title: A gripping tale of ribosomal frameshifting: extragenic suppressors of frameshift mutations spotlight P-site realignment.

text: Mutants of translation components which compensate for both -1 and +1 frameshift mutations showed the first evidence for framing malleability. Those compensatory mutants isolated in bacteria and yeast with altered tRNA or protein factors are reviewed here and are considered to primarily cause altered P-site realignment and not altered translocation. Though the first sequenced tRNA mutant which suppressed a +1 frameshift mutation had an extra base in its anticodon loop and led to a textbook "yardstick" model in which the number of anticodon bases determines codon size, this model has long been discounted, although not by all. Accordingly, the reviewed data suggest that reading frame maintenance and translocation are two distinct features of the ribosome. None of the -1 tRNA suppressors have anticodon loops with fewer than the standard seven nucleotides. Many of the tRNA mutants potentially affect tRNA bending and/or stability and can be used for functional assays, and one has the conserved C74 of the 3' CCA substituted. The effect of tRNA modification deficiencies on framing has been particularly informative. The properties of some mutants suggest the use of alternative tRNA anticodon loop stack conformations by individual tRNAs in one translation cycle. The mutant proteins range from defective release factors with delayed decoding of A-site stop codons facilitating P-site frameshifting to altered EF-Tu/EF1alpha to mutant ribosomal large- and small-subunit proteins L9 and S9. Their study is revealing how mRNA slippage is restrained except where it is programmed to occur and be utilized.


title: Selenium Deficiency via the TLR4/TRIF/NF-κB Signaling Pathway Leading to Inflammatory Injury in Chicken Spleen.

text: The aim of the present study was to investigate the effect of selenium (Se) deficiency on the expression of the toll-like receptor (TLR) signal transduction pathway in the spleen of chickens and explore the relationship between the TLR4/TRIF/NF-κB signaling pathway and inflammatory spleen injury. A total of 200 one-day-old healthy broilers were allocated to two groups. The experimental group was fed a self-made low-Se diet (0.004 mg/kg) while the control group was fed a complete formula feed (0.2 mg/kg) for 15, 25, 35, 45, and 55 days, respectively. We observed histopathological changes in the chicken spleens. The messenger RNA(mRNA) expression levels of 8 kinds of ChTLRs, myeloid differential protein-88 (MyD88), toll-interleukine-1 receptor domain-containing adapter-inducing interferon-β (TRIF), nuclear factor-κB (NF-κB), and cytokine (IL-6, TNF-α, IL-2, and IFN-γ) were detected via quantitative real-time PCR. Western blotting was used to detect the protein expression level of TLR4. Then principal component analysis (PCA) was used to analyze the correlation between the ChTLRs, MyD88, TRIF, and NF-κB. The results showed that the boundary between red pulp and white pulp was unclear, the number of lymphocytes decreased, and the nucleus was fragmented and dissolved in the experimental group at 25-55 days. At 15-45 days, the relative expression of TLR4 mRNA was higher than in the control group, and the difference was extremely significant on day 15 (P < 0.01).The relative expression of TRIF mRNA in the experimental group was higher than in the control group at 25-55 days, and the relative expression of NF-κB mRNA in the experimental group was higher than in the control group at 15-45 days. The relative expression of IL-6 mRNA in the experimental group was higher than in the control group at 15-45 days. The protein expression level of TLR4 in the experimental group was higher than in the control group at 15-45 days. The PCA results showed that there was a strong correlation between TLR4, TRIF, and component 1. The results suggest that TLR4 plays an important role in regulating the expression of inflammatory cytokines in the spleens of Se-deficient chickens, and Se deficiency may cause inflammatory injury through the TLR4/TRIF/NF-κB signaling pathway in chicken spleen.


Blood pressure, cholesterol guidelines face more delays.


Topic: Abdominal Wall Hernia - Prophylactic Mesh.


title: Technical aspects and short- and long-term outcomes of totally laparoscopic total gastrectomy for advanced gastric cancer: a single-institution retrospective study.

text: BACKGROUND D2 total gastrectomy combined with splenectomy or pancreaticosplenectomy reportedly increases morbidity and mortality. Totally laparoscopic total gastrectomy (TLTG) for advanced gastric cancer (AGC) remains controversial because of its technical difficulties and lack of long-term results. We determined the feasibility and safety of TLTG for AGC. METHODS A single-institution retrospective study was conducted. Ninety-two consecutive AGC patients who underwent radical TLTG were enrolled. The primary end point was morbidity. The patients were observed for 3 years following TLTG. We assessed short-term surgical and long-term outcomes, including 3-year overall survival rates (3yOS) and 3-year recurrence-free survival rates (3yRFS). RESULTS Early and late morbidities (Clavien-Dindo grade ≥3) were 26.1 and 6.5 %, respectively. Operative time, estimated blood loss, number of dissected lymph nodes, and postoperative hospital stay were 444 (278-694) min, 100 (0-2267) g, 48 (16-89), and 23 (9-136) days, respectively, and 3yOS and 3yRFS rates were 70.7 and 60.9 %, respectively. Factors associated with postoperative complications and 3yOS were operative time [OR 1.011 (1.006-1.017), p < 0.01] and cancer recurrence within 3 years [HR 312.191 (1.126-86573.245], p = 0.045], respectively. 3yRFS was associated with tumor size (≥50 mm) [HR 10.325 (1.328-80.289), p = 0.026], pathological N factor ≥2 [HR 3.188 (1.196-8.495), p = 0.02], and postoperative pancreatic fistula combined with intra-abdominal abscesses Clavien-Dindo grade ≥2; [HR 3.670 (1.440-9.351), p = 0.006]. CONCLUSIONS TLTG for AGC is sufficiently feasible and safe from both surgical and oncological point of view.


title: Combined laparoscopic-endoscopic placement of primary gastrojejunal feeding tubes in children: a preliminary report.

text: BACKGROUND Placement of a primary gastrojejunal tube (GJT) can be technically challenging and often requires an open procedure to negotiate the tube past the duodenal sweep into the jejunum. The alternative approach is to first place a gastrostomy tube (GT), which is then changed to a GJT under endoscopic or fluoroscopic guidance after waiting 6-8 weeks to allow the stoma to mature. We report a case series of primary GJT placement using a combined laparoscopic-endoscopic approach. SUBJECTS AND METHODS We retrospectively reviewed patients who underwent a combined laparoscopic-endoscopic primary GJT placement. Patients' demographics and relevant clinical information were analyzed. RESULTS Six patients (4 male, 2 female) were identified. The median age at the time of operation was 30.2 months (range, 28 days-10 years). Five GJTs were successfully placed laparoscopically/endoscopically, and one procedure was converted to open. The mean operative time was 84 minutes (range, 63-102 minutes). Postoperative abdominal radiography confirmed post-pyloric tube position in all patients. Feedings were initiated on the first postoperative day. One intraoperative complication required conversion to an open procedure. No patients developed postoperative complications. CONCLUSIONS Laparoscopic-endoscopic primary GJT placement is technically feasible and an excellent alternative in patients who require transpyloric feeding access.


V-Loc suture: a simple wound closure device for areola diameter and shape control in breast reduction and mastopexy.


title: Human mitochondrial RNA polymerase: evaluation of the single-nucleotide-addition cycle on synthetic RNA/DNA scaffolds.

text: The human mitochondrial RNA polymerase (h-mtRNAP) serves as both the transcriptase for expression and the primase for replication of mitochondrial DNA. As such, the enzyme is of fundamental importance to cellular energy metabolism, and defects in its function may be related to human disease states. Here we describe in vitro analysis of the h-mtRNAP kinetic mechanism for single, correct nucleotide incorporation. This was made possible by the development of efficient methods for expression and purification of h-mtRNAP using a bacterial system and by utilization of assays that rely on simple, synthetic RNA/DNA scaffolds without the need for mitochondrial transcription accessory proteins. We find that h-mtRNAP accomplishes single-nucleotide incorporation by using the same core steps, including conformational change steps before and after chemistry, that are prototypical for most types of nucleic acid polymerases. The polymerase binds to scaffolds via a two-step mechanism consisting of a fast initial-encounter step followed by a much slower isomerization that leads to catalytic competence. A substantial solvent deuterium kinetic isotope effect was observed for the forward reaction, but none was detectable for the reverse reaction, suggesting that chemistry is at least partially rate-limiting in the forward direction but not in the reverse. h-mtRNAP appears to exercise much more stringent surveillance over base than over sugar in determining the correctness of a nucleotide. The utility of developing the robust in vitro assays described here and of establishing a baseline of kinetic performance for the wild-type enzyme is that biological questions concerning h-mtRNAP may now begin to be addressed.


title: [2019-nCoV: new challenges from coronavirus].

text: The outbreak of pneumonia caused by the novel coronavirus (2019-nCoV) in Wuhan, Hubei province of China, at the end of 2019 shaped tremendous challenges to China's public health and clinical treatment. The virus belongs to the β genus Coronavirus in the family Corornaviridae, and is closely related to SARS-CoV and MERS-CoV, causing severe symptoms of pneumonia. The virus is transmitted through droplets, close contact, and other means, and patients in the incubation period could potentially transmit the virus to other persons. According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it's mechanism of cross-species spread might be related with angiotensin-converting enzyme Ⅱ (ACE2), which is consistent with the receptor SARS-CoV. After the outbreak of this disease, Chinese scientists invested a lot of energy to carry out research by developing rapid diagnostic reagents, identifying the characters of the pathogen, screening out clinical drugs that may inhibit the virus, and are rapidly developing vaccines. The emergence of 2019-nCoV reminds us once again of the importance of establishing a systematic coronavirus surveillance network. It also poses new challenges to prevention and control of the emerging epidemic and rapidly responses on scientific research.


title: Single incision laparoscopic-assisted right hemicolectomy: technique and application (with video).

text: PURPOSE Most commonly employed for surgery of the gallbladder and appendix, single-incision laparoscopic surgery (SILS) is rapidly evolving in the field of minimally invasive surgery. The purpose of this report is to describe the feasibility and technique for SILS right hemicolectomy, which has not been widely reported. METHODS We describe a laparoscopic right hemicolectomy with a modified single-incision technique for the management of a precancerous polyp of the ascending colon. RESULTS The procedure was successfully performed in 105 minutes using 3 transumbilical trocars placed through a single port, and readily available nonarticulating laparoscopic instruments. In addition, we review the literature of SILS procedures involving the colon and discuss differences between our approach and those reported elsewhere. CONCLUSIONS SILS is a feasible modality applicable to minimally invasive surgery of the colon and can offer benefits to the patient.


