title: A Multistep, Consensus-Based Approach to Organ Allocation in Liver Transplantation: Toward a "Blended Principle Model".

text: Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD-based system for governing organ allocation. Working groups of transplant surgeons and hepatologists prepared a list of statements for each topic, scoring their quality of evidence and strength of recommendation using the Centers for Disease Control grading system. A jury of Italian transplant surgeons, hepatologists, intensivists, infectious disease specialists, epidemiologists, representatives of patients' associations and organ-sharing organizations, transplant coordinators, and ethicists voted on and validated the proposed statements. After carefully reviewing the statements, a critical proposal for revising Italy's current liver allocation policy was prepared jointly by transplant surgeons and hepatologists.


title: [The Key Role of Taiwanese Nurses in Combating COVID-19 Pandemic].

text: As the COVID-19 pandemic continues to rage worldwide, Taiwan has achieved outstanding performance in controlling the spread of the outbreak domestically, earning global appreciation. Nurses on the frontlines deserve much of the credit for the ongoing success in fighting against this outbreak in Taiwan. Taiwan's success to date is grounded in proactive preparedness and deployment by the government and effective teamwork among government agencies, medical institutions, enterprises, and the public. Comprehensive containment strategies and preparedness have allowed nurses to effectively perform their duties and combat the pandemic. Nurses safeguard the public's health a myriad of ways, including implementing quarantine measures at air and seaports, conducting fever screenings, delivering inpatient isolation treatments, performing case contact tracing, providing community care services, and operating special chartered-flight services. The Taiwan Nurses Association (TWNA) provides vital lead in this pandemic response, advocating for the safety, health and wellbeing of nurses; highlighting the contributions and value of nurses; and enhancing the professional image and status of nurses. Furthermore, through its global platform, TWNA shares with peer organizations worldwide the content and efficacy of actions taken by the national government, the contributions of healthcare workers, and the support and encouragement received from the public in COVID-19 containment to demonstrate values of Taiwan and nursing.


title: RNA-Dependent RNA Polymerase as a Target for COVID-19 Drug Discovery.

text: COVID-19 respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly become a global health issue since it emerged in December 2019. While great global efforts are underway to develop vaccines and to discover or repurpose therapeutic agents for this disease, as of this writing only the nucleoside drug remdesivir has been approved under Emergency Use Authorization to treat COVID-19. The RNA-dependent RNA polymerase (RdRP), a viral enzyme for viral RNA replication in host cells, is one of the most intriguing and promising drug targets for SARS-CoV-2 drug development. Because RdRP is a viral enzyme with no host cell homologs, selective SARS-CoV-2 RdRP inhibitors can be developed that have improved potency and fewer off-target effects against human host proteins and thus are safer and more effective therapeutics for treating COVID-19. This review focuses on biochemical enzyme and cell-based assays for RdRPs that could be used in high-throughput screening to discover new and repurposed drugs against SARS-CoV-2.


title: A new procedure with stomach-lifting techniques to simplify laparoscopy-assisted distal gastrectomy and extraperigastric lymph node dissection for gastric cancer.

text: Laparoscopy-assisted gastrectomy with extraperigastric lymph node dissection for gastric cancer is a complicated procedure that generally requires advanced laparoscopic surgical skill. We devised a simplified but effective laparoscopic procedure that provides a better visual field to perform safe lymph node dissection more quickly. First, a mini-laparotomy is done and a clear visual field is created by pulling a mini-retractor to the right or left. The laparoscopic procedure is made easier and safer by taping the stomach body, and by using the fringe of an abdominal wall sealing device (Lapdisk) placed behind the stomach, and a scope holder for the snake-retractor. The lymph nodes along the common hepatic vessels, left gastric vessels, and celiac artery (extraperigastric lymph nodes) are then dissected laparoscopically. The suprapyloric and infrapyloric lymph nodes are dissected through the mini-laparotomy incision and gastroduodenostomy is done using an anastomotic device. We performed laparoscopy-assisted distal gastrectomy (LADG) in 70 patients with gastric carcinomas located in the distal stomach (mean body mass index: 24.3). The mean operating time was 170 min and blood loss was minimal. All patients recovered well with minimal pain and good postoperative quality of life. We conclude that our simple and practical procedure for LADG with extraperigastric lymph node dissection can be performed safely and easily.


[The protocol for prevention, diagnosis and treatment of liver injury in coronavirus disease 2019].


title: An ultra-rapid real-time RT-PCR method for detecting Middle East respiratory syndrome coronavirus using a mobile PCR device, PCR1100.

text: Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is usually diagnosed through highly sensitive and specific genetic tests such as real-time reverse transcription polymerase chain reaction (RT-PCR). Currently, two real-time RT-PCR assays targeting the upE and ORF1a regions of the MERS-CoV genome are widely used and are the standard assays recommended by the World Health Organization (WHO). The MERS outbreaks to date suggest that rapid diagnosis and subsequent isolation of infected patients, particularly superspreaders, are critical for containment. However, conventional real-time RT-PCR assays require large laboratory instruments, and amplification takes approximately 2 h. These are disadvantages for rapid diagnosis. Here, an ultra-rapid real-time RT-PCR test was established: a multiplex assay for upE and ORF1a running on the mobile PCR1100 device. As few as five copies of MERS-CoV RNA can be detected within 20 min using the WHO standard assays with similar sensitivity and specificity to those of a conventional real-time PCR instrument such as the LightCyler, enabling timely intervention to control MERS-CoV infection.


title: Increased body mass and depressive symptomatology are associated with hypercholesterolemia, among elderly individuals; results from the MEDIS study.

text: BACKGROUND Hypercholesterolemia is one of the most important factors causing cardiovascular disease (CVD). The aim of the present work was to evaluate the relationships between socio-demographic, clinical, lifestyle and depression status and the presence of hypercholesterolemia, among elderly individuals without known CVD. METHODS During 2005-2007, 1190 elderly (aged 65 to 100 years) men and women (from Cyprus, Mitilini, Samothraki, Cephalonia, Crete, Lemnos, Corfu and Zakynthos) were enrolled. Socio-demographic, clinical and lifestyle factors were assessed through standard procedures. Symptoms of depression were evaluated using the short-form of the Geriatric Depression Scale (GDS, range 0-15). Dietary habits were assessed through a semi-quantitative food frequency questionnaire. Hypercholesterolemia was defined as total serum cholesterol > 200 mg/dL or use of lipids lowering medication. RESULTS 44.6% of males and 61.9% of females had hypercholesterolemia (p < 0.001). Only, 63% of hypercholesterolemic participants were under special diet or pharmaceutical treatment. Hypercholisterolemic individuals had higher prevalence of obesity (43% vs. 25%), hypertension (76% vs. 57%) and diabetes (25% vs. 17%) compared with normal participants (p < 0.001). Furthermore, hypercholisterolemic participants showed higher depression levels (p = 0.002). After adjusting for various confounders, GDS score and BMI correlated with 13% (95%CI 0.98-1.30) and 14% (95%CI 0.99-1.31) higher likelihood of having hypercholesterolemia. CONCLUSION A considerable proportion of our elderly sample had hypercholesterolemia, while 1/3 of them were untreated. Furthermore, presence of hypercholesterolemia was correlated with depressive symptomatology and increased BMI.


MinIP technique may be helpful in diagnosing COVID-19.


title: Construct validation: simulation of thoracoscopic intrathoracic anastomosis.

text: BACKGROUND AND OBJECTIVES We sought to develop a simulation model that accurately replicates the challenges of the thoracoscopic intrathoracic anastomosis. This model is intended to serve as a teaching tool during the introduction to, and development of, the skills required to perform a thoracoscopic intrathoracic anastomosis during an Ivor Lewis minimally invasive esophagectomy. METHODS The simulation model uses porcine tissue placed within an artificial hemithorax and covered with a synthetic skin. The model is draped to simulate a realistic operative setting, and ports are placed in standard surgical fashion. Dissection of the esophagus from the mediastinum is then performed, followed by the creation of an esophagogastric anastomosis. The effectiveness of the training model was evaluated using volunteer general and thoracic surgery residents at varying stages of surgical training. The quality of the anastomoses created were evaluated using both objective and subjective criteria, and successful anastomoses were tested for leaks using hydrostatic pressure. RESULTS Objective evaluation showed that successful completion of the anastomosis task increased with the number of attempts, with 100% of participants successfully completing an anastomosis by the final attempt. The time to completion of a successful anastomosis also improved across successive attempts. Moreover, objective measures also showed improvement over time based on the graded quality of the completed anastomosis. CONCLUSION As surgical techniques continue to evolve, so must the means by which they are taught. This simulation model shows effectiveness in the training of general and thoracic surgery residents performing thoracoscopic intrathoracic anastomosis during the Ivor Lewis minimally invasive esophagectomy.


title: Treatment of blood blister aneurysms of the internal carotid artery with flow diversion.

text: BACKGROUND Blood blister aneurysms (BBA) are a rare subset of intracranial aneurysms that represent a therapeutic challenge from both a surgical and endovascular perspective. OBJECTIVE To report multicenter experience with flow diversion exclusively for BBA, located at non-branching segments along the anteromedial wall of the supraclinoidal internal carotid artery (ICA). METHODS Consecutive cases of BBA located at non-branching segments along the anteromedial wall of the supraclinoidal ICA treated with flow diversion were included in the final analysis. RESULTS 49 patients with 51 BBA of the ICA treated with devices to achieve the flow diversion effect were identified. 43 patients with 45 BBA of the ICA were treated with the pipeline embolization device and were included in the final analysis. Angiographic follow-up data were available for 30 patients (32 aneurysms in total); 87.5% of aneurysms (28/32) showed complete obliteration, 9.4% (3/32) showed reduced filling, and 3.1% (1/32) persistent filling. There was no difference between the size of aneurysm (≤2 mm vs >2 mm) or the use of adjunct coiling and complete occlusion of the aneurysm on follow-up (P=0.354 and P=0.865, respectively). Clinical follow-up data were available for 38 of 43 patients. 68% of patients (26/38) had a good clinical outcome (modified Rankin scale score of 0-2) at 3 months. There were 7 (16%) immediate procedural and 2 (5%) delayed complications, with 1 case of fatal delayed re-rupture after the initial treatment. CONCLUSIONS Our data support the use of a flow diversion technique as a safe and effective therapeutic modality for BBA of the supraclinoid ICA.


