title: Modified perineal linear stapler resection for external rectal prolapse.

text: Background rectal prolapse can cause bleeding and fecal incontinence that affects the life quality of patients. The treatment of external rectal prolapse is surgical. There are many procedures (abdominal or perineal) that can be used depending on the severity of the condition and patient tolerability for operation. In this study, a simple safe procedure is used for the treatment of the rectal prolapse in old, fragile and comorbid patients who cannot withstand the major surgeries and the risk of long-duration anesthesia. Methods from December 2016 to July 2019, 36 elderly comorbid patients with rectal prolapse were involved in this study which is performed in the GIT surgery unit of Zagazig University Hospital. A modified linear stapler resection technique is used for the rectal prolapse. Postoperative follow up was done for one year to evaluate the functional outcome, operative time, hospital stay duration and complications. Result this study was conducted on 36 patients; The median age was 75 years (range 48-95). The postoperative complication rate was 11.1%. The median operative time was 25 min and 4 days for the hospital stay. Fecal incontinence improved in more than 90% of patients and constipation disappeared in 66% of total constipating patients. Conclusion The modified perineal linear stapler resection for external rectal prolapse is a good, easy, rapid treatment for elderly comorbid patients with good functional outcomes.


title: Gastrointestinal metabolic surgery for the treatment of diabetic patients: a multi-institutional international study.

text: BACKGROUND Gastrointestinal metabolic surgery has been proposed for the treatment of not well-controlled type 2 diabetes mellitus (T2DM) patients with a body mass index (BMI) <35 kg/m(2). This study aims to describe recent experience with surgical treatment of T2DM in Asian centers. METHODS Patients aged 20 to 70 years with not well-controlled T2DM [glycated hemoglobin (HbA1C) >7.0%] and BMI < 35 kg/m(2) were included at five institutes between 2007 and 2010. The end point is T2DM remission, defined by fasting plasma glucose <110 mg/dl and HbA1C <6.0%. RESULTS Of the 200 patients, 172 (86%) underwent gastric bypass, 24 (12%) underwent sleeve gastrectomy, and the other 4 underwent adjustable banding. Laparoscopic access was used in all the patients. Gender (66.5% female), age (mean 45.0 ± 10.8), and HbA1C (mean 9.3 ± 1.9%) did not differ between the procedure among the groups. Until now, 87 patients had 1-year data. One year after surgery, the mean BMI decreased from 28.5 ± 3.0 to 23.4 ± 2.3 kg/m(2) and HbA1C decreased to 6.3 ± 0.5%. Remission of T2DM was achieved in 72.4% of the patients. Patients with a diabetes duration of <5 years had a better diabetes remission rate than patients with duration of diabetes >5 years (90.3% vs. 57.1%; p = 0.006). Patients with BMI > 30 kg/m(2) had a better diabetes remission rate than those with BMI < 30 kg/m(2) (78.7% vs. 62.5%; p = 0.027). Individuals who underwent gastric bypass loss more weight and had a higher diabetes remission rate than individuals who underwent restrictive-type procedures. Multivariate analysis confirmed that the duration of diabetes and the type of surgery predict the diabetes remission. No mortalities were reported and two (1.0%) patients had major morbidities. CONCLUSION Gastrointestinal metabolic surgery is an effective treatment for not well-controlled T2DM treatment. Diabetes remission is significantly higher in those with duration of diabetes less than 5 years and BMI > 30 kg/m(2).


title: ASGE guideline on the management of achalasia.

text: Achalasia is a primary esophageal motor disorder of unknown etiology characterized by degeneration of the myenteric plexus, which results in impaired relaxation of the esophagogastric junction (EGJ), along with the loss of organized peristalsis in the esophageal body. The criterion standard for diagnosing achalasia is high-resolution esophageal manometry showing incomplete relaxation of the EGJ coupled with the absence of organized peristalsis. Three achalasia subtypes have been defined based on high-resolution manometry findings in the esophageal body. Treatment of patients with achalasia has evolved in recent years with the introduction of peroral endoscopic myotomy. Other treatment options include botulinum toxin injection, pneumatic dilation, and Heller myotomy. This American Society for Gastrointestinal Endoscopy Standards of Practice Guideline provides evidence-based recommendations for the treatment of achalasia, based on an updated assessment of the individual and comparative effectiveness, adverse effects, and cost of the 4 aforementioned achalasia therapies.


title: Lack of agreement between gross visual and histological assessment of burn reepithelialization in a porcine burn model.

text: One of the most important and earliest measures of burn healing is wound reepithelialization. Reepithelialization is a vital determinant of wound infection and scarring. Reepithelialization is generally based on gross visual assessment; however, histological assessment remains the criterion standard. We hypothesized that there would be poor agreement (r < .4) between gross visual and histological assessments of burn reepithelialization in a porcine model. The study design was prospective observational using three anesthetized female pigs (20-25 kg). Forty-eight 2.5- × 2.5-cm burns were created on the flanks of pig's using an aluminum bar (150 g) preheated to 80°C for 20 seconds. Burns were treated with an occlusive or antimicrobial dressing and photographed at day 10 for determination of gross percentage reepithelialization in a 1-cm diameter circle in the center of the burn by two experienced clinicians masked to each other's measurements. A 10-mm full-thickness punch biopsy was taken from the center of the burns and evaluated by a board-certified dermatopathologist masked to clinical assessments. One clinician and the dermatopathologist repeated the assessments 1 month apart. The outcome was percentage wound reepithelialization at 10 days. The criterion standard was the histological assessment. Intraobserver and interobserver agreements were calculated with Pearson's correlation coefficients. A coefficient less than .4 was considered poor. Sixteen burns were created on each of three animals. Six wounds were excluded because of the presence of a thick eschar covering the burn, making the gross determination of reepithelialization impossible. Intraobserver agreement for histological reepithelialization was 0.96 (P < .001). Intraobserver agreement for gross visual assessment of reepithelialization was 0.75 (P < .001). Interobserver agreement for gross visual assessment of reepithelialization was 0.60 (P < .001). The agreement between gross visual and histological assessment of burn reepithelialization was -0.25. Although there was a good interobserver agreement for gross visual assessments, there was a poor agreement between gross visual and histological assessments of burn reepithelialization. Care should be used when determining burn reepithelialization based on gross visual assessments alone.


title: Avoiding Complications in Bone and Soft Tissue Ablation.

text: As with percutaneous ablation of tumors in the liver, lungs, and kidneys, ablation of bone and non-visceral soft tissue tumors carries risk, primarily from collateral damage to vital structures in proximity to the target tumor. Certain risks are of particular interest when ablating bone and non-visceral soft tissue tumors, namely neural or skin injury, bowel injury, fracture, and gas embolism from damaged applicators. Ablation of large volume tumors also carries special risk. Many techniques may be employed by the interventional radiologist to minimize complications when treating tumors in the musculoskeletal system. These methods include those to depict, displace, or monitor critical structures. Thus, measures to provide thermoprotection may be active, such as careful ablation applicator placement and use of various displacement techniques, as well as passive, including employment of direct temperature, radiographic, or neurophysiologic monitoring techniques. Cementoplasty should be considered in certain skeletal locations at risk of fracture. Patients treated with large volume tumors should be monitored for renal dysfunction and properly hydrated. Finally, ablation applicators should be cautiously placed in the constrained environment of intact bone.


title: Significance of thoracoscopy-assisted surgery with a minithoracotomy and hand-assisted laparoscopic surgery for esophageal cancer: the experience of a single surgeon.

text: BACKGROUND This retrospective study evaluated the surgical learning curve and outcomes of thoracolaparoscopic esophagectomy. PATIENTS AND METHODS The study group comprised a series of 92 patients with preoperatively diagnosed resectable thoracic esophageal cancer. Additionally, the surgical outcomes in 79 esophageal cancer patients receiving open esophagectomies were compared. All patients underwent thoracolaparoscopic esophagectomy in the lateral decubitus position. The short- and long-term outcomes were evaluated, and the surgical learning curve was assessed. RESULTS The total operation time was 477.8 ± 102.2 min, the thoracoscopic time was 157.9 ± 61.3 min, the total blood loss was 554.4 ± 280.5 ml, and the number of retrieved lymph nodes was 34.3 ± 14.3. Postoperative morbidity was observed in 23 patients. After the surgeon's first 40 cases, the surgical technique and short-term outcomes were stable. The 5-year disease-specific survival was 66.6% and the 5-year overall survival was 64.6% in patients receiving R0 thoracolaparoscopic esophagectomy. Comparison of 5-year disease-specific survival rate according to tumor-node-metastasis stage between patients receiving R0 thoracolaparoscopic esophagectomy and conventional open esophagectomy showed that there were no significant differences in survival in any stage between the two groups. Loco-regional recurrence was observed in 6 patients, distant recurrence in seven, and combined recurrence in nine after R0 thoracolaparoscopic esophagectomy. There was no significant difference in the pattern of recurrence between the two groups. CONCLUSIONS Thoracolaparoscopic esophagectomy for esophageal cancer was technically feasible and oncologically satisfactory, according to the surgical learning curve.


title: Novel therapeutic targets for SARS-CoV-2-induced acute lung injury: Targeting a potential IL-1β/neutrophil extracellular traps feedback loop.

text: Most COVID-19 infected individuals present with mild flu-like symptoms; however, 5-10% of cases suffer from life-threatening pneumonia and respiratory failure. The pathogenesis of SARS-CoV-2 and its pathology of associated acute lung injury (ALI), acute respiratory distress syndrome (ARDS), sepsis, coagulopathy and multiorgan failure is not known. SARS-CoV-2 is an envelope virus with S (spike), M (membrane), N (nucleocapsid) and E (envelop) proteins. In a closely related coronavirus (SARS-CoV), the transmembrane E protein exerts an important role in membrane-ionic transport through viroporins, deletion of which reduced levels of IL-1β and a remarkably reduced lung edema compared to wild type. IL-1β is generated by macrophages upon activation of intracellular NLRP3 (NOD-like, leucine rich repeat domains, and pyrin domain-containing protein 3), part of the functional NLRP3 inflammasome complex that detects pathogenic microorganisms and stressors, while neutrophils are enhanced by increasing levels of IL-1β. Expiring neutrophils undergo "NETosis", producing thread-like extracellular structures termed neutrophil extracellular traps (NETs), which protect against mild infections and microbes. However, uncontrolled NET production can cause acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), coagulopathy, multiple organ failure, and autoimmune disease. Herein, we present arguments underlying our hypothesis that IL-1β and NETs, mediated via NLRP3 inflammasomes, form a feed-forward loop leading to the excessive alveolar and endothelial damage observed in severe cases of COVID-19. Considering such assertions, we propose potential drug candidates that could be used to alleviate such pathologies. Considering that recent efforts to ascertain effective treatments of COVID-19 in severe patients has been less than successful, investigating novel avenues of treating this virus are essential.


