title: Complication rates and center enrollment volume in the carotid revascularization endarterectomy versus stenting trial.

text: BACKGROUND AND PURPOSE Evidence indicates that center volume of cases affects outcomes for both carotid endarterectomy and stenting. We evaluated the effect of enrollment volume by site on complication rates in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). METHODS The primary composite end point was any stroke, myocardial infarction, or death within 30 days or ipsilateral stroke in follow-up. The 477 approved surgeons performed >12 procedures per year with complication rates <3% for asymptomatic patients and <5% for symptomatic patients; 224 interventionists were certified after a rigorous 2 step credentialing process. CREST centers were divided into tertiles based on the number of patients enrolled into the study, with Group 1 sites enrolling <25 patients, Group 2 sites enrolling 25 to 51 patients, and Group 3 sites enrolling >51 patients. Differences in periprocedural event rates for the primary composite end point and its components were compared using logistic regression adjusting for age, sex, and symptomatic status within site-volume level. RESULTS The safety of carotid angioplasty and stenting and carotid endarterectomy did not vary by site-volume during the periprocedural period as indicated by occurrence of the primary end point (P=0.54) or by stroke and death (P=0.87). A trend toward an inverse relationship between center enrollment volume and complications was mitigated by adjustment for known risk factors. CONCLUSIONS Complication rates were low in CREST and were not associated with center enrollment volume. The data are consistent with the value of rigorous training and credentialing in trials evaluating endovascular devices and surgical procedures. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00004732.


title: Spatial analysis and GIS in the study of COVID-19. A review.

text: This study entailed a review of 63 scientific articles on geospatial and spatial-statistical analysis of the geographical dimension of the 2019 coronavirus disease (COVID-19) pandemic. The diversity of themes identified in this paper can be grouped into the following categories of disease mapping: spatiotemporal analysis, health and social geography, environmental variables, data mining, and web-based mapping. Understanding the spatiotemporal dynamics of COVID-19 is essential for its mitigation, as it helps to clarify the extent and impact of the pandemic and can aid decision making, planning and community action. Health geography highlights the interaction of public health officials, affected actors and first responders to improve estimations of disease propagation and likelihoods of new outbreaks. Attempts at interdisciplinary correlation examine health policy interventions for the siting of health/sanitary services and controls, mapping/tracking of human movement, formulation of appropriate scientific and political responses and projection of spatial diffusion and temporal trends. This review concludes that, to fight COVID-19, it is important to face the challenges from an interdisciplinary perspective, with proactive planning, international solidarity and a global perspective. This review provides useful information and insight that can support future bibliographic queries, and also serves as a resource for understanding the evolution of tools used in the management of this major global pandemic of the 21 Century. It is hoped that its findings will inspire new reflections on the COVID-19 pandemic by readers.


Does this recent randomised controlled trial of intermittent pneumatic compression devices really indicate that they are ineffective in critical care patients?


title: Bicavitary effusion secondary to liver lobe torsion in a dog.

text: We described the diagnosis and successful treatment of pleural and peritoneal effusion secondary to liver lobe torsion in a dog. A 12-year-old female spayed Borzoi dog was referred for heart failure. Emergency room thoracic and abdominal ultrasound showed a large volume of pleural effusion with mild peritoneal effusion and an abdominal mass. Pleural fluid analysis classified the effusion as exudative. A complete ultrasound revealed mild peritoneal effusion and decreased blood flow to the right liver lobe. Other causes of bicavitary effusion were ruled out based on blood work, ultrasound, echocardiogram, and computed tomography. The patient was taken to surgery and diagnosed with caudate liver lobe torsion and had a liver lobectomy. At the 2-week postoperative recheck, the patient was doing well and there was complete resolution of the pleural effusion. Liver lobe torsion is a rare occurrence in dogs and can be difficult to diagnose. Clinical signs are nonspecific for liver lobe torsion and patients may present in respiratory distress with significant pleural fluid accumulation. When assessing patients with pleural and peritoneal effusion, liver lobe torsion should be considered as a differential diagnosis.


title: The X protein of HBV induces HIV-1 long terminal repeat transcription by enhancing the binding of C/EBPβ and CREB1/2 regulatory proteins to the long terminal repeat of HIV-1.

text: Due to share the route of transmission, the prevalence of co-infection of hepatitis B virus (HBV) and human immunodeficiency virus-1 (HIV-1) is high with chronic HBV infection affecting nearly 10% of HIV-infected patient world wide, which has become a significant global health problem. However, the cellular and molecular mechanisms associated with HBV/HIV-1 co-infection are largely unclear. In this study, we provided evidence that HBV induces HIV-1 transcription through its X protein (HBx). We further explored the mechanism by which HBx activates HIV-1 transcription. Our results showed that C/EBP and CRE cis-regulatory elements in the long terminal repeats (LTR) of HIV-1 are required for the activation of HIV-1 transcription mediated by HBx. We also demonstrated that HBx regulates HIV-1 transcription through stimulating the binding of transcriptional regulatory proteins C/EBPβ, CREB1, and CREB2 to HIV-1 LTR and that co-activator CBP is required for such regulation. These findings provide new insights into our understanding the effect of HBx on the activation of HIV-1 transcription and also provide evidence of the potential role of HBV in HIV-1 replication during the course of HBV/HIV-1 co-infection.


title: Laparoscopic management of gastric band erosions: a 10-year series of 49 cases.

text: BACKGROUND Intragastric erosion is a rare but major complication of laparoscopic adjustable gastric band (LAGB) surgery for morbid obesity. Many techniques to treat this problem have been described, with little supporting evidence. The authors review their experience with laparoscopic removal of eroded gastric bands. METHODS The prospectively collected bariatric surgery database of the authors' practice was queried for the period January 2000 until February 2011, and the medical records for all patients with the diagnosis of band erosion were reviewed. Symptoms, time to erosion, interval between diagnosis and treatment, and complications of treatment were reviewed. All patients had undergone laparoscopy, cut-down onto the band, unclasping or division of the band near the buckle, removal of the band, and primary closure of the gastrotomy with omental patch reinforcement. RESULTS During the study period, 2,097 LAGB operations were performed and 53 (2.53%) of these resulted in intragastric erosion. All the bands placed were LapBands (Allergan, Inc., Irvine, CA, USA). Erosions occurred with 14 of the 10-cm bands, 11 of the Vanguard bands, 14 of the AP Small bands, and 14 of the AP Large bands. Three patients elected to have their revisional surgery elsewhere and thus were lost to follow-up evaluation. One patient declined to have her band removed. The remaining 49 patients were included in the analysis. The mean time from band placement to the diagnosis of erosion was 31.5 months, and the mean time from diagnosis to band removal was 32 days. The mean hospital stay was 4 days. The complications included one postoperative leak, four superficial wound infections, and one pleural effusion. There were no deaths. CONCLUSIONS This review demonstrates the safety of laparoscopic removal of eroded gastric bands with primary closure and omental patch repair. The time from diagnosis of erosion to treatment can be short, in contrast to endoscopic removal, in which the requirement for further erosion of the band to free the buckle often necessitates delayed treatment.


Zoos struggling after Covid-19.


title: Transabdominal ultrasound for pregnancy diagnosis in Reeves' muntjac deer.

text: Reeves' muntjac deer (Muntiacus reevesi) are a small cervid species native to southeast Asia, and are currently being investigated as a potential model of prion disease transmission and pathogenesis. Vertical transmission is an area of interest among researchers studying infectious diseases, including prion disease, and these investigations require efficient methods for evaluating the effects of maternal infection on reproductive performance. Ultrasonographic examination is a well-established tool for diagnosing pregnancy and assessing fetal health in many animal species(1-7), including several species of farmed cervids(8-19), however this technique has not been described in Reeves' muntjac deer. Here we describe the application of transabdominal ultrasound to detect pregnancy in muntjac does and to evaluate fetal growth and development throughout the gestational period. Using this procedure, pregnant animals were identified as early as 35 days following doe-buck pairing and this was an effective means to safely monitor the pregnancy at regular intervals. Future goals of this work will include establishing normal fetal measurement references for estimation of gestational age, determining sensitivity and specificity of the technique for diagnosing pregnancy at various stages of gestation, and identifying variations in fetal growth and development under different experimental conditions.


title: In Vivo Electroporation of Developing Mouse Retina.

text: In vivo electroporation enables the transformation of retinal tissue with engineered DNA plasmids, facilitating the selective expression of desired gene products. This method achieves plasmid transfer via the application of an external electrical field, which both generates a transient increase in the permeability of cell plasma membranes, and promotes the incorporation of DNA plasmids by electrophoretic transfer through the permeabilized membranes. Here we describe a method for the preparation, injection, and electroporation of DNA plasmids into neonatal mouse retinal tissue. This method can be utilized to perform gain of function or loss of function studies in the mouse. Experimental design is limited only by construct availability.


title: Reactive oxygen and nitrogen species during viral infections.

text: Oxygen and nitrogen radicals are frequently produced during viral infections. These radicals are not only a physiological mechanism for pathogen clearance but also result in many pathological consequences. Low concentrations of radicals can promote viral replication; however, high concentrations of radicals can also inhibit viral replication and are detrimental to the cell due to their mitogenic activity. We reviewed the detailed mechanisms behind oxygen and nitrogen radical production and focused on how viruses induce radical production. In addition, we examined the effects of oxygen and nitrogen radicals on both the virus and host. We also reviewed enzymatic and chemical detoxification mechanisms and recent advances in therapeutic antioxidant applications. Many molecules that modulate the redox balance have yielded promising results in cell and animal models of infection. This encourages their use in clinical practice either alone or with existing therapies. However, since the redox balance also plays an important role in host defence against pathogens, carefully designed clinical trials are needed to assess the therapeutic benefits and secondary effects of these molecules and whether these effects differ between different types of viral infections.


