title: Middle East Respiratory Syndrome Coronavirus Spike Protein Is Not Activated Directly by Cellular Furin during Viral Entry into Target Cells.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes host cellular proteases to enter cells. A previous report shows that furin, which is distributed mainly in the Golgi apparatus and cycled to the cell surface and endosomes, proteolytically activates the MERS-CoV spike (S) protein following receptor binding to mediate fusion between the viral and cellular membranes. In this study, we reexamined furin usage by MERS-CoV using a real-time PCR-based virus cell entry assay after inhibition of cellular proteases. We found that the furin inhibitor dec-RVKR-CMK blocked entry of MERS-CoV harboring an S protein lacking furin cleavage sites; it even blocked entry into furin-deficient LoVo cells. In addition, dec-RVKR-CMK inhibited not only the enzymatic activity of furin but also those of cathepsin L, cathepsin B, trypsin, papain, and TMPRSS2. Furthermore, a virus cell entry assay and a cell-cell fusion assay provided no evidence that the S protein was activated by exogenous furin. Therefore, we conclude that furin does not play a role in entry of MERS-CoV into cells and that the inhibitory effect of dec-RVKR-CMK is specific for TMPRSS2 and cathepsin L rather than furin.IMPORTANCE Previous studies using the furin inhibitor dec-RVKR-CMK suggest that MERS-CoV utilizes a cellular protease, furin, to activate viral glycoproteins during cell entry. However, we found that dec-RVKR-CMK inhibits not only furin but also other proteases. Furthermore, we found no evidence that MERS-CoV uses furin. These findings suggest that previous studies in the virology field based on dec-RVKR-CMK should be reexamined carefully. Here we describe appropriate experiments that can be used to assess the effect of protease inhibitors on virus cell entry.


Frequent occurrence of CD19-negative relapse after CD19 CAR T and consolidation therapy in 14 TP53-mutated r/r B-ALL children.


title: Prevalence and impact of high platelet reactivity in chronic kidney disease: results from the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents registry.

text: BACKGROUND Chronic kidney disease (CKD) is associated with increased rates of adverse events after percutaneous coronary intervention. We sought to determine the impact of CKD on platelet reactivity in clopidogrel-treated patients and whether high platelet reactivity (HPR) confers a similar or differential risk for adverse events among patients with CKD and non-CKD. METHODS AND RESULTS We performed a post hoc analysis of the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) registry, which included 8582 patients undergoing percutaneous coronary intervention with drug-eluting stents and platelet function testing using the VerifyNow assay. We compared HPR and its impact on ischemic and bleeding events >2 years among patients with CKD and non-CKD. Patients with CKD (n=1367) were older, more often female, diabetic, and had lower ejection fraction compared with their non-CKD counterparts (n=7043). Although HPR prevalence increased with worsening renal function in unadjusted analyses, these associations were no longer present after adjustment. Major adverse cardiac event rates at 2 years among those without CKD or HPR, HPR alone, CKD alone, and both CKD and HPR were 9.0%, 11.2%, 13.3%, and 17.5%, respectively (P<0.001). Associations between HPR and adverse events were uniform across CKD strata without evidence of interaction. CONCLUSIONS HPR is more common among those with versus without CKD, an association that is attributable to confounding risk factors that are more prevalent in CKD. The impact of HPR on ischemic and bleeding events is similar irrespective of CKD status. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.


title: Flu, Floods, and Fire: Ethical Public Health Preparedness.

text: Even as public health ethics was developing as a field, major incidents such as 9/11 and the SARS epidemic propelled discourse around public health emergency preparedness and response. Policy and practice shifted to a multidisciplinary approach, recognizing the broad range of potential threats to public health, including biological, physical, radiological, and chemical threats. This propelled the development of surveillance systems to detect incidents, laboratory capacities to rapidly test for potential threats, and therapeutic and social countermeasures to prepare for and respond to a range of hazards. In bringing public health ethics and emergency preparedness together, Emergency Ethics: Public Health Preparedness and Response adds depth and complexity to both fields. As global threats continue to emerge, the book, edited by Bruce Jennings, John D. Arras, Drue H. Barrett, and Barbara A. Ellis, will offer a vital compass.


title: Safety of gadolinium-based contrast material in sickle cell disease.

text: PURPOSE To assess the safety of intravenously administered gadolinium-based contrast material in sickle cell disease (SCD) patients. MATERIALS AND METHODS All pediatric and adult SCD patients evaluated by magnetic resonance imaging (MRI) at our institution between January 1995 and July 2009 were identified. The medical records of SCD patients who underwent contrast-enhanced MRI as well as an equal-sized cohort of SCD patients who underwent unenhanced MRI were reviewed for adverse (vaso-occlusive and hemolytic) events within 1 week following imaging. RESULTS Eight (five mild and three moderate) adverse events were documented within 1 week following contrast-enhanced MRI (38 patients and 61 contrast injections), while six (five mild and one moderate) similar events occurred within 1 week following unenhanced MRI (61 patients and 61 unenhanced MRI examinations). This difference in the number of adverse events was not statistically significant (odds ratio = 1.4; 95% confidence interval [CI] 0.4, 5.2). No severe adverse event occurred in either patient cohort. CONCLUSION Gadolinium-based contrast materials do not appear to be associated with increased risk of vaso-occlusive or hemolytic adverse events when administered to SCD patients. Larger, prospective studies using multiple gadolinium-based contrast materials would be useful to confirm the results of our investigation.


INFECTIOUS DISEASE. Camel vaccine offers hope to stop MERS.


title: [Clinical and coagulation characteristics in 7 patients with critical COVID-2019 pneumonia and acro-ischemia].

text: Objective: To investigate the clinical and coagulation characteristics in patients with critical Coronavirus disease 2019 (COVID-19) and acro-ischemia. Methods: The retrospective study included 7 critical COVID-19 patients with acro-ischemia in an intensive care unit (ICU) in Wuhan, from Feb 4 to Feb 15, 2020. The clinical and laboratory data before and during the ICU stay were analyzed. Results: The median age of 7 patients was 59 years and 4 of them were men. Three patients were associated with underlying comorbidities. Fever, cough, dyspnea and diarrhea were common clinical symptoms. All patients had acro-ischemia presentations including finger/toe cyanosis, skin bulla and dry gangrene. D-dimer, fibrinogen and fibrinogen degradation product (FDP) were significantly elevated in most patients. Prothrombin time was prolonged in 4 patients. D-dimer and FDP levels progressively elevated consistent with COVID-2019 exacerbation. Four patients were diagnosed with disseminated intravascular coagulation (DIC) . Low molecular weight heparin (LMWH) was administrated in 6 patients, which reduced D-dimer and FDP rather than improved clinical symptoms. Five patients died finally and the median time from acro-ischemia to death was 12 days. Conclusions: Coagulation parameters should be monitored closely in critical COVID-2019 patients. The timing and protocol of anticoagulation therapy are still under investigation based on more clinical data.


title: The development and impact of primary health care in China from 1949 to 2015: A focused review.

text: High-quality primary health care (PHC) services are associated with better health outcomes and positive health equity. Providing PHC services to all inhabitants is one of the Chinese government's health care objectives. However, an imbalance between people's increasing health needs and effective health service utilization exists in China. The objective of this review is to identify evidence for PHC development in China and to summarize the challenges as a reference for the future improvement of China's PHC system. Literature searches related to China's PHC were performed in PubMed, Web of Science, China National Knowledge Infrastructure, and Wan-fang databases. Related data were collected from the China Statistical Yearbook on Health and Family Planning 2003-2016, the China National Health Accounts Report 2015, and An Analysis Report of National Health Services Survey in China, 2013. The PHC network and the population's health have improved in China in recent years, with general practitioners as "gatekeepers" who have gradually taken the initiative to offer health services to residents. The limitation of input and shortages of resources and skilled health care providers may restrict the sustainable development of China's PHC system. Therefore, policy support from the government is necessary.


title: Plant-made virus-like particles bearing influenza hemagglutinin (HA) recapitulate early interactions of native influenza virions with human monocytes/macrophages.

text: INTRODUCTION Plant-made virus-like particles (VLP) bearing influenza virus hemagglutinins (HA) are novel vaccine candidates that induce cross-reactive humoral and poly-functional T cell responses. To better understand the mechanisms that underlie this broad immunogenicity we studied early interactions of VLPs bearing either H1 (A/California/07/2009 (H1N1)) or H5 (A/Indonesia/05/2005 (H5N1)) with a human monocytoid cell line (U-937 cells) and human monocyte-derived macrophages (MDMs) as model antigen-presenting cells (APC). METHODS AND RESULTS Using Vibrio cholerae sialidase and lectins that target α2,6- (Sambucus nigra lectin) or α2,3-linked sialic acids (Maackia amurensis lectin I), we demonstrated that VLPs bind to these APCs in a sialic acid-dependent manner. Using lysosomal markers and DiD-labelled VLPs, we found that attachment to the cell surface leads to internalization, trafficking to acidic cell compartments and fusion of the VLP lipid envelope with endosomal membranes. Incubation of MDMs with H1- but not H5-VLPs induced proliferation of autologous peripheral blood mononuclear cells suggesting antigen processing and stimulation of a memory T cell response. CONCLUSIONS Plant-made VLPs bearing influenza HA not only mimic the structure of influenza virions to some degree but also recapitulate key features of the initial virus-APC interaction. These observations may help to explain the balanced humoral and cellular responses to plant-made VLP vaccines.


title: Combination transarterial chemoembolization and microwave ablation improves local tumor control for 3- to 5-cm hepatocellular carcinoma when compared with transarterial chemoembolization alone.

text: PURPOSE To compare transarterial chemoembolization (TACE) monotherapy to combination TACE and microwave ablation (MWA) for local control of 3- to 5-cm hepatocellular carcinoma (HCC). METHODS Patients with HCC between 3 and 5 cm treated with TACE monotherapy or combination TACE + MWA at a single institution between 2007 and 2016 were retrospectively reviewed. Twenty-four HCCs (median diameter 3.8 cm) in 16 patients (13 males; median age 64 years) were treated using TACE monotherapy. Combination TACE + MWA was used to treat 23 HCCs (median diameter 4.2 cm) in 22 patients (18 males; median age 61 years). Microwave ablation was performed at a target time of two weeks following TACE. Individual tumors were followed by serial contrast-enhanced CT or MR. Response to treatment was evaluated on a tumor-by-tumor basis using mRECIST criteria with the primary outcome being local tumor progression (LTP). Data were analyzed using Fisher's exact test for categorical variables and Wilcoxon rank sum test for continuous variables. Time to LTP was estimated with the Kaplan-Meier method. RESULTS Relative to TACE monotherapy, TACE + MWA provided a trend toward both a lower rate of LTP (34.8% vs. 62.5%, p = 0.11) and a higher complete response rate (65.2% vs. 37.5%; p = 0.12). Time to LTP (22.3 months vs. 4.2 months; p = 0.001) was significantly longer in the TACE + MWA group compared to TACE monotherapy. CONCLUSIONS Combination therapy with TACE and microwave ablation improves local control and increases time to LTP for 3-5 cm HCC.