title: Practical resources for nurses and other health care providers involved in the care of children at risk for respiratory syncytial virus infection.

text: Health care staff and families with young children are often unware of the ease of respiratory syncytial virus (RSV) spread and potential clinical consequences of serious respiratory illness. Successful Canadian RSV prophylaxis (RSVP) programs (a) provide practical educational resources on RSV and respiratory disease that consider language and cultural barriers; (b) develop policies to identify all children eligible for RSVP with palivizumab; (c) emphasize compliance with RSVP, particularly during patient transfer between hospitals, community clinics, and remote outpost centers; and (d) establish collaborative networks to help ensure optimum RSVP compliance for all high-risk children. Herein, we share practical resources and key educational references for counseling of caregivers with infants or young children at risk for RSV infection, and health care providers participating in RSVP program development.


title: Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke.

text: OBJECTIVE To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset. METHODS We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as "target mismatch" if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up magnetic resonance imaging. RESULTS Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale [NIHSS] = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.1-20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5-27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4-140). INTERPRETATION The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849-856.


title: One-year experience with single incision laparoscopic cholecystectomy in a single center: without the use of inverse triangulation.

text: PURPOSE Single incision laparoscopic cholecystectomy (SILC) is generally performed with the use of inverse triangulation. In this study, we performed 3-channel or 4-channel SILC without the use of inverse triangulation. We evaluated the adequacy and feasibility of SILC using our surgical method. METHODS We retrospectively reviewed our series of 309 SILCs performed between March 2014 and February 2015. RESULTS Among 309 SILCs, male were 148 and female were 161 patients, mean age was 48.7 ± 15.3 years old and mean body mass index was 24.8 ± 3.8 kg/m(2). Forty patients had previously undergone abdominal surgery including 6 cases of upper abdominal surgery. SILC after percutaneous transhepatic gallbladder (GB) drainage was completed in 8.7% of cases. There were 10 cases of emergency SILC. SILC was performed for noncomplicated GB including symptomatic GB stone and polyp in 66.7% of cases, acute cholecystitis in 33.3%. Overall, 96.8% of procedures were successfully completed without additional port. The reason for addition of an extra port or open conversion included technical difficulties due to severe adhesion and bleeding. The mean operating time was 60.7 ± 22.3 minutes. The overall complication rate was 4.8%: 9 patients of wound seroma, 1 case of bile leakage from GB bed, 4 cases of intra-abdominal abscess or fluid collection, and 1 case of incisional hernia were developed. There was no case of common bile duct injury. CONCLUSION Our surgical method of SILC without the use of inverse triangulation is safe, feasible and effective technique.


title: Endovascular Therapy in Strokes with ASPECTS 5-7 May Result in Smaller Infarcts and Better Outcomes as Compared to Medical Treatment Alone.

text: INTRODUCTION Intra-arterial therapy (IAT) for large vessel occlusion strokes (LVOS) has been increasingly utilized. The benefit of IAT in patients with midrange Alberta Stroke Program Early Computed Tomography Score (ASPECTS) remains to be established. MATERIALS AND METHODS This was a retrospective analysis of LVOS with ASPECTS 5-7 treated with IAT (n = 86) or medical therapy alone (intravenous tissue plasminogen activator; n = 15) at two centers from 2009 to 2012. Definitions were as follows: symptomatic intracranial hemorrhage = any parenchymal hematoma; successful reperfusion = mTICI ≥2b; good and acceptable outcomes = 90-day mRS 0-2 and 0-3, respectively. Final infarct volumes (FIV) were calculated based on 24-hour CT/MRI scans. RESULTS Mean age (67 ± 14 vs. 67 ± 19 years) and baseline NIHSS (20 ± 5 vs. 20 ± 6) were similar in the two groups. Successful reperfusion was achieved in 58 (67%) IAT patients. Symptomatic and asymptomatic intracranial hemorrhage occurred in 9 (10%) and 31 (36%) IAT patients, respectively. The proportion of 90-day good and acceptable outcomes was 20 (17/86) and 33% (28/86), respectively. Successful IAT reperfusion was associated with smaller FIV (p = 0.015) and higher rates of good (p = 0.01) and acceptable (p = 0.014) outcomes. There was a strong trend towards a higher hemicraniectomy requirement in medically as compared to endovascularly treated patients (20 vs. 6%; p = 0.06) despite similar in-hospital mortality. The median FIV was significantly lower with IAT versus medical therapy [80 ml (interquartile range, 38-122) vs. 190 ml (121-267); p = 0.015]. CONCLUSIONS Despite a relatively low probability of achieving functional independence, IAT in LVOS patients with ASPECTS 5-7 appears to result in lower degrees of disability and may lessen the need for hemicraniectomy. Therefore, it may be a reasonable option for patients and families who favor a shift from severe to moderate disability.


title: Selection of helical braided flow diverter stents based on hemodynamic performance and mechanical properties.

text: BACKGROUND Although flow diversion is a promising procedure for the treatment of aneurysms, complications have been reported and it remains poorly understood. The occurrence of adverse outcomes is known to depend on both the mechanical properties and flow reduction effects of the flow diverter stent. OBJECTIVE To clarify the possibility of designing a flow diverter stent considering both hemodynamic performance and mechanical properties. MATERIALS AND METHODS Computational fluid dynamics (CFD) simulations were conducted based on an ideal aneurysm model with flow diverters. Structural analyses of two flow diverter models exhibiting similar flow reduction effects were performed, and the radial stiffness and longitudinal flexibility were compared. RESULTS In CFD simulations, two stents-Pore2-d35 (26.77° weave angle when fully expanded, 35 μm wire thickness) and Pore3-d50 (36.65°, 50 μm respectively)-demonstrated similar flow reduction rates (68.5% spatial-averaged velocity reduction rate, 85.0% area-averaged wall shear stress reduction rate for Pore2-d35, and 68.6%, 85.4%, respectively, for Pore3-d50). However, Pore3-d50 exhibited greater radial stiffness than Pore2-d35 (40.0 vs 21.0 mN/m at a 3.5 mm outer diameter) and less longitudinal flexibility (0.903 vs 0.104 N·mm bending moments at 90°). These measurements indicate that changing the wire thickness and weave angle allows adjustment of the mechanical properties while maintaining the same degree of flow reduction effects. CONCLUSIONS The combination of CFD and structural analysis can provide promising solutions for an optimized stent. Stents exhibiting different mechanical properties but the same flow reduction effects could be designed by varying both the weave angle and wire thickness.


title: Mechanical thrombectomy in nonagenarians with acute ischemic stroke.

text: BACKGROUND Mechanical thrombectomy (MT) is a safe and effective therapy for ischemic stroke. Nevertheless, very elderly patients aged ≥90 years were either excluded or under-represented in previous trials. It remains uncertain whether MT is warranted for this population or whether there should be an upper age limit. METHODS We retrospectively reviewed 79 patients with stroke aged ≥90 years from three neurointerventional centers who underwent MT between 2013 and 2017. Good functional outcome was defined as modified Rankin scale (mRS) ≤2 and assessed at 90-day follow-up. Successful recanalization was graded by Thrombolysis in Cerebral Infarction Scale (TICI) ≥2 b. Feasibility and safety assessments included unsuccessful recanalization attempts (TICI 0), time from groin puncture to recanalization, symptomatic intracranial hemorrhage (sICH), mortality, and intervention-related serious adverse events. RESULTS Only occlusions within the anterior circulation were included. Median time from groin puncture to recanalization was 39 min (IQR 25-57 min). The rate of successful recanalization (TICI ≥2 b) was 69.6% (55/79). Good functional outcome (mRS ≤2) at 90 days was observed in 16% (12/75) of patients. In-hospital mortality was 29.1% (23/79) and increased significantly at 90 days (46.7%, 35/75; p<0.001). sICH occurred in 5.1% (4/79) of patients. No independent predictor for good functional outcome (mRS ≤2) at 90 days was identified through logistic regression analysis. CONCLUSION MT in nonagenarians leads to high mortality rates and less frequently good functional outcome compared with younger patient cohorts in previous large randomized trials. However, MT appears to be safe and beneficial for a certain number of very elderly patients and therefore should generally not be withheld from nonagenarians.


title: Extensive Positive Selection Drives the Evolution of Nonstructural Proteins in Lineage C Betacoronaviruses.

text: UNLABELLED Middle East respiratory syndrome-related coronavirus (MERS-CoV) spreads to humans via zoonotic transmission from camels. MERS-CoV belongs to lineage C of betacoronaviruses (betaCoVs), which also includes viruses isolated from bats and hedgehogs. A large portion of the betaCoV genome consists of two open reading frames (ORF1a and ORF1b) that are translated into polyproteins. These are cleaved by viral proteases to generate 16 nonstructural proteins (nsp1 to nsp16) which compose the viral replication-transcription complex. We investigated the evolution of ORF1a and ORF1b in lineage C betaCoVs. Results indicated widespread positive selection, acting mostly on ORF1a. The proportion of positively selected sites in ORF1a was much higher than that previously reported for the surface-exposed spike protein. Selected sites were unevenly distributed, with nsp3 representing the preferential target. Several pairs of coevolving sites were also detected, possibly indicating epistatic interactions; most of these were located in nsp3. Adaptive evolution at nsp3 is ongoing in MERS-CoV strains, and two selected sites (G720 and R911) were detected in the protease domain. While position 720 is variable in camel-derived viruses, suggesting that the selective event does not represent a specific adaptation to humans, the R911C substitution was observed only in human-derived MERS-CoV isolates, including the viral strain responsible for the recent South Korean outbreak. It will be extremely important to assess whether these changes affect host range or other viral phenotypes. More generally, data herein indicate that CoV nsp3 represents a major selection target and that nsp3 sequencing should be envisaged in monitoring programs and field surveys. IMPORTANCE Both severe acute respiratory syndrome coronavirus (SARS-CoV) and MERS-CoV originated in bats and spread to humans via an intermediate host. This clearly highlights the potential for coronavirus host shifting and the relevance of understanding the molecular events underlying the adaptation to new host species. We investigated the evolution of ORF1a and ORF1b in lineage C betaCoVs and in 87 sequenced MERS-CoV isolates. Results indicated widespread positive selection, stronger in ORF1a than in ORF1b. Several selected sites were found to be located in functionally relevant protein regions, and some of them corresponded to functional mutations in other coronaviruses. The proportion of selected sites we identified in ORF1a is much higher than that for the surface-exposed spike protein. This observation suggests that adaptive evolution in ORF1a might contribute to host shifts or immune evasion. Data herein also indicate that genetic diversity at nonstructural proteins should be taken into account when antiviral compounds are developed.