title: Diversity, compositional and functional differences between gut microbiota of children and adults.

text: The gut microbiota has been shown to play diverse roles in human health and disease although the underlying mechanisms have not yet been fully elucidated. Large cohort studies can provide further understanding into inter-individual differences, with more precise characterization of the pathways by which the gut microbiota influences human physiology and disease processes. Here, we aimed to profile the stool microbiome of children and adults from two population-based cohort studies, comprising 2,111 children in the age-range of 9 to 12 years (the Generation R Study) and 1,427 adult individuals in the range of 46 to 88 years of age (the Rotterdam Study). For the two cohorts, 16S rRNA gene profile datasets derived from the Dutch population were generated. The comparison of the two cohorts showed that children had significantly lower gut microbiome diversity. Furthermore, we observed higher relative abundances of genus Bacteroides in children and higher relative abundances of genus Blautia in adults. Predicted functional metagenome analysis showed an overrepresentation of the glycan degradation pathways, riboflavin (vitamin B2), pyridoxine (vitamin B6) and folate (vitamin B9) biosynthesis pathways in children. In contrast, the gut microbiome of adults showed higher abundances of carbohydrate metabolism pathways, beta-lactam resistance, thiamine (vitamin B1) and pantothenic (vitamin B5) biosynthesis pathways. A predominance of catabolic pathways in children (valine, leucine and isoleucine degradation) as compared to biosynthetic pathways in adults (valine, leucine and isoleucine biosynthesis) suggests a functional microbiome switch to the latter in adult individuals. Overall, we identified compositional and functional differences in gut microbiome between children and adults in a population-based setting. These microbiome profiles can serve as reference for future studies on specific human disease susceptibility in childhood, adulthood and specific diseased populations.


title: Single-incision laparoscopic reversal of Hartmann procedure via the colostomy site only: first report.

text: BACKGROUND Transumbilical single-incision laparoscopic surgery (SILS) provides an alternative to traditional multiport laparoscopic surgery. The technique may also avoid some of the difficulties surrounding laparoscopic Hartmann reversal. This case represents the first SILS Hartmann reversal via the colostomy site. METHODS SILS Hartmann reversal was performed in a 56-year-old man with a history of resection for perforated diverticulitis. The procedure was performed via a single port placed into the former colostomy site. A combination of flexible and straight instruments was used. RESULTS The procedure was completed successfully with an operative time of 104 minutes. Recovery was uneventful, and the patient was discharged on postoperative day 5, with no complaints at follow-up. CONCLUSION SILS Hartmann procedure reversal via the colostomy site is safe. The approach avoids additional incisions and allows avoidance of dense adhesions to the previous midline incision--a new benefit of SILS, apart from cosmesis.


Letter to the Editor: COVID-19 and Perioperative Considerations.


title: Minimum Infectious Dose Determination of the Arkansas Delmarva Poultry Industry Infectious Bronchitis Virus Vaccine Delivered by Hatchery Spray Cabinet.

text: The Arkansas Delmarva Poultry Industry (ArkDPI) infectious bronchitis virus (IBV) vaccine is effective when administered by eye drop, where the vaccine virus is able to infect and replicate well in birds and is able to induce protection against homologous challenge. However, accumulating evidence indicates that the ArkDPI vaccine is ineffective when applied by hatchery spray cabinet using the same manufacturer-recommended dose per bird. For this study, we aimed to determine the minimum infectious dose for the spray-administered ArkDPI vaccine, which we designate as the dose that achieves the same level of infection and replication as the eye drop-administered ArkDPI vaccine. To this end, we used increasing doses of commercial ArkDPI vaccine to vaccinate 100 commercial broiler chicks at day of hatch, using a commercial hatchery spray cabinet. The choanal cleft of each bird was swabbed at 7 and 10 days postvaccination, and real-time reverse-transcriptase PCR was performed. We observed that the level of infection and replication with spray vaccination matches with that of eye drop vaccination when chicks received 100 times the standard dose for the commercial ArkDPI vaccine. We further examined the S1 spike gene sequence from a subset of reisolated ArkDPI vaccine virus samples and observed that certain nucleotide changes arise in vaccine viruses reisolated from chicks, as previously reported. This suggests that the ArkDPI vaccine has a certain virus subpopulation that, while successful at infecting and replicating in chicks, represents only a minor virus subpopulation in the original vaccine. Thus, the minimum infectious dose for the ArkDPI vaccine using a hatchery spray cabinet appears to be dependent on the amount of this minor subpopulation reaching the chicks.


title: Combining mathematics and empirical data to predict emergence of RNA viruses that differ in reservoir use.

text: RNA viruses may be particularly capable of contributing to the increasing biomedical problem of infectious disease emergence. Empirical studies and epidemiological models are informative for the understanding of evolutionary processes that promote pathogen emergence, but rarely are these approaches combined in the same study. Here, we used an epidemiology model containing observations of pathogen productivity in reservoirs, as a means to predict which pathogens should be most prone to emerge in a primary host such as humans. We employed as a model system a collection of vesicular stomatitis virus populations that had previously diverged in host-use strategy: specialists, directly selected generalists and indirectly selected (fortuitous) generalists. Using data from experiments where these viral strategists were challenged to grow on unencountered novel hosts in vitro, logistic growth models determined that the directly selected generalist viruses tended to grow best on model reservoirs. Furthermore, when we used the growth data to estimate average reproductive rate across secondary reservoirs, we showed that the combined approach could be used to estimate relative success of the differing virus strategists when encountering a primary host. Our study suggests that synergistic approaches combining epidemiological modelling with empirical data from experimental evolution may be useful for developing efforts to predict which types of pathogens pose the greatest probability of emerging in the future.


Reply to: Hedenstierna et al, Haouzi et al, Maley et al, Fowler et al, Bhatia and Mohammed, Bos, & Koumbourlis and Motoyama.


title: Attenuation of the pressor responses to laryngoscopy and endotracheal intubation with intravenous dexmedetomidine versus magnesium sulphate under bispectral index-controlled anaesthesia: A placebo-controlled prospective randomised trial.

text: Background and Aims Laryngoscopy and intubation cause sympathetic stimulation and arousal reactions. We evaluated the role of dexmedetomidine and magnesium sulphate on pressor responses to laryngoscopy and intubation as compared to placebo, when depth of anaesthesia was maintained at a constant bispectral index (BIS) range 40-50 (±5). Methods One hundred and twenty patients were randomised to receive either dexmedetomidine 1 μg/kg (Group DS), magnesium sulphate 30 mg/kg diluted in 100 ml saline (Group MS) or 100 ml normal saline (Group NS) 15 min before induction of anaesthesia in a double blind manner. After achieving BIS 40-50 (±5), laryngoscopy and intubation were performed. Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded pre-drug, after drug, at intubation, at intervals of 1 min till 5 min, then every 2 min till 10 min and every 10 min for 30 min. Statistical analysis was done using Chi-square test and one way analysis of variance. Results SBP, DBP and HR fell in the DS and MS groups. No significant changes in BP were seen in the NS group at induction and after intubation. HR rose in the NS group (P < 0.001) at induction from 86.35 ± 9.05 to 95.35 ± 11.60 at 2 min. Patients in DS and MS groups had significantly lower HR, SBP and DBP at laryngoscopy and intubation. Conclusion At BIS levels 40-50 (±5) there was no pressor response to intubation in the NS Group. Dexmedetomidine and magnesium sulphate significantly reduced the heart rate and blood pressure from baseline.


title: Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D, Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and Protect Mice from Ocular Challenge with HSV-1.

text: The RV144 HIV vaccine trial included a recombinant HIV glycoprotein 120 (gp120) construct fused to a small portion of herpes simplex virus 1 (HSV-1) glycoprotein D (gD) so that the first 40 amino acids of gp120 were replaced by the signal sequence and the first 27 amino acids of the mature form of gD. This region of gD contains most of the binding site for HVEM, an HSV receptor important for virus infection of epithelial cells and lymphocytes. RV144 induced antibodies to HIV that were partially protective against infection, as well as antibodies to HSV. We derived monoclonal antibodies (MAbs) from peripheral blood B cells of recipients of the RV144 HIV vaccine and showed that these antibodies neutralized HSV-1 infection in cells expressing HVEM, but not the other major virus receptor, nectin-1. The MAbs mediated antibody-dependent cellular cytotoxicity (ADCC), and mice that received the MAbs and were then challenged by corneal inoculation with HSV-1 had reduced eye disease, shedding, and latent infection. To our knowledge, this is the first description of MAbs derived from human recipients of a vaccine that specifically target the HVEM binding site of gD. In summary, we found that monoclonal antibodies derived from humans vaccinated with the HVEM binding domain of HSV-1 gD (i) neutralized HSV-1 infection in a cell receptor-specific manner, (ii) mediated ADCC, and (iii) reduced ocular disease in virus-infected mice.IMPORTANCE Herpes simplex virus 1 (HSV-1) causes cold sores and neonatal herpes and is a leading cause of blindness. Despite many trials, no HSV vaccine has been approved. Nectin-1 and HVEM are the two major cellular receptors for HSV. These receptors are expressed at different levels in various tissues, and the role of each receptor in HSV pathogenesis is not well understood. We derived human monoclonal antibodies from persons who received the HIV RV144 vaccine that contained the HVEM binding domain of HSV-1 gD fused to HIV gp120. These antibodies were able to specifically neutralize HSV-1 infection in vitro via HVEM. Furthermore, we showed for the first time that HVEM-specific HSV-1 neutralizing antibodies protect mice from HSV-1 eye disease, indicating the critical role of HVEM in HSV-1 ocular infection.


