title: A Randomized Controlled Study to Evaluate the Impact of Instrument and Laparoscope Length on Performance and Learning Curve in Single-Incision Laparoscopic Surgery.

text: INTRODUCTION The proximity of instrumentation in single-incision laparoscopic surgery (SILS) creates ergonomic challenges. An innovative method to reduce external collisions between instruments and handles is to use instruments of different lengths. This study evaluated the impact of instrument and laparoscope length on simulated SILS performance. METHODS Performance was assessed using peg transfer (PEG) and pattern cutting (CUT) tasks from the Fundamentals of Laparoscopic Surgery (FLS) curriculum. Following baseline testing, surgeons were randomized into 3 trial arms: Control--standard length instruments and standard length laparoscope; group 1--one long instrument, one standard length instrument and standard length laparoscope; and group 2--standard length instruments and long laparoscope. Two phases were undertaken using a validated SILS-modified FLS box trainer: phase 1--25 repetitions of PEG and phase 2--5 repetitions of CUT. FLS scoring parameters measured performance and the Imperial College Surgical Assessment Device (ICSAD) captured motion analysis of hands. RESULTS Twenty-three surgeons were recruited--control (n = 7), group 1 (n = 9), and group 2 (n = 7). No significant differences were observed in operative experience or baseline skills performance. Phase 1: Peak FLS score was significantly higher in group 1 compared with control (P = .009). Comparison of learning curves revealed learning plateau was significantly higher in group 1 compared with control (P = .010). Phase 2: Group 1 revealed a trend toward higher peak FLS scores over the control (P = .067). No significant differences in motion analysis of hands were demonstrated using ICSAD. CONCLUSIONS This study demonstrates that using instruments of different lengths can improve simulated SILS performance.


title: CD74-NRG1 fusions in lung adenocarcinoma.

text: UNLABELLED We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations, we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-β3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case, and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (P < 0.0001). Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment. SIGNIFICANCE CD74–NRG1 fusions may represent a therapeutic opportunity for invasive mucinous lung adenocarcinomas, a tumor with no effective treatment that frequently presents with multifocal unresectable disease.


title: Prolonged amelioration of acute lung allograft rejection by sequential overexpression of human interleukin-10 and hepatocyte growth factor in rats.

text: The effect of prolonged electroporation-mediated human interleukin-10 (hIL-10) overexpression 24 hours before transplantation, combined with sequential human hepatocyte growth factor (HGF) overexpression into skeletal muscle on day 5, on rat lung allograft rejection was evaluated. Left lung allotransplantation was performed from Brown-Norway to Fischer-F344 rats. Gene transfer into skeletal muscle was enhanced by electroporation. Three groups were studied: group I animals (n = 5) received 2.5 μg pCIK-hIL-10 (hIL-10/CMV [cytomegalovirus] early promoter enhancer) on day -1 and 80 μg pCIK-HGF (HGF/CMV early promoter enhancer) on day 5. Group II animals (n = 4) received 2.5 μg pCIK-hIL-10 and pUbC-hIL-10 (hIL-10/pUbC promoter) on day -1. Control group III animals (n = 4) were treated by sham electroporation on days -1 and 5. All animals received daily nontherapeutic intraperitoneal dose of cyclosporin A (2.5 mg/kg) and were sacrificed on day 15. Graft oxygenation and allograft rejection were evaluated. Significant differences were found between study groups in graft oxygenation (Pao(2)) (P = .0028; group I vs. groups II and III, P < .01 each). Pao(2) was low in group II (31 ± 1 mm Hg) and in group III controls (34 ± 10 mm Hg), without statistically significant difference between these 2 groups (P = .54). In contrast, in group I, Pao(2) of recipients sequentially transduced with IL-10 and HGF plasmids was much improved, with 112 ± 39 mm Hg (vs. groups II and III; P < .01 each), paralleled by reduced vascular and bronchial rejection (group I vs. groups II and III, P < .021 each). Sequential overexpression of anti-inflammatory cytokine IL-10, followed by sequential and overlapping HGF overexpression on day 5, preserves lung function and reduces acute lung allograft rejection up to day 15 post transplant as compared to prolonged IL-10 overexpression alone.


title: Mutation probability of cytochrome P450 based on a genetic algorithm and support vector machine.

text: The support vector machine (SVM), an effective statistical learning method, has been widely used in mutation prediction. Two factors, i.e., feature selection and parameter setting, have shown great influence on the efficiency and accuracy of SVM classification. In this study, according to the principles of a genetic algorithm (GA) and SVM, we developed a GA-SVM program and applied it to human cytochrome P450s (CYP450s), which are important monooxygenases in phase I drug metabolism. The program optimizes features and parameters simultaneously, and hence fewer features are used and the overall prediction accuracy is improved. We focus on the mutation of non-synonymous single nucleotide polymorphisms (nsSNPs) in protein sequences that appear to exhibit significant influences on drug metabolism. The final predictive model has a quite satisfactory performance, with the prediction accuracy of 61% and cross-validation accuracy of 73%. The results indicate that the GA-SVM program is a powerful tool in optimizing mutation predictive models of nsSNPs of human CYP450s.


Bioconcrete presages new wave in environmentally friendly construction.


Annals On Call - Surge Modeling for COVID-19.


title: Public health requirements for rapid progress in global health.

text: Effective public health interventions can save hundreds of millions of lives in developing countries, as well as create broad social and economic benefits. Unfortunately, public health approaches and solutions applied in developed countries are often assumed to be inappropriate or unattainable in developing countries. This has sometimes forestalled effective interventions in parts of the world where they are most needed, despite conditions that now facilitate lasting solutions to both long-standing and emerging global public health problems. Core public health functions are similar regardless of a country's income level. Although some resource-intensive approaches from industrialised nations are inappropriate in less developed countries, many basic public health measures achieved decades ago in developed countries are urgently needed, highly appropriate, extremely cost-effective and eminently attainable in developing countries today. About half of the disease burden in low and middle-income countries is now from non-communicable diseases, but non-communicable disease epidemics that will otherwise increase rapidly in the developing world can be avoided or reversed. Progress of public health in developing countries is possible, but will require sufficient funding and human resources; improved physical plant and information systems; effective programme implementation and regulatory capacity; and, most importantly, political will at the highest levels of government.


title: COVID-19 Pandemic: Experiences in China and implications for its prevention and treatment worldwide.

text: The outbreak of COVID-19 due to SARS-CoV-2 originally emerged in Wuhan in December, 2019. As of March 22, 2020, the disease had spread to 186 countries, with at least 305,275 confirmed cases. Although there has been a decline in the spread of the disease in China, the prevalence of COVID-19 around the world remains serious despite containment efforts undertaken by national authorities and the international community. In this article, we systematically review the brief history of COVID-19 and its epidemic and clinical characteristics, highlighting the strategies used to control and prevent the disease in China, which may help other countries respond to the outbreak. This pandemic emphasizes the need to be constantly alert to shifts in both the global dynamics and the contexts of individual countries, making sure that all are aware of which approaches are successful for the prevention, containment and treatment of new diseases, and being flexible enough to adapt the responses accordingly.


title: Hyponatremia: A Possible Immuno-Neuroendocrine Interface with COVID-19 in a Kidney Transplant Recipient.

text: There is fast-emerging, cumulative clinical data on coronavirus disease 2019 (COVID-19) in kidney transplant recipients. Although respiratory tract symptoms are often the initial presentation among kidney transplant recipients who contract COVID-19, other clinical features which may indicate underlying SARS-CoV-2-related inflammation, such as gastrointestinal symptoms, are not uncommon. Hyponatremia can develop and may reflect underlying inflammation. Interferon-6 is an important pro-inflammatory cytokine involved in the pathogenesis of severe COVID-19 complications and may play a role in the inappropriately higher secretion of antidiuretic hormone leading to hyponatremia. This pathway is the so-called immuno-neuroendocrine interface. Hyponatremia in COVID-19 has been reported in a few case series of non-kidney transplant patients and only one reported kidney transplant recipient. However, the clinical course and prognostic value of hyponatremia in this population is not described in detail. We report a kidney transplant recipient who was infected with COVID-19 and exhibited severe hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. Hyponatremia is one of the clinical presentations of COVID-19, although less common, and may occur more frequently in kidney transplant recipients. Thus the possible underlying immuno-neuroendocrine relationship related to the inflammatory process of COVID-19 leading to hyponatremia, and its prognostic value, are reviewed.


title: Experimental application of pulsed laser-induced water jet for endoscopic submucosal dissection: mechanical investigation and preliminary experiment in swine.

text: BACKGROUND AND AIM A current drawback of endoscopic submucosal dissection (ESD) for early-stage gastrointestinal tumors is the lack of instruments that can safely assist with this procedure. We have developed a pulsed jet device that can be incorporated into a gastrointestinal endoscope. Here, we investigated the mechanical profile of the pulsed jet device and demonstrated the usefulness of this instrument in esophageal ESD in swine. METHODS The device comprises a 5-Fr catheter, a 14-mm long stainless steel tube for generating the pulsed water jet, a nozzle and an optical quartz fiber. The pulsed water jet was generated at pulse rates of 3 Hz by irradiating the physiological saline (4°C) within the stainless steel tube with an holmium-doped yttrium-aluminum-garnet (Ho:YAG) laser at 1.1 J/pulse. Mechanical characteristics were evaluated using a force meter. The device was used only for the part of submucosal dissection in the swine ESD model. Tissues removed using the pulsed jet device and a conventional electrocautery device, and the esophagus, were histologically examined to assess thermal damage. RESULTS The peak impact force was observed at a stand-off distance of 40 mm (1.1 J/pulse). ESD using the pulsed jet device was successful, as the tissue specimens showed precise dissection of the submucosal layer. The extent of thermal injury was significantly lower in the dissected bed using the pulsed jet device. CONCLUSION The results showed that the present endoscopic pulsed jet system is a useful alternative for a safe ESD with minimum tissue injury.


title: Clinical outcome and wound healing following carpal tunnel decompression: a comparison of two common suture materials.

