title: Cidofovir gel as treatment of follicular spicules in multiple myeloma.

text: IMPORTANCE The cause of follicular spicules in multiple myeloma (MM) is not known. OBSERVATIONS We present a case of follicular spicules in a patient with MM, which is very reminiscent of trichodysplasia spinulosa caused by a polyomavirus. No trichodysplasia spinulosa-associated polyomavirus could be isolated from the skin lesions; however, the spicules were positive for Merkel cell carcinoma virus, which is also a polyomavirus. CONCLUSIONS AND RELEVANCE Follicular spicules in MM are probably not caused by the trichodysplasia spinulosa-associated virus. Merkel cell polyomavirus could contribute to the origin of this dermatosis.


title: Thirty-day readmission and reoperation after surgery for spinal tumors: a National Surgical Quality Improvement Program analysis.

text: OBJECTIVE The goal of this study was to use a large national registry to evaluate the 30-day cumulative incidence and predictors of adverse events, readmissions, and reoperations after surgery for primary and secondary spinal tumors. METHODS Data from adult patients who underwent surgery for spinal tumors (2011-2014) were extracted from the prospective National Surgical Quality Improvement Program (NSQIP) registry. Multivariable logistic regression was used to evaluate predictors of reoperation, readmission, and major complications (death, neurological, cardiopulmonary, venous thromboembolism [VTE], surgical site infection [SSI], and sepsis). Variables screened included patient age, sex, tumor location, American Society of Anesthesiologists (ASA) physical classification, preoperative functional status, comorbidities, preoperative laboratory values, case urgency, and operative time. Additional variables that were evaluated when analyzing readmission included complications during the surgical hospitalization, hospital length of stay (LOS), and discharge disposition. RESULTS Among the 2207 patients evaluated, 51.4% had extradural tumors, 36.4% had intradural extramedullary tumors, and 12.3% had intramedullary tumors. By spinal level, 20.7% were cervical lesions, 47.4% were thoracic lesions, 29.1% were lumbar lesions, and 2.8% were sacral lesions. Readmission occurred in 10.2% of patients at a median of 18 days (interquartile range [IQR] 12-23 days); the most common reasons for readmission were SSIs (23.7%), systemic infections (17.8%), VTE (12.7%), and CNS complications (11.9%). Predictors of readmission were comorbidities (dyspnea, hypertension, and anemia), disseminated cancer, preoperative steroid use, and an extended hospitalization. Reoperation occurred in 5.3% of patients at a median of 13 days (IQR 8-20 days) postoperatively and was associated with preoperative steroid use and ASA Class 4-5 designation. Major complications occurred in 14.4% of patients: the most common complications and their median time to occurrence were VTE (4.5%) at 9 days (IQR 4-19 days) postoperatively, SSIs (3.6%) at 18 days (IQR 14-25 days), and sepsis (2.9%) at 13 days (IQR 7-21 days). Predictors of major complications included dependent functional status, emergency case status, male sex, comorbidities (dyspnea, bleeding disorders, preoperative systemic inflammatory response syndrome, preoperative leukocytosis), and ASA Class 3-5 designation (p < 0.05). The median hospital LOS was 5 days (IQR 3-9 days), the 30-day mortality rate was 3.3%, and the median time to death was 20 days (IQR 12.5-26 days). CONCLUSIONS In this NSQIP analysis, 10.2% of patients undergoing surgery for spinal tumors were readmitted within 30 days, 5.3% underwent a reoperation, and 14.4% experienced a major complication. The most common complications were SSIs, systemic infections, and VTE, which often occurred late (after discharge from the surgical hospitalization). Patients were primarily readmitted for new complications that developed following discharge rather than exacerbation of complications from the surgical hospital stay. The strongest predictors of adverse events were comorbidities, preoperative steroid use, and higher ASA classification. These models can be used by surgeons to risk-stratify patients preoperatively and identify those who may benefit from increased surveillance following hospital discharge.


title: Reinforced staplers for distal pancreatectomy.

text: PURPOSE The safety and efficacy of reinforced staplers during distal pancreatectomy (DP) remain controversial because of the small sample size. This multicenter single-arm prospective study aims to evaluate the safety and efficacy of reinforced staplers with bioabsorbable material during DP. METHODS Between October 2014 and August 2015, 121 patients scheduled for DP were enrolled in this study at 11 institutions in Japan. The primary endpoint was the incidence of clinically relevant pancreatic fistula. Protocol treatment was defined as "distal pancreatectomy using reinforced staplers." RESULTS Per-protocol analysis of 105 patients was performed; 16 of the patients were excluded based on discontinuation of protocol treatment criteria. Clinically relevant pancreatic fistula occurred in 13 (12.4%) of 105 patients. The overall morbidity rate was 29.5% (31 of 105 patients) and severe complication (Clavien classification IIIa or more) was 10.5% (11/105). Mortality rate was 0%, although reoperations were performed on two patients (1.9%). Multivariate logistic regression analysis of independent risk factors for clinically relevant pancreatic fistula after DP using reinforced stapler closure was operative time more than 240 min (P = 0.047, odds ratio 5.79), registration numbers less than 10 (P = 0.046, odds ratio 13.01), and staple line hemorrhage (P = 0.003, odds ratio 16.34). CONCLUSION This study confirms the safety of reinforced staplers for pancreatic stump closure during DP. However, the efficacy of reinforced staplers for decreasing clinically relevant pancreatic fistula could not be drawn from this study. TRIAL REGISTRATION This prospective study was registered with ClinicalTrials.gov (NCT02270554) and UMIN Clinical Trial Registry (UMIN000015384).


title: Blood perfusion in Hewes tarsoconjunctival flaps in pigs measured by laser speckle contrast imaging.

text: Background Hewes flap is a tarsoconjunctival eyelid flap, based at the lateral canthal tendon, and rotated and stretched to repair lateral defects in the lower eyelid commonly following tumor surgery. The aim of the present study was to monitor perfusion in a Hewes flap during reconstruction, which to the best of our knowledge, has not previously been done. Methods A Hewes tarsoconjunctival eyelid flap was raised and the effects on blood perfusion of rotating the flaps by 90° and 180°, stretching the flaps with a force of 5 or 10 N, and repeated diathermic coagulation was monitored with laser speckle contrast imaging. Results Rotating the flaps by 90° did not significantly affect perfusion, while further rotation to 180° reduced blood perfusion to 75% of the baseline value. When the tarsoconjunctival flaps were both rotated 90° and stretched with 5 N, the perfusion was reduced even further, to 63%. A further reduction in perfusion, to 36%, was seen when the higher force of 10 N was applied. Diathermy decreased blood perfusion to 56% after being applied once. Successive applications led to further decreases: 43%, 31%, and 15%, after the second, third and fourth applications. Conclusions Perfusion in Hewes tarsoconjunctival flaps is affected by both rotation and stretching, but some perfusion is maintained despite these manipulations. Diathermy, however, has detrimental effects and should be avoided.


title: Toileting Behaviors Related to Urination in Women: A Scoping Review.

text: This scoping review explores the state of science regarding women's toileting behaviors, gaps in knowledge, and areas for future research. Online databases were searched to identify papers published in English between January 2010 through July 2019; the search identified 25 articles. The Toileting Behaviors-Women's Elimination Behaviors scale has been published in four validated language versions and used in 17 of the 25 studies. The most frequent behaviors include concern about public toilet cleanliness, delaying urination when busy or away from home, and using different toileting postures at and away from home. Determinants of toileting behaviors include environmental factors, chronic health conditions, and cognitive/psychological factors. Associations were found between toileting behaviors and lower urinary tract symptoms and between toileting postures and uroflowmetric parameters and post-void residual volume. Strategies that address modifiable determinants of toileting behaviors should be developed and tested in future research. Furthermore, little is known about the toileting behaviors and bladder health in older women and women from developing countries. Rigorous studies are needed to better understand the underlying mechanisms of toileting behaviors, the nature of associations between toileting behaviors and lower urinary tract symptoms, and effects of the environment on women's toileting behaviors.


title: Luminescent silicon nanostructures and COVID-19.

text: This Faraday Discussion volume is unique in the hundred plus year history of the Faraday Discussion series, being produced at a time of unprecedented circumstances worldwide and without the preceding Faraday Discussion conference having taken place.


title: Disease severity is associated with differential gene expression at the early and late phases of infection in nonhuman primates infected with different H5N1 highly pathogenic avian influenza viruses.

text: UNLABELLED Occasional transmission of highly pathogenic avian H5N1 influenza viruses to humans causes severe pneumonia with high mortality. To better understand the mechanisms via which H5N1 viruses induce severe disease in humans, we infected cynomolgus macaques with six different H5N1 strains isolated from human patients and compared their pathogenicity and the global host responses to the virus infection. Although all H5N1 viruses replicated in the respiratory tract, there was substantial heterogeneity in their replicative ability and in the disease severity induced, which ranged from asymptomatic to fatal. A comparison of global gene expression between severe and mild disease cases indicated that interferon-induced upregulation of genes related to innate immunity, apoptosis, and antigen processing/presentation in the early phase of infection was limited in severe disease cases, although interferon expression was upregulated in both severe and mild cases. Furthermore, coexpression analysis of microarray data, which reveals the dynamics of host responses during the infection, demonstrated that the limited expression of these genes early in infection led to a failure to suppress virus replication and to the hyperinduction of genes related to immunity, inflammation, coagulation, and homeostasis in the late phase of infection, resulting in a more severe disease. Our data suggest that the attenuated interferon-induced activation of innate immunity, apoptosis, and antigen presentation in the early phase of H5N1 virus infection leads to subsequent severe disease outcome. IMPORTANCE Highly pathogenic avian H5N1 influenza viruses sometimes transmit to humans and cause severe pneumonia with ca. 60% lethality. The continued circulation of these viruses poses a pandemic threat; however, their pathogenesis in mammals is not fully understood. We, therefore, investigated the pathogenicity of six H5N1 viruses and compared the host responses of cynomolgus macaques to the virus infection. We identified differences in the viral replicative ability of and in disease severity caused by these H5N1 viruses. A comparison of global host responses between severe and mild disease cases identified the limited upregulation of interferon-stimulated genes early in infection in severe cases. The dynamics of the host responses indicated that the limited response early in infection failed to suppress virus replication and led to hyperinduction of pathological condition-related genes late in infection. These findings provide insight into the pathogenesis of H5N1 viruses in mammals.


