title: Dexamethasone attenuated endotoxin-induced acute lung injury through inhibiting expression of inducible nitric oxide synthase.

text: Application of glucocorticoids in sepsis or severe infection is disputable in clinic. In this experiment, we studied the effect of dexamethasone on nitric oxide synthases and whether dexamethasone could attenuate endotoxin-induced acute lung injury (ALI). SD rats received 5 mg/kg lipopolisaccharide (LPS) injection. Then arterial oxygen partial pressure (PaO2), lung histology, lung tissue nitric oxide (NO) production and expression of nitric oxide synthases (NOS) were detected at 0.5, 1, 2, 3 or 4 h after LPS injection. PaO2 and lung injury deteriorated upon time. Production of NO in lung tissue increased significantly particularly in the first two hours, and this change was mainly due to the over-expression of inducible NOS (iNOS), but not endothelial NOS (eNOS). Furthermore, a tight positive correlation was observed between lung injury score (LIS) and NO production level in lung tissue. Dexamethasone could ameliorate PaO2 and lung damage evidently, which were paralleled by significant decreases in the production of NO and in the expression of iNOS mRNA. In conclusion, dexamethasone could effectively attenuate endotoxin-induced lung injury through inhibiting iNOS expression and activation in the very early stage of ALI.


title: Short-Term Outcomes of Laparoscopic Total Gastrectomy Performed by a Single Surgeon Experienced in Open Gastrectomy: Review of Initial Experience.

text: PURPOSE Laparoscopic total gastrectomy (LTG) is more complicated than laparoscopic distal gastrectomy, especially during a surgeon's initial experience with the technique. In this study, we evaluated the short-term outcomes of and learning curve for LTG during the initial cases of a single surgeon compared with those of open total gastrectomy (OTG). MATERIALS AND METHODS Between 2009 and 2013, 134 OTG and 74 LTG procedures were performed by a single surgeon who was experienced with OTG but new to performing LTG. Clinical characteristics, operative parameters, and short-term postoperative outcomes were compared between groups. RESULTS Advanced gastric cancer and D2 lymph node dissection were more common in the OTG than LTG group. Although the operation time was significantly longer for LTG than for OTG (175.7±43.1 minutes vs. 217.5±63.4 minutes), LTG seems to be slightly superior or similar to OTG in terms of postoperative recovery measures. The operation time moving average of 15 cases in the LTG group decreased gradually, and the curve flattened at 54 cases. The postoperative complication rate was similar for the two groups (11.9% vs. 13.5%). No anastomotic or stump leaks occurred. CONCLUSIONS Although LTG is technically difficult and operation time is longer for surgeons experienced in open surgery, it can be performed safely, even during a surgeon's early experience with the technique. Considering the benefits of minimally invasive surgery, LTG is recommended for early gastric cancer.


title: Development and validation of a risk prediction model to diagnose Barrett's oesophagus (MARK-BE): a case-control machine learning approach.

text: Background Screening for Barrett's Oesophagus (BE) relies on endoscopy which is invasive and has a low yield. This study aimed to develop and externally validate a simple symptom and risk-factor questionnaire to screen for patients with BE. Methods Questionnaires from 1299 patients in the BEST2 case-controlled study were analysed: 880 had BE including 40 with invasive oesophageal adenocarcinoma (OAC) and 419 were controls. This was randomly split into a training cohort of 776 patients and an internal validation cohort of 523 patients. External validation included 398 patients from the BOOST case-controlled study: 198 with BE (23 with OAC) and 200 controls. Identification of independently important diagnostic features was undertaken using machine learning techniques information gain (IG) and correlation based feature selection (CFS). Multiple classification tools were assessed to create a multi-variable risk prediction model. Internal validation was followed by external validation in the independent dataset. Findings The BEST2 study included 40 features. Of these, 24 added IG but following CFS, only 8 demonstrated independent diagnostic value including age, gender, smoking, waist circumference, frequency of stomach pain, duration of heartburn and acid taste and taking of acid suppression medicines. Logistic regression offered the highest prediction quality with AUC (area under the receiver operator curve) of 0.87. In the internal validation set, AUC was 0.86. In the BOOST external validation set, AUC was 0.81. Interpretation The diagnostic model offers valid predictions of diagnosis of BE in patients with symptomatic gastroesophageal reflux, assisting in identifying who should go forward to invasive testing. Overweight men who have been taking stomach medicines for a long time may merit particular consideration for further testing. The risk prediction tool is quick and simple to administer but will need further calibration and validation in a prospective study in primary care. Funding Charles Wolfson Trust and Guts UK.


title: Rotavirus infection as a frequent cause of neonatal fever.

text: BACKGROUND Fever rather than diarrhea or vomiting was the most common symptom of neonatal rotavirus (RV) infection in our previous study. We investigated whether RV infection is a major cause of neonatal fever and compared the clinical characteristics of bacterial infection, viral infection and unknown causes of neonatal fever. METHOD We reviewed the electronic medical records of 48 newborns aged ≤28 days who were admitted to the Special Care Nursery of Hanyang University Guri Hospital for fever (≥38°C) from 2005 to 2009. All the newborns underwent complete blood count, urinalysis, C-reactive protein, cultures of blood, urine, and cerebrospinal fluid as well as stool RV enzyme-linked immunosorbent assay. Respiratory virus polymerase chain reaction for cough or rhinorrhea, and stool culture for diarrhea were also done. RESULTS All the babies were term, with mean age 13 ± 8 days and peak body temperature 38.5 ± 0.5°C. The causes of neonatal fever were viral (44%), bacterial (10%) and unknown (46%). The viral infections included RV (n = 12), enterovirus (n = 6), respiratory syncytial virus (n = 2), and rhinovirus (n = 1). All the rotavirus genotypes were G4P[6]. Only three of 12 RV-infected febrile newborns had diarrhea. The bacterial infections included three cases of urinary tract infection (Escherichia coli, n = 2; Klebsiella pneumoniae, n = 1), and two cases of sepsis complicated with meningitis (all Streptococcus agalactiae). CONCLUSIONS RV infection is the most common single cause of neonatal fever. It may be necessary to include stool RV tests for febrile newborns.


title: Bowel preparation in "real-life" small bowel capsule endoscopy: a two-center experience.

text: BACKGROUND Video capsule endoscopy (VCE) is an established diagnostic tool for the investigation of small bowel (SB) pathology. Bowel preparation prior to VCE may improve visualization, transit time, and diagnostic yield. We aimed to evaluate the "real-life" experience comparing two different preparation protocols in patients undergoing SB VCE. METHODS We performed a retrospective analysis of prospectively collected data from SB VCE procedures, performed in two tertiary care medical centers in Israel. VCE procedures performed at "Sheba Medical Center" used a 2-L polyethylene glycol (PEG) bowel preparation (n=360) while VCEs performed at "Rambam Health Care campus" used a clear liquid diet plus 12-h fast protocol (n=500). A dichotomous preparation scale (adequate, inadequate) was used to classify cleansing quality. Data collection included patient and procedural details. The proportion of VCE procedures with adequate bowel preparation and the overall positive SB findings in the two different bowel preparation protocols were evaluated. RESULTS SB completion rates were higher in the PEG protocol (96% vs. 83%, P<0.001) and SB passage time was significantly faster in the PEG protocol (mean 217±73 vs. 238±77 min, P<0.001). Bowel preparation quality was similar between groups (8% vs. 7% inadequate preparation, P=0.591). Overall positive SB findings were similar between the two groups (57% clear liquid fasting only vs. 51% PEG protocol, P=0.119). CONCLUSION In this large cohort, a 2-L PEG protocol had similar preparation quality and diagnostic yield compared with clear liquid fasting.


title: The Pipeline Embolization Device for the treatment of posterior circulation fusiform aneurysms: lessons learned at a single institution.

text: OBJECT Vertebrobasilar fusiform aneurysms (VFAs) are rare lesions characterized by abnormal dilation and tortuosity of the vertebral and/or basilar arteries. Untreated, these aneurysms have a tendency to progress, often resulting in neurological symptoms or rupture leading to subarachnoid hemorrhage. The microsurgical treatment of these lesions can be difficult due to their location and the circumferential involvement of the arteries. These features make microsurgical treatment prone to high morbidity. The Pipeline Embolization Device (PED) has gained popularity for the treatment of aneurysms of the internal carotid artery. Its use in the posterior circulation has been limited, likely due to a fear of perforating artery occlusion. METHODS The authors retrospectively reviewed their database of patients treated with the PED and identified 12 patients who had VFAs. The clinical features, complications, and outcomes of these patients were analyzed. RESULTS At an average follow-up of 11 months, the mean modified Rankin Scale score was 1.9. Complete aneurysm occlusion was seen in 90% of the patients with radiographic follow-up. Three patients suffered new neurological deficits postoperatively. One of these patients died, while the remaining 2 demonstrated significant clinical improvement at follow-up. CONCLUSIONS With attention to the anatomy of perforating arteries, staged contralateral vertebral artery sacrifice, and adequate platelet inhibition, PED may be an effective treatment option-alone or in a hybrid construct with stents of less coverage for VFAs-with an acceptable complication rate.


title: Pseudoaneurysm in the Internal Maxillary Artery Occurring After Endoscopic Sinus Surgery.

text: Pseudoaneurysm is defined as blood leaking out of a vessel that does not have true 3 arterial walls like a true aneurysm, and is susceptible to rupture. Only 4 patients of pseudoaneurysm after endoscopic sinus surgery have been reported so far in English literature. Recently, the authors encountered a pseudoaneurysm in the internal maxillary artery after endoscopic sinus surgery, which was immediately and successfully managed with endovascular embolization. There was no bleeding or complications 6 months after the embolization.


