title: RNA pseudoknots and the regulation of protein synthesis.

text: RNA pseudoknots are structural elements found in almost all classes of RNA. Pseudoknots form when a single-stranded region in the loop of a hairpin base-pairs with a stretch of complementary nucleotides elsewhere in the RNA chain. This simple folding strategy is capable of generating a large number of stable three-dimensional folds that display a diverse range of highly specific functions in a variety of biological processes. The present review focuses on pseudoknots that act in the regulation of protein synthesis using cellular and viral examples to illustrate their versatility. Emphasis is placed on structurally well-defined pseudoknots that play a role in internal ribosome entry, autoregulation of initiation, ribosomal frameshifting during elongation and trans-translation.


title: Structures of PI4KIIIβ complexes show simultaneous recruitment of Rab11 and its effectors.

text: Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses. However, the structural basis for coordination of PI4K, GTPases, and their effectors is unknown. Here, we describe structures of PI4Kβ (PI4KIIIβ) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIβ interface is distinct compared with known structures of Rab complexes and does not involve switch regions used by GTPase effectors. Our data provide a mechanism for how PI4KIIIβ coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIβ to combat malaria.


title: Yersinia pestis can reside in autophagosomes and avoid xenophagy in murine macrophages by preventing vacuole acidification.

text: Yersinia pestis survives and replicates in phagosomes of murine macrophages. Previous studies demonstrated that Y. pestis-containing vacuoles (YCVs) acquire markers of late endosomes or lysosomes in naïve macrophages and that this bacterium can survive in macrophages activated with the cytokine gamma interferon. An autophagic process known as xenophagy, which destroys pathogens in acidic autophagolysosomes, can occur in naïve macrophages and is upregulated in activated macrophages. Studies were undertaken here to investigate the mechanism of Y. pestis survival in phagosomes of naïve and activated macrophages and to determine if the pathogen avoids or co-opts autophagy. Colocalization of the YCV with markers of autophagosomes or acidic lysosomes and the pH of the YCV were determined by microscopic imaging of infected macrophages. Some YCVs contained double membranes characteristic of autophagosomes, as determined by electron microscopy. Fluorescence microscopy showed that approximately 40% of YCVs colocalized with green fluorescent protein (GFP)-LC3, a marker of autophagic membranes, and that YCVs failed to acidify below pH 7 in naïve macrophages. Replication of Y. pestis in naïve macrophages caused accumulation of LC3-II, as determined by immunoblotting. While activation of infected macrophages increased LC3-II accumulation, it decreased the percentage of GFP-LC3-positive YCVs (approximately 30%). A viable count assay showed that Y. pestis survived equally well in macrophages proficient for autophagy and macrophages rendered deficient for this process by Cre-mediated deletion of ATG5, revealing that this pathogen does not require autophagy for intracellular replication. We conclude that although YCVs can acquire an autophagic membrane and accumulate LC3-II, the pathogen avoids xenophagy by preventing vacuole acidification.


Tracheal intubation of patients with COVID-19: global risks.


title: Elective procedures for prostate cancer in the time of Covid-19: a multidisciplinary team experience.

text: On March 29th 2020, 97,689 cases of COVID-19 have been diagnosed only in Italy, with 73,880 actually positive cases, a daily increase of 3815 cases, 27,386 hospitalized and 3906 patients in intensive care units, causing a total of 10,779 known deaths. In all urological departments, quickly inpatient and outpatient services have been significantly reduced. Even in this COVID-19 situation, urological neoplasm care must go on, but significant changes need to be made in the way some care is delivered. We compared diagnostic and therapeutic elective procedures requested and performed for PC management from our multidisciplinary team (MDT) during 1 month activity in the highest national level of COVID-19 infection (March 2020) and under restrictions for all the population, with the management performed in a no-COVID-19 month (March 2019) 1 year ago. The only management that did not received a significant reduction are medical therapies for advanced hormone sensitive (HS) or castration resistant (CR) PC. We describe our MDT identifications of elective undeferrable PC management in this COVID-19 time. These suggestions have been considered for a country (ITALY) under a rapid increase of COVID-19 cases and complications, but in a region with an actual lower impact (2914 actual positive and 1079 hospitalized cases) from the infection and in an hospital not completely converted to COVID-19 management. Indications should be different and restricted only to emergencies on the basis of COVID-19 pandemic situation and hospital involvement.


title: Transmission in the Origins of Bacterial Diversity, From Ecotypes to Phyla.

text: Any two lineages, no matter how distant they are now, began their divergence as one population splitting into two lineages that could coexist indefinitely. The rate of origin of higher-level taxa is therefore the product of the rate of speciation times the probability that two new species coexist long enough to reach a particular level of divergence. Here I have explored these two parameters of disparification in bacteria. Owing to low recombination rates, sexual isolation is not a necessary milestone of bacterial speciation. Rather, irreversible and indefinite divergence begins with ecological diversification, that is, transmission of a bacterial lineage to a new ecological niche, possibly to a new microhabitat but at least to new resources. Several algorithms use sequence data from a taxon of focus to identify phylogenetic groups likely to bear the dynamic properties of species. Identifying these newly divergent lineages allows us to characterize the genetic bases of speciation, as well as the ecological dimensions upon which new species diverge. Speciation appears to be least frequent when a given lineage has few new resources it can adopt, as exemplified by photoautotrophs, C1 heterotrophs, and obligately intracellular pathogens; speciation is likely most rapid for generalist heterotrophs. The genetic basis of ecological divergence may determine whether ecological divergence is irreversible and whether lineages will diverge indefinitely into the future. Long-term coexistence is most likely when newly divergent lineages utilize at least some resources not shared with the other and when the resources themselves will coexist into the remote future.


title: Laboratory Biosafety Considerations of SARS-CoV-2 at Biosafety Level 2.

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen that causes coronavirus disease 2019 (COVID-19), which was first detected in Wuhan, China. Recent studies have updated the epidemiologic and clinical characteristics of COVID-19 continuously. In China, diagnostic tests and laboratory tests of specimens from persons under investigation are usually performed in a biosafety level 2 environment. Laboratory staff may be at greater risk of exposure due to a higher concentration and invasiveness of emerging pathogens. Current infection prevention strategies are based on lessons learned from severe acute respiratory syndrome, expert judgments, and related regulations. This article summarizes biosafety prevention and control measures performed in severe acute respiratory syndrome coronavirus 2 testing activities and provides practical suggestions for laboratory staff to avoid laboratory-acquired infections in dealing with public health emergencies.


title: Activities of Thrombin and Factor Xa Are Essential for Replication of Hepatitis E Virus and Are Possibly Implicated in ORF1 Polyprotein Processing.

text: Hepatitis E virus (HEV) is a clinically important positive-sense RNA virus. The ORF1 of HEV encodes a nonstructural polyprotein of 1,693 amino acids. It is not clear whether the ORF1 polyprotein (pORF1) is processed into distinct enzymatic domains. Many researchers have attempted to understand the mechanisms of pORF1 processing. However, these studies gave various results and could never convincingly establish the mechanism of pORF1 processing. In this study, we demonstrated the possible role of thrombin and factor Xa in pORF1 processing. We observed that the HEV pORF1 polyprotein bears conserved cleavage sites of thrombin and factor Xa. Using a reverse genetics approach, we demonstrated that an HEV replicon having mutations in the cleavage sites of either thrombin or factor Xa could not replicate efficiently in cell culture. Further, we demonstrated in vitro processing when we incubated recombinant pORF1 fragments with thrombin, and we observed the processing of pORF1 polyprotein. The treatment of a liver cell line with a serine protease inhibitor as well as small interfering RNA (siRNA) knockdown of thrombin and factor Xa resulted in significant reduction in the replication of HEV. Thrombin and factor Xa have been well studied for their roles in blood clotting. Both of these proteins are believed to be present in the active form in the blood plasma. Interestingly, in this report, we demonstrated the presence of biologically active thrombin and factor Xa in a liver cell line. The results suggest that factor Xa and thrombin are essential for the replication of HEV and may be involved in pORF1 polyprotein processing of HEV.IMPORTANCE Hepatitis E virus (HEV) causes a liver disorder called hepatitis in humans, which is mostly an acute and self-limiting infection in adults. A high mortality rate of about 30% is observed in HEV-infected pregnant women in developing countries. There is no convincing opinion about HEV ORF1 polyprotein processing owing to the variability of study results obtained so far. HEV pORF1 has cleavage sites for two host cellular serine proteases, thrombin and factor Xa, that are conserved among HEV genotypes. For the first time, this study demonstrated that thrombin and factor Xa cleavage sites on HEV pORF1 are obligatory for HEV replication. Intracellular biochemical activities of the said serine proteases are also essential for efficient HEV replication in cell culture and must be involved in pORF1 processing. This study sheds light on the presence and roles of clotting factors with respect to virus replication in the cells.


title: A personal historical perspective of HIV.

text: All animal life on earth is thought to have a common origin and have common genetic mechanisms. Evolution has enabled differentiation of species. Pathogens likewise have evolved within various species and mostly come to a settled dynamic equilibrium such that co-existence results (pathogens ideally should not kill their hosts). Problems arise when pathogens jump species because the new host had not developed any resistance. These infections from related species are known as zoonoses. COVID-19 is the latest example of a virus entering another species but HIV (and various strains of influenza) were previous examples.


docid: qymkvfkq

title: Ultrasound assessment of subglottic region for estimation of appropriate endotracheal tube size in pediatric anesthesia.

text: BACKGROUND AND AIMS Endotracheal tube (ETT) selection in pediatric patients is mainly done with the age, height, or weight-based formula. We compared ultrasound assessment of the subglottic area to predict the outer diameter of the ETT, with that of modified Cole's formula. The aim of the study is to compare the appropriateness of uncuffed ETT selection based on modified Cole's formula with that of ultrasound assessment method of subglottic diameter in children undergoing surgical procedures under general anesthesia. MATERIAL AND METHODS This is a prospective, randomized, parallel group study. One hundred and fifty American Society of Anesthesiologists I and II patients of age 2-6 years were randomly allotted into two groups: Group A - ETT selection based on ultrasound assessment of subglottic diameter. Group B - ETT selection based on modified Cole's formula. The study parameters are the internal diameter and external diameter (OD) of the predicted ETT by the two methods and that of the appropriate size ETT used. RESULTS The incidence of appropriate tube selection was 74.7% in the ultrasound based group while it was 45.3% in the modified Cole's formula group. There was a strong correlation between OD of the optimal ETT used and the ultrasound assessed subglottic diameter. Bland-Altman analysis of OD of appropriately sized ETT and subglottic diameter by ultrasound assessment has a bias of 0.02 mm with limits of agreement of +1.78 to -1.74. CONCLUSION Ultrasonographic assessment of the subglottic diameter at the cricoid region is a better tool in predicting the appropriate size uncuffed ETT than modified Cole's formula.