title: Real-time in vivo imaging of early mucosal changes during ischemia-reperfusion in human jejunum.

text: BACKGROUND AND STUDY AIMS Small intestinal ischemia-reperfusion (IR) is a frequent, potentially life threatening phenomenon. There is a lack of non-invasive diagnostic modalities. For many intestinal diseases, visualizing the intestinal mucosa using endoscopy is gold standard. However, limited knowledge exists on small intestinal IR-induced, early mucosal changes. The aims of this study were to investigate endoscopic changes in human jejunum exposed to IR, and to study concordance between endoscopic appearance and histology. PATIENTS AND METHODS In 23 patients a part of jejunum, to be removed for surgical reasons, was isolated and selectively exposed to ischemia with 0, 30 or 120 minutes of reperfusion. In 3 patients, a videocapsule was inserted in the isolated segment before exposure to IR, to visualize the mucosa. Endoscopic view at several time points was related to histology (Heamatoxylin & Eosin) obtained from 20 patients. RESULTS Ischemia was characterized by loss of villous structure, mucosal whitening and appearance of punctate lesions. This was related to appearance of subepithelial spaces and breaches in the epithelial lining in the histological view. Early during reperfusion, the lumen filled with IR-damaged, shed cells and VCE showed mucosal erosions, hemorrhage and intraluminal debris. At 60 minutes of reperfusion, the only remaining signs of IR were loss of villous structure and small erosions, indicating rapid mucosal healing. CONCLUSIONS This study shows a unique, real-time in vivo endoscopic view of early mucosal changes during IR of the human small intestine. Future studies should evaluate its usefulness in diagnosis of patients suspected of IR.


Thursday posters.


title: Safety and effectiveness of 5-mm and 10-mm electrothermal bipolar vessel sealers (LigaSure) in laparoscopic resections for sigmoid colon and rectal cancers.

text: BACKGROUND LigaSure™ (Covidien, Mansfield, MA) has been used in cases undergoing laparoscopic colon and rectal resections. This study aims to analyze the efficacy and safety of the 5-mm and 10-mm devices. SUBJECTS AND METHODS Patients who received a laparoscopic or hand-assisted laparoscopic operation for a tumor located in the sigmoid colon or rectum since 2006 were abstracted from a prospectively designed database, and findings were analyzed in two groups based on size of the device used during the procedure. The videotapes of the procedures were watched, and operation reports were read to obtain further information on specific intra- and postoperative complications. Demographics, tumor and operation-related information, and postoperative data were compared. RESULTS Among 215 (128 [59.5%] males; median age, 59.5±13.8 years) patients, data obtained from the 5-mm (n=32) and 10-mm (n=183) groups were identical regarding demographics and data related to tumor (localization and stage) and operation (number of harvested lymph nodes, conversion rates, operation time, intraoperative bleeding, transfusion requirement, reoperation rates, complications, 30-day mortality, and length of hospital stay). However, more patients underwent an anterior resection in the 10-mm group than in the 5-mm group (31.7% versus 15.6%, P<.05). Further analyses found device-related bleeding in 8 (3.7%) cases (2 [6.3%] versus 6 [3.3%] in the 5-mm versus 10-mm group, respectively, P>.05), requiring further attempts for hemorrhage control (n=6), conversion to open surgery (n=1), or relaparotomy (n=1). CONCLUSIONS The 5-mm and 10-mm LigaSure devices are similarly effective and safe during laparoscopic sigmoid colon and rectal resections. Severe bleeding from larger vessels may be observed, requiring conversion to open surgery or relaparotomy.


title: How to manage the patients with unsatisfactory results after ethanol ablation for thyroid nodules: role of radiofrequency ablation.

text: PURPOSE Although ethanol ablation (EA) is effective in the treatment of cystic thyroid nodules, it is less effective in nodules with solid component. Therefore refractory cases with solid component require another treatment modality such as radiofrequency ablation (RFA), which is effective in both solid and cystic thyroid nodules. We prospectively evaluated the efficacy of additional RFA and factors related to volume reduction in patients showing unsatisfactory results after a single session of EA. MATERIALS AND METHODS Of 94 patients with predominantly cystic thyroid nodules who underwent EA, 20 patients underwent additional RFA because of incompletely resolved clinical problems (symptomatic score reduction <50%) and presence of residual solid component at 1-month follow-up on ultrasonography. Improvement of clinical symptoms and nodule volume reduction were evaluated 6 month later. We evaluated factors related to nodule volume reduction after EA and RFA. RESULTS RFA after a single session of EA was effective in reducing mean symptom score from 4.8 to 1.1 (p<0.001), mean cosmetic score from 3.5 to 1.4 (p<0.001) and mean nodule volume from 11.3 to 0.9 mL (p<0.001). The only independent factor related to volume reduction after EA was the presence of a solid component (p<0.001), and EA was less effective in nodules when solid component >20% (p=0.001). We identified no factors related to volume reduction after RFA. CONCLUSION RFA is effective in treatment of benign predominantly cystic thyroid nodules in patients whose clinical problems were incompletely resolved after EA.


Fighting the COVID-19 pandemic: An ophthalmologist's experience in an intensive care unit at the All India Institute of Medical Sciences.


title: Long term results of acute Achilles repair with triple-bundle technique and early rehabilitation protocol.

text: BACKGROUND The best treatment for acute rupture of the Achilles tendon is still under debate. Our purpose was to evaluate surgical triple-bundle technique in selected patients with full subcutaneous rupture of Achilles tendon. METHODS Sixty-six consecutive patients (56 men, 10 women; age range 20-61 years) with full unilateral rupture of the Achilles tendon were surgically treated by the triple-bundle technique. Seventy-four percent of the lesions occurred during sport activity. Each patient was assessed by: (1) The American Orthopaedic Foot and Ankle Society (AOFAS) score; (2) the Leppilahti score; (3) the range of movement measurement of ankle joint; (4) ipsilateral thigh, calf, and ankle circumferences compared to the contralateral limb; (5) functional evaluation with isokinetic dynamometry of both limbs. RESULTS 80.3% of the patients were fully satisfied (AOFAS ≥90) with treatment and resumed their previous level of sport. Concerning the outcomes, (1) the mean AOFAS score at 36 months was 93.9; (2) the mean Leppilahti score at 36 months was 91.8; (3) the mean difference in dorsiflexion and plantarflexion between the healthy side and the operated side was 4.3° and 6.9°, respectively. We observed calf muscle hypotrophy in two cases and scar complication in one. No re-ruptures occurred. Isokinetic tests performed 36 months after surgery showed a good restoration of plantarflexion. At univariate analysis AOFAS was influenced by age and difference between the healthy side and the operated side in dorsiflexion, plantarflexion, and circumference at all three levels and strenght at 60°/s. At univariate analysis, Leppilahti score confirmed the significant parameters of the AOFAS with the exception of age and difference of thigh circumference. The only predictive parameters in multivariate analysis were dorsiflexion difference (O.R. = 0.831; 95% C.I. 0.694-0.995; p = 0.044) and plantarflexion difference (O.R. = 0.777; 95% C.I. 0.631-0.958; p = 0.018). CONCLUSION In this case series the triple-bundle technique showed a low rate of complications and good functional restore tested with isokinetic tests. For these reasons afforded by biomechanical strength test reported in literature, this technique has to be considered a valid choice for the treatment of Achilles tendon rupture in young patients with a high level of sport activity.


title: A model describing the use of a bronchial blocking device and a sheathed bronchoscope for pulmonary aspiration studies in the Gottingen minipig.

text: The administration of test substances into a single lung, or lung lobe, allows the remaining untreated lung to act as an experimental control and effectively halves the number of animals required in a given experiment. It reduces the likelihood of early fatal pulmonary failure when noxious substances are studied which may lessen the need for replacement animals. However, the ease of substance administration and the subsequent analysis of its effects, for example by bronchoalveolar lavage or bronchoscopy, depend critically on the size of the animal model. The advantages of using minipigs; ease of handling, reduced housing requirements, genetic homogeneity, etc. are reduced if their diminutive size makes lung studies difficult. This article describes the use of a bronchial blocking device and a sheathed bronchoscope which enabled sterile endobronchial substance administration in Göttingen minipigs, and allowed pulmonary aspiration studies to be conducted with each animal acting as its own control.


title: Swine infectious agents in Tayassu pecari and Pecari tajacu tissue samples from Brazil.

text: Peccaries and pigs, Tayassuidae and Suidae respectively, diverged approximately one million years ago from a common ancestor. Because these families share some pathogens, peccaries can act as reservoirs of infectious pathogens for domestic and wild swine. We evaluated the presence of swine infectious agents in the spleen and lung tissues of white-lipped peccaries (WLP; Tayassu pecari) and collared peccaries (CP; Pecari tajacu) in Brazil. Samples from 10 adult CP and three WLP, which had been hunted by locals or hit by motor vehicles, were obtained from two free-ranging Brazilian populations. The samples were tested by PCR for Mycoplasma hyopneumoniae, Bordetella bronchiseptica, Pasteurella multocida, porcine circovirus 2 (PCV2), Suid herpesvirus 1 (SuHV-1), and porcine parvovirus (PPV). Positive samples were sequenced. Both species were negative for PPV and B. bronchiseptica and positive for PCV2 and SuHV-1. The lungs of two animals were positive for M. hyopneumoniae and P. multocida. This report is the first demonstration of PCV2 and SuHV-1 swine viruses and of M. hyopneumoniae and P. multocida bacteria in peccaries. One factor contributing to this detection was access to tissue samples, which is uncommon. The role of these infectious agents in peccaries is unknown and further epidemiologic studies should be performed. This study identified several infectious agents in peccaries and highlighted the importance of the tissue type used to detect pathogens.


title: Gastric Bypass Surgery Leads to Long-term Remission or Improvement of Type 2 Diabetes and Significant Decrease of Microvascular and Macrovascular Complications.

text: OBJECTIVES The aim of the study was to compare long-term outcomes of 2 groups of morbidly obese patients with type 2 diabetes mellitus-1 managed by Roux-en-Y gastric bypass surgery and a comparable group managed medically. METHODS The present study was a single-institution retrospective study. Of the 173 obese patients with type 2 diabetes mellitus undergoing gastric bypass surgery between January 2000 and July 2004, 78 patients (45%) were followed for at least 10 years. The control group consisted of 80 diabetic obese patients from the same period with similar body mass index, age, race, and severity of diabetes. The median follow-up was 11 years for both the groups. RESULTS The group undergoing gastric bypass surgery had greater percentage of excess weight loss than the control group-66% versus -1.6%, respectively. Forty-one patients (52.6%) in the surgery group had complete remission of diabetes and 5 (6.4%) had partial remission. Twelve patients (15.4%) had diabetes recurrence after initial remission. No patient in the control group had remission of diabetes. Compared with the control group, the group undergoing gastric bypass surgery had a significantly reduced incidence of microvascular complications-46.3% versus 11.5%, and macrovascular complications-20.3% versus 5%, respectively (P < 0.01). CONCLUSIONS In this study, we demonstrated that after 10 years of follow-up, Roux-en-Y gastric bypass surgery, compared with nonsurgical medical management, resulted in significantly greater weight loss, reduction in hemoglobin A1c, and use of antidiabetic medications, and very importantly a lower incidence of both microvascular and macrovascular complications in obese patients with type 2 diabetes.