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docid: vvaeewal

title: Respiratory pathogens and acute chest syndrome in children with sickle cell disease.

text: BACKGROUND Acute chest syndromes (ACS) may be associated with upper respiratory tract infections, but the epidemiology of viral and intracellular respiratory pathogens in children with sickle cell disease (SCD) is not precisely known. The aim of this study was to describe the epidemiology of viral and intracellular respiratory pathogens in children with SCD presenting with fever and/or ACS. MATERIALS AND METHODS An observational, prospective, single-centre cohort study with nested case-control analysis was conducted on children with SCD admitted from October 2016 to October 2017 for fever and/or ACS to the paediatric department of Robert Debré university hospital, Paris, France. They were screened for 20 respiratory pathogens by a multiplex PCR in the nasopharynx (FilmArray). RESULTS We included 101 children. M/F sex ratio of 0.45. The median age was 3.2 years (IQR: 1.4-8.2). At least one pathogen was isolated in 67 patients (67%). The most frequent viruses were as follows: rhinovirus (n=33), adenovirus (n=14), respiratory syncytial virus (n=13) and parainfluenza viruses (n=11). Mycoplasma pneumoniae was detected in one case. Twenty-three (23%) presented with or developed ACS. A nested case-control analysis was performed, after pairing ACS with non-ACS children for age and inclusion period. There was no statistical association between any viral detection or multiple viral infection, and ACS (p=0.51) even though parainfluenza viruses were twice as common in ACS. CONCLUSIONS Viral detection in febrile children with SCD is frequent, but its association with ACS was not demonstrated. In this study, M. pneumoniae was rare in young children with SCD experiencing ACS.


title: Adverse drug reactions associated with amitriptyline - protocol for a systematic multiple-indication review and meta-analysis.

text: BACKGROUND Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-the-counter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals. METHODS A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including < 100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using meta-regression (for indication, outcome, and time points) and I2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment. DISCUSSION We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations. SYSTEMATIC REVIEW REGISTRATION Submitted to PROSPERO; assignment is in progress.


title: Results of stent-assisted vs non-stent-assisted endovascular therapies in 489 cerebral aneurysms: single-center experience.

text: BACKGROUND Whether the addition of stenting to intracranial aneurysm coil embolization results in benefit in terms of occlusion rates or additional risk in terms of periprocedural adverse events is not clear. OBJECTIVE To report retrospectively analyzed results of endovascular aneurysm treatment comparing stent-assisted coiling with coiling without stents at our hospital from 2005 to 2009. METHODS In this retrospectively reviewed case series, aneurysms were grouped as intent-to-treat or initially treated with stent-assisted coiling (A) vs coiling alone (B) or as-treated-those that ultimately received a stent (C) or not (D). Complication and occlusion rates were compared between groups. Some patients crossed from group B to C after receiving stent placement at a later treatment following the initial therapeutic modality (without a stent). RESULTS In 459 patients, 489 aneurysms were treated by group as follows: A = 181, B = 308, C = 225, and D = 264. In stent groups (A and C), there were significantly lower frequencies of ruptured aneurysms (A vs B = 11% vs 62%, P < .001; C vs D = 20.4% vs 62.5%, P < .001) and more giant aneurysms (A vs B = 7.3% vs 1.0%, P = .001; C vs D = 5.9% vs 1.1%, P < .001). There was no statistically significant difference in permanent event-related morbidity (A vs B = 4.4% vs 4.2%, P = 1.0; C vs D = 4.4% vs 4.2%, P = 1.0). Average angiographic follow-up after last treatment was 18.2 ± 15 months (median = 14). Higher rates of complete occlusion at last angiographic follow-up were observed in stented aneurysms (A vs B = 64.6% vs 49.7%, P = .001; C vs D = 62.7% vs 48.9%, P = .003). CONCLUSION Stent-assisted aneurysm treatment resulted in higher total occlusion rates than non-stent-assisted treatment, with acceptable, comparable periprocedural event rates.


title: Mapping Antigenic Epitopes on the Human Bocavirus Capsid.

text: UNLABELLED Human bocaviruses (HBoV1 to -4) are emerging pathogens associated with pneumonia and/or diarrhea in young children. Currently, there is no treatment or vaccination, so there is a need to study these pathogens to understand their disease mechanisms on a molecular and structural level for the development of control strategies. Here, we report the structures of six HBoV monoclonal antibody (MAb) fragment complexes, HBoV1-15C6, HBoV2-15C6, HBoV4-15C6, HBoV1-4C2, HBoV1-9G12, and HBoV1-12C1, determined by cryo-electron microscopy and three-dimensional image reconstruction to 18.0- to 8.5-Å resolution. Of these, the 15C6 MAb cross-reacted with HBoV1, HBoV2, and HBoV4, while the 4C2, 12C1, and 9G12 MAbs recognized only HBoV1. Pseudoatomic modeling mapped the 15C6 footprint to the capsid surface DE and HI loops, at the 5-fold axis and the depression surrounding it, respectively, which are conserved motifs in Parvoviridae The footprints for 4C2, 12C1, and 9G12 span the surface loops that assemble portions of the 2-/5-fold wall (a raised surface feature between the 2-fold and 5-fold axes of symmetry) and the shoulder of the 3-fold protrusions. The MAb footprints, cross reactive and strain specific, coincide with regions with high and low sequence/structural identities, respectively, on the capsid surfaces of the HBoVs and identify potential regions for the development of peptide vaccines for these viruses. IMPORTANCE Human bocaviruses (HBoVs) may cause severe respiratory and gastrointestinal infections in young children. The nonenveloped parvovirus capsid carries determinants of host and tissue tropism, pathogenicity, genome packaging, assembly, and antigenicity important for virus infection. This information is currently unavailable for the HBoVs and other bocaparvoviruses. This study identifies three strain-specific antigenic epitopes on the HBoV1 capsid and a cross-reactive epitope on the HBoV1, HBoV2, and HBoV4 capsids using structures of capsid-antibody complexes determined using cryo-electron microscopy and image reconstruction. This is the first study to report the highly conserved parvovirus DE loop at the 5-fold axis as a determinant of antigenicity. Additionally, knowledge of the strain-specific and conserved antigenic epitopes of the bocaviruses can be instrumental in characterization of the virus life cycle, development of peptide vaccines, and generation of gene delivery vectors for cystic fibrosis given the strict tropism of HBoV1 for human airway epithelial cells.


title: Modeling the impact of simulated educational interventions on the use and abuse of pharmaceutical opioids in the United States: a report on initial efforts.

text: Three educational interventions were simulated in a system dynamics model of the medical use, trafficking, and nonmedical use of pharmaceutical opioids. The study relied on secondary data obtained in the literature for the period of 1995 to 2008 as well as expert panel recommendations regarding model parameters and structure. The behavior of the resulting systems-level model was tested for fit against reference behavior data. After the base model was tested, logic to represent three educational interventions was added and the impact of each intervention on simulated overdose deaths was evaluated over a 7-year evaluation period, 2008 to 2015. Principal findings were that a prescriber education intervention not only reduced total overdose deaths in the model but also reduced the total number of persons who receive opioid analgesic therapy, medical user education not only reduced overdose deaths among medical users but also resulted in increased deaths from nonmedical use, and a "popularity" intervention sharply reduced overdose deaths among nonmedical users while having no effect on medical use. System dynamics modeling shows promise for evaluating potential interventions to ameliorate the adverse outcomes associated with the complex system surrounding the use of opioid analgesics to treat pain.


title: Genomic epidemiology, evolution, and transmission dynamics of porcine deltacoronavirus.

text: The emergence of severe acute respiratory syndrome virus (SARS)-CoV-2 has shown once again that coronaviruses (CoVs) in animals are potential sources for epidemics in humans. Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen of swine with a worldwide distribution. Here, we implemented and described an approach to analyze the epidemiology of PDCoV following its emergence in the pig population. We performed an integrated analysis of full genome sequence data from 21 newly-sequenced viruses, along with comprehensive epidemiological surveillance data collected globally over the last 15 years. We found four distinct phylogenetic lineages of PDCoV, which differ in their geographic circulation patterns. Interestingly, we identified more frequent intra- and inter-lineage recombination and higher virus genetic diversity in the Chinese lineages compared with the US lineage where pigs are raised in different farming systems and ecological environments. Most recombination breakpoints are located in the ORF1ab gene rather than in genes encoding structural proteins. We also identified five amino acids under positive selection in the spike protein suggesting a role for adaptive evolution. According to structural mapping, three positively selected sites are located in the N-terminal domain of the S1 subunit, which is the most likely involved in binding to a carbohydrate receptor, while the other two are located in or near the fusion peptide of the S2 subunit and thus might affect membrane fusion. Finally, our phylogeographic investigations highlighted notable South-North transmission as well as frequent long-distance dispersal events in China that could implicate human-mediated transmission. Our findings provide new insights into the evolution and dispersal of PDCoV that contribute to our understanding of the critical factors involved in coronaviruses emergence. SIGNIFICANCE Coronaviruses (CoVs) exhibit a pronounced propensity for interspecies transmission as illustrated by important emerging viruses in humans such as severe acute respiratory syndrome virus (SARS)-CoV and Middle East respiratory syndrome virus (MERS)-CoV, as well as the recent SARS-CoV-2 that is causing a major human pandemic. A better understanding of the evolutionary process leading to viral emergence may help unravel the principles of cross-species transmission and therefore assist in preventing future introductions into new host populations. Here, we examined the evolution and spread of an emerging coronavirus that likely transmitted from birds to pigs and caused sustained epidemics in Asia and the United States. We integrated viral full genome sequence analysis and comprehensive surveillance data to examine the evolution of emerging porcine deltacoronavirus (PDCoV), and in particular the factors driving ongoing circulation and recent cases in China. We found evidence for adaptive evolution of this emerging virus in the absence of vaccine immune pressure, with important amino acids under positive selection, as well as frequent inter- and intra-lineage recombination events in the Asian lineages. Breeding patterns and ecological environment could play an important role in swine coronavirus evolution, leading to differences in recombination and population diversity. Using phylogeographic approaches, we further shed light on the dispersal history and dynamics of the China lineage of PDCoV. Our study provides a deeper understanding of the geographic dispersal of genetic lineages of PDCoV in China and suggests that southern China acted as a source of transmission. Modeling how the virus spread in China will allow the prioritization of areas for swine coronavirus surveillance in the future. These findings have important implications for preventing the emergence of coronaviruses in livestock and for controlling their spread in Asian countries.


title: Modeling of the Transmission of Coronaviruses, Measles Virus, Influenza Virus, Mycobacterium tuberculosis, and Legionella pneumophila in Dental Clinics.

