title: The heptad repeat 2 domain is a major determinant for enhanced human immunodeficiency virus type 1 (HIV-1) fusion and pathogenicity of a highly pathogenic HIV-1 Env.

text: Human immunodeficiency virus type 1 (HIV-1)-mediated depletion of CD4+ lymphocytes in an infected individual is the hallmark of progression to AIDS. However, the mechanism for this depletion remains unclear. To identify mechanisms of HIV-1-mediated CD4 T-cell death, two similar viral isolates obtained from a rapid progressor patient with significantly different pathogenic phenotypes were studied. One isolate (R3A) demonstrates enhanced pathogenesis in both in vivo models and relevant ex vivo lymphoid organ model systems compared to another isolate, R3B. The pathogenic determinants were previously mapped to the V5-gp41 envelope region, correlating functionally with enhanced fusion activity and elevated CXCR4 binding affinity. To further elucidate specific differences between R3A and R3B within the V5-gp41 domains that enhance CD4 depletion, R3A-R3B chimeras to study the V5-gp41 region were developed. Our data demonstrate that six residues in the ectodomain of R3A provide the major determinant for both enhanced Env-cell fusion and pathogenicity. Furthermore, three amino acid differences in the heptad repeat 2 (HR-2) domain of R3A determined its fusion activity and significantly elevated its pathogenic activity. The chimeric viruses with enhanced fusion activity, but not elevated CXCR4 affinity, correlated with high pathogenicity in the thymus organ. We conclude that the functional domain of a highly pathogenic HIV-1 Env is determined by mutations in the HR-2 region that contribute to enhanced fusion and CD4 T-cell depletion.


title: Pancreas Transplantation: Past, Present, Future.

text: Diabetes is the pandemic disease of the modern era, with 10% of these patients having type 1 diabetes mellitus. Despite the prevalence, morbidities, and associated financial burden, treatment options have not changed since the introduction of injectable insulin. To date, over 40,000 pancreas transplants have been performed globally. It remains the only known method for restoring glycemic control and thus curing type 1 diabetes mellitus. The aim of this review is to bring pancreatic transplantation out of the specialist realm, informing practitioners about this important procedure, so that they feel better equipped to refer suitable patients for transplantation and manage, counsel, and support when encountering them within their own specialty. This study was a narrative review conducted in October 2015, with OVID interface searching EMBASE and MEDLINE databases, using Timeframe: Inception to October 2015. Articles were assessed for clinical relevance and most up-to-date content, with articles written in English as the only inclusion criterion. Other sources used included conference proceedings/presentations and unpublished data from our institution (Oxford Transplant Centre). Pancreatic transplantation is growing and has quickly become the gold standard of care for patients with type 1 diabetes mellitus and renal failure. Significant improvements in quality of life and life expectancy make pancreatic transplant a viable and economically feasible intervention. It remains the most effective method of establishing and maintaining euglycemia, halting and potentially reversing complications associated with diabetes.


title: Clinical and oncological outcomes of single-incision vs. conventional laparoscopic surgery for rectal cancer.

text: BACKGROUND To evaluate the clinical and oncological outcomes of single-incision laparoscopic surgery (SILS) vs. conventional laparoscopic surgery (CLS) for patients with rectal cancer (RC) who underwent total mesorectal excision (TME) surgery. METHODS This was a retrospective case-control study of patients with RC operated between 12/2013 and 12/2017 in Ruijin Hospital North, Shanghai Jiaotong University School of Medicine. In total, 177 patients who underwent CLS and 51 who underwent SILS met the inclusion and exclusion criteria and were matched 1:1 using propensity score matching method (PSM). RESULTS Compared with the CLS group, the SILS group showed shorter operation time [105 (40) vs. 125 (55) min, P = 0.045], shorter total incision length [4 (1) vs. 6.5 (1.5) cm, P < 0.001], lower VAS score on POD2 [1 (1) vs. 2 (1), P < 0.001], shorter time to soft diet [7 (1) vs. 8 (2) days, P = 0.048], and shorter length of hospital stay [9 (2) vs. 11 (3) days, P < 0.001]. The postoperative complications were similar between two groups [1(2%) vs. 5 (9.8%), P = 0.205]. No readmissions or mortality in either group occurred within 30 days of surgery. All 102 specimens met the requirements of TME. No significant differences were observed in the pathologic outcomes between the two groups. The median follow-up period was 32.6 months in the SILS group and 36.8 months in the CLS group (P = 0.053). The 3-year disease-free survival rates and overall survival rates of the SILS and CLS groups were 89.8% vs. 96.0% (P = 0.224) and 90.9% vs. 96.9% (P = 0.146), respectively. CONCLUSIONS Compared with CLS, TME surgery for rectal cancer can be performed safely and effectively using the SILS technique with better cosmetic results, less postoperative pain, faster postoperative recovery, and acceptable clinical and oncological outcomes.


The aftermath.


title: In vitro evaluation of heat and moisture exchangers designed for spontaneously breathing tracheostomized patients.

text: BACKGROUND Heat and moisture exchangers (HMEs) are commonly used in chronically tracheostomized spontaneously breathing patients, to condition inhaled air, maintain lower airway function, and minimize the viscosity of secretions. Supplemental oxygen (O2) can be added to most HMEs designed for spontaneously breathing tracheostomized patients. We tested the efficiency of 7 HMEs designed for spontaneously breathing tracheostomized patients, in a normothermic model, at different minute ventilations (VE) and supplemental O2 flows. METHODS HME efficiency was evaluated using an in vitro lung model at 2 VE (5 and 15 L/min) and 4 supplemental O2 flows (0, 3, 6, and 12 L/min). Wet and dry temperatures of the inspiratory flow were measured, and absolute humidity was calculated. In addition, HME efficiency at 0, 12, and 24 h use was evaluated, as well as resistance to flow at 0 and 24 h. RESULTS The progressive increase in O2 flow from 0 to 12 L/min was associated with a reduction in temperature and absolute humidity. Under the same conditions, this effect was greater at lower VE. The HME with the best performance provided an absolute humidity of 26 mg H2O/L and a temperature of 27.8 °C. No significant changes in efficiency or resistance were detected during the 24 h evaluation. CONCLUSIONS The efficiency of HMEs in terms of temperature and absolute humidity is significantly affected by O2 supplementation and V(E).


title: Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study.

text: The recent outbreak of novel coronavirus disease -19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D-structures of key virous proteins are resolved. Taking the advantage of a recently released crystal structure of COVID-19 protease in complex with a covalently-bonded inhibitor, N3,1 I conducted virtual docking screening of approved drugs and drug candidates in clinical trials. For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an endpoint method called MM-PBSA-WSAS.2-4 Several promising known drugs stand out as potential inhibitors of COVID-19 protease, including Carfilzomib, Eravacycline, Valrubicin, Lopinavir and Elbasvir. Carfilzomib, an approved anti-cancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, -13.82 kcal/mol. Streptomycin, an antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (-3.82 kcal/mol) is not nearly as low as that of the neutral form (-7.92 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of -12.86 kcal/mol. Detailed receptor-ligand interactions were analyzed and hot spots for the receptor-ligand binding were identified. I found that one hotspot residue HIS41, is a conserved residue across many viruses including COVID-19, SARS, MERS, and HCV. The findings of this study can facilitate rational drug design targeting the COVID-19 protease.


title: Effect of surgical masks worn concurrently over N95 filtering facepiece respirators: extended service life versus increased user burden.

text: Growing concern over the availability of Respiratory protective devices (eg, filtering facepiece Respirators), in the face of the probable extreme demand brought on by a pandemic influenza, has prompted the suggestion that useful life of N95 filtering facepiece Respirator can be extended by the concurrent use of a surgical mask as an outer protective barrier over the Respirator. Personal protective equipment generally places a strain on the user, and the detrimental physiological and psychological burdens normally imposed by Respirator use could be magnified by the addition of an extra layer of protection such as a surgical mask. The issue of this potentially increased burden of the concurrent use of a surgical facemask with an N95 filtering facepiece Respirator is investigated to afford users the necessary information to make informed decisions Regarding the use of this Respiratory personal protective equipment in the face of large-scale outbreaks of Respiratory pathogens.


title: The Effect of Initial High vs. Low FiO2 on Breathing Effort in Preterm Infants at Birth: A Randomized Controlled Trial.

text: Background: Infants are currently stabilized at birth with initial low FiO2 which increases the risk of hypoxia and suppression of breathing in the first minutes after birth. We hypothesized that initiating stabilization at birth with a high O2 concentration, followed by titration, would improve breathing effort when compared to a low O2 concentration, followed by titration. Methods: In a bi-center randomized controlled trial, infants <30 weeks gestation were stabilized at birth with an initial O2 concentration of 30 or 100%, followed by oxygen titration. Primary outcome was minute volume of spontaneous breathing. We also assessed tidal volumes, mean inspiratory flow rate (MIFR) and respiratory rate with a respiratory function monitor in the first 5 min after birth, and evaluated the duration of mask ventilation in the first 10 min after birth. Pulse oximetry was used to measure heart rate and SpO2 values in the first 10 min. Hypoxemia was defined as SpO2 < 25th percentile and hyperoxemia as SpO2 >95%. 8-iso-prostaglandin F2α (8iPGF2α) was measured to assess oxidative stress in cord blood and 1 and 24 h after birth. Results: Fifty-two infants were randomized and recordings were obtained in 44 infants (100% O2-group: n = 20, 30% O2-group: n = 24). Minute volumes were significantly higher in the 100% O2-group (146.34 ± 112.68 mL/kg/min) compared to the 30% O2-group (74.43 ± 52.19 mL/kg/min), p = 0.014. Tidal volumes and MIFR were significantly higher in the 100% O2-group, while the duration of mask ventilation given was significantly shorter. Oxygenation in the first 5 min after birth was significantly higher in infants in the 100% O2-group [85 (64-93)%] compared to the 30% O2-group [58 (46-67)%], p < 0.001. The duration of hypoxemia was significantly shorter in the 100% O2-group, while the duration of hyperoxemia was not different between groups. There was no difference in oxidative stress marker 8iPGF2α between the groups. Conclusion: Initiating stabilization of preterm infants at birth with 100% O2 led to higher breathing effort, improved oxygenation, and a shorter duration of mask ventilation as compared to 30% O2, without increasing the risk for hyperoxia or oxidative stress. Clinical Trial Registration: This study was registered in www.trialregister.nl, with registration number NTR6878.