Coronavirus Disease 2019 Pandemic Acute Respiratory Distress Syndrome Survivors: Pain After the Storm?


title: Influenza-associated Hospitalizations and Deaths, Costa Rica, 2009-2012.

text: Data needed to guide influenza vaccine policies are lacking in tropical countries. We multiplied the number of severe acute respiratory infections by the proportion testing positive for influenza. There were ≈6,699 influenza hospitalizations and 803 deaths in Costa Rica during 2009-2012, supporting continuation of a national influenza vaccine program.


title: Preoperative Progressive Pneumoperitoneum Enables Defect Closure and Laparoscopic Repair of Large Parastomal Hernias.

text: PURPOSE Preoperative progressive pneumoperitoneum (PPP) has not been reported in the management of parastomal hernias; therefore, the present study evaluated its effectiveness in the surgical management of large parastomal hernias. PATIENTS AND METHODS This prospective, observational study included 23 consecutive patients with large parastomal hernias who underwent PPP between January 2016 and September 2018. The volume of parastomal hernia (VPH), volume of the abdominal cavity (VAC), and the VPH/VAC ratio were measured before and after PPP using abdominal computed tomography scan data. All the hernias were repaired by a laparoscopic or laparoscopic-open-laparoscopic approach using the intraperitoneal Sugarbaker technique. RESULTS Before and after PPP, the mean VPH was 1442 and 1581 mL (P<0.01), and the mean VAC was 5667 and 9194 mL (P<0.01). The VAC increased by 3527 mL (P<0.01) and was greater than the mean VPH before PPP. The VPH/VAC ratio after PPP was reduced at an average of 8.1% (P<0.01). Fascial closure was achieved in all patients, with no clinical evidence of elevated intra-abdominal pressures. The mean follow-up was 24 months (13 to 40 mo), and, to date, no hernia recurrences have been reported in these patients. CONCLUSIONS PPP is a feasible and useful tool in the surgical management of large parastomal hernias. It passively expands the abdominal volumes, thereby resulting in respiratory adaptation to elevated intra-abdominal pressures.


title: Effects of the COVID-19 pandemic and nationwide lockdown on trust, attitudes toward government, and well-being.

text: The contagiousness and deadliness of COVID-19 have necessitated drastic social management to halt transmission. The immediate effects of a nationwide lockdown were investigated by comparing matched samples of New Zealanders assessed before (Nprelockdown = 1,003) and during the first 18 days of lockdown (Nlockdown = 1,003). Two categories of outcomes were examined: (a) institutional trust and attitudes toward the nation and government and (b) health and well-being. Applying propensity score matching to approximate the conditions of a randomized controlled experiment, the study found that people in the pandemic/lockdown group reported higher trust in science, politicians, and police, higher levels of patriotism, and higher rates of mental distress compared to people in the prelockdown prepandemic group. Results were confirmed in within-subjects analyses. The study highlights social connectedness, resilience, and vulnerability in the face of adversity and has applied implications for how countries face this global challenge. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Preliminary Data Suggests That Biologics in Dermatology Are Not Associated With Adverse COVID-19 Outcomes.


title: Mass screening for fever in children: a comparison of 3 infrared thermal detection systems.

text: OBJECTIVES Infrared thermal detection systems (ITDSs) have been used with limited success outside the United States to screen for fever during recent outbreaks of novel infectious diseases. Although ITDSs are fairly accurate in detecting fever in adults, there is little information about their utility in children. METHODS In a pediatric emergency department, we compared temperatures of children (<18 years old) measured using 3 ITDSs (OptoTherm Thermoscreen, FLIR ThermoVision 360, and Thermofocus 0800H3) to standard, age-appropriate temperature measurements (confirmed fever defined as ≥38.0°C [oral or rectal], ≥37.0°C [axillary]). Measured temperatures were compared with parental reports of fever using descriptive, multivariate, and receiver operating characteristic analyses. RESULTS Of 855 patients, 400 (46.8%) had parent-reported fever, and 306 (35.8%) had confirmed fever. At optimal fever thresholds, OptoTherm and FLIR had sensitivity (83.0% and 83.7%, respectively) approximately equal to parental report (83.9%) and greater than Thermofocus (76.8%), and specificity (86.3% and 85.7%) greater than parental report (70.8%) and Thermofocus (79.4%). Correlation coefficients between traditional thermometry and ITDSs were 0.78 (OptoTherm), 0.75 (FLIR), and 0.66 (Thermofocus). CONCLUSIONS Compared with traditional thermometry, FLIR and OptoTherm were reasonably accurate in detecting fever in children and better predictors of fever than parental report. These findings suggest that ITDSs could be a useful noninvasive screening tool for fever in the pediatric age group.


title: From whole monoclonal antibodies to single domain antibodies: think small.

text: The development of therapeutic monoclonal antibodies over the last 35 years has led to the emergence of a new class of useful therapeutic molecules. These "first generation" antibodies have been obtained thanks to the conjugated and huge efforts of both academic and biotech researchers. About 30 monoclonal antibodies are currently approved for therapeutic use in Europe, USA, and China. Strikingly, only a restricted number of these antibodies are immunoglobulin fragments, single variable domains, or multiunit formats based on the engineering of immunoglobulin variable domains. In the present chapter, we will review the major steps of the therapeutic antibodies history and we will highlight the enormous potential of antibody fragments, either used as multiunits such as bispecific antibodies, single units, or as cell modifiers such as intrabodies or cell surface-expressed molecules.


title: Increase of Clostridium perfringens in association with Eimeria in haemorrhagic enteritis in Japanese beef cattle.

text: A coprological survey with detailed clinical observation of naturally occurring haemorrhagic enteritis (HE) cases was conducted to understand the pathophysiology of HE by clarifying the infection status of Eimeria and enteropathogenic bacteria in cattle. Faecal samples from 55 cases of HE and 26 clinically normal animals were collected, and a quantitative examination of Eimeria and potential enteropathogenic bacteria was performed. The number of Eimeria species oocysts per gram of faeces (OPG) exceeded 10,000 in 69.1 per cent of HE cases with a maximum of 1,452,500 OPG and Eimeria zuernii was found to be overwhelmingly dominant. A significant increase in faecal coliform count was observed in HE cases compared with clinically normal animals. Among the animals shedding >10,000 OPG, 42.9 per cent showed a remarkable increase in Clostridium perfringens abundance (>104 CFU/g) in the faeces. In the cases with C. perfringens detected, its abundance was positively correlated with Eimeria OPG and high C. perfringens abundance was always accompanied by high Eimeria OPG. E. zuernii is likely to play a crucial role in massive multiplication of C. perfringens in HE in cattle.


title: Phonon softening and higher-order anharmonic effect in the superconducting topological insulator SrxBi2Se3.

text: We report the anharmonic effect of the Raman-scattering spectrum in the low-carrier density superconductor SrxBi2Se3, which is dominated by quartic term. Compared to the parent Bi2Se3, the superconducting SrxBi2Se3crystals show obvious phonon softening in the three optical phonon modes A1g1, Eg2, and A1g2. Based on the simulations by the Fano function, we present a compelling evidence of the enhanced electron-phonon coupling in SrxBi2Se3for its smaller asymmetric parameterq. Moreover, an anomalous broadening and intensity antiresonance in the characteristic Raman peaks were observed as the temperature decreased to around 160 K. Thus, the superconducting topological material SrxBi2Se3represents a counterintuitive example where the electron-phonon interaction is strengthened by the accumulation of electron carriers.


title: Single-incision flexible endoscopy (SIFE) for detection and staging of peritoneal carcinomatosis.

text: OBJECTIVE To show the feasibility and the safety of peritoneal carcinomatosis (PC) evaluation by single-incision flexible endoscopy (SIFE) and to compare it to single-incision rigid endoscopy (SIRE). BACKGROUND Direct peritoneal visualization, either by laparotomy or laparoscopy, continues to be the gold standard in diagnosing PC. We reported, in animal study, that combining single-incision laparoscopic surgery and flexible endoscopy improved evaluation of the peritoneal cavity in a live porcine model and in four human cadavers. METHODS Patients, undergoing surgical exploration for diagnosis and staging of PC, were included in a prospective study. Using a superiority design a sample size of 47 patients was determined. Through a single incision, a standardized peritoneoscopy was conducted with rigid (SIRE) and with flexible endoscope (SIFE). Primary outcome was the access success rates for the 13 regions of the Peritoneal Carcinomatosis Index (PCI). RESULTS Overall access to the 13 regions of PCI was successful in 83 % of the cases with SIRE and in 91.1 % with SIFE (p < 10(-10)). SIFE access rates were superior to SIREs' in the regions: R1 (87.2 vs. 61.7 %, p = 0.002), R2 (87.2 vs. 66 %, p = 0.004), R3 (85.1 vs. 59.6 %, p = 0.001) and R6 (80.9 vs. 61.7 %, p = 0.008). The mean PCI was higher (p < 10(4)) with SIFE 12.77 (±11.97) than with SIRE 11.77 (±11.63). CONCLUSION This prospective, comparative study shows that SIFE was significantly superior to SIRE in the exploration of some difficult-to-access peritoneal areas, located in regions 1, 2, 3 and 6. These two minimally invasive staging procedures are safe, feasible and have to be seen as complementary rather than competing.


title: A Randomized, Double-blind, Non-inferiority Trial of Magnesium Sulphate versus Dexamethasone for Prevention of Postoperative Sore Throat after Lumbar Spinal Surgery in the Prone Position.

text: BACKGROUND Postoperative sore throat (POST) is a frequent complication of tracheal intubation, particularly after surgery in the prone position. We designed this study to validate the non-inferiority of magnesium sulphate against dexamethasone for prevention of POST after lumbar spinal surgery. METHODS One hundred and forty-six patients were randomly allocated to receive either magnesium or dexamethasone. Before anesthetic induction, the magnesium group (n = 73) received magnesium sulphate 30 mg/kg followed by 10 mg/kg/h by continuous infusion until the end of surgery. The dexamethasone group (n = 73) received dexamethasone 8 mg. The primary endpoint was the overall incidence of POST, which was assessed serially over 48 hr postoperatively. The predefined margin of non-inferiority for magnesium against dexamethasone was 15%. RESULTS Overall incidences of POST at rest (50.7% versus 49.3% in the magnesium and dexamethasone group, respectively, p = 0.869) and swallowing (65.8% versus 61.6% in the magnesium and dexamethasone group, respectively, p = 0.606) were not different between the groups. The upper limit of the 90% confidence interval, which must be lower than the predefined margin of non-inferiority to prove the non-inferiority of magnesium sulphate against dexamethasone, for at rest and swallowing were 14.97% (p = 0.0496) and 17.19% (p = 0.0854), respectively. The incidences and severities of POST and hoarseness were also not different between the groups throughout the study period. CONCLUSIONS Prophylactic magnesium sulphate appears to be non-inferior to dexamethasone for the prevention of POST at rest in patients undergoing lumbar spinal surgery in the prone position.