title: Laparoscopic early pregnancy diagnosis in the laboratory rat.

text: Timely and accurate diagnosis of pregnancy in the laboratory rat is an invaluable endpoint in embryological and reproductive toxicology studies. The purpose of the present study was to assess the feasibility, sensitivity, accuracy and safety of laparoscopic examination of the uterus for detecting pregnancy at an early stage, and defining the number of fetuses in surviving rat models. Female Wistar rats were subjected to a two-port laparoscopic examination of their uterus from day 6 to day 10 post-coitum (pc). Mean recovery time from anesthesia was 148 ± 66 s. A postoperative 4.0 ± 1.8% body weight loss was restored in 3.9 ± 1.3 days. Uterine bulges suggestive of underlying embryonic vesicles could be detected by day 7 pc with a 0% false-negative diagnosis. Comparison of the number of laparoscopically defined uterine bulges (fetal counts) with litter size revealed a 0% underestimation rate of fetal counts, and a 42.9-87.5% overestimation rate from day 7 to day 10 pc. In conclusion, the present study introduced the laparoscopic examination of the uterus and showed it to be a feasible, reliable and safe method of early pregnancy diagnosis in the laboratory rat by day 7 pc.


title: A serological assay to detect SARS-CoV-2 seroconversion in humans.

text: Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.


title: Tolerance and long-term MRI imaging of gadolinium-modified meshes used in soft organ repair.

text: BACKGROUND Synthetic meshes are frequently used to reinforce soft tissues. The aim of this translational study is to evaluate tolerance and long-term MRI visibility of two recently developed Gadolinium-modified meshes in a rat animal model. MATERIALS AND METHODS Gadolinium-poly-ε-caprolactone (Gd-PCL) and Gadolinium-polymethylacrylate (Gd-PMA) modified meshes were implanted in Wistar rats and their tolerance was assessed daily. Inflammation and biocompatibility of the implants were assessed by histology and immunohistochemistry after 30 days post implantation. Implants were visualised by 7T and 3T MRI at day 30 and at day 90. Diffusion of Gadolinium in the tissues of the implanted animals was assessed by Inductively Coupled Plasma Mass Spectrometry. RESULTS Overall Gd-PMA coated implants were better tolerated as compared to those coated with Gd-PCL. In fact, Gd-PMA implants were characterised by a high ratio collagen I/III and good vascularisation of the integration tissues. High resolution images of the coated mesh were obtained in vivo with experimental 7T as well as 3T clinical MRI. Mass spectrometry analyses showed that levels of Gadolinium in animals implanted with coated mesh were similar to those of the control group. CONCLUSIONS Meshes coated with Gd-PMA are better tolerated as compared to those coated with Gd-PCL as no signs of erosion or significant inflammation were detected at 30 days post implantation. Also, Gd-PMA coated meshes were clearly visualised with both 7T and 3T MRI devices. This new technique of mesh optimisation may represent a valuable tool in soft tissue repair and management.


title: Hemodynamic-morphological discriminant models for intracranial aneurysm rupture remain stable with increasing sample size.

text: BACKGROUND We previously established three logistic regression models for discriminating intracranial aneurysm rupture status based on morphological and hemodynamic analysis of 119 aneurysms. In this study, we tested if these models would remain stable with increasing sample size, and investigated sample sizes required for various confidence levels (CIs). METHODS We augmented our previous dataset of 119 aneurysms into a new dataset of 204 samples by collecting an additional 85 consecutive aneurysms, on which we performed flow simulation and calculated morphological and hemodynamic parameters, as done previously. We performed univariate significance tests on these parameters, and multivariate logistic regression on significant parameters. The new regression models were compared against the original models. Receiver operating characteristics analysis was applied to compare the performance of regression models. Furthermore, we performed regression analysis based on bootstrapping resampling statistical simulations to explore how many aneurysm cases were required to generate stable models. RESULTS Univariate tests of the 204 aneurysms generated an identical list of significant morphological and hemodynamic parameters as previously (from the analysis of 119 cases). Furthermore, multivariate regression analysis produced three parsimonious predictive models that were almost identical to the previous ones, with model coefficients that had narrower CIs than the original ones. Bootstrapping showed that 10%, 5%, 2%, and 1% convergence levels of CI required 120, 200, 500, and 900 aneurysms, respectively. CONCLUSIONS Our original hemodynamic-morphological rupture prediction models are stable and improve with increasing sample size. Results from resampling statistical simulations provide guidance for designing future large multi-population studies.


title: Successful airtraq use in an air medical transport system.

text: INTRODUCTION There is a large body of literature that shows that the AirTraq device achieves equal or superior rates of successful intubation in all classes of user. A recent prospective human trial of the device questioned the first pass success rate and whether effective training could occur outside the Operating Room (OR). The purpose of this study was to investigate the first pass success rate for intubation with the AirTraq (AT) device utilizing only mannequin training in an air ambulance setting from Aug. 1 2009 to Aug. 1 2012 and compare it to direct laryngoscopy (DL). HYPOTHESIS We hypothesize that the AirTraq device will be as effective overall as direct laryngoscopy, and that this requires no OR training to achieve. METHODS A retrospective chart review of 161 intubations by air ambulance flight nurses from Aug. 1, 2009 to Aug. 1, 2012 was conducted. Data regarding date of service, devices used, number of attempts, rescue device use, and complications was gathered and analyzed. The generalized estimating equation and the chi-squared test were used to evaluate the data. RESULTS 161 intubations were reviewed. 135 met inclusion criteria. Overall first pass success rate for AT was 82% (68/83) and DL was 74% (35/47). Overall first use success rate for AT was 79% (71/90) and DL was 70% (43/61). The overall success rate of intubation for any patient in which either AT or DL was attempted is 96% (130/135). CONCLUSION AirTraq was shown to be as effective as direct laryngoscopy. All air crew training for the AirTraq device was performed on mannequins. The successof the device compared to DL shows that mannequin training is sufficient to implement the AirTraq device for pre-hospital intubation.


title: Capnography Prevents Hypoxia during Sedation for Dental Treatment: A Randomized Controlled Trial.

text: Intravenous sedation is useful for dental treatment in patients with intellectual disabilities. However, it is often necessary to manage such patients with deep sedation because their cooperation cannot be obtained. During deep sedation, undetected hypoventilation can lead to severe complications, such as hypoxia. Recently, capnographic monitoring has been advocated as a useful technique for preventing hypoxia during sedation. This randomized control trial evaluated whether the use of capnography reduces the incidence of hypoxia during the deep sedation of patients for dental treatment. This study involved patients with intellectual disabilities who underwent dental treatment under sedation. The subjects were randomized to the intervention group (I-group) or control group (C-group). All of the patients underwent routine monitoring, as well as bispectral index (BIS) and capnographic monitoring; however, only an independent observer had access to the patients' capnographic data during the dental procedures. Sedation was maintained at a BIS of 50 to 70 by administration of propofol. In the I-group, the independent observer signaled to the dental anesthesiologist if the capnogram indicated that the patient had been suffering from alveolar hypoventilation or apnea for >15 s. In the C-group, the observer signaled to the dental anesthesiologist if the capnogram indicated that the patient had been suffering from alveolar hypoventilation or apnea for >60 s. In both groups, the dental anesthesiologists responded to the signals using appropriate airway management strategies. The primary endpoint of this study was the incidence of hypoxia during dental treatment, which was defined as oxygen saturation of <95%. Hypoxemic episodes occurred in 13.4% and 34.8% of cases in the I-group and C-group, respectively. The incidence of hypoxia was significantly lower in the I-group. These results suggest that capnographic monitoring during deep sedation for dental treatment prevents hypoxemic episodes by allowing the early detection of hypoventilation. Knowledge Transfer Statement: This is the first randomized controlled trial to examine whether the use of capnography reduces the incidence of hypoxia during deep sedation for dental treatment. The findings of this study can be used by clinicians to aid decision-making regarding dental sedation standards at individual clinics. Moreover, they can be used as high-level evidence during the production or updating of clinical guidelines for dental sedation by leading associations.


title: Interferon Regulatory Factor 1 Protects against Chikungunya Virus-Induced Immunopathology by Restricting Infection in Muscle Cells.

text: The innate immune system protects cells against viral pathogens in part through the autocrine and paracrine actions of alpha/beta interferon (IFN-α/β) (type I), IFN-γ (type II), and IFN-λ (type III). The transcription factor interferon regulatory factor 1 (IRF-1) has a demonstrated role in shaping innate and adaptive antiviral immunity by inducing the expression of IFN-stimulated genes (ISGs) and mediating signals downstream of IFN-γ. Although ectopic expression experiments have suggested an inhibitory function of IRF-1 against infection of alphaviruses in cell culture, its role in vivo remains unknown. Here, we infected Irf1 -/- mice with two distantly related arthritogenic alphaviruses, chikungunya virus (CHIKV) and Ross River virus (RRV), and assessed the early antiviral functions of IRF-1 prior to induction of adaptive B and T cell responses. IRF-1 expression limited CHIKV-induced foot swelling in joint-associated tissues and prevented dissemination of CHIKV and RRV at early time points. Virological and histological analyses revealed greater infection of muscle tissues in Irf1 -/- mice than in wild-type mice. The antiviral actions of IRF-1 appeared to be independent of the induction of type I IFN or the effects of type II and III IFNs but were associated with altered local proinflammatory cytokine and chemokine responses and differential infiltration of myeloid cell subsets. Collectively, our in vivo experiments suggest that IRF-1 restricts CHIKV and RRV infection in stromal cells, especially muscle cells, and that this controls local inflammation and joint-associated swelling.IMPORTANCE Interferon regulatory factor 1 (IRF-1) is a transcription factor that regulates the expression of a broad range of antiviral host defense genes. In this study, using Irf1 -/- mice, we investigated the role of IRF-1 in modulating pathogenesis of two related arthritogenic alphaviruses, chikungunya virus and Ross River virus. Our studies show that IRF-1 controlled alphavirus replication and swelling in joint-associated tissues within days of infection. Detailed histopathological and virological analyses revealed that IRF-1 preferentially restricted CHIKV infection in cells of nonhematopoietic lineage, including muscle cells. The antiviral actions of IRF-1 resulted in decreased local inflammatory responses in joint-associated tissues, which prevented immunopathology.


