title: Laparoscopic fundoplication compared with laparoscopic gastric bypass in morbidly obese patients with gastroesophageal reflux disease.

text: BACKGROUND Gastroesophageal reflux disease (GERD) is commonly associated with morbid obesity. Laparoscopic fundoplication is a standard surgical treatment for GERD, and laparoscopic gastric bypass has been shown to effectively resolve GERD symptoms in the morbidly obese. We sought to compare the in-hospital outcomes of morbidly obese patients who underwent laparoscopic fundoplication for the treatment of GERD versus laparoscopic gastric bypass for the treatment of morbid obesity and related conditions, including GERD, at U.S. academic medical centers. METHODS Using the "International Classification of Diseases, 9th Revision" procedural and diagnoses codes for morbidly obese patients with GERD, we obtained data from the University HealthSystem Consortium database for all patients who underwent laparoscopic fundoplication or laparoscopic gastric bypass from October 2004 to December 2007 (n=27,264). The outcome measures included the patient demographics, length of stay, in-hospital overall complications, mortality, risk-adjusted mortality ratio (observed to expected mortality), and hospital costs. RESULTS Compared with the patients who underwent laparoscopic gastric bypass, those who underwent laparoscopic fundoplication had a lower severity of illness score (P<.05). The overall in-hospital complications were significantly lower in the laparoscopic gastric bypass group (P<.05). The mean length of stay, observed mortality, risk-adjusted mortality, and hospital costs were comparable between the 2 treatment groups. CONCLUSION Laparoscopic gastric bypass is as safe as laparoscopic fundoplication for the treatment of GERD in the morbidly obese. Hence, morbidly obese patients with GERD should be referred for bariatric surgery evaluation and offered laparoscopic gastric bypass as a surgical option.


title: Needlescopic assisted internal ring suturing; a novel application of low-cost home-made instruments for pediatric inguinal hernia repair.

text: BACKGROUND Congenital inguinal hernia (CIH) is a commonly performed surgical procedure in infants and children. Single port laparoscopic hernia repair using percutaneous internal inguinal ring (IIR) suturing procedure is a widely employed technique for indirect inguinal hernia repair in children. The majority of extracorporeal techniques use extracorporeal knotting and burying the knot subcutaneously. This may result in many drawbacks. The aim of this multicenter study is to introduce a new technique for pediatric inguinal hernia repair using only needles without any laparoscopic instruments. PATIENTS AND METHODS This is a multicenter study which was conducted at Pediatric Surgical Departments of Al-Azhar, Mansoura, Alexandria and Tanta Universities during the period from January 2015 to June 2017. 314 patients with CIH underwent Needlescopic Assisted Internal Ring Suturing (NAIRS) after cauterization of the hernia sac at its neck. The main outcome measures were: feasibility, safety of the technique, operative time, recurrence rate, hydrocele and cosmetic results. RESULTS A total of 314 patients with CIH were corrected by NAIRS. They were 232 males and 82 females. The mean age was 28.12 ± 1.3 months (range 6-120 months). The mean operative time was 12.6 ± 1.7 min (range 8-15 min) for unilateral cases and 18.6 ± 1.7 min (range 14-20 min) for the bilateral repairs. All cases were completed laparoscopically without major intraoperative complications. No recurrence was detected in this study. No wound complications or umbilical hernias developed. Hydrocele occurred in five males (2.16%), without detection of testicular atrophy or iatrogenic ascent of the testis. CONCLUSION This preliminary study showed that NAIRS after cauterization of the neck of the hernia sac in infants and children is safe, feasible, reproducible with excellent cosmetic results.


title: Short-term effects of extracorporeal shock waves on microcirculation.

text: BACKGROUND Extracorporeal shock wave application (ESWA) has the potential to qualify as an adjuvant therapy option for soft tissue disorders such as chronic wounds. As of today, little is known about its exact mechanism of action. For a better understanding of the pathophysiology, we investigated the effect of ESWA on microcirculation and leukocyte-endothelial interaction. MATERIALS AND METHODS Intravital fluorescent microscopy was used to quantify microcirculatory parameters in the ears of hairless mice (n = 30). Values were obtained just before and 10 min after the ESWA (500 shots, 1 Hz, duration 500 s). Mice were randomly divided into three groups undergoing different shock wave intensities (energy flux density: control: 0.00 mJ/mm(2); low level: 0.015 mJ/mm(2); and higher level (hl): 0.04 mJ/mm(2); n = 10 mice per group). Histologic evaluations were taken after completion of the experiments. RESULTS A significant increase in the venular diameter was observed in both the groups that underwent ESWA compared with the control group (hl: 118%, low level: 117%, and control: 96%; P < 0.004). Edema formation increased significantly in group I (P = 0.002). ESWA provoked an arteriolar constriction (hl: 93% versus control: 104%; P = 0.019) 10 min after treatment. The highest value of venular blood flow was found in group hl. Moreover, shock waves increased significantly the number of sticking leukocytes immediately after application (hl: 274%, P = 0.003). CONCLUSIONS ESWA has a significant and immediate impact on microcirculation with endothelial integrity loss and increase of adherent leukocytes as part of a proinflammatory process. Although a dilation of venules was caused, arterioles primarily show a constriction. The study shows alterations in microcirculation that could help understand the mechanism of action in the future.


docid: unqlkckx

title: Robotic pursestring technique in low anterior resection.

text: PURPOSE Rectal division and anastomosis are difficult steps in a laparoscopic low anterior resection. This difficulty is due to the limitations of laparoscopic instrumentation within the anatomical confines of the pelvis. Robotic technology overcomes most of these limitations to simplify the procedure. We describe our technique of controlled rectal transection and robotic purse-string placement by use of the da Vinci Robotic system. METHODS Three patients with rectal cancer who were scheduled to undergo a robot-assisted low anterior resection were selected to undergo this procedure. Safety, feasibility, and immediate postoperative outcomes were assessed. RESULTS The procedure was successfully completed in all 3 patients with no intraoperative complications. One patient had a postoperative bilateral femoral neuropathy that resolved spontaneously. The mean operating time was 339.6 minutes, and all 3 patients were sent home by the fifth postoperative day. CONCLUSIONS The advanced surgical dexterity of the da Vinci Robot enables a controlled rectal transection and purse-string suture placement on the rectal stump. This achieves a right-angled rectal division and a secure, single-stapled anastomosis in a low anterior resection. The feasibility of this technique has been demonstrated in 3 patients, in whom this technique has been safely performed with acceptable results. A larger series of patients and a long-term follow-up is required to demonstrate an objective benefit.


title: Integrating genetic and epidemiological data to determine transmission pathways of foot-and-mouth disease virus.

text: Estimating detailed transmission trees that reflect the relationships between infected individuals or populations during a disease outbreak often provides valuable insights into both the nature of disease transmission and the overall dynamics of the underlying epidemiological process. These trees may be based on epidemiological data that relate to the timing of infection and infectiousness, or genetic data that show the genetic relatedness of pathogens isolated from infected individuals. Genetic data are becoming increasingly important in the estimation of transmission trees of viral pathogens due to their inherently high mutation rate. Here, we propose a maximum-likelihood approach that allows epidemiological and genetic data to be combined within the same analysis to infer probable transmission trees. We apply this approach to data from 20 farms infected during the 2001 UK foot-and-mouth disease outbreak, using complete viral genome sequences from each infected farm and information on when farms were first estimated to have developed clinical disease and when livestock on these farms were culled. Incorporating known infection links due to animal movement prior to imposition of the national movement ban results in the reduction of the number of trees from 41472 that are consistent with the genetic data to 1728, of which just 4 represent more than 95% of the total likelihood calculated using a model that accounts for the epidemiological data. These trees differ in several ways from those constructed prior to the availability of genetic data.


Global Health Diplomacy: A New Strategic Defense Pillar.


RNA therapeutics on the rise.


Covid-19: pregnant doctors should speak to occupational health, say experts.


title: Role of porcine reproductive and respiratory syndrome virus nucleocapsid protein in induction of interleukin-10 and regulatory T-lymphocytes (Treg).

text: Porcine reproductive and respiratory syndrome virus (PRRSV) infection induces interleukin (IL)-10 production and increased numbers of PRRSV-specific regulatory T-lymphocytes in infected pigs. In the present study, the roles of the nucleocapsid (N) protein in induction of IL-10 and CD4(+)CD25(+)Foxp3(+) lymphocytes (T(reg)) were investigated. Transfection of porcine monocyte-derived dendritic cells (MoDCs) and pulmonary alveolar macrophages (PAMs) with a plasmid encoding N protein resulted in significant upregulation of IL-10 gene expression in the gene-transfected cells. Structural conformation, but not nuclear localization, of the expressed N protein was indicated to be essential for the ability to induce IL-10. Furthermore, the presence of recombinant N proteins in cultured PBMCs increased the number of IL-10-producing lymphocytes. Strong induction of IL-10-producing cells and T(reg) was observed when using N protein-pulsed MoDCs, suggesting an important role of MoDCs in induction of IL-10 and T(reg) by the N protein. Neutralization of IL-10 by addition of an anti-IL-10 antibody in the culture system resulted in marked reduction of PRRSV-induced T(reg) in the cultured PBMCs. Together, the data demonstrate the immunomodulatory properties of the PRRSV N protein and the linkage between IL-10 production and development of PRRSV-induced T(reg). Our results reveal an immunomodulatory function of the PRRSV N protein that may contribute to the unique immunological outcome observed following PRRSV infection.


