title: Reduced Susceptibility to VIRIP-Based HIV-1 Entry Inhibitors Has a High Genetic Barrier and Severe Fitness Costs.

text: VIRIP has been identified as natural HIV-1 inhibitor targeting the gp41 fusion peptide. An optimized analogue (VIR-576) was effective in a phase I/II clinical trial and initial studies showed that HIV-1 resistance to VIRIP-based inhibitors has a high genetic barrier. Partially resistant CXCR4 (X4)-tropic HIV-1 NL4-3 variants could be obtained, however, after more than 15 months of passaging in MT-4 cells in the presence of another derivative (VIR-353). Sequence analyses identified the accumulation of seven mutations across the HIV-1 envelope glycoprotein but outside the gp41 fusion peptide. The authors suggested that the three initial alterations conferred resistance, while subsequent changes restored viral fitness. Here, we introduced these mutations individually and in combination into X4- and CCR5 (R5)-tropic HIV-1 constructs and determined their impact on VIR-353 and VIR-576 susceptibility, viral infectivity, replication fitness, and fusogenicity. We found that essentially all seven mutations contribute to reduced susceptibility to VIRIP-based inhibitors. HIV-1 constructs containing ≥4 changes were substantially more resistant to both VIRIP-based inhibitors and the VRC34.01 antibody targeting the fusion peptide. However, they were also much less infectious and fusogenic than those harboring only the three initial alterations. Furthermore, the additional changes attenuated rather than rescued HIV-1 replication in primary human cells. Thus, the genetic barrier to HIV-1 resistance against VIRIP-based inhibitors is higher than previously suggested, and mutations reducing viral susceptibility come at a severe fitness cost that was not rescued during long-term cell culture passage.IMPORTANCE Many viral pathogens are critically dependent on fusion peptides (FPs) that are inserted into the cellular membrane for infection. Initially, it was thought that FPs cannot be targeted for therapy because they are hardly accessible. However, an optimized derivative (VIR-576) of an endogenous fragment of α1-antitrypsin, named VIRIP, targeting the gp41 FP reduced viral loads in HIV-1-infected individuals. Characterization of HIV-1 variants selected during long-term cell-culture passage in the presence of a VIRIP derivative suggested that just three mutations in the HIV-1 Env protein might be sufficient for VIRIP resistance and that four subsequent changes restored viral fitness. Here, we show that all seven mutations contribute to reduced viral susceptibility to VIRIP-based inhibitors and demonstrate that the additional changes strongly impair rather than rescue HIV-1 infectivity, fusogenicity, and replication fitness. High genetic barrier to resistance and severe fitness cost support further clinical development of this class of antiviral agents.


title: Manual aspiration thrombectomy for basilar infarction in the setting of a persistent primitive hypoglossal artery: Case report and review of the literature.

text: BACKGROUND Persistent primitive hypoglossal artery (PPHA), a remnant of embryonal circulation, is a rare variant of the posterior cerebral circulation. Seven prior cases of posterior circulation stroke in the setting of PPHA have been described in the literature, with all but one case being attributable to atherosclerotic embolization from the internal carotid artery (ICA) through the PPHA. CASE DESCRIPTION We report a unique case of a young male with a PPHA presenting with a "top of the basilar" syndrome following the repair of his atrial septal defect who underwent emergent revascularization via endovascular mechanical aspiration thrombectomy. The patient underwent a successful aspiration thrombectomy with significant improvement in his clinical exam. CONCLUSIONS Considering the rarity of this persistent fetal anastamosis, it is important to be aware of the propensity for unusual presentations in the context of stroke, understand the management of the problem, and expeditiously treat the patient.


title: Robotic retroperitoneal partial nephrectomy: a step-by-step guide.

text: OBJECTIVE To describe a step-by-step guide for successful implementation of the retroperitoneal approach to robotic partial nephrectomy (RPN) PATIENTS AND METHODS: The patient is placed in the flank position and the table fully flexed to increase the space between the 12th rib and iliac crest. Access to the retroperitoneal space is obtained using a balloon-dilating device. Ports include a 12-mm camera port, two 8-mm robotic ports and a 12-mm assistant port placed in the anterior axillary line cephalad to the anterior superior iliac spine, and 7-8 cm caudal to the ipsilateral robotic port. RESULTS Positioning and port placement strategies for successful technique include: (i) Docking robot directly over the patient's head parallel to the spine; (ii) incision for camera port ≈1.9 cm (1 fingerbreadth) above the iliac crest, lateral to the triangle of Petit; (iii) Seldinger technique insertion of kidney-shaped balloon dilator into retroperitoneal space; (iv) Maximising distance between all ports; (v) Ensuring camera arm is placed in the outer part of the 'sweet spot'. CONCLUSION The retroperitoneal approach to RPN permits direct access to the renal hilum, no need for bowel mobilisation and excellent visualisation of posteriorly located tumours.


title: Porcine reproductive and respiratory syndrome virus (PRRSV) induces IL-12p40 production through JNK-AP-1 and NF-κB signaling pathways.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) mainly infects monocyte/macrophage cells and modulates cytokine production to regulate host immune response. IL-12p40 is the basic subunit of IL-12, a heterodimeric cytokine, which plays key roles in the cell-mediated immune response. In the present study, we demonstrated that PRRSV infection induced IL-12p40 production in vitro and in vivo. Subsequently, we showed that inhibitors of p38 MAPK, JNK, and NF-κB dramatically reduced PRRSV-induced IL-12p40 expression. To further characterize the molecular mechanism of IL-12p40 production induced by PRRSV infection, we cloned and analyzed the porcine IL-12p40 promoter, in which AP-1 and NF-κB motifs were found. In addition, both JNK-AP-1 and NF-κB signaling pathways were activated by PRRSV infection. Taken together, these data indicate that PRRSV induces IL-12p40 expression through the JNK-AP-1 and NF-κB signaling pathways. Our findings might facilitate our understanding of the molecular mechanisms of IL-12 production induced by PRRSV infection.


title: Management of bacterial infections in children with asthma.

text: Respiratory viruses are the single most common causes of asthma exacerbations in children. Rhinovirus-induced wheezing is a risk factor for chronic asthma, but its mechanism has remained unknown. Human bocavirus is a common finding in wheezing children, but its role as a respiratory pathogen is still unclear. Mycoplasma pneumoniae may, like viruses, induce wheezing and asthma exacerbation. Chlamydia pneumoniae and, in recent studies, Chlamydia trachomatis, may not only induce asthma exacerbations but may also be involved in the pathogenesis of chronic asthma. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are often involved in respiratory infections associated with wheezing, but there is no evidence for their active role in asthma pathogenesis or exacerbation. This review summarizes current knowledge on the association between respiratory infections and asthma in children, with a special focus on the role of antibiotics in incipient asthma, asthma exacerbation and chronic stable asthma.


title: COVID-19 safety in maternity care: lessons for the whole NHS.

text: John Tingle, Lecturer in Law, Birmingham Law School, University of Birmingham, discusses some recent reports in maternity care, which can be seen to also to have general application across all clinical specialities.


title: Short communication: immunogenicity of an inactivated influenza vaccine and postvaccination influenza surveillance in HIV-infected and noninfected children and adolescents.

text: Individuals infected with HIV are at higher risk for severe cases of seasonal influenza infection and should receive annual doses of vaccine. Our objectives were to evaluate the immunogenicity of an influenza vaccine in 37 HIV-infected patients (HIV group) compared to 29 uninfected individuals (control group) and to carry out a clinical and virological surveillance of influenza during a 6-month follow-up. Both groups received the vaccine recommended for the southern hemisphere in 2008. Antibody responses to antigens H1N1, H3N2, and B were measured in blood samples at vaccination (T0) and after 1 month (T1). Influenza surveillance was performed by weekly telephone calls for a follow-up period of 6 months. Nasal washes were taken from subjects with respiratory symptoms. The direct immunofluorescence assay in house polymerase chain reaction (PCR) and real-time PCR were used for the detection of different respiratory viruses. The median age of the participants was 13.3 years (sd = 2.2) and 12.1 years (sd = 1.3) for the HIV group and control group, respectively. One month after vaccination (T1), both groups showed significant increases in the antibody geometric mean titers (GMTs) for all antigens. However, healthy controls showed higher values for antigens A/H1N1 and A/H3N2 (p = 0.002 and 0.001, respectively). There was a higher increase in the percentage of HIV-uninfected subjects with protective A/H1N1 antibodies (96.6%) compared to HIV-infected vaccinees (67.6%) at T1 (p = 0.004). Rhinovirus (27.7%) and coronavirus (22.5%) were the most prevalent agents identified in HIV-infected individuals. In the control group, the viruses most frequently found were rhinovirus (24.2%) and adenovirus (21.2%). The seroprotection rate for the H1N1 antigen was higher in the control group, which also showed a greater increase in GMTs for H1N1 and H3N2 antigens after immunization. Viral agents were identified in 39/60 (65%) episodes of respiratory infections from the HIV-infected group and in 17/32 episodes (53.1%) from the control group (p = 0.273).


title: COVID-19 in Turkey: Lessons Learned.

text: Turkey reported its first COVID-19 case on March 10, 2020. We present here the mitigation efforts Turkey has undertaken so far, and also review the lessons learned for future proactive strategies. High number of intensive care unit beds and ventilators, national treatment algorithms, governmental support for free testing and medications, tedious contact-tracing with early detection and isolation of cases together with early shelter-in-place for the elderly and youngsters, and subsequent weekend curfews in selected cities have so far prevented the surge pressure on the health care system. At this phase, Turkey needs to adopt an evidence-based, proactive control system for an effective transition process to normalize the situation. Here, we underline the urgent need for detailed analysis of the national COVID-19 data and propose an epidemiologic investigation framework for better understanding, efficient control, and reliable forecasting of COVID-19 pandemic.


title: Robot-assisted laparoscopic myomectomy: current status.