title: Hybrid vaginal MA-NOS sleeve gastrectomy: technical note on the procedure in a patient.

text: BACKGROUND Standard sleeve gastrectomy for the morbidly obese is feasible and safe using the hybrid transvaginal minilaparoscopic-assisted natural orifice surgery (MA-NOS) with available laparoscopic/endoscopic instruments and technology as illustrated by this technical report on a female patient. METHODS The intervention was a transvaginal sleeve gastrectomy in a 67-year-old woman who was hypertensive, noninsulin-dependent with diabetes with morbid obesity (BMI, 37). Operative field view was maintained at all times with a gastroscope introduced through a transvaginal trocar. The surgeon positioned himself at the right side of the patient using a 2-mm needle port/mini-grasper placed in the left upper quadrant for traction of the greater curvature of the stomach. A 12-mm umbilical trocar was used as the port for insertion of the LigaSure device used for division of the short gastric vessels and the Endo-GIA stapler for creation of the gastric tube. The first assistant used a second mini-grasper for liver retraction and stomach positioning. The resected stomach was retrieved through the vagina. There were no intraoperative complications. The operative time was 150 minutes. RESULTS The advantages of minimally invasive surgery seemed to be enhanced with this hybrid laparoscopic approach. Postoperative course was uneventful. All component steps of a laparoscopic sleeve gastrectomy (LSG) were reproduced. The patient was discharged on the third postoperative day. CONCLUSIONS Transvaginal hybrid MA-NOS sleeve gastrectomy is both feasible and safe. The hybrid technique ensured safety during the performance of the procedure. MA-NOS is a potential option to avoid abdominal incisions and related complications for the laparoscopic resection of large intra-abdominal organs. Combined hybrid laparoscopic NOS for humans is currently a safe and reliable approach for major surgery through the NOS approach in female patients. Hybrid surgery allows controlled implementation of NOS techniques in clinical practice, providing a stepwise progression to the pure NOS approach once the appropriate technology has been developed. Additionally, it is the best way to stimulate the active development and evaluation of the underpinning technologies and instruments for these novel endoscopic surgical approaches. Appropriate clinical indications for these new procedures are yet to be defined. LSG is associated with short-term excess weight loss and resolution of comorbidities comparable to those obtained with other restrictive procedures. The performance of sleeve gastrectomy is an option in selected patients undergoing bariatric surgical treatment, particularly in the super obese and those who are considered high risk because of comorbid disease.


title: The differences in histological changes among pulmonary vessels divided with an energy device.

text: OBJECTIVES Histological changes after division of the pulmonary artery (PA) and the pulmonary vein (PV) using a vessel-sealing device are not fully understood. The goal of the present study was to clarify histologically and immunohistochemically how division with the device affects the wall layers of the pulmonary vasculature. METHODS This prospective cohort study analysed outcomes of 20 patients who underwent anatomical lung resection. After a single proximal ligation, the PA and the PV (diameter 2-7 mm) were divided using a LigaSure Blunt Tip (LSB). Histological findings and thermal damage were evaluated in vascular specimens from resected lungs. RESULTS The PA has a well-developed media with rich elastic fibres and a thin adventitia, whereas the PV has a thinner media and a thicker adventitia with abundant collagen fibres. Vascular division of the PAs and PVs appeared complete to the naked eye. However, in all divided PAs, the area adjacent to the sealed zone comprised only adventitia and thin disrupted media. Additionally, thermal energy generated by the LSB resulted in a wide area of thermal necrosis over the histologically fragile region in all cases. Conversely, the wall layers of all divided PVs were completely fused without disruption. Thermal spread and disruption did not significantly differ between small (2-4 mm) and large (5-7 mm) PAs [187 (150-253) vs 236 (190-275) μm, P = 0.22; 180 (138-200) vs 210 (161-305) μm, P = 0.22]. Histological changes differed significantly between the pulmonary vessels after division using the LSB. CONCLUSIONS Surgeons should consider that dividing the pulmonary vessels with a vessel-sealing device might have more histological impact on the layers of the wall of the PA than on those of the PV, although it remains unclear whether these findings constitute a clinical risk.


title: Nitrogenous subcutaneous emphysema caused by spray application of fibrin glue during retroperitoneal laparoscopic surgery.

text: We report a case of a patient treated by retroperitoneoscopic partial nephrectomy who developed nitrogenous subcutaneous emphysema (SCE) as a complication. The use of a nitrogen gas-pressured fibrin tissue adhesive applied as a spray caused excessively increased pressure in the closed retroperitoneal space and resulted in widespread SCE with protracted clinical course. To the best of our knowledge, this is the first report of nitrogenous SCE associated with pneumoperitoneum. The clinical significance of nitrogenous SCE is emphasized, and the risks associated with the use of fibrin glue as a spray during laparoscopic surgery are discussed.


title: Perioperative management of shock in two fontan patients with plastic bronchitis.

text: Plastic bronchitis is potentially a life-threatening complication of long-standing surgically palliated single ventricle congenital heart disease. Patients can present with hypoxia requiring urgent bronchoscopy for removal of bronchial casts. Perioperative care for these patients is challenging and anesthesia is associated with significant cardiac risk. As more surgically corrected single ventricle patients survive to adulthood, these patients are expected to present more frequently. This report details the perioperative management of 2 Fontan patients with hypoxia and significant plastic bronchitis disease burden.


Covid-19: Over 300 Italian doctors and scientists call for more testing.


'We need to be alert': Scientists fear second coronavirus wave as China's lockdowns ease.


title: Identifying process and outcome indicators of successful transitions from child to adult mental health services: protocol for a scoping review.

text: INTRODUCTION A significant proportion of youth need to transition from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS); however, the transition process is not well understood and often experienced poorly by youth. In the effort to design and evaluate standards of practice for transitions, there is a need to identify key elements of a successful transition. The objectives of this scoping review are to: (1) identify definitions of successful transitions from CAMHS to AMHS; and (2) identify indicators that have been used to measure CAMHS-AMHS transition care processes and quality, and outcomes. METHODS We will search 8 electronic bibliographic databases from 1980 to 2016 (eg, Medline, EMBASE, PsycINFO), professional associations, policy documents, and other grey literature to identify relevant material. We will include experimental, quasi-experimental, observational studies, and non-research studies (guidelines, narrative reviews, policy documents) examining the transition from CAMHS to AMHS. 2 raters will independently screen each retrieved title and abstract for eligibility using the study inclusion criteria (level 1), and then will independently assess full-text articles to determine if these meet the inclusion criteria (level 2). Data extraction will be completed and results will be synthesised both quantitatively and qualitatively. ETHICS AND DISSEMINATION The results of the scoping review will be used to develop a set of indicators that will be prioritised and evaluated in a Delphi consensus study. This will serve as a foundation for the development of the first instrument to assess the quality and success of CAMHS-AMHS transitions. Ethics approval is not required for this scoping study.


title: Effectiveness of workplace interventions in rehabilitating musculoskeletal disorders and preventing its consequences among workers with physical and sedentary employment: systematic review protocol.

text: BACKGROUND Musculoskeletal disorders (MSDs) are the leading cause of work disability and sickness absence worldwide. The prevalence of MSDs increases with age, consequently challenging sustainable employability among the growing ageing workforce. Knowledge of feasible and efficient workplace-based interventions to rehabilitate MSD or prevent its consequences is therefore warranted. This systematic review will evaluate the effectiveness of workplace-based interventions on MSDs and its consequences among adult workers with physical and sedentary work tasks, respectively. METHODS We will search the following bibliographic databases: PubMed (including the database 'MEDLINE') and Web of Science Core Collection (including the databases 'Science Citation Index Expanded', 'Social Sciences Citation Index' and 'Arts & Humanities Citation Index'). Manual searches will also be performed. We will include randomised controlled trials (RCTs) and non-RCTs reported in English in which (1) participants are adult workers with MSD, (2) interventions are aiming at rehabilitating pain symptoms of MSD or preventing the consequences of MSD and (3) interventions are initiated and/or carried out at the workplace. The review will adhere to the 'Preferred Reporting Items for Systematic reviews and Meta-Analyses' (PRISMA) guidelines for reporting systematic reviews and the Institute for Work and Health (IWH) guidelines for workplace-based interventions. For the primary evaluation of the review, the quality assessment and evidence synthesis will conform to the IWH guidelines. Secondary evaluation will include a meta-analysis (unless the included studies do not allow this due to heterogeneity) and employ the risk of bias domains recommended by Cochrane along with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach on the studies with pain intensity as an outcome. DISCUSSION This systematic review will provide knowledge on effective workplace-based interventions among physical and sedentary workers with MSD. RCTs are considered the most powerful experimental design in clinical trials, but solely including these may be too restrictive to understand effective workplace-based interventions where randomised and carefully controlled trials (RCTs) are not always possible. In order to maximize practical relevance, the selection process will, therefore, include both RCTs and non-RCTs and the quality assessment and evidence synthesis will conform to IWH guidelines focusing on developing practical guidelines for stakeholders. The result of this work will form the basis for industry-specific evidence-based recommendations on effective workplace-based interventions for rehabilitation of MSDs and its consequences that will later be operationalised into concrete and user-friendly practical tools for workplaces. SYSTEMATIC REVIEW REGISTRATION International Prospective Register of Systematic Reviews (PROSPERO) number CRD42018116752 .


title: What will it take to eliminate drug-resistant tuberculosis?