text: INTRODUCTION Debate exists amongst surgeons regarding the ideal suture material for skin closure in carpal tunnel decompression (CTD). This study compares wound related complications, patient satisfaction, and functional outcome following open carpal tunnel decompression in patients undergoing wound closure with either of two common absorbable and nonabsorbable suture types. MATERIALS AND METHODS 53 patients underwent CTD with either 4/0 polypropylene (ProleneTM, n = 28) or 4/0 polyglactin (Vicryl RapideTM, n = 25) for skin closure. QuickDASH, VAS satisfaction scores, and Southampton wound scores were assessed preoperatively and at 2 and 6 weeks postoperatively. RESULTS At 6 weeks the mean QuickDASH scores postoperatively were 18.54 and 17.70 for absorbable and nonabsorbable sutures, respectively, (P = 0.86). The mean VAS scores were 0.61 and 0.42 (P = 0.91), respectively. All patients achieved a Southampton wound score of 0 by 6 weeks except one, who achieved 1C in the nonabsorbable group, equivalent to mild erythema. There were no complications in either group. CONCLUSION Both suture types are safe and effective materials for CTD, and we recommend surgeons to choose according to personal preference, handling properties, and resources available for suture removal.


title: The molecular basis for public T-cell responses?

text: Public T-cell responses, in which T cells bearing identical T-cell receptors (TCRs) are observed to dominate the response to the same antigenic epitope in multiple individuals, have long been a focus of immune T-cell repertoire studies. However, the mechanism that enables the survival of a specific TCR from the diverse repertoire produced in the thymus through to its involvement in a public immune response remains unclear. In this Opinion article, we propose that the frequency of production of T cells bearing different TCRs during recombination has an important role in the sharing of TCRs in an immune response, with variable levels of 'convergent recombination' driving production frequencies.


title: Efficacy of intradermally administrated E2 subunit vaccines in reducing horizontal transmission of classical swine fever virus.

text: To investigate if intradermal (ID) vaccination and intramuscular (IM) vaccination result in a comparable reduction of horizontal transmission of classical swine fever virus (CSFV), two registered E2 subunit marker vaccines were examined. Vaccine A was a water-in-oil emulsion containing the E2 glycoprotein originating from the Alfort/Tübingen strain and vaccine B was a water-oil-water emulsion containing the E2 glycoprotein originating from the Brescia strain. Eight groups, of ten pigs each, were vaccinated with either vaccine A or B, intramuscularly (IM) or intradermally (ID). Two different vaccination-challenge intervals were used for each vaccine. Furthermore, one group was vaccinated with a tenfold ID dose of vaccine A and one non-vaccinated group served as a control group. Five pigs from each group were challenged with the moderately virulent CSFV strain Paderborn, while the remaining five pigs served as contacts. Using vaccine A, full transmission to all contact pigs in both ID vaccinated groups occurred. No virus transmission was observed when IM vaccinated pigs were challenged 14 days post-vaccination (14dpv) whereas only one out of five contact pig became infected when they were challenged 10dpv. Using vaccine B no virus transmission was observed when pigs were ID or IM vaccinated and challenged 10dpv. When challenged 3dpv full transmission occurred in the ID vaccinated group, whereas four out of five contact pigs became infected in the IM vaccinated group. This result indicates that ID vaccination does not result in better protection against horizontal CSFV transmission compared to IM vaccination, for the vaccines studied.


title: Robotics may overcome technical limitations of single-trocar surgery: an experimental prospective study of Nissen fundoplication.

text: OBJECTIVE To compare laparoscopic and robotic-assisted single-trocar access (STA) Nissen fundoplication in a porcine model. The STA procedure is an emerging concept in minimally invasive surgery that presents technical difficulties and challenges compared with traditional laparoscopy. Using multiple instruments inserted through a single trocar generates internal and external conflicts. Achieving triangulation requires the instruments and surgeon's hands to cross over at the point of entry. Robotic-assisted surgery may overcome these difficulties owing to its capability of dissociating the hands of the surgeon from the instruments. DESIGN Prospective study consisting of 18 randomly performed porcine STA Nissen fundoplications with and without robotic assistance. SETTING A research institute. PARTICIPANTS Three surgeons with different experience. MAIN OUTCOME MEASURES Operative time, intraoperative complications, and the number of conflicts between the instruments and/or hands of the surgeons. RESULTS All of the procedures were successfully completed. Mean operative time (45.6 +/- 11.2 vs 65.4 +/- 10.7 minutes; P = .03) and number of conflicts (1.0 +/- 0.9 vs 3.8 +/- 1.2; P < .001) were significantly reduced in the robotic series. CONCLUSIONS Use of the robotic platform allows the surgeon to select which hand will move which instrument. Inverting the control allows crossing of the instruments without any consequences to the surgeon. Moreover, this system offers instruments with multiple degrees of freedom. These factors could explain the clear improvement demonstrated in this study. As a result, robotics may play an essential part in the diffusion of STA surgery.


title: Pulmonary surfactant itself must be a strong defender against SARS-CoV-2.

text: Pulmonary surfactant is considered to be one of the soaps. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the other enveloped viruses become very weak against surfactant. The SARS virus binds to angiotensin-converting enzyme (ACE2) receptor and causes pneumonia. In the lung, the ACE2 receptor sits on the top of lung cells known as alveolar epithelial type II (AE2) cells. These cells play an important role in producing surfactant. Pulmonary surfactant is believed to regulate the alveolar surface tension in mammalian lungs. To our knowledge, AE2 cells are believed to act as immunoregulatory cells; however, pulmonary surfactant itself has not been believed to act as a defender against the enveloped viruses. This study hypothesises that pulmonary surfactant may be a strong defender of enveloped viruses. Therefore, old coronaviruses merely cause pneumonia. On the contrary, new SARS-CoV-2 can suppress the production of surfactant that binds to the ACE2 of AE2 cells. The coronavirus can survive in the lung tissue because of the exhaustion of pulmonary surfactant.


title: Rapid delayed growth of ruptured supraclinoid blister aneurysm after successful flow diverting stent treatment.

text: A 62-year-old woman presented with a subarachnoid hemorrhage secondary to a ruptured right supraclinoid internal carotid artery blister aneurysm. She was treated in an emergent fashion with two flow diverting pipeline embolization devices (PED) deployed in a telescoping fashion. CT angiography performed for unrelated reasons at 7 months showed successful treatment of the aneurysm without evidence of residual aneurysm. However, a follow-up digital subtraction angiogram performed at 9 months showed a large aneurysm in a modified position compared with the original aneurysm. This is the first case of rapid regrowth of a supraclinoid blister aneurysm after successful treatment with a PED, and demonstrates the need for close follow-up for similar aneurysms treated with this novel device.


Blocking angiotensin earlier with RAS blockers, statins, and heparin in high-risk COVID-19 patients: Is the remedy here?


title: Cold thermal oral stimulation produces immediate excitability in human pharyngeal motor cortex.

text: BACKGROUND Current strategies of swallowing therapy include facilitation of swallowing initiation by sensory modulation. Although thermal tactile oral stimulation is a common method to treat dysphagic patients to improve swallowing movement, little is known about the possible mechanisms. This study is aimed to investigate whether thermal oral (tongue) stimulation can modulate the cortico-pharyngeal neural motor pathway in humans. METHODS Eighteen healthy volunteers participated and were intubated with an intraluminal catheter for recording pharyngeal electromyography. Each participant underwent baseline transcranial magnetic stimulation (TMS) cortico-pharyngeal motor evoked potential (MEP) measurements bilaterally. MEPs were then measured during thermal stimulation over the dorsal tongue, applied using the Peltier device at three different temperatures; 45°C, 37°C, and 15°C, in a pre-ordered manner. Each of the three temperatures was given twice with a 5-min resting time between each trial. Averaged MEP amplitude changes were analyzed using ANOVA and post-hoc t-tests. KEY RESULTS Two-way repeated measures ANOVA with factors of Temperature × Trial in amplitude of MEP demonstrated a significant effect of Temperature both in the stronger (F2,34 = 5.775, P = .007) and weaker (F2,34 = 4.771, P = .017) pharyngeal hemispheres. Subsequent post-hoc tests showed the significant increase in pharyngeal MEPs at 15° compared to 37° in both hemispheres (P < .05). CONCLUSIONS & INFERENCES Cold oral stimulation was able to induce significant changes in pharyngeal cortical excitability, demonstrating evidence for a sensorimotor interaction between oral and pharyngeal cortical areas.


title: Phylogeography and population dynamics of dengue viruses in the Americas.

text: Changes in Dengue virus (DENV) disease patterns in the Americas over recent decades have been attributed, at least in part, to repeated introduction of DENV strains from other regions, resulting in a shift from hypoendemicity to hyperendemicity. Using newly sequenced DENV-1 and DENV-3 envelope (E) gene isolates from 11 Caribbean countries, along with sequences available on GenBank, we sought to document the population genetic and spatiotemporal transmission histories of the four main invading DENV genotypes within the Americas and investigate factors that influence the rate and intensity of DENV transmission. For all genotypes, there was an initial invasion phase characterized by rapid increases in genetic diversity, which coincided with the first confirmed cases of each genotype in the region. Rapid geographic dispersal occurred upon each genotype's introduction, after which individual lineages were locally maintained, and gene flow was primarily observed among neighboring and nearby countries. There were, however, centers of viral diversity (Barbados, Puerto Rico, Colombia, Suriname, Venezuela, and Brazil) that were repeatedly involved in gene flow with more distant locations. For DENV-1 and DENV-2, we found that a "distance-informed" model, which posits that the intensity of virus movement between locations is inversely proportional to the distance between them, provided a better fit than a model assuming equal rates of movement between all pairs of countries. However, for DENV-3 and DENV-4, the more stochastic "equal rates" model was preferred.


title: Physical health among people with serious mental illness in the face of COVID-19: Concerns and mitigation strategies.

