title: Technologies for plasma membrane proteomics.

text: Cell-cell and intracellular signaling are critical mechanisms by which an organism can respond quickly and appropriately to internal or environmental stimuli. Transmission of the stimulus to effector proteins must be coordinated, rapid and transient such that the response is not exaggerated and the overall balance of the cell or tissue is retained. Proteomics technology has traditionally been adept at analyzing effector proteins (such as cytoskeletal and heat shock proteins, and those involved in metabolic processes) in studies examining the effects of altered environmental or nutritional conditions, drugs, or genetic manipulation, since these proteins are often highly abundant, soluble and therefore amenable to analysis. Conversely, the proteins mediating the transmission of the signal have been generally under-represented, typically because of their low abundance. One mechanism that has overcome this to some extent is the advent of very high-resolution phosphoproteomics techniques, which have enabled temporal profiling of intracellular signal pathways via quantitative assessment of peptide phosphorylation sites. One group of proteins, however, that still remains under-represented in proteomics studies are those found in the plasma membrane (PM). Such proteins are crucial in sensing changes in the external environment and in stimulating the transmission of the signal intracellularly. This review examines PM proteins and appraises the proteomics approaches currently available for providing a comprehensive analysis of these crucial mediators of signal pathways. We discuss different strategies for enrichment and solubilization of these proteins and include discussion on cross-linking of PM complexes and glycoproteomics as the basis for purification prior to proteomic analyses.


title: Viral diagnosis in Indian livestock using customized microarray chips.

text: Viral diagnosis in Indian livestock using customized microarray chips is gaining momentum in recent years. Hence, it is possible to design customized microarray chip for viruses infecting livestock in India. Customized microarray chips identified Bovine herpes virus-1 (BHV-1), Canine Adeno Virus-1 (CAV-1), and Canine Parvo Virus-2 (CPV-2) in clinical samples. Microarray identified specific probes were further confirmed using RT-PCR in all clinical and known samples. Therefore, the application of microarray chips during viral disease outbreaks in Indian livestock is possible where conventional methods are unsuitable. It should be noted that customized application requires a detailed cost efficiency calculation.


title: First Case of Rhinocerebral Mucormycosis Caused by Lichtheimia ornata, with a Review of Lichtheimia Infections.

text: BACKGROUND Lichtheimia species are emerging opportunistic fungal pathogens in the Mucorales, causing serious skin and respiratory infections in immunocompromised patients. Established agents are Lichtheimia corymbifera and L. ramosa, while L. ornata is a novel agent. Available data on a species-specific analysis of Lichtheimia infections are limited. METHODS The first case of a fatal rhino-orbital-cerebral infection in a hematopoietic stem cell transplantation recipient caused by L. ornata is reported; the agent was identified by sequencing the ITS ribosomal region. We reviewed the literature on mucormycosis due to Lichtheimia species between 2009 and 2018, with an analysis of risk factors and epidemiological and clinical data. RESULTS In addition to our Lichtheimia ornata case, 44 cases of human Lichtheimia were analyzed. Lichtheimia predominated in Europe (68.2%), followed by Asia (16%), and Africa (9%). The most common underlying condition was hematological malignancy (36.3%), followed by trauma/major surgery (27.3%), while diabetes mellitus was rare (11.4%). Site of infection was mostly skin and soft tissues (45.5%) and lung (25%), while relatively few cases were disseminated (13.6%) or rhinocerebral (11.4%). Mortality (36.4%) was mainly due to disseminated and rhinocerebral infections. CONCLUSION In contrast to Rhizopus, the most common agent of mucormycosis recorded in patients with diabetes mellitus, Lichtheimia infections were primarily associated with hematological malignancies and major skin barrier damage. Given the fact that classical rhinocerebral mucormycosis remains difficult to treat, independent of causative species, timely application of amphotericin B accessory to debridement may be required for patient survival.


Will We Be Ready for the Next War?


title: A systematic review about costing methodology in robotic surgery: evidence for low quality in most of the studies.

text: OBJECTIVES The main objective of this review was to evaluate the methodological design in studies reporting resource use and costs related to robotic surgery in gynecology. METHODS Systematic searches were performed in the databases PubMed, Embase, Scopus, and The Centre for Reviews and Dissemination database for relevant studies before May 2016. The quality of the methodological design was assessed with items regarding methodology from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). The systematic review was reported according to the PRISMA guidelines. RESULTS Thirty-two relevant studies were included. None of the reviewed studied fully complied with the CHEERS methodological checklist. Background and objectives, Target population and subgroups and Setting and location were covered in sufficient details in all studies whereas the Study perspective, Justification of the time horizon, Discount rate, and Estimating resources and costs were covered in less than 50%. Most of the studies (29/32) used the health care sector perspective whereas the societal perspective was applied in three studies. The time horizon was stated in 18/32 of the studies. CONCLUSIONS The methodological quality of studies evaluating costs of robotic surgery was low. The longest follow-up was 4 months and in general, the use of detailed cost data were lacking in most of the investigations. Key determinants, such as purchasing, maintenance costs of the robotic platform, and the use of surgical equipment, were rarely reported. If health care cost analyses lack transparency regarding cost drivers included it may not provide a true foundation for decision-making.


title: Parasitic myomas.

text: OBJECTIVE To report a large case series of parasitic myomas and to examine their causes, associations, and risk factors. METHODS Retrospective chart review was performed on 12 patients found to have parasitic myomas between August 2000 and April 2008. The following data were systematically collected: surgery date; indications for surgery; number, dates, and types of prior surgeries; prior use of morcellation; and locations of parasitic myomas. Pathologic confirmation of all specimens was obtained. RESULTS Laparoscopic evaluation confirmed the presence of intraperitoneal and retroperitoneal myomas distinct from the uterus in 12 patients. Ten of the 12 patients had prior abdominal surgery. Eight patients had prior morcellation procedures; six performed laparoscopically, two performed by laparotomy. Three patients had multiple parasitic myomas, all of whom had a history of laparoscopic myomectomy with morcellation. The majority (14 of 15) of myomas were found in the pelvis, including two retroperitoneal myomas, one of which was embedded in the bladder. Six of 15 myomas were found along the gastrointestinal tract, and 1 of 15 was found in the upper abdomen. CONCLUSION Parasitic myomas may occur spontaneously as pedunculated subserosal myomas lose their uterine blood supply and parasitize to other organs. More parasitic myomas may be iatrogenically created after surgery, particularly surgery using morcellation techniques. With increasing rates of laparoscopic procedures, surgeons should be aware of the potential for iatrogenic parasitic myoma formation, their likely increasing frequency, and intraoperative precautions to minimize occurrence. LEVEL OF EVIDENCE III.


title: Use of a cap in single-balloon enteroscopy-assisted endoscopic retrograde cholangiography.

text: BACKGROUND AND STUDY AIM Cannulation of the native papilla in surgically altered anatomy is difficult in endoscopic retrograde cholangiography (ERC). There are limited data regarding the success of single-balloon enteroscopy-assisted ERC (SBE-ERC) in patients with a native papilla and Roux-en-Y gastric bypass. Use of a plastic cap may assist cannulation in these cases. The aim of the current study was to investigate the use of SBE-ERC with a cap (Cap-SBE-ERC) in patients with surgically altered anatomy referred for ERC. PATIENTS AND METHODS Patients with surgically altered anatomy (hepaticojejunostomy, gastric bypass surgery, and Whipple's surgery) who underwent Cap-SBE-ERC were identified from a prospectively maintained database. Outcomes were diagnostic and procedural success. Patients with a native papilla were compared with those with a biliary-enteric anastomosis. RESULTS Among 56 patients with surgically altered anatomy, high rates of diagnostic and procedural success were observed (78.6 % and 71.4 %, respectively). High diagnostic and procedural success rates of 72.7 % and 65.9 %, respectively, were also observed for patients with Roux-en-Y gastric bypass anatomy with a native papilla (n = 44). CONCLUSION High rates of diagnostic and procedural success were reported for SBE-ERC with the use of a cap, including a large subgroup of patients with Roux-en-Y gastric bypass and a native papilla.


title: Analysis of conversion factors in robotic-assisted rectal cancer surgery.

text: BACKGROUND Robotic surgical management of rectal cancer has a series of advantages which might facilitate the surgical approach to the pelvic cavity and reduce conversion rates. The aim of the present study is to identify independent factors for conversion during robotic rectal cancer surgery. METHODS A total of 67 patients underwent preoperative CT scan in order to obtain a three-dimensional image of the pelvis, the tumour and prostate. We measured maximum and minimum ilio-iliac, sacral promontory-pubis, coccyx-pubis diameters and maximum lateral axis. Further variables under consideration were age, BMI and use of neoadjuvant therapy. We recorded short-term follow-up outcomes of the resected tumour. RESULTS The present study included 67 patients (39 males) with an average age of 65.11 ± 10.30 years and a BMI of 27.70 ± 3.97 kg/m(2). Operative procedures included nine abdominoperineal resections and 58 low anterior resections. There were 15 (22.38 %) conversions. Mean operating time was 192.2 ± 42.73 min. Minimum ilio-iliac, maximum ilio-iliac, promontory-pubic and coccyx-pubis diameter as well as maximum lateral axis were 100.38 ± 7.65, 107.10 ± 10.01, 109.97 ± 9.20, 105.61 ± 9.27 and 129.01 ± 9.94 mm, respectively. Mean tumour volume was 37.06 ± 44.08 cc; mean prostate volume was 42.07 ± 17.49 cc. The univariate analysis of the variables showed a correlation between conversion and BMI and minimum ilio-iliac and coccyx-pubis diameters (p = 0.004, 0.047, 0.046). In the multivariate analysis, the only independent predictive factor for conversion was the BMI (p = 0.004).No correlation was found between conversion and sex, age, tumour volume or the rest of pelvic diameters. CONCLUSION BMI is an independent factor for conversion in robotic-assisted rectal cancer surgery.


title: Structure of Mpro from COVID-19 virus and discovery of its inhibitors.

text: A new coronavirus (CoV) identified as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan1-4. Currently there are no targeted therapeutics and effective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, we initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the COVID-19 virus main protease (Mpro). Mpro is a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus5,6. Here, we identified a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of COVID-19 virus Mpro in complex with this compound. Next, through a combination of structure-based virtual and high-throughput screening, we assayed over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro. Six of these compounds inhibited Mpro with IC50 values ranging from 0.67 to 21.4 μM. Ebselen also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available.