title: The Spatial Allocation of Hospitals With Negative Pressure Isolation Rooms in Korea: Are We Prepared for New Outbreaks?

text: BACKGROUND Allocation of adequate healthcare facilities is one of the most important factors that public health policymakers consider when preparing for infectious disease outbreaks. Negative pressure isolation rooms (NPIRs) are one of the critical resources for control of infectious respiratory diseases, such as the novel coronavirus disease 2019 (COVID-19) outbreak. However, there is insufficient attention to efficient allocation of NPIR-equipped hospitals. METHODS We aim to explore any insufficiency and spatial disparity of NPIRs in South Korea in response to infectious disease outbreaks based on a simple analytic approach. We examined the history of installing NPIRs in South Korea between the severe acute respiratory syndrome (SARS) outbreak in 2003 and the Middle East respiratory syndrome coronavirus (MERS-Cov) in 2015 to evaluate the allocation process and spatial distribution of NPIRs across the country. Then, for two types of infectious diseases (a highly contagious disease like COVID-19 vs. a hospital-based transmission like MERS-Cov), we estimated the level of disparity between NPIR capacity and demand at the sub-regional level in South Korea by applying the two-step floating catchment area (2SFCA) method. RESULTS Geospatial information system (GIS) mapping reveals a substantial shortage and misallocation of NPIRs, indicating that the Korean government should consider a simple but evidence-based spatial method to identify the areas that need NPIRs most and allocate funds wisely. The 2SFCA method suggests that, despite the recent addition of NPIRs across the country, there should still be more NPIRs regardless of the spread pattern of the disease. It also illustrates high levels of regional disparity in allocation of those facilities in preparation for an infectious disease, due to the lack of evidence-based approach. CONCLUSION These findings highlight the importance of evidence-based decision-making processes in allocating public health facilities, as misallocation of facilities could impede the responsiveness of the public health system during an epidemic. This study provides some evidence to be used to allocate the resources for NPIRs, the urgency of which is heightened in the face of rapidly evolving threats from the novel COVID-19 outbreak.


Total gastrectomy for locally advanced cancer: the pure laparoscopic approach.


title: Complete video-assisted thoracoscopic surgery lobectomy and its learning curve. A single center study introducing the technique in The Netherlands.

text: Data regarding the benefits for the complete video-assisted thoracic surgery (c-VATS) lobectomy over the open lobectomy are numerous. This article describes the experience of introducing this technique in a training hospital, the first reported cohort in The Netherlands. From March 2006 to November 2008, all patients operated on for proven or suspected lung cancer were analyzed. Prospective data from these patients were evaluated. A subgroup analysis for the c-VATS lobectomy is presented. A total of 184 operations were performed on 172 patients. In 122 (66.3%) of the operations the resection ended in a lobectomy of which 70 were done by complete thoracoscopic procedure. For the c-VATS lobectomy the mean operating time was 179 min, with a mean blood loss of 444 ml. The median hospital stay was four days. Complications were present in 10% of c-VATS lobectomies. No mortality was seen in the c-VATS group. After thorough evaluation and training, c-VATS lobectomy is a safe procedure that can be performed in a relatively low volume hospital. It has exceptional short-term benefits. For training purposes all operations must start thoracoscopically. All patients must be operated according the intention to treat method.


title: The Silk flow-diverter stent for endovascular treatment of intracranial aneurysms.

text: Flow diverter (FD) stents represent a new endovascular technique developed for the treatment of complex intracranial aneurysms (wide neck, fusiform, large, and giant aneurysms) that are challenging for classic endovascular techniques such as coiling, balloon-assisted coiling and stent-assisted coiling. Low porosity, high metal coverage, and high pore density are the main properties of FD stents. These properties induce hemodynamic changes redirecting the blood flow away from the aneurysm and into the parent artery leading to gradual thrombosis of the aneurysm. FD stents also provide scaffolding for subsequent neoendothelial proliferation, and vessel wall remodeling. This is considered as a paradigm shift compared to prior endovascular methods, which predominantly aimed at providing treatment inside the aneurysmal sac. This paper describes in detail the first released FD stent, the Silk flow-diverter stent (Balt Extrusion, Montmorency, France), its mechanism of action and deployment technique. It reviews the pertinent literature regarding safety, efficacy and potential risks and complications associated with the use of this stent.


COVID-19 Research in Brief: 24 April to 1 May, 2020.


Clozapine and COVID-19.


title: Single-stage laparoscopic adrenalectomy for pheochromocytoma and enucleation of a pancreatic neuroendocrine tumor in Von Hippel-Lindau disease: A case report.

text: Von Hippel-Lindau (VHL) disease is an inherited syndrome with autosomal-dominant transmission, characterized by central nervous system and retinal hemangioblastomas, visceral cysts and tumors. Optimal surgical treatment, including its timing, remains a controversial topic. The present study reports the case of a 67-year-old female patient with adrenal and pancreatic manifestations of VHL. A laparoscopic cortex-sparing left adrenalectomy for a 4-cm pheochromocytoma and pancreatic enucleation for pancreatic polypeptidoma of the pancreas tail were performed during the same operative procedure. The total operative time was 240 min. There were no operative complications, and the surgery was completed laparoscopically with minimal blood loss. A prolonged hospital stay was necessary to treat a grade C postoperative pancreatic fistula. The histopathological result was an adrenal pheochromocytoma and a well-differentiated neuroendocrine tumor, secreting pancreatic polypeptides. In conclusion, organ-sparing laparoscopic surgery is an important option for treating simultaneous lesions in several abdominal solid viscera, such as VHL disease, and the present case study represents, to the best of the authors' knowledge, the first report of single-stage laparoscopic adrenalectomy and pancreatic tumor enucleation.


Nosocomial transmission of severe acute respiratory syndrome: better quality of evidence is needed.


title: Creating visual explanations improves learning.

text: Many topics in science are notoriously difficult for students to learn. Mechanisms and processes outside student experience present particular challenges. While instruction typically involves visualizations, students usually explain in words. Because visual explanations can show parts and processes of complex systems directly, creating them should have benefits beyond creating verbal explanations. We compared learning from creating visual or verbal explanations for two STEM domains, a mechanical system (bicycle pump) and a chemical system (bonding). Both kinds of explanations were analyzed for content and learning assess by a post-test. For the mechanical system, creating a visual explanation increased understanding particularly for participants of low spatial ability. For the chemical system, creating both visual and verbal explanations improved learning without new teaching. Creating a visual explanation was superior and benefitted participants of both high and low spatial ability. Visual explanations often included crucial yet invisible features. The greater effectiveness of visual explanations appears attributable to the checks they provide for completeness and coherence as well as to their roles as platforms for inference. The benefits should generalize to other domains like the social sciences, history, and archeology where important information can be visualized. Together, the findings provide support for the use of learner-generated visual explanations as a powerful learning tool.


title: Targeting somatostatin receptors: preclinical evaluation of novel 18F-fluoroethyltriazole-Tyr3-octreotate analogs for PET.

text: UNLABELLED The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors has been increasing over the past 3 decades. Because of high densities of somatostatin receptors (sstr)--mainly sstr-2--on the cell surface of these tumors, (111)In-diethylenetriaminepentaacetic acid-octreotide scintigraphy has become an important part of clinical management. (18)F-radiolabeled analogs with suitable pharmacokinetics would permit PET with more rapid clinical protocols. METHODS We compared the affinity in vitro and tissue pharmacokinetics by PET of 5 structurally related (19)F/(18)F-fluoroethyltriazole-Tyr(3)-octreotate (FET-TOCA) analogs: FET-G-polyethylene glycol (PEG)-TOCA, FETE-PEG-TOCA, FET-G-TOCA, FETE-TOCA, and FET-βAG-TOCA to the recently described (18)F-aluminum fluoride NOTA-octreotide ((18)F-AIF-NOTA-OC) and the clinical radiotracer (68)Ga-DOTATATE. RESULTS All (19)F-fluoroethyltriazole-Tyr(3)-octreotate compounds retained high agonist binding affinity to sstr-2 in vitro (half-maximal effective concentration, 4-19 nM vs. somatostatin at 5.6 nM). Dynamic PET showed that incorporation of PEG linkers, exemplified by (18)F-FET-G-PEG-TOCA and (18)F-FETE-PEG-TOCA, reduced uptake in high sstr-2-expressing AR42J pancreatic cancer xenografts. (18)F-FET-βAG-TOCA showed the lowest nonspecific uptake in the liver. Tumor uptake increased in the order (68)Ga-DOTATATE < (18)F-AIF-NOTA ≤ (18)F-FET-βAG-TOCA < (18)F-FET-G-TOCA. The uptake of (18)F-FET-βAG-TOCA was specific: a radiolabeled scrambled peptide, (18)F-FET-βAG-[W-c-(CTFTYC)K], did not show tumor uptake; there was lower uptake of (18)F-FET-βAG-TOCA in AR42J xenografts when mice were pretreated with 10 mg of unlabeled octreotide per kilogram; and there was low uptake of (18)F-FET-βAG-TOCA in low sstr-2-expressing HCT116 xenografts. CONCLUSION We have developed novel fluoroethyltriazole-Tyr(3)-octreotate radioligands that combine high specific binding with rapid target localization and rapid pharmacokinetics for high-contrast PET. (18)F-FET-βAG-TOCA and (18)F-FET-G-TOCA are candidates for future clinical evaluation.