Letter: the irony of oral iron - not an underdog for post-gastrointestinal bleeding anaemia.


title: Managing Barrett's esophagus with radiofrequency ablation.

text: Barrett's esophagus (BE) is a well-established pre-malignant lesion for esophageal adenocarcinoma, a condition that carries a dismal five-year overall survival rate of less than 15%. Among several available methods to eliminate BE, radiofrequency ablation (RFA) provides the most efficient modality, since it has been demonstrated to successfully eradicate BE with or without dysplasia with acceptable safety, efficacy and durability profiles. In conjunction with proton pump therapy, this new technology has quickly become the standard care for patients with dysplastic BE. However, several technical questions remain about how to deploy RFA therapy for maximum effectiveness and long-term favorable outcomes for all stages of the disease. These include how to select patient for therapy, what the best protocol for RFA is, when to use other modalities, such as endoscopic mucosal resection, and what should be considered for refractory BE. This review addresses these questions with the perspective of the best available evidence matched with the authors' experience with the technology.


title: Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a "gray zone" approach.

text: BACKGROUND Respiratory arterial pulse pressure variations (PPV) are the best predictors of fluid responsiveness in mechanically ventilated patients during general anesthesia. However, previous studies were performed in a small number of patients and determined a single cutoff point to make clinical discrimination. The authors sought to test the predictive value of PPV in a large, multicenter study and to express it using a gray zone approach. METHODS The authors studied 413 patients during general anesthesia and mechanical ventilation in four centers. PPV, central venous pressure, and cardiac output were recorded before and after volume expansion (VE). Response to VE was defined as more than 15% increase in cardiac output after VE. The following approaches were used to determine the gray zones: resampled and two-graph receiver operator characteristic curves. The impact of changes in the benefit-risk balance of VE on the gray zone was also evaluated. RESULTS The authors observed 209 responders (51%) and 204 nonresponders (49%) to VE. The area under receiver operating characteristic curve was 0.89 (95% CI: 0.86-0.92) for PPV, compared with 0.57 (95% CI: 0.54-0.59) for central venous pressure (P < 10). The gray zone approach identified a range of PPV values (between 9% and 13%) for which fluid responsiveness could not be predicted reliably. These PPV values were seen in 98 (24%) patients. Changes in the cost ratio of VE moderately affected the gray zone limits. CONCLUSION Despite a strong predictive value, PPV may be inconclusive (between 9% and 13%) in approximately 25% of patients during general anesthesia.


title: Hysterectomy and salphingoopherectomy by Transvaginal Natural Orifice Transluminal Endoscopic Surgery(NOTES): Turkish surgeons' initial experience.

text: BACKGROUND The aim of this study was to evaluate the feasibility, safety, and early postoperative outcomes of hysterectomies and salpingo-oophorectomies using transvaginal natural orifice transluminal endoscopic surgery (vNOTES). MATERIALS AND METHODS The women undergoing vNOTES hysterectomies and salpingo-oophorectomies at a tertiary referral medical center between April 2016 and April 2017 were retrospectively analyzed. In all of the vNOTES procedures, a handmade glove port system comprised of a glove-wound retractor NOTES port was used. RESULTS Thirteen patients underwent gynecological procedures with benign indications via vNOTES. Of the 13 operations, 6 of the patients had salpingo-oophorectomies and 7 had hysterectomies, and all of the surgeries were performed by the same surgeon (Dr. Ahmet Kale). No conversion to a conventional laparoscopy or even a laparotomy was needed in any of the procedures. The mean operation time was 73.14 min in the hysterectomy patients and 40.8 min in the salpingo-oophorectomy patients. The mean drop in the hemoglobin (Hb) level was 1.4 g/dl in the hysterectomy patients and 1.6 g/dl in the salpingo-oophorectomy patients. For these patients undergoing vNOTES, the mean postoperative visual analog scale (VAS) pain score at 6 h was 4.38 and at 24 h it was 0.62. There were no intraoperative complications in any of the cases. The mean length of the hospital stay was 1.8 days in the hysterectomy patients and 1.5 days in the salpingo-oophorectomy patients. CONCLUSION The vNOTES procedure overcomes the surgical and technical difficulties of conventional vaginal surgery by incorporating the advantages of endoscopic surgery. Moreover, vNOTES uses inexpensive, reusable, handmade conventional laparoscopic instruments and avoids those problems related to abdominal wall incisions and trocar-related complications. Overall, this procedure results in high patient satisfaction, cosmetic advantages, and decreased postoperative pain.


title: Sequential exposure to bovine viral diarrhea virus and bovine coronavirus results in increased respiratory disease lesions: clinical, immunologic, pathologic, and immunohistochemical findings.

text: Bovine coronaviruses (BoCVs) have been found in respiratory tissues in cattle and frequently associated with bovine respiratory disease (BRD); however, pathogenesis studies in calves are limited. To characterize the pathogenesis and pathogenicity of BoCV isolates, we used 5 different BoCV strains to inoculate colostrum-deprived calves, ~ 2-5 wk of age. Later, to determine if dual viral infection would potentiate pathogenicity of BoCV, calves were inoculated with BoCV alone, bovine viral diarrhea virus (BVDV) alone, or a series of dual-infection (BVDV-BoCV) schemes. A negative control group was included in all studies. Clinical signs and body temperature were monitored during the study and samples collected for lymphocyte counts, virus isolation, and serology. During autopsy, gross lesions were recorded and fixed tissues collected for histopathology and immunohistochemistry; fresh tissues were collected for virus isolation. Results suggest increased pathogenicity for isolate BoCV OK 1776. Increased body temperature was found in all virus-inoculated groups. Lung lesions were present in calves in all dual-infection groups; however, lesions were most pronounced in calves inoculated with BVDV followed by BoCV inoculation 6 d later. Lung lesions were consistent with mild-to-moderate interstitial pneumonia, and immunohistochemistry confirmed the presence of BoCV antigen. Our studies demonstrated that BVDV-BoCV dual infection may play an important role in BRD pathogenesis, and timing between infections seems critical to the severity of lesions.


Redesigning Italy's regional Neurosciences networks in the COVID-19 era: a model for a future healthcare system or skating on thin ice?


title: The use of pyrosequencing for detection of hemagglutinin mutations associated with increased pathogenicity of H5N1 avian influenza viruses in mammals.

text: Hemagglutinin (HA) cleavage is critical for virulence of influenza viruses. The amino acid residue at the P6 position of the HA cleavage site (HACS) has been shown to be most variable and to have a direct correlation with the cleavage efficiency and pathogenicity of H5N1 avian influenza viruses (AIVs) in mammals. Among these amino acid variants, serine has been associated with the highest virulence in mammals, and its detection may serve as an indicator for H5N1 AIVs with high pathogenicity and potential public risk. We developed a rapid detection method based on reverse-transcription (RT)-PCR and pyrosequencing to detect a mutation at the HACS that is associated with increased pathogenicity of H5N1 AIVs in mammals. Herein, we provide a specific, sensitive, and reliable method for rapid detection of one of the virulence determinants associated with increased pathogenicity of H5N1 AIVs in mammals.


Patterns of IgG and IgM antibody response in COVID-19 patients.


Covid-19: doctors' visas are automatically extended for one year.


title: Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design.

text: Two members of the paramyxovirus family, Nipah virus (NiV) and Hendra virus (HeV), are recent additions to a growing number of agents of emergent diseases which use bats as a natural host. Identification of ephrin-B2 and ephrin-B3 as cellular receptors for these viruses has enabled the development of immunotherapeutic reagents which prevent virus attachment and subsequent fusion. Here we present the structural analysis of the protein and carbohydrate components of the unbound viral attachment glycoprotein of NiV glycoprotein (NiV-G) at a 2.2-A resolution. Comparison with its ephrin-B2-bound form reveals that conformational changes within the envelope glycoprotein are required to achieve viral attachment. Structural differences are particularly pronounced in the 579-590 loop, a major component of the ephrin binding surface. In addition, the 236-245 loop is rather disordered in the unbound structure. We extend our structural characterization of NiV-G with mass spectrometric analysis of the carbohydrate moieties. We demonstrate that NiV-G is largely devoid of the oligomannose-type glycans that in viruses such as human immunodeficiency virus type 1 and Ebola virus influence viral tropism and the host immune response. Nevertheless, we find putative ligands for the endothelial cell lectin, LSECtin. Finally, by mapping structural conservation and glycosylation site positions from other members of the paramyxovirus family, we suggest the molecular surface involved in oligomerization. These results suggest possible pathways of virus-host interaction and strategies for the optimization of recombinant vaccines.


title: Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guidelines.

text: 1: ESGE suggests using contrast-enhanced computed tomography (CT) as the first-line imaging modality on admission when indicated and up to the 4th week from onset in the absence of contraindications. Magnetic resonance imaging (MRI) may be used instead of CT in patients with contraindications to contrast-enhanced CT, and after the 4th week from onset when invasive intervention is considered because the contents (liquid vs. solid) of pancreatic collections are better characterized by MRI and evaluation of pancreatic duct integrity is possible. Weak recommendation, low quality evidence. 2: ESGE recommends against routine percutaneous fine needle aspiration (FNA) of (peri)pancreatic collections. Strong recommendation, moderate quality evidence. FNA should be performed only if there is suspicion of infection and clinical/imaging signs are unclear. Weak recommendation, low quality evidence. 3: ESGE recommends initial goal-directed intravenous fluid therapy with Ringer's lactate (e. g. 5 - 10 mL/kg/h) at onset. Fluid requirements should be patient-tailored and reassessed at frequent intervals. Strong recommendation, moderate quality evidence. 4: ESGE recommends against antibiotic or probiotic prophylaxis of infectious complications in acute necrotizing pancreatitis. Strong recommendation, high quality evidence. 5: ESGE recommends invasive intervention for patients with acute necrotizing pancreatitis and clinically suspected or proven infected necrosis. Strong recommendation, low quality evidence.ESGE suggests that the first intervention for infected necrosis should be delayed for 4 weeks if tolerated by the patient. Weak recommendation, low quality evidence. 6: ESGE recommends performing endoscopic or percutaneous drainage of (suspected) infected walled-off necrosis as the first interventional method, taking into account the location of the walled-off necrosis and local expertise. Strong recommendation, moderate quality evidence. 7: ESGE suggests that, in the absence of improvement following endoscopic transmural drainage of walled-off necrosis, endoscopic necrosectomy or minimally invasive surgery (if percutaneous drainage has already been performed) is to be preferred over open surgery as the next therapeutic step, taking into account the location of the walled-off necrosis and local expertise. Weak recommendation, low quality evidence. 8: ESGE recommends long-term indwelling of transluminal plastic stents in patients with disconnected pancreatic duct syndrome. Strong recommendation, low quality evidence. Lumen-apposing metal stents should be retrieved within 4 weeks to avoid stent-related adverse effects.Strong recommendation, low quality evidence.


Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement.


title: The pig as an experimental model for mid-dermal burns research.

text: This was a novel, prospective and interventional animal study designed to develop and evaluate a new infliction device for the experimental burn model. Four paired sets of contact burns measuring 36mm diameter were inflicted on the dorsum of an anesthetized pig using a stainless steel round bar heated up to 80-110°C. The bar was applied using a push-pull force gauge designed to control 1kgf mechanical force applied to the skin for a period of 20s. The left dorsum was used for macroscopic observation and the right dorsum was used for histopathological evaluation. A total of eight burns were covered with moist saline dressings and given daily treatments of xylocaine (lidocaine HCl) gel. This procedure was followed for a period of 24 days. Full-thickness biopsies were obtained for histologic analysis to determine the extent of injury. Statistical analysis showed a high correlation between the exposure temperature and histopathological assessment. The results found the depth of injury to the collagen (Seg1) correlated with the temperature (Ti) at which the burns was inflicted, Seg1=0.038Ti-2.57 (r=0.973, P<0.05). Also, the histological studies show a high correlation between the depth of collagen denaturation in wounds and the exposure temperature, Seg1=0.0268Ti-0.165 (r=0.991, P<0.05). This model is useful to assess more closely the therapeutic agents used for wound healing in experimental burn wounds.


title: Outcome of patients with large vessel occlusion in the anterior circulation and low NIHSS score.

text: BACKGROUND Optimal management of patients with large vessel occlusion (LVO) and low NIHSS score is unknown, which was the aim to investigate in this study. METHODS This is a retrospective analysis of a prospective single tertiary care centre 14-year cohort of patients with LVO in the anterior circulation and NIHSS score ≤ 5 on admission. Outcome was analysed according to primary intended therapy. RESULTS Among 185 patients (median age 67.4 years), 52.4% received primary conservative therapy (including 26.8% secondary reperfusion in case of secondary neurological deterioration), 12.4% IV thrombolysis (IVT) only and 35.1% primary endovascular therapy (EVT). 95 (51.4%) patients experienced neurological deterioration until 3 months. Primary-IVT-only and primary-EVT compared to conservative-therapy patients had better 3 months' outcome (54.5% vs. 30.8%: adjustedOR 6.02; adjustedp = 0.004 for mRS 0-1 and 54.7% vs. 30.8%: adjustedOR 5.09; adjustedp = 0.002, respectively). Also mRS shift analysis favored primary-IVT-only and primary-EVT patients (adjustedOR 6.25; adjustedp = 0.001 and adjustedOR 3.14; adjustedp = 0.003). Outcome in primary-IVT-only vs. primary-EVT patients did not differ significantly. Patients who received secondary EVT because of neurological deterioration after primary-conservative-therapy had worse 3 months' outcome than primary-EVT patients (20.8% vs. 30.8%: adjustedOR 0.24; adjustedp = 0.047 for mRS 0-1 and adjustedOR 0.31; adjustedp = 0.019 in mRS shift analysis). Survival and symptomatic intracranial haemorrhage did not differ amongst groups. CONCLUSIONS Our data indicate that primary IVT and/or EVT may be better than primary conservative therapy in patients with LVO in the anterior circulation and low NIHSS score. Furthermore, primary EVT was better than secondary EVT in case of neurological deterioration. There is an unmet need for RCTs to find the optimal therapy for this patient group.


title: Identification of B-cell epitopes in the NSP1 protein of porcine reproductive and respiratory syndrome virus.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) was divided into North American and European genotypes. NSP1 was an important non-structural protein of PRRSV, which was auto-cleaved from the replicase polyprotein into NSP1α and NSP1β subunits and played an important role in the immune suppression. In this study, six monoclonal antibodies (MAbs) against the recombinant PRRSV NSP1, expressed in Escherichia coli system, were screened out and identified. Western blot and IFA results indicated that 4 out of 6 MAbs recognized the recombinant NSP1α and 2 MAbs recognized NSP1β. Epitope mapping results indicated that MAb 4H2 recognized the linear epitopes E(54)EPLRW(59) in NSP1α, MAbs (2G5, 3E11 and 4D4) recognized the epitopes H(157)VLTNLP(163) in NSP1α, and MAbs 3C7 and 1H7 reacted with the epitopes 185aa to 232aa in NSP1β. Protein sequence alignment of NSP1 indicated E(54)EPLRW(59) was conserved in all North American PRRSV strains, whereas European type strains has variable amino acids in this region. The epitope H(157)VLTNLP(163) was relatively conserved among all PRRSV strains, except for a L162→S162 change in European type strains. The epitope 185-232aa was variable among North American PRRSV strains. These results may facilitate future investigations into the function of NSP1 of PRRSV and diagnostic methods for PRRSV infection.


The R0 journey: from 1950s malaria to COVID-19.


title: Institutional trust as a determinant of anxiety during the SARS crisis in Hong Kong.

text: The SARS crisis of 2003 in Hong Kong generated widespread public fear and escalated the efforts of government and medical institutions for infection control. As such, the role of the government and medical institution in preventing public fear and anxiety became prominent. As hypothesized, trust in the institutions is especially relevant to public fear and anxiety during the epidemic crisis. For testing hypotheses involving the role of institutional trust, a telephone survey during the crisis in April 2003 and another telephone survey after the crisis in June 2003 drew data from 9,402 Hong Kong adults for analysis. Results indicate the significant negative effects of trust in the government and trust in the medical institution on anxiety. Supporting the aforementioned hypothesis the effect of institutional trust in the government was significantly more negative on anxiety during the crisis than its aftermath. Hence, the government and medical institution are particularly responsible for anxiety reduction during the crisis.


title: Conservation Physiology and Conservation Pathogens: White-Nose Syndrome and Integrative Biology for Host-Pathogen Systems.

text: Conservation physiology aims to apply an understanding of physiological mechanisms to management of imperiled species, populations, or ecosystems. One challenge for physiologists hoping to apply their expertise to conservation is connecting the mechanisms we study, often in the laboratory, with the vital rates of populations in the wild. There is growing appreciation that infectious pathogens can threaten populations and species, and represent an important issue for conservation. Conservation physiology has much to offer in terms of addressing the threat posed to some host species by infectious pathogens. At the same time, the well-developed theoretical framework of disease ecology could provide a model to help advance the application of physiology to a range of other conservation issues. Here, I use white-nose syndrome (WNS) in hibernating North American bats as an example of a conservation problem for which integrative physiological research has been a critical part of research and management. The response to WNS highlights the importance of a well-developed theoretical framework for the application of conservation physiology to a particular threat. I review what is known about physiological mechanisms associated with mortality from WNS and emphasize the value of combining a strong theoretical background with integrative physiological studies in order to connect physiological mechanisms with population processes and thereby maximize the potential benefits of conservation physiology.


title: MDA5 Is Critical to Host Defense during Infection with Murine Coronavirus.

text: UNLABELLED Infection with the murine coronavirus mouse hepatitis virus (MHV) activates the pattern recognition receptors melanoma differentiation-associated gene 5 (MDA5) and Toll-like receptor 7 (TLR7) to induce transcription of type I interferon. Type I interferon is crucial for control of viral replication and spread in the natural host, but the specific contributions of MDA5 signaling to this pathway as well as to pathogenesis and subsequent immune responses are largely unknown. In this study, we use MHV infection of the liver as a model to demonstrate that MDA5 signaling is critically important for controlling MHV-induced pathology and regulation of the immune response. Mice deficient in MDA5 expression (MDA5(-/-) mice) experienced more severe disease following MHV infection, with reduced survival, increased spread of virus to additional sites of infection, and more extensive liver damage than did wild-type mice. Although type I interferon transcription decreased in MDA5(-/-) mice, the interferon-stimulated gene response remained intact. Cytokine production by innate and adaptive immune cells was largely intact in MDA5(-/-) mice, but perforin induction by natural killer cells and levels of interferon gamma, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in serum were elevated. These data suggest that MDA5 signaling reduces the severity of MHV-induced disease, at least in part by reducing the intensity of the proinflammatory cytokine response. IMPORTANCE Multicellular organisms employ a wide range of sensors to detect viruses and other pathogens. One such sensor, MDA5, detects viral RNA and triggers induction of type I interferons, chemical messengers that induce inflammation and help regulate the immune responses. In this study, we sought to determine the role of MDA5 during infection with mouse hepatitis virus, a murine coronavirus used to model viral hepatitis as well as other human diseases. We found that mice lacking the MDA5 sensor were more susceptible to infection than were mice with MDA5 and experienced decreased survival. Viral replication in the liver was similar in mice with and without MDA5, but liver damage was increased in MDA5(-/-) mice, suggesting that the immune response is causing the damage. Production of several proinflammatory cytokines was elevated in MDA5(-/-) mice, suggesting that MDA5 may be responsible for keeping pathological inflammatory responses in check.


title: An Analysis of Reliability and Accuracy of Muscle Thickness Ultrasonography in Critically Ill Children and Adults.

