title: Biosynthetic Nanostructured Cellulose Patch for Chest Wall Reconstruction: Five-Month Follow-up in a Porcine Model.

text: PURPOSE Ideal approaches and materials for reconstruction of large chest wall defects remain a topic of debate. We sought to explore the suitability of a reinforced nanostructured cellulose (NC) patch for chest wall reconstruction in an animal model. MATERIALS AND METHODS In four domestic pigs, a standardized 10 × 10 cm chest wall defect was created by resecting three rib segments. Subsequently the defect was reconstructed via a biosynthetic NC patch (16 × 12 cm) reinforced by polytetrafluoroethylene mesh. After 1, 2, 4, and 5 months respectively, gross examination of NC patches was performed following sacrifice of the animals. Specimens of NC patches and surrounding connective tissue underwent histological examinations after staining with Hematoxylin-eosin and Elastica van Gieson. RESULTS All animals survived their observation period without encountering major adverse events. On gross examination all NC patches were intact and well integrated into the surrounding tissue. Histological examination showed clearly demarked zones of foreign body reaction at the patch/host-tissue interface. After 5 months a slight increase in foreign body reaction, fibrous capsule formation and cellular infiltration were observed. No signs of fibroblast proliferation or neovascularization were seen within NC patches at any point. CONCLUSIONS Our findings suggest a quick healing process and good overall biocompatibility following NC patch implantation.NC might prove an efficient and suitable biomaterial for complex chest wall reconstruction.


title: Human and Murine IFIT1 Proteins Do Not Restrict Infection of Negative-Sense RNA Viruses of the Orthomyxoviridae, Bunyaviridae, and Filoviridae Families.

text: UNLABELLED Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5'-triphosphates (5'-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5'-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infected Ifit1(-/-) and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virus [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack of Ifit1 gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical between Ifit1(-/-) and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5' ends of IAV gene segments. The affinity for 5'-ppp RNA was approximately 10-fold lower than that for non-2'-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses. IMPORTANCE Negative-sense RNA viruses, including influenza virus and Ebola virus, have been responsible for some of the most deadly outbreaks in recent history. The host interferon response and induction of antiviral genes contribute to the control of infections by these viruses. IFIT1 is highly induced after virus infection and reportedly has antiviral activity against several RNA and DNA viruses. However, its role in restricting infection by negative-sense RNA viruses remains unclear. In this study, we evaluated the ability of IFIT1 to inhibit negative-sense RNA virus replication and pathogenesis both in vitro and in vivo. Detailed cell culture and animal studies demonstrated that IFIT1 is not a dominant restriction factor against three different families of negative-sense RNA viruses.


Safe anaesthesia for ERCP.


title: Polish Society of Gynecology and Obstetrics statement on safety measures and performance of ultrasound examinations in obstetrics and gynecology during the SARS-CoV-2 pandemic.

text: We present recommendations on performance and safety measures of ultrasound examinations in obstetrics and gynecology during the SARS COV-2 pandemic. The statement was prepared based on the current knowledge on the coronavirus by the Ultrasound Section of the Polish Society of Obstetrics and Gynecology. It has to be noted that the presented guidance is based on limited evidence and is primarily based on experiences published by authors from areas most affected by the virus thus far, such as China, Singapore, Hong Kong, and Italy. We realize that the pandemic situation is very dynamic. New data is published every day. Despite the imposed limitations related to the necessity of social distancing, it is crucial to remember that providing optimal care in safe conditions should remain the primary goal of healthcare providers. We plan to update the current guidelines as the situation develops.


title: Gold nanocages covered with thermally-responsive polymers for controlled release by high-intensity focused ultrasound.

text: This paper describes the use of Au nanocages covered with smart, thermally-responsive polymers for controlled release with high-intensity focused ultrasound (HIFU). HIFU is a highly precise medical procedure that uses focused ultrasound to heat and destroy pathogenic tissue rapidly and locally in a non-invasive or minimally invasive manner. The released dosage could be remotely controlled by manipulating the power of HIFU and/or the duration of exposure. We demonstrated localized release within the focal volume of HIFU by using gelatin phantom samples containing dye-loaded Au nanocages. By placing chicken breast tissues on top of the phantoms, we further demonstrated the feasibility of this system for controlled release at depths up to 30 mm. Because it can penetrate more deeply into soft tissues than near-infrared light, HIFU is a potentially more effective external stimulus for rapid, on-demand drug release.


title: When patients refuse COVID-19 testing, quarantine, and social distancing in inpatient psychiatry: clinical and ethical challenges.

text: The COVID-19 pandemic has introduced new ethical challenges in the care of patients with serious psychiatric illness who require inpatient treatment and who may have beeen exposed to COVID-19 or have mild to moderate COVID-19 but refuse testing and adherence to infection prevention protocols. Such situations increase the risk of infection to other patients and staff on psychiatric inpatient units. We discuss medical and ethical considerations for navigating this dilemma and offer a set of policy recommendations.


title: Natural killer T cell facilitated engraftment of rat skin but not islet xenografts in mice.

text: BACKGROUND We have studied cellular components required for xenograft survival mediated by anti-CD154 monoclonal antibody (mAb) and a transfusion of donor spleen cells and found that the elimination of CD4(+) but not CD8(+) cells significantly improves graft survival. A contribution of other cellular components, such as natural killer (NK) cells and natural killer T (NKT) cells, for costimulation blockade-induced xenograft survival has not been clearly defined. We therefore tested the hypothesis that NK or NKT cells would promote rat islet and skin xenograft acceptance in mice. METHODS Lewis rat islets or skin was transplanted into wild type B6 mice or into B6 mice that were Jalpha18(null), CD1(null), or beta2 microglobulin (beta2M)(null) NK 1.1 depleted, or perforin(null). Graft recipients were pretreated with an infusion of donor derived spleen cells and a brief course of anti-CD154 mAb treatments. Additional groups received mAb or cells only. RESULTS We first observed that the depletion of NK1.1 cells does not significantly interfere with graft survival in C57BL/6 (B6) mice. We used NKT cell deficient B6 mice to test the hypothesis that NKT cells are involved in islet and skin xenograft survival in our model. These mice bear a null mutation in the gene for the Jalpha18 component of the T-cell receptor. The component is uniquely associated with NKT cells. We found no difference in islet xenograft survival between Jalpha18(null) and wild type B6 mice. In contrast, median skin graft survival appeared shorter in Jalpha18(null) recipients. These data imply a role for Jalpha18(+) NKT cells in skin xenograft survival in treated mice. In order to confirm this inference, we tested skin xenograft survival in B6 CD1(null) mice because NKT cells are CD1 restricted. Results of these trials demonstrate that the absence of CD1(+) cells adversely affects rat skin graft survival. An additional assay in beta2M(null) mice demonstrated a requirement for major histocompatibility complex (MHC) class I expression in the graft host, and we demonstrate that CD1 is the requisite MHC component. We further demonstrated that, unlike reports for allograft survival, skin xenograft survival does not require perforin-secreting NK cells. CONCLUSIONS We conclude that MHC class I(+) CD1(+) Jalpha18(+) NKT cells promote the survival of rat skin but not rat islet xenografts. These studies implicate different mechanisms for inducing and maintaining islet vs. skin xenograft survival in mice treated with donor antigen and anti-CD154 mAb, and further indicate a role for NKT cells but not NK cells in skin xenograft survival.


docid: rsrmwjtt

title: Murine coronavirus induces type I interferon in oligodendrocytes through recognition by RIG-I and MDA5.

text: The murine coronavirus mouse hepatitis virus (MHV) induced the expression of type I interferon (alpha/beta interferon [IFN-alpha/beta]) in mouse oligodendrocytic N20.1 cells. This induction is completely dependent on virus replication, since infection with UV light-inactivated virus could no longer induce IFN-alpha/beta. We show that MHV infection activated both transcription factors, the IFN regulatory factor 3 (IRF-3) and nuclear factor kappaB (NF-kappaB), as evidenced by phosphorylation and nuclear translocation of IRF-3 and an increased promoter binding activity for IRF-3 and NF-kappaB. Furthermore, the cytoplasmic pattern recognition receptor retinoic acid-inducible gene I (RIG-I) was induced by MHV infection. Knockdown of RIG-I by small interfering RNAs blocked the activation of IRF-3 and subsequent IFN-alpha/beta production induced by MHV infection. Knockdown of another cytoplasmic receptor, the melanoma-differentiation-associated gene 5 (MDA5), by small interfering RNAs also blocked IFN-beta induction. These results demonstrate that MHV is recognized by both RIG-I and MDA5 and induces IFN-alpha/beta through the activation of the IRF-3 signaling pathway. However, knockdown of RIG-I only partially blocked NF-kappaB activity induced by MHV infection and inhibition of NF-kappaB activity by a decoy peptide inhibitor had little effect on IFN-alpha/beta production. These data suggest that activation of the NF-kappaB pathway might not play a critical role in IFN-alpha/beta induction by MHV infection in oligodendrocytes.


docid: dwyeqkfx

title: Oxygen supplies in disaster management.

text: Mass casualty events and disasters, both natural and human-generated, occur frequently around the world and can generate scores of injured or ill victims in need of resources. Of the available medical supplies, oxygen remains the critical consumable resource in disaster management. Strategic management of oxygen supplies in disaster scenarios remains a priority. Hospitals have large supplies of liquid oxygen and a supply of compressed gas oxygen cylinders that allow several days of reserve, but a large influx of patients from a disaster can strain these resources. Most backup liquid oxygen supplies are attached to the main liquid system and supply line. In the event of damage to the main system, the reserve supply is rendered useless. The Strategic National Stockpile supplies medications, medical supplies, and equipment to disaster areas, but it does not supply oxygen. Contracted vendors can deliver oxygen to alternate care facilities in disaster areas, in the form of concentrators, compressed gas cylinders, and liquid oxygen. Planning for oxygen needs following a disaster still presents a substantial challenge, but alternate care facilities have proven to be valuable in relieving pressure from the mass influx of patients into hospitals, especially for those on home oxygen who require only an electrical source to power their oxygen concentrator.


