title: Optimizing reperfusion in patients with STEMI: a critical evaluation of pharmacologic and non-pharmacologic strategies.

text: Among patients with ST-elevation myocardial infarction (STEMI), rapidly re-establishing normal coronary blood flow is of paramount importance. More than 25 % of hospitals in the USA do not have access to timely primary percutaneous coronary intervention, highlighting the need for clinicians to understand both pharmacologic and non-pharmacologic strategies for STEMI. This manuscript reviews the current state of the art in STEMI care, describing both pharmacologic and non-pharmacologic strategies for reperfusion.


title: Directed evolution of adeno-associated virus to an infectious respiratory virus.

text: Respiratory viruses evolve to maintain infectivity levels that permit spread yet prevent host and virus extinction, resulting in surprisingly low infection rates. Respiratory viruses harnessed as gene therapy vectors have illustrated this limitation. We used directed evolution in an organotypic human airway model to generate a highly infectious adeno-associated virus. This virus mediated gene transfer more than 100-fold better than parental strains and corrected the cystic fibrosis epithelial Cl(-) transport defect. Thus, under appropriate selective pressures, viruses can evolve to be more infectious than observed in nature, a finding that holds significant implications for designing vectors for gene therapy and for understanding emerging pathogens.


title: Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2.

text: Ebolavirus (Ebov), an enveloped virus of the family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates. The viral glycoprotein (GP) is solely responsible for virus-host membrane fusion, but how it does so remains elusive. Fusion occurs after virions reach an endosomal compartment where GP is proteolytically primed by cathepsins. Fusion by primed GP is governed by an internal fusion loop found in GP2, the fusion subunit. This fusion loop contains a stretch of hydrophobic residues, some of which have been shown to be critical for GP-mediated infection. Here we present liposome fusion data and NMR structures for a complete (54-residue) disulfide-bonded internal fusion loop (Ebov FL) in a membrane mimetic. The Ebov FL induced rapid fusion of liposomes of varying compositions at pH values at or below 5.5. Consistently, circular dichroism experiments indicated that the α-helical content of the Ebov FL in the presence of either lipid-mimetic micelles or small liposomes increases in samples exposed to pH ≤5.5. NMR structures in dodecylphosphocholine micelles at pH 7.0 and 5.5 revealed a conformational change from a relatively flat extended loop structure at pH 7.0 to a structure with an ∼90° bend at pH 5.5. Induction of the bend at low pH reorients and compacts the hydrophobic patch at the tip of the FL. We propose that these changes facilitate disruption of lipids at the site of virus-host cell membrane contact and, hence, initiate Ebov fusion.


title: Cyclovirus in nasopharyngeal aspirates of Chilean children with respiratory infections.

text: Some respiratory tract infections remain unexplained despite extensive testing for common pathogens. Nasopharyngeal aspirates (NPAs) from 120 Chilean infants from Santiago with acute lower respiratory tract infections were analysed by viral metagenomics, revealing the presence of nucleic acids from anelloviruses, adenovirus-associated virus and 12 known respiratory viral pathogens. A single sequence read showed translated protein similarity to cycloviruses. We used inverse PCR to amplify the complete circular ssDNA genome of a novel cyclovirus we named CyCV-ChileNPA1. Closely related variants were detected using PCR in the NPAs of three other affected children that also contained anelloviruses. This report increases the current knowledge of the genetic diversity of cycloviruses whose detection in multiple NPAs may reflect a tropism for human respiratory tissues.


title: Roles of Capsule Endoscopy and Single-Balloon Enteroscopy in Diagnosing Unexplained Gastrointestinal Bleeding.

text: BACKGROUND/AIMS The diagnostic algorithms used for selecting patients with obscure gastrointestinal bleeding (OGIB) for capsule endoscopy (CE) or balloon-assisted enteroscopy (BE) vary among facilities. We aimed to demonstrate the appropriate selection criteria of CE and single balloon-assisted enteroscopy (SBE) for patients with OGIB according to their conditions, by retrospectively comparing the diagnostic performances of CE and BE for detecting the source of the OGIB. METHODS We investigated 194 patients who underwent CE and/or BE. The rate of positive findings, details of the findings, accidental symptoms, and hemostasis methods were examined and analyzed. RESULTS CE and SBE were performed in 103 and 91 patients, respectively, and 26 patients underwent both examinations. The rate of positive findings was significantly higher with SBE (73.6%) than with CE (47.5%, p<0.01). The rate of positive findings was higher in overt bleeding cases than in occult bleeding cases for both BE and SBE. Among the overt bleeding cases, the rate was significantly higher in ongoing bleeding cases than in previous bleeding cases. CONCLUSIONS Both CE and SBE are useful to diagnose OGIB. For overt bleeding cases and ongoing bleeding cases, SBE may be more appropriate than CE because endoscopic diagnosis and treatment can be completed simultaneously.


docid: tjuekbgw

title: Inclusion Body Fusion of Human Parainfluenza Virus Type 3 Regulated by Acetylated α-Tubulin Enhances Viral Replication.

text: Viral inclusion bodies (IBs), or replication factories, are unique structures generated by viral proteins together with some cellular proteins as a platform for efficient viral replication, but little is known about the mechanism underlying IB formation and fusion. Our previous study demonstrated that the interaction between the nucleoprotein (N) and phosphoprotein (P) of human parainfluenza virus type 3 (HPIV3), an enveloped virus with great medical impact, can form IBs. In this study, we found that small IBs can fuse with each other to form large IBs that enhance viral replication. Furthermore, we found that acetylated α-tubulin interacts with the N-P complex and colocalizes with IBs of HPIV3 but does not interact with the N-P complex of human respiratory syncytial virus or vesicular stomatitis virus and does not colocalize with IBs of human respiratory syncytial virus. Most importantly, enhancement of α-tubulin acetylation using the pharmacological inhibitor trichostatin A (TSA), RNA interference (RNAi) knockdown of the deacetylase enzymes histone deacetylase 6 (HDAC6) and sirtuin 2 (SIRT2), or expression of α-tubulin acetyltransferase 1 (α-TAT1) resulted in the fusion of small IBs into large IBs and effective viral replication. In contrast, suppression of acetylation of α-tubulin by overexpressing HDAC6 and SIRT2 profoundly inhibited the fusion of small IBs and viral replication. Our findings offer previously unidentified mechanistic insights into the regulation of viral IB fusion by acetylated α-tubulin, which is critical for viral replication. IMPORTANCE Inclusion bodies (IBs) are unique structures generated by viral proteins and some cellular proteins as a platform for efficient viral replication. Human parainfluenza virus type 3 (HPIV3) is a nonsegmented single-stranded RNA virus that mainly causes lower respiratory tract disease in infants and young children. However, no vaccines or antiviral drugs for HPIV3 are available. Therefore, understanding virus-host interactions and developing new antiviral strategies are increasingly important. Acetylation on lysine (K) 40 of α-tubulin is an evolutionarily conserved modification and plays an important role in many cellular processes, but its role in viral IB dynamics has not been fully explored. To our knowledge, our findings are the first to show that acetylated α-tubulin enhances viral replication by regulating HPIV3 IB fusion.


title: Characteristics and Outcomes of Middle East Respiratory Syndrome Coronavirus Patients Admitted to an Intensive Care Unit in Jeddah, Saudi Arabia.

text: BACKGROUND An increasing number of patients are being infected with Middle East respiratory syndrome coronavirus (MERS-CoV) since the first case was identified in September 2012. We report the characteristics and outcomes of MERS-CoV-confirmed patients who developed critical illness requiring admission to an intensive care unit (ICU). METHODS We conducted a prospective cohort study of all MERS-CoV-confirmed cases who were admitted to our ICU from March 20, 2014, till June 1, 2014. Presenting symptoms, comorbid conditions, and details of their ICU stay were recorded. RESULTS Eight patients were admitted to the ICU with MERS-CoV infection. All had signs of respiratory distress with 7 requiring mechanical ventilation. Three patients were health care workers. In all, 6 patients had comorbid conditions and 5 patients developed multiorgan system failure (MOSF). In all, 5 patients expired, 2 were discharged alive, and 1 remained intubated at the end of the study period. CONCLUSIONS Middle East respiratory syndrome coronavirus carries a high mortality rate in patients who require ICU admission, with a significant number of patients developing MOSF. Further investigation is needed to determine optimal management guidelines for these patients.


docid: nmqhtaib

title: Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome.

text: PURPOSE Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV). METHODS A total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (Phigh) set at the last plateau airway pressure (Pplat), not to exceed 30 cmH2O) and low airway pressure ( Plow) set at 5 cmH2O; the release phase (Tlow) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10-14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; Pplat not exceeding 30 cmH2O; positive end-expiratory pressure (PEEP) guided by the PEEP-FiO2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, Pplat, respiratory system compliance, and patient outcomes. RESULTS Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8-22] vs. 2 (IQR 0-15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower Pplat, and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance). CONCLUSIONS Compared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased Pplat and reduced the duration of both mechanical ventilation and ICU stay.


title: Body composition after allogeneic haematopoietic cell transplantation/total body irradiation in children and young people: a restricted systematic review.

text: PURPOSE To collate evidence of changes in body composition following treatment of leukaemia in children, teenagers and young adults (CTYA, 0-24 years) with allogeneic haematopoietic stem cell transplant and total body irradiation (HSCT+TBI). METHODS Papers were identified by searching Medline and Google Scholar, reference lists/citations and contacting key authors, with no date or language restrictions. Inclusion criteria were as follows: leukaemia, HSCT+TBI, aged ≤ 24 years at HSCT and changes in body composition (total fat, central adiposity, adipose tissue function, muscle mass, muscle function). Quality was assessed using a brief Newcastle-Ottawa scale. RESULTS Of 900 papers, 20 were included: seven controlled, five uncontrolled studies and eight case reports. Study quality appeared good. There was little evidence of differences in total fat/weight for HSCT + TBI groups (compared to healthy controls/population norms/short stature controls). There was some evidence of significantly higher central adiposity and differences in adipose tissue function (compared to leukaemic/non-leukaemic controls). Muscle mass was significantly lower (compared to healthy/obese controls). Muscle function results were inconclusive but suggested impairment. Case reports confirmed a lipodystrophic phenotype. CONCLUSIONS Early remodelling of adipose tissue and loss of skeletal muscle are evident following HSCT + TBI for CTYA leukaemia, with extreme phenotype of overt lipodystrophy. There is some evidence for reduced muscle effectiveness. IMPLICATIONS FOR CANCER SURVIVORS Body composition changes in patients after HSCT + TBI are apparent by early adult life and link with the risk of excess cardiometabolic morbidity seen in adult survivors. Interventions to improve muscle and/or adipose function, perhaps utilizing nutritional manipulation and/or targeted activity, should be investigated.