title: Nuclear magnetic resonance structure shows that the severe acute respiratory syndrome coronavirus-unique domain contains a macrodomain fold.

text: The nuclear magnetic resonance (NMR) structure of a central segment of the previously annotated severe acute respiratory syndrome (SARS)-unique domain (SUD-M, for "middle of the SARS-unique domain") in SARS coronavirus (SARS-CoV) nonstructural protein 3 (nsp3) has been determined. SUD-M(513-651) exhibits a macrodomain fold containing the nsp3 residues 528 to 648, and there is a flexibly extended N-terminal tail with the residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. As a follow-up to this initial result, we also solved the structure of a construct representing only the globular domain of residues 527 to 651 [SUD-M(527-651)]. NMR chemical shift perturbation experiments showed that SUD-M(527-651) binds single-stranded poly(A) and identified the contact area with this RNA on the protein surface, and electrophoretic mobility shift assays then confirmed that SUD-M has higher affinity for purine bases than for pyrimidine bases. In a further search for clues to the function, we found that SUD-M(527-651) has the closest three-dimensional structure homology with another domain of nsp3, the ADP-ribose-1"-phosphatase nsp3b, although the two proteins share only 5% sequence identity in the homologous sequence regions. SUD-M(527-651) also shows three-dimensional structure homology with several helicases and nucleoside triphosphate-binding proteins, but it does not contain the motifs of catalytic residues found in these structural homologues. The combined results from NMR screening of potential substrates and the structure-based homology studies now form a basis for more focused investigations on the role of the SARS-unique domain in viral infection.


title: Killer cell immunoglobulin-like receptor (KIR) genotypes in patients with recurrent tonsillitis.

text: AIMS This study represents the first report on the distribution of killer cell immunoglobulin-like receptor (KIR) genotype among recurrent tonsillitis patients. We recruited 34 Lebanese pediatric patients diagnosed with recurrent tonsillitis and had their DNA typed using sequence-specific primer technique for the presence of 16 KIR loci. RESULTS We observed that 25 different KIR genotypes were present similar to the general control population with the same KIR gene content. There was no statistically significant difference in the distribution of the activating and inhibitory KIR genes between the two categories. Like in the general control population, we noted a predominance of the AB genotype; however, the KIR genotypic distribution among the tonsillitis patients was much more heterogeneous with even new genotypes not reported in the control group. CONCLUSIONS Although the sample size is small, this first study observes an interesting heterogeneous KIR gene profile in recurrent tonsillitis that warrants larger and further research in the area for the true biological and clinical significance of this observation.


title: Vision-Based Surgical Field Defogging.

text: Fogged surgical field visualization that is a common and potentially harmful problem can lead to inappropriate device use and incorrectly targeted tissue and increase surgical risks in endoscopic surgery. This paper aims to remove fog or smoke on endoscopic video sequences to augment and maintain a direct and clear visualization of the operating field. A new visibility-driven fusion defogging framework is proposed for surgical endoscopic video processing. This framework first recovers the visibility and enhances the contrast of hazy images. To address the color infidelity problem introduced by the visibility recovery, the luminances of the recovered and enhanced images are fused in the gradient domain, and the fused luminance is reconstructed by solving the Poisson equation in the frequency domain. The proposed method is evaluated on clinical videos that were collected from prostate cancer surgery. The experimental results demonstrate that the proposed framework defogs endoscopic images more robustly than currently available methods. Additionally, our method also provides an effective way to improve the visual quality of medical or high-dynamic range images.


title: Peripheral tissue oximetry: comparing three commercial near-infrared spectroscopy oximeters on the forearm.

text: Estimation of regional tissue oxygenation (rStO2) by near infrared spectroscopy enables non-invasive end-organ oxygen balance monitoring and could be a valuable tool in intensive care. However, the diverse absolute values and dynamics of different devices, and overall poor repeatability of measurements are a problem. The aim of the present study is to test the hypothesis that INVOS 5100C, FORE-SIGHT and NONIN EQUANOX 7600 have similar properties concerning absolute values, repeatability, and sensitivity to changes in rStO2. To test repeatability the sensors were repositioned 20 times during hemodynamic steady state on the adult forearm. Afterwards six vascular occlusions by inflation of an upper arm cuff were done to achieve low oxygenation in the forearm. Absolute values were compared by repeated-measures ANOVA, repeatability was estimated by the within-subject standard deviation, Sw, and response to changing oxygenation by the down slope of rStO2 during vascular occlusion in the respective arm. 10 healthy adults, 21-29 years old, with double skinfolds on the forearm less than 10 mm participated. The median rStO2 was 70.7% (interquartile range (IQR) 7.7%), 68.4% (IQR 8.4%), and 64.6% (IQR 4.8) with INVOS, NONIN, and FORE-SIGHT, respectively, the median rate of decline was 13.2%/min (IQR 9.6), 22.8 %/min (IQR 18.0), and 10.8%/min (IQR 6.0), and the same-site repeatability was 2.9% (95% CI 2.4-3.3), 4.6% (CI 3.9-5.3), and 2.0% (CI 1.7-2.3). INVOS gave significantly higher steady state values than FORE-SIGHT, and NONIN had the steepest decline in rStO2, but the poorest repeatability. Two measures of signal-to-noise were similar among devices. This suggests that good repeatability comes at the expense of low sensitivity to changes in oxygenation. Values of rStO2 on the forearm from INVOS, NONIN and FORE-SIGTH cannot be used interchangeably.


title: The Causes of Canine Myocarditis and Myocardial Fibrosis Are Elusive by Targeted Molecular Testing: Retrospective Analysis and Literature Review.

text: Myocarditis can cause death or permanent heart damage. As epidemiologic and etiopathologic data for canine myocarditis are lacking, we performed a retrospective study using nucleic acid extracted from archived (2007 to 2015) tissues from myocarditis cases and control dogs without myocardial lesions. Heart tissue from pediatric/juvenile and adult dogs was tested with a comprehensive panel of conventional and real-time polymerase chain reaction (PCR) assays targeting recognized agents of canine myocarditis based on a literature review and informed by the comparative epidemiology of human myocarditis. The PCR screen, which included canine parvovirus 2 (CPV-2), canine distemper virus, canine herpesvirus, Borrelia spp, West Nile virus, adenovirus, parainfluenza virus, pneumovirus, respiratory coronavirus, influenza virus, Bartonella spp, Rickettsia spp, Mycoplasma spp, and Neospora caninum, did not detect agents in 35 of 66 cases (53%; 95% confidence interval [CI], 41%-65%) and was frequently negative in adults (21/26); by comparison, agents were not detected in 27 of 57 controls (47%; 95% CI, 35%-60%). Canine distemper virus, herpesvirus, adenovirus, coronavirus, parainfluenza virus, Mycoplasma haemocanis, and N. caninum were occasionally detected in both cases and controls; thus, PCR detection was not considered to indicate causation. We previously reported that CPV-2 continues to be associated with myocarditis in young dogs despite widespread vaccination; in adults, CPV-2 was detected in 2 of 26 cases and 4 of 22 controls. As several agents were similarly detected in cases and controls, it is unclear if these are cardiopathogenic, incidental, or latent. West Nile virus was detected at the analytic limit in 1 adult case. We did not detect Borrelia spp, Bartonella spp, Rickettsia spp, or influenza A virus in the myocarditis cases. These data demonstrate the limitations of current targeted diagnostic tests and the need for additional research to identify unknown agents and develop testing strategies for canine myocarditis.


title: BacMam virus-based surface display of the infectious bronchitis virus (IBV) S1 glycoprotein confers strong protection against virulent IBV challenge in chickens.

text: Avian infectious bronchitis virus (IBV) is associated with production inefficiencies in domestic fowl, and causes massive economic losses to the poultry industry worldwide. Progress has been made in designing novel and efficient candidate vaccines to control IBV infection. BacMam virus, a modified baculovirus mediating transgene expression under the control of a mammalian promoter, has emerged as a versatile and safe vector during vaccine development. In previous work, we generated the BacMam virus Ac-CMV-S1, which expressed the S1 glycoprotein of IBV-M41. We showed that Ac-CMV-S1 induced excellent cellular immunity, but did not confer adequate protection in chickens compared with the conventional inactivated vaccine. In the current study, we generated an improved BacMam virus, BV-Dual-S1. This virus displayed the S1 glycoprotein on the baculovirus envelope, and was capable of expressing it in mammalian cells. BV-Dual-S1 elicited stronger humoral and cell-mediated immune responses, and showed greater capacity for induction of cytotoxic T lymphocyte responses, compared with Ac-CMV-S1 in specific pathogen-free chickens. A significant difference was not observed for protection rates between chickens immunized with BV-Dual-S1 (83%) or inactivated vaccine (89%) following challenge with virulent IBV-M41. Our findings show that the protective efficacy of BV-Dual-S1 could be significantly enhanced by baculovirus display technology. BacMam virus-based surface display strategies could serve as effective tools in designing vaccines against IB and other infectious diseases.


title: Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain.

text: The cerebral vascular system services the constant demand for energy during neuronal activity in the brain. Attempts to delineate the logic of neurovascular coupling have been greatly aided by the advent of two-photon laser scanning microscopy to image both blood flow and the activity of individual cells below the surface of the brain. Here we provide a technical guide to imaging cerebral blood flow in rodents. We describe in detail the surgical procedures required to generate cranial windows for optical access to the cortex of both rats and mice and the use of two-photon microscopy to accurately measure blood flow in individual cortical vessels concurrent with local cellular activity. We further provide examples on how these techniques can be applied to the study of local blood flow regulation and vascular pathologies such as small-scale stroke.