text: Drug-resistant tuberculosis (DR-TB) is challenging to diagnose, treat, and prevent, but this situation is slowly changing. If the world is to drastically reduce the incidence of DR-TB, we must stop creating new DR-TB as an essential first step. The DR-TB epidemic that is ongoing should also be directly addressed. First-line drug resistance must be rapidly detected using universal molecular testing for resistance to at least rifampin and, preferably, other key drugs at initial TB diagnosis. DR-TB treatment outcomes must also improve dramatically. Effective use of currently available, new, and repurposed drugs, combined with patient-centered treatment that aids adherence and reduces catastrophic costs, are essential. Innovations within sight, such as short, highly effective, broadly indicated regimens, paired with point-of-care drug susceptibility testing, could accelerate progress in treatment outcomes. Preventing or containing resistance to second-line and novel drugs is also critical and will require high-quality systems for diagnosis, regimen selection, and treatment monitoring. Finally, earlier detection and/or prevention of DR-TB is necessary, with particular attention to airborne infection control, case finding, and preventive therapy for contacts of patients with DR-TB. Implementing these strategies can overcome the barrier that DR-TB represents for global TB elimination efforts, and could ultimately make global elimination of DR-TB (fewer than one annual case per million population worldwide) attainable. There is a strong cost-effectiveness case to support pursuing DR-TB elimination; however, achieving this goal will require substantial global investment plus political and societal commitment at national and local levels.


title: Differences in Glycoprotein Complex Receptor Binding Site Accessibility Prompt Poor Cross-Reactivity of Neutralizing Antibodies between Closely Related Arenaviruses.

text: The glycoprotein complex (GPC) of arenaviruses, composed of stable signal peptide, GP1, and GP2, is the only antigen correlated with antibody-mediated neutralization. However, despite strong cross-reactivity of convalescent antisera between related arenavirus species, weak or no cross-neutralization occurs. Two closely related clade B viruses, Machupo virus (MACV) and Junín virus (JUNV), have nearly identical overall GPC architecture and share a host receptor, transferrin receptor 1 (TfR1). Given structural and functional similarities of the GP1 receptor binding site (RBS) of these viruses and the recent demonstration that the RBS is an important target for neutralizing antibodies, it is not clear how these viruses avoid cross-neutralization. To address this, MACV/JUNV chimeric GPCs were assessed for interaction with a group of α-JUNV GPC monoclonal antibodies (MAbs) and mouse antisera against JUNV or MACV GPC. All six MAbs targeted GP1, with those that neutralized JUNV GPC-pseudovirions competing with each other for RBS binding. However, these MAbs were unable to bind to a chimeric GPC composed of JUNV GP1 containing a small disulfide bonded loop (loop 10) unique to MACV GPC, suggesting that this loop may block MAbs interaction with the GP1 RBS. Consistent with this loop causing interference, mouse anti-JUNV GPC antisera that solely neutralized pseudovirions bearing autologous GP1 provided enhanced neutralization of MACV GPC when this loop was removed. Our studies provide evidence that loop 10, which is unique to MACV GP1, is an important impediment to binding of neutralizing antibodies and contributes to the poor cross-neutralization of α-JUNV antisera against MACV.IMPORTANCE Multiple New World arenaviruses can cause severe disease in humans, and some geographic overlap exists among these viruses. A vaccine that protects against a broad range of New World arenaviruses is desirable for purposes of simplicity, cost, and broad protection against multiple National Institute of Allergy and Infectious Disease-assigned category A priority pathogens. In this study, we sought to better understand how closely related arenaviruses elude cross-species neutralization by investigating the structural bases of antibody binding and avoidance. In our studies, we found that neutralizing antibodies against two New World arenaviruses, Machupo virus (MACV) and Junín virus (JUNV), bound to the envelope glycoprotein 1 (GP1) with JUNV monoclonal antibodies targeting the receptor binding site (RBS). We further show that altered structures surrounding the RBS pocket in MACV GP1 impede access of JUNV-elicited antibodies.


title: Angioplasty for renal artery stenosis in pediatric patients: an 11-year retrospective experience.

text: PURPOSE Studies of long-term percutaneous transluminal angioplasty (PTA) results have been less extensive in children than in adults. The authors sought to evaluate the outcomes of PTA for pediatric renovascular hypertension. MATERIALS AND METHODS The authors retrospectively evaluated 19 hypertensive children (ages 2-18 years) who underwent renal PTA from 1997-2009. Angiograms were reviewed in consensus to characterize lesions. This information was correlated with data from chart review to determine clinical outcomes. RESULTS Seven patients had neurofibromatosis type 1 (NF1), and 12 had fibromuscular dysplasia (FMD); one was lost to follow-up. Technical success was achieved in 29 of 32 lesions (91%). Cure of hypertension was achieved in seven of 18 patients (39%) and improvement in three (17%). There was a failed hypertension response in eight (44%): two with refractory stenosis, four with recurrent stenosis, and two with no response despite technical success. PTA was repeated in five children, all with failed response. Cure or improvement was seen in five of seven patients with NF1 and five of 11 with FMD. Most (nine of ten) patients with cure/improvement had single lesions or discrete lesions ≤ 10 mm. Residual stenosis < 10% was associated with cure/improvement (P = .0395). Three of five with bilateral and two of two with intraparenchymal disease demonstrated failure. The percentage of initial stenosis and presence of ostial lesions, aneurysms, or collaterals were not predictive of clinical response to PTA (P > .05). Cutting balloons were used after failure to efface with conventional balloons in seven patients and was successful in five of seven. CONCLUSIONS Despite a high rate of technical success, PTA provided a clinical benefit in a smaller majority of children. This study characterizes the utility of pediatric renal angioplasty and suggests criteria that may be prognostic of patient response.


title: Complications following 573 percutaneous renal radiofrequency and cryoablation procedures.

text: PURPOSE To review complications related to percutaneous renal tumor ablation. MATERIALS AND METHODS Prospectively collected data related to renal radiofrequency (RF) ablation and cryoablation procedures performed from May 2000 through November 2010 were reviewed. This included 573 renal ablation procedures performed in 533 patients to treat 633 tumors. A total of 254 RF ablation and 311 cryoablation procedures were performed; eight patients underwent simultaneous RF ablation and cryoablation. The mean age of patients at the time of the procedure was 70 years (range, 24-93 y), and 382 of 573 procedures (67%) were performed in male patients. Complications were recorded according to the Clavien-Dindo classification scheme. Duration of hospitalization was also documented. RESULTS Of the 573 procedures, 63 produced complications (11.0% overall complication rate). There were 66 reported complications, of which 38 (6.6% of total procedures) were Clavien-Dindo grade II-IV major complications; there were no deaths. Major complication rates did not differ statistically (P = .15) between cryoablation (7.7%; 24 of 311) and RF ablation (4.7%; 12 of 254). Of the complications related to cryoablation, bleeding and hematuria were most common. Bleeding during cryoablation was associated with advanced age, increased tumor size, increased number of cryoprobes, and central position (P < .05). Of those treated with RF ablation, nerve and urothelial injury were most common. Mean hospitalization duration was 1 day for RF ablation and cryoablation. CONCLUSIONS Complications related to percutaneous renal ablation are infrequent. Recognition of potential complications and associated risk factors can allow optimization of periprocedural care.


title: Inhibition of vaccinia virus replication by two small interfering RNAs targeting B1R and G7L genes and their synergistic combination with cidofovir.

text: In view of the threat of the potential use of variola virus in a terrorist attack, considerable efforts have been performed to develop new antiviral strategies against orthopoxviruses. Here we report on the use of RNA interference, either alone or in combination with cidofovir, as an approach to inhibit orthopoxvirus replication. Two selected small interfering RNAs (siRNAs), named siB1R-2 and siG7L-1, and a previously reported siRNA, i.e., siD5R-2 (which targets the viral D5R mRNA), were evaluated for antiviral activity against vaccinia virus (VACV) by plaque reduction and virus yield assays. siB1R-2 and siG7L-1, administered before or after viral infection, reduced VACV replication by more than 90%. Also, these two siRNAs decreased monkeypox virus replication by 95% at a concentration of 1 nM. siB1R-2 and siG7L-1 were demonstrated to specifically silence their corresponding transcripts, i.e., B1R and G7L mRNAs, without induction of a beta interferon response. Strong synergistic effects were observed when siB1R-2, siG7L-1, or siD5R-2 was combined with cidofovir. In addition, the antiviral activities of these three siRNAs were evaluated against VACV resistant to cidofovir and other acyclic nucleoside phosphonates. siG7L-1 and siD5R-2 remained active against four of five VACV mutants, while siB1R-2 showed activity against only one of the mutants. Our results showed that siRNAs are potent inhibitory agents in vitro, not only against wild-type VACV but also against several cidofovir-resistant VACV. Furthermore, we showed that a combined therapy using siRNA and cidofovir may be useful in the treatment of poxvirus infections.


title: Two-phase anaerobic co-digestion of food waste and sewage sludge.

text: The feasibility and performance of food waste and sewage sludge co-digestion were investigated to gain insight into their resource utilization. In this study, two-phase anaerobic digestion (TPAD) was operated under a total solids mixing ratio of 1:1 and different sludge retention times (SRTs). Results show that an acidogenic reactor with a 5-day SRT obtained the highest acidification efficiency, and its acetic acid content was dominant. The organic removal rate of a methanogenic reactor (MR) with a 20-day SRT and its corresponding TPAD system with a 25-day SRT were both the highest among the MRs and TPAD systems. Volatile solids and total chemical oxygen demand average removal efficiencies of the TPAD system with a 25-day SRT reached 64.7 and 60.8%, respectively. The MR with a 30-day SRT obtained the minimum ratio of volatile fatty acid to alkalinity (0.12). The methane content generated from the different MRs fluctuated at around 70%. All of the above results can provide reference for future research.


title: The recruitment of extra-intestinal cells to the injured mucosa promotes healing in radiation enteritis and chemical colitis in a mouse parabiosis model.

text: Mucosal healing occurs through migration and proliferation of cells within injured epithelium, yet these processes may be inadequate for mucosal healing after significant injury where the mucosa is denuded. We hypothesize that extra-intestinal cells can contribute to mucosal healing after injury to the small and large intestine. We generated parabiotic pairs between wild-type and tdTomato mice, which were then subjected to radiation-induced enteritis and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. We now show that as compared with singleton mice, mice with a parabiotic partner were protected against intestinal damage as revealed by significantly reduced weight loss, reduced expression of pro-inflammatory cytokines, reduced enterocyte apoptosis, and improved crypt proliferation. Donor cells expressed CD45-, Sca-1+, c-kit+, and CXCR4+ and accumulated around the injured crypts but did not transdifferentiate into epithelia, suggesting that extra-intestinal cells play a paracrine role in the healing response, while parabiotic pairings with Rag1-/- mice showed improved healing, indicating that adaptive immune cells were dispensable for mucosal healing. Strikingly, ablation of the bone marrow of the donor parabionts removed the protective effects. These findings reveal that the recruitment of extra-intestinal, bone marrow-derived cells into the injured intestinal mucosa can promote mucosal healing, suggesting novel therapeutic approaches for severe intestinal disease.