text: Robotic-assisted surgery has seen a rapid development and integration in the field of gynecology. Since the approval of the use of robot for gynecological surgery and considering its several advantages over conventional laparoscopy, it has been widely incorporated especially in the field of reproductive surgery. Uterine fibroids are the most common benign tumors of the female reproductive tract. Many reproductive-aged women with this condition demand uterine-sparing surgery to preserve their fertility. Myomectomy, the surgical excision of uterine fibroids, remains the only surgical management option for fibroids that entails preservation of fertility. In this review, we focus on the role of robotic-assisted laparoscopic myomectomy and its current status, in comparison with other alternative approaches for myomectomy, including open, hysteroscopic, and traditional laparoscopic techniques. Several different surgical techniques have been demonstrated for robotic myomectomy. This review endeavors to share and describe our surgical experience of using the standard laparoscopic equipment for robotic-assisted myomectomy, together with the da Vinci Robot system. For the ideal surgical candidate, robotic-assisted myomectomy is a safe minimally invasive surgical procedure that can be offered as an alternative to open surgery. The advantages of using the robot system compared to open myomectomy include a shorter length of hospital stay, less postoperative pain and analgesic use, faster return to normal activities, more rapid return of the bowel function, and enhanced cosmetic results due to smaller skin incision sizes. Some of the disadvantages of this technique include high costs of the robotic surgical system and equipment, the steep learning curve of this novel system, and prolonged operative and anesthesia times. Robotic technology is a novel and innovative minimally invasive approach with demonstrated feasibility in gynecological and reproductive surgery. This technology is expected to take the lead in gynecological surgery in the upcoming decade.


title: Naloxone-precipitated withdrawal enhances ERK phosphorylation in prefrontal association cortex and accumbens nucleus of morphine-dependent mice.

text: Mitogen-activated protein kinases (MAPK) can be activated by opioids such as morphine via opioid receptor, and their activations have been observed in synaptic plasticity, learning, memory and addiction. Long-term exposure to morphine may induce physical dependence, manifested as somatic withdrawal symptoms such as diarrhea, body weight loss, jumping and headshaking, when drug is deprived. Though morphine dependence and withdrawal have been extensively studied, their molecular mechanisms have not been fully elucidated. In the present study, the physical dependence on morphine was developed in mice by an intermittent, escalating procedure of morphine injections, and was measured by the body weight loss and the behavioral signs (jumping and headshaking). We found that the mice with chronic morphine administration experienced dramatic body weight loss, compared with the saline-treated controls. Naloxone-precipitated withdrawal led to more body weight loss, compared with spontaneous withdrawal. Naloxone-precipitated withdrawal mice showed significantly aggravated morphine-withdrawal symptoms (including jumping and heading shaking), compared with spontaneous withdrawal mice. MAPK pathway activities in the frontal association cortex (FrA), accumbens nucleus (Acb) and caudate putamen (CPu) were examined to probe into molecular mechanism for morphine dependence and withdrawal. Compared with saline-treated mice, morphine-dependent mice and spontaneous withdrawal mice, naloxone-precipitated withdrawal mice showed a significantly increased ERK phosphorylation in FrA and Acb, but not in CPu. However, the activities of other protein kinases in the MAPK pathway, including p38 and JNK, showed no changes in FrA, Acb and CPu of the mice during the chronic morphine dependence and withdrawal phases. These results suggest that the ERK phosphorylation in FrA and Acb may be associated with naloxone-precipitated withdrawal syndrome.


title: Evaluation of the learning curve for a board-certified veterinary surgeon performing laparoendoscopic single-site ovariectomy in dogs.

text: OBJECTIVE To define the learning curve and evaluate the outcome for a board-certified veterinary surgeon performing laparoendoscopic single-site (LESS) ovariectomy in dogs. DESIGN Retrospective case review and learning curve evaluation with a skill acquisition model. Animals-27 client-owned dogs. Procedures-Between April 2011 and December 2012, 27 dogs underwent elective LESS ovariectomy performed by a single experienced board-certified laparoscopic surgeon by means of the same technique. Medical records for these patients were reviewed to determine whether a learning curve could be detected. A commercially available multitrocar port was inserted through a 15- to 20-mm incision at the umbilicus, and LESS ovariectomy was performed with articulating graspers, a bipolar vessel-sealing device, and a 30° telescope. Surgical performance of the surgeon was quantified with an exponential skill acquisition model, and how skill was gained with repetition of the same novel surgical procedure was examined. RESULTS Median patient body weight was 20 kg (44 lb; range, 3.5 to 41 kg [7.7 to 90.2 lb]). Median surgical time was 35 minutes (range, 20 to 80 minutes). Median patient age was 314 days (range, 176 to 2,913 days). The skill acquisition model revealed that a comparable surgeon could reach 90% of optimal surgery performance after approximately 8 procedures (8.6, 95% confidence interval, 0.5 to 16.6 procedures). According to the model, with each surgery, surgical time would be expected to decrease by 27% (95% confidence interval, 2% to 52%). Complications were limited to minor hemorrhage due to a splenic laceration and a postoperative incisional infection. Follow-up information was available for all 27 cases. All owners were satisfied and indicated that they would pursue LESS ovariectomy again. CONCLUSIONS AND CLINICAL RELEVANCE The learning curve for LESS ovariectomy was short and definable. Short-term outcome was excellent. Results of this study suggested that an experienced laparoscopic surgeon may anticipate achieving proficiency with this technique after performing approximately 8 procedures.


title: SPECT- and fluorescence image-guided surgery using a dual-labeled carcinoembryonic antigen-targeting antibody.

text: UNLABELLED Intraoperative visualization techniques promise to significantly improve the detection and resection of tumors. In this study, we used an anti-carcinoembryonic antigen (CEA) antibody (MN-14) tagged with both a radiolabel ((111)In) and a fluorophore (IRDye 800CW) for radionuclide detection and intraoperative fluorescence imaging, respectively. METHODS For this purpose, we prepared and characterized the dual-labeled antibody (111)In-diethylenetriaminepentaacetic acid (DTPA)-MN-14-IRDye 800CW and performed 4 studies on mice with subcutaneous and intraperitoneal CEA-expressing tumors: a dose escalation study to determine the optimal MN-14 protein dose, a biodistribution study comparing dual-labeled MN-14 and radiolabeled MN-14, a study to determine the optimal time for SPECT and fluorescence imaging after injection of dual-labeled MN-14, and finally a SPECT and fluorescence image-guided surgery study using this dual-labeled antibody. RESULTS The optimal protein dose of dual-labeled MN-14 was 10 μg per mouse, yielding a tumor-to-blood ratio of 3.5 within 72 h. The biodistribution of (111)In-DTPA-MN-14-IRDye 800CW in mice with subcutaneous LS174T tumors showed tumor uptake after 3 d (19.7% ± 17.0% injected dose/g) comparable to that of (111)In-DTPA-MN-14 but higher accumulation in the liver. The optimal time for imaging after administration of the dual-labeled antibody was 2-3 d after injection. Finally, in mice with intraperitoneally growing LS174T tumor nodules that received (111)In-DTPA-MN-14-IRDye 800CW, intraperitoneal tumor nodules could be localized with SPECT imaging after 3 d and subsequently resected using fluorescence image-guided surgery. CONCLUSION Thus, we showed the feasibility for assessment and image-guided resection of CEA antigen-expressing tumors using dual-labeled MN-14. Both radionuclide detection and fluorescence imaging may provide useful information to improve localization of tumors and radical excision of tumor tissue. Because humanized MN-14 (labetuzumab) is available for clinical use, translation to a clinical setting is the next step.


Virology in the 21st century.


title: α-Defensins in human innate immunity.

text: Defensins are small, multifunctional cationic peptides. They typically contain six conserved cysteines whose three intramolecular disulfides stabilize a largely β-sheet structure. This review of human α-defensins begins by describing their evolution, including their likely relationship to the Big Defensins of invertebrates, and their kinship to the β-defensin peptides of many if not all vertebrates, and the θ-defensins found in certain non-human primates. We provide a short history of the search for leukocyte-derived microbicidal molecules, emphasizing the roles played by luck (good), preconceived notions (mostly bad), and proper timing (essential). The antimicrobial, antiviral, antitoxic, and binding properties of human α-defensins are summarized. The structural features of α-defensins are described extensively and their functional contributions are assessed. The properties of HD6, an enigmatic Paneth cell α-defensin, are contrasted with those of the four myeloid α-defensins (HNP1-4) and of HD5, the other α-defensin of human Paneth cells. The review ends with a decalogue that may assist researchers or students interested in α-defensins and related aspects of neutrophil function.


title: Experiences in managing arteriovenous malformations of the head and neck.

text: Arteriovenous malformations of the head and neck are difficult to treat and require a multidisciplinary approach. Interventional radiology can now be used to downgrade previously inoperable lesions to enable ablation, and the use of Onyx® (Covidien, Irvine, CA, USA), which has revolutionised their management by allowing precise obliteration of the nidus, has enabled the aggressive management of lesions in compromised anatomical areas. We report a series of 31 patients with lesions on the head and neck. They all presented with serious symptoms (Schobinger grade 2-3) and had embolisation with Onyx®. Some had additional operations. We describe the outcome including complications, and offer some lessons learned from our experience.


title: Capnographic Monitoring in Routine EGD and Colonoscopy With Moderate Sedation: A Prospective, Randomized, Controlled Trial.

text: OBJECTIVES Regulatory changes requiring the use of capnographic monitoring for endoscopic procedures using moderate sedation have placed financial challenges on ambulatory and hospital endoscopy centers across the United States due to the increased cost of training endoscopy personnel and purchasing both capnography-monitoring devices and specialized sampling ports. To date, there has been no published data supporting the use of capnographic monitoring in adult patients undergoing routine endoscopic procedures with moderate sedation. The aim of this randomized, parallel group assignment trial was to determine whether intervention based on capnographic monitoring improves detection of hypoxemia in patients undergoing routine esophagogastroduodenoscopy (EGD) or colonoscopy with moderate sedation. METHODS Healthy patients (ASA Physical Classification (ASAPS) I and II)) scheduled for routine outpatient EGD or colonoscopy under moderate sedation utilizing opioid and benzodiazepine combinations were randomly assigned to a blinded capnography alarm or open capnography alarm group. In both study arms, standard cardiopulmonary monitoring devices were utilized with additional capnographic monitoring. The primary end point was the incidence of hypoxemia defined as a fall in oxygen saturation (SaO2) to <90% for ≥10 s. Secondary outcomes included severe hypoxemia, apnea, disordered respirations, hypotension, bradycardia, and early procedure termination for any cause. RESULTS A total of 452 patients were randomized; 218 in the EGD and 234 in the colonoscopy groups; 75 subjects in the EGD group (35.9%) and 114 patients (49.4%) in the colonoscopy group were male, and average body mass index was 27.9 and 29.1 (kg/m(2)), respectively. The blinded and open alarm groups in each study arm were similar in regards to use of opioids and/or benzodiazepines and ASAPS classification. There was no significant difference in rates of hypoxemia between the blinded and open capnography arms for EGD (54.1% vs. 49.5; P=0.5) or colonoscopy (53.8 vs. 52.1%; P=0.79). CONCLUSIONS Capnographic monitoring in routine EGD or colonoscopy for ASAPS I and II patients does not reduce the incidence of hypoxemia (ClinicalTrials.gov number, NCT01994785).


