title: Fatal rupture of a brain arteriovenous malformation flow-related aneurysm during microcatheter removal: a rare complication.

text: Intracranial aneurysms are relatively frequently encountered in patients with brain arteriovenous malformations (BAVMs). They may be located on the circle of Willis, on arterial feeders, or even inside the nidus. Because BAVM-associated aneurysms represent a risk factor of bleeding, the question of the timing and modality of their management remains a matter of debate in unruptured BAVMs. The authors present a case of fatal periprocedural rupture of a flow-related aneurysm (FRA) during the removal of the microcatheter after injection of a liquid embolic agent. A 40-year-old man was treated at the authors' institution for the management of a Spetzler-Martin Grade III left unruptured frontal BAVM, revealed by seizures and a focal neurological deficit attributed to flow steal phenomenon. After a multidisciplinary meeting, endovascular treatment was considered to reduce the flow of the BAVM. A proximal FRA located on the feeding internal carotid artery (ICA) was purposely left untreated because it did not meet the criteria of the authors' institution for preventative treatment (i.e., small size [2.5 mm]). During embolization, at the time of microcatheter retrieval, and after glue injection, the aneurysm unexpectedly ruptured. The aneurysm's rupture was attributed to the stress (torsion/flexion) on the ICA caused by the microcatheter removal. Despite the attempts to manage the bleeding, the patient eventually died of the acute increase of intracranial pressure related to the massive subarachnoid hemorrhage. This case highlights a previously unreported mechanism of FRA rupture during BAVM embolization: the stress transmitted to the parent artery during the removal of the microcatheter.


title: Effect of an acute increase in central blood volume on cerebral hemodynamics.

text: Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (-26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight (P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance (r = -0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV.


title: Genetic diversity and phenotypic associations of feline caliciviruses from cats in Switzerland.

text: Feline calicivirus (FCV) is a common viral pathogen in domestic cats worldwide. The variable regions of the capsid (VP1) gene of FCV have one of the highest recorded rates of molecular evolution. Understanding the genetic diversity and phylogeny of FCV is a prerequisite to exploring the epidemiology and pathogenesis of this virus and to the development of efficacious vaccine strategies. In this study, we undertook a nationwide molecular characterization of FCV using for the first time nearly complete capsid (VP1) gene sequences. Sequences from 66 FCV samples were used to investigate the correlation between viral phylogeny and several traits, including geographic origin, signalment, husbandry, FCV vaccination and co-infections. Codon-based nucleotide alignment showed that individual nucleotides and their corresponding amino acid sites were either invariant or highly variable. Using a threshold of 20 % genetic distance in variable region E, FCV samples were grouped into 52 strains, 10 of which comprised two to three samples. Significant associations between FCV phylogeny and host characteristics were found, specifically the pedigree status of the cats, and two well-supported lineages were identified in which the current FCV strain definition was confounded. No correlation between viral genetic distances and geographic distances was evident. The greater resolution of the FCV phylogeny in this study compared to previous studies can be attributed to our use of more conserved regions of the capsid (VP1) gene; nonetheless, our results were still hampered by sequence saturation. The study highlights the need for whole-genome sequences for FCV phylogeny studies.


Wildlife consumption ban is insufficient.


title: Eight-Hour Continuous Normothermic Ex Vivo Kidney Perfusion Is a Safe Preservation Technique for Kidney Transplantation: A New Opportunity for the Storage, Assessment, and Repair of Kidney Grafts.