title: Is Bridging Necessary? A Pilot Study of Bridging versus Primary Stentriever-Based Endovascular Reperfusion in Large Anterior Circulation Strokes.

text: BACKGROUND We aimed to determine whether bridging provides additional benefits over primary stentriever-based endovascular reperfusion (SER) in patients with proximal middle cerebral artery (pMCA) strokes. METHODS Clinical and radiologic data from consecutive stroke patients with large anterior circulation infarcts involving the pMCA were analyzed. Stroke subtypes were categorized according to Trial of ORG 10172 in Acute Stroke Treatment criteria. Neurologic deficits were assessed with the National Institutes of Health Stroke Scale (NIHSS), and vessel recanalization was determined using the Thrombolysis in Cerebral Infarction scale at the end of SER. Good outcome was defined as a modified Rankin Scale (mRS) score of 2 or lesser. RESULTS Fifty-seven patients with a median age of 66 years were included. Of those, 24 received prior systemic tissue plasminogen activator and 33 received primary SER. Atrial fibrillation was more common in patients who underwent SER but there were no other between-group differences in baseline variables, procedure-related variables, or outcome parameters. Six patients died and 27 patients achieved an mRS of 2 or less at 90 days. Patients who were treated with tPA before SER needed less stentriever passes to recanalize the occluded vessel, but bridging did not impact the chances for either survival or favorable outcome. Age (odds ratio [OR], .92; 95% confidence interval [CI], .85-.98) and NIHSS score (OR, .12; 95% CI, .02-.78) were the only variables associated with outcome on multivariate analysis. CONCLUSIONS Primary SER and bridging resulted in equally high survival and good outcome rates. Our results suggest that the benefits of primary SER in such critically ill patients may bypass the need for bridging therapy and merit further study.


title: Using SELDI-TOF MS to identify serum biomarkers of rheumatoid arthritis.

text: OBJECTIVES No satisfactory biomarkers are currently available to screen for rheumatoid arthritis (RA). We have developed and evaluated surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) for detection and analysis of multiple proteins for distinguishing individuals with RA from control individuals. METHODS A total of 156 serum samples from 90 RA patients, 30 patients with ankylosing spondylitis (AS), and 36 healthy individuals were examined by SELDI technology. Spectral data were analysed by the support vector machine (SVM) approach and potential biomarkers were chosen for system training and were used to construct a diagnostic model. RESULTS Pattern 1, consisting of four protein peaks with m/z values of 3899, 4594, 7566, and 13,842, distinguished RA from the healthy samples with sensitivity of 90.0% and a specificity of 91.7%. Pattern 2, consisting of m/z peaks 4287 and 6471, distinguished RA from AS with a sensitivity of 86.7% and a specificity of 85.0%. CONCLUSION The combination of SELDI-TOF MS and SVM could facilitate the discovery of better biomarkers for RA and also provide a useful tool for molecular diagnosis in the future.


title: [Epidemiological characteristics of COVID-19 in Gansu province].

text: Objective: To understand the epidemiological characteristics of COVID-19 cases in different epidemic stages in Gansu province. Methods: Epidemiological investigation was conducted to collect the information of confirmed COVID-19 cases, including demographic, epidemiological and clinical information. Results: As of 25 February 2020, a total of 91 confirmed COVID-19 cases had been reported in Gansu. The epidemic of COVID-19 in Gansu can be divided as three different stages, i.e. imported case stage, imported-case plus indigenous case stage, and indigenous case stage. A total of 63 cases were clustered cases (69.23%), 3 cases were medical staff infected with non-occupational exposure. The initial symptoms included fever (54.95%, 50/91), cough (52.75%, 48/91), or fatigue (28.57%, 26/91), the proportion of each symptom showed a decreasing trend along with the three epidemic stages, but only the differences in proportions of fever (trend χ2=2.20, P<0.05) and fatigue (trend χ2=3.18, P<0.05) among the three epidemic stages were statistically significant. The cases with critical severe symptoms accounted for 42.85% (6/14), 23.73% (14/59) and 16.67% (3/18), respectively, in three epidemic stages, showed a decreasing trend (H=6.45, P<0.05). Also, the incubation period prolonged along with the epidemic stage (F=51.65, P<0.01), but the intervals between disease onset and hospital visit (F=5.32, P<0.01), disease onset and diagnosis (F=5.25, P<0.01) became shorter along with the epidemic stage. Additionally, the basic reproduction number (R0) had decreased from 2.61 in imported case stage to 0.66 in indigenous case stage. Conclusions: The COVID-19 epidemic in Gansu was caused by the imported cases, and about 2/3 cases were clustered ones. No medical worker was observed to be infected by occupational exposure. With the progression of COVID-19 epidemic in Gansu, the change in initial symptom and incubation period suggests, the early screening cannot only depend on body temperature monitoring.


title: Cerebral Venous Thrombosis Associated with COVID-19.

text: Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.


title: Feasibility of laparoscopic major hepatectomy for hepatic paragonimiasis: two case reports.

text: BACKGROUND Though accumulated evidence proved that laparoscopic major hepatectomy was technically feasible, it remains a challenging procedure and is limited to highly specialized centers. Paragonimiasis is one of the most important food-borne parasitic zoonoses caused by the trematode of the genus Paragonimus. Although hepatic paragonimiasis is rare, the previous studies had investigated hepatic paragonimiasis from different perspectives. However, the safety and feasibility of laparoscopic major hepatectomy for hepatic paragonimiasis have not yet been reported in the literature. METHODS We here present 2 cases of hepatic paragonimiasis at the deep parts of the liver with treatment by laparoscopic major hepatectomy. One case is a 32-year-old male patient who was admitted to the hospital due to upper abdominal discomfort without fever for 1 month. The clinical imaging revealed that there was a lesion about 5.9 × 3.7 cm in the boundary of right anterior lobe and right posterior lobe of the liver with rim enhancement and tract-like nonenhanced areas. The other one is a 62-year-old female patient who was referred to the hospital for 1 month of right upper abdominal pain and fever. The ultrasonography showed that there was a huge hypoechoic mass (about 10.8 × 6.3 cm) in middle lobe of the liver with tract-like nonenhanced areas. Both patients were from an endemic area of paragonimiasis and the proportion of eosinophil in the second case was increased. RESULTS The preoperative diagnosis of the first case was ambiguous and the hepatic paragonimiasis was considered for the second case. The first case underwent laparoscopic extended right posterior lobe hepatectomy and the other case underwent laparoscopic extended left hemihepatectomy. Both operations went very well and the operation times for the 2 cases were 275 minutes and 310 minutes, respectively. The 2 patients' postoperative recovery was smooth without major postoperative complications (such as, bleeding, bile leakage, and liver failure). Moreover, the 2 patients were discharged on the 6th day and 7th day after surgery, respectively. The postoperative histopathological examination manifested hepatic paragonimiasis in both patients. CONCLUSION This study suggests that the laparoscopic approach may be safe and technically feasible for hepatic paragonimiasis.


title: Helicobacter p ylori eradication treatment for gastric carcinoma prevention in asymptomatic or dyspeptic adults: systematic review and Bayesian meta-analysis of randomised controlled trials.

text: OBJECTIVES Recent meta-analyses of eradication therapy in Helicobacter pylori-infected adults reported significant reductions in gastric carcinoma risk. However, concerns about supporting unfocused screening and eradication programme in healthy, asymptomatic populations have arisen. We performed a systematic review and Bayesian meta-analysis to provide an accurate interpretation of randomised evidence on the preventive effectiveness of eradication therapy on gastric carcinoma risk. METHODS We searched databases including PubMed, Cochrane Central and Embase for reference and citation tracking without language restrictions, from inception through 31 July 2018. Paired investigators independently selected randomised controlled trials (RCTs) comparing eradication therapy with placebo or no treatment for asymptomatic or dyspeptic H. pylori-infected adults with no previous gastric carcinoma. The main outcome was gastric carcinoma incidence; secondary outcomes included gastric carcinoma-specific, non-gastric carcinoma and all-cause mortality. RESULTS A total of 5 population-based and 2 outpatient care-based RCTs involving 7303 adults were eligible. Eradication algorithms were heterogeneous, and unsuccessful eradication and reinfection were frequently observed. A Bayesian meta-analysis with competing risk outcomes found low-certainty evidence that eradication therapy might be more likely than control to reduce gastric carcinoma risk (HR=0.65; 95% credible interval (CrI) 0.41 to 1.0; I2 =11%). The CrIs included the null effects across the subgroup and sensitivity analyses, apart from those based on particular models that excluded two RCTs that enrolled subjects with specific histological findings only (HR=0.55; CrI 0.30 to 0.89; I2 =14%). The uncertainty of the average 41% risk reduction in gastric carcinoma-specific mortality included a clinically important mortality risk increase (HR=0.59 favouring eradication therapy; CrI 0.25 to 1.20; I2 =13%; low certainty). CONCLUSIONS There is insufficient evidence to support or refute the effectiveness of eradication therapy in preventing gastric carcinoma in H. pylori-infected, high-risk populations. Rigorously conducted large RCTs of healthy infected adults only would provide evidence of the true efficacy of successful eradication. PROSPERO registration number: CRD42014009245.


title: SUMO fusion technology for enhanced protein expression and purification in prokaryotes and eukaryotes.

text: The preparation of sufficient amounts of high-quality protein samples is the major bottleneck for structural proteomics. The use of recombinant proteins has increased significantly during the past decades. The most commonly used host, Escherichia coli, presents many challenges including protein misfolding, protein degradation, and low solubility. A novel SUMO fusion technology appears to enhance protein expression and solubility ( http://www.lifesensors.com ). Efficient removal of the SUMO tag by SUMO protease in vitro facilitates the generation of target protein with a native N-terminus. In addition to its physiological relevance in eukaryotes, SUMO can be used as a powerful biotechnology tool for enhanced functional protein expression in prokaryotes and eukaryotes.


title: 18F-FLT and 18F-FDG positron emission tomography for the imaging of advanced well-differentiated gastro-entero-pancreatic endocrine tumours.