title: Pharmacokinetics-Based Adjusted Versus Standard Dose of Ribavirin Does Not Improve Virologic Response Rates in Chronic Hepatitis C Genotype 4 Patients: A Randomized Controlled Trial.

text: Optimal doses of Ribavirin (RBV) for hepatitis C virus (HCV) treatment are not known. To assess the safety and efficacy of PegIFNalfa-2a in combination with an adjusted (ADJ) RBV dose based on early pharmacokinetics versus a fixed standard (STD) dose of RBV in chronic HCV genotype (GT) 4-naive patients in a randomized trial. One hundred eighty-one patients were randomized. The baseline variables were similar in both arms and females were 50.3% of the patients, 76.5% had minimal-moderate fibrosis (F0-2). Sustained virologic response (SVR) was achieved in 99 (54.7%) subjects. SVR was seen in 50/90 (55.6%) of ADJ dose of RBV and 49/91 (53.9%) of STD dose subjects. Prematurely withdrawal or discontinuation of treatment prematurely in the ADJ RBV arm occurred in 11/90 patients (12.2%) compared with 6/91 subjects (6.6%) in the STD arm (P = 0.214). Similarly, virologic relapse was seen in 14/90 (15.6%) patients of the ADJ arm and 12/91 (13.2%) of the STD arm. Anemia grade 3-4 was seen in 36.7% in ADJ versus 17.6% in STD arm (P = 0.003). Occurrence of rapid virologic response and absences of F4 fibrosis predicted SVR in a univariate analysis. However, age, gender, weight, presence of diabetes, baseline alanine aminotransferase, and vitamin D levels were not significantly different in patients achieving SVR. ADJ higher doses of RBV based on its early pharmacokinetics-based RBV do not improve SVR rates in HCV GT4 treated in combination with peg-IFN alpha-2-a versus STD therapy. Patients on ADJ higher doses of RBV experienced higher rates of anemia and require more erythropoietin without increasing SVR.


title: Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States.

text: Porcine epidemic diarrhea virus (PEDV) was detected in May 2013 for the first time in U.S. swine and has since caused significant economic loss. Obtaining a U.S. PEDV isolate that can grow efficiently in cell culture is critical for investigating pathogenesis and developing diagnostic assays and for vaccine development. An additional objective was to determine which gene(s) of PEDV is most suitable for studying the genetic relatedness of the virus. Here we describe two PEDV isolates (ISU13-19338E and ISU13-22038) successfully obtained from the small intestines of piglets from sow farms in Indiana and Iowa, respectively. The two isolates have been serially propagated in cell culture for over 30 passages and were characterized for the first 10 passages. Virus production in cell culture was confirmed by PEDV-specific real-time reverse-transcription PCR (RT-PCR), immunofluorescence assays, and electron microscopy. The infectious titers of the viruses during the first 10 passages ranged from 6 × 10(2) to 2 × 10(5) 50% tissue culture infective doses (TCID50)/ml. In addition, the full-length genome sequences of six viruses (ISU13-19338E homogenate, P3, and P9; ISU13-22038 homogenate, P3, and P9) were determined. Genetically, the two PEDV isolates were relatively stable during the first 10 passages in cell culture. Sequences were also compared to those of 4 additional U.S. PEDV strains and 23 non-U.S. strains. All U.S. PEDV strains were genetically closely related to each other (≥99.7% nucleotide identity) and were most genetically similar to Chinese strains reported in 2011 to 2012. Phylogenetic analyses using different genes of PEDV suggested that the full-length spike gene or the S1 portion is appropriate for sequencing to study the genetic relatedness of these viruses.


Cancer Treatment Adaptations in the COVID-19 Era.


title: Bats host diverse parvoviruses as possible origin of mammalian dependoparvoviruses and source for bat-swine interspecies transmission.

text: Compared to the enormous species diversity of bats, relatively few parvoviruses have been reported. We detected diverse and potentially novel parvoviruses from bats in Hong Kong and mainland China. Parvoviruses belonging to Amdoparvovirus, Bocaparvovirus and Dependoparvovirus were detected in alimentary, liver and spleen samples from 16 different chiropteran species of five families by PCR. Phylogenetic analysis of partial helicase sequences showed that they potentially belonged to 25 bocaparvovirus, three dependoparvovirus and one amdoparvovirus species. Nearly complete genome sequencing confirmed the existence of at least four novel bat bocaparvovirus species (Rp-BtBoV1 and Rp-BtBoV2 from Rhinolophus pusillus, Rs-BtBoV2 from Rhinolophus sinicus and Rol-BtBoV1 from Rousettus leschenaultii) and two novel bat dependoparvovirus species (Rp-BtAAV1 from Rhinolophus pusillus and Rs-BtAAV1 from Rhinolophus sinicus). Rs-BtBoV2 was closely related to Ungulate bocaparvovirus 5 with 93, 72.1 and 78.7 % amino acid identities in the NS1, NP1 and VP1/VP2 genes, respectively. The detection of bat bocaparvoviruses, including Rs-BtBoV2, closely related to porcine bocaparvoviruses, suggests recent interspecies transmission of bocaparvoviruses between bats and swine. Moreover, Rp-BtAAV1 and Rs-BtAAV1 were most closely related to human AAV1 with 48.7 and 57.5 % amino acid identities in the rep gene. The phylogenetic relationship between BtAAVs and other mammalian AAVs suggests bats as the ancestral origin of mammalian AAVs. Furthermore, parvoviruses of the same species were detected from multiple bat species or families, supporting the ability of bat parvoviruses to cross species barriers. The results extend our knowledge on the diversity of bat parvoviruses and the role of bats in parvovirus evolution and emergence in humans and animals.


title: Radiofrequency ablation plus drug-eluting beads transcatheter arterial chemoembolization for the treatment of single large hepatocellular carcinoma.

text: BACKGROUND Our aim was to evaluate the effectiveness of the single-step combined therapy with radiofrequency ablation and drug-eluting beads transarterial chemoembolization in single hepatocellular carcinoma (HCC) larger than 3cm. Secondary aim was to compare the results with those obtained in a matched population treated with drug-eluting beads transarterial chemoembolization alone. METHODS 40 consecutive cirrhotic patients with single HCC were prospectively enrolled and treated. Twenty-three patients had tumours between 3 and 5cm (Group A), and 17 larger than 5cm (Group B). Twenty cirrhotic patients with single HCC treated only with chemoembolization formed the control group. RESULTS Complete response at 1 month was achieved in 32/40 tumours (80%). During follow-up, complete response was maintained in 25 patients (25/40, 62.5%), and this rate was higher in Group A (69.6% vs 53%, p=0.008). The group treated with combined therapy showed a significantly lower 2-year recurrence (48.1% vs 78.2%, p<0.001) and significantly higher survival (91.1% vs 60.6%, p=0.004) than the group treated with chemoembolization alone. CONCLUSIONS Balloon-occluded-radiofrequency ablation plus drug-eluting beads transarterial chemoembolization is an effective treatment of HCC larger than 3cm not amenable to surgical resection, providing better results than transarterial chemoembolization alone. The best results are achieved in tumours up to 5cm.


Changes in SARS-CoV-2 Positivity Rate in Outpatients in Seattle and Washington State, March 1-April 16, 2020.


Response to letter to the editor.


docid: cdyvevon

title: Cocirculation of Influenza C Viruses with Distinct Internal Genome Constellations in Iwate Prefecture, Japan, in 2016.


Choosing Wisely in the COVID-19 Era: Preventing Harm to Healthcare Workers.


title: Conformational changes in the capsid of a calicivirus upon interaction with its functional receptor.

text: Nonenveloped viral capsids are metastable structures that undergo conformational changes during virus entry that lead to interactions of the capsid or capsid fragments with the cell membrane. For members of the Caliciviridae, neither the nature of these structural changes in the capsid nor the factor(s) responsible for inducing these changes is known. Feline junctional adhesion molecule A (fJAM-A) mediates the attachment and infectious viral entry of feline calicivirus (FCV). Here, we show that the infectivity of some FCV isolates is neutralized following incubation with the soluble receptor at 37 degrees C. We used this property to select mutants resistant to preincubation with the soluble receptor. We isolated and sequenced 24 soluble receptor-resistant (srr) mutants and characterized the growth properties and receptor-binding activities of eight mutants. The location of the mutations within the capsid structure of FCV was mapped using a new 3.6-A structure of native FCV. The srr mutations mapped to the surface of the P2 domain were buried at the protruding domain dimer interface or were present in inaccessible regions of the capsid protein. Coupled with data showing that both the parental FCV and the srr mutants underwent increases in hydrophobicity upon incubation with the soluble receptor at 37 degrees C, these findings indicate that FCV likely undergoes conformational change upon interaction with its receptor. Changes in FCV capsid conformation following its interaction with fJAM-A may be important for subsequent interactions of the capsid with cellular membranes, membrane penetration, and genome delivery.


title: Acute subarachnoid hemorrhage in posterior condylar canal dural arteriovenous fistula: imaging features with endovascular management.

text: A 43-year-old man presented with acute subarachnoid hemorrhage. He was investigated and found to have a rare posterior condylar canal dural arteriovenous fistula (DAVF). DAVFs of the posterior condylar canal are rare. Venous drainage of the DAVF was through a long, tortuous, and aneurysmal bridging vein. We describe the clinical presentation, cross sectional imaging, angiographic features, and endovascular management of this patient. The patient was treated by transarterial embolization of the fistula through the ascending pharyngeal artery. This is the first report of an acutely bled posterior condylar canal DAVF treated by transarterial Onyx embolization with balloon protection in the vertebral artery. The patient recovered without any neurological deficit and had an excellent outcome. On 6 month follow-up angiogram, there was stable occlusion of the dural fistula.


