 cm (range, 0.8-4.0 cm). There were two successfully treated systemic complications: a chest infection and an exacerbation of asthma. There were no local complications. Mean follow-up was 38 months (range, 6-132 months). The median survival duration and 1-, 3-, and 5-year survival rates were 59 months and 97%, 84%, 40%, respectively, after ablation; and 63 months, 100%, 88%, and 54%, respectively, from the diagnosis of liver metastases. History of liver resection did not impact survival. CONCLUSIONS RF ablation of solitary liver metastases 4 cm or smaller can be performed with minimal morbidity and results in excellent long-term survival, approaching that of surgical resection, even in patients who are not surgical candidates.


docid: dezzigmx

title: [Analysis of CT features of 15 Children with 2019 novel coronavirus infection].

text: Objective: To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV. They were admitted to the third people's Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed. Results: Among the 15 children, there were 5 males and 10 females, aged from 4 to 14 years old. Five of the 15 children were febrile and 10 were asymptomatic on first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammation lesions. Seven cases of small nodular ground glass opacities and 2 cases of speckled ground glass opacities were found. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. Other 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities. Conclusions: The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.


title: Neuroimaging of headaches associated with vascular disorders.

text: Headaches from vascular causes need to be differentiated from primary headaches because a misdiagnosis may lead to dire consequences for the patient. Neuroimaging is critical in identifying patients with vascular headaches and identifying the nature of the pathologic disorder causing these headaches. In addition, the imaging findings guide the physician regarding the optimal treatment modality for these lesions. This review summarizes the nuances of differentiating patients with secondary headaches related to vascular disease and discusses pertinent neuroimaging studies.


It is not the time for science fiction.


title: Surgical management of haemorrhoids: an Italian survey of over 32 000 patients over 17 years.

text: AIM The management of haemorrhoids has changed significantly in the last two decades as a result of new insights into their pathophysiology and the availability of new surgical devices. The aim of this survey was to evaluate changes in the management of haemorrhoids in Italy over the last 17 years. METHOD An electronic database which recorded details of management relating to the severity of haemorrhoids between 2000 and 2016 was obtained from 18 of 34 colorectal surgeons who were invited to participate. RESULTS A total of 32 458 patients were treated for haemorrhoids by 18 expert coloproctologists during a 17-year period. Patients were classified as Grade II (7542, 23.2%), Grade III(15 360, 47.3%) and Grade IV (9556, 29.4%). Grade II haemorrhoids were treated with rubber band ligation in over 90% of the cases, and patients with Grade IV had a Milligan-Morgan (MM) haemorrhoidectomy in over 90% of the cases. In Grade III, the use of stapled haemorrhoidopexy progressively decreased from 30% to 35% (between 2000 and 2007) to 5% of the cases. Meanwhile, commencing from 2006 the use of Doppler-guided haemorrhoid artery ligation (DGHAL) with mucopexy increased progressively from 6% to 24%. Over the years, the percentage of MM haemorrhoidectomy remained consistent at between 65% and 70% of the cases. CONCLUSION Relevant changes in the surgical choice of haemorrhoid treatment have occurred in Italy over the last 17 years. MM haemorrhoidectomy remains the most frequently performed procedure for Grade III haemorrhoids. Stapled haemorrhoidopexy has become much less popular in contrast to DGHAL with mucopexy which is being performed much more frequently.


title: Sleeve gastrectomy improves glucose homeostasis in Zucker diabetic fatty rats.

text: BACKGROUND Bariatric surgery improves glucose homeostasis, but the mechanism of action is poorly understood. The aim of this study was to assess the effect of sleeve gastrectomy (SG) on glucose homeostasis in two obese populations of rats. METHODS Two strains of rats [Zucker fatty (ZF) and Zucker diabetic fatty (ZDF)] were each divided into two groups: sham and SG. Food intake was measured daily, and weight was measured bi-weekly. Oral glucose tolerance testing (OGTT) was performed before and 45 days after surgery. RESULTS In both strains of rats, there was no statistical difference in food intake and weight gain between the sham and SG rodents before and after surgery. In ZF rats, there was no change in fasting glucose or OGTT area under the curve (AUC) before or 45 days after surgery. In the ZDF rodents, the mean preoperative fasting glucose and OGTT AUC was 204 ± 25 and 25,441 ± 2,648, respectively. At 45 days after surgery, mean fasting glucose significantly increased in the sham (sham = 529 ± 26, p = 0.0003) but not in the SG rodents (SG = 289 ± 46, p = 0.1113). In ZDF sham animals, OGTT at 45 days showed a higher AUC compared to before surgery (44,983 ± 6,338, p = 0.006), whereas in ZDF SG rodents, the increase in AUC glucose approached but did not reach statistical significance (35,553 ± 3,925, p = 0.06). CONCLUSIONS In ZF and ZDF rodents, SG did not influence food intake and weight evolution. In ZDF rodents, diabetes progressed in the sham group but not in the SG group.