Sanitization of glaucoma clinic instruments in COVID-19 era.


title: Clinical orthodontic management during the COVID-19 pandemic.

text: OBJECTIVES To provide a comprehensive summary of the implications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) on orthodontic treatment, contingency management, and provision of emergency orthodontic treatment, using currently available data and literature. MATERIALS AND METHODS Orthodontically relevant sources of information were searched using electronic databases including PubMed and Google Scholar and current reports from major health bodies such as Centers of Disease Control and Prevention, World Health Organization, National Institutes of Health, and major national orthodontic associations. RESULTS Where available, peer-reviewed and more recent publications were given priority. Due to the rapidly evolving nature of COVID-19 and limitations in quality of evidence, a narrative synthesis was undertaken. Relevant to orthodontics, human-to human transmission of SARS-CoV-2 occurs predominantly through the respiratory tract via droplets, secretions (cough, sneeze), and or direct contact, where the virus enters the mucous membrane of the mouth, nose, and eyes. The virus can remain stable for days on plastic and stainless steel. Most infected persons experience a mild form of disease, but those with advanced age or underlying comorbidities may suffer severe respiratory and multiorgan complications. CONCLUSIONS During the spread of the COVID-19 pandemic, elective orthodontic treatment should be suspended and resumed only when permitted by federal, provincial, and local health regulatory authorities. Emergency orthodontic treatment can be provided by following a contingency plan founded on effective communication and triage. Treatment advice should be delivered remotely first when possible, and where necessary, in-person treatment can be performed in a well-prepared operatory following the necessary precautions and infection prevention and control (IPAC) protocol.


title: Laparoscopic resection for rectal cancer: a case-matched study.

text: INTRODUCTION The field of laparoscopic rectal cancer surgery is expanding. We compare short-term and early oncological outcomes after laparoscopic versus open resection in carefully matched rectal cancer patients. METHODS All consecutive patients undergoing elective laparoscopic resection for rectal cancer were reviewed. Laparoscopic resections were matched 1:1 to open resections by age, gender, American Society of Anesthesiologists class, body mass index, neoadjuvant chemoradiation, and type of surgery. Data were analyzed using Fisher's exact, chi-square, Wilcoxon rank-sum tests, and Kaplan-Meier estimates. P-value <0.05 was considered statistically significant. RESULTS Ninety-one rectal cancer patients with laparoscopic resection were included, 59% were male, and median age was 62 years. Conversion rate was 18.7%. Laparoscopic and open surgery had similar 30-day morbidity and mortality except wound infection, which was lower for the laparoscopic group (p = 0.02). Laparoscopic surgery had similar 30-day readmissions but shorter total length of hospital stay (5 versus 7 days, p < 0.01), time to first flatus (3 versus 4.5 days, p = 0.001), and time to first bowel movement (4 versus 5 days, p = 0.05) when compared with open surgery. The 3-year disease-free survival, local recurrence, and distant recurrence rates were also similar between the two groups. CONCLUSION Laparoscopic surgery can be safely performed for rectal cancer, with better postoperative recovery and acceptable early oncological outcomes. Results from large ongoing randomized trials with longer follow-up time are pending to better define oncologic outcomes.


Will medical tourism survive covid-19?


title: Evaluation of Alere i Influenza A&B for rapid detection of influenza viruses A and B.

text: Rapid and accurate diagnosis of influenza is important for infection control, as well as for patient management. Alere i Influenza A&B is an isothermal nucleic acid amplification-based integrated system for detection and differentiation of influenza virus A and influenza virus B. The performance of the Alere i Influenza A&B was screened using frozen nasopharyngeal-swab specimens collected in viral transport medium (VTM) that were originally tested fresh with the FilmArray Respiratory Panel (RP) assay during the 2012-2013 influenza outbreak. In total, 360 VTM specimens were selected for Alere i Influenza A&B testing: 40 influenza virus A H1N1-2009 (influenza virus A-1), 40 influenza virus A H3N2 (influenza virus A-3), 37 influenza virus A "equivocal" or "no subtype detected" (influenza virus A-u), 41 influenza virus B, and 202 influenza virus-negative specimens, as initially determined by the FilmArray RP assay. The Alere assay showed sensitivities of 87.2%, 92.5%, 25.0%, and 97.4% for influenza virus A-1, influenza virus A-3, influenza virus A-u, and influenza virus B, respectively, after discordant resolution by Prodesse ProFLU+ PCR. The specificities were 100% for both influenza virus A and influenza virus B. In general, the Alere i Influenza A&B provided good sensitivity, although the assay did show poorer sensitivity with samples determined to have low influenza virus A titers by Prodesse ProFlu+ PCR (a mean real-time PCR threshold cycle [CT] value of 31.9 ± 2.0), which included the majority of the samples called influenza virus A "equivocal" or "no subtype detected" by a single BioFire FilmArray RP test. The integrated, rapid, and simple characteristics of the Alere i Influenza A&B assay make it a potential candidate for point-of-care testing, with a test turnaround time of less than 15 min.


title: Differential Effects of Content-Oriented Versus User-Oriented Social Media on Risk Perceptions and Behavioral Intentions.

text: Social media have become increasingly important in risk and crisis situations. However, little is known about which types of social media have greater influence on risk perceptions and behaviors. This study pursues two goals related to this question. The first is to explicate the cognitive mechanism underlying the process through which exposure to risk information on social media shapes people's behavioral intentions. The second is to determine whether exposures to risk information on two different types of social media-content-oriented social media focusing on shared interests versus user-oriented social media focusing on social relationships-have different effects on people's risk perceptions and behavioral intentions. Analyzing survey data from 688 adults from the general population of South Korea in the context of carcinogenic hazards, we found that self-reported content-oriented social media exposure (to risk information) was significantly related to both personal-level and societal-level risk perceptions. In addition, content-oriented social media exposure was associated with behavioral intentions indirectly through risk perceptions. However, user-oriented social media exposure had no impact on risk perceptions and behavioral intentions, either directly or indirectly through risk perceptions.


title: Advanced imaging to extend the therapeutic time window of acute ischemic stroke.

text: Reperfusion therapy for acute stroke has evolved from the initial use of intravenous tissue plasminogen activator (tPA) within 3 hours of symptom onset to more recent guideline-recommended use up to 4.5 hours. In addition, endovascular therapy is increasingly utilized for stroke treatment and is typically initiated up to 8 hours after onset. Recent studies demonstrate that imaging of the ischemic penumbra with diffusion/perfusion magnetic resonance imaging (MRI) can identify subgroups of patients who are likely to improve following successful reperfusion (Target Mismatch profile) and others who are at increased risk for hemorrhage and poor clinical outcomes (Malignant profile). New data indicate that stent retriever devices provide better recanalization efficacy and clinical outcomes than the previously available mechanical thrombectomy devices. Going forward, we believe that the use of penumbral imaging with validated MRI techniques, as well as the currently less well-validated computed tomography (CT) perfusion approach, will maximize benefit and reduce the risk of adverse events and poor outcomes when used both early after stroke onset and at later time points. New trials that feature diffusion/perfusion MRI or CT perfusion-based patient selection for treatment with intravenous tPA and or endovascular therapies versus nonreperfused control groups are planned or in progress. We predict that these trials will confirm the hypothesis that penumbral imaging can enhance patient selection and extend the therapeutic time window for acute ischemic stroke.


title: LAPAROSCOPIC DISTAL PANCREATECTOMY WITH SPLEEN PRESERVATION.

text: BACKGROUND Laparoscopic distal pancreatectomy has been the choice for resection of distal pancreas lesions due many advantages over open approach. Spleen preservation technique seems minimizes infectious complications in long-term outcome. AIM To present the results of laparoscopic distal pancreatectomies with spleen preservation by Kimura´s technique (preservation of spleen blood vessels) performed by single surgical team. METHODS Retrospective case series aiming to evaluate both short and long-term outcomes of laparoscopic distal pancreatectomies with spleen preservation. RESULTS A total of 54 laparoscopic distal pancreatectomies were performed, in which 26 were laparoscopic distal pancreatectomies with spleen preservation by Kimura´s technique. Mean age was 47.9 years-old (21-75) where 61.5% were female. Mean BMI was 28.5 kg/m² (18-38.8). Mean diameter of lesion was 4.3 cm (1.8-7.5). Mean operative time was 144.1 min (90-200). Intraoperative bleeding was 119.2 ml (50-600). Conversion to laparotomy 3% (n=1). Postoperative morbidity was 11.5%. Postoperative mortality was null. Mean of hospital stay was 4.8 days (2-14). Mean time of follow-up period was 19.7 months (2-60). There was no neoplasm recurrence or mortality on evaluated period. There was no infectious complication. CONCLUSION Laparoscopic distal pancreatectomy with spleen and splenic vessels preservation is feasible, safe, and effective procedure. This technique presented both low morbidity and null mortality on this sample. There were neither infectious complications nor neoplasm recurrence on long-term follow-up period.


title: Effect of multipurpose solutions against Acinetobacter carrying QAC genes.

text: PURPOSE Acinetobacter has low virulence but causes infections in subjects with reduced immunity. It has been reported in ocular infections including those of patients using contact lenses. Treatment is difficult because Acinetobacter is frequently multidrug resistant. Antibiotic-resistant strains frequently also harbor genes for antiseptic resistance (quaternary ammonium compound [QAC]) genes. Because Acinetobacter is part of the normal flora, it may contaminate contact lens and accessories. This study aims to investigate carriage rates of QAC genes in household and clinical isolates of Acinetobacter and to determine the effectiveness of two multipurpose solutions (MPSs) for soft lenses against organisms carrying QAC genes. METHODS DNA was extracted from 11 bathroom isolates and 15 clinical isolates and amplified by polymerase chain reaction to determine the presence of qacEΔ1. Gene-positive and gene-negative control strains were used to challenge the two MPSs, and minimum inhibitory concentrations (MICs) of these organisms to benzalkonium chloride and chlorhexidine gluconate were determined. RESULTS More than 90% of isolates carried qacEΔ1. The MICs of clinical isolates were higher than those of isolates of bathrooms. Both MPSs were able to produce a 3-log reduction in the numbers of all isolates. CONCLUSIONS Although most isolates carried qacEΔ1 and elevated MICs to benzalkonium chloride and chlorhexidine gluconate were observed, all were susceptible to both MPSs tested. However, if there were to be poor compliance with care procedures, it is probable that such organisms could survive in the presence of diluted or expired solutions.


title: NASAL SWAB AS PREFERRED CLINICAL SPECIMEN FOR COVID-19 TESTING IN CHILDREN.

