title: A Systematic Review: The Management and Outcomes of Ileal Pouch Strictures.

text: Background Restorative proctocolectomy with ileal pouch-anal anastomosis removes the diseased tissue in ulcerative colitis but also allows gastrointestinal continuity and stoma-free living. Pouch strictures are a complication with a reported incidence of 5-38%. The three areas where pouch strictures occur are in the pouch inlet, mid-pouch and pouch-anal anastomosis. Aim To undertake a systematic review of the literature and to identify management strategies available for pouch-anal, mid-pouch and pre-pouch ileal strictures and their outcomes. Methods A computer-assisted search of the online bibliographic databases MEDLINE and EMBASE limited to 1966 to February 2016 was performed. Randomized controlled trials, cohort studies, observational studies and case reports were considered. Those where data could not be extracted were excluded. Results Twenty-two articles were considered eligible. Pouch-anal strictures have been initially managed using predominately dilators which include bougie and Hegar dilators with various surgical procedures advocated when initial dilatation fails. Mid-pouch strictures are relatively unstudied with both medical, endoscopic and surgical management reported as successful. Pouch inlet strictures can be safely managed using a combined medical and endoscopic approach. Conclusion The limited evidence available suggests that pouch-anal strictures are best treated in a stepwise fashion with initial treatment to include digital or instrumental dilatation followed by surgical revision or resection. Management of mid-pouch strictures requires a combination of medical, endoscopic and surgical management. Pouch inlet strictures are best managed using a combined medical and endoscopic approach. Future studies should compare different treatment modalities on separate stricture locations to enable an evidenced-based treatment algorithm.


title: Nonviral methods for siRNA delivery.

text: RNA interference (RNAi) as a mechanism to selectively degrade mRNA (mRNA) expression has emerged as a potential novel approach for drug target validation and the study of functional genomics. Small interfering RNAs (siRNA) therapeutics has developed rapidly and already there are clinical trials ongoing or planned. Although other challenges remain, delivery strategies for siRNA become the main hurdle that must be resolved prior to the full-scale clinical development of siRNA therapeutics. This review provides an overview of the current delivery strategies for synthetic siRNA, focusing on the targeted, self-assembled nanoparticles which show potential to become a useful and efficient tool in cancer therapy.


title: Esophagojejunal reconstruction after total gastrectomy for gastric cancer using a transorally inserted anvil delivery system.

text: INTRODUCTION Total gastrectomy (TG) is commonly performed for the treatment of patients with gastric cancer. However, reconstruction of the esophagojejunal (EJ) anastomosis can be technically demanding, with reported anastomotic leak rates in the Western world still approaching 10-15%. We report our experience using the transoral anvil delivery system (OrVil™) for creation of the EJ anastomosis after TG. METHODS From 2007 to 2011, 48 consecutive patients with gastric cancer underwent open (n=31) or laparoscopic (n=17) TG. EJ reconstruction was performed with the transoral anvil deliver system (OrVil™) in an end-to-side fashion. Demographic, clinic, and perioperative data were obtained from a prospectively maintained database. RESULTS Of the 48 patients, 83% were male. Median age at resection was 64 years. Median body mass index was 27.1 kg/m2. Seventy-nine percent (n=38) of patients had at least one comorbidity. Fifteen patients (31%) had at least one perioperative complication. There was one perioperative death (2%) following a duodenal stump leak. There were four EJ leaks (8%) and two EJ stenoses (independent of leak; 4%). There was one EJ leak (6%) and one EJ stenosis (6%) following a case that was first attempted laparoscopically. There were no deaths as a consequence of an EJ leak. CONCLUSIONS The use of the transoral anvil delivery system during EJ reconstruction is a safe and effective option for reconstruction after open or laparoscopic TG with acceptable mortality and morbidity. The anastomotic leak rate appears to be comparable to that of other techniques.


title: Recent advances in neuroendovascular therapy.

text: The field of neurointerventional surgery has grown in recent years. Endovascular therapies for both ischemic stroke and intracranial aneurysms have become important components in the multimodal treatment of these conditions. Familiarity with these treatment options by general neurologists is important for patient care. This article reviews recent trials and devices representing important advances in the field.


title: Complications and nutrient deficiencies two years after sleeve gastrectomy.

text: BACKGROUND The aim of this systematic study was to investigate patient outcomes and nutritional deficiencies following sleeve gastrectomy (SG) during a median follow-up of two years. METHODS Over a period of 56 months, all consecutive patients who underwent SG were documented in this prospective, single-center, observational study. The study endpoints included complication rates, nutritional deficiencies and percentage of excess weight loss (%EWL). RESULTS From September 26, 2005 to May 28, 2009, 100 patients (female: male = 59:41) with a mean age of 43.6 years (range: 22-64) and a preoperative BMI of 52.3 kg/² (range: 36-77) underwent SG. The mean operative time was 86.4 min (range: 35-275). Major complications were observed in 8.0 % of the patients. During the follow-up period, 25 patients (25.0 %) underwent a second bariatric intervention (22 DS and 3 RYGBP). Out of the total 100 patients, 48 % were supplemented with iron, 33 % with zinc, 34 % with a combination of calcium carbonate and cholecalciferol, 24 % with vitamin D, 42 % with vitamin B12 and 40 % with folic acid. The patients who received only a SG (n = 75) had %EWL of 53.6, 65.8 and 62.6 % after 6, 12 and 24 months, respectively. CONCLUSIONS SG is a highly effective bariatric intervention for morbidly obese patients. Nutritional deficiencies resulting from the procedure can be detected by routine nutritional screening. Results of the study show that Vitamin B12 supplementation should suggested routinely.


title: Diagnostic strategies for healthcare-associated pneumonia.

text: The first point of a good diagnostic strategy for healthcare-associated pneumonia (HCAP) is correct classification of patients with specific criteria, as suggested by the last American Thoracic Society/ Infectious Diseases Society of America (ATS/IDSA) guidelines. However, clinical practice and recent literature have suggested new risk factors for multidrug-resistant infection (MRI): the presence of permanent indwelling devices, prior antibiotic use in the last 3 months, chronic and advanced pulmonary diseases (chronic obstructive pulmonary disease, bronchiectasis, etc.), history of alcoholism, and immunosuppression. The clinical presentation in HCAP patients is often unusual (mild respiratory symptoms and frequent extrapulmonary manifestations) due to different factors: advanced age, neurological disorders, and multiple chronic comorbidities. Moreover, HCAP commonly presents a worse clinical course than community-acquired pneumonia, a prolonged length of stay, and a mortality rate close to hospital-acquired pneumonia. Chest radiography and routine laboratory markers (including C-reactive protein) are always needed for clinical evaluation and severity assessment. The clinical use of new biomarkers of infection and sepsis (procalcitonin, etc.) is currently being investigated. Extensive microbiological testing to overcome the high prevalence of MRI in HCAP, including urinary antigens for Legionella and Streptococcus pneumoniae; blood cultures; Gram staining and low respiratory tract secretions (sputum, tracheobronchial aspirate, fibrobronchial aspirate, protected specimen brush, bronchoalveolar lavage); and cultures for aerobic, anaerobic, mycobacterial, and fungal pathogens are recommended, whereas the indication for serology tests for respiratory viruses and atypical pathogens is low. By contrast, the new polymerase chain reaction-based techniques for the rapid identification (2 to 4 hours) of microbial pathogens in respiratory samples (nasopharyngeal swab, bronchoalveolar lavage) seem to be the most innovative future perspective in the diagnostics of HCAP.


title: A Comparative Study of CG CryoDerm and AlloDerm in Direct-to-Implant Immediate Breast Reconstruction.

text: BACKGROUND To date, various types of acellular dermal matrix (ADM) have been developed for clinical use. AlloDerm is the most familiar type of ADM to most surgeons in breast reconstruction. It is prepared by freeze-drying. CG CryoDerm is the first form of ADM that requires no drying process. Therefore, theoretically, it has a higher degree of preservation of the dermal structures than AlloDerm. We conducted this study to compare the clinical course and postoperative outcomes of patients who underwent direct-to-implant breast reconstructions using AlloDerm and those who did using CG CryoDerm. METHODS We performed a retrospective analysis of the medical records in a consecutive series of 50 patients who underwent direct-to-implant breast reconstruction using AlloDerm (n=31) or CryoDerm (n=19). We then compared the clinical course and postoperative outcomes of the two groups based on the overall incidence of complications and the duration of drainage. RESULTS The mean follow-up period was 16 months. There were no significant differences in the overall incidence of complications (seroma, infection, skin flap necrosis, capsular contracture, and implant loss) between the two groups. Nor was there any significant difference in the duration of drainage. CONCLUSIONS CG CryoDerm has the merits of short preparation time and easy handling during surgery. Our results indicate that CG CryoDerm might be an alternative allograft material to AlloDerm in direct-to-implant breast reconstruction.


title: Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via the spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014, and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains. Like the RBD of prototype EMC2012 (EMC-RBD), all five RBDs maintained good antigenicity and functionality, the ability to bind RBD-specific neutralizing monoclonal antibodies (MAbs) and the DPP4 receptor, and high immunogenicity, able to elicit S-specific antibodies. They induced potent neutralizing antibodies cross-neutralizing 17 MERS pseudoviruses expressing S proteins of representative human and camel MERS-CoV strains identified during the 2012-2015 outbreaks, 5 MAb escape MERS-CoV mutants, and 2 live human MERS-CoV strains. We then constructed two RBDs mutated in multiple key residues in the receptor-binding motif (RBM) of RBD and demonstrated their strong cross-reactivity with anti-EMC-RBD antibodies. These RBD mutants with diminished DPP4 binding also led to virus attenuation, suggesting that immunoevasion after RBD immunization is accompanied by loss of viral fitness. Therefore, this study demonstrates that MERS-CoV RBD is an important vaccine target able to induce highly potent and broad-spectrum neutralizing antibodies against infection by divergent circulating human and camel MERS-CoV strains. IMPORTANCE MERS-CoV was first identified in June 2012 and has since spread in humans and camels. Mutations in its spike (S) protein receptor-binding domain (RBD), a key vaccine target, have been identified, raising concerns over the efficacy of RBD-based MERS vaccines against circulating human and camel MERS-CoV strains. Here, we constructed five vaccine candidates, designated 2012-RBD, 2013-RBD, 2014-RBD, 2015-RBD, and Camel-RBD, containing single or multiple mutations in the RBD of representative human and camel MERS-CoV strains during the 2012-2015 outbreaks. These RBD-based vaccine candidates maintained good functionality, antigenicity, and immunogenicity, and they induced strong cross-neutralizing antibodies against infection by divergent pseudotyped and live MERS-CoV strains, as well as antibody escape MERS-CoV mutants. This study provides impetus for further development of a safe, highly effective, and broad-spectrum RBD-based subunit vaccine to prevent MERS-CoV infection.