Training in the year of the eye: the impact of the COVID-19 pandemic on ophthalmic education.


docid: btnyvuth

title: (18)F-FDG microPET imaging differentiates between septic and aseptic wound healing after orthopedic implant placement: a longitudinal study of an implant osteomyelitis in the rabbit tibia.

text: BACKGROUND AND PURPOSE (18)F-FDG PET is a widely used tool for molecular imaging of oncological, cardiovascular, and neurological disorders. We evaluated (18)F-FDG microPET as an implant osteomyelitis imaging tool using a Staphylococcus aureus-induced peroperative implant infection in rabbits. METHODS Intramedullary titanium nails were implanted in contaminated and uncontaminated (control) proximal right tibiae of rabbits. Tibiae were quantitatively assessed with microPET for (18)F-FDG uptake before and sequentially at 1, 3, and 6 weeks after surgery. Tracer uptake was assessed in soft tissue and bone in both treatment groups with an additional comparison between the operated and unoperated limb. MicroPET analysis was combined with radiographic assessment and complementary histology of the tibiae. RESULTS At the first postoperative week, the (18)F-FDG uptake in the contaminated implant group was significantly higher than the preoperative measurement, without a significant difference between the contaminated and uncontaminated tibiae. From the third postoperative week onward, (18)F-FDG uptake allowed discrimination between osteomyelitis and postoperative aseptic bone healing, as well as quantification of the infection at distinct locations around the implant. INTERPRETATION (18)F-FDG-based microPET imaging allows differentiation between deep infection and undisturbed wound healing after implantation of a titanium intramedullary nail in this rabbit model. Furthermore, our results indicate that (18)F-FDG PET may provide a tool in human clinical diagnostics and for the evaluation of antimicrobial strategies in animal models of orthopedic implant infection.


title: Comparison of therapeutic results from radiofrequency ablation and stereotactic body radiotherapy in solitary lung tumors measuring 5 cm or smaller.

text: BACKGROUNDS This retrospective study was conducted to compare the clinical outcomes of radiofrequency ablation (RFA) with those of stereotactic body radiotherapy (SBRT) in patients with lung tumors. METHODS Local tumor progression, adverse events, and overall survival were compared in patients who underwent either RFA or SBRT for a single lung tumor measuring 5 cm or smaller. This study was approved by the institutional review boards of two institutions. Informed consent was waived. RESULTS During September 2009 to June 2012, 48 patients [30 males and 18 females, with a mean age ± standard deviation (SD) of 75.0 ± 7.5 years] underwent RFA at one institution and 47 patients (21 males and 26 females, with a mean age ± SD of 77.0 ± 7.5 years) underwent SBRT in another. The mean maximum tumor diameter ± SD was 2.0 ± 0.8 cm (range 0.6-3.9 cm) in the RFA group, and 2.1 ± 0.9 cm (range 0.8-4.7 cm, p = 0.539) in the SBRT group. The RFA and SBRT groups showed similar 3-year local tumor progression [9.6%, 95% confidence interval (CI) 3.6-23.9% vs. 7.0%, 95% CI 0.2-20.2%, p = 0.746] and overall survival rates (86.4%, 95% CI 69.2-94.3% vs. 79.6%, 95% CI 60.6-90.1%, p = 0.738). No factor significantly affected local tumor progression. A maximum tumor size of 2 cm was identified as a prognostic factor in both univariate and multivariate analyses. No death was related to treatment procedures. Major complication rates (Grade 3 adverse events) of the RFA (10.4%, 5/48) and SBRT (8.5%, 4/47, p > 0.999) groups were similar. CONCLUSION For lung tumor patients, lung RFA provided local tumor control and survival that were similar to those achieved using SBRT, with equal safety.


Evaluation of a video-based curriculum for laparoscopic biliary surgery: a pilot study from the SAGES MIS Web Learning Center.


title: Emergency Care Systems: The missing link for effective treatment of COVID-19 in Africa.

text: Cases of COVID-19 are rising quickly on the African continent. A critical element of any health system response to such a surge of active cases is the existence of functional emergency care systems. Yet, these systems are markedly underdeveloped in African countries. This short letter reviews the key role emergency medicine plays in epidemic disease response and actions that ministries of health can take now to shore up gaps in emergency care capacity to avoid needless death and suffering of COVID-19 patients.


title: Single-port transumbilical laparoscopic appendectomy: a preliminary multicentric comparative study in 87 patients with acute appendicitis.

text: Introduction. Laparoscopic appendectomy (LA) has been performed in many approaches such as open, laparoscopic and recently Single Port Access (SPAA). In order to elucidate its potential advantages, we compared the two laparoscopic approaches. Methods. 87 patients were included in a multicentric study for suspected appendicitis in order to perform (SPAA) appendectomy or laparoscopic appendectomy (LA). All outcomes, including blood loss, operative time, complications, and length of stay and pain were recorded prospectively. Results. There were 46 patients in the SPAA group and 41 in the LAG with a mean operative time of 40,4 minutes in the SPAA group and 35,0 minutes in the LA group. Only one patient was converted to an open approach. We described only 2 complications. Pain was graded 2,8 in the SPAA group and 2,9 in the LA group, according to the AVS after 24 hours. Patients in the SPAA Group were more satisfied (7,5 versus 6,9) (P < 0.05). Same results were found for the cosmetic result (8,6 versus 7,4) (P < 0.05). Conclusion. Using the single port approach feasible and safe. The true benefit of the technique should be assessed by new randomised controlled trials.


Evaluation of RdRp & ORF-1b-nsp14-based real-time RT-PCR assays for confirmation of SARS-CoV-2 infection: An observational study.


title: Mathematical modelling of COVID-19 transmission and mitigation strategies in the population of Ontario, Canada.

text: BACKGROUND Physical-distancing interventions are being used in Canada to slow the spread of severe acute respiratory syndrome coronavirus 2, but it is not clear how effective they will be. We evaluated how different nonpharmaceutical interventions could be used to control the coronavirus disease 2019 (COVID-19) pandemic and reduce the burden on the health care system. METHODS We used an age-structured compartmental model of COVID-19 transmission in the population of Ontario, Canada. We compared a base case with limited testing, isolation and quarantine to scenarios with the following: enhanced case finding, restrictive physical-distancing measures, or a combination of enhanced case finding and less restrictive physical distancing. Interventions were either implemented for fixed durations or dynamically cycled on and off, based on projected occupancy of intensive care unit (ICU) beds. We present medians and credible intervals from 100 replicates per scenario using a 2-year time horizon. RESULTS We estimated that 56% (95% credible interval 42%-63%) of the Ontario population would be infected over the course of the epidemic in the base case. At the epidemic peak, we projected 107 000 (95% credible interval 60 760-149 000) cases in hospital (non-ICU) and 55 500 (95% credible interval 32 700-75 200) cases in ICU. For fixed-duration scenarios, all interventions were projected to delay and reduce the height of the epidemic peak relative to the base case, with restrictive physical distancing estimated to have the greatest effect. Longer duration interventions were more effective. Dynamic interventions were projected to reduce the proportion of the population infected at the end of the 2-year period and could reduce the median number of cases in ICU below current estimates of Ontario's ICU capacity. INTERPRETATION Without substantial physical distancing or a combination of moderate physical distancing with enhanced case finding, we project that ICU resources would be overwhelmed. Dynamic physical distancing could maintain health-system capacity and also allow periodic psychological andeconomic respite for populations.


title: Differences in the frequency of genetic variants associated with iron imbalance among global populations.

text: Iron deficiency anaemia is a major health problem affecting approximately 1.2 billion people worldwide. Young children, women of reproductive age and pregnant women living in sub-Saharan Africa are the most vulnerable. It is estimated that iron deficiency accounts for half of anaemia cases. Apart from nutritional deficiency, infection, inflammation and genetic factors are the major drivers of anaemia. However, the role of genetic risk factors has not been thoroughly investigated. This is particularly relevant in African populations, as they carry high genetic diversity and have a high prevalence of anaemia. Multiple genetic variations in iron regulatory genes have been linked to impaired iron status. Here we conducted a literature review to identify genetic variants associated with iron imbalance among global populations. We compare their allele frequencies and risk scores and we investigated population-specific selection among populations of varying geographic origin using data from the Keneba Biobank representing individuals in rural Gambia and the 1000 Genomes Project. We identified a significant lack of data on the genetic determinants of iron status in sub-Saharan Africa. Most of the studies on genetic determinants of iron status have been conducted in Europeans. Also, we identified population differences in allele frequencies in candidate putative genetic risk factors. Given the disproportionately high genetic diversity in African populations coupled with their high prevalence of iron deficiency, there is need to investigate the genetic influences of low iron status in Sub-Saharan Africa. The resulting insights may inform the future implementation of iron intervention strategies.


title: Antibody binding site mapping of SARS-CoV spike protein receptor-binding domain by a combination of yeast surface display and phage peptide library screening.

text: The receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein plays an important role in viral infection, and is a potential major neutralizing determinant. In this study, three hybridoma cell lines secreting specific monoclonal antibodies against the RBD of the S protein were generated and their exact binding sites were identified. Using yeast surface display, the binding sites of these antibodies were defined to two linear regions on the RBD: S(337-360) and S(380-399). Using these monoclonal antibodies in phage peptide library screening identified 10 distinct mimotopes 12 amino acids in length. Sequence comparison between native epitopes and these mimotopes further confirmed the binding sites, and revealed key amino acid residues involved in antibody binding. None of these antibodies could neutralize the murine leukemia virus pseudotyped expressing the SARS-CoV spike protein (MLV/SARS-CoV). However, these mAbs could be useful in the diagnosis of SARS-CoV due to their exclusive reactivity with SARS-CoV. Furthermore, this study established a feasible platform for epitope mapping. Yeast surface display combined with phage peptide library screening provides a convenient strategy for the identification of epitope peptides from certain antigenic proteins.


title: Entry of a novel marine DNA virus, Singapore grouper iridovirus, into host cells occurs via clathrin-mediated endocytosis and macropinocytosis in a pH-dependent manner.

text: UNLABELLED Iridoviruses are nucleocytoplasmic DNA viruses which cause great economic losses in the aquaculture industry but also show significant threat to global biodiversity. However, a lack of host cells has resulted in poor progress in clarifying iridovirus behavior. We investigated the crucial events during virus entry using a combination of single-virus tracking and biochemical assays, based on the established virus-cell infection model for Singapore grouper iridovirus (SGIV). SGIV infection in host cells was strongly inhibited when cells were pretreated with drugs blocking clathrin-mediated endocytosis, including sucrose and chlorpromazine. Inhibition of key regulators of macropinocytosis, including Na(+)/H(+) exchanger, Rac1 GTPase, p21-activated kinase 1 (PAK1), protein kinase C (PKC), and myosin II, significantly reduced SGIV uptake. Cy5-labeled SGIV particles were observed to colocalize with clathrin and macropinosomes. In contrast, disruption of cellular cholesterol by methyl-β-cyclodextrin and nystatin had no effect on virus infection, suggesting that SGIV entered grouper cells via the clathrin-mediated endocytic pathway and macropinocytosis but not via caveola-dependent endocytosis. Furthermore, inhibitors of endosome acidification such as chloroquine and bafilomycin A1 blocked virus infection, indicating that SGIV entered cells in a pH-dependent manner. In addition, SGIV particles were observed to be transported along both microtubules and actin filaments, and intracellular SGIV motility was remarkably impaired by depolymerization of microtubules or actin filaments. The results of this study for the first time demonstrate that not only the clathrin-dependent pathway but also macropinocytosis are involved in fish DNA enveloped virus entry, thus providing a convenient tactic for exploring the life cycle of DNA viruses. IMPORTANCE Virus entry into host cells is critically important for initiating infections and is usually recognized as an ideal target for the design of antiviral strategies. Iridoviruses are large DNA viruses which cause serious threats to ecological diversity and the aquaculture industry worldwide. However, the current understanding of iridovirus entry is limited and controversial. Singapore grouper iridovirus (SGIV) is a novel marine fish DNA virus which belongs to genus Ranavirus, family Iridoviridae. Here, using single-virus tracking technology in combination with biochemical assays, we investigated the crucial events during SGIV entry and demonstrated that SGIV entered grouper cells via the clathrin-mediated endocytic pathway in a pH-dependent manner but not via caveola-dependent endocytosis. Furthermore, we propose for the first time that macropinocytosis is involved in iridovirus entry. Together, this work not only contributes greatly to understating iridovirus pathogenesis but also provides an ideal model for exploring the behavior of DNA viruses in living cells.