The Message of the Covid Pandemic.


title: Endovascular treatment for traumatic scalp arteriovenous fistulas: results with Onyx embolization.

text: BACKGROUND Arteriovenous fistulas of the scalp (S-AVFs) are rare lesions and may occur spontaneously or secondary to trauma. The use of Onyx for the treatment of S-AVFs is not well established at this time. We discuss three cases of traumatic S-AVFs treated successfully with Onyx embolization alone or in association with coils. METHODS The database of patients treated at the Baptist Cardiac and Vascular Institute, Miami, Florida, was reviewed. All patients with traumatic S-AVFs treated with Onyx were included. RESULTS Two men and one woman with progressive enlarging pulsatile mass with bruit or tinnitus had angiographic evidence of S-AVF and were treated. In two patients the S-AVFs were secondary to hair transplantation. They were treated with Onyx-18 embolization as the single treatment modality. One patient with S-AVF resulting from temporomandibular joint arthroscopy was treated with coils and subsequent Onyx-34 embolization. In one patient, transarterial microcatheterization and injection of Onyx-18 was performed. In another patient, the intra-arterial approach was prevented by arterial vessel tortuosity. Therefore, access to the fistula was obtained through direct puncture of a large frontal vein; contrast injection confirmed the positioning of the needle within the draining vein of the AVF and Onyx-18 was then injected while the outflow vein was compressed. In the third patient in this series, coils were deployed to allow safer and more controlled injection of Onyx-34. No procedure related complications were noted. Post-embolization angiography demonstrated successful and complete occlusion of the AVF immediately after treatment. Follow-up revealed complete resolution of the symptoms. CONCLUSIONS Our experience in this small series indicates that endovascular treatment of S-AVFs with Onyx is rapid, safe, and highly effective.


title: STINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapy.

text: Recent advancements in the field of immunotherapy have yielded encouraging results for the treatment of advanced cancers. Cyclic dinucleotides (CDNs) are a powerful new class of immunotherapy drugs known as STING (Stimulator of Interferon Genes) agonists, currently in clinical trials. However, previous studies of CDNs in murine cancer models have required multiple injections, and improve survival only in relatively nonaggressive tumor models. Therefore, we sought to improve the efficacy of CDN immunotherapy by developing a novel biomaterial we call "STINGel." STINGel is an injectable peptide hydrogel that localizes and provides controlled release of CDN delivery, showing an 8-fold slower release rate compared to a standard collagen hydrogel. The carrier hydrogel is a positively charged, MultiDomain Peptide (MDP) which self-assembles to form a nanofibrous matrix and is easily delivered by syringe. The highly localized delivery of CDN from this nanostructured biomaterial affects the local histological response in a subcutaneous model, and dramatically improves overall survival in a challenging murine model of head and neck cancer compared to CDN alone or CDN delivered from a collagen hydrogel. This study demonstrates the feasibility of biomaterial-based immunotherapy platforms like STINGel as strategies for increasing the efficacy of CDN immunotherapies.


title: [Contagiousness and secondary attack rate of 2019 novel coronavirus based on cluster epidemics of COVID-19 in Guangzhou].

text: Objective: To analyze the contagiousness and secondary attack rate of 2019 novel coronavirus in cluster epidemics in Guangzhou and provide evidence for the prevention and control of COVID-19. Methods: All the individuals identified to be infected with 2019-nCoV in Guangzhou, including confirmed cases and asymptomatic cases, were included and classified as imported cases and local cases. The first case of each cluster epidemic was defined as index case, and the number of subsequent infections was calculated to evaluate the contagiousness and secondary attack rate of 2019 novel coronavirus in the shortest incubation period of 1-3 days. Results: As of 18 February, 2020, a total of 349 cases of 2019-nCoV infection, including 339 confirmed cases (97.13%) and 10 asymptomatic cases (2.87%) were reported in Guangzhou. There were 68 clusters involving 217 2019-nCoV infection cases (210 confirmed cases and 7 asymptomatic cases). The median number of subsequent infections caused by an index case in a cluster epidemic was 3, among which 2 were confirmed cases and 1 was asymptomatic cases, respectively. The average number of contagiousness was 2.18 in shorted incubation period of 1-3 days (The average number of infected cases were 2.18 cases by the index case in a cluster epidemic), the average infection number in family members was 1.86, and the infection ratio of family member transmission was 85.32% (1.86/2.18). The secondary attack rate in close contacts with shortest incubation period of 1-3 days was 17.12%-18.99%, the secondary attack rate in family members was 46.11%-49.56%. Conclusions: The cluster epidemic of COVID-19 in Guangzhou mainly occurred in families, the contagiousness was high. It is necessary to strengthen the prevention and control to reduce the community transmission of COVID-19.


title: Detection of different genotypes of infectious bronchitis virus and of infectious bursal disease virus in European broilers during an epidemiological study in 2013 and the consequences for the diagnostic approach.

text: To gather recent data regarding the infectious bronchitis (IB) and infectious bursal disease (IBD) situation in Europe, a large-scale field epidemiological survey using diagnostic samples has been implemented in 2013 for about six months in several European countries: France, Germany, Greece, Italy, the Netherlands, Poland, Portugal, the Republic of Ireland, Spain and the UK. In 234 flocks that were sampled, strains from 10 different IBV genotypes were detected: the 793B genotype was detected most frequently, followed by QX, Massachusetts (Mass) and the Xindadi-like strains. Strains belonging to the Q1, Ark, D274, D1466, Italy-02 and B1648 genotypes were detected as well, although less frequently. The separate sampling of tracheas and kidneys for IBV detection using reverse transcriptase PCR was very useful, as different genotypes or significant differences in sequences of the same genotype were detected between both organs. The data of this survey also provided valuable information about the replication of IBD vaccines and subsequent infectious bursal disease virus (IBDV) antibody responses under field conditions. The detection of five non-vvIBDV field strains of two different genotypes shows the presence of non-vvIBDV non-vaccine strains, which can easily be undetected in Europe due to the focus on sampling of clinically ill birds. Detection of vaccine virus in the bursa and antibody response to the IBD vaccination in flocks that had been vaccinated by the drinking water with a live attenuated vaccine compared to a vaccination in the hatchery using an immune-complex vaccine showed a delayed replication of the vaccines that had been applied by the drinking water, indicating mistakes in the timing and/or application of the vaccines.


title: Bio-organism sensing via surface enhanced Raman spectroscopy on controlled metal/polymer nanostructured substrates.

text: A new class of nonlithographically prepared surface enhanced Raman spectroscopy (SERS) substrates based on metalized, nanostructured poly(p-xylylene) films has been developed and optimized for surface plasmon response with a view to applications of SERS detection of microbial pathogens, specifically, bacteria and viruses. The main emphasis has been on achieving high spot to spot, sample to sample reproducibility of the SERS signals while maintaining useful enhancement factors. The use of these surfaces, metalized with either Ag or Au, provides a noninvasive and nondestructive method for spectral fingerprint analyses of both bacteria and viruses. Examples are given for the detection of bacteria (E. coli and B. cereus) and viruses (respiratory syncytial virus and Coxsackievirus). Our method is able to distinguish Gram positive from Gram negative bacterial strains as well as enveloped and nonenveloped viruses. The results demonstrate the development of a new class of SERS substrates which can provide rapid, selective identification of infectious agents without amplification of cultures.


title: "Small stem cells" in adult tissues: very small embryonic-like stem cells stand up!

text: This review summarizes information regarding the rare population of very small embryonic-like stem cells (VSELs) that has been identified in adult tissues, emphasizing both their unique morphological features and potential biological significance. We focus on their pluripotent nature and expression of markers characteristic for embryonic stem cells (ESCs), epiblast (EP)SCs, and primordial germ cells (PGCs). Furthermore, we will discuss their rank in the developmental hierarchy of the SC compartment as well as their relationship to other bone marrow-derived, primitive, nonhematopoietic SCs including: (i) endothelial progenitor cells (EPCs); (ii) mesenchymal (M)SCs; (iii) multipotent adult progenitor cells (MAPCs); (iv) marrow-isolated adult multilineage inducible (MIAMIs) cells; (v) multipotent adult (MA)SCs; and (vi) OmniCytes. We will also present different populations of very "small SCs" that have been recently described in the literature (e.g., spore-like cells and Lin(-)/ALDH(high) long-term repopulating hematopoietic SCs).


Covid-19: death rate is 0.66% and increases with age, study estimates.


title: Medium-Term Results of Laparoscopic Sleeve Gastrectomy: a Matched Comparison with Gastric Bypass.

text: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is considered a primary bariatric surgery and is increasingly being performed worldwide; however, long-term data regarding the durability of this procedure are inadequate. Here, we report the long-term results of LSGs in comparison to those of gastric bypass surgeries. METHODS A prospectively collected bariatric database from Ming-Shen General Hospital was retrospectively studied. Five hundred nineteen morbidly obese patients (mean age 36.0 ± 9.1 years old (14-71), 74.6 % female, mean body mass index (BMI) 37.5 ± 6.1 kg/m(2)) underwent LSG as a primary bariatric procedure from 2006 to 2012 at our institute. The operative parameters, weight loss, laboratory data, and quality of life were followed. Another two matched groups of laparoscopic Roux-en-Y gastric bypass (RYGB) and laparoscopic single anastomosis (mini-) gastric bypass (SAGB) patients who were matched in terms of age, sex, and BMI were recruited for comparisons. RESULTS The mean surgical time for LSG was 113.5 ± 31.3 min, and the mean blood loss was 49.1 + 100.9 ml. The rate of major complications was 1.6 %, and the average length of the postoperative stay was 3.0 ± 1.7 days. The operation times of the RYGB patients were longer than those of both the LSG and SAGB patients. The RYGB and SAGB patients experienced higher major complication rate than the LSG patients. The weight loss of the LSG patient at 5 years was 28.3 + 8.9 %, and the mean BMI was 27.1 + 4.3. The RYGB patients exhibited a 5-year weight loss similar to the LSG patients, and the SAGB patients exhibited greater weight loss than both of the other groups. Both the RYGB and SAGB patients exhibited significantly better glycemic control and lower blood lipids than the LSG patients, but the LSG patients exhibited a lesser micronutrient deficiency than the RYGB and SAGB groups. All three of the groups exhibited improved quality of life at 5 years after surgery, and there was no significant between-group difference in this measure. CONCLUSIONS LSG appears to be an ideal bariatric surgery, and the efficacy of this surgery is not inferior to that of gastric bypass.