text: BACKGROUND Muscle wasting starts already within the first week in critically patients and is strongly related to poor outcome. Nevertheless, the early detection of muscle wasting is difficult. Therefore, we investigated the reliability and accuracy of ultrasonography to evaluate skeletal muscle wasting in critically ill children and adults. METHODS This prospective observational study enrolled 30 sedated critically ill children and 14 critically ill adults. Two independent investigators made 210 ultrasonographical assessments of muscle thigh thickness. Inter- and intraobserver reliability and cutoff levels were calculated as a function of muscle thickness and the expected reduction in muscle size (predefined at 20% and 30%). RESULTS Mean ± SD muscle thickness was 1.67 ± 0.55 cm in the pediatric and 2.10 ± 0.85 cm in the adult population. The median absolute interobserver variability was 0.07 cm (interquartile range [IQR], 0.04-0.20 cm) in the pediatric population and 0.05 cm (IQR, 0.03-0.09 cm) in the adult population. However, the absolute intraobserver accuracy had a 95% confidence interval of 0.43 cm in children and 0.22 cm in adults. Only a 30% decrease (0.50 cm) in muscle thickness can be detected in critically ill children. CONCLUSION Although the interobserver variability is acceptable in the pediatric population, the intraobserver variability is too large with respect to the expected reduction in muscle thickness. In adults, ultrasonography may be a reliable tool for early detection of muscle mass wasting.


title: Thoracic duct embolization for nontraumatic chylous effusion: experience in 34 patients.

text: BACKGROUND Thoracic duct embolization (TDE) is an acceptable alternative procedure for treating traumatic chylothorax. The purpose of this study is to demonstrate efficacy of TDE in treating nontraumatic chylous effusions. METHODS A retrospective review of 34 patients was conducted assessing technical and clinical success of TDE for nontraumatic chylous effusions. RESULTS Thirty-four patients (mean age, 59 years; 27 female patients) with nontraumatic chylous effusions underwent TDE. Presentations included 21 unilateral chylothoraces (61.8%), nine bilateral chylothoraces (26.5%), two isolated chylopericardiums (5.9%), and two pleural effusions with chylopericardium (5.9%). TDE was technically successful in 24 of 34 patients (70.6%). The thoracic duct could not be catheterized in four of 34 (11.8%). Cisterna chyli was not visualized in six of 34 patients (17.6%), and, thus, TDE was not attempted. Follow-up was available for 32 patients. Four lymphangiographic patterns were observed: (1) normal thoracic duct in 17.6% of patients (six of 34), (2) occlusion of thoracic duct in 58.8% (20 of 34), (3) failure to opacify thoracic duct in 17.6% (six of 34), and (4) extravasation of chyle in 5.9% (two of 34). Clinical success varied with the lymphangiographic pattern. The clinical success rate was 16% (one of six) in cases of normal thoracic duct, 75% (15 of 20 patients) in occlusions of the thoracic duct, 16% (one of six) in cases of failure to opacify the thoracic duct, and 50% in two cases of chyle extravasation. Lymphangiography alone cured two patients (6.5%). CONCLUSION TDE was most successful in cases of thoracic duct occlusion and extravasation. Lymphangiography is important for identifying the cause of chylous effusions and selecting patients who benefit most from TDE.


title: Recurrence of "cured" dural arteriovenous fistulas after Onyx embolization.

text: Endovascular embolization with Onyx has been increasingly used to treat intracranial and spinal dural arteriovenous fistulas (DAVFs). Several case series have been published in recent years reporting high DAVF cure rates with this technique. Although it is seldom reported, DAVF recurrence may occur despite initial "cure." The authors present 3 separate cases of a recurrent DAVF after successful transarterial Onyx embolization. Despite adequate Onyx penetration into the fistula and draining vein, these cases demonstrate that DAVF recanalization may reappear with filling from previous or newly recruited arterial feeders. Other published reports of DAVF recurrence are examined, and potential contributory factors are discussed. These cases highlight the need for awareness of this possible phenomenon and suggest that follow-up angiography should be considered in patients treated with catheter embolization.


title: Dental care during the coronavirus disease 2019 (COVID-19) outbreak: operatory considerations and clinical aspects.

text: OBJECTIVES This paper is aimed at addressing the urgent need to develop a protocol that will address the operatory and clinical aspects of dental care during the Coronavirus disease 2019 (COVID-19) outbreak. DATA SOURCES The epidemiology, clinical signs and symptoms, and modes of transmission of COVID-19 are presented. This protocol was established as an international collaboration of three dental universities: Hadassah School of Dental Medicine, Israel; University of Rochester Medical Center, USA; and the University of Pennsylvania, USA. This protocol is based on a detailed review of the existing English language literature as well on the logistic and clinical experience of each facility and the opinion of the authors. The protocol is designed for a hospital setting and includes considerations related to dental treatment in both healthy subjects and those suspected or diagnosed with COVID-19. The first part of this review discusses operatory considerations; the second part discusses general dental clinical aspects; the third part discusses endodontic considerations; and the fourth part discusses surgical aspects. This protocol may be applicable to other future similar pandemics. CONCLUSION Logistic and clinical steps are required to provide dental care during the COVID-19 outbreak while preventing cross-contamination and protecting the dental team during the provision of care.


title: Antiviral effect of sinefungin on in vitro growth of feline herpesvirus type 1.

text: Feline herpesvirus type 1 (FHV-1) causes a potentially fatal disease in cats. Through the use of virus inhibition and cytotoxicity assays, sinefungin, a nucleoside antibiotic, was assessed for its potential to inhibit the growth of FHV-1. Sinefungin inhibited in vitro growth of FHV-1 most significantly over other animal viruses, such as feline infectious peritonitis virus, equine herpesvirus, pseudorabies virus and feline calicivirus. Our results revealed that sinefungin specifically suppressed the replication of FHV-1 after its adsorption to the host feline kidney cells in a dose-dependent manner without obvious cytotoxicity to the host cells. This antibiotic can potentially offer a highly effective treatment for animals infected with FHV-1, providing alternative medication to currently available antiviral therapies.


title: Two-year outcomes after percutaneous coronary intervention of calcified lesions with drug-eluting stents.

text: BACKGROUND Percutaneous coronary intervention (PCI) of lesions with coronary arterial calcification (CAC) is common and has been historically associated with an increased risk of adverse events. Whether the association between target lesion calcification (CAC) and outcomes differ across drug-eluting stent generation or between patients with high vs. low residual platelet reactivity (PR) remains unknown. We assessed the association of CAC with adverse ischemic and bleeding events among patients undergoing contemporary PCI with drug-eluting stents (DES). METHODS We included all 8582 patients who underwent successful PCI with DES in the prospective ADAPT-DES study. Patients were grouped according to whether or not they had CAC. We used a multivariable logistic regression analysis to determine independent predictors of CAC. We assessed the 2-year risk of major adverse cardiac events (MACE: Death, myocardial infarction, or stent thrombosis) and bleeding by constructing Kaplan-Meier curves and fitting unadjusted and adjusted Cox proportional hazards models. We assessed the influence of DES generation and PR on the effect of CAC on outcomes by including interaction terms in the models. RESULTS CAC was present in 2644 (30.8%) patients. Age, smoking, hypertension, hyperlipidemia, insulin-treated diabetes, hemodialysis, and peripheral artery disease were independent predictors of CAC. Having a CAC was associated with increased unadjusted and adjusted hazards for 2-year MACE and bleeding. The association between CAC and ischemic outcomes was consistent across DES generations and PR (pinteraction>0.05). CONCLUSION Contemporary DES PCI of calcified lesions is common and is associated with an increased risk of ischemic and bleeding complications.


title: Differential Changes in Gut Microbiota After Gastric Bypass and Sleeve Gastrectomy Bariatric Surgery Vary According to Diabetes Remission.

text: BACKGROUND It is unclear whether specific gut microbiota is associated with remission of type 2 diabetes (T2D) after distinct types of bariatric surgery. AIMS The aim of this study is to examine gut microbiota changes after laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery in obese patients with T2D. METHODS Whole-metagenome shotgun sequencing of DNA fragments using Illumina HiSeq2000 was obtained from stool samples collected from 14 obese T2D patients pre-operatively (while on very low calorie diet) and 1 year after randomisation to laparoscopic SG (n = 7) or RYGB (n = 7). Resulting shotgun reads were annotated with Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS Body weight reduction and dietary change was similar 1 year after both surgery types. Identical proportions (n = 5/7) achieved diabetes remission (HbA1c < 48 mmol/mol without medications) 1 year after RYGB and SG. RYGB resulted in increased Firmicutes and Actinobacteria phyla but decreased Bacteroidetes phyla. SG resulted in increased Bacteroidetes phyla. Only an increase in Roseburia species was observed among those achieving diabetes remission, common to both surgery types. KEGG Orthology and pathway analysis predicted contrasting and greater gut microbiota metabolism changes after diabetes remission following RYGB than after SG. Those with persistent diabetes post-operatively had higher Desulfovibrio species pre-operatively. CONCLUSIONS Overall, RYGB produces greater and more predicted favourable changes in gut microbiota functional capacity than SG. An increase in Roseburia species was the only compositional change common to both types of surgery among those achieving diabetes remission.


title: Prevention of exacerbations in patients with COPD and vitamin D deficiency through vitamin D supplementation (PRECOVID): a study protocol.

text: BACKGROUND Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties. Vitamin D deficiency is a common problem in patients with COPD. Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients. However, subgroup analyses suggested protective effects in vitamin D deficient patients. Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients. METHODS/DESIGN We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study. The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L). Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period. Visits will be performed at baseline, at 6 months and at 12 months after randomisation. Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure. Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken. The primary outcome will be exacerbation rate. DISCUSSION This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients. Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation. Secondly, the immunomodulatory effects of vitamin D on host immune response of COPD patients and underlying mechanisms will be studied. Finally, the effects on physical functioning will be examined. TRIAL REGISTRATION This trial is registered in ClinicalTrials.gov, ID number NCT02122627 . Date of Registration April 2014.


title: Miller Fisher syndrome in a toddler with influenza A (pH1N1) infection.

text: A 17-month-old previously healthy child presented with a 2-day history of inability to fully open his eyes and slight gait ataxia. In the month preceding admission, he had had low grade, intermittent fevers, followed by a nonproductive cough and sneezing. During hospital admission he lost deep tendon reflexes and was unable to walk. Lumbar puncture revealed abnormally high protein, and a nasopharyngeal specimen was positive for influenza A (pH1N1). He received intravenous immunoglobulin and oseltamivir with clinical improvement. Although it is difficult to ascertain whether pH1N1 or another microorganism was responsible for this toddler's neurologic syndrome, this is the first reported case of Miller Fisher syndrome associated with pH1N1. During pandemics, one may expect to see an increased incidence of uncommon neurologic complications of influenza.