text: COVID-19 can worsen the physical health of individuals with serious mental illness, a vulnerable group already facing physical health disparities. COVID-19 is further reducing access to physical health care due to shutdown of services deemed "non-urgent" and overcrowding of emergency services. Management of chronic diseases, highly prevalent in this group, is undermined due to exacerbation of psychiatric disorders, reduction in availability of social support, and worsening of negative social determinants of health. In this commentary, we discuss the challenges experienced by this group and offer mitigation strategies to reduce: (1) inequalities in access to physical health care; and (2) disruptions to the management of chronic physical conditions in the face of COVID-19. Recommendations include coordinated efforts by health authorities, primary and mental health care organizations, researchers, policymakers, and other stakeholders. These efforts should ensure equitable access to physical health care and implementation of innovative programs to protect the physical health of people with serious mental illness during and following the pandemic.


title: Understanding the Outcomes of Supplementary Support Services in Palliative Care for Older People. A Scoping Review and Mapping Exercise.

text: CONTEXT Supplementary support services in palliative care for older people are increasingly common, but with no recommended tools to measure outcomes, nor reviews synthesising anticipated outcomes. Common clinically focussed tools may be less appropriate. OBJECTIVE To identify stakeholder perceptions of key outcomes from supplementary palliative care support services, then map these onto outcome measurement tools to assess relevance and item redundancy. METHODS A scoping review using Arksey and O'Malley's design. EMBASE, CINAHL, MEDLINE and PSYCHinfo searched using terms relating to palliative care, qualitative research and supplementary support interventions. Papers imported into Endnote™, and Covidence™ used by two reviewers to assess against inclusion criteria. Included papers were imported into NVivo™, and thematically coded to identify key concepts underpinning outcomes. Each item within contender outcome measurement tools was assessed against each concept. RESULTS 60 included papers focused on advance care planning, guided conversations, and volunteer befriending services. Four concepts were identified: enriching relationships; greater autonomy and perceived control; knowing more; and improved mental health. Mapping concepts to contender tool items revealed issues of relevance and redundancy. Some tools had no redundant items, but mapped only to two of four outcome themes, others mapped to all concepts, but with many redundant questions. Tools such as ICECAP-SCM and McGill Quality of Life had high relevance and low redundancy. CONCLUSIONS Pertinent outcome concepts for these services and population are not well represented in commonly used outcome measurement tools, and this may have implications in appropriately measuring outcomes. This review and mapping method may have utility in fields where selecting appropriate outcome tools can be challenging.


title: [Application of Reyanning Mixture in evaluating combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome].

text: In the previous research, our laboratory established a mouse model combining disease with syndrome of human coronavi-rus pneumonia with pestilence attacking the lung syndrome, based on the national traditional Chinese medicine clinical classification of Novel Coronavirus Infected Pneumonia Diagnosis and Treatment Plan. In this study, a mouse model combining disease with syndrome of human coronavirus pneumonia with pestilence attacking the lung syndrome was used to evaluate the effectiveness of Reyanning Mixture to provide animal experimental support for clinical application. Mice were divided into normal group, 229 E infection group, cold-dampness group, cold-dampness+229 E infection group(the model group), Reyanning high and low dose groups. The cold-dampness group, cold-dampness+229 E infection group, two Reyanning groups were given cold and damp stimulation for 7 days. On the 5 th day, the 229 E infection group, cold-dampness+229 E infection group, and two Reyanning groups were infected with HCoV-229 E virus. Reyanning was administered for 3 days, starting from the day of infection. Blood was collected on the 4 th day and the lung tissue was dissected to calculate the lung index and inhibition rate; flow cytometry was used to detect the percentage of T and B lymphocytes in peripheral blood; RT-PCR was used to detect the nucleic acid virus load in lung tissue; ELISA was used to detect motilin and gastrin in serum, and inflammatory factors TNF-α, IFN-γ, IL-6, IL-10 in lung tissue proteins. Reyanning Mixture could reduce the lung index(P<0.01) of coronavirus pneumonia mice with pestilence attacking the lung; it could significantly increase the percentage of CD8~+ T lymphocytes and CD4~+ T lymphocytes in peripheral blood of model mice(P<0.05, P<0.01). The low dose of Reyanning could effectively increase the percentage of total B lymphocytes(P<0.05), reduce virus load in lung tissue of model mice(P<0.01), reduce the levels of TNF-α, IFN-γ, IL-6, IL-10 in the lung tissue of model mice(P<0.01), reduce the content of motilin in the serum of model mice(P<0.01). Reyanning Mixture convey a better effect in treating coronavirus pneumonia mice with pestilence attacking the lung. It manifested obvious effects in improving lung lesions, enhancing the gastrointestinal function of mice, improving the autoimmune function of mice, and reducing the expression of inflammatory factors in vivo, which could provide evidences for clinical research.


title: Slowly progressive lymphohistiocytic meningoencephalomyelitis in 21 adult cats presenting with peculiar neurological signs.

text: Twenty-one cats presented with a history of slowly progressive neurological signs characterised by a stiff extended tail, behavioural changes, and spastic and ataxic gait. All cats had outdoor access and lived in the same geographical rural area in north-east Scotland. Histological findings were consistent with lymphohistiocytic meningoencephalomyelitis. Immunohistochemistry ruled out 15 pathogens and showed a significant expression of the interferon-inducible Mx protein, suggesting an as yet unidentified infective or environmental immunogenic trigger as the possible causative agent. The late age at onset (mean 9 years), the very slow progression of clinical signs (mean 11 months) and the peculiar clinical presentation (particularly the posture of the tail) have not been reported previously in cats with lymphohistiocytic meningoencephalomyelitis.


title: Right renal vein extension with cryopreserved external iliac artery allografts in living-donor kidney transplantations.

text: INTRODUCTION A short right renal vein remains a challenge for renal transplant surgery, especially in the living donor. Our objective was to report on a new technique to solve this problem. TECHNICAL CONSIDERATIONS We describe our experience with the use of cryopreserved iliac artery grafts for right renal vein extension. Two renal grafts from living donors with a short right renal vein were subjected to an extension with a cryopreserved external iliac artery allograft. There were no perioperative or postoperative complications. There were also no changes in ischemia times. The renal implantation was performed easily and conveniently using our standard technique. For the first and second procedures, at 3 and 3.5 years after surgery, respectively, both vascular grafts maintain good patency, and the renal function of both recipients is optimal. CONCLUSION Tissue-banked cryopreserved cadaveric vessels can be a useful tool in renal transplant surgery. The use of a cryopreserved iliac artery for renal vein extension is a simple and effective new technique that can be added to the pool of surgical solutions for a short renal vein in living-donor kidney transplantation. To our knowledge, this is the first time that the use of such grafts for this purpose has been described.


title: Validation of Suitable Reference Genes for Assessing Gene Expression of MicroRNAs in Lonicera japonica.

text: MicroRNAs (miRNAs), which play crucial regulatory roles in plant secondary metabolism and responses to the environment, could be developed as promising biomarkers for different varieties and production areas of herbal medicines. However, limited information is available for miRNAs from Lonicera japonica, which is widely used in East Asian countries owing to various pharmaceutically active secondary metabolites. Selection of suitable reference genes for quantification of target miRNA expression through quantitative real-time (qRT)-PCR is important for elucidating the molecular mechanisms of secondary metabolic regulation in different tissues and varieties of L. japonica. For precise normalization of gene expression data in L. japonica, 16 candidate miRNAs were examined in three tissues, as well as 21 cultivated varieties collected from 16 production areas, using GeNorm, NormFinder, and RefFinder algorithms. Our results revealed combination of u534122 and u3868172 as the best reference genes across all samples. Their specificity was confirmed by detecting the cycling threshold (C t) value ranges in different varieties of L. japonica collected from diverse production areas, suggesting the use of these two reference miRNAs is sufficient for accurate transcript normalization with different tissues, varieties, and production areas. To our knowledge, this is the first report on validation of reference miRNAs in honeysuckle (Lonicera spp.). Restuls from this study can further facilitate discovery of functional regulatory miRNAs in different varieties of L. japonica.


title: Pandemic Anxiety: How Can I Help?

text: The COVID-19 pandemic has aroused a level of anxiety and uncertainty that spans demographics and diagnoses. Because the coronavirus is a novel variant, the expert scientific community presents to the public as uncertain and inconsistent in information and ways to deal with potential infection, which creates disbelief and uncertainty. The most consistent recommendation is physical distancing and self-imposed isolation to reduce the spread. However, such isolation also adds to individual and community distress. This column focuses on the neurobiological explanations for anxiety, complications to pre-existing psychiatric disorders, sub diagnostic states of stress and anxiety generally and with health care providers, and pharmacological and nonpharmacological ways of addressing this anxiety. [Journal of Psychosocial Nursing and Mental Health Services, 58(7), 7-10.].


title: Percutaneous radiofrequency ablation of painful osseous metastases: a multicenter American College of Radiology Imaging Network trial.

text: BACKGROUND The study was conducted to determine whether radiofrequency ablation (RFA) can safely reduce pain from osseous metastatic disease. METHODS The single-arm prospective trial included patients with a single painful bone metastasis with unremitting pain with a score >50 on a pain scale of 0-100. Percutaneous computed tomography-guided RFA of the bone metastasis to temperatures >60 degrees C was performed. Endpoints were the toxicity and pain effects of RFA before and at 2 weeks, 1 month, and 3 months after RFA. RESULTS Fifty-five patients completed RFA. Grade 3 toxicities occurred in 3 of 55 (5%) patients. RFA reduced pain at 1 and 3 months for all pain assessment measures. The average increase in pain relief from pre-RFA to 1-month follow-up is 26.3 (95% confidence interval [CI], 17.7-34.9; P < .0001), and the increase from pre-RFA to 3-month follow-up is 16.38 (95% CI, 3.4-29.4; P = .02). The average decrease in pain intensity from pre-RFA to 1-month follow-up was 26.9 (P < .0001) and 14.2 for 3-month follow-up (P = .02). The odds of lower pain severity at 1-month follow-up were 14.0 (95% CI, 2.3-25.7; P < .0001) times higher than at pre-RFA, and the odds at 3-month follow-up were 8.0 (95% CI, 0.9-15.2; P < .001) times higher than at pre-RFA. The average increase in mood from pre-RFA to 1-month follow-up was 19.9 (P < .0001) and 14.9 to 3-month follow-up (P = .005). CONCLUSIONS This cooperative group trial strongly suggests that RFA can safely palliate pain from bone metastases.