title: Delayed laparoscopic repair of a traumatic flank hernia: A case report and review of the literature.

text: INTRODUCTION The traumatic abdominal wall hernia is a rare injury typically due to a high-energy blunt trauma mechanism. There is a lack of consensus on the appropriate management of these patients. PRESENTATION OF THE CASE A 43-year-old male was evaluated for a left flank bulge eight months after a motorcycle collision. He was diagnosed with a traumatic abdominal wall hernia at time of injury that was managed non-operatively. He noticed a left flank bulge two months after his collision that progressively worsened in size and in discomfort. The patient underwent laparoscopic repair of the traumatic flank hernia. His postoperative course was uneventful and there was no recurrence at 3 years. DISCUSSION Historically, exploratory laparotomy was considered necessary in patients diagnosed with a traumatic abdominal wall hernia at time of injury due to the high-percentage of concomitant intra-abdominal injuries. More recent studies suggest that some patients with a traumatic abdominal wall hernia may be safely managed non-operatively. A minority of these patients will require surgery for symptoms or complications related to the hernia and laparoscopic repair performed in a delayed fashion appears to have improved outcomes when compared to those that undergo repair at time of injury. CONCLUSION There is growing evidence supporting a non-operative management strategy in patients with a traumatic abdominal wall hernia who do not have a clear indication for abdominal surgery. These patients may be safely observed with delayed laparoscopic repair using synthetic mesh reserved for traumatic abdominal wall hernias that become symptomatic.


title: Contemporary prevalence of infectious agents in laboratory mice and rats.

text: Periodic health screening of rodents used in research is necessary due to the consequences of unwanted infections. One determinant of the risk of infection for any given agent is its prevalence; other factors being equal, a prevalent agent is more likely than a rare one to be introduced to a research facility and result in infection. As an indicator of contemporary prevalence in laboratory populations of rats and mice, the rate of positive results in the samples received at a major commercial rodent diagnostic laboratory was compiled for this paper. Although samples from laboratory rodent vendors have been excluded, results are tabulated from samples from more than 500,000 mice and 80,000 rats submitted over several years from pharmaceutical, biotechnology, academic, and governmental institutions in North America and Europe, allowing meaningful determination of which agents are common in the research environment versus which agents are rare. In mice, commonly detected infectious agents include mouse norovirus, the parvoviruses, mouse hepatitis virus, rotavirus, Theiler's murine encephalomyelitis virus, Helicobacter spp., Pasteurella pneumotropica, and pinworms. In rats, commonly detected infectious agents include 'rat respiratory virus', the parvoviruses, rat theilovirus, Helicobacter spp., P. pneumotropica, and pinworms. A risk-based allocation of health-monitoring resources should concentrate frequency and/or sample size on these high-risk agents, and monitor less frequently for the remaining, lower-risk, infectious agents.


title: HIV-1 transmission by dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is regulated by determinants in the carbohydrate recognition domain that are absent in liver/lymph node-SIGN (L-SIGN).

text: In this study, we identify determinants in dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) necessary for human immunodeficiency virus, type 1 (HIV-1), transmission. Although human B cell lines expressing DC-SIGN efficiently capture and transmit HIV-1 to susceptible target cells, cells expressing the related molecule liver/lymph node-specific ICAM-3-grabbing nonintegrin (L-SIGN) do not. To understand the differences between DC-SIGN and L-SIGN that affect HIV-1 interactions, we developed Raji B cell lines expressing different DC-SIGN/L-SIGN chimeras. Testing of the chimeras demonstrated that replacement of the DC-SIGN carbohydrate-recognition domain (CRD) with that of L-SIGN was sufficient to impair virus binding and prevent transmission. Conversely, the ability to bind and transmit HIV-1 was conferred to L-SIGN chimeras containing the DC-SIGN CRD. We identified Trp-258 in the DC-SIGN CRD to be essential for HIV-1 transmission. Although introduction of a K270W mutation at the same position in L-SIGN was insufficient for HIV-1 binding, an L-SIGN mutant molecule with K270W and a C-terminal DC-SIGN CRD subdomain transmitted HIV-1. These data suggest that DC-SIGN structural elements distinct from the oligosaccharide-binding site are required for HIV-1 glycoprotein selectivity.


ICU triage in an impending crisis: uncertainty, pre-emption and preparation.


title: Ongoing clinical studies of minimally invasive surgery for gastric cancer in Japan.

text: Since the development of laparoscopy-assisted distal gastrectomy (LADG) with lymph node dissection for gastric cancer in Japan, this type of surgery is improving and evolving. To establish high-quality evidence of laparoscopic gastrectomy (LAG) in the field of gastric cancer treatments, two large-scale, prospective randomized controlled trials have been performed in Japan; the Japan Clinical Oncology Study Group (JCOG) 0912 for early disease and the Japanese Laparoscopic Surgery Study Group (JLSSG) 0901 for advanced disease. Analyses using mega-data from the National Clinical Database (NCD) have also been carried out as a clinical study to clarify the safety of LAG. Furthermore, as advanced laparoscopic techniques have been developed, prospective clinical studies are being performed with regard to laparoscopy-assisted total gastrectomy (LATG), robotic gastrectomy, and minimally invasive surgery with sentinel node (SN) navigation. This review summarizes the current status of minimally invasive surgeries for gastric cancer based on the latest ongoing clinical trials in Japan.


docid: qcnmhvof

title: Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection.

text: Tick-borne encephalitis virus (TBEV) is a member of the genus Flavivirus. It can cause serious infections in humans that may result in encephalitis/meningoencephalitis. Although several studies have described the involvement of specific genes in the host response to TBEV infection in the central nervous system (CNS), the overall network remains poorly characterized. Therefore, we investigated the response of DAOY cells (human medulloblastoma cells derived from cerebellar neurons) to TBEV (Neudoerfl strain, Western subtype) infection to characterize differentially expressed genes by transcriptome analysis. Our results revealed a wide panel of interferon-stimulated genes (ISGs) and pro-inflammatory cytokines, including type III but not type I (or II) interferons (IFNs), which are activated upon TBEV infection, as well as a number of non-coding RNAs, including long non-coding RNAs. To obtain a broader view of the pathways responsible for eliciting an antiviral state in DAOY cells we examined the effect of type I and III IFNs and found that only type I IFN pre-treatment inhibited TBEV production. The cellular response to TBEV showed only partial overlap with gene expression changes induced by IFN-β treatment - suggesting a virus-specific signature - and we identified a group of ISGs that were highly up-regulated following IFN-β treatment. Moreover, a high rate of down-regulation was observed for a wide panel of pro-inflammatory cytokines upon IFN-β treatment. These data can serve as the basis for further studies of host-TBEV interactions and the identification of ISGs and/or lncRNAs with potent antiviral effects in cases of TBEV infection in human neuronal cells.


title: EAPCI Position Statement on Invasive Management of Acute Coronary Syndromes during the COVID-19 pandemic.

text: The coronavirus disease 2019 (COVID-19) pandemic poses an unprecedented challenge to healthcare worldwide. The infection can be life threatening and require intensive care treatment. The transmission of the disease poses a risk to both patients and healthcare workers. The number of patients requiring hospital admission and intensive care may overwhelm health systems and negatively affect standard care for patients presenting with conditions needing emergency interventions. This position statements aims to assist cardiologists in the invasive management of acute coronary syndrome (ACS) patients in the context of the COVID-19 pandemic. To that end, we assembled a panel of interventional cardiologists and acute cardiac care specialists appointed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and from the Acute Cardiovascular Care Association (ACVC) and included the experience from the first and worst affected areas in Europe. Modified diagnostic and treatment algorithms are proposed to adapt evidence-based protocols for this unprecedented challenge. Various clinical scenarios, as well as management algorithms for patients with a diagnosed or suspected COVID-19 infection, presenting with ST- and non-ST-segment elevation ACS are described. In addition, we address the need for re-organization of ACS networks, with redistribution of hub and spoke hospitals, as well as for in-hospital reorganization of emergency rooms and cardiac units, with examples coming from multiple European countries. Furthermore, we provide a guidance to reorganization of catheterization laboratories and, importantly, measures for protection of healthcare providers involved with invasive procedures.


docid: lfdrhbce

title: Long-term outcomes of laparoscopic sleeve gastrectomy: a Lebanese center experience.

text: BACKGROUND Long-term data of laparoscopic sleeve gastrectomy (LSG) are still scarce in the Middle East. OBJECTIVES The aim of this study was to assess the efficacy and safety at 5 years and beyond. SETTING Tertiary referral hospital between April 2007 and March 2015. METHODS A retrospective review of 76 patients who underwent LSG at the senior author's institution between April 2007 and March 2010. RESULTS Mean preoperative body mass index (BMI) was 42.8±7.1 kg/m2. Follow-up rates were 90.4%, 86.3%, and 77.8% at 5, 6, and 7 years, respectively. Percentage of excess weight loss (%EWL) was 69.8%±28.7% at 5 years, 70.6%±32.7% at 6 years, and 76.6%±21.2% at 7 years, respectively. Mean total weight loss was 26.5%±8.7%, 24.9%±8.8%, and 26.6%±6.0% at 5, 6, and 7 years, respectively. %EWL at 5-years was significantly higher for patients with a preoperative BMI<45 kg/m2 (83.1% versus 46.3%, P<.0001). LSG improved or resolved diabetes, hypertension, and asthma in 87.5%, 68%, and 81.7% of patients, respectively. New onset gastroesophageal acid reflux disease developed in 21.2% of patients. Long-term complications included hiatal hernias necessitating repair (1.4%), incisional hernias (2.7%), and symptomatic gallstones (9.6%), as well as depression necessitating admission (4.1%). CONCLUSION In the present patient population, LSG resulted in satisfactory %EWL and co-morbidity resolution after 5 years. The results were excellent for patients with a BMI<45 kg/m2. De novo acid reflux symptoms developed in 1 of 5 patients. Cholelithiasis necessitating cholecystectomy was the most common long-term complication.


