title: Mannan-binding lectin deficiency modulates the humoral immune response dependent on the genetic environment.

text: Mannan-binding lectin (MBL) is a plasma protein implicated in innate immune defence against a broad range of microorganisms, including viruses. It is also thought that MBL plays a role in the recruitment of the specific clonal immune response. This was studied by injecting soluble hepatitis B surface antigen (HBsAg) intravenously into mice deficient in both MBL-A and MBL-C (MBL DKO mice). The MBL DKO animals on mixed genetic background (SV129EvSv x C57BL/6) produced higher antibody titres than the wild-type littermates. After primary challenge with the antigen the immunoglobulin M anti-HBsAg antibody titres were threefold higher in the MBL DKO mice than in the wild-type mice. Following the boost, the immunoglobulin G anti-HBsAg antibody titres were 10-fold higher in the MBL DKO mice, suggesting that MBL plays a role in a negative feedback regulation of adaptive immunity. However, the modulating effect of MBL was dependent on the genetic environment. The MBL DKO mice backcrossed on a C57BL/6 background showed the opposite response with the MBL DKO mice now producing fewer antibodies than the wild-type animals, whereas MBL deficiency in mice with the SV129EvSv background did not show any effect in antibody production. These findings indicate that the modifying effect of MBL on the humoral immune response is influenced by the genetic environment.


title: Preparing for the aftermath of COVID-19: Shifting risk and downstream health consequences.

text: Due to the COVID-19 pandemic, the public is currently living through a collective continuous traumatic stressor. Objective risk levels shift with each new piece of data regarding the coronavirus. These data points are communicated through public health officials and the media, easily accessible through modern advanced technology including online news and push notifications. When objective risk changes, individuals must reappraise their subject risk levels. Updating subjective risk levels several times per week is linked to ambiguity of the situation and uncertainty in daily life. The uncertainty and potential feelings of uncontrollability is linked to heightened anxiety. The continuous stress, anxiety, and uncertainty may have several negative downstream mental and physical health effects nationwide. The health care sector must begin preparing for the long-term consequences of the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Comparison of the Idaho Technology FilmArray system to real-time PCR for detection of respiratory pathogens in children.

text: The FilmArray Respiratory Panel (RP) multiplexed nucleic acid amplification test (Idaho Technology, Inc., Salt Lake City, UT) was compared to laboratory-developed real-time PCR assays for the detection of various respiratory viruses and certain bacterial pathogens. A total of 215 frozen archived pediatric respiratory specimens previously characterized as either negative or positive for one or more pathogens by real-time PCR were examined using the FilmArray RP system. Overall agreement between the FilmArray RP and corresponding real-time PCR assays for shared analytes was 98.6% (kappa = 0.92 [95% confidence interval (CI), 0.89 to 0.94]). The combined positive percent agreement was 89.4% (95% CI, 85.4 to 92.6); the negative percent agreement was 99.6% (95% CI, 99.2 to 99.8). The mean real-time PCR threshold cycle (C(T)) value for specimens with discordant results was 36.46 ± 4.54. Detection of coinfections and correct identification of influenza A virus subtypes were comparable to those of real-time PCR when using the FilmArray RP. The greatest comparative difference in sensitivity was observed for adenovirus; only 11 of 24 (45.8%; 95% CI, 27.9 to 64.9) clinical specimens positive for adenovirus by real-time PCR were also positive by the FilmArray RP. In addition, upon testing 20 characterized adenovirus serotypes prepared at high and low viral loads, the FilmArray RP did not detect serotypes 6 and 41 at either level and failed to detect serotypes 2, 20, 35, and 37 when viral loads were low. The FilmArray RP system is rapid and extremely user-friendly, with results available in just over 1 h with almost no labor involved. Its low throughput is a significant drawback for laboratories receiving large numbers of specimens, as only a single sample can be processed at a time with one instrument.


What does COVID mean for UK mental health care?


title: How do Funeral Practices impact Bereaved Relatives' Mental Health, Grief and Bereavement? A Mixed Methods Review with Implications for COVID-19.

text: Those who are bereaved during the current COVID-19 pandemic are subject to restrictions on funeral sizes and practices. We conducted a rapid review synthesising the quantitative and qualitative evidence regarding the effect of funeral practices on bereaved relatives' mental health and bereavement outcomes. Searches of MEDLINE, PsycINFO, KSR Evidence, and COVID-related resources were conducted. 805 records were screened; 17 studies of variable quality were included. Current evidence regarding the effect of funeral practices on bereaved relatives' mental health and bereavement outcomes is inconclusive. Five observational studies found benefits from funeral participation while six did not. However, qualitative research provides additional insight: the benefit of after-death rituals including funerals depends on the ability of the bereaved to shape those rituals and say goodbye in a way which is meaningful for them. Findings highlight the important role of funeral officiants during the pandemic. Research is needed to better understand the experiences and sequalae of grief and bereavement during COVID-19.


title: Single-incision laparoscopic cholecystectomy: a cost comparison.

text: BACKGROUND Single-incision laparoscopic cholecystectomy (SILC) should not cost more or less than traditional laparoscopic cholecystectomy (LC). METHODS Retrospective cost data were collected from the accounting records of a single institution. A direct comparison of LC and SILC was conducted. Data on the SILC cases converted to LC were included. The total operating room (OR) cost (actual cost to the hospital for equipment, time, and personnel) and the total OR charges (total derived from the OR cost plus a margin to cover overhead costs beyond material costs) were examined. The total hospital charges (OR charges plus hospital charges accrued in the perioperative period) also were included. Descriptive statistics were used to analyze the data, with p values less than 0.05 considered statistically significant. RESULTS Over a period of 19 months, 116 cases of minimally invasive cholecystectomy were evaluated. Of the 116 patients, 48 underwent LC during the first half of that period, and 68 patients underwent SILC during the second half of that period. Nine of the single-incision procedures were converted to traditional LC, for a 13% conversion rate. The groups were well matched from a demographics standpoint, with no significant differences in age, gender, body mass index (BMI), diagnoses, American Society of Anesthesiology (ASA) class, or payment. Comparison of all attempted SILCs, including those converted, with all LCs showed no significant difference in cost category totals. A significant difference among all cost variables was found when SILCs were compared with SILCs that required conversion to LC. A significant difference among the cost variables also was found when LCs were compared with converted SILCs. CONCLUSION The cost for SILC did not differ significantly from that for LC when standard materials were used and the duration of the procedure was considered. Converted cases were significantly more expensive than completed SILC and LC cases.


title: Prospective study of influenza C in hospitalized children.

text: We present a prospective study of influenza C virus infections in hospitalized children in Spain during 6 years, including the pandemic influenza A (H1N1) pdm. Influenza C infections accounted for 13.3% of influenza-positive cases. The patients with simple influenza C infection were clinically similar to other influenza types, but a high rate of coinfection (81%) makes it difficult to assess its clinical role.


COVID-19 and the CRISPR Community Response.


How research funders are tackling coronavirus disruption.


SYMPLICITY HTN-3 results to be announced: a mystery or a story foretold?


title: Laparoendoscopic single-site surgery: adult hernia mesh repair with homemade single port.

text: BACKGROUND Laparoendoscopic single-site surgery (LESS) is a novel technique developed to reduce the port-related morbidities and improve the cosmetic outcomes of laparoscopic surgery. To date, no series of LESS inguinal hernia repair has been published or documented. This study aimed to determine the safety and feasibility of LESS technique for inguinal hernia repairs. METHODS Between December 2008 and March 2009, LESS procedures for inguinal hernia repair through a transumbilical incision were performed for 16 patients with symptomatic inguinal hernias. The initial 9 cases were performed by a transabdominal preperitoneal method and the remaining 7 were completed with a totally extraperitoneal approach. All procedures were accessed with our homemade single port for simultaneous passage of laparoscope and instruments. RESULTS All procedures were completed successfully without conversion to standard laparoscopic or open surgery. These patients ranged in age from 21 to 80 years (median, 46.5 y) with a male to female ratio of 15:1. A total of 24 inguinal hernias, including 3 complicated types, were repaired. The median operative time was 83.5 minutes (range, 52 to 150 min). Two of the 16 patients suffered postoperative complications (12.5%). Most patients were discharged home on the second postoperative day. No port-related complications occurred. The cosmetic results were excellent. CONCLUSIONS In our experience, LESS procedures for inguinal hernia repair shows this technique to be both safe and feasible, even for complicated cases. More studies are needed to compare LESS inguinal hernia repair with standard laparoscopic techniques.


title: Hypothetical targets and plausible drugs of Coronavirus infection caused by SARS-CoV-2.

text: The world is confronting a dire situation due to the recent pandemic of the novel coronavirus disease (SARS-CoV-2) with the mortality rate passed over 470,000. Attaining efficient drugs evolve in parallel to the understanding of the SARS-CoV-2 pathogenesis. The current drugs in the pipeline and some plausible drugs are overviewed in this paper. Although different types of antiviral targets are applicable for SARS-CoV-2 drug screenings, the more promising targets can be considered as 3C-like main protease (3CL protease) and RNA polymerase. The remdesivir could be considered the closest bifunctional drug to the provisional clinical administration for SARS-CoV-2. The known molecular targets of the SARS-CoV-2 include fourteen targets while four molecules of angiotensin-converting enzyme 2 (ACE2), cathepsin L, 3CL protease and RNA-dependent RNA polymerase (RdRp) are suggested as more promising potential targets. Accordingly, dual-acting drugs as an encouraging solution in drug discovery are suggested. Emphasizing the potential route of SARS-CoV-2 infection and virus entry related factors like integrins, cathepsin and ACE2 seems valuable. The potential molecular targets of each phase of the SARS-CoV-2 life cycle are discussed and highlighted in this paper. Much progress in understanding the SARS-CoV-2 and molecular details of its life cycle followed by the identification of new therapeutic targets are needed to lead us to an efficient approach in anti-SARS-CoV-2 drug discovery.


title: Hand Eczema Pandemic Caused by SARS-CoV-2 Hygiene Measures: The Setup of a Hand Eczema Helpline for Hospital Personnel.

text: Hand eczema, also known as hand dermatitis, often results from a combination of causes, including genetics (atopic constitution), irritating substances and contact allergens. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). As current evidence suggests that SARS-CoV-2 can be transmitted through contaminated hands, the World Health Organization recommends frequent handwashing with soap and water, or hand-rubbing with an alcohol based hand rub.


title: The clinical application of the sliding loop technique for renorrhaphy during robot-assisted laparoscopic partial nephrectomy: Surgical technique and outcomes.