title: An observational study of the optimal placement of a cerebral oximeter probe to avoid the frontal sinus in children.

text: The frontal sinus is an airspace behind the brow ridge in the skull and can affect the accuracy of the regional cerebral oxygen saturation measurements. We evaluated the optimal location for placement of a cerebral oximeter probe while avoiding the frontal sinus in pediatric patients. This retrospective observational study included 203 pediatric patients aged 3-17 years who had undergone brain computed tomography from November 2010 to December 2015. The patients were divided into five subgroups based on their age. The frontal sinus height was measured from the superior orbital rim. Pneumatization of the frontal sinus was not visible in 78% (3-5 years) and 22% (6-8 years) of the patients. The mean (SD) of the frontal sinus height was 5.9 (3.4), 9.5 (4.1), 14.0 (6.2) 18.6 (8.4), and 21.1 (7.9) mm in the 3-5, 6-8, 9-11, 12-14, and 15-17 year age-groups, respectively. Age was positively correlated with the frontal sinus height (r = 0.61, P < 0.001, 95% confidence interval [CI] 0.513-0.688). A frontal sinus height shorter than 1, 2, and 3 cm were seen in 10 of 11 (91%), 69 of 74 (94%), and 108 of 118 (90%) patients aged 3-5, 6-10, and 11-17 years, respectively. When oximeter probes are applied in pediatric patients, placement based on age can help avoid the frontal sinus.


title: Mid-Term Outcomes of Single-Port versus Conventional Three-Port Video-Assisted Thoracoscopic Surgery for Primary Spontaneous Pneumothorax.

text: BACKGROUND The benefits of video-assisted thoracoscopic surgery (VATS) have been demonstrated over the past decades; as a result, VATS has become the gold-standard treatment for primary spontaneous pneumothorax (PSP). Due to improvements in surgical technique and equipment, single-port VATS (s-VATS) is emerging as an alternative approach to conventional three-port VATS (t-VATS). The aim of this study was to evaluate s-VATS as a treatment for PSP by comparing operative outcomes and recurrence rates for s-VATS versus t-VATS. METHODS Between March 2013 and December 2015, VATS for PSP was performed in 146 patients in Kyungpook National University Hospital. We retrospectively reviewed the medical records of these patients. RESULTS The mean follow-up duration was 13.4±6.5 months in the s-VATS group and 28.7±3.9 months in the t-VATS group. Operative time (p<0.001), the number of staples used for the operation (p=0.001), duration of drainage (p=0.001), and duration of the postoperative stay (p<0.001) were significantly lower in the s-VATS group than in the t-VATS group. There was no difference in the overall recurrence-free survival rate between the s-VATS and t-VATS groups. CONCLUSION No significant differences in operative outcomes and recurrence rates were found between s-VATS and t-VATS for PSP. Therefore, we cautiously suggest that s-VATS may be an appropriate alternative to t-VATS in the treatment of PSP.


title: On the dose calculation at the cellular level and its implications for the RBE of (99m)Tc and ¹²³I.

text: PURPOSE Based on the authors' previous findings concerning the radiotoxicity of(99m)Tc, the authors compared the cellular survival under the influence of this nuclide with that following exposure to the Auger electron emitter (123)I. To evaluate the relative biological effectiveness (RBE) of both radionuclides, knowledge of the absorbed dose is essential. Thus, the authors present the dose calculations and discuss the results based on different models of the radionuclide distribution. Both different target volumes and the influence of the uptake kinetics were considered. METHODS Rat thyroid PC Cl3 cells in culture were incubated with either(99m)Tc or (123)I or were irradiated using 200 kV x-rays in the presence or absence of perchlorate. The clonogenic cell survival was measured via colony formation. In addition, the intracellular radionuclide uptake was quantified. Single-cell dose calculations were based on Monte Carlo simulations performed using Geant4. RESULTS Compared with external radiation using x-rays (D37 = 2.6 Gy), the radionuclides (99m)Tc (D37 = 3.5 Gy), and (123)I (D37 = 3.8 Gy) were less toxic in the presence of perchlorate. In the absence of perchlorate, the amount of activity a37 that was necessary to reduce the surviving fraction (SF) to 0.37 was 22.8 times lower for (99m)Tc and 12.4 times lower for (123)I because of the dose increase caused by intracellular radionuclide accumulation. When the cell nucleus was considered as the target for the dose calculation, the authors found a RBE of 2.18 for (99m)Tc and RBE = 3.43 for (123)I. Meanwhile, regarding the dose to the entire cell, RBE = 0.75 for (99m)Tc and RBE = 1.87 for (123)I. The dose to the entire cell was chosen as the dose criterion because of the intracellular radionuclide accumulation, which was found to occur solely in the cytoplasm. The calculated number of intracellular decays per cell was (975 ± 109) decays/MBq for (99m)Tc and (221 ± 82) decays/MBq for (123)I. CONCLUSIONS The authors' data indicate that extra-nuclear targets to Auger electrons exist, which is obvious from our dose calculations. When considering the dose to the cell nucleus, the authors found an enhanced RBE for(99m)Tc and (123)I relative to acute x-ray irradiation and pure extracellular irradiation with both radionuclides. Surprisingly, the authors did not find any radionuclide accumulation in the cell nucleus, indicating that there are additional radiosensitive targets besides the DNA. In addition, the authors demonstrated the necessity of cellular dose calculations in radiobiological experiments using unsealed radionuclides and identified the relevant parameters.


title: Physicomechanical evaluation of absorbable and nonabsorbable barrier composite meshes for laparoscopic ventral hernia repair.

text: BACKGROUND This study aimed to compare the physicomechanical properties of composite prostheses for laparoscopic ventral hernia repair (LVHR) through standard testing and a proposed classification system. METHODS Seven prostheses (four with absorbable barriers and 3 with nonabsorbable barriers) were evaluated. The barrier layer was removed, after which the area of the interstices and the diameter of the filaments were determined. The barrier layer was left intact during thickness, density, suture retention strength, tear resistance, uniaxial tensile, and ball-burst testing. Specimens were oriented parallel or perpendicular to their longest dimension during testing. One-way analysis of variance (ANOVA) with Tukey's posttest or an unpaired, two-tailed t-test was performed to determine whether differences existed due to mesh or orientation, and a p value<0.05 was considered significant. RESULTS Significant differences were observed between mesh types and due to the orientation of the mesh during testing. Of the absorbable barrier meshes, Bard Sepramesh IP Composite demonstrated the greatest suture retention and tear strengths, followed by C-QUR mesh. Of the permanent barrier meshes, DUALMESH demonstrated the greatest suture retention strength in the perpendicular direction, followed by Bard Composix E/X. DUALMESH and Bard Composix E/X demonstrated equivalent suture retention strength in the parallel direction and equivalent tear resistance in both testing directions. All meshes demonstrated tensile strengths greater than the physiologically relevant range of 16-32 N/cm. CONCLUSIONS This study provided a basic understanding of how the structural aspects of each mesh design influence functionality. Differences between composite barrier prostheses commonly used for LVHR were observed due to barrier type, mesh type, and orientation. A set of standard testing techniques and a classification system also were presented to define fully the properties of these materials.


title: Preparing Students for a More Public Health-Aware Market in Response to COVID-19.

text: The COVID-19 pandemic has made the public more aware of public health and the role its professionals play in addressing the pandemic. Schools and programs in public health have a new opportunity to recruit, train, and sustain the public health workforce. Academic public health can further educate the public and prepare students for meaningful careers through interprofessional education and practice-based learning.


docid: vnoxgspf

title: A Semicircular Incision in the Superior Umbilical Fold for SILS Preserves the Umbilical Profile.

text: Background. Single Incision Laparoscopic Surgery (SILS) has been highlighted in the recent literature as a means of performing a range of common, minimal access, paediatric surgical procedures. The primary attraction is the absence of visible scarring. Aim. This study aims to describe a cosmetically advantageous means of SILS port placement in children, which preserves the umbilical profile. Methods. We describe a paediatric case series utilising a semicircular incision in the superior umbilical fold for SILS procedures. The linea alba is exposed over 2 cm just superior to the umbilical ring and stay sutures are applied. A vertical incision is made over this distance without entering the umbilical ring. Data were recorded prospectively in a Microsoft Excel database. Results. Twenty-one cases were performed in a 1-year period. Ten appendicectomies, 5 ovarian/paraovarian cystectomies, 2 Palomo procedures, 3 nephrectomy/heminephrectomies, and 1 Meckel's diverticulectomy were performed. There was 1 wound infection. No incisional hernias occurred. Discussion. We believe that our technique, which maintains the integrity of the umbilical ring and allows preservation of the umbilical profile, offers a distinct cosmetic advantage over other incisions for SILS which distort it. Conclusion. We have demonstrated the aesthetic benefits of utilising a superior umbilical-fold incision for SILS in children.


title: Mental Symptoms in Different Health Professionals During the SARS Attack: A Follow-up Study.

text: AIM The aims of the study were to assess the psychological impact of SARS bio-disaster on healthcare workers. METHODS The participants were 127 healthcare workers who had taken care of suspected SARS patients. All participants completed the Chinese Health Questionnaire (CHQ), Eysenck Personality Questionnaire, and Parental Bonding Instrument at the first stage and the CHQ again a year later. RESULTS Healthcare workers that had mental symptoms at follow-up reported the symptoms were associated with daily-life stress and not the SARS crisis. The physicians had more somatic symptoms than nurses, suggesting different professions have different impact on mental health. Additionally, individual's early maternal attachment and neuroticism were found to have greater effect on mental health of life-threatening stress. CONCLUSIONS Life-threatening and daily-life stress show two different patterns of influence on mental health. These results provided a preclinical model for understanding, and preventing, human stress-related psychiatric disorders in the future.