title: Laparoscopic completion total gastrectomy for remnant gastric cancer following pancreaticoduodenectomy for bile duct cancer: a case report.

text: Laparoscopic completion total gastrectomy following pancreaticoduodenectomy (PD) has not been reported. A 73-year-old male who underwent PD 25 years ago for distal common bile duct cancer visited a surgical department for remnant gastric cancer. A previous reconstruction was performed with pancreaticojejunostomy (PJ), gastrojejunostomy and Braun anastomosis, i.e., jejunojejunostomy (JJ), between the afferent and efferent jejunal limb to prevent bile reflux into the remnant stomach. Adhesiolysis was initially performed to secure the surgical view. Lymph node dissections around the splenic artery, splenic hilum, celiac axis, left gastric artery, and common hepatic artery were performed. The PJ site was well visualized and safely preserved. Esophagojejunostomy was performed with an OrVil system. Specimen retrieval, Roux-limb preparation and JJ were performed through an extended umbilicus trocar site. A final pathologic examination revealed a 5.5-cm serosa-exposed tumor (T4a) without lymph node metastasis. The patient was discharged on postoperative day 7 without any complications.


title: Restoring gut physiology in short bowel patients: from bench to clinical application of autologous intestinal reconstructive procedures.

text: Introduction: Short bowel syndrome represents the leading aetiology that causes intestinal failure both in children and adults. Total parenteral nutrition support has dramatically improved the prognosis for these patients but, if related irreversible complications occur, the alternative is represented by surgery and/or transplantation. Areas covered: Autologous gastrointestinal reconstructive procedures are a feasible, alternative approach with good long-term outcome data in experienced surgical centres. Expert commentary: Ongoing innovative efforts have driven the surgical options for successful autologous reconstructive surgery: bowel elongation/tapering techniques (LILT,STEP and the new SILT) together with the "reversed bowel segment" procedure are now recognized procedures and all must be tailored to the individual patient needs to obtain the optimal result in terms of enteral autonomy. Background laboratory experimentation with new procedures e.g. options for bowel dilation techniques and distraction-induced enterogenesis, may provide additional management and treatment modalities.


title: Seeing beyond the gut: An unusual cause of massive hematemesis.

text: We report the clinical details, imaging findings, and management of a 74-year-old male who had recurrent episodes of massive hematemesis secondary to rupture of a cavernous internal carotid artery (ICA) aneurysm. Ruptured ICA aneurysms may present with epistaxis. However, intracranial aneurysmal rupture with hematemesis as the presenting complaint has not been described previously in the literature. In this case report we describe the pathophysiology of cerebral aneurysm as a cause of hematemesis and its management.


title: Altered white matter microarchitecture in the cingulum bundle in women with primary dysmenorrhea: A tract-based analysis study.

text: Primary dysmenorrhea (PD), as characterized by painful menstrual cramps without organic causes, is associated with central sensitization and brain function changes. Previous studies showed the integrated role of the default mode network (DMN) in the pain connectome and its key contribution on how an individual perceives and copes with pain disorders. Here, we aimed to investigate whether the cingulum bundle connecting hub regions of the DMN was disrupted in young women with PD. Diffusion tensor imaging was obtained in 41 PD patients and 41 matched healthy controls (HC) during their periovulatory phase. The production of prostaglandins (PGs) was obtained in PD patients during their pain-free and pain phases. As compared with HC, PD patients had similar scores of pain intensity, anxiety, and depression in their pain-free phase. However, altered white matter properties mainly located in the posterior section of the cingulum bundle were observed in PD. Besides PGs being related to menstrual pain, a close relationship was found between the white matter properties of the cingulum bundle during the pain-free phase and the severity of the menstrual pain in PD patients. Our study suggested that PD had trait changes of white matter integrities in the cingulum bundle that persisted beyond the time of menstruation. We inferred that altered anatomical connections may lead to less-flexible communication within the DMN, and/or between the DMN and other pain-related brain networks, which may result in the central susceptibility to develop chronic pain conditions in PD's later life. Hum Brain Mapp 38:4430-4443, 2017. © 2017 Wiley Periodicals, Inc.