text: PURPOSE To report the initial clinical outcomes of the newly devised sliding loop technique (SLT) used for renorrhaphy in patients who underwent robot-assisted laparoscopic partial nephrectomy (RALPN) for small renal mass. MATERIALS AND METHODS We reviewed the surgical videos and medical charts of 31 patients who had undergone RALPN with the SLT renorrhaphy performed by two surgeons (CWJ and CK) between January 2014 and October 2014. SLT renorrhaphy was performed after tumor excision and renal parenchymal defect repair. Assessed outcomes included renorrhaphy time (RT), warm ischemic time, perioperative complications, and perioperative renal function change. RT was defined as interval from the end of bed suture to the renal artery declamping. RESULTS In all patients, sliding loop renorrhaphy was successfully conducted without conversions to radical nephrectomy or open approaches. Mean renorrhaphy and warm ischemic time were 9.0 and 22.6 minutes, respectively. After completing renorrhaphy, there were no adverse events such as dehiscence of approximated renal parenchyma, renal parenchymal tearing, or significant bleeding. Furthermore, no postoperative complications or significant renal function decline were observed as of the last follow-up for all patients. The limitations of this study include the small volume case series, the retrospective nature of the study, and the heterogeneity of surgeons. CONCLUSIONS From our initial clinical experience, SLT may be an efficient and safe renorrhaphy method in real clinical practice. Further large scale, prospective, long-term follow-up, and direct comparative studies with other techniques are required to confirm the clinical applicability of SLT.


title: An alarming retraction rate for scientific publications on Coronavirus Disease 2019 (COVID-19).

text: The ongoing Coronavirus Disease 2019 (COVID-19) global pandemic has triggered a flurry of associated research publications, numbering to ~137 papers a day since February 2020. This rate of publication appears to be exceptionally high, when compared to research papers published on other similar topics. Searches of COVID-19-associated publications on PubMed and Retraction Watch Database indicate that the retraction record appearance rate for COVID-19-related research is also exceptionally high compared to other related research topics in viral epidemics/pandemics and surpasses the basal level of about 4 in 10,000 papers. This finding serves as a reminder and caution against any lapses in the standard of work, peer review, and publication of COVID-19-related research.


title: Continuous learning through platforms.

text: The health crisis situation we have experienced caused by the SARSCoV-2 virus has changed our daily life in numerous aspects, including those related to training (undergraduate, postgraduate, and continuing education, etc). Training activities, conferences, lectures, face-to-face workshops were suspended until the Health Situation was over. Alternatives to face-to-face training were needed to guarantee the continuity of these activities. Online training, teaching and evaluation emerged as a relatively fast, simple, operational and flexible solution. Universities and faculties promoted online teaching through virtual classes. The Spanish Society of Hospital Pharmacy supported this initiative by signing an agreement with the Board of Deans and Chancellors of Pharmacy to make it possible for undergraduate students to continue their studies and supervised practices in hospital pharmacy departments. Specialized training was affected. Pharmacy residency programs were significantly modified by hospital pharmacies to be able to provide the new clinical and research activities required, everyday, by the pandemic situation. Postgraduate and residency training were also negatively affected. Again, online activities made up for restrictions to face-to-face teaching and training. The Spanish Society of Hospital Pharmacy promoted continuing education and provided updated information on the SARS-CoV-2 virus through its website. Thus, numerous virtual sessions, lectures and webinars have been held, and high-quality material was offered to provide up-todate knowledge, on the pharmacological management of patients with COVID-19. Online teaching and education has demonstrated to be an invaluable tool for hard times. During the lockdown, technology has kept us closer and has emerged as an ally. Many of us have found a new means of communication, information, and training. The Spanish Society of Hospital Pharmacy has substantially contributed to make it possible.


title: Good neurological outcome despite very low regional cerebral oxygen saturation during resuscitation--a prospective preclinical trial in 29 patients.

text: BACKGROUND Noninvasive regional cerebral oxygen saturation (rSO2) measurement using near-infrared spectroscopy (NIRS) might inform on extent and duration of cerebral hypoxia during cardiopulmonary resuscitation (CPR). This information may be used to guide resuscitation efforts and may carry relevant early prognostic information. METHODS We prospectively investigated non-traumatic out-of-hospital cardiac arrest (OHCA) patients on scene. NIRS was started either during CPR or shortly after (<2 min) return of spontaneous circulation (ROSC) by emergency medical service (EMS). Outcome was determined at intensive care unit (ICU) discharge and 6 months after cardiac arrest. RESULTS A total of 29 OHCA patients were included. In 23 patients NIRS was started during CPR and in 6 patients immediately after ROSC. 18 (62.1%) patients did not reach ROSC. Initial rSO2 during CPR was very low (<50% in all 23 patients, < 30% in 19 of 23 patients) with no significant difference between patients achieving ROSC and those who did not. Of five patients with ROSC, in whom NIRS was recorded during CPR, two reached a good six-months outcome (initial rSO2 22%) and three died during the ICU stay (initial rSO2 15, 16 and 46%). In six patients with NIRS started immediately after ROSC (<2 min), rSO2 was substantially higher (54-85 %) than in patients during CPR (p = 0.006). DISCUSSION AND CONCLUSION Initial frontal brain rSO2 determined by NIRS during CPR was generally very low and recovered rapidly after ROSC. Very low initial rSO2 during CPR was compatible with good neurological outcome in our limited cohort of patients. Further studies are needed to assess in larger cohorts and more detail the implications of very low initial rSO2 during CPR on scene.


title: Endovascular Reconstruction of Extrahepatic Portal Vein in Noncirrhotic and Nonmalignant Chronic Portal Vein Thrombosis Secondary to an Iatrogenic Stenotic Lesion.

text: Portal vein (PV) thrombosis (PVT) in the absence of liver disease or thrombophilia is rare. We report a 57-year-old male with a history of stage 3 chronic kidney disease who presented at the emergency department 18 months after abdominal surgery with progressive abdominal pain and distention. Computed tomography revealed PVT with multiple collaterals and moderate ascites. He had undergone partial gastrectomy and gastrojejunal anastomosis at an outside facility for gastrointestinal stromal tumors that caused an iatrogenic stenotic lesion in the PV. The patient underwent balloon angioplasty and endovascular deployment of an 8 mm × 100 mm Viabahn covered stent (W. L. Gore and Associates, Flagstaff, Arizona) in the extrahepatic PV via a transhepatic approach; the device allowed complete restoration of prograde portal flow with clinical improvement. At 6 months from the intervention, he remains symptom-free with normal liver function tests and patent endoprosthesis on antiplatelet therapy.


title: Pharmacokinetics and Safety Assessment of l-Tetrahydropalmatine in Cocaine Users: A Randomized, Double-Blind, Placebo-Controlled Study.

text: Cocaine use disorder (CUD) remains a significant public health challenge. l-Tetrahydropalmatine (l-THP), a well-tolerated and nonaddictive compound, shows promise for the management of CUD. Its pharmacologic profile includes blockade at dopamine and other monoamine receptors and attenuation of cocaine self-administration, reinstatement, and rewarding properties in rats. This study evaluated the safety of l-THP in human cocaine users and its influence on the safety and pharmacokinetics (PK) of cocaine. Twenty-four cocaine-using adult men were randomized to receive l-THP (30 mg twice a day orally) or placebo double-blind for 4 days, with an intranasal cocaine (40 mg) challenge on the fourth day. Safety and tolerability were evaluated using vital signs, ECG, clinical laboratory tests, and standardized self-report instruments. Peripheral venous blood was collected periodically and later assayed for l-THP and cocaine using highly sensitive and specific ultraperformance liquid chromatography-fluorescence detection (UPLC-FLD) methods. Twenty subjects completed the study, of whom 19 provided complete PK data. The short 3.5-day course of l-THP was safe and well tolerated and did not affect cocaine's PK or its acute cardiovascular effects. The cocaine AUC0→∞ was 211.5 and 261.4 h·ng/mL, and the Cmax was 83.3 and 104.5 ng/mL for the l-THP and placebo groups, respectively. In addition there were no significant differences in the number of side effects reported in each group (l-THP group 22 [48%], placebo group 24 [52%]) or vital signs including, heart rate, blood pressure, complete blood count, or ECG. These findings suggest that oral THP has promise for further development as a treatment for CUD.


title: Popularity of suture materials among residents and faculty members of a postdoctoral periodontology program.

text: AIM The aim of the present study was to determine the favoritism of suture materials among a group of clinicians at a teaching institution. METHODS The surveys included 11 absorbable and nine non-absorbable sutures. The surveyor was asked to select his or her suture preferences when it comes to using it in 13 different, commonly-performed surgical procedures. RESULTS The surveys showed overall preferences for non-absorbable versus absorbable sutures. Chromic Gut with a 4-0 diameter thread reverse cutting FS2 needle was the most favored suture. For periodontal bone grafts and hard tissue ridge augmentation, polytetrafluoroethylene with a 4-0 thread and FS2 needle was preferred. For autogenous gingival grafts, gingival allografts, connective tissue grafts, frenectomy and frenoplasty, Chromic Gut with 5-0 diameter thread reverse cutting P3 needle was favored. For extraction socket preservation, soft tissue canine exposure, ridge augmentation, and dental implants, Chromic Gut with 4-0 diameter thread reverse cutting FS2 needle was preferred, and for sinus augmentation, Vicryl with a 4-0 diameter thread reverse cutting FS2 needle was favored. CONCLUSION Absorbable sutures were preferred in the majority of periodontal procedures; however, non-absorbable sutures were favored in procedures that required longer healing or better stability of the flap edges in cases of periodontal and ridge augmentation.


title: Effect of Limb Position on Measurements of the Quadriceps Muscle Length/Femoral Length Ratio in Normal Beagle Dogs.

text: OBJECTIVES Dogs with patella alta reportedly have a shorter extensor mechanism than normal dogs. The present study aimed to measure the length of the extensor mechanism and to assess the effect of limb position on the quadriceps muscle length (QML)/femoral bone length (FL) ratio. STUDY DESIGN Three-dimensional computed tomography images were taken of 12 Beagle dogs. Each dog underwent computed tomographic imaging 24 times with different limb positions. The QML/FL was measured on each image, along with the hip flexion-extension, hip abduction-adduction and stifle flexion-extension angles. Multiple regression analysis was used to determine the effect of these angles on the QML/FL. RESULTS The QML/FL was increased with the hip extended (standardized partial regression coefficient 0.855 with linear plotting, 0.829 with log plotting) and with the stifle flexed (standardized partial regression coefficient 0.814 with linear plotting, 0.800 with log plotting). The partial regression coefficient of the hip abduction-adduction angle was small, indicating a small impact on the QML/FL. The 95% confidence range of the QML/FL with the hip extended and stifle flexed was 0.87 to 1.00 (mean ± standard deviation: 0.93 ± 0.03). CONCLUSION The QML/FL was more influenced by joint angles when the hip was flexed or the stifle was extended. Hence, these positions should be avoided when evaluating the QML/FL so that the QML is less altered by slight positioning disparities.