text: BACKGROUND Hypothermic kidney storage causes preservation injury and is poorly tolerated by renal grafts. We investigated whether static cold storage (SCS) can be safely replaced with a novel technique of pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) in heart-beating donor kidney transplantation. METHODS Right kidneys were removed from 30 kg Yorkshire pigs in a model of heart-beating donation and either preserved in cold histidine-tryptophan-ketoglutarate solution for 8 hours (n = 5), or subjected to 8 hours of pressure-controlled NEVKP (n = 5) followed by renal heterotopic autotransplantation. RESULTS During NEVKP, physiologic perfusion conditions were maintained with low intrarenal resistance and normal electrolyte and pH parameters. Aspartate aminotransferase and lactate dehydrogenase as injury markers were below the detectable analyzer range (<4 and <100 U/L, respectively). Perfusate lactate concentration decreased from baseline until the end of perfusion (10.38 ± 0.76 mmol/L vs 1.22 ± 0.26 mmol/L; P < 0.001). Posttransplantation, animals transplanted with NEVKP versus SCS grafts demonstrated similar serum creatinine peak levels (NEVKP, 2.0 ± 0.5 vs SCS 2.7 ± 0.7 mg/dL; P = 0.11) and creatinine clearance on day 10 (NEVKP, 65.9 ± 18.8 mL/min vs SCS 61.2 ± 15.6 mL/min; P = 0.74). After 10 days of follow-up, animals transplanted with NEVKP grafts had serum creatinine and blood urea nitrogen values comparable to their basal levels (P = 0.49 and P = 0.59), whereas animals transplanted with SCS grafts had persistently elevated serum creatinine and blood urea nitrogen when compared with basal levels (P = 0.01 and P = 0.03). CONCLUSIONS Continuous pressure-controlled NEVKP is feasible and safe in good quality heart-beating donor kidney grafts. It maintains a physiologic environment and excellent graft function ex vivo during preservation without causing graft injury.


title: Protective myoelectric activity at performing upper limb neurodynamic test 1 in breast cancer survivors. A cross-sectional observational study.

text: Myoelectric activity and range of motion during ULNT1 were recorded in 62 breast cancer (BC) survivors who had axillary lymph node dissection (n = 30) or sentinel lymph node biopsy (n = 32) within the previous 18 months, and 63 age-matched healthy women. BC survivors' symptoms were reproduced by ULNT1 and exhibited greater myoelectric activity in the biceps brachii than healthy women (MD (95% CI): 21,26 (10,83-31,70)). No differences between the axillary lymph node dissection and sentinel lymph node biopsy groups (MD (95% CI): 8,47 (-7,84-24,79)) were found. Myoelectric activity in the triceps brachii was greater in the sentinel lymph node biopsy group (MD (95% CI): 2,70 (-2,06-7,60)). BC survivors exhibited less shoulder and elbow range of motion during ULNT1 than healthy women. Increased upper limb nerve mechanosensitivity in BC survivors was associated with a greater protective muscle response during ULNT1.


title: Characterization of Epitope-Specific Anti-Respiratory Syncytial Virus (Anti-RSV) Antibody Responses after Natural Infection and after Vaccination with Formalin-Inactivated RSV.

text: UNLABELLED Antibodies against the fusion (F) protein of respiratory syncytial virus (RSV) play an important role in the protective immune response to this important respiratory virus. Little is known, however, about antibody levels against multiple F-specific epitopes induced by infection or after vaccination against RSV, while this is important to guide the evaluation of (novel) vaccines. In this study, we analyzed antibody levels against RSV proteins and F-specific epitopes in human sera and in sera of vaccinated and experimentally infected cotton rats and the correlation thereof with virus neutralization. Analysis of human sera revealed substantial diversity in antibody levels against F-, G (attachment)-, and F-specific epitopes between individuals. The highest correlation with virus neutralization was observed for antibodies recognizing prefusion-specific antigenic site Ø. Nevertheless, our results indicate that high levels of antibodies targeting other parts of the F protein can also mediate a potent antiviral antibody response. In agreement, sera of experimentally infected cotton rats contained high neutralizing activity despite lacking antigenic site Ø-specific antibodies. Strikingly, vaccination with formalin-inactivated RSV (FI-RSV) exclusively resulted in the induction of poorly neutralizing antibodies against postfusion-specific antigenic site I, although antigenic sites I, II, and IV were efficiently displayed in FI-RSV. The apparent immunodominance of antigenic site I in FI-RSV likely explains the low levels of neutralizing antibodies upon vaccination and challenge and may play a role in the vaccination-induced enhancement of disease observed with such preparations. IMPORTANCE RSV is an importance cause of hospitalization of infants. The development of a vaccine against RSV has been hampered by the disastrous results obtained with FI-RSV vaccine preparations in the 1960s that resulted in vaccination-induced enhancement of disease. To get a better understanding of the antibody repertoire induced after infection or after vaccination against RSV, we investigated antibody levels against fusion (F) protein, attachment (G) protein, and F-specific epitopes in human and animal sera. The results indicate the importance of prefusion-specific antigenic site Ø antibodies as well as of antibodies targeting other epitopes in virus neutralization. However, vaccination of cotton rats with FI-RSV specifically resulted in the induction of weakly neutralizing, antigenic site I-specific antibodies, which may play a role in the enhancement of disease observed after vaccination with such preparations.