Falling usage of hospital-based emergency care during the COVID-19 pandemic in the UK.


Who Should Undergo Chronic Total Occlusion Percutaneous Coronary Intervention?: The EXPLORation Continues.


title: Long-term efficacy, safety, and tolerability of L-methylfolate calcium 15 mg as adjunctive therapy with selective serotonin reuptake inhibitors: a 12-month, open-label study following a placebo-controlled acute study.

text: OBJECTIVE To evaluate remission and recovery, safety, and tolerability for up to 12 months of open-label adjunctive L-methylfolate calcium 15 mg. METHOD Subjects in this analysis were adult outpatients (18-65 years) enrolled from 2 acute, double-blind, placebo-controlled trials comparing adjunctive L-methylfolate and placebo for DSM-IV major depressive disorder (MDD) with an inadequate response to monotherapy selective serotonin reuptake inhibitor (SSRI). Subjects who completed the acute trial were offered to enroll in a 12-month, open-label treatment phase with L-methylfolate and continued SSRI treatment, with scheduled visits for efficacy, safety, and tolerability every 12 weeks. Subjects were enrolled between September 2006 and February 2010. Efficacy outcomes included predefined criteria for response, remission, recovery, relapse, and recurrence. Subjects treated with adjunctive L-methylfolate 15 mg were included in the efficacy analysis. RESULTS Of 68 subjects who met criteria for the 12-month open-label phase, 38% (n = 26) achieved full recovery, and none experienced a recurrence of MDD. For subjects entering the open-label phase in remission (n = 11), 91% (n = 10) achieved full recovery with L-methylfolate 15 mg, and none experienced a relapse or recurrence. Among 57 subjects who entered the open-label phase as nonremitted, 61% (n = 35) achieved remission. Of subjects who entered the open-label phase with a response without remission (n = 4), 50% (n = 2) had full recovery, and of subjects entering the open-label phase with no response (n = 53), 26% (n = 14) met recovery criteria. CONCLUSIONS Adjunctive L-methylfolate 15 mg/d may be an early option in patients who fail to adequately respond to antidepressant monotherapy, with preliminary evidence demonstrating sustained remission and sustained recovery. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00321152.


title: Live virus vaccines based on a vesicular stomatitis virus (VSV) backbone: Standardized template with key considerations for a risk/benefit assessment.

text: The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viral and other microbial pathogens in their genome (so-called "chimeric virus vaccines"). Many such viral vector vaccines are now at various stages of clinical evaluation. Here, we introduce an attenuated form of recombinant vesicular stomatitis virus (rVSV) as a potential chimeric virus vaccine for HIV-1, with implications for use as a vaccine vector for other pathogens. The rVSV/HIV-1 vaccine vector was attenuated by combining two major genome modifications. These modifications acted synergistically to greatly enhance vector attenuation and the resulting rVSV vector demonstrated safety in sensitive mouse and non-human primate neurovirulence models. This vector expressing HIV-1 gag protein has completed evaluation in two Phase I clinical trials. In one trial the rVSV/HIV-1 vector was administered in a homologous two-dose regimen, and in a second trial with pDNA in a heterologous prime boost regimen. No serious adverse events were reported nor was vector detected in blood, urine or saliva post vaccination in either trial. Gag specific immune responses were induced in both trials with highest frequency T cell responses detected in the prime boost regimen. The rVSV/HIV-1 vector also demonstrated safety in an ongoing Phase I trial in HIV-1 positive participants. Additionally, clinical trial material has been produced with the rVSV vector expressing HIV-1 env, and Phase I clinical evaluation will initiate in the beginning of 2016. In this paper, we use a standardized template describing key characteristics of the novel rVSV vaccine vectors, in comparison to wild type VSV. The template facilitates scientific discourse among key stakeholders by increasing transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines.


title: Health Care Provider Knowledge and Attitudes Regarding Reporting Diseases and Events to Public Health Authorities in Tennessee.

text: CONTEXT In the United States, state laws require health care providers to report specific diseases and events to public health authorities, a fundamental facet of disease surveillance. However, reporting by providers is often inconsistent, infrequent, and delayed. OBJECTIVE To examine knowledge, attitudes, and practices regarding provider disease reporting and to understand current barriers to provider disease reporting. DESIGN A cross-sectional study was conducted via an anonymous, standardized electronic survey. SETTING The survey was conducted at Vanderbilt University Medical Center, a large, tertiary academic medical center in Nashville, Tennessee. PARTICIPANTS Health care providers in 4 specialties (internal medicine, pediatrics, obstetrics-gynecology, and emergency medicine). MAIN OUTCOME MEASURE(S) Knowledge of and attitudes regarding provider reporting of diseases to public health authorities in Tennessee. RESULTS The majority of providers acknowledged they cared for patients with reportable diseases (362/435, 83.2%) and believed that it was their responsibility to report to public health authorities (429/436, 98.4%); however, less than half had ever reported a case (206/436, 47.2%). The median percent correct on the knowledge assessment of Tennessee reportable diseases and conditions was 81.3% (interquartile range = 68.8-87.5). Providers cited a lack of knowledge of which diseases are reportable (186/429, 43.3%) and the logistics of reporting (153/429, 35.7%) as the primary barriers for compliance. CONCLUSION Most providers acknowledged they cared for patients with reportable diseases and believed they had an obligation to report to public health authorities. However, a lack of knowledge about reporting was frequently described as a limitation to report effectively. Many knowledge deficits were significantly greater among residents than other providers.The policy and practice implications of these findings include a demonstrated need for education of providers about disease reporting as well as development of more convenient reporting mechanisms. Fundamental knowledge of reportable disease requirements and procedures is critical for participation in the broader public health system.


title: Treatment with octreotide does not reduce tumor uptake of (68)Ga-DOTATATE as measured by PET/CT in patients with neuroendocrine tumors.

text: UNLABELLED We hypothesized that (68)Ga-DOTATATE uptake of neuroendocrine tumors is sensitive to therapy with a nonradioactive somatostatin analog. METHODS (68)Ga-DOTATATE PET/CT was used to examine 105 patients, 35 of whom had been pretreated with long-acting octreotide. The maximum standardized uptake value (SUV(max)) of target tissues, as well as metastases, was compared between the groups of patients with (group 1) and without (group 2) octreotide treatment. RESULTS The SUV(max) of the spleen and liver was significantly lower in group 1 than in group 2 (both P < 0.001). There were no significant group differences in SUV(max) for primary tumors (28.6 ± 6.8 vs. 32.9 ± 31.5) or metastases in the liver (27.2 ± 14.8 vs. 25.7 ± 10.7), lymph nodes (41.4 ± 19.5 vs. 25.0 ± 6.3), or skeleton (39.5 ± 22.0 vs. 15.4 ± 7.8). In 9 patients available for intraindividual comparison, tumor uptake was unaffected by treatment with somatostatin analogs (21.7 vs. 20.6; P = 0.93). CONCLUSION Treatment with a long-acting somatostatin analog did not significantly reduce (68)Ga-DOTATATE binding in neuroendocrine tumors but tended to improve the tumor-to-background ratio.


title: Emergent Start Peritoneal Dialysis for End-Stage Renal Disease: Outcomes and Advantages.

text: BACKGROUND/AIMS Initiating renal replacement therapy in late referred patients with central venous catheter (CVC) hemodialysis (HD) causes serious complications. In urgent start peritoneal dialysis, initiating peritoneal dialysis (PD) within 14 days of catheter insertion still needs HD with CVC. We initiated Emergent start PD (ESPD) with Automated PD (APD) at our center within 48 h from the time of presentation. METHODS A prospective, case-controlled, intention-to-treat study with 56 patients was conducted between March 2016 and August 2017. Group A (24 patients) underwent conventional PD 14 days after catheter insertion. Group B (32 patients), underwent ESPD with APD. Exit site leak (ESL), catheter blockage, and peritonitis at 90 days were primary outcomes. Technique survival was secondary outcome. RESULTS Baseline characteristics were similar with 3 episodes of ESLs (9.4%) in the study group and none in the control group (p = 0.123). Catheter blockage (16.7%-Group A, 25%-Group B) and peritonitis (none vs. 9.4% in study group) were similar in terms of statistical details just as technique survival (95%-Group A, 88.2%-Group B at 90 days). CONCLUSION ESPD with APD in the unplanned patient is an appropriate approach.


title: Food waste disposal units in UK households: the need for policy intervention.

text: The EU Landfill Directive requires Member States to reduce the amount of biodegradable waste disposed of to landfill. This has been a key driver for the establishment of new waste management options, particularly in the UK, which in the past relied heavily on landfill for the disposal of municipal solid waste (MSW). MSW in the UK is managed by Local Authorities, some of which in a less conventional way have been encouraging the installation and use of household food waste disposal units (FWDs) as an option to divert food waste from landfill. This study aimed to evaluate the additional burden to water industry operations in the UK associated with this option, compared with the benefits and related savings from the subsequent reductions in MSW collection and disposal. A simple economic analysis was undertaken for different FWD uptake scenarios, using the Anglian Region as a case study. Results demonstrated that the significant savings from waste collection arising from a large-scale uptake of FWDs would outweigh the costs associated with the impacts to the water industry. However, in the case of a low uptake, such savings would not be enough to cover the increased costs associated with the wastewater provision. As a result, this study highlights the need for policy intervention in terms of regulating the use of FWDs, either promoting them as an alternative to landfill to increase savings from waste management, or banning them as a threat to wastewater operations to reduce potential costs to the water industry.


docid: jsyngwut

title: How the noninflammasome NLRs function in the innate immune system.

text: NLR (nucleotide-binding domain, leucine-rich repeat-containing) proteins have rapidly emerged as central regulators of immunity and inflammation with demonstrated relevance to human diseases. Much attention has focused on the ability of several NLRs to activate the inflammasome complex and drive proteolytic processing of inflammatory cytokines; however, NLRs also regulate important inflammasome-independent functions in the immune system. We discuss several of these functions, including the regulation of canonical and noncanonical NF-kappaB activation, mitogen-activated protein kinase activation, cytokine and chemokine production, antimicrobial reactive oxygen species production, type I interferon production, and ribonuclease L activity. We also explore the mechanistic basis of these functions and describe current challenges in the field.