title: Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review.

text: Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.


title: Modulation of the renin-angiotensin-aldosterone system in sepsis: a new therapeutic approach?

text: IMPORTANCE OF THE FIELD Severe sepsis is characterized by relative hypotension associated with a high cardiac output, peripheral vasodilation, and organ dysfunction. The renin-angiotensin-aldosterone system (RAAS) is primarily activated to increase blood pressure, but recently potential pro-inflammatory effects of angiotensin II have attracted interest because of the reported association between angiotensin II levels and organ failure and mortality in sepsis. RAAS antagonists could represent a new therapeutic option in this setting. AREAS COVERED IN THIS REVIEW The role of RAAS activation in severe sepsis and septic shock, and the potential benefits (and risks) of using RAAS antagonists. WHAT THE READER WILL GAIN Insight into RAAS function in severe sepsis and the potential for RAAS inhibitors to be used as an adjunctive therapy in patients with severe sepsis, with discussion of promising results from animal models of sepsis. TAKE HOME MESSAGE Use of RAAS antagonists is an emerging therapeutic option in severe sepsis because these agents may reduce endothelial damage, organ failure, and mortality. However, timing of administration of RAAS antagonists is important because reduced RAAS function may contribute to refractive hypotension later on in septic shock and benefits of RAAS antagonists seem to be restricted to the early phases of sepsis.


title: Etiology and Outcome of Diffuse Acute Infectious Bronchiolitis in Adults.

text: RATIONALE The etiology and outcome of diffuse acute infectious bronchiolitis (DAIB) in adults is not well known. OBJECTIVES To retrospectively review adult patients with DAIB without pneumonia, document the etiologies and outcomes, and assess the relation between DAIB and postinfectious bronchiolitis obliterans. METHODS We retrospectively analyzed medical records of 1,664 patients with lower respiratory tract infections admitted to our institution in Saitama, Japan. DAIB was diagnosed when patients developed acute feverish lower respiratory tract infection and chest computed tomography demonstrated mainly multiple centrilobular nodules in four or more lobes. Pneumonia was diagnosed when patients developed acute feverish lower respiratory tract infection and chest computed tomography demonstrated consolidation and/or ground-glass opacities with or without centrilobular nodules. MEASUREMENTS AND MAIN RESULTS Of the 1,664 patients, 20 (1.2%) and 1,644 (98.8%) patients were diagnosed as having DAIB and pneumonia, respectively. Of the 20 patients with DAIB, the etiology was determined in 16 (80%): 13 (65.0%) had a single pathogen and 3 (15.0%) had two pathogens. Detected organisms included Mycoplasma pneumoniae in eight (40.0%) patients, influenza virus in two (10.0%), influenza virus and Streptococcus pneumoniae in two (10.0%), Haemophilus influenzae in three (15.0%), and respiratory syncytial virus and rhinovirus in one (5.0%) patient. All patients improved and none developed postinfectious bronchiolitis obliterans. CONCLUSIONS The three most common etiologies of DAIB in the studied adults were M. pneumoniae, influenza virus, and H. influenzae. None of the patients with DAIB developed postinfectious bronchiolitis obliterans.


title: COVID 19 and Nepal: Identification of Critical Public Health Measures.

text: The COVID-19 pandemic is unfolding at an unprecedented pace. The unprecedented threat provides an opportunity to emerge with robust health systems. Nepal has implemented several containment measures such as Rapid Response Team formulation; testing; isolation; quarantine; contact tracing;surveillance, establishment of COVID-19 Crisis Management Centre and designation of dedicated hospitals to gear up for the pandemic. The national public health emergency management mechanisms need further strengthening with the proactive engagement of relevant ministries; we need a strong, real-time national surveillance system and capacity building of a critical mass of health care workers; there is a need to further assess infection prevention and control capacity; expand the network of virus diagnostic laboratories in the private sector with adequate surge capacity;implement participatory community engagement interventions and plan for a phased lockdown exit strategy enabling sustainable suppression of transmission at low-level and enabling in resuming some parts of economic and social life.


title: Current status of endovascular stroke treatment.

text: The management of acute ischemic stroke is rapidly developing.Although acute ischemic stroke is a major cause of adult disability and death, the number of patients requiring emergency endovascular intervention remains unknown, but is a fraction of the overall stroke population. Public health initiatives endeavor to raise public awareness about acute stroke to improve triage for emergency treatment, and the medical community is working to develop stroke services at community and academic medical centers throughout the United States. There is an Accreditation Council for Graduate Medical Education–approved pathway for training in endovascular surgical neuroradiology, the specialty designed to train physicians specifically to treat cerebrovascular diseases. Primary and comprehensive stroke center designations have been defined, yet questions remain about the best delivery model. Telemedicine is available to help community medical centers cope with the complexity of stroke triage and treatment. Should comprehensive care be provided at every community center, or should patients with complex medical needs be triaged to major stroke centers with high-level surgical,intensive care, and endovascular capabilities? Although the answers to these and other questions about stroke care delivery remain unanswered owing to the paucity of empirical data, we are convinced that stroke care regionalization is crucial for delivery of high-quality comprehensive ischemic stroke treatment. A stroke team available 24 hours per day, 7 days per week requires specialty skills in stroke neurology, endovascular surgical neuroradiology, neurosurgery, neurointensive care, anesthesiology, nursing, and technical support for optimal success. Several physician groups with divergent training backgrounds (i.e., interventional neuroradiology, neurosurgery,neurology, peripheral interventional radiology, and cardiology) lay claim to the treatment of stroke patients,particularly the endovascular or interventional methods. Few would challenge neurologists over the responsibility for emergency evaluation and triage of stroke victims for intra intravenous fibrinolysis, even though emergency physicians are most commonly the first to evaluate these patients. There are many unanswered questions about the role of imaging in defining best treatment. Perfusion imaging with CT or MRI appears to have relevance even though its role remains undefined and is the subject of ongoing research. Meanwhile, investigators are exploring new, and perhaps more specific,imaging methods with cerebral metabolic rate of oxygen and cellular acid-base imbalance. There are currently 6 ongoing trials of stroke intervention, many with proprietary technologies and private funding, competing for the same patient population as multicenter trials funded by the NIH. At the same time, much of the interventional stroke treatment currently occurs outside of trials in the community and academic settings without the collection of much-needed data. Market forces will certainly shape future stroke therapy, but it is unclear whether the current combination of private and public funding for these endeavors is the best method of development.


title: Relationship of workplace incivility, stress, and burnout on nurses' turnover intentions and psychological empowerment.

text: This study explored the relationships among perceived workplace incivility, stress, burnout, perceived turnover intentions, and perceived level of psychological empowerment among acute care nurses (medical-surgical and critical care) in community and tertiary hospitals through the lens of complexity science. An exploratory study was conducted, and findings demonstrate significant relationships among workplace incivility, stress, burnout, turnover intentions, total years of nursing experience, and RN education levels. Creating targeted retention strategies and policies that will be sensitive to the needs and interests of nurses at high risk for leaving their organizations is imperative for nurse executives.


title: Safety and feasibility of adjunctive dexamethasone infusion into the adventitia of the femoropopliteal artery following endovascular revascularization.

text: OBJECTIVE Restenosis following endovascular treatment of the femoropopliteal segment is associated with the inflammatory response produced in the artery wall at the time of the procedure. Although local drug delivery to the superficial femoral and popliteal arteries promises improved patency, data are currently limited. We hypothesized that improved percutaneous delivery of an anti-inflammatory compound into the adventitia of the femoropopliteal at the time of endovascular treatment would be safe, feasible, and decrease the inflammatory response. METHODS This was a prospective, investigator-initiated, phase I, first-in-man study testing the safety and feasibility of percutaneous adventitial delivery of dexamethasone. Following successful intervention, an adventitial microinfusion catheter was advanced over a 0.014-inch wire to the treated segment. Its microneedle (0.9 mm long × 140-μm diameter) was deployed into the adventitia to deliver dexamethasone (4 mg/mL) mixed with contrast agent (80:20 ratio), providing fluoroscopic visualization. The primary safety outcome measure was freedom from vessel dissection, thrombosis, or extravasation while the primary efficacy outcome was duplex-determined binary restenosis defined as a peak systolic velocity ratio >2.5. RESULTS Twenty patients with Rutherford clinical category 2-5 enrolled in this study. The mean age was 66, and 55% had diabetes mellitus. Treated lesion length was 8.9 ± 5.3 cm, and 50% were chronic total occlusions. Eighty percent of treated lesions were in the distal superficial femoral or popliteal arteries. All lesions were treated by balloon angioplasty with provisional stenting (n = 6) for suboptimal result. Three patients were treated with atherectomy as well. A mean of 1.6 ± 1.1 mg (0.5 ± 0.3 mL) of dexamethasone sodium phosphate was injected per centimeter of lesion length. In total, a mean of 12.1 ± 6.1 mg of dexamethasone was injected per patient. The mean number of injections required per lesion was 3.0 ± 1.3 cm, minimum one and maximum six injections. There was 100% technical success of drug delivery and no procedural or drug-related adverse events. The mean Rutherford score decreased from 3.1 ± .7 (median, 3.0) preoperatively to .5 ± .7 at 6 months (median, 0.0; P < .00001). Over this same time interval, the index leg ankle-brachial index increased from .68 ± .15 to .89 ± .19 (P = .0003). The preoperative C-reactive protein in this study was 6.9 ± 8.5 indicating severe baseline inflammation, which increased to 14.0 ± 23.1 mg/L (103% increase) at 24 hours following the procedure. However, this increase did not reach statistical significance of P = .14. Two patients met the primary efficacy end point of loss of primary patency by reoccluding their treated segment of the index lesion during the follow-up period. CONCLUSIONS Adventitial drug delivery via a microinfusion catheter is a safe and feasible alternative to intimal-based methods for adjunctive treatment in the femoropopliteal segment. The 6-month preliminary results suggest perivascular dexamethasone treatment may improve outcomes following angioplasty to the femoral and popliteal arteries, and support further clinical investigation of this approach.