Why G6PD Deficiency Should Be Screened Before COVID-19 Treatment With Hydroxychloroquine?


title: Variation in critical care services across North America and Western Europe.

text: OBJECTIVE Critical care represents a large percentage of healthcare spending in developed countries. Yet, little is known regarding international variation in critical care services. We sought to understand differences in critical care delivery by comparing data on the distribution of services in eight countries. DESIGN Retrospective review of existing national administrative data. We identified sources of data in each country to provide information on acute care hospitals and beds, intensive care units and beds, intensive care admissions, and definitions of intensive care beds. Data were all referenced and from as close to 2005 as possible. SETTING United States, France, United Kingdom, Canada, Belgium, Germany, The Netherlands, and Spain. PATIENTS Not available. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS No standard definition existed for acute care hospital or intensive care unit beds across countries. Hospital beds varied three-fold from 221/100,000 population in the United States to 593/100,000 in Germany. Adult intensive care unit beds also ranged seven-fold from 3.3/100,000 population in the United Kingdom to 24.0/100,000 in Germany. Volume of intensive care unit admissions per year varied ten-fold from 216/100,000 population in the United Kingdom to 2353/100,000 in Germany. The ratio of intensive care unit beds to hospital beds was highly correlated across all countries except the United States (r = .90). There was minimal correlation between the number of intensive care unit beds per capita and health care spending per capita (r = .45), but high inverse correlation between intensive care unit beds and hospital mortality for intensive care unit patients across countries (r = -.82). CONCLUSIONS Absolute critical care services vary dramatically between countries with wide differences in both numbers of beds and volume of admissions. The number of intensive care unit beds per capita is not strongly correlated with overall health expenditure, but does correlate strongly with mortality. These findings demonstrate the need for critical care data from all countries, as they are essential for interpretation of studies, and policy decisions regarding critical care services.


title: Transgene expression in the genome of Middle East respiratory syndrome coronavirus based on a novel reverse genetics system utilizing Red-mediated recombination cloning.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a high-priority pathogen in pandemic preparedness research. Reverse genetics systems are a valuable tool to study viral replication and pathogenesis, design attenuated vaccines and create defined viral assay systems for applications such as antiviral screening. Here we present a novel reverse genetics system for MERS-CoV that involves maintenance of the full-length viral genome as a cDNA copy inserted in a bacterial artificial chromosome amenable to manipulation by homologue recombination, based on the bacteriophage λ Red recombination system. Based on a full-length infectious MERS-CoV cDNA clone, optimal genomic insertion sites and expression strategies for GFP were identified and used to generate a reporter MERS-CoV expressing GFP in addition to the complete set of viral proteins. GFP was genetically fused to the N-terminal part of protein 4a, from which it is released during translation via porcine teschovirus 2A peptide activity. The resulting reporter virus achieved titres nearly identical to the wild-type virus 48 h after infection of Vero cells at m.o.i. 0.001 (1×105 p.f.u. ml-1 and 3×105 p.f.u. ml-1, respectively), and allowed determination of the 50 % inhibitory concentration for the known MERS-CoV inhibitor cyclosporine A based on fluorescence readout. The resulting value was 2.41 µM, which corresponds to values based on wild-type virus. The reverse genetics system described herein can be efficiently mutated by Red-mediated recombination. The GFP-expressing reporter virus contains the full set of MERS-CoV proteins and achieves wild-type titres in cell culture.