text: Dental health care workers are in close contact to their patients and are therefore at higher risk for contracting airborne infectious diseases. The transmission rates of airborne pathogens from patient to dental health care workers are unknown. With the outbreaks of infectious diseases, such as seasonal influenza, occasional outbreaks of measles and tuberculosis, and the current pandemic of the coronavirus disease COVID-19, it is important to estimate the risks for dental health care workers. Therefore, the transmission probability of these airborne infectious diseases was estimated via mathematical modeling. The transmission probability was modeled for Mycobacterium tuberculosis, Legionella pneumophila, measles virus, influenza virus, and coronaviruses per a modified version of the Wells-Riley equation. This equation incorporated the indoor air quality by using carbon dioxide as a proxy and added the respiratory protection rate from medical face masks and N95 respirators. Scenario-specific analyses, uncertainty analyses, and sensitivity analyses were run to produce probability rates. A high transmission probability was characterized by high patient infectiousness, the absence of respiratory protection, and poor indoor air quality. The highest transmission probabilities were estimated for measles virus (100%), coronaviruses (99.4%), influenza virus (89.4%), and M. tuberculosis (84.0%). The low-risk scenario leads to transmission probabilities of 4.5% for measles virus and 0% for the other pathogens. From the sensitivity analysis, it shows that the transmission probability is strongly driven by indoor air quality, followed by patient infectiousness, and the least by respiratory protection from medical face mask use. Airborne infection transmission of pathogens such as measles virus and coronaviruses is likely to occur in the dental practice. The risk magnitude, however, is highly dependent on specific conditions in each dental clinic. Improved indoor air quality by ventilation, which reduces carbon dioxide, is the most important factor that will either strongly increase or decrease the probability of the transmission of a pathogen.


title: Mid-term follow-up of staged bilateral internal carotid artery aneurysm treatment with Pipeline embolization.

text: BACKGROUND Endovascular treatment of large complex morphology aneurysms is challenging. High recanalization rates have been reported with techniques such as stent-assisted coiling and balloon-assisted coiling. Flow diverter devices have been introduced to improve efficacy outcomes and recanalization rates. Thromboembolic complications and in-device stenosis are certainly more worrisome when treatment of bilateral internal carotid arteries has been performed. This study aimed to report our experience with mid-term imaging follow-up of staged bilateral Pipeline embolization device placement for the treatment of bilateral internal carotid artery aneurysms. METHODS We reviewed the clinical, angiographic, and follow-up imaging data in all consecutive patients treated with bilateral internal carotid artery aneurysms who underwent elective Pipeline embolization. RESULTS Six female patients were treated, harboring a total of 13 aneurysms. Of these, 60% were asymptomatic. Diplopia and headache were the most common symptoms. The most common location was the paraclinoid segment (6/13), including by cavernous segment (4/13) and ophthalmic segment (2/13). Successful delivery of the device was achieved in 12 cases. Difficult distal access precluded the deployment of the device in one case. The treatment was always staged with at least eight weeks' difference between the two procedures. All aneurysm necks were covered completely. There were no periprocedural complications. Angiographic follow-up ranged between 3 and 12 months, and computed tomography angiogram follow-up ranged between 2 and 24 months. Complete aneurysm occlusion was achieved in all cases. CONCLUSION In our series, Pipeline deployment for the treatment of bilateral internal carotid artery aneurysms in a staged fashion is safe and feasible. Mid-term imaging follow-up showed permanent occlusion of all the treated aneurysms.


title: Single surgeon experience with robot-assisted ureteroureterostomy for pathologies at the proximal, middle, and distal ureter in adults.

text: PURPOSE To describe our initial experience with robot-assisted ureteroureterostomy (RUU) at the proximal, middle, and distal ureter. MATERIALS AND METHODS Twelve consecutive patients underwent RUU by a single surgeon (D.D.E.) between July 2009 and November 2012. Indications included three iatrogenic injuries, two impacted stones, two ureterovaginal fistulas, two idiopathic ureteral strictures refractory to conservative treatment, one primary transitional cell carcinoma of the ureter, one colon cancer metastasis to the ureter, and one invasive endometriosis. There were two proximal, three middle, and seven distal ureteral pathologies. RESULTS Tension-free anastomosis was achieved in all 12 patients. All patients with proximal and middle ureteral pathology received concomitant downward nephropexy (DN) as a standard part of RUU. Mean age of patients at the time of surgery was 52 years (range 30-69), mean body mass index was 30.0 kg/m(2) (range 21-38), mean operative room time was 190 minutes (range 104-354), mean estimated blood loss was 181 mL (range 50-400), and mean length of excised ureter on pathologic analysis was 2.0 cm (range 1.0-4.5). There was one intraoperative complication in which liver and gallbladder laceration occurred during trocar placement. Mean length of hospital stay was 1.4 days (range 1-5), and there were no postoperative complications. Mean follow up was 10 months (range 3-36). One patient had a ureteral stricture recurrence at 7 months postoperatively that led to renal unit loss and eventual nephrectomy. CONCLUSION RUU is feasible, safe, and demonstrates good outcomes for pathologies at the proximal, middle, and distal ureter. Concomitant DN during RUU may assist in achieving a tension-free anastomosis for proximal and middle ureteral repairs.


title: A human coronavirus responsible for the common cold massively kills dendritic cells but not monocytes.

text: Human coronaviruses are associated with upper respiratory tract infections that occasionally spread to the lungs and other organs. Although airway epithelial cells represent an important target for infection, the respiratory epithelium is also composed of an elaborate network of dendritic cells (DCs) that are essential sentinels of the immune system, sensing pathogens and presenting foreign antigens to T lymphocytes. In this report, we show that in vitro infection by human coronavirus 229E (HCoV-229E) induces massive cytopathic effects in DCs, including the formation of large syncytia and cell death within only few hours. In contrast, monocytes are much more resistant to infection and cytopathic effects despite similar expression levels of CD13, the membrane receptor for HCoV-229E. While the differentiation of monocytes into DCs in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4 requires 5 days, only 24 h are sufficient for these cytokines to sensitize monocytes to cell death and cytopathic effects when infected by HCoV-229E. Cell death induced by HCoV-229E is independent of TRAIL, FasL, tumor necrosis factor alpha, and caspase activity, indicating that viral replication is directly responsible for the observed cytopathic effects. The consequence of DC death at the early stage of HCoV-229E infection may have an impact on the early control of viral dissemination and on the establishment of long-lasting immune memory, since people can be reinfected multiple times by HCoV-229E.


title: Technical feasibility and application of mechanical thrombectomy with the Solitaire FR Revascularization Device in acute basilar artery occlusion.

text: BACKGROUND AND PURPOSE Acute BAO is a devastating neurological condition associated with a poor clinical outcome and a high mortality rate. Recanalization has been identified as a major prognostic factor for good outcome in BAO. Mechanical thrombectomy using retrievable stents is an emerging treatment option for acute stroke. First clinical trials using stent retrievers have shown promising high recanalization rates. However, these studies mainly included large artery occlusions in the anterior circulation with only a few or single cases of BAO. Therefore, the purpose of this study was to evaluate technical feasibility, safety, and efficacy of mechanical thrombectomy using retrievable stent in the treatment of acute BAO. MATERIALS AND METHODS Fourteen consecutive patients with BAO undergoing endovascular therapy using retrievable stents (Solitaire FR Revascularization Device) were included. Additional multimodal treatment approaches included thromboaspiration, intravenous and/or intra-arterial thrombolysis, and PTA/ permanent stent placement. Recanalization rates after multimodal therapy and stent retrieval were determined. Clinical outcome and mortality were assessed 3 months after treatment. RESULTS Median patient age was 64.5 years (range 55-85). Median NIHSS score at presentation was 21 (range 5-36). Overall, successful recanalization (TICI 3 or 2b) was achieved in all patients (TICI 3 in 78.6%, 11/14). In 4 patients (28.6%), insufficient recanalization after stent retrieval was due to an underlying atherosclerotic stenosis. Additional deployment of a permanent intracranial stent was performed in 3 patients (21.4%) and PTA alone in 1 patient (7.1%), resulting in final TICI 3 in 1 patient and TICI 2b in 3 patients. Stent retrieval alone was performed in 4 patients (28.6%). Average number of device passes was 1.3 (range 1-3). Median procedure time to maximal recanalization was 47 minutes (range 10-252). No device-related complications or thromboembolic occlusion of a previously unaffected artery occurred. There was no symptomatic intracranial hemorrhage. At 3 months, good functional outcome (mRS 0-2) was observed in 28.6% (4/14); overall mortality was 35.7% (5/14). CONCLUSIONS A multimodal endovascular approach using retrievable stents in BAO has high recanalization rates, with very low complication rates. Underlying atherothrombotic stenotic lesions of the basilar artery may still necessitate additional permanent stent placement to achieve complete recanalization.


title: Differences of energy expenditure while sitting versus standing: A systematic review and meta-analysis.

text: Background Replacing sitting with standing is one of several recommendations to decrease sedentary time and increase the daily energy expenditure, but the difference in energy expenditure between standing versus sitting has been controversial. This systematic review and meta-analysis aimed to determine this difference. Designs and methods We searched Ovid MEDLINE, Ovid Embase Scopus, Web of Science and Google Scholar for observational and experimental studies that compared the energy expenditure of standing versus sitting. We calculated mean differences and 95% confidence intervals using a random effects model. We conducted different predefined subgroup analyses based on characteristics of participants and study design. Results We identified 658 studies and included 46 studies with 1184 participants for the final analysis. The mean difference in energy expenditure between sitting and standing was 0.15 kcal/min (95% confidence interval (CI) 0.12-0.17). The difference among women was 0.1 kcal/min (95% CI 0.0-0.21), and was 0.19 kcal/min (95% CI 0.05-0.33) in men. Observational studies had a lower difference in energy expenditure (0.11 kcal/min, 95% CI 0.08-0.14) compared to randomised trials (0.2 kcal/min, 95% CI 0.12-0.28). By substituting sitting with standing for 6 hours/day, a 65 kg person will expend an additional 54 kcal/day. Assuming no increase in energy intake, this difference in energy expenditure would be translated into the energy content of about 2.5 kg of body fat mass in 1 year. Conclusions The substitution of sitting with standing could be a potential solution for a sedentary lifestyle to prevent weight gain in the long term. Future studies should aim to assess the effectiveness and feasibility of this strategy.