Clinical Management of Nonrespiratory Diseases in the COVID-19 Pandemic: What Have We Done and What Needs to Be Done? (Re: Telemed J E Health [Epub ahead of print]; DOI: 10.1089/tmj.2020.0106).


title: Pulmonary Embolism and Increased Levels of d-Dimer in Patients with Coronavirus Disease.

text: We report 3 patients with coronavirus disease who had a decline in respiratory status during their hospital course that responded well to intravenous steroids and interleukin-6 receptor antagonist therapy. These patients later showed development of persistent hypoxia with increased levels of d-dimer levels and were given a diagnosis of pulmonary embolisms.


title: Crystal structures of two coronavirus ADP-ribose-1''-monophosphatases and their complexes with ADP-Ribose: a systematic structural analysis of the viral ADRP domain.

text: The coronaviruses are a large family of plus-strand RNA viruses that cause a wide variety of diseases both in humans and in other organisms. The coronaviruses are composed of three main lineages and have a complex organization of nonstructural proteins (nsp's). In the coronavirus, nsp3 resides a domain with the macroH2A-like fold and ADP-ribose-1"-monophosphatase (ADRP) activity, which is proposed to play a regulatory role in the replication process. However, the significance of this domain for the coronaviruses is still poorly understood due to the lack of structural information from different lineages. We have determined the crystal structures of two viral ADRP domains, from the group I human coronavirus 229E and the group III avian infectious bronchitis virus, as well as their respective complexes with ADP-ribose. The structures were individually solved to elucidate the structural similarities and differences of the ADRP domains among various coronavirus species. The active-site residues responsible for mediating ADRP activity were found to be highly conserved in terms of both sequence alignment and structural superposition, whereas the substrate binding pocket exhibited variations in structure but not in sequence. Together with data from a previous analysis of the ADRP domain from the group II severe acute respiratory syndrome coronavirus and from other related functional studies of ADRP domains, a systematic structural analysis of the coronavirus ADRP domains was realized for the first time to provide a structural basis for the function of this domain in the coronavirus replication process.


title: Accuracy of methemoglobin detection by pulse CO-oximetry during hypoxia.

text: BACKGROUND Methemoglobin in the blood cannot be detected by conventional pulse oximetry, although it can bias the oximeter's estimate (Spo2) of the true arterial functional oxygen saturation (Sao2). A recently introduced "Pulse CO-Oximeter" (Masimo Rainbow SET(R) Radical-7 Pulse CO-Oximeter, Masimo Corp., Irvine, CA) is intended to additionally monitor noninvasively the fractional carboxyhemoglobin and methemoglobin content in blood. The purpose of our study was to determine whether hypoxia affects the new device's estimated methemoglobin reading accuracy, and whether the presence of methemoglobin impairs the ability of the Radical-7 and a conventional pulse oximeter (Nonin 9700, Nonin Medical Inc., Plymouth, MN) to detect decreases in Sao2. METHODS Eight and 6 healthy adults were included in 2 study groups, respectively, each fitted with multiple sensors and a radial arterial catheter for blood sampling. In the first group, IV administration of approximately 300 mg sodium nitrite increased subjects' methemoglobin level to a 7% to 8% target and hypoxia was induced to different levels of Sao2 (70%-100%) by varying fractional inspired oxygen. In the second group, 15% methemoglobin at room air and 80% Sao2 were targeted. Pulse CO-oximeter readings were compared with arterial blood values measured using a Radiometer multiwavelength hemoximeter. Pulse CO-oximeter methemoglobin reading performance was analyzed by observing the incidence of meaningful reading errors at the various hypoxia levels. This was used to determine the impact on predictive values for detecting methemoglobinemia. Spo2 reading bias, precision, and root mean square error were evaluated during conditions of elevated methemoglobin. RESULTS Observations spanned 66.2% to 99% Sao2 and 0.6% to 14.4% methemoglobin over the 2 groups (170 blood draws). Masimo methemoglobin reading bias and precision over the full Sao2 span was 7.7% +/- 13.0%. Best accuracy was found in the 95% to 100% Sao2 range (1.9% +/- 2.5%), progressing to its worst in the 70% to 80% range (24.8% +/- 15.6%). Occurrence of methemoglobin readings in error >5% increased over each 5-point decrease in Sao2 (P < 0.05). Masimo Spo2 readings were biased -6.3% +/- 3.0% in the 95% to 100% Sao2 range with 4% to 8.3% methemoglobin. Both the Radical-7 and Nonin 9700 pulse oximeters accurately detected decreases in Sao(2) <90% with 4% to 15% methemoglobin, despite displaying low Spo2 readings when Sao2 was >95%. CONCLUSIONS The Radical-7's methemoglobin readings become progressively more inaccurate as Sao2 decreases <95%, at times overestimating true values by 10% to 40%. Elevated methemoglobin causes the Spo2 readings to underestimate Sao2 similar to conventional 2-wavelength pulse oximeters at high saturation. Spo2 readings from both types of instruments continue to trend downward during the development of hypoxemia (Sao2 <90%) with methemoglobin levels up to 15%.


title: Characterization and Preoperative Risk Analysis of Leiomyosarcomas at a High-Volume Tertiary Care Center.

text: INTRODUCTION Uterine morcellation in minimally invasive surgery has recently come under scrutiny because of inadvertent dissemination of malignant tissue, including leiomyosarcomas commonly mistaken for fibroids. Identification of preoperative risk factors is crucial to ensure that oncologic care is delivered when suspicion for malignancy is high, while offering minimally invasive hysterectomies to the remaining patients. OBJECTIVES The aim of this study was to characterize risk factors for uterine leiomyosarcomas by reviewing preoperative, intraoperative, and postoperative data with an emphasis on the presence of concurrent fibroids. METHODS A retrospective case-control study of women undergoing hysterectomy with pathologic diagnosis of uterine leiomyosarcoma at a tertiary care center between January 2005 and April 2014. RESULTS Thirty-one women were identified with leiomyosarcoma and matched to 124 controls. Cases with leiomyosarcoma were more likely to have undergone menopause and to present with larger uteri (19- vs 9-week sized), with the most common presenting complaint being a pelvic mass (35.5% vs 8.9%). Controls were ten times more likely to have undergone a tubal ligation (30.6% vs 3.2%). Endometrial sampling detected malignancy preoperatively in only 50% of cases. Leiomyosarcomas were more commonly present when pelvic masses were identified in addition to fibroids on preoperative imaging. Most leiomyosarcoma cases (77.4%) were performed by oncologists via an abdominal approach (83.9%), with only 2 of 31 leiomyosarcomas being morcellated. Comparative analysis of preoperative imaging and postoperative pathology showed that in patients with leiomyosarcoma, fibroids were misdiagnosed 58.1% of the time, and leiomyosarcomas arose directly from fibroids in only 6.5% of cases. CONCLUSIONS Leiomyosarcoma risk factors include older age/postmenopausal status, enlarged uteri of greater than 10 weeks, and lack of previous tubal ligation. Preoperative testing failed to definitively identify leiomyosarcomas, although the presence of synchronous pelvic masses in fibroid uteri should raise clinical suspicion. Given the difficulty of preoperative identification, future efforts should focus on the development of safer minimally invasive techniques for uterine morcellation.


title: Characterization of doxycycline-mediated inhibition of Marfan syndrome-associated aortic dilation by multiphoton microscopy.

text: Marfan syndrome (MFS) is a connective tissue disorder that results in aortic root widening and aneurysm if unmanaged. We have previously reported doxycycline, a nonselective matrix metalloproteinases (MMPs) inhibitor, to attenuate aortic root widening and improve aortic contractility and elasticity in MFS mice. We were also first to use multiphoton microscopy, a non-invasive and label-free imaging technique, to quantify and link the aortic ultrastructure to possible changes in the skin dermis. Here, we aimed to assess the effects of long-term doxycycline treatment on the aortic ultrastructure and skin dermis of MFS mice through immunohistochemical evaluation and quantification of elastic and collagen content and morphology using multiphoton microscopy. Our results demonstrate a rescue of aortic elastic fiber fragmentation and disorganization accompanied by a decrease in MMP-2 and MMP-9 expression within the aortic wall in doxycycline-treated MFS mice. At 12 months of age, reduced skin dermal thickness was observed in both MFS and control mice, but only dermal thinning in MFS mice was rescued by doxycycline treatment. MMP-2 and MMP-9 expression was reduced in the skin of doxycycline-treated MFS mice. A decrease in dermal thickness was found to be positively associated with increased aortic root elastin disorganization and wall thickness. Our findings confirm the beneficial effects of doxycycline on ultrastructural properties of aortic root as well as on skin elasticity and structural integrity in MFS mice.


title: Interventional therapy for venous thromboembolism.

text: Advances in image-guided, catheter-based interventions have shown great potential to improve outcomes in patients with venous thromboembolism. Catheter-directed thrombolysis has been shown in one randomized controlled trial to reduce the risk of post-thrombotic syndrome in patients with acute lower extremity deep vein thrombosis; data from a larger national institute of health trial are expected in early 2017. The use of catheter-directed thrombolysis is also being increasingly considered for patients with submassive or massive pulmonary embolism. Preliminary studies suggest that endovascular stent placement and ablative therapies may be used to reduce symptoms and improve quality of life in severely affected patients with established post-thrombotic syndrome. In this article, we summarize the risks and benefits of endovascular venous thromboembolism therapies as currently understood, highlight clinical situations where their benefit may outweigh risks, and describe ongoing and upcoming pivotal research initiatives with multidisciplinary participation.


title: Endovascular treatment of carotid-cavernous fistulas.

text: Endovascular management has become the treatment of choice for carotid-cavernous fistulas regardless of the fistula type. The endovascular method offers numerous options that render it capable of treating each fistula type by choosing an adequate technique. This advantage along with the advancement in the field has led to fewer complications with higher success rate.