title: Thoracoscopic repair of recurrent bochdalek diaphragmatic hernias in children.

text: BACKGROUND Recurrent herniation is a well-known complication following the initial repair of congenital diaphragmatic hernias (CDHs). The role of minimally invasive surgical techniques in recurrent CDH remains undefined. The purpose of this study was to evaluate our early experience with thoracoscopic repair compared with traditional open repair in children with recurrent CDH. SUBJECTS AND METHODS We retrospectively reviewed all recurrent Bochdalek CDH cases (n=24) managed at a single tertiary-care referral center between January 1990 and March 2011. Children who underwent thoracoscopic repair for recurrent CDH were identified, and their data were compared by the unpaired t test and the two-sided Fisher's exact test, as appropriate, with those of children who underwent open repair. Significance was defined as P<.05. RESULTS Thoracoscopic repair was attempted in 6 (25%) children with recurrent CDH. Four (67%) repairs were successfully completed without conversion to an open procedure. The mean age at thoracoscopic repair was 11.5 months (range, 8.1-16.1 months). The mean operative time was 191 minutes (range, 94-296 minutes), and all children were extubated within 24 hours. The mean hospital length of stay was 3.75 days (range, 1-6 days). There were no deaths or subsequent recurrences after a mean follow-up of 26.5 months (range, 14.3-41.3 months). There were no statistical differences in any of the measured outcome variables when compared with the open repair group. CONCLUSIONS Our initial experience suggests that thoracoscopic repair is a feasible alternative to open repair in selected children with recurrent Bochdalek diaphragmatic hernias.


title: Application of Topic Modeling to Tweets as the Foundation for Health Disparity Research for COVID-19.

text: We randomly extracted publicly available Tweets mentioning COVID-19 related terms (n=2,558,474 Tweets) from Tweet corpora collected daily using an API from Jan 21st to May 3rd, 2020. We applied a clustering algorithm to publicly available Tweets authored by African Americans (n=1,763) to detect topics and sentiment applying natural language processing (NLP). We visualized fifteen topics (four themes) using network diagrams (Newman modularity 0.74). Compared to the COVID-19 related Tweets authored by others, positive sentiments, cohesively encouraging online discussions (e.g., Black strong 27.1%, growing up Blacks 22.8%, support Black business 17.0%, how to build resilience 7.8%), and COVID-19 prevention behaviors (e.g., masks 4.7%, encouraging social distancing 9.4%) were uniquely observed in African American Twitter communities. Application of topic modeling techniques to streaming social media Twitter provides the foundation for research team insights regarding information and future virtual based intervention and social media based health disparity research for COVID-19.


title: Multicenter, Prospective, Longitudinal Study of the Recurrence, Surgical Site Infection, and Quality of Life After Contaminated Ventral Hernia Repair Using Biosynthetic Absorbable Mesh: The COBRA Study.

text: OBJECTIVE The aim of the study was to evaluate biosynthetic absorbable mesh in single-staged contaminated (Centers for Disease Control class II and III) ventral hernia (CVH) repair over 24 months. BACKGROUND CVH has an increased risk of postoperative infection. CVH repair with synthetic or biologic meshes has reported chronic biomaterial infections and high hernia recurrence rates. METHODS Patients with a contaminated or clean-contaminated operative field and a hernia defect at least 9 cm had a biosynthetic mesh (open, sublay, retrorectus, or intraperitoneal) repair with fascial closure (n = 104). Endpoints included overall Kaplan-Meier estimates for hernia recurrence and postoperative wound infection rates at 24 months, and the EQ-5D and Short Form 12 Health Survey (SF-12). Analyses were conducted on the intent-to-treat population, and health outcome measures evaluated using paired t tests. RESULTS Patients had a mean age of 58 years, body mass index of 28 kg/m, 77% had contaminated wounds, and 84% completed 24-months follow-up. Concomitant procedures included fistula takedown (n = 24) or removal of infected previously placed mesh (n = 29). Hernia recurrence rate was 17% (n = 16). At the time of CVH repair, intraperitoneal placement of the biosynthetic mesh significantly increased the risk of recurrences (P ≤ 0.04). Surgical site infections (19/104) led to higher risk of recurrence (P < 0.01). Mean 24-month EQ-5D (index and visual analogue) and SF-12 physical component and mental scores improved from baseline (P < 0.05). CONCLUSIONS In this prospective longitudinal study, biosynthetic absorbable mesh showed efficacy in terms of long-term recurrence and quality of life for CVH repair patients and offers an alternative to biologic and permanent synthetic meshes in these complex situations.