title: Mechanical thrombectomy for acute stroke in childhood: how much does restricted diffusion matter?

text: Mechanical thrombectomy holds promise for children with large cerebral arterial occlusions, although there are few reports in this population. We report a case of retrievable stent-assisted mechanical thrombectomy in a 5-year-old with basilar artery occlusion, despite late presentation and extensive initial diffusion-weighted imaging (DWI) restriction. This resulted in successful Thrombolysis in Cerebral Infarction 2B reperfusion and excellent clinical outcome. At 6-week follow-up he was completely back to baseline with no residual deficits (pediatric stroke outcome measure=0, modified Rankin scale=0). At 3-month follow-up the patient has not had any recurrent stroke or concern for stroke-like symptoms. We review the literature on mechanical thrombectomy and DWI changes in acute stroke in early to middle childhood (<12 years old).


title: New procedures for uterine prolapse.

text: Traditionally, vaginal hysterectomy and Manchester repair were the surgical approaches to treating uterine prolapse; however, both are associated with a relatively high subsequent vaginal vault recurrence. Laparoscopic uterine suspension is a new way of maintaining uterine support. Many women are keen to keep their uterus for a variety of reasons, including maintaining reproductive capability and the belief that the uterus, cervix, or both, may play a part of their gender identity. Non-removal of the uterus may retain functional (e.g. bowel, bladder and sexual) benefits. Therefore, the concept of uterine preservation for pelvic-organ prolapse has been of interest to pelvic-floor surgeons for many decades. In this review, we provide an overview of the available evidence on treating uterine prolapse surgically. We describe techniques to support the vault during hysterectomy, and examine the evidence for uterine-sparing surgery. Comparative outcomes for vaginal, abdominal and laparoscopic routes will be made.


title: Comparison of prenatal and postnatal treatments of spina bifida in Poland--a non-randomized, single-center study.

text: OBJECTIVE The aim of this study was a comparison of the outcomes of intrauterine myelomeningocele (MMC) repairs (IUMR) in type II Chiari malformation (II CM) fetuses with clinical data of newborns and infants operated on postnatally. METHODS The study group (SG) comprised 46 pregnant women whose type II CM children underwent IUMR, while 47 pregnant women whose type II CM children were operated on postnatally constituted the control group (CG). A total of 24 SG and 20 CG patients reached the endpoint of the study. RESULTS High incidence of prelabor rupture of membranes (24 (52.2%), CI: 3.74 (1.69-8.26) (p < 0.001) was noted in the group of prenatal surgeries as compared to controls. The need for ventriculoperitoneal shunt implantation was statistically significantly lower (p < 0.008) in the group of children after IUMR as compared to controls (5 (27.8%) and 16 (80%), respectively, CI: 0.35 (0.16-0.75). None of the postnatally treated CG children can walk without adaptive equipment. In contrast, two children from the SG (2 (11.1%) CI: 1.86 (1.00-3.48) p < 0.05) are able to walk independently. CONCLUSIONS Prenatal MMC closure significantly lowers further adverse evolution of the II CM. Further studies are needed, especially on preventive measures for preterm labor and iatrogenic preterm prelabor rupture of membranes (iPPRM) in the postoperative course of IUMR.


title: Design and evaluation of sifuvirtide, a novel HIV-1 fusion inhibitor.

text: Enfuvirtide (T20) is the first and only HIV-1 fusion inhibitor approved for clinical use, but it can easily induce drug resistance limiting its practical application. A novel anti-HIV peptide, termed sifuvirtide, was designed based on the three-dimensional structure of the HIV-1 gp41 fusogenic core conformation. Here we report its in vitro anti-HIV potency, its mechanism of action, as well as the results from Phase Ia clinical studies. We demonstrated that sifuvirtide inhibited HIV-1-mediated cell-cell fusion in a dose-dependent manner and exhibited high potency against infections by a wide range of primary and laboratory-adapted HIV-1 isolates from multiple genotypes with R5 or X4 phenotypes. Notably, sifuvirtide was also highly effective against T20-resistant strains. Unlike T20, sifuvirtide could efficiently block six-helix bundle formation in a dominant negative fashion. These results suggest that sifuvirtide has a different mechanism of action from that of T20. Phase Ia clinical studies of sifuvirtide (FS0101) in 60 healthy individuals demonstrated good safety, tolerability, and pharmacokinetic profiles. A single dose regimen (5, 10, 20, 30, and 40 mg) by subcutaneous injection once daily at abdominal sites was well tolerated without serious adverse events. Pharmacokinetic studies of single and multiple administration of sifuvirtide showed that its decay half-lives were 20.0 +/- 8.6 h and 26.0 +/- 7.9 h, respectively. In summary, sifuvirtide has potential to become an ideal fusion inhibitor for treatment of HIV/AIDS patients, including those with HIV-1 strains resistant to T20.


Curbing Youth E-cigarette Use Must Remain a Priority.


title: Is intraoperative neural monitoring necessary for exploration of the superior laryngeal nerve?

text: BACKGROUND We aimed to evaluate the contribution of intraoperative neuromonitoring to the visual and functional identification of the external branch of the superior laryngeal nerve and the effect on postoperative voice changes. METHODS The prospective data of 221 patients (183 women, 38 men) who underwent thyroid operation with intraoperative neuromonitoring for exploration of the external branch of the superior laryngeal nerve were evaluated retrospectively. The surface endotracheal tube-based Medtronic NIM3 (Medtronic, Jacksonville, FL) intraoperative neuromonitoring device was used. The function of the external branch of the superior laryngeal nerve was evaluated by cricothyroid muscle twitch. Additionally, the contribution of the external branch of the superior laryngeal nerve to vocal cord adduction was evaluated using electromyographic records. RESULTS A total of 374 (95.2%) of 393 external branch of the superior laryngeal nerves were identified; 145 (36.9%) external branch of the superior laryngeal nerves were identified visually before being stimulated with a probe, and 130 (33.1%) external branch of the superior laryngeal nerves were identified visually after being identified with a probe. Although 99 (25.2%) external branch of the superior laryngeal nerves were identified with a probe, they were not visualized. Intraoperative neuromonitoring provided meaningful contributions to visual (P = .001) and functional (P = .001) identification of the external branch of the superior laryngeal nerve. Positive electromyographic responses were recorded from 257 external branch of the superior laryngeal nerves (68.7%). After the patients with recurrent laryngeal nerve palsy were excluded, voice changes were detected in 6 (3.3%) of 184 patients with identified external branch of the superior laryngeal nerves and 3 (20%) of 15 patients in whom at least 1 external branch of the superior laryngeal nerve could not be identified with intraoperative neuromonitoring. CONCLUSION Intraoperative neuromonitoring provided an important contribution to the visual and functional identification of the external branch of the superior laryngeal nerve. Intraoperative neuromonitoring is a helpful adjunct for identifying the external branch of the superior laryngeal nerve.


title: A new method for the radiochemical purity measurement of ¹¹¹In-pentetreotide.

text: OBJECTIVES AND METHODS The recommended method for the measurement of radiochemical purity (RCP) of ¹¹¹In-labelled pentetreotide is thin-layer chromatography with a silica gel as the stationary phase and a 0.1 N sodium citrate solution (pH 5) as the mobile phase. According to the supplier's instructions, the mobile phase must be prepared before the test is carried out, and the recommended stationary phase is off-market. We propose a new method for RCP measurement in which the mobile phase is acid citrate dextrose, solution A, which does not need to be prepared beforehand, and thin-layer chromatography is performed with a silica gel-impregnated glass fibre sheet as the stationary phase. We used both methods to measure the percentages of radiopharmaceutical and impurities. RESULTS The range of RCP values obtained was 98.0-99.9% (mean=99.3%) by the standard method and 98.1-99.9% (mean=99.2%) by the new method. We observed no differences between the RCP values of both methods (P=0.070). CONCLUSION The proposed method is suitable for RCP testing because it yields results that are in good agreement with those of the standard method and because it is easier to perform as the mobile-phase solution need not be prepared in advance.


title: Development of a Taqman RT-PCR assay for the detection and quantification of negatively stranded RNA of human enteroviruses: evidence for false-priming and improvement by tagged RT-PCR.

text: Human enteroviruses are among the most common viruses infecting humans. These viruses are known to be able to infect a wide range of tissues and are believed to establish persistent infections. Enteroviruses are positive-sense single-stranded RNA viruses whose replication involves the synthesis of negative strand intermediates. Therefore, the specific detection of negatively stranded viral RNA in tissues or cells is a reliable marker of active enteroviral replication. The present report presents the development of a real-time RT-PCR allowing the specific detection and quantification of negatively stranded viral RNA. Since it was known that specific amplification of single-stranded RNA can be made difficult by false-priming events leading to false-positive or overestimated results, the assay was developed by using a tagged RT primer. This tagged RT-PCR was shown to be able to amplify specifically negative RNA of enteroviruses grown in cell cultures by preventing the amplification of cDNAs generated by false-priming.


title: Intraoperative tissue oxygenation and postoperative outcomes after major non-cardiac surgery: an observational study.

text: BACKGROUND The relationship between tissue oxygen saturation (StO(2)) and serious postoperative complications remains unclear. We tested the hypothesis that perioperative in patients undergoing major non-cardiac surgery is inversely related to serious surgical outcomes. METHODS We enrolled 124 patients, ASA physical status ≤IV, having elective major non-cardiac surgeries with general anaesthesia. An InSpectra Model 650 StO(2) monitor (Hutchinson Technology, Hutchinson, MN, USA) was used to measure at the thenar eminence throughout surgery and for two postoperative hours. Our primary outcome was a composite of 30 day mortality and serious in-hospital complications. The secondary outcome was an a priori subset of the primary composite outcome representing infectious and wound-healing complications. Multivariable logistic regression was used to evaluate the associations between our primary and secondary outcomes and time-weighted average (TWA) and minimum . RESULTS Patients were 61 (12), mean (SD) yr old. The minimum was inversely associated with our primary composite outcome (P=0.02). The estimated odds ratio (97.5% CI) of having any major postoperative morbidity was 0.82 (0.67, 1.00) for a 5% increase in the minimum . In contrast, TWA was not significantly associated with major postoperative morbidity (P=0.35). Furthermore, neither TWA (P=0.65) nor minimum (P=0.70) was significantly associated with wound complications. CONCLUSIONS Minimum perioperative peripheral tissue oxygenation predicted a composite of major complications and mortality from major non-cardiac surgery. This is an observational association and whether clinical interventions to augment tissue oxygenation will improve outcomes remains to be determined.