title: Transumbilical scarless surgery with thoracic trocar: easy and low-cost.

text: PURPOSE Single-site laparoscopic surgery has become increasingly common. We herein report an easy and low-cost thoracic trocar technique (TTT) for these types of procedures and recommend the simpler name "transumbilical scarless surgery" (TUSS) to minimize confusion in nomenclature. METHODS We retrospectively reviewed patients who underwent TUSS by TTT using a thoracic trocar and surgical glove in our hospital between November 2011 and November 2012. Operating time, postoperative stay, and complications were detailed. RESULTS A total of 101 TUSS by TTT were successfully performed, comprising appendectomy (n = 63), ovarian cyst excision (n = 7), splenectomy (n = 5), nephroureterectomy (n = 5), orchidopexy (n = 4), pyeloplasty (n = 3), nephrolithotomy (n = 2), orchiectomy (n = 2), varicocelectomy (n = 2), lymphangioma excision (n = 2), ureterectomy (n = 1), Morgagni diaphragmatic hernia repair (n = 1), ovarian detorsion (n = 1), antegrade continence enema (n = 1), intestinal resection anastomosis (n = 1), and intestinal duplication excision (n = 1). Kirschner wires were used for some organ traction. Nine patients required an additional port, but no major complications occurred. The postoperative stay (mean ± standard deviation) was 3.2 ± 1.4 days, and operating time was 58.9 ± 38.3 minutes. CONCLUSION We recommend the simpler name of TUSS to minimize confusion in nomenclature for all transumbilical single-incision laparoendoscopic surgeries. TTT is an easy and low-cost TUSS technique.


title: Accuracy and precision of buccal pulse oximetry.

text: OBJECTIVE We sought to describe the accuracy and precision of buccal pulse oximetry (SbpO(2)) compared with arterial oxygen saturation (SaO(2)) and pulse oximetry (SpO(2)) in healthy adults at normoxemia and under 3 induced hypoxemic conditions. METHODS In this prospective, correlational study, SbpO(2), SaO(2), and SpO(2) values were recorded at normoxemia and at three hypoxemic conditions (SpO(2)=90%, 80%, and 70%) for 53 healthy, nonsmoking adults who were without cardiac or pulmonary disease, baseline hypoxemia, peripheral edema, dyshemoglobinemia, and fever. Bland-Altman analyses were used to assess agreement and precision between SbpO(2) and SaO(2) measures and between SbpO(2) and SpO(2) measures. Data were adjusted to account for a lag time between buccal and finger sites. RESULTS When comparing SbpO(2) and SaO(2) values, mean differences of -1.8%, .3%, 2.4%, and 2.6% were evident at the normoxemia, 90%, 80%, and 70% levels, respectively. When comparing SbpO(2) and SpO(2) values, the mean differences were -1.4%, .1%, 3.3%, and 4.7% at the normoxemia, 90%, 80%, and 70% levels, respectively. The SbpO(2) and SaO(2) values met a priori precision criteria (1.6%; 95% confidence limit, -4.9% to 1.3%) at normoxemia. The SbpO(2) and SpO(2) values met precision criteria at normoxemia (1.5%; 95% confidence limit, -4.4% to 1.5%) and 90% (1.9%; 95% confidence limit, -3.6% to 3.8%) conditions, but exceeded precision criteria at the other tested conditions. On average, SpO(2) lagged 21 seconds behind SbpO(2). CONCLUSION Buccal oximetry is an inaccurate and imprecise method of assessing SpO(2) when oxygen saturation is <90%. The divergence between SbpO(2) and both SaO(2) or SpO(2) values increased as hypoxemia worsened. The buccal method overestimated oxygen saturation in proportion to the degree of hypoxemia. Such overestimates may lead nurses to conclude falsely that a patient's arterial oxygen saturation is acceptable when further assessment or intervention is warranted.


title: Back to the Future: Principles on Resuming Outpatient Services in the COVID-19 Era.

text: The rapidly changing health care climate related to coronavirus disease 2019 (COVID-19) has resulted in numerous changes to health care systems and in practices that protect both the public and the workers who serve in hospitals around the country. As a result, these past few months have seen a drastic reduction in outpatient visits. With phased reopening and appropriate guidance, health care systems are attempting to return to normal. The experiences and lessons learned are described, and we provide guiding principles to allow for a safe and effective return to outpatient care.


Clonal spread of Geomyces destructans among bats, midwestern and southern United States.


title: Influence of Bayesian optimization on the performance of propofol target-controlled infusion.

text: Background Target controlled infusion (TCI) systems use population-based pharmacokinetic (PK) models that do not take into account inter-individual residual variation. This study compares the bias and inaccuracy of a population-based vs a personalized TCI propofol titration using Bayesian adaptation. Haemodynamic and hypnotic stability, and the prediction probability of alternative PK models, was studied. Methods A double-blinded, prospective randomized controlled trial of 120 subjects undergoing cardiac surgery was conducted. Blood samples were obtained at 10, 35, 50, 65, 75 and 120 min and analysed using a point-of-care propofol blood analyser. Bayesian adaptation of the PK model was applied at 60 min in the intervention group. Median (Absolute) Performance Error (Md(A)PE) was used to evaluate the difference between bias and inaccuracy of the models. Haemodynamic (mean arterial pressure [MAP], heart rate) and hypnotic (bispectral index [BIS]) stability was studied. The predictive performance of four alternative propofol PK models was studied. Results MdPE and MdAPE did not differ between groups during the pre-adjustment period (control group: 6.3% and 16%; intervention group: 5.4% and 18%). MdPE differed in the post-adjustment period (12% vs. -0.3%), but MdAPE did not (18% vs. 15%). No difference in heart rate, MAP or BIS was found. Compared with the other models, the Eleveld propofol PK model (patients) showed the best prediction performance. Conclusions When an accurate population-based PK model was used for propofol TCI, Bayesian adaption of the model improved bias but not precision. Clinical trial registration Dutch Trial Registry NTR4518.


title: Transumbilical pure single-port laparoscopic donor nephrectomy.

text: Transumbilical single-port laparoscopic donor nephrectomy (SPLDN) is a novel, rapidly evolving, minimally invasive treatment modality for kidney transplantation. This method causes minimal parietal injury, has cosmetic advantages, and allows rapid recovery because of low postoperative pain and short hospital stay. Like other abdominal surgeries, when conducted by experienced laparoscopic surgeons, it can meet the same graft requirements as conventional laparoscopic surgery. Here, we report the first two cases of transumbilical SPLDN at Daejeon St. Mary's Hospital, The Catholic University of Korea. We used the umbilicus as a common path for laparoscopic procedures and as a route for specimen retrieval. The operating times were 230 and 265 minutes in cases 1 and 2, respectively. No intra- or postoperative complications were noted. In case 1, the wound length was 4 cm and duration of hospitalization was 2 days. In case 2, the wound length was only 2.5 cm, and the duration of hospitalization was only 1 day.


title: Ebola virus modulates transforming growth factor β signaling and cellular markers of mesenchyme-like transition in hepatocytes.

text: UNLABELLED Ebola virus (EBOV) causes a severe hemorrhagic disease in humans and nonhuman primates, with a median case fatality rate of 78.4%. Although EBOV is considered a public health concern, there is a relative paucity of information regarding the modulation of the functional host response during infection. We employed temporal kinome analysis to investigate the relative early, intermediate, and late host kinome responses to EBOV infection in human hepatocytes. Pathway overrepresentation analysis and functional network analysis of kinome data revealed that transforming growth factor (TGF-β)-mediated signaling responses were temporally modulated in response to EBOV infection. Upregulation of TGF-β signaling in the kinome data sets correlated with the upregulation of TGF-β secretion from EBOV-infected cells. Kinase inhibitors targeting TGF-β signaling, or additional cell receptors and downstream signaling pathway intermediates identified from our kinome analysis, also inhibited EBOV replication. Further, the inhibition of select cell signaling intermediates identified from our kinome analysis provided partial protection in a lethal model of EBOV infection. To gain perspective on the cellular consequence of TGF-β signaling modulation during EBOV infection, we assessed cellular markers associated with upregulation of TGF-β signaling. We observed upregulation of matrix metalloproteinase 9, N-cadherin, and fibronectin expression with concomitant reductions in the expression of E-cadherin and claudin-1, responses that are standard characteristics of an epithelium-to-mesenchyme-like transition. Additionally, we identified phosphorylation events downstream of TGF-β that may contribute to this process. From these observations, we propose a model for a broader role of TGF-β-mediated signaling responses in the pathogenesis of Ebola virus disease. IMPORTANCE Ebola virus (EBOV), formerly Zaire ebolavirus, causes a severe hemorrhagic disease in humans and nonhuman primates and is the most lethal Ebola virus species, with case fatality rates of up to 90%. Although EBOV is considered a worldwide concern, many questions remain regarding EBOV molecular pathogenesis. As it is appreciated that many cellular processes are regulated through kinase-mediated phosphorylation events, we employed temporal kinome analysis to investigate the functional responses of human hepatocytes to EBOV infection. Administration of kinase inhibitors targeting signaling pathway intermediates identified in our kinome analysis inhibited viral replication in vitro and reduced EBOV pathogenesis in vivo. Further analysis of our data also demonstrated that EBOV infection modulated TGF-β-mediated signaling responses and promoted "mesenchyme-like" phenotypic changes. Taken together, these results demonstrated that EBOV infection specifically modulates TGF-β-mediated signaling responses in epithelial cells and may have broader implications in EBOV pathogenesis.


Covid-19 and Diabetes in Hawaii.