[Combating coronavirus disease 2019: voice of critical care medicine].


title: Comparison of the major postoperative complications between laparoscopic distal and total gastrectomies for gastric cancer using Clavien-Dindo classification.

text: BACKGROUND Laparoscopy-assisted total gastrectomy (LATG) has not been as popular as laparoscopy-assisted distal gastrectomy (LADG) because of its undetermined safety and postoperative complications compared with LADG. Therefore, LATG requires further study. PATIENTS AND METHODS A total of 663 patients who underwent LADG or LATG for gastric cancer in a single institution from April 2004 to April 2014 were included. The clinicopathologic characteristics and risk factors related to major complications (Clavien-Dindo grade ≥ IIIa) were analyzed between the LADG (n = 569) and LATG groups (n = 94). RESULTS The incidence of major postoperative complications was significantly higher for LATG (LADG vs. LATG: 8.1 vs. 18.1 %, P = 0.002). Although postoperative bleeding was not different between the groups (3.2 vs. 3.2 %, P = 0.991), the incidence of bowel leakage was significantly higher for LATG (2.6 vs. 6.8 %, P = 0.028). Leakage from the anastomosis site was more frequent following LATG (5.3 %) compared with LADG (0.5 %) (P < 0.001). Leakage from the duodenal stump tended to be more frequent, though not significant, for LADG (2.0 vs. 1.1 %, P = 0.602). Advanced gastric cancer, LATG, and longer operation time were significant factors that affected the incidence of postoperative complications in a univariate analysis. In multivariate analysis, there were no independent risk factors, but LATG was nearly a significant, independent risk factor (odds ratio 1.89; 95 % CI 0.965-3.71, P = 0.063). CONCLUSION More major complications were observed for LATG, particularly with esophagojejunostomy. These results show that LATG is more invasive than LADG in terms of the postoperative morbidity. More caution and experience are needed when performing LATG.


title: Management of patients with COVID-19 in the medical ICU.

text: COVID-19 management practices devised for the medical intensive care unit (ICU) are centered on two main goals: ensuring caregiver safety and providing the highest quality patient care through adherence to evidence-based best practices. Rapid, sweeping changes for successful management are based on creating an educational platform to introduce and then further cement these concepts through a unified approach to clinical care. Creating a culture change in a short period of time requires overcoming a host of challenges; however, the result is a more unified and focused approach.


title: Low-impact laparoscopic cholecystectomy is associated with decreased postoperative morbidity in patients with sickle cell disease.

text: BACKGROUND Laparoscopic cholecystectomy (LC) is one of the most frequent surgeries performed in patients with sickle cell disease (SCD). LC in SCD patients is associated with a particularly high postoperative morbidity. The aim of the present study is to assess the safety and feasibility of cholecystectomy performed by mini-laparoscopy with low- and stable-pressure pneumoperitoneum (MLC + LSPP) and to compare the rate of postoperative SCD-related morbidity with standard LC. METHODS Thirty-five consecutive SCD patients admitted between November 2015 and March 2017 for cholelithiasis requiring surgery were compared with an historical cohort of 126 SCD patients who underwent LC for the same indication. Operative variables, postoperative outcomes, patient and surgeon satisfaction, and costs were evaluated. RESULTS MLC + LSPP exhibited a mean operative time comparable to LC (p = 0.169). Operative blood loss was significantly reduced in the MLC + LSPP group, and the suction device was rarely used (p = 0.036). SCD-related morbidity (including acute chest syndrome) was significantly higher in the LC group compared with the MLC + LSPP group (18.3 vs. 2.9%; p = 0.029). The mean times to resume ambulation (p = 0.018) and regular diet (p = 0.045) were significantly reduced in the MLC + LSPP group. The mean incision length (all trocars combined) was 28.22 mm for MLC + LSPP and 49.64 mm for LC patients (p < 0.0001). Multivariate regression analysis demonstrated that the only significant predictor of postoperative SCD-related morbidity was the surgical approach (odds ratio: 9.24). Patient and surgeon satisfaction were very high for MLC + LSPP. The mean total cost per patient (surgery and hospitalization) was not different between groups (p = 0.084). CONCLUSION MLC + LSPP in SCD patients appears to be safe and feasible. Compared with LC, MLC + LSPP in SCD patients is associated with a significantly reduced incidence of postoperative SCD-related morbidity and more rapid ambulation and return to regular diet without increasing the total costs per patient.


title: Putting It All Together: Clinical Considerations in the Care of Critically Ill Obstetric Patients with COVID-19.

text: Pregnant patients with severe acute respiratory syndrome coronavirus 2, the virus responsible for the clinical condition newly described in 2019 as coronavirus disease 2019 (COVID-19) and illness severity to warrant intensive care have a complex disease process that must involve multiple disciplines. Guidelines from various clinical societies, along with direction from local health authorities, must be considered when approaching the care of an obstetric patient with known or suspected COVID-19. With a rapidly changing landscape, a simplified and cohesive perspective using guidance from different clinical society recommendations regarding the critically-ill obstetric patient with COVID-19 is needed. In this article, we synthesize various high-level guidelines of clinical relevance in the management of pregnant patients with severe disease or critical illness due to COVID-19. KEY POINTS: · When caring for severely ill obstetric patients with coronavirus disease 2019 (COVID-19), one must be well versed in the complications that may need to be managed including, but not limited to adult respiratory distress syndrome with need for mechanical ventilation, approach to refractory hypoxemia, hemodynamic shock, and multiorgan system failure.. · Prone positioning can be done safely in gravid patients but requires key areas of support to avoid abdominal compression.. · For the critically ill obstetric patient with COVID-19, the focus should be on supportive care as a bridge to recovery rather than delivery as a solution to recovery..


title: Ebola Virus Stability on Surfaces and in Fluids in Simulated Outbreak Environments.

text: We evaluated the stability of Ebola virus on surfaces and in fluids under simulated environmental conditions for the climate of West Africa and for climate-controlled hospitals. This virus remains viable for a longer duration on surfaces in hospital conditions than in African conditions and in liquid than in dried blood.


title: Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED.

text: OBJECTIVE To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. METHODS We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. RESULTS Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%-4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60-0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45-54 years without additional risk factors to more than 10% in patients aged 75-84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59-0.63) and slightly underestimated major bleeding risk. CONCLUSIONS The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding.


title: Efficient isolation and chondrogenic differentiation of adult mesenchymal stem cells with fibrin microbeads and micronized collagen sponges.

text: BACKGROUND Mesenchymal stem cells (MSCs) have been demonstrated to potentially undergo chondrogenic differentiation. We propose a new matrix for stem cell-based chondrogenesis using dense fibrin microbeads (FMBs) combined with grounded dehydrothermally crosslinked collagen sponges (micronized collagen). METHODS In this study, MSCs were isolated from bone marrow of transgenic green fluorescent protein C57/Bl mice by FMBs in high yield. After 48 h in slowly rotating suspension culture, micronized collagen was added. RESULTS The cells on the FMBs migrated to the collagen pieces and formed aggregates that developed into cartilage-like structures. Following chondrogenic differentiation, alcian blue staining and collagen type II immunohistochemistry demonstrated the presence of chondrocytes in the 3D structures. PCR for the expression of aggrecan and collagen type II genes supported these findings. The in vitro structures that formed were used for ectopic subdermal implantation in wild-type C57/Bl mice. However, the chondrogenic markers faded relative to the pre-implant in vitro structures. CONCLUSION We propose that FMBs with micronized collagen could serve as a simple technology for MSC isolation and chondrogenesis as a basis for implantation.


title: Studies of the "chain reversal regions" of the avian sarcoma/leukosis virus (ASLV) and ebolavirus fusion proteins: analogous residues are important, and a His residue unique to EnvA affects the pH dependence of ASLV entry.

text: Most class I fusion proteins exist as trimers of dimers composed of a receptor binding and a fusion subunit. In their postfusion forms, the three fusion subunits form trimers of hairpins consisting of a central coiled coil (formed by the N-terminal helices), an intervening sequence, and a region containing the C helix (and flanking strands) that runs antiparallel to and packs in the grooves of the N-terminal coiled coil. For filoviruses and most retroviruses, the intervening sequence includes a "chain reversal region" consisting of a short stretch of hydrophobic residues, a Gly-Gly pair, a CX(6)CC motif, and a bulky hydrophobic residue. Maerz and coworkers (A. L. Maerz, R. J. Center, B. E. Kemp, B. Kobe, and P. Poumbourios, J. Virol. 74:6614-6621, 2000) proposed a model for this region of human T-cell leukemia virus type 1 (HTLV-1) Env in which expulsion of the final bulky hydrophobic residue is important for early conformational changes and specific residues in the chain reversal region are important for forming the final, stable trimer of hairpins. Here, we used mutagenesis and pseudovirus entry assays to test this model for the avian retrovirus avian sarcoma/leukosis virus (ASLV) and the filovirus ebolavirus Zaire. Our results are generally consistent with the model proposed for HTLV-1 Env. In addition, we show with ASLV EnvA that the bulky hydrophobic residue following the CX(6)CC motif is required for the step of prehairpin target membrane insertion, whereas other residues are required for the foldback step of fusion. We further found that a His residue that is unique to the chain reversal region of ASLV EnvA controls the pH at which ASLV entry occurs.


title: A Novel Window Technique Using CO2 Laser, and a Review of Methods for Nail Matrix Biopsy of Longitudinal Melanonychia.

text: BACKGROUND Nail matrix histopathological examination is essential to diagnose longitudinal melanonychia (LM). Several methods for nail matrix biopsy have been introduced but are often difficult to perform because of their invasiveness and technical difficulty. Therefore, a less invasive and novel biopsy technique is needed. OBJECTIVE To introduce a window technique for nail matrix biopsy. MATERIALS AND METHODS We retrospectively reviewed the medical records and histopathological specimens of patients with LM who underwent the window technique for nail matrix biopsy at our institution between September 2015 and December 2016. RESULTS Eleven cases from 10 patients with LM were subjected to our tailored window technique assisted by carbon dioxide (CO2) laser and dermoscopy. We performed nail plate dermoscopy to select the biopsy site and used CO2 laser to create the window in the proximal nail plate. Nail matrix pigmentation was carefully investigated using intraoperative dermoscopy. The technique established appropriate diagnosis in 11 LM cases, without significant complications, as follows: melanoma in situ (4 cases) and nail matrix activation (7 cases). CONCLUSION The window technique assisted by CO2 laser and dermoscopy can be a minimally invasive and effective method for nail matrix LM biopsy under local anesthesia.


title: On the future contents of a small journal of histochemistry.

text: In the last three years, more than 70,000 scientific articles have been published in peer reviewed journals on the application of histochemistry in the biomedical field: most of them did not appear in strictly histochemical journals, but in others dealing with cell and molecular biology, medicine or biotechnology. This proves that histochemistry is still an active and innovative discipline with relevance in basic and applied biological research, but also demonstrates that especially the small histochemical Journals should likely reconsider their scopes and strategies to preserve their authorship. A review of the last three years volumes of the European Journal of Histochemistry, taken as an example of a long-time established small Journal, confirmed that the published articles were widely heterogeneous in their topics and experimental models, as in this Journal's tradition. This strongly suggests that a Journal of histochemistry should keep its role as a forum open to an audience as broad as possible, publishing papers on cell and tissue biology in a wide variety of models. This will improve knowledge of the basic mechanisms of development and differentiation, while helping to increase the number of potential authors since scientists who generally do not use histochemistry in their research will find hints for the applications of histochemical techniques to novel still unexplored subjects.