title: A totally laparoscopic distal gastrectomy can be an effective way of performing laparoscopic gastrectomy in obese patients (body mass index≥30).

text: BACKGROUND In the surgical treatment of gastric cancer, obesity is known to be a predictive factor for poor early surgical outcomes. To evaluate the more effective modality of laparoscopic gastrectomy in obese patients, we compared the early surgical outcomes of laparoscopy-assisted and totally laparoscopic gastrectomy. METHODS We retrospectively analyzed early surgical outcomes in 1,480 consecutive patients who underwent distal gastrectomy for gastric cancer between April 2004 and July 2010. To compare surgical outcomes of laparoscopy-assisted distal gastrectomy (LADG) with those of totally laparoscopic distal gastrectomy (TLDG) in 76 obese patients (LADG, n = 39; TLDG, n=37), the patients were classified as either obese or nonobese. The obesity was defined using the WHO classification BMI cutoff of 30 kg/m2. RESULTS In the analysis of surgical outcomes of the LADG group, there were significant differences between the obese and nonobese groups with respect to operative time (P=0.004, obese, 171.8 min; nonobese, 141.0 min), time to first flatus (P=0.027, obese, 3.3 days; nonobese, 3.1 days), commencement of soft diet (P=0.040, obese, 4.6 days; nonobese, 4.0 days), postoperative complication rate (P=0.045, obese, 15.4%; nonobese, 6.5%), and postoperative hospital stay (P=0.014, obese, 8.9 days; nonobese, 7.2 days). In TLDG group, on the other hand, there were no significant differences in surgical outcomes between the groups. CONCLUSION Based on these findings, early surgical outcomes of LADG were strongly influenced by the obesity. TLDG without minilaparotomy, however, was unaffected by the obesity. These findings strongly suggest that TLDG could be a safe procedure to avoid the impact of obesity.


David Oliver: Covid-19 will make us stop some activities for good.


title: A laparoscopic vagus-preserving Merendino procedure for early esophageal adenocarcinoma.

text: INTRODUCTION Laparoscopic vagal preserving oesophagectomy is a recognised treatment option for high-grade dysplasia of the oesophagus. A jejunal interposition, as described by Alvin Merendino in 1955, aims to substitute the lower oesophageal sphincter, thereby treating physiological disorders such as reflux oesophagitis. METHODS We aimed to combine these procedures in the treatment of an otherwise healthy patient, who presented with high-grade dysplasia on surveillance endoscopy, with particular reference to technical feasibility and to Quality of Life as assessed by the Gastrointestinal Quality of Life Index (GIQLI). RESULTS We performed a laparoscopic vagus preserving Merendino procedure with sentinel lymph node biopsy. The patient made an entirely uncomplicated recovery and was discharged on day 7. His pathological specimen reported intramucosal carcinoma and high-grade dysplasia within Barrett's oesophagus. 0/4 lymph nodes were involved. His GIQLI scores preoperatively, at 2 and 4 weeks postoperatively, were 111, 98 and 105, respectively. His weight at the corresponding times was 69.8, 63.2 and 62.7 kg. CONCLUSION A laparoscopic vagal preserving Merendino procedure is technically feasible. It also offers a physiologically advantageous procedure for the patient.


Palliative care in advanced coronavirus disease in intensive care units.


title: Feasibility of a novel tacking method of securing mesh in transabdominal preperitoneal inguinal hernia repair: Secure tacking against recurrence.

text: INTRODUCTION Postoperative chronic pain is an important outcome of hernia surgery. In laparoscopic hernia surgery, either fixation outside the trapezoid of disaster or no fixation is recommended to avoid postoperative pain. To avoid recurrence are transabdominal preperitoneal (TAPP) hernia repair, the myopectineal orifice must be covered with mesh during TAPP, but lifting or shrinking of the mesh can lead to recurrence. The aim of this study was to evaluate the feasibility of a novel technique for mesh fixation to prevent the mesh from lifting off. METHODS After the preperitoneal space was created during TAPP, the anatomy of the lateral cutaneous nerve of the thigh or the femoral branch of the genitofemoral nerve within the trapezoid of disaster was checked. The mesh was tacked at the trapezoid of disaster without nerve injury, and the mesh was fixed with circumferential tacking. We call this procedure secure tacking against recurrence (STAR). We treated 391 adult patients (478 hernias) with TAPP repair; novel tacking was used in some patients (STAR group, 236 hernias). The results of the STAR group were retrospectively compared with those of patients in whom we did not use this novel tacking (conventional group, 242 hernias). RESULTS There was no postoperative chronic pain in either group. There were no cases of hernia recurrence in the STAR group, but there were four cases of hernia recurrence in the conventional group (0% vs 1.7%, P = 0.047). These four recurrences consisted of indirect hernia and mesh lifting on the lateral side. CONCLUSION The STAR procedure is feasible and safety as a standard procedure for securing the mesh during TAPP.


title: Next generation sequencing driven successful combined treatment with laparoscopic surgery and immunotherapy for relapsed stage IVB cervical and synchronous stage IV lung cancer.

text: BACKGROUND The treatment of patients with multiple synchronous tumors is challenging and complex. The use of next generation sequencing (NGS) may help in identification of germline mutations in genes involved in a common etiology for both tumors thus allowing a common effective therapeutic strategy. PATIENTS AND METHODS We describe the unexpected positive results obtained in a young woman with relapsed chemo-resistant stage IVB cervical and synchronous stage IV lung cancer, who underwent an interdisciplinary approach including palliative surgery with laparoscopic total pelvic exenteratio followed by a chemo-immunotherapy protocol with the anti-Programmed Death (PD)-1 antibody nivolumab plus metronomic cyclophosphamide. The treatment choice was based on tumor PD-Ligand 1 assessment and NGS analysis for the identification of potential treatment targets. Outcomes included tumor objective response and patient-centered outcomes (pain, performance status and overall quality of life). RESULTS Laparoscopic surgery obtained an immediate symptom control and allowed the early start of medical treatment. One month after combined therapy start the patient achieved a significant improvement in performance status, pain, overall Quality of life and after 3 months she resumed working. After 3 and 6 months of treatment we observed an objective dimensional and metabolic response. Currently, after 24 months (and 48 cycles of nivolumab) the patient is continuing to benefit from treatment: she is in complete remission, with good performance status and she is working and leading a self-dependent life. CONCLUSION Our study strongly affirms the efficacy of an interdisciplinary approach including surgical and innovative medical strategies based on immunotherapy in patients with advanced chemo-resistant synchronous cervical and lung cancer. The present findings support the use of NGS to drive a targeted rational treatment especially in heavily pre-treated patients.


Human bocavirus: increasing evidence for virulence.


title: Chloroquine in COVID-19: the evidence.

text: To the Editor The Coronavirus disease 2019 (COVID-19) has been declared as a pandemic by World Health Organisation (WHO). The global mortality has increased, especially in countries like Italy and Iran. With the increasing morbidity and mortality, search for a cure has been the global demand.


title: Comparison of outcomes for single-incision laparoscopic inguinal herniorrhaphy and traditional three-port laparoscopic herniorrhaphy at a single institution.

text: BACKGROUND Evidence in the literature regarding the potential of single-incision laparoscopic (SILS) inguinal herniorrhaphy currently is limited. A retrospective comparison of SILS and traditional multiport laparoscopic (MP) inguinal hernia repair was conducted to assess the safety and feasibility of the minimally invasive laparoscopic technique. METHODS All laparoscopic inguinal hernia repairs performed by three surgeons at a single institution during 4 years were reviewed. Statistical evaluation included descriptive analysis of demographics including age, gender, body mass index (BMI), and hernia location (uni- or bilateral), in addition to bivariate and multivariate analyses of surgical technique and outcomes including operative times, conversions, and complications. RESULTS The study compared 129 patients who underwent SILS inguinal hernia repair and 76 patients who underwent MP inguinal hernia repair. The cases included 190 men (92.68 %) with a mean age of 55.36 ± 18.01 years (range, 8-86 years) and a mean BMI of 26.49 ± 4.33 kg/m(2) (range, 17.3-41.7 kg/m(2)). These variables did not differ significantly between the SILS and MP cohorts. The average operative times for the SILS and MP unilateral cases were respectively 57.51 and 66.96 min. For the bilateral cases, the average operative times were 81.07 min for SILS and 81.38 min for MP. A multivariate analysis using surgical approach, BMI, case complexity, and laterality as the covariates demonstrated noninferiority of the SILS technique in terms of operative time (p = 0.031). No conversions from SILS to MP occurred, and the rates of conversion to open procedure did not differ significantly between the cohorts (p = 1.00, Fisher's exact test), nor did the complication rates (p = 0.65, χ (2)). CONCLUSIONS As shown by the findings, SILS inguinal herniorrhaphy is a safe and feasible alternative to traditional MP inguinal hernia repair and can be performed successfully with similar operative times, conversion rates, and complication rates. Prospective trials are essential to confirm equivalence in these areas and to detect differences in patient-centered outcomes.