The Importance of Proper Death Certification During the COVID-19 Pandemic.


title: Does robotic-assisted transabdominal preperitoneal (R-TAPP) hernia repair facilitate contralateral investigation and repair without compromising patient morbidity?

text: Inguinal hernia repair (IHR) is performed through either an open or minimally invasive approach (MIS). MIS allows for exploration and potential repair of an occult contralateral hernia. The aim of this study is to evaluate complications associated with intraoperative contralateral exploration and repair through robotic-assisted (da Vinci®) IHR. 652 robotic-assisted inguinal hernia procedures were uniformly and retrospectively collected from seven surgeons. Incidental contralateral findings were evaluated and populations with and without contralateral findings were compared in terms of demographics, operative characteristics and complications. This case series includes the earliest cases in each surgeon's robotic-assisted IHR experience. Seventy-one percent (71%) of patients presented with a unilateral hernia. Intraoperative/incidental contralateral ("occult") hernias were found in 12.3% of patients with a unilateral diagnosis. For patients with and without contralateral findings, there were no significant differences in demographics and baseline health characteristics. Perioperative morbidity was statistically similar between groups: intraoperative complications (0 vs 0.5%, p = 1.000), postoperative complications prior to discharge (0 vs 3.2%, p = 0.38) and from discharge through 30 days (5.3 vs 4.0%, p = 0.72), as well as readmissions and reoperations related to the repair within 30 days. Differences in setting of care, length of stay, rate of blood transfusions, concomitant procedures and conversions were nonsignificant. Mean operative time was longer in patients with a contralateral hernia by 19 min (p < 0.0001). Intraoperative contralateral exploration and subsequent repair during robotic-assisted IHR does not compromise perioperative patient morbidity. These study results support the increasing evidence for repair of contralateral, incidentally discovered inguinal hernias.Clinicaltrials.Gov ID number: NCT02684448.


title: Coexistence of Ovarian Granulose Cell Tumor, Congenital Adrenal Hyperplasia, and Triple Translocation: Is a Consequence or Coincidence?

text: PURPOSE Congenital adrenal hyperplasia (CAH) is rare autosomal recessive disease. CAH due to 21-hydroxylase deficiency accounts for 95% of cases. We aimed to share the first case of coexistence of simple virilizing-type congenital adrenal hyperplasia [I172N mutation in the CYP21A], triple translocation [t(9;11;12)], and ovarian granulose cell tumor. METHODS A 59-year-old female patient was presented to our clinic, complaining with abdominal pain and distension. Physical examination revealed palpable abdominal mass, virilism, ambiguous genitalia, clitoramegaly, and hyperpigmentation. Contrast-enhanced abdominal computed tomography showed a giant mass originating from the right tubo-ovarian structure. RESULTS The patient was operated in the light of the clinico-radiological features mentioned above. A giant mass weighing 3500 g was detected on the right tubo-ovarian structure during laparotomy, and mass was excised with right tubo-ovarian structure. Immunohistochemical examination revealed ovarian granulosa cell tumor. The high serum concentration of 17-OH progesterone was measured at baseline and after 250-μg bolus of synthetic ACTH. In genetic analysis, we screened for six-point mutations, large deletions, and non-common mutations using restriction fragment length polymorphism (RFLP) methods, PCR, and sequencing of CYP21 gene respectively. The patient was detected to be homozygous for the I172N mutation. In addition, 50% of the metaphases examined had triple translocation [t(9;11;12)]. CONCLUSION The coexistence of congenital adrenal hyperplasia, triple chromosomal translocations, and ovarian granulosa cell tumor has not been described previously. This coexistence may be a sign of a new syndrome.


title: Laparoscopic Single-Site Surgery in Pediatric Urology: Where Do We Stand Today?

text: Since the first description of the laparoendoscopic single-site surgery (LESS) in the pediatric urology population, various authors have shared their experiences and results. We aim to provide a review of current studies of LESS and share our experience with this modality. The current literature describes the use of LESS for most surgeries performed in the pediatric urology population with similar results to open and standard laparoscopic surgery. The authors have described their experiences with transabdominal and retroperitoneal nephrectomy, nephroureterectomy, pyeloplasty, orchidopexy, varicocelectomy, and renal cyst decortication. In our experience, LESS has taken a role for extirpative surgery since we use other modalities for upper tract reconstruction. The data available has validated LESS as safe and has demonstrated similar results to standard laparoscopic surgery and open surgery with better cosmetic results.


title: Stent fractures after superficial femoral artery stenting: risk factors and impact on patency.

text: PURPOSE To determine the risk factors and clinical impact of stent fractures after superficial femoral artery (SFA) stenting. METHODS From May 2009 to June 2012, 171 consecutive patients (mean age 74.5±7.8, years; 106 men) who presented with SFA stenosis or occlusion in 205 limbs underwent stent implantation in the SFA at a single center. Stent fractures were determined by radiography and classified into types I through V. Loss of patency was assessed by duplex ultrasonography (>2.4 peak systolic velocity ratio) or angiography (percent diameter stenosis >50%). RESULTS The 12- and 24-month primary patency rates were 49.8% and 43.4%, respectively. Stent fractures occurred in 12.5% and 26.8% per limb (6.6% and 19.4% per stent) at 12 and 24 months, respectively. Primary patency was numerically worse in the stent fracture group but not statistically different from the group without fractures at 2 years. Primary patency for different classes of stent fracture were 30.8% (type I), 50.0% (type II), and 31.3% (type III-V). Hyperlipidemia (p=0.001), TransAtlantic Inter-Society Consensus II classification (p=0.007), chronic total occlusion (CTO; p<0.001), proximal lesion location (p=0.008), lesion calcification (p=0.025), total stent length (p=0.005), stent diameter (p=0.001), and number of stents (p=0.001) were statistically significant predictors of stent fracture. Multivariate analysis showed that CTO (hazard ratio 0.173, 95% confidence interval 0.042 to 0.716, p=0.015) was an independent predictor of stent fracture. CONCLUSION Stent fractures occur more frequently in patients with CTOs after treatment of longer stented lesions. Although multivariate analysis showed that CTO was the only independent predictor regardless of stent length or number, the stent fracture rate was numerically higher in the severe calcification and proximal SFA lesion subgroups. Stent fracture did not appear to affect long-term patency rates, but this is yet to be confirmed with further follow-up.


title: A phase 2 study of lower-dose, indomethacin submicron particle capsules demonstrates early onset of acute pain relief.

text: OBJECTIVES Nonsteroidal anti-inflammatory drugs are efficacious for the treatment of acute and chronic pain; however, they have the potential for serious adverse events (AEs). The objective of this study was to evaluate the efficacy and safety of investigational, lower-dose, indomethacin submicron particle capsules compared with placebo in a study of patients with postsurgical pain. MATERIALS AND METHODS This phase 2, multicenter, randomized, double-blind, single-dose, and placebo-controlled study enrolled 203 patients (18 to 50 y old) following extraction of ≥ 2 third molars who experienced moderate-to-severe pain intensity ≤ 6 hours after surgery. Patients received indomethacin submicron particle capsules (20 or 40 mg), celecoxib 400 mg, or placebo. The primary efficacy endpoint was the sum of total pain relief over 0 to 8 hours (TOTPAR-8) determined from the area under the curve for pain relief over 0 to 8 hours following administration of the study drug, where pain relief was measured on a 0 to 4 scale. Safety and tolerability were also assessed. RESULTS Mean ± SE TOTPAR-8 scores were 10.8 ± 1.4 (indomethacin submicron particle capsules 20 mg), 12.6 ± 1.3 (indomethacin submicron particle capsules 40 mg), 14.8 ± 1.3 (celecoxib), and 3.0 ± 1.3 (placebo; P<0.001 for active treatments vs. placebo). Indomethacin submicron particle capsules treatment groups demonstrated better mean TOTPAR over 4 hours than placebo (P<0.001). Similar rates and profiles of treatment-emergent AEs were reported by patients across treatment groups. DISCUSSION Lower-dose, indomethacin submicron particle capsules provide good overall pain relief in patients with postsurgical pain and are generally well tolerated. Indomethacin submicron particle capsules are a potentially promising option for treatment of acute pain and warrant further study.


title: Autophagy: controlling cell fate in rheumatic diseases.

text: Autophagy, an endogenous process necessary for the turnover of organelles, maintains cellular homeostasis and directs cell fate. Alterations to the regulation of autophagy contribute to the progression of various rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), osteoarthritis (OA) and systemic sclerosis (SSc). Implicit in the progression of these diseases are cell-type-specific responses to surrounding factors that alter autophagy: chondrocytes within articular cartilage show decreased autophagy in OA, leading to rapid cell death and cartilage degeneration; fibroblasts from patients with SSc have restricted autophagy, similar to that seen in aged dermal fibroblasts; fibroblast-like synoviocytes from RA joints show altered autophagy, which contributes to synovial hyperplasia; and dysregulation of autophagy in haematopoietic lineage cells alters their function and maturation in SLE. Various upstream mechanisms also contribute to these diseases by regulating autophagy as part of their signalling cascades. In this Review, we discuss the links between autophagy, immune responses, fibrosis and cellular fates as they relate to pathologies associated with rheumatic diseases. Therapies in clinical use, and in preclinical or clinical development, are also discussed in relation to their effects on autophagy in rheumatic diseases.


title: Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study.

text: OBJECTIVES To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. DESIGN A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. SETTING EPIC II included 1265 intensive care units in 76 countries. PATIENTS Patients in participating intensive care units on study day. INTERVENTIONS None. MEASUREMENT AND MAIN RESULTS Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. CONCLUSION Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use.


A Ph.D. on hold-indefinitely.