Potential of chloroquine and hydroxychloroquine to treat COVID-19 causes fears of shortages among people with systemic lupus erythematosus.


title: EKG Electrode as a Tactile Locator of Stoma after Decannulation: A Pilot Study.

text: Objective We aimed to evaluate the use of an electrocardiogram (EKG) electrode over decannulation dressings covering the stoma to improve speech intelligibility and volume and reduce air escape by facilitating identification of the "sweet spot" of the dressing. No objective data exist for patient outcomes with use of the EKG electrode dressing. Methods This prospective study included head and neck oncology patients at a tertiary hospital who received a tracheostomy. A standard tracheostomy decannulation dressing was placed followed by an EKG electrode. A speech pathologist evaluated speech volume via sound-level meter and captured speech intelligibility for random sentence-level speech. A blinded reviewer scored speech samples for intelligibility. Patients completed a 4-question satisfaction survey. Results Four patients completed the study. Based on the survey, the patients favored the button, with the lowest scores being 8.5 out of 10. Speech understanding was 48.5% without the button and 83% with the button. Normal speech volume was 73.75 dB without the button and 77.75 dB with the button. Loud speech volume was 80.75 dB without the button and 87 dB with the button. Discussion This pilot study shows objective benefits of the EKG button as well as improved patient satisfaction. Inexpensive and low maintenance, the EKG electrode provides better occlusion of stoma dressing with easier localization. Implications for Practice Dissemination of our results will aim to improve quality and patient outcomes following decannulation.


title: Post-traumatic amaurosis secondary to paraophthalmic internal carotid artery pseudoaneurysm treated with pipeline embolization device.

text: During evaluation for monocular visual loss, a 48-year-old woman was found to have a posttraumatic paraophthalmic internal carotid artery (ICA) pseudoaneurysm. She underwent reconstruction of the ophthalmic segment of the right ICA with a Pipeline embolization device but her vision did not return.


title: Publisher Correction: Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.

text: An amendment to this paper has been published and can be accessed via a link at the top of the paper.


title: Expression of B-cell-associated genes in peripheral blood mononuclear cells of patients with symptomatic pulmonary embolism.

text: The aim of the present study was to identify differentially expressed B‑cell‑associated genes in peripheral blood mononuclear cells and investigate the gene expression characteristics of the different stages of B‑cell activation. A total of 20 patients with pulmonary embolisms (PE) and 20 age‑ and gender‑matched controls were enrolled in the present study. Human complementary DNA microarray analysis was used in order to detect the differential expression of B‑cell‑associated genes between the PE and control groups. Messenger (m)RNA expression was detected for 82 genes involved in B‑cell activation. The results showed that PE patients exhibited significantly increased expression levels of the B‑cell receptor genes LYN, CD22, SYK, BTK, PTPRC and NFAM1, whereas expression levels of FYN, FCRL4 and LAX1 were significantly decreased compared to those of the control group. Expression levels of T‑cell‑dependent B‑cell‑activation genes, including EMR2, TNFSF9, CD86, ICOSLG, CD37 and CD97, were significantly upregulated in PE patients, whereas SPN mRNA expression was significantly downregulated compared with those of the control group. LILRA1 and TLR9 T cell‑independent B‑cell activation mRNAs were significantly upregulated in PE patients compared with those of the control group. In addition, the expression levels of B‑cell‑activation regulator genes, including CR1, LILRB4 and VAV1, were significantly increased, whereas SLAMF7 expression levels were significantly decreased in PE patients compared with those of the control group. Furthermore, the expression levels of B‑cell‑activation‑associated cytokine genes demonstrated a significant upregulation of LTA and IL10 and downregulation of L1A, IFNA5, IFNA6, IFNA8, IFNA14, IL2, IL13 and IFNG in PE patients compared to those of the control group. In conclusion, the differential gene expression at different stages of B‑cell activation between healthy controls and PE patients indicated that B‑cell function was reduced or disorganized in patients with symptomatic PE.


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title: A Computationally Designed Serological Assay for Porcine Epidemic Diarrhea Virus.

text: The periodic emergence of new infectious agents and the genetic and antigenic evolution of existing agents necessitate the improvement of technology for the rapid development of diagnostic assays. The porcine epidemic diarrhea virus (PEDV) emerged in the United States in 2013, causing severe economic damage to the pork industry. The primary goal of this study was to develop methods to reduce the lead time for serological assay development. An approach involving the computational prediction of diagnostic targets, followed by a rapid synthesis of antigens, was adopted to achieve this objective. To avoid cross-reactivity with other closely related swine coronaviruses, the N protein sequences of PEDV were analyzed to identify sequences unique to PEDV. The potential antigenicity of the identified sequence was predicted computationally using the Jameson-Wolf method. A sequence with a high antigenic index was rapidly synthesized using an in vitro transcription and translation system to yield the diagnostic antigen. The computationally designed enzyme-linked immunosorbent assay (ELISA) was validated using 169 field sera, whose statuses were determined by a PEDV-specific immunofluorescence assay. Comparison of the computationally designed ELISA to a conventionally developed ELISA, using bacterially expressed N protein, and to the immunofluorescence assay showed a high degree of agreement among the three tests (mean kappa statistic, 0.842). The sensitivity and specificity, compared to the conventionally developed assay, were 90.62 and 95.18, respectively. Therefore, the described approach is useful in reducing the development time for serological assays in the face of an infectious disease outbreak.


title: [Renal LESS surgery: Slight modification or surgical revolution?].

text: OBJECTIVE to present our initial experience of laparoendoscopic single site (LESS) renal surgery. METHODS between May 2009 and March 2010, nine nephrectomies and one cyst decortication were performed in nine patients. Eight of the procedures were done with three 5mm trocars inserted through a unique peri-umbilical incision. In two cases, a specific single-port device was used. All operations were achieved with a 5-mm 30° lens and conventional laparoscopic instruments. The specimens were entrapped in a 10mm endoscopic bag and extracted through the umbilical incision. RESULTS mean age was 56 years old. Mean BMI was 23.5 [19-34]. Mean operative time was 149min [80-240], and estimated blood loss was 90ml [20-250]. None of the patients required blood transfusion. Mean length of stay was 4.1 days [3-5]. Only one major complication occurred (functional occlusion). One conversion to conventional laparoscopy was necessary in a case of inflammatory kidney. Histologic exam showed benign lesions (cyst and non functional kidney) in seven cases, and papillary carcinoma in three cases. CONCLUSION LESS surgery is feasible. Its advantages over conventional laparoscopy are not clear. LESS is a new procedure that should benefit from the improvement of technical instrumentation.


title: Hematology of Free-ranging and Managed Texas Horned Lizards ( Phrynosoma cornutum).

text: The Texas horned lizard ( Phrynosoma cornutum) is a threatened species in Texas, US (federal category C2). Causes for population declines in this species are likely multiple. Disease and health assessments using traditional methods, including hematology, have been minimally studied in Phrynosoma spp. Apparently healthy, free-ranging Texas horned lizard from four locations in Texas ( n=53) and captive Texas horned lizards maintained at the Fort Worth Zoo ( n=16) were sampled to establish hematologic reference intervals. Within the populations studied, total leukocyte, heterophil, and eosinophil counts were higher in managed compared to free-ranging lizards. Leukocyte and heterophil counts of all lizards were lower during the ovipositional months of June and July.


title: Combined Balloon Test Occlusion and SPECT Analysis for Carotid Sacrifice: Angiographic Predictors for Success or Failure?

text: Objectives To evaluate angiographic patterns that may predict the success or failure of carotid artery balloon test occlusion (BTO) and single-photon emission computed tomography (SPECT) analysis for carotid sacrifice. Study Design This is a retrospective nonrandomized study. Study Setting Conducted at the University of California Davis Medical Center, Sacramento, California. Patients A total of 31 patients, ranging from 24 to 83 years of age, with a mean age of 61 years (22 men, 9 women) with head and neck cancer (26 patients), malignant glomus tumor (1 patient) or giant carotid aneurysms (4 patients) as possible candidates for surgical carotid artery sacrifice were evaluated from September 2005 to September 2012. Methods All patients underwent unilateral internal carotid artery balloon test occlusion with SPECT analysis (20 mCi technetium 99m-hexamethyl propyleneamine oxime [HMPAO]) imaging before and during carotid occlusion. Carotid angiography with carotid cross-compression (manual compression of the cervical artery contralateral to the side of contrast injection) was used to analyze filling through the anterior communicating artery to the contralateral hemisphere. Intervention The balloon occlusion was terminated in two patients because of deterioration of the neurologic exam. Main Outcome Measures All patients who passed the neurologic examination during BTO and also passed the SPECT occlusive study underwent successful carotid sacrifice without neurologic sequelae. Patients failing the occlusive neurologic examination and/or the SPECT study elected chemoradiation, with the exception of one patient who underwent a successful carotid bypass graft and carotid resection. Results The success of carotid sacrifice in patients passing both the occlusive test and the SPECT analysis for carotid sacrifice was 100%. Three patients failed both the BTO and the SPECT, with two demonstrating no anterior circulation cross-fill, but one showed some cross-fill. Six additional patients passed the BTO but failed the SPECT, with poor cross-fill in five patients. In addition, three patients who had excellent cross-fill through the anterior communicating artery to the contralateral hemisphere failed the SPECT examination in two cases and failed both tests in another case.


title: [Transmission of Influenza A].

text: The pandemic influenza A 2009 virus led to new discussions about proper protection measures in hospitals and in the general population. To implement efficacious protection measures against the influenza A virus, we have to know its way of transmission. Influenza A transmission occurs primarily via droplets and contact. However, several experimental studies and observations of outbreaks indicate that influenza can also be transmitted through the airborne route (via aerosols). The possibility of airborne transmission of influenza should be taken in consideration for pandemic influenza planning and recommendations. In case of influenza epidemics with high (or not yet defined) mortality, exposed healthcare personnel should be protected using precautions against airborne transmission, including the use of FFP2 (N95) respirators.


title: Combined endothelial and epithelial barrier disruption of the colon may be a contributing factor to the Ebola sepsis-like syndrome.

text: After an initial febrile viral syndrome, infection with Ebola virus often induces an explosive late "Ebola sepsis-like syndrome" which appears very similar to some phenotypes of bacterial sepsis and is commonly fatal. It is possible that direct and diffuse viral infection of both the endothelium and epithelium of the colon may cause sufficient disruption of both the endothelial and epithelial barriers to induce exposure or leakage of endotoxin and bacterial antigens to, or into, the vascular system precipitating or exacerbating the Ebola sepsis-like syndrome. If colonic barrier disruption or vascular exposure of bacterial antigens from the colon is found to comprise an important mechanism of the Ebola sepsis-like syndrome, protocolized timed decontamination of the bowel with or without timed prophylactic antibiotics might warrant investigation.


title: Observed Cost and Variations in Short Term Cost-Effectiveness of Therapy for Ischemic Stroke in Interventional Management of Stroke (IMS) III.