text: PURPOSE Gastro-entero-pancreatic (GEP) endocrine tumours are a heterogenous group of tumours of variable localization and prognosis. It has been suggested that positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) may have a prognostic value and help to identify patients at risk of progression. [18F]fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) has been recently developed as a PET proliferation tracer. At present, there are no studies investigating its role in GEP. The aim of this prospective study was to assess the value of 18F-FLT-PET for the evaluation of GEP. MATERIALS AND METHODS Ten patients with biopsy-proven locally advanced or metastasized, well-differentiated GEP neuroendocrine tumours were prospectively enrolled and scheduled for 18F-FDG and 18F-FLT-PET. Images were compared with other conventional diagnostic procedures, namely computed tomography, ultrasound, somatostatin receptor scintigraphy and with clinical and diagnostic follow-up. RESULTS Evaluation criteria were interpreted in terms of assumed presence of tumoral tissue. According to the patient's status, FDG was positive in five out of the seven patients with stable disease and in two out of the three patients with progressive disease. No positive case was identified by 18F-FLT in either the primary or the metastatic tumour site, whatever the status of patients, and this was probably a reflection of the slow proliferation rate of tumours. CONCLUSION These preliminary data suggest that 18F-FLT-PET is not a suitable tracer for the evaluation of advanced well-differentiated GEP tumours. FDG showed good diagnostic performance but does not help to identify patients at risk of progression.


title: Multimodality management of a polyfunctional pancreatic endocrine carcinoma with markedly elevated serum vasoactive intestinal polypeptide and calcitonin levels.

text: We present an unusual case of a 52-year-old woman with severe, uncontrollable, refractory diarrhea attributable to pancreatic endocrine carcinoma (ECA) with markedly elevated serum vasoactive intestinal polypeptide (VIP) and calcitonin levels. After initial correction of fluid and electrolyte abnormalities, the patient was treated with high-dose octreotide. Shortly thereafter, due to the intractable nature of her diarrhea, she underwent cytoreductive hepatic surgery. The pancreatosplenectomy specimen showed a poorly differentiated ECA of the distal pancreas, immunoreactive for synaptophysin, CD56, and S100 protein, with morphologically similar hepatic and lymph node metastases. Postoperatively, her diarrhea improved, along with decline in serum VIP and calcitonin levels. Systemic chemotherapy with etoposide and cisplatin did not result in any radiographic and biochemical improvement. Having radiologically stable disease with depot-octreotide and short-acting octreotide (Sandostatin), she was subjected to peptide receptor radiotherapy with [177Lu-DOTA0,Tyr]octreotate (LuTate) that resulted in marked clinical and biochemical improvement, along with dramatic reduction in the number and size of hepatic metastases. In summary, this is a unique case of metastatic VIP- and calcitonin-secreting pancreatic ECA with dramatic sustained clinical, biochemical, and objective tumor response to peptide receptor radionuclide therapy.


title: Recent Advances in Pediatric Ventilatory Assistance.

text: In this review on respiratory assistance, we aim to discuss the following recent advances: the optimization and customization of mechanical ventilation, the use of high-frequency oscillatory ventilation, and the role of noninvasive ventilation. The prevention of ventilator-induced lung injury and diaphragmatic dysfunction is now a key aspect in the management of mechanical ventilation, since these complications may lead to higher mortality and prolonged length of stay in intensive care units. Different physiological measurements, such as esophageal pressure, electrical activity of the diaphragm, and volumetric capnography, may be useful objective tools to help guide ventilator assistance. Companies that design medical devices including ventilators and respiratory monitoring platforms play a key role in knowledge application. The creation of a ventilation consortium that includes companies, clinicians, researchers, and stakeholders could be a solution to promote much-needed device development and knowledge implementation.


title: A NEW TREATMENT MODALITY TO REDUCE ACUTE TONSILLITIS HEALING TIME.

text: BACKGROUND AND OBJECTIVE Acute tonsillitis is one of the most common reasons for application to otorhinolaryngology clinics. In the treatment of acute tonsillitis, supportive therapies are mostly used. As antibiotic therapy, penicillin or erythromycin can be used. The aim of this study is to decrease the clinical recovery time of acute tonsillitis by providing parenteral treatment and daily cleaning of tonsillar lesions. MATERIAL AND METHODS Patients with an age range of 15-60 years were included in the study. The patients were divided into two groups. The first group used an i.v. combination of ampicillin + sulbactam and the tonsillar membranes of patients were cleaned daily. The second group used only the i.v. combination of ampicillin + sulbactam. RESULTS Patients who received antibiotherapy and debridement had a clinical improvement of 90% on the 2nd treatment day and 95% on the 5th treatment day. The patients receiving only antibiotics had a clinical improvement of 65% on the 5th treatment day and 75% on the 7th treatment day. The recovery time of both groups was significantly different (p < 0.05). CONCLUSION The solution and technique used in this clinical study showed that patients with acute tonsillitis could recover in a very short time without any complications.


title: Respiratory care year in review 2010: part 2. Invasive mechanical ventilation, noninvasive ventilation, pediatric mechanical ventilation, aerosol therapy.

text: The purpose of this paper is to review the recent literature related to invasive mechanical ventilation, NIV, pediatric mechanical ventilation, and aerosol therapy. Topics covered related to invasive mechanical ventilation topics include the role of PEEP in providing lung protection during mechanical ventilation, unconventional modes for severe hypoxemia, and strategies to improve patient-ventilator interactions. Topics covered related to NIV include real-life NIV use, NIV and extubation failure, and NIV and pandemics. For pediatric mechanical ventilation, the topics addressed are NIV, invasive respiratory support, and inhaled nitric oxide. Topics covered related to aerosol therapy include short-acting β-adrenergic agents, long-acting β-adrenergic agents, long-acting antimuscarinic agents, inhaled corticosteroid therapy, phosphodiesterase type 4 (PDE4) inhibitors, long-acting β-adrenergic plus inhaled corticosteroid, long-acting antimuscarinic plus inhaled corticosteroid, nebulized hypertonic saline, inhaled mannitol, and inhaled antibiotic therapy. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of Respiratory Care.


title: Keyhole Supraorbital Craniotomy for Aneurysm Clipping in the Setting of Bypass for Moyamoya Disease.

text: BACKGROUND In 3%-15% of patients with moyamoya disease, aneurysms occur throughout the circle of Willis. In moyamoya patients treated with a superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass, treatment of a new or an enlarging aneurysm can be complicated by the presence of the bypass and by limitations on the use of standard frontotemporal craniotomies to gain access to the aneurysm. Furthermore, endovascular access can be limited by the presence of fragile moyamoya vessels and precluded by atresia of large vessels. CASE DESCRIPTION A 45-year-old female patient with a history of moyamoya disease and previous left STA-MCA bypass presented with an enlarging left superior cerebellar artery aneurysm. We used a keyhole supraorbital craniotomy as a minimally invasive route to treat this aneurysm of the circle of Willis, with minimal interruption to the existing bypass or collateral circulation. CONCLUSIONS In patients with moyamoya disease who have existing STA-MCA bypass and de novo or expanding aneurysms, treatment is fraught with challenges. We advocate the use of a minimally invasive keyhole supraorbital craniotomy with an eyebrow incision for aneurysms associated with moyamoya disease occurring on the proximal anterior cerebral and middle cerebral arteries, the anterior communicating artery, the basilar apex, the posterior communicating artery, the proximal superior cerebellar artery, and the posterior cerebral artery.


title: Efficient -2 frameshifting by mammalian ribosomes to synthesize an additional arterivirus protein.

text: Programmed -1 ribosomal frameshifting (-1 PRF) is a gene-expression mechanism used to express many viral and some cellular genes. In contrast, efficient natural utilization of -2 PRF has not been demonstrated previously in eukaryotic systems. Like all nidoviruses, members of the Arteriviridae (a family of positive-stranded RNA viruses) express their replicase polyproteins pp1a and pp1ab from two long ORFs (1a and 1b), where synthesis of pp1ab depends on -1 PRF. These polyproteins are posttranslationally cleaved into at least 13 functional nonstructural proteins. Here we report that porcine reproductive and respiratory syndrome virus (PRRSV), and apparently most other arteriviruses, use an additional PRF mechanism to access a conserved alternative ORF that overlaps the nsp2-encoding region of ORF1a in the +1 frame. We show here that this ORF is translated via -2 PRF at a conserved G_GUU_UUU sequence (underscores separate ORF1a codons) at an estimated efficiency of around 20%, yielding a transframe fusion (nsp2TF) with the N-terminal two thirds of nsp2. Expression of nsp2TF in PRRSV-infected cells was verified using specific Abs, and the site and direction of frameshifting were determined via mass spectrometric analysis of nsp2TF. Further, mutagenesis showed that the frameshift site and an unusual frameshift-stimulatory element (a conserved CCCANCUCC motif 11 nucleotides downstream) are required to direct efficient -2 PRF. Mutations preventing nsp2TF expression impair PRRSV replication and produce a small-plaque phenotype. Our findings demonstrate that -2 PRF is a functional gene-expression mechanism in eukaryotes and add another layer to the complexity of arterivirus genome expression.


title: Intravenous versus inhalational maintenance of anaesthesia for postoperative cognitive outcomes in elderly people undergoing non-cardiac surgery.