title: A 14-year Prospective Study of Human Coronavirus Infections in Hospitalized Children: Comparison With Other Respiratory Viruses.

text: BACKGROUND Human coronaviruses (HCoVs) have been recognized as causative agents of respiratory tract infections.Our aim was to describe HCoV infections in hospitalized children in a prospective surveillance study for 14 years and compare them with other respiratory viruses. METHODS As a part of an ongoing prospective study to identify the etiology of viral respiratory infections in Spain, we performed the analysis of HCoV infections in children hospitalized in a secondary hospital in Madrid, between October 2005 and June 2018. Clinical data of HCoV patients were compared with those infected by rhinovirus, respiratory syncytial virus and influenza. RESULTS The study population consisted of 5131 hospitalizations for respiratory causes in children. A total of 3901 cases (75.9%) had a positive viral identification and 205 cases (4.1%) were positive for HCoV. Only 41 cases (20%) of HCoV infection were detected as single infections. Episodes of recurrent wheezing were the most common diagnosis, and 112 children (54%) had hypoxia. Clinical data in HCoV cases were similar to those associated with rhinovirus; however, patients with HCoV were younger. Other viruses were associated with hypoxia more frequently than cases with HCoV; high fever was more common in influenza infections and bronchiolitis in respiratory syncytial virus group. Although a slight peak of circulation appears mostly in winter, HCoV has been detected throughout the year as well. CONCLUSIONS HCoV infections represent a small fraction of respiratory infections that require hospitalization in children and their characteristics do not differ greatly from other respiratory viral infections.


title: GANP-mediated recruitment of activation-induced cytidine deaminase to cell nuclei and to immunoglobulin variable region DNA.

text: AID (activation-induced cytidine deaminase) catalyzes transcription-dependent deamination of C --> U in immunoglobulin variable (IgV) regions to initiate somatic hypermutation (SHM) in germinal center B-cells. SHM is essential in generating high affinity antibodies. Here we show that when coexpressed with GANP (germinal center-associated nuclear protein) in COS-7 cells, AID is transported from the cytoplasm and concentrated in the nucleus. GANP forms a complex with AID in cotransfected cells in vivo and in vitro. We have isolated AID mutants that bind with reduced affinity to GANP compared with wild type AID. One of these mutants, AID (D143A) binds GANP with a 10-fold lower affinity compared with wild type AID yet retains substantial C-deamination activity in vitro. Mutant AID (D143A) remains localized predominantly in the cytoplasm when coexpressed with GANP. Exogenous expression of GANP in Ramos B-cells promotes binding of AID to IgV DNA and mRNA and increases SHM frequency. These data suggest that GANP may serve as an essential link required to transport AID to B-cell nuclei and to target AID to actively transcribed IgV regions.