COVID-19 Outbreak Associated with Air Conditioning in Restaurant, Guangzhou, China, 2020.


title: A Validation Study for the Use of ROS1 Immunohistochemical Staining in Screening for ROS1 Translocations in Lung Cancer.

text: INTRODUCTION The presence of ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) rearrangements in lung cancers confers sensitivity to ROS kinase inhibitors, including crizotinib. However, they are rare abnormalities (in ∼1% of non-small cell lung carcinomas) that are typically identified by fluorescence in situ hybridization (FISH), and so screening using immunohistochemical (IHC) staining would be both cost- and time-efficient. METHODS A cohort of lung tumors negative for other common mutations related to targeted therapies were screened to assess the sensitivity and specificity of IHC staining in detecting ROS1 gene rearrangements, enriched by four other cases first identified by FISH. A review of published data was also undertaken. RESULTS IHC staining was 100% sensitive (95% confidence interval: 48-100) and 83% specific (95% confidence interval: 86-100) overall when an h-score higher than 100 was used. Patients with ROS1 gene rearrangements were younger and typically never-smokers, with the tumors all being adenocarcinomas with higher-grade architectural features and focal signet ring morphologic features (two of five). Four patients treated with crizotinib showed a partial response, with three also showing a partial response to pemetrexed. Three of four patients remain alive at 13, 27, and 31 months, respectively. CONCLUSION IHC staining can be used to screen for ROS1 gene rearrangements, with patients herein showing a response to crizotinib. Patients with tumors that test positive according to IHC staining but negative according to FISH were also identified, which may have implications for treatment selection.


title: Retrieval of a migrated N-butyl-2 cyanoacrylate cast using a snare-kit system during dural AVF embolization: A case report.

text: N-butyl-2 cyanoacrylate (NBCA) is a liquid embolic material that is widely used in various endovascular procedures because of its permanent and rapid vascular occluding effect regardless of the coagulation profile of the patient. However, NBCA migration to unintended vessels may result in serious complications. This report describes the retrieval of a migrated NBCA cast from the transverse-sigmoid sinus during dural arteriovenous fistula embolization using a transvenous snaring technique.


title: The experiences of physical rehabilitation in individuals with spinal cord injuries: a qualitative thematic synthesis.

text: PURPOSE The purpose of this thematic synthesis review was to identify and synthesise published qualitative research on the perspectives of individuals with spinal cord injuries with respect to physical rehabilitation interventions. MATERIALS AND METHODS The peer-reviewed literature was searched across seven databases and identified abstracts were independently screened by two reviewers. A thematic synthesis methodology was used to code and synthesise the results from the included studies. RESULTS In total, 7233 abstracts were identified; 31 articles were selected for inclusion, representing 26 physical rehabilitation interventions. The methodological quality of studies was moderate (Standards for Reporting Qualitative Research mean ± standard deviation = 14.39 ± 3.61). The four main themes developed were: (1) Benefits of physical rehabilitation, (2) Challenges of physical rehabilitation, (3) Need for support, and (4) Issue of control. CONCLUSIONS This qualitative thematic synthesis provides key insights into the experiences of individuals with spinal cord injuries who received physical rehabilitation. Recommendations for practice, based on the findings, include creating a diverse, encouraging, and educational physical rehabilitation experience with supportive staff who focus on communication and person-centred care. Implications for Rehabilitation Physical rehabilitation provides psychological as well as physical benefits to people with spinal cord injuries, including motivation, hope, improved self-confidence, and acceptance. Challenges identified during physical rehabilitation for people with spinal cord injuries, such as comparisons, negative emotions, recovery expectations, and slow progress, should be addressed by healthcare professionals to ensure person-centred care. People with spinal cord injuries identified a need for support from health care professionals, family, and friends, as well other people with spinal cord injuries. There is an issue of control in physical rehabilitation for people with spinal cord injuries, which can result in a fight with oneself or with healthcare professionals to regain the control that has been lost.


Editorial: How Fragile We Are.


title: Gastric reflux: association with aspiration and oral secretion pH as marker of reflux: a descriptive correlational study.

text: BACKGROUND Gastric reflux leading to pulmonary aspiration is a frequent event in mechanically ventilated, gastric-fed patients, which can lead to ventilator-associated complications and pneumonia. OBJECTIVES The objectives of this study were to determine the association between gastric reflux and aspiration using the presence of pepsin in oral or tracheal secretions as a marker of reflux or aspiration and to determine the association between the pH (range, 0-14) and the presence of pepsin in oral secretions. METHODS A descriptive correlational study was conducted in mechanically ventilated surgical or medical patients receiving gastric tube feedings. Oral secretions were suctioned hourly and tracheal secretions every 2 to 3 hours for 12-hour periods over 1 to 2 days in 15 patients. RESULTS There were 142 paired samples of oral tracheal secretions. A majority of samples (60%) had the same results, with 32% both pepsin-positive and 27% both pepsin-negative. The range of pH measurements was 4 to 8, with a mean of 6.3 ± 0.05. Ninety oral specimens had a pH of 4 to 6. Forty-seven of the oral specimens with pH measures between 4 and 6 (52%) were pepsin-positive. The correlation of pH percent pepsin-positive oral secretions was not significant. CONCLUSION Aspiration events were more frequent than reflux events. Measurement of actual pepsin concentration to detect new reflux and aspiration events is recommended in future studies. Bedside pH measures of oral secretions are not a valid marker of gastric reflux.


title: Probe-based confocal laser endomicroscopy and fluorescence-based enhanced reality for real-time assessment of intestinal microcirculation in a porcine model of sigmoid ischemia.

text: BACKGROUND AND AIM Surgeons currently rely on visual clues to estimate the presence of sufficient vascularity for safe anastomosis. We aimed to assess the accuracy of endoluminal confocal laser endomicroscopy (CLE) and laparoscopic fluorescence-based enhanced reality (FLER), using near-infrared imaging and fluorescence from injected Indocyanine Green, to identify the transition from ischemic to vascular areas in a porcine model of mesenteric ischemia. METHODS Six pigs underwent 1-h sigmoid segmental ischemia. The ischemic area was evaluated by clinical assessment and FLER to determine presumed viable margins. For each sigmoid colon, 5 regions of interest (ROIs) were identified: ischemic (ROI 1), presumed viable margins ROI 2a (distal) and 2b (proximal), and vascular areas 3a (distal) and 3b (proximal). After injection of fluorescein, CLE scanning of the mucosa from the ischemic area toward viable margins was performed. Capillary blood samples were obtained by puncturing the serosa at the ROIs, and capillary lactates were measured with the EDGE(®) analyzer. RESULTS Capillary lactates were significantly higher at ROI 1 (4.91 mmol/L) when compared to resection margins (2.8 mmol/L; mean difference: 2.11; p < 0.05) identified by FLER. There was no significant difference in lactates between ROI1 and resection margins identified by clinical evaluation. In 50 % of cases, ROI 2aCLINIC-2bCLINIC were considered to match (<1 cm distance) with ROI 2aFLER-2bFLER. Confocal analysis revealed specific clues to identify the transition from ischemic to viable areas corresponding to those assessed by FLER in 11/12 cases versus 7/12 for those identified by clinical evaluation. CONCLUSIONS In this experimental model, FLER and CLE were more accurate than clinical evaluation to delineate bowel vascularization.


title: Studying Closed Hydrodynamic Models of "In Vivo" DNA Perfusion in Pig Liver for Gene Therapy Translation to Humans.

text: INTRODUCTION Expressing exogenous genes after naked DNA delivery into hepatocytes might achieve sustained and high expression of human proteins. Tail vein DNA injection is an efficient procedure for gene transfer in murine liver. Hydrodynamic procedures in large animals require organ targeting, and improve with liver vascular exclusion. In the present study, two closed liver hydrofection models employing the human alpha-1-antitrypsin (hAAT) gene are compared to reference standards in order to evaluate their potential clinical interest. MATERIAL AND METHODS A solution of naked DNA bearing the hAAT gene was retrogradely injected in 7 pig livers using two different closed perfusion procedures: an endovascular catheterization-mediated procedure (n = 3) with infrahepatic inferior vena cava and portal vein blockage; and a surgery-mediated procedure (n = 4) with completely sealed liver. Gene transfer was performed through the suprahepatic inferior cava vein in the endovascular procedure and through the infrahepatic inferior vena cava in the surgical procedure. The efficiency of the procedures was evaluated 14 days after hydrofection by quantifying the hAAT protein copies per cell in tissue and in plasma. For comparison, samples from mice (n = 7) successfully hydrofected with hAAT and healthy human liver segments (n = 4) were evaluated. RESULTS Gene decoding occurs efficiently using both procedures, with liver vascular arrest improving its efficiency. The surgically closed procedure (sealed organ) reached higher tissue protein levels (4x10^5- copies/cell) than the endovascular procedure, though the levels were lower than in human liver (5x10^6- copies/cell) and hydrofected mouse liver (10^6- copies/cell). However, protein levels in plasma were lower (p<0.001) than the reference standards in all cases. CONCLUSION Hydrofection of hAAT DNA to "in vivo" isolated pig liver mediates highly efficient gene delivery and protein expression in tissue. Both endovascular and surgically closed models mediate high tissue protein expression. Impairment of protein secretion to plasma is observed and might be species-related. This study reinforces the potential application of closed liver hydrofection for therapeutic purposes, provided protein secretion improves.


title: Abandoning Prophylactic Abdominal Drainage after Hepatic Surgery: 10 Years of No-Drain Policy in an Enhanced Recovery after Surgery Environment.

text: BACKGROUND Routine prophylactic abdominal drainage after hepatic surgery is still being debated, as it may be unnecessary, possibly harmful, and uncomfortable for patients. This study evaluated the safety of a no-drain policy after liver resection within an Enhanced Recovery after Surgery (ERAS) programme. METHODS All hepatectomies performed without prophylactic drainage during 2005-2014 were included. Primary end points were resection-surface-related (RSR) morbidity, defined as the presence of postoperative biloma, hemorrhage or abscess, and reinterventions. Secondary end points were length of stay, total postoperative morbidity, the composite end point of liver surgery-specific complications, readmissions, and 90-day mortality. Uni- and multivariate analyses were performed to identify independent risk factors for RSR morbidity. A systematic search was performed to compare the results of this study to literature. RESULTS A total of 538 resections were included in the study. The RSR complication and reintervention rate was 15 and 12%, respectively. Major liver resection (≥3 segments) was an independent risk factor for the development of RSR morbidity (OR 3.01, 95% CI 1.61-5.62; p = 0.001) and need for RSR reintervention (OR 3.02, 95% CI 1.59-5.73; p = 0.001). CONCLUSION RSR morbidity, mortality, and reintervention rates after liver surgery without prophylactic drainage in patients, treated within an ERAS programme, were comparable to previously published data. A no-drain policy after partial hepatectomy seems safe and feasible.


title: The role of extracorporeal membrane oxygenation circulatory support in the 'crash and burn' patient: from implantation to weaning.