text: BACKGROUND The use of anaesthetics in the elderly surgical population (more than 60 years of age) is increasing. Postoperative delirium, an acute condition characterized by reduced awareness of the environment and a disturbance in attention, typically occurs between 24 and 72 hours after surgery and can affect up to 60% of elderly surgical patients. Postoperative cognitive dysfunction (POCD) is a new-onset of cognitive impairment which may persist for weeks or months after surgery.Traditionally, surgical anaesthesia has been maintained with inhalational agents. End-tidal concentrations require adjustment to balance the risks of accidental awareness and excessive dosing in elderly people. As an alternative, propofol-based total intravenous anaesthesia (TIVA) offers a more rapid recovery and reduces postoperative nausea and vomiting. Using TIVA with a target controlled infusion (TCI) allows plasma and effect-site concentrations to be calculated using an algorithm based on age, gender, weight and height of the patient.TIVA is a viable alternative to inhalational maintenance agents for surgical anaesthesia in elderly people. However, in terms of postoperative cognitive outcomes, the optimal technique is unknown. OBJECTIVES To compare maintenance of general anaesthesia for elderly people undergoing non-cardiac surgery using propofol-based TIVA or inhalational anaesthesia on postoperative cognitive function, mortality, risk of hypotension, length of stay in the postanaesthesia care unit (PACU), and hospital stay. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11), MEDLINE (1946 to November 2017), Embase (1974 to November 2017), PsycINFO (1887 to November 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA We included randomized controlled trials (RCTs) with participants over 60 years of age scheduled for non-cardiac surgery under general anaesthesia. We planned to also include quasi-randomized trials. We compared maintenance of anaesthesia with propofol-based TIVA versus inhalational maintenance of anaesthesia. DATA COLLECTION AND ANALYSIS Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias, and synthesized findings. MAIN RESULTS We included 28 RCTs with 4507 randomized participants undergoing different types of surgery (predominantly cardiovascular, laparoscopic, abdominal, orthopaedic and ophthalmic procedures). We found no quasi-randomized trials. Four studies are awaiting classification because we had insufficient information to assess eligibility.All studies compared maintenance with propofol-based TIVA versus inhalational maintenance of anaesthesia. Six studies were multi-arm and included additional TIVA groups, additional inhalational maintenance or both. Inhalational maintenance agents included sevoflurane (19 studies), isoflurane (eight studies), and desflurane (three studies), and was not specified in one study (reported as an abstract). Some studies also reported use of epidural analgesia/anaesthesia, fentanyl and remifentanil.We found insufficient reporting of randomization methods in many studies and all studies were at high risk of performance bias because it was not feasible to blind anaesthetists to study groups. Thirteen studies described blinding of outcome assessors. Three studies had a high of risk of attrition bias, and we noted differences in the use of analgesics between groups in six studies, and differences in baseline characteristics in five studies. Few studies reported clinical trials registration, which prevented assessment of risk of selective reporting bias.We found no evidence of a difference in incidences of postoperative delirium according to type of anaesthetic maintenance agents (odds ratio (OR) 0.59, 95% confidence interval (CI) 0.15 to 2.26; 321 participants; five studies; very low-certainty evidence); we noted during sensitivity analysis that using different time points in one study may influence direction of this result. Thirteen studies (3215 participants) reported POCD, and of these, six studies reported data that could not be pooled; we noted no difference in scores of POCD in four of these and in one study, data were at a time point incomparable to other studies. We excluded one large study from meta-analysis because study investigators had used non-standard anaesthetic management and this study was not methodologically comparable to other studies. We combined data for seven studies and found low-certainty evidence that TIVA may reduce POCD (OR 0.52, 95% CI 0.31 to 0.87; 869 participants).We found no evidence of a difference in mortality at 30 days (OR 1.21, 95% CI 0.33 to 4.45; 271 participants; three studies; very low-certainty evidence). Twelve studies reported intraoperative hypotension. We did not perform meta-analysis for 11 studies for this outcome. We noted visual inconsistencies in these data, which may be explained by possible variation in clinical management and medication used to manage hypotension in each study (downgraded to low-certainty evidence); one study reported data in a format that could not be combined and we noted little or no difference between groups in intraoperative hypotension for this study. Eight studies reported length of stay in the PACU, and we did not perform meta-analysis for seven studies. We noted visual inconsistencies in these data, which may be explained by possible differences in definition of time points for this outcome (downgraded to very low-certainty evidence); data were unclearly reported in one study. We found no evidence of a difference in length of hospital stay according to type of anaesthetic maintenance agent (mean difference (MD) 0 days, 95% CI -1.32 to 1.32; 175 participants; four studies; very low-certainty evidence).We used the GRADE approach to downgrade the certainty of the evidence for each outcome. Reasons for downgrading included: study limitations, because some included studies insufficiently reported randomization methods, had high attrition bias, or high risk of selective reporting bias; imprecision, because we found few studies; inconsistency, because we noted heterogeneity across studies. AUTHORS' CONCLUSIONS We are uncertain whether maintenance with propofol-based TIVA or with inhalational agents affect incidences of postoperative delirium, mortality, or length of hospital stay because certainty of the evidence was very low. We found low-certainty evidence that maintenance with propofol-based TIVA may reduce POCD. We were unable to perform meta-analysis for intraoperative hypotension or length of stay in the PACU because of heterogeneity between studies. We identified 11 ongoing studies from clinical trials register searches; inclusion of these studies in future review updates may provide more certainty for the review outcomes.


title: MDCT Venography Evaluation of a Rare Collateral Vein Draining from the Left Subclavian Vein to the Great Cardiac Vein.

text: Congenital vascular anomalies of the venous drainage in the chest affect both cardiac and non-cardiac structures. Collateral venous drainage from the left subclavian vein to the great cardiac vein is a rare venous drainage pattern. These anomalies present a diagnostic challenge. Multi-detector computed tomography (MDCT) is useful in the diagnosis and treatment planning of these clinically complex disorders. We present a case report of an 18-year-old Caucasian male who came to our institute for evaluation of venous drainage patterns to the heart. We describe the contrast technique of bilateral dual injection MDCT venography and the imaging features of the venous drainage patterns to the heart.


title: Is small tidal volume with low positive end expiratory pressure during one-lung ventilation an effective ventilation method for endoscopic thoracic surgery?

text: BACKGROUND The present study will focus on the rationale for the use of small tidal volume with 6 cmH2O positive end expiratory pressure (PEEP) with the changes of arterial oxygen tension, plateau airway pressure, and static lung compliance during one lung ventilation for endoscopic thoracic surgery. METHODS Forty-three patients were intubated with a double-lumen endobronchial tube. After positioning the patients in the lateral decubitus, one-lung ventilation was started with 100% oxygen, tidal volume 10 ml/kg without PEEP; arterial oxygen tension, plateau airway pressure, and static compliance were checked as baseline values (T0). Fifteen minutes later, same parameters were measured (T15). The tidal volume had changed to 6 ml/kg with 6 cmH2O PEEP. Fifteen minutes later, the same parameters were measured (T30). RESULTS Oxygen tension had decreased at T15 (282.1 ± 83.4 mmHg) compared to T0 (477.2 ± 82.4 mmHg) (P < 0.0001), but was maintained at T30 (270.4 ± 81.9 mmHg). There was no difference in peak inspiratory pressure at T15 or T30 compared to T0, plateau airway pressure was increased at T15 and T30 (P < 0.05) and static lung compliance was decreased at T15 and T30 (P < 0.0001). CONCLUSIONS In carrying out one-lung ventilation for thoracic surgery using an endoscope, the addition of a PEEP of 6 cmH2O in the dependent lung, while reducing the tidal volume of 6 ml/kg, both oxygen tension and lung compliance are maintained without increasing the plateau airway pressure. Protective lung ventilation is useful for one lung ventilation.


docid: jgcjscjq

title: Assessment of Healthcare Workers' Levels of Preparedness and Awareness Regarding COVID-19 Infection in Low-Resource Settings.

text: COVID-19, caused by the SARS-CoV-2 virus, is spreading rapidly worldwide, with devastating consequences for patients, healthcare workers, health systems, and economies. As it reaches low- and middle-income countries, the pandemic puts healthcare workers at high risk and challenges the abilities of healthcare systems to respond to the crisis. This study measured levels of knowledge and preparedness regarding COVID-19 among physicians and nurses. A cross-sectional survey was conducted among healthcare workers in Libya between February 26 and March 10, 2020. We obtained 1,572 valid responses of a possible 2,000 (78.6%) participants from 21 hospitals, of which 65.1% were from physicians and 34.9% from nurses. The majority of participants (70%) used social media as a source of information. A total of 47.3% of doctors and 54.7% of nurses received adequate training on how to effectively use personal protective equipment. Low confidence in managing suspected COVID-19 patients was reported by 83.8% of participants. Furthermore, 43.2% of healthcare workers were aware of proper hand hygiene techniques. Less than 7% of participants received training on how to manage COVID-19 cases, whereas 20.6% of doctors and 26.3% of nurses felt that they were personally prepared for the outbreak. Awareness and preparedness for the pandemic were low among frontline workers during the study. Therefore, an effective educational training program should be implemented to ensure maintenance of appropriate practices during the COVID-19 pandemic.


title: Mapping South African public health research (1975 - 2014).

text: BACKGROUND Since 1994, South Africa (SA) has faced up to the challenge of building a strong economy, to which public health provides an important underpinning. Objectives. To map the scientific research in public health in SA after the end of apartheid and to present the links between the different financing/funding systems. METHODS Bibliographic analyses utilising the Web of Science of papers published during the period 1975 - 2014, analyses of journals, most cited articles, authors, publication years, organisations, funding agencies, countries and keywords, and mapping of the relations between countries involved in public health research and of the Web of Science Categories using VOSviewer. RESULTS I accessed 2 246 articles published between 1975 and 2014, the majority of which were published after 2007. The main countries of research were the USA, SA, Switzerland and the UK, representing the main network collaborations. The relevant keywords were HIV, woman, child, program/programme, rural, tuberculosis, district and sex. CONCLUSIONS Public health research in SA reached a high level 16 years after the end of apartheid. The chief field that emerged was the spread of HIV, including mother-to-child transmission, and the policies applied to all districts of SA, through a network of institutions between the USA and SA.


docid: ztbkjcex

title: PPAR-gamma expression in peritoneal endometriotic lesions correlates with pain experienced by patients.

text: Endometriosis is a significant gynecologic condition that can cause both pain and infertility and affects up to 15% of women during their reproductive years. In peritoneal endometriotic lesions, the expression of peroxisome proliferation-activated receptor gamma, a nuclear receptor with antiinflammatory and neuroprotective roles, is positively correlated with the pain reported by patients.


title: Evidence too weak to guide surgical treatment decisions for anterior cruciate ligament injury: a systematic review of the risk of new meniscal tears after anterior cruciate ligament injury.