Zika and the Risk of Microcephaly.


title: Ablative Therapies for Renal Tumors: Patient Selection, Treatment Planning, and Follow-Up.

text: The increased use of abdominal imaging has led to a major increase in small renal tumors incidence particularly in the elderly population. Their management is evolving with the development of percutaneous ablation, particularly radiofrequency ablation, cryoablation, and microwave ablation. The typical indications that must be validated by a multidisciplinary committee include solid tumors less than 3cm in patients with multiple comorbidity factors (including age), contraindications to surgery, hereditary renal cancer, bilateral renal tumors, solitary kidney, pre-existing chronic kidney disease, or at high risk of predialysis renal function after partial nephrectomy. As tumor ablation offers almost similar oncologic outcome when compared with surgery, new indications are appearing such as larger tumors, benign, or cystic neoplasms. The biopsy of solid renal masses is recommended in most cases. Careful and systematic treatment planning is required to avoid complications, paying specific attention of the relationships to the bowel structures, and urinary tract. Specific maneuvers can be necessary such as gas or liquid dissection and pyeloperfusion. The technique of ablation depends on availability, training, and tumor size and location, with a preference to cryotherapy for central and large lesions. Evaluation of therapeutic efficacy relies on contrast-enhanced imaging (computed tomography, magnetic resonance imaging or even ultrasound). The follow-up must be continued up to 10 years after ablation. The overall efficacy is more than 90% with a reduced complication rate less than 10%. Renal tumor percutaneous ablation is sparing the renal function and should be the preferred treatment in the case of pre-existing chronic kidney disease.


title: Fatal measles pneumonitis during Hodgkin's lymphoma.

text: The treatment of measles pneumonitis in immunocompromised adults is not established. We describe a patient with Hodgkin's lymphoma who developed acute pneumonia during a measles infection. On day 13, intravenous ribavirin and immunoglobulins were administrated. On day 18, the patient developed acute respiratory failure. An examination of transbronchial pulmonary biopsies showed Warthin-Finkeldey giant cells that are pathognomonic of measles pneumonitis. The patient died despite aggressive supportive care. Our case and a review of literature show that measles pneumonitis is routinely fatal in patients with cancer. We suggest that antiviral drugs should be considered as soon as the diagnosis has been established.


title: Occlusive dressings and the healing of standardized abrasions.

text: CONTEXT Acute skin trauma during sport participation, resulting in partial-thickness abrasions, is common. The limited investigations focusing on the acute wound environment and dressing techniques and the subsequent lack of evidence-based standards complicate clinical wound care decisions. OBJECTIVE To examine the effects of occlusive dressings on healing of standardized, partial-thickness abrasions. DESIGN Controlled, counterbalanced, repeated-measures design. SETTING University laboratory. PATIENTS OR OTHER PARTICIPANTS Sixteen healthy women (n = 10) and men (n = 6). INTERVENTION(S) Four standardized, partial-thickness abrasions were inflicted. Film, hydrogel, and hydrocolloid occlusive dressings and no dressing (control) were applied. Participants returned on postwound days 1, 3, 5, 7, 10, and 14 for digital imaging. Wound healing time was measured by change in wound contraction (cm(2)) and change in wound color (chromatic red) and luminance in red, green, and blue color values. MAIN OUTCOME MEASURE(S) Wound contraction, color (chromatic red), and luminance. RESULTS A day-by-dressing interaction was found for wound contraction, color, and luminance. Post hoc testing indicated that the film and hydrocolloid dressings produced greater wound contraction than the hydrogel and no dressing on days 7 and 10. Film, hydrogel, and hydrocolloid dressings also resulted in greater wound contraction than the control on day 14. Hydrocolloid dressings produced smaller measures of color and greater measures of luminance than no dressing on day 7. Film, hydrogel, and hydrocolloid dressings also resulted in smaller measures of color and greater measures of luminance compared with no dressing on days 10 and 14. CONCLUSIONS When compared with the control (no dressing), the film, hydrogel, and hydrocolloid occlusive dressings were associated with a faster healing rate of partial-thickness abrasions across time measured by wound contraction, color, and luminance. Overall, these data indicate that occlusive dressings were more effective in healing than no dressing was.


title: Covid Musings.

text: Many of us have watched scientists, health professionals and policy makers debate, and struggle on how to manage the Covid-19 pandemic. In that context, I've thought about what lessons I've learned from SETAC and my training as a scientist, and how they are relevant to this pandemic. Below are my three main points. This article is protected by copyright. All rights reserved.


The Moral Imperative to Include Pregnant Women in Clinical Trials of Interventions for COVID-19.


title: Novel 5-arylcarbamoyl-2-methylisoxazolidin-3-yl-3-phosphonates as nucleotide analogues.

text: A series of 5-substituted 3-phosphonylated isoxazolidines have been obtained via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-heteroaromatic acrylamides. Good trans/cis diastereoselectivities (d.e. 58-76%) of isomeric (3-diethoxyphosphoryl)isoxazolidines were observed. cis- and trans-Isoxazolidine phosphonates were evaluated for their antiviral activity against a broad range of DNA and RNA viruses but were found inactive. Their cytostatic activity toward L1210, CEM, and HeLa cells was also established, and compounds cis-12r and trans-11r having a 2,2-difluorobenzo[d][1,3]dioxole moiety slightly inhibited proliferation of HeLa cells at IC50 values of 186 and 179 μM, respectively.


title: Extracellular loops of BtuB facilitate transport of vitamin B12 through the outer membrane of E. coli.

text: Vitamin B12 (or cobalamin) is an enzymatic cofactor essential both for mammals and bacteria. However, cobalamin can be synthesized only by few microorganisms so most bacteria need to take it up from the environment through the TonB-dependent transport system. The first stage of cobalamin import to E. coli cells occurs through the outer-membrane receptor called BtuB. Vitamin B12 binds with high affinity to the extracellular side of the BtuB protein. BtuB forms a β-barrel with inner luminal domain and extracellular loops. To mechanically allow for cobalamin passage, the luminal domain needs to partially unfold with the help of the inner-membrane TonB protein. However, the mechanism of cobalamin permeation is unknown. Using all-atom molecular dynamics, we simulated the transport of cobalamin through the BtuB receptor embedded in an asymmetric and heterogeneous E. coli outer membrane. To enhance conformational sampling of the BtuB loops, we developed the Gaussian force-simulated annealing method (GF-SA) and coupled it with umbrella sampling. We found that cobalamin needs to rotate in order to permeate through BtuB. We showed that the mobility of BtuB extracellular loops is crucial for cobalamin binding and transport and resembles an induced fit mechanism. Loop mobility depends not only on the position of cobalamin but also on the extension of luminal domain. We provided atomistic details of cobalamin transport through the BtuB receptor showing the essential role of the mobility of BtuB extracellular loops. A similar TonB-dependent transport system is used also by many other compounds, such as haem and siderophores, and importantly, can be hijacked by natural antibiotics. Our work could have implications for future delivery of antibiotics to bacteria using this transport system.


Staff Morale and Well-Being During the COVID-19 Pandemic.


title: Keeping it in check: chronic viral infection and antiviral immunity in the brain.

text: It is becoming clear that the manner by which the immune response resolves or contains infection by a pathogen varies according to the tissue that is affected. Unlike many peripheral cell types, CNS neurons are generally non-renewable. Thus, the cytolytic and inflammatory strategies that are effective in controlling infections in the periphery could be damaging if deployed in the CNS. Perhaps for this reason, the immune response to some CNS viral infections favours maintenance of neuronal integrity and non-neurolytic viral control. This modified immune response - when combined with the unique anatomy and physiology of the CNS - provides an ideal environment for the maintenance of viral genomes, including those of RNA viruses. Therefore, it is possible that such viruses can reactivate long after initial viral exposure, contributing to CNS disease.


Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China.


title: Noninvasive cerebral oximetry during endovascular therapy for acute ischemic stroke: an observational study.

text: Implementing endovascular stroke care often impedes neurologic assessment in patients who need sedation or general anesthesia. Cerebral near-infrared spectroscopy (NIRS) may help physicians monitor cerebral tissue viability, but data in hyperacute stroke patients receiving endovascular treatment are sparse. In this observational study, the NIRS index regional oxygen saturation (rSO2) was measured noninvasively before, during, and after endovascular therapy via bilateral forehead NIRS optodes. During the study period, 63 patients were monitored with NIRS; 43 qualified for analysis. Before recanalization, 10 distinct rSO2 decreases occurred in 11 patients with respect to time to intubation. During recanalization, two kinds of unilateral rSO2 changes occurred in the affected hemisphere: small peaks throughout the treatment (n=14, 32.6%) and sustained increases immediately after recanalization (n=2, 4.7%). Lower area under the curve 10% below baseline was associated with better reperfusion status (thrombolysis in cerebral infarction ≥ 2b, P=0.009). At the end of the intervention, lower interhemispheric rSO2 difference predicted death within 90 days (P=0.037). After the intervention, higher rSO2 variability predicted poor outcome (modified Rankin scale > 3, P=0.032). Our findings suggest that bi-channel rSO2-NIRS has potential for guiding neuroanesthesia and predicting outcome. To better monitor local revascularization, an improved stroke-specific set-up in future studies is necessary.


title: Severe Acute Respiratory Syndrome Coronavirus 2 Prevalence, Seroprevalence, and Exposure Among Evacuees from Wuhan, China, 2020.

text: To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States.


title: Rare codons in uORFs of baculovirus p13 gene modulates downstream gene expression.

text: The p13 gene is a group II nucleopolyhedroviruses (NPVs) specific gene and featured by containing upstream mini ORFs (uORF) in its 5' UTR region. However, there are almost no reports published on the functions of the uORFs of p13 gene. In this study, the Luciferase Reporter Assay System was employed to investigate how the mini ORFs of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) p13 gene (Ha-p13) and its rare codons regulated the downstream gene expression. After the coding sequence of uORFs in the Ha-p13 gene was fused to the luciferase reporter gene in the expression vector pGL3 and the plasmid DNA was then transfected into the Hz-AM1 cells, the translation of the fusion protein could be initiated from the start codon of the uORFs. The uAUG and its context in uORF2 seemed to be more efficient for translation initiation than that in uORF1. Mutation of the start codons in one or both of uORFs (uORF1 or uORF2) could significantly increase the expression of the downstream reporter gene. The start codon mutation in uORF1 produced a higher reporter gene expression than that in uORF2, indicating that the uORF1 could be a stronger inhibitor than the uORF2, and the length of uORFs seemed not to be crucial for down-regulating translation. The expression of both uORFs could co-regulate the associated gene expression. Substituting the rare codons in uORF1, uORF2 or both with less rare codons dramatically increased the expression of the downstream reporter gene. Rare codon mutations in both uORFs were much more efficient in up-regulating the associate gene expression than mutations in either of the two uORFs alone.