title: Etomidate for short pediatric procedures in the emergency department.

text: OBJECTIVE This study aimed to prospectively determine the etomidate dose associated with adequate sedation and few significant respiratory events for procedures of short duration in children. METHODS This is a prospective cohort study in an urban pediatric emergency department of patients 4 to 18 years requiring sedation and analgesia for painful procedures of short duration. Patients received fentanyl 1 μg/kg followed by intravenously administered etomidate 0.1 to 0.2 mg/kg as a loading dose. An additional dose of etomidate 0.1 mg/kg was intravenously administered if needed. The level of sedation was determined by The Children's Hospital of Wisconsin Sedation Score. The primary outcome was to determine the etomidate dose associated with an adequate level of sedation and procedural completion. RESULTS Sixty patients were enrolled. The most frequent procedure was fracture reduction (50/60, 83.3%). Procedures were successfully completed for 59 (98.3%) of 60 patients. The initial dose of etomidate associated with adequate sedation was 0.2 mg/kg intravenously administered for 33 (66.7%) of 50 patients requiring fracture reduction and for 6 (60.0%) of 10 patients receiving a procedure other than fracture reduction. Respiratory depression was noted in 9 (16.4%) of 55 patients, and oxygen desaturation was noted in 23 (39.0%) of 59 patients. Of 58 patients, 21 (36.2%) experienced a respiratory adverse event requiring brief intervention including oxygen supplementation, stimulation, and/or airway repositioning. No patient experienced a significant adverse respiratory event, defined as positive pressure ventilation. Median time to discharge-ready was 21 minutes. CONCLUSIONS For short-duration painful emergency department procedures, etomidate 0.2 mg/kg intravenously administered after fentanyl was associated with effective sedation, successful procedural completion, and readily managed respiratory adverse events in children.


title: Adhesions to sutures, tackers, and glue for intraperitoneal mesh fixation: an experimental study.

text: PURPOSE Intraperitoneal mesh fixation for hernia repair is associated with adhesion formation. In this experimental study, adhesions against absorbable and non-absorbable fixation methods were compared. METHODS Six commercially available fixation methods were placed intraperitoneally in rats with a small pore polypropylene mesh coated on one side with ePTFE (Intramesh T1(®)). Two non-absorbable fixation methods: Prolene(®) (polypropylene) sutures and Protack(®) (titanium) tackers. Four absorbable methods: Vicryl(®) sutures (polyglactin), Absorbatack(®) and Permasorb(®) tackers (both mixes of lactic and glycolic acids) and Tisseel Duo(®) (fibrin glue). Adhesions and histology were studied at 7 and 90 days follow-up. In addition, fixation methods were placed without mesh, in order to study the reaction to the fixation method per se. RESULTS No adhesion formation, but also inadequate mesh fixation was found with Tisseel Duo(®), which had been completely resorbed at 7 days follow-up. Vicryl(®) sutures could no longer be detected at 90 days follow-up and were associated with a favorable adhesion profile. All other fixation methods were still intact 90 days after implantation. When placed without mesh, adhesion formation was significantly less than placed with a mesh (18 vs. 93 %, P < 0.001). Without mesh, adhesions were worst with Permasorb(®) tackers. CONCLUSIONS Absorbable fixation methods such as polyglactin sutures and fibrin glue show a favorable adhesion profile compared to longer-term absorbable or non-absorbable fixation methods. However, before using fibrin glue as a single fixation method more research is required.


Don't Forget About Us: Perspectives on Social Distancing in Assisted Living and Long-Term Care Facilities From Rural Nurse Practitioners.


title: Antiviral drug discovery: broad-spectrum drugs from nature.

text: Covering: up to April 2014. The development of drugs with broad-spectrum antiviral activities is a long pursued goal in drug discovery. It has been shown that blocking co-opted host-factors abrogates the replication of many viruses, yet the development of such host-targeting drugs has been met with scepticism mainly due to toxicity issues and poor translation to in vivo models. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can efficiently treat a wide range of viral infections by blocking specific host functions has re-bloomed. Here we critically review the state-of-the-art in broad-spectrum antiviral drug discovery. We discuss putative targets and treatment strategies, with particular focus on natural products as promising starting points for antiviral lead development.


title: Benefits of xiphoidectomy in total gastrectomy: Technical note.

text: OBJECTIVE The esophago-gastric junction may be challenging during total gastrectomy due to gastric cancer. This situation may compromise the security of both the dissection and anastomosis. The purpose of this study was to investigate the usefulness of xiphoidectomy to overcome this issue. MATERIAL AND METHODS The files of patients who underwent total gastrectomy + D2 lymph node dissection due to proximal gastric cancer or cardia cancer between April 2002-December 2013 were retrospectively evaluated. We assessed the outcome in patients with xiphoidectomy in addition to the midline incision in terms of xiphoidectomy technique, xiphoidectomy time, and operative and postoperative complications. RESULTS Thirty cases were identified to undergo xiphoidectomy. Nineteen patients were male and 11 were female, with a mean age of 51 (21-80) years. The time required for xiphoidectomy was 7-15 minutes (mean 8.7 minutes). The mean additional time required for the closure of the incision in cases with xiphoidectomy was 2 minutes. There was minimal arterial bleeding from the diaphragmatic surface in one patient, which was controlled by electrocautery. Only two patients developed wound infection. CONCLUSION Performing xiphoidectomy is quite easy, after a certain learning phase. The operative time was 7-15 minutes longer due to excision of xiphoid and closure of the related defect. Minor hemorrhage was a problem during surgery. There were no early or late post-operative complications. We suggest that the procedure is beneficial in selected cases with requirement of a wider operative field or better exposure of the esophago-gastric junction during total gastrectomy for gastric cancer, and recommend removal of the xiphoid bone.


Covid-19: Government must plan for schools to reopen, say paediatricians.


Ethics and Economic Growth in the Age of COVID 19: What Is a Just Society to Do?


Hydroxychloroquine for covid-19: the end of the line?


title: Community-acquired pneumonia.

text: PURPOSE OF REVIEW This review examines the epidemiology, diagnosis, prognosis, treatment and prevention of community-acquired pneumonia (CAP) in adults. RECENT FINDINGS CAP is a significant cause of morbidity and mortality. Streptococcus pneumoniae is the most common CAP pathogen; however, microbial cause varies by geographic location and host factors. Identification of a microbial cause in CAP remains challenging - 30-65% of cases do not have a pathogen isolated. The use of molecular techniques in addition to culture, serology and urinary antigen testing has improved diagnostic yield. Scoring systems are useful for CAP prognostication and site of care decisions. Studies evaluating novel biomarkers including pro-B-type natriuretic peptide and procalcitonin suggest potential adjunctive roles in CAP prognosis. Guideline-based treatment for CAP has changed little in recent years. Effective and timely antimicrobial therapy is crucial in optimizing outcomes and should be based on local antimicrobial susceptibility patterns. Macrolides may have additional anti-inflammatory properties and a mortality benefit in severe CAP. Preventive strategies include immunization and modification of specific patient risk factors. SUMMARY CAP is common and causes considerable morbidity and mortality. A comprehensive approach including advanced diagnostic testing, effective and timely antimicrobial therapy and prevention is required to optimize CAP outcomes.


India expands use of controversial drug for coronavirus despite safety concerns.


title: Temporary femoral artery bifurcation shunting following penetrating trauma.

text: Penetrating common femoral artery injuries are life-threatening, especially when the femoral bifurcation has been destroyed. In the presence of other associated injuries which preclude immediate definitive vascular reconstruction, temporary arterial shunting may be useful. Presently available shunts, however, are tubular and allow for distal perfusion to only one vessel. We have utilized a modified bifurcated hemodialysis catheter (Mahurkar MAXID; Tyco Healthcare, Mansfield, Mass) to successfully provide simultaneous perfusion from the proximal common femoral artery to both the superficial and deep femoral vessels. Such catheters are readily available in most institutions, can be quickly modified, and are easy use in urgent trauma situations.


title: Conservation needs to evolve to survive in the post-pandemic world.

text: Human activities have transformed Planet Earth to the extent that the functioning of its climate has been altered and a quarter of species face extinction (IPBES, 2019). These climate and biodiversity crises, which are interrelated and mutually reinforcing (Gardner et al. 2020), in turn have serious repercussions for humans, weakening the provision of ecosystem services and ultimately jeopardizing human civilization (Gowdy, 2020).


title: Middle-term prognosis in patients with ulcerative colitis who achieved clinical and endoscopic remission by budesonide rectal foam.

text: BACKGROUND Budesonide foam is effective in inducing clinical remission in ulcerative colitis (UC) patients with active proctosigmoiditis. The aim of this study was to evaluate the duration of remission and predictors of relapse in UC patients who achieved clinical remission and mucosal healing by 6-week treatment with topical budesonide. METHODS This is a retrospective, observational, multicenter study with a 2-year follow-up period. UC patients who were treated with budesonide foam in phase 2 or phase 3 clinical trials and achieved both clinical remission and mucosal healing were enrolled. RESULTS Among 84 patients who met the eligibility criteria, 60 participated in the study. Eighteen of the 60 patients (30.0%; 95% confidence interval [CI]: 18.9-43.2) experienced no relapse (i.e., maintenance of remission) during the 2-year follow-up period. The median relapse-free survival time was 0.82 years (95% CI: 0.51-1.52). Of 37 patients with a Mayo endoscopic subscore of 0 after inducing remission with budesonide foam, 25 (67.6%) relapsed within 2 years. Patients with a disease duration of <1 year experienced a worse clinical outcome than patients with a disease duration of >5 years, and the hazard ratio was 2.38 (95% CI: 1.04-5.45). CONCLUSION This is the first study to evaluate the short- to middle-term prognosis in UC patients who achieved mucosal healing with topical preparations. After inducing remission by budesonide foam, treatment for maintaining remissions and strict follow-up may be needed for patients with shorter disease duration.