title: Adverse effects of fibrin sealants in thoracic surgery: the safety of a new fibrin sealant: multicentre, randomized, controlled, clinical trial.

text: OBJECTIVES The safety of fibrin sealants (FS) has been questioned in the light of recent reports of adverse effects. We evaluated the safety of a new FS in a randomized controlled trial (RCT). METHODS Multicentre, open-label Phase II/III RCT to evaluate the safety of the new FS. The trial was approved by the Ethic Committee of each three participating Centre. FS includes two components (component 1: fibrinogen; component 2: thrombin), each of them subjected to two viral inactivation procedures. Out of 200 screened patients, 185 eligible patients (49 females, 136 males), aged between 18 and 75 years, undergoing major thoracic surgery were randomized to receive FS (#91 patients) as an adjuvant for air leak control or no treatment (#94 patients, control group). Safety variables were: percentage of subjects with adverse events associated with the therapy; formation of antibodies against bovine aprotinin; vital signs (blood pressure, body temperature, heart and respiratory rate); laboratory parameters. RESULTS Overall operative mortality was 3.2% (6/185), 1.1% in the FS group and 5.3% in the control group, respectively. Twenty patients (22%) had adverse events in the FS group and 22 (23.4%) in the control group. Atrial fibrillation (five patients in the FS group and four in the control group) and hyperpyrexia (five and seven patients, respectively, in the two groups) were the most common adverse events. No patient reported thromboembolic events (pulmonary embolism or deep vein thrombosis) during the in hospital stay or within 1 month from discharge. None of the adverse events was considered as treatment related. The formation of bovine aprotinin antibodies was reported in a total of 34 patients (37.4%) in the FS group and was not related to any adverse effect. CONCLUSIONS The present RCT did not show any increased risk of adverse events, and of surgical complications, related to the use of the new FS.


title: Variable ventilation enhances ventilation without exacerbating injury in preterm lambs with respiratory distress syndrome.

text: BACKGROUND As compared with constant respiratory rate (RR) and tidal volume (V(T)) during controlled conventional mechanical ventilation (CV), variable ventilation (VV) using the same breath-to-breath minute volume but variable V(T) and RRs enhances ventilation efficiency in preterm lambs. We hypothesized that if V(T) was adjusted to target permissive hypercarbia, VV would result in more efficient gas exchange without increasing inflammatory and injurious responses in the lung. METHODS Preterm lambs at 129 d gestation were anesthetized, tracheotomized, and randomized to either CV (n = 8) or VV (n = 8) using the same initial average V(T) and RR. Lung mechanics and gas exchange were measured intermittently, and average V(T) was adjusted to target partial pressure of arterial carbon dioxide (PaCO2) of 40-50 mm Hg for 3 h. Lung injury and inflammation were assessed from bronchoalveolar lavage fluid, lung tissue, and peripheral blood. RESULTS VV achieved permissive hypercarbia using a lower average V(T), peak inspiratory pressure, and elastance (increased compliance) as compared with CV. Oxygenation and markers of lung tissue inflammation or injury were not different apart from a lower wet:dry tissue ratio in the VV lungs. CONCLUSIONS VV improves ventilation efficiency and in vivo lung compliance in the ovine preterm lung without increasing lung inflammation or lung injury.


title: A randomized controlled trial of capnography during sedation in a pediatric emergency setting.

text: OBJECTIVE Data suggest that capnography is a more sensitive measure of ventilation than standard modalities and detects respiratory depression before hypoxemia occurs. We sought to determine if adding capnography to standard monitoring during sedation of children increased the frequency of interventions for hypoventilation, and whether these interventions would decrease the frequency of oxygen desaturations. METHODS We enrolled 154 children receiving procedural sedation in a pediatric emergency department. All subjects received standard monitoring and capnography, but were randomized to whether staff could view the capnography monitor (intervention) or were blinded to it (controls). Primary outcome were the rate of interventions provided by staff for hypoventilation and the rate of oxygen desaturation less than 95%. RESULTS Seventy-seven children were randomized to each group. Forty-five percent had at least 1 episode of hypoventilation. The rate of hypoventilation per minute was significantly higher among controls (7.1% vs 1.0%, P = .008). There were significantly fewer interventions in the intervention group than in the control group (odds ratio, 0.25; 95% confidence interval [CI], 0.13-0.50). Interventions were more likely to occur contemporaneously with hypoventilation in the intervention group (2.26; 95% CI, 1.34-3.81). Interventions not in time with hypoventilation were associated with higher odds of oxygen desaturation less than 95% (odds ratio, 5.31; 95% CI, 2.76-10.22). CONCLUSION Hypoventilation is common during sedation of pediatric emergency department patients. This can be difficult to detect by current monitoring methods other than capnography. Providers with access to capnography provided fewer but more timely interventions for hypoventilation. This led to fewer episodes of hypoventilation and of oxygen desaturation.


title: A systematic review of factors that enable psychological safety in healthcare teams.

text: PURPOSE The current systematic review will identify enablers of psychological safety within the literature in order to produce a comprehensive list of factors that enable psychological safety specific to healthcare teams. DATA SOURCES A keyword search strategy was developed and used to search the following electronic databases PsycINFO, ABI/INFORM, Academic search complete and PubMed and grey literature databases OpenGrey, OCLC WorldCAT and Espace. STUDY SELECTION Peer-reviewed studies relevant to enablers of psychological safety in healthcare setting that were published between 1999 and 2019 were eligible for inclusion. Covidence, an online specialized systematic review website, was used to screen records. Data extraction, quality appraisal and narrative synthesis were conducted on identified papers. DATA EXTRACTION Thirty-six relevant studies were identified for full review and data extraction. A data extraction template was developed and included sections for the study methodology and the specific enablers identified within each study. RESULTS OF DATA SYNTHESIS Identified studies were reviewed using a narrative synthesis. Within the 36 articles reviewed, 13 enablers from across organizational, team and individual levels were identified. These enablers were grouped according to five broader themes: priority for patient safety, improvement or learning orientation, support, familiarity with colleagues, status, hierarchy and inclusiveness and individual differences. CONCLUSION This systematic review of psychological safety literature identifies a list of enablers of psychological safety within healthcare teams. This list can be used as a first step in developing observational measures and interventions to improve psychological safety in healthcare teams.


title: Should chest compressions be considered an aerosol-generating procedure? A literature review in response to recent guidelines on personal protective equipment for patients with suspected COVID-19.

text: There is disagreement between international guidelines on the level of personal protective equipment (PPE) required for chest compressions for patients with suspected COVID-19. This discrepancy centres on whether they are considered to be an aerosol-generating procedure (AGP), thus requiring airborne protection to prevent transmission to healthcare workers (HCWs). The need to don higher-level PPE has to be weighed against the resulting delay to emergency treatment.We performed a literature search on this topic which found eight relevant studies. All were observational with low patient numbers and multiple confounding factors, but describe cases of acute respiratory infection transmission during chest compressions. One systematic review concluded that chest compressions were not an AGP. Two simulated studies (released as preprints) potentially demonstrate aerosol generation. Given that there is evidence for infection transmission during chest compressions, we conclude that a precautionary approach with appropriate PPE is necessary to protect HCW from contracting a potentially fatal infection.


title: Critical care in the austere environment: providing exceptional care in unusual places.

text: BACKGROUND War and other disasters are inexorably linked to illness and injury. As a consequence of this, healthcare providers will be challenged to provide advanced physiological support to preserve human life. Given the mobility and modularity of modern medical systems, the ability to provide critical care outside of the confines of traditional hospitals under such circumstances has become not only a reality and periodic necessity, but an expectation. Austerity amplifies the complexity of providing high-level critical care, because resources are frequently limited, providers are asked to fill unexpected roles determined by necessity, security may be threatened, and the population at risk and their afflictions can be highly diverse. DISCUSSION Our current deployed military medical experience and a review of published literature pertaining to civilian medical disaster response efforts support these stated challenges. The fundamentals of successful critical care practice in unusual settings include proper planning with an emphasis on attention to detail, the careful management of all resources, using the proper equipment, leveraging aeromedical evacuation assets, and employing the right people with the right skills. SUMMARY Adherence to sound, evidence-based, routine practice, within bounds of the circumstances, must underscore everything.


title: Bovine plasmacytoid dendritic cells are the major source of type I interferon in response to foot-and-mouth disease virus in vitro and in vivo.

text: Type I interferons (alpha/beta interferons [IFN-α/β]) are the main innate cytokines that are able to induce a cellular antiviral state, thereby limiting viral replication and disease pathology. Plasmacytoid dendritic cells (pDCs) play a crucial role in the control of viral infections, especially in response to viruses that have evolved mechanisms to block the type I IFN signal transduction pathway. Using density gradient separation and cell sorting, we have highly enriched a population of bovine cells capable of producing high levels of biologically active type I IFN. These cells represented less than 0.1% of the total lymphocyte population in blood, pseudoafferent lymph, and lymph nodes. Phenotypic analysis identified these cells as bovine pDCs (CD3(-) CD14(-) CD21(-) CD11c(-) NK(-) TCRδ(-) CD4(+) MHC II(+) CD45RB(+) CD172a(+) CD32(+)). High levels of type I IFN were generated by these cells in vitro in response to Toll-like receptor 9 (TLR-9) agonist CpG and foot-and-mouth disease virus (FMDV) immune complexes. In contrast, immune complexes formed with UV-inactivated FMDV or FMDV empty capsids failed to elicit a type I IFN response. Depletion of CD4 cells in vivo resulted in levels of type I IFN in serum early during FMDV infection that were significantly lower than those for control animals. In conclusion, pDCs interacting with immune-complexed virus are the major source of type I interferon production during acute FMDV infection in cattle.


title: Testing the hypothesis of tissue selectivity: the intersection-union test and a Bayesian approach.