title: Tracking respiratory mechanics around natural breathing rates via variable ventilation.

text: Measuring respiratory resistance and elastance as a function of time, tidal volume, respiratory rate, and positive end-expiratory pressure can guide mechanical ventilation. However, current measurement techniques are limited since they are assessed intermittently at non-physiological frequencies or involve specialized equipment. To this end, we introduce ZVV, a practical approach to continuously track resistance and elastance during Variable Ventilation (VV), in which frequency and tidal volume vary from breath-to-breath. ZVV segments airway pressure and flow recordings into individual breaths, calculates resistance and elastance for each breath, bins them according to frequency or tidal volume and plots the results against bin means. ZVV's feasibility was assessed clinically in five human patients with acute lung injury, experimentally in five mice ventilated before and after lavage injury, and computationally using a viscoelastic respiratory model. ZVV provided continuous measurements in both settings, while the computational study revealed <2% estimation errors. Our findings support ZVV as a feasible technique to assess respiratory mechanics under physiological conditions. Additionally, in humans, ZVV detected a decrease in resistance and elastance with time by 12.8% and 6.2%, respectively, suggesting that VV can improve lung recruitment in some patients and can therefore potentially serve both as a dual diagnostic and therapeutic tool.


title: Thromboembolic complications with Pipeline Embolization Device placement: impact of procedure time, number of stents and pre-procedure P2Y12 reaction unit (PRU) value.

text: BACKGROUND Thromboembolic events after Pipeline Embolization Device (PED) placement remain a feared complication among neuroendovascular surgeons. This study aimed to investigate potential risk factors for thromboembolic events in patients undergoing PED placement. METHODS Medical records of patients who underwent PED placement from April 2011 to August 2013 were reviewed. Variables including pre-procedure P2Y12 reaction unit (PRU) value, procedure time, number of PEDs deployed and perioperative neurovascular complications were recorded. Multivariate analysis was performed to identify risk factors for perioperative thromboembolic complications. RESULTS Seventy-four patients were identified. Six patients (8.1%) had changes in neurological status after PED placement including five (6.8%) thromboembolic complications and one (1.4%) delayed intracranial hemorrhage; 50.9% of patients had diffusion-weighted imaging (DWI) changes on post-procedural MRI. Longer procedure time (>116 min) and multiple PED placements (>1) were statistically significant risk factors for symptomatic thromboembolic events (p<0.01). A pre-procedural PRU value >208 had an OR of 11.32 (95% CI 0.06 to 212.57) for symptomatic thromboembolic complications, but the result was not statistically significant. CONCLUSIONS DWI changes on MRI occurred at a much higher rate than new neurological symptoms following PED placement. Longer procedure time and multiple PED deployment are associated with higher risks of new neurological changes due to thromboembolic events. There was a trend for an increased risk of a symptomatic thromboembolic event in patients with pre-procedural PRU values >208. Reloading (clopidogrel 600 mg) patients with preoperative PRU >208 was safe and may have a protective effect on thromboembolic events.


title: The accuracy of haemoglobin A1c as a screening and diagnostic test for gestational diabetes: a systematic review and meta-analysis of test accuracy studies.

text: PURPOSE OF REVIEW Gestational diabetes mellitus (GDM) is associated with adverse pregnancy complications. Accurate screening and diagnosis of gestational diabetes are critical to treatment, and in a pandemic scenario like coronavirus disease 2019 needing a simple test that minimises prolonged hospital stay. We undertook a meta-analysis on the screening and diagnostic accuracy of the haemoglobin A1c (HbA1c) test in women with and without risk factors for gestational diabetes. RECENT FINDINGS Unlike the oral glucose tolerance test, the HbA1c test is simple, quick and more acceptable. There is a growing body of evidence on the accuracy of HbA1c as a screening and diagnostic test for GDM. We searched Medline, Embase and Cochrane Library and selected relevant studies. Accuracy data for different thresholds within the final 23 included studies (16 921 women) were pooled using a multiple thresholds model. Summary accuracy indices were estimated by selecting an optimal threshold that optimises either sensitivity or specificity according to different scenarios. SUMMARY HbA1c is more useful as a specific test at a cut-off of 5.7% (39 mmol/mol) with a false positive rate of 10%, but should be supplemented by a more sensitive test to detect women with GDM.


title: Laparoendoscopic single-site nephrectomy with the aid of intraabdominal retractors.

text: OBJECTIVES To evaluate the feasibility and clinical efficacy of a novel intraabdominal retractor device in laparoendoscopic single-site nephrectomy(LESS-N). METHODS Between February 2012 and February 2017, 98 patients underwent LESS-N in our institution, including 38 patients with benign renal disease and 60 patients with malignant renal disease. 39 were performed conventional LESS-N(C-LESS-N) and 59 were performed intraabdominal retractor-assisted LESS-N(IAR-LESS-N). Demographic data, and perioperative and postoperative data were collected and analyzed retrospectively. RESULTS All the procedures were completed successfully. In C-LESS-N group, four patients were added one 5-mm additional trocar and two patients were converted to open surgery. In IAR-LESS-N group, no patients required additional trocars or conversion to open surgery. The mean operative time was lower in IAR-LESS-N group than that in C-LESS-N group (94.2 min vs 127.4 min, P < 0.05). The mean renal vascular management time declined from 25.4 min in C-LESS-N group to 18.4 min in IAR-LESS-N group (P < 0.05). The mean estimated blood loss was 128.6 ml in C-LESS-N group and 102.3 ml in IAR-LESS-N group (P < 0.05). Two patients in C-LESS-N group required blood transfusion, while none of the patients in IAR-LESS-N group did. No severe postoperative complications occurred in both groups. Study limitations included retrospective study, short follow-up, and accumulated surgical experience and skills. CONCLUSIONS Intraabdominal retractors allow performance of LESS-N with improved working space, quicker renal hilar management, and shortened total operative time. It is expected that the application of intraabdominal retractors, along with the new robotic platform might revive LESS and translate into a renewed future interest of LESS.


title: Enterovirus 2Apro targets MDA5 and MAVS in infected cells.

text: UNLABELLED RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppress interferon production is incompletely understood. MDA5 has been suggested to undergo caspase- and proteasome-mediated degradation during poliovirus infection. Additionally, MAVS is reported to be cleaved during infection with coxsackievirus B3 (CVB3) by the CVB3 proteinase 3C(pro), whereas MAVS cleavage by enterovirus 71 has been attributed to 2A(pro). As yet, a detailed examination of the RLR pathway as a whole during any enterovirus infection is lacking. We performed a comprehensive analysis of crucial factors of the RLR pathway, including MDA5, RIG-I, LGP2, MAVS, TBK1, and IRF3, during infection of CVB3, a human enterovirus B (HEV-B) species member. We show that CVB3 inhibits the RLR pathway upstream of TBK1 activation, as demonstrated by limited phosphorylation of TBK1 and a lack of IRF3 phosphorylation. Furthermore, we show that MDA5, MAVS, and RIG-I all undergo proteolytic degradation in CVB3-infected cells through a caspase- and proteasome-independent manner. We convincingly show that MDA5 and MAVS cleavages are both mediated by CVB3 2A(pro), while RIG-I is cleaved by 3C(pro). Moreover, we show that proteinases 2A(pro) and 3C(pro) of poliovirus (HEV-C) and enterovirus 71 (HEV-A) exert the same functions. This study identifies a critical role of 2A(pro) by cleaving MDA5 and MAVS and shows that enteroviruses use a common strategy to counteract the interferon response in infected cells. IMPORTANCE Human enteroviruses (HEVs) are important pathogens that cause a variety of diseases in humans, including poliomyelitis, hand, foot, and mouth disease, viral meningitis, cardiomyopathy, and more. Like many other viruses, enteroviruses target the host immune pathways to gain replication advantage. The MDA5/MAVS pathway is responsible for recognizing enterovirus infections in the host cell and leads to expression of type I interferons (IFN-I), crucial antiviral signaling molecules. Here we show that three species of HEVs all employ the viral proteinase 2A (2A(pro)) to proteolytically target MDA5 and MAVS, leading to an efficient blockade upstream of IFN-I transcription. These observations suggest that MDA5/MAVS antagonization is an evolutionarily conserved and beneficial mechanism of enteroviruses. Understanding the molecular mechanisms of enterovirus immune evasion strategies will help to develop countermeasures to control infections with these viruses in the future.


title: Four-channel single incision laparoscopic cholecystectomy using a snake retractor: comparison between 3- and 4-channel SILC 4-channel single incision cholecystectomy.

text: PURPOSE Single incision laparoscopic cholecystectomy (SILC) is a widely used method of performing cholecystectomy. A common technique used in SILC is a 3-channel method. However, exposure of Calot's triangle is limited in conventional 3-channel SILC. Therefore, we herein report the adequacy and feasibility of 4-channel SILC using a snake retractor. METHODS Four hundred and fifteen SILC cases were performed between April 2010 and February 2013. We performed 326 SILC cases between April 2010 and September 2012 using the 3-channel method. We introduced a snake retractor for liver traction in October 2012, and 89 cases of 4-channel SILC using snake retractor have been performed since. RESULTS Thirty patients (9.2%) in the 3-channel SILC group, and 23 patients (25.8%) in the 4-channel SILC group, were treated with percutaneous transhepatic gallbladder drainage insertion because of acute inflammation of the gallbladder (GB) before operation (P < 0.001). The mean operating time was 53.0 ± 25.8 minutes in the 3-channel SILC group and 51.9 ± 18.6 minutes in the 4-channel SILC group (P = 0.709). In the 3-channel SILC group, mean hospital stay was 3.0 ± 3.3 days whereas it was 2.6 ± 0.9 days in the 4-channel SILC group (P = 0.043). There were a total 9 cases (2.1%) of additional port usages, 6 cases (1.8%) in the 3-channel SILC group and 3 cases (3.4%) in the 4-channel SILC group (P = 0.411), due to cystic artery bleeding and bile leakage from gallbladder bed, but there were no open conversions. CONCLUSION Benign diseases of the GB can be operated on using SILC with the 4-channel method using a snake retractor.