title: Immunocompromised patients and coronavirus disease 2019: a review and recommendations for dental health care.

text: In less than four months, an unprecedented pandemic changed the world scenario, closing institutions and commerce, paralyzing sports championships, blocking frontiers, and putting almost all populations in a house quarantine regimen. Immunocompromised patients are within the high-risk group to severe outcomes from COVID-19. However, there is no clear evidence of the association between impaired immune host status and complications from SARS-CoV-2 infection so far. The virus is transmitted by inhalation or direct contact with infected secretions, and therefore the dental office is a highly susceptible environment for such transmission. Here, we review the literature and discuss immunological COVID-19 related issues. We also make suggestions for immunocompromised patients' support in this new emerging context of clinical dental practice. Until comprehensive findings are published, individuals with impaired immunity should be considered as high-risk. Cross infection control procedures for the clinical care of immunocompromised patients should follow the same guidelines that are being proposed for immunocompetent ones. However, during the active outbreak, people under immunosuppressive conditions should not receive elective procedures, even if they do not have symptoms or exposure history to COVID-19, and in case of emergence, care must be done in a separate airborne room. In the pos-pandemic phase, the dental care general recommendations should be the same for all subjects. Changes in the current guidelines have been proposed to SARS-CoV-2 infection control in order to provide the best and safe dental practice. However, they still need to be validated by future studies.


title: [Construction and evaluation of a novel diagnosis process for 2019-Corona Virus Disease].

text: Objective: To construct and evaluate a diagnosis process for 2019-Corona Virus Disease (COVID-19). Methods: A continuous cohort of adults and adolescent (≥12 years) who screened COVID-19 was included in Xiangya Hospital of Central South University from January 23 to February 3, 2020 in which cases were divided the test library and the verification library. Their gender, age, onset time were recorded. Take epidemiological history, fever, and the blood lymphocytes decline as clinical indicators, used CT to evaluate the possibility of COVID-19 and range of lung involvement. According to the current national standards, throat swabs of suspected cases were collected and the nucleic acid of COVID-19 was detected by reverse transcription-polymerase chain reaction (RT-PCR). The Xiangya process was constructed according to multi-index, compared with clinical indicators, CT results and national standards, the efficiency of detecting confirmed cases were verified in the test and verification library. Results: A continuous cohort of 382 adults who screened COVID-19 was included in which 261 cases were in the test library and 121 cases were in the verification library. In the 382 cases, 192 were males (50.3%) and 190 were females (49.7%), with a median age of 35 years (range: 15-92 years). There were 183 cases (47.9%) with epidemiological history, 275 cases (72.0%) with fever, 212 cases (55.5%) with decreased hemolytic lymphocytes, CT positive 114 cases (29.8%), 43 cases (11.3%) with positive CT-COVID-19, and 30 cases (7.9%) with positive throat swab nucleic acid. Compared with clinical indicators, the sensitivity and specificity of CT were 0.950 and 0.704, respectively. The accuracy of CT to make a definite diagnosis was higher than that of epidemiological history, fever, and blood lymph count decline (0.809 vs 0.660, 0.532, 0.596, P=0.001, 0.002, 0.003, respectively). The sensitivity of this process and the program recommended by the Health Commission all were high (all were 1.000) , and the specificity and accuracy of the process were higher than the program recommended by the Health Commission (0.872 vs 0.765, 0.778 vs 0.592, both P<0.001). The CT-COVID-19 would have reduced the missed diagnosis rate caused by false negative of nucleic acid test (31 vs 64, difference rate 51.6%), the positive rate of nucleic acid test was 64.5% (20/31). In validation library, the specificity and accuracy of the Xiangya process was 0.967, the positive rate of nucleic acid test was 76.9% (10/13). Conclusions: The Xiangya process can predict the nucleic acid test results of COVID-19 well, and can be applied as a reliable basis for confirmed cases detection in adults and adolescent (≥12 years) in areas other than Hubei during the epidemic period of COVID-19. The cohort size needs to be increased for further validation.


title: The 'pit-crew' model for improving door-to-needle times in endovascular stroke therapy: a Six-Sigma project.

text: BACKGROUND Delays in delivering endovascular stroke therapy adversely affect outcomes. Time-sensitive treatments such as stroke interventions benefit from methodically developed protocols. Clearly defined roles in these protocols allow for parallel processing of tasks, resulting in consistent delivery of care. OBJECTIVE To present the outcomes of a quality-improvement (QI) process directed at reducing stroke treatment times in a tertiary level academic medical center. METHODS A Six-Sigma-based QI process was developed over a 3-month period. After an initial analysis, procedures were implemented and fine-tuned to identify and address rate-limiting steps in the endovascular care pathway. Prospectively recorded treatment times were then compared in two groups of patients who were treated 'before' (n=64) or 'after' (n=30) the QI process. Three time intervals were measured: emergency room (ER) to arrival for CT scan (ER-CT), CT scan to interventional laboratory arrival (CT-Lab), and interventional laboratory arrival to groin puncture (Lab-puncture). RESULTS The ER-CT time was 40 (±29) min in the 'before' and 26 (±15) min in the 'after' group (p=0.008). The CT-Lab time was 87 (±47) min in the 'before' and 51 (±33) min in the 'after' group (p=0.0002). The Lab-puncture time was 24 (±11) min in the 'before' and 15 (±4) min in the 'after' group (p<0.0001). The overall ER-arrival to groin-puncture time was reduced from 2 h, 31 min (±51) min in the 'before' to 1 h, 33 min (±37) min in the 'after' group, (p<0.0001). The improved times were seen for both working hours and off-hours interventions. CONCLUSIONS A protocol-driven process can significantly improve efficiency of care in time-sensitive stroke interventions.


title: Leucine-rich α2-glycoprotein overexpression in the brain contributes to memory impairment.

text: We previously reported increase in leucine-rich α2-glycoprotein (LRG) concentration in cerebrospinal fluid is associated with cognitive decline in humans. To investigate relationship between LRG expression in the brain and memory impairment, we analyzed transgenic mice overexpressing LRG in the brain (LRG-Tg) focusing on hippocampus. Immunostaining and Western blotting revealed age-related increase in LRG expression in hippocampal neurons in 8-, 24-, and 48-week-old controls and LRG-Tg. Y-maze and Morris water maze tests indicated retained spatial memory in 8- and 24-week-old LRG-Tg, while deteriorated in 48-week-old LRG-Tg compared with age-matched controls. Field excitatory postsynaptic potentials declined with age in LRG-Tg compared with controls at 8, 24, and 48 weeks. Paired-pulse ratio decreased with age in LRG-Tg, while increased in controls. As a result, long-term potentiation was retained in 8- and 24-week-old LRG-Tg, whereas diminished in 48-week-old LRG-Tg compared with age-matched controls. Electron microscopy observations revealed fewer synaptic vesicles and junctions in LRG-Tg compared with age-matched controls, which became significant with age. Hippocampal LRG overexpression contributes to synaptic dysfunction, which leads to memory impairment with advance of age.


title: SARS-CoV-2, which induces COVID-19, causes kawasaki-like disease in children: role of pro-inflammatory and anti-inflammatory cytokines.

text: Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic coronavirus disease 2019 (COVID-19). In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis. These clinical signs are mediated by pro-inflammatory cytokines. In recent studies it has been noted that COVID-19 pandemic can affect patients of all ages, including children (even if less severely) who were initially thought to be immune. Kawasaki disease is an autoimmune acute febrile inflammatory condition, which primarily affects young children. The disease can present immunodeficiency with the inability of the immune system to fight inflammatory pathogens and leads to fever, rash, alterations of the mucous membranes, conjunctiva infection, pharyngeal erythema, adenopathy, and inflammation. In the COVID-19 period, virus infection aggravates the condition of Kawasaki disease, but it has also been noted that children affected by SARS-V-2 may develop a disease similar to Kawasaki's illness. However, it is uncertain whether the virus alone can give Kawasaki disease-like forms. As in COVID-19, Kawasaki disease and its similar forms are mediated by pro-inflammatory cytokines produced by innate immunity cells such as macrophages and mast cells (MCs). In light of the above, it is therefore pertinent to think that by blocking pro-inflammatory cytokines with new anti-inflammatory cytokines, such as IL-37 and IL-38, it is possible to alleviate the symptoms of the disease and have a new available therapeutic tool. However, since Kawasaki and Kawasaki-like diseases present immunodeficiency, treatment with anti-inflammatory/immunosuppressant molecules must be applied very carefully.


title: Molecular biogeography of planktonic and benthic diatoms in the Yangtze River.

text: BACKGROUND Diatoms are of great significance to primary productivity in oceans, yet little is known about their biogeographic distribution in oligotrophic rivers. RESULTS With the help of metabarcoding analysis of 279 samples from the Yangtze River, we provided the first integral biogeographic pattern of planktonic and benthic diatoms over a 6030 km continuum along the world's third largest river. Our study revealed spatial dissimilarity of diatoms under varying landforms, including plateau, mountain, foothill, basin, foothill-mountain, and plain regions, from the river source to the estuary. Environmental drivers of diatom communities were interpreted in terms of photosynthetically active radiation, temperature, channel slope and nutrients, and human interference. Typical benthic diatoms, such as Pinnularia, Paralia, and Aulacoseira, experienced considerable reduction in relative abundance downstream of the Three Gorges Dam and the Xiluodu Dam, two of the world's largest dams. CONCLUSIONS Our study revealed that benthic diatoms are of particular significance in characterizing motile guild in riverine environments, which provides insights into diatom biogeography and biogeochemical cycles in large river ecosystems.