Diagnostic laparoscopy complicated by group A streptococcal necrotizing fasciitis.


title: [Which sampling method for the upper respiratory tract specimen should be taken to diagnose patient with COVID-19?]

text: Coronavirus disease 2019 (COVID-19) is raging in China, especially in Hubei Province, which has resulted great dangers in people's life and national economy. According to the guidelines drafted by China's Center for Disease prevention and Control (CDC), the positive nucleic acid test is need to the diagnosis of patient with COVID-19. Upper respiratory tract specimens are the main sources for nucleic acid detection. However, based on international guidelines of COVID-19 , no recommended level of upper respiratory tract sampling method is proposed. Therefore, which kind of sampling methods should be chosen to help the COVID-19 diagnosis and which way is the most secure for doctors and nurses is our concern. In this review, we analyzed a total of 10 literatures on the sampling methods of upper respiratory tract related to infectious diseases such as severe acute respiratory syndrome coronavirus (SARS), middle east respiratory syndrome coronavirus (MERS), and influenza A (H1N1), which were spread worldwide in past years. Literatures were collected from the three dimensions of sampling method, sampling time, and sampling safety. It was found that among all the upper respiratory sampling methods, nasopharyngeal aspirate (NPA) had a higher positive rate within 2 weeks of symptom onset, while combined nasal and oropharyngeal swabs (NS + OPS) was the least harmful to medical staff during sampling. We wish this review is helpful for the prevention of COVID-19.


title: Democratic transitions, health institutions, and financial protection in the emerging economies: insights from Asia.

text: In recent years, several emerging economies have introduced national health insurance programs ensuring access to health care while offering financial protection from out-of-pocket and catastrophic expenses. Nevertheless, in several nations these expenses continue to increase. While recent research has emphasized the lack of funding, poor policy design and corruption as the main culprits, little is known about the politics of establishing federal regulatory agencies ensuring that state governments adhere to national insurance reimbursement and coverage procedures. This article fills in this lacuna by providing an alternative perspective, one that accounts for differences between nations in the creation of regulatory institutions, with an emphasis instead on governing elite strategies to campaign on access to health care during transitions to democracy, civil societal mobilization, constitutional constraints and the national electoral incentives to overcome ineffective decentralization processes. The cases of Indonesia and China are introduced as examples of how and why their differences in this political process accounted for Indonesia's success and China's failure to ensure financial protection.


title: Animal-based food systems are unsafe: SARS-CoV-2 fosters the debate on meat consumption.

text: The current pandemic restarts a debate on permanently banning wildlife consumption in an effort to prevent further public health threats. In this commentary, we offer two ideas to enhance the discussion on foodborne zoonotic diseases in food systems. First, we focus on the probable consequences that the loss of access to wildlife could cause to the status of food and nutrition security of many people in developing countries that rely on bushmeat to subsist. Second, we argue that all animal-based food systems, especially the ones based on intensive husbandry, present food safety threats. To ban the access to bushmeat without a rational analysis of all human meat production and consumption in the global animal-based food system will not help us to prevent future outbreaks.


title: Microbial air quality and bacterial surface contamination in ambulances during patient services.

text: OBJECTIVES We sought to assess microbial air quality and bacterial surface contamination on medical instruments and the surrounding areas among 30 ambulance runs during service. METHODS We performed a cross-sectional study of 106 air samples collected from 30 ambulances before patient services and 212 air samples collected during patient services to assess the bacterial and fungal counts at the two time points. Additionally, 226 surface swab samples were collected from medical instrument surfaces and the surrounding areas before and after ambulance runs. Groups or genus of isolated bacteria and fungi were preliminarily identified by Gram's stain and lactophenol cotton blue. Data were analyzed using descriptive statistics, t-test, and Pearson's correlation coefficient with a p-value of less than 0.050 considered significant. RESULTS The mean and standard deviation of bacterial and fungal counts at the start of ambulance runs were 318±485cfu/m(3) and 522±581cfu/m(3), respectively. Bacterial counts during patient services were 468±607cfu/m(3) and fungal counts were 656±612cfu/m(3). Mean bacterial and fungal counts during patient services were significantly higher than those at the start of ambulance runs, p=0.005 and p=0.030, respectively. For surface contamination, the overall bacterial counts before and after patient services were 0.8±0.7cfu/cm(2) and 1.3±1.1cfu/cm(2), respectively (p<0.001). The predominant isolated bacteria and fungi were Staphylococcus spp. and Aspergillus spp., respectively. Additionally, there was a significantly positive correlation between bacterial (r=0.3, p<0.010) and fungal counts (r=0.2, p=0.020) in air samples and bacterial counts on medical instruments and allocated areas. CONCLUSIONS This study revealed high microbial contamination (bacterial and fungal) in ambulance air during services and higher bacterial contamination on medical instrument surfaces and allocated areas after ambulance services compared to the start of ambulance runs. Additionally, bacterial and fungal counts in ambulance air showed a significantly positive correlation with the bacterial surface contamination on medical instruments and allocated areas. Further studies should be conducted to determine the optimal intervention to reduce microbial contamination in the ambulance environment.


title: Percutaneous Re-positioning of Dislocated Port-Catheters in Patients with Dysfunctional Central-Vein Port-Systems.

text: PURPOSE Observational analysis of percutaneous repositioning of displaced port-catheters in patients with dysfunctional central-venous port-systems. METHODS A total of 1061 patients with dysfunctional venous pectoral port-systems were referred for port-angiography. Dislocated port-catheters were identified in 37 (3.5 %) patients (11 males, mean age 58.1 ± 7.2 [range 48-69] years; 26 females, 57.0 ± 13.5 [range 24-75] years) 3.9 ± 6.6 months (range 1 day-26 months) after port-implantation. Percutaneous repositioning in all patients was performed by transfemoral catheter maneuvers, snaring, or wire-assisted long-loop snaring. Primary endpoint was successful repositioning. Safety endpoints included port-damage or procedure-related complications. Follow-up encompassed routine clinical and radiological controls, including chest X-ray or computed tomography for 12.9 ± 17.9 (range 1-81) months. RESULTS Clinical signs of port-dysfunction due to dislocation of port-catheters included difficult aspiration in 23 (62.2 %), resistance or inability to inject in 17 (46.0 %), and pain during injection in 2 (5.4 %) patients. Primary technical success for repositioning displaced port-catheters was 97.3 % (36/37 patients). In 1 (2.7 %) patient, repositioning failed due to complete embedding of the port-catheter in an extensive chronic jugular vein thrombosis (Paget-von-Schroetter syndrome) that prevented endovascular access to the port-catheter. Redisplacement occurred after initial successful repositioning: immediately in two patients due to a too short port-catheter (two-tailed Fisher's exact-test, p = 0.0101), and in two patients with appropriate catheter-length after 5, resp. 7 months. No procedure-associated complications, e.g., port-catheter disconnection or disruption, occurred. CONCLUSIONS Repositioning of dysfunctional displaced central-venous port-catheters with appropriate catheter-length is safe and effective. Even challenging conditions, e.g., wall-adherent port-catheter tip or a thrombosed catheter-bearing vein are feasible. Repositioning of too short port-catheters is ineffective.


title: Herpes simplex virus 1 serine/threonine kinase US3 hyperphosphorylates IRF3 and inhibits beta interferon production.

text: Viral infection initiates a series of signaling cascades that lead to the transcription of interferons (IFNs), finally inducing interferon-stimulated genes (ISGs) to eliminate viruses. Viruses have evolved a variety of strategies to modulate host IFN-mediated immune responses. Herpes simplex virus 1 (HSV-1) US3, a Ser/Thr kinase conserved in alphaherpesviruses, was previously reported to counteract host innate immunity; however, the molecular mechanism is elusive. In this study, we report that US3 blocks IFN-β production by hyperphosphorylating IFN regulatory factor 3 (IRF3). Ectopic expression of US3 protein significantly inhibited Sendai virus (SeV)-mediated activation of IFN-β and IFN-stimulated response element (ISRE) promoters and the transcription of IFN-β, ISG54, and ISG56. US3 was also shown to block SeV-induced dimerization and nuclear translocation of IRF3. The kinase activity was indispensable for its inhibitory function, as kinase-dead (KD) US3 mutants K220M and D305A could not inhibit IFN-β production. Furthermore, US3 interacted with and hyperphosphorylated IRF3 at Ser175 to prevent IRF3 activation. Finally, the US3 KD mutant viruses were constructed and denoted K220M or D305A HSV-1, respectively. Cells and mice infected with both mutant viruses produced remarkably larger amounts of IFN-β than those infected with wild-type HSV-1. For the first time, these findings provide convincing evidence that US3 hyperphosphorylates IRF3, blocks the production of IFN-β, and subverts host innate immunity.


title: Minimally Invasive Thumb-sized Pterional Craniotomy for Surgical Clip Ligation of Unruptured Anterior Circulation Aneurysms.

text: Less invasive surgical approaches for intracranial aneurysm clipping may reduce length of hospital stay, surgical morbidity, treatment cost, and improve patient outcomes. We present our experience with a minimally invasive pterional approach for anterior circulation aneurysms performed in a major tertiary cerebrovascular center and compare the results with an aged matched dataset from the Nationwide Inpatient Sample (NIS). From August 2008 to December 2012, 22 elective aneurysm clippings on patients ≤55 years of age were performed by the same dual fellowship-trained cerebrovascular/endovascular neurosurgeon. One patient (4.5%) experienced transient post-operative complications. 18 of 22 patients returned for follow-up imaging and there were no recurrences through an average duration of 22 months. A search in the NIS database from 2008 to 2010, also for patients aged ≤55 years of age, yielded 1,341 hospitalizations for surgical clip ligation of unruptured cerebral aneurysms. Inpatient length of stay and hospital charges at our institution using the minimally invasive thumb-sized pterional technique were nearly half that of NIS (length of stay: 3.2 vs 5.7 days; hospital charges: $52,779 vs. $101,882). The minimally invasive thumb-sized pterional craniotomy allows good exposure of unruptured small and medium-sized supraclinoid anterior circulation aneurysms. Cerebrospinal fluid drainage from key subarachnoid cisterns and constant bimanual microsurgical techniques avoid the need for retractors which can cause contusions, localized venous infarctions, and post-operative cerebral edema at the retractor sites. Utilizing this set of techniques has afforded our patients with a shorter hospital stay at a lower cost compared to the national average.