docid: uubpqzhp

title: Modified tube gastropexy using a mushroom-tipped silicone catheter for management of gastric dilatation-volvulus in dogs.

text: OBJECTIVES To report the short- and long-term complications and clinical outcomes of a cohort of dogs managed for gastric dilatation-volvulus using a modified right-sided tube gastropexy technique. MATERIALS AND METHODS Retrospective case series. RESULTS Of 31 dogs treated, 29 (93·5%) had an excellent short-term outcome, and gastric dilatation-volvulus did not recur in any dog. Twenty-six dogs (84%) were initially fed via the gastrostomy tube postoperatively; three (9·7%) suffered a major complication including septic peritonitis (n=1), and premature tube removal (n=2). Fourteen dogs (45·1%) had minor complications including mild, self-limiting discharge from the stoma site in 13. CLINICAL SIGNIFICANCE Modified tube gastropexy using a mushroom-tipped silicone catheter is an effective and safe surgical method for the management of gastric dilatation-volvulus. The gastrostomy tube allowed early enteral feeding and easy administration of medications, including gastroprotectants.


docid: sylrvvni

title: Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study.

text: OBJECTIVE The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram. METHOD This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures. RESULTS Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (-6.4 [SD=6.4] compared with -3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group. CONCLUSIONS Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.


Commentary: Restructuring residency training in ophthalmology during COVID-19 era: Challenges and opportunities.


title: Baicalin Attenuates Blood-Brain Barrier Disruption and Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke Rats with Delayed t-PA Treatment: Involvement of ONOO--MMP-9 Pathway.

text: Tissue plasminogen activator (t-PA) has a restrictive therapeutic window within 4.5 h after ischemic stroke with the risk of hemorrhagic transformation (HT) and neurotoxicity when it is used beyond the time window. In the present study, we tested the hypothesis that baicalin, an active compound of medicinal plant, could attenuate HT in cerebral ischemia stroke with delayed t-PA treatment. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 4.5 h and then continuously received t-PA infusion (10 mg/kg) for 0.5 h and followed by 19-h reperfusion. Baicalin (50, 100, 150 mg/kg) was administrated via femoral vein at 4.5 h after MCAO cerebral ischemia. Delayed t-PA infusion significantly increased the mortality rate, induced HT, blood-brain barrier (BBB) damage, and apoptotic cell death in the ischemic brains and exacerbated neurological outcomes in cerebral ischemia-reperfusion rats at 24 h after MCAO cerebral ischemia. Co-treatment of baicalin significantly reduced the mortality rates, ameliorated the t-PA-mediated BBB disruption and HT. Furthermore, baicalin showed to directly scavenge peroxynitrite and inhibit MMP-9 expression and activity in the ischemic brains with the delayed t-PA treatment. Baicalin had no effect on the t-PA fibrinolytic function indicated by t-PA activity assay. Taken together, baicalin could attenuate t-PA-mediated HT and improve the outcomes of ischemic stroke treatment possibly via inhibiting peroxynitrite-mediated MMP-9 activation.


title: Bioethics and the Hypothesis of Extended Health.

text: Dominant views about the nature of health and disease in bioethics and the philosophy of medicine have presumed the existence of a fixed, stable, individual organism as the bearer of health and disease states, and as such, the appropriate target of medical therapy and ethical concern. However, recent developments in microbial biology, neuroscience, the philosophy of cognitive science, and social and personality psychology have produced a novel understanding of the individual and its fluid boundaries. Drawing on converging evidence from these disciplines, and following recent research in public health, we argue that certain features of our biological and social environment can be so tightly integrated as to constitute a unit of care extending beyond the intuitive boundaries of skin and skull. This paper develops and defends the Hypothesis of Extended Health (HEH), which denies the claim that health and disease states are predicated solely on the internal functioning of an organism. If this is correct, then the targets of medical invention and ethical concern are wider and more diverse than is usually assumed.


title: Trimethylene carbonate-caprolactone conduit with poly-p-dioxanone microfilaments to promote regeneration after spinal cord injury.

text: Spinal cord injury (SCI) is often associated with scarring and cavity formation and therefore bridging strategies are essential to provide a physical substrate for axonal regeneration. In this study we investigated the effects of a biodegradable conduit made from trimethylene carbonate and ε-caprolactone (TC) containing poly-p-dioxanone microfilaments (PDO) with longitudinal grooves on regeneration after SCI in adult rats. In vitro studies demonstrated that different cell types including astrocytes, meningeal fibroblasts, Schwann cells and adult sensory dorsal root ganglia neurons can grow on the TC and PDO material. For in vivo experiments, the TC/PDO conduit was implanted into a small 2-3 mm long cavity in the C3-C4 cervical segments immediately after injury (acute SCI) or at 2-5 months after initial surgery (chronic SCI). At 8 weeks after implantation into acute SCI, numerous 5HT-positive descending raphaespinal axons and sensory CGRP-positive axons regenerated across the conduit and were often associated with PDO microfilaments and migrated host cells. Implantation into chronically injured SCI induced regeneration mainly of the sensory CGRP-positive axons. Although the conduit had no effect on the density of OX42-positive microglial cells when compared with SCI control, the activity of GFAP-positive astrocytes was reduced. The results suggest that a TC/PDO conduit can support axonal regeneration after acute and chronic SCI even without addition of exogenous glial or stem cells. STATEMENT OF SIGNIFICANCE Biosynthetic conduits can support regeneration after spinal cord injury but often require addition of cell therapy and neurotrophic factors. This study demonstrates that biodegradable conduits made from trimethylene carbonate and ε-caprolactone with poly-p-dioxanone microfilaments alone can promote migration of different host cells and stimulate axonal regeneration after implantation into acute and chronic spinal cord injury. These results can be used to develop biosynthetic conduits for future clinical applications.


title: Treatment of yellow fever virus with an adenovirus-vectored interferon, DEF201, in a hamster model.

text: Interferon (IFN) is an innate immune response protein that is involved in the antiviral response during viral infection. Treatment of acute viral infections with exogenous interferon may be effective but is generally not feasible for clinical use due to many factors, including cost, stability, and availability. To overcome these limitations, an adenovirus type 5-vectored consensus alpha IFN, termed DEF201, was constructed as a potential way to deliver sustained therapeutic levels of systemic IFN. To demonstrate the efficacy of DEF201 against acute flaviviral disease, various concentrations of the construct were administered as a single intranasal dose prior to virus infection, which resulted in a dose-responsive, protective effect in a hamster model of yellow fever virus (YFV) disease. A DEF201 dose of 5×10(7) PFU/animal administered intranasally just prior to YFV challenge protected 100% of the animals, while a 10-fold lower DEF201 dose exhibited lower, although significant, levels of protection. Virus titers in the liver and serum and levels of serum alanine aminotransferase were all significantly reduced as a result of DEF201 administration at all doses tested. No toxicity, as indicated by weight loss or gross morbidity, was observed in non-YFV-infected animals treated with DEF201. Protection of YFV-infected animals was observed when DEF201 was delivered as early as 7 days prior to virus challenge and as late as 2 days after virus challenge, demonstrating effective prophylaxis and therapy in a hamster model of disease. Overall, it appears that DEF201 is effective in the treatment of YFV in a hamster model.


title: Laparoscopic proximal gastrectomy for early gastric cancer.

text: The incidence of proximal early gastric cancer (EGC) is increasing, and while laparoscopic proximal gastrectomy (LPG) has been performed as a surgical option, it is not yet the standard treatment, because there is no established common reconstruction method following proximal gastrectomy (PG). We reviewed the English-language literature to clarify the current status and problems associated with LPG in treating proximal EGC. This procedure is considered indicated for EGC located in the upper third of the stomach with clinical T1N0, but not when it can be treated endoscopically. No operative mortality or conversion to open surgery was reported in our review, suggesting that this procedure is technically feasible. The most frequent postoperative complication involved problems with anastomoses, possibly caused by the technical complexity of the reconstruction. Although various reconstruction methods following open PG (OPG) and LPG have been reported, there is no standard reconstruction method. Well-designed multicenter, randomized, controlled, prospective trials to evaluate the various reconstruction methods are necessary.


title: COVID-19 Pandemic and Impending Global Mental Health Implications.

text: The increase in organisms transference and infectious pandemics across the globe have been accelerated by an increase in travel, international exchange and global changes in earth's climate. COVID-19, a virus caused by the novel coronavirus that was initially identified on December 2019, in Wuhan city of China is currently affecting 146 territories, states and countries raising distress, panic and increasing anxiety in individuals exposed to the (actual or supposed) peril of the virus across the globe. Fundamentally, these concerns ascend with all infections, including those of flu and other agents, and the same worldwide safeguards are compulsory and suggested for protection and the prevention of further diffusion. However, media has underlined COVID-19 as rather an exclusive threat, which has added to panic and stress in masses which can lead to several mental health issues like anxiety, obsessive compulsive disorder and post-traumatic stress disorder which should be contained immediately in its initial phases.


title: A review of extraaxial developmental venous anomalies of the brain involving dural venous flow or sinuses: persistent embryonic sinuses, sinus pericranii, venous varices or aneurysmal malformations, and enlarged emissary veins.