text: BACKGROUND Examination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12-month follow-up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke) III Trial. METHODS AND RESULTS Prospective data collected for a prespecified economic analysis of the trial were used. Data included hospital billing records for the initial stroke admission and subsequent detailed resource use after the acute hospitalization collected at 3, 6, 9, and 12 months. Cost of follow-up care varied 6-fold for patients in the lowest (0-1) and highest (20+) National Institutes of Health Stroke Scale category at 5 days, and by modified Rankin Scale at 3 months. The kind of resources used postdischarge also varied between treatment groups. Incremental short-term cost-effectiveness ratios varied greatly when treatments were compared for patient subgroups. Patient subgroups predefined by stroke severity had incremental cost-effectiveness ratios of $97 303/quality-adjusted life year (severe stroke) and $3 187 805/quality-adjusted life year (moderately severe stroke). CONCLUSIONS Detailed economic and resource utilization data from IMS III provide powerful evidence for the large effect that patient outcome has on the economic value of medical and endovascular reperfusion therapies. These data can be used to inform process improvements for stroke care and to estimate the cost-effectiveness of endovascular therapy in the US health system for stroke intervention trials. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Registration number: NCT00359424.


title: Robot-assisted enucleation of gigantic liver hemangiomas: Case series of 3 patients.

text: INTRODUCTION Liver hemangiomas are benign liver lesions that require surgical excision when large and symptomatic. Often, these tumors are removed through large anatomical resections which sacrifice more liver parenchyma than needed. Tumor enucleation, which takes advantage of a digitoclasia-like technique along the plane between the tumor pseudo-capsule and liver parenchyma, poses challenges when performed laparoscopically. We propose a parenchymal sparing, minimally invasive, robotic-assisted technique to remove liver hemangiomas. PRESENTATION OF CASES Three male patients with symptomatic hemangiomas were treated in our center between 2015 and 2018. The lesions were located in segment II, III and segment IV-V respectively. Robotic-assisted hemangioma enucleation was accomplished successfully in all three patients. The procedures were performed with a parenchyma-sparing intent and a formal segmentectomy was not required. There were no conversions to open surgery. DISCUSSION The robotic platform provides a powerful tool in the enucleation of liver hemangiomas. The enhanced vision and the superior suturing ability allow to develop safely the plane between the tumor pseudo-capsule and the liver parenchyma, with outstanding selective control of all the vascular supply and drainage encountered during the dissection. Furthermore, precision of the hilar dissection allows selective lobar or sectorial arterial control which helps minimize intraoperative bleeding. CONCLUSION In our experience, robot-assisted enucleation of liver hemangiomas offers low morbidity, fast recovery, excellent cosmetic results, and it could become a therapeutic option when the location of the hemangioma allows this approach.


title: Benchmark Study for the Cysteine-Histidine Proton Transfer Reaction in a Protein Environment: Gas Phase, COSMO, QM/MM Approaches.

text: Proton transfer reactions are of crucial interest for the investigation of proteins. We have investigated the accuracy of commonly used quantum chemical methods for the description of proton transfer reactions in different environments (gas phase, COSMO, QM/MM) using the proton transfer between the catalytic dyad residues cysteine 145 and histidine 41 of SARS coronavirus main protease as a case study. The test includes thermodynamic, kinetic, and structural properties. The study comprises computationally demanding ab initio approaches (HF, CC2, MP2, SCS-CC2, SCS-MP2, CCSD(T)), popular density functional theories (BLYP, B3LYP, M06-2X), and semiempirical methods (MNDO/d, AM1, RM1, PM3, PM6). The approximated coupled cluster approach LCCSD(T) is taken as a reference method. We find that the robustness of the tested methods with respect to the environment correlates well with the level of theory. As an example HF, CC2, MP2, and their SCS variants show similar errors for gas phase, COSMO, or QM/MM computations. In contrast for semiempirical methods, the errors strongly diversify if one goes from gas phase to COSMO or QM/MM. Particular problems are observed for the recent semiempirical methods PM6 and RM1, which show the best performance for gas phase calculations but possess larger errors in conjunction with COSMO. Finally, a combination of SCS-MP2 and B3LYP or M06-2X allows reliable estimates about remaining errors.


Les liaisons dangereuses and the danger of deductions: The interplay between cardiovascular disease and COVID-19.


title: Real-Time Ultrasound Improves Accuracy of Caudal Block in Children.

text: BACKGROUND Caudal block, the most common regional anesthetic in children, is predominantly performed using palpation to determine placement. The efficacy of the palpation technique is unknown with respect to block success. While ultrasound has been suggested for use during caudal block, its use is infrequent. METHODS A single-blinded prospective observational trial was performed evaluating provider success rate of caudal blocks placed by palpation alone. After needle insertion and partial local anesthetic injection, an ultrasound was performed to confirm correct location. RESULTS A total of 109 caudal blocks were performed during the prospective observational study. Success rate for caudal blocks done by palpation alone was 78.9% as confirmed by ultrasound. In 21.1% of caudal blocks, the provider incorrectly judged the needle to be in the caudal space as confirmed with ultrasound. CONCLUSIONS Real-time ultrasound visualization of local anesthetic injection provides reliable and immediate confirmation during caudal block in children.


title: Filovirus entry into cells - new insights.

text: Filoviruses are hemorrhagic fever-causing agents that produce enveloped virions with a filamentous morphology. The viral surface glycoprotein, GP, orchestrates the surprisingly complex process by which filoviruses gain access to the cytoplasm of their host cells. GP mediates viral attachment to cells through multiple, redundant interactions with cell-surface factors. GP then induces virion internalization by a process that resembles cellular macropinocytosis. Within the endo/lysosomal pathway, GP undergoes a series of structural rearrangements, controlled by interactions with host factors, that prime and activate it to bring about fusion between the viral and cellular lipid bilayers. Membrane fusion delivers the viral nucleocapsid core into the cytoplasm, which is the site of filovirus replication. This review summarizes our understanding of the filovirus entry mechanism, with emphasis on recent findings.


title: Pulse oximetry in bronchiolitis: is it needed?

text: Infants admitted to health-care centers with acute bronchiolitis are frequently monitored with a pulse oximeter, a noninvasive method commonly used for measuring oxygen saturation. The decision to hospitalize children with bronchiolitis has been largely influenced by pulse oximetry, despite its questionable diagnostic value in delineating the severity of the illness. Many health-care providers lack the appropriate clinical fundamentals and limitations of pulse oximetry. This deficiency in knowledge might have been linked to changes in the management of bronchiolitis. The aim of this paper is to provide the current evidence on the role of pulse oximetry in bronchiolitis. We discuss the history, fundamentals of operation, and limitations of the apparatus. A search of the Google Scholar, Embase, Medline, and PubMed databases was carried out for published articles covering the use of pulse oximetry in bronchiolitis.


title: Specimen processing during laparoscopic renal surgery: a review of techniques and technologies.

text: Laparoscopic surgery has well-defined benefits for patients and has become accepted over time as a standard access strategy for the management of benign and malignant urologic diseases. Unlike in open surgery, the surgeon is often faced with the additional challenges of specimen retrieval and extraction at the end of laparoscopic extirpative procedures. This final step often requires significant laparoscopic skill to entrap and safely extract the laparoscopic specimens. Failure to apply safe exit steps at the end of a laparoscopic procedure may lead to significant morbidity. The aim of this review is to explore the different techniques and technologies available for laparoscopic kidney retrieval, entrapment and safe extraction.


title: Reevaluation of needlescopic surgery.

text: BACKGROUND Although the use of single-incision laparoscopic surgery (SILS) has spread rapidly, most procedures employ additional needlescopic instruments to ensure safety and shorten the operation time. Therefore, on the basis of results obtained in our department, the present study was conducted to reevaluate the current state of needlescopic surgery (NS) to improve the cosmetic results and postoperative quality of life of patients and to reduce cost and degree of stress on surgeons. METHODS Between May 1998 and February 2011, we performed NS in 202 patients. The diagnoses included gallbladder diseases in 151 patients, spontaneous pneumothorax in 11, thyroid tumor and axillary lymph node metastases in 10 patients each, splenic cyst and appendicitis in 4 patients each, idiopathic thrombocytopenic purpura and postoperative abdominal wall hernia in 3 patients each, primary aldosteronism and hepatic cyst in 2 patients each, and adhesional bowel obstruction and gastric stromal tumor in 1 patient each. Under general anesthesia, one 12-mm and tow or three 2- or 3-mm ports were introduced into the operative field. The specimen was retrieved via the 12-mm wound using a plastic bag. RESULTS The operations were completed in all patients without the need to convert to an open procedure. In 8 (5.3%) of the 151 cholecystectomies, a change to 5-mm instruments was required. There were no perioperative complications. Pertinent technical points included avoidance of direct organ mobilization to minimize injury, rotation of the operating table and utilization of organ gravity to create a better operative field, minimum use of needlescope to ensure safe maneuvering, and improvement of the bi-hand technique. CONCLUSIONS NS is a safe and feasible procedure that allows experienced surgeons to achieve minimally invasive surgery with low morbidity, without the need to convert to a conventional or open procedure.


docid: zrkztmnf

title: Improved quality and diagnostic confidence achieved by use of dose-reduced gadolinium blood-pool agents for time-resolved intracranial MR angiography.

text: BACKGROUND AND PURPOSE Time-resolved MRA with the use of bolus injection of paramagnetic agents has proved valuable in neurovascular imaging. Standard contrast agents have limited blood-pool residence times, motivating the development of highly protein-bound blood-pool agents with greater relaxivity and longer intravascular residence, affording improved image quality at lesser doses. This study represents the first comparison of blood-pool agents to standard agents in time-resolved cerebral MRA. MATERIALS AND METHODS One hundred datasets were acquired at 1.5 T by use of a standardized, time-resolved MRA protocol. Patients received either unit dosing of a standard extracellular agent at 0.1 mmol/kg or a blood-pool agent at 0.03 mmol/kg. Peak arterial and venous enhancement phases were identified and subsequently scored qualitatively by use of a 4-point Likert scale, with attention to 6 vascular segments: 1) intracranial ICA; 2) MCA M1; 3) MCA M2; 4) MCA M3; 5) deep cerebral veins; and 6) dural venous sinuses. RESULTS Fifty MR angiographies were acquired with each agent. No significant differences were found between agents in generation of uncontaminated arteriograms. Blood-pool agents, at 67% dose reduction, were of significantly greater quality across most vascular segments, including ICA (P = .019), M2 (P = .003), and M3 (P < .01). Superiority in the M1 segment approached significance (P = .059). Significantly better venographic quality was noted for deep venous structures (P = .016) with the use of blood-pool agents. CONCLUSIONS Blood-pool agents provide superior demonstration of most intracranial vessels in time-resolved MRA compared with standard agents, at reduced doses. The greater relaxation enhancement and more favorable dosing profile make blood-pool agents superior to standard agents for use in cerebral time-resolved MRA.