title: Ifema hospital model. Implementation and start-up of the Pharmacy Department.

text: On the 20th of March 2020, triggered by the public health emergency declared, the Health Authorities in Madrid reported a legal instruction (Orden 371/2020) indicating the organization of a provisional hospital to admit patients with COVID-19 at the Trade Fair Institution (IFEMA). Several pharmacists working in the Pharmacy and Medical Devices Department of the Madrid Regional Health Service were called to manage the Pharmacy Department of the abovementioned hospital. Required permissions to set up a PD were here authorized urgently. Tackling human and material resources, and computer systems for drug purchase and electronic prescription, were some of the initial issues that hindered the pharmaceutical provision required for patients from the very day one. Once the purchase was assured, mainly by direct purchase from suppliers, drug dispensing up to 1,250 hospitalized patients (25 nursing units) and 8 ICU patients was taken on. Dispensing was carried out through either drug stocks in the nursing units or individual patient dispensing for certain drugs. Moreover, safety issues related to prescription were considered, and as the electronic prescription was implemented we attained 100% prescriptions review and validation. The constitution of a multidisciplinary Pharmacy and Therapeutics Committee let agree to a pharmacotherapy guide, pres cription protocols, therapeutic equivalences, interactions, and drug dispensing circuits. The Pharmacy Department strategy was to ensure a very quick response to basic tasks keeping the aim to offer a pharmaceutical care of the highest quality whenever possible. Working under a health emergency situation, with many uncertainties and continuous pressure was a plight. However, the spirit of collaboration in and out of the Pharmacy Department was aligned with the whole hospital motivation to offer the highest quality of healthcare. These were possibly the keys to allow caring for almost 4,000 patients during the 42 days that the hospital lasted.


title: GlycoPep MassList: software to generate massive inclusion lists for glycopeptide analyses.

text: Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. One major challenge in these experiments is collecting the requisite MS/MS data. The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. DDA results in limited glycopeptide coverage. Semi-targeted data acquisition is an alternative experimental approach that can alleviate this difficulty. However, due to the massive heterogeneity of glycopeptides, it is not obvious how to expediently generate inclusion lists for these types of analyses. To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. The utility of the software was tested by conducting comparisons between semi-targeted and untargeted data-dependent analysis experiments on a variety of proteins, including IgG, a protein whose glycosylation must be characterized during its production as a biotherapeutic. When the GlycoPep MassList software was used to generate inclusion lists for LC-MS/MS experiments, more unique glycopeptides were selected for fragmentation. Generally, ∼30 % more unique glycopeptides can be analyzed per protein, in the simplest cases, with low background. In cases where background ions from proteins or other interferents are high, usage of an inclusion list is even more advantageous. The software is freely publically accessible. Graphical abstract Software increases the number of glycopeptides that get selected for MS/MS analysis.


title: Return to play after acute infectious disease in football players.

text: Acute infectious diseases are common in athletes and can impair their ability to train and to compete. Furthermore, continuing exercise during infectious diseases may lead to prolongation or aggravation of illness with severe acute or chronic organ manifestations. Therefore, even simple infectious diseases require a sufficient period of convalescence and recovery, during which exercise may be not allowed. Nowadays, especially in professional football with high pressures on players, staff and clubs due to broad public interests as well as financial constraints, the return-to-play decision is of utmost significance. Based on previous suggestions and our own experience within amateur and professional athletes and football players, this article aims to give a short overview on return-to-play decisions after common acute infectious diseases in football players.


title: Kerala's response to COVID-19.

text: The response of Kerala state to COVID-19, led by the health department, was nested in larger social mobilization. Kerala has developed a strong government health system. Learning from managing the Nipah outbreaks, Kerala took effective prevention measures early. Local governments, actively involved in public health in Kerala, played an active role in controlling the epidemic and in cushioning the impact on the poor. Transparency in information and willingness of the government to take the people into confidence has contributed to enhancing trust in the government. These strengths will stand Kerala in good stead as it prepares to manage the next wave of COVID-19 infections.


title: Within host RNA virus persistence: mechanisms and consequences.

text: In a prototypical response to an acute viral infection it would be expected that the adaptive immune response would eliminate all virally infected cells within a few weeks of infection. However many (non-retrovirus) RNA viruses can establish 'within host' persistent infections that occasionally lead to chronic or reactivated disease. Despite the importance of 'within host' persistent RNA virus infections, much has still to be learnt about the molecular mechanisms by which RNA viruses establish persistent infections, why innate and adaptive immune responses fail to rapidly clear these infections, and the epidemiological and potential disease consequences of such infections.


Psychiatry in the COVID-19 Era.


title: LAPAROSCOPIC SALPINGECTOMY IN TWO CAPTIVE LEOPARDS (PANTHERA PARDUS) USING A SINGLE PORTAL ACCESS SYSTEM.

text: Laparoscopic salpingectomy was performed in two adult leopards (Panthera pardus) using a single portal access system, with a multicannulated single-incision laparoscopic surgery port, without any complications. The poorly developed ovarian bursa provided easy access to the uterine tube for salpingectomy. Laparoscopic salpingectomy can be safely performed in the leopard using a single portal access system.


title: Vaccination of dogs with Duramune DAPPi+LC protects against pathogenic canine parvovirus type 2c challenge.

text: In this study, we determined whether vaccination with Duramune DAPPi+LC containing canine parvovirus (CPV) type 2b protects against challenge with virulent CPV antigenic type 2c. Seven healthy dogs, seronegative for CPV2, were enrolled into two treatment groups; five were vaccinated twice, 21 days apart, with minimum titre vaccine, and two were given saline. Dogs were challenged with CPV 2c three weeks later. Clinical observations, body weight and rectal temperature measurements, blood samples for serology and white blood cell counts and faecal samples for virus excretion were collected. Control dogs remained seronegative until challenge; vaccinated dogs seroconverted and were positive for antibodies to CPV2 from day 21. Four days after challenge, clinical signs associated with parvovirus infection (vomiting, paroxysmal shivering, depression, loose stools) were observed in the control dogs. Both animals were withdrawn from the study for welfare reasons one day later. On day 47, leucopenia was observed in controls, with white blood cell counts less than 50 per cent prechallenge values. No specific clinical sign of parvovirus infection were observed in the vaccinated dogs, nor was (detectable) challenge virus shed in faeces suggesting that antibodies generated contributed sterilising immunity. We conclude that vaccination of dogs with Duramune DAPPi+LC protects against challenge with a virulent field strain of CPV 2c.


title: Publication of reviews synthesizing child health evidence (PORSCHE): a survey of authors to identify factors associated with publication in Cochrane and non-Cochrane sources.

text: BACKGROUND Cochrane Child Health maintains a register of child-relevant Cochrane systematic reviews (SRs) to provide a comprehensive source of high-quality evidence. However, a large number of SRs are published outside of The Cochrane Collaboration (Cochrane), impacting the comprehensiveness of the Cochrane Database of Systematic Reviews (CDSR). We surveyed authors who published child-relevant SRs with Cochrane and elsewhere in the medical literature to (1) understand their experiences in preparing and publishing SRs and (2) identify factors influencing choice of publication venue. METHODS We identified SRs published in the CDSR for the most recent complete year prior to our study (2013; n = 145). We searched the medical literature and randomly selected the same number of SRs published the same year. We developed an internet-based survey and contacted the corresponding author of each review via email. Data were analyzed descriptively. Qualitative analysis elicited common themes from open-ended questions. RESULTS Seventy-six (26 %) responded: 41 % Cochrane, 42 % non-Cochrane, and 17 % published in both venues. Among respondents who published their SR in both venues (n = 13), 46 % found it easier to publish in a non-Cochrane journal, 15 % easier with Cochrane, and 31 % similar. Main reasons for conducting SRs with Cochrane (n = 44) were Cochrane's positive reputation (82 %) and good impact factor (66 %). Among respondents who published their SR in a non-Cochrane journal (n = 32), most frequent reasons for not conducting their SR with Cochrane were time required to follow Cochrane processes (25 %), lack of knowledge about how to conduct an SR with Cochrane (19 %), administrative processes (16 %), and perception that non-Cochrane journals yielded more interest (16 %). Among respondents who published their SR in a non-Cochrane journal (n = 32), 78 % did not register their review and 22 % did not prepare a protocol. CONCLUSIONS Key reasons for publishing in Cochrane are its positive reputation and impact factor. Reasons for publishing in non-Cochrane sources include lack of familiarity or challenges with the Cochrane processes and desire to publish in a source more directly relevant to the topic of interest. End users looking for evidence in the form of SRs need to be aware that there is a vast number of SRs published across the medical literature. Efforts to optimize the identification of SRs in non-Cochrane sources (e.g., through effective labeling or protocol/review registration) and their content will help end users find the necessary synthesized evidence to support clinical practice.


title: Ultrastructural Pathology of Oligodendroglial Cells in Traumatic and Hydrocephalic Human Brain Edema: A Review.

text: Oligodendroglial cell changes in human traumatic brain injuries and hydrocephalus have been reviewed and compared with experimental brain edema. Resting unreactive oligodendrocytes, reactive oligodendrocytes, anoxic-ischemic oligodendrocytes, hyperthrophic phagocytic oligodendrocytes, and apoptotic oligodendrocytes are found. Anoxic-ischemic oligodendrocytes exhibit enlargement of endoplasmic reticulum, Golgi complex, and enlargement and disassembly of nuclear envelope. They appear in contact with degenerated myelinated axons. Hypertrophic phagocytic oligodendrocytes engulf degenerated myelinated axons exerting myelinolytic effects. A continuum oncotic and apoptotic cell death type leading to necrosis is observed. The vasogenic and cytotoxic components of brain edema are discussed in relation to oligodendroglial cell changes and reactivity.


title: Electroretinography during embolization of an ophthalmic arteriovenous fistula.

text: BACKGROUND Intraoperative neuromonitoring (IONM) is used for real-time evaluation of neuronal tracts and reflexes in the anesthetized patient, when a neurologic exam is not possible. Changes in IONM signals forewarn of possible neurological deficit. This real-time feedback allows for immediate alterations in therapeutic technique by the treating physician. Transcranial visual evoked potentials are not reliable for evaluating the integrity of the prechiasmatic visual system. Electroretinography (ERG) has been used in animal models for monitoring retinal ischemia and can be used in humans as well to monitor for prechiasmatic ischemia of the retinae and optic nerves. CASE DESCRIPTION We present a case where ERG signal amplitude and latency changed during ophthalmic arteriovenous fistula embolization, resulting in an intraprocedural decision to refrain from embolization of additional arterial pedicles to preserve vision. After awakening from general anesthesia, the patient had no deficits in visual acuity or field testing, but did complain of transient pain with eye movement that resolved the next day and worsened with episodes of blood pressure elevation. CONCLUSIONS ERG may be helpful for detecting prechiasmatic ischemic changes during endovascular procedures and may provide early warning signs to the surgeon before the onset of permanent retinal damage. Further investigation is needed to assess the utility of ERG monitoring during the treatment of orbital and periorbital vascular lesions.