text: The first pediatric study demonstrating significantly higher positivity rate of nasal (mid-turbinate) swab testing over oropharyngeal swab testing in detecting SARS-CoV-2 (Fisher exact test 0.046, Cohen K 0.43, confidence interval 95%, 0.014-0.855). Benefits might include lower collection-related hazard for healthcare workers. We recommend it as preferred choice for swab-based SARS-CoV-2 testing in children.


title: Selection and Application of Tissue microRNAs for Nonendoscopic Diagnosis of Barrett's Esophagus.

text: BACKGROUND & AIMS MicroRNA (miRNA) is highly stable in biospecimens and provides tissue-specific profiles, making it a useful biomarker of carcinogenesis. We aimed to discover a set of miRNAs that could accurately discriminate Barrett's esophagus (BE) from normal esophageal tissue and to test its diagnostic accuracy when applied to samples collected by a noninvasive esophageal cell sampling device. METHODS We analyzed miRNA expression profiles of 2 independent sets of esophageal biopsy tissues collected during endoscopy from 38 patients with BE and 26 patients with normal esophagus (controls) using Agilent microarray and Nanostring nCounter assays. Consistently up-regulated miRNAs were quantified by real-time polymerase chain reaction in esophageal tissues collected by Cytosponge from patients with BE vs without BE. miRNAs were expressed from plasmids and antisense oligonucleotides were expressed in normal esophageal squamous cells; effects on proliferation and gene expression patterns were analyzed. RESULTS We identified 15 miRNAs that were significantly up-regulated in BE vs control tissues. Of these, 11 (MIR215, MIR194, MIR 192, MIR196a, MIR199b, MIR10a, MIR145, MIR181a, MIR30a, MIR7, and MIR199a) were validated in Cytosponge samples. The miRNAs with the greatest increases in BE tissues (7.9-fold increase in expression or more, P < .0001: MIR196a, MIR192, MIR194, and MIR215) each identified BE vs control tissues with area under the curve (AUC) values of 0.82 or more. We developed an optimized multivariable logistic regression model, based on expression levels of 6 miRNAs (MIR7, MIR30a, MIR181a, MIR192, MIR196a, and MIR199a), that identified patients with BE with an AUC value of 0.89, 86.2% sensitivity, and 91.6% specificity. Expression level of MIR192, MIR196a, MIR199a, combined that of trefoil factor 3, identified patients with BE with an AUC of 0.93, 93.1% sensitivity, and 93.7% specificity. Hypomethylation was observed in the promoter region of the highly up-regulated cluster MIR192-MIR194. Overexpression of these miRNAs in normal esophageal squamous cells increased their proliferation, via GRHL3 and PTEN signaling. CONCLUSIONS In analyses of miRNA expression patterns of BE vs non-BE tissues, we identified a profile that can identify Cytosponge samples from patients with BE with an AUC of 0.93. Expression of MIR194 is increased in BE samples via epigenetic mechanisms that might be involved in BE pathogenesis.


title: Oct4+ stem/progenitor swine lung epithelial cells are targets for influenza virus replication.

text: We isolated stem/progenitor epithelial cells from the lungs of 4- to 6-week-old pigs. The epithelial progenitor colony cells were surrounded by mesenchymal stromal cells. The progenitor epithelial colony cells expressed stem cell markers such as octamer binding transcription factor 4 (Oct4) and stage-specific embryonic antigen 1 (SSEA-1), as well as the epithelial markers pancytokeratin, cytokeratin-18, and occludin, but not mesenchymal (CD44, CD29, and CD90) and hematopoietic (CD45) markers. The colony cells had extensive self-renewal potential and had the capacity to undergo differentiation to alveolar type I- and type II-like pneumocytes. Additionally, these cells expressed sialic acid receptors and supported the active replication of influenza virus, which was accompanied by cell lysis. The lysis of progenitor epithelial cells by influenza virus may cause a marked reduction in the potential of progenitor cells for self renewal and for their ability to differentiate into specialized cells of the lung. These observations suggest the possible involvement of lung stem/progenitor cells in influenza virus infection.


title: COVID-19 Exposes the Cracks in Our Already Fragile Mental Health System.

text: The coronavirus pandemic has caused enormous concern among many people. Every morning, we are met with an increasing deluge of dire news about the most recent number of people to contract COVID-19 and to die from it, decreases in the stock market, and countries implementing broad travel restrictions and stay-at-home orders.1,2 The current state of affairs is having a negative effect on the mental well-being of our country's residents. It also highlights the policy gaps in our current system that inhibit the vital conditions for well-being and resiliency.3 Although the primary focus has rightfully been on stopping the spread of COVID-19, we should also quickly prepare to address the mental toll the pandemic is taking on individuals and communities across the country. (Am J Public Health. Published online ahead of print May 21, 2020: e1-e2. doi:10.2105/AJPH.2020.305699).


title: The role of hysteroscopy during COVID-19 outbreak: Safeguarding lives and saving resources.

text: COVID-19 was was declared a pandemic by the World Health Organization (WHO) during its 51st situation report on March 11, 2020.[1] One purpose of the report was to advise restructuring of healthcare services by limiting them to urgent or emergent cases in order to reduce pressure on the intensive care units (ICU) of hospitals treating COVID-19-positive patients.


title: Presence of viral RNA of SARS-CoV-2 in conjunctival swab specimens of COVID-19 patients.

text: Purpose To detect the presence of viral RNA of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in conjunctival swab specimens of coronavirus disease-19 (COVID-19) patients. Methods Forty-five COVID-19 patients positive for real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 in nasopharyngeal swab with or without ocular manifestations were included in the study. The conjunctival swab of each patient was collected by an ophthalmologist posted for COVID duty. Results Out of 45 patients, 35 (77.77%) were males and the rest were females. The mean age was 31.26 ± 12.81 years. None of the patients had any ocular manifestations. One (2.23%) out of 45 patients was positive for RT-PCR SARS-CoV-2 in the conjunctival swab. Conclusion This study shows that SARS-CoV-2 can be detected in conjunctival swabs of confirmed cases of COVID-19 patients. Though the positivity rate of detecting SARS-CoV-2 in conjunctival swabs is very less, care should be exercised during the ocular examination of patients of COVID-19.


Preventing aspiration during peroral endoscopic myotomy.


title: Characterization of a sialate-O-acetylesterase (NanS) from the oral pathogen Tannerella forsythia that enhances sialic acid release by NanH, its cognate sialidase.

text: Tannerella forsythia, a Gram-negative member of the Bacteroidetes has evolved to harvest and utilize sialic acid. The most common sialic acid in humans is a mono-N-acetylated version termed Neu5Ac (5-N-acetyl-neuraminic acid). Many bacteria are known to access sialic acid using sialidase enzymes. However, in humans a high proportion of sialic acid contains a second acetyl group attached via an O-group, i.e. chiefly O-acetylated Neu5,9Ac2 or Neu5,4Ac2. This diacetylated sialic acid is not cleaved efficiently by many sialidases and in order to access diacetylated sialic acid, some organisms produce sialate-O-acetylesterases that catalyse the removal of the second acetyl group. In the present study, we performed bioinformatic and biochemical characterization of a putative sialate-O-acetylesterase from T. forsythia (NanS), which contains two putative SGNH-hydrolase domains related to sialate-O-acetylesterases from a range of organisms. Purification of recombinant NanS revealed an esterase that has activity against Neu5,9Ac2 and its glycolyl form Neu5Gc,9Ac. Importantly, the enzyme did not remove acetyl groups positioned at the 4-O position (Neu5,4Ac2). In addition NanS can act upon complex N-glycans released from a glycoprotein [erythropoietin (EPO)], bovine submaxillary mucin and oral epithelial cell-bound glycans. When incubated with its cognate sialidase, NanS increased sialic acid release from mucin and oral epithelial cell surfaces, implying that this esterase improves sialic acid harvesting for this pathogen and potentially other members of the oral microbiome. In summary, we have characterized a novel sialate-O-acetylesterase that contributes to the sialobiology of this important human pathogen and has potential applications in the analysis of sialic acid diacetylation of biologics in the pharmaceutical industry.


title: Elimination of bovine viral diarrhoea virus in New Zealand: a review of research progress and future directions.

text: The major impacts of bovine viral diarrhoea (BVD) on cattle health and production have prompted many countries to embark on national elimination programmes. These programmes typically involve identifying and removing persistently infected (PI) cattle in infected herds and implementing biosecurity measures, such as pre- or post-movement testing. In order to design a systematic national control programme to eliminate BVD in New Zealand, which achieves the greatest benefits to the industries at the lowest cost to individual farmers, an accurate understanding is necessary of the epidemiology, economics and social motivation for BVD control in New Zealand. In this article we briefly review the pathogenesis of BVD, transmission and diagnosis of BVD virus infection, and effectiveness of vaccination. We summarise the current state of knowledge of the prevalence, risk factors for transmission, and financial impacts of BVD in New Zealand. We describe control programmes in Europe and then discuss the challenges that must be addressed to design a cost-effective national control programme to eliminate BVD in New Zealand.


title: Assessment of the impact of media coverage in coronavirus-related Google Trends: Infodemiology study.

text: BACKGROUND The influence of media coverage in online searches may hamper the role of Google Trends (GT) for Covid-19 monitoring. OBJECTIVE To assess whether Covid-19-related GT - particularly on ageusia and anosmia - were primarily related to media coverage or with epidemic trends. METHODS We retrieved GT data for searches on "coronavirus", "cough", "anosmia" and "ageusia", plotting them for a period of 5 years. In addition, we analysed the trends of those queries for 17 countries throughout the year of 2020, particularly concerning rises and peaks of searches. For anosmia and ageusia, we assessed whether the respective GT correlated with Covid-19 cases and deaths both throughout 2020 and specifically before March 16, 2020 (i.e., the date when the media started reporting that those symptoms could be associated with Covid-19). RESULTS Over the last five years, peaks of "coronavirus" GT were only observed during the Winter of 2020. Rises and peaks in "coronavirus" searches were similar in time in the 17 different assessed countries, irrespectively of their epidemic situation. In 15 of these countries, rises in "anosmia" and "ageusia" GT occurred in the same week or one week after they were identified in the media as symptoms of Covid-19. Analysing data prior to March 16, 2020, anosmia/ageusia GT were found to have variable correlation with Covid-19 cases and deaths in the different countries. CONCLUSIONS Covid-19-related GT is more related to media coverage than with epidemic trends. CLINICALTRIAL