New WHO guidelines on emergency triage assessment and treatment.


title: Quantitative modeling of virus evolutionary dynamics and adaptation in serial passages using empirically inferred fitness landscapes.

text: We describe a stochastic virus evolution model representing genomic diversification and within-host selection during experimental serial passages under cell culture or live-host conditions. The model incorporates realistic descriptions of the virus genotypes in nucleotide and amino acid sequence spaces, as well as their diversification from error-prone replications. It quantitatively considers factors such as target cell number, bottleneck size, passage period, infection and cell death rates, and the replication rate of different genotypes, allowing for systematic examinations of how their changes affect the evolutionary dynamics of viruses during passages. The relative probability for a viral population to achieve adaptation under a new host environment, quantified by the rate with which a target sequence frequency rises above 50%, was found to be most sensitive to factors related to sequence structure (distance from the wild type to the target) and selection strength (host cell number and bottleneck size). For parameter values representative of RNA viruses, the likelihood of observing adaptations during passages became negligible as the required number of mutations rose above two amino acid sites. We modeled the specific adaptation process of influenza A H5N1 viruses in mammalian hosts by simulating the evolutionary dynamics of H5 strains under the fitness landscape inferred from multiple sequence alignments of H3 proteins. In light of comparisons with experimental findings, we observed that the evolutionary dynamics of adaptation is strongly affected not only by the tendency toward increasing fitness values but also by the accessibility of pathways between genotypes constrained by the genetic code.


title: Isolation of chicken astrovirus from specific pathogen-free chicken embryonated eggs.

text: Astroviruses have been associated with enteric disorders in many animal species, including chickens. Here, we describe the isolation, propagation, and pathological characteristics of chicken astrovirus (CAstV) in specific pathogen free (SPF) chicken embryonated eggs (CEE) from chickens with diarrhea and runting-stunting syndrome. The CEE were inoculated via the yolk sac route. Viral confirmation was carried out using PCR techniques and transmission electron microscopy negative staining with ammonium molybdate. The intestinal contents were screened for CAstV, and differential diagnostic testing was performed for avian nephritis virus, avian rotavirus, avian reovirus, chicken parvovirus, infectious bronchitis virus, and fowl adenovirus Group I to detect co-infection with other infectious agents. Seven- or 14-day-old CEEs presented with hemorrhages, edema, a gelatinous aspect, deformities, and dwarfism. The supporting membranes did not show any alterations. Here, we have described the isolation of CAstV and its pathological characteristics in SPF CEE.


title: Single-incision versus conventional laparoscopic sigmoid colectomy: a case-matched series.

text: BACKGROUND Single-incision laparoscopic surgery is an emerging modality that has proven to be safe and feasible for colon resection in multiple case reports and series. Nonetheless, comparative analyses with established techniques are limited in the published literature. We evaluated the efficacy of single-incision laparoscopic colectomy (SILC) for the treatment of sigmoid disease through a matched-case comparison with conventional laparoscopic colectomy (CLC). METHODS Twenty patients who underwent single-incision laparoscopic sigmoid resection for benign or malignant disease between July 2009 and September 2010 were matched to patients who underwent conventional laparoscopic sigmoid colectomy. Demographic, intraoperative, and postoperative data were assessed. RESULTS Twenty SILC and CLC cases each were paired based on gender (p < 1.0), age (p < 0.47), pathology (p < 1.0), and surgical procedure (p < 1.0). Ten patients (50%) in the SILC group and eight patients (40%) in the CLC group had a history of prior abdominal surgery (p < 0.53). There were no conversions to open surgery; however, one SILC procedure (5%) required conversion to CLC (p < 0.31). There was no significant difference in mean operating time between groups (p < 0.80). Mean estimated blood loss was significantly lower for SILC compared to CLC (p < 0.007). Mean lymph node extraction was comparable between groups in the subset of patients with malignant disease (p < 0.68). Two postoperative complications were encountered in each group. The mean length of hospital stay for SILC and CLC was 3.2 ± 1.0 and 3.8 ± 2.1 days, respectively (p < 0.25). There were no readmissions or reoperative interventions in either group. CONCLUSION Compared with conventional laparoscopic technique, single-incision laparoscopic surgery results in similar intraoperative and postoperative outcomes. The technique avoids use of multiple trocar sites and may safely be performed in patients with a history of previous abdominal surgery while maintaining a short length of hospital stay and low complication rate.