Anesthesia and Alzheimer's disease: time to wake up!


Prevalence and Severity of Coronavirus Disease 2019 (COVID-19) Illness in Symptomatic Pregnant and Postpartum Women Stratified by Hispanic Ethnicity.


title: Autophagosome supports coxsackievirus B3 replication in host cells.

text: Recent studies suggest a possible takeover of host antimicrobial autophagy machinery by positive-stranded RNA viruses to facilitate their own replication. In the present study, we investigated the role of autophagy in coxsackievirus replication. Coxsackievirus B3 (CVB3), a picornavirus associated with viral myocarditis, causes pronounced intracellular membrane reorganization after infection. We demonstrate that CVB3 infection induces an increased number of double-membrane vesicles, accompanied by an increase of the LC3-II/LC3-I ratio and an accumulation of punctate GFP-LC3-expressing cells, two hallmarks of cellular autophagosome formation. However, protein expression analysis of p62, a marker for autophagy-mediated protein degradation, showed no apparent changes after CVB3 infection. These results suggest that CVB3 infection triggers autophagosome formation without promoting protein degradation by the lysosome. We further examined the role of the autophagosome in CVB3 replication. We demonstrated that inhibition of autophagosome formation by 3-methyladenine or small interfering RNAs targeting the genes critical for autophagosome formation (ATG7, Beclin-1, and VPS34 genes) significantly reduced viral replication. Conversely, induction of autophagy by rapamycin or nutrient deprivation resulted in increased viral replication. Finally, we examined the role of autophagosome-lysosome fusion in viral replication. We showed that blockage of the fusion by gene silencing of the lysosomal protein LAMP2 significantly promoted viral replication. Taken together, our results suggest that the host's autophagy machinery is activated during CVB3 infection to enhance the efficiency of viral replication.


The challenges and opportunities of teaching "generation y".


title: Preventing the soldiers of health care from becoming victims on the pandemic battlefield: respirators or surgical masks as the armor of choice.

text: The respiratory protective equipment necessary to protect health care workers from the novel swine-origin influenza A (H1N1) virus is not known. The knowledge gap created by this unanswered question has caused substantial debate and controversy on a global scale, leading public health organizations to feel pressured into issuing decisive recommendations despite a lack of supportive data. Changes in clinical practice caused by public health guidance during such high-profile events can be expected to establish a new standard of care. Also possible is an unforeseen gradual transition to widespread N95 respirator use, driven by public health pressures instead of science, for all outbreaks of influenza or influenza-like illness. Therefore, public health organizations and other influential institutions should take care to avoid making changes to established practice standards, if possible, unless these changes are bolstered by sound scientific evidence. Until definitive comparative effectiveness clinical trials are conducted, the answer to this question will continue to remain elusive. In the meantime, relying on ethical principles that have been substantiated over time may help guide public health and clinical decisions.


title: Beyond the uterine environment: a nonhuman primate model to investigate maternal-fetal and neonatal outcomes following chronic intrauterine infection.

text: BackgroundIntrauterine infection is a significant cause of early preterm birth. We have developed a fetal-neonatal model in the rhesus macaque to determine the impact of chronic intrauterine infection with Ureaplasma parvum on early neonatal reflexes and brain development.MethodsTime-mated, pregnant rhesus macaques were randomized to be inoculated with U. parvum (serovar 1; 105 c.f.u.) or control media at ~120 days' gestational age (dGA). Neonates were delivered by elective hysterotomy at 135-147 dGA (term=167d), stabilized, and cared for in our nonhuman primate neonatal intensive care unit. Neonatal reflex behaviors were assessed from birth, and fetal and postnatal brain magnetic resonance imaging (MRI) was performed.ResultsA total of 13 preterm and 5 term macaque infants were included in the study. Ten preterm infants survived to 6 months of age. U. parvum-infected preterm neonates required more intensive respiratory support than did control infants. MRI studies suggested a potential perturbation of brain growth and white matter maturation with exposure to intra-amniotic infection.ConclusionWe have demonstrated the feasibility of longitudinal fetal-neonatal studies in the preterm rhesus macaque after chronic intrauterine infection. Future studies will examine long-term neurobehavioral outcomes, cognitive development, neuropathology, and in vivo brain imaging to determine the safety of antenatal antibiotic treatment for intrauterine infection.


title: Staple line coverage after bullectomy for primary spontaneous pneumothorax: a randomized trial.

text: BACKGROUND Thoracoscopic wedge resection is generally accepted as a standard surgical procedure for primary spontaneous pneumothorax. Because of the relatively high recurrence rate after surgery, additional procedures such as mechanical pleurodesis or visceral pleural coverage are usually applied to minimize recurrence, although mechanical pleurodesis has some potential disadvantages. The aim of this study was to clarify whether an additional coverage procedure on the staple line after thoracoscopic bullectomy prevents postoperative recurrence compared with additional pleurodesis. METHODS A total of 1,414 patients in 11 hospitals with primary spontaneous pneumothorax undergoing thoracoscopic bullectomy were enrolled. After bullectomy with staplers, patients were randomly assigned to either the coverage group (n = 757) or the pleurodesis group (n = 657). In the coverage group, the staple line was covered with absorbable cellulose mesh and fibrin glue. The pleurodesis group underwent additional mechanical abrasion on the parietal pleura. RESULTS The coverage group and the pleurodesis group showed comparable surgical outcomes. After a median follow-up of 19.5 months, the postoperative 1-year recurrence rate was 9.5% in the coverage group and 10.7% in the pleurodesis group. The 1-year recurrence rate requiring intervention was 5.8% in the coverage group and 7.8% in the pleurodesis group. The coverage group showed better recovery from pain. CONCLUSIONS In terms of postoperative recurrence rate, visceral pleural coverage after thoracoscopic bullectomy was not inferior to mechanical pleurodesis. Visceral pleural coverage may potentially replace mechanical pleurodesis, which has potential disadvantages such as disturbed normal pleural physiology.


title: Self-Gripping Meshes for Lichtenstein Repair. Do We Need Additional Suture Fixation?

text: BACKGROUND The Lichtenstein repair is a frequently used treatment of inguinal hernias. In recent years, there has been an increasing tendency to apply self-gripping meshes (s.g). In many cases, additional suture of the mesh is carried out; however, it is uncertain what the benefits or potential risks of this actually are. METHODS The evaluation was undertaken on the basis of the Herniamed register, and covered all unilateral Lichtenstein operations between 01.09.2009 up to 30.09.2013. The analysis only included patients with whom s.g. meshes with resorbable micro hooks had been used (Progrip(®), Covidien) and who had undergone a full 1-year follow-up examination (80.15 %). RESULTS In total, 2095 patients were suitable for analysis, of which 816 (38.95 %) cases received an additional suture fixation (Fix). With increasing hernia size, more frequent fixation took place (29.97 % of hernias <1.5 cm vs. 46.65 % of hernias >3 cm, p < 0.001). The recurrence rates 1 year after surgery did not show any significant differences (Fix. 0.86 % vs. No Fix. 1.17 %; p = 0.661) with and without fixation, even when being adjusted for covariables. Likewise, no differences were noted in terms of postoperative complications (Fix. 5.15 % vs. No Fix. 5.08 %; p = 1.0). In addition, the numbers of patients needing to be treated after 1 year for chronic pain were also comparable (Fix. 2.33 % vs. No Fix. 2.97 %; p = 0.411). CONCLUSION Within the group that did not have additional suture fixation of self-gripping meshes (No Fix.), the length of operations was on average 8 min shorter (p < 0.001). No differences could be observed in terms of postoperative complications, treatment requiring chronic pain and recurrence rates.


title: Mechanism of Selective Enzyme Inhibition through Uncompetitive Regulation of an Allosteric Agonist.

text: Classical uncompetitive inhibitors are potent pharmacological modulators of enzyme function. Since they selectively target enzyme-substrate complexes (E:S), their inhibitory potency is amplified by increasing substrate concentrations. Recently, an unconventional uncompetitive inhibitor, called CE3F4R, was discovered for the exchange protein activated by cAMP isoform 1 (EPAC1). Unlike conventional uncompetitive inhibitors, CE3F4R is uncompetitive with respect to an allosteric effector, cAMP, as opposed to the substrate (i.e., CE3F4R targets the E:cAMP rather than the E:S complex). However, the mechanism of CE3F4R as an uncompetitive inhibitor is currently unknown. Here, we elucidate the mechanism of CE3F4R's action using NMR spectroscopy. Due to limited solubility and line broadening, which pose major challenges for traditional structural determination approaches, we resorted to a combination of protein- and ligand-based NMR experiments to comparatively analyze EPAC mutations, inhibitor analogs, and cyclic nucleotide derivatives that trap EPAC at different stages of activation. We discovered that CE3F4R binds within the EPAC cAMP-binding domain (CBD) at a subdomain interface distinct from the cAMP binding site, acting as a wedge that stabilizes a cAMP-bound mixed-intermediate. The mixed-intermediate includes attributes of both the apo/inactive and cAMP-bound/active states. In particular, the intermediate targeted by CE3F4R traps a CBD's hinge helix in its inactive conformation, locking EPAC into a closed domain topology that restricts substrate access to the catalytic domain. The proposed mechanism of action also explains the isoform selectivity of CE3F4R in terms of a single EPAC1 versus EPAC2 amino acid difference that destabilizes the active conformation of the hinge helix.


title: BTK inhibitors in cancer patients with COVID19: "The winner will be the one who controls that chaos" (Napoleon Bonaparte).

text: As the SARS-CoV-2 (COVID19) pandemic spreads and the number of Bruton's tyrosine kinase inhibitor (BTKi)-treated COVID19 affected patients grows, we must consider the pros and cons of BTKi discontinuation for our patients. In favor of BTKi continuation, BTK plays an active role in macrophage polarization. By modulating key transcription factors, BTK may regulate macrophage polarization downstream of classic M1 and M2 polarizing stimuli and mitigate the hyperinflammatory state associated with COVID19. In favor of BTKi discontinuation, we note a potentially increased risk of secondary infections or impaired humoral immunity. We hypothesize that the potential benefit of blunting a hyper-inflammatory response to SARS-CoV-2 through attenuation of M1 polarization outweighs the potential risk of impaired humoral immunity, not to mention the risk of rapid progression of B-cell malignancy following BTKi interruption. Based on this, we suggest continuing BTKi in patients with COVID19.