title: Transient stop-flow arm arterial-venous equilibrium pressure measurement: determination of precision of the technique.

text: Transient stop-flow arm arterial-venous equilibrium pressure (Pmsf-arm) is a validated technique for measuring the mean systemic filling pressure (Pmsf). Pmsf is a functional measure of the effective intravascular volume status. This study aims to assess the precision of the Pmsf-arm measurement. Pmsf-arm was measured by inflating a pneumatic tourniquet around the upper arm 50 mmHg above systolic pressure for 60 s, four times consecutively, with an interval of 5 min. Arterial (Pa) and venous pressure (Pv) were recorded every 10 s. Pa-Pv difference was calculated to determine the stop-flow time. The coefficient error (CE) was determined and used to derive the least significant change (LSC) in Pmsf-arm that this technique could reliably detect. The rANOVA test was used to compare repeated measurements of the four determinations of Pmsf-arm. 80 measurements of Pmsf-arm were studied in 20 patients. Pa and Pv equalised after 60 s of inflation (Pa-Pv difference 0 ± 0.01 mmHg). There were no significant differences of Pmsf-arm values among determinations. For a single measurement, the CE was 5 % (±2 %) and the LSC was 14 % (±5 %). Averaging two, three and four measurements the CE improves to 4 % (±1 %), 3 % (±1 %) and 3 % (±1 %) respectively, and the LSC was reduced to 10 % (±4 %), 8 % (±3 %) and 7 % (±3 %) respectively. One measurement of Pmsf-arm can reliably detect changes on Pmsf-arm of 14 %. The precision of Pmsf-arm technique improves when averaging two or three measurements.


Self-treatment for acute coronary syndrome: why not?


David Oliver: Covid-19 has made news out of old news.


High-pressure carbon dioxide pneumoperitoneum before major liver resection in a rat model is not realistic and cannot be transposed to humans when studying liver regeneration.


An elderly couple with COVID-19 pneumonia treated in Singapore: contrasting clinical course and management.


title: Genetic and environmental influences on the developmental trajectory of callous-unemotional traits from childhood to adolescence.

text: BACKGROUND This study examined the genetic and environmental influences underlying baseline level and developmental course of callous-unemotional (CU) traits across childhood and adolescence. METHODS The data on 8,958 twin pairs (3,108 MZ twin pairs and 5,850 DZ twin pairs) from the Twins Early Development Study were analysed. CU traits were assessed at ages 7, 9, 12 and 16 by mothers and analysed using a biometric latent growth model. RESULTS Individual differences in the baseline level of CU traits were highly heritable (76.5%), while the heritability of the developmental course of CU traits was moderate (43.6%). The genetic influences on baseline level and developmental course of CU traits were mostly nonoverlapping. Nonshared environment made a modest contribution to the baseline level of CU traits (21.7%). Nonshared environmental influences on the developmental course of CU traits were moderate (43.2%), with nearly half of them being the same as those influencing the baseline level and just over half being specific. Shared environmental effects did not contribute to systematic change across childhood and adolescence but were rather age-specific. CONCLUSIONS Our findings demonstrate that rather than only being conceptualized as factors of stability, genes also play a dynamic role in explaining systematic change in CU traits. Genetic effects for the initial risk and subsequent development of CU traits are not the same. In addition to genetic factors, nonshared environmental influences play an important role in explaining why some children will increase or maintain their CU traits over time, whereas other will desist. New genetic and environmental influences with age suggest that repeated, age-tailored interventions may be required throughout development to make a lasting difference in the presentation of CU traits and associated outcomes.


title: ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 appropriate use criteria for cardiac radionuclide imaging: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Associa

text: The American College of Cardiology Foundation (ACCF), along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical scenarios where cardiac radionuclide imaging (RNI) is frequently considered. This document is a revision of the original Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging (SPECT MPI) Appropriateness Criteria, published 4 years earlier, written to reflect changes in test utilization and new clinical data, and to clarify RNI use where omissions or lack of clarity existed in the original criteria. This is in keeping with the commitment to revise and refine appropriate use criteria (AUC) on a frequent basis. The indications for this review were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Sixty-seven clinical scenarios were developed by a writing group and scored by a separate technical panel on a scale of 1 to 9 to designate appropriate use, inappropriate use, or uncertain use. In general, use of cardiac RNI for diagnosis and risk assessment in intermediate- and high-risk patients with coronary artery disease (CAD) was viewed favorably, while testing in low-risk patients, routine repeat testing, and general screening in certain clinical scenarios were viewed less favorably. Additionally, use for perioperative testing was found to be inappropriate except for high selected groups of patients. It is anticipated that these results will have a significant impact on physician decision making, test performance, and reimbursement policy, and will help guide future research.


title: Transcriptome Profiling of the Virus-Induced Innate Immune Response in Pteropus vampyrus and Its Attenuation by Nipah Virus Interferon Antagonist Functions.

text: UNLABELLED Bats are important reservoirs for several viruses, many of which cause lethal infections in humans but have reduced pathogenicity in bats. As the innate immune response is critical for controlling viruses, the nature of this response in bats and how it may differ from that in other mammals are of great interest. Using next-generation transcriptome sequencing (mRNA-seq), we profiled the transcriptional response of Pteropus vampyrus bat kidney (PVK) cells to Newcastle disease virus (NDV), an avian paramyxovirus known to elicit a strong innate immune response in mammalian cells. The Pteropus genus is a known reservoir of Nipah virus (NiV) and Hendra virus (HeV). Analysis of the 200 to 300 regulated genes showed that genes for interferon (IFN) and antiviral pathways are highly upregulated in NDV-infected PVK cells, including genes for beta IFN, RIG-I, MDA5, ISG15, and IRF1. NDV-infected cells also upregulated several genes not previously characterized to be antiviral, such as RND1, SERTAD1, CHAC1, and MORC3. In fact, we show that MORC3 is induced by both IFN and NDV infection in PVK cells but is not induced by either stimulus in human A549 cells. In contrast to NDV infection, HeV and NiV infection of PVK cells failed to induce these innate immune response genes. Likewise, an attenuated response was observed in PVK cells infected with recombinant NDVs expressing the NiV IFN antagonist proteins V and W. This study provides the first global profile of a robust virus-induced innate immune response in bats and indicates that henipavirus IFN antagonist mechanisms are likely active in bat cells. IMPORTANCE Bats are the reservoir host for many highly pathogenic human viruses, including henipaviruses, lyssaviruses, severe acute respiratory syndrome coronavirus, and filoviruses, and many other viruses have also been isolated from bats. Viral infections are reportedly asymptomatic or heavily attenuated in bat populations. Despite their ecological importance to viral maintenance, research into their immune system and mechanisms for viral control has only recently begun. Nipah virus and Hendra virus are two paramyxoviruses associated with high mortality rates in humans and whose reservoir is the Pteropus genus of bats. Greater knowledge of the innate immune response of P. vampyrus bats to viral infection may elucidate how bats serve as a reservoir for so many viruses.


title: Development, characterization, and application of monoclonal antibodies against severe acute respiratory syndrome coronavirus nucleocapsid protein.

text: Five monoclonal antibodies (MAbs) against recombinant nucleocapsid protein (NP) of severe acute respiratory syndrome (SARS)-causing coronavirus (CoV) were developed by hybridoma technology. Epitope mapping by Western blotting showed that these anti-SARS-CoV NP MAbs bind to distinct domains of NP. These anti-SARS-CoV NP MAbs, with their high specificity, are potentially ideal candidates for developing early and sensitive diagnostic assays for SARS-CoV.


title: 35th Annual Pediatric Infectious Diseases Society Awards.

text: The following is a compilation of the 2013 Pediatric Infectious Diseases Society Awards presented on Monday, May 6, 2013 during the Pediatric Academic Societies meeting in Washington, DC. Award summaries were adapted from submissions provided by the nominating physician.


title: Dexmedetomidine pharmacokinetics in the obese.

text: PURPOSE This study aims to characterize the influence of body weight and composition on the pharmacokinetics of dexmedetomidine. METHODS Twenty obese patients and 20 non-obese patients scheduled for elective laparoscopic surgery were given dexmedetomidine infusion schemes. Venous blood samples were taken during and after dexmedetomidine administration. Population pharmacokinetic modeling was undertaken to investigate fat free mass (FFM) and normal fat mass (NFM) as size descriptors of volumes and clearances using non-linear mixed effects modeling. NFM partitions total body weight into FFM and fat mass calculated from total body weight (TBW) minus FFM. The relative influence of fat mass compared to FFM is described by the fraction of fat mass that makes fat equivalent to FFM (Ffat). RESULTS Theory-based allometric scaling using FFM best described weight and body composition differences in clearances and volumes A negative effect of fat mass of with an exponential parameter of -0.00541/kg (95 % CI -0.0118 to -0.00246) was estimated for clearance which indicates increased fat mass is associated with impairment of clearance. CONCLUSIONS The use of theory-based allometry with predictions of fat free mass has been able to separate the influences of weight and body composition and indicates that size-normalized clearance of dexmedetomidine is impaired in patients who are obese.