COVID-19 Pandemic: Is This a Good Time for Implementation of Home Programs for Children's Rehabilitation in Low- and Middle-Income Countries?


COVID-19 and flu, a perfect storm.


title: Validation of an 'endovascular-first' approach to spinal dural arteriovenous fistulas: an intention-to-treat analysis.

text: BACKGROUND/OBJECTIVE Spinal dural arteriovenous fistulas (SDAVFs) require pretreatment angiography; embolization can be performed in the same session. To validate this approach, obliteration and morbidity rates of 'endovascular-first' (embolization and microsurgery in the case of embolization failures) must be compared with rates for 'microsurgery-first' (microsurgical ligation without attempted embolization) approaches. METHODS We reviewed our institutional database (January 1998-October 2015) for SDAVFs, performing an intention-to-treat analysis comparing endovascular-first and microsurgery-first approaches. RESULTS A total of 71 patients underwent surgical and/or endovascular treatment for SDAVFs. All SDAVFs were ultimately occluded. Of 35 patients under consideration for an endovascular-first approach, radicular artery anatomy or anterior spinal artery embolization risk precluded attempting embolization in seven cases (20%). Among 28 patients undergoing embolization, angiographic non-opacification of the fistula was noted in 18 (64%). Fourteen patients had obliteration with excellent casting of the draining vein (50%) and did not undergo surgery. There were no significant differences in total complications (9% vs 11%; p=1.0) or permanent complications (3% vs 4%; p=1.0) after attempted endovascular and surgical treatment. Based on an intention-to-treat analysis, there were no significant differences in total complications (11% vs 14%; p=1.0), permanent complications (6% vs 3%; p=0.61), or the symptomatic resolution/improvement rate (80% vs 78%; p=1.0) between endovascular-first and microsurgery-first groups. CONCLUSIONS Our results support attempted embolization of SDAVFs prior to consideration of microsurgery, allowing for a less invasive treatment option in the same session as diagnostic angiography.


title: Vitamin D3 induces vitamin D receptor and HDAC11 binding to relieve the promoter of the tight junction proteins.

text: Intestinal epithelial barrier dysfunction and vitamin D (VitD)-deficiency play a critical role in a large number of diseases. The histone deacetylases (HDAC) are associated with a large number of immune diseases. This study tests a hypothesis that the interaction between VitD and HDAC is associated with the regulation of epithelial barrier functions. In this study, human intestinal epithelial cell line, T84 cells, was cultured into monolayers to be used as a model to test the epithelial barrier functions. We observed that in a VitD-deficient environment, the T84 monolayer barrier function was compromised. Exposure to calcitriol (the active form of VitD3) in the culture increased the expression of VitD receptor (VDR) in T84 cells. In a VitD-sufficient environment, VDR formed a complex with histone deacetylase-11 (HDAC11); the complex was markedly decreased in a VitD-deficient environment. We also observed that significantly more binding of HDAC11 to the promoter of the tight junction proteins inhibit the gene transcription activities of these loci in the VitD-deficient environment, which were abolished by the presence of calcitriol in the culture. In conclusion, the interaction between VDR and HDAC11 plays a crucial role in the maintenance of the epithelial barrier integrity.


title: Comparative Post-operative Pain Analysis Between Coblator Assisted and Bipolar Diathermy Tonsillectomy in Paediatric Patients.

text: Tonsillectomy is one of the commonly performed otolaryngological operations. Despite a range of different techniques post-operative pain remains a major side-effect of this operation. Coblation assisted tonsillectomy is a latest technique of tonsillectomy. This technique is said to be associated with less intra-operative bleeding and less postoperative morbidity. We conducted a study in 100 patients to compare the pain scores between coblation assisted and bipolar diathermy tonsillectomy by FLACC score and Wong Baker scale score. The data so collected was statistically analysed using a t test and p values were calculated. The p value was highly significant (p < 0.001) for both scores in coblation assisted tonsillectomy 6 h postoperatively and on 1st postoperative day (p < 0.05). On 7th post-operative day however there was no significant difference in post-operative pain score using FLACC score in both groups but Wong baker scale scores were still significant. We concluded that post-operative pain was less with coblator assisted tonsillectomy as compared to bipolar diathermy tonsillectomy at least in early post-operative period.


title: Pearls and pitfalls in managing right heart failure in cardiac surgery.

text: PURPOSE OF REVIEW To review the recent insights in the evaluation and management of perioperative (RHF). RECENT FINDINGS Recent studies highlight the potential role of myocardial deformation imaging in the evaluation of patients at risk of postoperative RHF. There is also a growing interest to study the value of load-adaptation indices of the right heart in the setting of pulmonary hypertension or left ventricular assist device implantation. Finally, the field of temporary extracorporeal life support devices for RHF is rapidly evolving and new strategies are emerging. SUMMARY An integrated approach for assessing the cardiopulmonary axis combining imaging, hemodynamic and tissue perfusion monitoring is emerging, as particularly helpful in the field. Several developments in the field of temporary right heart support including the pumpless interventional lung assist membrane ventilator are offering new opportunities to support the right-heart pulmonary circulation. Future multicenter studies are needed to develop more effective preventive and therapeutic strategies for RHF.


title: Optimization of image-guided targeting in renal focal therapy.

text: Focal renal therapy for small renal masses (T(1a) or T(1b)) has been used as primary treatment for patients with comorbidities who are considered poor candidates for surgical resection. With a continuing effort toward optimization of minimally invasive nephron-sparing modalities, the effort to expand the patient pool will continue. As long-term results of renal ablative therapies become available and the safety, precision, and efficacy become well established, renal ablation may be used with increasing frequency for a wider group of patients. When this happens, high-quality imaging for localization and targeting of these renal lesions will become the central core of the treatment, with emphasis on superior results, accurate positioning of the probe, precise localization of the tumor, and real-time intraoperative monitoring of outcomes.


Response to Letter to the editor: Lung Ultrasound in COVID-19 Patients - More Shadows Than Information - Letter to the Editor on the Article "W. LU et al. Ultraschall in Med. 2020 Apr 15".


title: Repurposing Proteostasis-Modifying Drugs to Prevent or Treat Age-Related Dementia: A Systematic Review.

text: Background: Dementia has a significant impact on quality of life of older individuals. Impaired proteostasis has been implicated as a potential cause of dementia, that can be therapeutically targeted to improve patient outcomes. This review aimed to collate all current evidence of the potential for targeting proteostasis with repurposed drugs as an intervention for age-related dementia and cognitive decline. Methods: PubMed, Web of Science and Embase databases were searched from inception until 4th July 2017 for studies published in English. Interventional studies of repurposed proteostasis-modifying drugs in Alzheimer's disease (AD), Parkinson's disease (PD), Lewy Body disease, vascular dementia, and cognitive aging, in either animal models or humans with change in cognition as the outcome were included. The SYRCLE and Cochrane tools were used to assess risk of bias for included studies. Results: Overall 47 trials, 38 animal and 9 human, were isolated for inclusion in this review. Drugs tested in animals and humans included lithium, rapamycin, rifampicin, and tyrosine kinase inhibitors. Drugs tested only in animals included Macrophage and Granulocyte-Macrophage Colony Stimulating Factors, methylene blue, dantrolene, geranylgeranylacetone, minocycline and phenylbutyric acid. Lithium (n = 10 animal, n = 6 human) and rapamycin (n = 12 animal, n = 1 human) were the most studied proteostasis modifying drugs influencing cognition. Nine of ten animal studies of lithium showed a statistically significant benefit in Alzheimer's models. Rapamycin demonstrated a significant benefit in models of vascular dementia, aging, and Alzheimer's, but may not be effective in treating established Alzheimer's pathology. Lithium and nilotinib had positive outcomes in human studies including Alzheimer's and Parkinson's patients respectively, while a human study of rifampicin in Alzheimer's failed to demonstrate benefit. Microdose lithium showed a strongly significant benefit in both animals and humans. While the risk of bias was relatively low in human studies, the risk of bias in animal studies was largely unclear. Conclusion: Overall, the collective findings support the hypothesis that targeting proteostasis for treatment of dementia may be beneficial, and therefore future studies in humans with repurposed proteostasis modifying drugs are warranted. Larger human clinical trials focusing on safety, efficacy, tolerability, and reproducibility are required to translate these therapeutics into clinical practice.


title: Building the Systematic Review Core in an academic health sciences library.

text: Background The authors present efforts to build capacity at our institution for conducting systematic reviews and other forms of evidence synthesis through partnerships and a recharge model. This report describes how we successfully created and launched a for-fee systematic review core at our library. Case Presentation Throughout 2014 and 2015, library leadership proposed different models for getting institutional and financial support for librarians and staff to better support university researchers conducting systematic reviews. Though well received, initial requests for financial support were not funded. The executive director of the Health Sciences Library released two years' worth of salary and benefits to fund an evidence synthesis and retrieval librarian position. With this new position, the team formed a charge-back core facility in partnership with our university's Clinical Translation and Science Award hub. A series of procedural decisions and operational changes helped the group achieve success. Within eighteen months after launching the Systematic Review Core, we reached maximum capacity with more than twenty ongoing reviews. Discussion Assigning a dollar value to our expertise put us on par with other subject matter experts on campus and actually drove demand. We could act as paid consultants in research projects and shifted the perception of librarians from service providers to research partners. Affiliating with our partners was key to our success and boosted our ability to strengthen our campus' research infrastructure.


title: Characterization of African bat henipavirus GH-M74a glycoproteins.