title: Ultrasound imaging versus palpation method for diagnostic lumbar puncture in neonates and infants: a systematic review and meta-analysis.

text: Importance Lumbar puncture (LP) failure rates vary and can be as high as 65%. Ultrasound guidance could increase the success of performing LP. Objective To summarise the evidence on the use of ultrasound guidance versus palpation method for LP. Data sources We searched computerised databases and published indexes, registries and references identified from bibliographies of pertinent articles without any language restrictions to find studies that compared ultrasound guidance to palpation method for performing an LP. Study selection Studies were included if they were randomised or quasirandomised trials in neonates and infants that compared ultrasound guidance with palpation method for performing an LP. Data extraction and synthesis Standardised data collection tool was used for data extraction, and two reviewers independently assessed the quality of the studies. Main outcomes and measures The primary outcome was the risk of LP failure, while the risk of traumatic tap, needle redirections/reinsertions and procedure durations were secondary outcomes. Results Data from four studies and 308 participants is included in the analysis. Ultrasound imaging reduced the risk of LP failure, risk ratio of 0.58 (95% CI 0.15 to 2.28), but it was not statistically significant (p=0.44). Ultrasound imaging significantly reduced the risk of a traumatic tap risk ratio of 0.33 (95% CI 0.13 to 0.82) and p=0.02. The included studies had low to moderate quality; the studies differed based on mean age and with variability on outcome definition. Conclusions and relevance This meta-analysis suggests that ultrasound imaging has no effect in increasing lumbar success but is beneficial in reducing the risk of traumatic taps in neonates and infants. Trial registration number CRD42017055800.


title: Aligned nanofibrillar collagen scaffolds - Guiding lymphangiogenesis for treatment of acquired lymphedema.

text: Secondary lymphedema is a common disorder associated with acquired functional impairment of the lymphatic system. The goal of this study was to evaluate the therapeutic efficacy of aligned nanofibrillar collagen scaffolds (BioBridge) positioned across the area of lymphatic obstruction in guiding lymphatic regeneration. In a porcine model of acquired lymphedema, animals were treated with BioBridge scaffolds, alone or in conjunction with autologous lymph node transfer as a source of endogenous lymphatic growth factor. They were compared with a surgical control group and a second control group in which the implanted BioBridge was supplemented with exogenous vascular endothelial growth factor-C (VEGF-C). Three months after implantation, immunofluorescence staining of lymphatic vessels demonstrated a significant increase in lymphatic collectors within close proximity to the scaffolds. To quantify the functional impact of scaffold implantation, bioimpedance was used as an early indicator of extracellular fluid accumulation. In comparison to the levels prior to implantation, the bioimpedance ratio was significantly improved only in the experimental BioBridge recipients with or without lymph node transfer, suggesting restoration of functional lymphatic drainage. These results further correlated with quantifiable lymphatic collectors, as visualized by contrast-enhanced computed tomography. They demonstrate the therapeutic potential of BioBridge scaffolds in secondary lymphedema.


COVID-19 Awakens a New Focus on Surge Capacity Blood Glucose Testing and the Critical Role of Telehealth in Self-Management.


title: Cuffless Blood Pressure Monitoring from an Array of Wrist Bio-impedance Sensors using Subject-Specific Regression Models: Proof of Concept.

text: Continuous and beat-to-beat monitoring of blood pressure (BP), compared to office-based BP measurement, provides significant advantages in predicting future cardiovascular disease. Traditional BP measurement methods are based on a cuff, which is bulky, obtrusive and not applicable to continuous monitoring. Measurement of pulse transit time (PTT) is one of the prominent cuffless methods for continuous BP monitoring. PTT is the time taken by the pressure pulse to travel between two points in an arterial vessel which is correlated with the BP. In this paper, we present a new cuffless BP method using an array of wrist-worn bio-impedance sensors placed on the radial and the ulnar arteries of the wrist to monitor the arterial pressure pulse from the blood volume changes at each sensor site. BP was accurately estimated by using AdaBoost regression model based on selected arterial pressure pulse features such as transit time, amplitude and slope of the pressure pulse which are dependent on the cardiac activity and the vascular properties of the wrist arteries. A separate model was developed for each subject based on calibration data to capture the individual variations of BP parameters. In this pilot study, data was collected from 10 healthy participants with age ranges from 18 to 30 years after exercising using our custom low-noise bio-impedance sensing hardware. Post-exercise BP was accurately estimated with an average correlation coefficient and root mean square error (RMSE) of 0.77 and 2.6 mmHg for the diastolic BP and 0.86 and 3.4 mmHg for the systolic BP.