Targeted degraders clear first safety hurdles.


title: Split-dose bowel preparation with polyethylene glycol for colonoscopy performed under propofol sedation. Is there an optimal timing?

text: OBJECTIVE Aspiration risk, especially with propofol sedation, remains a concern after split-dose bowel preparation of up to 1 L polyethylene glycol for the procedure. We aimed to identify the ideal timing of bowel preparation to achieve optimal colon cleansing with no increased risk of aspiration. METHODS A total of 892 consecutive patients undergoing simultaneous esophagogastroduodenoscopy (EGD) and colonoscopy were prospectively recruited. Residual gastric volume (RGV) and pH of gastric contents were measured at EGD, and patients' characteristics, runway time (duration between completion of the final liter of bowel preparation and colonoscopy commencement), and cleansing quality were recorded. RESULTS A shorter runway time resulted in better colon cleansing (r = -0.124, P < 0.001). No correlation between runway time and RGV or pH was found (r = -0.017, P = 0.62 and r = -0.030, P = 0.47, respectively). RGV and pH did not differ significantly with runway time of 4 or 5 h. RGV with runway time ≤3 h was 35.9 ± 11.8 mL and 17.4 ± 0.6 mL after runway time >3 h (P < 0.001). No aspiration pneumonia occurred. The only factors independently related to higher RGV were younger age and male sex. CONCLUSIONS The consumption of bowel preparation agent within 3-4 h before propofol sedation resulted in a similar RGV and pH as those achieved by more prolonged fasting, with no increased risk of aspiration even in patients perceived to be at high risk.


title: COVID-19: Generate and apply local modelled Transmission and Morbidity effects to provide an estimate of the variation in overall Relative Healthcare Resource Impact at General Practice Granularity.

text: INTRODUCTION Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the name given to the 2019 novel coronavirus. COVID-19 is the name given to the disease associated with the virus. SARS-CoV-2 is a new strain of coronavirus not been previously identified in humans. METHODS Two key factors, case incidence and case morbidity were analysed for England. When taken together they give an estimate of relative demand on healthcare utilisation. To analyse case incidence, the latest values for indicators that could be associated with infection transmission rates were collected from the Office of National Statistics (ONS) and Quality Outcome Framework (QOF) sources. These included population density, %age>16, at fulltime work/education, %age over 60, %BME ethnicity, social deprivation as IMD2019, location as latitude/longitude, and patient engagement as %self-confident in their own long-term condition management. Average case morbidity was calculated. To provide a comparative measure of overall healthcare resource impact, individual GP practice impact scores were compared against the median practice. RESULTS The case incidence regression is a dynamic situation but it currently shows that Urban, %Working and age>60 were the strongest determinants of case incidence. The local population comorbidity remains unchanged. The range of relative healthcare impact was wide with 80% of practices falling at 20%-250% of the national median. Once practice population numbers were included we found that the top 33% of GP practices supporting 45% of the patient population would require 68% of COVID-19 healthcare resources. The model provides useful information about the relative impact of Covid-19 on healthcare workload at GP practice granularity in all parts of England. CONCLUSION Covid-19 is impacting on the utilisation of health/social care resources across the world. This model provides a way of predicting relative local levels of disease burden based on defined criteria, thereby providing a method for targeting limited care resources to optimise national/regional/local responses to the COVID-19 outbreak.


title: Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate.

text: Autophagy is a cellular response to starvation which generates autophagosomes to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy can provide an innate defence against virus infection, or conversely autophagosomes can promote infection by facilitating assembly of replicase proteins. We demonstrate that the avian coronavirus, Infectious Bronchitis Virus (IBV) activates autophagy. A screen of individual IBV non-structural proteins (nsps) showed that autophagy was activated by IBV nsp6. This property was shared with nsp6 of mammalian coronaviruses Mouse Hepatitis Virus, and Severe Acute Respiratory Syndrome Virus, and the equivalent nsp5-7 of the arterivirus Porcine Reproductive and Respiratory Syndrome Virus. These multiple-spanning transmembrane proteins located to the endoplasmic reticulum (ER) where they generated Atg5 and LC3II-positive vesicles, and vesicle formation was dependent on Atg5 and class III PI3 kinase. The vesicles recruited double FYVE-domain containing protein (DFCP) indicating localised concentration of phosphatidylinositol 3 phosphate, and therefore shared many features with omegasomes formed from the ER in response to starvation. Omegasomes induced by viral nsp6 matured into autophagosomes that delivered LC3 to lysosomes and therefore recruited and recycled the proteins needed for autophagosome nucleation, expansion, cellular trafficking and delivery of cargo to lysosomes. The coronavirus nsp6 proteins activated omegasome and autophagosome formation independently of starvation, but activation did not involve direct inhibition of mTOR signalling, activation of sirtuin1 or induction of ER stress.


title: Virus-induced translational arrest through 4EBP1/2-dependent decay of 5'-TOP mRNAs restricts viral infection.

text: The mosquito-transmitted bunyavirus, Rift Valley fever virus (RVFV), is a highly successful pathogen for which there are no vaccines or therapeutics. Translational arrest is a common antiviral strategy used by hosts. In response, RVFV inhibits two well-known antiviral pathways that attenuate translation during infection, PKR and type I IFN signaling. Despite this, translational arrest occurs during RVFV infection by unknown mechanisms. Here, we find that RVFV infection triggers the decay of core translation machinery mRNAs that possess a 5'-terminal oligopyrimidine (5'-TOP) motif in their 5'-UTR, including mRNAs encoding ribosomal proteins, which leads to a decrease in overall ribosomal protein levels. We find that the RNA decapping enzyme NUDT16 selectively degrades 5'-TOP mRNAs during RVFV infection and this decay is triggered in response to mTOR attenuation via the translational repressor 4EBP1/2 axis. Translational arrest of 5'-TOPs via 4EBP1/2 restricts RVFV replication, and this increased RNA decay results in the loss of visible RNA granules, including P bodies and stress granules. Because RVFV cap-snatches in RNA granules, the increased level of 5'-TOP mRNAs in this compartment leads to snatching of these targets, which are translationally suppressed during infection. Therefore, translation of RVFV mRNAs is compromised by multiple mechanisms during infection. Together, these data present a previously unknown mechanism for translational shutdown in response to viral infection and identify mTOR attenuation as a potential therapeutic avenue against bunyaviral infection.


Covid-19 in care homes: the many determinants of this perfect storm.


title: Rats susceptible to virus-induced asthma have a persistent virus-induced change in the predominant pulmonary form of the NF-κB inhibitor IκBα.

text: Weanling Brown Norway (BN) rats are susceptible to persistent steroid-responsive pulmonary abnormalities following resolution of an acute respiratory virus infection. In contrast, Fischer 344 (F344) rats recover without complications. Previous studies determined that NF-κB activation and subunit composition were markedly different between these 2 rat strains. This study examined whether viral infection also resulted in altered pulmonary expression of IκBα and IκBβ, 2 inhibitory regulators of NF-κB. Western blot analyses of total pulmonary protein extracted from BN and F344 rats at 7, 10, and 14 days after inoculation (n = 5 per group) did not reveal virus-induced differences in IκBβ expression. In contrast, a lower molecular weight form of IκBα appeared in the BN rats at 14 days postinfection, and it was still present at 21 days after infection (n = 5 per group). The change in IκBα expression observed in the susceptible BN but not the resistant F344 animals occurs when the epithelium is proliferating during the repair phase, and it correlates with the development of the persistent virus-induced airway inflammation and pulmonary functional abnormalities. These results further implicate differential regulation of NF-κB in the pathogenesis of virus-induced asthma.


title: Influenza virus polymerase: Functions on host range, inhibition of cellular response to infection and pathogenicity.

text: The viral polymerase is an essential complex for the influenza virus life cycle as it performs the viral RNA transcription and replication processes. To that end, the polymerase carries out a wide array of functions and associates to a large number of cellular proteins. Due to its importance, recent studies have found numerous mutations in all three polymerase protein subunits contributing to virus host range and pathogenicity. In this review, we will point out viral polymerase polymorphisms that have been associated with virus adaptation to mammalian hosts, increased viral polymerase activity and virulence. Furthermore, we will summarize the current knowledge regarding the new set of proteins expressed from the viral polymerase genes and their contribution to infection. In addition, the mechanisms used by the virus to counteract the cellular immune response in which the viral polymerase complex or its subunits are involved will be highlighted. Finally, the degradative process induced by the viral polymerase on the cellular transcription machinery and its repercussions on virus pathogenicity will be of particular interest.


title: Open versus minimally invasive esophagectomy: clinical outcomes for locally advanced esophageal adenocarcinoma.

text: BACKGROUND We compared oncologic and surgical outcome between minimally invasive esophagectomy (MIE) and the Ivor Lewis-type open approach (OE) in the treatment of locally advanced esophageal adenocarcinoma (EAC). MATERIALS AND METHODS Of 284 patients undergoing surgery for EAC between 2003 and 2013, the 153 selected with locally advanced EAC were 74 MIEs and 79 OEs [median age, 66 for MIE, 63 for OE (p = 0.009)]. Neoadjuvant therapy was given to 82% of MIEs and 78% of OEs. In the OE group, 86% was male, and in the MIE group, 78%. Data assessed were oncologic, intraoperative, and postoperative. RESULTS Mortality at 30 days was 3% for MIE and 1% for OE; and 90-day mortality was 4% for MIE and 5% for OE. The complication rate for MIE was 50%, and 60% for OE (p = 0.181). The pneumonia rate was 18% for MIE and 19% for OE; leak rate was 7% for MIE and 6% for OE; conduit necrosis was 0 for MIE and 3% for OE; and rate of airway-conduit fistula was 3% for MIE and 1 % for OE. Median blood loss (MIE 300 vs. OE 800, p < 0.0001), overall stay (MIE 13 vs. OE 14, p = 0.040), and harvested lymph nodes (MIE 20 vs. OE 22, p = 0.021) all were in favor of MIE. Median ICU stay and operative time did not differ. Neither did overall (OS) nor recurrence-free (RFS) 3-year survival differs significantly (MIE 64% vs. OS OE 49%, MIE 57% vs. RFS OE 53%). CONCLUSIONS In our institution, MIE appears to produce oncologic and survival results similar to those of OE. Shorter length of stay and less operative blood loss may reduce costs for MIE.