text: OBJECTIVE To investigate the risk of new meniscal tears after treatment for anterior cruciate ligament (ACL) injury, in children and adults with and without ACL reconstruction. DESIGN Prognosis systematic review (PROSPERO registration number CRD42016036788). METHODS We searched Embase, Ovid Medline, Cochrane, CINAHL, SPORTDiscus, PEDro and Google Scholar from inception to 3rd May 2018. Eligible articles included patients with ACL injury (diagnosis confirmed by MRI and/or diagnostic arthroscopy), reported the number of meniscal tears at the time of ACL injury diagnosis/start of treatment and reported the number of new meniscal tears that subsequently occurred. Articles with fewer than 20 patients at follow-up, and articles limited to ACL revision surgery or multi-ligament knee injuries were excluded. Two independent reviewers screened articles, assessed eligibility, assessed risk of bias and extracted data. We judged the certainty of evidence using the Grading of Recommendations Assessment Development and Evaluation (GRADE) working group methodology. RESULTS Of 75 studies included in the systematic review, 54 studies with 9624 patients and 501 new meniscal tears were appropriate for quantitative analysis. Heterogeneity precluded data pooling. The risk of new meniscal tears was 0%-21% when follow-up was <2 years, 0%-29% when follow-up was 2 to 5 years, 5%-52% when follow-up was 5 to 10 years and 4%-31% when follow-up was longer than 10 years. The proportion of studies with high risk of selection, misclassification and detection bias was 84%, 69% and 68%, respectively. Certainty of evidence was very low. CONCLUSION New meniscal tears occurred in 0%-52% of patients between 4 months and 20 years (mean 4.9±4.4 years) following treatment for ACL injury. The certainty of evidence was too low to guide surgical treatment decisions. This review cannot conclude that the incidence of new meniscal tears is lower if ACL injury is treated with surgery compared with treatment with rehabilitation only.


title: Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD-ACE2 receptor interaction.

text: Human coronavirus NL63 (NL63), a member of the group I coronaviruses, may cause acute respiratory diseases in young children and immunocompromised adults. Like severe acute respiratory syndrome coronavirus (SARS-CoV), NL63 also employs the human angiotensin-converting enzyme 2 (hACE2) receptor for cellular entry. To identify residues in the spike protein of NL63 that are important for hACE2 binding, this study first generated a series of S1-truncated variants, examined their associations with the hACE2 receptor and subsequently mapped a minimal receptor-binding domain (RBD) that consisted of 141 residues (aa 476-616) towards the C terminus of the S1 domain. The data also demonstrated that the NL63 RBD bound to hACE2 more efficiently than its full-length counterpart and had a binding efficiency comparable to the S1 or RBD of SARS-CoV. A further series of RBD variants was generated using site-directed mutagenesis and random mutant library screening assays, and identified 15 residues (C497, Y498, V499, C500, K501, R518, R530, V531, G534, G537, D538, S540, E582, W585 and T591) that appeared to be critical for the RBD-hACE2 association. These critical residues clustered in three separate regions (designated RI, RII and RIII) inside the RBD, which may represent three receptor-binding sites. These results may help to delineate the molecular interactions between the S protein of NL63 and the hACE2 receptor, and may also enhance our understanding of the pathogenesis of NL63 and SARS-CoV.


title: Initial experience in single-incision transumbilical laparoscopic liver resection: indications, potential benefits, and limitations.

text: Background. Single-incision transumbilical laparoscopic liver resection (SITLLR) has been recently described in limited series. We report our experience in SITLLR and discuss the future of this approach in terms of indications, potential benefits, and limitations, with a special reference to laparoscopic liver resection (LLR). Patients and Methods. Six patients underwent SITLLR. Indications were biliary cysts (3 cases), hydatid cysts (2), and colorectal liver metastasis (1). Procedures consisted in cysts unroofing, left lateral lobectomy, pericystectomy, and wedge resection. SITLLR was performed with 11 mm reusable trocar, 10 or 5 mm 30° scopes, 10 mm ultrasound probe, curved reusable instruments, and straight disposable bipolar shears. Results. Neither conversion to open surgery nor insertion of supplementary trocars was necessary. Median laparoscopic time was 105.5 minutes and median blood loss 275 mL. Median final umbilical scar length was 1.5 cm, and median length of stay was 4 days. No early or late complications occurred. Conclusion. SITLLR remains a challenging procedure. It is feasible in highly selected patients, requiring experience in hepatobiliary and laparoscopic surgery and skills in single-incision laparoscopy. Apart from cosmetic benefit, our experience and literature review did not show significant advantages if compared with multiport LLR, underlying that specific indications remain to be established.


title: Systemic Prophylactic Antibiotics for the Modified Introducer Method for Percutaneous Endoscopic Gastrostomy: A Prospective, Randomized, Double-Blind Study.

text: BACKGROUND Percutaneous endoscopic gastrostomy (PEG) is the most common method of enteral nutrition in patients who require long-term tube feeding. According to meta-analyses, administration of systemic prophylactic antibiotics for PEG reduces peristomal infection. However, with several recent developments in the procedure and instruments, the risk of infection might have been reduced. The aim of this study was to evaluate the use of systemic antibiotic prophylaxis for a modified introducer method of PEG. METHODS This prospective, randomized, double-blind trial assessed 278 patients undergoing PEG for inclusion. Ninety-one patients with an indication for PEG who gave informed consent to participate were randomized. Forty-six patients received prophylactic ampicillin and 45 patients received a placebo. A modified introducer method of PEG using a Seldinger PEG kit was performed. The primary outcome was the occurrence of clinically evident wound infection within 3 days after PEG. RESULTS Wound infection within 3 days was observed in none in the prophylaxis group and in 1 patient in the control group (P=0.4945). There was no significant difference between 2 groups in the other parameters, including peristomal infection within 7 days, overall infection, white blood cell counts, C-reactive protein level, and successive rate of finishing antibiotics. CONCLUSIONS For wound infection within 3 days, noninferiority of the placebo group to the antibiotics group was preliminarily suggested with our criteria, but not for peristomal infection within 7 days. More strict criteria for noninferiority should be examined in a further large sample study.


title: Efficacy of Mass Quarantine as Leverage of Health System Governance During COVID-19 Outbreak: A Mini Policy Review.

text: On January 23, 2020, the Chinese government announced the city lockdown of Wuhan. Since then, there have been controversial debates among experts about the efficacy of mass quarantine, the oldest and probably one of the most effective methods for controlling infectious disease outbreaks. The impact of health policymaking section of health system governance becomes visible to all stakeholders and the public in such emergency contexts. The success and failure of such policies should be evaluated in order to find the proper course of action for the local and international communities. In this review, we aim to investigate the efficacy of mass quarantine in China during the coronavirus disease 2019 (COVID-19) pandemic. We found good quality evidence for the effectiveness of mass quarantine during the current stage of COVID-19 pandemic, and these strategies seem to have been highly effective in controlling the spread of the disease.


title: Prediction of infarction and reperfusion in stroke by flow- and volume-weighted collateral signal in MR angiography.

text: BACKGROUND AND PURPOSE In proximal anterior circulation occlusive strokes, collateral flow is essential for good outcome. Collateralized vessel intensity in TOF- and contrast-enhanced MRA is variable due to different acquisition methods. Our purpose was to quantify collateral supply by using flow-weighted signal in TOF-MRA and blood volume-weighted signal in contrast-enhanced MRA to determine each predictive contribution to tissue infarction and reperfusion. MATERIALS AND METHODS Consecutively (2009-2013), 44 stroke patients with acute proximal anterior circulation occlusion met the inclusion criteria with TOF- and contrast-enhanced MRA and penumbral imaging. Collateralized vessels in the ischemic hemisphere were assessed by TOF- and contrast-enhanced MRA using 2 methods: 1) visual 3-point collateral scoring, and 2) collateral signal quantification by an arterial atlas-based collateral index. Collateral measures were tested by receiver operating characteristic curve and logistic regression against 2 imaging end points of tissue-outcome: final infarct volume and percentage of penumbra saved. RESULTS Visual collateral scores on contrast-enhanced MRA but not TOF were significantly higher in patients with good outcome. Visual collateral scoring on contrast-enhanced MRA was the best rater-based discriminator for final infarct volume < 90 mL (area under the curve, 0.81; P < .01) and percentage of penumbra saved >50% (area under the curve, 0.67; P = .04). Atlas-based collateral index of contrast-enhanced MRA was the overall best independent discriminator for final infarct volume of <90 mL (area under the curve, 0.94; P < .01). Atlas-based collateral index combining the signal of TOF- and contrast-enhanced MRA was the overall best discriminator for effective reperfusion (percentage of penumbra saved >50%; area under the curve, 0.89; P < .001). CONCLUSIONS Visual scoring of contrast-enhanced but not TOF-MRA is a reliable predictor of infarct outcome in stroke patients with proximal arterial occlusion. By atlas-based collateral assessment, TOF- and contrast-enhanced MRA both contain predictive signal information for penumbral reperfusion. This could improve risk stratification in further studies.


Partha Kar: Covid-19-we must keep faith in our experts.


title: Robotic distal pancreatectomy: Comparison of spleen-preservation by the Warshaw technique and splenectomy.

text: BACKGROUND Outcomes after robotic distal pancreatectomy with spleen preservation (RDP-SP) by the Warshaw technique and with splenectomy (RDP-S) were compared. METHODS All the data for patients undergoing robotic distal pancreatectomy (RDP) were prospectively collected. RESULTS A total of 66 patients were included, with 33 in each group. The console time was significantly shorter in the RDP-SP group than in the RDP-S group (165 minutes vs. 220 minutes). The median blood loss was 50 cm3 in the RDP-SP group and 100 cm3 in the RDP-S group. The surgical morbidity was significantly lower in RDP-SP group (18% vs. 58%). Spleen infarction (15%), gastric varices (6%) and perigastric varices (45%) after RDP-SP were not associated with any subsequent complication. Postoperative platelet count and white blood cell (WBC) count were significantly higher in the RDP-S group. CONCLUSIONS Both RDP-SP and RDP-S are feasible in selected patients. RDP-SP is feasible and time-saving. Although gastric/perigastric varices and spleen infarction are not uncommon after RDP-SP, they appear to be clinically irrelevant.