Covid-19 and the Need for Health Care Reform.


title: Living donor liver transplantation: effect of the type of liver graft donation on donor mortality and morbidity.

text: To investigate the influence of the type of liver graft donation on donor mortality and morbidity. The clinical course of 87 living liver donors operated on at our center between 2002 and 2009 was retrospectively analysed and data pertaining to all complications were retrieved. No donor mortality was observed and no donor suffered any life-threatening complication. Four donors (4.6%) developed biliary leakage, nine (10.3%) had to be readmitted to hospital and six (6.9%) required some or other type of reoperation related to the previous liver donation. Reoperations included incisional or diaphragmatic hernia repair (n = 4), biliary leakage repair (n = 1) and segmental colon resection combined with diaphragmatic hernia repair (n = 1). There was a statistically significant difference in hospital stay (P < 0.001), autologous blood transfusions (P < 0.001) and operating time (P < 0.005) when right lobe donations (Segments V-VIII) were compared with left lobe (Segments II-IV) and left lateral lobe (Segments II-III) donations, whereas no difference was found between these groups regarding hospital readmission, operative revisions and the incidence or severity of complications. Right lobe donation was associated with prolonged hospital stay, increased blood transfusions and prolonged operating time when compared with left and left lateral lobe donation, whereas donor mortality and morbidity did not differ between these groups.


title: [Clinical feature changes of a COVID-19 patient from mild to critical condition and cardiopulmonary pathological results].

text: Objective: To analyse the clinical history, laboratory tests and pathological data of a patient who suffered from novel coronavirus pneumonia(COVID-19) and provide reference for the clinical treatment of similar cases. Methods: Data of clinical manifestation, laboratory examination, bronchoscopy, echocardiography and cardiopulmonary pathological results were retrospectively reviewed in a case of COVID-19 with rapid exacerbation from mild to critical condition. Results: This patient hospitalized at day 9 post 2019 novel coronavirus(2019-nCoV) infection, experienced progressive deterioration from mild to severe at day 11, severe to critical at day 18 and underwent extracorporeal membrane oxygenation(ECMO) and continuous renal replacement therapy(CRRT) as well as heart lung transplantation during day 28-45 day post infection, and died on the second day post heart and lung transplantation. The patient had suffered from hypertension for 8 years. At the early stage of the disease, his symptoms were mild and the inflammatory indices increased and the lymphocyte count decreased continuously. The patient's condition exacerbated rapidly with multi-organ infections, and eventually developed pulmonary hemorrhage and consolidation, pulmonary hypertension, right heart failure, malignant ventricular arrhythmias, liver dysfunction, etc. His clinical manifestations could not be improved despite viral RNAs test results became negative. The patient underwent lung and heart transplantation and finally died of multi organ failure at the second day post lung and heart transplantation. Pathological examination indicated massive mucus, dark red secretions and blood clots in bronchus. The pathological changes were mainly diffused pulmonary hemorrhagic injuries and necrosis, fibrosis, small vessel disease with cardiac edema and lymphocyte infiltration. Conclusions: The clinical course of COVID-19 can exacerbate rapidly from mild to critical with lung, liver and heart injuries. Steadily increased inflammation indices are suggestive of irreversible disease progression and worse outcome. In the early stages of the disease, the progress of the disease should be closely observed and evaluated, and the factors related to the progress of the disease should be identified and managed.


Pelvic floor reconstruction with bilateral gracilis flaps following extralevator abdominoperineal excision - a video vignette.


title: A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research.

text: To inform evidence-based practice in health care, guidelines and policies require accurate identification, collation, and integration of all available evidence in a comprehensive, meaningful, and time-efficient manner. Approaches to evidence synthesis such as carefully conducted systematic reviews and meta-analyses are essential tools to summarize specific topics. Unfortunately, not all systematic reviews are truly systematic, and their quality can vary substantially. Since well-conducted evidence synthesis typically involves a complex set of steps, we believe formulating a cohesive, step-by-step guide on how to conduct a systemic review and meta-analysis is essential. While most of the guidelines on systematic reviews focus on how to report or appraise systematic reviews, they lack guidance on how to synthesize evidence efficiently. To facilitate the design and development of evidence syntheses, we provide a clear and concise, 24-step guide on how to perform a systematic review and meta-analysis of observational studies and clinical trials. We describe each step, illustrate it with concrete examples, and provide relevant references for further guidance. The 24-step guide (1) simplifies the methodology of conducting a systematic review, (2) provides healthcare professionals and researchers with methodologically sound tools for conducting systematic reviews and meta-analyses, and (3) it can enhance the quality of existing evidence synthesis efforts. This guide will help its readers to better understand the complexity of the process, appraise the quality of published systematic reviews, and better comprehend (and use) evidence from medical literature.


title: Currently available and experimental dyes for intraoperative near-infrared fluorescence imaging of the ureters: a systematic review.

text: BACKGROUND Iatrogenic ureteral injury (IUI) following abdominal surgery has a relatively low incidence, but is associated with high risks of morbidity and mortality. Conventional assessment of IUI includes visual inspection and palpation. This is especially challenging during laparoscopic procedures and has translated into an increased risk of IUI. The use of near-infrared fluorescent (NIRF) imaging is currently being considered as a novel method to identify the ureters intraoperatively. The aim of this review is to describe the currently available and experimental dyes for ureter visualization and to evaluate their feasibility of using them and their effectiveness. METHODS This article adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for systematic reviews. A systematic literature search was performed in the PubMed database. All included articles were screened for eligibility by two authors. Three clinical trial databases were consulted to identify ongoing or completed unpublished trials. Risk of bias was assessed for all articles. RESULTS The search yielded 20 articles on ureter visualization. Two clinically available dyes, indocyanine green (ICG) and methylene blue (MB), and eight experimental dyes were described and assessed for their feasibility to identify the ureter. Two ongoing clinical trials on CW800-BK and one trial on ZW800-1 for ureter visualization were identified. CONCLUSIONS Currently available dyes, ICG and MB, are safe, but suboptimal for ureter visualization based on the route of administration and optical properties, respectively. Currently, MB has potential to be routinely used for ureter visualization in most patients, but (cRGD-)ZW800-1 holds potential for this role in the future, owing to its exclusive renal clearance and the near absence of background. To assess the benefit of NIRF imaging for reducing the incidence of IUI, larger patient cohorts need to be examined.


title: Emergency Radiology During the COVID-19 Pandemic: The Canadian Association of Radiologists Recommendations for Practice.

text: Coronavirus Disease 2019 (COVID-19) is the disease caused by the novel coronavirus officially named the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), declared as a pandemic by the World Health Organization on March 11, 2020. The COVID-19 pandemic presents an unprecedented challenge to emergency radiology practice. The continuity of an effective emergency imaging service for both COVID-19 and non-COVID-19 patients is essential, while adhering to best infection control practices. Under the direction of the Board of the Canadian Association of Radiologists, this general guidance document has been synthesized by collaborative consensus of a group of emergency radiologists. These recommendations aim to assist radiologists involved in emergency diagnostic imaging to help mitigate the spread of COVID-19 and continue to add value to patient care in the emergency setting.


title: The bovine immunodeficiency virus rev protein: identification of a novel lentiviral bipartite nuclear localization signal harboring an atypical spacer sequence.

text: The bovine immunodeficiency virus (BIV) Rev protein (186 amino acids [aa] in length) is involved in the nuclear exportation of partially spliced and unspliced viral RNAs. Previous studies have shown that BIV Rev localizes in the nucleus and nucleolus of infected cells. Here we report the characterization of the nuclear/nucleolar localization signals (NLS/NoLS) of this protein. Through transfection of a series of deletion mutants of BIV Rev fused to enhanced green fluorescent protein and fluorescence microscopy analyses, we were able to map the NLS region between aa 71 and 110 of the protein. Remarkably, by conducting alanine substitution of basic residues within the aa 71 to 110 sequence, we demonstrated that the BIV Rev NLS is bipartite, maps to aa 71 to 74 and 95 to 101, and is predominantly composed of arginine residues. This is the first report of a bipartite Rev (or Rev-like) NLS in a lentivirus/retrovirus. Moreover, this NLS is atypical, as the length of the sequence between the motifs composing the bipartite NLS, e.g., the spacer sequence, is 20 aa. Further mutagenesis experiments also identified the NoLS region of BIV Rev. It localizes mainly within the NLS spacer sequence. In addition, the BIV Rev NoLS sequence differs from the consensus sequence reported for other viral and cellular nucleolar proteins. In summary, we conclude that the nucleolar and nuclear localizations of BIV Rev are mediated via novel NLS and NoLS motifs.


title: 3D absorbed dose distribution estimated by Monte Carlo simulation in radionuclide therapy with a monoclonal antibody targeting synovial sarcoma.