text: In recent years, novel henipavirus-related sequences have been identified in bats in Africa. To evaluate the potential of African bat henipaviruses to spread in non-bat mammalian cells, we compared the biological functions of the surface glycoproteins G and F of the prototype African henipavirus GH-M74a with those of the glycoproteins of Nipah virus (NiV), a well-characterized pathogenic member of the henipavirus genus. Glycoproteins are central determinants for virus tropism, as efficient binding of henipavirus G proteins to cellular ephrin receptors and functional expression of fusion-competent F proteins are indispensable prerequisites for virus entry and cell-to-cell spread. In this study, we analysed the ability of the GH-M74a G and F proteins to cause cell-to-cell fusion in mammalian cell types readily permissive to NiV or Hendra virus infections. Except for limited syncytium formation in a bat cell line derived from Hypsignathus monstrosus, HypNi/1.1 cells, we did not observe any fusion. The highly restricted fusion activity was predominantly due to the F protein. Whilst GH-M74a G protein was found to interact with the main henipavirus receptor ephrin-B2 and induced syncytia upon co-expression with heterotypic NiV F protein, GH-M74a F protein did not cause evident fusion in the presence of heterotypic NiV G protein. Pulse-chase and surface biotinylation analyses revealed delayed F cleavage kinetics with a reduced expression of cleaved and fusion-active GH-M74a F protein on the cell surface. Thus, the F protein of GH-M74a showed a functional defect that is most likely caused by impaired trafficking leading to less efficient proteolytic activation and surface expression.


title: Clinical response after laparoscopic fenestration of symptomatic hepatic cysts: a systematic review and meta-analysis.

text: BACKGROUND Laparoscopic fenestration is one of the treatment options for symptomatic hepatic cysts, either solitary or in context of polycystic liver disease (PLD), but indications, efficacy and surgical techniques are under debate. METHODS A systematic literature search (1950-2017) of PubMed, Embase, Web of Science and the Cochrane Library was performed (CRD42017071305). Studies assessing symptomatic relief or symptomatic recurrence after laparoscopic fenestration in patients with symptomatic, non-parasitic, hepatic cysts were included. Complications were scored according to Clavien-Dindo. Methodological quality was assessed by Newcastle-Ottawa scale (NOS) for cohort studies. Pooled estimates were calculated using a random effects model for meta-analysis. RESULTS Out of 5277 citations, 62 studies with a total of 1314 patients were included. Median NOS-score was 6 out of 9. Median follow-up duration was 30 months. Symptomatic relief after laparoscopic fenestration was 90.2% (95% CI 84.3-94.9). Symptomatic recurrence was 9.6% (95% CI 6.9-12.8) and reintervention rate was 7.1% (95% CI 5.0-9.4). Post-operative complications occurred in 10.8% (95% CI 8.1-13.9) and major complications in 3.3% (95% CI 2.1-4.7) of patients. Procedure-related mortality was 1.0% (95% CI 0.5-1.6). In a subgroup analysis of PLD patients (n = 146), symptomatic recurrence and reintervention rates were significantly higher with respective rates of 33.7% (95% CI 18.7-50.4) and 26.4% (95% CI 12.6-43.0). Complications were more frequent in PLD patients, with a rate of 29.3% (95% CI 16.0-44.5). CONCLUSIONS Laparoscopic fenestration is an effective procedure for treatment of symptomatic hepatic cysts with a low symptomatic recurrence rate. The symptomatic recurrence rate and risk of complications are significantly higher in PLD patients.


title: 'Let us Help'- Why Senior Medical Students are the Next Step in Battling the COVID-19 Pandemic.

text: As senior medical students in the UK, we read Dr Stein's letter on the novel coronavirus (COVID-19) 2 and began wondering where we fit in, in this pandemic. As the government heads into a 'war footing' 13 , there is an increased need for medical staff. There is speculation of bringing back retired doctors, many of who fall into at risk categories. With clinical placement and exams cancelled, we are determined to use our hard-earned skills in some way, to help in what is the biggest global emergency of our lifetime.


Telemedicine in cardiology in the time of coronavirus disease 2019: a friend that everybody needs.


ACP Journal Club: adding neurovascular thrombectomy to IV t-PA reduced disability in acute ischemic stroke.


title: One thousand consecutive mini-gastric bypass: short- and long-term outcome.

text: There is growing evidence that mini-gastric bypass (MGB) is a safe and effective procedure. Operative outcome and long-term follow-up of a consecutive cohort of patients who underwent MGB are reported. The data on 1,000 patients who underwent MGB from November 2005 to January 2011 at an academic institution were reviewed. Mean age was 33.15 ± 10.17 years (range, 14-72), preoperative BMI was 42.5 ± 6.3 kg/m(2) (range, 26-75), mean preoperative weight was 121.6 ± 23.8 kg (range, 71-240), and 663 were women. Operative time and length of stay for primary vs. revisional MGB were 89 ± 12.8 min vs. 144 ± 15 min (p < 0.01) and l.85 ± 0.8 day vs. 2.35 ± 1.89 day (p < 0.01). No deaths occurred within 30 days of surgery. Short-term complications occurred in 2.7% for primary vs. 11.6% for revisionnal MGB (p < 0.01). Five (0.5%) patients presented with leakage from the gastric tube but none had anastomotic leakage. Four (0.4%) patients, all with revisional MGB, presented with severe bile reflux and were cured by stapling the afferent loop and by a latero-lateral jejunojejunostomy. Excessive weight loss occurred in four patients; two were reversed and two were converted to sleeve gastrectomy. Maximal percent excess weight loss (EWL) of 72.5% occurred at 18 months. Weight regain subsequently occurred with a mean variation of -3.9% EWL at 60 months. The 50% EWL was achieved for 95% of patients at 18 months and for 89.8% at 60 months. MGB is an effective, relatively low-risk, and low-failure bariatric procedure. In addition, it can be easily revised, converted, or reversed.


title: A pilot study comparing anatomic failure after sacrocolpopexy with absorbable or permanent sutures for vaginal mesh attachment.

text: OBJECTIVES To describe anatomic failure rates for sacrocolpopexy in groups receiving either delayed absorbable or permanent monofilament suture for mesh attachment to the vagina. METHODS We reviewed the medical records of 193 women who underwent sacrocolpopexy with 2 different types of sutures attaching polypropylene mesh to the vagina: delayed absorbable sutures (median follow-up, 43 weeks) and permanent sutures (median follow-up, 106 weeks). Vaginal apical failure was defined as Point C greater than or equal to half of the total vaginal length. Anterior-posterior compartmental failures were defined as Point Ba and/or Point Bp more than 0 cm. Fisher exact and χ2 tests were used to compare failure rates. There were no documented suture erosions in the delayed absorbable monofilament suture group during the review period. Two patients in the permanent suture group were found to have permanent suture in the bladder more than 30 weeks after the index procedure. RESULTS Failure rates for the 45 subjects in the delayed absorbable group and 148 subjects in the permanent suture group were similar (4.4% vs 3.4%, p = 0.74) and not statistically different in any compartment: apical (0% vs 1.4%, p = 0.43), anterior (4.4% vs 2%, p = 0.38), or posterior (0% vs 1.4%, p = 0.43). CONCLUSIONS Delayed absorbable monofilament suture appears to be a reasonable alternative to permanent suture for mesh attachment to the vagina during sacrocolpopexy. The use of delayed absorbable suture could potentially prevent complications of suture erosion into the bladder or vagina remote from the time of surgery.


'all in this together': Mental Health Nurses struggle for equitable access to the Medicare Benefit Schedule.


title: Resource-poor settings: infrastructure and capacity building: care of the critically ill and injured during pandemics and disasters: CHEST consensus statement.

text: BACKGROUND Planning for mass critical care (MCC) in resource-poor or constrained settings has been largely ignored, despite their large populations that are prone to suffer disproportionately from natural disasters. Addressing MCC in these settings has the potential to help vast numbers of people and also to inform planning for better-resourced areas. METHODS The Resource-Poor Settings panel developed five key question domains; defining the term resource poor and using the traditional phases of disaster (mitigation/preparedness/response/recovery), literature searches were conducted to identify evidence on which to answer the key questions in these areas. Given a lack of data upon which to develop evidence-based recommendations, expert-opinion suggestions were developed, and consensus was achieved using a modified Delphi process. RESULTS The five key questions were then separated as follows: definition, infrastructure and capacity building, resources, response, and reconstitution/recovery of host nation critical care capabilities and research. Addressing these questions led the panel to offer 33 suggestions. Because of the large number of suggestions, the results have been separated into two sections: part 1, Infrastructure/Capacity in this article, and part 2, Response/Recovery/Research in the accompanying article. CONCLUSIONS Lack of, or presence of, rudimentary ICU resources and limited capacity to enhance services further challenge resource-poor and constrained settings. Hence, capacity building entails preventative strategies and strengthening of primary health services. Assistance from other countries and organizations is needed to mount a surge response. Moreover, planning should include when to disengage and how the host nation can provide capacity beyond the mass casualty care event.


title: Left middle lobectomy for bronchiectasis in a patient with Kartagener syndrome: a case report.

text: BACKGROUND Kartagener syndrome (KS) is a rare disorder characterized by the triad of chronic sinusitis, bronchiectasis, and situs inversus. CASE PRESENTATION A 23-year-old man was admitted to our hospital because of recurrent cough with purulent expectoration, which had occurred intermittently for the past ten years. During the past 3 years, the episode frequency was 3-4 times per year. He was diagnosed with pulmonary infection and bronchiectasis of the left upper lobe, situs inversus, and KS. We concluded that the damaged left middle lobe was the source of repeat pulmonary infections. Thus the left middle lobe resection was performed to remove the source of the lung infection. CONCLUSIONS The post-operative course was successful and pneumonia was apparently resolved during the 6 months' follow-up period. We further describe this case in the following report.


title: Sustainable reduction of nasal colonization and hand contamination with Staphylococcus aureus in food handlers, 2002-2011.

text: A longitudinal study of nasal colonization and hand contamination of food handlers with Staphylococcus aureus commenced in 2002 prior to the outbreak of severe acute respiratory syndrome. In the follow-up in 2003 when hygiene measures were strictly implemented, significant reductions in carriage were observed. To investigate if this change was sustained, nasal and hand carriage rates were compared between the earlier studies and a further sampling in 2011. The initial nasal carriage rate was 35% and hand contamination 41·2%, decreasing to 23·5% and 11·6%, respectively in 2003 (P < 0·001). In 2011, nasal carriage was similar to 2003 (22·9%), while hand contamination dropped further to 3·7% (P < 0·001). Spa-typing revealed 39 types in 2002 and 42 in 2011. This study reveals that the marked reduction in colonization had been sustained. This may be attributed to reduced opportunities for spread due to enhanced hygiene and reinforces its importance for control of disease.


title: Posteriorly tunneled dialysis catheters for permanent use in cognitively impaired patients undergoing hemodialysis.