title: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry combined with magnetic beads for detecting serum protein biomarkers in parkinson's disease.

text: BACKGROUND Biomarkers for neurodegenerative diseases are essential to facilitate disease diagnosis. Application of proteomics has greatly hastened the search for novel biomarkers. In this study, new potential biomarkers were discovered, and a diagnostic pattern was established for idiopathic Parkinson's disease (PD) by using proteomic technology. METHODS Serum proteins from PD patients and controls were captured by magnetic bead-based weak cation exchange. The molecular weight of the proteins in bead-binding fraction was detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Biomarker Wizard 3.1 and Biomarker Patterns Software were used for data analysis and constructing a model of biomarkers. A blinded testing set was used to validate the model. RESULTS A total of 17 discriminating m/z peaks related to PD were identified. The model based on the 5 biomarkers generated an excellent separation between PD and healthy controls with 98.36% for the sensitivity and 83.05% for the specificity. Blind test data demonstrated the model could recognize patients with PD with a sensitivity of 85.0% and a specificity of 70.0%. CONCLUSIONS The preliminary data suggested a potential application of MALDI-TOF-MS combined with magnetic beads. The model comprising 5 promising biomarkers can differentiate individuals with PD and the healthy subjects precisely.


title: A study of long-term stability and antimicrobial activity of chlorhexidine, polyhexamethylene biguanide, and silver nanoparticle incorporated in sericin-based wound dressing.

text: In this study, three kinds of antiseptics which were 0.05% chlorhexidine, 0.2% polyhexamethylene biguanide (PHMB), or 200 ppm silver nanoparticle was introduced to incorporate in the sericin-based scaffold to produce the antimicrobial dressing for the treatment of infected chronic wound. The effects of antiseptic incorporation on the stability, release of sericin, and short-term and long-term (6 months) antimicrobial activity of the sericin dressing against gram-negative and gram-positive bacteria were investigated. We showed that the incorporation of each antiseptic did not have significant effect on the internal morphology (pore size ~ 73-105 μm), elasticity (Young's modulus ~ 200-500 kPa), and the sericin release behavior of the sericin-based dressing. The release of sericin from the dressing was prolonged over 120 h and thereafter. Comparing among three antiseptics, 0.05% chlorhexidine incorporated in the sericin dressing showed the highest immediate and long-term (6 months) antimicrobial effect (largest inhibition zone) against most bacteria either gram-positive or gram-negative bacteria. The in vivo safety test following ISO10993 standard (Biological evaluation of medical devices - Part 6: Tests for local effects after implantation) confirmed that the sericin dressing incorporating 0.05% chlorhexidine did not irritate to tissue, comparing with the commercial material used generally in clinic (Allevyn®, Smith & Nephew). We suggested the sericin dressing incorporating 0.05% chlorhexidine for the treatment of infected chronic wound. Chlorhexidine would reduce the risk of infection while the sericin may promote wound healing.


title: Psychiatric morbidity after surgery for inflammatory bowel disease: A systematic review.

text: AIM To examine the evidence about psychiatric morbidity after inflammatory bowel disease (IBD)-related surgery. METHODS PRISMA guidelines were followed and a protocol was published at PROSPERO (CRD42016037600). Inclusion criteria were studies describing patients with inflammatory bowel disease undergoing surgery and their risk of developing psychiatric disorder. RESULTS Twelve studies (including 4340 patients) were eligible. All studies were non-randomized and most had high risk of bias. Patients operated for inflammatory bowel disease had an increased risk of developing depression, compared with surgical patients with diverticulitis or inguinal hernia, but not cancer. In addition, patients with Crohn's disease had higher risk of depression after surgery compared with non-surgical patients. Patients with ulcerative colitis had higher risk of anxiety after surgery compared with surgical colorectal cancer patients. Charlson comorbidity score more than three and female gender were independent predictors for depression and anxiety following surgery. CONCLUSION The review cannot give any clear answer to the risks of psychiatric morbidity after surgery for IBD studies with the lowest risk of bias indicated an increased risk of depression among surgical patients with Crohn's disease and increased risk of anxiety among patients with ulcerative colitis.


Novel corona virus disease (COVID-19) in pregnancy: What clinical recommendations to follow?


title: Hepatitis C virus-induced autophagy is independent of the unfolded protein response.

text: Hepatitis C virus (HCV) has been shown to induce autophagy and the unfolded protein response (UPR), but the mechanistic link between the induction of these two cellular processes remains unclear. We demonstrate here that HCV infection induces autophagy, as judged by accumulation of lipidated LC3-II, and that this induction occurs rapidly after infection, preceding the stimulation of the UPR, which occurs only at later stages, after the viral envelope glycoproteins have been expressed to high levels. Furthermore, both genotype 1b and 2a subgenomic replicons expressing nonstructural (NS3-5B) proteins and JFH-1 virus lacking the envelope glycoproteins potently induced autophagy in the absence of detectable UPR. This ability was also shared by a subgenomic replicon derived from the related GB virus B (GBV-B). We also show that small interfering RNA (siRNA)-mediated silencing of the key UPR inducer, Ire1, has no effect on HCV genome replication or the induction of autophagy, further demonstrating that the UPR is not required for these processes. Lastly, we demonstrate that the HCV replicase does not colocalize with autophagosomes, suggesting that the induction of autophagy is not required to generate the membrane platform for HCV RNA replication.


title: Hospital preparedness and management of patients affected by viral haemorrhagic fever or smallpox at the Lazzaro Spallanzani Institute, Italy.

text: The US cases of anthrax in 2001 and the recent severe acute respiratory syndrome outbreak have heightened the need for preparedness and response to naturally emerging and re-emerging infections or deliberately released biological agents. This report describes the response model of the Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (INMI), Rome, Italy for managing patients suspected of or affected by smallpox or viral haemorrhagic fever (VHF) either in the context of an intentional release or natural occurrence. The INMI is Italy's leading hospital in its preparedness and response plan to bioterrorism-related infectious agents. All single and double rooms of INMI are equipped with negative air pressure, sealed doors, high efficiency particulate air (HEPA) filters and a fully-equipped anteroom; moreover, a dedicated high isolation unit with a laboratory next door for the initial diagnostic assays is available for admission of sporadic patients requiring high isolation. For patient transportation, two fully equipped ambulances and two stretcher isolators with a negative pressure section are available. Biomolecular and traditional diagnostic assays are currently performed in the biosafety level 3/4 (BSL 3/4) laboratories. Continuing education and training of hospital staff, consistent application of infection control practices, and availability of adequate personnel protective equipment are additional resources implemented for the care of highly infectious patients and to maintain the readiness of an appropriately trained workforce to handle large scale outbreaks.


title: Fabrication of Self-healing Hydrogel from Quaternized N-[3(Dimethylamino)propyl]methacrylamide Copolymer for Antimicrobial and Drug Release Applications.

text: Self-healing hydrogels have attracted great attentions in recent years because of their wide application in bioscience and bio-technology. In this study, P(DMAPMA-stat-DAA)were synthesized by RAFT polymerization and quaternized to import antimicrobial properties. Then quaternized P(DMAPMA-stat-DAA) were used to prepare hydrogel containing acylhydrazone groups with PEO diacylhydrazide as cross-linking agent. The acylhydrazone groups imparted a variety of properties including group responsiveness, and self-healing properties to the hydrogel. At the same time, the quaternary ammonium endowed the hydrogel with antimicrobial property. The mechanical property, self-healing properties and antimicrobial property of hydrogels were investigated intensively. Results showed hydrogels formed in neutral conditions and luminescent property was introduced with PEO23 DNH cross-linking. The hydrogels showed controlled pH sensitive DOX·HC l and Ovalbumin (OVA) release profile. Also, the hydrogel showed antimicrobial property and may have important applications in the biomedical field in the near future. This article is protected by copyright. All rights reserved.


title: Safety of Single-Site Laparoscopic Surgery Requiring Perioperative Heparinization in Colorectal Cancer: Propensity Score-Matched Analysis.

text: BACKGROUND We assessed the feasibility and safety of single-site laparoscopic surgery for patients with colorectal cancer who required perioperative heparinization. METHODS This retrospective study reviewed the medical records of 390 patients who underwent single-site laparoscopic surgery for colorectal cancer from January 2010 to December 2016. Antithrombotic drugs were stopped preoperatively and heparin was administered according to the operative risk of each patient, based on consultation with the cardiologist physician or neurosurgeon. Propensity score modeling was utilized to adjust for baseline characteristics. RESULTS Of 390 patients, 29 were treated with standard bridging intravenous heparin therapy. Propensity matching identified 119 patients: 22 patients in the heparinization group and 97 in the control group. The matched groups were not significantly different in operation times, bleeding volumes, or conversion rate. The mean postoperative hospital stay was 17.9 days in the heparinization group and 9.5 days in the control group (p = 0.034). Postoperative bleeding was observed in 4 patients (18.2%) in the heparinization group and 11 patients (11.4%) in the control group (p = 0.646), while other complications were similar in the two study groups (p = 0.502). Of these other complications, thromboembolic events were observed in two patients in the heparinization group and one patient in the control group. CONCLUSIONS We found that single-site laparoscopic surgery for colorectal cancer with heparinization was feasible and safe. Heparinization did not increase the risk of postoperative bleeding complications, but postoperative hospital stay was prolonged.


title: Large-Scale Label-Free Quantitative Mapping of the Sputum Proteome.

text: Analysis of induced sputum supernatant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSE applied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The "core" sputum proteome (proteins detected in ≥40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in ≥3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSE is influenced by several factors, with some proteins being measured in all participants' samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.