Good things come in threes (and sometimes fours): Update on renin-angiotensin-aldosterone system inhibitors and COVID-19.


title: Clinical effects of rhinovirus infections.

text: Rhinovirus is the major cause of common cold and frequently associates with acute wheezing, otitis media, sinusitis, and pneumonia. High prevalence of rhinovirus in hospitalized children and adults has been documented recently. We screened children > or =1 month of age, hospitalized for any infection, for the presence of rhinoviruses and recruited 24 families with > or =2 children for a 3-week follow-up study. Rhinovirus was detected in 46 (28%) of 163 hospitalizations by study children. Most rhinovirus-positive children (85%) had respiratory symptoms. During the follow-up, rhinoviruses were detected in virtually all children and in one-half of adults in families with a rhinovirus-positive index child, but commonly also in families with a rhinovirus-negative index child. Melting temperature and sequence analysis revealed the transmission routes of the viruses and showed that several virus types could circulate in the families simultaneously. Our studies corroborate the major contribution of rhinovirus to hospitalization of children, most often because of wheezing. Young children with respiratory symptoms are major spreaders of rhinovirus in family setting.


title: Why US Health Care Should Think Globally.

text: Why should health care systems in the United States engage with the world's poorest populations abroad while tremendous inequalities in health status and access are pervasive domestically? Traditionally, three arguments have bolstered global engagement: (1) a moral obligation to ensure opportunities to live, (2) a duty to protect against health threats, and (3) a desire to protect against economic downturns precipitated by health crises. We expand this conversation, arguing that US-based clinicians, organizational stewards, and researchers should engage with and learn from low-resource settings' systems and products that deliver high-quality, cost-effective, inclusive care in order to better respond to domestic inequities. Ultimately, connecting "local" and "global" efforts will benefit both populations and is not a sacrifice of one for the other.


How to prioritize urological surgeries during epidemics: Lessons learned from the Toronto SARS outbreak in 2003.


title: Laparoscopic adrenalectomy: Norwegian single-center experience of 242 procedures.

text: BACKGROUND The last 15 years have been characterized by a rapid expansion of minimally invasive surgery as treatment for adrenal diseases. During these years, both indications and surgical techniques have shown improvements. This study analyzed an 11-year single-center experience with laparoscopic adrenalectomy. MATERIALS AND METHODS Between January 1997 and April 2008, 242 laparoscopic adrenalectomies were performed in 220 patients at Rikshospitalet University Hospital. Of these, 192 patients were operated on for benign lesions, 23 for malignant lesions, and in 5 cases "en bloc" adrenalectomies were performed. Benign lesions included 136 hormonally active lesions (41 pheochromocytomas, 48 Conn adenomas, 25 Cushing adenomas, and 18 patients with Cushing's disease) and 56 with hormonally inactive lesions (among them, 47 nonfunctional adenomas). Malignant lesions included 16 adrenal metastases and 7 adrenocortical carcinomas. RESULTS All adrenalectomies were completed laparoscopically. The median time of unilatateral adrenalectomy was 85 (range, 35-325) minutes. The median blood loss was 0 (range, 0-1100) mL. There were 6 intraoperative and 7 postoperative minor complications. The number of complications did not differ between the types of adrenal pathology. Only 19% of the patients required opioids postoperatively. Per- and postoperative parameters were homogeneous among patients with different adrenal lesions. The patients with adrenocortical carcinoma had a distinctive intraoperative course with an evidently longer operative time and higher blood loss. The median postoperative hospital stay was 2 (range, 1-15) days. Hospital stay was the only postoperative parameter where a difference was found between patients with different adrenal lesions. The patients with carcinoma, pheochromocytoma, and Cushing's disease had the longest median postoperative stay, respectively, 5 (range, 2-6), 3 (range, 1-15), and 3 (range, 2-6) days. CONCLUSIONS Laparoscopic adrenalectomy is a safe, effective procedure providing improved fast and uncomplicated patient recovery independent of the type of adrenal lesion. Laparoscopic adrenalectomy can be easily introduced and may soon replace traditional open surgery in specialized centers.