text: MOTIVATION Finding genes that are preferentially expressed in a particular tissue or condition is a problem that cannot be solved by standard statistical testing procedures. A relatively unknown procedure that can be used is the intersection-union test (IUT). However, two disadvantages of the IUT are that it is conservative and it conveys only the information of the least differing target tissue-other tissue pair. RESULTS We propose a Bayesian procedure that quantifies how much evidence there is in the overall expression profile for selective over-expression. In a small simulation study, it is shown that the proposed method outperforms the IUT when it comes to finding selectively expressed genes. An application to publicly available data consisting of 22 tissues shows that the Bayesian method indeed selects genes with functions that reflect the specific tissue functions. The proposed method can also be used to find genes that are underexpressed in a particular tissue. AVAILABILITY Both MATLAB and R code that implement the IUT and the Bayesian procedure in an efficient way, can be downloaded at http://ppw.kuleuven.be/okp/software/BayesianIUT/.


docid: ageunebj

title: Minimally Invasive Ivor Lewis Esophagectomy Without Patient Repositioning.

text: INTRODUCTION The standard technique for Ivor Lewis minimally invasive esophagectomy involves a two-stage approach necessitating repositioning mid-procedure. TECHNIQUE We describe our technique for a one-stage hand-assisted minimally invasive esophagectomy that allows sequential access to the chest and abdomen within the same surgical field, eliminating the need for repositioning. The patient is positioned in a "corkscrew" configuration with the abdomen supine and the chest rotated to the left to allow access to the right chest. The abdomen and chest are prepped into a single operative field. This technique allows sequential access to the abdomen for gastric mobilization, chest for division of the esophagus, abdomen for construction of the gastric conduit, and chest for intrathoracic anastomosis. CONCLUSION This approach enables extracorporeal construction of the conduit, which helps ensure a clear distal margin on the specimen and facilitates conduit length by placing the stomach on stretch during stapling.


Cardiac Troponin I is an Independent Predictor for Mortality in Hospitalized Patients with Coronavirus Disease 2019.


title: The association between community mental health nursing and hospital admissions for people with serious mental illness: a systematic review.

text: BACKGROUND Relapse prevention is an important objective in the management of serious mental illness (SMI). While community mental health nurses (CMHN) might be well-placed to support people with SMI in averting relapse, no systematic reviews have examined this association. AIM To review the evidence from studies reporting an association between CMHN exposure and hospitalisation of persons living with SMI (a proxy for relapse). METHODS Searches were undertaken in ten bibliographic databases and two clinical trial registries. We included studies of patients with SMI, where CMHN was the exposure, and the outcome was relapse (i.e. readmission to a psychiatric inpatient facility). Quality assessment of included studies was completed using two risk-of-bias measures. RESULTS Two studies met the inclusion criteria. Studies were rated as being of low-moderate methodological quality. There was insufficient evidence to conclude that community mental health nursing reduced the risk of admission to psychiatric inpatient facilities. CONCLUSIONS The review found no evidence that CMHN was associated with higher or lower odds of admission to psychiatric inpatient facilities among patients with SMI. The findings of the review point to a need for further research to investigate the impact of CMHN exposure and relapse in people with SMI. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017058694.


Climate change brings the specter of new infectious diseases.


title: Does continuous infusion of local anaesthesia improve pain control and walking distance after coronary artery bypass graft surgery? A randomised controlled trial.

text: OBJECTIVES To evaluate the effects of continuous infusion of ropivacaine compared to sham infusion or usual care on pain scores before and after physiotherapy treatment, distance walked and time to discharge from physiotherapy, after coronary artery bypass graft (CABG) surgery. DESIGN Prospective, randomised, double blind controlled trial. SETTING AND PARTICIPANTS Seventy-five participants who underwent CABG surgery with left internal mammary artery grafts were allocated, to the ropivacaine group (n=26), the sham group (n=25), or usual care group (n=24). Participants in the ropivacaine group received 0.5% ropivacaine and participants in the sham group received normal saline, both as continuous infusions via two parasternally tunnelled catheters for 96hours continuously. The usual care group did not receive a device. All groups had patient-controlled analgesia and/or oral analgesia. RESULTS Seventy-two participants completed the study. There was no significant between-group differences in pain scores, distance walked on any post operative day (POD) or number of participants discharged from physiotherapy by POD 4. For the group as a whole there was a significant linear decrease in pain score from mean (SD) 42 (24) mm on POD1 to 15 (16) mm on POD4 (p<0.001), (MD 27mm, 95% CI 22 to 32) and walking distance increased from 1 (5) m on POD1 to 183 (239) m on POD4 (p<0.001) MD 181m, 95% CI 126 to 236). CONCLUSION Infusion of ropivacaine post CABG surgery was unable to reduce pain, increase distance walked or reduce time to physiotherapy discharge compared to sham or usual care. Trial registration number ACTRN12612001243808.


docid: zfpdyymc

title: Depression, anxiety, stress, and dysmenorrhea: a protocol for a systematic review.

text: BACKGROUND Dysmenorrhea is one of the most common menstrual disorders and is influenced by various factors. Psychological disorders including anxiety, depression, and stress have been suggested as influencing dysmenorrhea, but previous findings are inconsistent. This study will investigate the relationship between depression/anxiety/stress and dysmenorrhea using a systematic review and meta-analysis. METHODS Online databases including PsycINFO, Scopus, PubMed, Science Direct, ProQuest, ISI Web of Knowledge, and Embase will be searched. Appropriate keywords and MeSH terms will be used to retrieve the journal papers published from 1990 until the end of December 2019. To improve search coverage, the reference lists of all included studies will be reviewed to find eligible papers. Inclusion criteria include the following: descriptive, cohort, case-control, and cross-sectional studies; the relationship between depression/anxiety/stress and dysmenorrhea being an objective of the study; and published in peer-reviewed journals. The paper selection, data extraction, and quality assessment of selected studies will be performed independently by two researchers, and disagreements will be resolved through discussions. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the quality of selected studies. A quantitative synthesis will be performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) via the STATA software, if retrieving enough number of studies with no severe methodological heterogeneities. Otherwise, qualitative synthesis will be used to report the findings. DISCUSSION To the best of our knowledge, this will be the first systematic review on this topic. Performing an inclusive search in major databases over a wide timescale is one key strength of the proposed study and will maximize the coverage of the original research studies on this topic. Results of present study are expected to lead to deeper understanding the relationship between common mental health conditions and dysmenorrhea. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42018102199.


docid: bpzvckpw

title: Muscular workload of veterinary students during simulated open and laparoscopic surgery: A pilot study.

text: OBJECTIVE To compare upper extremity muscle activity and workload between simulated open surgery, multiple port laparoscopic surgery (MLS), and single incision laparoscopic surgery (SLS) techniques in veterinary students. STUDY DESIGN Pilot study. POPULATION Veterinary students (n = 10) from years 1 to 4. METHODS Bipolar skin surface electrodes were fixed bilaterally to the forearm flexor, forearm extensor, biceps brachii, triceps brachii, and upper trapezius muscles. Electromyography data were recorded during one repetition of 2 simulated surgical exercises via open surgery, MLS, and SLS. Participants completed a validated workload survey after each simulated surgical technique. Muscle activity and perceived workload were compared between surgical techniques with 1-way ANOVAs and Fisher's LSD post hoc tests. RESULTS Muscle activity during peg transfer was higher with MLS and SLS compared to simulated open surgery in the right and left forearm extensors (both P < .0001), right (P < .0001) and left biceps (P = .0005), right triceps (P = .0004), and right upper trapezius muscles (P = .0211). Similar results were found for the right and left forearm extensors (both P < .0001), right (P = .0381) and left (P = .0147) forearm flexors, right biceps (P < .0001), and right triceps (P = .0004) during a simulated suture task. Participants found laparoscopic techniques more mentally demanding, physically demanding, complex, and stressful compared to a simulated open surgical technique. CONCLUSION In veterinary students, average muscle activity and perceived workload were highest using MLS and SLS compared to an open surgical technique when performing simulated surgical exercises in a laparoscopic box trainer.


COVID-19 lockdown dropped the rate of paediatric asthma admissions.


title: [Pathogen reduction for platelets: available techniques and recent developments].

text: The will to reach for blood components a microbiological safety comparable to that of plasma-derived drugs led to the development of numerous pathogen reduction research programs for red blood cells and\or platelets in the 1990s. A consensus conference organized in 2007 allowed to define the main steps and precautions to be taken for the implementation of these processes. In the specific case of platelet concentrates, three processes stay this day in the run, even if they are not at the same development stage. A process using ultraviolet C only is at the stage of preclinical studies. The Mirasol® process, based on the activation of riboflavin by exposure to ultraviolet A and ultraviolet B is CE marked (class IIb), and a clinical study was published in 2010. The Intercept® process, involving the activation of a psoralen molecule by exposure to ultraviolet A, is CE marked (class III) since 2002, and has been licensed in France since 2005, in Germany since 2005 and in Switzerland since 2010. At least 12 clinical studies have been published. In regard to this last pathogen reduction process, the medical and scientific documentation, from in vitro investigations to post-marketing observational studies, is much more developed than the corresponding documentation of some innovative processes at the time of their generalization, such as the SAG-mannitol solution for red cell concentrates in 1979, leukoreduction filters for platelets and red cells concentrates in the 1990s, the solvent detergent therapeutic plasma in 1992 or the methylene blue therapeutic plasma in 2006.


docid: tbalawbj

title: Catheter tip malposition after percutaneous placement of tunneled hemodialysis catheters.

text: The percutaneous catheterization of central veins is increasingly used in nephrological practice as a temporary or permanent vascular access. The aim of our study was to present and to analyze episodes of catheter tip malposition during percutaneous tunneled hemodialysis catheter insertion in the large, unselected group of patients. All patients who underwent the procedure of catheter insertion in our department during year 2012 were analyzed retrospectively. One hundred four tunneled hemodialysis catheters were inserted in 101 patients. In 58 patients, the catheter was inserted at the initiation of hemodialysis therapy as the first access and in 46 the catheter was placed because of the failure of the existing one. In 68 patients, the catheter was inserted into the right internal jugular vein and in 20 patients into the left internal jugular vein (LIJV). Subclavian veins were used in five cases and femoral veins in 11 cases. Malposition of the catheter tips occurred in six patients. In all cases, the LIJV was cannulated. In two cases, the catheter tip malposition was in the right innominate vein and in four cases in the azygos vein. Our data demonstrate that with the blind insertion of tunneled hemodialysis catheters, the risk of catheter tip malposition is significantly higher with the left side insertion. As catheter insertion through the LIJV holds very high (30%) risk of the tip malposition, it should always be performed under the fluoroscopic control.