title: Single-port video-assisted thoracoscopic surgery for a huge epiphrenic esophageal diverticulum.

text: Epiphrenic esophageal diverticulum is uncommon disease, which is defined as the herniation of the mucosa and submucosa through the muscle layers of the esophageal wall in distal third of the esophagus. Traditionally, thoracotomy has been the preferred surgical approach. Recently, many surgeons have attempted minimally invasive surgeries for epiphrenic esophageal diverticula. They reported that minimally invasive surgery (MIS) for epiphrenic esophageal diverticula was a safe and feasible approach which had many advantages. There are various options of surgical approaches for MIS of epiphrenic diverticula. However, the best surgical approach remains uncertain. We report the case of a huge epiphrenic esophageal diverticulum, which was successfully treated by single-port video-assisted thoracoscopic surgery (VATS).


docid: bqyfrlsr

title: Flavivirus replication complex assembly revealed by DNAJC14 functional mapping.

text: DNAJC14 is an Hsp40 family member that broadly modulates flavivirus replication. The mechanism by which DNAJC14 stoichiometrically participates in flavivirus replication complex (RC) formation is unknown; both reduced and elevated levels result in replication inhibition. Using yellow fever virus (YFV), we demonstrate that DNAJC14 redistributes and clusters with YFV nonstructural proteins via a transmembrane domain and a newly identified membrane-binding domain (MBD), which both mediate targeting to detergent-resistant membranes. Furthermore, the RC and DNAJC14 reside as part of a protein interaction network that remains after 1% Triton solubilization. Mutagenesis studies demonstrate that entry into this protein interaction network requires the DNAJC14 C-terminal self-interaction domain. Fusion of the DNAJC14 MBD and self-interaction domain with another Hsp40 family protein is sufficient to confer YFV-inhibitory activity. Our findings support a novel model of DNAJC14 action that includes specific membrane targeting of both DNAJC14 and YFV replication proteins, the formation of protein interactions, and a microdomain-specific chaperone event leading to RC formation. This process alters the properties of the RC membrane and results in the formation of a protein scaffold that maintains the RC.


title: Healing of Aneurysm after Treatment Using Flow Diverter Stent : Histopathological Study in Experimental Canine Carotid Side Wall Aneurysm.

text: Objective Despite widespread use of flow diverters (FDs) to treat aneurysms, the exact healing mechanism associated with FDs remains poorly understood. We aim to describe the healing process of aneurysms treated using FDs by demonstrating the histopathologic progression in a canine aneurysm model. Methods Twenty-one side wall aneurysms were created in common carotid artery of eight dogs and treated with two different FDs. Angiographic follow-ups were done immediately after placement of the device, 4 weeks and 12 weeks. At last follow-up, the aneurysm and the device-implanted parent artery were harvested. Results Histopathologic findings of aneurysms at 4 weeks follow-up showed intra-aneurysm thrombus formation in laminating fashion, and neointimal thickening at the mid-segment of aneurysm. However, there are inhomogenous findings in aneurysms treated with the same type of FD showing same angiographic outcomes. At 12 weeks, aneurysms of complete and near-complete occlusion revealed markedly shrunken aneurysm filled with organized connective tissues with thin neointima. Aneurysms of incomplete occlusion at 12 weeks showed small amount of organized thrombus around fringe neck and large empty space with thick neointmal formation. Neointimal thickness and diameter stenosis was not significantly different between the groups of FD specification and follow-up period. Conclusion Intra-aneurysmal thrombus formation and organization seem to be an important factor for the complete occlusion of aneurysms treated using the FD. Neointimal formation could occur along the struts of the FD independently of intra-aneurysmal thrombus formation. However, neointimal formation could not solely lead to complete aneurysm healing.


title: Glucose Modifies the Effect of Endovascular Thrombectomy in Patients With Acute Stroke.

text: Background and Purpose- Hyperglycemia is a negative prognostic factor after acute ischemic stroke but is not known whether glucose is associated with the effects of endovascular thrombectomy (EVT) in patients with large-vessel stroke. In a pooled-data meta-analysis, we analyzed whether serum glucose is a treatment modifier of the efficacy of EVT in acute stroke. Methods- Seven randomized trials compared EVT with standard care between 2010 and 2017 (HERMES Collaboration [highly effective reperfusion using multiple endovascular devices]). One thousand seven hundred and sixty-four patients with large-vessel stroke were allocated to EVT (n=871) or standard care (n=893). Measurements included blood glucose on admission and functional outcome (modified Rankin Scale range, 0-6; lower scores indicating less disability) at 3 months. The primary analysis evaluated whether glucose modified the effect of EVT over standard care on functional outcome, using ordinal logistic regression to test the interaction between treatment and glucose level. Results- Median (interquartile range) serum glucose on admission was 120 (104-140) mg/dL (6.6 mmol/L [5.7-7.7] mmol/L). EVT was better than standard care in the overall pooled-data analysis adjusted common odds ratio (acOR), 2.00 (95% CI, 1.69-2.38); however, lower glucose levels were associated with greater effects of EVT over standard care. The interaction was nonlinear such that significant interactions were found in subgroups of patients split at glucose < or >90 mg/dL (5.0 mmol/L; P=0.019 for interaction; acOR, 3.81; 95% CI, 1.73-8.41 for patients < 90 mg/dL versus 1.83; 95% CI, 1.53-2.19 for patients >90 mg/dL), and glucose < or >100 mg/dL (5.5 mmol/L; P=0.004 for interaction; acOR, 3.17; 95% CI, 2.04-4.93 versus acOR, 1.72; 95% CI, 1.42-2.08) but not between subgroups above these levels of glucose. Conclusions- EVT improved stroke outcomes compared with standard treatment regardless of glucose levels, but the treatment effects were larger at lower glucose levels, with significant interaction effects persisting up to 90 to 100 mg/dL (5.0-5.5 mmol/L). Whether tight control of glucose improves the efficacy of EVT after large-vessel stroke warrants appropriate testing.


title: Distinct effects of knocking down MEK1 and MEK2 on replication of herpes simplex virus type 2.

text: During infection, viruses hijack various host cell components and programs for their amplification, among which is the canonical ERK signaling pathway, mainly consisting of three tiered serine/threonine kinases, Raf, MEK and ERK. MEK1 and MEK2 are two isoforms of the kinase operating immediately upstream of ERK, and connecting Raf and ERK by phosphorylating ERK. Previous studies have suggested that different isoforms of MEK have distinct biological functions, although their in vitro kinase function may be redundant. However, little is known about the isoform-specific effects of these kinases on viral propagation. In this study, we showed that herpes simplex virus type 2 (HSV-2) infection of human embryonic kidney (HEK) 293 cells induced a sustained activation of ERK1/2. Inhibition of this ERK activation by U0126, a specific inhibitor of MEK1/2, severely impaired virus production. A similar reduction of virus production was also seen following transfection of cells with siRNAs for MEK1/2. Interestingly, a specific knockdown of MEK1 with siRNAs caused a marked inhibition of viral titers, viral proteins and virus-induced cytopathic effect (CPE), whereas silencing MEK2 had little effect. Therefore, our results demonstrate that MEK1 and MEK2 act differently and that HSV-2 hijacks host MEK1 for its own amplification. To our knowledge, this is the first report showing inhibition of HSV-2 replication by targeting human MEK1. This study also suggests that MEK1 could be a potential target for anti-HSV-2 therapy, which may minimize damage to the host cells engendered by targeting both MEK1 and MEK2.


title: Penetrating neck injury to the superior thoracic artery managed by video-assisted thoracoscopic surgery.

text: Penetrating trauma to the axillary artery and its branches is uncommon and associated with high morbidity and mortality. Open exploration is mandated in hemodynamically unstable patients, but surgical exposure can be difficult due to the concentration of vital structures and complex anatomy in this region. Computed tomographic angiography is a potential diagnostic modality in hemodynamically stable patients. In these patients, endovascular therapies may provide a feasible means of controlling hemorrhage while minimizing surgical complications. A high incidence of concomitant intrathoracic injury has resulted in an expanding role for video-assisted thoracoscopic surgery. In this paper, we present a case of penetrating injury to the superior thoracic artery that was not amenable to endovascular therapy and was ultimately managed with thoracoscopic surgery.


The Great Influenza: The Epic Story of the Deadliest Plague in History.


docid: tnjmbsmn

title: Laparoscopic ileostomy in severe, obscure gastrointestinal hemorrhage: diagnostic laparoscopic ileostomy.

text: HYPOTHESIS Laparoscopic diverting ileostomy should help define whether a severe, obscure gastrointestinal hemorrhage is in the upper or lower gastrointestinal tract in preparation for subtotal resection without increasing risk of patient morbidity and mortality. DESIGN Case reports. SETTING University hospital. PATIENTS Patient 1 is an 83-year-old woman. Patient 2 is a 75-year-old woman. Both were admitted to the hospital for massive gastrointestinal hemorrhage, which required multiple blood transfusions. Extensive workup revealed multiple diverticula in the small and large intestines without identification of any source of active bleeding in either patient. INTERVENTION Laparoscopic exploration of the abdominal cavity was performed. The terminal ileum at the ileocecal valve was identified and, 5 cm proximal to the ileocecal valve, the small bowel was transected. The distal end staple line was secured in end-to-side fashion to the proximal end, and the proximal end was brought out as an end ileostomy. Patients were then observed for bleeding into the ostomy bag or in the rectum. MAIN OUTCOME MEASURE Localization of the source of bleeding as upper or lower, occurrence of surgical complications, and clinical outcome. RESULTS No intraoperative complications occurred in either patient. Patient 1 had significant bleeding into her ileostomy bag on postoperative day 1. She was taken back to the operating room for empirical small bowel resection. She was discharged, had no further bleeding, and underwent closure of the ileostomy 2 months later. The postoperative course of patient 2 was complicated by a small parastomal abscess that resolved with percutaneous drainage and antibiotics. Patient 2 returned on postoperative day 22 with bleeding in the rectum. She was taken to the operating room for laparoscopic total colectomy with ileosigmoid anastomosis and ileostomy closure. Both patients recovered uneventfully and had no recurrent bleeding. CONCLUSIONS Our experience with these 2 patients suggests that in cases in which the risk of blind resection appears ill-advised, laparoscopic compartmentalization of the small bowel from the colon via end ileostomy may be safely performed.