text: PURPOSE OF REVIEW In advanced cardiogenic shock, early mechanical circulatory support may prevent multiorgan failure and death. In this article, we are describing our experience with extracorporeal membrane oxygenation (ECMO) application. RECENT FINDINGS Venoarterial ECMO has been used successfully as a therapeutic option for patients with advanced cardiogenic shock and cardiac arrest. SUMMARY In this review, based on the daily routine of the Hershey group using ECMO for therapy of advanced cardiogenic shock, the application of ECMO is described. The aim is to share our hands-on experience during emergent implantation and to contribute to the knowledge within the field of mechanical circulatory support.


title: Switching Monopolar Radiofrequency Ablation Using a Separable Cluster Electrode in Patients with Hepatocellular Carcinoma: A Prospective Study.

text: OBJECTIVE This study was conducted to evaluate the outcomes of multi-channel switching RFA using a separable cluster electrode in patients with HCC. METHODS From November 2011 to July 2013, 79 patients with 98 HCCs < 5 cm were enrolled and treated with RFA using a multi-channel switching radiofrequency system and a separable cluster electrode under the guidance of a real-time fusion imaging system. The primary and secondary endpoints were the 3-year local tumor progression (LTP) rate and recurrence-free survival (RFS) rate, respectively. For post hoc analyses, LTP, RFS, and major complication rates were retrospectively compared with a historical control group treated with RFA using the same radiofrequency system but with multiple internally-cooled electrodes. RESULTS The technique success rate of the 98 tumors was 100%. Cumulative 1-year, 2-year, and 3-year LTP rates were 3.4%, 6.9%, and 12.4%, respectively. For patient-level data, cumulative 1-year, 2-year, and 3-year RFS rates were 83.9%, 68.6%, and 45.4%, respectively. On post hoc analyses, none of the baseline characteristics showed a significant difference between the separable cluster electrode and multiple internally-cooled electrodes group. Cumulative LTP and RFS rates of the two groups also showed no significant difference (p = 0.401 and p = 0.881, respectively). Finally, major complication rates of the separable cluster electrode group (5.0%, 4/79) and multiple internally-cooled electrodes group (5.9%, 4/74) were also comparable (p = 1.000). CONCLUSION Switching monopolar RFA using a separable cluster electrode is a feasible and efficient technique for the treatment of HCCs smaller than 5 cm, providing comparable local tumor control to multiple internally-cooled electrodes. TRIAL REGISTRATION ClinicalTrials.gov NCT02745483.


Suggestions for Combatting COVID-19 by Natural Means in the Absence of Standard Medical Regimens.


title: In-House Three-Dimensional Printing Workflow for Face Shield During COVID-19 Pandemic.

text: From the beginning of the year 2020, the world was affected by a coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, leading to a shortage of personal protective equipment (PPE) at a global level, and thus generating exposure of health professionals to this extremely contagious virus. Within this context, the present work seeks to present an alternative for the production of face shields "face shields," in which it recommends its production "in house" through 3D printing, in principle initiated by Prusa Research, where we download your project of support of facial protectors, proceeding with printing through the 3D printer Gtmax3D Core H5. The authors produced a face shield in ABS, in a total time of 3 hours and 44 minutes. Thus, the model presented proved to be feasible, at a low cost, adding to the list of possibilities to produce inputs necessary to maintain the fight against this epidemic.


Robotic renal transplant recipient surgery with vaginally inserted allograft.


title: The fecal virome of pigs on a high-density farm.

text: Swine are an important source of proteins worldwide but are subject to frequent viral outbreaks and numerous infections capable of infecting humans. Modern farming conditions may also increase viral transmission and potential zoonotic spread. We describe here the metagenomics-derived virome in the feces of 24 healthy and 12 diarrheic piglets on a high-density farm. An average of 4.2 different mammalian viruses were shed by healthy piglets, reflecting a high level of asymptomatic infections. Diarrheic pigs shed an average of 5.4 different mammalian viruses. Ninety-nine percent of the viral sequences were related to the RNA virus families Picornaviridae, Astroviridae, Coronaviridae, and Caliciviridae, while 1% were related to the small DNA virus families Circoviridae, and Parvoviridae. Porcine RNA viruses identified, in order of decreasing number of sequence reads, consisted of kobuviruses, astroviruses, enteroviruses, sapoviruses, sapeloviruses, coronaviruses, bocaviruses, and teschoviruses. The near-full genomes of multiple novel species of porcine astroviruses and bocaviruses were generated and phylogenetically analyzed. Multiple small circular DNA genomes encoding replicase proteins plus two highly divergent members of the Picornavirales order were also characterized. The possible origin of these viral genomes from pig-infecting protozoans and nematodes, based on closest sequence similarities, is discussed. In summary, an unbiased survey of viruses in the feces of intensely farmed animals revealed frequent coinfections with a highly diverse set of viruses providing favorable conditions for viral recombination. Viral surveys of animals can readily document the circulation of known and new viruses, facilitating the detection of emerging viruses and prospective evaluation of their pathogenic and zoonotic potentials.


title: Fast-Acting Sublingual Zolpidem for Middle-of-the-Night Wakefulness.

text: Sleep disorders (somnipathies) are conditions characterized by disruptions of sleep quality or of sleep pattern. They can involve difficulty falling asleep (prolonged sleep onset latency), difficulty staying asleep (disturbance of sleep maintenance), sleep of poor quality (unrefreshing), or combinations of these and can lead to poor health and quality of life problems. A subtype of sleep-maintenance insomnia is middle-of-the-night wakefulness, a relatively common occurrence. Zolpidem, a nonbenzodiazepine benzodiazepine receptor agonist, allosterically modulates an ion channel and increases the influx of Cl(-), thereby dampening the effect of excitatory (sleep disrupting) input. Recently, product label changes to some zolpidem containing products have been implemented by the FDA in order to reduce the risk associated with their morning after residual side effects. A new formulation of zolpidem tartrate (Intermezzo) sublingual tablet, an approved product indicated exclusively for the treatment of middle-of-the-night wakefulness and difficulty returning to sleep, did not have its label changed. We present a short summary of its basic science and clinical attributes in light of the recent regulatory changes for zolpidem products.


title: Scale-up bioprocess development for production of the antibiotic valinomycin in Escherichia coli based on consistent fed-batch cultivations.

text: BACKGROUND Heterologous production of natural products in Escherichia coli has emerged as an attractive strategy to obtain molecules of interest. Although technically feasible most of them are still constrained to laboratory scale production. Therefore, it is necessary to develop reasonable scale-up strategies for bioprocesses aiming at the overproduction of targeted natural products under industrial scale conditions. To this end, we used the production of the antibiotic valinomycin in E. coli as a model system for scalable bioprocess development based on consistent fed-batch cultivations. RESULTS In this work, the glucose limited fed-batch strategy based on pure mineral salt medium was used throughout all scales for valinomycin production. The optimal glucose feed rate was initially detected by the use of a biocatalytically controlled glucose release (EnBase® technology) in parallel cultivations in 24-well plates with continuous monitoring of pH and dissolved oxygen. These results were confirmed in shake flasks, where the accumulation of valinomycin was highest when the specific growth rate decreased below 0.1 h(-1). This correlation was also observed for high cell density fed-batch cultivations in a lab-scale bioreactor. The bioreactor fermentation produced valinomycin with titers of more than 2 mg L(-1) based on the feeding of a concentrated glucose solution. Valinomycin production was not affected by oscillating conditions (i.e. glucose and oxygen) in a scale-down two-compartment reactor, which could mimic similar situations in industrial bioreactors, suggesting that the process is very robust and a scaling of the process to a larger industrial scale appears a realistic scenario. CONCLUSIONS Valinomycin production was scaled up from mL volumes to 10 L with consistent use of the fed-batch technology. This work presents a robust and reliable approach for scalable bioprocess development and represents an example for the consistent development of a process for a heterologously expressed natural product towards the industrial scale.


Understanding cancer genetics through a global collaboration.


title: Comparison of tumor cell numbers and 22C3 PD-L1 expression between cryobiopsy and transbronchial biopsy with endobronchial ultrasonography-guide sheath for lung cancer.

text: BACKGROUND We previously reported cryobiopsy (Cryo) with endobronchial ultrasonography-guide sheath (EBUS-GS) for peripheral pulmonary lesions (PPLs) provides significantly larger tissues than transbronchial biopsy (TBB) and provides high quantity and quality DNA for gene analysis by next generation sequencing. However, the tumor cell yields and programmed death ligand 1 (PD-L1) expression between each approach have not been compared. Here, we assessed the tumor cell numbers and PD-L1 expression for Cryo with EBUS-GS for PPLs and TBB in patients with lung cancer. METHODS Sixteen patients were enrolled in this prospective study from June to November 2017 at Tokyo Women's Medical University Hospital. The number of tumor cells from a single biopsy, total number of tumor cells, average number of tumor cells, and 22C3 PD-L1 expression (≥ 50% and ≥ 1%) were compared between Cryo and TBB. RESULTS The numbers of tumor cells from a single biopsy, total numbers of tumor cells, and average numbers of tumor cells obtained by Cryo were significantly larger than those obtained by TBB (Cryo [means ± standard errors of the means]: 1321 ± 303.7, 1981 ± 411.7, and 1406 ± 310.3; TBB: 208.8 ± 38.24, 1044 ± 189.0, and 208.8 ± 37.81; P < 0.0001, P = 0.0474, P = 0.0006, respectively). PD-L1 ≥ 50% and ≥ 1% patients for Cryo were 18.8 and 56.3%, respectively, whereas those for TBB were 12.5 and 37.5%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, concordance, and κ coefficient based on Cryo for TBB were 66.7, 100, 100, 92.9, 93.8%, and 0.7647, respectively, for PD-L1 ≥ 50%; and 44.4, 71.4, 66.7, 50, 56.3%, and 0.1515, respectively, for PD-L1 ≥ 1%. CONCLUSION Cryo with EBUS-GS may be a useful diagnostic approach for lung cancer, with advantages over TBB for gene analysis and whole exon sequencing. Particularly, it could contribute to patients taking pembrolizumab as first-line therapy when PD-L1 was negative by evaluating TBB specimens. It could also provide ample tissue for PD-L1 expression analysis in addition to accurate diagnosis and gene analysis.


title: Effect of early tracheostomy on clinical outcomes in critically ill lung transplant recipients.