Reconsidering Risks of Gun Ownership and Suicide in Unprecedented Times.


title: Prognostic prediction models for pregnancy complications in women with gestational diabetes: a protocol for systematic review, critical appraisal and meta-analysis.

text: BACKGROUND Gestational diabetes (GDM) is increasingly common and has significant implications during pregnancy and for the long-term health of the mother and offspring. However, it is a heterogeneous condition with inter-related factors including ethnicity, body mass index and gestational weight gain significantly modifying the absolute risk of complications at an individual level. Predicting the risk of pregnancy complications for an individual woman with GDM presents a useful adjunct to therapeutic decision-making and patient education. Diagnostic prediction models for GDM are prevalent. In contrast, prediction models for risk of complications in those with GDM are relatively novel. This study will systematically review published prognostic prediction models for pregnancy complications in women with GDM, describe their characteristics, compare performance and assess methodological quality and applicability. METHODS Studies will be identified by searching MEDLINE and Embase electronic databases. Title and abstract screening, full-text review and data extraction will be completed independently by two reviewers. The included studies will be systematically assessed for risk of bias and applicability using appropriate tools designed for prediction modelling studies. Extracted data will be tabulated to facilitate qualitative comparison of published prediction models. Quantitative data on predictive performance of these models will be synthesised with meta-analyses if appropriate. DISCUSSION This review will identify and summarise all published prognostic prediction models for pregnancy complications in women with GDM. We will compare model performance across different settings and populations with meta-analysis if appropriate. This work will guide subsequent phases in the prognosis research framework: further model development, external validation and model updating, and impact assessment. The ultimate model will estimate the absolute risk of pregnancy complications for women with GDM and will be implemented into routine care as an evidence-based GDM complication risk prediction model. It is anticipated to offer value to women and their clinicians with individualised risk assessment and may assist decision-making. Ultimately, this systematic review is an important step towards a personalised risk-stratified model-of-care for GDM to allow preventative and therapeutic interventions for the maximal benefit to women and their offspring, whilst sparing expense and harm for those at low risk. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42019115223.


The Spread of COVID-19 in the Italian Population: Anxiety, Depression, and Post-traumatic Stress Symptoms.


Managing Ebola: Lessons Learned from the SARS Epidemic.


title: Robotic Sleeve Gastrectomy for Morbid Obesity.

text: OBJECTIVE To determine the weight loss, and complications as well as to exemplify the use of vessel sealer and the triple stapler establish the safety and efficacy of vessel sealer for robotic surgery and triple stapler in robotic sleeve gastrectomy. STUDY DESIGN Observational case series. PLACE AND DURATION OF STUDY Private Koru Hospital, Ankara, Turkey, from December 2015 till January 2016. METHODOLOGY Twenty robotic sleeve gastrectomy was performed. Demographics, body mass index, comorbidities, docking time, surgical time, leaks, bleeding, stapler number, strictures, mortality, conversion, weight loss, and hospital length of stay were included for data collection. RESULTS The mean age and body mass index were 40.73 ±11.2 years and 44.75 ±8.38 Kg/m2, respectively. Postoperative trocar site (assistance port) bleeding occurred in one patient. There were no conversions, stricture, leakage or mortality. The mean number of staplers used was 6.27 ±0.46 and excess body weight loss (EWL%) at three months was 24.91 ±2.84 kg. CONCLUSION Robotic surgery for obesity surgery was safe during our initial experience and use of vessel sealer and triple stapler was effective, safe and facilitates procedure in obese patients.


Coronavirus (COVID-19) Pandemic: What the Nuclear Medicine Departments Should Know.


Difficult intubation and anesthetic management in an adult patient with undiagnosed congenital tracheal stenosis: a case report.


title: Liver lobe torsion in pet rabbits: clinical consequences, diagnosis, and treatment.

text: This article reviews diagnosis and management of liver lobe torsion in rabbits. Practitioners should recommend initial diagnostics including radiographs and blood work on rabbits presenting with nonspecific signs of gastrointestinal (GI) stasis to better determine possible etiology and make the best treatment recommendations. If hepatic enzyme elevation is found in a rabbit with GI stasis, abdominal ultrasound is recommended to rule out liver lobe torsion. Prompt diagnosis and liver lobectomy are recommended for best outcome in rabbits with liver lobe torsion.


title: Feasibility and Safety of a New Chest Drain Wound Closure Method with Knotless Sutures.

text: Background A method of wound closure using knotless suture material in the chest tube site has been introduced at our center, and is now widely used as the primary method of closing chest tube wounds in video- assisted thoracic surgery (VATS) because it provides cosmetic benefits and causes less pain. Methods We included 109 patients who underwent VATS pulmonary resection at Samsung Medical Center from October 1 to October 31, 2016. Eighty-five patients underwent VATS pulmonary resection with chest drain wound closure utilizing knotless suture material, and 24 patients underwent VATS pulmonary resection with chest drain wound closure by the conventional method. Complications related to the chest drain wound were compared between the 2 groups. Results There were 2 cases of pneumothorax after chest tube removal in both groups (8.3% in the conventional group, 2.3% in the knotless suture group; p=0.172) and there was 1 case of wound discharge due to wound dehiscence in the knotless suture group (0% in the conventional group, 1.2% in the knotless suture group; p=0.453). There was no reported case of chest tube dislodgement in either group. The complication rates were non-significantly different between the 2 groups. Conclusion The results for the complication rates of this new chest drain wound closure method suggest that this method is not inferior to the conventional method. Chest drain wound closure using knotless suture material is feasible based on the short-term results of the complication rate.


title: Design and implementation of the Resuscitation Outcomes Consortium Pragmatic Airway Resuscitation Trial (PART).

text: Airway management is an important component of resuscitation from out-of-hospital cardiac arrest (OHCA). The optimal approach to advanced airway management is unknown. The Pragmatic Airway Resuscitation Trial (PART) will compare the effectiveness of endotracheal intubation (ETI) and Laryngeal Tube (LT) insertion upon 72-h survival in adult OHCA. Encompassing United States Emergency Medical Services agencies affiliated with the Resuscitation Outcomes Consortium (ROC), PART will use a cluster-crossover randomized design. Participating subjects will include adult, non-traumatic OHCA requiring bag-valve-mask ventilation. Trial interventions will include (1) initial airway management with ETI and (2) initial airway management with LT. The primary and secondary trial outcomes are 72-h survival and return of spontaneous circulation. Additional clinical outcomes will include airway management process and adverse events. The trial will enroll a total of 3000 subjects. Results of PART may guide the selection of advanced airway management strategies in OHCA.


title: Advances in laparoscopic colorectal surgery: a review on NOTES and transanal extraction of specimen.

text: Laparoscopic colorectal surgery has rapidly developed since the 1980s. Relative to open surgery, it offers the benefits of less invasiveness and earlier recovery. However, when a mini-laparotomy wound is needed to retrieve the specimen, the benefits of minimally invasive surgery may be compromised as a result of pain- and wound-related complications. The introduction of natural orifice transluminal endoscopic surgery (NOTES) makes "scarless" surgery a possibility; pain- and wound-related complications are totally abolished. However, a number of technical issues need to be overcome before this technique can be used widely. The development of natural orifice specimen extraction surgery abandons the need for a specimen-retrieval incision and helps overcome the technical hurdles of NOTES. As a bridge between true "scarless" surgery and conventional laparoscopic surgery, hybrid procedures combining laparoscopic resection and natural orifice specimen extraction surgery currently play an important role in minimally invasive colorectal surgery.


Harnessing Our Humanity - How Washington's Health Care Workers Have Risen to the Pandemic Challenge.


Ethical guidelines for COVID-19 tracing apps.


Sick time.


title: Vertical sleeve gastrectomy improves indices of metabolic disease in rodent model of surgical menopause.

text: OBJECTIVE Although women are the most common recipients of weight loss surgeries for the amelioration of the comorbidities of obesity, few studies have addressed the efficacy of these procedures with specific attention to reproductive stage. Here we ask in a rodent model of vertical sleeve gastrectomy (VSG) whether improvements to metabolic health are realized in women having received surgical menopause. Specifically we were interested in knowing whether rats made menopausal through surgical means would exhibit persistent hepatic steatosis as reported in previously pregnant, freely cycling female VSG rats or if it is resolved as reported in male VSG rats. METHODS All the rats first received ovariectomy (OVX) and then were placed on high-fat diet before either sham or VSG surgery (N = 12, 9) and then were monitored for resolution of obesity-related comorbidities. RESULTS VSG was sufficient to reduce weight and adiposity in OVX females in comparison to obese rats (P < 0.001). Glucose tolerance (P < 0.05) was improved in OVX-VSG females with no change in insulin sensitivity. Both circulating (P < 0.01) and hepatic triglyceride (P < 0.01) levels were also reduced after VSG. Liver integrity was improved in OVX-VSG in comparison to OVX-obese as reflected by reduced aspartate aminotransferase levels (P < 0.05). The ability of mitochondria to generate adenosine triphosphate was maintained, and an increase in complex IV may decrease the production of mitochondrial reactive oxygen species. CONCLUSIONS Taken together, VSG in OVX rats experience many positive benefits including the resolution of hepatic steatosis that persists in reproductively intact female rats after VSG.


docid: jiivaiwi

title: Hierarchical Poincaré analysis for anaesthesia monitoring.