title: A preliminary study of silver sodium zirconium phosphate polyurethane foam wound dressing on wounds of the distal aspect of the forelimb in horses.

text: OBJECTIVE To determine if application of silver sodium zirconium phosphate polyurethane semi-occlusive foam (SPF) dressing would improve measures of wound healing and decrease bacterial contamination compared with a non-adherent, absorbent dressing applied to wounds created on the distal aspect of the equine limb. STUDY DESIGN Controlled randomized experimental study. ANIMALS Adult Quarter Horse and Thoroughbred horses (n = 5). METHODS One 6.25 cm(2) wound was created on the dorsomedial aspect of the proximal metacarpus on each forelimb. A SPF dressing was applied to 1 randomly assigned limb as a treatment and a non-adherent, absorbent dressing was applied to the opposite limb as control. Bandages were changed every 3 days for 60 days. Granulation tissue was scored every 3 days, wound area measured every 6 days, and wound bed was cultured every 12 days. RESULTS SPF-treatment wounds had significantly decreased wound area and decreased granulation tissue scores when evaluated <30 days and over the 60 day study, although complete wound healing times were not significantly different. Bacteria were cultured from all wounds at varying times throughout the study. CONCLUSIONS The SPF wound dressing improved some measures of wound healing compared with the control dressing, most significantly during the first 30 days. This suggests that the SPF wound dressing may be useful in the early management of wounds on the equine lower limb. Further studies using the SPF dressing are needed to characterize the temporal and cellular effects on wound healing and evaluate this dressing in a clinical environment.


title: Canadian Stroke Best Practice Recommendations: Hyperacute Stroke Care Guidelines, Update 2015.

text: The 2015 update of the Canadian Stroke Best Practice Recommendations Hyperacute Stroke Care guideline highlights key elements involved in the initial assessment, stabilization, and treatment of patients with transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and acute venous sinus thrombosis. The most notable change in this 5th edition is the addition of new recommendations for the use of endovascular therapy for patients with acute ischemic stroke and proximal intracranial arterial occlusion. This includes an overview of the infrastructure and resources required for stroke centers that will provide endovascular therapy as well as regional structures needed to ensure that all patients with acute ischemic stroke that are eligible for endovascular therapy will be able to access this newly approved therapy; recommendations for hyperacute brain and enhanced vascular imaging using computed tomography angiography and computed tomography perfusion; patient selection criteria based on the five trials of endovascular therapy published in early 2015, and performance metric targets for important time-points involved in endovascular therapy, including computed tomography-to-groin puncture and computed tomography-to-reperfusion times. Other updates in this guideline include recommendations for improved time efficiencies for all aspects of hyperacute stroke care with a movement toward a new median target door-to-needle time of 30 min, with the 90th percentile being 60 min. A stronger emphasis is placed on increasing public awareness of stroke with the recent launch of the Heart and Stroke Foundation of Canada FAST signs of stroke campaign; reinforcing the public need to seek immediate medical attention by calling 911; further engagement of paramedics in the prehospital phase with prehospital notification to the receiving emergency department, as well as the stroke team, including neuroradiology; updates to the triage and same-day assessment of patients with transient ischemic attack; updates to blood pressure recommendations for the hyperacute phase of care for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The goal of these recommendations and supporting materials is to improve efficiencies and minimize the absolute time lapse between stroke symptom onset and reperfusion therapy, which in turn leads to better outcomes and potentially shorter recovery times.


Focal Cerebral Arteriopathy in a COVID-19 Pediatric Patient.


Using socioeconomics to counter health disparities arising from the covid-19 pandemic.


title: Homologs of aminoacyl-tRNA synthetases acylate carrier proteins and provide a link between ribosomal and nonribosomal peptide synthesis.

text: Aminoacyl-tRNA synthetases (aaRSs) are ancient and evolutionary conserved enzymes catalyzing the formation of aminoacyl-tRNAs, that are used as substrates for ribosomal protein biosynthesis. In addition to full length aaRS genes, genomes of many organisms are sprinkled with truncated genes encoding single-domain aaRS-like proteins, which often have relinquished their canonical role in genetic code translation. We have identified the genes for putative seryl-tRNA synthetase homologs widespread in bacterial genomes and characterized three of them biochemically and structurally. The proteins encoded are homologous to the catalytic domain of highly diverged, atypical seryl-tRNA synthetases (aSerRSs) found only in methanogenic archaea and are deprived of the tRNA-binding domain. Remarkably, in comparison to SerRSs, aSerRS homologs display different and relaxed amino acid specificity. aSerRS homologs lack canonical tRNA aminoacylating activity and instead transfer activated amino acid to phosphopantetheine prosthetic group of putative carrier proteins, whose genes were identified in the genomic surroundings of aSerRS homologs. Detailed kinetic analysis confirmed that aSerRS homologs aminoacylate these carrier proteins efficiently and specifically. Accordingly, aSerRS homologs were renamed amino acid:[carrier protein] ligases (AMP forming). The enzymatic activity of aSerRS homologs is reminiscent of adenylation domains in nonribosomal peptide synthesis, and thus they represent an intriguing link between programmable ribosomal protein biosynthesis and template-independent nonribosomal peptide synthesis.


title: Postoperative effects of laparoscopic sleeve gastrectomy in morbid obese patients with type 2 diabetes.

text: BACKGROUND Laparoscopic Sleeve Gastrectomy has become one of the most popular bariatric surgery types and helps treating not only obesity but also endocrinological diseases related to obesity. Therefore we aimed to evaluate the effects of laparoscopic sleeve gastrectomy on the treatment of type 2 diabetes. METHODS All patients, who underwent morbid obesity surgery during 2013-2014 and had a HbA1c >6 % were included in this prospective study. Demographical data, usage of oral antidiabetic drugs or insulin were recorded, and laboratory findings as HbA1c and fasting plasma glucose were evaluated preoperatively and postoperatively at the 6th and 12th months. Diabetes remission criteria were used to assess success of the surgical treatment. RESULTS Totally 88 patients were included in this study. 55 patients were using oral antidiabetic drugs and 33 patients were using insulin. At the 6th month complete remission was observed in 80 (90.9 %), partial remission in 3 (3.4 %) and persistent diabetes in 5 (5.6 %) patients. At the 12th month complete remission was observed in 84 (95.4 %), partial remission in 1 (1.1 %) and persistent diabetes in 3 (3.4 %) patients. CONCLUSIONS This study indicated that laparoscopic sleeve gastrectomy surgery achieved a complete remission of diabetes in 95.4 % patients having type 2 diabetes during a 1 year fallow up period. However, complete remission of type 2 diabetes has been reported as 80 % during long term fallow up in the literature. In our opinion this rate may change with longer follow up periods and studies involving more patients suffering type 2 diabetes.


title: Identification of patient venous thromboembolism risk across the continuum of care.

text: Venous thromboembolism (VTE) complications are the leading cause of preventable in-hospital mortality and morbidity in the United States. Initiatives by the National Quality Forum, the Joint Commission, and the Surgical Care Improvement Project aim to improve the prevention of VTE and emphasize the need to recognize the risk of the condition in hospitalized patients. In clinical practice, individual risk assessment using a validated scoring system provides patients with the best care in the prevention of VTE. This is accomplished by a weighted scoring of risk factors, selection of the most appropriate prevention strategy for patients at risk, and regular risk review across the continuum of care. All hospitals should have a local, written, care pathway which assesses inpatient risk of VTE as early as possible upon admission and identifies members of the health care team responsible for applying risk assessment. Venous thromboembolism risk should be regularly reassessed for any changes in the level of risk, with extended out-of-hospital prophylaxis considered for patients with continued risk factors, such as prolonged immobility or illness, treated at home, or in a long-term care facility. Finally, a mandatory alert system requiring the clinician to address the issue of prophylaxis before any orders are carried out by the nursing staff is one way to protect all hospitalized patients.


Persistence of viral RNA in stool samples from patients recovering from covid-19.


title: A systematic review of the effectiveness of employer-led interventions for drug misuse.

text: AIMS Employers in the United States incur substantial costs associated with substance use disorders. Our goal was to examine the effectiveness of employer-led interventions to reduce the adverse effects of drug misuse in the workplace. METHODS We conducted a systematic review of studies that evaluated the effectiveness of recommended workplace interventions for opioids and related drugs: employee education, drug testing, employee assistance programs, supervisor training, written workplace drug-free policy, and restructuring employee health benefit plans. We searched PubMed MEDLINE, EMBASE (embase.com), PsycINFO (Ebsco), ABI Inform Global, Business Source Premier, EconLit, CENTRAL, Web of Science (Thomson Reuters), Scopus (Elsevier), Proquest Dissertations, and Epistemonikos from inception through May 8, 2019, with no date or language restrictions. We included randomized controlled trials, quasi-experimental studies, and cross-sectional studies with no language or date restrictions. The Downs and Black questionnaire was used to assess the quality of included studies. The results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. RESULTS In all, 27 studies met our inclusion criteria and were included in the systematic review. Results were mixed, with each intervention shown to be effective in at least one study, but none showing effectiveness in over 50% of studies. Studies examining the impact of interventions on workplace injuries or accidents were more commonly reported to be effective. Although four studies were randomized controlled trials, the quality of all included studies was "fair" or "poor." CONCLUSIONS Despite the opioid epidemic, high-quality studies evaluating the effectiveness of employer-led interventions to prevent or reduce the adverse effects of substance use are lacking. Higher quality and mixed methods studies are needed to determine whether any of the interventions are generalizable and whether contextual adaptations are needed. In the meantime, there is a reason to believe that commonly recommended, employer-led interventions may be effective in some environments.


title: A bench study of the effects of leak on ventilator performance during noninvasive ventilation.