text: OBJECTIVES The purpose of this study was to evaluate the effect of early tracheostomy in patients following lung transplantation and to determine its optimal timing and influence on clinical outcomes. METHODS We retrospectively reviewed records of 96 adult patients who underwent lung transplantation at our institution between August 2008 and January 2016. Time-to-tracheostomy was defined based on timing of the procedure: "early" if less than 3 days or "late" if 3 or more days after lung transplantation. RESULTS Forty-nine patients (51%) underwent tracheostomy 3.2 ± 1.8 days after lung transplantation. Among these patients, 21 patients (42.9%) underwent early tracheostomy and 28 patients (57.1%) underwent late tracheostomy. Multivariable logistic regression analysis indicated that preoperative performance status was a significant predictor for tracheostomy (p = 0.006, odds ratio 2.72). Patients in the early tracheostomy group began walking (p = 0.003) and oral feeding (p = 0.0006) earlier and had a shorter duration of mechanical ventilation (p = 0.04) and shorter length of intensive care unit (p = 0.01) and hospital stay (p = 0.04) than patients in the late tracheostomy group. No significant differences in postoperative walking (p = 0.06), oral feeding (p = 0.17), or length of hospital stay (p = 0.37) were observed between patients who underwent early tracheostomy and those who did not undergo tracheostomy. CONCLUSIONS Early tracheostomy following lung transplantation decreased both intensive care and hospital stay, due to improved postoperative recovery, even in patients with poor preoperative conditions. Furthermore, length of hospital stay in patients with early tracheostomy was similar to that of patients without tracheostomy after lung transplantation.


title: Mutations in the GM1 binding site of simian virus 40 VP1 alter receptor usage and cell tropism.

text: Polyomaviruses are nonenveloped viruses with capsids composed primarily of 72 pentamers of the viral VP1 protein, which forms the outer shell of the capsid and binds to cell surface oligosaccharide receptors. Highly conserved VP1 proteins from closely related polyomaviruses recognize different oligosaccharides. To determine whether amino acid changes restricted to the oligosaccharide binding site are sufficient to determine receptor specificity and how changes in receptor usage affect tropism, we studied the primate polyomavirus simian virus 40 (SV40), which uses the ganglioside GM1 as a receptor that mediates cell binding and entry. Here, we used two sequential genetic screens to isolate and characterize viable SV40 mutants with mutations in the VP1 GM1 binding site. Two of these mutants were completely resistant to GM1 neutralization, were no longer stimulated by incorporation of GM1 into cell membranes, and were unable to bind to GM1 on the cell surface. In addition, these mutant viruses displayed an infection defect in monkey cells with high levels of cell surface GM1. Interestingly, one mutant infected cells with low cell surface GM1 more efficiently than wild-type virus, apparently by utilizing a different ganglioside receptor. Our results indicate that a small number of mutations in the GM1 binding site are sufficient to alter ganglioside usage and change tropism, and they suggest that VP1 divergence is driven primarily by a requirement to accommodate specific receptors. In addition, our results suggest that GM1 binding is required for vacuole formation in permissive monkey CV-1 cells. Further study of these mutants will provide new insight into polyomavirus entry, pathogenesis, and evolution.


title: Improving the diagnostic accuracy of hiatal hernia in patients undergoing bariatric surgery.

text: BACKGROUND Surgical correction of hiatal hernia (HH) during bariatric surgery has been found to improve patient outcomes and decrease reoperation rate. Although barium esophagram is more sensitive than endoscopy for detection of HH, accurate preoperative diagnosis remains a challenge. The aim of this study is to determine whether diagnostic accuracy improves by utilizing right anterior oblique (RAO) esophagram technique instead of the commonly used upright technique when comparing to the gold standard of intraoperative detection. METHODS All patients undergoing bariatric surgery were prospectively evaluated for HH by barium esophagram. After the first 69 patients, the technique was changed from upright to RAO. Hiatal hernia was assessed intraoperatively by laxity of the phrenoesophageal ligament and, if present, was repaired posteriorly. Two board-certified radiologists specializing in gastrointestinal radiology, who were blinded to the intraoperative results, retrospectively reviewed the esophagrams. Consensus reads were utilized for divergent opinions. Sensitivity and specificity were calculated for each technique. RESULTS Between 2008 and 2010, a total of 388 patients underwent preoperative esophagrams (69 upright, 388 RAO). For upright esophagram, sensitivity was 50 % and specificity was 97 %. For RAO esophagram, sensitivity was 70 % and specificity was 77 %. RAO had a lower percentage of false negatives (11 vs. 21 %) than upright esophagram. CONCLUSIONS The use of RAO technique for preoperative esophagram is more sensitive for diagnosis of hiatal hernia than upright esophagram. If surgeons desire routine preoperative esophagram, RAO technique is the best.


title: Human cytomegalovirus exploits interferon-induced transmembrane proteins to facilitate morphogenesis of the virion assembly compartment.

text: UNLABELLED Recently, interferon-induced transmembrane proteins (IFITMs) have been identified to be key effector molecules in the host type I interferon defense system. The invasion of host cells by a large range of RNA viruses is inhibited by IFITMs during the entry step. However, the roles of IFITMs in DNA virus infections have not been studied in detail. In this study, we report that human cytomegalovirus (HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment (vAC) during infection of human fibroblasts. We found that IFITMs were expressed constitutively in human embryonic lung fibroblasts (MRC5 cells). HCMV infection inhibited IFITM protein accumulation in the later stages of infection. Overexpression of an IFITM protein in MRC5 cells slightly enhanced HCMV production and knockdown of IFITMs by RNA interference reduced the virus titer by about 100-fold on day 8 postinfection, according to the findings of a virus yield assay at a low multiplicity of infection. Virus gene expression and DNA synthesis were not affected, but the typical round structure of the vAC was not formed after the suppression of IFITMs, thereby resulting in defective virion assembly and the production of less infectious virion particles. Interestingly, the replication of herpes simplex virus, a human herpesvirus that is closely related to HCMV, was not affected by the suppression of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a specific pathway required for HCMV replication. IMPORTANCE HCMV is known to repurpose the interferon-stimulated genes (ISGs) viperin and tetherin to facilitate its replication. Our results expand the range of ISGs that can be exploited by HCMV for its replication. This is also the first report of a proviral function of IFITMs in DNA virus replication. In addition, whereas previous studies showed that IFITMs modulate virus entry, which is a very early stage in the virus life cycle, we identified a new function of IFITMs during the very late stage of virus replication, i.e., virion assembly. Virus entry and assembly both involve vesicle transport and membrane fusion; thus, a common biochemical activity of IFITMs is likely to be involved. Therefore, our findings may provide a new platform for dissecting the molecular mechanism of action of IFITMs during the blocking or enhancement of virus infection, which are under intense investigation in this field.


title: Bariatric surgery: risks and rewards.

text: CONTEXT Over 23 million Americans are afflicted with severe obesity, i.e. their body mass index (in kilograms per square meter) values exceed 35. Of even greater concern is the association of the adiposity with comorbidities such as diabetes, hypertension, cardiopulmonary failure, asthma, pseudotumor cerebri, infertility, and crippling arthritis. OBJECTIVE Diets, exercise, behavioral modification, and drugs are not effective in these individuals. This article examines the effect of surgery on the control of the weight and the comorbidities, as well as the safety of these operations. INTERVENTIONS Although the article focuses on the outcomes of the three most commonly performed operations, i.e. adjustable gastric banding, the gastric bypass, and the biliopancreatic bypass with duodenal switch, it aims for perspective with the inclusion of abandoned and current investigational procedures, a review of the complications, and an emphasis on the appropriate selection of patients. POSITIONS: Ample evidence, including controlled randomized studies, now document that bariatric surgery produces durable weight loss exceeding 100 lb (46 kg), full and long-term remission of type 2 diabetes in over 80% with salutary effects on the other comorbidities as well with significant reductions in all-cause mortality. Although the severely obese present with serious surgical risks, bariatric surgery is performed safely with a 0.35% 90-d mortality in Centers of Excellence throughout the United States-similar to the complication rates after cholecystectomy. CONCLUSIONS Until better approaches become available, bariatric surgery is the therapy of choice for patients with severe obesity.


title: Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain.

text: Even though the early reports from China provided advance warning of what was to come, the COVID-19 pandemic has spread throughout the world with devastating consequences. Emergency measures are being implemented to reduce the magnitude of the public health crisis, prevent healthcare facilities from becoming overwhelmed and reduce the death toll of the disease. Containment strategies to mitigate viral transmission and emergency measures to increase the capacity of each country to provide intensive care are at the forefront of the public health management of the epidemic, even though the detrimental social and psychological effects of quarantine are evident on a global scale. Optimal management of critically ill patients with COVID-19 is also unclear, and the initial suggestion for early intubation as in typical ARDS may have caused significant harm. The management of mild cases of confirmed infection is another point of controversy, as drugs which may be repurposed for COVID-19 treatment have significant, potentially irreversible toxic effects and their use in mild cases of a viral illness which is typically self-limited may be harmful.


title: Lifting of social distancing measures: Perspectives from Vietnam.

text: While many nations are struggling to slow the transmission rate of the COVID-19, Vietnam has seen no new locally-acquired cases since April 16. After implementing 22 days of nationwide social distancing, on April 23, the government of Vietnam announced the easing of social distancing measures. This allows the country to restart its socio-economic activities in a gradual, prudent manner. Domestic tourism and exports of agricultural and anti-COVID-19 medical products take priority over the other sectors in this post-pandemic economic recovery. Importantly, the country needs to stay vigilant on the fight against the disease to prevent a possibility of another outbreak.


title: Coil embolization of a traumatic arteriovenous fistula of the lower extremity.

text: Arteriovenous fistulas (AVFs) are unusual connections between the arterial and venous system that bypass the normal anatomic capillary beds. This case report presents an arteriovenous fistula of the lower extremity caused by a penetrating injury. The patient was diagnosed by Duplex ultrasonography. Diagnostic catheterization of the affected limb showed a high-flow AVF between the left profunda femoris artery and left femoral vein with a deep femoral vein aneurysm measuring 9x4 cm. The AVF was successfully treated with coil embolization.


title: Retrograde jejunogastric decompression after esophagectomy is superior to nasogastric drainage.