text: Although the degree of dispersion in Poincaré plots of electroencephalograms (EEG), termed the Poincaré-index, detects the depth of anaesthesia, the Poincaré-index becomes estranged from the bispectral index (BIS) at lighter anaesthesia levels. The present study introduces Poincaré-index20-30 Hz, targeting the 20- to 30-Hz frequency, as the frequency range reported to contain large electromyogram (EMG) portions in frontal EEG. We combined Poincaré-index20-30 Hz with the conventional Poincaré-index0.5-47 Hz using a deep learning technique to adjust to BIS values, and examined whether this layered Poincaré analysis can provide an index of anaesthesia level like BIS. A total of 83,867 datasets of these two Poincaré-indices and BIS-monitor-derived parameters were continuously obtained every 3 s from 30 patients throughout general anaesthesia, and were randomly divided into 75% for a training dataset and 25% for a test dataset. Two Poincaré-indices and two supplemental EEG parameters (EMG70-110 Hz, suppression ratio) in the training dataset were trained in a multi-layer perceptron neural network (MLPNN), with reference to BIS as supervisor. We then evaluated the trained MLPNN model using the test dataset, by comparing the measured BIS (mBIS) with BIS predicted from the model (PredBIS). The relationship between mBIS and PredBIS using the two Poincaré-indices showed a tight linear regression equation: mBIS = 1.00 × PredBIS + 0.15, R = 0.87, p < 0.0001, root mean square error (RMSE) = 7.09, while the relationship between mBIS and PredBIS simply using the original Poincaré-index0.5-47 Hz was weaker (R = 0.82, p < 0.0001, RMSE = 7.32). This suggests the 20- to 30-Hz hierarchical Poincaré analysis has potential to improve on anaesthesia depth monitoring constructed by simple Poincaré analysis.


title: PP-9 NORMAL VALUES OF 3D HIGH-RESOLUTION ANORECTAL MANOMETRY IN CHIDREN.

text: BACKGROUND AND AIMS 3D high-resolution anorectal manometry (3D HRAM) provides a 3D topographic image of pressure along the anal canal. The aim of the study was to determine normal values of 3D HRAM in children. METHODS Children without any symptoms arising from the lower gastrointestinal tract were prospectively enrolled in the study. Manometry procedures were performed using a rigid probe (Covidien/Medtronic, Ireland) without premedication. Pressure within the anal canal and 3D images of sphincters were measured. If possible, defecation dynamics and thresholds of sensation were evaluated. Data were expressed as the mean (±SD). RESULTS A total of 61 children (34 males; age: 2-17 years, mean: 8.28 years) were studied. The mean resting and squeeze sphincter pressures were 83.43 (±23.23) mmHg and 191 (±64.21) mmHg, respectively. The mean length of the anal canal was 2.62 (±0.68) cm and correlated with age (r = 0.49, p < 0.0001). The mean rectal balloon volume to elicit recto-anal inhibitory reflex was 15.66 (±10.9) cc. The first sensation, urge and discomfort were observed at 24.42 (±23.98) cc, 45.91 (±34.55) cc and 91.58 (±50.17) cc of the balloon volume, respectively. The mean resting pressure of the puborectalis muscle was 71.54 (±14.58) mmHg while the mean squeeze pressure was 134.10 (±35.2) mmHg. A positive correlation between age and balloon volume needed to elicit discomfort was determined (r = 0.49, p < 0.001). CONCLUSION Normative data of 3D HRAM in children without symptoms arising from the lower gastrointestinal tract were established. There were no significant differences in pressure results between males and females.


title: Natural and experimental Helicobacter pullorum infection in Brown Norway rats.

text: Helicobacter pullorum is an enterohepatic Helicobacter species (EHS) that was recently reported as a naturally acquired infection in mice. Faecal samples from 18 out of 20 Brown Norway (BN) rats, housed in the same barrier as the H. pullorum-infected mice, were positive for H. pullorum using species-specific PCR. In addition, we determined whether H. pullorum was able to persistently colonize the gastrointestinal tract and/or biliary tree and elicit tissue inflammation as well as a serum IgG response in BN rats. Six (four male, two female) 6-week-old, H. pullorum-negative BN rats were orally dosed with 4×10(8) c.f.u. of H. pullorum every other day for a total of three doses. At 2 weeks post-infection, all rats were H. pullorum-positive by faecal PCR. Five out of the six BN rats remained H. pullorum-positive for the entire 30 week study. PCR analysis of tissue collected at necropsy confirmed that the colon and caecum were the primary sites of H. pullorum colonization. Rats that were persistently colonized by H. pullorum had a sustained H. pullorum-specific IgG response measured by ELISA. Intestinal or hepatic pathology associated with H. pullorum infection was not noted. To our knowledge, this is the first report documenting that rats can be persistently colonized with an EHS that also infects humans.


title: Dormant micro arteriovenous malformations lead to recurrent cerebral haemorrhage.

text: INTRODUCTION Some micro arteriovenous malformations (AVMs) located in deep brain are undetectable. How to choose a proper timing to detect these AVMs remains unclear. CASE DESCRIPTION A 21-year-old male patient was admitted to our center for intraventricular haematoma. Digital subtraction angiographies (DSAs) were performed one week and one month respectively after his haemorrhage, but no positive results were obtained. The patient was hospitalized for re-haemorrhage six years later. A micro AVM with two diffused niduses was detected and embolised three months after his re-haemorrhage. The patient recovered without any neurological deficit. DISCUSSION AND EVALUATION Compressive effects of haematoma and spontaneous obliteration of AVMs might play pivotal roles in negative DSA results. CONCLUSIONS Strategic and timely use of DSA could identify some dormant re-haemorrhagic AVMs.


title: Malabsorption and intestinal adaptation after one anastomosis gastric bypass compared with Roux-en-Y gastric bypass in rats.

text: The technically easier one-anastomosis (mini) gastric bypass (MGB) is associated with similar metabolic improvements and weight loss as the Roux-en-Y gastric bypass (RYGB). However, MGB is controversial and suspected to result in greater malabsorption than RYGB. In this study, we compared macronutrient absorption and intestinal adaptation after MGB or RYGB in rats. Body weight and food intake were monitored and glucose tolerance tests were performed in rats subjected to MGB, RYGB, or sham surgery. Carbohydrate, protein, and lipid absorption was determined by fecal analyses. Intestinal remodeling was evaluated by histology and immunohistochemistry. Peptide and amino acid transporter mRNA levels were measured in the remodeled intestinal mucosa and those of anorexigenic and orexigenic peptides in the hypothalamus. The MGB and RYGB surgeries both resulted in a reduction of body weight and an improvement of glucose tolerance relative to sham rats. Hypothalamic orexigenic neuropeptide gene expression was higher in MGB rats than in RYGB or sham rats. Fecal losses of calories and proteins were greater after MGB than RYGB or sham surgery. Intestinal hyperplasia occurred after MGB and RYGB with increased jejunum diameter, higher villi, and deeper crypts than in sham rats. Peptidase and peptide or amino acid transporter genes were overexpressed in jejunal mucosa from MGB rats but not RYGB rats. In rats, MGB led to greater protein malabsorption and energy loss than RYGB. This malabsorption was not compensated by intestinal overgrowth and increased expression of peptide transporters in the jejunum.


title: The unacknowledged incidence of laparoscopic stapler malfunction.

text: BACKGROUND Laparoscopic instruments are being used with increasing frequency. Our surgeons recently experienced several independent adverse events involving the laparoscopic linear stapler. Although the Food and Drug Administration maintains a Manufacturer and User Facility Device Experience (MAUDE) database to track such voluntary reports, many events are not reported and the true incidence of adverse events is unknown. We attempted to determine how frequently minimally invasive surgeons have experienced technical problems with a laparoscopic stapler. METHODS Following IRB approval, we electronically distributed an anonymous 10-question survey to the 124 minimally invasive program directors listed in the Fellowship Council database. The questions focused on personal or peer experience with laparoscopic stapler malfunction, frequency and type of malfunction, device manufacturer, whether the operation was altered, and root cause analysis of the event. RESULTS Forty-four of the 124 program directors (35%) completed the survey. The majority reported personal or peer experience (86%) with a linear stapler not releasing (66%) or not firing (73%) after application, with 27% of the respondents noting that this occurred three or more times. The malfunction was not related to type of load, straight (23%) or reticulating (32%) model, or manufacturer (Ethicon 30%, Covidien 36%). One quarter of the respondents noted that the malfunction caused them to significantly alter their operative procedure, and 30% reported that they received no helpful feedback from the manufacturer despite contacting it. CONCLUSIONS Most minimally invasive surgeons have experienced laparoscopic linear stapler malfunction and 25% have had to significantly alter the planned operative procedure due to the malfunction.


title: Radiological approach to COVID-19 pneumonia with an emphasis on chest CT.

text: Coronavirus disease 2019 (COVID-19) has recently become a worldwide outbreak with several millions of people infected and more than 160.000 deaths. A fast and accurate diagnosis in this outbreak is critical to isolate and treat patients. Radiology plays an important role in the diagnosis and management of the patients. Among various imaging modalities, chest CT has received attention with its higher sensitivity and specificity rates. Shortcomings of the real-time reverse transcriptase-polymerase chain reaction test, including inappropriate sample collection and analysis methods, initial false negative results, and limited availability has led to widespread use of chest CT in the diagnostic algorithm. This review summarizes the role of radiology in COVID-19 pneumonia, diagnostic accuracy of imaging, and chest CT findings of the disease.


title: The plight of patients with lupus nephritis in Wuhan, China.

text: The number of cases of SARS-CoV2 infection is rising rapidly globally. Severe disease and high fatality are observed in older patients and with comorbid conditions (1).


title: Global regulation of alternative RNA splicing by the SR-rich protein RBM39.

text: BACKGROUND RBM39 is a serine/arginine-rich RNA-binding protein that is highly homologous to the splicing factor U2AF65. However, the role of RBM39 in alternative splicing is poorly understood. METHODS In this study, RBM39-mediated global alternative splicing was investigated using RNA-Seq and genome-wide RBM39-RNA interactions were mapped via cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq) in wild-type and RBM39-knockdown MCF-7 cells. RESULTS RBM39 was involved in the up- or down-regulation of the transcript levels of various genes. Hundreds of alternative splicing events regulated by endogenous RBM39 were identified. The majority of these events were cassette exons. Genes containing RBM39-regulated alternative exons were found to be linked to G2/M transition, cellular response to DNA damage, adherens junctions and endocytosis. CLIP-Seq analysis showed that the binding site of RBM39 was mainly in proximity to 5' and 3' splicing sites. Considerable RBM39 binding to mRNAs encoding proteins involved in translation was observed. Of particular importance, ~20% of the alternative splicing events that were significantly regulated by RBM39 were similarly regulated by U2AF65. CONCLUSIONS RBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65. GENERAL SIGNIFICANCE The current study offers a genome-wide view of RBM39's regulatory function in alternative splicing. RBM39 may play important roles in multiple cellular processes by regulating both alternative splicing of RNA molecules and transcript levels.