title: Statistical analysis plan for evaluating different intensities of blood pressure control in the ENhanced Control of Hypertension And Thrombolysis strokE stuDy.

text: BACKGROUND The ENhanced Control of Hypertension And Thrombolysis strokE study (ENCHANTED) trial was initiated as a 2 × 2 partial-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial to evaluate in thrombolysis-eligible acute ischemic stroke (AIS) patients whether: (1) Arm A - low-dose (0.6 mg/kg body weight) intravenous (iv) alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage (sICH) compared with standard-dose (0.9 mg/kg body weight) iv alteplase; and (2) Arm B - early intensive blood pressure (BP) lowering (systolic target 130-140 mmHg) has superior efficacy and lower risk of ICH compared with guideline-recommended BP control (systolic target <180 mmHg). Arm A was completed in 2016; Arm B is now concluding. OBJECTIVE To outline in detail and make public the predetermined statistical analysis plan (SAP) for the 'BP control' arm of this study. METHODS All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be outlined, and for each item, statistically relevant descriptive elements will be described. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described. RESULTS A SAP was developed for the results of the BP control arm of this study that is transparent, available to the public, verifiable, and predetermined before completion of data collection. CONCLUSIONS We have developed a predetermined SAP for the ENCHANTED BP control arm to be followed to avoid analysis bias arising from prior knowledge of the study findings. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (NCT01422616); ISRCTN Register (ISRCTN82387104); Australian New Zealand Clinical Trial Registry (ACTRN12611000236998); EU Clinical Trials Register (2011-005545-12); and Clinical Trials Registry - India (REF/2017/05/014334).


title: New magnetic-resonance-imaging-visible poly(ε-caprolactone)-based polyester for biomedical applications.

text: A great deal of effort has been made since the 1990s to enlarge the field of magnetic resonance imaging. Better tissue contrast, more biocompatible contrast agents and the absence of any radiation for the patient are some of the many advantages of using magnetic resonance imaging (MRI) rather than X-ray technology. But implantable medical devices cannot be visualized by conventional MRI and a tool therefore needs to be developed to rectify this. The synthesis of a new MRI-visible degradable polymer is described by grafting an MR contrast agent (DTPA-Gd) to a non-water-soluble, biocompatible and degradable poly(ε-caprolactone) (PCL). The substitution degree, calculated by (1)H nuclear magnetic resonance and inductively coupled plasma-mass spectrometry, is close to 0.5% and proves to be sufficient to provide a strong and clear T1 contrast enhancement. This new MRI-visible polymer was coated onto a commercial mesh for tissue reinforcement using an airbrush system and enabled in vitro MR visualization of the mesh for at least 1 year. A stability study of the DTPA-Gd-PCL chelate in phosphate-buffered saline showed that a very low amount of gadolinium was released into the medium over 52 weeks, guaranteeing the safety of the device. This study shows that this new MRI-visible polymer has great potential for the MR visualization of implantable medical devices and therefore the post-operative management of patients.


title: Zenker's diverticulum: flexible versus rigid repair.

text: Zenker's diverticula (ZDs) are a relatively common cause of cervical dysphagia. Diagnosis is best by a good upper GI exam though upper endoscopy should be performed as well. Treatment is either by open, transcervical approaches or trans-oral. Over the past 20 years, transoral approach has mostly replace transcervical approaches due to less pain, no scarring and a rapid recovery. Transoral approaches are either using rigid access or flexible endoscopy. Today, the most common approach is transoral stapling using a 12 mm laparoscopic linear cutting stapler. This has the drawbacks of requiring extreme neck extension, the massive size of the stapler making visualization mostly impossible and the current staple design that does not cut/staple all the way to the end of the blades-resulting in a residual pouch. Flexible endoscopy allows a more tailored approach under direct vision, the myotomy can even be extended beyond the diverticulum and onto the esophageal wall to minimize the risk of incomplete myotomy. Experienced endoscopists report high technical success and low complication. Success rates are similar but maybe slightly higher than with ridged transoral approaches or open surgery. Today, flexible endoscopic Zenkers is our preferred initial approach-with open or ridged being reserved for special indications.


Advanced hemodynamic monitoring in the critically ill patient: Nice to have or need to treat?


title: Structural and functional analysis of intra-articular interzone tissue in axolotl salamanders.

text: OBJECTIVE Knowledge of mechanisms directing diarthrodial joint development may be useful in understanding joint pathologies and identifying new therapies. We have previously established that axolotl salamanders can fully repair large articular cartilage lesions, which may be due to the presence of an interzone-like tissue in the intra-articular space. Study objectives were to further characterize axolotl diarthrodial joint structure and determine the differentiation potential of interzone-like tissue in a skeletal microenvironment. DESIGN Diarthrodial joint morphology and expression of aggrecan, brother of CDO (BOC), type I collagen, type II collagen, and growth/differentiation factor 5 (GDF5) were examined in femorotibial joints of sexually mature (>12 months) axolotls. Joint tissue cellularity was evaluated in individuals from 2 to 24 months of age. Chondrogenic potential of the interzone was evaluated by placing interzone-like tissue into 4 mm tibial defects. RESULTS Cavitation reached completion in the femoroacetabular and humeroradial joints, but an interzone-like tissue was retained in the intra-articular space of distal limb joints. Joint tissue cellularity decreased to 7 months of age and then remained stable. Gene expression patterns of joint markers are broadly similar in developing mammals and mature axolotls. When interzone-like tissue was transplanted into critical size skeletal defects, an accessory joint developed within the defect site. CONCLUSIONS These experiments indicate that mature axolotl diarthrodial joints are phenotypically similar to developing synovial joints in mammals. Generation of an accessory joint by interzone-like tissue suggests multipotent cellular differentiation potential similar to that of interzone cells in the mammalian fetus. The data support the axolotl as a novel vertebrate model for joint development and repair.


Can Covid Catalyze an Educational Transformation? Competency-Based Advancement in a Crisis.


title: Trainees' perspectives of assessment messages: a narrative systematic review.

text: OBJECTIVES This study was designed as a narrative systematic literature review of medical specialist trainees' perspectives of the assessment messages they receive in the context of clinical performance assessments. The aim of the study was to determine if trainees value the information they receive through the formats designed to promote their development and, if not, the reasons for this. METHODS The authors searched the ERIC, EMBASE, Ovid MEDLINE and PsycINFO databases for articles published up to 16 June 2018 that present original data on trainees' perspectives of the assessment messages they receive in the context of work-based assessments (WBAs) and in-training assessments (ITAs) used within their training programmes. All authors screened 938 abstracts and 139 full-text articles were assessed after this. Descriptions of quantitative data and thematic analysis of qualitative data were used to present the opinions of trainees. RESULTS Thirty-three articles met the inclusion criteria. Twenty-six articles (79%) described trainees' perspectives in the context of WBA and the remaining articles referred to ITA formats. Wide-ranging opinions were reported. The analysis categorised these into three themes: trainees value developmental assessment messages; trainees become disengaged when assessment messages are not developmental, and trainees' views depend on the environment, the assessor and themselves. Some trainees reported that the assessment messages were valuable and provided input on their performance to guide their development, but many disagreed. In particular, the trainee's own level of engagement with the assessments influenced his or her perspectives on the messages received. CONCLUSIONS Trainees do not universally perceive that clinical performance assessments provide them with the valuable developmental input on their performance they were designed to do. Factors related to the environment, the assessor and themselves influence their perspectives.


title: Severe COVID-19 in a pregnant patient admitted to hospital in Wuhan.

text: In December 2019, an outbreak of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, Hubei Province, China. This virus strain causes the respiratory illness coronavirus disease 2019 (COVID-19). Despite significant research efforts in this field, there is limited data on COVID-19 in pregnancy. This article presents a case of a pregnant woman from Wuhan infected with SARS-CoV-2, including her symptoms, pregnancy outcome, and treatment strategy.


title: Natural Orifice Trans-Luminal Endoscopic Surgery in the esophagus.

text: As limited as are the studies regarding peritoneal Natural Orifice Trans-Luminal Endoscopic Surgery, mediastinal transluminal experiments are certainly in their infancy. The authors evaluate the parallel development of minimally invasive thoracic surgery with regard to its counterpart in peritoneal laparoscopy to NOTES. Transesophageal interventions by both endosonographic and direct visualization are examined in the context of minimally invasive surgery and mediastinal NOTES. Techniques of viscerotomy creation, visualization, and closure are examined with particular emphasis on mediastinal structures. The state of current interventions is examined. Finally, current morbidity (including infectious complications) and survival outcomes are examined in those animals that have undergone transesophageal exploration.


title: Producing Independent, Systematic Review Evidence: Cochrane's Response to COVID-19.

text: Bad advice can lead to tragedy, such as death from taking an unproven medication.1 Now, more than ever, public health policies should be based on the best available evidence. Consumers, clinicians, and policymakers need balanced information that is free of commercial influence to make decisions about the best ways to prevent the spread and manage the symptoms and clinical consequences of COVID-19. The benefits and harms of each decision must be considered. Public health measures such as isolation, quarantine, and social distancing have fundamentally changed the way we live. (Am J Public Health. Published online ahead of print May 14, 2020: e1-e2. doi:10.2105/AJPH.2020.305734).


title: Bovine ephemeral fever rhabdovirus α1 protein has viroporin-like properties and binds importin β1 and importin 7.