title: Gynecological prevention and control model based on ward rearrangement and zoning management in pandemic period of COVID-19.

text: By 25th April 2020, the outbreak of COVID-19 caused 2719897 confirmed cases and 187705 deaths globally, remarkably more than Severe Acute Respiratory Syndrome (SARS) (8273 cases, 775 deaths) and Middle East Respiratory Syndrome (MERS) (1139 cases, 431 deaths) in 2003 and 2013, respectively. Gynecology is a specialty department with a large number of critical and severe patients. Consequently, it is of preeminent importance to formulate the in-patient management process. Rearranging the gynecological wards and managing ward partition, as well as the medical protection measures in specialized areas, are suitable for the current prevention and control for COVID-19 pandemic and the therapeutic requirements of patients. To effectively minimize nosocomial infections during the COVID- 19 pandemic period, our department implemented a novel prevention strategy based on the ward redesign and partition management. With this model, our department effectively protected the safety and health of patients and medical care staff from cross and nosocomial infection in the hospital. Now we would like to share the experience and strategies we implemented as following.


title: Complex ventral hernia repair with a human acellular dermal matrix.

text: PURPOSE The ideal approach to complex ventral hernia repair is frequently debated. Differences in processing techniques among biologic materials may impact hernia repair outcomes. This study evaluates the outcomes of hernia repair with a terminally sterilized human acellular dermal matrix (TS-HADM) (AlloMax(®) Surgical Graft, by C. R. Bard/Davol, Inc., Warwick, RI, USA) treated with low-dose gamma irradiation. METHODS A single-arm multi-center retrospective observational study of patients undergoing hernia repair with TS-HADM was performed. Data analyses were exploratory only; no formal hypothesis testing was pre-specified. RESULTS Seventy-eight patients (43F, 35M) underwent incisional hernia repair with a TS-HADM. Mean follow-up was 20.5 months. Preoperative characteristics include age of 56.6 ± 11.1 years, BMI 36.7 ± 9.9 kg/m(2), and mean hernia defect size 187 cm(2). Sixty-five patients underwent component separation technique (CST) with a reinforcing graft. Overall, 21.8% developed recurrences. Recurrences occurred in 15% of patients repaired with CST. Major wound complications occurred in 31% of patients overall. Based upon CDC surgical wound classification, major wound complications were seen in 26, 40, 56, and 50% of Class 1, 2, 3, and 4 wounds, respectively. No grafts required removal. CONCLUSIONS Hernia recurrences are not uncommon following complex abdominal wall reconstruction. Improved outcomes are seen when a TS-HADM is utilized as reinforcement to primary fascial closure.


title: Feasibility and cost effectiveness of ambulatory laparoscopic cholecystectomy. A retrospective cohort study.

text: Ambulatory surgery is an efficient, safe and widely performed procedure; this study would shows the advantages of the ambulatory laparoscopic cholecystectomy procedure from the point of view of patients and the Hospital/National Health System. Materials and Methods: Single-center retrospective cohort study including 288 patients who underwent laparoscopic-cholecystectomy at **** from January 2016 to July 2018. Ambulatory LC were compared to well-matched inpatient procedures performed in the same study period. The primary endpoints was the 30-day readmission rate. Secondary endpoints were the discharge rate in the ambulatory group, the post-operative complications rate and cost effectiveness. Results: 120/288 (41.7%) patients underwent ambulatory laparoscopic cholecystectomy. Thirty-two (26.7%) patients who underwent ambulatory laparoscopic cholecystectomy had major preoperative comorbidities and 35 (29.2%) had undergone prior abdominal surgery. The readmission rates for ambulatory patients and inpatients were 0.8% and 1.7% (p = 0.56), respectively; 104 (86.7%) ambulatory patients were discharged successfully on the same day. The two groups showed the same post-operative complication rate (p = 0.40). Ambulatory procedures resulted in related cost savings of more than 300% for the hospital and a remarkable financial benefit for the National Italian Healthcare System, accounting for savings exceeding € 27 000 per year. Conclusions: Ambulatory laparoscopic cholecystectomy is safe and cost effective. Since a third of ambulatory patients showed comorbidity or previous abdominal surgery, we believe that this procedure may be performed safely in a tertiary HPB centre, even in complex patients.


title: Assessing activity and inhibition of Middle East respiratory syndrome coronavirus papain-like and 3C-like proteases using luciferase-based biosensors.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with an outbreak of more than 90 cases of severe pneumonia with high mortality (greater than 50%). To date, there are no antiviral drugs or specific therapies to treat MERS-CoV. To rapidly identify potential inhibitors of MERS-CoV replication, we expressed the papain-like protease (PLpro) and the 3-chymotrypsin-like protease (3CLpro) from MERS-CoV and developed luciferase-based biosensors to monitor protease activity in cells. We show that the expressed MERS-CoV PLpro recognizes and processes the canonical CoV-PLpro cleavage site RLKGG in the biosensor. However, existing CoV PLpro inhibitors were unable to block MERS-CoV PLpro activity, likely due to the divergence of the amino acid sequence in the drug binding site. To investigate MERS-CoV 3CLpro activity, we expressed the protease in context with flanking nonstructural protein 4 (nsp4) and the amino-terminal portion of nsp6 and detected processing of the luciferase-based biosensors containing the canonical 3CLpro cleavage site VRLQS. Importantly, we found that a small-molecule inhibitor that blocks replication of severe acute respiratory syndrome (SARS) CoV and murine CoV also inhibits the activity of MERS-CoV 3CLpro. Overall, the protease expression and biosensor assays developed here allow for rapid evaluation of viral protease activity and the identification of protease inhibitors. These biosensor assays can now be used to screen for MERS-CoV-specific or broad-spectrum coronavirus PLpro and 3CLpro inhibitors.


title: Robotic Intracorporeal Padua Ileal Bladder: Surgical Technique, Perioperative, Oncologic and Functional Outcomes.

text: BACKGROUND Robot-assisted radical cystectomy (RARC) with intracorporeal neobladder reconstruction is a challenging procedure. The need for surgical skills and the long operative times have led to concern about its reproducibility. OBJECTIVE To illustrate our technique for RARC and totally intracorporeal orthotopic Padua ileal bladder. DESIGN, SETTING, AND PARTICIPANTS From August 2012 to February 2014, 45 patients underwent this technique at a single tertiary referral centre. SURGICAL PROCEDURE RARC, extended pelvic lymph node dissection, and intracorporeal partly stapled neobladder. Surgical steps are demonstrated in the accompanying video. MEASUREMENTS Demographics, clinical, and pathological data were collected. Perioperative, 2-yr oncologic and 2-yr functional outcomes were reported. RESULTS AND LIMITATIONS Intraoperative transfusion or conversion to open surgery was not necessary in any case and intracorporeal neobladder was successfully performed in all 45 patients. Median operative time was 305min (interquartile range [IQR]: 282-345). Median estimated blood loss was 210ml (IQR: 50-250). Median hospital stay was 9 d (IQR: 7-12). The overall incidence of perioperative, 30-d and 180-d complications were 44.4%, 57.8%, and 77.8%, respectively, while severe complications occurred in17.8%, 17.8%, and 35.5%, respectively. Two-yr daytime and night-time continence rates were 73.3% and 55.5%, respectively. Two-yr disease free survival, cancer specific survival, and overall survival rates were 72.5%, 82.3%, and 82.4%, respectively. The small sample size and high caseload of the centre might affect the reproducibility of these results. CONCLUSIONS Our experience supports the feasibility of totally intracorporeal neobladder following RARC. Operative times and perioperative complication rates are likely to be reduced with increasing experience. PATIENT SUMMARY We report the outcomes of our first 45 consecutive patients who underwent robot-assisted radical cystectomy with intracorporeal neobladders. Perioperative, oncologic, and functional outcomes support this technique as a feasible and safe surgical option in tertiary referral centres.


title: The consequences of COVID-19 for gastroenterology nursing.

text: Jennie Burch, Head of Gastrointestinal Nurse Education, St Mark's Hospital, London (jburch1@nhs.net), discusses the ramifications of coronavirus and the guidelines available to professionals working in gastroenterology.


title: Laparoscopic treatment of annular pancreas in adults: report of a case.

text: The annular pancreas in adults is a rare congenital anomaly that is detected after development of complications, such as gastric outlet obstruction, recurrent pancreatitis, and peptic ulcer. Duodenal bypass is the procedure of choice for treating duodenal obstruction caused by the annular pancreas in both children and adults. Duodenoduodenostomy is routinely performed in neonates and children. In adults, duodenojejunostomy or gastrojejunostomy are recommended, because the duodenum is less mobile. We report a case of annular pancreas in a 33-year-old male that was successfully treated with laparoscopic gastrojejunostomy.


title: Impact of intracellular hemin on N-type inactivation of voltage-gated K+ channels.

text: N-type inactivation of voltage-gated K+ channels is conferred by the N-terminal "ball" domains of select pore-forming α subunits or of auxiliary β subunits, and influences electrical cellular excitability. Here, we show that hemin impairs inactivation of K+ channels formed by Kv3.4 α subunits as well as that induced by the subunits Kvβ1.1, Kvβ1.2, and Kvβ3.1 when coexpressed with α subunits of the Kv1 subfamily. In Kvβ1.1, hemin interacts with cysteine and histidine residues in the N terminus (C7 and H10) with high affinity (EC50 100 nM). Similarly, rapid inactivation of Kv4.2 channels induced by the dipeptidyl peptidase-like protein DPP6a is also sensitive to hemin, and the DPP6a mutation C13S eliminates this dependence. The results suggest a common mechanism for a dynamic regulation of Kv channel inactivation by heme/hemin in N-terminal ball domains of Kv α and auxiliary β subunits. Free intracellular heme therefore has the potential to regulate cellular excitability via modulation of Kv channel inactivation.


title: Comparison of the Performance of Common Measures of Weight Regain After Bariatric Surgery for Association With Clinical Outcomes.