Urgent call to clinicians and researchers: 2020 acuity required when assessing and reporting laboratory abnormalities in COVID-19.


title: Treating resistant hypertension: role of renal denervation.

text: Arterial hypertension is the most prevalent risk factor associated with increased cardiovascular morbidity and mortality. Although pharmacological treatment is generally well tolerated, 5%-20% of patients with hypertension are resistant to medical therapy, which is defined as blood pressure above goal (>140/90 mmHg in general; >130-139/80-85 mmHg in patients with diabetes mellitus; >130/80 mmHg in patients with chronic kidney disease) despite treatment with ≥3 antihypertensive drugs of different classes, including a diuretic, at optimal doses. These patients are at significantly higher risk for cardiovascular events, in particular stroke, myocardial infarction, and heart failure, as compared with patients with nonresistant hypertension. The etiology of resistant hypertension is multifactorial and a number of risk factors have been identified. In addition, resistant hypertension might be due to secondary causes such as primary aldosteronism, chronic kidney disease, renal artery stenosis, or obstructive sleep apnea. To identify patients with resistant hypertension, the following must be excluded: pseudo-resistance, which might be due to nonadherence to medical treatment; white-coat effect; and inaccurate measurement technique. Activation of the sympathetic nervous system contributes to the development and maintenance of hypertension by increasing renal renin release, decreasing renal blood flow, and enhancing tubular sodium retention. Catheter-based renal denervation (RDN) is a novel technique specifically targeting renal sympathetic nerves. Clinical trials have demonstrated that RDN significantly reduces blood pressure in patients with resistant hypertension. Experimental studies and small clinical studies indicate that RDN might also have beneficial effects in other diseases and comorbidities, characterized by increased sympathetic activity, such as left ventricular hypertrophy, heart failure, metabolic syndrome and hyperinsulinemia, atrial fibrillation, obstructive sleep apnea, and chronic kidney disease. Further controlled studies are required to investigate the role of RDN beyond blood pressure control.


title: Risk of Incident Cancer in Inflammatory Bowel Disease Patients Starting Anti-TNF Therapy While Having Recent Malignancy.

text: BACKGROUND Patients with inflammatory bowel disease (IBD) and history of malignancy within the last 5 years are usually contraindicated for receiving anti-tumor necrosis factor (anti-TNF) agents. The aim of this study is to assess survival without incident cancer in a cohort of IBD patients exposed to anti-TNF while having previous malignancy within past 5 years. METHODS Data from IBD patients with previous malignancy diagnosed within the last 5 years before starting an anti-TNF agent were collected through a Groupe d'Etude Thérapeutiques des Affections Inflammatoires du tube Digestif multicenter survey. Inclusion date corresponded to the first anti-TNF administration after cancer diagnosis. RESULTS Twenty centers identified 79 cases of IBD patients with previous malignancy diagnosed 17 months (median; range: 1-65) before inclusion. The most frequent cancer locations were breast (n = 17) and skin (n = 15). After a median follow-up of 21 (range: 1-119) months, 15 (19%) patients developed incident cancer (8 recurrent and 7 new cancers), including 5 basal-cell carcinomas. Survival without incident cancer was 96%, 86%, and 66% at 1, 2, and 5 years, respectively. Crude incidence rate of cancer was 84.5 (95% CI, 83.1-85.8) per 1000 patient-years. CONCLUSIONS In a population of refractory IBD patients with recent malignancy, anti-TNF could be used taking into account a mild risk of incident cancer. Pending prospective and larger studies, a case-by-case joint decision taken with the oncologist is recommended for managing these patients in daily practice.


title: Transsacral rectocele following combined neurinoma resection: A case report.

text: INTRODUCTION This report describes for the first time a case of a transsacral rectocele after combined abdominotranssacral tumour resection. Furthermore, we demonstrate a method for laparoscopic defect repair. PRESENTATION OF CASE A 44-year-old Caucasian female presented to our hospital with strange gurgling sounds and a painless subdermal swelling in her lower back after resection of a presacral neurinoma two years earlier. Magnetic resonance imaging (MRI) showed a huge rectocele through a sacral defect extending into the subcutaneous tissue. We performed a laparoscopic defect repair with the implantation of a self-fixating mesh graft. Five days after surgery, the patient was discharged in a good general condition. Five months after the operation, a follow-up MRI showed a good postoperative result with the correct position of the rectum. DISCUSSION The repair of transsacral prolapses with attachment of a mesh is complicated by the high rigidity of the pelvis and its surrounding structures. The key criteria in choosing the method of operative approach are the size and content of the prolapse. Huge sacral defects with bowel prolapses require a transabdominal approach to enable repositioning the bowel into the abdomen and excluding bowel injuries and inner hernias. CONCLUSION A laparoscopic approach provides a good intraoperative visibility for a safe retrorectal preparation and mesh graft repair of sacral defects.


title: Novel microRNAs encoded by duck enteritis virus.

text: Duck enteritis virus (DEV) is an important herpesvirus pathogen associated with acute, highly contagious lethal disease in waterfowls. Using a deep sequencing approach on RNA from infected chicken embryo fibroblast cultures, we identified several novel DEV-encoded micro (mi)RNAs. Unlike most mardivirus-encoded miRNAs, DEV-encoded miRNAs mapped mostly to the unique long region of the genome. The precursors of DEV miR-D18 and miR-D19 overlapped with each other, suggesting similarities to miRNA-offset RNAs, although only the DEV-miR-D18-3p was functional in reporter assays. Identification of these novel miRNAs will add to the growing list of virus-encoded miRNAs enabling the exploration of their roles in pathogenesis.


title: Umbilical arteriovenous malformation: a case report and literature review.

text: Arteriovenous malformations can lead to life-threatening complications, particularly in neonates. Only a few case reports document arteriovenous malformations of the umbilicus, all presenting with complications and necessitating urgent surgical intervention. We report the case of a neonate with an incidentally noted umbilical arteriovenous malformation, treated with laparoscopic assisted resection.


title: Social Vulnerability and Racial Inequality in COVID-19 Deaths in Chicago.

text: Although the current COVID-19 crisis is felt globally, at the local level, COVID-19 has disproportionately affected poor, highly segregated African American communities in Chicago. To understand the emerging pattern of racial inequality in the effects of COVID-19, we examined the relative burden of social vulnerability and health risk factors. We found significant spatial clusters of social vulnerability and risk factors, both of which are significantly associated with the increased COVID-19-related death rate. We also found that a higher percentage of African Americans was associated with increased levels of social vulnerability and risk factors. In addition, the proportion of African American residents has an independent effect on the COVID-19 death rate. We argue that existing inequity is often highlighted in emergency conditions. The disproportionate effects of COVID-19 in African American communities are a reflection of racial inequality and social exclusion that existed before the COVID-19 crisis.


title: Assessment of severity of ICU-acquired pneumonia and association with etiology.

text: OBJECTIVES We evaluated the association between severity of illness and microbial etiology of ICU-acquired pneumonia to define if severity should be used to guide empiric antibiotic choices. DESIGN Prospective observational study. SETTING ICUs of a university hospital. PATIENTS Three hundredy forty-three consecutive patients with ICU-acquired pneumonia clustered, according to the presence of multidrug resistant pathogens. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Two hundred eight patients had ventilator-associated pneumonia and 135 had nonventilator ICU-acquired pneumonia. We determined etiology in 217 patients (63%). The most frequent pathogens were Pseudomonas aeruginosa, Enterobacteriaceae, and methicillin-sensitive and methicillin-resistant Staphylococcus aureus. Fifty-eight patients (17%) had a multidrug-resistant causative agent. Except for a longer ICU stay and a higher rate of microbial persistence at the end of the treatment in the multidrug-resistant group, no differences were found in clinical and inflammatory characteristics, severity criteria, and mortality or survival between patients with and without multidrug-resistant pathogens, even after adjusting for potential confounders. Patients with higher severity scores (Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment) and septic shock at onset of pneumonia had significantly lower 28- and 90-day survival and higher systemic inflammatory response. The results were similar when only patients with microbial diagnosis were considered, as well as when stratified into ventilator-associated pneumonia and nonventilator ICU-acquired pneumonia. CONCLUSIONS In patients with ICU-acquired pneumonia, severity of illness seems not to affect etiology. Risk factors for multidrug resistant, but not severity of illness, should be taken into account in selecting empiric antimicrobial treatment.


title: Endoscopic saphenous vein and radial harvest: state-of-the-art.

text: PURPOSE OF REVIEW Over the past decade, there has been an increased adoption of minimally invasive techniques for saphenous vein and radial artery procurement during coronary artery bypass surgery, albeit concerns have been raised about the potential detrimental effects of the endoscopic approach when compared with the conventional 'open' technique. The aim of the present review is to analyse the current available techniques and evidence about the impact of an endoscopic approach on conduit quality and clinical outcomes. RECENT FINDINGS At present, the available techniques for endoscopic vessel harvesting can be based on a sealed or non-sealed concept, for both saphenous vein and radial artery procurement. Despite the proven advantages of a minimally invasive approach in terms of reduced incidence of wound complications, pain reduction and improved cosmetic results, some studies questioned the impact of this technique in terms of potential graft damage, thus impairing the longevity of the graft itself. SUMMARY Endoscopic conduit harvesting can be performed safely and effectively with the currently available techniques, albeit a careful knowledge of the pitfalls of each technique is mandatory. Since there is ample evidence in literature that a minimally invasive approach for saphenous vein and radial artery procurement is not associated with an increased risk of graft damage and related failure in the mid-long term, the endoscopic technique should be adopted as the approach of choice for saphenous vein and radial artery harvesting in coronary artery bypass graft surgery.