title: Comparison of Different Techniques of Pancreatic Stump Management in Robot-Assisted Pancreaticoduodenectomy.

text: Background Various technical improvements have decreased the morbidity and mortality after pancreaticoduodenectomy. However, postoperative pancreatic fistula (POPF) is the most feared complication, and the ideal technique for pancreatic reconstruction is undetermined. The aim of this study was to identify the risk factors and incidence of POPF with different types of pancreatic stump management after robot-assisted pancreaticoduodenectomy (RAPD). Materials and Methods This study is a retrospective review of consecutive patients who underwent RAPD at the University of Illinois Hospital and Health Sciences System between September 2007 and January 2016. The cohort was divided based on the type of pancreatic stump management: pancreatic duct occlusion with cyanoacrylate glue (CG), pancreaticojejunostomy (PJ), posterior pancreaticogastrostomy (PPG), and transgastric pancreaticogastrostomy (TPG). Results The cohort included 69 patients: pancreatic duct occlusion with CG (n = 18), PJ (n = 12), PPG (n = 11), and TPG (n = 28). Pancreatic duct diameter < 3 mm and duct occlusion with CG were identified as risk factors for POPF (p < 0.05). The incidence of POPF was lower when TPG and PJ were performed (p < 0.001). Conclusions Reconstruction with PJ and TPG had better results compared to pancreatic duct occlusion with CG and PPG. However, TPG was the technique of choice and showed comparable results to PJ.


title: Liver regeneration therapy through the hepatic artery-infusion of cultured bone marrow cells in a canine liver fibrosis model.

text: BACKGROUND We previously reported regenerative therapies for decompensated cirrhosis based on peripheral venous drip infusion using non-cultured whole bone marrow (BM) cells, or the less invasive cultured BM-derived mesenchymal stem cells (BMSCs). Here, we assessed the efficacy and safety of hepatic arterial infusion using cultured autologous BMSCs, comparing it with peripheral infusion, using our established canine liver fibrosis model. METHODS Canine BM cells were harvested and cultured, and the resultant BMSCs were returned to carbon tetrachloride (CCl4)-induced liver cirrhosis model canines via either a peripheral vein (Vein group) or hepatic artery (Artery group). A variety of assays were performed before and 4, 8, and 12 weeks after BMSC infusion, and liver fibrosis and indocyanine green (ICG) half-life (t1/2) were compared to those in a control group that received CCl4 but not BMSCs. The safety of this approach was evaluated by contrast-enhanced computed tomography (CT) and serial blood examinations after infusion. RESULTS Four weeks after infusing BMSCs, a significant improvement was observed in the Vein group (n = 8) compared to outcome in the Control group (n = 10), along with a decrease in ICG t1/2. In the Artery group (n = 4), ICG t1/2 was significantly shorter than that in the Vein group at 8 weeks (Δt1/2: -3.8 ± 1.7 min vs. +0.4 ± 2.4 min; p < 0.01) and 12 weeks (Δt1/2: -4.2 ± 1.7 min vs. +0.4 ± 2.7 min; p < 0.01) after BMSC administration. Post-infusion contrast-enhanced CT showed no liver infarction, and blood tests showed no elevations in either serum lactate dehydrogenase concentrations or hypercoagulability. CONCLUSIONS We confirmed the efficacy and safety of the hepatic arterial infusion of cultured autologous BMSCs using a canine model, thereby providing non-clinical proof-of-concept.


Doctors' deaths from covid-19 should be reported to the coroner.


docid: qwfudhgq

title: Neurological complications of coronavirus and COVID-19.

text: INTRODUCTION Clinical and experimental studies have shown that the coronavirus family has a certain tropism for the central nervous system. Seven types of coronavirus can infect humans. DEVELOPMENT Coronaviruses are not always confined to the respiratory tract, and under certain conditions they can invade the central nervous system and cause neurological pathologies. The potential for neuroinvasion is well documented in most human coronaviruses (OC-43, 229E, MERS and SARS) and in some animal coronaviruses (porcine haemagglutinating encephalomyelitis coronavirus). Neurological symptoms have been reported in patients affected by COVID-19, such as headache, dizziness, myalgia and anosmia, as well as cases of encephalopathy, encephalitis, necrotising haemorrhagic encephalopathy, stroke, epileptic seizures, rhabdomyolysis and Guillain-Barre syndrome, associated with SARS-CoV-2 infection. CONCLUSIONS Future epidemiological studies and case records should elucidate the real incidence of these neurological complications, their pathogenic mechanisms and their therapeutic options.


title: The general movements assessment in term and late-preterm infants diagnosed with neonatal encephalopathy, as a predictive tool of cerebral palsy by 2 years of age: a scoping review protocol.

text: BACKGROUND Prediction of long-term neurodevelopmental outcomes remains an elusive goal for neonatology. Clinical and socioeconomic markers have not proven to be adequately reliable. The limitation in prognostication includes those term and late-preterm infants born with neonatal encephalopathy. The General Movements Assessment tool by Prechtl has demonstrated reliability for identifying infants at risk for neuromotor impairment. This tool is non-invasive and cost-effective. The purpose of this study is to identify the published literature on how this tool applies to the prediction of cerebral palsy in term and late-preterm infants diagnosed with neonatal encephalopathy and so detect the research gaps. METHODS We will conduct a systematic scoping review for data on sensitivity, specificity, positive, and negative predictive value and describe the strengths and limitations of the results. This review will consider studies that included infants more than or equal to 34 + 0 weeks gestational age, diagnosed with neonatal encephalopathy, with a General Movements Assessment done between birth to six months of life and an assessment for cerebral palsy by at least 2 years of age. Experimental and quasi-experimental study designs including randomized controlled trials, non-randomized controlled trials, before and after studies, interrupted time-series studies and systematic reviews will be considered. Case reports, case series, case control, and cross-sectional studies will be included. Text, opinion papers, and animal studies will not be considered for inclusion in this scoping review as this is a highly specific and medical topic. Studies in the English language only will be considered. Studies published from at least 1970 will be included as this is around the time when the General Movements Assessment was first introduced in neonatology as a potential predictor of neuromotor outcomes. We will search five databases (MEDLINE, Embase, PsychINFO, Scopus, and CINAHL). Two reviewers will conduct all screening and data extraction independently. The articles will be categorized according to key findings and a critical appraisal performed. DISCUSSION The results of this review will guide future research to improve early identification and timely intervention in infants with neonatal encephalopathy at risk of neuromotor impairment. SYSTEMATIC REVIEW REGISTRATION Title registration with Joanna Briggs Institute https://joannabriggs.org/ebp/systematic_review_register .


Covid-19: Public health agencies review whether vitamin D supplements could reduce risk.


title: Sulfocerebrosides upregulate liposome uptake in human astrocytes without inducing a proinflammatory response.

text: Astrocytes are involved in the pathogenesis of demyelinating diseases, where they actively regulate the secretion of proinflammatory factors, and trigger the recruitment of immune cells in the central nervous system (CNS). Antigen presentation of myelin-derived proteins has been shown to trigger astrocyte response, suggesting that astrocytes can directly sense demyelination. However, the direct response of astrocytes to lipid-debris generated during demyelination has not been investigated. The lipid composition of the myelin sheath is distinct, presenting significant amounts of cerebrosides, sulfocerebrosides (SCB), and ceramides. Studies have shown that microglia are activated in the presence of myelin-derived lipids, pointing to the possibility of lipid-induced astrocyte activation. In this study, a human astrocyte cell line was exposed to liposomes enriched in each myelin lipid component. Although liposome uptake was observed for all compositions, astrocytes had augmented uptake for liposomes containing sulfocerebroside (SCB). This enhanced uptake did not modify their expression of human leukocyte antigen (HLA) molecules or secretion of chemokines. This was in contrast to changes observed in astrocyte cells stimulated with IFNγ. Contrary to human monocytes, astrocytes did not internalize beads in the size-range of liposomes, indicating that liposome uptake is lipid specific. Epifluorescence microscopy corroborated that liposome uptake takes place through endocytosis. Soluble SCB were found to partially block uptake of liposomes containing this same lipid. Endocytosis was not decreased when cells were treated with cytochalasin D, but it was decreased by cold temperature incubation. The specific uptake of SCB in the absence of a proinflammatory response indicates that astrocytes may participate in the trafficking and regulation of sulfocerebroside metabolism and homeostasis in the CNS.