Coronavirus disruptions reverberate through research.


title: Combined experimental and theoretical study of long-range interactions modulating dimerization and activity of yeast geranylgeranyl diphosphate synthase.

text: We present here how two amino acid residues in the first helix distal from the main dimer interface modulate the dimerization and activity of a geranylgeranyl diphosphate synthase (GGPPs). The enzyme catalyzes condensation of farnesyl diphosphate and isopentenyl diphosphate to generate a C(20) product as a precursor for chlorophylls, carotenoids, and geranylgeranylated proteins. The 3D structure of GGPPs from Saccharomyces cerevisiae reveals an unique positioning of the N-terminal helix A, which protrudes into the other subunit and stabilizes dimerization, although it is far from the main dimer interface. Through a series of mutants that were characterized by analytic ultracentrifugation (AUC), the replacement of L8 and I9 at this helix with Gly was found sufficient to disrupt the dimer into a monomer, leading to at least 10(3)-fold reduction in activity. Molecular dynamics simulations and free energy decomposition analyses revealed the possible effects of the mutations on the protein structures and several critical interactions for maintaining dimerization. Further site-directed mutagenesis and AUC studies elucidated the molecular mechanism for modulating dimerization and activity by long-range interactions.


title: Exploitation of fibrin-based signaling niche for deriving progenitors from human adipose-derived mesenchymal stem cells towards potential neural engineering applications.

text: Adipose-derived mesenchymal stem cells (hADMSC) retaining proliferation and multi-differentiation potential may support the central nervous system (CNS) regeneration. Multipotency of MSC may result in both desirable and undesirable cells, post-transplantation. A better strategy to attain desired cells may be in vitro commitment of hADMSCs to uni-/bi- potent neural progenitor cells (NPCs), prior to transplantation. Derivation of stable NPCs may require a suitable niche eliciting proliferation and differentiation signals. The present study designed a biomimetic niche comprising insoluble fibrin supported adhesion matrix and exogenously added growth factors (GFs) for deriving different neural cells and established the role of Notch and Wnt signals for proliferation and differentiation of hADMSCs, respectively. The stable transformation of hADMSCs into neurospheres (NS) comprising Nestin+ve NPCs was achieved consistently. Slight modifications of niche enable differentiation of NS to NPCs; NPCs to neurons; NPCs to oligodendrocyte progenitor cells (OPCs); and OPCs to oligodendrocytes (OLG). Fibrin plays a crucial role in the conversion of hADMSC to NS and NPCs to OPCs; but, not essential for OPC to OLG maturation. Co-survival and cell-cell interaction of NPC derived neurons and OPCs promoting OLG maturation is illustrated. The designed biomimetic niche shows the potential for directing autologous ADMSCs to neural cells for applications in regenerative medicine.


title: A curative-intent endoscopic surgery for postradiation nasopharyngeal necrosis in patients with nasopharyngeal carcinoma.

text: BACKGROUND Postradiation nasopharyngeal necrosis (PRNN) is a severe complication after radiotherapy in patients with nasopharyngeal carcinoma (NPC), which can severely affect the quality of life and threaten the patient's life. Only 13.4%-28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced an innovative curative-intent endoscopic surgery for PRNN patients and evaluated its clinical efficacy. METHODS Clinical data of 72 PRNN patients who underwent radical endoscopic necrectomy, followed by reconstruction using a posterior pedicle nasal septum and floor mucoperiosteum flap were analyzed to determine the efficacy of this surgery. The endpoints were complete re-epithelialization of the nasopharyngeal defect, relief of headache, and overall survival (OS). RESULTS All surgeries were successfully performed without any severe postoperative complications or death. The median value of numeric rating scales of pain decreased from 8 before surgery to 0 after surgery (P < 0.001). Fifty-one patients (70.8%) achieved complete re-epithelialization of the nasopharyngeal defect. The number of cycles of radiotherapy (odds ratio [OR], 7.254; 95% confidence interval [CI] 1.035-50.821; P = 0.046), postoperative pathological result (OR, 34.087; 95% CI 3.168-366.746; P = 0.004), and survival status of flap (OR, 261.179; 95% CI 17.176-3971.599; P < 0.001) were independent risk factors of re-epithelialization of the nasopharyngeal defects. Postoperative pathological result (hazard ratio [HR], 5.018; 95% CI 1.970-12.782; P = 0.001) was an independent prognostic factor for OS. The 2-year OS rate of the entire cohort was 77.9%. CONCLUSION Curative-intent endoscopic necrectomy followed by construction using the posterior pedicle nasal septum and floor mucoperiosteum flap is a novel, safe, and effective treatment of PRNN in patients with NPC.


title: Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus.

text: Hepatitis C virus (HCV) infects ∼2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human mAbs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies to HCV.


Exercising Heart and Head in Managing Coronavirus Disease 2019 in Wuhan.


title: Factors influencing door-to-imaging time: analysis of the safe implementation of treatments in Stroke-EAST registry.

text: BACKGROUND Brain imaging is logistically the most difficult step before thrombolysis. To improve door-to-needle time (DNT), it is important to understand if (1) longer door-to-imaging time (DIT) results in longer DNT, (2) hospitals have different DIT performances, and (3) patient and hospital characteristics predict DIT. METHODS Prospectively collected data in the Safe Implementation of Treatments in Stroke-EAST (SITS-EAST) registry from Central/Eastern European countries between 2008 and 2011 were analyzed. Hospital characteristics were obtained by questionnaire from each center. Patient- and hospital-level predictors of DIT of 25 minutes or less were identified by the method of generalized estimating equations. RESULTS Altogether 6 of 9 SITS-EAST countries participated with 4212 patients entered into the database of which 3631 (86%) had all required variables. DIT of 25 minutes or less was achieved in 2464 (68%) patients (range, 3%-93%; median, 65%; and interquartile range, 50%-80% between centers). Patients with DIT of 25 minutes or less had shorter DNT (median, 60 minutes) than patients with DIT of more than 25 minutes (median, 86 minutes; P < .001). Four variables independently predicted DIT of 25 minutes or less: longer time from stroke onset to admission (91-180 versus 0-90 minutes; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.8), transport time of 5 minutes or less (OR, 2.9; 95% CI, 1.7-4.7) between the place of admission and a computed tomography (CT) scanner, no or minimal neurologic deficit before stroke (OR, 1.3; 95% CI, 1.02-1.5), and diabetes mellitus (OR, .8; 95% CI, .7-.97). CONCLUSIONS DIT should be improved in patients arriving early and late. Place of admission should allow transport time to a CT scanner under 5 minutes.


title: Anesthesia and COVID-19: What We Should Know and What We Should Do.

text: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was first reported in Wuhan, Hubei, China, and has spread to more than 200 other countries around the world. COVID-19 is a highly contagious disease with continuous human-to-human transmission. The origin of the virus is unknown. Airway manipulations and intubations, which are common during anesthesia procedures may increasingly expose anesthesia providers and intensive care unit team members to SARS-CoV-2. Through a comprehensive review of existing studies on COVID-19, this article presents the epidemiological and clinical characteristics of COVID-19, reviews current medical management, and suggests ways to improve the safety of anesthetic procedures. Owing to the highly contagious nature of the virus and the lack of therapeutic drugs or vaccines, precautions should be taken to prevent medical staff from COVID-19.


title: Personalized Prehospital Triage in Acute Ischemic Stroke.

text: Background and Purpose- Direct transportation to a center with facilities for endovascular treatment might be beneficial for patients with acute ischemic stroke, but it can also cause harm by delay of intravenous treatment. Our aim was to determine the optimal prehospital transportation strategy for individual patients and to assess which factors influence this decision. Methods- We constructed a decision tree model to compare outcome of ischemic stroke patients after transportation to a primary stroke center versus a more distant intervention center. The optimal strategy was estimated based on individual patient characteristics, geographic location, and workflow times. In the base case scenario, the primary stroke center was located at 20 minutes and the intervention center at 45 minutes. Additional sensitivity analyses included an urban scenario (10 versus 20 minutes) and a rural scenario (30 versus 90 minutes). Results- Direct transportation to the intervention center led to better outcomes in the base case scenario when the likelihood of a large vessel occlusion as a cause of the ischemic stroke was >33%. With a high likelihood of large vessel occlusion (66%, comparable with a Rapid Arterial Occlusion Evaluation score of 5 or above), the benefit of direct transportation to the intervention center was 0.10 quality-adjusted life years (=36 days in full health). In the urban scenario, direct transportation to an intervention center was beneficial when the risk of large vessel occlusion was 24% or higher. In the rural scenario, this threshold was 49%. Other factors influencing the decision included door-to-needle times, door-to-groin times, and the door-in-door-out time. Conclusions- The preferred prehospital transportation strategy for suspected stroke patients depends mainly on the likelihood of large vessel occlusion, driving times, and in-hospital workflow times. We constructed a robust model that combines these characteristics and can be used to personalize prehospital triage, especially in more remote areas.


Iatrogenic intramural esophageal dissection secondary to insertion of nasogastric tubes and the transorally inserted anvil during robot-assisted total gastrectomy.


title: Percutaneous Image-guided Surgery Training: Model IHU-DAICIM.

text: The evolution of guided imaging surgery is well known in recent years. As the field of action becomes more specific, learning and teaching are also more specific. State-of-the-art medical training should be mandatory in the field of general medicine and surgery in particular. In this work, we report on how to create a model for the formation of guided surgery by images in a simple and fast way, and its implementation by young surgeons. Pig models have been used in which collections made by bovine small intestine and simulated tumor lesions have been placed. Several types of image-guided procedures have been performed. No major complications were found during the development of the model or during its use. It is possible to develop a quick, simple, and safe living training model that can be used immediately after preparation.


title: Middle East respiratory syndrome: knowledge to date.

text: OBJECTIVE To provide a conceptual and clinical review of Middle East respiratory syndrome. DATA SOURCES Peer-reviewed articles were identified through searches of PubMed using the terms "Middle East respiratory syndrome," "coronavirus respiratory illness in Saudi Arabia," and "novel (beta) coronavirus and human coronavirus Erasmus Medical Center". In addition, articles were searched on the websites of the World Health Organization and the U.S. Centers for Disease Control and Prevention using the terms "Middle East respiratory syndrome" and "novel coronavirus in Middle East." The reference lists of these articles and relevant review articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION Final references were selected for inclusion in the review on the basis of their relevance. DATA SYNTHESIS The emerging Middle East respiratory syndrome coronavirus causes severe pulmonary disease with multiorgan involvement and a high fatality rate. Within months after its emergence, Middle East respiratory syndrome coronavirus was reported in several countries worldwide in people who had traveled from the Middle East. Middle East respiratory syndrome coronavirus is considered a zoonotic virus that has crossed the species barrier to humans, but the pathogenesis and the routes of transmission are not completely understood. There is currently no recommended treatment for Middle East respiratory syndrome coronavirus, although supportive treatment has played an important role. CONCLUSIONS This syndrome has raised global public health concerns about the dissemination of an emerging infectious disease and highlights the need for a coordinated global response to contain such a disease threat.