title: A systematic review of the effectiveness of promoting water intake to reduce sugar-sweetened beverage consumption.

text: Objective To examine whether the promotion of water intake could reduce sugar-sweetened beverage (SSB) consumption or purchases independent of interventions that target SSBs. Methods Seven databases were systematically searched. Included studies used water promotion as the primary intervention; used a controlled trial, single group pre-post, or prospective cohort study design; included a measure of SSB consumption or purchase; enrolled human participants of any age who lived in high-income or middle-income countries; contained original data; and appeared in a peer-reviewed English-language article published from 1 January 2000 to January 4, 2019. The search yielded 7068 publications, from which 108 were chosen for full-text review. Seventeen were included in this review. Results Nine of the 17 studies were randomized controlled trials, six were nonrandomized controlled trials, and 2 were single-group pre-post studies. Participants were primarily children and adolescents. Interventions included water provision, education or promotion activities. Ten of 17 studies were at low or some/moderate risk of bias. Seven studies showed a statistically significant decrease in SSB consumption of which only 2 were at low or some/moderate risk of bias. Conclusions This review found limited evidence that interventions aimed solely at increasing water consumption reduce SSB intake. Further research is needed to investigate whether interventions that combine water promotion and SSB reduction strategies could be synergistic for reducing SSB intake.


title: South African report of first case of chromoblastomycosis caused by Cladosporium (syn Cladophialophora) carrionii infection in a cat with feline immunodeficiency virus and lymphosarcoma.

text: This report describes a 6-year-old neutered male feline immunodeficiency-positive cat with repeated abdominal and thoracic effusions. The cat was diagnosed with and treated for lymphosarcoma but remission was short-lived and, on re-evaluation, a fungal peritoneal exudate was noted. Cytology of the organisms is described and the culture elucidated Cladosporium carrionii, an important cause of chromoblastomycosis. Treatment with itraconazole was unsuccessful in this case.


title: Ciclosporin and the cat: Current understanding and review of clinical use.

text: Practical relevance: Ciclosporin (CsA) is a systemic immuno-modulatory drug widely used to treat immune-mediated diseases in humans and veterinary species. CsA was registered for use in cats in the USA and Europe in 2011, and is indicated for the treatment of chronic allergic dermatitis at a recommended daily dose of 7 mg/kg PO. AUDIENCE This review will be of interest to all veterinarians working with cats, given the wide range of potential applications of CsA and its safety profile. Although the drug is currently only licensed to treat chronic allergic dermatitis in cats, a small number of reports describe its use in non-dermatological conditions. Evidence base: This article reviews the mechanism of action, pharmacokinetics, drug interactions, adverse effects and clinical use of CsA, both for the licensed indication and for off-label use in the feline patient. Information presented has been summarised from the existing literature on CsA, with specific interest in studies carried out in cats. For its licensed indication, chronic allergic dermatitis, evidence provided includes randomised, placebo or prednisolone-controlled studies (EBM grade I) and prospective or retrospective open trials.


title: New Radiofrequency Device to Reduce Bleeding after Core Needle Biopsy: Experimental Study in a Porcine Liver Model.

text: OBJECTIVE To evaluate the in vivo efficiency of the biopsy tract radiofrequency ablation for hemostasis after core biopsy of the liver in a porcine liver model, including situations with bleeding tendency and a larger (16-gauge) core needle. MATERIALS AND METHODS A preliminary study was performed using one pig to determine optimal ablation parameters. For the main experiment, four pigs were assigned to different groups according to heparinization use and biopsy needle caliber. In each pig, 14 control (without tract ablation) and 14 experimental (tract ablation) ultrasound-guided core biopsies were performed using either an 18- or 16-gauge needle. Post-biopsy bleeding amounts were measured by soaking up the blood for five minutes. The results were compared using the Mann-Whitney U test. RESULTS The optimal parameters for biopsy tract ablation were determined as a 2-cm active tip electrode set at 40-watt with a tip temperature of 70-80℃. The bleeding amounts in all experimental groups were smaller than those in the controls; however they were significant in the non-heparinized pig biopsied with an 18-gauge needle and in two heparinized pigs (p < 0.001). In the heparinized pigs, the mean blood loss in the experimental group was 3.5% and 13.5% of the controls biopsied with an 18- and 16-gauge needle, respectively. CONCLUSION Radiofrequency ablation of hepatic core biopsy tract ablation may reduce post-biopsy bleeding even under bleeding tendency and using a larger core needle, according to the result from in vivo porcine model experiments.


docid: zbgeepxd

title: Retrospective analysis of pleural effusion in cats.

text: OBJECTIVES Pleural effusion is a common presenting cause for feline patients in small animal practice. The objectives of this study were to identify possible correlations between the aetiology of effusion and clinical and laboratory findings. METHODS In this retrospective study of 306 cats diagnosed with pleural effusion of established aetiology, cats were divided into six major groups: cardiac disease (CD), feline infectious peritonitis (FIP), neoplasia, pyothorax, chylothorax and miscellaneous. Clinical, laboratory and radiographic parameters were compared between groups. RESULTS CD was the most common aetiology (35.3%), followed by neoplasia (30.7%), pyothorax (8.8%), FIP (8.5%), chylothorax (4.6%) and miscellaneous diseases (3.7%). In 26 (8.5%) cats, more than one underlying disease was diagnosed as a possible aetiology for pleural effusion. Cats with FIP were significantly younger than those with CD ( P <0.001) and neoplasia ( P <0.001). Cats with CD were presented with a significantly lower body temperature compared with cats with FIP ( P = 0.022). Cats with CD had significantly higher serum alanine aminotransferase activity compared with all other cats (FIP and pyothorax, P <0.001; neoplasia and chylothorax, P = 0.02) and serum alkaline phosphatase activity compared with the pyothorax ( P <0.001) and FIP groups ( P = 0.04), and significantly lower protein concentrations (FIP, pyothorax and neoplasia, P <0.001; chylothorax, P = 0.04 ) and nucleated cell counts in the effusion than all other groups (pyothorax and neoplasia, P <0.001; chylothorax, P = 0.02; FIP, P = 0.04).The glucose level in the effusion of cats with pyothorax was significantly lower than glucose levels in patients with CD, neoplasia and chylothorax ( P <0.001). Of 249 cats with a follow-up of at least 10 days, 55.8% died or were euthanased during that time. CONCLUSIONS AND RELEVANCE CD and neoplasia were the most common causes for feline pleural effusion. Age, liver enzymes, as well as cell count, protein and glucose levels in the effusion can aid in the investigation of underlying aetiologies.


Intestinal torsion diagnosed in dairy cattle from different herds in Northern Ireland.


docid: nuycyuqc

title: Radiofrequency ablation of liver cancers adjacent to the gallbladder without gallbladder isolation under contrast-enhanced ultrasound monitoring: a preliminary study.

text: PURPOSE The purpose of this study was to investigate the feasibility, safety and efficacy of intra-procedural contrast-enhanced ultrasound (CEUS) monitoring of the radiofrequency ablation (RFA) of liver cancers adjacent to gallbladder (GB) without GB isolation. MATERIALS AND METHODS From May 2016 to July 2017, patients with liver cancers adjacent to GB (≤10 mm) who intended to undergo ultrasound-guided RFA without GB isolation in our hospital were prospectively enrolled. During the RFA procedures, CEUS was employed to evaluate the therapeutic response and the perfusion of the intact GB wall. The outcomes of GB and liver cancers were followed up and recorded. RESULTS 23 patients (18 male, 5 female) with 23 liver cancers (mean 18 mm, range 8-34 mm) adjacent to GB were enrolled. There were 12 tumors that abutted the GB while 11 tumors located within 10 mm of the GB. After the RFA procedures, intra-procedural CEUS evaluation demonstrated the perfusion of the GB wall was intact in all 23 patients and technical success rate of RFA was 100% (23/23). According to the contrast-enhanced CT/MR one month after RFA, the technical efficacy rate was 100% (23/23). During the follow-up period (range: 12-23 months, median: 17 months), no local tumor progression occurred and no major complications arised. Overall survival at 1-year was 100%. Thickening of GB wall was detected in 11 patients. The thickness of GB wall returned to the pre-ablation level in five patients. CONCLUSION CEUS-monitored RFA of liver cancers adjacent to GB without GB isolation was feasible, safe and effective.


title: The effects of CO2-insufflation with 5 and 10 mmHg during thoracoscopy on cerebral oxygenation and hemodynamics in piglets: an animal experimental study.

text: OBJECTIVE To evaluate the effect of CO2-insufflation with 5 and 10 mmHg on cerebral oxygenation and hemodynamics in neonates. BACKGROUND An increasing percentage of surgical interventions in neonates are performed by minimal invasive techniques. Recently, concerns have been raised regarding a decrease of cerebral oxygenation in neonates during thoracoscopy as a result of CO2-insufflation. METHODS This was an animal experimental study. Piglets were anesthetized, intubated, ventilated, and surgically prepared for CO2-insufflation. Insufflation was done with 5 or 10 mmHg CO2 during 1 h. Arterial saturation (SaO2), heart rate (HR), mean arterial blood pressure (MABP), and cerebral oxygenation (rScO2) were monitored. CFTOE, an estimator of cerebral oxygen extraction ((SaO2 - rScO2)/SaO2)), was calculated. Arterial blood gases were drawn every 15': pre (T0), during (T1-T4) and after CO2-insufflation (T5). RESULTS Ten piglets (4 kg) were randomized for 5 (P5) and 10 (P10) mmHg CO2-insufflation. Two P10 piglets needed resuscitation after insufflation, none P5. Linear mixed-effect modeling of paCO2, pH, and SaO2 showed that values were dependent on time and time squared (p < 0.001) but were not different between the 5 and 10 mmHg groups. Analysis demonstrated significant changes over time in heart rate and MABP between the 5 and 10 mmHg groups, with a significant higher heart rate and lower blood pressure in the 10 mmHg group (p < 0.001). For rScO2 and cFTOE, no group differences could be demonstrated, but a significant effect of time was found: rScO2 increased and cFTOE decreased (p < 0.001). CONCLUSIONS Insufflation of CO2 during thoracoscopy with 10 mmHg caused more severe hemodynamic instability and seems to be related with a decrease of cerebral perfusion as represented by a higher oxygen extraction. CO2-insufflation of 5 mmHg for thoracoscopy seems to have no adverse effects on cerebral oxygenation.