text: Bovine ephemeral fever virus (BEFV) is an arthropod-borne rhabdovirus that is classified as the type species of the genus Ephemerovirus. In addition to the five canonical rhabdovirus structural proteins (N, P, M, G, and L), the large and complex BEFV genome contains several open reading frames (ORFs) between the G and L genes (α1, α2/α3, β, and γ) encoding proteins of unknown function. We show that the 10.5-kDa BEFV α1 protein is expressed in infected cells and, consistent with previous predictions based on its structure, has the properties of a viroporin. Expression of a BEFV α1-maltose binding protein (MBP) fusion protein in Escherichia coli was observed to inhibit cell growth and increase membrane permeability to hygromycin B. Increased membrane permeability was also observed in BEFV-infected mammalian cells (but not cells infected with an α1-deficient BEFV strain) and in cells expressing a BEFV α1-green fluorescent protein (GFP) fusion protein, which was shown by confocal microscopy to localize to the Golgi complex. Furthermore, the predicted C-terminal cytoplasmic domain of α1, which contains a strong nuclear localization signal (NLS), was translocated to the nucleus when expressed independently, and in an affinity chromatography assay employing a GFP trap, the full-length α1 was observed to interact specifically with importin β1 and importin 7 but not with importin α3. These data suggest that, in addition to its function as a viroporin, BEFV α1 may modulate components of nuclear trafficking pathways, but the specific role thereof remains unclear. Although rhabdovirus accessory genes occur commonly among arthropod-borne rhabdoviruses, little is known of their functions. Here, we demonstrate that the BEFV α1 ORF encodes a protein which has the structural and functional characteristics of a viroporin. We show that α1 localizes in the Golgi complex and increases cellular permeability. We also show that BEFV α1 binds importin β1 and importin 7, suggesting that it may have a yet unknown role in modulating nuclear trafficking. This is the first functional analysis of an ephemerovirus accessory protein and of a rhabdovirus viroporin.


title: [Analysis of application of herd immunity as a control strategy for COVID-19].

text: Novel coronavirus spreads very fast and is not easy to control. It has spread over 200 countries or territories. China has taken action to implement containment strategies, including active COVID-19 case finding, tracing, and 14-day quarantine of close contacts, and home isolation of 1.39 billion of people countywide for at least 2 weeks, etc. The combination of these strategies has brought the epidemic under control in China. The United Kingdom had deliberately not implemented containment measures for a while, instead opting to allow herd immunity strategy to develop over time. This is a "do-nothing" strategy whereby the virus is allowed to move through communities naturally until certain proportion of people has been infected, and the epidemic ends without intervention. The author assesses containment strategies versus this herd immunity strategy in real-world application to the COVID-19 epidemic. The author suggests an innovative strategy to balance controlling the epidemic and preventing impediment to economic and social development.


title: Incidence, Patterns, and Associations Between Dual-Antiplatelet Therapy Cessation and Risk for Adverse Events Among Patients With and Without Diabetes Mellitus Receiving Drug-Eluting Stents: Results From the PARIS Registry.

text: OBJECTIVES The aim of this study was to examine the frequency and clinical impact of different cessation patterns of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents among patients with and those without diabetes mellitus (DM). BACKGROUND Early DAPT suspension after percutaneous coronary intervention increases the risk for major adverse cardiac events. However, temporal variability in risk and relation to DAPT cessation patterns among patients with DM remain unclear. METHODS Using data from the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) registry, 1,430 patients with DM (34%) and 2,777 without DM (66%) treated with drug-eluting stents were identified. DAPT cessation modes were classified as temporary interruption (<14 days), disruption because of bleeding or poor compliance, and physician-recommended discontinuation. RESULTS During 2-year follow-up, DM was associated with an increased risk for thrombotic events but a similar risk for bleeding. The cumulative incidence of DAPT cessation was significantly lower in patients with versus those without DM (50.1% vs. 55.4%; p < 0.01), driven largely by less frequent physician-guided discontinuation beyond 1 year. In contrast, 2-year rates of interruption and disruption were similar between groups. When DAPT was interrupted or discontinued under physician guidance, the risk for major adverse cardiac events was unchanged compared with patients with DM on uninterrupted DAPT. Conversely, when DAPT was disrupted, the risk for major adverse cardiac events increased compared with uninterrupted DAPT, regardless of diabetic status, with no evidence of statistical interaction. CONCLUSIONS DAPT cessation patterns vary according to diabetic status, with less frequent physician-guided discontinuation among patients with DM. The presence of DM does not emerge as a modifier of cardiovascular risk after DAPT cessation.


title: Rapid generation of a mouse model for Middle East respiratory syndrome.

text: In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6-8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections.


title: Advances in Detection of Infectious Agents by Aptamer-based Technologies.

text: Infectious diseases still remain one of the biggest challenges for human health. Accurate and early detection of infectious pathogens are crucial for transmission control, clinical diagnosis and therapy. For a traditional reason, most immunological and microbiological laboratories are equipped with instruments designated for antibody-based assays in detection of infectious pathogens or clinical diagnosis. Emerging aptamer-based technologies have pushed a shift from antibody-based to aptamer-based assays due to equal specificity, even better sensitivity, lower manufacturing cost and more flexibility in amending for chemiluminescent, electrochemical or fluorescent detection in a multifaceted and high throughput fashion in comparison of aptamer-based to antibody-based assays. The nature of aptamer-based technologies is particularly suitable for point-of-care testing in remote areas at warm or hot atmosphere, and mass screening for potential infection in pandemic of emerging infectious agents, such as SARS-CoV or SARS-CoV-2 in an epicenter or other regions. This review intends to summarize currently available aptamer-based technologies in detection of bacterial, viral and protozoan pathogens for research and clinical application. It is anticipated that potential technologies will be further optimized and validated for clinical translation in meeting increasing demands for prompt, precise and reliable detection of specific pathogens in various atmospheric conditions.


title: Safety and Efficacy of Laparoscopic Radiofrequency Ablation for Hepatic Hemangiomas: A Multicenter Retrospective Study.

text: INTRODUCTION Radiofrequency ablation (RFA) is an effective and minimally invasive technique for the management of hepatic hemangiomas (HHs). This study aims to assess the safety and efficacy of laparoscopic RFA for HHs. MATERIAL AND METHODS Forty-four patients with 50 hepatic hemangiomas (5-10 cm in diameter) undergoing laparoscopic RFA from January 2012 to May 2015 at three tertiary hospitals in China were retrospectively analyzed. RESULTS Thirty-three patients with subcapsular hemangiomas were treated with a laparoscopic approach, and 11 patients with lesions in the liver parenchyma were treated with a combined laparoscopy and an ultrasound-guided percutaneous approach. No conversion to open surgery or two-step surgery occurred during the study period. Patients with small hemangiomas (< 7 cm) required a significantly shorter operating time (71.1 ± 20.18 min vs. 106 ± 23.55 min, p = 0.000) and fewer punctures compared with patients with large hemangiomas (> 7 cm) (4.61 ± 1.09 vs. 6.73 ±1.01, P < 0.05). According to the Dindo-Clavien classification, 15 patients experienced 34 Grade 1 complications, and two had complications of Grade 3a. All complications were resolved by conservative treatment. Forty-three (86.0%) HHs in 38 patients were completely ablated after RFA, and 7 (14.0%) HHs in 6 patients were incompletely ablated. All patients were followed up for 6-24 months (mean 15 ± 6 months). CONCLUSION The data showed that laparoscopic RFA is an effective treatment for small (< 10 cm) HHs. While the incidence of postoperative complications remains high, the majority of complications are minor. Patients undergoing laparoscopic RFA for HHs, even for the small ones, should be carefully selected.


Reflections on ethical challenges associated with the Ebola epidemic.


title: Radiofrequency ablation for hepatocellular carcinoma measuring 2 cm or smaller: results and risk factors for local recurrence.

text: OBJECTIVE The purpose of this study was to evaluate the risk factors for local recurrence with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) measuring ≤2 cm. METHODS This study involved 234 patients with 274 HCCs measuring ≤2 cm who had undergone RFA as the initial treatment. The mean tumor diameter was 1.478 cm. The median follow-up period was 829 days. We evaluated the post-RFA cumulative local recurrence rate and analyzed the risk factors contributing to clinical outcomes. RESULTS Cumulative local recurrence rates were 9, 19 and 19% at 1, 2 and 3 years, respectively. Among the 145 cases with a complete safety margin (SM) after RFA, only 4 developed local tumor recurrence and the cumulative rates of local tumor recurrence at 1, 2 and 3 years were 2, 3 and 3%, respectively. Among the 129 cases with incomplete SM, local tumor recurrence developed in 34 and the cumulative rates of local tumor progression at 1, 2 and 3 years were 14, 36 and 36%, respectively. In multivariate analysis, significant risk factors were tumor location (liver surface), irregular gross type and SM <5 mm. CONCLUSION Even with HCC measuring ≤2 cm, location and gross type of tumor should be carefully evaluated before RFA is performed.


Coronavirus puts drug repurposing on the fast track.


title: A Naturally Occurring Recombinant Enterovirus Expresses a Torovirus Deubiquitinase.

text: Enteroviruses (EVs) are implicated in a wide range of diseases in humans and animals. In this study, a novel enterovirus (enterovirus species G [EVG]) (EVG 08/NC_USA/2015) was isolated from a diagnostic sample from a neonatal pig diarrhea case and identified by using metagenomics and complete genome sequencing. The viral genome shares 75.4% nucleotide identity with a prototypic EVG strain (PEV9 UKG/410/73). Remarkably, a 582-nucleotide insertion, flanked by 3Cpro cleavage sites at the 5' and 3' ends, was found in the 2C/3A junction region of the viral genome. This insertion encodes a predicted protease with 54 to 68% amino acid identity to torovirus (ToV) papain-like protease (PLP) (ToV-PLP). Structural homology modeling predicts that this protease adopts a fold and a catalytic site characteristic of minimal PLP catalytic domains. This structure is similar to those of core catalytic domains of the foot-and-mouth disease virus leader protease and coronavirus PLPs, which act as deubiquitinating and deISGylating (interferon [IFN]-stimulated gene 15 [ISG15]-removing) enzymes on host cell substrates. Importantly, the recombinant ToV-PLP protein derived from this novel enterovirus also showed strong deubiquitination and deISGylation activities and demonstrated the ability to suppress IFN-β expression. Using reverse genetics, we generated a ToV-PLP knockout recombinant virus. Compared to the wild-type virus, the ToV-PLP knockout mutant virus showed impaired growth and induced higher expression levels of innate immune genes in infected cells. These results suggest that ToV-PLP functions as an innate immune antagonist; enterovirus G may therefore gain fitness through the acquisition of ToV-PLP from a recombination event.IMPORTANCE Enteroviruses comprise a highly diversified group of viruses. Genetic recombination has been considered a driving force for viral evolution; however, recombination between viruses from two different orders is a rare event. In this study, we identified a special case of cross-order recombination between enterovirus G (order Picornavirales) and torovirus (order Nidovirales). This naturally occurring recombination event may have broad implications for other picornaviral and/or nidoviral species. Importantly, we demonstrated that the exogenous ToV-PLP gene that was inserted into the EVG genome encodes a deubiquitinase/deISGylase and potentially suppresses host cellular innate immune responses. Our results provide insights into how a gain of function through genetic recombination, in particular cross-order recombination, may improve the ability of a virus to evade host immunity.