title: Detailed spatial characterization of superficial hip muscle activation during walking: A multi-electrode surface EMG investigation of the gluteal region in healthy older adults.

text: PURPOSE A multi-electrode array was used to generate spatially resolved Surface electromyography (SEMG) data of the hip muscles in healthy older adults. The cohort was meant to serve as an age-matched, normal control population for future surgical and rehabilitative studies in patients undergoing total hip arthroplasty, in view of the large, continuously increasing number of hip joint replacements. METHODS Bilateral hip muscle SEMG activity, including tensor fasciae latae (TFL), gluteus medius (Gmed), and gluteus maximus (Gmax), was measured during locomotion on a walkway at self-selected slow, normal, and fast walking speeds (age-matched cohort of 29 females and 25 males). Eight equally-spaced, vertically oriented bipolar channels were applied on a horizontal line at mid-distance between iliac crest and greater trochanter (length 17.5 cm; named P1 to P8). Time-independent parameters (e.g., mean amplitude) were derived from the amplitude curves expressed as root mean square. RESULTS The acquired SEMG data were not significantly influenced by gender (p = 0.202) or side (p = 0.313) and were therefore pooled. The most ventral to central electrode positions P1 to P5, representing TFL and ventral to central Gmed, showed the highest mean amplitude levels (averaged over the whole stride; 0.001 < p < 0.027 against P6 to P8; Bonferroni-adjusted paired t-test) at all walking speeds. Also, the respective curves showed two distinct amplitude peaks (representing load acceptance and hip stabilization during mid-stance), with a continuous increase of the first peak from P1 to P4 (most pronounced at fast speed) and the second peak from P1 to P3. Independently of the underlying individual muscles, both peaks displayed a continuous time shift from the most dorsal P8 to the most ventral P1 position, with the peaks for the ventral positions occurring at later time points during the normalized stride. CONCLUSIONS The continuously changing activation patterns of the superficial muscles in the gluteal region during walking may reflect function-driven, finely tuned coordination patterns of neighboring muscles and muscle segments, rather than independent activation of anatomically defined muscles. This may be important for the definition of specific target parameters for the improvement and/or normalization of muscle function during training and post-injury rehabilitation.


title: A Case of Prenatally Diagnosed Wilms Tumor Managed With Laparoscopic Nephrectomy.

text: We present a case of prenatally diagnosed Wilms tumor, with subsequent operative approach and management. The patient was referred to our institution with an abnormal prenatal renal ultrasound. Computed tomography scan after delivery showed a multifocal enhancing left renal mass. The patient underwent an uncomplicated left laparoscopic radical nephrectomy and retroperitoneal lymph node sampling using a novel hidden incision endoscopic surgery technique. Final pathology revealed favorable histology stage II Wilms tumor. The patient underwent adjuvant chemotherapy with vincristine and dactinomycin based on the EE4A regimen. We highlight the diagnostic pathway, perioperative management, surgical approach, and early postoperative follow-up in this case report.


title: Evaluation of Perivascular Adhesion Formation in New Zealand White Rabbits Using Oxiplex and DuraSeal Xact Adhesion Barrier System.

text: BACKGROUND Adhesion formation after spine surgery is a result of normal wound healing that may place patients at increased risk for complications during revision surgery. Preventing adhesions could reduce the risk of complications during revision surgery, and possibly reduce the need for revision procedures. This study evaluates the ability of DuraSeal Xact Adhesion Barrier System (DSX) (Covidien, Mansfield, Massachusetts) and Oxiplex/SP gel (OX) (FzioMed, San Luis Obispo, California) to affect the extent and severity of postoperative perivascular adhesion development in an anterior spinal surgical rabbit model. METHODS We determined the extent and severity of postoperative adhesion development 34 days after surgery in 12 male New Zealand White rabbits randomly assigned to intraoperative treatment with either DSX or OX, or to an untreated control group. Adhesion severity and extent were scored on scale from 0 (none) to 3 (severe). RESULTS The extent and severity of adhesions in the DSX group were significantly less than in the untreated control group. The DSX group mean extent score was 1.3 ± 0.5 (vs 2.5, P = .01) and the mean severity score was 1.25 ± 0.5 (vs 2.8, P = .005). The extent and severity of adhesions in the OX group were not significantly different from the control group. CONCLUSION In this study, we found DSX to be the most effective compound in preventing adhesion formation after anterior spine surgery. CLINICAL RELEVANCE Extrapolating these results in rabbits to humans, less scarring between the major blood vessels could decrease the rate of complications in revision spine procedures.


title: Local Decision Making for Implementing Social Distancing in Response to Outbreaks.

text: OBJECTIVES Social distancing is the practice of restricting contact among persons to prevent the spread of infection. This study sought to (1) identify key features of preparedness and the primary concerns of local public health officials in deciding to implement social distancing measures and (2) determine whether any particular factor could explain the widespread variation among health departments in responses to past outbreaks. METHODS We conducted an online survey of health departments in the United States in 2015 to understand factors influencing health departments' decision making when choosing whether to implement social distancing measures. We paired survey results with data on area population demographic characteristics and analyzed them with a focus on broad trends. RESULTS Of 600 health departments contacted, 150 (25%) responded. Of these 150 health departments, 63 (42%) indicated that they had implemented social distancing in the past 10 years. Only 10 (7%) health departments had a line-item budget for isolation or quarantine. The most common concern about social distancing was public health impact (n = 62, 41%). Concerns about law, politics, finances, vulnerable populations, and sociocultural issues were each identified by 7% to 10% of health departments. We were unable to clearly predict which factors would influence these decisions. CONCLUSIONS Variations in the decision to implement social distancing are likely the result of differences in organizational authority and resources and in the primary concerns about implementing social distancing. Research and current social distancing guidelines for health departments should address these factors.


title: Wire Atrial Septostomy.

text: Both balloon atrial septostomy and static balloon dilation are often ineffective in creating a large atrial septal defect in patients with a thickened atrial septum. In such situations, blade atrial septostomy and atrial septal stenting are alternative treatments. We have devised and performed a new technique, called wire atrial septostomy, which uses a thin soft wire to create a large defect. The details of the procedure are presented.


Covid-19: Mental health consequences of pandemic need urgent research, paper advises.


Introducing a new era of ischemic stroke care.


title: Robotic-assisted and laparoscopic ventral rectopexy in the treatment of rectal prolapse: a matched-pairs study of operative details and complications.

text: BACKGROUND Laparoscopic ventral rectopexy has been proven to be safe and effective in the treatment of rectal prolapse or intussusception. Robotic-assisted surgery may offer potential benefits to this operation. This study describes the comparison of robotic-assisted and conventional laparoscopic ventral rectopexy in terms of clinical parameters, operative details, postoperative complications and short-term outcomes. METHODS Twenty patients operated on for rectal prolapse or intussusception using the Da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale CA, USA) were prospectively followed for 3 months. The cases were pair-matched with laparoscopically operated controls from registry files. RESULTS Mean operating time was 159 min (standard deviation; ±37 SD) and 153 min (±33 SD) and mean total time in the operating theatre 231 min (±39 SD) and 234 min (±41 SD) for robotic-assisted and laparoscopic operations, respectively. Mean blood loss was 25 ml (±49 SD) in robotic-assisted and 37 ml (±50 SD) in laparoscopic procedures. There was one (5 %) significant complication in each group. Mean length of hospital stay was 3.1 (±2 SD) and 3.3 (±1.3 SD) days for the robotic-assisted and laparoscopic groups, respectively. The subjective benefit rate was the same in both groups: 16/20 (80 %). One patient in the robotic-assisted group continued to have symptoms of obstructed defecation, and there was one recurrence of prolapse in the laparoscopic group. CONCLUSIONS Robotic-assisted laparoscopic ventral rectopexy is safe, feasible and not more time consuming than the laparoscopic technique even at the beginning of the learning curve. The short-term results are comparable with those of laparoscopy. We found no arguments to support the routine use of robotic assistance in rectopexy operations.


title: Effectiveness of Fertility Awareness-Based Methods for Pregnancy Prevention: A Systematic Review.

text: OBJECTIVE To summarize best available prospective data on typical and perfect use effectiveness of fertility awareness-based methods for avoiding pregnancy. DATA SOURCES We conducted a systematic review of studies published in English, Spanish, French, or German by June 2017 in MEDLINE, EMBASE, CINAHL, Web of Science, and ClinicalTrials.gov. METHODS OF STUDY SELECTION We reviewed 8,755 unique citations and included 53 studies that contained 50 or greater women using a specific fertility awareness-based method to avoid pregnancy, calculated life table pregnancy probabilities or Pearl rates, and prospectively measured pregnancy intentions and outcomes. We systematically evaluated study quality. TABULATION, INTEGRATION, AND RESULTS Of 53 included studies, we ranked 0 high quality, 21 moderate quality, and 32 low quality for our question of interest. Among moderate-quality studies, first-year typical use pregnancy rates or probabilities per 100 woman-years varied widely: 11.2-14.1 for the Standard Days Method, 13.7 for the TwoDay Method, 10.5-33.6 for the Billings Ovulation Method, 4-18.5 for the Marquette Mucus-only Method, 9.0-9.8 for basal body temperature methods, 13.2 for single-check symptothermal methods, 11.2-33.0 for Thyma double-check symptothermal methods, 1.8 for Sensiplan, 25.6 for Persona, 2-6.8 for the Marquette Monitor-only Method, and 6-7 for the Marquette Monitor and Mucus Method. First-year perfect use pregnancy rates or probabilities among moderate-quality studies were 4.8 for the Standard Days Method, 3.5 for the TwoDay Method, 1.1-3.4 for the Billings Ovulation Method, 2.7 for the Marquette Mucus Method, 0.4 for Sensiplan, 12.1 for Persona, and 0 for the Marquette Monitor. CONCLUSION Studies on the effectiveness of each fertility awareness-based method are few and of low to moderate quality. Pregnancy rates or probabilities varied widely across different fertility awareness-based methods (and in some cases, within method types), even after excluding low-quality studies. Variability across populations studied precludes comparisons across methods.


title: Measurement of novel biomarkers of neuronal injury and cerebral oxygenation after routine vaginal delivery versus cesarean section in term infants.