title: Application of decision rules on diagnosis and prognosis of renal colic: a systematic review and meta-analysis.

text: Renal colic is a prevalent emergency department presentation resulting from urolithiasis. Clinical decision rules for the diagnosis of urolithiasis were developed to help clinicians with better judgment. In this systematic review, we assessed the performance of prediction rules on urolithiasis diagnosis and prognosis. MEDLINE, Embase, Web of Science, and Scopus were searched for studies on the performance of a clinical decision tool for diagnosis or prognosis of urolithiasis. Performance and accuracy of the rules were the key outcomes of interest. Databases were searched from inception to March 2019. Of the 4980 articles reviewed, 28 studies were included in the present analysis. Twenty-one studies were on urolithiasis diagnosis (including eight studies on STONE rule), and 10 studies reported urolithiasis outcomes. Studies were at low to moderate risk of bias. The pooling of data on STONE showed that the prevalence of urolithiasis in low, moderate, and high risk groups were: 12% (95% confidence interval 9%-15%), 53% (95% confidence interval 43%-62%), and 83% (95% confidence interval 75%-91%), respectively. In the high risk score group, prevalence of clinically important alternative diagnosis was 1% (95% confidence interval 0%-2%) and 11% (95% confidence interval 8%-13%) of patients needed intervention. STONE scoring system is useful in estimating the prevalence of urolithiasis but high heterogeneity among the studies makes it unsuitable for application. Other decision tools were poorly studied and cannot be recommended for clinical use.


title: Identification and characterization of novel porcine astroviruses (PAstVs) with high prevalence and frequent co-infection of individual pigs with multiple PAstV types.

text: Many astrovirus (AstV) species are associated with enteric disease, although extraintestinal manifestations in mammalian and avian hosts have also been described. In this study, the prevalence rates of porcine AstV types 1-5 (PAstV1-PAstV5) were investigated using faecal samples from 509 pigs of which 488 (95.9%) came from farms with a history of diarrhoea. All of the five known PAstV types were found to circulate in pigs in the USA, and co-infection of a single pig with two or more PAstV types was frequently observed. A high overall prevalence of 64.0% (326/509) of PAstV RNA-positive samples was detected, with 97.2% (317/326) of the PAstV RNA-positive pigs infected with PAstV4. Further genomic sequencing and characterization of the selected isolates revealed low sequence identities (49.2-89.0%) with known PAstV strains, indicating novel types or genotypes of PAstV2, PAstV4 and PAstV5. Some new features of the genomes of the PAstVs were also discovered. The first complete genome of a PAstV3 isolate was obtained and showed identities of 50.5-55.3% with mink AstV and the novel human AstVs compared with 38.4-42.7% with other PAstV types. Phylogenetic analysis revealed that PAstV1, PAstV2 and PAstV3 were more closely related to AstVs from humans and other animals than to each other, indicating past cross-species transmission and the zoonotic potential of these PAstVs.


title: Current role of ultrasound in the diagnosis of hepatocellular carcinoma.

text: Ultrasonography (US) is a major, sustainable hepatocellular carcinoma (HCC) surveillance method as it provides inexpensive, real-time, and noninvasive detection. Since US findings are based on pathological features, knowledge of pathological features is essential for delivering a correct US diagnosis. Recent advances in US equipment have made it possible to provide more information, such as malignancy potential and accurate localization diagnosis of HCC. Evaluation of malignancy potential is important to determine the treatment strategy, especially for small HCC. Diagnosis of blood flow dynamics using color Doppler and contrast-enhanced US is one of the most definitive approaches for evaluating HCC malignancy potential. Recently, a new Doppler microvascular imaging technique, superb microvascular imaging, which can detect Doppler signals generated by low-velocity blood flow, was developed. A fusion imaging system, another innovative US technology, has already become an indispensable technology over the last few years not only for US-guided radiofrequency ablation but also for the detection of small, invisible HCC. This article reviews the evidence on the use of ultrasound and contrast-enhanced ultrasound with Sonazoid for the practical management of HCC.


title: Complete thoracoscopic diaphragm plication using carbon dioxide insufflation: report of a case.

text: Diaphragm plication has become the accepted treatment for major respiratory impairment caused by diaphragmatic eventration and paralysis. Various open and minimally invasive plication techniques have been described and while video-assisted thoracoscopic diaphragm plication appears to be a safe and effective alternative to open surgery, the workspace is limited. We describe how we performed complete thoracoscopic diaphragm plication using carbon dioxide (CO2) insufflation for a patient with unilateral diaphragmatic eventration. Using CO2 insufflation seems to dramatically improve the workspace.