Dental sleep medicine perspectives post-COVID-19: interprofessional adaptation and directions.


title: LigaSure Hemorrhoidectomy for Symptomatic Hemorrhoids: First Pediatric Experience.

text: Hemorrhoids are uncommon in children. Third and fourth degree symptomatic hemorrhoids may be surgically excised. We describe the first experience of using LigaSure (Covidien, Mansfield, Massachusetts, United States) to perform hemorrhoidectomies in children. LigaSure hemorrhoidectomy has been well described in adults and is found to be superior in patient tolerance as compared with conventional hemorrhoidectomy.


title: COVID-19 Challenges Basic Researchers.

text: As COVID-19 continues to surge, cancer scientists engaged in basic research face unique challenges. At centers throughout the United States, investigators are confronting difficult decisions about which experiments to continue, while securing supplies and creating contingency plans for a complete shutdown.


title: Arthroplasty infection by Priopionibacterium granulosum treated with reimplantation despite ongoing purulent-appearing fluid collection.

text: We present the first case of infection in a native or prosthetic joint by Propionibacterium granulosum in which a patient developed symptoms of prosthetic hip infection 5 years after primary surgery. The patient required multiple operative debridements to eradicate the infection and was successfully reimplanted despite an ongoing purulent-appearing, although sterile, fluid collection at the time of reimplantation. There is no clinical or laboratory evidence of infection at 3 years post-reimplantation, and the patient has a well-functioning total hip arthroplasty. P granulosum is a low-virulence but highly-inflammatory organism. It seems to produce a large fluid collection that may require multiple debridements. To our knowledge, there are no reported cases of native or prosthetic joint infection from P granulosum. We present the first case here.


title: Variable versus conventional lung protective mechanical ventilation during open abdominal surgery (PROVAR): a randomised controlled trial.

text: BACKGROUND Experimental studies showed that controlled variable ventilation (CVV) yielded better pulmonary function compared to non-variable ventilation (CNV) in injured lungs. We hypothesized that CVV improves intraoperative and postoperative respiratory function in patients undergoing open abdominal surgery. METHODS Fifty patients planned for open abdominal surgery lasting >3 h were randomly assigned to receive either CVV or CNV. Mean tidal volumes and PEEP were set at 8 ml kg-1 (predicted body weight) and 5 cm H2O, respectively. In CVV, tidal volumes varied randomly, following a normal distribution, on a breath-by-breath basis. The primary endpoint was the forced vital capacity (FVC) on postoperative Day 1. Secondary endpoints were oxygenation, non-aerated lung volume, distribution of ventilation, and pulmonary and extrapulmonary complications until postoperative Day 5. RESULTS FVC did not differ significantly between CVV and CNV on postoperative Day 1, 61.5 (standard deviation 22.1) % vs 61.9 (23.6) %, respectively; mean [95% confidence interval (CI)] difference, -0.4 (-13.2-14.0), P=0.95. Intraoperatively, CVV did not result in improved respiratory function, haemodynamics, or redistribution of ventilation compared to CNV. Postoperatively, FVC, forced expiratory volume at the first second (FEV1), and FEV1/FVC deteriorated, while atelectasis volume and plasma levels of interleukin-6 and interleukin-8 increased, but values did not differ between groups. The incidence of postoperative pulmonary and extrapulmonary complications was comparable in CVV and CNV. CONCLUSIONS In patients undergoing open abdominal surgery, CVV did not improve intraoperative and postoperative respiratory function compared with CNV. CLINICAL TRIAL REGISTRATION NCT 01683578.


title: Characteristics of an epidemic outbreak with a large initial infection size.

text: A deterministic model proposed in previous literatures to approximate the well-known Richards model is investigated. However, the model assumption of small initial value for infection size is released in the current manuscript. Taking the advantage of the closed form of solutions, we establish the epidemic characteristics of disease transmission: the outbreak size, the peak size and the turning point for the cumulative infected cases. It is shown that the usual disease outbreak threshold condition (the basic reproduction number R0 is greater than unity) fails to fully guarantee the existence of peaking time and turning point when the initial infection size is not relatively small. The epidemic characteristics not only depend on R0 but also on another index, the net reproduction number R0*.


Impact of COVID-19 pandemic on medical postgraduate training in the United States.


title: Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario.

text: Background The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.


How Community-Based Health Systems Embrace Research During the COVID-19 Pandemic.


title: Coronavirus Disease Outbreak in Call Center, South Korea.

text: We describe the epidemiology of a coronavirus disease (COVID-19) outbreak in a call center in South Korea. We obtained information on demographic characteristics by using standardized epidemiologic investigation forms. We performed descriptive analyses and reported the results as frequencies and proportions for categoric variables. Of 1,143 persons who were tested for COVID-19, a total of 97 (8.5%, 95% CI 7.0%-10.3%) had confirmed cases. Of these, 94 were working in an 11th-floor call center with 216 employees, translating to an attack rate of 43.5% (95% CI 36.9%-50.4%). The household secondary attack rate among symptomatic case-patients was 16.2% (95% CI 11.6%- 22.0%). Of the 97 persons with confirmed COVID-19, only 4 (1.9%) remained asymptomatic within 14 days of quarantine, and none of their household contacts acquired secondary infections. Extensive contact tracing, testing all contacts, and early quarantine blocked further transmission and might be effective for containing rapid outbreaks in crowded work settings.


title: Neutron-activatable holmium-containing mesoporous silica nanoparticles as a potential radionuclide therapeutic agent for ovarian cancer.

text: UNLABELLED Mesoporous silica nanoparticles (MSNs) were explored as a carrier material for the stable isotope (165)Ho and, after neutron capture, its subsequent therapeutic radionuclide, (166)Ho (half-life, 26.8 h), for use in radionuclide therapy of ovarian cancer metastasis. METHODS (165)Ho-MSNs were prepared using (165)Ho-acetylacetonate and MCM-41 silica particles, and stability was determined after irradiation in a nuclear reactor (reactor power, 1 MW; thermal neutron flux of approximately 5.5 × 10(12) neutrons/cm(2)s). SPECT/CT and tissue biodistribution studies were performed after intraperitoneal administration of (166)Ho-MSNs to SKOV-3 ovarian tumor-bearing mice. Radiotherapeutic efficacy was studied by using PET/CT with (18)F-FDG to determine tumor volume and by monitoring survival. RESULTS The holmium-MSNs were able to withstand long irradiation times in a nuclear reactor and did not release (166)Ho after significant dilution. SPECT/CT images and tissue distribution results revealed that (166)Ho-MSNs accumulated predominantly in tumors (32.8% ± 8.1% injected dose/g after 24 h; 81% ± 7.5% injected dose/g after 1 wk) after intraperitoneal administration. PET/CT images showed reduced (18)F-FDG uptake in tumors, which correlated with a marked increase in survival after treatment with approximately 4 MBq of (166)Ho-MSNs. CONCLUSION The retention of holmium in nanoparticles during irradiation and in vivo after intraperitoneal administration as well as their efficacy in extending survival in tumor-bearing mice underscores their potential as a radiotherapeutic agent for ovarian cancer metastasis.


title: Clinical presentation and treatment outcomes of spinal epidural arteriovenous fistulas.

text: OBJECTIVE Spinal epidural arteriovenous fistulas (SEDAVFs) constitute a rare but treatable cause of vascular myelopathy and are a different subtype from the more common Type I spinal dural AVFs. The purpose of this study was to review a consecutive series of SEDAVFs from a single institution and report on the clinical presentations, functional status, and treatment outcomes. METHODS The authors identified all SEDAVFs treated at their institution from 2005 to 2015. SEDAVFs were defined as spinal AVFs in which the fistulous connection occurred in the epidural venous plexus. The clinical presentation, functional status, immediate treatment outcomes, and long-term neurological outcomes were analyzed. RESULTS Twenty-four patients with SEDAVFs were included in this study. The patients' mean age at presentation was 66.9 years. The most common presenting symptoms were pain and numbness (22 patients, 91.7%), followed by lower-extremity weakness (21 patients, 87.5%). The mean duration of symptoms prior to diagnosis was 11.8 months. Eighteen patients (75.0%) were treated with endovascular therapy alone, 4 (16.7) with surgery, and 2 (8.3%) with a combination of techniques. There was 1 major treatment-related complication (4.2%). Fifteen patients (62.5%) had improvement in disability, and 12 patients (54.5%) had improvement in sensory symptoms. CONCLUSIONS SEDAVFs often present with lower-extremity motor dysfunction and sensory symptoms. With the availability of newer liquid embolic agents, these lesions can be effectively treated with endovascular techniques. Surgery is also effective at treating these lesions, especially in situations where endovascular embolization fails or is not safe and in patients presenting with mass effect from compressive varices.