Acute Lower Gastrointestinal Bleeding.


docid: jsphdtod

title: Interaction of hydroxychloroquine with SARS-CoV2 functional proteins using all-atoms non-equilibrium alchemical simulations.

text: Using a combination of enhanced sampling molecular dynamics techniques and non-equilibrium alchemical transformations with full atomistic details, we have shown that hydroxychloroquine (HCQ) may act as a mild inhibitor of important functional proteins for SARS-CoV2 replication, with potency increasing in the series PLpro, 3CLpro, RdRp. By analyzing the bound state configurations, we were able to improve the potency for the 3CLpro target, designing a novel HCQ-inspired compound, named PMP329, with predicted nanomolar activity. If confirmed in vitro, our results provide a molecular rationale for the use of HCQ or of strictly related derivatives in the treatment of Covid-19.


title: Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis.

text: Transplantation of major histocompatibility complex-mismatched mouse neural precursor cells (NPCs) into mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in rapid rejection that is mediated, in part, by T cells. However, the contribution of the innate immune response to allograft rejection in a model of viral-induced neurological disease has not been well defined. Herein, we demonstrate that the natural killer (NK) cell-expressing-activating receptor NKG2D participates in transplanted allogeneic NPC rejection in mice persistently infected with JHMV. Cultured NPCs derived from C57BL/6 (H-2(b) ) mice express the NKG2D ligand retinoic acid early precursor transcript (RAE)-1 but expression was dramatically reduced upon differentiation into either glia or neurons. RAE-1(+) NPCs were susceptible to NK cell-mediated killing whereas RAE-1(-) cells were resistant to lysis. Transplantation of C57BL/6-derived NPCs into JHMV-infected BALB/c (H-2(d) ) mice resulted in infiltration of NKG2D(+) CD49b(+) NK cells and treatment with blocking antibody specific for NKG2D increased survival of allogeneic NPCs. Furthermore, transplantation of differentiated RAE-1(-) allogeneic NPCs into JHMV-infected BALB/c mice resulted in enhanced survival, highlighting a role for the NKG2D/RAE-1 signaling axis in allograft rejection. We also demonstrate that transplantation of allogeneic NPCs into JHMV-infected mice resulted in infection of the transplanted cells suggesting that these cells may be targets for infection. Viral infection of cultured cells increased RAE-1 expression, resulting in enhanced NK cell-mediated killing through NKG2D recognition. Collectively, these results show that in a viral-induced demyelination model, NK cells contribute to rejection of allogeneic NPCs through an NKG2D signaling pathway.


Telehealth in Oncology During the COVID-19 Outbreak: Bringing the House Call Back Virtually.


title: Jaw Opening Decreases Window to the Deep Parotid Lobe.

text: To describe the relationship between jaw opening and access to the deep parotid window, we identified the following distances in 10 human skulls: symphysis to angle of mandible, mastoid tip to angle of mandible, angle of mandible to condylar process, and mastoid tip to condylar process. With the jaw closed and open, these distances were measured with 1 to 3 wooden blocks, each measuring 1 cm, between the upper and lower incisors. The triangular deep parotid area formed by the last 3 distances was calculated. A repeated measures analysis of variance showed a significant decrease in the deep parotid area with increasing interincisal distance ( P < .01). A generalized estimating equation model demonstrated a statistically significant decreasing area of the deep parotid window with increasing interincisal distance. These results suggest that nasal intubation may improve access to the parotid window.


title: Multiple concurrent bilateral groin hernias in a single patient; a case report and a review of uncommon groin hernias: A possible source of persistent pain after successful repair.

text: INTRODUCTION The wide use of laparoscopy for groin hernia repair has unveiled "hidden hernias" silently residing in this area. During the open repair of the presenting hernia, the surgeon was often unaware of these occult hernias. These patients postoperatively may present with unexplained chronic groin or pelvic pain. PRESENTATION OF CASE Rare groin hernias are defined according to their anatomical position. Challenges in the diagnosis and management of occult rare groin hernias are discussed. These problems are illustrated by a unique case report of multiple (six) coexisting groin hernias, whereof five were occult and two were rare. DISCUSSION Rare groin hernias are uncommon because they are difficult to diagnose clinically and are not routinely looked for. They are often occult and may coexist with other inguinal hernias, thus posing a diagnostic and treatment challenge to the surgeon, especially if there is persistent groin pain after "successful" repair. MRI is the most accurate preoperative and postoperative diagnostic tool, if there is a clinical suspicion that the patient might have an occult hernia. CONCLUSION Preperitoneal endoscopic approach is the recommended method in confirming the diagnosis and management of occult groin hernias. A sound knowledge of groin anatomy and a thorough preperitoneal inspection of all possible sites for rare groin hernias are needed to diagnose and repair all defects. The preperitoneal mesh repair with adequate overlap of all hernia orifices is the recommended treatment of choice.


title: A cost-effective analysis of fibrin sealants versus no sealant following open right hemihepatectomy for colorectal liver metastases.

text: BACKGROUND There is paucity of data regarding the cost-effectiveness of fibrin sealants during liver surgery. This study aimed to assess the cost-effectiveness of fibrin sealants following right hemihepatectomy for colorectal liver metastases. METHOD A prospectively maintained database between 2004 and 2013 was reviewed to identify patients who underwent a right hemihepatectomy with and without fibrin sealant application. Perioperative and post-operative outcomes were analysed to assess its cost-effectiveness. RESULTS One hundred and sixty-three right hemihepatectomies were performed, of which 79 were in the fibrin sealant treatment group and 84 were in the no sealant group. No difference was seen between fibrin sealant and no sealant with regard to bile leak (P = 0.366), intra-abdominal collections (P = 0.200) and overall post-operative complications (P = 0.480). Operating costs were significantly cheaper in the no sealant group (P = 0.010). There was no difference seen in median post-operative stay between fibrin sealant versus no treatment (8 versus 9 days, P = 0.327), median total bed cost (£3900 versus £4300, P = 0.400), mean transfusion cost per patient (P = 0.201) and overall cost (£6706.15 versus £6555.80, P = 0.792). CONCLUSION Fibrin sealant application to cut surface during liver surgery confers no cost benefit and their routine use may not be recommended.


title: Distal Pancreatectomy Combined with Multivisceral Resection Is Associated with Postoperative Complication Rates and Survival Comparable to Those After Standard Procedures.

text: BACKGROUND For pancreatic tumors located in the body or tail of the pancreas, distal pancreatectomy (DP) remains the surgical procedure of choice to achieve radical tumor removal. Purpose of this study was to evaluate outcome and overall survival of patients who underwent DP combined with multivisceral resection (MVR). METHODS Retrospective single-center case-matched analysis. Between January 1994 and June 2014, 494 consecutive patients were entered into a prospective database, and 126 patients undergoing DP + MVR (cases) were matched with 126 patients undergoing DP (controls) for gender, age, and underlying final diagnosis. RESULTS There were no significant differences in patient demographics. Rates of postoperative pancreatic fistula (POPF) (36 (28.6%) vs. 29 (23.0%); p = 0.388) and postpancreatectomy hemorrhage (PPH) (7 (5.5%) vs. 5 (3.9%); p = 0.769) did not reveal any significant differences. Although operative time (237.8 ± 57.9 vs. 203.5 ± 34.5; p < 0.001) and the necessity for intraoperative transfusions (18 (14.3%) vs. 5 (4.0%); p < 0.001) was significantly higher, the number of patients with major complications (the Clavien-Dindo ≥ 3) was not increased (27 (19.8%) vs. 20 (15.9%); p = 0.332) in the DP + MVR group. Midterm survival analysis indicated no significant difference for adenocarcinoma and neuroendocrine tumors for either group. CONCLUSION DP + MVR is a feasible and safe surgical procedure to achieve radical tumor removal and can offer beneficial survival outcomes. Although operative time and intraoperative transfusions are enhanced, POPF, PPH, or major complications (the Clavien-Dindo ≥ 3) are not significantly increased after DP + MVR. DP + MVR can therefore be recommended in selected patients for resection of extended tumors within the concept of interdisciplinary strategies.


title: Estimation of the bispectral index by anesthesiologists: an inverse turing test.

text: BACKGROUND Processed electroencephalographic indices, such as the bispectral index (BIS), are potential adjuncts for assessing anesthetic depth. While BIS® monitors might aid anesthetic management, unprocessed or nonproprietary electroencephalographic data may be a rich source of information for clinicians. We hypothesized that anesthesiologists, after training in electroencephalography interpretation, could estimate the index of a reference BIS as accurately as a second BIS® monitor (twin BIS®) (Covidien Medical, Boulder, CO) when provided with clinical and electroencephalographic data. METHODS Two sets of electrodes connected to two separate BIS® monitors were placed on the foreheads of 10 surgical patients undergoing general anesthesia. Electroencephalographic parameters, vital signs, and end-tidal anesthetic gas concentrations were recorded at prespecified time points, and were provided to two sets of anesthesiologists. Ten anesthesiologists received brief structured training in electroencephalograph interpretation and 10 were untrained. Although electroencephalographic waveforms and open-source processed electroencephalograph metrics were provided from the reference BIS®, both groups were blinded to BIS values and were asked to estimate BIS. RESULTS The trained anesthesiologists averaged as close to or closer to the reference BIS® compared with the twin BIS® monitor for 34% of their BIS estimates versus 26% for the untrained anesthesiologists. Using linear mixed effects model analysis, there was a statistically significant difference between the trained and untrained anesthesiologists (P = 0.02), but no difference between the twin BIS® monitor and trained anesthesiologists (P = 0.9). CONCLUSION With limited electroencephalography training and access to clinical data, anesthesiologists can estimate the BIS almost as well as a second BIS® monitor. These results reinforce the potential utility of training anesthesia practitioners in unprocessed electroencephalogram interpretation.