title: Ticagrelor in Acute Stroke or Transient Ischemic Attack in Asian Patients: From the SOCRATES Trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

text: BACKGROUND AND PURPOSE In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), ticagrelor was not superior to aspirin. Because of differences in patient demographics and stroke disease pattern in Asia, outcomes of ticagrelor versus aspirin were assessed among Asian patients in a prespecified exploratory analysis. METHODS Baseline demographics, treatment effects, and safety of ticagrelor and aspirin were assessed among Asian patients. Differences in outcomes between groups were assessed using Cox proportional hazard model. RESULTS A total of 3858 (29.2%) SOCRATES participants were recruited in Asia. Among the Asian patients, the primary end point event occurred in 186 (9.6%) of the 1933 patients treated with ticagrelor, versus 224 (11.6%) of the 1925 patients treated with aspirin (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99). The exploratory P value for treatment-by-region interaction was 0.27. The primary end point event rate in the Asian subgroup was numerically higher than that in the non-Asian group (10.6% versus 5.7%; nominal P<0.01). Among the Asian patients, the rate of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeding was similar in the ticagrelor group and the aspirin group (0.6% versus 0.8%; hazard ratio, 0.76; 95% confidence interval, 0.36-1.61). CONCLUSIONS The event rates were numerically higher in the Asian patients. Among the Asian patients with acute stroke or transient ischemic attacks, there was a trend toward a lower hazard ratio in reducing risk of the primary end point of stroke, myocardial infarction, or death in the ticagrelor group. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.


title: Cadaveric validation of porcine model suggests noninvasive positive pressure ventilation may be safe following esophagectomy.

text: BACKGROUND We previously used a pig model to demonstrate that noninvasive positive pressure ventilation (NPPV) may be a safe alternative to endotracheal intubation (ET). We sought to validate our model by quantifying the pressure threshold of esophageal anastomoses in human cadavers as a step before a clinical trial. METHODS We performed stapled side-to-side, functional end-to-end esophageal anastomoses in 10 cadaveric specimens from autopsy. With intraluminal pressure monitoring, we insufflated the anastomosis with air until a leak was observed, and measured the maximum tolerated pressure. RESULTS Cadaveric esophageal anastomoses tolerated 101±39 cmH2O (range, 63-140 cmH2O) of pressure before leak was observed. The maximum pressure threshold ranged from 59 to 246 cmH2O. The leak was always at the anastomosis. There was no significant difference in pressure threshold between cadaveric and previously described porcine anastomoses. CONCLUSIONS We created a human cadaveric model that in conjunction with our porcine data demonstrates that a human esophageal anastomosis can tolerate manifold higher pressures than are delivered to the esophagus by NPPV. This is the final step before a trial of NPPV in patients following esophagectomy.


title: Swallowing behaviours and feeding environment in relation to communication development from early infancy to 6 years of age: a scoping review protocol.

text: INTRODUCTION Understanding the influences of early swallowing function and feeding environment on the development of communication will enhance prevention and intervention initiatives for young children. This scoping review will help elucidate key elements affecting the developmental trajectory of communicative systems, typically robust and well-developed by formal school entry. We aim to (1) map the current state of the literature in a growing field of interest that has the potential to advance knowledge translation, (2) identify existing gaps and (3) provide research direction for future investigations surrounding feeding-swallowing functions and environment that support or forestall communication development in young children. METHODS AND ANALYSIS We are proposing a scoping review to identify the breadth and depth of the existing literature regarding swallowing-feeding functions and environment relative to the onset and progression of communicative behaviours from infancy to 6 (<6;0) years of age. Our protocol delineates rigorous methods according to Arskey and O'Malley's framework and includes elaborations by Levac and colleagues. We will search the literature based on 10 databases, 17 peer-reviewed journals, 4 conference proceedings and 6 grey literature sources. Two authors will independently screen abstracts and review full articles, remaining blind to each other's results. A third author will contribute to resolving any discrepant results from both the abstract and article review. Subsequently, we will extract data and chart information from accepted articles using a pre-established data collection form. We will stratify results according to healthy versus impaired swallowing-feeding functions and communication development. ETHICS AND DISSEMINATION Our scoping review does not require ethical approval. We will disseminate our final study results through international and national conference presentations, publication in a peer-reviewed journal and knowledge translation activities with stakeholders.


title: POMC: The Physiological Power of Hormone Processing.

text: Pro-opiomelanocortin (POMC) is the archetypal polypeptide precursor of hormones and neuropeptides. In this review, we examine the variability in the individual peptides produced in different tissues and the impact of the simultaneous presence of their precursors or fragments. We also discuss the problems inherent in accurately measuring which of the precursors and their derived peptides are present in biological samples. We address how not being able to measure all the combinations of precursors and fragments quantitatively has affected our understanding of the pathophysiology associated with POMC processing. To understand how different ratios of peptides arise, we describe the role of the pro-hormone convertases (PCs) and their tissue specificities and consider the cellular processing pathways which enable regulated secretion of different peptides that play crucial roles in integrating a range of vital physiological functions. In the pituitary, correct processing of POMC peptides is essential to maintain the hypothalamic-pituitary-adrenal axis, and this processing can be disrupted in POMC-expressing tumors. In hypothalamic neurons expressing POMC, abnormalities in processing critically impact on the regulation of appetite, energy homeostasis, and body composition. More work is needed to understand whether expression of the POMC gene in a tissue equates to release of bioactive peptides. We suggest that this comprehensive view of POMC processing, with a focus on gaining a better understanding of the combination of peptides produced and their relative bioactivity, is a necessity for all involved in studying this fascinating physiological regulatory phenomenon.


title: Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment.

text: Extracellular RNAs participate in intercellular communication, and are being studied as promising minimally invasive diagnostic markers. Several studies in recent years showed that tRNA halves and distinct Y RNA fragments are abundant in the extracellular space, including in biofluids. While their regulatory and diagnostic potential has gained a substantial amount of attention, the biogenesis of these extracellular RNA fragments remains largely unexplored. Here, we demonstrate that these fragments are produced by RNase 1, a highly active secreted nuclease. We use RNA sequencing to investigate the effect of a null mutation of RNase 1 on the levels of tRNA halves and Y RNA fragments in the extracellular environment of cultured human cells. We complement and extend our RNA sequencing results with northern blots, showing that tRNAs and Y RNAs in the non-vesicular extracellular compartment are released from cells as full-length precursors and are subsequently cleaved to distinct fragments. In support of these results, formation of tRNA halves is recapitulated by recombinant human RNase 1 in our in vitro assay. These findings assign a novel function for RNase 1, and position it as a strong candidate for generation of tRNA halves and Y RNA fragments in biofluids.


title: Robot-assisted laparoscopic Mitrofanoff appendicovesicostomy technique and outcomes of extravesical and intravesical approaches.

text: BACKGROUND With growing experience in pediatric robotic surgery, select centers are now performing robot-assisted, laparoscopic Mitrofanoff appendicovesicostomy (RALMA). OBJECTIVE We present our technique and outcomes of RALMA with or without enterocystoplasties and compare stomal outcomes between two different approaches of the appendicovesical anastomosis: an extravesical (EV) anterior bladder approach and an intravesical (IV) posterior bladder approach. DESIGN, SETTING, AND PARTICIPANTS Data from 18 children who have undergone RALMA since 2008 were retrospectively reviewed. RALMA was performed by one surgeon in an academic setting. SURGICAL PROCEDURE The appendix was anastomosed on the posterior wall of the bladder intravesically when concomitant enterocystoplasty was done. Otherwise, the appendix was anastomosed extravesically on the anterior wall of the bladder. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome measured was the overall continence rate. Secondary outcomes included the overall complication rate and stomal complications. RESULTS AND LIMITATIONS The entire cohort included 18 patients (10 IV, 8 EV). The mean overall operative time was 494.1 min. The mean overall length of hospitalization was 5.2 d. There were five immediate, postoperative complications (all Clavien grade 1): three postoperative ilea, one stomal site infection, and one clogged suprapubic catheter. Median follow-up was 24.2 mo. The overall stomal continence rate was 94.4%. One patient from the IV group required dextranomer/hyaluronic acid copolymer for stomal incontinence. Among the eight patients in the EV cohort, there was one stomal complication of stomal stenosis (Clavien grade 1). Among the 10 patients in the IV cohort, there were two stomal complications requiring revisions (both Clavien grade 3): parastomal hernia and stomal stenosis. Limitations of the study include retrospective design, small number of patients, and lack of direct comparison of approaches given the nature of the surgery. CONCLUSIONS Our updated outcomes of RALMA with or without enterocystoplasty continue to be encouraging, with a 94.4% continence rate. We believe that anterior EV reimplantation is a feasible option in isolated RALMA.


title: COVID-19: A Window of Opportunity for Positive Healthcare Reforms.

text: The current coronavirus disease 2019 (COVID-19) pandemic is testing healthcare systems like never before and all efforts are now being put into controlling the COVID-19 crisis. We witness increasing morbidity, delivery systems that sometimes are on the brink of collapse, and some shameless rent seeking. However, besides all the challenges, there are also possibilities that are opening up. In this perspective, we focus on lessons from COVID-19 to increase the sustainability of health systems. If we catch the opportunities, the crisis might very well be a policy window for positive reforms. We describe the positive opportunities that the COVID-19 crisis has opened to reduce the sources of waste for our health systems: failures of care delivery, failures of care coordination, overtreatment or low-value care, administrative complexity, pricing failures and fraud and abuse. We argue that current events can canalize some very needy reforms to make our systems more sustainable. As always, political policy windows are temporarily open, and so swift action is needed, otherwise the opportunity will pass and the vested interests will come back to pursue their own agendas. Professionals can play a key role in this as well.