text: Cognitively impaired patients often pull at their dialysis catheters when the catheters are tunneled over the anterior chest. To potentially circumvent this, a technique was developed that tunnels the catheter posteriorly, over the patient's shoulder. A total of 32 posteriorly tunneled catheters were placed in 12 patients. The mean catheter use interval was 164 days, with a total of 5,248 catheter use days. Indications for nonelective catheter removals were catheter dysfunction (n = 7; 23.3%), removal by the patient (n = 7; 23.3%), infection (n = 5; 16.7%), and inadvertent dislodgment (n = 1; 3.3%). Only six of the 12 patients were able to dislodge their catheters. The procedure described here reduced catheter manipulation and extended catheter viability in these patients.


title: Percutaneous microwave ablation of hepatocellular carcinoma with a gas-cooled system: initial clinical results with 107 tumors.

text: PURPOSE To retrospectively review the results of hepatocellular carcinoma (HCC) treatment with a high-power, gas-cooled, multiantenna-capable microwave device. MATERIALS AND METHODS A total of 107 HCCs in 75 patients (65 men) with a mean age of 61 years (range, 44-82 y) were treated via percutaneous approach. Combination microwave ablation and transarterial chemoembolization was performed for 22 tumors in 19 patients with tumors larger than 4 cm (n = 10), tumors larger than 3 cm with ill-defined margins (n = 7), or lesions not identified with ultrasonography (n = 5). Mean tumor size was 2.1 cm (range, 0.5-4.2 cm), with median follow-up of 14 months, for ablation alone; compared with 3.7 cm (range, 1.0-7.0 cm) and 12 months, respectively, for combination therapy. All procedures were performed with a single microwave system (Certus 140) with one to three 17-gauge antennas. RESULTS Mean ablation time was 5.3 minutes (range, 1-11.5 min). All treatments were considered technically successful in a single session. Primary technique effectiveness rates were 91.6% (98 of 107) overall, 93.7% (89 of 95) for tumors 4 cm or smaller, and 75.0% (nine of 12) for tumors larger than 4 cm; and 91.8% (78 of 85) for ablation alone and 90.9% (20 of 22) for combination therapy. There was no major complication or procedure-related mortality. The overall survival rate was 76.0% at a median 14-month clinical follow-up, with most deaths related to end-stage liver disease (n = 11) or multifocal HCC (n = 5). CONCLUSIONS Treating HCC with a gas-cooled, multiantenna-capable microwave ablation device is safe, with promising treatment effectiveness.


title: The application of the V-Loc closure device for gastrointestinal sutures: a preliminary study.

text: BACKGROUND Leakage is one of the major complications in gastrointestinal surgery. This preliminary study compared a new barbed absorbable thread for gastrointestinal sutures with monofil suture material in a cadaver model. METHODS In this study, mechanical experiments were performed in 20 recently deceased individuals. Incisions were made in the small intestine, colon, and stomach, and then sutures were created with the V-Loc closure device and monofil suture material. Intestinal bursting pressure was measured by inserting a balloon and slowly filling it with air until there was a dehiscence, or wall or suture rupture. RESULTS The bursting pressures differed significantly between the two sutures in the small intestine, showing the advantage of the V-Loc closure device, which had a mean bursting pressure of 116.2 mmHg compared with 110 mmHg for the monofil suture (p = 0.003). The mean bursting pressure did not differ significantly between the two sutures in the colon and the stomach. The mean bursting pressures for the V-Loc closure device were 141.3 mmHg (stomach) and 137.2 mmHg (colon) compared with the monofil suture material bursting pressures of 133 mmHg (stomach) and 134.8 mmHg (colon). CONCLUSIONS Because the bursting strength of the sutures created with monofil suture material differs significantly from that of the V-Loc closure device, the V-Loc suture material should be used for gastrointestinal sutures. Although the two sutures did not differ significantly in the colon or the stomach, the V-Loc closure device should be used for these as well because its advantages may overrule those of the monofil suture. No knot tying is required, and the operating time can be shorter. Especially for laparoscopic surgery, the V-Loc closure device is recommended.


title: Inhibition of heat-shock protein 90 reduces Ebola virus replication.

text: Ebola virus (EBOV), a negative-sense RNA virus in the family Filoviridae, is known to cause severe hemorrhagic fever in humans and other primates. Infection with EBOV causes a high mortality rate and currently there is no FDA-licensed vaccine or therapeutic treatment available. Recently, heat-shock protein 90 (Hsp90), a molecular chaperone, was shown to be an important host factor for the replication of several negative-strand viruses. We tested the effect of several different Hsp90 inhibitors including geldanamycin, radicicol, and 17-allylamino-17-demethoxygeldanamycin (17-AAG; a geldanamycin analog) on the replication of Zaire EBOV. Our results showed that inhibition of Hsp90 significantly reduced the replication of EBOV. Classic Hsp90 inhibitors reduced viral replication with an effective concentration at 50% (EC(50)) in the high nanomolar to low micromolar range, while drugs from a new class of Hsp90 inhibitors showed markedly more potent inhibition. These compounds blocked EBOV replication with an EC(50) in the low nanomolar range and showed significant potency in blocking replication in primary human monocytes. These results validated that Hsp90 is an important host factor for the replication of filoviruses and suggest that Hsp90 inhibitors may be therapeutically effective in treating EBOV infection.


title: Management of anastomotic leak after low anterior resection with transanal endoscopic microsurgical (TEM) debridement and repair.

text: Anastomotic leak after low anterior resection (LAR) in patients with rectal cancer who have received neoadjuvant chemoradiation can be challenging to treat and can lead to the creation of a permanent stoma. We report the case of a post-operative anastomotic leak after a Baker-type anastomosis during a low anterior resection was successfully managed with transanal endoscopic microsurgical (TEM) debridement and repair. TEM can be a successful endoluminal alternative treatment in the management of anastomotic leak after LAR and can prevent the morbidity associated with re-exploration and colostomy.


title: Comparison of definitive-intent finely fractionated and palliative-intent coarsely fractionated radiotherapy as adjuvant treatment of feline microscopic injection-site sarcoma.

text: OBJECTIVES The aim of this retrospective, bi-institutional study was to evaluate the progression-free interval in a cohort of cats with postoperative microscopic injection-site sarcoma (ISS) treated with two different radiotherapy protocols. METHODS Included in the study were cats with ISSs undergoing macroscopic surgical removal and subsequent electron beam radiotherapy treatment with either a finely fractionated protocol (48 or 52.8 Gy over 4 weeks delivered in 12 or 16 fractions) or a coarsely fractionated protocol (36 Gy over 3 weeks administered in six fractions). Medical records were reviewed and follow-up information was collected. The Kaplan-Meier method and log-rank test were used to compare the progression-free interval (PFI) between the two protocols and to test the influence of many clinical variables. RESULTS Fifty-nine cats were included; 38 underwent a finely fractionated protocol and 21 a coarsely fractionated protocol. PFI was not significantly different between the two groups. Overall PFI was 2000 days (2000 vs 540 days; P = 0.449). When only first-occurrence cases were included, median PFI was significantly longer in the finely fractionated group compared with the coarsely fractionated group (1430 vs 540 days; P = 0.007). In cats that underwent multiple surgeries PFI was not different between protocols (233 vs 395 days; P = 0.353). CONCLUSIONS AND RELEVANCE Cats with first-occurrence ISSs appear to benefit from postoperative finely fractionated radiotherapy. The same benefit was not evident in cats that underwent multiple surgeries and we think a coarsely fractionated protocol would be indicated in these cases.


title: [Suggestions for emergency operation of otorhinolaryngology head and neck during the period of prevention and control of 2019 novel coronavirus].

text: 2019新型冠状病毒（2019 novel coronavirus，2019-nCoV）感染已被纳入《中华人民共和国传染病防护法》规定的乙类传染病，并采取甲类传染病预防控制措施。耳鼻咽喉头颈外科急症食管异物、呼吸道异物、鼻出血、喉阻塞合并呼吸困难及头颈部外伤发病率相对较高，部分可迅速危及生命的急症需紧急手术。本文根据新型冠状病毒肺炎诊疗方案（试行第五版），在疫情蔓延地区结合华中科技大学同济医学院附属协和医院耳鼻咽喉科急诊手术处理的经验，现总结制订了新型冠状病毒防控期间耳鼻咽喉头颈外科急症手术诊疗建议，以期在新型冠状病毒防控期间提高耳鼻咽喉头颈外科急症的救治成功率及减少或避免围手术期医护人员新型冠状病毒感染可能。.


title: Flexible tip guides and intermediate catheters: two center experience and a proposed taxonomy.

text: BACKGROUND Stable access to target lesions is foundational to endovascular therapy, be it in hemorrhagic or ischemic disease. Continued evolution in access technology has resulted in next generation catheters that afford improved trackability and proximal support. OBJECTIVE Assess safety and patterns of use at two high volume centers, and conceptualize usage patterns. MATERIALS AND METHODS A retrospective review of 608 cases in which a 'next generation' catheter was used during 2008-2010 at Cleveland Clinic (Cleveland, Ohio, USA) and throughout 2009-2010 at Emory University Hospital (Atlanta, Georgia, USA) was conducted, and the cases classified by indication. Catheter placement, distal most location, and related complications were recorded and experience summarized. We also reviewed the differences in the catheters and the rationale for catheter selection, as well as relative costs for each approach. RESULTS 311 Neuron 053, 166 Neuron 070, 36 distal access catheter (DAC) 3.9 F, 61 DAC 4.3 F, and 34 DAC 5.2 F catheters were deployed. Of these, 459 placements were in the anterior circulation, 130 in the posterior circulation, 11 in the external carotid artery, and eight were used intravenously. Complication rates were 9/131 (6.9%) for the DAC catheter group, 16/311 (5.1%) for the Neuron 053 group, and 14/166 (8.4%) for the Neuron 070 group (p=0.37, χ(2) test). CONCLUSIONS Next generation access catheters possess characteristics that blend qualities of traditional microcatheters and stiff guide catheters. There was no statistically significant difference in complication rates between the various catheter families in this small retrospective review, and the complication rates were similar to historical complication rates.


title: Partial Aneurysmectomy of Venous Aneurysms in Arteriovenous Dialysis Fistulas.