title: The foreign body response: at the interface of surgery and bioengineering.

text: BACKGROUND The surgical implantation of materials and devices has dramatically increased over the past decade. This trend is expected to continue with the broadening application of biomaterials and rapid expansion of aging populations. One major factor that limits the potential of implantable materials and devices is the foreign body response, an immunologic reaction characterized by chronic inflammation, foreign body giant cell formation, and fibrotic capsule formation. METHODS The English literature on the foreign body response to implanted materials and devices is reviewed. RESULTS Fibrotic encapsulation can cause device malfunction and dramatically limit the function of an implanted medical device or material. Basic science studies suggest a role for immune and inflammatory pathways at the implant-host interface that drive the foreign body response. Current strategies that aim to modulate the host response and improve construct biocompatibility appear promising. CONCLUSIONS This review article summarizes recent basic science, preclinical, and clinicopathologic studies examining the mechanisms driving the foreign body response, with particular focus on breast implants and synthetic meshes. Understanding these molecular and cellular mechanisms will be critical for achieving the full potential of implanted biomaterials to restore human tissues and organs.


Complex Pseudomonas population structure in cystic fibrosis airway infections.


title: Catheter-based renal denervation for treatment of resistant hypertension.

text: Hypertension is a common disease associated with important cardiovascular complications. Persistent blood pressure of 140/90 or higher despite combined use of a reninangiotensin system blocker, calcium channel blocker and a diuretic at highest tolerated doses constitutes resistant hypertension. Excess sympathetic activity plays an important pathogenic role in resistant hypertension in addition to contributing to the development of metabolic problems, in particular diabetes. Reduction of renal sympathetic activity by percutaneous catheter-based radiofrequency ablation via the renal arteries has been shown in several studies to decrease blood pressure in patients with resistant hypertension, and importantly is largely free of significant complications. However, longer term follow-up is required to confirm both long-term safety and efficacy.


title: Effects of hip and head position on ankle range of motion, ankle passive torque, and passive gastrocnemius tension.

text: Ankle joint range of motion (ROM) is notably influenced by the position of the hip joint. However, this result remains unexplained. Thus, the aim of this study was to test if the ankle passive torque and gastrocnemius muscle tension are affected by the hip and the head positions. The torque and the muscle shear elastic modulus (measured by elastography to estimate muscle tension) were collected in nine participants during passive ankle dorsiflexions performed in four conditions (by combining hip flexion at 90 or 150°, and head flexed or neutral). Ankle maximum dorsiflexion angle significantly decreased by flexing the hip from 150 to 90° (P < 0.001; mean difference 17.7 ± 2.5°), but no effect of the head position was observed (P > 0.05). Maximal passive torque and shear elastic modulus were higher with the hip flexed at 90° (P < 0.001). During submaximal ROM, no effects of the head and hip positioning (P > 0.05) were found for both torque and shear elastic modulus at a given common ankle angle among conditions. Shifts in maximal ankle angle due to hip angle manipulation are not related neither to changes in passive torque nor tension of the gastrocnemius. Further studies should be addressed to better understand the functional role of peripheral nerves and fasciae in the ankle ROM limits.


title: Real-time electrical impedance variations in women with and without breast cancer.

text: The chaotic vascular network surrounding malignant tumors leads to pulsatile blood flow patterns that differ from those in benign regions of the breast. This study aimed to determine if high-speed electrical impedance tomography (EIT) is able to detect conductivity changes associated with cyclic blood-volume changes and to gauge the potential of using these signatures to differentiate malignant from benign regions within the breast. EIT imaging of pulsating latex membranes submerged in saline baths provided initial validation of its use for tracking temporally varying conductivities. Nineteen women (10 with cancer, nine without) were imaged with EIT over the course of several heartbeats in synchrony with pulse-oximetry acquisition. Eight parameters ( rs, ϕ(rt,max), rt,max, Plow:full, Phigh:full, Plow:high) relating the conductivity images and pulse-oximeter signatures were extracted and used as a means of comparing malignant and benign regions of the breast. Significant differences between malignant and benign regions of interest were noted in seven of the eight parameters. The maximum correlation between conductivity and pulse-oximeter signals, rt,max , was observed to be the optimal discriminating parameter with a receiver operating characteristic area under the curve of 0.8 and a specificity of 81% at a sensitivity of 77%. Assessing the dynamic conductivity of breast may provide additional clinical utility to that of standard imaging modalities, but further investigation is necessary to better understand the biophysical mechanisms leading to the observed conductivity changes.


title: The outcomes of two robotic platforms performing transanal minimally invasive surgery for rectal neoplasia: a case series of 21 patients.

text: Colorectal cancer remains the third most common cancer effecting adults. Surgical guidelines recommend transanal excision of early rectal neoplasia up to 8 cm from the anal verge. A retrospective review of two novel approaches for transanal robotic local excision with R0 resections of rectal cancers which was, on average, higher than 8 cm. Twenty-one cases of robotic assisted transanal surgery for early stage disease (T0-T1, N0) were reviewed. The first 10 cases performed with the da Vinci® Si robotic platform between 2013 and 2016, and the first 11 cases performed using the Flex® Medrobotics platform between August 2017 and August 2018. The average distance from the anal verge was 11.1 cm and 9.5 cm for the da Vinci® Si and Flex® Colorectal Drive, respectively. The average operative time was 167.6 min for the da Vinci® Si and 110.1 min for the Flex® Colorectal Drive; the average EBL was 37.5 cc and 9.1 cc for the da Vinci® Si and Flex® Colorectal Drive. In the da Vinci® series, four cases required intraoperative conversion. In the Flex® series, one case was aborted due to unfavorable robotic positioning. All margins were histologically negative when surgically complete with no recurrences to date. Transanal robotic surgery may provide a method to address rectal lesions farther from the anal verge than previously described. The Flex® Colorectal Drive platform may provide superior ability to navigate the nonlinear anatomy of the rectum and distal sigmoid colon.


Imported Novel Coronavirus Infections: Observation on Active and Passive Case Detection in Thailand.


title: Increase in cerebral oxygenation during advanced life support in out-of-hospital patients is associated with return of spontaneous circulation.

text: INTRODUCTION By maintaining sufficient cerebral blood flow and oxygenation, the goal of cardiopulmonary resuscitation (CPR) is to preserve the pre-arrest neurological state. To date, cerebral monitoring abilities during CPR have been limited. Therefore, we investigated the time-course of cerebral oxygen saturation values (rSO₂) during advanced life support in out-of-hospital cardiac arrest. Our primary aim was to compare rSO₂ values during advanced life support from patients with return of spontaneous circulation (ROSC) to patients who did not achieve ROSC. METHODS We performed an observational study to measure rSO₂ using Equanox (Nonin, Plymouth, MI) from the start of advanced life support in the pre-hospital setting. RESULTS rSO₂ of 49 consecutive out-of-hospital cardiac arrest patients were analyzed. The total increase from initial rSO₂ value until two minutes before ROSC or end of advanced life support efforts was significantly larger in the group with ROSC 16% (9 to 36) compared to the patients without ROSC 10% (4 to 15) (P = 0.02). Mean rSO₂ from the start of measurement until two minutes before ROSC or until termination of advanced life support was higher in patients with ROSC than in those without, namely 39% ± 7 and 31% ± 4 (P = 0.05) respectively. CONCLUSIONS During pre-hospital advanced life support, higher increases in rSO₂ are observed in patients attaining ROSC, even before ROSC was clinically determined. Our findings suggest that rSO₂ could be used in the future to guide patient tailored treatment during cardiac arrest and could therefore be a surrogate marker of the systemic oxygenation state of the patient.


title: Laparoscopic Parenchyma-sparing Liver Resection for Colorectal Metastases.

text: Background Laparoscopic liver resection (LLR) of colorectal liver metastases (CLM) is increasingly performed in specialized centers. While there is a trend towards a parenchyma-sparing strategy in multimodal treatment for CLM, its role is yet unclear. In this study we present short- and long-term outcomes of laparoscopic parenchyma-sparing liver resection (LPSLR) at a single center. Patients and methods LLR were performed in 951 procedures between August 1998 and March 2017 at Oslo University Hospital, Oslo, Norway. Patients who primarily underwent LPSLR for CLM were included in the study. LPSLR was defined as non-anatomic hence the patients who underwent hemihepatectomy and sectionectomy were excluded. Perioperative and oncologic outcomes were analyzed. The Accordion classification was used to grade postoperative complications. The median follow-up was 40 months. Results 296 patients underwent primary LPSLR for CLM. A single specimen was resected in 204 cases, multiple resections were performed in 92 cases. 5 laparoscopic operations were converted to open. The median operative time was 134 minutes, blood loss was 200 ml and hospital stay was 3 days. There was no 90-day mortality in this study. The postoperative complication rate was 14.5%. 189 patients developed disease recurrence. Recurrence in the liver occurred in 146 patients (49%), of whom 85 patients underwent repeated surgical treatment (liver resection [n = 69], ablation [n = 14] and liver transplantation [n = 2]). Five-year overall survival was 48%, median overall survival was 56 months. Conclusions LPSLR of CLM can be performed safely with the good surgical and oncological results. The technique facilitates repeated surgical treatment, which may improve survival for patients with CLM.


title: Social determinants of common metabolic risk factors (high blood pressure, high blood sugar, high body mass index and high waist-hip ratio) of major non-communicable diseases in South Asia region: a systematic review protocol.