text: This paper is a narrative review of extraaxial developmental venous anomalies (eDVAs) of the brain involving dural venous flow or sinuses: persistent embryonic sinuses, sinus pericranii, enlarged emissary veins, and venous varices or aneurysmal malformations. The article highlights the natural history, anatomy, embryology, imaging, clinical implications, and neurosurgical significance of these lesions, which the authors believe represent a continuum, with different entities characterized by distinct embryopathologic features. The indications and surgical management options are discussed for these individual intracranial pathologies with relevant illustrations, and a novel classification is proposed for persistent falcine sinus (PFS). The role of neurointervention and/or microsurgery in specific cases such as sinus pericranii and enlarged emissary veins of the skull is highlighted. A better understanding of the pathophysiology and developmental anatomy of these lesions can reduce treatment morbidity and mortality. Some patients, including those with vein of Galen malformations (VOGMs), can present with the added systemic morbidity of a high-output cardiac failure. Although VOGM is the most studied and classified of the above-mentioned eDVAs, the authors believe that grouping the former with the other venous anomalies/abnormalities listed above would enable the clinician to convey the exact morphophysiological configuration of these lesions, predict their natural history with respect to evolving venous hypertension or stroke, and extrapolate invaluable insights from VOGM treatment to the treatment of other eDVAs. In recent years, many of these symptomatic venous malformations have been treated with endovascular interventions, although these techniques are still being refined. The authors highlight the broad concept of eDVAs and hope that this work will serve as a basis for future studies investigating the role of evolving focal venous hypertension/global intracranial hypertension and possibilities of fetal surgical intervention in these cases.


title: Evaluation of crosslinked and non-crosslinked biologic prostheses for abdominal hernia repair.

text: INTRODUCTION Abdominal wall defects and incisional hernias represent a challenging problem. Currently, several commercially available biologic prostheses are used clinically for hernia repair. We compared the performance and efficacy of two non-crosslinked meshes in ventral hernia repair to two crosslinked prostheses in a rodent model. METHODS Animals were divided into 12 groups (4 matrix types and 3 termination time-points per matrix). A ventral defect was carefully created and overlapped with the biologic prosthesis. RESULTS Major complications were seroma induction (3 mesh types), implant extrusion (1 mesh type), severe inflammatory and immune responses (non-crosslinked mesh), fibrosis and mineralisation (3 mesh types). After inflammation resolution, 3 of the matrices tested supported hernia healing but with marked tissue and temporal differences. AlloDerm(®*) and Surgisis Gold™ showed tissue reactivity with the host and a rapid rate of matrix remodelling. Bard CollaMend™(*) Implant proved to be inept for hernia repair under the conditions tested. Permacol™ biological implant integration with host tissue increased over time, supporting hernia healing with strength of tissue, and appears to be a safe prosthetic material for ventral hernia repair based on the results of this rodent study.


title: Treatment of Intracranial Aneurysms With Pipeline Embolization Device: Newer Applications and Technical Advances.

text: OPINION STATEMENT Pipeline embolization device (PED) is a flow diverter used in the endovascular treatment of intracranial aneurysms, particularly those with unfavorable configurations. It works by causing progressive flow redirection leading to thrombosis within the aneurysm. PED was initially approved for adults with large or giant wide-necked (≥4 mm or no discernible neck) aneurysms of the internal carotid artery (ICA) from the petrous to the superior hypophyseal segments. Studies have shown a superior aneurysm occlusion rate of 85 % at 6 months for the PED and mortality ranging from 2.6 to 4 %. There appears to be a knowledge gap in terms of the duration of dual antiplatelet therapy and efficacy of assessing platelet inhibition. However, increasing operator experience and favorable longer-term outcome data have led to the exploration of PED for a wide array of off-label uses. Given the paucity of good-quality studies comparing PED with other endovascular/surgical treatment options, several multicenter randomized trials are currently underway to answer these important questions.


Schistosomiasis haematobium, Corsica, France.


title: Likelihood of achieving a 50%, 60%, or 70% estimated live birth rate threshold with 1 or 2 cycles of planned oocyte cryopreservation.

text: PURPOSE To characterize the likelihood of cryopreserving enough oocytes for 50%, 60%, or 70% estimated live birth rate (eLBR) with 1-2 planned oocyte cryopreservation (Pl-OC) cycles. METHODS We performed a retrospective cohort study utilizing all patients completing ≥ 1 Pl-OC cycle from 2016 to 2018 at a large single-center OC program. Subjects were categorized by age at retrieval and number of cycles. We extrapolated age-based oocyte thresholds for 50%, 60%, or 70% eLBR from previously published data. We calculated the proportion of subjects overall, and for each age group, whose number of frozen oocytes was greater than or equal to their age-based threshold for a 50%, 60%, or 70% eLBR after 1 and 2 cycles. OR for 60% eLBR with one cycle was calculated for age and AMH cutoff values and corroborated with logistic regression. RESULTS A total of 1241 subjects, completing 1799 Pl-OC cycles, were included. With one cycle, 66% (819/1241) achieved ≥ 50% eLBR and 51% (634/1241) achieved 70% eLBR. With two cycles, 79.6% (988/1241) attained ≥ 50% eLBR and 65.5% (813/1241) achieved 70% eLBR. Achieving 50%, 60%, or 70% eLBR with 1-2 cycles was significantly associated with both age (p < 0.001) and AMH (p < 0.001). Age < 37.5 and AMH > 1.995 were independently associated with attaining 60% eLBR with one cycle (age: OR 13.73; 95%CI 9.16-20.57, p < 0.001; AMH: OR 7.32; 95% CI 5.50-9.76, p < 0.001). CONCLUSIONS Younger age and higher AMH were associated with achieving 50%, 60%, or 70% eLBR thresholds with Pl-OC. Nevertheless, almost all subjects were successfully able to preserve enough oocytes for ≥ 50% eLBR in 1-2 cycles.


title: Mechanical analysis of the formation of forceps and scope for single-port laparoscopic surgery.

text: BACKGROUND The aim of this study is to demonstrate a shaft formation of forceps and scope which provides higher degree of freedom of motion for single-port laparoscopic surgery (SPLS). The key to smoothly performing SPLS lies in understanding the formation in which the shaft conflict is minimized. However, there have been no reported studies on conflict reduction in SPLS from a shaft formation perspective. METHODS When performing SPLS, 3 instruments are passed into a narrow space, only 2 patterns of shaft formation can be obtained: a formation in which the 3 instruments rotate clockwise or counterclockwise (rotation formation) or a formation in which 1 instrument passes between the other 2 (cross formation). So motion spaces of the instruments in rotation formation compared with that in cross formation were tested using engineering methods. The range of the forceps' motion was assumed to be the space covered by the forceps till collision occurred between the moving forceps and either the other fixed forceps or the fixed scope. Examination of the range of movement of the scope was conducted in the same manner. The motion space with the area on the x-y horizontal is evaluated, as viewed from the peritoneal umbilicus port entry area. RESULTS The motion area of each instrument in rotation formation is 1.9 to 2.6 times wider than that in cross formation. CONCLUSIONS Rotation formation provides high degree of freedom of motion for SPLS.


title: Mango By-Products As Natural Source of Valuable Odor-Active Compounds.

text: BACKGROUND In order to seek natural and cheap sources of odor-active compounds, the aromatic potential of mango by-products was evaluated. A chemical characterization of volatile compounds of mango peel and seed were performed in comparison with mango pulp by HS-SPME/GC-MS. RESULTS More than 60 volatile compounds were detected in mango by-products whose aromatic activity was estimated by means of odorant activity values (OAVs). Results pointed out mango peel as a valuable matrix on odor-active compounds which were found even in larger quantities than in edible mango fraction. 3-Carene was the predominant compound although other compounds such as decanal, 1-octen-3-one, nonanal, limonene, β-damascenone and 2-nonenal were the most odor-active compounds in mango peel. The greatest aromatic impact with sensorial features described as fresh/herbaceous, fruity, floral and resinous was found in peel mango. CONCLUSION The exceptional flavoring potential of mango peel by-product opens a door for its use and revalorization as natural flavoring ingredient in food and cosmetic industries. This article is protected by copyright. All rights reserved.


Plastic stents in the treatment of benign esophageal conditions.


title: Costs associated with functional gastrointestinal disorders and related signs and symptoms in infants: a systematic review protocol.

text: INTRODUCTION Functional gastrointestinal disorders (FGIDs) and FGID-related signs and symptoms have a fundamental impact on the psychosocial, physical and mental well-being of infants and their parents alike. Recent reviews and studies have indicated that FGIDs and related signs and symptoms may also have a substantial impact on the budgets of third-party payers and/or parents. The objective of this systematic review is to investigate these costs. METHODS AND ANALYSIS The population of interest is healthy term infants (under 12 months of age) with colic, regurgitation and/or functional constipation. Outcomes of interest will include the frequency and volume of reported treatments, the cost to third-party payers and/or parents for prescribed or over the counter treatments, visits to health professionals and changes in infant formula purchases, and the loss of income through time taken off work and out of pocket costs. Relevant studies will be identified by searching databases from 2005 onwards (including MEDLINE, EMBASE, PsycINFO, NEXIS, DARE, Health Technology Assessment database, National Health Service Economic Evaluation Database and others), conferences from the previous 3 years and scanning reference lists of eligible studies. Study selection, data extraction and quality assessment will be conducted by two independent reviewers and disagreements resolved in discussion with a third reviewer. Quality assessment will involve study design-specific checklists. Relevant studies will be summarised narratively and presented in tables. An overview of treatments and costs will be provided, with any geographical or other differences highlighted. An assessment of how the totals for cost differ across countries and elements that contribute to the differences will be generated. ETHICS AND DISSEMINATION This is a systematic review of published studies that will be submitted for publication to a peer-reviewed journal. Ethical committee approval is not required. TRIAL REGISTRATION NUMBER CRD42016033119.


title: When an emerging disease becomes endemic.

text: Epidemics, such as HIV in the early 1980s and Ebola in 2014, inspire decisive government investment and action, and individual and societal concern, sometimes bordering on panic. By contrast, endemic diseases, such as HIV in 2017 and tuberculosis, struggle to maintain the same attention. For many, the paradox is that endemic disease, in its totality, continues to impose a far higher public health burden than epidemic disease. Overall, the swift political response to epidemics has resulted in success. It has proven possible to eradicate epidemic diseases, often without the availability of vaccines and other biomedical technologies. In recent times, only HIV has made the transition from epidemic to endemic, but diseases that have existed for centuries continue to cause most of the infectious disease burden.


title: Assessment of sites of marrow and extramedullary hematopoiesis by hybrid imaging in primary myelofibrosis patients.