text: Importance Estimates of weight regain following bariatric surgery vary widely. Objective To describe weight regain after reaching nadir weight following Roux-en-Y gastric bypass (RYGB) surgery and compare weight regain measures for association with outcomes. Design, Setting, and Participants Prospective cohort study of 2458 adults who underwent bariatric surgery at 10 hospitals in 6 US cities between March 2006 and April 2009. Assessments were conducted within 30 days' presurgery, at 6 months' postsurgery, and then annually until January 2015. Of the 1703 participants who underwent RYGB surgery, 1406 (83%) were followed up for 5 years or longer and had 5 or more weight measurements (excluding those who died or underwent surgical reversal). Exposures Weight regain assessed by 5 continuous measures (weight in kilograms, body mass index [BMI], percentage of presurgery weight, percentage of nadir weight, and percentage of maximum weight lost) and 8 dichotomous measures (per established thresholds) were compared in relation to clinical outcomes based on statistical significance, magnitude of association, and model fit. Main Outcomes and Measures Progression of diabetes, hyperlipidemia, and hypertension and declines in physical and mental health-related quality of life and satisfaction with surgery. Results Among the 1406 participants who underwent RYGB surgery, the median age was 47 years (25th-75th percentile, 38-55 years) and the median BMI was 46.3 (25th-75th percentile, 42.3-51.8) prior to surgery. Most participants were female (80.3%) and white (85.6%). The median follow-up was 6.6 years (25th-75th percentile, 5.9-7.0 years). The median percentage of maximum weight loss was 37.4% (25th-75th percentile, 31.6%-43.3%) of presurgery weight and occurred a median of 2.0 years after RYGB surgery (25th-75th percentile, 1.0-3.2 years). The rate of weight regain was highest during the first year after reaching nadir weight, but weight regain continued to increase throughout follow-up (range, a median of 9.5% of maximum weight lost [25th-75th percentile, 4.7%-17.2%] to 26.8% of maximum weight lost [25th-75th percentile, 16.7%-41.5%] 1 to 5 years after reaching nadir weight). The percentage of participants who regained weight depended on threshold (eg, 5 years after nadir weight, 43.6% regained ≥5 BMI points; 50.2% regained ≥15% of nadir weight; and 67.3% regained ≥20% of maximum weight lost). Compared with other continuous weight regain measures, the percentage of maximum weight lost had the strongest association and best model fit for all outcomes except hyperlipidemia, which had a slightly stronger association with BMI. Of the dichotomous measures, 20% or greater of maximum weight lost performed better or similarly with most of the outcomes, and was the second best measure for hyperlipidemia (after ≥10 kg of weight) and hypertension (after ≥10% of maximum weight lost). Conclusions and Relevance Among a large cohort of adults who underwent RYGB surgery, weight regain quantified as percentage of maximum weight lost performed better for association with most clinical outcomes than the alternatives examined. These findings may inform standardizing the measurement of weight regain in studies of bariatric surgery.


title: Advancing Preparedness for Highly Hazardous Contagious Diseases: Admitting 10 Simulated Patients with MERS-CoV.

text: The Ebola outbreak of 2014-2016 highlighted the need for the development of a more robust healthcare infrastructure in the United States to provide isolation care for patients infected with a highly hazardous contagious disease. Routine exercises and skills practice are required to effectively and safely prepare care teams to confidently treat this special population of patients. The Nebraska Biocontainment Unit (NBU) at Nebraska Medicine in Omaha has been conducting exercises since 2005 when the unit was opened. Previous activities and exercises conducted by the Nebraska Biocontainment Unit have focused on transporting and caring for up to 3 patients with Ebola virus disease or other special pathogens. Changes in regional and national mandates, as well as the increased potential for receiving multiple patients at once, at a single location, have resulted in a greater demand to exercise protocols for the treatment of multiple patients. This article discusses in detail the planning, execution, and outcomes of a full-scale exercise involving 10 simulated patients with a highly infectious pathogen transmitted by the airborne route.


Surgeon preferences for liver transection: is there an ideal technique?


title: Pipeline embolization device deployment via an envoy distal access XB guiding catheter-biaxial platform: A technical note.

text: With the increased reliance on the Pipeline embolization device (PED) for the treatment of complex intracranial aneurysms, our experience in managing intraoperative complications and challenges continues to accumulate amid a scarcity of reports on rescue strategies and innovative techniques. We describe the case of a 50-year-old woman who presented for elective repeat embolization of a right posterior communicating artery aneurysm with some residual aneurysmal filling. During the procedure the patient developed severe vasospasm due to vessel irritation and this led us to proceed to deploy the PED through a biaxial construct composed of the 6 French Envoy MPD DA XB, and the Marksman catheters. The biaxial construct in select patients may provide the required stability while eliminating the need for an intermediate catheter, minimizing embolic risk, and allowing for less irritation to the vessel. Larger studies are required for further validation.


title: Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome.

text: RATIONALE Corticosteroid therapy is commonly used among critically ill patients with Middle East Respiratory Syndrome (MERS), but its impact on outcomes is uncertain. Analyses of observational studies often do not account for patients' clinical condition at the time of corticosteroid therapy initiation. OBJECTIVES To investigate the association of corticosteroid therapy on mortality and on MERS coronavirus RNA clearance in critically ill patients with MERS. METHODS ICU patients with MERs were included from 14 Saudi Arabian centers between September 2012 and October 2015. We performed marginal structural modeling to account for baseline and time-varying confounders. MEASUREMENTS AND MAIN RESULTS Of 309 patients, 151 received corticosteroids. Corticosteroids were initiated at a median of 3.0 days (quartile 1 [Q1]-Q3, 1.0-7.0) from ICU admission. Patients who received corticosteroids were more likely to receive invasive ventilation (141 of 151 [93.4%] vs. 121 of 158 [76.6%]; P < 0.0001) and had higher 90-day crude mortality (112 of 151 [74.2%] vs. 91 of 158 [57.6%]; P = 0.002). Using marginal structural modeling, corticosteroid therapy was not significantly associated with 90-day mortality (adjusted odds ratio, 0.75; 95% confidence interval, 0.52-1.07; P = 0.12) but was associated with delay in MERS coronavirus RNA clearance (adjusted hazard ratio, 0.35; 95% CI, 0.17-0.72; P = 0.005). CONCLUSIONS Corticosteroid therapy in patients with MERS was not associated with a difference in mortality after adjustment for time-varying confounders but was associated with delayed MERS coronavirus RNA clearance. These findings highlight the challenges and importance of adjusting for baseline and time-varying confounders when estimating clinical effects of treatments using observational studies.


Bridging the Gap: Training and Education in the Pathology and Cytopathology Sphere.


title: Variability of interferon-λ induction and antiviral activity in Nipah virus infected differentiated human bronchial epithelial cells of two human donors.

text: Highly pathogenic Nipah virus (NiV) generally causes severe encephalitis in humans. Respiratory symptoms are infrequently observed, likely reflecting variations in infection kinetics in human airways. Supporting this idea, we recently identified individual differences in NiV replication kinetics in cultured airway epithelia from different human donors. As type III interferons (IFN-λ) represent major players in the defence mechanism against viral infection of the respiratory mucosa, we studied IFN-λ induction and antiviral activity in NiV-infected primary differentiated human bronchial epithelial cells (HBEpCs) cultured under air-liquid interface conditions. Our studies revealed that IFN-λ was upregulated in airway epithelia upon NiV infection. We also show that IFN-λ pretreatment efficiently inhibited NiV replication. Interestingly, the antiviral activity of IFN-λ varied in HBEpCs from two different donors. Increased sensitivity to IFN-λ was associated with higher expression levels of IFN-λ receptors, enhanced phosphorylation of STAT1, as well as enhanced induction of interferon-stimulated gene expression. These findings suggest that individual variations in IFN-λ receptor expression affecting IFN responsiveness can play a functional role for NiV replication kinetics in human respiratory epithelial cells of different donors.


title: Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer.

text: BACKGROUND With the well established shift to neoadjuvant treatment for locally advanced rectal cancer, there is increasing focus on the use of radiosensitizers to improve the efficacy and tolerability of radiotherapy. There currently exist few randomized data exploring novel radiosensitizers to improve response and it is unclear what the clinical endpoints of such trials should be. METHODS A qualitative systematic review was performed according to the PRISMA guidelines using preset search criteria across the PubMed, Cochrane and Scopus databases from 1990 to 2017. Additional results were generated from the reference lists of included papers. RESULTS A total of 123 papers were identified, of which 37 were included; a further 60 articles were obtained from additional referencing to give a total of 97 articles. Neoadjuvant radiosensitization for locally advanced rectal cancer using fluoropyrimidine-based chemotherapy remains the standard of treatment. The oral derivative capecitabine has practical advantages over 5-fluorouracil, with equal efficacy, but the addition of a second chemotherapeutic agent has yet to show a consistent significant efficacy benefit in randomized clinical assessment. Preclinical and early-phase trials are progressing with promising novel agents, such as small molecular inhibitors and nanoparticles. CONCLUSION Despite extensive research and promising preclinical studies, a definite further agent in addition to fluoropyrimidines that consistently improves response rate has yet to be found.


title: Together we stand: Suicide risk and suicide prevention among Israeli older adults during and after the COVID-19 world crisis.

text: The outbreak of COVID-19 has increased potential risks for depression and suicide among older adults. In this paper, we discuss the specific risk factors and current status of older adults in Israel in light of the COVID-19 crisis. Following that, we suggest establishing relevant and effective measures for suicide assessment, intervention, and prevention to avert experiences of loneliness, thwarted belongingness, and perceived burdensomeness and thus prevent suicides during and after the crisis. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Correlation between cerebral blood volume values and outcomes in endovascular therapy for acute ischemic stroke.

text: BACKGROUND Neurointerventionalists do not agree about the optimal imaging protocol when evaluating patients with acute stroke for potential endovascular revascularization. Preintervention cerebrovascular blood volume (CBV) has been shown to predict outcomes in patients undergoing intra-arterial stroke therapies. OBJECTIVE To determine whether CBV can predict hemorrhagic transformation and clinical outcomes in patients selected for endovascular therapy for acute ischemic middle cerebral artery (MCA) stroke using a CT perfusion (CTP)-based imaging protocol. METHODS We retrospectively reviewed cases of acute ischemic stroke due to MCA M1 segment occlusion and correlated favorable clinical outcomes (modified Rankin scale (mRS) ≤2) and radiographic outcomes with preintervention CBV values. All patients underwent whole-brain (320-detector-row) CTP imaging, and absolute CBV values of the affected and contralateral MCA territories were obtained separately for the cortical and basal ganglia regions. RESULTS Relative CBV (rCBV) of the MCA cortical regions was significantly lower in patients with poor clinical outcomes than in those with favorable clinical outcomes (0.87±0.21 vs 1.02±0.09, p=0.0003), and a negative correlation was found between rCBV values and mRS score severity. rCBV of the basal ganglia region was significantly lower in patients with hemorrhagic infarction (p=0.004) and parenchymal hematoma (p=0.04) than in those without hemorrhagic transformation. CONCLUSIONS We found that cortical CBV loss is predictive of poor clinical outcomes, whereas basal ganglia CBV loss is predictive of hemorrhagic transformation but without translation into poor clinical outcomes. Our study findings support published results of baseline preintervention CBV as a predictor of outcomes in patients undergoing intra-arterial stroke therapies.