Get your obstetric inpatient and outpatient units ready for COVID-19.


title: Synthesis of antiviral perfluoroalkyl derivatives of teicoplanin and vancomycin.

text: The limited scope of antiviral drugs and increasing problem of antiviral drug resistance represent a global health threat. Glycopeptide antibiotics and their lipophilic derivatives have emerged as relevant inhibitors of diverse viruses. Here, we describe a new strategy for the synthesis of dual hydrophobic and lipophobic derivatives of glycopeptides, to produce selective antiviral agents without membrane-disrupting activity. Perfluorobutyl and perfluorooctyl moieties through linkers of different length were attached to azido derivatives of vancomycin aglycone and teicoplanin pseudoaglycone, and the new derivatives were evaluated against a diverse panel of viruses. The teicoplanin derivatives displayed strong anti-influenza virus activity at non-toxic concentrations. Some of the perfluoroalkylated glycopeptides were also active against a few other viruses such as herpes simplex virus or coronavirus. These data encourage further exploration of glycopeptide analogues for broad antiviral application.


title: Robot-Assisted Radical Hysterectomy in Cervical Carcinoma: The Belgian Experience.

text: OBJECTIVE The purpose of this study was to report the experience and oncological outcome of robot-assisted radical hysterectomies (RRHs) for cervical cancer performed in Belgium. METHODS Patients undergoing RRH for cervical cancer (n = 109) were prospectively collected between July 2007 and April 2014 in the 5 Belgian centers performing RRH for cervical cancer. RESULTS The median age of the patients was 46 years (range, 31-80 years). Histological types included squamous cell carcinoma in 61 patients, adenocarcinoma in 22 patients, adenosquamous in 8 patients, endometrioid carcinoma in 2 patients, and other types (n = 16). The International Federation of Gynecology and Obstetrics stage distribution was IA (n = 9), stage IB1 (n = 71), stage IB2 (n = 4), stage II (n = 24), and unknown (n = 1). Twenty-four patients received adjuvant therapy, 17 patients underwent radiochemotherapy, and 7 underwent adjuvant radiation. Eighteen patients relapsed, and 5 died of disease. The median follow-up was 27.5 months (range, 3-82 months). The 2- and 5-year overall survivals were 96% and 89%, respectively. The 2- and 5-year disease-free survivals (DFSs) were 88% and 72%, respectively. The 2-year DFS per stage was 100% for IA, 88% for IB1, 100% for IB2, and 83% for II. The 5-year DFS per stage was 100% for stage IA and 75% for IB1. The complications were as expected for radical hysterectomy. CONCLUSIONS This series confirms the feasibility and safety of RRH not only in cervical cancer stage IA to IB1, but also after neoadjuvant chemotherapy in stage IB2 to IIB.


docid: gqpthudl

title: Insects: true pioneers in anti-infective therapy and what we can learn from them.


title: Adjudin-preconditioned neural stem cells enhance neuroprotection after ischemia reperfusion in mice.

text: BACKGROUND Transplantation of neural stem cells (NSCs) has been proposed as a promising therapeutic strategy for the treatment of ischemia/reperfusion (I/R)-induced brain injury. However, existing evidence has also challenged this therapy on its limitations, such as the difficulty for stem cells to survive after transplantation due to the unfavorable microenvironment in the ischemic brain. Herein, we have investigated whether preconditioning of NSCs with adjudin, a small molecule compound, could enhance their survivability and further improve the therapeutic effect for NSC-based stroke therapy. METHOD We aimed to examine the effect of adjudin pretreatment on NSCs by measuring a panel of parameters after their transplantation into the infarct area of ipsilateral striatum 24 hours after I/R in mice. RESULTS We found that pretreatment of NSCs with adjudin could enhance the viability of NSCs after their transplantation into the stroke-induced infarct area. Compared with the untreated NSC group, the adjudin-preconditioned group showed decreased infarct volume and neurobehavioral deficiency through ameliorating blood-brain barrier disruption and promoting the expression and secretion of brain-derived neurotrophic factor. We also employed H2O2-induced cell death model in vitro and found that adjudin preconditioning could promote NSC survival through inhibition of oxidative stress and activation of Akt signaling pathway. CONCLUSION This study showed that adjudin could be used to precondition NSCs to enhance their survivability and improve recovery in the stroke model, unveiling the value of adjudin for stem cell-based stroke therapy.


title: Serological Evidence of Lyssavirus Infection among Bats in Nagaland, a North-Eastern State in India.

text: Bats are known to be reservoirs of several medically important viruses including lyssaviruses. However, no systematic surveillance for bat rabies has been carried out in India, a canine rabies endemic country with a high burden of human rabies. Surveillance for rabies virus (RABV) infection in bats was therefore carried out in Nagaland, a north-eastern state in India at sites with intense human-bat interfaces during traditional bat harvests. Brain tissues and sera from bats were tested for evidence of infection due to RABV. Brain tissues were subjected to the fluorescent antibody test for detection of viral antigen and real-time reverse transcriptase PCR for presence of viral RNA. Bat sera were tested for the presence of rabies neutralizing antibodies by the rapid fluorescent focus inhibition test. None of the bat brains tested (n = 164) were positive for viral antigen or viral RNA. However, rabies neutralizing antibodies were detected in 4/78 (5·1%) bat sera tested, suggesting prior exposure to RABV or related lyssaviruses. The serological evidence of lyssaviral infection in Indian bats may have important implications in disease transmission and rabies control measures, and warrant extensive bat surveillance to better define the prevalence of lyssaviral infection in bats.


docid: puivycve

title: Comparative Effectiveness of Laparoscopic Sleeve Gastrectomy on Morbidly Obese, Super-Obese, and Super-Super Obese Patients for the Treatment of Morbid Obesity.

text: BACKGROUNDS The management of super-super obese patients is challenging for bariatric surgeons. Laparoscopic sleeve gastrectomy (LSG) is feasible as two-stage treatment for high-risk patients. However, its efficacy as a stand-alone procedure in super-super obese (SSO) patients is controversial. The study objective was to demonstrate the safety and efficacy of LSG in super-obese (SO) and SSO patients. METHODS A retrospective analysis was performed of consecutive patients undergoing LSG. The patients were classified into three groups: morbidly obese (MO), SO, and SSO. The patients' data, including each patient's characteristics, body mass index (BMI), preoperative comorbidities, postoperative complications, the resolution of comorbidities, percentage of excess weight loss (%EWL), and total weight loss (%TWL) were compared between groups. RESULTS Of the 186 patients, 163 (87.6%) were followed up for 41.2 ± 7.3 months (range 33-54 months). The mean BMI was 52.6 kg/m2. Eighty-three patients (50.9%) were MO, 52 (31.9%) were SO, and 28 (17.2%) were SSO. The groups were similar in terms of preoperative characteristics and postoperative complications. The mean %TWL were lower for the SSO group with no significant difference. The mean %TWL at 12, 24, 36, and 41.2 months postoperatively was 34.7, 34.4, 31.4, and 29.6% in SSO group, respectively. Also, the %EWL for the SSO group was significantly lower (48.3%) at the end of the follow-up period. However, the rate of significant improvement or complete resolution of comorbidities was similar in all groups. CONCLUSION Although %EWL was lower in the SSO group, LSG was a feasible and safe stand-alone bariatric surgical procedure for the resolution of comorbidities in MO, SO, and SSO patients.


title: Minimally invasive surgery for congenital cystic adenomatoid malformations - early experience.

text: PURPOSE The aim of this study is to present our experience with minimally invasive surgery (MIS) for congenital cystic adenomatoid malformations (CCAMs). METHODS The medical records of infants under 2 years of age who underwent operation for a CCAM from 2009 to 2014 were retrospectively reviewed. RESULTS MIS (9 of thoracoscopy and 1 of laparoscopy) was performed for 10 infants (male:female = 7:3) with CCAM. CCAM were discovered prenatally around gestational age of 24.7 weeks. The median gestational age was 38.6 weeks, and the median body weight was 2,817.5 g. None had respiratory distress after birth. The median age at the time of operation was 0.94 years (range: 8 days-1.66 years). Two underwent the operation during the neonatal period; one because of a coexisting large esophageal duplication cyst and the other due to diagnostic uncertainty. While awaiting operation, 5 of CCAM had grown without respiratory symptoms, and 2 infants had experienced pneumonia. The mean operative time was 98 minutes (range: 70-227 minutes), and there were no conversions or perioperative complications. The infants resumed enteral feeding within 2 days and were discharged within 7 days, except for 1 infant who underwent esophageal duplication cyst excision. During the follow-up period, there were no cases of either remnant lesions or respiratory symptoms. CONCLUSION MIS for CCAMs is safe and feasible, with excellent cosmesis and short hospital stays. Increasing experience with various MIS procedures will widen the indications for MIS in lung pathology.


title: An Update on Bariatric Surgery.

text: Obesity is a serious problem facing patients and healthcare providers around the globe. Bariatric surgery has been an increasingly popular choice in the management of obesity, and the last five years have seen an enormous amount of research on the various procedures. Recently bariatric surgery has been recognized as an important modifier of the metabolic and hormonal states associated with obesity's comorbidities. Consequently, research regarding the effect of bariatric procedures on type 2 diabetes mellitus, dyslipidemia, and the inflammatory state has become more plentiful. As bariatric surgery has matured, a growing body of evidence and experience has accrued. A change in the relative popularity of the four major laparoscopic bariatric procedures; sleeve gastrectomy, roux-en-Y gastric bypass, adjustable gastric band, and biliopancreatic diversion with duodenal switch has taken place. This has been driven by technical factors, as well as the individual procedures' efficacy in weight-loss and improvement in comorbidities. Weight recidivism is an increasingly recognized problem as patients are followed for longer periods following their bariatric operations. This important and costly problem has roots in both technical and patient related factors.


title: Early experience with COVID-19 in kidney transplantation recipients: update and review.

text: INTRODUCTION little is known on the risk factors, clinical presentation, therapeutic protocols, and outcomes of kidney transplantation recipients (KTRs) who become infected by SARS-CoV-2. PURPOSE to provide an updated view regarding the early experience obtained from the management of KTRs with COVID-19. MATERIALS AND METHODS A narrative review was conducted using PubMed database to identify relevant articles written in English/Spanish, and published through May 15, 2020. Search terms included: "coronavirus", "severe acute respiratory syndrome coronavirus 2", "SARS-CoV-2", "COVID-19", "COVID", "renal transplantation", and "kidney transplantation". Case series were considered eligible, and case reports excluded. Thirty-four articles were included in the review. RESULTS KTRs should be considered immunocompromised hosts: potential risk for infection, non-negligible comorbidity, and exposure to long-term immunosuppression. Only single center small retrospective experiences are still available regarding KTRs with COVID-19. SARS-CoV-2 symptoms in KTRs are similar to that observed for the general population, being fever and cough the most frequently observed. Mild-to-moderate symptomatic KTRs can be managed in an outpatient setting, while patients exhibiting severe symptoms must be addmited to hospital. More rapid clinical progression, and higher complication and death rates have been observed for hospitalized KTRs, requiring hemodyalisis or ventilatory support. Lymphopenia, elevated serum markers (C-reactive protein, procalcitonin, IL-6, D-dimer), and chest-X-ray findings consistent with pneumonia are linked to worse prognosis. A number of antiviral therapies have been used. However, it is difficult to draw meaningful conclusions regarding their efficacy at this point. Baseline immunosupression regimen should be adjusted in a case-by-case manner. However, it poses a significant challenge.


title: What we know so far: COVID-19 current clinical knowledge and research.

text: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.


title: The Potential Impact & Availability of Sexual Health Services During the COVID-19 Pandemic.