title: Paediatric computer-assisted retroperitoneoscopic nephrectomy compared with open surgery.

text: PURPOSE Computer-assisted laparoscopic surgery (CALS) in children is increasingly used and has proven to be feasible and safe. However, its full potential remains unclear and clinical comparative studies hardly exist. The aim of this study was to prospectively evaluate our experience with CALS for performing retroperitoneal nephrectomies in children when compared with controls undergoing open surgery in terms of safety, operative time, blood loss, opoid requirements, the duration of hospital stay and complications. CHILDREN AND METHODS Computer-assisted retroperitoneoscopic nephrectomy was undertaken in ten consecutive children, mean age at the time of surgery 6.4 (SD ± 4.5) years, and compared with a retrospectively collected control group of all other children, mean age 3.9 (SD ± 4.6) years, who underwent the same procedure by conventional open surgery between the years 2005 and 2009. The endpoint of the study was 1 month postoperatively. RESULTS Nephrectomies were performed in all the children and no child was excluded from the study. There was no per-operative complication in any of the groups. The median (range) operative time was 202 (128-325) and 72 (44-160) min for the CALS and open group, respectively. The blood loss was minimal (<20 ml) for all the patients. The postoperative opoid requirements did not differ. The median (range) postoperative hospital stay was 1 (1-4) and 2 (1-7) days for the CALS and the open group, respectively. One complication in the form of an urinoma appeared 5 days after surgery in the CALS group. CONCLUSION Computer-assisted retroperitoneoscopic nephrectomy is a safe, feasible and effective procedure in children. Even though operative times are longer the patients benefit from the lower morbidity, improved cosmetics and shorter hospitalization associated with the minimally invasive approach.


title: Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial.

text: BACKGROUND Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. METHODS NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. FINDINGS Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22-1·36), and the risk was similar for those without known PFO (1·06; 0·84-1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51-8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69-4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24-0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. INTERPRETATION Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. FUNDING Bayer and Janssen.


How has the COVID-19 pandemic improved evidence-based-medicine awareness among undergraduate medical students?


docid: orgpaipx

title: SARS-CoV2 bilateral pneumonia: chest X-ray evolution.


title: The structures of two archaeal type IV pili illuminate evolutionary relationships.

text: We have determined the cryo-electron microscopic (cryo-EM) structures of two archaeal type IV pili (T4P), from Pyrobaculum arsenaticum and Saccharolobus solfataricus, at 3.8 Å and 3.4 Å resolution, respectively. This triples the number of high resolution archaeal T4P structures, and allows us to pinpoint the evolutionary divergence of bacterial T4P, archaeal T4P and archaeal flagellar filaments. We suggest that extensive glycosylation previously observed in T4P of Sulfolobus islandicus is a response to an acidic environment, as at even higher temperatures in a neutral environment much less glycosylation is present for Pyrobaculum than for Sulfolobus and Saccharolobus pili. Consequently, the Pyrobaculum filaments do not display the remarkable stability of the Sulfolobus filaments in vitro. We identify the Saccharolobus and Pyrobaculum T4P as host receptors recognized by rudivirus SSRV1 and tristromavirus PFV2, respectively. Our results illuminate the evolutionary relationships among bacterial and archaeal T4P filaments and provide insights into archaeal virus-host interactions.


title: Noninvasive molecular imaging of cell death in myocardial infarction using 111In-GSAO.

text: Acute insult to the myocardium is associated with substantial loss of cardiomyocytes during the process of myocardial infarction. In this setting, apoptosis (programmed cell death) and necrosis may operate on a continuum. Because the latter is characterized by the loss of sarcolemmal integrity, we propose that an appropriately labeled tracer directed at a ubiquitously present intracellular moiety would allow non-invasive definition of cardiomyocyte necrosis. A trivalent arsenic peptide, GSAO (4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid), is capable of binding to intracellular dithiol molecules such as HSP90 and filamin-A. Since GSAO is membrane impermeable and dithiol molecules abundantly present intracellularly, we propose that myocardial localization would represent sarcolemmal disruption or necrotic cell death. In rabbit and mouse models of myocardial infarction and post-infarct heart failure, we employed In-111-labelled GSAO for noninvasive radionuclide molecular imaging. (111)In-GSAO uptake was observed within the regions of apoptosis seeking agent- (99m)Tc-Annexin A5 uptake, suggesting the colocalization of apoptotic and necrotic cell death processes.


From Containment to Mitigation of COVID-19 in the US.


title: Posttreatment Infarct Volumes when Compared with 24-Hour and 90-Day Clinical Outcomes: Insights from the REVASCAT Randomized Controlled Trial.

text: BACKGROUND AND PURPOSE Endovascular therapy has become the standard of care for patients with disabling anterior circulation ischemic stroke due to proximal intracranial thrombi. Our aim was to determine whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in posttreatment infarct volume in the Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT) trial. MATERIALS AND METHODS The REVASCAT trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 206 enrolled subjects (endovascular treatment, n = 103; control, n = 103), posttreatment infarct volume was measured in 204 subjects. Posttreatment infarct volumes were compared with treatment assignment and recanalization status. Appropriate statistical models were used to assess the relationship among baseline clinical and imaging variables, posttreatment infarct volume, the 24-hour NIHSS score, and functional status with the 90-day modified Rankin Scale score. RESULTS The median posttreatment infarct volume in all subjects was 23.7 mL (interquartile range = 68.9 mL) and 16.3 mL (interquartile range = 50.2 mL) in the endovascular treatment arm and 38.6 mL (interquartile range = 74.9 mL) in the control arm (P = .02 for endovascular treatment versus control subjects). Baseline NIHSS (P < .01), site of occlusion (P < .03), baseline NCCT ASPECTS (P < .01), and recanalization status (P = .02) were independently associated with posttreatment infarct volume. Baseline NIHSS (P < .01), time from symptom onset to randomization (P = .02), treatment type (P = .04), and recanalization status (P < .01) were independently associated with the 24-hour NIHSS scores. The 24-hour NIHSS score strongly mediated the relationship between treatment type and 90-day mRS (P < .01 for indirect effect when adjusted for age), while posttreatment infarct volume did not (P = .26). CONCLUSIONS Endovascular treatment saves brain and improves 90-day clinical outcomes primarily through a beneficial effect on the 24-hour stroke severity.


title: Reconstituted biosynthesis of the nonribosomal macrolactone antibiotic valinomycin in Escherichia coli.

text: The structural complexity of nonribosomal peptides (NRPs) impeding economic chemical synthesis and poor cultivability of source organisms limits the development of bioprocesses for novel bioactive compounds. Since nonribosomal peptide synthetases (NRPSs) assemble NRPs from simple amino acid building blocks, heterologous expression of NRPSs in a robust and easy to manipulate expression host is an attractive strategy to make pharmaceutically relevant NRPs more accessible and is also a basis for engineering of these enzymes to generate novel synthetic bioactive compounds. Here we show a systematic approach for the heterologous expression of the 654 kDa heterodimeric valinomycin synthetase (VlmSyn) from Streptomyces tsusimaensis in a soluble and active form in Escherichia coli. VlmSyn activity and precursor requirements were determined in vitro and provided evidence for a previously proposed model of valinomycin biosynthesis. In vivo production of recombinant valinomycin, a macrolactone antibiotic with reported antifungal, antibacterial, and antiviral activities, was achieved using an engineered E. coli strain growing in inexpensive media and independent of the supplementation with precursors and further optimization of the cultivation conditions. Tailoring of VlmSyn in E. coli paves the way to the production of novel valinomycin analogues in the future.


title: Anastomosis by use of compression anastomosis ring (CAR™ 27) in laparoscopic surgery for left-sided colonic tumor.

text: PURPOSE The safety and efficacy of the compression anastomosis ring (CAR™ 27) had been demonstrated by animal studies. This study was designed to evaluate clinical validity of the CAR™ 27 anastomosis in laparoscopic surgery for patients with left-sided colonic neoplasm. METHODS Intracorporeal anastomosis using the CAR™ 27 (CAR group) was performed in 66 patients (male 35; median age, 64.5 years), and short-term results were compared with consecutive 116 patients (male 70; median age, 64 years) where the anastomosis was constructed by double stapling technique using a circular stapler for the same indications (stapled group). RESULTS There were no statistically significant differences between the two groups in terms of gender, age, and distribution of pathologic lesion. The laparoscopic procedures, pathologic diagnosis/stage, and length of operation time and postoperative hospital stay were comparable between the two groups. Conversion rate in the CAR and stapled group was 3% and 6%, respectively. There was no surgical mortality in either group. No intraoperative complications associated with the CAR™ 27 anastomosis were encountered. One patient in the CAR group was complicated by anastomotic leakage and none in the stapled group (p = 0.36). There was intestinal obstruction in two patients, in whom one required re-operation for entrapped small bowel adhesions within pelvis. No patient in either group showed symptomatic anastomotic stricture. CONCLUSIONS The anastomosis using the CAR™ 27 is an innovative technique. The CAR™ 27 anastomosis in patients undergoing laparoscopic colectomy for left-sided colonic tumor proved to be a safe and efficacious alternative to the standard double stapling technique.


title: Stagnation of treatment times over a decade: results of a pooled analysis from the MERCI registry, MERCI, TREVO, and TREVO 2 trials.

text: BACKGROUND There has been a growing interest in improving systems of care for the endovascular treatment of acute ischemic stroke. We analyzed data from previous registries and studies to determine if there has been an improvement in times to reperfusion with increasing experience. METHODS We analyzed the pooled data from the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI), MERCI Registry and Thrombectomy Revascularization of Large Vessel Occlusions (TREVO), and TREVO 2 trials and assessed times from last known normal to puncture, from hospital arrival to puncture, and procedure duration by year to determine if there has been a reduction in times. Demographic, radiographic, and clinical information were also assessed in a multivariate regression analysis to determine the predictors of good outcomes defined as a modified Rankin Scale score of 0-2 at 3 months. RESULTS 1248 patients of mean age 68±14 years and median NIH Stroke Scale score 18 were analyzed from 2001 to 2011. Procedure times showed a significant improvement while last known normal to puncture times remained static. In multivariate logistic regression analysis, longer last known normal to puncture time and longer procedure duration were associated with a decreased chance of a good outcome (OR 0.84, 95% CI 0.76 to 0.92, p=0.0004 and OR 0.75, 95% CI 0.61 to 0.91, p=0.0040, respectively). CONCLUSIONS Despite a reduction in procedure times, there has not been a corresponding improvement in overall last known normal to puncture times over a 10-year period. The current study shows that there are many opportunities to create more efficient endovascular stroke systems of care in trials.