How to turn competitors into collaborators.


title: Managing the apparent and hidden difficulties of weaning from mechanical ventilation.

text: BACKGROUND In anaesthetized patients scheduled for surgery, tracheal intubation is performed with the expectation of subsequent smooth extubation. In critically ill patients, separation from the ventilator is often gradual and the time chosen for extubation may be either delayed or premature. Thus, weaning is challenging, represents a large part of the ventilation period and concerns all mechanically ventilated patients surviving their stay. DEFINITIONS AND MANAGEMENT Weaning may be stratified in three groups according to its difficulty and duration. In simple weaning the main issue is to detect the soonest time to start separation from the ventilator; this is frequently impeded by poor sedation management and excessive ventilator assistance. A two-step diagnostic approach is the most efficacious: screening for ascertained readiness to wean is confirmed by a diagnostic test simulating the post-extubation period, best performed by unassisted breathing (no PEEP). In case of test failure (difficult weaning), a structured and thorough diagnostic work-up regarding potentially reversible pathologies is required with a focus on cardiovascular dysfunction or fluid overload at the time of separation from the ventilator, respiratory or global muscle weakness and underlying infection. Prolonged weaning is exceptionally time- and resource-consuming, needs to properly appraise psychological problems, sleep and nutrition, and is probably best performed in specialized units. CONCLUSIONS Adequately managing simple and difficult weaning requires one to think about ICU policies in terms of sedation, fluid balance and having a systematic screening strategy; it also needs an individualized approach to understand and treat the failing patients. Prolonged weaning requires a holistic approach.


title: Dexamethasone contributes to the patient management after ambulatory laryngeal microsurgery by reducing sore throat.

text: This study was planned to evaluate the preventive effect of dexamethasone for sore throat after ambulatory laryngeal microsurgery. One hundred and ten patients scheduled for ambulatory laryngeal microsurgery under general anesthesia were randomly divided into two groups, group S1 and group D1. Patients in the group D1 were injected with 0.2 mg/kg of intravenous dexamethasone before the induction of anesthesia. The incidences and severities of sore throat were measured using verbal rating scale (VRS) at 1 h and through phone calls at 6 h after the operation. The patients who requested analgesics in the recovery room were measured VRS shortly before administration of medicine. The patients in group S1 and group D1 who did not receive rescue analgesics were enrolled in group S6 and group D6, respectively, and evaluated 6 h after the surgery. There were no significant differences in the incidence and severity scores of sore throat during 1 h after the end of operation between group S1 and group D1. But at 6 h, the patients in the group D6 had lower incidence of sore throat than those in group S6 significantly (P = 0.003). Furthermore, the patients in the group D6 had lower severity of sore throat than those in group S6 significantly at 6 h (P = 0.001). In conclusion, prophylactic administration of intravenous dexamethasone is appeared to have efficacy for the management of sore throat in the early post-discharge period following ambulatory laryngeal microsurgery.


Covid-19: research methods must be flexible in a crisis.


Missing the Target.


Future perfect? Improving preparedness through the experiences of the influenza A (H1N1) 2009 pandemic.


title: Sublethal oligodendrocyte injury: A reversible condition in multiple sclerosis?

text: OBJECTIVE Degeneration of oligodendroglial distal processes has been identified as an early event in multiple sclerosis (MS) lesion development. Our objective was to further define the development of the "dying-back" oligodendrocyte lesion in situ and to model the development and potential reversibility of such responses using dissociated cultures of adult human brain-derived oligodendrocytes. METHODS In situ analyses were performed on glutaraldehyde-fixed thin sections of clinically acute and pathologically active cases of MS. In vitro studies were conducted using adult human brain-derived oligodendrocytes challenged by metabolic stress conditions (low nutrient/glucose). RESULTS In situ analyses indicated a spectrum of myelin changes in the presence of morphologically intact oligodendrocytes; these included degeneration of the inner cytoplasmic tongue with increasing sizes of intramyelinic bleb formation that could result in radial fractures of the myelin sheath. Macrophages with ingested myelin fragments were identified only once the fragmentation was established. In vitro studies indicated that oligodendrocyte process retraction, which was linked to reduced glycolytic respiratory activity, is reversible until a critical time point. Subsequent cell death was not linked to caspase-3-dependent programs. Gene expression studies conducted at the latest reversible time point revealed reduced expression of pathways associated with cell process outgrowth and myelination, as well as with metabolic activity. INTERPRETATION Our findings reveal the potential to protect and possibly restore myelin elaborated by existent oligodendrocytes in early and evolving MS lesions, and suggest the necessity of ongoing studies of the mechanisms underlying subsequent adult human oligodendrocyte cell death. Ann Neurol 2017;81:811-824.


title: Microcirculation measured by vascular occlusion test during desflurane-remifentanil anesthesia is superior to that in propofol-remifentanil anesthesia in patients undergoing thoracic surgery: subgroup analysis of a prospective randomized study.

text: General anesthesia can affect microcirculatory properties. However, differential effects on the microcirculation according to the anesthetic technique used during thoracoscopic surgery have not been well documented. We conducted a randomized clinical trial in which the effects of desflurane and propofol, both with remifentanil, on systemic arterial oxygenation during one-lung ventilation were compared in patients undergoing thoracoscopic surgery. As a subgroup analysis, we compared the effects of two commonly used anesthetic techniques, desflurane-remifentanil (n = 52) and propofol-remifentanil (n = 48), on tissue oxygen saturation using a vascular occlusion test in patients undergoing thoracoscopic surgery. Tissue oxygen saturation was higher in the desflurane than the propofol group (mean ± standard deviation, 83 ± 6 vs. 80 ± 9, 84 ± 6 vs. 76 ± 10, and 87 ± 7 vs. 77 ± 10 % at 30 and 60 min of one-lung ventilation and at two-lung ventilation; adjusted p = 0.026, <0.001, and <0.001, respectively). The recovery slope during the vascular occlusion test, reflecting microvascular reperfusion adequacy, was higher in the desflurane than the propofol group during surgery (mean difference, 0.5 %/s; 95 % CI 0.0-0.9 %/s; p = 0.037). Desflurane-remifentanil anesthesia is associated with better microcirculation than propofol-remifentanil anesthesia in patients undergoing thoracoscopic surgery.


title: Impact of anesthesia on mortality during endovascular clot removal for acute ischemic stroke.

text: BACKGROUND Endovascular clot retrieval is a technique available for removing intracranial arterial occlusions in acute ischemic stroke (AIS). This rescue therapy can be performed with moderate conscious sedation (CS) or general anesthesia (GA). The effect of GA on clinical outcome in AIS remains controversial. Therefore, we retrospectively investigated whether the use of CS or GA during endovascular intervention for AIS influenced outcomes. METHODS Patients who underwent emergent endovascular intervention for intracranial arterial occlusion during the years 2006 to 2012 were included in this study. Statistical analysis using the Spearman ρ was performed to examine demographic data and clinical outcomes between patients in the GA and CS groups. Binary logistic regression was used to determine the predictors of mortality. RESULTS A total of 109 patients fit the inclusion criteria. Among them, 35 patients had GA and 74 patients had CS. Patients needing intubation upon admission for airway protection were more likely to receive GA (P<0.001). The duration of the procedure and the time-to-revascularization from symptom onset were significantly longer in the GA group. Mortality was higher in the GA group compared with the CS group (40% vs. 22%, P=0.045). Multivariate analysis, controlled for confounding variables, identified GA and elevated postprocedure glucose level to be significant predictors of mortality. CONCLUSIONS Larger prospectively randomized multicenter trials evaluating the effects of GA and CS on clinical and radiographic outcomes seems warranted.


docid: cbgqmlwm

title: The ability of bispectral index to detect intra-operative wakefulness during isoflurane/air anaesthesia, compared with the isolated forearm technique.

text: Clinical signs are unreliable for guiding anaesthetic administration and it is suggested that using the bispectral index can improve anaesthetic delivery. In the current study, isoflurane administration was guided to a bispectral index range of 55-60. Intra-operative responsiveness, as assessed by the isolated forearm technique, was compared with whether the bispectral index predicted/identified a patient's appropriate hand movements in response to commands. Thirty-four women underwent major gynaecological surgery with isoflurane/air and atracurium. Eleven women responded on 32 occasions with appropriate hand movements to commands given during surgery, of which the bispectral index detected 17 (sensitivity 53%). The bispectral index suggested consciousness 660 times in the absence of any movement responses (specificity 69%). The positive predictive value of the bispectral index was 3%. The median (IQR [range]) bispectral index value associated with an intra-operative response was significantly lower than that associated with eye opening after surgery: 60 (50-68 [36-83]) vs 77 (75-84 [59-90]), respectively (p = 2.25 × 10(-8)). Conversely, end-tidal isoflurane concentration was significantly higher at intra-operative response than at eye opening: 0.3 (0.3-0.4 [0.2-0.9]) vs 0.2 (0.1-0.2 [0.1-0.3]), respectively (p = 7.36 × 10(-8)). For patients who responded more than once during surgery, the bispectral index value associated with a response was not constant. No patient had recall for surgery or the taped commands, and only one could remember dreaming (a good dream). Titrating isoflurane to target a bispectral index range of 55-60 may result in an unacceptable number of patients who are conscious during surgery (albeit without recall).


title: Evolution in health and medicine Sackler colloquium: The comparative genomics of viral emergence.

text: RNA viruses are the main agents of emerging and re-emerging diseases. It is therefore important to reveal the evolutionary processes that underpin their ability to jump species boundaries and establish themselves in new hosts. Here, I discuss how comparative genomics can contribute to this endeavor. Arguably the most important evolutionary process in RNA virus evolution, abundant mutation, may even open up avenues for their control through "lethal mutagenesis." Despite this remarkable mutational power, adaptation to diverse host species remains a major adaptive challenge, such that the most common outcome of host jumps are short-term "spillover" infections. A powerful case study of the utility of genomic approaches to studies of viral evolution and emergence is provided by influenza virus and brought into sharp focus by the ongoing epidemic of swine-origin H1N1 influenza A virus (A/H1N1pdm). Research here reveals a marked lack of surveillance of influenza viruses in pigs, coupled with the possibility of cryptic transmission before the first reported human cases, such that the exact genesis of A/H1N1pdm (where, when, how) is uncertain.


title: Single-stage bilateral thoracic surgery via a combined VATS and open approach for left central bronchogenic carcinoma with carinal invasion: report of two cases.

text: BACKGROUND Surgery for patients with left central bronchogenic carcinoma invading the carina is challenging due to the complexity of left sleeve pneumonectomy, carinal resection, and airway reconstruction and management. Here we describe a modified approach to overcome this problem. CASE PRESENTATION Between March 2011 and September 2012, two patients with left central bronchogenic carcinoma invading the carina underwent single-stage bilateral thoracic surgery via a combined approach incorporating video-assisted thoracic surgery (VATS) and thoracotomy in our hospital. We reviewed our experience with this type of surgery and analyze its outcomes. CONCLUSIONS Single-stage, bilateral thoracic surgery incorporating video assisted thoracic surgery (VATS) and thoracotomy provides optimal exposure of the operative field, reduces surgical trauma, and ensures the integrity of tumor excision and exactness of tracheobronchial anastomosis. This may be a safe and feasible alternative for left carinal pneumonectomy.