Another New Esophagitis: The Lymphocyte Gets Its Turn.


title: Insect cell technology is a versatile and robust vaccine manufacturing platform.

text: Baculovirus and insect cell culture technologies have mostly been limited to research laboratories for the transient expression of target proteins for drug development purposes. With the renaissance of the vaccine field and the regulatory acceptance of recombinant DNA technology, the baculovirus expression system has been more broadly adopted for the development of subunit vaccines, including virus-like particles. In the numerous clinical trials extensively discussed and cross-referenced in this article, product quality, safety and efficacy have been demonstrated for many candidate vaccines targeting infectious diseases. The 2007 market authorization of Cervarix, a bivalent human papillomavirus virus-like particle vaccine against cervical cancer, was a critical milestone for the regulatory acceptance of insect cell technology in manufacturing human vaccines, opening the door to the approval of more baculovirus-derived vaccines. Insect cell technology is now a dominant platform for veterinary vaccines. This article covers the application of recombinant baculovirus as vectored vaccines to mediate systemic and mucosal immune responses through the display or expression of foreign antigens. We will probably observe increasingly more baculovirus-derived products and market licensing of safe and efficacious vaccines.


title: The Equilibration of PCO2 in Pigs Is Independent of Lung Injury and Hemodynamics.

text: OBJECTIVES In mechanical ventilation, normoventilation in terms of PCO2 can be achieved by titration of the respiratory rate and/or tidal volume. Although a linear relationship has been found between changes in respiratory rate and resulting changes in end-tidal cO2 (△PetCO2) as well as between changes in respiratory rate and equilibration time (teq) for mechanically ventilated patients without lung injury, it is unclear whether a similar relationship holds for acute lung injury or altered hemodynamics. DESIGN We performed a prospective randomized controlled animal study of the change in PetCO2 with changes in respiratory rate in a lung-healthy, lung-injury, lung-healthy + altered hemodynamics, and lung-injury + altered hemodynamics pig model. SETTING University research laboratory. SUBJECTS Twenty mechanically ventilated pigs. INTERVENTIONS Moderate lung injury was induced by injection of oleic acid in 10 randomly assigned pigs, and after the first round of measurements, cardiac output was increased by approximately 30% by constant administration of noradrenalin in both groups. MEASUREMENTS AND MAIN RESULTS We systematically increased and decreased changes in respiratory rate according to a set protocol: +2, -4, +6, -8, +10, -12, +14 breaths/min and awaited equilibration of Petco2. We found a linear relationship between changes in respiratory rate and △PetCO2 as well as between changes in respiratory rate and teq. A two-sample t test resulted in no significant differences between the lung injury and healthy control group before or after hemodynamic intervention. Furthermore, exponential extrapolation allowed prediction of the new PetCO2 equilibrium and teq after 5.7 ± 5.6 min. CONCLUSIONS The transition between PetCO2 equilibria after changes in respiratory rate might not be dependent on moderate lung injury or cardiac output but on the metabolic production or capacity of cO2 stores. Linear relationships previously found for lung-healthy patients and early prediction of PetCO2 equilibration could therefore also be used for the titration of respiratory rate on the PetCO2 for a wider range of pathologies by the physician or an automated ventilation system.


title: Adhesion of Microdroplets on Water-Repellent Surfaces toward the Prevention of Surface Fouling and Pathogen Spreading by Respiratory Droplets.

text: Biofouling caused by the adhesion of respiratory microdroplets generated in sneezing and coughing plays an important role in the spread of many infectious diseases. Although water-repellent surfaces are widely used for the long-term repellency of aqueous solutions, their repellency to pathogen-containing microdroplets is elusive. In this work, microdroplets from picoliter to nanoliter were successfully generated in a controlled manner to mimic the exhaled microdroplets in sneezing and coughing, which allowed us to evaluate the adhesion of microdroplets on both superhydrophobic and lubricant-infused "slippery" surfaces for the first time. The impact and retention of water microdroplets on the two water-repellent surfaces are compared and investigated. Microdroplet-mediated surface biofouling and pathogen transmission were also demonstrated. Our results suggested that the adhesion of microdroplets should be duly considered in the design and application of water-repellent surfaces on biofouling prevention.


title: Nurses' preparedness for infectious disease outbreaks: A literature review and narrative synthesis of qualitative evidence.

text: AIMS AND OBJECTIVES To explore the core components that constitute nurses' preparedness in an epidemic event. BACKGROUND Healthcare service providers have worked to augment efforts to protect the public from the impact of epidemic events. While constituting the major healthcare taskforce, nurses are frequently tasked with fronting the response to an infectious disease outbreak. Given the crucial role of nurses in the management of prevailing epidemics, the constituents of their preparedness in epidemic events should be identified. DESIGN A systematic search was undertaken to identify eligible studies from the literature. A narrative synthesis approach was employed to extract and synthesise findings of the reviewed qualitative studies. METHODS Seven qualitative studies on nurses' experience and perceptions of epidemic events were examined for scientific quality using the Critical Appraisal Skills Programme Qualitative Checklist. Findings of these studies were synthesised adopting a narrative synthesis approach. RESULTS Three interplaying themes were identified as follows: (i) personal resources, (ii) workplace resources and (iii) situational influences. The findings suggest that an effective epidemic outbreak response would require further effort to reinforce the interplay between individual nurses, healthcare institutions and the governments. CONCLUSIONS The practical interplay among individual nurses, healthcare institutions and the governments is crucial in establishing an effective epidemic response. Further research on the understanding of the dynamic process of preparedness development is recommended to set future directions in research. RELEVANCE TO CLINICAL PRACTICE This study offers important insights for devising future strategies in enhancing nurses' preparedness and response to an epidemic event. These include recommendations on providing education and training to nurses regarding infectious diseases, fostering institutional assistance and support in an outbreak and revising government policies and planning.


title: Thermal ablation: update and technique at a high-volume institution.

text: In the era of nephron-sparing surgery for small renal tumors, thermal ablation is gaining popularity. Both cryoablation and radiofrequency ablation have well-demonstrated short-term oncologic efficacy and safety. This article shares the current literature and the radiofrequency ablation technique at a high-volume institution. Cases are presented that illustrate solutions to obstacles frequently encountered during percutaneous ablation of renal masses.


title: Sidestream capnographic monitoring reduces the incidence of arterial oxygen desaturation during propofol ambulatory anesthesia for surgical abortion.

text: BACKGROUND This study investigated whether early intervention based on additional use of sidestream capnography could reduce the incidence of oxygen desaturation and hypoxic events in patients receiving propofol anesthesia during surgical abortion. MATERIAL/METHODS We recruited 704 ASAI-III female patients, 18-52 years old and scheduled for planned painless surgical abortion, and randomized them into a control group (n=359) receiving standard monitoring and an experimental group (n=341) receiving standard monitoring and additional capnography. Exclusion criteria were preexisting cardiovascular disease, preexisting hypotension, bradycardia or arrhythmia, and drug allergy. Anesthesia was induced in all patients with propofol using target-controlled infusion at a target propofol plasma concentration of 4 μg/ml. All patients received flurbiprofen axetil 50 mg and 0.5 μg/kg fentanyl 5 min before anesthesia. Bispectral index was used and maintained between 45 and 60. Main outcome measures were apnea or abnormal ventilation status, rate of oxygen desaturation, occurrence of hypoxia and severe hypoxia, and perioperative side effects. RESULTS The experimental group had significantly higher rate of apnea or abnormal ventilation, significantly lower rate of oxygen desaturation, and significant lower occurrence of hypoxia and severe hypoxia compared to the control group. We found no statistically significant differences between the 2 groups in the rates of increased oxygen supplementation, assisted ventilation, bradycardia, hypotension, dosage of atropine, dosage of ephedrine or phenylephrine, and the amount of propofol consumed. CONCLUSIONS Sidestream capnographic monitoring improves early detection of alterations in ventilation parameters and reduces the incidence of oxygen desaturation and hypoxemia resulting from propofol anesthesia during surgical abortion.