text: BACKGROUND During noninvasive ventilation (NIV), leak around the mask may cause inadequate ventilatory support or patient-ventilator asynchrony such as auto-triggering. Some NIV ventilators may be better than others at compensating for leak. METHODS We bench studied 3 NIV ventilators (Vision, Carina, and Trilogy100) and 2 ICU ventilators (Puritan Bennett 840 and Evita XL) to assess how they coped with 2 leak levels and zero leak during NIV. With a 2-bellows-in-a-box lung model we simulated spontaneous breathing with tidal volumes of 300 mL and 500 mL, at pressure support of 0 and 10 cm H(2)O and PEEP of 5 and 10 cm H(2)O. We affixed the airway opening of the lung model to the mouth of a mannequin head and secured a mask on the mannequin face. We created a medium leak and a large leak with different size holes, and measured PEEP in the presence of leak. We also measured the actual pressure-support values and calculated the deviations from the set pressure-support value and the pressure-time product (PTP) of the airway opening pressure below and above baseline. RESULTS With the medium leak only the Vision and Carina maintained the set PEEP and pressure support. With the large leak the pressure support was decreased with all the tested ventilators. With the larger leak and pressure support of 10 cm H(2)O the PTP below baseline for triggering increased with 2 ventilators, and the PTP above baseline for supporting the patient's inspiratory effort decreased with all 5 ventilators. The larger tidal volume increased the PTP below baseline with all 5 ventilators and at all leak sizes. CONCLUSIONS Some of the ventilators compensated for leak better than others. With the larger leak none of the ventilators maintained the set PEEP or pressure support.


title: ABCD: Update of the 2009 guidelines on prevention and management of feline infectious diseases.

text: OVERVIEW In this article, the ABCD guidelines published in the JFMS Special Issue of July 2009 (Volume 11, Issue 7, pages 527-620) are updated by including previously unavailable and novel information. For a better picture, the reader is advised to consult that issue before focusing on the novel features.


title: Otitis and meningoencephalitis associated with infectious coryza ( Avibacterium paragallinarum) in commercial broiler chickens.

text: Infectious coryza, caused by Avibacterium paragallinarum, is an acute respiratory disease of poultry that can result in substantial morbidity, mortality, and economic losses. In March 2017, the Turlock branch of the California Animal Health and Food Safety laboratory system encountered an unusual clinical and pathologic presentation of infectious coryza in 6 live, 29-d-old, commercial broiler chickens that were submitted for diagnostic investigation. Antemortem evaluation revealed severe neurologic signs, including disorientation, torticollis, and opisthotonos. Swollen head-like syndrome and sinusitis were also present. Histologically, severe sinusitis, cranial osteomyelitis, otitis media and interna, and meningoencephalitis were noted, explaining the clinical signs described. A. paragallinarum was readily isolated from the upper and lower respiratory tract, brain, and cranial bones. Infectious bronchitis virus (IBV) was also detected by PCR, and IBV was isolated in embryonated chicken eggs. Based on sequencing analysis, the IBV appeared 99% homologous to strain CA1737. A synergistic effect between A. paragallinarum and IBV, resulting in exacerbation of clinical signs and increased mortality, may have occurred in this case. A. paragallinarum should be considered among the possible causes of neurologic signs in chickens. Appropriate media should be used for bacterial isolation, and the role of additional contributing factors and/or complicating agents should be investigated in cases of infectious coryza.


title: Mechanical thrombectomy using the Solitaire stent in a left main coronary artery: A novel approach to coronary thrombus retrieval.

text: The Solitaire stent is a self-expanding nitinol, fully retrievable stent that was originally designed for applications in cerebral circulation. Expanded indications for its use in mechanical embolectomy during acute ischemic stroke have proven safe and effective. Herein, we describe a novel use of this stent to perform a mechanical thrombectomy of a large left main coronary artery thrombus. © 2016 Wiley Periodicals, Inc.


title: ImmunoSPECT and immunoPET of IGF-1R expression with the radiolabeled antibody R1507 in a triple-negative breast cancer model.

text: UNLABELLED The insulinlike growth factor 1 receptor (IGF-1R) is a new target for the treatment of breast cancer. Patients with breast cancer lesions that express IGF-1R may benefit from treatment with anti-IGF-1R antibodies. Therefore, the aim of the present study was to develop a noninvasive, in vivo imaging method, using radiolabeled antibodies, to visualize IGF-1R expression. METHODS R1507 is a monoclonal antibody directed against the IGF-1R. In vitro, the affinity and internalization kinetics of (111)In-R1507 were determined using the IGF-1R-expressing triple-negative breast cancer cell line SUM149. In vivo, the pharmacodynamics of (111)In-R1507 and (125)I-R1507 were determined in mice with subcutaneous SUM149 tumors. (111)In-R1507 SPECT and (89)Zr-R1507 PET images of mice with subcutaneous SUM149 tumors were acquired at 1, 3, and 7 d after injection. RESULTS (111)In-R1507 (concentration required to inhibit binding by 50%, 0.1 nM) was slowly internalized by SUM149 cells. (111)In-R1507 specifically and efficiently accumulated in the SUM149 xenografts: the tumor uptake was 20 percentage injected dose per gram (%ID/g), 33 %ID/g, and 31 %ID/g at 1, 3, and 7 d after injection, respectively. (125)I-R1507 accumulated in the tumor less efficiently. Small-animal SPECT and small-animal PET of mice clearly visualized the subcutaneous SUM149 xenograft, with increasing contrast at later time points. CONCLUSION (111)In-R1507 and (89)Zr-R1507 are new tracers to noninvasively determine IGF-1R expression in vivo in breast cancer xenografts using SPECT and PET. In the future, these techniques may enable patient selection for IGF-1R-targeted therapy.


title: Endovascular management of carotid artery dissections with the use of new generation stents and protection systems.

text: Dissection of the internal carotid artery (ICA) is a rare disease, but in young patients is responsible for about 20% of cerebral events. We presented three different cases of ICA dissection, including one iatrogenic and two spontaneous ones, which were successfully managed endovascularly, with the use of different techniques, different protection devices and stents. In this article, the clinical management and details of procedures were described.


title: Rewarming from therapeutic hypothermia induces cortical neuron apoptosis in a swine model of neonatal hypoxic-ischemic encephalopathy.

text: The consequences of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy are poorly understood. Adverse effects from suboptimal rewarming could diminish neuroprotection from hypothermia. Therefore, we tested whether rewarming is associated with apoptosis. Piglets underwent hypoxia-asphyxia followed by normothermic or hypothermic recovery at 2 hours. Hypothermic groups were divided into those with no rewarming, rewarming at 0.5 °C/hour, or rewarming at 4 °C/hour. Neurodegeneration at 29 hours was assessed by hematoxylin and eosin staining, TUNEL assay, and immunoblotting for cleaved caspase-3. Rewarmed piglets had more apoptosis in motor cortex than did those that remained hypothermic after hypoxia-asphyxia. Apoptosis in piriform cortex was greater in hypoxic-asphyxic, rewarmed piglets than in naive/sham piglets. Caspase-3 inhibitor suppressed apoptosis with rewarming. Rapidly rewarmed piglets had more caspase-3 cleavage in cerebral cortex than did piglets that remained hypothermic or piglets that were rewarmed slowly. We conclude that rewarming from therapeutic hypothermia can adversely affect the newborn brain by inducing apoptosis through caspase mechanisms.


title: Autonomic testing for prediction of competition performance in Paralympic athletes.

text: While we now appreciate that autonomic dysfunction can impact wheelchair rugby performance, this is currently not being assessed during classification, largely due to lack of a standardized and evidence-based strategy to assess autonomic function. Our aim, therefore, was to establish the optimal autonomic testing protocol that best predicts cardiovascular capacity during competition by comprehensively examining autonomic function in elite wheelchair rugby athletes with cervical SCI and thereby enhance the standardized classification. Twenty-six individuals with cervical SCI (C4-C8; AIS A, B, C) participated in this study during the 2015 Parapan American Games in Toronto, Canada. Clinic autonomic testing included: sympathetic skin responses, baseline hemodynamics, orthostatic challenge test, and cold-pressor tests. Further, we completed standard motor/sensory assessments and obtained each participants' International Wheelchair Rugby Federation classification. These clinic metrics were correlated to in-competition heart rate monitoring obtained during competition. The current study provides novel evidence that the change in systolic blood pressure during an orthostatic challenge test predicts approximately 50% of the in-competition peak heart rate (P<.001). Conversely, International Wheelchair Rugby Federation classification was poorly associated with in-competition peak heart rate (R2 =.204; P<.05). Autonomic testing provides deep insight regarding preserved autonomic control after SCI that is associated with performance in elite wheelchair rugby athletes. As such, incorporating assessments of cardiovascular capacity in classification will help to ensure a level playing field and may obviate the need for practices such as boosting to gain an advantage due to poor cardiovascular control.


title: Icariin Protects against Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats.

text: BACKGROUND/AIMS Glucocorticoid (GC)-related osteonecrosis of the femoral head (ONFH) is a common complication following administration of steroids to treat many diseases. Our previous study demonstrated that icariin (ICA) might have a beneficial effect on the bone marrow mesenchymal stem cells (BMSCs) of patients with steroid-associated osteonecrosis. In this study, we investigated the underlying mechanisms of ICA associated with the potential enhancement of osteogenesis and anti-adipogenesis in GC-related ONFH. METHODS In vitro cell proliferation was evaluated by CCK-8 assay. Alizarin red S and alkaline phosphatase (ALP) activity were used to measure osteogenic differentiation, while adipogenic differentiation was revealed by oil red O staining and TG content assay. The expression level of osteogenesis-associated genes and PPARγ was evaluated by RT-qPCR, western blotting and immunofluorescence. A total of 30 female SD rats were randomly separated into three groups: a control group, a methylprednisolone (MPS) group and a MPS + ICA group. Serum ALP and TG (triglyceride), micro-CT scanning, histological and immunohistochemical analyses were performed in the animal model. RESULTS In the in vitro study, ICA promoted proliferation, improved osteogenic differentiation and suppressed adipogenic differentiation of BMSCs treated with MPS. The group treated with MPS and 10-6 M ICA expressed higher levels of Runx2, ALP, bone morphogenetic protein (BMP) 2, and OC and lower expression of PPARγ than the MPS group. In the in vivo study, ICA prevented bone loss in a rat model of GC-related ONFH as shown by micro-CT scanning, histological and immunohistochemical analyses. CONCLUSIONS ICA is an effective compound for promoting bone repair and preventing or delaying the progression of GC-associated ONFH in rats. This effect can be explained by its ability to improve the balance between adipogenesis and osteogenesis, indicating that ICA is an effective candidate for management of GC-associated ONFH.