title: Current status of percutaneous endoscopic gastrostomy (PEG) in a general hospital in Japan: a cross-sectional study.

text: BACKGROUND There has been debate over the indications for percutaneous endoscopic gastrostomy (PEG) in recent years in Japan. In addition, the level of satisfaction of patients and patient's family after PEG remains unclear. The aim of this study was to investigate the current status of PEG and the level of satisfaction of patients and patients' families after PEG in Japan. METHODS We reviewed the existing data of all patients who underwent PEG tube insertion at Yuri Kumiai General Hospital (Akita, Japan) between February 2000 and December 2010. We examined the following points: underlying diseases requiring PEG, levels of consciousness, and performance status. We also sent a questionnaire to the patients and patient's families to ask about their satisfaction with and thoughts about PEG. RESULTS The data of 545 patients who underwent PEG were reviewed. There were 295 men and 250 women, with a mean age of 77.2 ± 11.4 years. PEG was indicated most frequently for cerebrovascular disorders (48.2%, 239/545). There were 515 (94.4%, 515/545) patients showing consciousness disturbance and 444 (81.5%, 444/545) bedridden patients. The questionnaire was answered by one patient himself and 316 patients' families. When asked, "Was performing PEG a good decision?", 57.5% (182/316) of the patients' families answered yes. Meanwhile, when patients' family members were asked if they would wish to undergo PEG if they were in the same condition as the patient, 28.4% (90/316) answered yes, whereas 55.3% (175/316) answered no. CONCLUSIONS Few patients were able to make their own decision about PEG tube placement because of consciousness disturbance. As a result, many family members of the patients did not want to experience PEG for themselves. Future studies should be performed to clarify the quality of life and ethical aspects associated with PEG.


title: Occlusion Location of Middle Cerebral Artery Stroke and Outcome after Endovascular Treatment.

text: BACKGROUND The aim of this study was to analyze the influence of the location of middle cerebral artery (MCA) occlusion on recanalization, complications and outcome after endovascular therapy. METHODS Four-hundred sixty-four patients with acute MCA occlusions were treated with endovascular therapy. RESULTS Two-hundred ninety-three patients had M1 occlusions, 116 had M2, and 55 had M3/4 occlusions. Partial or complete recanalization was more frequently achieved in M1 (76.8%) than in M2 (59.1%) or M3/4 (47.3%, p < 0.001) occlusions, but favorable outcome (modified Rankin Scale 0-2) was less frequent in M1 (50.9%) than M2 (63.7%) or M3/4 (72.7%, p = 0.018) occlusions. Symptomatic intracerebral hemorrhage (ICH) did not differ between occlusion sites, but asymptomatic ICH was more common in M1 (22.6%) than in M2 occlusions (8.6%, p = 0.003). Recanalization was associated with favorable outcome in M1 (p < 0.001) and proximal M2 (p = 0.003) but not in distal M2 or M3/4 occlusions. CONCLUSIONS Recanalization with endovascular therapy was more frequently achieved in patients with proximal than distal MCA occlusions, but recanalization was associated with favorable outcome only in M1 and proximal M2 occlusions. Outcome was better with distal than proximal occlusions. This study shows that recanalization can be used as a surrogate marker for clinical outcome only in patients with proximal occlusions.


title: Laparoscopic sleeve gastrectomy for a large gastrointestinal stromal tumor.

text: The biological behavior of gastrointestinal stromal tumor (GIST) makes resection of the tumor with adequate margins, a mode of curative treatment. GIST does not have lymphatic permeation. Hence, the goal of therapy is complete resection of visible and microscopic disease, which can be achieved by adequate tumor-free margins. Laparoscopic management of large GIST tumors is discouraged because of the fear of spillage of the tumor or rupture of the tumor capsule while handling a large tumor and thus causing metastasis.


Covid-19: Nine in 10 pregnant women with infection when admitted for delivery are asymptomatic, small study finds.


title: Automatic aortic anastomosis with an innovative computer-controlled circular stapler for surgical treatment of aortic aneurysm.

text: OBJECTIVE This study applied a computer-controlled mechanical stapler to vascular end-to-end anastomosis to achieve an automatic aortic anastomosis between the aorta and an artificial graft. In this experimental study, we created a mechanical end-to-end anastomotic model and assessed the strength of the anastomotic site under high pressure. METHODS We used a computer-controlled circular stapler named iDrive (Power Medical Interventions, Covidien plc, Dublin, Ireland) for the anastomosis between the porcine aorta and an artificial graft. Then the mechanically stapled group (group A) and the manually sutured group (group B) were compared 10 times, and we assessed the differences at several levels of pressure. RESULTS To use a mechanical stapler in vascular anastomosis, some special preparations of both the aorta and the artificial graft are necessary to narrow the open end before the procedures. To solve this problem, we established a specially designed purse-string suture for both and finally established end-to-end vascular anastomosis. The anastomosis speed of group A was statistically significantly faster than that of group B (P < .01). The group A anastomotic sites also showed significantly more tolerance to high pressure than those of group B. CONCLUSIONS The computer-controlled stapling device enabled reliable anastomosis of the aorta and the artificial graft. This study showed that mechanical vascular anastomosis with the iDrive was sufficiently strong and safe relative to manual suturing.


title: Minor stroke due to large artery occlusion. When is intravenous thrombolysis not enough? Results from the SITS International Stroke Thrombolysis Register.

text: Purpose Beyond intravenous thrombolysis, evidence is lacking on acute treatment of minor stroke caused by large artery occlusion. To identify candidates for additional endovascular therapy, we aimed to determine the frequency of non-haemorrhagic early neurological deterioration in patients with intravenous thrombolysis-treated minor stroke caused by occlusion of large proximal and distal cerebral arteries. Secondary aims were to establish risk factors for non-haemorrhagic early neurological deterioration and report three-month outcomes in patients with and without non-haemorrhagic early neurological deterioration. Method We analysed data from the SITS International Stroke Thrombolysis Register on 2553 patients with intravenous thrombolysis-treated minor stroke (NIH Stroke Scale scores 0-5) and available arterial occlusion data. Non-haemorrhagic early neurological deterioration was defined as an increase in NIH Stroke Scale score ≥4 at 24 h, without parenchymal hematoma on follow-up imaging within 22-36 h. Findings The highest frequency of non-haemorrhagic early neurological deterioration was seen in 30% of patients with terminal internal carotid artery or tandem occlusions (internal carotid artery + middle cerebral artery) (adjusted odds ratio: 10.3 (95% CI 4.3-24.9), p < 0.001) and 17% in extracranial carotid occlusions (adjusted odds ratio 4.3 (2.5-7.7), p < 0.001) versus 3.1% in those with no occlusion. Proximal middle cerebral artery-M1 occlusions had non-haemorrhagic early neurological deterioration in 9% (adjusted odds ratio 2.1 (0.97-4.4), p = 0.06). Among patients with any occlusion and non-haemorrhagic early neurological deterioration, 77% were dead or dependent at three months. Conclusions Patients with minor stroke caused by internal carotid artery occlusion, with or without tandem middle cerebral artery involvement, are at high risk of disabling deterioration, despite intravenous thrombolysis treatment. Acute vessel imaging contributes usefully even in minor stroke to identify and consider endovascular treatment, or intensive monitoring at a comprehensive stroke centre, for patients at high risk of neurological deterioration.


title: Comparison of liver parenchymal ablation and tissue necrosis in a cadaveric bovine model using the Harmonic Scalpel, the LigaSure, the Cavitron Ultrasonic Surgical Aspirator and the Aquamantys devices.

text: OBJECTIVES The amount of tissue that is ablated or necrosed at the line of parenchymal transection is of clinical significance in the interpretation of resection margin status following hepatic resection. The aim of this study was to define the extent of parenchymal ablation and necrosis in liver tissue using the Harmonic Scalpel, the LigaSure, the Cavitron Ultrasonic Surgical Aspirator (CUSA) and the Aquamantys dissector ex vivo. METHODS Mounted blocks of non-perfused bovine liver were transected using the Harmonic Scalpel, LigaSure, CUSA and Aquamantys devices. Outcome measures included parenchymal ablation (ablation band widths and weights) and tissue necrosis band widths along the line of transection. Each experiment was replicated five times. RESULTS All devices were associated with parenchymal ablation (Harmonic Scalpel, 4.73 ± 1.62 mm; LigaSure, 4.55 ± 2.02 mm; CUSA, 7.16 ± 2.87 mm; Aquamantys, 4.75 ± 1.43 mm) and tissue necrosis (Harmonic Scalpel, 1.07 ± 0.46 mm; LigaSure, 1.36 ± 0.36 mm; CUSA, 0.81 ± 0.21 mm; Aquamantys, 0.81 ± 0.36 mm). CONCLUSIONS The Harmonic Scalpel, LigaSure, CUSA and Aquamantys devices were associated with bands of tissue loss along the hepatic parenchymal transection line in this benchtop cadaveric model. This should be taken into account in the interpretation of resection margin status following liver resection.


title: Short term depression, presynaptic inhibition and local neuron diversity play key functional roles in the insect antennal lobe.

text: As the oldest, but least understood sensory system in evolution, the olfactory system represents one of the most challenging research targets in sensory neurobiology. Although a large number of computational models of the olfactory system have been proposed, they do not account for the diversity in physiology, connectivity of local neurons, and several recent discoveries in the insect antennal lobe, a major olfactory organ in insects. Recent studies revealed that the response of some projection neurons were reduced by application of a GABA antagonist, and that insects are sensitive to odor pulse frequency. To account for these observations, we propose a spiking neural circuit model of the insect antennal lobe. Based on recent anatomical and physiological studies, we included three sub-types of local neurons as well as synaptic short-term depression (STD) in the model and showed that the interaction between STD and local neurons resulted in frequency-sensitive responses. We further discovered that the unexpected response of the projection neurons to the GABA antagonist is the result of complex interactions between STD and presynaptic inhibition, which is required for enhancing sensitivity to odor stimuli. Finally, we found that odor discrimination is improved if the innervation of the local neurons in the glomeruli follows a specific pattern. Our findings suggest that STD, presynaptic inhibition and diverse physiology and connectivity of local neurons are not independent properties, but they interact to play key roles in the function of antennal lobes.