Spotlight on Jails: COVID-19 Mitigation Policies Needed Now.


title: Urinary Phthalate Metabolites in Common Bottlenose Dolphins (Tursiops truncatus) From Sarasota Bay, FL, USA.

text: Phthalates are chemical additives to common consumer goods including cleaning products, cosmetics, personal care products, and plastic. Because they are not chemically bound to these products and are widely used, the potential for environmental contamination is significant. Phthalates and their metabolites have been associated with endocrine disruption and reproductive impairment, among other adverse health effects, in laboratory animals and human epidemiologic studies. Common bottlenose dolphins (Tursiops truncatus) are vulnerable to environmental pollutants due to their apex position in the food chain, long life spans, and habitat overlap with developed coastal areas. The objective of this study was to quantify phthalate metabolite concentrations in urine collected from bottlenose dolphins in Sarasota Bay, Florida, during May 2016 (n = 7) and May 2017 (n = 10). Screening of nine phthalate monoester metabolites in bottlenose dolphin urine was performed by liquid chromatography tandem mass spectrometry using methods adapted from those used for analyzing human samples. At least one phthalate metabolite was detected in 71% of the dolphins sampled across both years, with the highest concentrations detected for monoethyl phthalate (MEP; GM = 5.4 ng/ml; 95%CI: 1.3-22.0 ng/ml) and mono-(2-ethylhexyl) phthalate (MEHP; GM = 1.9 ng/ml; 95%CI: 1.1-3.2 ng/ml). These data demonstrate exposure to two of the most commonly used phthalates in commercial manufacturing, diethyl phthalate (DEP) and di-2-ethylhexyl phthalate (DEHP). This study establishes methods for urinary detection of phthalate metabolites in marine mammals and provides baseline data to address a significant and growing, yet poorly understood, health threat to marine wildlife.


docid: jybycapp

title: Single-incision laparoscopic appendectomy is comparable to conventional laparoscopic and laparotomic appendectomy: our single center single surgeon experience.

text: Several studies have demonstrated the clinical and technical benefits of the laparoscopic surgery for complicated and uncomplicated appendicitis. Our retrospective study included 12 patient who underwent SILS appendectomy (SILS-A), 14 who received conventional laparoscopic surgery (VL-A), and 12 who received laparotomic appendectomy (OA); performed in all cases by the same surgeon (C.F.). The aim of this study was the comparison between this three different surgical techniques on same features: post operative leukocytosis, post operative pain, need abdominal drainage, esthetic viewpoint, incidence of complication, hospital stay. The results showed no significant differences between SILS-A and VLS-A, while an evident improvement shows versus O-A, even though not statistically significative. SILS was more effective in decreasing the risk of postoperative wound infection.


title: Defining clinically relevant cerebral hemorrhage after thrombolytic therapy for stroke: analysis of the National Institute of Neurological Disorders and Stroke tissue-type plasminogen activator trials.

text: BACKGROUND AND PURPOSE Several definitions have been proposed to distinguish clinically relevant from incidental cerebral hemorrhagic transformation after thrombolytic therapy for acute ischemic stroke. We investigated which definition best identifies cerebral hemorrhages that alter long-term functional outcome in the National Institute of Neurological Disorders and Stroke (NINDS) tissue-type plasminogen activator (tPA) trials. METHODS We analyzed 4 candidate hemorrhage definitions for which the NINDS tPA trials public data set had relevant data. For each, we identified tPA-treated patients having that hemorrhage type and compared their actual functional outcomes at 90 days with their predicted outcomes had they not received tPA and not had the hemorrhage. Projected outcomes without tPA were based on a 17-variable prognostic model derived from the NINDS tPA trials placebo group. RESULTS Among the 312 patients treated with intravenous tPA, 33 (10.6%) experienced any radiological intracerebral hemorrhage <36 hours of treatment, 16 (5.1%) a radiological parenchymal hematoma, 20 (6.4%) a NINDS tPA trials-defined symptomatic intracerebral hemorrhage, 12 (3.8%) an European-Australian Cooperative Acute Stroke Study 2 (ECASS2)-defined symptomatic intracerebral hemorrhage, and 6 (1.9%) a modified version of the Safe Implementation of Thrombolysis in Stroke Monitoring Study (mSITS-MOST)-defined symptomatic intracerebral hemorrhage. The ECASS2 and mSITS-MOST definitions identified the largest hemorrhage-related change in 90-day modified Rankin Scale scores (2.26-0.32=1.94, P=0.0001; 2.81-0.63=2.18, P=0.0002, respectively). These definitions also distinguished the largest hemorrhage-related change in 90-day mortality (64.7%-7.6%=57.1%; P=0.0004 for ECASS2; 68.4%-19.5%=48.9%; P=0.0152 for mSITS-MOST). CONCLUSIONS The ECASS2 and mSITS-MOST symptomatic intracerebral hemorrhage definitions, which combine radiological features and occurrence of substantial early neurological deterioration, best identify tPA hemorrhages that alter final patient outcome.


title: SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome.

text: Coronaviruses (CoV) have recently emerged as potentially serious pathogens that can cause significant human morbidity and death. The severe acute respiratory syndrome (SARS)-CoV was identified as the etiologic agent of the 2002-2003 international SARS outbreak. Yet, how SARS evades innate immune responses to cause human disease remains poorly understood. In this study, we show that a protein encoded by SARS-CoV designated as open reading frame-9b (ORF-9b) localizes to mitochondria and causes mitochondrial elongation by triggering ubiquitination and proteasomal degradation of dynamin-like protein 1, a host protein involved in mitochondrial fission. Also, acting on mitochondria, ORF-9b targets the mitochondrial-associated adaptor molecule MAVS signalosome by usurping PCBP2 and the HECT domain E3 ligase AIP4 to trigger the degradation of MAVS, TRAF3, and TRAF 6. This severely limits host cell IFN responses. Reducing either PCBP2 or AIP4 expression substantially reversed the ORF-9b-mediated reduction of MAVS and the suppression of antiviral transcriptional responses. Finally, transient ORF-9b expression led to a strong induction of autophagy in cells. The induction of autophagy depended upon ATG5, a critical autophagy regulator, but the inhibition of MAVS signaling did not. These results indicate that SARS-CoV ORF-9b manipulates host cell mitochondria and mitochondrial function to help evade host innate immunity. This study has uncovered an important clue to the pathogenesis of SARS-CoV infection and illustrates the havoc that a small ORF can cause in cells.


title: Delayed neurological deficits after endovascular placement of a pipeline embolisation device: clinical manifestation and treatment.

text: Endovascular treatment has been the mainstay of therapy for repair of both ruptured and unruptured cerebral aneurysms. Flow diverter devices offer a new option for the treatment of complex aneurysms that were previously not amenable to coiling. Procedural adverse effects include intracranial haemorrhage and ischaemic stroke, which usually occur on the same day. Delayed complications are rare. We report a case of a patient who underwent placement of a pipeline embolisation device and developed delayed neurological deficits, which were thought to be an inflammatory reaction to the hydrophilic coating used in guidewires and microcatheters. Our patient was treated with a course of steroids, with improvement of her neurological deficits and resolution of MRI findings. As the use of flow diverter devices has increased, variable and delayed complications of such therapy are increasingly being reported in the literature.


title: The role of Hedgehog-responsive fibroblasts in facial nerve regeneration.

text: BACKGROUND Facial nerve paralysis is a significant cause of morbidity, affecting facial appearance, emotional expression, speech, oral competence, and vision. A more complete understanding of the complex cellular events required for successful nerve regeneration may reveal new therapeutic targets. The role of fibroblasts in regeneration, and the process by which the nerve reforms its three-dimensional structure after a transection injury, are not fully understood. The Hedgehog signaling pathway has been shown to mediate nerve sheath formation during development. We therefore sought to characterize the role of Hedgehog-responsive cells following transection of the facial nerve. METHODS Two transgenic mouse lines with reporters for the downstream effector of Hedgehog signaling, Gli1, were used. The animals underwent a unilateral facial nerve transection injury, and the contralateral side served as a control. Facial nerves were analyzed via immunohistochemistry and immunofluorescence at predetermined time points as the facial nerve regenerated after the transection injury. RESULTS There was a statistically significant increase in Gli1+ cells both at the site of injury and within the distal nerve segment over time. Gli1+ cells are fibroblasts within the nerve and appear to contribute to the reformation of the nerve sheath after injury. CONCLUSION These findings describe a key signaling pathway by which fibroblasts participate in motor nerve regeneration. Fibroblasts that reside within the nerve respond to injury and may represent a novel therapeutic target in the context of facial nerve regeneration after transection injury.


title: Quantification of sodium pentobarbital residues from equine mortality compost piles.