text: BACKROUND Radiolabeled OTSA101, a monoclonal antibody targeting synovial sarcoma (SS) developed by OncoTherapy Science, was used to treat relapsing SS metastases following a theranostic procedure: in case of significant 111In-OTSA101 tumor uptake and favorable biodistribution, patient was randomly treated with 370/1110 MBq 90Y-OTSA101. Monte Carlo-based 3D dosimetry integrating time-activity curves in VOI was performed on 111In-OTSA101 repeated SPECT/CT. Estimated absorbed doses (AD) in normal tissues were compared to biological side effects and to the admitted maximal tolerated absorbed dose (MTD) in normal organs. Results in the tumors were also compared to disease evolution. RESULTS Biodistribution and tracer quantification were analyzed on repeated SPECT/CT acquisitions performed after injection of 111In-OTSA101 in 19/20 included patients. SPECT images were warped to a common coordinates system with deformable registration. Volumes of interest (VOI) for various lesions and normal tissues were drawn on the first CT acquisition and reported to all the SPECT images. Tracer quantification and residence time of 111In-OTSA101 in VOI were used to evaluate the estimated absorbed doses per MBq of 90Y-OTSA101 by means of Monte Carlo simulations (GATE). A visual scale analysis was applied to assess tumor uptake (grades 0 to 4) and results were compared to the automated quantification. Results were then compared to biological side effects reported in the selected patients treated with 90Y-OTSA101 but also to disease response to treatment. After screening, 8/20 patients were treated with 370 or 1110 MBq 90Y-OTSA101. All demonstrated medullary toxicity, only one presented with transient grade 3 liver toxicity due to disease progression, and two patients presented with transient grade 1 renal toxicity. Median absorbed doses were the highest in the liver (median, 0.64 cGy/MBq; [0.27 -1.07]) being far lower than the 20 Gy liver MTD, and the lowest in bone marrow (median, 0.09 cGy/MBq; [0.02 -0.18]) being closer to the 2 Gy bone marrow MTD. Most of the patients demonstrated progressive disease on RECIST criteria during patient follow-up. 111In-OTSA101 tumors tracer uptake visually appeared highly heterogeneous in inter- and intra-patient analyses, independently of tumor sizes, with variable kinetics. The majority of visual grades corresponded to the automated computed ones. Estimated absorbed doses in the 95 supra-centimetric selected lesions ranged from 0.01 to 0.71 cGy per injected MBq (median, 0.22 cGy/MBq). The maximal tumor AD obtained was 11.5 Gy. CONCLUSIONS 3D dosimetry results can explain the observed toxicity and tumors response. Despite an intense visual 111In-OTSA101 liver uptake, liver toxicity was not the dose limiting factor conversely to bone marrow toxicity. Even though tumors 111In-OTSA101 avidity was visually obvious for treated patients, the low estimated tumors AD obtained by 3D dosimetry explain the lack of tumor response.


title: Surgical simulation in Africa: the feasibility and impact of a 3-day fundamentals of laparoscopic surgery course.

text: INTRODUCTION The use of laparoscopy in resource-restricted countries has increased in recent years. Although simulation is now considered an important adjunct to operating-room-based training for learning laparoscopic skills, there is very little literature assessing the use of simulation in resource-restricted countries. The purpose of this study was to determine the feasibility and impact of a 3-day Fundamentals of Laparoscopic Surgery (FLS) course in Botswana, Africa. METHODS A total of 20 surgeons and trainees participated in a 3-day FLS course. A pretest FLS score was obtained for each subject, followed by 2 days of practice with feedback. A final FLS posttest score was then obtained. Participants also watched the FLS instructional CD-ROM and took the written test on day 3. RESULTS Mean posttest scores were significantly higher than pretest scores for each FLS task and for the total normalized FLS simulator score (285 +/- 94 versus 132 +/- 92, p < 0.001). The mean score on the written test was 242 (116). In total, only two surgeons achieved a passing score on both the cognitive and skills assessment required to obtain FLS certification. CONCLUSION To our knowledge, this is the first time the FLS program has been taught in Africa. We have shown that giving the FLS course in a resource-restricted country is feasible and resulted in a significant improvement in FLS technical skills after 3 days. Most surgeons, however, still did not reach FLS passing scores, indicating that more than 3 days will be required in future courses to help surgeons obtain FLS certification.


Glycerol kinase deficiency in adult hypoglycemic acidemia.


How countries are using genomics to help avoid a second coronavirus wave.


Blockbuster expectations for hepatitis B therapeutic vaccine.


Covid-19: UK's response has so far cost "unprecedented" £124.3bn.


Developing a vaccine for covid-19.


title: Oxidative stress in bisphenol AF-induced cardiotoxicity in zebrafish and the protective role of N-acetyl N-cysteine.

text: Research has shown that there is a relationship between bisphenol A (BPA) exposure and the incidence of cardiovascular diseases. However, the effect of bisphenol AF (BPAF), a main substitute for BPA, on heart development remains unclear. In this study, the cardiotoxicity of BPAF was evaluated in zebrafish in vivo and in human cardiac myocytes (HCMs) in vitro. Our results showed that BPAF at a concentration of 200 μg/L results in cardiotoxicity, including a reduced number of cardiomyocytes and endocardial cells in the heart, and reduced heart size in two transgenic zebrafish models (myl7:: dsred2-nuc and fli1a::nGFP). An increase in apoptosis was observed along with antioxidant enzyme inhibition and lipid peroxidation. In addition, the mRNA expression levels of several key genes involved in cardiac development were suppressed by BPAF treatment. In the HCM cell model, BPAF at 2 mg/L induced reactive oxygen species generation, antioxidant enzyme inhibition, mitochondrial dysfunction and oxidative DNA damage. These adverse outcomes can be attenuated by the antioxidant N-acetyl-L-cysteine (NAC), suggesting that oxidative stress is involved in BPAF-induced cardiotoxicity. These data indicated that BPAF exposure increased oxidative stress and apoptosis and that it suppressed the expression of genes involved in cardiac development, which may play crucial roles in the mechanisms of BPAF-induced cardiotoxicity.


title: Rethinking the Importance of the Individual within a Community of Data.

text: The Covid-19 crisis has underscored the importance of the collection and analysis of clinical and research data and specimens for ongoing work. The federal government recently completed a related revision of the human subjects research regulations, founded in the traditional principles of research ethics, but in this commentary, we argue that the analysis underpinning this revision overemphasized the importance of informed consent, given the low risks of secondary research. Governing the interests of a community is different from governing the interests of individuals, and here we suggest that, moving forward, the analyses of the risks of secondary research protocols be assessed from the perspective of the former.


title: Pure single-port laparoscopic surgery or mix of techniques?

text: PURPOSE Laparoendoscopic single-site surgery (LESS) has emerged in the recent years as an alternative approach to conventional laparoscopic surgery which is accompanied by additional advantages over laparoscopy. In this work we attempt to review the current literature and to investigate the possible combination of LESS to other currently available approaches such as natural orifice transluminal endoscopic surgery (NOTES), needlescopic and robotic laparoscopic surgery. METHODS Extensive literature search on the topics of LESS, hybrid and pure NOTES, Needlescopic-assisted LESS and "Robot-assisted LESS" took place. Additionally, the accumulated experience from 118 LESSs performed in our departments is presented in an attempt to provide evidence regarding the mix of technique in LESS in urology. RESULTS The challenging nature of LESS limits the broader application and acceptance. Expanding experience in single-site surgery has currently provided tools such as transvaginal access, needlescopic instruments and robot assistance that can aid LESS and enhance its efficiency without compromising any of its advantages. A mix of these techniques with LESS could ease the stiff learning curve of the second and benefit not only its performance but also the adaptation of LESS as a standard practice. CONCLUSION Pure LESS although feasible, remains a technical challenge for the surgeon, preventing the widespread application of the technique. The goal of urologists on LESS surgery should not be the purity of LESS approach, but the superiority against already established techniques. A mix of techniques could be a key for the documentation of the advantages of LESS over conventional laparoscopy.


title: Assessment of fever in the returning traveller.

text: Evaluation of people returning from trips abroad with fever is an important skill for all general physicians given the increasing trend in foreign travel. This evaluation should comprise a detailed travel history, thorough clinical examination, appropriate initial tests and a knowledge of when to ask for further advice. An understanding of the incubation periods of common imported infections and a syndromic approach to patients' symptoms is helpful in order to narrow down the likely diagnosis. The need to implement relevant infection control precautions has been highlighted by the recent Middle East respiratory syndrome coronavirus and Ebola virus disease outbreaks.


title: Bicomponent Conformal Electrode for Radiofrequency Sequential Ablation and Circumferential Separation of Large Tumors in Solid Organs: Development and In Vitro Evaluation.

text: OBJECTIVE Complete destruction of large tumors by radiofrequency ablation (RFA) with surrounding tumor-free margin is difficult because of incomplete or nonuniform heating due to both heat-sink effect of circulating blood and limitations of existing RF electrode design. A new RF electrode is described to overcome this limitation. METHODS A bicomponent conformal (BCC) RFA probe providing sectorial sequential ablation followed by circumferential cutting is designed and evaluated. Three-dimensional finite-element analysis model was developed with temperature feedback-controlled simulation of RFA for electrode design and optimization. The prototype bipolar BCC probe with three embedded thermocouples was constructed and evaluated in tissue-mimicking phantoms. RESULTS Maximum tissue temperature was kept <100 ºC with power applied <15 W. A 10-min ablation time was used for each sequence and after four sequential RFA, a large ablation zone of 55 cm3 was achieved. Our experiment confirmed that lesions exceeding 3.7 cm could be ablated and separated from the surrounded tissue. CONCLUSION The new BCC probe is, thus, capable of controlled ablation followed by circumferential separation of the lesions, when required. SIGNIFICANCE The results of these experiments provide the proof of concept validation that the BCC probe has the potential to ablate by sequential heating tumors in solid organs >3.5 cm then separate them by electrosurgical cutting from the surrounding normal parenchyma. The combined RF ablation and physical separation could completely destroy the cancer cells at the ablation site, thus, avoid any local recurrence of cancer. It requires further in vivo validation studies in large animals.


title: Diagnosis of pulmonary embolism: planar images generated from V/Q SPECT are not a reliable substitute for traditional planar V/Q scan.

text: OBJECTIVES The use of summed planar images generated from single-photon emission computed tomography (SPECT) ventilation/perfusion (V/Q) scintigraphy has been proposed as a substitute for planar V/Q scans in order to use the revised PIOPED interpretation criteria when only SPECT acquisition is performed in patients with suspected pulmonary embolism. The aim was to evaluate the accuracy of angular summed planar scans in comparison with true planar images. METHODS Patients included in the 'SPECT study' assessing the diagnostic performance of V/Q SPECT were analysed. Angular summed planar images were generated from SPECT acquisition data and compared with true planar scans. RESULTS Angular summed planar images were successfully generated for 246 patients. Regarding interobserver variability, the interpretation result was different for 15 (6%) summed planar scans with an excellent degree of agreement (κ=0.92; 95% confidence interval 0.88-0.96). With regard to intermodality interpretation variability between conventional planar and angular summed images, the result was different for 63 (26%) of 246 patients with an intermodality degree of agreement of κ=0.66 (95% confidence interval 0.58-0.73). CONCLUSION Planar images generated from SPECT V/Q scintigraphy are not a reliable substitute for true planar V/Q images.