text: AIMS It remains unclear if mode of delivery can have any impact on the neonatal brain. Our aim was to determine in term newborns any differences based on mode of delivery in either neuronal injury biomarkers, phosphorylated axonal neurofilament heavy chain (pNF-H) and ubiquitin C-terminal hydrolase (UCHL1), or brain oxygenation values, regional cerebral tissue oxygen saturation (CrSO2) and cerebral fractional tissue oxygen extraction (CFOE). METHODS An Institutional Review Board approved prospective observational pilot study of well newborns. Serum pNF-H and UCHL1 levels were measured on the day following delivery. CrSO2 values along with CFOE values were also measured using near-infrared spectroscopy (NIRS) and pulse oximetry. RESULTS There were 22 subjects, 15 born vaginally and seven born by cesarean section. No difference was found in mean pNF-H (107.9±54.3 pg/mL vs. 120.2±43.3 pg/mL, P=0.66) or mean UCHL1 (4.0±3.5 pg/mL vs. 3.0±2.2 pg/mL, P=0.68). No difference was found in mean CrSO2 (80.8±5.3% vs. 80.8±5.6%, P=0.99) or mean CFOE (0.17±0.06 vs. 0.15±0.08, P=0.51). CONCLUSIONS We found no difference in neuronal injury markers between term neonates born vaginally compared to those born by cesarean section. From a neurologic standpoint, this supports current obstetric practice guidelines that emphasize vaginal birth as the preferred delivery method whenever possible.


title: Operative Treatment of Type 2 Endoleaks Involving the Inferior Mesenteric Artery.

text: BACKGROUND We report the results of the operative treatment for type 2 endoleak (T2E) involving the inferior mesenteric artery (IMA) using the transarterial embolization (TAE) or the video laparoscopic ligation (VLS). METHODS Between January 2005 and December 2015, we retrospectively analyzed 901 patients treated with endovascular aortic repair (EVAR): 883 (98%) had 1 valid postoperative radiologic evaluation, at least. All patients with operative repair for IMA-related T2E entered the final analysis. Indication of their operative repair was sac enlargement (>5 mm within 6 months or >1 cm from the preoperative diameter, irrespectively of the postoperational time) and/or its persistence >12 months. RESULTS We detected 192 (21.7%) T2Es, overall. We identified 37 (4.2%) IMA-related T2Es, and treated 21 cases (VLS n = 11, TAE n = 10). Aneurysm-related mortality and major or minor morbidity was never observed. Time of intervention did not differ significantly (minutes, VLS = 97 ± 46 vs. TAE = 95 ± 21, P = 0.901). Hospitalization was significantly lower in the TAE group (days, 4 ± 2 vs. 1 ± 0.4, P < 0.001). No patient was lost at a mean follow-up of 46 ± 32 months (range, 1-110; median, 48). At last follow-up, sac diameter was significantly more stable in the VLS (mm, 60 ± 10 vs. 55 ± 7, P = 0.593) than that in the TAE group (mm, 57 ± 9 vs. 63 ± 10, P = 0.050). The IMA-related T2E reintervention rate was not significantly different between the groups (VLS, n = 0 [0%] vs. TAE, n = 2 [20.0%], P = 0.213). Secondary aortic reintervention rate was 28.6% (n = 6), and secondary open conversion rate was 9.5% (VLS, n = 1 [9.1%] vs. TAE, n = 1 [10.0%], P = 1). CONCLUSIONS In authors' experience, operative treatment of IMA-related T2E was safe; VLS proved to be effective and durable in sealing this type of T2E. Patients receiving correction of IMA-related T2E after EVAR remained at risk for development of any type of endoleaks, as well as at risk of reintervention.


title: Patients with cancer in the COVID-19 era: the clinical trial issue.

text: Coronavirus disease 2019 (COVID-19) hospital reorganization may result in reduced ability for the hospital to fully use its armamentarium for battling cancer. Thus different therapeutic modalities have been recommended. During the pandemic, despite regulatory agencies' recommendations, several considerations and doubts remain for oncologic clinical trials. Considering patients who had been enrolled before the pandemic, and who plan to take the study medication, the situation becomes complicated. These patients should undergo monitoring visits, blood sampling, questionnaire, physical examination, and drug and radiation administration. To avoid deviations from the protocol and trial discontinuation, follow-up should be performed regularly, in concordance with safety guidelines. Here we report several considerations.


title: Cerebral oximetry and postoperative delirium after cardiac surgery: a randomised, controlled trial.

text: Postoperative delirium is associated with increased morbidity and mortality. We hypothesised that restoration of regional cerebral oxygen desaturation would reduce the incidence of postoperative delirium in elderly patients after cardiac surgery. After institutional ethics review board approval and informed consent, a double-blinded, prospective, randomised, controlled trial was conducted in patients ≥ 60 years of age undergoing cardiac surgery with cardiopulmonary bypass. In the intervention group, an algorithm was commenced if regional cerebral oxygen saturation decreased below 75% of baseline value for 1 min or longer. In the control group, the cerebral oximetry monitor screen was electronically blinded. Assessment of delirium was performed with confusion assessment method for intensive care unit or confusion assessment method after discharge from intensive care unit at 12-h intervals for seven postoperative days. Postoperative delirium was present in 30 out of 123 (24.4%) and 31 out of 126 (24.6%) patients in the intervention and control groups, respectively, odds ratio 0.98 (95%CI 0.55-1.76), p = 0.97. Postoperative delirium was present in 20 (71%) out of 28 and in 41 (18%) out of 221 patients with baseline regional cerebral oxygen saturation ≤ 50, or > 50%, respectively, p = 0.0001. Higher baseline regional cerebral oxygen saturation and body mass index were protective against postoperative delirium. Restoration of regional cerebral oxygen desaturation did not result in lower postoperative delirium after cardiac surgery. Pre-operative regional cerebral oxygen saturation ≤ 50% was associated with increased postoperative delirium rates in elderly patients following cardiac surgery.


title: National Response to COVID-19 in the Republic of Korea and Lessons Learned for Other Countries.

text: In the first two months of the COVID-19 pandemic, the Republic of Korea (South Korea) had the second highest number of cases globally yet was able to dramatically lower the incidence of new cases and sustain a low mortality rate, making it a promising example of strong national response. We describe the main strategies undertaken and selected facilitators and challenges in order to identify transferable lessons for other countries working to control the spread and impact of COVID-19. Identified strategies included early recognition of the threat and rapid activation of national response protocols led by national leadership; rapid establishment of diagnostic capacity; scale-up of measures for preventing community transmission; and redesigning the triage and treatment systems, mobilizing the necessary resources for clinical care. Facilitators included existing hospital capacity, the epidemiology of the COVID-19 outbreak, and strong national leadership despite political changes and population sensitization due to the 2015 Middle East respiratory syndrome-related coronavirus (MERS-CoV) epidemic. Challenges included sustaining adequate human resources and supplies in high-caseload areas. Key recommendations include (1) recognize the problem, (2) establish diagnostic capacity, (3) implement aggressive measures to prevent community transmission, (4) redesign and reallocate clinical resources for the new environment, and (5) work to limit economic impact through and while prioritizing controlling the spread and impact of COVID-19. South Korea's strategies to prevent, detect, and respond to the pandemic represent applicable knowledge that can be adopted by other countries and the global community facing the enormous COVID-19 challenges ahead.


title: Achieving a golden mean: mechanisms by which coronaviruses ensure synthesis of the correct stoichiometric ratios of viral proteins.

text: In retroviruses and the double-stranded RNA totiviruses, the efficiency of programmed -1 ribosomal frameshifting is critical for ensuring the proper ratios of upstream-encoded capsid proteins to downstream-encoded replicase enzymes. The genomic organizations of many other frameshifting viruses, including the coronaviruses, are very different, in that their upstream open reading frames encode nonstructural proteins, the frameshift-dependent downstream open reading frames encode enzymes involved in transcription and replication, and their structural proteins are encoded by subgenomic mRNAs. The biological significance of frameshifting efficiency and how the relative ratios of proteins encoded by the upstream and downstream open reading frames affect virus propagation has not been explored before. Here, three different strategies were employed to test the hypothesis that the -1 PRF signals of coronaviruses have evolved to produce the correct ratios of upstream- to downstream-encoded proteins. Specifically, infectious clones of the severe acute respiratory syndrome (SARS)-associated coronavirus harboring mutations that lower frameshift efficiency decreased infectivity by >4 orders of magnitude. Second, a series of frameshift-promoting mRNA pseudoknot mutants was employed to demonstrate that the frameshift signals of the SARS-associated coronavirus and mouse hepatitis virus have evolved to promote optimal frameshift efficiencies. Finally, we show that a previously described frameshift attenuator element does not actually affect frameshifting per se but rather serves to limit the fraction of ribosomes available for frameshifting. The findings of these analyses all support a "golden mean" model in which viruses use both programmed ribosomal frameshifting and translational attenuation to control the relative ratios of their encoded proteins.


title: SAGES TAVAC safety and efficacy analysis confocal laser endomicroscopy.

text: BACKGROUND Confocal laser endomicroscopy (CLE) is a novel endoscopic adjunct that allows real-time in vivo histological examination of mucosal surfaces. By using intravenous or topical fluorescent agents, CLE highlights certain mucosal elements that facilitate an optical biopsy in real time. CLE technology has been used in different organ systems including the gastrointestinal tract. There has been numerous studies evaluating this technology in gastrointestinal endoscopy, our aim was to evaluate the safety, value, and efficacy of this technology in the gastrointestinal tract. METHODS The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Technology and Value Assessment Committee (TAVAC) performed a PubMed/Medline database search of clinical studies involving CLE in May of 2018. The literature search used combinations of the keywords: confocal laser endomicroscopy, pCLE, Cellvizio, in vivo microscopy, optical histology, advanced endoscopic imaging, and optical diagnosis. Bibliographies of key references were searched for relevant studies not covered by the PubMed search. Case reports and small case series were excluded. The manufacturer's website was also used to identify key references. The United States Food and Drug Administration (U.S. FDA) Manufacturer And User facility and Device Experience (MAUDE) database was searched for reports regarding the device malfunction or injuries. RESULTS The technology offers an excellent safety profile with rare adverse events related to the use of fluorescent agents. It has been shown to increase the detection of dysplastic Barrett's esophagus, gastric intraepithelial neoplasia/early gastric cancer, and dysplasia associated with inflammatory bowel disease when compared to standard screening protocols. It also aids in the differentiation and classification of colorectal polyps, indeterminate biliary strictures, and pancreatic cystic lesions. CONCLUSIONS CLE has an excellent safety profile. CLE can increase the diagnostic accuracy in a number of gastrointestinal pathologies.


title: Single-incision laparoscopic right colectomy: an efficient technique.