Pakistan's Combat and Comeback Against COVID-19.


title: Design of Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS).

text: RATIONALE Cryptogenic ischemic strokes constitute 20-30% of ischemic strokes, the majority of which are embolic strokes of undetermined source. The standard preventive treatment in these patients is usually acetylsalicylic acid. AIM The Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) is designed to determine whether the oral thrombin inhibitor dabigatran, taken within three-months after embolic stroke of undetermined source, is superior to acetylsalicylic acid for prevention of recurrent stroke and to characterize the safety of dabigatran in this setting. DESIGN Prospective, randomized, double-blind, multicenter trial in approximately 6000 patients and 550 centers with embolic stroke of undetermined source. Subjects are randomized to dabigatran or acetylsalicylic acid and treated for an expected minimum of six-months and up to approximately three-years. It is an event-driven trial aiming for 353 adjudicated primary outcome events. STUDY OUTCOMES The primary efficacy outcome is time to first recurrent stroke (ischemic, hemorrhagic, or unspecified). Key secondary outcomes are time to first ischemic stroke and time to first occurrence in the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death. The primary safety outcome is major hemorrhage, including symptomatic intracranial hemorrhage. DISCUSSION Acetylsalicylic acid is the most common antithrombotic given to patients with embolic strokes of undetermined source to reduce recurrence risk. This trial will determine whether anticoagulation with dabigatran is more effective than acetylsalicylic acid, and acceptably safe.


title: Awake intubation and awake prone positioning of a morbidly obese patient for lumbar spine surgery.

text: We describe the awake fibreoptic intubation followed by awake prone positioning of a woman weighing 180 kg with body mass index of 62 kg.m(-2) requiring emergency lumbar discectomy for cauda equina syndrome. This approach was taken to overcome difficulties in transfering an anaesthetised patient on to the operating table. Following topical anaesthesia with lidocaine and low-dose remifentanil infusion, oral intubation was performed using a split oral airway to guide the fibrescope. The patient positioned herself on the Jackson operating table, following which general anaesthesia was induced. This technique optimised protection of the patient's eyes and other pressure areas while preventing undue cardiorespiratory compromise. The patient tolerated the procedure well, and later confirmed that she would consent to undergoing the same procedure again if further surgery became necessary.


title: Endocrine significance of SARS-CoV-2's reliance on ACE2.

text: The current COVID-19 pandemic is the most disruptive event in the last 50 years with global impact on healthcare and world economies. It is caused by SARS-CoV-2, a coronavirus that uses angiotensin converting enzyme 2 (ACE2), as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review, summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, pituitary and thyroid diseases.


title: Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: results from a single Italian Centre study on tocilizumab versus standard of care

text: OBJECTIVE: Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or “cytokine storm”. Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. METHODS: Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). RESULTS: In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were 3 deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and 1 serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p < 0.0001 for both) and higher neutrophils and lower lymphocyte levels (p = 0.04 and p = 0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. CONCLUSION: Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key.


title: Spatial methods for infectious disease outbreak investigations: systematic literature review.

text: Investigations of infectious disease outbreaks are conventionally framed in terms of person, time and place. Although geographic information systems have increased the range of tools available, spatial analyses are used relatively infrequently. We conducted a systematic review of published reports of outbreak investigations worldwide to estimate the prevalence of spatial methods, describe the techniques applied and explore their utility. We identified 80 reports using spatial methods published between 1979 and 2013, ca 0.4% of the total number of published outbreaks. Environmental or waterborne infections were the most commonly investigated, and most reports were from the United Kingdom. A range of techniques were used, including simple dot maps, cluster analyses and modelling approaches. Spatial tools were usefully applied throughout investigations, from initial confirmation of the outbreak to describing and analysing cases and communicating findings. They provided valuable insights that led to public health actions, but there is scope for much wider implementation and development of new methods.


title: Transvaginal specimen extraction after combined laparoscopic splenectomy and hysterectomy: Introduction to NOSE (Natural Orifice Specimen Extraction) in a community hospital.

text: INTRODUCTION Developments in the field of minimally invasive surgery have led to interest in NOTES (natural orifice transluminal endoscopic surgery). Even as technologies continue to evolve and develop, interest in some of the advantages of specimen retrieval transvaginally has been roused and we describe a case of combined laparoscopic splenectomy and hysterectomy with transvaginal retrieval of both specimens. PRESENTATION OF CASE Patient underwent laparoscopic splenectomy and robot-assisted hysterectomy with transvaginal delivery of specimens. Total operative time was 245min with no complications. Closure of the colpotomy was achieved laparoscopically. Post-operative course was unremarkable. Patient has done well clinically at 18 months follow-up except for an episode of post-coital spotting, which resolved spontaneously. DISCUSSION We explored the technical feasibility of concurrent laparoscopic splenectomy and hysterectomy along with transvaginal retrieval of both solid organs without morcellation. We wanted to illustrate the fact that transvaginal organ extraction may be performed safely in a community or district hospital with standard instruments without incurring additional cost, morbidity or increased operating time. CONCLUSION Transvaginal specimen retrieval was technically easy to accomplish. Our patient has not experienced any infectious complications or sexual dysfunction to date. For surgeons exploring an alternative to transabdominal specimen retrieval, transvaginal NOSE is an attractive proposition with several advantages. When combined with a gynecological procedure that involves a colpotomy, this may present a unique opportunity to explore the utility of NOSE.


title: Stomach intestinal pylorus sparing surgery (SIPS) with laparoscopic fundoplication (LF): a new approach to gastroesophageal reflux disease (GERD) in the setting of morbid obesity.

text: The increase in the prevalence of obesity and gastroesophageal reflux disease (GERD) has paralleled one another. Laparoscopic fundoplication (LF) (Nissen or Toupet) is a minimally invasive form of anti-reflux surgery. The duodenal switch is a highly effective weight loss surgery with a proven record of long term weight loss success. However, fundoplication alone does not give satisfactory results when used for GERD in morbidly obese patients. Here we present a novel approach combining stomach intestinal pylorus sparing surgery (SIPS) with LF for morbidly obese patients with GERD. The data from patients who underwent the SIPS procedure along with LF in past year was retrospectively analyzed. The variables collected were age, sex, height, weight, intra-operative and post-operative complications, length of stay, operative time, and estimated blood loss. All revisions were excluded. Descriptive statistics such as mean and standard deviation were used to analyze the data. The total sample size of the study was 5 patients, with a mean age of 59.6 ± 16.4 years, a mean weight of 292.1 ± 73.6 lbs., and a mean body mass index (BMI) of 43.4 ± 6.3. Weight loss patterns were the same as those without LF. All the 5 patients had resolution or improvement in their GERD symptoms within 6 months. SIPS with LF provides substantial and sustained weight loss and GERD resolution. Long term follow ups and further study on this novel surgical technique is recommended.


title: The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review.

text: Lactate's role in the brain is understood as a contributor to brain energy metabolism, but it may also regulate the cerebral microcirculation. The purpose of this systematic review was to evaluate evidence of lactate as a physiological effector within the normal cerebral microcirculation in reports ranging from in vitro experiments to in vivo studies in animals and humans. Following pre-registration of a review protocol, we systematically searched the PubMed, EMBASE, and Cochrane databases for literature covering themes of 'lactate', 'the brain', and 'microcirculation'. Abstracts were screened, and data extracted independently by two individuals. We excluded studies evaluating lactate in disease models. Twenty-eight papers were identified, 18 of which were in vivo animal experiments (65%), four on human studies (14%), and six on in vitro or ex vivo experiments (21%). Approximately half of the papers identified lactate as an augmenter of the hyperemic response to functional activation by a visual stimulus or as an instigator of hyperemia in a dose-dependent manner, without external stimulation. The mechanisms are likely to be coupled to NAD+ /NADH redox state influencing the production of nitric oxide. Unfortunately, only 38% of these studies demonstrated any control for bias, which makes reliable generalizations of the conclusions insecure. This systematic review identifies that lactate may act as a dose-dependent regulator of cerebral microcirculation by augmenting the hyperemic response to functional activation below 5 mmol/kg, and by initiating a hyperemic response above 5 mmol/kg. OPEN SCIENCE BADGES: This article has received a badge for *Pre-registration* because it made the data publicly available. The data can be accessed at www.radboudumc.nl/getmedia/53625326-d1df-432c-980f-27c7c80d1a90/THollyer_lactate_protocol.aspx. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.


title: Management of gastric conduit dehiscence with self-expanding metal stents: a case report on salvaging the gastric conduit.

text: BACKGROUND Three-hole minimally invasive esophagectomy (3HMIE) is one of the most radical procedures in gastrointestinal surgery. It involves thoracoscopic dissection of the esophagus followed by creation of a gastric conduit in the abdomen with anastomosis in the neck, and is associated with significant morbidity. Gastric conduit dehiscence is one of the most morbid complications following esophagectomy. Historically, the standard of care in this situation has been conduit diversion with delayed esophageal reconstruction. CASE PRESENTATION Here, we report two patients with a timely diagnosis of gastric conduit dehiscence of staple line after 3HMIE who were salvaged successfully with endoscopic placement of self-expanding metal stents. CONCLUSION Endoscopic stents may be used in selected cases of gastric conduit dehiscence after 3HMIE to salvage the conduit.


title: Immunoinformatics and its relevance to understanding human immune disease.

text: Immunology research is characterized by the production of increasingly vast amounts of data, fuelled by genomics and proteomics projects and large-scale screening of pathogen- and antigen-host interactions. The need to store, manage and analyze this rapidly growing resource of experimental, clinical and epidemiologic data has given rise to the field known as immunoinformatics. Immunoinformatics represents computational methods and resources that are used in the study of immune function. It lies at the intersection of experimental and computational sciences and encompasses domain-specific databases, computational models and strategies drawn from artificial intelligence. For example, computational or artificial intelligence models are increasingly being used to simulate and improve our understanding of immune system behavior, such as antigen processing and presentation, as well as for analysis of host and pathogen genomes. Systemic models focus on simulating the behavior of cells or whole organs and can be used for applications such as tracking the course of infection or optimization of immunization protocols. Immunomics, the large-scale screening of immune processes, which includes powerful immunoinformatic tools, offers great promise for future translation of basic immunology research advances into clinical practice. Immunoinformatics is central to the research fields of immunogenomics, immunoproteomics and computational vaccinology.


title: Technical Feasibility of Enterotomy Closure with Knotless Barbed Suture Material (V-Loc 180) in Esophagojejunostomy Using Linear Stapler during Totally Laparoscopic Total Gastrectomy for Gastric Cancer.