Foam dressing as a suturing model.


title: Endovascular Management of Tandem Occlusion Stroke Related to Internal Carotid Artery Dissection Using a Distal to Proximal Approach: Insight from the RECOST Study.

text: BACKGROUND AND PURPOSE Internal carotid artery dissection is a common cause of stroke in young adults. It may be responsible for tandem occlusion defined by a cervical steno-occlusive carotid wall hematoma associated with an intracranial large-vessel stroke. Intravenous thrombolysis is associated with a poor clinical outcome in these cases, and endovascular treatment has not been specifically evaluated to date. Our aim was to evaluate endovascular treatment technical and clinical efficiency in this specific occlusion topography, in comparison with treatment of isolated anterior circulation stroke. MATERIALS AND METHODS As part of our ongoing prospective stroke data base started in August 2009 (Prognostic Factors Related to Clinical Outcome Following Thrombectomy in Ischemic Stroke [RECOST] Study), we analyzed all carotid artery dissection tandem occlusion strokes and isolated anterior circulation occlusions. All patients were selected for endovascular treatment according to clinical-radiologic mismatch, NIHSS ≥ 7 and DWI-ASPECTS ≥5, within 6 hours after onset. For carotid artery dissection, the revascularization procedure consisted first of distal recanalization by a stent retriever in the intracranial vessel. Following assessment of the circle of Willis, internal carotid artery stent placement was only performed in case of insufficiency. Carotid artery dissection treatment efficacy, safety, and clinical outcome were compared with the results of the isolated anterior circulation occlusion cohort. RESULTS Two hundred fifty-eight patients with an anterior circulation stroke were analyzed, including 57 with tandem occlusions (22%); among them, 20 were carotid artery dissection-related occlusions (7.6%). The median age of patients with tandem occlusions with internal carotid dissection was 52.45 versus 66.85 years for isolated anterior circulation occlusion (P < .05); the mean initial NIHSS score was 17.53 ± 4.11 versus 17.55 ± 4.8 (P = .983). The median DWI-ASPECTS was 6.05 versus 6.64 (P = .098), and the average time from onset to puncture was 4.38 for tandem occlusions versus 4.53 hours in isolated anterior circulation occlusion (P = .704). Complication rates and symptomatic intracranial hemorrhage were comparable in both groups (5% versus 3%, P = .49). The duration of the procedure was significantly prolonged in case of tandem occlusion (80.69 versus 65.45 minutes, P = .030). Fourteen patients with carotid artery dissection (70%) had a 3-month mRS of ≤ 2, without a significant difference from patients with an isolated anterior circulation occlusion (44%, P = .2). Only 5 carotid artery dissections (25%) necessitated cervical stent placement. No early ipsilateral stroke recurrence was recorded, despite the absence of stent placement in 15 patients (75%) with carotid artery dissection. CONCLUSIONS Mechanical endovascular treatment of carotid artery dissection tandem occlusions is safe and effective compared with isolated anterior circulation occlusion stroke therapy. Hence, a more conservative approach with stent placement only in cases of circle of Willis insufficiency may be a reliable and safe strategy.


title: [Clinical analysis of kidney injury in patients with COVID-19].

text: Objective: To investigate the relationship between novel coronavirus pneumonia (COVID-19) and kidney injury. Methods: A retrospective analysis was performed on COVID-19 confirmed patients in the Central Theater Command General Hospital of Chinese PLA on March 12, 2020. A total of 87 hospitalized COVID-19 confirmed patients were enrolled in the study, and they were hospitalized at least one week. The recorded information included clinical data and indicators of kidney-related laboratory tests. Results: The average age of patients was (65.2±17.1) years, and 34.5% (30/87) patients were ≥ 75 years old and 31.0% (27/87) patients were 60~74 years old. Male and female patients accounted for 59.8% (52/87) and 40.2% (35/87), respectively. There were 29.9% (26/87) and 12.6% (11/87) patients who had already showed mild elevation of blood urea nitrogen (BUN) and serum creatinine (SCr) at admission. Moreover, 25.3% (22/87) and 4.6% (4/87) patients still exhibited mild elevation of BUN and SCr one week after admission. However, 28.7% (25/87) patients showed an elevation of BUN one week later after admission, though their BUN levels were normal at admission. Likewise, 16.1% (14/87) patients showed an elevation of SCr one week later after admission, while their SCr levels were normal at admission. Only two patients had an increase of SCr ≥26.5 μmol/L, and both of them were over 75 years old. Conclusions: COVID-19 patients with severe acute kidney injury are uncommon. However, attention should be paid to acute kidney injury of the elderly patients in the diagnosis and treatment of COVID-19.


title: Coronary CT radiation dose reduction strategies at an Australian Tertiary Care Center - improvements in radiation exposure through an evidence-based approach.

text: INTRODUCTION Coronary CT Angiography (CCTA) is a rapidly increasing technique for coronary imaging; however, it exposes patients to ionising radiation. We examined the impact of dose reduction techniques using ECG-triggering, kVp/mAs reduction and high-pitch modes on radiation exposure in a large Australian tertiary CCTA service. METHODS Data on acquisition modes and dose exposure were prospectively collected on all CCTA scans from November 2009 to March 2014 at an Australian tertiary care centre. A dose reduction algorithm was developed using published techniques and implemented with education of medical staff, radiographers and referrers. Associations of CCTA acquisition to radiation over time were analysed with multivariate regression. Specificity in positive CCTA was assessed by correlation with invasive coronary angiography. RESULTS 3333 CCTAs were analysed. Mean radiation dose decreased from 8.4 mSv to 5.3, 4.4, 3.7, 2.9 and 2.8 mSv (P < 0.001) per year. Patient characteristics were unchanged. Dose reduction strategies using ECG-triggering, kVp/mAs reduction accounted for 91% of the decrease. High-pitch scanning reduced dose by an additional 9%. Lower dose was independently related to lower kVp, heart rate, tube current modulation, BMI, prospective triggering and high-pitch mode (P < 0.01). CCTA specificity remained unchanged despite dose reduction. CONCLUSION Implementation of evidence-based CCTA dose reduction algorithm and staff education programme resulted in a 67% reduction in radiation exposure, while maintaining diagnostic specificity. This approach is widely applicable to clinical practice for the performance of CCTA.


title: Utilization of Clinical Trials Registries in Obstetrics and Gynecology Systematic Reviews.

text: OBJECTIVE To evaluate the use of clinical trials registries in published obstetrics and gynecologic systematic reviews and meta-analyses. METHODS We performed a metaepidemiologic study of systematic reviews between January 1, 2007, and December 31, 2015, from six obstetric and gynecologic journals (Obstetrics & Gynecology, Obstetrical & Gynecological Survey, Human Reproduction Update, Gynecologic Oncology, British Journal of Obstetrics and Gynaecology, and American Journal of Obstetrics & Gynecology). All systematic reviews included after exclusions were independently reviewed to determine whether clinical trials registries had been included as part of the search process. Studies that reported using a trials registry were further examined to determine whether trial data were included in the analysis of these systematic reviews. RESULTS Our initial search resulted in 292 articles, which was narrowed to 256 after exclusions. Of the 256 systematic reviews meeting our selection criteria, 47 (18.4%) used a clinical trials registry. Eleven of the 47 (23.4%) systematic reviews found unpublished data and two included unpublished data in their results. CONCLUSION A majority of systematic reviews in clinical obstetrics and gynecology journals do not conduct searches of clinical trials registries or do not make use of data obtained from these searches. Failure to make use of such data may lead to an inaccurate summary of available evidence and may contribute to an overrepresentation of published, statistically significant outcomes.


COVID-19 stigma induced by press releases in Japan: It's time to reconsider risk communication learned from the Fukushima Daiichi Nuclear Disaster.


title: Utility of qSOFA and modified SOFA in severe malaria presenting as sepsis.

text: Sepsis can be caused by malaria infection, but little is known about the utility of the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) and SOFA score in malaria. We conducted a prospective observational study from March 2013 to February 2017 to examine adults admitted with community-acquired infection in a tertiary-care hospital in Ubon Ratchathani, Northeast Thailand (Ubon-sepsis). Subjects were classified as having sepsis if they had a modified SOFA score ≥2 within 24 hours of admission. Serum was stored and later tested for malaria parasites using a nested PCR assay. Presence of severe malaria was defined using modified World Health Organization criteria. Of 4,989 patients enrolled, 153 patients (3%) were PCR positive for either Plasmodium falciparum (74 [48%]), P. vivax (69 [45%]), or both organisms (10 [7%]). Of 153 malaria patients, 80 were severe malaria patients presenting with sepsis, 70 were non-severe malaria patients presenting with sepsis, and three were non-severe malaria patients presenting without sepsis. The modified SOFA score (median 5; IQR 4-6; range 1-18) was strongly correlated with malaria severity determined by the number of World Health Organization severity criteria satisfied by the patient (Spearman's rho = 0.61, p<0.001). Of 80 severe malaria patients, 2 (2.5%), 11 (14%), 62 (77.5%) and 5 (6%), presented with qSOFA scores of 0, 1, 2 and 3, respectively. Twenty eight-day mortality was 1.3% (2/153). In conclusion, qSOFA and SOFA can serve as markers of disease severity in adults with malarial sepsis. Patients presenting with a qSOFA score of 1 may also require careful evaluation for sepsis; including diagnosis of cause of infection, initiation of medical intervention, and consideration for referral as appropriate.


title: A Framework for Evidence Synthesis Programs to Respond to a Pandemic.

text: The coronavirus disease 2019 (COVID-19) pandemic requires making rapid decisions based on sparse and rapidly changing evidence. Evidence synthesis programs conduct systematic reviews for guideline developers, health systems clinicians, and decision-makers that usually take an average 6 to 8 months to complete. We present a framework for evidence synthesis programs to respond to pandemics that has proven feasible and practical during the COVID-19 response in a large multistate health system employing more than 78,000 people. The framework includes four components: an approach for conducting rapid reviews, a repository of rapid reviews, a registry for all original studies about COVID-19, and twice-weekly prioritized update of new evidence sent to key stakeholders. As COVID-19 will not be our last pandemic, we share the details of this framework to allow replication in other institutions and re-implementation in future pandemics.


title: Epicardial adipose tissue and metabolic syndrome: An update protocol for systematic review and meta-analysis.

text: BACKGROUND The prevalence of metabolic syndrome (MetS) and MetS-related stroke is set to increase dramatically in coming decades. MetS is a complex disease that includes endothelial dysfunction, insulin resistance, diabetes, hypertension, ectopic obesity, and dyslipidaemia, and an increased risk of cardiovascular events. However, there are no systematic analyses, or well-conducted meta-analyses to evaluate the relationship between epicardial adipose tissue (EAT) and (MetS). The aim of this study is to examine this association of EAT with MetS in different ages and sex. METHODS The update systematic review, and meta-analysis will be conducted using published studies that will be identified from electronic databases (ie, PubMed, EMBASE, Web of Science, and Google Scholar. Studies that firstly, examined the association between EAT and MetS, secondly, focus on cohort, case-control, and cross-sectional studies, thirdly, were conducted among in adults aged between 40 and 70 years, fourth, provided sufficient data for calculating ORs or relative risk with a 95% CI, fifth, were published as original articles written in English or other languages, and sixth, have been published until January year 2018 will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted based on discussions among investigators. RESULTS Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. This study will provide a high quality synthesis on the association of EAT and MetS. CONCLUSION This systematic review will provide evidence to assess whether there is a strong association of EAT and MetS, and its components.


title: Microsecond thermal ablation of skin for transdermal drug delivery.

text: Thermal ablation is a promising mechanism to increase permeability of the skin's outer barrier layer of stratum corneum while sparing deeper living tissues. In this study, finite element modeling predicted that the skin surface should only be heated on the microsecond timescale in order to avoid significant temperature rises in living cells and nerve endings in deeper tissue. To achieve such short thermal pulses, we developed a microdevice that rapidly heats a few microliters of water by an electrical discharge and ejects the resulting superheated steam at the skin surface on a timescale on the order of 100 μs. According to its design, we showed that this microdevice selectively removed stratum corneum of cadaver skin without significantly removing deeper tissue. This one-dimensional depth control was supplemented through the use of a masking film containing 100 μm-diameter holes placed on the skin surface during ablation to define the ablated skin area and thereby provide three-dimensional control over tissue removal. Using this approach, thermal ablation increased skin permeability to sulforhodamine B and bovine serum albumin by at least 1000-fold in vitro. We conclude that microsecond thermal ablation of skin can selectively remove stratum corneum and thereby dramatically increase skin permeability for transdermal drug delivery.