text: Sodium pentobarbital, a euthanasia drug, can persist in animal carcasses following euthanasia and can cause secondary toxicosis to animals that consume the remains. This experiment was conducted to observe the effects of composting on euthanized horse carcass degradation and sodium pentobarbital residues in compost material up to 367 d. Six separate compost bins were constructed on pastureland. Three bins served as the control while 3 served as the treatment. The carbonaceous material, or bulking agent, consisted of hardwood chips mixed with yard waste wetted to approximately 50% moisture content. Bulking agent was added to each bin at a depth of 0.46 m, creating the pad. A licensed veterinarian provided 6 horse carcasses for use in the experiment. These horses had required euthanasia for health reasons. All horses were weighed and then sedated with an intravenous injection of 8 mL of xylazine. After sedation the 3 horses in the treatment group were euthanized by intravenous injection of 60 mL of sodium pentobarbital. The 3 control group horses were anesthetized by intravenous injection of 15 mL of ketamine hydrochloride and then humanely euthanized by precise gunshot to the temporal lobe. Following euthanasia, each carcass was placed on the center of the pad and surrounded with 0.6 m of additional bulking agent. Serum and liver samples were obtained immediately following death. Compost samples were obtained on d 7, 14, 28, 56, 84, 129, 233, and 367 while soil samples were obtained on d -1 and 367. Each sample was analyzed for sodium pentobarbital concentration. Compost pile and ambient temperatures were also recorded. Composting successfully degraded soft tissue with only large bones remaining. Data illustrate that sodium pentobarbital was detectable up to 367 d in compost piles with no clear trend of concentration reduction. Drug residues were detected in soil samples indicating that sodium pentobarbital leached from the carcass and through the pad. These findings confirm the persistence of sodium pentobarbital from equine mortality compost piles and emphasize the importance of proper carcass management of animals euthanized with a barbiturate to reduce environmental impact and secondary toxicosis.


title: Serum protein S100 as marker of postoperative delirium after off-pump coronary artery bypass surgery: secondary analysis of two prospective randomized controlled trials.

text: BACKGROUND To investigate the predictive value of S100 (biochemical marker of neuroglial injury) for the occurrence of postoperative delirium (POD) in patients undergoing off-pump coronary artery bypass (OPCAB)-surgery. METHODS We enrolled 92 patients older than 18 years undergoing elective OPCAB-surgery. Serum-levels of S100 were determined at baseline (BL), end of surgery (EOS) and on the first postoperative day (PD1). Postoperatively, all-patients were evaluated daily until PD5 for the presence of POD using the confusion assessment method (CAM) or the confusion assessment method for the intensive care unit (CAM-ICU) for patients in the intensive care unit (ICU). RESULTS The overall incidence of POD was 21%. S100-values on PD1 significantly predicted the occurrence of POD during the later hospital stay [area under the curve (AUC)=0.724 (95% confidence interval (CI): 0.619-0.814); p=0.0001] with an optimal cut-off level of 123 pg mL-1 (sensitivity 100%, specificity 44%). Below this value, the absence of POD was predicted correctly in 43.66% of patients without POD [negative predictive value (NPV) of 100% (95%CI: 88.8%-100.0%) - positive predictive value of 29.8% (95%CI: 18.4%-43.4%) and likelihood ratio (LR) of the negative result of 0.0]. CONCLUSIONS S100-levels <123 pg mL-1 measured on PD1 reliably rule out the development of POD after elective OPCAB-surgery. This finding warrants testing whether S100-levels could be used for a risk stratification of cardiac surgical patients and for the initiation of preventive measures against POD in patients with high postoperative S100-levels.


Early Fatal Hemorrhage After Endovascular Treatment of a Giant Aneurysm with Flow Diverter Device and Coils.


title: Oseltamivir overuse at a Chicago hospital during the 2009 influenza pandemic and the poor predictive value of influenza-like illness criteria.

text: We report on the overuse of oseltamivir at Rush University Medical Center, Chicago during the 2009 H1N1 influenza pandemic. Of 210 patients with suspected influenza who underwent respiratory virus reverse transcription polymerase chain reaction (RT-PCR) testing, 113 (54%) received empiric oseltamivir therapy. However, only 50 treated patients (44%) had laboratory confirmed 2009 H1N1. Factors associated with oseltamivir use included a younger median age (including age < 5 y), subjective fever, cough, rhinorrhea, myalgias, higher median temperature, and fulfilment of the US Centers For Disease Control and Prevention (CDC) influenza-like illness (ILI) criteria. However, on multivariate analysis, only subjective fever (p = 0.006, odds ratio (OR) 3.1, 95% confidence interval (CI) 1.4-6.7) and fulfilment of CDC ILI criteria (p = 0.001, OR 3.6, 95% CI 1.7-7.5) were significantly associated with the receipt of oseltamivir. The CDC ILI criteria had a poor positive predictive value of 43% (95% CI 33.3-53.3) for 2009 H1N1. While the ILI criteria are a useful epidemiologic tool, it is too imprecise for direct patient care.


title: Intracranial electrical impedance tomography: a method of continuous monitoring in an animal model of head trauma.

text: BACKGROUND Electrical impedance tomography (EIT) is a method that can render continuous graphical cross-sectional images of the brain's electrical properties. Because these properties can be altered by variations in water content, shifts in sodium concentration, bleeding, and mass deformation, EIT has promise as a sensitive instrument for head injury monitoring to improve early recognition of deterioration and to observe the benefits of therapeutic intervention. This study presents a swine model of head injury used to determine the detection capabilities of an inexpensive bedside EIT monitoring system with a novel intracranial pressure (ICP)/EIT electrode combination sensor on induced intraparenchymal mass effect, intraparenchymal hemorrhage, and cessation of brain blood flow. Conductivity difference images are shown in conjunction with ICP data, confirming the effects. METHODS Eight domestic piglets (3-4 weeks of age, mean 10 kg), under general anesthesia, were subjected to 4 injuries: induced intraparenchymal mass effect using an inflated, and later, deflated 0.15-mL Fogarty catheter; hemorrhage by intraparenchymal injection of 1-mL arterial blood; and ischemia/infarction by euthanasia. EIT and ICP data were recorded 10 minutes before inducing the injury until 10 minutes after injury. Continuous EIT and ICP monitoring were facilitated by a ring of circumferentially disposed cranial Ag/AgCl electrodes and 1 intraparenchymal ICP/EIT sensor electrode combination. Data were recorded at 100 Hz. Two-dimensional tomographic conductivity difference (Δσ) images, rendered using data before and after an injury, were displayed in real time on an axial circular mesh. Regions of interest (ROI) within the images were automatically selected as the upper or lower 5% of conductivity data depending on the nature of the injury. Mean Δσ within the ROIs and background were statistically analyzed. ROI Δσ was compared with the background Δσ after an injury event using an unpaired, unequal variance t test. Conductivity change within an ROI after injury was likewise compared with the same ROI before the injury making use of unpaired t tests with unequal variance. RESULTS Eight animal subjects were studied, each undergoing 4 injury events including euthanasia. Changes in conductivity due to injury showed expected pathophysiologic effects in an ROI identified within the middle of the left hemisphere; this localization is reasonable given the actual site of injury (left hemisphere) and spatial warping associated with estimating a 3-dimensional conductivity distribution in 2-dimensional space. Results are shown as mean ± 1 SD. When averaged across all 8 animals, balloon inflation caused the mean Δσ within the ROI to shift by -11.4 ± 10.9 mS/m; balloon deflation by +9.4 ± 8.8 mS/m; blood injection by +19.5 ± 11.5 mS/m; death by -12.6 ± 13.2 mS/m. All induced injuries were detectable to statistical significance (P < 0.0001). CONCLUSION This study confirms that the bedside EIT system with ICP/EIT combination sensor can detect induced trauma. Such a technique may hold promise for further research in the monitoring and management of traumatically brain-injured individuals.


The power of prediction markets.


title: Implementation of the trans-abdominal partial extra-peritoneal (TAPE) technique in laparoscopic lumbar hernia repair.

text: BACKGROUND There is still not any standardized operative strategy that is well-accepted all over the world for lumbarhernia. We are here to investigate the feasibility of the trans-abdominal partial extra-peritoneal (TAPE) technique in lumbar hernia repair. METHODS The TAPE technique was applied to 14 patients with lumbar hernia from May 2009 until January 2014. The surgical technique was described in details and follow-ups were performed for further evaluation. RESULTS The mean age of the 14 patients was 68 ± 8 years, with the average BMI 25.5 ± 2.1 kg/m(2). The etiology study showed that 13 cases after surgical operations and one case after trauma. The average size of the hernia defect was 86.8 ± 46.4 cm(2), while the mean size of the mesh implanted was 275 ± 61.2 cm(2). The mean operative time was 59.2 ± 8.2 min. There was no intra-operative visceral injury in this serial of cases. There was no conversion case and all patients accepted the TAPE technique successfully. The VAS was 3.8 ± 1.9 and 2.2 ± 1.6 on POD1 and POD3, respectively. The mean post-operative hospital stay was 4.0 ± 1.3 days. The median follow-up time was 33 months. All patients returned to unrestricted movement within 2 weeks after surgery. During the follow-ups, no complication as bulge, seroma, hematoma, wound infection, abscess in surgical area and chronic pain, nor recurrence was observed. CONCLUSIONS According to our experience in this series of investigations, the TAPE could be a feasible and easy-to-learn technique which can be applied to most of the lumbar hernia repairs.