title: Ebola in West Africa.

text: Ebola viral disease (EVD) is a severe and life-threatening disease. The current Ebola outbreak in West Africa entered its second year and is unprecedented because it is the largest one in history, involved urban centers and affected a large number of health care workers. It quickly escalated from medical into a humanitarian, social, economic, and security crisis. The primary pillars to prevent EVD are: early diagnosis, isolation of patients, contact tracing and monitoring, safe burials, infection prevention and control and social mobilization. The implementation of all these components was challenged in the field. Key lessons from this Ebola outbreak are that countries with weak health care systems can't withstand the major outbreaks; preparedness to treat the first confirmed cases is a national emergency; all control measures must be coordinated together and community engagement is the great factor to combat this disease.


title: VEGF-C and VEGF-C156S in the pro-lymphangiogenic growth factor therapy of lymphedema: a large animal study.

text: INTRODUCTION VEGF-C156S, a lymphangiogenesis-specific form of vascular endothelial growth factor C (VEGF-C), has been considered as a promising candidate for the experimental pro-lymphangiogenic treatment, as it lacks potential angiogenic effects. As a precursor to future clinical trials, the therapeutic efficacy and blood vascular side effects of VEGF-C and VEGF-C156S were compared in a large animal model of secondary lymphedema. Combination of lymphatic growth factor treatment and autologous lymph node transfer was used to normalize the lymphatic anatomy after surgical excision of lymphatic tissue. METHODS Lymph vessels around the inguinal lymph node of female domestic pigs were destroyed in order to impair the normal lymphatic drainage from the hind limb. Local injections of adenoviruses (Ad) encoding VEGF-C or VEGF-C156S were used to enhance the regrowth of the lymphatic vasculature. AdLacZ (β-galactosidase) and saline injections served as controls. RESULTS Both VEGF-C and VEGF-C156S induced growth of new lymphatic vessels in the area of excision, although lymphangiogenesis was notably stronger after VEGF-C treatment. Also the transferred lymph nodes were best-preserved in the VEGF-C-treated pigs. Despite the enlargement of blood vessels following the VEGF-C therapy, no signs of sprouting angiogenesis or increased blood vascular permeability in the form of increased wound exudate volumes were observed. CONCLUSIONS Our results show that VEGF-C provides the preferred alternative for growth factor therapy of lymphedema when compared to VEGF-C156S, due to the superior lymphangiogenic response and minor blood vessel effects. Furthermore, these observations suggest that activation of both VEGFR-2 and VEGFR-3 might be needed for efficient lymphangiogenesis.


Time to Purposefully Plan Ahead: A Call for Quality in Research.


title: Monopolar stray energy in robotic surgery.

text: INTRODUCTION Stray energy transfer from monopolar radiofrequency energy during laparoscopy can be potentially catastrophic. Robotic surgery is increasing in popularity; however, the risk of stray energy transfer during robotic surgery is unknown. The purpose of this study was to (1) quantify stray energy transfer using robotic instrumentation, (2) determine strategies to minimize the transfer of energy, and (3) compare robotic stray energy transfer to laparoscopy. METHODS In a laparoscopic trainer, a monopolar instrument (L-hook) was activated with DaVinci Si (Intuitive, Sunnyvale, CA) robotic instruments. A camera and assistant grasper were inserted to mimic a minimally invasive cholecystectomy. During activation of the L-hook, the non-electric tips of the camera and grasper were placed adjacent to simulated tissue (saline-soaked sponge). The primary outcome was change in temperature from baseline (°C) measured nearest the tip of the non-electric instrument. RESULTS Simulated tissue nearest the robotic grasper increased an average of 18.3 ± 5.8 °C; p < 0.001 from baseline. Tissue nearest the robotic camera tip increased (9.0 ± 2.1 °C; p < 0.001). Decreasing the power from 30 to 15 W (18.3 ± 5.8 vs. 2.6 ± 2.7 °C, p < 0.001) or using low-voltage cut mode (18.3 ± 5.8 vs. 3.1 ± 2.1 °C, p < 0.001) reduced stray energy transfer to the robotic grasper. Desiccating tissue, in contrast to open air activation, also significantly reduced stray energy transfer for the grasper (18.3 ± 5.8 vs. 0.15 ± 0.21 °C, p < 0.001) and camera (9.0 ± 2.1 vs. 0.24 ± 0.34 °C, p < 0.001). CONCLUSIONS Stray energy transfer occurs during robotic surgery. The assistant grasper carries the highest risk for thermal injury. Similar to laparoscopy, stray energy transfer can be reduced by lowering the power setting, utilizing a low-voltage cut mode instead of coagulation mode and avoiding open air activation. These practical findings can aid surgeons performing robotic surgery to reduce injuries from stray energy.


title: Evaluating and optimizing the consolidated framework for implementation research (CFIR) for use in low- and middle-income countries: a systematic review.

text: BACKGROUND The Consolidated Framework for Implementation Research (CFIR) is a determinants framework that may require adaptation or contextualization to fit the needs of implementation scientists in low- and middle-income countries (LMICs). The purpose of this review is to characterize how the CFIR has been applied in LMIC contexts, to evaluate the utility of specific constructs to global implementation science research, and to identify opportunities to refine the CFIR to optimize utility in LMIC settings. METHODS A systematic literature review was performed to evaluate the use of the CFIR in LMICs. Citation searches were conducted in Medline, CINAHL, PsycINFO, CINAHL, SCOPUS, and Web of Science. Data abstraction included study location, study design, phase of implementation, manner of implementation (ex., data analysis), domains and constructs used, and justifications for use, among other variables. A standardized questionnaire was sent to the corresponding authors of included studies to determine which CFIR domains and constructs authors found to be compatible with use in LMICs and to solicit feedback regarding ways in which CFIR performance could be improved for use in LMICs. RESULTS Our database search yielded 504 articles, of which 34 met final inclusion criteria. The studies took place across 21 countries and focused on 18 different health topics. The studies primarily used qualitative study designs (68%). Over half (59%) of the studies applied the CFIR at study endline, primarily to guide data analysis or to contextualize study findings. Nineteen (59%) of the contacted authors participated in the survey. Authors unanimously identified culture and engaging as compatible with use in global implementation research. Only two constructs, patient needs and resources and individual stages of change were commonly identified as incompatible with use. Author feedback centered on team level influences on implementation, as well as systems characteristics, such as health system architecture. We propose a "Characteristics of Systems" domain and eleven novel constructs be added to the CFIR to increase its compatibility for use in LMICs. CONCLUSIONS These additions provide global implementation science practitioners opportunities to account for systems-level determinants operating independently of the implementing organization. Newly proposed constructs require further reliability and validity assessments. TRIAL REGISTRATION PROSPERO, CRD42018095762.


docid: etgwlbro

title: Comparison of stent free cell area and cerebral lesions after unprotected carotid artery stent placement.

text: OBJECTIVE This study evaluates the correlation between closed, semi-closed and open-cell stent design and the association between stent type and clinical outcome as well as magnetic resonance imaging (MRI) findings. DESIGN A total of 194 patients who underwent unprotected carotid artery stenting (CAS) as well as diffusion-weighted magnetic resonance imaging (DW-MRI) before and after intervention were retrospectively reviewed. MATERIALS AND METHODS Three stent designs were studied: closed cell, semi-closed cell and open cell. Spearman's Rho test was performed between the stent free cell area and the number and area of ischaemic lesions found after intervention. Adverse events were evaluated. RESULTS There was no significant difference in clinical outcome between the three stent groups (Zilver, Cook Europe, Denmark; Smart, Codman, MA; and Wallstent, Stryker, MN, USA). A significant correlation was found between the stent free cell area and the number and area of new ischaemic lesions on DW-MRI (P = 0.023). There were significantly fewer new lesions with an open-cell design (Zilver; 12.76 mm(2) free cell area) than with a closed-cell design (Wallstent; 1.08 mm(2) free cell area). CONCLUSIONS Open-cell stent was related to a lower number and area of silent cerebral ischaemic lesions after unprotected CAS. However, clinical outcome, measured by incidence of adverse events and clinical neurologic assessment, was not significantly different between patients with different stent designs.


title: Resilience training for hospital workers in anticipation of an influenza pandemic.

text: BACKGROUND Well before the H1N1 influenza, health care organizations worldwide prepared for a pandemic of unpredictable impact. Planners anticipated the possibility of a pandemic involving high mortality, high health care demands, rates of absenteeism rising up to 20-30% among health care workers, rationing of health care, and extraordinary psychological stress. METHOD The intervention we describe emerged from the recognition that an expected influenza pandemic indicated a need to build resilience to maintain the health of individuals within the organization and to protect the capacity of the organization to respond to extraordinary demands. Training sessions were one component of a multifaceted approach to reducing stress through effective preparation and served as an evidence based platform for our hospital's response to the H1N1 pandemic. RESULTS The training was delivered to more than 1250 hospital staff representing more than 22 departments within the hospital. The proportion of participants who felt better able to cope after the session (76%) was significantly higher than the proportion who felt prepared to deal confidently with the pandemic before the session (35%). Ten key themes emerged from our qualitative analysis of written comments, including family-work balance, antiviral prophylaxis, and mistrust or fear towards health care workers. CONCLUSIONS Drawing on what we learned from the impact of SARS on our hospital, we had the opportunity to improve our organization's preparedness for the pandemic. Our results suggest that an evidence-based approach to interventions that target known mediators of distress and meet standards of continuing professional development is not only possible and relevant, but readily supportable by senior hospital administration.