Covid-19: Deaths in the community approach 20 000 in the UK.


title: Parenteral vaccination of mammalian livestock with Newcastle disease virus-based vector vaccines offers optimal efficacy and safety.

text: Newcastle disease virus (NDV) is an avian virus that is being evaluated as a vaccine vector for the delivery of foreign genes in mammals. The use of NDV as a vaccine vector in these species offers two major advantages. First, NDV is highly attenuated in mammals, rendering its use inherently safe. Second, mammals lack pre-existing NDV immunity, which minimizes the risk of vaccination failure. NDV-vector vaccines are generally administered to mammals via the respiratory route. We recently showed that intramuscular vaccination with NDV-based Rift Valley fever virus (RVFV) vaccines provides complete protection in mice and induces neutralizing antibodies in sheep and cattle, the main target species of RVFV. Here, we discuss the use of NDV as a vaccine vector for applications in mammalian livestock with an emphasis on the vaccination route. We also report the results of novel experiments that underscore our notion that vaccination via a parenteral route is more effective than immunization via the respiratory route.


title: Prevalence and genomic characteristics of a novel reassortment mammalian orthoreovirus type 2 in diarrhea piglets in Sichuan, China.

text: Mammalian orthoreovirus (MRV), which can infect almost all mammals, is a zoonotic virus. In this study, six strains of type 2 MRV (MRV2) were isolated from 7 diarrhea piglets from a farm that had an outbreak of diarrhea in piglets in 2018, which tested negative for porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and porcine group A rotavirus (RAV). The MRV2 isolate infected neonatal piglets, in which it induced severe diarrhea, while the virus was detected in multiple organs of piglets. Moreover, the complete genome of an MRV2 isolate was obtained, which was a novel reassortant MRV strain of human MRV, porcine MRV, chamois MRV, bat MRV, and mink MRV based on the nucleotide identity and phylogenetic tree. The S1 gene of isolate had eight unique amino acid mutations compared with available MRV2 S1 in the GenBank. To investigate the prevalence of this MRV2, 78 samples of diarrhea feces were collected from 10 pig farms in seven regions of Sichuan province. The obtained results showed that the positive rate of samples was 14% (11/78), and positive rate of farms was 60% (6/10), while the amplified fragments shared the identical amino acid mutations with the isolated strain, thus suggesting that this MRV2 strain was already prevalent in Sichuan province. The present study was first to isolate a pig-derived type 2 MRV strain in China, obtaining the complete genome of this strain, which furthers our understanding of the MRV2 epidemic and evolution.


title: Endovascular thrombectomy in the setting of aortic dissection.

text: BACKGROUND Recent studies have validated the use of endovascular thrombectomy in large vessel ischemic stroke provided patients are selected appropriately. However, to our knowledge, there have been no previously reported cases of endovascular thrombectomy in patients with aortic dissection. We report three such cases, two with chronic aortic dissections (including one with a history of Marfan syndrome) and another with an acute type B dissection. METHODS Case studies and review of relevant literature. RESULTS Three patients with a history of aortic dissection presented with acute onset right middle cerebral artery syndromes, two of whom had chronic aortic dissections that were status-post graft repair, while a third had an acute type B aortic dissection that had been managed with a femoral-to-femoral bypass. None of the three were candidates for intravenous tissue plasminogen activator. All three were found to have proximal right M1 occlusions on non-invasive imaging and were taken for endovascular thrombectomy via transfemoral, transradial, and transbrachial approaches, respectively. All three had successful recanalization (with Thrombolysis In Cerebral Infarction (TICI) 2b, TICI 3, and TICI 2b flow, respectively) along with clinical improvement, and none had procedure-related complications. CONCLUSIONS These three cases suggest that endovascular thrombectomy is feasible and can be done safely and efficaciously in patients with aortic dissections and those with Marfan syndrome, although the risks and benefits should be considered as part of any decision-making process. Given that endovascular therapy for acute stroke is now in many situations part of standard care, further studies will be necessary to delineate more precise inclusion and exclusion criteria.


title: Sleep spindle activity and cognitive performance in healthy children.

text: STUDY OBJECTIVES To investigate the association between indices of sleep spindle activity and cognitive performance in a sample of healthy children. DESIGN Correlational. Intelligence (Stanford-Binet) and neurocognitive functioning (NEPSY) were assessed, with sleep variables being measured during overnight polysomnography. SETTING Hospital sleep laboratory. PARTICIPANTS Twenty-seven healthy children (mean age 8.19 y; 14 female, 13 male). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Participants underwent a single night of overnight polysomnography after completing measures of intelligence and neurocognitive functioning. Sleep spindles were visually identified by an experienced sleep scoring technician and separated algorithmically into fast (> 13 Hz) and slow spindle (< 13 Hz) categories. The number of fast spindles was significantly correlated with narrative memory (r(s) = 0.38) and sensorimotor functioning (-0.43). Mean central frequency of spindles was also significantly correlated with sensorimotor functioning (-0.41), planning ability (-0.41), and working memory (-0.54). CONCLUSIONS Basal sleep spindle activity is associated with different aspects of cognitive performance in children. To the extent that these associations in a pediatric population are different from what is known in adult sleep may play an important role in development.


title: Randomized clinical trial of fibrin glue versus tacked fixation in laparoscopic groin hernia repair.

text: BACKGROUND Preliminary studies have indicated clinical advantages of mesh fixation using fibrin glue in transabdominal preperitoneal groin hernia repair (TAPP) compared with tack fixation. The aim of this randomized double-blinded, controlled, clinical trial is to compare fibrin glue with tacks fixation of mesh during TAPP. METHODS One hundred and twelve men with unilateral inguinal hernia were enrolled. Primary outcome was pain during coughing on postoperative day 1. Secondary outcomes were postoperative scores of pain at rest, discomfort, and fatigue (day 1 and cumulated day 0-3), incidence of moderate/severe nausea and/or vomiting, foreign-body sensation, and recurrence after 6 months. Outcome measures were assessed by visual analogue scale (VAS, 0-100 mm), verbal rating scale (no, light, moderate or severe) and numerical rating scales (NRS, 1-10). RESULTS One hundred patients were available for analysis. The fibrin group (n = 50) had significantly less pain during coughing on day 1 compared with the tacks group (n = 50) [median 23 (range 0-80) vs 35 (2-100) mm] (p = 0.020). Moreover, day 1 scores and all cumulated scores of pain during rest, discomfort, and fatigue were significantly lower in the fibrin group compared with the tacks group (all p-values ≤ 0.02). There was no significant difference in the incidence of nausea and/or vomiting (p > 0.05) or recurrence (fibrin glue n = 2, tacks n = 0, p = 0.241). Incidence of foreign-body sensation was significantly lower in the fibrin group at 1 month (p = 0.006). CONCLUSIONS Fibrin glue compared with tacks fixation improved the early postoperative outcome after TAPP. The trial was registered at clinicaltrials.gov NCT01000116.


title: Acute respiratory distress syndrome and pneumothorax.

text: Acute respiratory distress syndrome (ARDS) can occur during the treatment of several diseases and in several interventional procedures as a complication. It is a difficult situation to handle and special care should be applied to the patients. Mechanical ventilation is used for these patients and several parameters are changed constantly until compliance is achieved. However, a complication that is observed during the application of positive airway pressure is pneumothorax. In our current work we will present definition and causes of pneumothorax in the setting of intensive care unit (ICU). We will identify differences and similarities of this situation and present treatment options.


title: Duodenal stump fistula after gastrectomy for gastric cancer: risk factors, prevention, and management.

text: PURPOSE A duodenal stump fistula is one of the most severe complications after gastrectomy for gastric cancer. We aimed to analyze the risk factors for this problem, and to identify the methods used for its prevention and management. METHODS We retrospectively reviewed the clinical data of 716 consecutive patients who underwent curative gastrectomy with a duodenal stump for gastric cancer between 2008 and 2013. RESULTS A duodenal stump fistula occurred in 16 patients (2.2%) and there were 2 deaths in this group. Univariate analysis revealed age >60 years (odds ratio [OR], 3.09; 95% confidence interval [CI], 0.99-9.66), multiple comorbidities (OR, 4.23; 95% CI, 1.50-11.92), clinical T stage (OR, 2.91; 95% CI, 1.045-8.10), and gastric outlet obstruction (OR, 8.64; 95% CI, 2.61-28.61) to be significant factors for developing a duodenal stump fistula. Multivariate analysis identified multiple comorbidities (OR, 3.92; 95% CI, 1.30-11.80) and gastric outlet obstruction (OR, 5.62; 95% CI, 1.45-21.71) as predictors of this complication. CONCLUSION Multiple comorbidities and gastric outlet obstruction were the main risk factors for a duodenal stump fistula. Therefore, preventive methods and aggressive management should be applied for patients at high risk.


title: Acute and critical limb ischemia: when time is limb.

text: Acute and critical limb ischemia post significant rates of morbidity and death, and need to be promptly recognized and treated to avoid amputation. Perfusion should be thoroughly assessed using multiple methods, and patients should be considered for revascularization (angioplasty or bypass surgery) to restore blood perfusion. Underlying conditions that need to be assessed and treated include cardiovascular disease, diabetes, and infection.