title: Ensuring competency: are fundamentals of laparoscopic surgery training and certification necessary for practicing surgeons and operating room personnel?

text: BACKGROUND Certification in fundamentals of laparoscopic surgery (FLS) is required by the American board of surgery for graduating residents. This study aimed to evaluate the feasibility and need for certifying practicing surgeons and to assess proficiency of operating room (OR) personnel. METHODS Through a patient safety and health care delivery effectiveness grant, investigators at four state medical schools received funding for FLS certification of all attending surgeons and OR personnel credentialed in laparoscopy. Data were voluntarily collected under an institutional review board-approved protocol. Surgeons performed a single repetition of the FLS tasks oriented to the FLS proficiency-based curriculum and online cognitive materials and were encouraged to self-practice. The FLS certification examination was administered 2 months later under standard conditions. Operating room nurses and scrub technicians were enrolled in a curriculum with cognitive materials and a multistation skills practicum. Baseline and completion questionnaires were administered. Performance was assessed using signed-rank and χ(2) analysis. RESULTS The study aimed to enroll 99 surgeons. Subsequently, 87 surgeons completed at least one portion of the curriculum, 72 completed the entire curriculum (73% compliance), 83 completed the baseline skills assessment, and 27 (33%) failed. The self-reported practice time was 3.7 ± 2.5 h. At certification (n = 76), skills performance had improved from 317 ± 102.9 to 402 ± 54.2 (p < 0.0001). One surgeon (1.3%) failed the skills certification, and nine (11.8%) failed the cognitive exam. Remediation was completed by six surgeons. Of the 64 enrolled OR personnel, 22 completed the curriculum (34% compliance). All achieved proficiency at skills, and 60% passed the cognitive exam. CONCLUSIONS This study demonstrated that FLS certification for practicing surgeons and proficiency verification for OR personnel are feasible. A baseline skills failure rate of 33% and a certification failure rate of 13% suggest that FLS certification may be necessary to ensure surgeon competency. Fortunately, with only moderate practice, significant improvement can be achieved.


title: Thrombocytopenia as an initial manifestation of Covid-19; Case Series and Literature review.

text: Covid-19 has emerged as a global threat that has claimed millions of lives until now. Haematological manifestation as an initial presentation of this deadly virus is not frequently reported in the literature. We hereby report a case series of asymptomatic patients with severe thrombocytopenia which was later found to be Covid induced.


title: Treatment of an internal carotid artery aneurysm with a flow diverter through a double lumen balloon catheter.

text: Background Double lumen balloon catheters (DLBCs) are currently used in the treatment of intracranial aneurysms, especially when involving balloon or stent-assisted coiling. The existing DLBCs allow the delivery of self-expandable stents but do not offer the possibility to deploy flow-diverters. Despite the increasing use and success of flow-diverters, there have been numerous reports of procedural complications such as early in-stent thrombosis or delayed distal embolization. It seems that these complications can be avoided by correct stent positioning and adequate wall apposition, achieved either by manoeuvres with the microguidewire and/or microcatheter or by performing balloon angioplasty following an exchange guidewire manoeuvre. Objective Report the use of a new DLBC able to deliver a flow-diverter. Methods A 41-year-old woman presented to our hospital with binocular horizontal diplopia for two weeks and reduced visual acuity. A left internal carotid artery aneurysm involving the cavernous and ophthalmic segments was found, with a maximum height of 19 mm and a broad 8 mm neck. It presented extra- and intra-dural components and the parent vessel was significantly narrowed. A decision was made to perform endovascular treatment of the aneurysm with placement of a flow diverter through a DLBC. Results Patency and adequate expansion of the flow diverter with evident intra-aneurysmal contrast stasis was observed in the final angiogram. No peri-procedural complications were observed. Conclusion This is a technical note demonstrating the feasibility of a new device to deploy a flow diverter, aiming to improve wall apposition and stent configuration without the need of additional devices or exchange manoeuvres.


title: Successful coronary artery bypass operation in a SARS-COV-2 infected patient with acute coronary syndrome.

text: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is overwhelming healthcare resources and infrastructure worldwide. Earlier reports have demonstrated complicated postoperative courses and high fatality rates in patients undergoing emergent cardiothoracic surgery who were diagnosed postoperatively with COVID-19. These reports raise the possibility that active COVID-19 might precipitate a catastrophic pathophysiological response to infection in the postoperative period and lead to unfavorable surgical outcomes. Hence, it is imperative to screen patients with SARS-CoV-2 infection before surgery and to carefully monitor them in the postoperative period to identify any signs of active COVID-19. In this report, we present the successful outcome of coronary artery bypass grafting (CABG) operation in a patient with asymptomatic SARS-CoV-2 infection presenting with an acute coronary syndrome and requiring urgent surgical intervention. We employed a thorough strategy to identify subclinical COVID-19 disease, and after confirming the absence of active disease, proceeded with the CABG operation. The patient outcome was successful with the absence of any overt COVID-19 manifestations in the postoperative period.


Unequal detection of HIV type 1 group O infection by simple rapid tests.


title: Massively parallel sequencing for monitoring genetic consistency and quality control of live viral vaccines.

text: Intrinsic genetic instability of RNA viruses may lead to the accumulation of revertants during manufacture of live viral vaccines, requiring rigorous quality control to ensure vaccine safety. Each lot of oral poliovirus vaccine (OPV) is tested for neurovirulence in animals and also for the presence of neurovirulent revertants. Mutant analysis by PCR and restriction enzyme cleavage (MAPREC) is used to measure the frequency of neurovirulent mutations at the 5' untranslated region (UTR) of the viral genome that correlate with the level of neurovirulence determined by the monkey neurovirulence test. However, MAPREC can only monitor mutations at a few genomic loci and miss mutations at other sites that could adversely affect vaccine quality. Here we propose to use massively parallel sequencing (MPS) for sensitive detection and quantification of all mutations in the entire genome of attenuated viruses. Analysis of vaccine samples and reference preparations demonstrated a perfect agreement with MAPREC results. Quantitative MPS analysis of validated reference preparations tested by MAPREC produced identical results, suggesting that the method could take advantage of the existing reference materials and be used as a replacement for the MAPREC procedure in lot release of OPV. Patterns of mutations present at a low level in vaccine preparations were characteristic of seed viruses used for their manufacture and could be used for identification of individual batches. This approach may represent the ultimate tool for monitoring genetic consistency of live viral vaccines.


title: Michael Acceptors Tuned by the Pivotal Aromaticity of Histidine to Block COVID19 Activity.

text: COVID protease (SARS-CoV-2 Mpro) has been checked to be blocked by inhibitors, and with particular successful performance by α-ketoamide derivative substrates like 13b of Hilgenfeld and coworkers. After the biological characterization, here DFT calculations do not only explain how the inhibitor 13b produces a thermodynamically favorable interaction, but how to reach it kinetically. The controversial and unprovable concept of aromaticity here enjoys being the agent that rationalizes the seemingly innocent role of histidine (His41 of Mpro). Not only does it have a H-bond with the hydroxyl group, but it is the proton carrier of the thiol of Cys145 at almost zero energy cost that favours the interaction with the inhibitor that acts as a Michael acceptor.


title: Differences in Sense of Belonging, Pride, and Mental Health in the Daegu Metropolitan Region due to COVID-19: Comparison between the Presence and Absence of National Disaster Relief Fund.

text: Korea's Daegu Metropolitan City once had the second highest rate of COVID-19 infection after Wuhan in China. Following the outbreak, the government provided the first national disaster relief fund to citizens as financial aid. This study investigated whether the sense of regional belonging, pride, and mental health among 550 citizens of Daegu differed between the times before and after COVID-19, based on the presence or absence of the disaster relief fund. Frequency analysis, descriptive statistical analysis, and t-tests were conducted using the SPSS 25.0 program. Results showed that the sense of belonging was higher after COVID-19 than before, while pride was lower. Individuals who received the disaster relief fund showed higher levels of regional belonging and pride with statistical significance. The prevalence of melancholy and depression increased after COVID-19, but the presence or absence of the fund did not lead to a significant difference. Thus, in case of a future national disaster level, provision of the disaster relief fund can raise the sense of regional belonging and pride, in order to elicit communication among local residents toward overcoming difficulties. Furthermore, during challenging disaster situations, central and local governments should provide diverse programs for the citizens' mental health care.


title: Prevention and therapy of COVID-19 via exogenous estrogen treatment for both male and female patients.

text: The presented work summarizes the results of studies underlining the crucial role of estrogen receptor (ER) signaling in both innate and adaptive immune responses as well as in tissue repairing processes during respiratory virus infection. Experimental studies justify that among respiratory virus infected mice, a weaker ER signaling leads to increased morbidity and mortality in both males and females. In animal experiments, estrogen treatment silences the inflammatory reactions and decreases virus titers leading to improved survival rate; it seems to be an ideal prevention and therapy against COVID-19. We should overcome the widespread reluctance to estrogen therapy as we have a unique estrogen formula; conjugated estrogens, or conjugated equine estrogens available under the brand name of Premarin deriving from natural sources. Premarin can exert similar ER upregulative and gene repairing power like endogenous estrogen without any risk for adverse reactions. Premarin is capable of stopping the COVID-19 pandemic.


title: Gastric antral vascular ectasia: the evolution of therapeutic modalities.

text: Gastric Antral Vascular Ectasia (GAVE) may be an enigmatic source of non-variceal upper GI bleeding associated with various systemic diseases such as connective tissue disorders, liver disease, and chronic renal failure. Successful treatment of GAVE continues to be a challenge and has evolved through the years. Currently, given the rapid response, safety, and efficacy, endoscopic ablative modalities have largely usurped medical treatments as first-line therapy, particularly using argon plasma coagulation. However, other newer ablative modalities such as radiofrequency ablation, cryotherapy, and band ligations are promising. This paper is an overview of GAVE and its various endoscopic and medical therapies.