text: PURPOSE Laparoscopic right colectomy has an established patient benefit. We sought to demonstrate that a single-incision approach to laparoscopic right colectomy is safe, reproducible, and efficient. METHODS Photographs were acquired from cases to depict a step-by-step approach. We collected operative, pathologic, and postoperative outcomes from 8 patients who underwent a single-incision laparoscopic right colectomy. RESULTS There were no intraoperative complications nor deaths and 3 complications postoperatively. The average return of bowel function and length of stay was 3 and 5 days, respectively. Pathologic assessment revealed negative margins and an average of 17 lymph nodes harvested from the specimens. CONCLUSIONS Single-incision laparoscopic right colectomy is an evolving technique and likely to supplant conventional laparoscopic colectomy because of its equivalent and reproducible outcomes and the ease of the procedure. We depict our preferred method and review the current literature of single-incision right colectomy.


title: Intra-arterial mechanical thrombectomy stent retrievers and aspiration devices in the treatment of acute ischaemic stroke: A systematic review and meta-analysis with trial sequential analysis.

text: Purpose Intra-arterial mechanical thrombectomy combined with appropriate patient selection (image-based selection of acute ischaemic stroke patients with large artery occlusion) yields improved clinical outcomes. We conducted a systematic review and meta-analysis, with trial sequential analysis to understand the benefits, risks and impact of new trials reporting in 2016 on the magnitude/certainty of the estimates for clinical effectiveness and safety of mechanical thrombectomy. Method Random effects' models were conducted of randomised clinical trials comparing mechanical thrombectomy (stent retriever or aspiration devices) with/without adjuvant intravenous thrombolysis with intravenous thrombolysis and other forms of best medical/supportive care in the treatment of acute ischaemic stroke. Study inclusion and risk of bias were assessed independently by two reviewers. Functional independence (modified Rankin Scale 0-2) and mortality at 90 days, including symptomatic intracranial haemorrhage rate were extracted. Trial sequential analysis established the strength of the evidence derived from the meta-analyses. Findings Eight trials of mechanical thrombectomy with a total sample size of 1841 (916 patients treated with mechanical thrombectomy and 925 treated without mechanical thrombectomy) fulfilled review inclusion criteria. The three most recent trials more precisely defined the effectiveness of mechanical thrombectomy (modified Rankin Scale 0 to 2; OR = 2.07, 95% CI = 1.70 to 2.51 based on data from eight trials versus OR = 2.39, 95% CI = 1.88 to 3.04 based on data from five trials). Meta-analyses showed no effect on mortality (OR = 0.81, 95% CI = 0.61 to 1.07) or symptomatic intracranial haemorrhage (OR = 1.22, 95% CI = 0.80 to 1.85) as found in analysis of first five trials. Trial sequential analysis indicated that the information size requirement was fulfilled to conclude the evidence for mechanical thrombectomy is robust. Discussion The impact of three recent trials on effectiveness and safety of mechanical thrombectomy was a more precise pooled effect size for functional independence. Trial sequential analysis demonstrated sufficient evidence for effectiveness and safety of mechanical thrombectomy. Conclusion No further trials of mechanical thrombectomy versus no mechanical thrombectomy are indicated to establish clinical effectiveness. Uncertainty remains as to whether mechanical thrombectomy reduces mortality or increases risk of symptomatic intracranial haemorrhage.


title: Food waste co-digestion with sewage sludge--realising its potential in the UK.

text: The application of anaerobic co-digestion of food waste with sewage sludge, although well established in many European countries, is still in its infancy in the UK. This process has many benefits to offer, with a successful application often associated with increased renewable energy potential, outweighing constraints associated with the variability of food waste and its handling requirements prior to co-digestion. With both regulations and water infrastructures designed and constructed on the basis of linear views and sectorial requirements and conditions and technologies from the past in many parts of the world, in the UK, sewage sludge and food waste digestion operations are also under very different regulatory and management regimes. With sustainability requiring that we do not address single issues in isolation, but through a systems approach that delivers integrated solutions, co-digestion of food waste with sewage sludge could become such a solution. If carefully applied, co-digestion can deliver beneficial synergies for the water industry and authorities responsible for food waste management. The collaboration of all relevant stakeholders and regulators to support changes to current regulatory frameworks to enable this, is proposed as the way forward, particularly as their complexity has been identified as the major hurdle to the implementation of co-digestion in the UK.


Management of recurrent inguinal hernias.


title: An outbreak of gastroenteritis by emerging norovirus GII.2[P16] in a kindergarten in Kota Kinabalu, Malaysian Borneo.

text: Outbreaks of diarrhea in kindergartens are underreported and frequently go unnoticed in developing countries. To better understand the etiology this study was performed during an outbreak of diarrhea in a kindergarten in Sabah, Malaysia. Outbreak investigation was performed according to the standard procedures. In this outbreak a total of 34 (36.5%) children and 4 (30.8%) teachers suffered from gastroenteritis. Stool samples from seven children and 13 teachers were tested for rotavirus and norovirus. During the investigation stool samples were collected and sent in cold chain to the laboratory. The samples were subjected to rotavirus enzyme linked immunosorbent assay, and reverse transcription PCR for norovirus. All samples were negative for rotavirus but positive for norovirus. To determine the genogroup and genotype of norovirus, nucleotide sequencing of the amplicons was performed. All norovirus from the outbreak was of genotype GII.2[16]. To determine the relatedness of the strains phylogenetic analysis was done using neighbor-joining method. Phylogenetically these strains were highly related to GII.2[P16] noroviruses from China and Japan. This study provided evidence that a diarrheal outbreak in a kindergarten was caused by GII.2[P16] norovirus which is an emerging strain in East Asia and Europe.


Expanding the definition of covid-19 deaths will show the true effect of the pandemic.


title: Rhesus theta-defensin prevents death in a mouse model of severe acute respiratory syndrome coronavirus pulmonary disease.

text: We evaluated the efficacy of rhesus theta-defensin 1 (RTD-1), a novel cyclic antimicrobial peptide, as a prophylactic antiviral in a mouse model of severe acute respiratory syndrome (SARS) coronavirus (CoV) lung disease. BALB/c mice exposed to a mouse-adapted strain of SARS-CoV demonstrated 100% survival and modest reductions in lung pathology without reductions in virus titer when treated with two intranasal doses of RTD-1, while mortality in untreated mice was approximately 75%. RTD-1-treated, SARS-CoV-infected mice displayed altered lung tissue cytokine responses 2 and 4 days postinfection compared to those of untreated animals, suggesting that one possible mechanism of action for RTD-1 is immunomodulatory.


title: Influence of elastic lumbar support belts on trunk muscle function in patients with non-specific acute lumbar back pain.

text: BACKGROUND A well-known supportive treatment for acute nonspecific back pain, elastic back support belts, are valued for their ability to accelerate natural self-healing, but there are concerns of a deconditioning effect due to their reliance on passive stabilization. METHODS To evaluate the systematic effects of elastic abdominal belts on the trunk musculature, a total of 36 persons with acute lumbar back pain (no longer than one week) were divided into two groups: an abdominal belt wearing group (B) and a non-abdominal belt wearing control group (C). All were examined over a period of three weeks at three time points: T1 just after assignment, T2 one week later, and T3 further two weeks later. Surface EMG (sEMG) was used to record trunk muscle activation when walking on a treadmill at walking speeds of 2, 3, 4, 5, and 6 km/h. Similarly, pain intensity (VAS) and functional impairment (ODI) over time were recorded in both groups. RESULTS Over the observation period, a slight advantage for decreased pain intensity (C: p<0.05 T2 vs. T1; B: p<0.01 T2 vs. T1, p<0.05 T3 vs. T1) and decreased functional impairment (Cohen's d vs. T1, C: T2 0.45, T3 0.86; B: T2 1.1, T3 1.0) was observed for the belt group. For the belt group both oblique abdominal muscles exhibited significantly lower sEMG throughout the observation period (external abdominal oblique muscle: (T1), T2, (T3), internal abdominal oblique muscle: T1, (T2), (T3)) and the sEMG for the back muscles ranged from unchanged to slightly elevated for this group, but never reached statistical significance. DISCUSSION The reduced abdominal amplitude levels in the belt group likely result from the permanent elastic stabilization provided by the belt: the required elevated intra-abdominal pressure to enhance spinal stability is then provided by lessened abdominal muscle activity complemented by the belt's elastic support. With regard to the back muscles, the belt, due to its movement-restricting effect, tends to activate the paravertebral musculature. In this respect, the effect of elastic abdominal belts on the trunk muscles is not uniform. Therefore, the present results suggest that the effect of elastic abdominal belts appears to be more of a temporary neutral alteration of trunk muscle coordination, with some trunk muscles becoming more active and others less, and not a case of uniform deconditioning as is suspected.


Strategy for the difficult-to-reach ileal pouch-anal anastomosis: technical steps of an in vivo application of a mesenteric-lengthening technique.


title: Remote Access Robotic Facelift Thyroidectomy: A Multi-institutional Experience.

text: BACKGROUND Robotic facelift thyroidectomy (RFT) was developed as a new surgical approach to the thyroid gland using a remote incision site. Early favorable results led to this confirmatory multi-institutional experience. METHODS Prospectively collected data on consecutive patients undergoing RFT in five North American academic endocrine surgical practices were compiled. Surgical indications, operative times, final pathology, nodule size, complications, and postoperative management (drain use and length of hospital stay) were evaluated. RESULTS A total of 102 RFT procedures were undertaken in 90 patients. All but one of the patients (98.9 %) were female, and the mean age was 41.9 ± 13.1 years (range 12-69 years). The indication for surgery was nodular disease in 91.2 % of cases; 8.8 % were completion procedures performed for a diagnosis of cancer. The mean size of the largest nodule was 1.9 cm (range 0-5.6 cm). The mean total operative time for a thyroid lobectomy was 162 min (range 82-265 min). No permanent complications occurred. There were 4 cases (3.9 %) of transient recurrent laryngeal nerve weakness, no cases of hypocalcemia, and 3 (2.9 %) hematomas. There were no conversions to an anterior cervical approach. The majority of patients were managed on an outpatient basis (61.8 %) and without a drain (65.7 %). CONCLUSIONS RFT is technically feasible and safe in selected patients. RFT can continue to be offered to carefully selected patients as a way to avoid a visible cervical scar. Future prospective studies to compare this novel approach to other remote access approaches are warranted.


title: Transrectal guidance of the ovaries reduces operative time during bovine laparoscopic ovariectomy.