Video-assisted thoracoscopic lobectomy using a standardized three-port anterior approach - The Copenhagen experience.


Is mandatory vaccination legal in time of epidemic?


title: Cross-species transmission of poultry pathogens in backyard farms: ducks as carriers of chicken viruses.

text: In backyard farms of Lao People's Democratic Republic, mixed-species rearing of poultry is a breeding-ground for cross-species transmission. Here, the epidemiology of viruses circulating among backyard poultry in Vientiane Province was assessed to guide future control strategies. Oral/tracheal and cloacal swabs, collected from 605 poultry (308 ducks, 297 chickens) between 2011 and 2015, were screened by PCR for Newcastle disease virus (NDV), Coronavirus (CoV) and Chicken Anemia Virus (CAV). Chicken sera were screened for anti-NDV antibodies by ELISA. Statistical and phylogenetic analyses revealed transmission patterns and relationships. Closely related strains co-circulated in chickens and ducks. While CoV RNA was detected in oral/tracheal swabs of 9.3% of the chickens and 2.4% of the ducks, rates were higher in fecal swabs of both species (27.3% and 48.2%). RNA of Infectious bronchitis virus (IBV) and duck CoV was found in fecal swabs of chickens (19.7% and 7.1%) and of ducks (4.1% and 44.1%). Moreover, DNA of the generally chicken-specific CAV was detected in oral/tracheal swabs of chickens (18.1%) and sporadically of ducks (2.4%). Despite serological evidence of NDV circulation or vaccination (86.9%), NDV RNA was not detected. We found a high prevalence and indication for cross-species transmission of different CoV strains in backyard poultry. Interestingly, ducks served as biological or at least mechanical carrier of viral strains closely related not only to IBV, but also to CAV. Animal containment and poultry species separation could be first steps to avoid cross-species transmission and emergence of novel strains with broad host range and enhanced pathogenicity.


title: Identification and Monitoring of International Travelers During the Initial Phase of an Outbreak of COVID-19 - California, February 3-March 17, 2020.

text: The threat of introduction of coronavirus disease 2019 (COVID-19) into the United States with the potential for community transmission prompted U.S. federal officials in February 2020 to screen travelers from China, and later Iran, and collect and transmit their demographic and contact information to states for follow-up. During February 5-March 17, 2020, the California Department of Public Health (CDPH) received and transmitted contact information for 11,574 international travelers to 51 of 61 local health jurisdictions at a cost of 1,694 hours of CDPH personnel time. If resources permitted, local health jurisdictions contacted travelers, interviewed them, and oversaw 14 days of quarantine, self-monitoring, or both, based on CDC risk assessment criteria for COVID-19. Challenges encountered during follow-up included errors in the recording of contact information and variation in the availability of resources in local health jurisdictions to address the substantial workload. Among COVID-19 patients reported to CDPH, three matched persons previously reported as travelers to CDPH. Despite intensive effort, the traveler screening system did not effectively prevent introduction of COVID-19 into California. Effectiveness of COVID-19 screening and monitoring in travelers to California was limited by incomplete traveler information received by federal officials and transmitted to states, the number of travelers needing follow-up, and the potential for presymptomatic and asymptomatic transmission. More efficient methods of collecting and transmitting passenger data, including electronic provision of flight manifests by airlines to federal officials and flexible text-messaging tools, would help local health jurisdictions reach out to all at-risk travelers quickly, thereby facilitating timely testing, case identification, and contact investigations. State and local health departments should weigh the resources needed to implement incoming traveler monitoring against community mitigation activities, understanding that the priorities of each might shift during the COVID-19 pandemic.


title: Pyogranulomatous cystitis associated with Toxoplasma gondii infection in a cat after renal transplantation.

text: CASE DESCRIPTION An 8-year-old spayed female domestic shorthair cat was evaluated for azotemia and a suspected mass in the urinary bladder 6 weeks after receiving a renal transplant. Ultrasonography revealed a mass at the ureteroneocystostomy site, and the mass was excised. Both the donor and recipient cats were seronegative for Toxoplasma gondii-specific IgG antibodies prior to transplantation. CLINICAL FINDINGS Histologic evaluation of the mass revealed lesions indicative of extensive necrotizing pyogranulomatous cystitis with numerous intralesional T gondii tachyzoites and bradyzoite cysts. TREATMENT AND OUTCOME Treatment with clindamycin was initiated; however, the cat's clinical condition continued to decline, and it was euthanized 9 days after the mass was excised. Necropsy revealed T gondii cysts within the renal allograft and the transplanted ureter, with no evidence of systemic spread of organisms. CLINICAL RELEVANCE Toxoplasmosis should be considered as a differential diagnosis for azotemia in feline renal transplant recipients regardless of the results of assays for T gondii antibodies in the serum of donors or recipients. This report illustrated the need for improved screening of donor and recipient cats and the importance of minimizing exposure to potential sources of T gondii after transplantation.


title: Totally minimally invasive Ivor-Lewis esophagectomy with single-utility incision video-assisted thoracoscopic surgery for treatment of mid-lower esophageal cancer.

text: The study aims to evaluate the safety and availability of totally minimally invasive Ivor-Lewis esophagectomy (MIIE) with single-utility incision video-assisted thoracoscopic surgery. Forty-one patients with mid-lower thoracic esophageal cancer were prospectively treated with totally MIIE. Two stages of laparoscopic-thoracoscopic procedures were performed. The first 29 patients were treated with four-port video-assisted thoracoscopic surgery (Group 1); the others were treated with single-utility incision video-assisted thoracoscopic surgery (Group 2). Short-term clinicopathological outcomes were examined. All patients had negative tumor margins and were pathologically staged from T1N0M0 to T3N2M0. Among Group 1, there was one conversion to open surgery. The mean duration of surgery was 268.4 ± 37.8 minutes, and mean blood loss was 207.2 ± 74.1 mL without significant differences between groups. The average thoracic or abdominal lymph node yield was 12.6 ± 7.1 or 6 ± 5.8, respectively. The median postoperative hospital stay was 7 days. No mortalities occurred. Minor morbidity complicated by late-stage gastroparesis occurred in two patients (4.9%) after discharge. Major morbidities, including intestinal obstruction and anastomotic leakage, occurred in three patients (7.3%) after discharge. Among Group 2, the average operative duration was 275.4 ± 31.2 minutes, and the mean blood loss was 220 ± 94.9 mL. One patient developed late-stage anastomotic leakage. The average thoracic or abdominal lymph node yield was 14.7 ± 8.8 and 6.3 ± 5.7, respectively. No statistically significant differences were identified between Group 1 and Group 2. MIIE with single-utility incision video-assisted thoracoscopic surgery is feasible in patients with mid-lower thoracic esophageal cancer without compromising the extent of surgical resection and perioperative outcomes.


title: The BMA COVID-19 ethical guidance: a legal analysis.

text: The paper considers the recently published British Medical Association Guidance on ethical issues arising in relation to rationing of treatment during the COVID-19 Pandemic. It considers whether it is lawful to create policies for the rationing and withdrawal of treatment, and goes on to consider how such policies might apply in practice. Legal analysis is undertaken of certain aspects of the Guidance which appear to misunderstand the law in respect of withdrawing treatment.


WHO warns that averting flu pandemic may be harder as surveillance switches to covid-19.


docid: wlpoxabu

title: Air pollution and COVID-19: Is the connect worth its weight?

text: Primary route of transmission of SARS-CoV-2 among humans is droplets and direct contact. Airborne transmission of this virus is not established conclusively and so is the role of airborne particulate matter. This commentary examines the existing evidence about the role of particulate matter pollutants in SARS-CoV-2 transmission. PM2.5and other small particulate matter have been shown to carry viable virus particles in the air and incriminated in spread of measles and SARS coronavirus. Empirical evidence has been provided regarding role of air pollution in accelerated transmission of SARS-CoV-2 in Italy as well as Wuhan. Lockdown-related reduction in PM2.5levels in ambient air may have contributed to reduce transmission of SARS-CoV-2. High PM2.5levels in the past might have added to SARS-CoV-2 related mortality due to air pollution relate comorbidities. Post-lockdown increase in PM2.5levels may accelerate covid-19 transmission and can add to the burden of COVID-19 morbidity and mortality.


title: Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review.

text: Importance The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.


title: [First case of COVID-19 treated with tocilizumab in Iceland].

text: A gentleman in his early fifties became ill with flu-like symptoms after vacationing abroad and was diagnosed with COVID-19 after returning to Iceland. A few days later he was admitted to the University Hospital, Landspitali, due to worsening respiratory symptoms and severe fatigue. A computed tomography scan of lthe lungs showed diffuse bilateral consolidations and ground glass changes. He developed respiratory failure and was transferred to the intensive care unit where he received further treatment, including tocilizumab (IL-6 receptor inhibitor). He subsequently showed clinical improvement and did not require endotracheal intubation.


title: Aquatic cycling-What do we know? A scoping review on head-out aquatic cycling.

text: Over the past few years, aquatic cycling has become a trending fitness activity. However, the literature has not been reviewed exhaustively. Therefore, using scoping review methodology, the aim of this review was to explore the current state of the literature concerning aquatic cycling. This study specifically focused on study designs, populations and outcomes. A comprehensive search of seven databases (PubMed, MEDLINE, Cinahl, Embase, PEDro,Web of Science, WorldCat) was conducted up to 30th September 2016. GoogleScholar, World Cat, ResearchGate, specific aquatic therapy websites and aquatic therapy journals were searched to identify additional literature. Full-text publications in English, German or Dutch were included. Studies were included when the intervention involved head-out cycling carried out in 10° to 35° Celsius water. Exclusion criteria were the use of wet suits or confounding interventions that would affect participants' homeostasis. 63 articles were included and the study parameters of these studies were summarized. Using three grouping themes, included studies were categorised as 1) single session tests comparing aquatic versus land cycling, or 2) aquatic cycling only sessions investigating different exercise conditions and 3) aquatic cycling intervention programmes. Although the experimental conditions differed noticeably across the studies, shared characteristics were identified. Cardiovascular parameters were investigated by many of the studies with the results suggesting that the cardiac demand of aquatic cycling seems similar to land-based cycling. Only six studies evaluated the effect of aquatic cycling interventions. Therefore, future research should investigate the effects of aquatic cycling interventions, preferably in individuals that are expected to gain health benefits from aquatic cycling. Moreover, this comprehensive outline of available literature could serve as a starting point for systematic reviews or clinical studies on the effects of aquatic cycling on the cardiovascular responses.