Norovirus, gastroenteritis, and indoor environmental quality.


title: Treatment of weight regain following roux-en-Y gastric bypass: revision of pouch, creation of new gastrojejunostomy and placement of proximal pericardial patch ring.

text: In the literature, weight regain or failure of weight loss has been reported in up to 35% of patients after Roux-en-Y gastric bypass (RYGB). Several revisional procedures have been suggested to reinitiate further weight loss in this group of patients, and placing a silastic ring around the pouch proximal to the gastrojejunostomy is one among those procedures. The aim of our study is to evaluate and compare the safety and efficacy of salvage banding using a pericardial patch after RYGB for further weight loss. Between December 2009 and April 2013, a total of 46 patients underwent revision with pericardial patch ring after RYGB for weight regain/failure of weight loss. A retrospective review of a prospectively collected database was performed, noting the outcomes and complications of the procedure. The mean body mass index at the time of revision was 40.1 ± 6.8 kg/m2. Mean percentage of excess weight loss was 23.4 ± 15.7%, 39.0 ± 27.4%, and 18.9 ± 20.5% at 6, 12 and 24 months after revision, respectively. Eight (17.4%) patients required a total of 11 readmissions due to nausea, vomiting, dysphagia and abdominal pain. Six (13.0%) patients underwent a total of six reoperations, including four patients with laparoscopic removal of the pericardial patch and another revision of RYGB, and two patients with repair of perforated ulcers. Revision with pericardial patch ring after gastric bypass for weight regain or failure of weight loss may not be feasible, safe and effective.


title: Ecoepidemics overcoming the species barrier and being subject to harvesting.

text: An ecoepidemiological model in which the disease can be transmitted from one population to another one is considered. Linear harvesting on all the populations is considered. By means of numerical simulations, the role of the epidemiological parameters as well as that of harvesting are investigated. Some relevant consequences of harvesting on the system dynamics are discovered.


title: Coming to terms with nonsteroidal anti-inflammatory drug gastropathy.

text: Despite well known complications, oral nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most commonly prescribed medications in the US for musculoskeletal disorders such as osteoarthritis. Although there has been a recent focus on the cardiovascular and renal complications associated with these agents, NSAID gastropathy continues to be a particular concern in many patients, especially those at increased risk for serious adverse events, including the elderly. Complicating the diagnosis of NSAID gastropathy is its silent course, which, up to half of the time, is asymptomatic. Several strategies are currently employed by physicians to mitigate the risk of serious gastrointestinal events. These include either addition of a proton pump inhibitor to current nonselective NSAID therapy or the use of a cyclo-oxygenase-2-selective NSAID. Although these agents are effective at mitigating the overall risk of gastrointestinal adverse events, they fail to address NSAID-related cardiovascular and renal risks. Due to their reduced systemic absorption, topical NSAIDs may present a viable option for patients at increased risk for serious NSAID-related adverse events, including gastropathy.


title: Using transcranial magnetic stimulation to map the cortical representation of lower-limb muscles.

text: Objective To evaluate the extent to which transcranial magnetic stimulation (TMS) can identify discrete cortical representation of lower-limb muscles in healthy individuals. Methods Motor evoked potentials were recorded from resting vastus medialis, rectus femoris, vastus lateralis, medial and lateral hamstring, and medial and lateral gastrocnemius muscles on the right leg of 16 young healthy adults using bipolar surface electrodes. TMS was delivered through a 110-mm double-cone coil at 63 sites over the left hemisphere. Location and size of cortical representation and number of discrete peaks were quantified. Results Within the quadriceps group there was a main effect of muscle on anterior-posterior centre of gravity (p = 0.010), but the magnitude of the difference was small. There was also a main effect of muscle on medial-lateral hotspot (p = 0.027) and map volume (p = 0.047), but no post-hoc tests were significant. The topography of each lower-limb muscle was complex and variable across individuals. Conclusions TMS delivered with a 110-mm double-cone coil could not reliably identify discrete cortical representations of resting lower-limb muscles when responses were measured using bipolar surface electromyography. Significance The characteristics of the cortical representation provide a basis against which to evaluate cortical reorganisation in clinical populations.


title: Stereotactic radiofrequency ablation.

text: PURPOSE To describe the technique of percutaneous stereotactic radiofrequency ablation (SRFA) and its application in a patient with an unresectable multifocal intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS A 72-year-old man presented with two nodules of an ICC with a maximum diameter of 10 and 4 cm, respectively. To produce overlapping ablation areas and cover the entire tumor volume, 18 paths for the placement of radiofrequency ablation (RFA) probes at multiple locations were planned on 2D and 3D reconstructions of the computed tomographic (CT) data. The 15-gauge coaxial needles were advanced through the aiming device to the preplanned depth. A control CT fused to the planning CT data confirmed correct needle placements. RFA was performed with an impedance-based multiple-electrode RFA system. Fusion of the contrast-enhanced control CT with the planning CT showed an appropriate zone of ablation. RESULTS Besides a mild asymptomatic pleural effusion, no complications occurred. Twenty-seven months after the first RFA, two new small distant liver metastases were successfully treated by SRFA. Currently, 38 months after diagnosis and 36 months after the first SRFA, the patient is free of detectable disease. CONCLUSION SRFA seems to offer an effective treatment option in selected patients with even unresectable ICC.


Reply to: doi: 10.1007/s00464-013-3111-4: TEM or TAMIS: what is the future of transanal endoscopic surgery?


title: Predictors of functional dependence despite successful revascularization in large-vessel occlusion strokes.

text: BACKGROUND AND PURPOSE High revascularization rates in large-vessel occlusion strokes treated by mechanical thrombectomy are not always associated with good clinical outcomes. We evaluated predictors of functional dependence despite successful revascularization among patients with acute ischemic stroke treated with thrombectomy. METHODS We analyzed the pooled data from the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO), and TREVO 2 trials. Successful revascularization was defined as thrombolysis in cerebral infarction score 2b or 3. Functional dependence was defined as a score of 3 to 6 on the modified Rankin Scale at 3 months. We assessed relationship of demographic, clinical, angiographic characteristics, and hemorrhage with functional dependence despite successful revascularization. RESULTS Two hundred and twenty-eight patients with successful revascularization had clinical outcome follow-up. The rates of functional dependence with endovascular success were 48.6% for Trevo thrombectomy and 58.0% for Merci thrombectomy. Age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06 per 1-year increase), National Institutes of Health Stroke Scale score (odds ratio, 1.08; 95% confidence interval, 1.02-1.15 per 1-point increase), and symptom onset to endovascular treatment time (odds ratio, 1.11; 95% confidence interval, 1.01-1.22 per 30-minute delay) were predictors of functional dependence despite successful revascularization. Symptom onset to reperfusion time beyond 5 hours was associated with functional dependence. All subjects with symptomatic intracranial hemorrhage had functional dependence. CONCLUSIONS One half of patients with successful mechanical thrombectomy do not have good outcomes. Age, severe neurological deficits, and delayed endovascular treatment were associated with functional dependence despite successful revascularization. Our data support efforts to minimize delays to endovascular therapy in patients with acute ischemic stroke to improve outcomes. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00318071, NCT01088672, and NCT01270867.


title: Detection and Occurrence of Indicator Organisms and Pathogens.

text: This review summarizes the literature pertaining to the occurrence and detection of indicator organisms and pathogens published during 2014. It is organized into the following sections: i) detection and quantification of fecal indicators and waterborne pathogens, ii) microbial source tracking (MST) using genotypic and phenotypic methods, iii) antibiotic resistant bacteria (ARB), iv) live vs. dead cell differentiation methods, and v) next generation sequencing (NGS).


David Oliver: Covid-19 has highlighted the NHS's strengths and weaknesses.


title: A systematic review of non-pharmacological interventions to improve nighttime sleep among residents of long-term care settings.

text: BACKGROUND Disturbances in sleep and circadian rhythms are common among residents of long-term care facilities. In this systematic review, we aim to identify and evaluate the literature documenting the outcomes associated with non-pharmacological interventions to improve nighttime sleep among long-term care residents. METHODS The Preferred Reporting Items for Systematic Reviews guided searches of five databases (MEDLINE, Embase, CINAHL, Scopus, and Cochrane Library) for articles reporting results of experimental or quasi-experimental studies conducted in long-term care settings (nursing homes, assisted-living facilities, or group homes) in which nighttime sleep was subjectively or objectively measured as a primary outcome. We categorized each intervention by its intended use and how it was administered. RESULTS Of the 54 included studies evaluating the effects of 25 different non-pharmacological interventions, more than half employed a randomized controlled trial design (n = 30); the others used a pre-post design with (n = 11) or without (n = 13) a comparison group. The majority of randomized controlled trials were at low risk for most types of bias, and most other studies met the standard quality criteria. The interventions were categorized as environmental interventions (n = 14), complementary health practices (n = 12), social/physical stimulation (n = 11), clinical care practices (n = 3), or mind-body practices (n = 3). Although there was no clear pattern of positive findings, three interventions had the most promising results: increased daytime light exposure, nighttime use of melatonin, and acupressure. CONCLUSIONS Non-pharmacological interventions have the potential to improve sleep for residents of long-term care facilities. Further research is needed to better standardize such interventions and provide clear implementation guidelines using cost-effective practices.


title: Immunosuppression drug advice and COVID-19: are we doing more harm than good?

text: The National Institute for Health and Care Excellence guidelines advise stopping immunosuppressive drugs for confirmed or suspected COVID-19 patients with autoimmune and inflammatory disorders. This may not be in the patient's best interest, given the potential long-term consequences of not managing chronic conditions, and immunosuppression may even be protective in those affected with COVID-19.


title: Management of facial trauma: lessons of war.

text: Soft tissue trauma of the head and neck is encountered frequently by the battlefield head and neck surgeon. Repair of the soft tissue (as well as bony fractures) of the head and neck is undertaken with the intent of providing return of form and function to the injured patient. Aggressive management of head and neck wounds is necessary to prevent excessive tissue loss due to ischemia or infection. Fortunately, the battlefield head and neck surgeon is armed with an array of surgical advances including local, regional, and free tissue grafts as well as advances in wound care and wound care products to treat the head and neck trauma patient. Typical outcome measures after head and neck trauma include ability to speak with appropriate articulation, ability to swallow and breathe without difficulty, and acceptable facial cosmesis. Advances in timing of repair have enabled patients to return to a premorbid condition earlier with improved results.


title: Illness progression, recent stress, and morphometry of hippocampal subfields and medial prefrontal cortex in major depression.

text: BACKGROUND Longitudinal studies of illness progression in patients with major depressive disorder (MDD) indicate that the onset of subsequent depressive episodes becomes increasingly decoupled from external stressors. A possible mechanism underlying this phenomenon is that multiple episodes induce long-lasting neurobiological changes that confer increased risk for recurrence. Prior morphometric studies have frequently reported volumetric reductions in patients with MDD--especially in medial prefrontal cortex (mPFC) and the hippocampus--but few studies have investigated whether these changes are exacerbated by prior episodes. METHODS In a sample of 103 medication-free patients with depression and control subjects with no history of depression, structural magnetic resonance imaging was performed to examine relationships between number of prior episodes, current stress, hippocampal subfield volume and cortical thickness. Volumetric analyses of the hippocampus were performed using a recently validated subfield segmentation approach, and cortical thickness estimates were obtained using vertex-based methods. Participants were grouped on the basis of the number of prior depressive episodes and current depressive diagnosis. RESULTS Number of prior episodes was associated with both lower reported stress levels and reduced volume in the dentate gyrus. Cortical thinning of the left mPFC was associated with a greater number of prior depressive episodes but not current depressive diagnosis. CONCLUSIONS Collectively, these findings are consistent with preclinical models suggesting that the dentate gyrus and mPFC are especially vulnerable to stress exposure and provide evidence for morphometric changes that are consistent with stress-sensitization models of recurrence in MDD.