COVID-19 and smoking: a high-risk association.


title: Methylene Blue for Refractory Shock in Children: A Systematic Review and Survey Practice Analysis.

text: OBJECTIVES Shock refractory to fluid and catecholamine therapy has significant morbidity and mortality in children. The use of methylene blue to treat refractory shock in children is not well described. We aim to collect and summarize the literature and define physicians' practice patterns regarding the use of methylene blue to treat shock in children. DESIGN We conducted a systematic search of MEDLINE, Embase, PubMed, Web of Science, Cochrane for studies involving the use of methylene blue for catecholamine-refractory shock from database inception to 2019. Collected studies were analyzed qualitatively. To describe practice patterns of methylene blue use, we electronically distributed a survey to U.S.-based pediatric critical care physicians. We assessed physician knowledge and experience with methylene blue. Survey responses were quantitatively and qualitatively evaluated. SETTING Pediatric critical and cardiac care units. PATIENTS OR SUBJECTS Patients less than or equal to 25 years old with refractory shock treated with methylene blue. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS One-thousand two-hundred ninety-three abstracts met search criteria, 139 articles underwent full-text review, and 24 studies were included. Studies investigated refractory shock induced by a variety of etiologies and found that methylene blue was generally safe and increased mean arterial blood pressure. There is overall lack of studies, low number of study patients, and low quality of studies identified. Our survey had a 22.5% response rate, representing 125 institutions. Similar proportions of physicians reported using (40%) or never even considering (43%) methylene blue for shock. The most common reasons for not using methylene blue were unfamiliarity with this drug, its proper dosing, and lack of evidentiary support. CONCLUSIONS Methylene blue appears safe and may benefit children with refractory shock. There is a stark divide in familiarity and practice patterns regarding its use among physicians. Studies to formally assess safety and efficacy of methylene blue in treating pediatric shock are warranted.


title: High school intervention for influenza biology and epidemics/pandemics: impact on conceptual understanding among adolescents.

text: Understanding real-life issues such as influenza epidemiology may be of particular interest to the development of scientific knowledge and initiation of conceptual changes about viruses and their life cycles for high school students. The goal of this research project was to foster the development of adolescents' conceptual understanding of viruses and influenza biology. Thus, the project included two components: 1) pre- and posttests to determine students' conceptions about influenza biology, epidemics/pandemics, and vaccination; and 2) design an intervention that supports conceptual change to promote improvements in influenza knowledge based on these primary conceptions. Thirty-five female students from a high school biology class participated in a series of instructional activities and pre- and posttest assessments. Results from the pretest indicated that high school students exhibit a limited understanding of concepts related to viruses. Six weeks after an intervention that promoted active learning, results from a posttest showed that conceptions about influenza are more accurately related to the provided scientific knowledge. Although adolescents have nonscientific models to explain influenza biology, we showed that a carefully designed intervention can affect students' knowledge as well as influence the implementation of health education programs in secondary schools.


title: Fondaparinux Sodium Compared With Low-Molecular-Weight Heparins for Perioperative Surgical Thromboprophylaxis: A Systematic Review and Meta-analysis.

text: Background Fondaparinux sodium has been compared with low-molecular-weight heparins ( LMWH ) in randomized controlled trials for perioperative surgical thromboprophylaxis. However, the results from these studies are inconsistent in terms of efficacy and safety to reach a clinical decision. The objective of this study was to systematically review the randomized controlled trials comparing the efficacy and safety of fondaparinux and LMWH for perioperative surgical thromboprophylaxis. Methods and Results Systematic search in various databases was done to identify randomized controlled trials comparing fondaparinux and LMWH published during the years 2000 to 2017. Outcomes of interest in this study included venous thromboembolism up to day 15, all-cause mortality up to day 90, major bleeding, and minor bleeding during the treatment period. Analyses were performed with the relative odds based on a random-effects model using Mantel-Haenszel statistics. Results were presented as odds ratios with their 95% CIs. The assessment of study quality was performed as per Cochrane collaboration. After screening 10 644 articles, 12 randomized controlled trials including 14 906 patients were included in the final analyses. Pooled analyses showed the odds of venous thromboembolism in the fondaparinux group were 0.49 times the odds in LMWH group ( OR =0.49 [0.38-0.64]). However, the odds of major bleeding in the fondaparinux group were 1.48 times the odds in the LMWH group ( OR =1.48 [1.15-1.90]). Conclusions Fondaparinux was associated with a superior efficacy in terms of reduction of venous thromboembolism in this meta-analysis. However, it was also associated with increased odds of major bleeding.


title: Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection.

text: The interferons (IFNs) are a primary defense against pathogens because of the strong antiviral activities they induce. IFNs can be classified into three groups: type I, type II and type III, according to their genetic, structural, and functional characteristics and their receptors on the cell surface. The type I IFNs are the largest group and include IFN-α, IFN-β, IFN-ε, IFN-ω, IFN-κ, IFN-δ, IFN-τ and IFN-ζ. The use of IFNs for the treatment of viral infectious diseases on their antiviral activity may become an important therapeutic option, for example, IFN-α is well known for the successful treatment of hepatitis B and C virus infections, and interest is increasing in the antiviral efficacy of other novel IFN classes and their potential applications. Therefore, in this review, we summarize the recent progress in the study of the biological activities of all the type I IFN classes and their potential applications in the treatment of infections with immunodeficiency virus, hepatitis viruses, and influenza viruses.


title: Management of endovenous heat-induced thrombus using a classification system and treatment algorithm following segmental thermal ablation of the small saphenous vein.

text: OBJECTIVE We evaluated our experience with segmental radiofrequency ablation (RFA) of the small saphenous vein (SSV), a less common procedure than great saphenous vein ablation, and developed a classification system and algorithm for endovenous heat-induced thrombus (EHIT), based on modifications of our prior algorithm of EHIT following great saphenous ablation. METHODS Endovenous ablation was performed on symptomatic patients with incompetent SSVs following a minimum of 3 months of compression therapy. Demographic data, risk factors, CEAP classification, procedure details, and follow-up data were recorded. A four-tier classification system and treatment algorithm was developed, based on EHIT proximity to the popliteal vein. RESULTS Eighty limbs (in 76 patients) were treated with RFA of the SSV between January 2008 and August 2012. Duplex ultrasound was performed between 24 and 72 hours postprocedure in all patients. Ablation was successful in 98.7% (79/80) of procedures. Sixty-eight (85%) patients had level A closures (≥ 1 mm caudal to popliteal vein) and 10 patients (13%) had level B closures (flush with popliteal vein) and were observed. Two limbs (3%) had EHIT extending into the popliteal vein (level C) and were treated with outpatient low-molecular-weight heparin anticoagulation. Thrombus retracted to the level of the saphenopopliteal junction in both patients following a short course of anticoagulation. No patient developed an occlusive deep vein thrombosis (DVT) (level D). Mean follow-up period was 6.2 months; no patient had small saphenous recanalization, occlusive DVT, or pulmonary embolus. The presence or absence of the Giacomini vein was not predictive of level B and C closure. CONCLUSIONS RFA of the SSV in symptomatic patients has a high success rate with a low risk of DVT. A classification system and treatment protocol based on the level of EHIT in relation to the saphenopopliteal junction is useful in managing patients. The approach to patients with thrombus flush with the popliteal vein or bulging has not been previously defined; our outcomes were excellent, using our treatment algorithm.


title: Low-dose SoluMatrix diclofenac in the treatment of osteoarthritis: A 1-year, open-label, Phase III safety study.

text: INTRODUCTION Diclofenac is used for the treatment of osteoarthritis (OA); however, like other nonsteroidal anti-inflammatory drugs (NSAIDs) it can be associated with serious dose-related adverse events (AEs). Low-dose SoluMatrix® diclofenac has been developed to provide efficacy at lower diclofenac doses. A recently published Phase III study evaluated the efficacy and safety of SoluMatrix diclofenac 35 mg twice daily (b.i.d.) and thrice daily (t.i.d.) in patients with OA pain treated for 12 weeks. METHODS This Phase III multicenter, open-label study assessed the safety of SoluMatrix diclofenac in patients with OA dosed up to 52 weeks (ClinicalTrials.gov: NCT01510912). The study enrolled 602 chronic NSAID/acetaminophen users, aged ≥40 years with OA of the knee or hip. Patients received SoluMatrix diclofenac 35 mg b.i.d., which could be increased to t.i.d. and subsequently reduced to b.i.d. as needed. Safety assessments included AEs, vital signs, physical examination findings, 12-lead electrocardiogram, and clinical laboratory test results. Patient-reported outcomes were evaluated by the Short Form-36 (SF-36). RESULTS A total of 601 patients received SoluMatrix diclofenac; 373 of 601 patients (62.1%) received treatment for ≥11 months. The most frequent AEs included upper respiratory tract infection, headache, urinary tract infection, diarrhea, nasopharyngitis, and nausea. Serious gastrointestinal, cardiovascular, renal, and hepatic AEs were uncommon. A small proportion (99 patients, 16.5%) of patients discontinued participation in the study due to AEs. Clinically meaningful improvements from baseline in Physical Component Summary Scores of the SF-36 were noted at week 12 and were sustained through week 52. Improvements in six of the eight individual physical and mental SF-36 domains were also noted. CONCLUSION SoluMatrix diclofenac treatment for up to 1 year was generally well tolerated in patients with OA pain and associated with improvement in quality of life measures. TRIAL REGISTRATION www.clinicaltrials.gov identifier: NCT01510912.


Health geography: supporting public health policy and planning.


title: Lymph Node Positivity in Appendiceal Adenocarcinoma: Should Size Matter?

text: BACKGROUND The management algorithm for appendiceal adenocarcinoma is not well defined. This study sought to determine whether tumor size or depth of invasion better correlates with the presence of lymph node metastases in appendiceal adenocarcinoma, and to compare these rates with colon adenocarcinoma. STUDY DESIGN A retrospective review of the National Cancer Database was performed to identify patients with appendiceal or colonic adenocarcinoma from 2004 to 2013 who underwent surgical resection. Cases were categorized by tumor size and by T stage. Rates of lymph node metastases were examined as a function of size and T stage. RESULTS A total of 3,402 appendiceal and 314,864 colonic cases were identified. For appendiceal adenocarcinoma, larger tumor size was associated with higher T stage: Pearson correlation of 0.41 (95% CI 0.408 to 0.414; p < 0.001). Lymph node metastases were present in 19.1%, 27.8%, 39.6%, 39.4%, 42.4% and 39.1% for tumor sizes <1 cm, >1 to 2 cm, >2 to 3 cm, >3 to 4 cm, >4 to 5 cm, and >5 cm, respectively. Lymph node metastases were present in 0%, 11.2%, 12.3%, 35.5%, and 40.0% for in situ, T1, T2, T3, and T4 tumors, respectively. There was no difference in the rates of lymph node metastases between appendiceal and colonic adenocarcinoma for tumor sizes <3 cm, or for in situ and T1 tumors. Rates of lymph node metastases are higher in colonic adenocarcinoma for tumor sizes >3 cm and for T2, T3, and T4 tumors (p < 0.01). CONCLUSIONS In appendiceal adenocarcinoma, the rate of lymph node metastases is substantial, even for small tumors. Tumor size should play no role in the decision of whether to perform a hemicolectomy. Appendectomy alone does not produce an adequate lymph node sample. Right hemicolectomy should be performed for all appendiceal adenocarcinomas.