text: BACKGROUND Prevalence of non-communicable diseases has been increasing at a greater pace in developing countries and, in particular, the South Asia region. Various behavioral, social and environmental factors present in this region perpetuate common metabolic risk factors of non-communicable diseases. This study will identify social determinants of common metabolic risk factors of major non-communicable diseases in the context of the South Asian region and map their causal pathway. METHODS A systematic review of selected articles will be carried out following Cochrane guidelines. Review will be guided by Social Determinants of Health Framework developed by the World Health Organization to extract social determinants of metabolic risk factors of non-communicable diseases from studies. A distinct search strategy will be applied using key words to screen relevant studies from online databases. Primary and grey literature published from the year 2000 to 2016 and studies with discussion on proximal and distal determinants of non-communicable risk factors among adults of the South Asia region will be selected. They will be further checked for quality, and a matrix illustrating contents of selected articles will be developed. Thematic content analysis will be done to trace social determinants and their interaction with metabolic risk factors. Findings will be illustrated in causal loop diagrams with social determinants of risk factors along with their interaction (feedback mechanism). DISCUSSION The review will describe the interplay of social determinants of common NCD metabolic risk factors in the form of causal loop diagram. Findings will be structured in two parts: the first part will explain the linkage between proximal determinants with the metabolic risk factors and the second part will describe the linkage among the risk factors, proximal determinants and distal determinants. Evidences across different regions will be discussed to compare and validate and/or contrast the findings. Possible bias and limitations of this study will also be discussed. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017067212.


title: Severe acute respiratory syndrome coronavirus papain-like protease suppressed alpha interferon-induced responses through downregulation of extracellular signal-regulated kinase 1-mediated signalling pathways.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLpro), a deubiquitinating enzyme, reportedly blocks poly I : C-induced activation of interferon regulatory factor 3 and nuclear factor kappa B, reducing interferon (IFN) induction. This study investigated type I IFN antagonist mechanism of PLpro in human promonocytes. PLpro antagonized IFN-α-induced responses such as interferon-stimulated response element- and AP-1-driven promoter activation, protein kinase R, 2'-5'-oligoadenylate synthetase (OAS), interleukin (IL)-6 and IL-8 expression, and signal transducers and activators of transcription (STAT) 1 (Tyr701), STAT1 (Ser727) and c-Jun phosphorylation. A proteomics approach demonstrated downregulation of extracellular signal-regulated kinase (ERK) 1 and upregulation of ubiquitin-conjugating enzyme (UBC) E2-25k as inhibitory mechanism of PLpro on IFN-α-induced responses. IFN-α treatment significantly induced mRNA expression of UBC E2-25k, but not ERK1, causing time-dependent decrease of ERK1, but not ERK2, in PLpro-expressing cells. Poly-ubiquitination of ERK1 showed a relationship between ERK1 and ubiquitin proteasome signalling pathways associated with IFN antagonism by PLpro. Combination treatment of IFN-α and the proteasome inhibitor MG-132 showed a time-dependent restoration of ERK1 protein levels and significant increase of ERK1, STAT1 and c-Jun phosphorylation in PLpro-expressing cells. Importantly, PD098059 (an ERK1/2 inhibitor) treatment significantly reduced IFN-α-induced ERK1 and STAT1 phosphorylation, inhibiting IFN-α-induced expression of 2'-5'-OAS in vector control cells and PLpro-expressing cells. Overall results proved downregulation of ERK1 by ubiquitin proteasomes and suppression of interaction between ERK1 and STAT1 as type I IFN antagonist function of SARS-CoV PLpro.


title: [Septic shock with multiple organ failure after returning from Southeast Asia].

text: For a patient recently returned from a tropical country in intensive care, the leading hypothesis for a fever leading to multiple organ failure is evidently malaria. Nonetheless, many other causes are possible and should be considered: parasites, viruses, and bacteria. A multidisciplinary discussion between specialists in emergency medicine, radiology, pathology, and infectious diseases is essential to start appropriate treatment as quickly as possible without impairing the patient's prognosis.


title: Physical activity in wheelchair-using youth with spina bifida: an observational study.

text: BACKGROUND Even though typically developing youth are already at risk for physical inactivity, youth with spina bifida may be even at higher risk as a consequence of their reduced mobility. No objective data is available for youth with spina bifida who use a manual wheelchair, so the seriousness of the problem is unknown. The purpose of this observational study was to quantify physical activity in wheelchair-using youth with spina bifida and evaluate the intensity of activities. METHODS Fifty-three children and adolescents (5-19 years) with spina bifida who use a manual wheelchair for daily life, long distances or sports were included. To assess time spent in several types of activities VitaMove data of 34 participants were used and were presented as time spent sedentary and time spent physically active. This was compared to reference data of typically developing youth. To assess time spent in several intensities Actiheart data of 36 participants were used. The intensities were categorized according to the American College of Sports Medicine, ranging from very light intensity to near to maximal intensity. Data of 25 participants were used to combine type of activity and intensity. RESULTS Children and adolescents with spina bifida who use a manual wheelchair were more sedentary (94.3% versus 78.0% per 24 h, p < 0.000) and less physically active (5.0% versus 12.2% per 24 h, p < 0.000) compared to typically developing peers. Physical activity during weekend days was worse compared to school days; 19% met the Guidelines of Physical Activity during school days and 8% during weekend days. The intensities per activity varied extensively between participants. CONCLUSIONS Children and adolescents with spina bifida who use a manual wheelchair are less physically active and more sedentary than typically developing youth. The physical activity levels on school days seem to be more favorable than the physical activity levels on a weekend day. The low levels of physical activity need our attention in pediatric rehabilitation practice. The different intensities during activities indicate the importance of individually tailored assessments and interventions.


title: Biologic variability of cardiac troponin I in healthy dogs and dogs with different stages of myxomatous mitral valve disease using standard and high-sensitivity immunoassays.

text: BACKGROUND Biologic variability (BV) is one aspect of interpreting changes in biomarker concentrations known to be clinically important in people with cardiac disease, but it has not been adequately addressed in dogs so far. OBJECTIVES The purpose of the study was to determine BV of cardiac troponin I (cTnI) in healthy dogs and dogs with 3 stages of myxomatous mitral valve disease (MMVD). METHODS Healthy dogs and dogs with 3 stages of MMVD were prospectively assigned to groups based on comprehensive clinical evaluation using current guidelines. Concentrations of cTnI were measured hourly, daily, and weekly using standard and high-sensitivity immunoassays. Within- (CVI ) and between-subject (CVG ) coefficients of variability, percent reference change value (RCV), and index of individuality (IoI) were calculated. RESULTS All 10 healthy dogs and 76/112 (68%) of samples from 28 MMVD dogs had cTnI concentrations below the limit of detection (LOD) using a standard sensitivity immunoassay. Only 49/160 (31%) of healthy dog samples and no MMVD samples had cTnI below the high-sensitivity immunoassay LOD. Data analysis for the high-sensitivity immunoassay revealed CVI of 48.1%, CVG of 60.1%, RCV of 134.0%, and IoI of 0.804 in healthy dogs. In MMVD dogs, CVI was 39.6%, CVG was 80.7%, RCV was 110%, and IoI was 0.494. Of all MMVD dogs, those with Stage B2 had the lowest RCV of 91%. CONCLUSIONS Biologic variability affects cTnI concentrations in healthy dogs and dogs with MMVD. Consideration of BV may be clinically relevant when monitoring individual changes in cTnI values, using high-sensitivity immunoassays.


title: Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis.

text: BACKGROUND Dengue and West Nile viruses are highly cross-reactive and have numerous parallels in geography, potential vector host (Aedes family of mosquitoes), and initial symptoms of infection. While the vast majority (> 80%) of both dengue and West Nile virus infections result in asymptomatic infections, a minority of individuals experience symptomatic infection and an even smaller proportion develop severe disease. The mechanisms by which these infections lead to severe disease in a subset of infected individuals is incompletely understood, but individual host differences including genetic factors and immune responses have been proposed. We sought to identify genetic risk factors that are associated with more severe disease outcomes for both viruses in order to shed light on possible shared mechanisms of resistance and potential therapeutic interventions. METHODS We applied a search strategy using four major databases (Medline, PubMed, Embase, and Global Health) to find all known genetic associations identified to date with dengue or West Nile virus disease. Here we present a review of our findings and a meta-analysis of genetic variants identified. RESULTS We found genetic variations that are significantly associated with infections of these viruses. In particular we found variation within the OAS1 (meta-OR = 0.83, 95% CI: 0.69-1.00) and CCR5 (meta-OR = 1.29, 95% CI: 1.08-1.53) genes is significantly associated with West Nile virus disease, while variation within MICB (meta-OR = 2.35, 95% CI: 1.68-3.29), PLCE1 (meta-OR = 0.55, 95% CI: 0.42-0.71), MBL2 (meta-OR = 1.54, 95% CI: 1.02-2.31), and IFN-γ (meta-OR = 2.48, 95% CI: 1.30-4.71), is associated with dengue disease. CONCLUSIONS Despite substantial heterogeneity in populations studied, genes examined, and methodology, significant associations with genetic variants were found across studies within both diseases. These gene associations suggest a key role for immune mechanisms in susceptibility to severe disease. Further research is needed to elucidate the role of these genes in disease pathogenesis and may reveal additional genetic factors associated with disease severity.


title: Uncovering mutation-specific morphogenic phenotypes and paracrine-mediated vessel dysfunction in a biomimetic vascularized mammary duct platform.

text: The mammary gland is a highly vascularized tissue capable of expansion and regression during development and disease. To enable mechanistic insight into the coordinated morphogenic crosstalk between the epithelium and vasculature, we introduce a 3D microfluidic platform that juxtaposes a human mammary duct in proximity to a perfused endothelial vessel. Both compartments recapitulate stable architectural features of native tissue and the ability to undergo distinct forms of branching morphogenesis. Modeling HER2/ERBB2 amplification or activating PIK3CA(H1047R) mutation each produces ductal changes observed in invasive progression, yet with striking morphogenic and behavioral differences. Interestingly, PI3KαH1047R ducts also elicit increased permeability and structural disorganization of the endothelium, and we identify the distinct secretion of IL-6 as the paracrine cause of PI3KαH1047R-associated vascular dysfunction. These results demonstrate the functionality of a model system that facilitates the dissection of 3D morphogenic behaviors and bidirectional signaling between mammary epithelium and endothelium during homeostasis and pathogenesis.