title: Outcomes of laparoscopic Roux-en-Y gastric bypass versus laparoscopic adjustable gastric banding in adolescents.

text: BACKGROUND The goal of this study is to compare the outcomes of laparoscopic adjustable gastric banding (LAGB) and laparoscopic Roux-en-Y gastric bypass (LRYGB) in obese adolescents. METHODS We performed a retrospective review of all adolescents between the ages of 15 and 19 who underwent LAGB or LRYGB at our university affiliated Bariatric Center of Excellence from 2002 to 2011. Postsurgical weight loss at 1, 3, 6, 12, 18, and 24 months was noted and expressed as percentage of excess weight loss (% EWL). RESULTS Thirty-two patients underwent LRYGB and 23 underwent LAGB. The LAGB group was younger (18.6 ± 0.6 versus 17.2 ± 1.5) than the LRYGB group. Other preoperative demographic factors including body mass index, gender, ethnicity, and comorbidities were similar between the two groups. The average % EWL was superior in the LRYGB group compared to the LAGB group at all time points studied (p < 0.05), although at 2-year follow-up, only 16% (5/32) LRYGB and 30% (7/23) LAGB patients were available for follow-up. Three patients with type II diabetes mellitus underwent LRYGB and all experienced remission of their diabetes. The number of complications requiring interventions was similar between the two groups. CONCLUSIONS In our study, adolescents undergoing LRYGB achieved superior weight loss compared to LAGB in the short-term follow-up. The complication rate for LAGB was similar compared to LRYGB. More studies are needed to monitor the long-term effects of these operations on adolescents before definitive recommendations can be made.


title: Performance of portable ventilators at altitude.

text: BACKGROUND Aeromedical transport of critically ill patients requires continued, accurate performance of equipment at altitude. Changes in barometric pressure can affect the performance of mechanical ventilators calibrated for operation at sea level. Deploying ventilators that can maintain a consistent tidal volume (VT) delivery at various altitudes is imperative for lung protection when transporting wounded war fighters to each echelon of care. METHODS Three ventilators (Impact 731, Hamilton T1, and CareFusion Revel) were tested at pediatric (50 and 100 mL) and adult (250-750 mL) tidal VTs at 0 and 20 cm H₂O positive end expiratory pressure and at inspired oxygen of 0.21 and 1.0. Airway pressure, volume, and flow were measured at sea level as well as at 8,000, 16,000, and 22,000 ft (corresponding to barometric pressures of 760, 564, 412, and 321 mm Hg) using a calibrated pneumotachograph connected to a training test lung in an altitude chamber. Set VT and delivered VT as well as changes in VT at each altitude were compared by t test. RESULTS The T1 delivered VT within 10% of set VT at 8,000 ft. The mean VT was less than set VT at sea level as a result of circuit compressible volume with the Revel and the 731. Changes in VT varied widely among the devices at sea level and at altitude. Increasing altitudes resulted in larger VT than set for the Revel and the T1. The 731 compensated for changes in altitude delivered VT within 10% at the adult settings at all altitudes. CONCLUSION Altitude compensation is an active software algorithm. Only the 731 actively accounts for changes in barometric pressure to maintain the set VT at all tested altitudes.


title: Ablation for hepatocellular carcinoma: validating the 3-cm breakpoint.

text: BACKGROUND Although many previous studies on local ablation outcomes for hepatocellular carcinoma (HCC) have dichotomized tumor size with a 3-cm cutoff to determine prognostic significance, a growing number of reports describe excellent outcomes for larger tumors. To address the logic of this 3-cm cutoff beyond small single-center experiences, we stratified patients by 1-cm tumor size intervals and hypothesized that disease-specific survival (DSS) would not vary significantly between adjacent groups. METHODS Patients treated with local ablation for T1 HCC (≤8 cm) were identified from the surveillance, epidemiology, and end results database (2004-2008). Log-rank tests and multivariable Cox proportional hazards models were used to compare DSS curves of adjacent study groups. RESULTS There were 1,083 patients included in the study (26 % female, median age: 62 years). The 3-year DSS was significantly lower in patients with 3- to 4-cm tumors compared to 2- to 3-cm tumors (58 vs. 72 %, p = 0.002). In adjusted models, DSS did not vary significantly between any size intervals up to 3 cm. Patients with 3- to 4-cm tumors, however, had a poorer prognosis compared with patients with 2- to 3-cm tumors (hazard ratio: 1.6, 95 % confidence interval: 1.18-2.18, p = 0.002). DSS also fell when tumor size increased from 5-6 to 6-7 cm (53 vs. 21 %, 0.006). CONCLUSIONS This study emphasizes the 3-cm size, and possibly the 6-cm size, as informative predictive thresholds when ablating HCC, because variability of DSS occurred specifically at these tumor sizes. Future research in this field should either adopt a 3-cm breakpoint or provide evidence for alternative thresholds.


title: Modeling bimodal vessel effects on radio and microwave frequency ablation zones.

text: A bench liver model is presented that separates the thermal and electrical effects of large blood vessels within radio and microwave frequency ablation boundaries. The model includes a cylindrical tissue environment with a 5 mm vessel placed parallel to and 15 mm way from either a Covidien Energy-based Devices Evident MW Ablation Percutaneous Antenna or a CoolTip RF Ablation Single Electrode Kit. An array of fiber optic thermal probes is used to monitor radial temperature profile on the vessel and non-vessel sides of the ablation zone. Circulating blood exhibits higher electrical conductivity than surrounding liver tissue and provides a significant means for transport of thermal energy. Data from the thermal probes indicate key performance differentiators between MW and RF ablation modalities when they are used next to large blood vessels clarifying the difference between thermal and electrical energy sink. The results suggest RFA is susceptible to both the thermal and electrical energy sink effects of large vasculature while MWA is only susceptible to thermal sink. Ablation zone boundaries were distorted on both the vessel and non-vessel sides with RFA whereas with MWA only the vessel side is affected.


title: Laparoscopic treatment of duodenal injury caused by gunshot.

text: Duodenal injury in most cases, presents as a complex trauma of all adjacent organs which it is generally treated with a midline laparotomy though laparoscopic treatment in selected cases might be beneficial. We present a case of haemodynamically stable patient who suffered abdominal gunshot injury causing grade II trauma of the liver and penetrating wound of the first part of the duodenum and was treated laparoscopically. We believe that laparoscopic primary or assisted repair of injured duodenum is an appropriate surgical option in haemodynamically stable patients who sustain focal abdominal trauma.


title: Care of newborns born to mothers with COVID-19 infection; a review of existing evidence.

text: Background: The novel Coronavirus disease 2019 (COVID-19) pandemic is already wreaking havoc on families and communities' welfare. It is critical to discuss newborn care of infected mothers with COVID-19 based on the latest international guidelines and national guidelines of countries with the highest incidence of COVID-19 cases.Objective: We discuss how to care for a newborn of a suspected or infected mother with COVID-19 using existing evidence.Method: As of 16 April 2020, we reviewed articles and guidelines related to COVID-19 in the reproductive health field, mother, and newborn health. Our review yielded in 10 categories (i) the risk of diagnostic procedures in suspected mothers on fetus/infant health, (ii) the risk of intrauterine or postpartum transmission to the fetus/infant, (iii) appropriate method and delivery time in women with confirmed COVID-19, (iv) umbilical cord clamping and skin to skin contact, (v) clinical manifestations of infected infants, (vi) confirmation of infection in a suspected neonate/infant, (vii) instructions for infant's care and how to feed her/him, (viii) bathing the baby, (ix) the criteria of discharging baby from the hospital, (x) the impact of isolation on the maternal mental health.Results: Our findings showed that the possibility of intrauterine or perinatal transmission of COVID-19 is still questionable and ambiguous. However, what has been agreed upon in the existing texts and guidelines is that the close contact of mother and infant after birth can transmit the virus to the baby through droplets or micro-droplets.Conclusions: Based on our findings, it is recommended to separate the baby from the mother with confirmed (or suspected) COVID-19 infection for at least 2 weeks. Since the motivation and stable situation of mothers allow breastfeeding during the isolation, infected mothers should be taught about breast expression skills, common breast problems, the symptoms of their baby's infection, and the principles of personal hygiene to protect the infant against COVID-19 infection.


title: Avoiding airway obstruction after pediatric adenotonsillectomy.

text: OBJECTIVE To evaluate the efficacy of a protocol designed to prevent post-adenotonsillectomy airway obstruction in small children with obstructive sleep apnea. DESIGN Computerized retrospective review of single surgeon case series. SETTING Tertiary children's medical center. METHODS Children with sleep study proven obstructive sleep apnea or children under the age of 3 years with clinically suspected obstructive sleep apnea were treated according to a protocol that included: (1) rapid bloodless tonsillectomy; (2) repeated release of the tonsillar retractor; (3) avoidance of uvular edema; (4) routine intra-operative intranasal oxymetazoline, and placement of nasal airway; (5) extended recovery room observation. Primary outcome measures were (1) avoidance of unexpected intensive care unit admission; (2) post-extubation pulmonary edema; (3) aspiration pneumonia. RESULTS During the period March 2004-August 2007, 864 children underwent adenotonsillectomy by a single surgeon-604 for the indication of obstructive sleep apnea or adenotonsillar hypertrophy with obstruction. Two hundred and ten were under the age of 3 years or had sleep study proven obstructive sleep apnea. There were two unexpected admissions to the pediatric intensive care unit for persistent upper airway obstruction-none required intubation. No child developed post-obstructive pulmonary edema. Three children were treated for infiltrates consistent with aspiration pneumonitis. CONCLUSION Most cases of post-extubation pulmonary edema and pneumonia can be avoided in young children and those with mild-to-moderate obstructive sleep apnea following a protocol that anticipates and avoids precipitating causes of upper airway obstruction.