text: As the COVID-19 pandemic causes upheaval in New York City (NYC), one consequence is the accessibility of sexual health services. The NYC STD Prevention Training Center at Columbia University administered an online provider survey to understand how the COVID-19 pandemic is affecting the availability of sexual health care services regionally.


title: Use of the Nerve Integrity Monitor during Thyroid Surgery Aids Identification of the External Branch of the Superior Laryngeal Nerve.

text: BACKGROUND The external branch of the superior laryngeal nerve (EBSLN) is at risk during thyroid surgery. Despite meticulous dissection and visualization, the EBSLN can be mistaken for other structures. The nerve integrity monitor (NIM) allows EBSLN confirmation with cricothyroid twitch on stimulation. AIMS The aim of this study was to assess any difference in identification of EBSLN and its anatomical sub-types by dissection alone compared to NIM-aided dissection. METHODS Routine intra-operative nerve monitoring (IONM) was used, when available, for 228 consecutive thyroid operations (129 total thyroidectomies, 99 hemi-thyroidectomies) over a 10-month period. EBSLN identification by dissection alone (with NIM confirmation of cricothyroid twitch) and by NIM-assisted dissection was recorded prospectively. Anatomical sub-types were defined by the Cernea classification. RESULTS Of 357 nerves at risk, 97.2 % EBSLNs (95 % confidence interval [CI], 95.5-98.9) were identified by visualization and NIM-aided dissection compared to 85.7 % (95 % CI, 82.1-89.3) identified by dissection alone (<0.001). EBSLN frequency was 34 % for type 1, 55 % for type 2a, and 11 % for type 2b. All identified EBSLNs were stimulated to confirm a cricothyroid twitch after superior thyroid vessel ligation. CONCLUSION Using the NIM and meticulous dissection of the upper thyroid pole improves EBSLN identification. As the EBSLN is at risk during thyroidectomy and can lead to voice morbidity, the NIM can aid identification of the EBSLN and provide a functional assessment of the EBSLN after thyroid resection.


title: Outbreak of acute respiratory disease caused by Mycoplasma pneumoniae on board a deployed U.S. navy ship.

text: We identified 179 cases of acute respiratory illness including 50 cases of radiographically confirmed pneumonia over the course of 4 months on a deployed U.S. Navy vessel. Laboratory tests showed Mycoplasma pneumoniae to be the etiological agent. This report represents the first published description of a shipboard outbreak of this pathogen.


title: Multimodal treatment strategies for complex pediatric cerebral arteriovenous fistulas: contemporary case series at Barrow Neurological Institute.

text: OBJECT Pediatric cerebral arteriovenous fistulas (AVFs) are rare but potentially lethal vascular lesions. Management strategies for these lesions have undergone considerable evolution in the last decade with the advent of new endovascular, surgical, and radiosurgical technologies. This study sought to review current treatment strategies and long-term clinical outcomes at a high-volume cerebrovascular institute. METHODS A retrospective chart review was performed on patients with a diagnosis of cerebral AVF from 1999 to 2012. Patients with carotid-cavernous fistulas, vein of Galen malformations, and age > 18 years were excluded from final analysis. Medical history, surgical and nonsurgical treatment, and clinical outcomes were documented. Pre- and postoperative angiograms were analyzed to assess for obliteration of the fistula. RESULTS Seventeen patients with pial AVFs (29.4%), dural AVFs (64.7%), or mixed pial/dural AVFs (5.9%) were identified. The majority of lesions were paramedian (70.6%) and supratentorial (76.5%). The study population had a mean age of 6.4 years, with a slight male predominance (52.9%), and the most common presenting symptoms were seizures (23.5%), headaches (17.6%), congestive heart failure (11.7%), and enlarging head circumference (11.7%). Among patients who underwent intervention (n = 16), 56.3% were treated with endovascular therapy alone, 6.3% were treated with open surgery alone, and 37.5% required a multimodal approach. Overall, 93.8% of the treated patients received endovascular treatment, 43.8% received open surgery, and 12.5% received radiosurgery. Endovascular embolysates included Onyx (n = 5), N-butyl cyanoacrylate (NBCA; n = 4), or coil embolization (n = 7) with or without balloon assistance (n = 2). Complete angiographic obliteration was achieved in 87.5% at the last follow-up evaluation (mean follow-up 3.1 years). One infant with incomplete AVF obliteration died of congestive heart failure, and 1 patient with complete obliteration died of acute sinus thrombosis, with an overall complication rate of 18.8%. CONCLUSIONS Pediatric cerebral AVFs are challenging neurosurgical lesions. Although advancements in endovascular therapy in the last decade have greatly changed the natural course of this disease, a multidisciplinary approach remains necessary for a large subset of patients. Surgeon experience with a thorough analysis of preoperative imaging is paramount to achieving acceptable clinical outcomes.


School Nurses: Living the Framework During COVID-19.


title: Do stock prices drive people crazy?

text: This is the first research to examine a potential relation between stock market volatility and mental disorders. Using data on daily incidences of mental disorders in Taiwan over 4000 days from 1998 through 2009 to assess the time-series relation between stock price movements and mental disorders, we observe that stock price fluctuation clearly affects the hospitalization of mental disorders. We find that during a 12-year follow-up period, a low stock price index, a daily fall in the stock price index and consecutive daily falls in the stock price index are all associated with greater of mental disorders hospitalizations. A 1000-point fall in the TAIEX (Taiwan Stock Exchange Capitalization Weighted Stock Index) increases the number of daily mental disorders hospitalizations by 4.71%. A 1% fall in the TAIEX in one single day increases daily hospitalizations for mental disorders by 0.36%. When the stock price index falls one consecutive day, it causes a daily increase of approximately 0.32% hospitalizations due to mental disorders on that day. Stock price index is found to be significant for both gender and all age groups. In addition, daily change is significant for both gender and middle-age groups, whereas accumulated change is significant for males and people aged 45-64. Stockholdings can help people accumulate wealth, but they can also increase mental disorders hospitalizations. In other words, stock price fluctuations do drive people crazy.


title: Laparoscopic versus Open Radical Nephrectomy in T2 Renal Cell Carcinoma: Long-Term Oncologic Outcomes.

text: PURPOSE Laparoscopic radical nephrectomy (LRN) has become the standard technique for radical nephrectomies for T1 renal tumors (7 cm or less). We extended our experience with LRN to T2 renal tumors (greater than 7 cm) and compared the efficacy and long-term oncologic outcomes with those of open radical nephrectomy (ORN) for T2 clear renal cell carcinoma (RCC) in the same period. MATERIALS AND METHODS We retrospectively analyzed the data from 33 patients who underwent LRN and 35 patients who underwent ORN in our institution from January 2003 to June 2006 for T2N0M0 RCC. We compared long-term oncologic outcomes between the two groups. RESULTS The median follow-up periods were 60.0 months (range, 48.0-77.0 months) and 65.6 months (range, 56.0-77.0 months) in the LRN and ORN groups, respectively. There were no statistically significant differences between the two groups in the patients' demographic data. There were no significant differences in the 5-year overall survival rate, the cancer-specific survival rate, or the recurrence-free survival rate. CONCLUSIONS Our results suggest that LRN for the management of T2 RCC is feasible and efficacious and that the long-term oncologic outcomes of LRN are comparable to those of ORN.


title: Feedback from physical activity monitors to enhance amount of physical activity in adults-a protocol for a systematic review and meta-analysis.

text: OBJECTIVE The use of physical activity monitors (PAMs) in the adult population is increasing rapidly and previous systematic reviews are outdated. The objective of this systematic review and meta-analysis is to estimate the effect of PAM-based interventions on physical activity behavior in adults. Furthermore, the impact of intervention, study, and participants characteristics will be investigated. METHODS AND DESIGN Randomized controlled trials and randomized cross-over trials including adult participants will be included if the study compares any PAM-based intervention where the participants receive feedback on their physical activity level measured by PAMs, to control interventions where participants do not receive feedback from PAMs. This protocol is detailed according to the recommendations of the Cochrane Handbook, and it is reported according to the preferred reporting items for systematic reviews and meta-analyses protocols statement. The results from the literature search will be presented in a PRISMA flow chart. The effects from individual studies will be summarized in a random effects meta-analysis and the impact of diagnosis of the participants, type of feedback, type of intervention, and control intervention will be investigated in stratified meta-analysis and meta-regressions analysis. The results on daily physical activity, moderate to vigorous physical activity, sedentary time, and adverse events will be presented in a summary of findings table. DISCUSSION The results will be useful to researchers, policy makers, and health care professionals when the intention is to increase physical activity in the adult population. PROSPERO REGISTRATION CRD42018102719.


title: Evaluation of antibodies against feline coronavirus 7b protein for diagnosis of feline infectious peritonitis in cats.

text: OBJECTIVE To determine whether expression of feline coronavirus (FCoV) 7b protein, as indicated by the presence of specific serum antibodies, consistently correlated with occurrence of feline infectious peritonitis (FIP) in cats. SAMPLE POPULATION 95 serum samples submitted for various diagnostic assays and 20 samples from specific-pathogen-free cats tested as negative control samples. PROCEDURES The 7b gene from a virulent strain of FCoV was cloned into a protein expression vector. The resultant recombinant protein was produced and used in antibody detection assays via western blot analysis of serum samples. Results were compared with those of an immunofluorescence assay (IFA) for FCoV-specific antibody and correlated with health status. RESULTS Healthy IFA-seronegative cats were seronegative for antibodies against the 7b protein. Some healthy cats with detectable FCoV-specific antibodies as determined via IFA were seronegative for antibodies against the 7b protein. Serum from cats with FIP had antibodies against the 7b protein, including cats with negative results via conventional IFA. However, some healthy cats, as well as cats with conditions other than FIP that were seropositive to FCoV via IFA, were also seropositive for the 7b protein. CONCLUSIONS AND CLINICAL RELEVANCE Expression of the 7b protein, as indicated by detection of antibodies against the protein, was found in most FCoV-infected cats. Seropositivity for this protein was not specific for the FCoV virulent biotype or a diagnosis of FIP.


title: Changing the route of hysterectomy into a minimal invasive approach.