Person-to-person spread of the MERS coronavirus--an evolving picture.


title: Expression of Ifnlr1 on Intestinal Epithelial Cells Is Critical to the Antiviral Effects of Interferon Lambda against Norovirus and Reovirus.

text: Lambda interferon (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects is unclear. Here, we sought to identify IFN-λ-responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1 We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity. IEC Ifnlr1 expression also determines the efficacy of IFN-λ in resolving persistent murine norovirus (MNoV) infection and regulates fecal shedding and viral titers in tissue. Thus, the expression of Ifnlr1 by IECs is necessary for the response to both endogenous and exogenous IFN-λ. We further demonstrate that IEC Ifnlr1 expression is required for the sterilizing innate immune effects of IFN-λ by extending these findings in Rag1-deficient mice. Finally, we assessed whether our findings pertained to multiple viral pathogens by infecting mice specifically lacking IEC Ifnlr1 expression with reovirus. These mice phenocopied Ifnlr1-null animals, exhibiting increased intestinal tissue titers and enhanced reovirus fecal shedding. Thus, IECs are the critical cell type responding to IFN-λ to control multiple enteric viruses. This is the first genetic evidence that supports an essential role for IECs in IFN-λ-mediated control of enteric viral infection, and these findings provide insight into the mechanism of IFN-λ-mediated antiviral activity.IMPORTANCE Human noroviruses (HNoVs) are the leading cause of epidemic gastroenteritis worldwide. Type III interferons (IFN-λ) control enteric viral infections in the gut and have been shown to cure mouse norovirus, a small-animal model for HNoVs. Using a genetic approach with conditional knockout mice, we identified IECs as the dominant IFN-λ-responsive cells in control of enteric virus infection in vivo Upon murine norovirus or reovirus infection, Ifnlr1 depletion in IECs largely recapitulated the phenotype seen in Ifnlr1-/- mice of higher intestinal tissue viral titers and increased viral shedding in the stool. Moreover, IFN-λ-mediated sterilizing immunity against murine norovirus requires the capacity of IECs to respond to IFN-λ. These findings clarify the mechanism of action of this cytokine and emphasize the therapeutic potential of IFN-λ for treating mucosal viral infections.


title: Orthopedic surgery residents' perception of online education in their programs during the COVID-19 pandemic: should it be maintained after the crisis?

text: Background and purpose - During the COVID-19 pandemic, most of the teaching centers in Chile have shifted to online resources. We decided to do a survey on orthopedic residents regarding this type of education to assess for strengths and weaknesses of digital education in orthopedic programs.Methods - A survey was performed targeting 110 orthopedic residents belonging to different training programs around the country. 100 residents completed the survey.Results - 86% stated that their programs are using online education. When asked in detail, 86% had been involved in webinars, 28% had received online presentations, 12% had participated in online tests, and 7% had evaluated patients. Webinars were rated (1 = very unsatisfactory, 10 = very satisfactory) with a mean grade of 8.1 (1-10), online presentations 7.3 (1-10), online tests 3.8 (1-8), and online patient evaluations 2.9 (1-9). When asked if, after the end of the pandemic, they would continue using the online modalities, 82% would continue attending webinars, 72% would continue watching online presentations, 27% would continue performing online tests, and 33% of the residents would continue performing online evaluations of patients.Interpretation - Even though resident evaluation of online activities is positive, face-to-face theoretical activities are still valued as a necessary complement for orthopedic residency education.


title: Investigating the use of ultrasonography for the antenatal diagnosis of structural congenital anomalies in low-income and middle-income countries: systematic review protocol.

text: Introduction Congenital anomalies are the fifth leading cause of mortality in children under 5 years globally. The greatest burden is faced by those in developing countries, where over 95% of deaths occur. Many of these deaths may have been preventable through antenatal diagnosis and early intervention. This study aims to conduct a systematic review that investigates the use of antenatal ultrasound to diagnose congenital anomalies and improve the health outcomes of infants in low-income and middle-income countries (LMICs). Methods and analysis A systematic literature review will be conducted using three search strings: (1) structural congenital anomalies, (2) LMICs and (3) antenatal diagnosis. Four electronic databases will be searched: MEDLINE, Embase, PubMed and the Cochrane Library. Title, abstract and full-text screening will be undertaken in duplicate by two reviewers independently using Covidence. Consensus will be sought from the wider authorship for discrepancies. Data extraction will be undertaken by the principal investigator. The primary analysis will focus on the availability and effectiveness of antenatal ultrasound for structural congenital anomalies. Secondary outcomes will include neonatal morbidity and mortality, termination rates and referral rates for further antenatal care. Descriptive statistics and a narrative synthesis will be included in the final report. The methodological quality of the included studies will be evaluated using the Cochrane-approved Risk of Bias for Non-Randomised Studies of Intervention and Risk of Bias in Randomised Trials V.2.0 tools. Ethics and dissemination Ethical approval is not required for conducting the systematic review as there will be no direct collection of data from individuals. The results will be submitted for publication in a scientific journal and presented internationally. Conclusion This is the first study, to our knowledge, to systematically review current literature on the use of antenatal ultrasound for the detection of congenital anomalies in LMICs. This is vital to define current practice, highlight global disparities and evaluate effects on health outcomes for infants in low-resource settings. PROSPERO registration number CRD42019105620.


title: Colorectal cancer.

text: Colorectal cancer had a low incidence several decades ago. However, it has become a predominant cancer and now accounts for approximately 10% of cancer-related mortality in western countries. The 'rise' of colorectal cancer in developed countries can be attributed to the increasingly ageing population, unfavourable modern dietary habits and an increase in risk factors, such as smoking, low physical exercise and obesity. New treatments for primary and metastatic colorectal cancer have emerged, providing additional options for patients; these treatments include laparoscopic surgery for primary disease, more-aggressive resection of metastatic disease (such as liver and pulmonary metastases), radiotherapy for rectal cancer, and neoadjuvant and palliative chemotherapies. However, these new treatment options have had limited impact on cure rates and long-term survival. For these reasons, and the recognition that colorectal cancer is long preceded by a polypoid precursor, screening programmes have gained momentum. This Primer provides an overview of the current state of the art of knowledge on the epidemiology and mechanisms of colorectal cancer, as well as on diagnosis and treatment.


title: Nursing home-acquired pneumonia: a review of risk factors and therapeutic approaches.

text: OBJECTIVE To review the risk factors, etiologic profile, treatment approaches, and guidelines for the management of nursing home-acquired pneumonia (NHAP). RESEARCH DESIGN AND METHODS A search of the current literature was conducted using the MEDLINE and Embase databases. This search, limited to studies performed in humans and published in English between January 1, 1990 and October 31, 2009, included the terms 'acquired pneumonia', 'associated pneumonia', 'nursing home', 'long-term care', 'institution', and 'healthcare'. RESULTS Older age, male gender, swallowing difficulty, and inability to take oral medications are all significant risk factors for pneumonia. Medications such as antipsychotics and anticholinergics, histamine receptor blockers and proton pump inhibitors have also been linked to higher risk of pneumonia. The etiology of NHAP overlaps with that of community-acquired pneumonia (CAP), with Streptococcus pneumoniae and Haemophilus influenzae as predominant pathogens in long-term care facilities. In patients who require hospitalization, Chlamydophila pneumoniae, Staphylococcus aureus, and influenza virus have also been identified. In contrast, the etiology of severe NHAP overlaps with that of hospital-acquired pneumonia (HAP), with S. aureus, including methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, and enteric Gram-negative bacilli as important causative pathogens. Therapy is dependent on disease severity and, on the treatment setting. Respiratory fluoroquinolones or β-lactams plus a macrolide are recommended in patients with NHAP. Patients hospitalized with severe NHAP may require triple combination therapy that covers both MRSA and P. aeruginosa. However, there is little evidence of the clinical superiority of one regimen over another, making it challenging to establish guidelines for the treatment of NHAP in the nursing home setting. CONCLUSION There is a pressing need for clinical trials of antibiotic therapy in nursing home patients that would help establish uniform guidelines to standardize therapy in the nursing home setting.


Preparing for COVID-19 Related Drug Shortages.