title: Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method.

text: Four human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) are associated with a range of respiratory outcomes, including bronchiolitis and pneumonia. Their epidemiologies and clinical characteristics are poorly described and are often reliant on case reports. To address these problems, we conducted a large-scale comprehensive screening for all four coronaviruses by analysis of 11,661 diagnostic respiratory samples collected in Edinburgh, United Kingdom, over 3 years between July 2006 and June 2009 using a novel four-way multiplex real-time reverse transcription-PCR (RT-PCR) assay. Coronaviruses were detected in 0.3 to 0.85% of samples in all age groups. Generally, coronaviruses displayed marked winter seasonality between the months of December and April and were not detected in summer months, which is comparable to the pattern seen with influenza viruses. HCoV-229E was the exception; detection was confined to the winter of 2008 and was sporadic in the following year. There were additional longer-term differences in detection frequencies between seasons, with HCoV-OC43 predominant in the first and third seasons and HCoV-HKU1 dominating in the second (see Results for definitions of seasons). A total of 11 to 41% of coronaviruses detected were in samples testing positive for other respiratory viruses, although clinical presentations of coronavirus monoinfections were comparable to those of viruses which have an established role in respiratory disease, such as respiratory syncytial virus, influenza virus, and parainfluenza viruses. The novel multiplex assay for real-time pan-coronavirus detection enhances respiratory virus diagnosis, overcomes potential diagnostic problems arising through seasonal variation in coronavirus frequency, and provides novel insights into the epidemiology and clinical implications of coronaviruses.


title: Resilience in a time of crisis.

text: An expert in resiliency psychology discusses stress and resilience in nursing today, including advice on bolstering resilience and recovery during the COVID-19 pandemic.


title: Structural basis of receptor recognition by SARS-CoV-2.

text: A novel SARS-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans1,2. A key to tackling this epidemic is to understand the virus's receptor recognition mechanism, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor - human ACE2 (hACE2)3,4. Here we determined the crystal structure of the SARS-CoV-2 receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex with hACE2. Compared with the SARS-CoV RBD, a hACE2-binding ridge in SARS-CoV-2 RBD takes a more compact conformation; moreover, several residue changes in SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD/hACE2 interface. These structural features of SARS-CoV-2 RBD enhance its hACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses hACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in hACE2 recognition shed light on potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies targeting receptor recognition by SARS-CoV-2.


docid: gbcmrkfr

title: Assessment of changes in energy metabolism parameters provoked by carbon tetrachloride in Wistar rats and the protective effect of white grape juice.

text: The objective of this study was to evaluate the effect of organic and conventional grape juices consumption on the behavior of rats and their neuroprotective effect on the activity of brain energy metabolism enzymes in different brain areas of adult rats on the experimental model of hepatic encephalopathy. Male Wistar rats (90-days-old) were treated once a day with conventional or organic white grape juice by gavage for 14 days (7 μL/g). On the 15th day the rats received carbon tetrachloride (CCl4) in a single dose of 3.0 mL/kg. Cerebral cortex, hippocampus and cerebellum were dissected to measure the activity of creatine kinase (CK) and pyruvate kinase (PK). No changes in feeding behavior were observed after the treatment with the grapes juices. However, there was an increase in grooming behavior in the open field test provoked by both juices. CCl4 inhibited CK activity in cerebral cortex and hippocampus of the rats and CCl4 also reduced PK activity in all brain structures studied. Furthermore, both white grape juices prevented the decrease in the activity of CK and PK. Therefore, we can suggest that organic and conventional white grape juices could restore the activity of enzymes with a central role in brain energy metabolism.


title: Easy slip-knot: a new simple tying technique for deep sutures.

text: BACKGROUND Knot-tying in the deep operative field is very complicated because of the narrow working space during endoscopic transsphenoidal surgery. We present a novel technique for tying deep knots called the "easy slip-knot," which was developed from a knot used to tie fishing lines. METHOD After threading the dura, an easy slip-knot is made outside the nostril. One end of the string is pulled, the knot then naturally slips, and should reach the operative field without needing a knot-pusher. FINDINGS This method is not complicated, is easily applied to the operative field by slipping the knot into position, and is able to tie sutures securely. CONCLUSIONS The easy slip-knot should be useful for endoscopic surgery.