text: BACKGROUND Nasogastric tubes (NG) are commonly used for maintaining conduit decompression after esophagectomy. We investigated the use of retrograde tube gastrostomy (RG) after esophagectomy. METHODS Patients underwent either NG or RG placement for postoperative conduit decompression. Both tubes were maintained on low continuous suction. RESULTS Between 2000 and 2008, 306 patients underwent esophagectomy with reconstruction. One hundred ninety-three patients underwent NG and 113 underwent RG placement. The 2 groups were comparable in age, gender, tumor stage, and smoking status. Patients in the NG group were more likely to have received neoadjuvant therapy and to have a thoracotomy for esophagectomy. The incidence of respiratory complications was lower in the retrograde group compared with the NG group: Pneumonia, 9 of 113(8.0%) vs 50 of 193 (25.9%), p<0.001; respiratory failure requiring bronchoscopy or reintubation, 12 of 113 (10.8%) vs 46 of 193 (23.8%), p=0.004; aspiration, 4 of 113 (3.5%) vs 20 of 193 (10.4%), p=0.045. The incidence of cardiac dysrhythmias was also lower in the retrograde group (18 of 113 [15.9%] vs 69 of 193 [35.8%], p<0.001). The incidence of wound complications, myocardial infarction, stroke, and conduit necrosis-anastomotic leak was similar between groups. In a multivariate regression model an NG tube was the strongest predictor for postoperative pneumonia (odds ratio 3.27, 95% confidence interval 1.50 to 7.12). The other predictors were prior chest surgery, smoking, and thoracotomy incision. There were 4 minor complications related to the retrograde tube (wound infection n=1, broken tube requiring endoscopy n=2, tube caught in anastomosis detected intraoperatively n=1). CONCLUSIONS Retrograde gastrostomy decompression of the conduit after esophagectomy is effective and diminishes complications compared with NG tube drainage.


title: Postmortem Examination in Two Cases of Death Related to 2019-nCoV Infection and the Experience of On-site Protection.

text: Abstract


title: Endovascular Treatment of Large and Giant Carotid Aneurysms with Flow-Diverter Stents Alone or in Combination with Coils: A Multicenter Experience and Long-Term Follow-up.

text: BACKGROUND Although flow diverters (FDs) have been widely accepted by neurointerventionists, their safety has yet to be fully defined. Stratification by aneurysm size and location is essential for correct evaluation of treatment outcomes and risks of flow diversion. OBJECTIVE To compare neurological and anatomic outcomes and evaluate the risk of complications after endovascular treatment of large or giant internal carotid artery (ICA) aneurysms with FD/FDs alone or together with coil embolization. METHODS We reviewed all patients with large or giant, ruptured or unruptured ICA aneurysms who underwent endovascular treatment with flow diversion alone (group A) or with concomitant coiling (group B) in 4 international institutions between 2010 and 2015. Anatomic outcome was evaluated using the Byrne scale on digital subtraction angiography and/or angioMRI and/or angioCT scans 3, 6, 12, and 24 months postoperatively. RESULTS We collected 44 patients with large or giant ICA aneurysms. Four patients (9%) presented with aneurysmal subarachnoid hemorrhage (SAH). FD/FDs were used alone in 26 patients and in combination with coil embolization in the 18 remaining patients. The mortality rate due to procedure-related and/or neurological complications was 2.2%. Twelve months after the procedure, 88.6% (n = 39) of patients had a favorable neurological outcome. One year after the procedure, the aneurysm was completely occluded in 72.7% of patients: 61.5% (16/18) in group A and 88.9% (16/26) in group B. CONCLUSION Clinical outcomes and rates of intraoperative and postoperative complications did not differ significantly between the groups. Better anatomic results using FD/FDs combined with coils were documented 6 months after the procedure; this option seems to provide a higher aneurysm occlusion rate and reduce the need for retreatment.


title: Lycorine sensitizes CD40 ligand-protected chronic lymphocytic leukemia cells to bezafibrate- and medroxyprogesterone acetate-induced apoptosis but dasatanib does not overcome reported CD40-mediated drug resistance.

text: BACKGROUND Tumor cells in chronic lymphocytic leukemia accumulate in the periphery through the proliferation of a minority of cells in lymph nodes. The proliferative and survival signals in these proliferation centers include interactions with T lymphocytes expressing CD40 ligand. We have demonstrated that the low toxicity combination of bezafibrate and medroxyprogesterone acetate induces mitochondrial superoxide-mediated apoptosis of non-CD40-liganded cells but not of cells exposed to CD40 ligand. Here, we assessed the ability of dasatinib and lycorine to restore bezafibrate- and medroxyprogesterone acetate- induced apoptosis in cells exposed to CD40 ligand. In parallel experiments we compared the ability of dasatinib to induce apoptosis of cells co-treated with fludarabine. DESIGN AND METHODS Primary chronic lymphocytic leukemia and peripheral blood mononuclear cells were exposed to drug combinations for 72 hours on control and CD40 ligand-expressing fibroblast monolayers. Cells were harvested and analyzed for apoptosis and levels of mitochondrial superoxide using flow cytometry. In some experiments cells were removed from CD40 ligand at 48 hours, retreated and analyzed after a further 24 hours. The effect of CD40 ligand and drug treatments on mitochondrial superoxide levels were assessed. RESULTS As previously described, dasatinib rendered cells sensitive to fludarabine but only when CD40 ligand was removed for the last 24 hours of culture. In contrast, lycorine restored the bezafibrate- and medroxyprogesterone acetate-induced apoptosis associated with mitochondrial superoxide even during continuous exposure to CD40 ligand. Furthermore, combined bezafibrate, medroxyprogesterone acetate and lycorine had little effect against normal peripheral blood mononuclear cells, whereas dasatinib with fludarabine induced high levels of apoptosis. CONCLUSIONS Our data indicate the potential of bezafibrate, medroxyprogesterone acetate and lycorine as novel therapy in chronic lymphocytic leukemia and have important implications for the reported potential of c-abl kinase inhibitors in this disease.


title: [Expression analysis of 2019-nCoV related ACE2 and TMPRSS2 in eye tissues].

text: Objective: Angiotensin converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) are the key proteins for 2019-nCoV entry into host cells. To evaluate the potential infection risk of 2019-nCoV on ocular surface, we compared ACE2 and TMPRSS2 expression among different eye tissues. Methods: Experimental article. Thirty mice were assigned to male, female, aging, diabetic and non-diabetic groups, with 6 mice in each group. Real-time PCR was performed to quantify ACE2 and TMPRSS2 gene expression in conjunctiva, cornea, lacrimal gland, iris, lens, retina, lung, heart, kidney, and liver from male mice. Immunohistochemistry staining was applied to visualize the distribution of the two proteins in different mice tissues, and in human corneal and conjunctival sections. Published transcriptome datasets were extracted to generate the expression comparasion of ACE2 and TMPRSS2 between human conjunctival and corneal tissues, and results were analyzed with Mann-Whitney U test. Female mice, aging mice, STZ-induced diabetic mice, diabetic group control mice were also subjected to ACE2 expression analysis. Results were analyzed using Student's t-test. Results: The expression of ACE2 and TMPRSS2 genes were the highest in conjunctiva among all the six mice eye tissues explored. The expression of these two genes in conjunctiva were lower than that in kidney and lung. ACE2 and TMPRSS2 shared similar expression pattern with the staining concentrated in corneal epithelium, conjunctival epithelium and lacrimal gland serous cells. The expression levels of ACE2 showed sex-difference. Female mice had lower ACE2 in conjunctiva and cornea than male mice, with the expression levels taking only 43% (t=3.269, P=0.031) and 63% (t=4.080, P=0.015) of that in the male conjunctiva and cornea, respectively. Diabetic mice expressed more ACE2 in conjunctiva (1.21-fold, P>0.05) and lacrimal gland (1.10-fold, P>0.05) compared with the control group. No significant difference on ACE2 expression was found between the aging and young adult mice. The expression level of human conjunctiva ACE2 and TMPRSS2 were significantly higher than that in the cornea (P=0.007), with 5.74-fold and 12.84-fold higher in the conjunctiva than in the corneal epithelium cells, which resembled the situation in mice. Conclusion: The observation of high-level ACE2 and TMPRSS2 expression in conjunctiva among the 6 eye tissues examined suggests that conjunctiva serves as an infection target tissue of 2019-nCoV. (Chin J Ophthalmol, 2020, 56:).


title: Antibody-induced conformational changes in herpes simplex virus glycoprotein gD reveal new targets for virus neutralization.

text: As the receptor-binding protein of herpes simplex virus (HSV), gD plays an essential role in virus entry. In its native state, the last 56 amino acids of the ectodomain C terminus (C-term) occlude binding to its receptors, herpesvirus entry mediator (HVEM) and nectin-1. Although it is clear that movement of the C-term must occur to permit receptor binding, we believe that this conformational change is also a key event for triggering later steps leading to fusion. Specifically, gD mutants containing disulfide bonds that constrain the C-term are deficient in their ability to trigger fusion following receptor binding. In this report, we show that two newly made monoclonal antibodies (MAbs), MC2 and MC5, have virus-neutralizing activity but do not block binding of gD to either receptor. In contrast, all previously characterized neutralizing anti-gD MAbs block binding of gD to a receptor(s). Interestingly, instead of blocking receptor binding, MC2 significantly enhances the affinity of gD for both receptors. Several nonneutralizing MAbs (MC4, MC10, and MC14) also enhanced gD-receptor binding. While MC2 and MC5 recognized different epitopes on the core of gD, these nonneutralizing MAbs recognized the gD C-term. Both the neutralizing capacity and rate of neutralization of virus by MC2 are uniquely enhanced when MC2 is combined with MAb MC4, MC10, or MC14. We suggest that MC2 and MC5 prevent gD from performing a function that triggers later steps leading to fusion and that the epitope for MC2 is normally occluded by the C-term of the gD ectodomain.


title: Splenic aneurysms: natural history and treatment techniques.

text: True splenic artery aneurysms (SAA) are a rare, but potentially fatal, pathology. They are the third most common type of abdominal aneurysm, after aneurysms of the aorta and of the iliac artery, and account for almost the all aneurysms of visceral arteries. True aneurysms account for 60% of SAA and affect four times as many women as men, generally related to increased incidental or symptomatic findings that coincide with use of ultrasonography in pregnancy. Among pregnant patients, mortality after rupture is 65-75%, with fetal mortality exceeding 90%. There are multiple etiologies and it is believed that hormonal influences and changes in portal flow during gestation play an important role in development of SAA. This review discusses their history, epidemiology, pathophysiology, and diagnosis and current treatment techniques.


title: Apneic oxygen insufflation decreases the incidence of hypoxemia during one-lung ventilation in open and thoracoscopic pulmonary lobectomy: A randomized controlled trial.