text: We investigated noninvasive procedures by hybrid imaging to assess the sites of active or inactive hematopoiesis in patients with primary myelofibrosis (PMF). To this end, we used two radionuclides, technetium 99m ((99m) Tc) and indium 111-chloride ((111) In-Cl3 ), coupled with single-photon emission tomography/computed tomography (SPECT/CT). We studied five patients with PMF and one with secondary myelofibrosis (MF). The classical pattern of lower fixation of both tracers at the axial skeleton where the myelofibrotic process occurs and the reactivation of sites of active hematopoiesis at the distal skeleton were confirmed. Coupling both radionuclides to SPECT/CT imaging allowed for more precise visualization of the sites of extramedullary hematopoiesis as those observed in the spleen and liver. Splenic high uptake of (111) In-Cl3 coupled with SPECT/CT represents a pathognomonic feature of PMF. We conclude that, the hybrid imaging procedures that we studied might constitute an alternative noninvasive method for the screening of the whole-body marrow and, by this way, to assess the impact of targeted therapies in PMF patients in whom it is well known that the distribution of the hematopoietic active areas is disturbed. Hybrid imaging could also be useful for diagnostic purposes in cases of early PMF or in suspected cases of myelofibrosis secondary to polycythemia vera or essential thrombocythemia.


title: Camera navigation and cannulation: validity evidence for new educational tasks to complement the Fundamentals of Laparoscopic Surgery program.

text: BACKGROUND Experts identified camera navigation and cannulation as important skills that are not assessed by the Fundamentals of Laparoscopic Surgery (FLS) hands-on examination. The purpose of this study was to create metrics for and evaluate the validity for two new tasks: camera navigation (N) and cannulation (C), and to explore the potential value of adding these tasks to the FLS program. METHODS Participants were assessed by two raters during performance of N and C in addition to the five standard FLS tasks. They also completed a questionnaire regarding the educational value of the new tasks. Validity evidence was assessed by comparing performance between Novice (PGY 1 and 2) and Experienced (PGY 3 and higher) participants, and by correlating new task scores with standard FLS scores. The ability to predict level of training using scores was evaluated by regression analysis. RESULTS Sixty subjects participated from five North American centers. Inter-rater reliabilities for both tasks were 0.99. Novice and Experienced participants scored 74 ± 17.8 versus 85 ± 8.3 (p < 0.01) and 21 ± 17.3 versus 39 ± 20.1 (p < 0.01) on N and C tasks, respectively. Correlations with total FLS scores for N and C were 0.39 and 0.53, respectively. Prediction of training level using the combination of all seven tasks was 52.6 % (R (2) = 0.526, p < 0.01), adding an additional 2.2 % to the five FLS tasks. Of 55 participants with laparoscopic experience, 51 % reported N to be similar in difficulty to reality. Of 28 participants who perform intraoperative cholangiograms, 43 % found C to be more difficult than reality. Most (70 %) participants thought the new tasks added value to FLS. CONCLUSIONS This study provides preliminary validity evidence for the metrics of these new tasks. The value of adding these tasks to the FLS manual skills assessment is marginal in terms of predicting level of training.


title: U.S. High-Level Isolation Unit Clinical Laboratory Capabilities Update.

text: In late 2014, 56 hospitals in the United States were designated by state and federal public health authorities as specially designed high-level isolation units (HLIUs) equipped with advanced infrastructure, laboratory capabilities, and trained staff to care for patients with highly hazardous communicable diseases (HHCDs), such as Ebola virus disease. This survey describes the clinical laboratory support capabilities of U.S. HLIUs, including the specific test menus that HLIUs have identified to safely manage HHCD patients and the locations where such testing would be performed. In spring 2016, a survey was electronically distributed, as a fillable pdf file, to the 56 U.S. HLIUs. Site representatives completed the surveys, and data were coded and analyzed in an electronic spreadsheet, using descriptive statistics. Thirty-six HLIUs (64%) responded, and 33 completed the laboratory capabilities section. Thirty-one HLIUs (94%) had performed risk analyses for all laboratory procedures and equipment. Twenty-nine (88%) had decontamination procedures specified for all laboratory equipment used for patients with suspected or confirmed HHCDs. On-site laboratories in 27 HLIUs (81%) had the capacity to inventory and to securely store HHCD patient specimens. Ten HLIUs (31%) had at least one test they would conduct within the patient isolation room. The high-risk nature of HHCDs and the occupational exposures that may occur in clinical laboratories demand advanced preparation and risk assessment of work practices, laboratory equipment, and instrumentation by HLIU laboratories. Although risk analyses of clinical laboratory testing and equipment that HLIUs have conducted have likely focused on those for Ebola virus, HLIUs must be prepared to revise their current procedures for other HHCDs.


Time to unite behind BVA veterinary leaders.


COVID-19 research in Africa.


title: Design, synthesis, antiviral, and cytostatic evaluation of novel isoxazolidine analogues of C-nucleotides.

text: 5-Aryl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesised from N-methyl-C-diethoxyphosphorylnitrone and vinyl aryls in good yields. Isoxazolidine phosphonates obtained herein were evaluated for activity against a broad range of DNA and RNA viruses. None of the compounds were endowed with antiviral activity nor cytostatic activity at 100 to 250 μM concentrations.


docid: zrxkgoou

title: Safety, feasibility, and short-term outcomes of single port access colorectal surgery: a single institutional case-matched study.

text: BACKGROUND Feasibility of single port access (SPA) colorectal surgery has been established for various procedures from ileocecal resection to proctectomy. Nevertheless, its benefits compared to conventional laparoscopy still need to be assess. The aim of this study was to compare SPA to conventional colorectal laparoscopic surgery in a single institutional case-matched study. METHODS From July 2009 to July 2010, 25 SPA colorectal resections were matched on main predictive risk factors of postoperative complications, in a one to two fashion, with patient having the same procedure for the same indication by conventional laparoscopy. RESULTS Patient characteristics were comparable between both groups. SPA was successfully performed in 24 of 25 patients, with a need to conversion to standard laparoscopy in one case (4%). SPA was associated with a significantly shorter median operative time (130 vs 180 min, p = 0.04) and hospital stay (6 vs 7 days, p = 0.005). Postoperative morbidity rates were similar between the two groups (4% vs 16%, p = 0.25). CONCLUSION SPA colorectal resection can be safely performed in selected patients with results comparable to those observed after conventional laparoscopic surgery. However, larger studies including randomized controlled trail are needed to demonstrate possible benefits of SPA colorectal resection over conventional colorectal laparoscopic surgery.


title: Exudative cloacitis in the kakapo (Strigops habroptilus) potentially linked to Escherichia coli infection.

text: AIM To investigate the initiating causes of cloacitis (inflammation of the cloaca) in kakapo (Strigops habroptilus). METHODS Metagenomics using unbiased RNA or DNA sequencing was applied to faecal material from an 11-year-old female kakapo with exudative cloacitis, and a pool of eight birds (male and female aged 1-20 years) with no current signs or history of the disease. Faecal material from the diseased bird was collected pre- and post-treatment. For RNA sequencing, extracted RNA/DNA was subject to DNase, and the remaining RNA reverse transcribed to cDNA and subject to multiple displacement amplification prior to sequencing. RESULTS No significant alignment to any known avian virus sequence was obtained from any faecal samples. However significant BLAST alignments to five bacteriophages known to infect enterobacteria were obtained. Strong evidence was obtained for the presence of the bacteriophage Escherichia phage TL-2011b, a bacteriophage known to occur in Escherichia coli causing outbreaks of foodborne disease in humans, in the sample from the diseased bird, but not the non-diseased pool. Differences in E. coli community structure between the diseased bird and the non-diseased pool were also apparent. CONCLUSIONS Escherichia coli infection of human origin is suggested as a possible cause of exudative cloacitis, although confirmatory work is required to test this hypothesis.


docid: ufrkxwfb

title: Effects of Fractional Inspired Oxygen on Cerebral Oxygenation in Preterm Infants following Delivery.

text: OBJECTIVES To explore regional cerebral oxygen saturations (rcSO2) in preterm neonates initially stabilized with 0.3 fractionated inspired oxygen (FiO2) concentrations. We hypothesized that those infants who received >0.3 FiO2 during stabilization following delivery would have relatively higher rcSO2 postdelivery compared with those stabilized with a lower FiO2. STUDY DESIGN A single center prospective observational study of 47 infants born before 32 weeks. Using near infrared spectroscopy, rcSO2 values were recorded immediately after birth. All preterm infants were initially given 0.3 FiO2 and were divided into 2 groups according to subsequent FiO2 requirements of either ≤0.3 or >0.3 FiO2. Using a mixed-effects model, we compared the difference between the groups over time. Also, the area measures below 55% (hypoxia) and above 85% (hyperoxia) were compared between the groups. RESULTS The mean (SD) gestation was 29.4 (1.6) weeks and the mean (SD) weight was 1.3 (0.4) kg. Less than one-half of the infants (20/45; 43%) required ≤0.3 FiO2. In the delivery suite, the median (IQR) rcSO2 in the low and high FiO2 groups were 81% (66%-86%) and 72% (62%-86%), respectively. Patients in the high FiO2 group had a larger rcSO2 area below 55% (P = .01). There was a significant difference in rcSO2 between the groups (P < .05), with the low group having higher rcSO2 values initially, but this difference changed over time. In the neonatal intensive care unit (NICU), rcSO2 values were lower by 7.1% (CI 12.13 to 2.06%) P = .008 in the high FiO2 group. CONCLUSIONS Infants given >0.3 FiO2 had more cerebral hypoxia than infants requiring ≤0.3 FiO2 but no difference in the degree of cerebral hyperoxia, both in the delivery suite and the NICU. This suggests that a more rapid increase in oxygen titration maybe be required initially for preterm infants.


title: Laparoscopic and endoscopic cooperative surgery for cholecystogastric fistula: A case report.