New developments in the epidemiology, diagnosis, treatment and prevention of respiratory tract infections.


title: Utilization of second derivative photoplethysmographic features for myocardial infarction classification.

text: Myocardial infarction (MI) is a common disease that causes morbidity and mortality. The current tools for diagnosing this disease are improving, but still have some limitations. This study utilised the second derivative of photoplethysmography (SDPPG) features to distinguish MI patients from healthy control subjects. The features include amplitude-derived SDPPG features (pulse height, ratio, jerk) and interval-derived SDPPG features (intervals and relative crest time (RCT)). We evaluated 32 MI patients at Pusat Perubatan Universiti Kebangsaan Malaysia and 32 control subjects (all ages 37-87 years). Statistical analysis revealed that the mean amplitude-derived SDPPG features were higher in MI patients than in control subjects. In contrast, the mean interval-derived SDPPG features were lower in MI patients than in the controls. The classifier model of binary logistic regression (Model 7), showed that the combination of SDPPG features that include the pulse height (d-wave), the intervals of "ab", "ad", "bc", "bd", and "be", and the RCT of "ad/aa" could be used to classify MI patients with 90.6% accuracy, 93.9% sensitivity and 87.5% specificity at a cut-off value of 0.5 compared with the single features model.


title: Diet and physical activity in pregnancy and offspring's cardiovascular health: a systematic review.

text: There is increasing evidence linking maternal diet and physical activity before and during pregnancy with offspring's cardiovascular health. Although many studies examined this association, the evidence has not been reviewed systematically. We therefore undertook a systematic review to synthesize evidence examining the association of maternal diet and physical activity before and during pregnancy with offspring's blood pressure and vascular health. We systematically searched the databases MEDLINE and EMBASE from inception to June 30, 2017. Eligibility screening, data extraction and quality assessment were performed by two independent reviewers. A total of 19 articles were included comprising three randomized controlled trials and 16 observational studies. Of the studies that examined the association of interest, 60% (three out of five studies) showed that high maternal carbohydrate intake was associated with higher offspring's blood pressure. Maternal protein intake during pregnancy was negatively associated with offspring carotid intima-media thickness in two out of two studies. No consistent findings for maternal fatty acid intake were found. There were too few studies to draw conclusions on energy intake, fibre intake, protein/carbohydrate ratio, specific foods, dietary patterns and maternal physical activity. Heterogeneity in exposure and outcome assessment hampered pooling. Also, owing to the observational nature of most studies, causality cannot be established. Harmonization of valid exposure and outcome measurements, and the development of core outcome sets are needed to enable more robust conclusions.


title: Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis.

text: BACKGROUND Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.


Mechanical Thrombectomy for Acute Ischemic Stroke: Are We Done?


title: Development of an enzyme-linked immunosorbent assay-based test with a cocktail of nucleocapsid and spike proteins for detection of severe acute respiratory syndrome-associated coronavirus-specific antibody.

text: A new enzyme-linked immunosorbent assay (ELISA)-based immunoglobulin G (IgG)-plus-IgM antibody detection test for severe acute respiratory syndrome (SARS) has been developed by using a cocktail of four recombinant polypeptides as the antigen. These recombinant fragments were designed as parts of two different structural proteins from SARS-associated coronavirus (SARS-CoV). One recombinant polypeptide, S251-683, was designed as part of the spike glycoprotein, and the other three polypeptides comprised almost the whole nucleocapsid protein, avoiding the last 25 C-terminal amino acids. Immunization with a cocktail of these four polypeptides yielded a specific polyclonal antibody that is able to recognize SARS-CoV-infected cells by an immunofluorescence assay. This polypeptide cocktail was also used to set up an ELISA-based IgG-plus-IgM antibody detection test, which showed 99% specificity and 90% sensitivity upon evaluation using sera from 100 healthy negative controls and 20 SARS patients. Separate immunoreactivity assays with each recombinant polypeptide demonstrated that a combination of N and S protein fragments was more suitable than the individual peptides for developing a serological assay for SARS-CoV.


docid: grcftnug

title: Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids.

text: Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to mutant PIK3CA genotype. Oncogenic PIK3CA results in an increase in arachidonic acid and a concomitant overproduction of eicosanoids, acting to promote cell proliferation beyond a cell-autonomous manner. Mechanistically, mutant PIK3CA drives a multimodal signaling network involving mTORC2-PKCζ-mediated activation of the calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes with fatty acid-free diet to restore immunogenicity and selectively reduce mutant PIK3CA-induced tumorigenicity. Besides highlighting the potential for metabolic phenotyping in stratified medicine, this study reveals an important role for activated PI3K signaling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction.


title: Single-site multiport combined splenectomy and cholecystectomy with conventional laparoscopic instruments: Case series and review of literature.

text: INTRODUCTION Conventional laparoscopic procedures have been used for splenic diseases and concomitant gallbladder stones, frequently in patients with hereditary spherocytosis since 1990's. The aim of this study is to evaluate the feasibility of single-site surgery with conventional instruments in combined procedures. PRESENTATION OF CASE SERIES Six consecutive patients who scheduled for combined cholecystectomy and splenectomy because of hereditary spherocytosis or autoimmune hemolytic anemia were included this study. Both procedures were performed via trans-umbilical single-site multiport approach using conventional instruments. All procedures completed successfully without conversion to open surgery or conventional laparoscopic surgery. An additional trocar was required for only one patient. The mean operation time was 190min (150-275min). The mean blood loss was 185ml (70-300ml). Median postoperative hospital stay was two days. No perioperative mortality or major complications occurred in our series. Recurrent anemia, hernia formation or wound infection was not observed during the follow-up period. DISCUSSION Nowadays, publications are arising about laparoscopic or single site surgery for combined diseases. Surgery for combined diseases has some difficulties owing to the placement of organs and position of the patient during laparoscopic surgery. Single site laparoscopic surgery has been proposed to have better cosmetic outcome, less postoperative pain, greater patient satisfaction and faster recovery compared to standard laparoscopy. CONCLUSION We consider that single-site multiport laparoscopic approach for combined splenectomy and cholecystectomy is a safe and feasible technique, after gaining enough experience on single site surgery.


Patient in hospital for over a year must leave for community care, says judge.


Northern Ireland disease surveillance report, July to September 2013.


title: Wheezing in infants: frequency, clinical characteristics and treatment.

text: OBJECTIVE To estimate the frequency and describe the clinical characteristics and respective treatments of previous history of wheezing. METHODS Infants aged 6-23 months with upper respiratory tract complaints and reporting previous wheezing were followed-up retrospectively. Data were registered on a validated standardized form. RESULTS Out of 451 infants, 164 (36.4%; 95%CI:31.9-41.0) had a report of prior history of wheezing, 148 (32.8%; 95%CI:28.5-37.4) during the first year of life. The mean age at the first episode of wheezing was 5.3±3.9 months. Among those who had had their first episode before 12 months of age, 38.5% reported 3 to 6 episodes and 14.2% > 6 episodes. Mean age at first episode was lower for those with ≥ 3 episodes in comparison with those with ≤ 2 episodes (3.2±2.7 vs. 5.7±2.5 months, p < 0.001). CONCLUSION One third of the infants reported wheezing during the first year of life. The earlier the first episode occurs, the more frequently wheezing recurs.


title: Sonographic diagnosis of abscess following breast-conserving surgery with insertion of nonabsorbable mesh.

text: Immediate mesh insertion has been recently used for breast reconstruction after breast-conserving surgery. We report a case of abscess formation following immediate nonabsorbable mesh insertion with breast-conserving surgery. In this article, we demonstrate multimodal breast imaging features and pathologic correlations of the case. In addition, we illustrate characteristic sonographic findings of nonabsorbable mesh fibers to differentiate them from a gossypiboma caused by a retained surgical sponge or tumor recurrence.


title: Laparoscopic surgery for submucosal tumor near the esophagogastric junction.

text: BACKGROUND Laparoscopic surgery is widely accepted as a treatment for gastric submucosal tumors (SMTs). However, laparoscopy is not easily applied to tumors near the esophagogastric junction (EGJ). This study was conducted to evaluate laparoscopic techniques for treating SMTs near the EGJ. SUBJECTS AND METHODS Between March 2008 and August 2012 at the Asan Medical Center, Seoul, Korea, we performed laparoscopic surgery on 71 patients who had SMTs located within 3 cm of the EGJ. The laparoscopic approach chosen depended on the position of the tumor, which was located accurately by preoperative diagnosis. RESULTS None of the patients required conversion to open surgery. Of the 71 patients in the study, 66 had laparoscopic wedge resection (LAPWR), 4 had laparoscopic enucleation, and 1 had laparoscopic proximal gastrectomy. Two patients had intraoperative events during LAPWR. One had EGJ stricture, which required laparoscopic esophagogastrostomy. The other had a muscle defect of the posterior wall of the distal esophagus, and the defect was covered using fundus-like fundoplication. All patients had tumor-free resection margins, and there were no deaths. CONCLUSIONS Laparoscopic resection of SMTs near the EGJ may be performed safely. The laparoscopic approach used depends on the location and size of the tumor and on the extent of gastric resection.


docid: gmwzjlzc

title: Top EU scientist ousted over plans for coronavirus research.


title: International comparison of guidelines for managing neonates at the early phase of the SARS-CoV-2 pandemic.

text: BACKGROUND The COVID-19 pandemic threatens global newborn health. We describe the current state of national and local protocols for managing neonates born to SARS-CoV-2-positive mothers. METHODS Care providers from neonatal intensive care units on six continents exchanged and compared protocols on the management of neonates born to SARS-CoV-2-positive mothers. Data collection was between March 14 and 21, 2020. We focused on central protocol components, including triaging, hygiene precautions, management at delivery, feeding protocols, and visiting policies. RESULTS Data from 20 countries were available. Disease burden varied between countries at the time of analysis. In most countries, asymptomatic infants were allowed to stay with the mother and breastfeed with hygiene precautions. We detected discrepancies between national guidance in particular regarding triaging, use of personal protection equipment, viral testing, and visitor policies. Local protocols deviated from national guidance. CONCLUSIONS At the start of the pandemic, lack of evidence-based guidance on the management of neonates born to SARS-CoV-2-positive mothers has led to ad hoc creation of national and local guidance. Compliance between collaborators to share and discuss protocols was excellent and may lead to more consensus on management, but future guidance should be built on high-level evidence, rather than expert consensus. IMPACT At the rapid onset of the COVID19 pandemic, all countries presented protocols in place for managing infants at risk of COVID19, with a certain degree of variations among regions. A detailed review of ad hoc guidelines is presented, similarities and differences are highlighted. We provide a broad overview of currently applied recommendations highlighting the need for international context-relevant coordination.