Surgery in the COVID-19 Phase 2 Italian scenario: lessons learned in Northern Italy spoke hospitals.


title: Quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR) in translational oncology: lung cancer perspective.

text: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) is rapidly becoming a basic method in lung cancer research. Analysis of transcriptional activity of tumor cells or detection of tumor markers by this technique has the potential to change lung cancer diagnosis and treatment. Quantitative RT-PCR is characterized by unparalleled sensitivity and specificity, with very reliable reproducibility. Its prime advantage for gene expression analysis is its broad dynamic range of 10(7)-fold. Moreover, it is cost-effective, feasible in every day laboratory routine and efficient in terms of biological material consumption. Still, there are a number of methodological aspects that need to be carefully considered before it can sensibly be implemented into clinical practice. Three major technical issues: the choice of chemistries, gene expression data normalization and statistical processing of the results will be specifically highlighted in this review. Further, clinical applications of qRT-PCR will be thoroughly discussed: detection and staging of lung cancer and construction and validation of prognostic and predictive gene expression signatures.


title: The Anesthetic Challenges of Lung Biopsy-Associated Intrathoracic Hemorrhage in a Child With Suprasystemic Pulmonary Hypertension.

text: Children with suspected pulmonary hypertension must undergo extensive and invasive evaluations to establish a definitive diagnosis. A previously healthy 4-year old girl, newly diagnosed with suprasystemic pulmonary hypertension required multiple lung biopsies. Each procedure was associated with significant bleeding. The challenging anesthetic management of lung biopsy in the presence of suprasystemic pulmonary hypertension is described.


title: Energy Status and Body Composition Across a Collegiate Women's Lacrosse Season.

text: Little data is available regarding the energy and nutritional status of female collegiate team sport athletes. Twenty female NCAA Division II lacrosse athletes (mean ± SD: 20.4 ± 1.8 years; 68.8 ± 8.9 kg; 168.4 ± 6.6 cm; 27.9 ± 3% body fat) recorded dietary intake and wore a physical activity monitor over four consecutive days at five different time points (20 days total) during one academic year. Body composition, bone health, and resting metabolic rate were assessed in conjunction with wearing the monitor during off-season, pre-season, and season-play. Body fat percentage decreased slightly during the course of this study (p = 0.037). Total daily energy expenditure (TDEE) (p < 0.001) and activity energy expenditure (AEE) (p = 0.001) energy were found to change significantly over the course of the year, with pre-season training resulting in the highest energy expenditures (TDEE: 2789 ± 391 kcal/day; AEE: 1001 ± 267 kcal/day). Caloric (2124 ± 448 kcal/day), carbohydrate (3.6 ± 1.1 g/kg), and protein (1.2 ± 0.3 g/kg) intake did not change over the course of the year (p > 0.05). Athletes self-reported a moderate negative energy balance (366⁻719 kcal/day) and low energy availability (22.9⁻30.4 kcal/kg FFM) at each measurement period throughout the study. Reported caloric and macronutrient intake was low given the recorded energy expenditure and macronutrient intake recommendations for athletes. Athletic support staff should provide athletes with appropriate fueling strategies, particularly during pre-season training, to adequately meet energy demands.


The race to unravel the United States' biggest coronavirus outbreak.


title: Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring.

text: Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected COVID-19. Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We performed a case series of COVID-19 positive/suspected patients admitted between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine, or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett's) using 12-lead ECGs. Critical QTc prolongation was defined as: a) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and b) increased QTc of ≥60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Of 490 COVID-19 positive/suspected patients, 314 (64%) received either/both drugs, and 98 (73 COVID-19 positive, 25 suspected) met study criteria (age 62±17 yrs, 61% male). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448±29 ms and increased to 459±36 ms (p=0.005) with medications. Significant prolongation was observed only in men (18±43 ms vs -0.2±28 ms in women, p=0.02). 12% of patients reached critical QTc prolongation. Changes in QTc were highest with the combination compared to either drug, with much greater prolongation with combination vs. azithromycin (17±39 vs. 0.5±40 ms, p=0.07). No patients manifested torsades de pointes. Conclusions Overall 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients should be carefully assessed.


title: Role of embolization in the treatment of renal masses.

text: Renal arterial embolization (RAE) performed for the treatment of renal masses has been proven to be a safe and effective technique, with several decades of experience. RAE is well tolerated with few complications, particularly if the time interval from embolization to surgery is reduced to less than 48 hours. Review of the literature suggests that RAE is also extremely effective for palliation of symptoms in the setting of nonoperative advanced stage renal cell carcinoma. In addition, this technique plays a large role in the management of angiomyolipomas that are symptomatic or at risk of spontaneous rupture. To date, RAE has not been evaluated in a randomized controlled setting, which has contributed to its underutilization. All of these potential benefits warrant the need for prospective studies for further validation.


title: Indications for use and cost-effectiveness of pathogen-reduced ABO-universal plasma.

text: PURPOSE OF REVIEW Donor selection and viral screening methods combined with pathogen reduction have increased the safety of pooled plasma to a level which makes reintroduction of ABO-universal plasma an important option. RECENT FINDINGS Solvent detergent-treated pooled plasma has proved to be well suited for the production of pathogen-reduced ABO-universal plasma. One such product, Bioplasma FDP, was licensed in South Africa in 1994 and has since 1996 been in successful clinical use. A clinical study with this product and two studies with the European product, Uniplas, have confirmed the efficacy and safety of pathogen-reduced ABO-universal plasma. SUMMARY Pooling of plasma enables the production of ABO-universal plasma. Pathogen reduction with solvent detergent eliminates lipid-enveloped viruses, whereas neutralizing antibodies in the plasma pool and nucleic acid amplification testing ensures the safety for recognized nonlipid-enveloped viruses. Pooling also eliminates transfusion-associated acute lung injury (the leading cause of plasma transfusion-related death), reduces immunologic/allergic adverse events by 60-80% and standardizes plasma protein content. Thus, in addition to ABO compatibility, pathogen-reduced ABO-universal plasma has important supplementary benefits that improve the product's cost-effectiveness.


title: Simulation with standardized patients to prepare undergraduate nursing students for mental health clinical practice: An integrative literature review.

text: OBJECTIVE To evaluate the available evidence supporting the efficacy of using simulation with standardized patients to prepare nursing students for mental health clinical practice. DESIGN Integrative literature review. DATA SOURCES A systematic search of the electronic databases CINAHL (EBSCOhost), Embase, MEDLINE, PsycINFO, and SveMed+ was conducted to identify empirical studies published until November 2016. Multiple search terms were used. Original empirical studies published in English and exploring undergraduate nursing students' experiences of simulation with standardized patients as preparation for mental health nursing practice were included. A search of reference lists and gray literature was also conducted. In total, 1677 studies were retrieved; the full texts of 78 were screened by 2 of the authors, and 6 studies reminded in the review. REVIEW METHODS The authors independently reviewed the studies in three stages by screening the titles, abstracts, and full texts, and the quality of the included studies was assessed in the final stage. Design-specific checklists were used for quality appraisal. The thematic synthesizing method was used to summarize the findings of the included studies. RESULTS The studies used four different research designs, both qualitative and quantitative. All studies scored fairly low in the quality appraisal. The five themes identified were enhanced confidence, clinical skills, anxiety regarding the unknown, demystification, and self-awareness. CONCLUSIONS The findings of this study indicate that simulation with standardized patients could decrease students' anxiety level, shatter pre-assumptions, and increase self-confidence and self-awareness before entering clinical practice in mental health. More high-quality studies with larger sample sizes are required because of the limited evidence provided by the six studies in the present review.


title: Antibody fragments, expressed by a fowl adenovirus vector, are able to neutralize infectious bursal disease virus.

text: Single-chain variable fragments (scFv) contain the heavy and light chain variable domains of immunoglobulin, joined by a short peptide linker. Previously, our laboratory has produced neutralizing scFv to epitopes of infectious bursal disease virus (IBDV). The in vitro delivery and expression of one of these scFv with and without the C(H)2-C(H)4 Fc domain of chicken IgY attached (scFv-Fc) by a serotype 8 fowl adenovirus (FAdV-8) vector was investigated in the present study. A panel of FAdV-8 vectors was constructed, each containing a different transgene (scFv or scFv-Fc), a different promoter to drive scFv and scFv-Fc transcription (CMVie or the fowl adenovirus major late promoter), and a different sized, right-hand end genomic deletion (52 bp or 2.3 kb). This panel was used to establish what effect these variables had on protein production, viral replication and scFv transcription, as measured by enzyme-linked imunosorbent assay and real-time polymerase chain reaction. Our results showed that, using a FAdV-8 vector containing the optimal CMVie promoter/2.3 kb deletion combination, we successfully expressed a secreted form of both scFv and scFv-Fc that were able to neutralize IBDV both in vitro and in ovo. These studies indicate that the FAdV-8 vector may be a promising candidate to deliver and express therapeutic molecules such as scFv and scFv-Fc in vivo in poultry.


title: Cerebral arteriovenous malformations in the era of embolization for angiographic cure: a single-center experience in Egypt.