Advancing care for bipolar disorder today and breakthroughs in access and treatments tomorrow with mobile health and smartphone apps.


title: Infection Control for CT Equipment and Radiographers' Personal Protection During the Coronavirus Disease (COVID-19) Outbreak in China.

text: OBJECTIVE. Because CT plays an important role in diagnosis, isolation, treatment, and effective evaluation of coronavirus disease (COVID-19), infection prevention and control management of CT examination rooms is important. CONCLUSION. We describe modifications to the CT examination process, strict disinfection of examination rooms, arrangement of waiting areas, and efforts to increase radiographers' awareness of personal protection made at our institution during the COVID-19 outbreak. In addition, we discuss the potential of using artificial intelligence in imaging patients with contagious diseases.


title: Modelling the elimination of hepatitis C as a public health threat in Iceland: A goal attainable by 2020.

text: BACKGROUND & AIMS In Iceland a nationwide program has been launched offering direct-acting antiviral (DAA) treatment for everyone living with hepatitis C virus (HCV). We estimate (i) the time and treatment scale-up required to achieve the World Health Organization's HCV elimination target of an 80% reduction in incidence; and (ii) the ongoing frequency of HCV testing and harm reduction coverage among people who inject drugs (PWID) required to minimize the likelihood of future HCV outbreaks occurring. METHODS We used a dynamic compartmental model of HCV transmission, liver disease progression and the HCV cascade of care, calibrated to reproduce the epidemic of HCV in Iceland. The model was stratified according to injecting drug use status, age and stage of engagement. Four scenarios were considered for the projections. RESULTS The model estimated that an 80% reduction in domestic HCV incidence was achievable by 2030, 2025 or 2020 if a minimum of 55/1,000, 75/1,000 and 188/1,000 PWID were treated per year, respectively (a total of 22, 30 and 75 of the estimated 400 PWID in Iceland per year, respectively). Regardless of time frame, this required an increased number of PWID to be diagnosed to generate enough treatment demand, or a 20% scale-up of harm reduction services to complement treatment-as-prevention incidence reductions. When DAA scale-up was combined with annual antibody testing of PWID, the incidence reduction target was reached by 2024. Treatment scale-up with no other changes to current testing and harm reduction services reduced the basic reproduction number of HCV from 1.08 to 0.59, indicating that future outbreaks would be unlikely. CONCLUSION HCV elimination in Iceland is achievable by 2020 with some additional screening of PWID. Maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that outbreaks are unlikely to occur once elimination targets have been reached. LAY SUMMARY In Iceland, a nationwide program has been launched offering treatment for the entire population living with hepatitis C virus (HCV). A mathematical model was used to estimate the additional health system requirements to achieve the HCV elimination targets of the World Health Organization (WHO), as well as the year that this could occur. With some additional screening of people who inject drugs, Iceland could reach the WHO targets by 2020, becoming one of the first countries to achieve HCV elimination. The model estimated that once elimination targets were reached, maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that future HCV outbreaks are unlikely to occur.


title: Morphological analysis of mouse hepatitis virus A59-induced pathology with regard to viral receptor expression.

text: Mouse hepatitis virus, strain A59 (MHV-A59), is a coronavirus that triggers in susceptible mice a wide variety of pathologies, including hepatitis, thymus involution, B lymphocyte polyclonal activation and, after intra-cerebral inoculation, transient demyelination. One receptor that mediates entry of the virus into target cells has been identified: it is a glycoprotein of the carcinoembryonic antigen family, called Bgp1a. The availability of antibodies recognizing this molecule permits the analysis of its cellular expression and of the relationship between receptor expression and pathology induced by the virus. Bgp1a is found on epithelial and endothelial cells as well as on B lymphocytes and macrophages. In the liver, Bgp1a expression correlates well with infection of hepatocytes and endothelial cells, leading to the development of hepatitis. However, other cells expressing this molecule, such as central nervous system endothelial cells, are not infected by the virus. This observation may explain how the blood-brain barrier prevents dissemination of MHV-A59 from the general circulation into the brain. Thymic atrophy results from apoptosis of immature double-positive T lymphocytes which might be caused indirectly by infection of a small proportion of thymus epithelial cells that express Bgp1a rather than by infection of T cells that do not express the receptor. Finally, polyclonal activation of B lymphocytes, leading to increased secretion of antibodies of the IgG2a isotype, involves a cascade of events, including cytokine secretion, that may result from the interaction of MHV-A59 with B cells and macrophages that express Bgp1a. Therefore, after viral infection, cellular expression of Bgp1a may have different results: cell lysis; alteration of cellular functions that may lead to indirect death of other cell types, or resistance to infection.


title: Severe Pneumonia Treated Succesfully with Levofloxacin and Oseltamivir During Flu Epidemic.

text: Viral pneumonia is an important cause of community acquired pneumonias (CAP). It's not only specific to childhood period. Although immunocompromised adults are susceptible; all young and healthy adults are at risk. Viral pneumonias are usually underestimated due to lack of diagnostic modalities so a clinician must be aware of. Co-infection of viruses and bacteria is not uncommon and can be mortal especially in a flu epidemic, therefore, in the absence of diagnostic tools initiating to anti-viral treatment without delay is important.


title: New technique of diaphragmatic plication by means of uniportal video-assisted thoracoscopic surgery.

text: Diaphragmatic plication has been a well employed method for the treatment of diaphragmatic eventration and/or paralysis. Uniportal thoracoscopic procedures seem to offer substantial benefit in terms of postoperative pain and cosmesis with similar outcomes as other surgical techniques. A 60-year-old female patient was referred to our clinic for the surgical treatment of diaphragmatic eventration of an unknown cause. The patient was referred to our institution from another hospital, where she had undergone a femoro-popliteal and crural bypass which was unsuccessful, requiring amputation of her leg. Following surgery, she was unable to breath spontaneously without any specific reason. Cranial magnetic resonance imaging showed no pathology and the neurologists did not have a diagnosis for her comatose state. There was consensus in both hospitals that surgical plication of her elevated diaphragm might be the only option for respiratory improvement. We performed a double-lined diaphragmatic plication procedure by means of uniportal video-assisted thoracic surgery technique with CO2 insufflation using GelPort. Despite the time-consuming adhesiolysis and the need for lung suturing at the end of the procedure, the operative time was 120 min. Oxygenation remarkably improved after the operation, yet the patient remained in comatose state. She was referred back to the hospital where she had initially begun her therapy for further recovery.


title: Contemporary management of adult-acquired buried penis.

text: OBJECTIVES To describe our buried penis repair technique that includes penile release, tissue resection, wound closure, and penile reconstruction. PATIENTS AND METHODS In all, 73 patients were treated from 2007 to 2017. Patients can be categorised into five stages: Stage I, involves only a phimotic band; Stage 2, required excision of diseased penile skin with split-thickness skin grafting (STSG); Stage 3, requires scrotal excision; Stage 4, requires escutcheonectomy; and Stage 5, requires panniculectomy. Successful treatment hinges on adequate excision of diseased skin and de-bulking followed by replacement of deficient skin with STSG. RESULTS In all, 36 of 73 (49%) patients had Stage 1-3 disease, whilst 37 of 73 (51%) were Stage 4-5. There were complications within the first 30 days in 44 of 73 (60%) patients. In all, 62 of 73 (85%) patients either had no complications or Clavien-Dindo grade I-II complications and nine (12%) had complications beyond 30 days. Only five of 36 (14%) patients with Stage 1-3 disease had complications. One patient developed recurrent phimosis. CONCLUSION The buried penis is a challenging surgical entity where conservative treatment will most likely lead to failure. Surgery is the only means for a lasting cure in these patients and should be used as a first-line treatment. One should expect complications postoperatively, especially within the first 30 days; however, these are mostly limited to Clavien-Dindo grade I-II complications.


title: Atypical RNA Elements Modulate Translational Readthrough in Tobacco Necrosis Virus D.

text: Tobacco necrosis virus, strain D (TNV-D), is a positive-strand RNA virus in the genus Betanecrovirus and family Tombusviridae The production of its RNA-dependent RNA polymerase, p82, is achieved by translational readthrough. This process is stimulated by an RNA structure that is positioned immediately downstream of the recoding site, termed the readthrough stem-loop (RTSL), and a sequence in the 3' untranslated region of the TNV-D genome, called the distal readthrough element (DRTE). Notably, a base pairing interaction between the RTSL and the DRTE, spanning ∼3,000 nucleotides, is required for enhancement of readthrough. Here, some of the structural features of the RTSL, as well as RNA sequences and structures that flank either the RTSL or DRTE, were investigated for their involvement in translational readthrough and virus infectivity. The results revealed that (i) the RTSL-DRTE interaction cannot be functionally replaced by stabilizing the RTSL structure, (ii) a novel tertiary RNA structure positioned just 3' to the RTSL is required for optimal translational readthrough and virus infectivity, and (iii) these same activities also rely on an RNA stem-loop located immediately upstream of the DRTE. Functional counterparts for the RTSL-proximal structure may also be present in other tombusvirids. The identification of additional distinct RNA structures that modulate readthrough suggests that regulation of this process by genomic features may be more complex than previously appreciated. Possible roles for these novel RNA elements are discussed.IMPORTANCE The analysis of factors that affect recoding events in viruses is leading to an ever more complex picture of this important process. In this study, two new atypical RNA elements were shown to contribute to efficient translational readthrough of the TNV-D polymerase and to mediate robust viral genome accumulation in infections. One of the structures, located close to the recoding site, could have functional equivalents in related genera, while the other structure, positioned 3' proximally in the viral genome, is likely limited to betanecroviruses. Irrespective of their prevalence, the identification of these novel RNA elements adds to the current repertoire of viral genome-based modulators of translational readthrough and provides a notable example of the complexity of regulation of this process.


Risk 2005 conference.


title: Hybrid technique using a Satinsky clamp for right-sided transperitoneal hand-assisted laparoscopic donor nephrectomy: comparison with left-sided standard hand-assisted laparoscopic technique.

text: OBJECTIVE To introduce our hybrid technique using a Satinsky clamp for right-sided hand-assisted laparoscopic donor nephrectomy (HALDN) and to compare its effectiveness and safety with those of standard left-sided HALDN. METHODS We conducted a retrospective analysis of 253 patients, who underwent HALDN (51 right and 202 left) from January 2003 to December 2012. Perioperative outcomes including operative time, estimated blood loss, warm ischemic time, hospital stay, complications, and recovery of renal function in recipients were collected and compared between the right hybrid HALDN (rhHALDN) and left-sided HALDN groups. RESULTS The procedure was performed successfully in all 253 patients. No statistical difference in the mean operation time (224.3 vs 217.5 minutes), estimated blood loss (128.1 vs 123.6 mL), warm ischemic time (3.3 vs 3.1 minutes), average time to oral intake (2.4 vs 2.1 days), and mean hospital stay (4.9 vs 5.5 days) was observed between the rhHALDN and left-sided HALDN groups (P >.05). Perioperative complication rates were not statistically different between rhHALDN (2 intraoperative, 3 postoperative; 9.8%) and left-sided HALDN (6 intraoperative, 22 postoperative; 13.9%) group (P = .328). No significant difference in mean serum creatinine level and glomerular filtration rate in recipients from postoperative day 1 to 1 year was observed between the 2 groups. CONCLUSION The perioperative outcomes of rhHALDN using a Satinsky clamp were comparable with those of the left-sided standard HALDN. This hybrid technique can be a technically safe and feasible option for minimally invasive organ donation when right kidney donation is indicated.