title: Per anal endoscopic rectopexy for treatment of complete rectal prolapse: A preliminary report.

text: We describe Per Anal Endoscopic Rectopexy (PAER), a new treatment for complete rectal prolapse, which involves fixing the anterior rectal wall to the under-surface of the anterior abdominal wall and posterior rectal wall to the sacrum, through a submucosal tunnel (both endoluminally). This is a prospective single-centre pilot study done at a tertiary care centre. A total of 12 patients with a mean age of 48 years underwent the procedure. Constipation and incontinence were present in 8 and 4 patients, respectively and a significant improvement was seen in both following the procedure. A significant decrease in anorectal angle and its descent was also observed on post procedure magnetic resonance defecography. One patient had partial recurrence of prolapse. No major morbidity was observed. PAER is a minimally invasive and safe option for rectal prolapse, which needs to be validated in more patients over a longer follow up period.


title: Two palmitylated cysteine residues of the severe acute respiratory syndrome coronavirus spike (S) protein are critical for S incorporation into virus-like particles, but not for M-S co-localization.

text: The endodomain of several coronavirus (CoV) spike (S) proteins contains palmitylated cysteine residues and enables co-localization and interaction with the CoV membrane (M) protein. Depalmitylation of mouse hepatitis virus S proteins abolished this interaction, resulting in the failure of S incorporation into virions. In contrast, an immunofluorescence assay (IFA) showed that depalmitylated severe acute respiratory syndrome coronavirus (SCoV) S proteins still co-localized with the M protein in the budding site. Here, we determined the ability of depalmitylated SCoV S mutants to incorporate S into virus-like particles (VLPs). IFA confirmed that all SCoV S mutants co-localized with the M protein intracellularly. However, the mutants lacking two cysteine residues (C(1234/1235)) failed to incorporate S into VLPs. This indicated that these palmitylated cysteines are essential for S incorporation, but are not involved in S co-localization mediated by the M protein. Our findings suggest that M-S co-localization and S incorporation occur independently of one another in SCoV virion assembly.


title: Stable mammalian producer cell lines for structural biology.

text: The mammalian cell lines HEK293 and CHO have become important expression hosts in structural biology. Generating stable mammalian cell lines remains essential for studying the function and structure of recombinant proteins, despite the emergence of highly efficient transient transfection protocols. Production with stable cell lines can be scaled up easily and high volumetric product yield can be achieved. Protein structure reports of the past two years that used stable cell lines were surveyed for this review. Well-established techniques and novel approaches for generating stable cell lines and stable cell pools are presented, including cell sorting, site-specific recombination, transposons, the Lentivirus system and phage integrases. Host cell line optimization by endoglycosidase overexpression and sequence-specific genome engineering is highlighted.


title: An 81 nucleotide deletion in SARS-CoV-2 ORF7a identified from sentinel surveillance in Arizona (Jan-Mar 2020).

text: On January 26 2020, the first Coronavirus Disease 2019 (COVID-19) case was reported in Arizona (3rd case in the US) (1).….


title: Villous mucinous cystadenoma of the appendix in a postmenopausal woman.

text: OBJECTIVE To present the case of a postmenopausal woman, who was suspected of having an ovarian cyst. Instead, a cystadenoma of the appendix was discovered during laparoscopy. METHODS A 64-year-old postmenopausal nulliparous woman was admitted to our hospital because of a cystic lesion, which had been detected in the course of a routine gynecological examination. The patient underwent vaginal ultrasound, magnetic resonance tomography, and laparoscopy. RESULTS During vaginal ultrasound, a dumbbell-shaped anechogenic cystic structure 70 x 32 x 22 mm in diameter was found in the region of the right adnexa. Magnetic resonance tomography revealed no additional information. During diagnostic laparoscopy, the cystic lesion was found to be a distended appendix. A laparoscopic appendectomy was performed. Subsequent histological analysis revealed a villous mucinous cystadenoma of the appendix with low-grade intraepithelial neoplasia. CONCLUSION Gynecologists should routinely consider this disease in the differential diagnosis of right lower dumbbell abdominal cysts. Eleven percent to 20% of mucoceles are caused by mucinous cystadenocarcinomas, which carry the risk of peritoneal tumor implantation caused by rupture or laparoscopic resection. Therefore, it should be mandatory that a general surgeon be involved in the laparoscopic procedure and the conversion to laparotomy for resection of the structure.


title: Reduction in distal emboli with proximal flow control during mechanical thrombectomy: a quantitative in vitro study.

text: BACKGROUND AND PURPOSE To evaluate the impact of proximal flow control on efficacy and safety of mechanical thrombectomy in an in vitro middle cerebral artery occlusion. METHODS Three independent variables, including clot type, device (Merci Retriever, Solitaire FR, and Trevo devices), and use of a balloon guide catheter, were used to ascertain the impact of proximal flow control on the size and number of distal emboli generated during thrombectomy. Secondary end points were the recanalization rate and amount of flow restored. RESULTS Use of the balloon guide catheter during thrombectomy of the fragile, hard clot significantly reduced the formation of large distal emboli with a diameter >1 mm, regardless of the device used (P<0.01). Applying aspiration via the balloon guide catheter in place of the conventional guide catheter resulted in a significant increase of flow reversal (P<0.0001). Prior to thrombectomy, deployment of the stent-trievers produced immediate flow restoration through the soft and hard clot occlusions, 69.2 ± 27.3 and 45.5 ± 22.8 mL/min, respectively, that was preserved after the balloon inflation because of collateral flow via the posterior communication artery. After deployment but before thrombectomy, no flow was restored when using the Merci Retriever. After thrombectomy, complete flow restoration was achieved in a majority of cases. The Merci Retriever required more thrombectomy attempts to achieve hard clot removal compared with the stent-trievers when the conventional guide catheter was used (1.5 versus 1.1). CONCLUSIONS The risk of distal embolization was significantly reduced with the use of the balloon guide catheter.


Machine learning can help get COVID-19 aid to those who need it most.


title: Harnessing the Digital Exhaust: Incorporating wellness into the pharma model.

text: The increasing availability of devices capable of tracking biomarkers presents major opportunities in contemporary healthcare. Herein we advocate a new role for the pharmaceutical industry to capitalize on these opportunities and in doing so incorporate wellness and patient engagement programs into their standard business models. Medical grade decision making using diagnostic, prognostic, and monitoring biomarkers will require coordinated approaches between the pharmaceutical and technology industries and the careful design of longitudinal clinical studies to validate their efficacy. These studies will also require data capture, archiving, curating and sharing on a previously unprecedented scale, and raise additional concerns with regard to data security and ownership. Concurrently, systems-based approaches to the capture and interpretation of a new class of digital biomarkers are emerging, and hold promise for heightened levels of patient engagement and remote sensing. Collectively, if these new opportunities are approached within the context of the patient-provider ecosystem, major repositioning of the pharmaceutical industry may be possible in the near term.


title: Spike protein, S, of human coronavirus HKU1: role in viral life cycle and application in antibody detection.

text: We recently described the discovery, genome, clinical features, genotypes and evolution of a novel and global human respiratory virus named human coronavirus HKU1 (HCoV-HKU1) which is not yet culturable. We expressed a C-terminal FLAG-tagged CoV-HKU1 spike (S) protein by the Semliki Forest Virus (SFV) system and investigated its maturation profile. Pulse chase labeling revealed that S-FLAG was expressed as high-mannose N-glycans of monomers and trimers. It was predominantly cleaved into subdomains S1 and S2 during maturation. S1 was secreted into the medium. Immunofluorescence analysis visualized S along the secretory pathway from endoplasmic reticulum to plasma membrane. Cleavage of S and release of HCoV-HKU1 S pseudotyped virus were inhibited by furin or furin-like enzyme inhibitors. The cell-based expressed full-length S-FLAG could be recognized by the convalescent serum obtained from a patient with HCoV-HKU1 pneumonia. The data suggest that the native form of HCoV-HKU1 spike expressed in our system can be used in developing serological diagnostic assay and in understanding the role of S in the viral life cycle.


title: Quantifying the cost of laparoscopic inguinal hernia repair.

text: BACKGROUND Laparoscopic inguinal hernia repair has been widely adopted. While the clinical advantages and disadvantages are well-quantified, the economic cost is less well-studied. METHODS A retrospective audit and case review of a single-centre public hospital consecutive case series was performed using data captured from real-time stock usage tracking technology and review of electronic medical records. RESULTS Laparoscopic inguinal hernia repair requires 11-min (21%) extra theatre time and costs $1268 (370%) more for single-use disposable equipment and prostheses. CONCLUSIONS Laparoscopic inguinal hernia repair does not require significantly more theatre time, but has a higher short-term in-hospital cost. Repair technique should be tailored according to patient factors.


title: Simulation-guided preparations for the management of suspected or confirmed COVID-19 cases in the obstetric emergency theater.

text: Aims: The coronavirus 2019 infection (COVID-19) global outbreak has resulted in unprecedented pressures on health services, the need to prepare for the worst-case scenario, and the need for health experts to utilize their knowledge and expertise to fight this virus. The simulation training objective of this study was to enhance the neonatal, maternity, and anesthetics teams' preparedness for the management of the emergency delivery of pregnant women with suspected or confirmed COVID-19 infection.Methods: Three clinical simulation training sessions were conducted in March 2020 at the University Hospital Plymouth, Plymouth, UK. The neonatal, maternity, and anesthetics clinical teams participated in these joint training sessions in the obstetric emergency theater.Results: Each session lasted for around an hour. Suggestions were discussed and recommendations made. The key changes were: first, floor plan adjustment, increase of the clinical area by converting some offices to clinical spaces, and standard operating procedures for transporting patients; second, enhancement of the efficiency of the communication and coordination between the clinical teams; third, availability of extra support for the staff in the Central Delivery Suite (CDS); and fourth, introduction of a neonatal care pathway to manage neonatal resuscitation in such an emergency.Conclusions: Collaboration and joint training between the different clinical teams involved in the care of suspected or confirmed COVID-19 patients was proven to be one of the most effective ways of improving performance.