text: The main objective of this study was to evaluate the effects of transrectal guidance of the ovaries by an assistant on operative time during bovine laparoscopic ovariectomy. Twenty four clinically healthy Holstein dairy cows were divided randomly into two groups. In the transrectal guidance group, an assistant grasped the ovaries via the transrectal route and pulled them to a position where they could be visualized with a camera. On the other hand, the control group was operated without guidance. The time required to remove both ovaries in the guidance group was shorter than that in the control group (P<0.01). We concluded that laparoscopic ovariectomy with transrectal guidance of the ovaries can substantially shorten operative time, thereby greatly contributing to animal welfare and to reducing the burden on the operator.


title: A domain-based model for predicting large and complex pseudoknotted structures.

text: Pseudoknotted structures play important structural and functional roles in RNA cellular functions at the level of transcription, splicing and translation. However, the problem of computational prediction for large pseudoknotted folds remains. Here we develop a domain-based method for predicting complex and large pseudoknotted structures from RNA sequences. The model is based on the observation that large RNAs can be separated into different structural domains. The basic idea is to first identify the domains and then predict the structures for each domain. Assembly of the domain structures gives the full structure. The use of the domain-based approach leads to a reduction of computational time by a factor of about ~N ( 2) for an N-nt sequence. As applications of the model, we predict structures for a variety of RNA systems, such as regions in human telomerase RNA (hTR), internal ribosome entry site (IRES) and HIV genome. The lengths of these sequences range from 200-nt to 400-nt. The results show good agreements with the experiments.


title: Effect of inspiratory muscle-loaded exercise training on peak oxygen uptake and ventilatory response during incremental exercise under normoxia and hypoxia.

text: Background Although numerous studies have reported the effect of inspiratory muscle training for improving exercise performance, the outcome of whether exercise performance is improved by inspiratory muscle training is controversial. Therefore, this study investigated the influence of inspiratory muscle-loaded exercise training (IMLET) on peak oxygen uptake (VO2peak), respiratory responses, and exercise performance under normoxic (N) and hypoxic (H) exercise conditions. We hypothesised that IMLET enhances respiratory muscle strength and improves respiratory response, thereby improving VO2peak and work capacity under H condition. Methods Sixteen university track runners (13 men and 3 women) were randomly assigned to the IMLET (n = 8) or exercise training (ET) group (n = 8). All subjects underwent 4 weeks of 20-min 60% VO2peak cycling exercise training, thrice per week. IMLET loaded 50% of maximal inspiratory pressure during exercise. At pre- and post-training periods, subjects performed exhaustive incremental cycling under normoxic (N; 20.9 ± 0%) and hypoxic (H; 15.0 ± 0.1%) conditions. Results Although maximal inspiratory pressure (PImax) significantly increased after training in both groups, the extent of PImax increase was significantly higher in the IMLET group (from 102 ± 20 to 145 ± 26 cmH2O in IMLET; from 111 ± 23 to 127 ± 23 cmH2O in ET; P < 0.05). In both groups, VO2peak and maximal work load (Wmax) similarly increased both under N and H conditions after training (P < 0.05). Further, the extent of Wmax decrease under H condition was lower in the IMLET group at post-training test than at pre-training (from - 14.7 ± 2.2% to - 12.5 ± 1.7%; P < 0.05). Maximal minute ventilation in both N and H conditions increased after training than in the pre-training period. Conclusions Our IMLET enhanced the respiratory muscle strength, and the decrease in work capacity under hypoxia was reduced regardless of the increase in VO2peak.


title: Sequential endovascular thrombectomy approach (SETA) to acute ischemic stroke: preliminary single-centre results and cost analysis.

text: INTRODUCTION We report the preliminary results of a single-centre experience in the endovascular treatment (ET) of acute ischemic stroke (AIS) with a sequential endovascular thrombectomy approach (SETA), which comprehends a direct aspiration first-pass technique (ADAPT) eventually followed by stent retriever thrombectomy. MATERIALS AND METHODS We prospectively analyzed data from 16 patients with severe to moderate AIS and CT angiography demonstration of large intracranial vessel occlusion treated with SETA between July 2013 and March 2014. We evaluated recanalization rate, clinical outcome after 90 days as well as differential costs of aspiration and stent-assisted thrombectomy. RESULTS A group of 16 patients met the eligibility criteria to undergo ET with a baseline NIHSS score of 22 (range 12-39). In 15/16 cases, we obtained target vessel recanalization, 11 cases with ADAPT technique alone. Modified rankin score (mRS) at 90 days follow-up was ≤2 in 9/16 patients (56%). ADAPT technique had a lower device-related cost than stent-assisted thrombectomy leading to an overall saving of -2,747.28 . CONCLUSIONS Our preliminary data suggest that a SETA beginning with direct aspiration could be useful to optimize ET of stroke in terms of invasiveness, safety and cost-effectiveness allowing recanalization with low complication rate.


title: Hydrothermal Duodenal Mucosal Resurfacing: Role in the Treatment of Metabolic Disease.

text: The duodenum has become recognized as a metabolic signaling center that is involved in regulating insulin action and, therefore, insulin resistance states such as type 2 diabetes. Bariatric surgery and other manipulations of the upper intestine, in particular the duodenum, have shown that limiting nutrient exposure or contact in this key region exerts powerful metabolic effects. Early human clinical trial data suggest that endoscopic hydrothermal duodenal mucosal resurfacing is well tolerated in human subjects and has an acceptable safety profile. This article describes the rationale for this endoscopic approach and its early human use, including safety, tolerability, and early efficacy.


title: West Nile virus entry requires cholesterol-rich membrane microdomains and is independent of alphavbeta3 integrin.

text: West Nile virus (WNV) has been the leading cause of viral encephalitis in the United States since 1999. The endocytic processes involved in the internalization of infectious WNV by various cell types are not well characterized, and the involvement of cholesterol-rich membrane microdomains, or lipid rafts, in the life cycle of WNV has not been investigated previously. In this study, we found that the depletion of cellular cholesterol levels by brief treatment with methyl-beta-cyclodextrin resulted in a 100-fold reduction of the titers of infectious WNV released into the culture supernatant, as well as a reduction in the number of WNV genome copies in the cholesterol-depleted cells. The addition of exogenous cholesterol to cholesterol-depleted cells reversed this effect. Cholesterol depletion postinfection did not affect WNV growth, suggesting that the effect occurs at the level of WNV entry. We also showed that while WNV entry did not require alphavbeta3 integrin and focal adhesion kinase, WNV particles failed to be internalized by cholesterol-depleted cells. Finally, we showed the colocalization of the WNV envelope protein and cholera toxin B, which is internalized in a lipid raft-dependent pathway, in microdomain clusters at the plasma membrane. These data suggest that WNV utilizes lipid rafts during initial stages of internalization and that the lipid rafts may contain a factor(s) that may enhance WNV endocytosis.


title: Technique of pelvic lymphadenectomy after robot-assisted laparoscopic prostatectomy for prostate cancer.

text: Pelvic lymphadenectomy for prostate cancer is an important tool in the prognostication of the disease in selected patients who are at risk of occult lymph node metastases. This procedure, usually performed in conjunction with radical prostatectomy, had progressed successfully from an open approach to the current robot-assisted approach. The following article and accompanying video describe the surgical technique of robot-assisted pelvic lymphadenectomy for prostate cancer. We also discuss the indications, patient selection, preparation, complications, and tips to avoid the major pitfalls in the procedure.


Sustaining essential healthcare in Africa during the COVID-19 pandemic.


title: Aetiology of influenza-like illness in adults includes parainfluenzavirus type 4.

text: Influenza viruses cause significant morbidity and mortality in adults each winter. At the same time, other respiratory viruses circulate and cause respiratory illness with influenza-like symptoms. Human respiratory syncytial virus (HRSV), human parainfluenza viruses (HPIV) and human metapneumovirus have all been associated with morbidity and mortality in adults, including nosocomial infections. This study evaluated 154 respiratory specimens collected from adults with influenza-like/acute respiratory illness (ILI) seen at the Edward Hines Jr VA Hospital, Hines, IL, USA, during two successive winters, 1998-1999 and 1999-2000. The samples were tested for ten viruses in two nested multiplex RT-PCRs. One to three respiratory viruses were detected in 68 % of the samples. As expected, influenza A virus (FLU-A) infections were most common (50 % of the samples), followed by HRSV-A (16 %). Surprisingly, HPIV-4 infections (5.8 %) were the third most prevalent. Mixed infections were also relatively common (11 %). When present, HPIV infections were approximately three times more likely to be included in a mixed infection than FLU-A or HRSV. Mixed infections and HPIV-4 are likely to be missed using rapid diagnostic tests. This study confirms that ILI in adults and the elderly can be caused by HRSV and HPIVs, including HPIV-4, which co-circulate with FLU-A.


Responding to COVID-19 pandemic: Why a strong health system is required.


title: The Potential for Remotely Mentored Patient-Performed Home Self-Monitoring for New Onset Alveolar-Interstitial Lung Disease.

text: Purpose: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is an acute respiratory illness. Although most infected persons are asymptomatic or have only mild symptoms, some patients progress to devastating disease; such progression is difficult to predict or identify in a timely manner. COVID-19 patients who do not require hospitalization can self-isolate at home. Calls from one disease epicenter identify the need for homebased isolation with telemedicine surveillance to monitor for impending deterioration. Methodology: Although the dominant approach for these asymptomatic/paucisymptomatic patients is to monitor oxygen saturation, we suggest additionally considering the potential merits and utility of home-based imaging. Chest computed tomography is clearly impractical, but ultrasound has shown comparable sensitivity for lung involvement, with major advantages of short and simple procedures, low cost, and excellent repeatability. Thoracic ultrasound may thus allow remotely identifying the development of pneumonitis at an early stage of illness and potentially averting the risk of insidious deterioration to severe pneumonia and critical illness while in home isolation. Conclusions: Lung sonography can be easily performed by motivated nonmedical caregivers when directed and supervised in real time by experts. Remote mentors could thus efficiently monitor, counsel, and triage multiple home-based patients from their "control center." Authors believe that this approach deserves further attention and study to reduce delays and failures in timely hospitalization of home-isolated patients.


title: Reconstruction of urethral defects using a fascia lata autograft in a dog.

text: A castrated male Shih-Tzu dog was presented for evaluation of urine leakage after urethrotomy. A fistula with urine leakage was identified in the perineal region. On retrograde urethrography, the contrast extravasated from the penile urethra into the subcutaneous tissue of the perineum. Urine leakage with urethrocutaneous fistula was diagnosed. During surgery, the disrupted urethra wall and two urethral defects were identified. A fascia lata autograft was used, rather than primary repair of the urethra. Two pieces of fascia lata were harvested and sutured to the urethral defects. The fistula was treated with debridement and drainage. No evidence of urine leakage and dysuria was noted 6 months postoperatively. Thus, this case report describes successful urethral reconstruction using a fascia lata autograft.