Taking out the trash.


Laparoscopic revision of biliopancreatic diversion with duodenal switch and management of postoperative complications.


title: Respiratory syncytial and influenza viruses in children under 2 years old with severe acute respiratory infection (SARI) in Maputo, 2015.

text: INTRODUCTION Although respiratory syncytial virus (RSV) and influenza virus (influenza) infections are one of the leading causes of Severe Acute Respiratory Infections (SARI) and death in young children worldwide, little is known about the burden of these pathogens in Mozambique. MATERIAL AND METHODS From January 2015 to January 2016, nasopharyngeal swabs from 450 children, aged ≤2 years, who had been admitted to the Pediatric Department of the Maputo Central Hospital (HCM) in Mozambique, suffering with SARI were enrolled and tested for influenza and RSV using a real-time PCR assay. RESULTS Influenza and RSV were detected in 2.4% (11/450) and 26.7% (113/424) of the participants. Children with influenza were slightly older than those infected with RSV (10 months in influenza-infected children compared to 3 months in RSV-infected children); male children were predominant in both groups (63.6% versus 54.9% in children with influenza and RSV, respectively). There was a trend towards a higher frequency of influenza (72.7%) and RSV (93.8%) cases in the dry season. Bronchopneumonia, bronchitis and respiratory distress were the most common diagnoses at admission. Antibiotics were administered to 27,3% and 15,9% of the children with influenza and RSV, respectively. Two children, of whom, one was positive for RSV (aged 6 months) and another was positive for Influenza (aged 3 months) died; both were children of HIV seropositive mothers and had bronchopneumonia. CONCLUSIONS Our data demonstrated that RSV, and less frequently influenza, occurs in children with SARI in urban/sub-urban settings from southern Mozambique. The occurrence of deaths in small children suspected of being HIV-infected, suggests that particular attention should be given to this vulnerable population. Our data also provide evidence of antibiotics prescription in children with respiratory viral infection, which represents an important public health problem and calls for urgent interventions.


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title: Herbal medicine (Danggui Shaoyao San) for treating primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials.

text: Danggui Shaoyao San (DSS), a traditional herbal prescription, has long been used to treat menopause-related symptoms, including dysmenorrhea. We conducted a systematic review of randomized controlled trials to evaluate the efficacy of DSS for dysmenorrhea. We searched the following electronic databases through October 2015: PubMed; EMBASE; the Cochrane Library; AMED; five Korean databases (KoreaMed, DBPIA, OASIS, RISS, and KISS); three Chinese databases (CNKI, Wan Fang Database, and VIP), and one Japanese database (CiNii). The Cochrane criteria were used to assess the risk of bias for the individual studies. All randomized clinical trials (RCTs) of DSS or modified DSS were included. Data from all articles were extracted by two independent reviewers. Meta-analysis was used to pool the data. A total of 746 potentially relevant studies were identified, and four RCTs met our inclusion criteria. All of the included RCTs had a high risk of bias across their domains. Three RCTs showed favourable effects of DSS on response rate compared with conventional medicine, and a meta-analysis showed that DSS had superior effects compared to analgesics (RR: 1.31, 95%CI, 1.06-1.63, I(2)=73%). One RCT showed a beneficial effect of DSS on pain compared with placebo control. Our systematic review and meta-analysis provided suggestive evidence of the superiority of DSS over analgesics or placebo for dysmenorrhea. The quality of evidence for this finding was low to moderate because of a high risk of bias.


On the Frontlines of the Coronavirus Disease 2019 (COVID-19) Crisis-The Many Faces of Leadership.


title: Shrinkage of Nasal Mucosa and Cartilage During Formalin Fixation.

text: BACKGROUND After resection, specimens are subjected to formalin fixation during histological processing. This procedure can result in tissue shrinkage, with the amount of shrinkage related to tissue composition and tissue type. AIMS To evaluate the shrinkage of nasal mucosa and cartilage tissue and compare differences in shrinkage after resection, after formalin fixation, and during microscopic examination to understand differences in the rate of shrinkage of different tissue types. STUDY DESIGN Animal experimentation. METHODS Fresh nasal septa were excised from sheep (10 mm diameter in 40 sheep and 20 mm diameter in 40 sheep). The mucosa was separated from one side of the cartilage, with the contralateral mucosa remaining attached to the cartilage. Specimen diameters were measured in situ, after resection, after fixation for 6 or 24 hours (10% formalin), and during microscopic examination. RESULTS There were no differences between the in situ and after resection diameters of any tissue components (free mucosa, mucosa attached to cartilage, and cartilage) of all nasal specimens (10- or 20-mm diameter and 6- or 24-hour fixation). However, significant shrinkage occurred between resection and after-fixation. Regarding tissue specimens that were fixed for different durations (6 or 24 hours), we observed a significantly smaller mean tissue diameter in specimens fixed for 24 hours versus those fixed for 6 hours for mucosa attached to cartilage (in the 10-mm diameter after-fixation samples), free mucosa (in the 20-mm diameter after-fixation samples), mucosa attached to cartilage (in the 20-mm diameter after-fixation and microscopic measurement samples), and cartilage (in the 20-mm diameter after-fixation samples). Tissue shrinkage was greatest in free mucosal tissue and least in cartilage. CONCLUSION These results should be considered when evaluating patients undergoing surgical procedures for nasal cavity and paranasal sinus malignancies. Surgical margins should be measured before fixation or evaluated if possible before fixation and shrinkage.


title: Mapping inhibitor binding modes on an active cysteine protease via nuclear magnetic resonance spectroscopy.

text: Cruzain is a member of the papain/cathepsin L family of cysteine proteases, and the major cysteine protease of the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. We report an autoinduction methodology that provides soluble cruzain in high yields (>30 mg/L in minimal medium). These increased yields provide sufficient quantities of active enzyme for use in nuclear magnetic resonance (NMR)-based ligand mapping. Using circular dichroism and NMR spectroscopy, we also examined the solution-state structural dynamics of the enzyme in complex with a covalently bound vinyl sulfone inhibitor (K777). We report the backbone amide and side chain carbon chemical shift assignments of cruzain in complex with K777. These resonance assignments were used to identify and map residues located in the substrate binding pocket, including the catalytic Cys25 and His162. Selective [(15)N]Cys, [(15)N]His, and [(13)C]Met labeling was performed to quickly assess cruzain-ligand interactions for a set of eight low-molecular weight compounds exhibiting micromolar binding or inhibition. Chemical shift perturbation mapping verified that six of the eight compounds bind to cruzain at the active site. Three different binding modes were delineated for the compounds, namely, covalent, noncovalent, and noninteracting. These results provide examples of how NMR spectroscopy can be used to screen compounds for fast evaluation of enzyme-inhibitor interactions to facilitate lead compound identification and subsequent structural studies.


title: Preoperative ultrasound measurements predict the feasibility of gallbladder extraction during transgastric natural orifice translumenal endoscopic surgery cholecystectomy.

text: BACKGROUND Extraction of a gallbladder through an endoscopic overtube during natural orifice translumenal endoscopic surgery (NOTES) transgastric cholecystectomy avoids potential injury to the esophagus. This study examined the rate of successful gallbladder specimen extraction through an overtube and hypothesized that preoperative ultrasound findings could predict successful specimen passage. METHODS Gallbladder specimens from patients undergoing laparoscopic cholecystectomy were measured, and an attempt was made to pull the specimens through a commercially available overtube with an inner diameter of 16.7-mm. A radiologist blinded to the outcomes reviewed the available preoperative ultrasound measurements from these patients. Ultrasound dimensions including gallbladder length, width, and depth; wall thickness; common bile duct diameter; and size of the largest gallstone (LGS) were recorded. Multiple logistic regression analysis was performed to determine whether ultrasound findings and patient characteristics (age, body mass index [BMI], and sex) could predict the ability of a specimen to pass through the overtube. RESULTS Of 57 patients, 44 (77%) who had preoperative ultrasounds available for electronic review were included in the final analysis. Gallstones were present in 35 (79%) of these 44 patients. Intraoperative gallbladder perforation occurred in 18 (41%) of the 44 patients, and 16 (36%) of the 44 gallbladders could be extracted through the overtube. Measurement of LGS was possible for 23 patients, and indeterminate gallstone size (IGS) was determined for 12 patients. The rate for passage of perforated versus intact gallbladders was similar (40% vs. 23%; p = 0.054). The LGS (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.02-1.33; p = 0.021) and IGS (OR, 22.97; 95% CI, 1.99-265.63; p = 0.025) predicted failed passage on multivariate logistic regression analysis. The passage rate was 80% for LGS smaller than 10 mm or no stones present, 18% for LGS 10 mm or larger, and 8% for IGS (p < 0.001). CONCLUSION A majority of cholecystectomy specimens cannot pass through an endoscopic overtube. Preoperative ultrasound findings can predict successful specimen extraction. An IGS or a gallstone 10 mm or larger should be considered a relative contraindication to transgastric NOTES cholecystectomy.


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