title: Triterpenoid gene expression and phytochemical content in Iranian licorice under salinity stress.

text: Licorice is a well-known medicinal plant, containing various secondary metabolites of triterpenoid and phenolic families. The aim of this study is to evaluate the effect of salinity stress on the expression of key genes involved in the biosynthetic pathway of triterpenoids such as glycyrrhizin, betulinic acid, soyasaponins, and phytosterols in licorice root, as well as providing a phonemic platform to characterize antioxidant properties, glycyrrhizin, and total phenolic content. This study also includes measuring the gene expression level and glycyrrhizin content in leaves and roots of control plants. The studied genes included squalene synthase (SQS1 and SQS2), β-amyrin synthase (bAS), lupeol synthase (LUS), cycloartenol synthase (CAS), β-amyrin 11-oxidase (CYP88D6), and β-amyrin 24-hydroxylase (CYP93E6). Our results revealed that all of the mentioned genes were upregulated following the stress condition with different transcription rates. The highest increase (12-fold) was observed for the expression of the LUS gene, which is related to the betulinic acid pathway. Also, the highest content of glycyrrhizin was observed at 72 h post-treatment, which was consistent with the upregulated transcription levels of the glycyrrhizin pathway genes especially SQS1 and CYP88D6 at the same time. Correlation and stepwise regression analysis proved the key role of SQS1 gene in the biosynthetic pathway of glycyrrhizin. Antioxidant activity and phenolic content also were increased following stress condition. A comparison between the expression levels of SQS1 and other genes involved in the production of glycyrrhizin, phytosterols, and soyasaponins revealed a similar transcription trend, which shows the gene expression in the roots was significantly higher than the leaves. In contrast, SQS2 and LUS genes displayed a higher expression in leaf tissues. The genes related to betulinic acid biosynthetic pathway exhibited an expression rate different from other triterpenoid pathway genes, which could be observed in the leaves and roots of control plants and the roots of salt-treated plants. Furthermore, results showed that these two SQS genes have different expression rates due to different plant tissues (roots and leaves) and stress conditions. Importantly, in contrast to previous reports, we detected the glycyrrhizin in leaf tissues. This result may indicate the presence of a different genetic background in native Iranian licorice germplasm.


title: Transient expression systems for plant-derived biopharmaceuticals.

text: In the molecular farming area, transient expression approaches for pharmaceutical proteins production, mainly recombinant monoclonal antibodies and vaccines, were developed almost two decades ago and, to date, these systems basically depend on Agrobacterium-mediated delivery and virus expression machinery. We survey here the current state-of-the-art of this research field. Several vectors have been designed on the basis of DNA- and RNA-based plant virus genomes and viral vectors are used both as single- and multicomponent expression systems in different combinations depending on the protein of interest. The obvious advantages of these systems are ease of manipulation, speed, low cost and high yield of proteins. In addition, Agrobacterium-mediated expression also allows the production in plants of complex proteins assembled from subunits. Currently, the transient expression methods are preferential over any other transgenic system for the exploitation of large and unrestricted numbers of plants in a contained environment. By designing optimal constructs and related means of delivery into plant cells, the overall technology plan considers scenarios that envisage high yield of bioproducts and ease in monitoring the whole spectrum of upstream production, before entering good manufacturing practice facilities. In this way, plant-derived bioproducts show promise of high competitiveness towards classical eukaryotic cell factory systems.


title: Magnetic Resonance Mediated Radiofrequency Ablation.

text: To introduce magnetic resonance mediated radiofrequency ablation (MR-RFA), in which the MRI scanner uniquely serves both diagnostic and therapeutic roles. In MR-RFA scanner-induced RF heating is channeled to the ablation site via a Larmor frequency RF pickup device and needle system, and controlled via the pulse sequence. MR-RFA was evaluated with simulation of electric and magnetic fields to predict the increase in local specific-absorption-rate (SAR). Temperature-time profiles were measured for different configurations of the device in agar phantoms and ex vivo bovine liver in a 1.5 T scanner. Temperature rise in MR-RFA was imaged using the proton resonance frequency method validated with fiber-optic thermometry. MR-RFA was performed on the livers of two healthy live pigs. Simulations indicated a near tenfold increase in SAR at the RFA needle tip. Temperature-time profiles depended significantly on the physical parameters of the device although both configurations tested yielded temperature increases sufficient for ablation. Resected livers from live ablations exhibited clear thermal lesions. MR-RFA holds potential for integrating RF ablation tumor therapy with MRI scanning. MR-RFA may add value to MRI with the addition of a potentially disposable ablation device, while retaining MRI's ability to provide real time procedure guidance and measurement of tissue temperature, perfusion, and coagulation.


title: Tract length predicts successful closure with anal fistula plug in cryptoglandular fistulas.

text: PURPOSE Collagen anal fistula plug treatment of transsphincteric fistulas produces variable results. The purpose of our study was to determine whether long-tract fistulas (>4 cm) correlated with successful closure. METHODS All patients undergoing transsphincteric cryptoglandular fistula repair with anal fistula plugs were enrolled in a prospective database. Patients with Crohn's disease were excluded. Fistula tract length was measured intraoperatively by subtracting the remaining plug length from the original plug size. All procedures used standardized techniques and postoperative care pathways. The primary outcome was complete fistula closure assessed through both postoperative outpatient visits and a follow-up telephone questionnaire. RESULTS Forty-one patients with 42 fistula tracks were enrolled over a 39-month period. Complete closure was achieved in 18 of 42 (43%) fistulas at a mean follow-up of 25 months. Closure was not associated with gender, age, tract location, duration of seton, or length of follow-up. Successful closure was significantly associated with increased tract length, because fistulas longer than 4 cm were nearly 3 times more likely to heal compared with shorter fistulas ((14/23, 61%) vs (4/19, 21%), P = .004; relative risk = 2.8; 95% CI 1.14-7.03). CONCLUSIONS Anal fistula plug repair of cryptoglandular anorectal fistulas is more successful for long-tract fistulas. Although the overall success is modest, limiting surgical indications to fistulas exceeding 4 cm may maximize benefits of the plug technique.


title: Triamcinolone acetonide activates an anti-inflammatory and folate receptor-positive macrophage that prevents osteophytosis in vivo.

text: INTRODUCTION Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently reduce osteophytosis. Although widely applied in clinical care, the mechanism through which TA exerts this effect remains unknown. In this animal study, we investigated the in vivo effects of TA injections on macrophage activation, osteophyte development and joint degeneration. Furthermore, in vitro macrophage differentiation experiments were conducted to further explain working mechanisms of TA effects found in vivo. METHODS Osteoarthritis was induced in rat knees using papain injections and a running protocol. Untreated and TA-treated animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes. Synovial macrophage activation was measured in vivo using folate receptor β (FRβ)-targeted single-photon emission computed tomography/computed tomography. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology. To further explain the outcomes of our in vivo study, TA on macrophages was also studied in vitro. These cultured macrophages were either M1- or M2-activated, and they were analyzed using fluorescence-activated cell sorting for CD163 and FRβ expression as well as for messenger RNA (mRNA) expression of interleukin (IL)-10. RESULTS Our in vivo study showed that intra-articular injections with TA strongly enhanced FRβ(+) macrophage activation. Despite stimulated macrophage activation, osteophyte formation was fully prevented. There was no beneficial effect of TA against cartilage degradation or subchondral bone sclerosis. In vitro macrophage cultures showed that TA strongly induced monocyte differentiation towards CD163(+) and FRβ(+) macrophages. Furthermore, TA-stimulated M2 macrophages showed enhanced IL-10 expression at the mRNA level. CONCLUSIONS TA injections potently induce a CD163(+)- and FRβ(+)-activated macrophage with anti-inflammatory characteristics such as reduced IL-10 production in vitro and lack of osteophytosis in vivo.


title: The diagnosis and prevalence of persistent infection with bovine viral diarrhoea virus in South African feedlot cattle.

text: Bovine viral diarrhoea virus (BVDV) infection is an important viral infection affecting the cattle industry today. The prevalence of this infection in South African feedlots is unknown. Ear notch biopsies were collected from chronic poor doers and animals that appeared unthrifty upon entering feedlots, as well as animals entering the hospital pen with respiratory disease for the first time. A total of 1690 samples were collected: 1074 from the former category and 616 from the latter. A routine immunohistochemistry staining protocol showed that 49 animals tested positive, of which 43 (4%) came from the feedlot entry group and six (1%) from the hospitalised group. The prevalence of persistently infected cattle from this selected, nonrandom sample entering six large South African feedlots was found to be 2.9%, which is higher than the international rule of thumb that 0.5% of all cattle entering feedlots are persistently infected. There was no clear correlation between persistent infection and respiratory disease. Serum samples were also collected when possible and 10 positive cases were found. Results from enzyme-linked immunosorbent assays for antigen and antibody performed on these sera correlated well with those from the immunohistochemistry staining method in six cases, but in four cases the animals tested falsely positive owing to nonspecific staining. Immunohistochemistry staining on ear notch biopsies is thus a reliable diagnostic method to identify persistently infected animals with BVDV, but the pathologist should be aware of nonspecific positive staining.


title: The Metastatic Spine Disease Multidisciplinary Working Group Algorithms.

text: The Metastatic Spine Disease Multidisciplinary Working Group consists of medical and radiation oncologists, surgeons, and interventional radiologists from multiple comprehensive cancer centers who have developed evidence- and expert opinion-based algorithms for managing metastatic spine disease. The purpose of these algorithms is to facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding the use of available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation. This consensus document details the evidence supporting the Working Group algorithms and includes illustrative cases to demonstrate how the algorithms may be applied.