text: Background Embolization for cerebral arteriovenous malformations (AVMs) has evolved in the last decade with evolution in both equipment and material. Embolization targets have expanded to include angiographic cure. Methods To discuss the technical and management outcomes of our first cerebral AVM case series treated with embolization. The clinical, angiographic, treatment, and outcome variables of consecutive cerebral arteriovenous malformation cases, treated with curative embolization, between January 2011 and June 2017 in one regional center, were retrospectively analyzed. Results In 21 patients, 21 AVMs were identified, and 13 patients (61.9%) were males. The mean of the age was 34.24 ± 12.99. Fifteen patients (71.4%) had a history of intracranial hemorrhage, and 10 (47.6%) patients had seizures. Sixteen patients (76.2%) were at grade 1 of modified Rankin Scale (mRS) at admission. The median for modal Spetzler-Martin grade was 2. The average number of arterial feeders was 3. Direct arteriovenous fistulas were found in 4 cases (19.0%). Venous aneurysms were found in 4 cases (19.0%). Seventeen AVMs (80.9%) were considered high bleeding risk lesions. Forty-three embolization sessions were done. Early hemorrhage occurred in 3 sessions (7.0%). Vessel perforation occurred 1 session (2.3%). Poor outcome occurred in 1 patient that was discharged at grade 3 mRS. Angiographic cure was achieved in 9 patients (42.9%). The average size reduction was 65%. Conclusions Onyx embolization could serve as a curative option for AVM treatment with accepted morbidity and mortality.


title: Identification of in vivo-interacting domains of the murine coronavirus nucleocapsid protein.

text: The coronavirus nucleocapsid protein (N), together with the large, positive-strand RNA viral genome, forms a helically symmetric nucleocapsid. This ribonucleoprotein structure becomes packaged into virions through association with the carboxy-terminal endodomain of the membrane protein (M), which is the principal constituent of the virion envelope. Previous work with the prototype coronavirus mouse hepatitis virus (MHV) has shown that a major determinant of the N-M interaction maps to the carboxy-terminal domain 3 of the N protein. To explore other domain interactions of the MHV N protein, we expressed a series of segments of the MHV N protein as fusions with green fluorescent protein (GFP) during the course of viral infection. We found that two of these GFP-N-domain fusion proteins were selectively packaged into virions as the result of tight binding to the N protein in the viral nucleocapsid, in a manner that did not involve association with either M protein or RNA. The nature of each type of binding was further explored through genetic analysis. Our results defined two strongly interacting regions of the N protein. One is the same domain 3 that is critical for M protein recognition during assembly. The other is domain N1b, which corresponds to the N-terminal domain that has been structurally characterized in detail for two other coronaviruses, infectious bronchitis virus and the severe acute respiratory syndrome coronavirus.


title: Factors Influencing Physician Practices' Adoption of Behavioral Health Integration in the United States: A Qualitative Study.

text: BACKGROUND Behavioral health integration is uncommon among U.S. physician practices despite recent policy changes that may encourage its adoption. OBJECTIVE To describe factors influencing physician practices' implementation of behavioral health integration. DESIGN Semistructured interviews with leaders and clinicians from physician practices that adopted behavioral health integration, supplemented by contextual interviews with experts and vendors in behavioral health integration. SETTING 30 physician practices, sampled for diversity on specialty, size, affiliation with parent organizations, geographic location, and behavioral health integration model (collaborative or co-located). PARTICIPANTS 47 physician practice leaders and clinicians, 20 experts, and 5 vendors. MEASUREMENTS Qualitative analysis (cyclical coding) of interview transcripts. RESULTS Four overarching factors affecting physician practices' implementation of behavioral health integration were identified. First, practices' motivations for integrating behavioral health care included expanding access to behavioral health services, improving other clinicians' abilities to respond to patients' behavioral health needs, and enhancing practice reputation. Second, practices tailored their implementation of behavioral health integration to local resources, financial incentives, and patient populations. Third, barriers to behavioral health integration included cultural differences and incomplete information flow between behavioral and nonbehavioral health clinicians and billing difficulties. Fourth, practices described the advantages and disadvantages of both fee-for-service and alternative payment models, and few reported positive financial returns. LIMITATION The practice sample was not nationally representative and excluded practices that did not implement or sustain behavioral health integration, potentially limiting generalizability. CONCLUSION Practices currently using behavioral health integration face cultural, informational, and financial barriers to implementing and sustaining behavioral health integration. Tailored, context-specific technical support to guide practices' implementation and payment models that improve the business case for practices may enhance the dissemination and long-term sustainability of behavioral health integration. PRIMARY FUNDING SOURCE American Medical Association and The Commonwealth Fund.


title: Managing Complications in Abdominoplasty: A Literature Review.

text: BACKGROUND Abdominoplasty, with or without liposuction, is among the most frequently performed aesthetic procedures. Its main objective is to improve the body contour by means of excising redundant skin and fat tissue. Although abdominoplasty is considered a safe procedure with high satisfaction rates, intraoperative and postoperative complications can become a challenge for the surgical team. The aim of this article is to offer a synopsis of the most common complications arising after abdominoplasty, along with evidence-based guidelines about how to prevent and treat them. METHODS A systematic MEDLINE search strategy was designed using appropriate Medical Subject Headings (MeSH) terms, and references were scanned for further relevant articles. RESULTS According to the published case series, local complications are considerably more common than complications with systemic repercussions. Approximately 10% to 20% of patients suffer a local complication following abdominoplasty, while fewer than 1% suffer a systemic complication. Prevention and management strategies are critically discussed for complications including seroma, haematoma, infection, skin necrosis, suture extrusions, hypertrophic scars, neurological symptoms, umbilical anomalies, deep venous thrombosis and pulmonary thromboembolism, respiratory distress, and death. CONCLUSIONS The complications of abdominoplasty vary in severity and in the impact they have on the aesthetic outcomes. Recommendations for prevention and management are based on various levels of evidence, with a risk of observer bias. However, most complications can be treated appropriately following the current standards, with satisfactory results.


title: Utility of Flexible Bronchoscopic Cryobiopsy for Diagnosis of Diffuse Parenchymal Lung Diseases.

text: BACKGROUND Initial reports of transbronchial cryobiopsy for diffuse parenchymal lung disease (DPLD) suggest the diagnostic yield approaches that of surgical lung biopsy (SLB) with an excellent safety profile. Centers performing cryobiopsy differ significantly in procedure technique; an optimal technique minimizing complications but still capable of diagnosing a wide range of DPLDs has not been established. We evaluated our practice of flexible bronchoscopic cryobiopsy in a primarily outpatient setting for patients who required a tissue diagnosis for DPLD of uncertain etiology. METHODS Consecutive patients with indeterminate DPLD who underwent bronchoscopic cryobiopsy at a large academic medical center from January 2012 to August 2015 were retrospectively analyzed. Rates of confident histopathologic diagnosis, confident multidisciplinary consensus diagnosis, management change, and complications were determined. RESULTS One hundred four cases were identified. Confident histopathologic diagnoses were established in 44% (46/104) and confident multidisciplinary consensus diagnoses in 68% (71/104). Usual interstitial pneumonia (19/104) and idiopathic pulmonary fibrosis (22/104) were the most common histopathologic and consensus diagnoses, respectively. Five subjects proceeded to SLB after cryobiopsy which was diagnostic in 3. Results of cryobiopsies changed management in 70% (73/104). Complications occurred in 8 cases with no death. CONCLUSIONS Cryobiopsy during outpatient flexible bronchoscopy facilitated confident multidisciplinary consensus diagnosis of DPLD in more than two thirds of cases, and appears sufficient to establish the histopathologic diagnosis of usual interstitial pneumonia, with a complication rate that compares favorably to that reported for SLB.


title: CANDO and the infinite drug discovery frontier.

text: The Computational Analysis of Novel Drug Opportunities (CANDO) platform (http://protinfo.org/cando) uses similarity of compound-proteome interaction signatures to infer homology of compound/drug behavior. We constructed interaction signatures for 3733 human ingestible compounds covering 48,278 protein structures mapping to 2030 indications based on basic science methodologies to predict and analyze protein structure, function, and interactions developed by us and others. Our signature comparison and ranking approach yielded benchmarking accuracies of 12-25% for 1439 indications with at least two approved compounds. We prospectively validated 49/82 'high value' predictions from nine studies covering seven indications, with comparable or better activity to existing drugs, which serve as novel repurposed therapeutics. Our approach may be generalized to compounds beyond those approved by the FDA, and can also consider mutations in protein structures to enable personalization. Our platform provides a holistic multiscale modeling framework of complex atomic, molecular, and physiological systems with broader applications in medicine and engineering.


title: Alginate dressings for healing diabetic foot ulcers.

text: BACKGROUND Foot ulcers in people with diabetes mellitus are a common and serious global health issue. Dressings form a key part of ulcer treatment, with clinicians and patients having many different types to choose from including alginate dressings. A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use. OBJECTIVES To compare the effects of alginate wound dressings with no wound dressing or alternative dressings on the healing of foot ulcers in people with diabetes mellitus. SEARCH METHODS We searched The Cochrane Wounds Group Specialised Register (searched 4 January 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4); Ovid MEDLINE (1950 to December Week 3 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, January 03, 2012); Ovid EMBASE (1980 to 2011 Week 52); and EBSCO CINAHL (1982 to 30 December 2011). There were no restrictions based on language or date of publication. SELECTION CRITERIA Published or unpublished randomised controlled trials (RCTs) that have compared the effects on ulcer healing of alginate dressings with alternative wound dressings or no dressing in the treatment of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, risk of bias assessment and data extraction. MAIN RESULTS We included six studies (375 participants) in this review; these compared alginate dressings with basic wound contact dressings, foam dressings and a silver-containing, fibrous-hydrocolloid dressing. Meta analysis of two studies found no statistically significant difference between alginate dressings and basic wound contact dressings: risk ratio (RR) 1.09 (95% CI 0.66 to 1.80). Pooled data from two studies comparing alginate dressings with foam dressings found no statistically significant difference in ulcer healing (RR 0.67, 95% CI 0.41 to 1.08). There was no statistically significant difference in the number of diabetic foot ulcers healed when an anti-microbial (silver) hydrocolloid dressing was compared with a standard alginate dressing (RR 1.40, 95% CI 0.79 to 2.47). All studies had short follow-up times (six to 12 weeks), and small sample sizes. AUTHORS' CONCLUSIONS Currently there is no research evidence to suggest that alginate wound dressings are more effective in healing foot ulcers in people with diabetes than other types of dressing however many trials in this field are very small. Decision makers may wish to consider aspects such as dressing cost and the wound management properties offered by each dressing type e.g. exudate management.