text: INTRODUCTION Cholecystoenteric fistula (CEF) is rare in biliary tract surgery, and cholecystogastric fistula (CGF) is the rarest form of CEF. Although open cholecystectomy with the closure of the fistula is the gold standard treatment for nonobstructing biliary-enteric fistulas, the optimal treatment for CGF has not been established. Laparoscopic and endoscopic cooperative surgery (LECS), a minimally invasive surgery for gastric submucosal tumors, reportedly helps achieve favorable postoperative outcomes. This report presents a case wherein CGF was treated with LECS. CASE PRESENTATION An-84-year-old man with a history of chemotherapy for ileocecal diffuse large B cell lymphoma presented with fever and abdominal pain. He was diagnosed with cholangitis, and endoscopic lithotripsy was performed. Abdominal contrast-enhanced computed tomography revealed gastric wall thickening close to the gallbladder, indicating a malignant lymphoma. Esophagogastroduodenoscopy revealed a concavity on the anterior wall of the antrum of the stomach. Direct endoscopic cholangiography, which was performed by the injection of a contrast medium into the concavity, confirmed the concavity to be a CGF. Cholecystectomy with the closure of the fistula using the LECS was performed to check for suture line leakage and the positional relation of the suture line and the pylorus. The resected specimen showed acute and chronic cholecystitis without malignancy. The patient did not experience postoperative complications in the subsequent 3 months. DISCUSSION Resection and closure of the fistula using LECS were performed successfully. CONCLUSION LECS can be performed for CGF. LECS enables intraoperative observation of the fistula and suture line, and thus reduces postoperative complications.


title: Restoring antiviral immunity with adoptive transfer of ex-vivo generated T cells.

text: PURPOSE OF REVIEW Latent viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus (ADV) often reactivate in immunocompromised patients, contributing to poor clinical outcomes. A rapid reconstitution of antiviral responses via adoptive transfer of virus-specific T cells (VSTs) can prevent or eradicate even refractory infections. Here, we evaluate this strategy and the associated methodological, manufacturing and clinical advances. RECENT FINDINGS From the early pioneering but cumbersome efforts to isolate CMV-specific T cell clones, new approaches and techniques have been developed to provide quicker, safer and broader-aimed ex-vivo antigen-specific cells. New manufacturing strategies, such as the use of G-Rex flasks or 'priming' with a library of overlapping viral peptides, allow for culturing greater numbers of cells that could be patient-specific or stored in cell banks for off-the-shelf applications. Rapid isolation of T cells using major histocompatibility complex tetramer or cytokine capture approaches, or genetic reprogramming of cells to target viral antigens can accelerate the generation of potent cellular products. SUMMARY Advances in the ex-vivo generation of VSTs in academic medical centres and as off-the-shelf blood bank-based or commercially produced reagents are likely to result in broader accessibility and possible manufacturing cost reduction of these cell products, and will open new therapeutic prospects for vulnerable and critically ill immunocompromised patients.


Reperfusion therapy for acute ischemic stroke: how should we react to the Third Interventional Management of Stroke (IMS III) trial?


title: Single-port laparoscopic surgery for inflammatory bowel disease.

text: Background. Single Port Laparoscopic Surgery (SPLS) is being increasingly employed in colorectal surgery for benign and malignant diseases. The particular role for SPLS in inflammatory bowel disease (IBD) has not been determined yet. In this review article we summarize technical aspects and short term results of SPLS resections in patients with Crohn's disease or ulcerative colitis. Methods. A systematic review of the literature until January 2012 was performed. Publications were assessed for operative techniques, equipment, surgical results, hospital stay, and readmissions. Results. 34 articles, published between 2010 and 2012, were identified reporting on 301 patients with IBD that underwent surgical treatment in SPLS technique. Surgical procedures included ileocolic resections, sigmoid resections, colectomies with end ileostomy or ileorectal anastomosis, and restorative proctocolectomies with ileum-pouch reconstruction. There was a wide variety in the surgical technique and the employed equipment. The overall complication profile was similar to reports on standard laparoscopic surgery in IBD. Conclusions. In experienced hands, single port laparoscopic surgery appears to be feasible and safe for the surgical treatment of selected patients with IBD. However, evidence from prospective randomized trials is required in order to clarify whether there is a further benefit apart from the avoidance of additional trocar incisions.


Covid-19: Doctors should not face investigation for refusing to see patients over lack of PPE, says indemnifier.


title: The SARS crisis: reflections of Hong Kong nurses.

text: BACKGROUND Severe acute respiratory syndrome (SARS) exerted a massive toll on Hong Kong's healthcare system in 2003. AIM This research examines front-line nurses' reflections on the time of SARS in Hong Kong in order to articulate: (1) the nature and complexity of their experience, and (2) what lessons can be learned for future disease crises. METHODS Personal reflective essays written in 2004 by seven senior nurses studying a part-time Masters in Nursing degree at a Hong Kong university were analysed using a form of content analysis. FINDINGS The nurses' stories report immense personal costs on nurses, on their families and on the wider community. The analysis of the narratives was used to build a model, indicating how nurses' personal lives were 'sandwiched' between, on the one hand, their commitment to families and local community and, on the other hand, their professional commitment to the needs of a health system in crisis. CONCLUSION In dealing with future health crises, it is imperative that a multilevel approach be taken.


title: Penile rehabilitation for postprostatectomy erectile dysfunction.

text: BACKGROUND Despite efforts to preserve the neurovascular bundles with nerve-sparing surgery, erectile dysfunction remains common following radical prostatectomy. Postoperative penile rehabilitation seeks to restore erectile function but results have been conflicting. OBJECTIVES To evaluate the effects of penile rehabilitation strategies in restoring erectile function following radical prostatectomy for prostate cancer. SEARCH METHODS We performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase), the Cochrane Library, Web of Science, clinical trial registries (ClinicalTrials.gov, International Clinical Trials Registry Platform) and a grey literature repository (Grey Literature Report) from their inception through to 3 January 2018. We also searched the reference lists of other relevant publications and abstract proceedings. We applied no language restrictions. SELECTION CRITERIA We included randomised or quasi-randomised trials with a parallel or cross-over design. DATA COLLECTION AND ANALYSIS We used standard Cochrane methodological procedures. Two review authors independently screened the literature, extracted data, assessed risk of bias and rated quality of evidence according to GRADE on a per-outcome basis. Primary outcomes were self-reported potency, erectile function measured by validated questionnaires (with potency defined as an International Index of Erectile Function (IIEF-EF) score of 19 or greater and or an IIEF-5 of score of 17 or greater) and serious adverse events. For all quality of life assessments on a continuous scale, higher values indicated better quality of life. MAIN RESULTS We included eight randomised controlled trials with 1699 participants across three comparisons. This abstract focuses on the primary outcomes of this review only.Scheduled phosphodiesterase type 5 inhibitors (PDE5I) versus placebo or no treatmentScheduled PDE5I may have little or no effect on short-term (up to 12 months) self-reported potency (risk ratio (RR) 1.13, 95% confidence interval (CI) 0.91 to1.41; very low quality evidence), which corresponds to 47 more men with self-reported potency per 1000 (95% CI 33 fewer to 149 more) and short-term erectile function as assessed by a validated instrument (RR 1.11, 95% CI 0.80 to 1.55; very low quality evidence), which corresponds to 28 more men per 1000 (95% CI 50 fewer to 138 more), but we are very uncertain of both of these findings. Scheduled PDE5I may result in fewer serious adverse events compared to placebo (RR 0.32, 95% CI 0.11 to 0.94; low quality evidence), though this does not appear biologically plausible and may represent a chance finding. We are also very uncertain of this finding. We found no long-term (longer than 12 months) data for any of the three primary outcomes.Scheduled PDE5I versus on-demand PDE5I Daily PDE5I appears to result in little to no difference in both short-term and long-term (greater than 12 months) self-reported potency (short term: RR 0.97, 95% CI 0.62 to 1.53; long term: RR 1.00, 95% CI 0.60 to 1.67; both very low quality evidence); this corresponds to nine fewer men with self-reported short-term potency per 1000 (95% CI 119 fewer to 166 more) and zero fewer men with self-reported long-term potency per 1000 (95% CI 153 fewer to 257 more). We are very uncertain of these findings. Daily PDE5I appears to result in little to no difference in short-term and long-term erectile function (short term: RR 1.00, 95% CI 0.65 to 1.55; long term; RR 0.74, 95% CI 0.48 to 1.14; both very-low quality evidence), which corresponds to zero men with short-term erectile dysfunction per 1000 (95% CI 80 fewer to 125 more) and 119 fewer men with long-term erectile dysfunction per 1000 (95% CI 239 fewer to 64 more). We are very uncertain of these findings. Scheduled PDE5I may result in little or no effects on short-term adverse events (RR 0.69 95% CI 0.12 to 4.04; very low quality evidence), which corresponds to seven fewer men with short-term serious adverse events (95% CI 18 fewer to 64 more), but we are very uncertain of these findings. We found no long-term data for serious adverse events.Scheduled PDE5I versus scheduled intraurethral prostaglandin E1At short-term follow-up, daily PDE5I may result in little or no effect on self-reported potency (RR 1.10, 95% CI 0.79, to 1.52; very low quality evidence), which corresponds to 46 more men per 1000 (95% CI 97 fewer to 241 more). Daily PDE5I may result in a small improvement of erectile function (RR 1.64, 95% CI 0.84 to 3.20; very low quality evidence), which corresponds to 92 more men per 1000 (95% CI 23 fewer to 318 more) but we are very uncertain of both these findings. We found no long-term (longer than 12 months) data for any of the three primary outcomes.We found no evidence for any other comparisons and were unable to perform any of the preplanned subgroup analyses based on nerve-sparing approach, age or baseline erectile function. AUTHORS' CONCLUSIONS Based on mostly very-low and some low-quality evidence, penile rehabilitation strategies consisting of scheduled PDE5I use following radical prostatectomy may not promote self-reported potency and erectile function any more than on demand use.


title: Pre-arrest and intra-arrest prognostic factors associated with survival after in-hospital cardiac arrest: systematic review and meta-analysis.