text: OBJECTIVE Hypoxemia is common during one-lung ventilation (OLV) for thoracic surgery. When hypoxemia occurs, surgery is interrupted for rescue ventilation. Apneic oxygen insufflation (AOI), which provides O2 without applying pressure, may prevent hypoxemia and does not interrupt surgery. The aim of this study was to determine the effectiveness of the AOI technique for preventing hypoxemia during OLV in thoracic surgery. METHODS Patients undergoing open or thoracoscopic pulmonary lobectomy from September to December 2015 were included. Patients were assigned randomly to a non-AOI group or an AOI group (n = 45 each). OLV was initiated and at the 15-minute mark (OLV15), patients in the AOI group received oxygen insufflation at 3 L/min to the nonventilated lung for 30 minutes (OLV45). The primary endpoint was the occurrence of hypoxemia (SaO2 <90%) during OLV. RESULTS The demographic and operative data were similar between the 2 groups. The incidence of hypoxemia was greater in the non-AOI than the AOI group (18% vs 0%; P = .009). ΔPaO2 (the difference in partial pressure of oxygen in arterial blood between OLV 45 and 15 minutes) was smaller in the AOI than the non-AOI group (-29 mm Hg vs -69 mm Hg; P = .005). Duration of surgery and incidence of complications did not vary between groups. CONCLUSIONS AOI decreases the incidence of hypoxemia and improves arterial oxygenation during OLV for open and thoracoscopic surgery. AOI may be a valuable option to prevent hypoxemia. It can be used before relying on continuous positive airway pressure or intermittent two-lung ventilation and result in fewer interruptions in surgery.


title: Single-port retrieval of peritoneal foreign body using SILS port: report of a case.

text: Foreign body retrieval surgery sometimes does not need excision and reconstruction of the gastrointestinal tract. To avoid unnecessarily large incisions is now feasible for such retrieval surgery. We report herein a case of a patient who underwent retrieval surgery with a single-incision laparoscopic surgery (SILS) to minimize surgical incision. Our case concerns a 72-year-old female with a 3 cm length needle incidentally discovered as a peritoneal foreign body without any apparent symptoms. Retrieval was performed safely with SILS port inserted through a 2.5 cm transverse incision below the umbilicus. Two flexible forceps introduced through the SILS port offer easy operation for retrieving foreign bodies even if dissection or other surgical maneuvers are required. Our technique of abdominal foreign body retrieval with the SILS port is a useful clinical application of minimally invasive surgery for such cases.


title: Pig lung transplant survival model.

text: Although lung transplant is a life-saving therapy for some patients, primary graft dysfunction (PGD) is a leading cause of mortality and morbidity soon after a transplant. Ischemia reperfusion injury is known to be one of the most critical factors in PGD development. PGD is by definition an acute lung injury syndrome that occurs during the first 3 d following lung transplantation. To successfully translate laboratory discoveries to clinical practice, a reliable and practical large animal model is critical. This protocol describes a surgical technique for swine lung transplantation and postoperative management for a further 3 d post transplant. The protocol includes the background and rationale, required supplies, and a detailed description of the donor operation, transplant surgery, postoperative care, and sacrifice surgery. A pig lung transplant model is reliably produced in which the recipients survive for 3 d post transplant. This 3-d survival model can be used by lung transplant researchers to assess the development of PGD and to test therapeutic strategies targeting PGD. In total, the protocol requires 5 h for the surgeries, plus ~2 h in total for the postoperative care.


title: Structure, photodynamic reaction and DNA photocleavage properties of a nitrosyl iron-sulfur cluster (Me4N)2[Fe2S2(NO)4]: A DFT calculation and experimental study.

text: Density functional theory calculations were performed on the structure of the nitrosyl iron-sulfur cluster (Me4N)2[Fe2S2(NO)4]. The IR spectra were assigned and the electronic ground-state properties in different solvents were analyzed. Dynamic conversion of [Fe2S2(NO)4]2- was analyzed quantitatively using the time-resolved IR spectra in different solvents. Photo irradiation and polarity of solvent obviously affect the reaction rates, which are faster in CH3CN and CH3OH than those in DMSO and water. The calculated orbital energies of HOMOs are higher and those of LUMO-HOMO gap are smaller in CH3CN and CH3OH than those in DMSO and water, which is consistent with the reaction rate and explains the experimental observation. Moreover, the photo-induced nitric oxide (NO) release and cluster conversion was identified using EPR spectra. The photocleavage of pBR322 DNA was observed, both NO and oxygen related free radicals play key roles in the process. The study provides an effective method to monitor the photodynamic reactions for better understanding of the physiological activity of nitrosyl iron-sulfur clusters.


Is stratified shielding from covid-19 feasible and ethical?


title: Handling uncertainty and ambiguity in the COVID-19 pandemic.

text: The 2019 novel coronavirus outbreak is unprecedented. Yet some look to ready-made models to address it. This creates confusion about more adaptive responses that reflect an uncertain and ambiguous context. Those assessing associated mental health challenges must be wary of overdiagnosis. Handling the pandemic well, requires engaging the public as mature partners. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Margin size is an independent predictor of local tumor progression after ablation of colon cancer liver metastases.

text: PURPOSE This study was designed to evaluate the relationship between the minimal margin size and local tumor progression (LTP) following CT-guided radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLM). METHODS An institutional review board-approved, HIPPA-compliant review identified 73 patients with 94 previously untreated CLM that underwent RFA between March 2003 and May 2010, resulting in an ablation zone completely covering the tumor 4-8 weeks after RFA dynamic CT. Comparing the pre- with the post-RFA CT, the minimal margin size was categorized to 0, 1-5, 6-10, and 11-15 mm. Follow-up included CT every 2-4 months. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the effect of the minimal margin size, tumor location, size, and proximity to a vessel on LTP. RESULTS Forty-five of 94 (47.9 %) CLM progressed locally. Median LTP-free survival (LPFS) was 16 months. Two-year LPFS rates for ablated CLM with minimal margin of 0, 1-5 mm, 6-10 mm, 11-15 mm were 26, 46, 74, and 80 % (p < 0.011). Minimal margin (p = 0.002) and tumor size (p = 0.028) were independent risk factors for LTP. The risk for LTP decreased by 46 % for each 5-mm increase in minimal margin size, whereas each additional 5-mm increase in tumor size increased the risk of LTP by 22 %. CONCLUSIONS An ablation zone with a minimal margin uniformly larger than 5 mm 4-8 weeks postablation CT is associated with the best local tumor control.


title: Near-term pregnant women's attitude toward, concern about and knowledge of the COVID-19 pandemic.

text: Background: COVID-19 is a novel type of the coronavirus family with an incompletely described clinical course. Little is known about the psychological aspects, particularly for vulnerable populations including pregnant women.Objectives: To understand the attitude, concerns, and knowledge of the non-infected pregnant women toward the COVID-19 outbreak in order to constitute base data for detailed counseling and to develop targeted messages.Patients and methods: This cross-sectional survey research presented analysis of prospectively collected data yielded at a single tertiary "Coronavirus Pandemic Hospital" referral center for a ten days period following the first confirmed death due to the COVID-19 pandemic in Turkey. Non-infected women with a confirmed pregnancy over 30th gestational week were consecutively included. A patient-reported non-validated questionnaire formed by the expert committee that includes 15 specific questions was used. Non-infected, pregnant women over 30th gestational week who applied to the outpatient clinic were consecutively included. A total of 213 women were enrolled, 37 were excluded: 7 for being in the first trimester, 3 were illiterate, and 27 were Syrian refugees having difficulties in translation.Results: A total of 172 pregnant women were included. Overall, four women refused to participate to the survey (1.9%). The mean age was 27.5 ± 5.3 years. Median gestational week and parity were 35 ± 11 weeks and 1 ± 2, respectively. Pregnant women were observed to trust the authorities (65%) and the healthcare staff (92.4%), and their respect was increased (82.5%) during the outbreak. Majority of the women (87.2%) comply with the self-quarantine rules. Half of the women (52%) reported that they felt vulnerable and predominantly were concerned (80%). Approximately one-third of the women constantly keep thinking that they may get infected (35.5%) or they might get infected during/following the delivery or their baby might get infected after being born (42%). Half of the women (50%) were reported that they either had no idea about or think the breastfeeding is not safe during the outbreak. About 45% of the women were confused or had doubts about if the mode of delivery may be affected by the pandemic. Greater part of the participants does not know if COVID-19 might cause birth defects (76%) or preterm birth (64.5%). Counseling flow keys helping pregnant women to overcome misleads, regarding the COVID-19 outbreak is proposed.Conclusions: Non-infected pregnant women with a viable pregnancy at near term were observed to have positive attitude and compliance toward the COVID-19 outbreak and frontline healthcare staff; increased concern and vulnerability; and restricted knowledge about the pregnancy-related outcomes. While the clinical evidence was growing rapidly, this data may guide obstetricians and midwives to perceive what accurate information should be provided to the pregnant women.


title: Dental Care and Oral Health under the Clouds of COVID-19.

text: KNOWLEDGE TRANSFER STATEMENT This commentary provides a timely evidence-based overview on the impact of COVID-19 on dental care and oral health and identifies gaps in protection of patients and staff in dental settings. Oral symptoms are prominent before fever and cough occur. Dental professionals may play an important role in early identification and diagnosis of patients with COVID-19.


title: Neurocognitive and behavioural outcomes in offspring exposed to maternal pre-existing diabetes: a systematic review and meta-analysis.

text: AIMS/HYPOTHESIS We performed a systematic review and meta-analysis to determine whether exposure to maternal pre-existing diabetes in pregnancy is associated with neurocognitive or behavioural outcomes in offspring. METHODS We searched MEDLINE, EMBASE, PsychINFO, the Cochrane Database of Systematic Reviews and Scopus for studies that examined any neurocognitive or behavioural outcomes in offspring of mothers with pre-existing diabetes in pregnancy in accordance with a published protocol (PROSPERO CRD42018109038). Title and abstract review, full-text review and data extraction were performed independently and in duplicate. Risk of bias was assessed using the Newcastle-Ottawa scale. Meta-analyses of summary measures were performed using random-effects models. RESULTS Nineteen articles including at least 18,681 exposed and 2,856,688 control participants were identified for inclusion. Exposure to maternal pre-existing diabetes in pregnancy was associated with a lower pooled intelligence quotient in the offspring (pooled weighted mean difference -3.07 [95% CI -4.59, -1.55]; I2 = 0%) and an increased risk of autism spectrum disorders (effect estimate 1.98 [95% CI 1.46, 2.68]; I2 = 0%). There was also an increased risk of attention deficit/hyperactivity disorder (pooled HR 1.36 [95% CI 1.19, 1.55]; I2 = 0%), though this was based on only two studies. Although most studies were found to be high quality in terms of participant selection, in many studies, comparability of cohorts and adequacy of follow-up were sources of bias. CONCLUSIONS/INTERPRETATION There is evidence to suggest that in utero exposure to maternal pre-existing diabetes is associated with some adverse neurocognitive and behavioural outcomes. It remains unclear what the role of perinatal factors is and the degree to which other environmental factors contribute to these findings.