text: PURPOSE Intra-corporeal esophagojejunostomy (EJ) using a linear stapler creates a stapler entry hole that requires secure closure during the totally laparoscopic total gastrectomy (TLTG) procedure for gastric cancer. Since a standard method has not been established yet, the feasibility of using V-loc 180 (Covidien, Mansfield, MA, USA) suture material was evaluated in this study. MATERIALS AND METHODS During January 2012 to March 2015, 25 patients who underwent linear stapling EJ and V-loc 180 closure of remaining enterotomy were included in this study. Basic clinico-pathological characteristics, surgical outcomes, and short-term complications were analyzed. RESULTS The mean patient age was 60.4 ± 8.5 years. Nineteen males and six females were included in this study. The mean body mass index was 25.3 ± 2.3 kg/m2. There were 22 stage-I, 2 stage-II, and 1 stage-III gastric cancer patients. The mean operation time was 240.5 ± 44.6 min, and the time for anastomosis was 38.8 ± 11.2 min. The procedures were successfully performed in all cases without any intra-operative complications. There was one case of EJ leakage that occurred at the corner of EJ staple line and not at the enterotomy closure site. CONCLUSIONS The closure of the remaining enterotomy site using V-loc 180 suture following linear stapler EJ is technically feasible and safe during the TLTG procedure. However, further experience and results from other surgeons are necessary to generalize this procedure.


title: Epidemiology of COVID-19 in an Urban Dialysis Center.

text: BACKGROUND During the coronavirus disease 2019 (COVID-19) epidemic, many countries have instituted population-wide measures for social distancing. The requirement of patients on dialysis for regular treatment in settings typically not conducive to social distancing may increase their vulnerability to COVID-19. METHODS Over a 6-week period, we recorded new COVID-19 infections and outcomes for all adult patients receiving dialysis in a large dialysis center. Rapidly introduced control measures included a two-stage routine screening process at dialysis entry (temperature and symptom check, with possible cases segregated within the unit and tested for SARS-CoV-2), isolated dialysis in a separate unit for patients with infection, and universal precautions that included masks for dialysis nursing staff. RESULTS Of 1530 patients (median age 66 years; 58.2% men) receiving dialysis, 300 (19.6%) developed COVID-19 infection, creating a large demand for isolated outpatient dialysis and inpatient beds. An analysis that included 1219 patients attending satellite dialysis clinics found that older age was a risk factor for infection. COVID-19 infection was substantially more likely to occur among patients on in-center dialysis compared with those dialyzing at home. We observed clustering in specific units and on specific shifts, with possible implications for aspects of service design, and high rates of nursing staff illness. A predictive epidemic model estimated a reproduction number of 2.2; cumulative cases deviated favorably from the model from the fourth week, suggesting that the implemented measures controlled transmission. CONCLUSIONS The COVID-19 epidemic affected a large proportion of patients at this dialysis center, creating service pressures exacerbated by nursing staff illness. Details of the control strategy and characteristics of this epidemic may be useful for dialysis providers and other institutions providing patient care.


Student mental health in the midst of the COVID-19 pandemic: A call for further research and immediate solutions.


Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines: Setting Expectations Appropriately.


title: No infectious risk of COVID-19 patients with long-term fecal 2019-nCoV nucleic acid positive.

text: OBJECTIVE It has recently been reported that some COVID-19 patients have long-term positive fecal nucleic acid after discharging from the hospital with negative nucleic acid in the respiratory tract, but it is unclear whether COVID-19 patients with positive long-term fecal nucleic acid tests have the risk of self-infection. PATIENTS AND METHODS From January 25, 2020 to March 9, 2020, 5 COVID-19 patients with negative respiratory tract nucleic acid and positive fecal nucleic acid were observed and studied to explore whether these patients can re-infect themselves. Five patients with COVID-19 accompanied by diarrhea as the main gastrointestinal symptoms were carefully observed through clinical symptoms, imaging and other auxiliary examinations. The RT-PCR technology was used to continuously detect fecal and respiratory viral nucleic acids. The IgM antibody was detected on the 7th day of admission and IgM/IgG at the time of discharge. RESULTS All 5 patients had symptoms of fever and diarrhea upon admission. The fecal nucleic acid was positive, as well as the throat swab was positive. All COVID-19 patients had positive IgM antibodies on the 7th day of admission and positive IgM and IgG at the time of discharge, and there were no abnormalities in the gastrointestinal examination on discharge. All 5 fecal nucleic acid tests were positive at the time of discharge. After continuous dynamic follow-up for 3-15 days, no clinical symptoms recurred, and the last nucleic acid test was negative. CONCLUSIONS There is no risk of self-infection for COVID-19 patients with long-term 2019-nCoV nucleic acid positive in feces.


title: Protective immunity to H7N9 influenza viruses elicited by synthetic DNA vaccine.

text: Despite an intensive vaccine program influenza infections remain a major health problem, due to the viruses' ability to change its envelope glycoprotein hemagglutinin (HA), through shift and drift, permitting influenza to escape protection induced by current vaccines or natural immunity. Recently a new variant, H7N9, has emerged in China causing global concern. First, there have been more than 130 laboratory-confirmed human infections resulting in an alarmingly high death rate (32.3%). Second, genetic changes found in H7N9 appear to be associated with enabling avian influenza viruses to spread more effectively in mammals, thus transmitting infections on a larger scale. Currently, no vaccines or drugs are effectively able to target H7N9. Here, we report the rapid development of a synthetic consensus DNA vaccine (pH7HA) to elicit potent protective immunity against the H7N9 viruses. We show that pH7HA induces broad antibody responses that bind to divergent HAs from multiple new members of the H7N9 family. These antibody responses result in high-titer HAI against H7N9. Simultaneously, this vaccine induces potent polyfunctional effector CD4 and CD8T cell memory responses. Animals vaccinated with pH7HA are completely protected from H7N9 virus infection and any morbidity associated with lethal challenge. This study establishes that this synthetic consensus DNA vaccine represents a new tool for targeting emerging infection, and more importantly, its design, testing and development into seed stock for vaccine production in a few days in the pandemic setting has significant implications for the rapid deployment of vaccines protecting against emerging infectious diseases.


title: Epstein-barr virus encodes three bona fide ubiquitin-specific proteases.

text: Manipulation of the ubiquitin proteasome system (UPS) is emerging as a common theme in viral pathogenesis. Some viruses have been shown to encode functional homologs of UPS enzymes, suggesting that a systematic identification of these products may provide new insights into virus-host cell interactions. Ubiquitin-specific proteases, collectively known as deubiquitinating enzymes (DUBs), regulate the activity of the UPS by hydrolyzing ubiquitin peptide or isopeptide bonds. The prediction of viral DUBs based on sequence similarity with known enzymes is hampered by the diversity of viral genomes. In this study sequence alignments, pattern searches, and hidden Markov models were developed for the conserved C- and H-boxes of the known DUB families and used to search the open reading frames (ORFs) of Epstein-Barr virus (EBV), a large gammaherpesvirus that has been implicated in the pathogenesis of a broad spectrum of human malignancies of lymphoid and epithelial cell origin. The searches identified a limited number of EBV ORFs that contain putative DUB catalytic domains. DUB activity was confirmed by functional assays and mutation analysis for three high scoring candidates, supporting the usefulness of this bioinformatics approach in predicting distant homologues of cellular enzymes.


title: Bridging Therapy Versus Direct Mechanical Thrombectomy in Patients with Acute Ischemic Stroke due to Middle Cerebral Artery Occlusion: A Clinical-Histological Analysis of Retrieved Thrombi.

text: Mechanical thrombectomy (MT) is effective in managing patients with acute ischemic stroke (AIS) caused by large-vessel occlusions and allows for valuable histological analysis of thrombi. However, whether bridging therapy (pretreatment with intravenous thrombolysis before MT) provides additional benefits in patients with middle cerebral artery (MCA) occlusion remains unclear. Therefore, this study aimed to compare the effects of direct MT and bridging therapy, and to elucidate the correlation between thrombus composition and stroke subtypes. Seventy-three patients with acute ischemic stroke who received MT, were eligible for intravenous thrombolysis, and had MCA occlusion were included. We matched 21 direct MT patients with 21 bridging therapy patients using propensity score matching and compared their 3rd-month clinical outcomes. All MCA thrombi (n = 45) were histologically analyzed, and the red blood cell (RBC) and fibrin percentages were quantified. We compared the clot composition according to stroke etiology (large-artery atherosclerosis and cardioembolism) and intravenous thrombolysis application. The baseline characteristics showed no difference between groups except for a higher atrial fibrillation rate and NIHSS score on admission in the direct MT group. We performed a supportive analysis using propensity score matching but could not find any differences in the functional outcome, mortality, and intracerebral hemorrhage. In the histological clot analysis, the cardioembolic clots without intravenous thrombolysis pretreatment had higher RBC (P = 0.042) and lower fibrin (P = 0.042) percentages than the large-artery atherosclerosis thrombi. Similar findings were observed in the thrombi treated with recombinant tissue plasminogen activator (P = 0.012). In conclusion, there was no difference in the functional outcomes between the direct MT and bridging therapy groups. However, randomized trials are needed to elucidate the high ratio of cardioembolism subtype in our group of patients. The histological MCA thrombus composition differed between cardioembolism and large-artery atherosclerosis, and this finding provides valuable information on the underlying pathogenesis and thrombus origin.


title: Magnetic-assisted single-port sleeve gastrectomy.

text: BACKGROUND Sleeve gastrectomy is a recent, purely restrictive procedure in bariatric surgery that has shown results similar to gastric bypass over the short and middle term. At the same time, single-port access surgery has fostered the development of new techniques and methods seeking better cosmetic results and less postoperative pain, while maintaining the satisfactory results obtained by the standard laparoscopic approach. One of the problems associated to single-access surgery is the lack of traction and the difficulties to retract the liver. The authors' aim was to try to avoid additional trocars or sutures in order to perform pure single-incision surgery, using 2 magnetic forceps. METHODS The authors present the case of a 51-year-old morbidly obese female (body mass index = 44.82) who underwent a pure single-access laparoscopic sleeve gastrectomy with no additional trocars or sutures and assisted by 2 neodymium magnetic forceps: one to retract the liver and the other to retract the stomach in order to provide sufficient triangulation for adequate exposure of the surgical field during dissection. RESULTS The procedure was completed in 120 minutes. No preoperative or postoperative complications were recorded, and the patient was discharged 2 days after surgery. CONCLUSION Single-port access sleeve gastrectomy assisted by magnetic forceps is feasible and safe in the hands of experienced laparoscopic surgeons, solving one of the problems associated to this type of surgery, that is, the need for an additional trocar and needles or sutures to retract the liver and stomach in order to perform the operation.