title: A review of the valorization and management of industrial spent catalyst waste in the context of sustainable practice: The case of the State of Kuwait in parallel to European industry.

text: Industrial solid waste management encompasses a vital part of developed and developing countries strategies alike. It manages waste generated from vital industries and governs the hazardous waste generated as a major component of integrated waste management strategies. This article reviews the practices that govern the management approaches utilized in the developed world for industrial spent catalysts. It critically assesses the current situation of waste management within the developing world region focusing on the industrial waste component, in a novel attempt to crucially develop a strategy for a way forward based on best practices and future directions with major European industries. The review also draws parallels with European countries to compare their practices with those of the State of Kuwait, which rely solely on landfilling for the management of its industrial waste. Spent catalysts recovery methods are discussed at length covering conventional methods of valuable metals and chemicals recovery (e.g., hydrometallurgical, solid-liquid and liquid-liquid extraction) as well as biological recovery methods. A major gap exists within regulations that govern the practice of managing industrial waste in Kuwait, where it is essential to start regulating industries that generate spent catalysts in-view of encouraging the establishment of valorization industries for metal and chemical recovery. This will also create a sustainable practice within state borders, and can reduce the environmental impact of landfilling such waste in Kuwait.


title: Is disruption of sleep quality a consequence of severe Covid-19 infection? A case-series examination.

text: The Covid-19 outbreak put enormous stress on the health system worldwide, and objective data to handle the emergency are still needed. We aimed to objectively assess the consequence of severe symptoms of Covid-19 infection on sleep quality through wrist actigraphy monitoring of four patients during the sub-acute recovery stage of the disease. The sleep of those patients who had experienced the most severe respiratory symptoms and who had needed prolonged intensive care unit (ICU) stay showed lower Sleep Efficiency and Immobility Time and higher Fragmentation Index compared to those patients who had experienced only mild respiratory symptoms and not requiring ICU stay. Wrist actigraphy assessment provided important clinical information about the sleep and activity levels of Covid-19 patients during the post-acute rehabilitation management.


title: Retrotranslocation of prion proteins from the endoplasmic reticulum by preventing GPI signal transamidation.

text: Neurodegeneration in diseases caused by altered metabolism of mammalian prion protein (PrP) can be averted by reducing PrP expression. To identify novel pathways for PrP down-regulation, we analyzed cells that had adapted to the negative selection pressure of stable overexpression of a disease-causing PrP mutant. A mutant cell line was isolated that selectively and quantitatively routes wild-type and various mutant PrPs for ER retrotranslocation and proteasomal degradation. Biochemical analyses of the mutant cells revealed that a defect in glycosylphosphatidylinositol (GPI) anchor synthesis leads to an unprocessed GPI-anchoring signal sequence that directs both ER retention and efficient retrotranslocation of PrP. An unprocessed GPI signal was sufficient to impart ER retention, but not retrotranslocation, to a heterologous protein, revealing an unexpected role for the mature domain in the metabolism of misprocessed GPI-anchored proteins. Our results provide new insights into the quality control pathways for unprocessed GPI-anchored proteins and identify transamidation of the GPI signal sequence as a step in PrP biosynthesis that is absolutely required for its surface expression. As each GPI signal sequence is unique, these results also identify signal recognition by the GPI-transamidase as a potential step for selective small molecule perturbation of PrP expression.


title: Volatile isoflurane sedation in cerebrovascular intensive care patients using AnaConDa(®): effects on cerebral oxygenation, circulation, and pressure.

text: PURPOSE The anesthetic-conserving device AnaConDa(®), a miniature vaporizer, allows volatile sedation in the intensive care unit (ICU). We investigated the effects of isoflurane sedation on cerebral and systemic physiology parameters in neuromonitored ICU stroke patients. METHODS Included in the study were 19 consecutive ventilated patients with intracerebral hemorrhage (12), subarachnoid hemorrhage (4), and ischemic stroke (3) who were switched from intravenous propofol or midazolam to inhalative isoflurane sedation for an average of 3.5 days. During the sedation transition, the following parameters were assessed: mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), middle cerebral artery mean flow velocity (MFV) and cerebral fractional tissue oxygen extraction (FTOE), as well as systemic cardiopulmonary parameters and administered drugs. RESULTS After the first hour, mean ICP showed an increase of 2.1 mmHg that was not clinically relevant. Likewise, MFV did not change. MAP and CPP, however, decreased by 6.5 and 6.3 mmHg, respectively. FTOE was reduced slightly from 0.24 to 0.21 (p = 0.03). Over an observation period of 12 h, ICP remained stable, while MAP and thus CPP showed distinct decreases (CPP: -10 mmHg at 6 h, p < 0.001; -7.5 mmHg at 12 h, p = 0.005, when compared to preswitch levels) despite a 1.5-fold increase in vasopressor administration. CONCLUSIONS We suggest that that it is possible to reach sufficient sedation levels in cerebrovascular ICU patients by applying volatile isoflurane long-term without a relevant increase in ICP, if baseline ICP values are low or only moderately elevated. However, caution should be exercised in view of isoflurane's decreasing effect on MAP and CPP. Multimodal neuromonitoring is strongly recommended when applying this off-label sedation method.


title: Impact of Thrombus Length on Outcomes After Intra-Arterial Aspiration Thrombectomy in the THERAPY Trial.

text: BACKGROUND AND PURPOSE Increasing thrombus length (TL) impedes recanalization after intravenous (IV) thrombolysis. We sought to determine whether the clinical benefit of aspiration thrombectomy relative to IV r-tPA (recombinant tissue-type plasminogen activator) may be greater at longer TL. METHODS THERAPY was a randomized trial of aspiration thrombectomy plus IV r-tPA versus IV r-tPA alone in large-vessel stroke patients with prospective TL measurement ≥8 mm. In this post hoc study, we evaluated the association of TL with trial end points and potential endovascular treatment effect, using univariate, multivariable, and multiplicative interaction analyses. RESULTS TL data were available for all 108 patients (28% internal carotid artery, 62% M1, and 10% M2). Median TL was 14.0 mm (interquartile range, 9.7-19.5 mm). Longer TL was associated with worse outcome (90-day modified Rankin Scale score: odds ratio, 1.24 per 5-mm TL increment; 95% confidence interval, 1.04-1.52; P=0.02), even after adjusting for key outcome predictors (adjusted P=0.004). Longer TL was also associated with more serious adverse events (adjusted P=0.01), more symptomatic hemorrhages (adjusted P=0.03), and increased mortality (adjusted P=0.01). No significant relationship was observed between TL and angiographic reperfusion (modified thrombolysis in cerebral ischemia 2b-3), but greater TL was associated with longer endovascular procedural times (ρ=0.36; P=0.045). Increasing TL was associated with greater aspiration thrombectomy treatment effect (interaction term P=0.03). This might be related to a potentially stronger adverse effect of increasing TL on 90-day modified Rankin Scale for patients treated with IV r-tPA (ρ=0.39; P=0.01) compared with intra-arterial therapy (ρ=0.20; P=0.165). CONCLUSIONS Ischemic stroke patients with longer symptomatic thrombi have worse 90-day clinical outcomes but may have a greater relative benefit of aspiration thrombectomy over IV r-tPA alone. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.


docid: yoegijfa

title: Polyester composite mesh for laparoscopic paraesophageal hernia repair.

text: Recent evidence supports the use of prosthetic reinforcement material during laparoscopic hiatal hernia repair; however, the search for appropriate prosthetic materials is still under investigation. In this article, the technical feasibility and the short-term outcomes of the use of polyester composite mesh for crural reinforcement was determined. A small series of patients with large paraesophageal hiatal hernias underwent laparoscopic repair with mesh (5 males; mean age = 62 +/- 10 years; mean body mass index = 29 +/- 1 kg/m2, and mean American Society of Anesthesiologists = 3 +/- .4). There were no postoperative complications, deaths, or evidence of hernia recurrence documented by barium study at a median follow-up of 9 months. The use of the polyester composite mesh is technically feasible, has excellent intracorporeal handling characteristics, and holds suture readily. The short-term outcomes of the use of the polyester composite mesh for paraesophageal hernia repair reinforcement appeared to be favorable and are encouraging.


docid: osifkqxl

title: Preliminary information on prevention of infections caused by SARS-COV-2 virus in endoscopic laboratories.

text: INTRODUCTION On 11 March 2020, the Director-General of the World Health Organization (WHO) announced COVID-19 (Coronavirus Disease 2019) as a global pandemic Currently, no vaccines are available and there is little evidence of the efficacy of potential therapeutic agents. Furthermore, there is presumably no pre-existing immunity in the population to the new coronavirus, and it is as-sumed that everyone in the population is susceptible. OBJECTIVE The aim of the procedures described in the article is to minimize the risk of human-to-human transmission of the SARS-CoV-2 (Severe acute respiratory syndrome - coronavirus 2) virus during procedures carried out in endoscopic laboratories. BRIEF DESCRIPTION OF THE STATE OF THE ART SARS-CoV-2 infection can be asymptomatic, cause severe pneumonia, or lead to death. Symptoms of COVID-19 range from none (asymptomatic) to severe pneumonia and it can be fatal. Case studies to-date indicate that this infection causes a mild illness (i.e. pneumonia or mild pneumonia) in approximately 80% of cases, and most cases recove; 14% have a more severe illness, 6% experience a critical illness. The vast majority of the most serious illnesses and deaths have occurred among the elderly and people with other chronic underlying diseases. Average progression times include: • in mild cases: from the onset of symptoms to recovery in almost 2 weeks; • in severe cases: from the onset of symptoms to recovery in 3-6 weeks, and from symptoms to death in 2-8 weeks. CONCLUSIONS Special precautions should be taken and procedures followed when performing invasive medical procedures in endoscopic laboratories in patients with specific or clinically probable SARS-CoV-2 infection. This article contains up-to-date information as at 04/04/2020.