text: Upper extremity native arteriovenous fistulas (AVFs) continue to be the standard of care for hemodialysis patient's access. Although autogenous fistulas are superior to catheters and synthetic grafts, they are not without their own complications. One complication is venous aneurysms that can lead to skin erosion, bleeding, and site loss. Although traditionally repaired with ligation, interposition grafts, or stent placement, in this article, we discuss our experience with aneurysmorrhaphy utilizing a thoracoabdominal (TA) stapler. Thirteen aneurysms were treated with the TA stapler at a single, nonuniversity hospital for all patients from 2012 to 2014. The average aneurysm diameter was 3.6 cm, and the average fistula age was 57.9 months. There were no bleeding complications or recurrences. The primary patency was 80% at 6 months, with a primary assisted patency of 90% during the same time frame. Aneurysmorrhaphy with the TA stapler appears to be a safe and viable option for the treatment of venous aneurysms associated with AVFs.


title: Quantitative lung SPECT applied on simulated early COPD and humans with advanced COPD.

text: BACKGROUND Reduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), reflected as inhomogeneities in the single-photon emission computed tomography (SPECT) lung image, is correlated to disease advancement. An analysis method for measuring these inhomogeneities is proposed in this work. The first aim was to develop a quantitative analysis method that could discriminate between Monte Carlo simulated normal and COPD lung SPECT images. A second aim was to evaluate the ability of the present method to discriminate between human subjects with advanced COPD and healthy volunteers. METHODS In the simulated COPD study, different activity distributions in the lungs were created to mimic the healthy lung (normal) and different levels of COPD. Gamma camera projections were Monte Carlo simulated, representing clinically acquired projections of a patient who had inhaled 125 MBq 99mTc-Technegas followed by a 10-min SPECT examination. Reconstructions were made with iterative ordered subset expectation maximisation. The coefficient of variance (CV) was calculated for small overlapping volumes covering the 3D reconstructed activity distribution. A CV threshold value (CVT) was calculated as the modal value of the CV distribution of the simulated normal. The area under the distribution curve (AUC), for CV values greater than CVT, AUC(CVT), was then calculated. Moreover, five patients with advanced emphysema and five healthy volunteers inhaled approximately 75 MBq 99mTc-Technegas immediately before the 20-min SPECT acquisition. In the human study, CVT was based on the mean CV distribution of the five healthy volunteers. RESULTS A significant difference (p < 0.001) was found between the Monte-Carlo simulated normal and COPD lung SPECT examinations. The present method identified a total reduction of ventilation of approximately 5%, not visible to the human eye in the reconstructed image. In humans the same method clearly discriminated between the five healthy volunteers and five patients with advanced COPD (p < 0.05). CONCLUSIONS While our results are promising, the potential of the AUC(CVT) method to detect less advanced COPD in patients needs further clinical studies.


title: PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice.

text: Viral vector-based vaccines that induce protective CD8+ T cell immunity can prevent or control pathogenic SIV infections, but issues of preexisting immunity and safety have impeded their implementation in HIV-1. Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells (DCs) by fusing soluble PD1 with HIV-1 GAG p24 antigen. As compared with non-DC-targeting vaccines, intramuscular immunization via electroporation (EP) of the fusion DNA in mice elicited consistently high frequencies of GAG-specific, broadly reactive, polyfunctional, long-lived, and cytotoxic CD8+ T cells and robust anti-GAG antibody titers. Vaccination conferred remarkable protection against mucosal challenge with vaccinia GAG viruses. Soluble PD1-based vaccination potentiated CD8+ T cell responses by enhancing antigen binding and uptake in DCs and activation in the draining lymph node. It also increased IL-12-producing DCs and engaged antigen cross-presentation when compared with anti-DEC205 antibody-mediated DC targeting. The high frequency of durable and protective GAG-specific CD8+ T cell immunity induced by soluble PD1-based vaccination suggests that PD1-based DNA vaccines could potentially be used against HIV-1 and other pathogens.


title: Cerebral blood flow velocity and oxygenation correlate predominantly with right ventricular function in cooled neonates with moderate-severe hypoxic-ischemic encephalopathy.

text: The relationship between right ventricular (RV) function and cerebral blood flow (CBF) velocity and cerebral oxygenation was assessed in neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). Echocardiographic, transcranial Doppler, and hemodynamic data from 37 neonates with moderate-severe HIE + TH were reviewed. Twenty healthy newborns served as controls. Cardiac dysfunction in HIE + TH was characterized by a predominant RV dysfunction, with concomitantly reduced CBF velocity. A significant correlation was found between CBF velocity and tricuspid annular plane systolic excursion (TAPSE), RV output (RVO), and stroke volume (SVRV), as well as with left ventricular output and stroke volume. Brain oxygenation (rSO2) correlated significantly with RVO, SVRV, TAPSE, ejection fraction, and fractional shortening, whereas cerebral fractional tissue oxygen extraction (FTOEc) correlated with RVO, SVRV, RV myocardial performance index, and superior vena cava flow. CBF velocity and cerebral NIRS correlations were stronger with parameters of right ventricular performance.Conclusion: CBF velocity and brain oxygenation correlate predominantly with RV function in HIE + TH. This suggests a preferential contribution of RV performance to cerebral hemodynamics in this context.What is Known:• Neonates with hypoxic ischemic encephalopathy frequently exhibit alterations of cardiac function and cerebral blood flow.• These are considered organ-specific consequences of perinatal asphyxia.What is New:• We show that cerebral blood flow velocity and brain oxygenation are correlated predominantly with right ventricular function during therapeutic hypothermia.• This suggests a potential direct contribution of right ventricular performance to cerebral hemodynamics in this context.


title: Mixed-Methods Systematic Review of Behavioral Interventions in Low- and Middle-Income Countries to Increase Family Support for Maternal, Infant, and Young Child Nutrition during the First 1000 Days.

text: Fathers, grandmothers, and other family members' influence on maternal, infant, and young child nutrition (MIYCN) is widely recognized, yet synthesis of the effectiveness of engaging them to improve nutrition practices during the first 1000 d is lacking. We examined the impact of behavioral interventions to engage family members in MIYCN in low- and middle-income countries through a mixed-methods systematic review. We screened 5733 abstracts and included 35 peer-reviewed articles on 25 studies (16 with quantitative and 13 with qualitative data). Most quantitative studies focused on early breastfeeding, primarily engaging fathers or, less often, grandmothers. Most found positive impacts on exclusive breastfeeding rates and family members' knowledge and support. The few quantitative studies on complementary feeding, maternal nutrition, and multiple outcomes also suggested benefits. Qualitative themes included improved nutrition behaviors, enhanced relationships, and challenges due to social norms. Interventions engaging family members can increase awareness and build support for MIYCN, but more rigorous study designs are needed. This systematic review is registered at PROSPERO as CRD42018090273, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=90273.


The peer review at high risk from COVID-19 - are we socially distancing from scientific quality control?


title: [Practice and Reflection on the Battle against COVID-19 by Guangdong Medical Aid Team in the city of Honghu].

text: 新型冠状病毒肺炎疫情暴发以来，全国上下开展了一场史无前例的抗疫阻击战。本文阐述了广东驰援湖北洪湖市医疗队在党中央、各级政府关于疫情防控的决策部署下，结合当地实际情况，迅速制定出有针对性的抗疫行动方案，并通过切实实施防控举措，取得了较好的成效，形成了"政府统筹、专家主导、数据支撑、全民参与"的新冠肺炎防控洪湖模式，以期为我国县级城市提供切实可行的疫情防控参考。.


title: Biochemical evidences for M1-, M17- and M18-like aminopeptidases in marine invertebrates from Cuban coastline.

text: Metallo-aminopeptidases (mAPs) control many physiological processes. They are classified in different families according to structural similarities. Neutral mAPs catalyze the cleavage of neutral amino acids from the N-terminus of proteins or peptide substrates; they need one or two metallic cofactors in their active site. Information about marine invertebrate's neutral mAPs properties is scarce; available data are mainly derived from genomics and cDNA studies. The goal of this work was to characterize the biochemical properties of the neutral APs activities in eight Cuban marine invertebrate species from the Phyla Mollusca, Porifera, Echinodermata, and Cnidaria. Determination of substrate specificity, optimal pH and effects of inhibitors (1,10-phenanthroline, amastatin, and bestatin) and cobalt on activity led to the identification of distinct neutral AP-like activities, whose biochemical behaviors were similar to those of the M1 and M17 families of mAPs. Additionally, M18-like glutamyl AP activities were detected. Thus, marine invertebrates express biochemical activities likely belonging to various families of metallo-aminopeptidases.


title: Comparison of tranexamic acid plasma concentrations when administered via intraosseous and intravenous routes.

text: INTRODUCTION There is a lack of information regarding intraosseous (IO) administration of tranexamic acid (TXA). Our hypothesis was that a single bolus IO injection of TXA will have a similar pharmacokinetic profile to TXA administered at the same dose IV. METHODS Sixteen male Landrace cross swine (mean body weight 27.6±2.6kg) were divided into an IV group (n=8) and an IO group (n=8). Each animal received 30mg/kg TXA via an IV or IO catheter, respectively. Jugular blood samples were collected for pharmacokinetic analysis over a 3h period. The maximum TXA plasma concentration (Cmax) and corresponding time as well as distribution half-life, elimination half-life, area under the curve, plasma clearance and volume of distribution were calculated. One- and two-way analysis of variance for repeated measures (time, group) with Tukey's and Bonferonni post hoc tests were used to compare TXA plasma concentrations within and between groups, respectively. RESULTS Plasma concentrations of TXA were significantly higher (p<0.0001) in the IV group during the TXA infusion. Cmax occurred at 4min after initiation of the bolus in the IV group (9.36±3.20ng/μl) and at 5min after initiation of the bolus in the IO group (4.46±0.49ng/μl). Plasma concentrations were very similar from the completion of injection onwards. There were no significant differences between the two administration routes for any other pharmacokinetic variables measured. CONCLUSION The results of this study support pharmacokinetic bioequivalence of IO and IV administration of TXA.


title: Teaching Public Health Will Never Be the Same.

text: Students will likely be flocking to public health courses and programs in upcoming semesters. The coronavirus disease 2019 (COVID-19) pandemic has piqued the interest of many in society, among them college students. Students who have an interest in health, medicine, or science now may see public health as a viable career option, especially with numerous public health researchers being featured in stories and social media around the globe. Although this is an important moment for our field and discipline, universities training future public health professionals will need to recalibrate how they approach their teaching in the aftermath of the COVID-19 pandemic. (Am J Public Health. Published online ahead of print May 14, 2020: e1-e2. doi:10.2105/AJPH.2020.305710).