Prenatal Air Pollution and Child Lung Function: The Impossible Search for a Vulnerable Trimester.


title: Premature infants born at <25 weeks of gestation may be compromised by currently recommended resuscitation techniques.

text: AIM Standard resuscitation guidelines are based on data from a range of gestational ages. We sought to evaluate the effectiveness of our delivery room resuscitation protocol across a range of gestational ages in preterm infants born at <29 weeks. METHODS We performed an observational study of prospectively collected video recordings of 73 preterm infants. The percentage of bradycardic patients, time to reach target oxygen saturation and the extent of all interventions were compared between three gestational age groups: 22-24 weeks (n = 22), 25-26 weeks (n = 27) and 27-28 weeks (n = 24). RESULTS Although the same resuscitation protocol was followed for all infants, bradycardic infants born <25 weeks responded poorly and required significantly longer to reach oxygen saturation targets of >70%, >80% and >90% (p < 0.03). They required significantly more interventions and had higher rate of death (p < 0.05) and severe intraventricular haemorrhage (p < 0.03). Significantly lower heart rate and oxygen saturation values were found in infants with intraventricular haemorrhage. CONCLUSION Current recommendations for resuscitation may fail to achieve timely lung aeration in infants born at the borderline of viability, leading to higher mortality and morbidity. Sustained inflation and delayed cord clamping may be effective alternatives.


title: Endoscopic haemostasis: an overview of procedures and clinical scenarios.

text: Acute gastrointestinal bleeding is among the most urgent situations in daily gastroenterological practise. Endoscopy plays a key role in the diagnosis and treatment of such cases. Endoscopic haemostasis is probably the most important technical challenge that must be mastered by gastroenterologists. It is essential for both the management of acute gastrointestinal haemorrhage and the prevention of bleeding during high-risk endoscopic procedures. During the last decade, endoscopic haemostasis techniques and tools have grown in parallel with the number of devices available for endotherapy. Haemostatic powders, over-the-scope clips, haemostatic forceps, and other emerging technologies have changed daily practise and complement the standard available armamentarium (injectable, thermal, and mechanical therapy). Although there is a lack of strong evidence-based information on these procedures because of the difficulty in designing statistically powerful trials on this topic, physicians must be aware of all available devices to be able to choose the best haemostatic tool for the most effective procedure. We herein present an overview of procedures and clinical scenarios to optimise the management of gastrointestinal bleeding in daily practise.


title: In Vitro Response of Human Peripheral Blood Mononuclear Cells (PBMC) to Collagen Films Treated with Cold Plasma.

text: The implantation of biomedical devices, including collagen-based implants, evokes an inflammatory response. Despite inflammation playing an important role in the early stages of wound healing, excessive and non-resolving inflammation may lead to the poor performance of biomaterial implants in some patients. Therefore, steps should be taken to control the level and duration of an inflammatory response. In this study, oxygen and nitrogen gas plasmas were employed to modify the surface of collagen film, with a view to modifying the surface properties of a substrate in order to induce changes to the inflammatory response, whilst maintaining the mechanical integrity of the underlying collagen film. The effects of cold plasma treatment and resultant changes to surface properties on the non-specific inflammatory response of the immune system was investigated in vitro in direct contact cell culture by the measurement of protein expression and cytokine production after one and four days of human peripheral blood mononuclear cell (PBMC) culture. The results indicated that compared to oxygen plasma, nitrogen plasma treatment produced an anti-inflammatory effect on the collagen film by reducing the initial activation of monocytes and macrophages, which led to a lower production of pro-inflammatory cytokines IL-1β and TNFα, and higher production of anti-inflammatory cytokine IL-10. This was attributed to the combination of the amino chemical group and the significant reduction in roughness associated with the introduction of the nitrogen plasma treatment, which had an effect on the levels of activation of the adherent cell population.


Pneumonitis and extreme failure to thrive.


title: Work-related Mental Consequences: Implications of Burnout on Mental Health Status Among Health Care Providers.

text: INTRODUCTION Burnout can create problems in every aspect of individual's' human life. It may have an adverse effect on interpersonal and family relations and can lead to a general negative attitude towards life. AIM The purpose of this study is to investigate whether burnout is associated with the mental health status of health care providers. MATERIAL AND METHODS The sample in this study consisted of 240 health care employees. The Greek version of Maslach's Burnout Inventory (MBI) was used for measuring burnout levels and the Greek version of the Symptoms Rating Scale for Depression and Anxiety (SRSDA) questionnaire was used to evaluate health care providers' mental health status. Descriptive statistics were initially generated for sample characteristics. Normality was checked by the Kolmogorov-Smirnov test and data was processed with parametric tests. General linear models with MBI dimensions as independent variables and SRSDA subscales as dependent variables were used to determine the relation between burnout and mental health status. Statistics were processed with SPSS v. 17.0 (SPSS, Chicago, IL, USA). Statistical significance was set at p=0.05. RESULTS The average age of the sample is 40.00±7.95 years. Regarding gender the percentage of men is 21.40% (N=49) and of women is 78.60% (N=180). Overall the professional burnout of health care workers is moderate. The mean score for emotional exhaustion is 26.41, for personal accomplishment 36.70 and for depersonalization 9.81. The mean for each subscale of SRSDA is 8.23±6.79 for Depression Beck-21, 3.96±4.26 for Depression Beck-13, 4.91±4.44 for Melancholia, 6.32±4.35 for Asthenia and 6.36±4.72 for Anxiety. The results of general linear models with the MBI dimensions as independent variables and the SRSDA subscales as dependent variables are shown that emotional exhaustion and personal accomplishment are statistically correlated with all subscales of SRSDA, while depersonalization is not correlated with any SRSDA subscale. CONCLUSIONS Burnout appears to implicate mental health status of healthcare providers in work index. Emotional exhaustion is the burnout dimension that is correlated the most with employees' mental health.


title: Robot-assisted laparoscopic radical cystectomy with complete intracorporeal urinary diversion.

text: Robot-assisted radical cystectomy with intracorporeal urinary diversion (RARC-ICUD) has only recently been explored as a viable surgical option for patients with muscle-invasive bladder cancer seeking satisfactory oncologic control while benefiting from minimally invasive surgical techniques. Inspired by earlier open and laparoscopic work, initial descriptions of RARC-ICUD were published in 2003, and have since been followed by multiple larger case series which have suggested promising outcomes for our patients. However, the rate of adoption has remained relatively slow when compared to other robot-assisted procedures such as the radical prostatectomy, likely owing to longer operative times, operative complexity, costs, and uncertainty regarding oncologic efficacy. The operative technique for RARC-ICUD has evolved over the past decade and several high-volume centers have shared tips to improve efficiency and make the operation possible for a growing number of urologists. Though there are still questions regarding economic costs, effectiveness, and generalizability of outcomes reported in published data, a growing dataset has brought us ever closer to the answers. Here, we present our current operative technique for RARC-ICUD and discuss the state of the literature so that the urologist may hold an informed discussion with his or her patients.


title: Prevalence, Presentation and Treatment of 'Balloon Undilatable' Chronic Total Occlusions: Insights from a Multicenter US Registry.

text: BACKGROUND The prevalence, treatment and outcomes of balloon undilatable chronic total occlusions (CTOs) have received limited study. METHODS We examined the prevalence, clinical and angiographic characteristics, and procedural outcomes of percutaneous coronary interventions (PCIs) for balloon undilatable CTOs in a contemporary multicenter US registry. RESULTS Between 2012 and 2017 data on balloon undilatable lesions were available for 425 consecutive CTO PCIs in 415 patients in whom guidewire crossing was successful: 52 of 425 CTOs were balloon undilatable (12%). Mean patient age was 65 ± 10 years and most patients were men (84%). Patients with balloon undilatable CTOs were more likely to be diabetic (67 vs. 41%, P < 0.001) and have heart failure (44 vs. 28%, P = 0.027). Balloon undilatable CTOs were longer (40 mm [interquartile range, IQR 20-50] vs. 30 [IQR 15-40], P = 0.016), more likely to have moderate/severe calcification (87 vs. 54%, P < 0.001), and had higher J-CTO score (3.2 ± 1.1 vs. 2.5 ± 1.3, P < 0.001) and PROGRESS-CTO complications score (3.9 ± 1.7 vs. 3.1 ± 2.0, P < 0.005). They were associated with lower technical and procedural success (92 vs. 98%, P = 0.024; and 88 vs. 96%, P = 0.034, respectively) and higher risk for in-hospital major adverse events (8 vs. 2%, P = 0.008) due to higher perforation rates. The most frequent treatments for balloon undilatable CTOs were high pressure balloon inflations (64%), rotational atherectomy (31%), laser (21%), and cutting balloons (15%). CONCLUSIONS Balloon undilatable CTOs are common and are associated with lower success and higher complication rates.


title: Single-port access laparoscopic staging operation for a borderline ovarian tumor.

text: Minimally invasive surgery is widely used in benign gynecologic diseases and may be used in malignancies. We performed a single-port access laparoscopy staging - bilateral salpingo-oophorectomy, laparoscopy-assisted vaginal hysterectomy, bilateral pelvic lymphadenectomy, infracolic omentectomy, and washing cytology - in a borderline ovarian tumor. The number of harvested pelvic lymph nodes were twenty-three and there were no intraoperative or postoperative complications. Single-port access laparoscopic staging may be performed in selected patients. The efficacy, safety, and potential benefits of this technique should be evaluated in further trials.


title: Development of a 124I-labeled version of the anti-PSMA monoclonal antibody capromab for immunoPET staging of prostate cancer: Aspects of labeling chemistry and biodistribution.

text: Correct staging of prostate cancer is an unmet clinical need. Radionuclide targeting of prostate-specific membrane antigen (PSMA) with 111In-labeled capromab pendetide (ProstaScint) is a clinical option for prostate cancer staging. We propose the use of 124I-labeled capromab to decrease the retention of radioactivity in healthy organs (due to the non-residualizing properties of the radiolabel). The use of 124I as a label should increase imaging sensitivity due to the advantages of PET as an imaging modality. Capromab targets the intracellular domain of PSMA; accumulation of radioactivity in the tumor should not depend on internalization of the antigen/antibody complex. Capromab was iodinated, and its targeting properties were compared with indium labeled counterpart in LNCaP xenografts in dual isotope mode. PSMA-negative xenografts (PC3) were used as a negative control. Radioiodinated capromab bound to PSMA specifically. Biodistribution of 125I/111In-capromab showed a more rapid clearance of iodine radioactivity from liver, spleen, kidneys, bones, colon tissue, as well as tumors. Maximum tumor uptake (13±8% ID/g for iodine and 29±9% ID/g for indium) and tumor-to-non-tumor ratios for both agents were measured 5 days post-injection (pi). High tumor accumulation and low uptake of radioactivity in normal organs were confirmed using microPET/CT 5 days pi of 124I-capromab.


Should Pediatric Patients Be Prioritized When Rationing Life-Saving Treatments During the COVID-19 Pandemic?