text: OBJECTIVE To determine associations between important pre-arrest and intra-arrest prognostic factors and survival after in-hospital cardiac arrest. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline, PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systematic Reviews from inception to 4 February 2019. Primary, unpublished data from the United Kingdom National Cardiac Arrest Audit database. STUDY SELECTION CRITERIA English language studies that investigated pre-arrest and intra-arrest prognostic factors and survival after in-hospital cardiac arrest. DATA EXTRACTION PROGRESS (prognosis research strategy group) recommendations and the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist were followed. Risk of bias was assessed by using the QUIPS tool (quality in prognosis studies). The primary analysis pooled associations only if they were adjusted for relevant confounders. The GRADE approach (grading of recommendations assessment, development, and evaluation) was used to rate certainty in the evidence. RESULTS The primary analysis included 23 cohort studies. Of the pre-arrest factors, male sex (odds ratio 0.84, 95% confidence interval 0.73 to 0.95, moderate certainty), age 60 or older (0.50, 0.40 to 0.62, low certainty), active malignancy (0.57, 0.45 to 0.71, high certainty), and history of chronic kidney disease (0.56, 0.40 to 0.78, high certainty) were associated with reduced odds of survival after in-hospital cardiac arrest. Of the intra-arrest factors, witnessed arrest (2.71, 2.17 to 3.38, high certainty), monitored arrest (2.23, 1.41 to 3.52, high certainty), arrest during daytime hours (1.41, 1.20 to 1.66, high certainty), and initial shockable rhythm (5.28, 3.78 to 7.39, high certainty) were associated with increased odds of survival. Intubation during arrest (0.54, 0.42 to 0.70, moderate certainty) and duration of resuscitation of at least 15 minutes (0.12, 0.07 to 0.19, high certainty) were associated with reduced odds of survival. CONCLUSION Moderate to high certainty evidence was found for associations of pre-arrest and intra-arrest prognostic factors with survival after in-hospital cardiac arrest. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42018104795.


title: Coping with future epidemics: Tai chi practice as an overcoming strategy used by survivors of severe acute respiratory syndrome (SARS) in post-SARS Hong Kong.

text: BACKGROUND Although SARS had been with a controversial topic for a decade at the time of this study, numerous SARS survivors had not yet physically, psychologically or socially recovered from the aftermath of SARS. Among chronically ill patients, the use of complementary and alternative medicine (CAM) is reported to be widespread. However, extremely little is known about the use of CAM by SARS survivors in the post-SARS period and even less is known about how the use of CAM is related to the unpleasant social and medical-treatment experiences of SARS survivors, their eagerness to re-establish social networks, and their awareness to prepare for future epidemics. OBJECTIVE To investigate the motivations for practising tai chi among SARS survivors in post-SARS Hong Kong. DESIGN, SETTING AND PARTICIPANTS Using a qualitative approach, I conducted individual semi-structured interviews with 35 SARS survivors, who were purposively sampled from a tai chi class of a SARS-patient self-help group in Hong Kong. RESULTS Health concerns and social experiences motivated the participants to practise tai chi in post-SARS Hong Kong. Experiencing health deterioration in relation to SARS-associated sequelae, coping with unpleasant experiences during follow-up biomedical treatments, a desire to regain an active role in recovery and rehabilitation, overcoming SARS-associated stigmas by establishing a new social network and preparing for potential future stigmatization and discrimination were the key motivators for them. CONCLUSION The participants practised tai chi not only because they sought to improve their health but also because it provided a crucial social function and meaning to them.


Neurosurgery at the time of COVID-19: how this pandemic infectious disease is influencing neurosurgical activities and patient management.


docid: umkauphp

title: Computer-aided drug design of falcipain inhibitors: virtual screening, structure-activity relationships, hydration site thermodynamics, and reactivity analysis.

text: Falcipains (FPs) are hemoglobinases of Plasmodium falciparum that are validated targets for the development of antimalarial chemotherapy. A combined ligand- and structure-based virtual screening of commercial databases was performed to identify structural analogs of virtual screening hits previously discovered in our laboratory. A total of 28 low micromolar inhibitors of FP-2 and FP-3 were identified and the structure-activity relationship (SAR) in each series was elaborated. The SAR of the compounds was unusually steep in some cases and could not be explained by a traditional analysis of the ligand-protein interactions (van der Waals, electrostatics, and hydrogen bonds). To gain further insights, a statistical thermodynamic analysis of explicit solvent in the ligand binding domains of FP-2 and FP-3 was carried out to understand the roles played by water molecules in binding of these inhibitors. Indeed, the energetics associated with the displacement of water molecules upon ligand binding explained some of the complex trends in the SAR. Furthermore, low potency of a subset of FP-2 inhibitors that could not be understood by the water energetics was explained in the context of poor chemical reactivity of the reactive centers of these compounds. The present study highlights the importance of considering energetic contributors to binding beyond traditional ligand-protein interactions.


title: The COVID-19 pandemic: growth patterns, power law scaling, and saturation.

text: More and more countries show a significant slowdown in the number of new COVID-19 infections due to effective governmentally instituted lockdown and social distancing measures. We have analyzed the growth behavior of the top 25 most affected countries by means of a local slope analysis and found three distinct patterns that individual countries follow depending on the strictness of the lockdown protocols: rise and fall, power law, or logistic. For countries showing power law growth we have determined the scaling exponents. For countries that showed a strong slowdown in the rate of infections we have extrapolated the expected saturation of the total number of infections and the expected final date. Three different extrapolation methods (logistic, parabolic, and cutoff power law) were used. All methods agree on the order of magnitude of saturation and end dates. Global infection rates are analyzed with the same methods. The relevance and accuracy of these extrapolations is discussed.


title: The lysine residues within the human ribosomal protein S17 sequence naturally inserted into the viral nonstructural protein of a unique strain of hepatitis E virus are important for enhanced virus replication.

text: UNLABELLED Hepatitis E virus (HEV) is an important but extremely understudied human pathogen. Due largely to the lack of an efficient cell culture system for HEV, the molecular mechanisms of HEV replication and pathogenesis are poorly understood. Recently, a unique genotype 3 strain of HEV recovered from a chronically infected patient was adapted for growth in HepG2C3A human hepatoma cells. The adaptation of the Kernow C-1 P6 HEV to propagate in HepG2C3A cells selected for a rare virus recombinant that contains an insertion of a 171-nucleotide sequence encoding amino acids 21 to 76 of the human ribosomal protein S17 (RPS17) within the hypervariable region (HVR) of the HEV ORF1 protein. When the RPS17 insertion was placed into a strain of genotype 1 HEV which infects only humans, it expanded the host range of the virus, allowing it to infect cell lines from multiple animal species, including cow, dog, cat, chicken, and hamster. In this study, we utilized forward and reverse genetics to attempt to define which aspects of the RPS17 insertion allow for the ability of the Kernow C-1 P6 HEV to adapt in cell culture and allow for expanded host tropism. We demonstrate that the RPS17 sequence insertion in HEV bestows novel nuclear/nucleolar trafficking capabilities to the ORF1 protein of Kernow P6 HEV and that lysine residues within the RPS17 insertion, but not nuclear localization of the ORF1 protein, correlate with the enhanced replication of the HEV Kernow C-1 P6 strain. The results from this study have important implications for understanding the mechanism of cross-species infection and replication of HEV. IMPORTANCE HEV is an important pathogen worldwide. The virus causes high mortality (up to 30%) in pregnant women and has been recognized to cause chronic hepatitis in immunocompromised populations. The life cycle of HEV has been understudied due to a lack of sufficient cell culture systems in which to propagate the virus. Recently, insertions and rearrangements of the hypervariable region (HVR) within the HEV genome, allowing for cell culture adaptation and expansion of the host range, have been reported. We utilized these cell culture-adapted HEV strains to assess how the HVR may be involved in virus replication and host range. We provide evidence that insertion of the RPS17 sequence in HEV likely confers nuclear trafficking capabilities to the nonstructural protein of the virus and that lysine residues within the RPS17 insertion are important for enhanced replication of the virus. These data will help to elucidate the mechanism of cross-species infection of HEV in the future.


title: Treatments for COVID-19: emerging drugs against the coronavirus.

text: The Coronavirus disease 19 (COVID-19) outbreak has been recognized as a global threat to public health. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and no effective therapies currently exist against this novel viral agent. Along with extensive public health measures, an unprecedented global effort in identifying effective drugs for the treatment is being implemented. Potential drug targets are emerging as the result of a fast-evolving understanding of SARS-CoV-2 virology, host response to the infection, and clinical course of the disease. This brief review focuses on the latest and most promising pharmacological treatments against COVID-19 currently under investigation and discuss their potential use based on either documented efficacy in similar viral infections, or their activity against inflammatory syndromes. Ongoing clinical trials are also emphasized.


Philosophy Problems Become Real During the COVID-19 Pandemic.


title: ASPS clinical practice guideline summary on breast reconstruction with expanders and implants.

text: LEARNING OBJECTIVES After reading this article, participants should be able to: 1. Understand the evidence regarding the timing of expander/implant breast reconstruction in the setting of radiation therapy. 2. Discuss the implications of a patient's risk factors for possible outcomes and complications of expander/implant breast reconstruction. 3. Implement proper prophylactic antibiotic protocols. 4. Use the guidelines to improve their own clinical outcomes and reduce complications. SUMMARY In March of 2013, the Executive Committee of the American Society of Plastic Surgeons approved an evidence-based guideline on breast reconstruction with expanders and implants, as developed by a guideline-specific work group commissioned by the society's Health Policy Committee. The guideline addresses ten clinical questions: patient education, immediate versus delayed reconstruction, risk factors, radiation therapy, chemotherapy, hormonal therapy, antibiotic prophylaxis, acellular dermal matrix, monitoring for cancer recurrence, and oncologic outcomes associated with implant-based reconstruction. The evidence indicates that patients undergoing mastectomy should be offered a preoperative referral to a plastic surgeon. Evidence varies regarding the association between postoperative complications and timing of postmastectomy expander/implant breast reconstruction. Evidence is limited regarding the optimal timing of expand/implant reconstruction in the setting of radiation therapy but suggests that irradiation to the expander or implant is associated with an increased risk of postoperative complications. Evidence also varies regarding the association between acellular dermal matrix and surgical complications in the setting of postmastectomy expander/implant reconstruction. Data support the use of an appropriate preoperative antibiotic, but antibiotics should be discontinued within 24 hours of the procedure, unless a surgical drain is present. Furthermore, postmastectomy expander/implant breast reconstruction does not adversely affect oncologic outcomes.


[The Impact of the COVID-19 Pandemic on Mental Health].