text: Objective. To describe the route of hysterectomy in a county hospital and evaluate the shift towards a minimal invasive approach. Design. Retrospective cohort study. Setting. A county hospital in Norway. Population. All women were scheduled for hysterectomy. Methods. Audit the route of hysterectomy in the period 2004-2012. Analyze the outcome of total laparoscopic hysterectomies. Main Outcome Measures. Complications after total laparoscopic hysterectomy. Results. A shift towards a minimal invasive approach has been achieved during the study period. In 2012 only 17.4% of the hysterectomies were performed abdominally, compared to yearly percentages of above 50% in the period 2004-2009. Laparoscopic supracervical hysterectomy was introduced in 2003, but the percentage of abdominal hysterectomy remained above 50% until total laparoscopic hysterectomy was introduced in 2010. Since the introduction of total laparoscopic hysterectomy in April 2010, 58 procedures have been performed. There have been no major complications. Two vaginal vault hematomas and one case of urinary tract infection were reported. Conclusions. It is possible for a county hospital to alter their praxis and perform mini-invasive hysterectomies, but it requires dedicated gynecologists. This change to an advanced procedure like total laparoscopic hysterectomy could be achieved without patients suffering from major complications.


title: Investigation of a Cluster of Severe Respiratory Disease Referred from Uganda to Kenya, February 2017.

text: On February 22, 2017, Hospital X-Kampala and US CDC-Kenya reported to the Uganda Ministry of Health a respiratory illness in a 46-year-old expatriate of Company A. The patient, Mr. A, was evacuated from Uganda to Kenya and died. He had recently been exposed to dromedary camels (MERS-CoV) and wild birds with influenza A (H5N6). We investigated the cause of illness, transmission, and recommended control. We defined a suspected case of severe acute respiratory illness (SARI) as acute onset of fever (≥38°C) with sore throat or cough and at least one of the following: headache, lethargy, or difficulty in breathing. In addition, we looked at cases with onset between February 1 and March 31 in a person with a history of contact with Mr. A, his family, or other Company A employees. A confirmed case was defined as a suspected case with laboratory confirmation of the same pathogen detected in Mr. A. Influenza-like illness was defined as onset of fever (≥38°C) and cough or sore throat in a Uganda contact, and as fever (≥38°C) and cough lasting less than 10 days in a Kenya contact. We collected Mr. A's exposure and clinical history, searched for cases, and traced contacts. Specimens from the index case were tested for complete blood count, liver function tests, plasma chemistry, Influenza A(H1N1)pdm09, and MERS-CoV. Robust field epidemiology, laboratory capacity, and cross-border communication enabled investigation.


title: Bidirectional Jejunojejunal Anastomosis Prevents Early Small Bowel Obstruction Due to the Kinking After Closure of the Mesenteric Defect in the Laparoscopic Roux-en-Y Gastric Bypass.

text: BACKGROUND The closure of the mesenteric defects (CMD) in Roux-en-Y gastric bypass (RYGB) reduces the risk of small bowel obstruction (SBO) due to internal hernia but might be associated with an increased risk of early SBO triggered by the jejunojejunal anastomosis (JJS) kinking. The aim of this study was to assess how enlarging the JJS with a bidirectional linear stapling can aid in avoiding the risk of early SBO by kinking. MATERIALS AND METHODS This retrospective cohort study concerns 1327 patients who underwent RYGB with CMD between May 2007 and August 2016. The first 626 patients (group A) had a unidirectional JJS. The following 701 patients (group B) had a bidirectional side-to-side JJS and a hand-sewn closure of the remaining defect. We compared early SBO between the two groups. RESULTS Eleven (1.75%) early SBO due to the JJS kinking occurred in group A, whereas none occurred in group B (p = 0.0012). Thirty-nine early postoperative complications happened in group A versus 32 in group B (p = 0.17). Nine (1.2%) digestive bleedings occurred in group B versus two (0.3%) in group A (OR = 4.05 [0.87-18], p = 0.054). Average operating time was 81 min [37-330] in group A and 77 min [33-240] in group B. CONCLUSION Enlarging the JJS with a bidirectional linear stapling is associated with a reduced risk of early SBO due to the anastomosis kinking. However, it could be related to an increased risk of digestive bleedings.


title: Generation and characterization of a diabody targeting the αvβ6 integrin.

text: The αvβ6 integrin is up-regulated in cancer and wound healing but it is not generally expressed in healthy adult tissue. There is increasing evidence that it has a role in cancer progression and will be a useful target for antibody-directed cancer therapies. We report a novel recombinant diabody antibody fragment that targets specifically αvβ6 and blocks its function. The diabody was engineered with a C-terminal hexahistidine tag (His tag), expressed in Pichia pastoris and purified by IMAC. Surface plasmon resonance (SPR) analysis of the purified diabody showed affinity in the nanomolar range. Pre-treatment of αvβ6-expressing cells with the diabody resulted in a reduction of cell migration and adhesion to LAP, demonstrating biological function-blocking activity. After radio-labeling, using the His-tag for site-specific attachment of (99m)Tc, the diabody retained affinity and targeted specifically to αvβ6-expressing tumors in mice bearing isogenic αvβ6 +/- xenografts. Furthermore, the diabody was specifically internalized into αvβ6-expressing cells, indicating warhead targeting potential. Our results indicate that the new αvβ6 diabody has a range of potential applications in imaging, function blocking or targeted delivery/internalization of therapeutic agents.


docid: rinlrdra

title: Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus.

text: The mortality of human infection by influenza A/H5N1 virus can exceed 80%. The high mortality and its poor response to the neuraminidase inhibitor oseltamivir have been attributed to uncontrolled virus-induced cytokine storm. We challenged BALB/c mice with 1,000 LD50 of influenza A/Vietnam/1194/04. Survival, body weight, histopathology, inflammatory markers, viral loads, T lymphocyte counts, and neutralizing antibody response were documented in infected mice treated individually or in combination with zanamvir, celecoxib, gemfibrozil, and mesalazine. To imitate the real-life scenario, treatment was initiated at 48 h after viral challenge. There were significant improvements in survival rate (P = 0.02), survival time (P < 0.02), and inflammatory markers (P < 0.01) in the group treated with a triple combination of zanamivir, celecoxib, and mesalazine when compared with zanamivir alone. Zanamivir with or without immunomodulators reduced viral load to a similar extent. Insignificant prolongation of survival was observed when individual agents were used alone. Significantly higher levels of CD4+ and CD8+ T lymphocytes and less pulmonary inflammation were also found in the group receiving triple therapy. Zanamivir alone reduced viral load but not inflammation and mortality. The survival benefits of adding celecoxib and mesalazine to zanamivir could be caused by their synergistic effects in reducing cytokine dysfunction and preventing apoptosis. Combinations of a neuraminidase inhibitor with these immunomodulators should be considered in randomized controlled treatment trials of patients suffering from H5N1 infection.


title: The N-terminal region of severe acute respiratory syndrome coronavirus protein 6 induces membrane rearrangement and enhances virus replication.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) accessory protein 6 (p6) is a 63-amino-acid multifunctional Golgi-endoplasmic reticulum (ER) membrane-associated protein, with roles in enhancing virus replication and in evading the innate immune response to infection by inhibiting STAT1 (signal transducer and activator of transcription factor 1) translocation to the nucleus. Here, we demonstrate that p6 has an N-terminal region-cytoplasm-C-terminal region-cytoplasm configuration with residues 2 to 37 likely membrane embedded. Expression of p6, or of its N-terminal 41-amino-acid region, in the absence of other viral proteins, induced the formation of membranous structures, some of which were similar to double membrane vesicles involved in virus replication. Consistent with a role in virus replication, p6 partially colocalized with nonstructural protein 3 (nsp3), a marker for virus replication complexes. Further, while the C-terminal region is required for preventing STAT1 translocation to the nucleus, our results also indicated that the N-terminal 18 amino acids were necessary for maximal inhibition. Collectively, these results support the notion that p6 is a two-domain protein, although the function of each is not completely independent of the other.


title: Expanding CAPD in Low-Resource Settings: A Distance Learning Approach.

text: BACKGROUND Despite growing need, treatment for end-stage renal disease is limited in low- and middle-income countries due to resource restraints. We describe the development of an educational curriculum and quality improvement program to support continuous ambulatory peritoneal dialysis (CAPD) performed primarily by non-nephrology providers in Sri Lanka. METHODS We developed a program of education, outcome tracking, and expert consultation to support providers in Kandy, Sri Lanka. Education included videos and in-person didactics covering core topics in CAPD. Event-tracking sheets recorded root causes and management of infections and hospitalizations. Conferences reviewed clinical cases and overall clinic management. We evaluated the patient census, peritonitis rates, and root causes and management of infections over 1 year. RESULTS The curriculum was published through the International Society of Nephrology online academy. High provider turnover limited curriculum assessments. The CAPD patient census rose from 63 to 116 during the year. The peritonitis rate declined significantly, from 0.8 episodes per patient-year in the first 6 months to 0.4 in the latter 6 months, though the most common root causes of peritonitis, related to contamination events and hygiene, persisted. The appropriate ascertainment of culture data and prescription of antibiotics also increased. CONCLUSIONS Our project supported the expansion of a CAPD program in a resource-limited setting, while also improving peritonitis outcomes. Ongoing challenges include ensuring a durable educational system for rotating providers, tracking outcomes beyond peritonitis, and formalizing management protocols. Our program can serve as an example of how established dialysis programs can support the burgeoning work of providers in resource-limited setting.


title: Impact of Environmental Enrichment Devices on NTP In Vivo Studies.

text: The goal of this study was to determine whether the use of nesting material or polycarbonate shelters as enrichment devices would have an impact on end points commonly measured during the conduct of the National Toxicology Program (NTP) 13-week studies. The study design was consistent with the NTP 13-week toxicity studies. Harlan Sprague-Dawley (HSD) rats and their offspring and B6C3F1/N mice were assigned to control (unenriched) and enriched experimental groups. Body weight, food and water consumption, behavioral observations, fecal content, clinical pathology, gross pathology, organ weights, and histopathology were evaluated. Enriched male mice and male and female rats exhibited decreased feed intake without a subsequent decrease in body weight; this may have been the result of the nesting material reducing the effect of cold stress, thereby allowing for more efficient use of feed. There were statistical differences in some hematological parameters; however, these were not considered physiologically relevant since all values were within the normal range. Gross pathology and histopathological findings were background changes and were not considered enrichment-related. Nesting material and shelters were used frequently and consistently and allowed animals to display species-typical behavior. There was no significant impact on commonly measured end points in HSD rats and B6C3F1/N mice given enrichment devices.