Reducing opioid abuse and diversion.


title: Safety and efficacy of the Pipeline Embolization Device in 100 small intracranial aneurysms.

text: OBJECT Flow diverters are increasingly used for treatment of intracranial aneurysms. In most series, the Pipeline Embolization Device (PED) was used for the treatment of large, giant, complex, and fusiform aneurysms. Little is known about the use of the PED in small aneurysms. The purpose of this study was to assess the safety and efficacy of the PED in small aneurysms (≤ 7 mm). METHODS A total of 100 consecutive patients were treated with the PED at the authors' institution between May 2011 and September 2013. Data on procedural safety and efficacy were retrospectively collected. RESULTS The mean aneurysm size was 5.2 ± 1.5 mm. Seven patients (7%) had sustained a subarachnoid hemorrhage. All except 5 aneurysms (95%) arose from the anterior circulation. The number of PEDs used was 1.2 per aneurysm. Symptomatic procedure-related complications occurred in 3 patients (3%): 1 distal parenchymal hemorrhage that was managed conservatively and 2 ischemic events. At the latest follow-up (mean 6.3 months), 54 (72%) aneurysms were completely occluded (100%), 10 (13%) were nearly completely occluded (≥ 90%), and 11 (15%) were incompletely occluded (< 90%). Six aneurysms (8%) required further treatment. Increasing aneurysm size (OR 3.8, 95% CI 0.99-14; p = 0.05) predicted retreatment. All patients achieved a favorable outcome (modified Rankin Scale Score 0-2) at follow-up. CONCLUSIONS In this study, treatment of small aneurysms with the PED was associated with low complication rates and high aneurysm occlusion rates. These findings suggest that the PED is a safe and effective alternative to conventional endovascular techniques for small aneurysms. Randomized trials with long-term follow-up are necessary to determine the optimal treatment that leads to the highest rate of obliteration and the best clinical outcomes.


Developing a SARS-CoV-2 Vaccine at Warp Speed.


title: Thallium Labeled Citrate-Coated Prussian Blue Nanoparticles as Potential Imaging Agent.

text: Background The aim of this study was to develop and characterize a nanoparticle-based image-contrast platform which is biocompatible, chemically stable, and accessible for radiolabeling with 201Tl. We explored whether this nanoparticle enhanced the T1 signal which might make it an MRI contrast agent as well. Methods The physical properties of citrate-coated Prussian blue nanoparticles (PBNPs) (iron(II);iron(III);octadecacyanide) doped with 201Tl isotope were characterized with atomic force microscopy, dynamic light scattering, and zeta potential measurement. PBNP biodistribution was determined by using SPECT and MRI following intravenous administration into C57BL6 mice. Activity concentrations (MBq/cm3) were calculated from the SPECT scans for each dedicated volume of interest (VOI) of liver, kidneys, salivary glands, heart, lungs, and brain. Results PBNP accumulation peaked at 2 hours after injection predominantly in the kidneys and the liver followed by a gradual decrease in activity in later time points. Conclusion We synthetized, characterized, and radiolabeled a Prussian blue-based nanoparticle platform for contrast material applications. Its in vivo radiochemical stability and biodistribution open up the way for further diagnostic applications.


title: Initial experience with the use of remote control monitoring and general anesthesia during radiosurgery for pediatric patients.

text: The demand for general anesthesia in pediatric radiosurgery has been increasing, but the issues involved are not highlighted well in the medical literature. We developed remotely controlled monitoring and anesthesia techniques, and applied our system to three pediatric patients who underwent Gamma Knife radiosurgery with automated settings. Based on the perioperative safety management, the following issues are of considerable concern: to avoid emotional trauma associated with the treatment, to secure airway patency in a variety of head positions, and to apply all standard monitors. In this report, we describe the details of our project with a comprehensive literature review.


title: Giant midline abdominal incisional herniae repair through combined retro-rectus mesh placement and components separation: experience from a single centre.

text: AIMS Giant midline abdominal wall incisional herniae require repair/reconstruction to restore the structural and functional continuity of the anterior abdominal wall. We describe here our approach to these demanding cases through a combined retro-rectus mesh placement and components separation and their overall functional outcome. METHODS A retrospective analysis of a prospectively collected data was carried out and 28 patients who underwent giant (≥15 cm) midline incisional hernia reconstruction were identified in a large district general hospital between 2007 and 2013 with a median follow-up of 34 (6-76) months. RESULTS Demographic data of our series include age of 60 (median) (30-87) years with a M:F ratio of 12:16, length of symptomatic hernia 18 (median) (12-36) months, more than two previous laparotomies (15), bowel obstructive symptoms (7) and recurrent herniation (7). BMI recorded was 32 (median) (24-46) and ASA of II (median) (I-III). Co-morbidities included cardiac disease (6), diabetes (6), respiratory disease (4) and systemic immunocompromise (2). Operative and technical details showed operative duration to be 180 (median) min, cranio-caudal rectus sheath defect 21 (median) cm, transverse rectus sheath defect 15 (median) cm, cross-sectional area of fascial defect 300 (median) cm(2) and size of mesh 690 (median) cm(2). Seven (25 %) developed short-term post operative complications: grade I seromata all resolving spontaneously (5); grade II superficial wound infections (2). Twenty-five (89 %) were completely asymptomatic at 34 (median) months' follow-up; 2 (7 %) reported mild pain, but not limiting any activity; 1 (4 %) described pain occasionally limiting activity. There was no clinical recurrence with one patient developing global bulging. CONCLUSIONS Our series is comparable to the literature in patient cohort demographics, co-morbidity and risk factor profile; however, we demonstrate an excellent intermediate term outcome with no clinical recurrence and an improvement in quality of life, through their ability to perform normal day to day activities.


Use of personal protective equipment during the COVID-19 pandemic.


COVID-19 Pandemic, Unemployment, and Civil Unrest: Underlying Deep Racial and Socioeconomic Divides.


Revisiting Legal Foundations of Crisis Standards of Care.


title: Femoropopliteal Artery Stent Thrombosis: Report From the Excellence in Peripheral Artery Disease Registry.

text: BACKGROUND There are limited data on femoropopliteal artery stent thrombosis (ST), which is a serious adverse outcome of peripheral artery interventions. METHODS AND RESULTS Index procedures resulting in femoropopliteal ST were compared with stent procedures without subsequent ST in the Excellence in Peripheral Artery Disease registry. The study data had a total of 724 cases of stent procedures and 604 unique patients. Femoropopliteal ST occurred in 26 of 604 patients (4.3%) over a median follow-up of 6 months post procedure. ST was more likely to occur in men (96.3% versus 82.2%; P=0.026) and to have an initial intervention for chronic total occlusions (88.5% versus 64.0%; P=0.01). There was no significant difference in ST between drug-coated and bare-metal stents (4.4% versus 3.4%; P=0.55), but the rate of ST was significantly higher with self-expanding covered stent grafts compared with bare-metal stents (10.6% versus 3.4%; P=0.02). ST was significantly associated with an increased risk of 12-month major adverse limb events (hazard ratio, 4.99; 95% confidence interval, 2.31-10.77; P<0.001) compared with no ST. On multivariate analysis, treatment of chronic total occlusion lesions (odds ratio, 3.46; 95% confidence interval, 0.98-12.20; P=0.05) and in-stent restenosis lesions (odds ratio, 5.30; 95% confidence interval, 1.83-15.32; P=0.002) were independently associated with an increased risk of ST. CONCLUSIONS In a multicenter peripheral interventional registry, femoropopliteal ST occurred in 4.3% of patients who underwent stent procedures, and it was associated with treatment of chronic total occlusions and in-stent restenosis lesions, and had higher 12-month major adverse limb events. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01904851.


title: Knowledge, attitudes and practices concerning Middle East respiratory syndrome among Umrah and Hajj pilgrims in Samsun, Turkey, 2015.

text: We performed a questionnaire study to determine knowledge, attitudes and practices concerning Middle East respiratory syndrome (MERS) among people intending to participate in the Hajj or Umrah Muslim pilgrimages. Of the 381 respondents aged between 17 and 85 years, 55% had never heard of MERS, while only one in three knew that it is a respiratory disease. Approximately half were insufficiently informed about protective measures. Prospective pilgrims do not seem prepared to take such precautions.


title: New stent retriever devices.

text: Acute ischemic stroke (AIS) is among the leading causes of adult death and number one cause of severe disability in the United States. In 1995 physicians had their first available Food and Drug Administration (FDA) approved treatment for AIS in the form of intravenous tissue plasminogen activator (IV-tPA). Since then, there has been an explosion of interest into endovascular mechanical thrombectomy as a potential treatment of stroke. Beginning in 2004 with the Merci Retriever, there have been multiple devices tested for this purpose. In 2012, the FDA approved two new devices-the Trevo Pro and Solitaire stent retrievers-after they were shown to have superior rates of recanalization when compared to the Merci device. In this article we will highlight the similarities and differences in the devices themselves, and the trials that brought them into use. Lastly, we will briefly touch on the future of mechanical embolectomy and considerations for future trial designs and patient selection.


title: Straightforward thiol-mediated protein labelling with DTPA: Synthesis of a highly active 111In-annexin A5-DTPA tracer.

text: BACKGROUND Annexin A5 (anxA5) has been found useful for molecular imaging of apoptosis and other biological processes. METHODS Here, we report an optimised two-step synthesis of annexin A5-diethylene triamine pentaacetic acid (DTPA) (anxA5-DTPA) for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging with a single purification step. The use of a recombinant annexin A5 (cys-anxA5) with a single thiol group allowed regionally specific coupling, without affecting the binding domain of cys-anxA5. RESULTS The metal complexing capacity of anxA5-DTPA was investigated by labelling with 111In3+ and Eu3+. Binding of modified anxA5-DTPA to apoptotic cells was tested in competition experiments with a fluorescent anxA5 derivative (anxA5-FITC) using flow cytometry and compared with that of wildtype anxA5 or non-binding anxA5-DTPA (M1234-anxA5-DTPA). The binding affinity to apoptotic cells of the anxA5-DTPA conjugate does not differ from that of wildtype anxA5. CONCLUSIONS This two-step synthesis of annexin A5-DTPA resulted in biologically active anxA5-DTPA, which can be labelled with radionuclides for use in SPECT and PET imaging.