Tackling the threat of COVID-19 in Africa: an urgent need for practical planning.


title: Predictive performance of a new pharmacokinetic model for propofol in underweight patients during target-controlled infusion.

text: BACKGROUND In a previous study, the modified Marsh and Schnider models respectively showed negatively- and positively-biased predictions in underweight patients. To overcome this drawback, we developed a new pharmacokinetic propofol model-the Choi model-for use in underweight patients. In the present study, we evaluated the predictive performance of the Choi model. METHODS Twenty underweight patients undergoing elective surgery received propofol via TCI using the Choi model. The target effect-site concentrations (Ces) of propofol were 2.5, 3, 3.5, 4, 4.5, and 2 μg/mL. Arterial blood samples were obtained at least 10 minutes after achieving pseudo-steady-state. Predicted propofol concentrations with the modified Marsh, Schnider, and Eleveld pharmacokinetic models were obtained by simulation (Asan pump, version 2.1.3; Bionet Co. Ltd., Seoul, Korea). The predictive performance of each model was assessed by calculation of four parameters: inaccuracy, divergence, bias, and wobble. RESULTS A total of 119 plasma samples were used to determine the predictive performance of the Choi model. Our evaluation showed that the pooled median (95% CI) bias and inaccuracy were 4.0 (-4.2 to 12.2) and 23.9 (17.6-30.3), respectively. The pooled biases and inaccuracies of the modified Marsh, Schnider, and Eleveld models were clinically acceptable. However, the modified Marsh and Eleveld models consistently produced negatively biased predictions in underweight patients. In particular, the Schnider model showed greater inaccuracy at a target Ce ≥ 3 µg/mL. CONCLUSION The new propofol pharmacokinetic model (the Choi model) developed for underweight patient showed adequate performance for clinical use.


title: Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China.

text: UNLABELLED Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been identified in bats in China, Europe, and Africa, most have a genetic organization significantly distinct from human/civet SARS CoVs in the receptor-binding domain (RBD), which mediates receptor binding and determines the host spectrum, resulting in their failure to cause human infections and making them unlikely progenitors of human/civet SARS CoVs. Here, a viral metagenomic analysis of 268 bat rectal swabs collected from four counties in Yunnan Province has identified hundreds of sequences relating to alpha- and betacoronaviruses. Phylogenetic analysis based on a conserved region of the RNA-dependent RNA polymerase gene revealed that alphacoronaviruses had diversities with some obvious differences from those reported previously. Full genomic analysis of a new SARS-like CoV from Baoshan (LYRa11) showed that it was 29,805 nucleotides (nt) in length with 13 open reading frames (ORFs), sharing 91% nucleotide identity with human/civet SARS CoVs and the most recently reported SARS-like CoV Rs3367, while sharing 89% with other bat SARS-like CoVs. Notably, it showed the highest sequence identity with the S gene of SARS CoVs and Rs3367, especially in the RBD region. Antigenic analysis showed that the S1 domain of LYRa11 could be efficiently recognized by SARS-convalescent human serum, indicating that LYRa11 is a novel virus antigenically close to SARS CoV. Recombination analyses indicate that LYRa11 is likely a recombinant descended from parental lineages that had evolved into a number of bat SARS-like CoVs. IMPORTANCE Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been discovered in bats worldwide, there are significant different genic structures, particularly in the S1 domain, which are responsible for host tropism determination, between bat SARS-like CoVs and human SARS CoVs, indicating that most reported bat SARS-like CoVs are not the progenitors of human SARS CoV. We have identified diverse alphacoronaviruses and a close relative (LYRa11) to SARS CoV in bats collected in Yunnan, China. Further analysis showed that alpha- and betacoronaviruses have different circulation and transmission dynamics in bat populations. Notably, full genomic sequencing and antigenic study demonstrated that LYRa11 is phylogenetically and antigenically closely related to SARS CoV. Recombination analyses indicate that LYRa11 is a recombinant from certain bat SARS-like CoVs circulating in Yunnan Province.


title: Impact of lockdown measures during COVID-19 on air quality- A case study of India.

text: A novel infectious coronavirus disease (COVID-19) identified in late 2019 has now been labelled as a global pandemic by World Health Organization (WHO). The COVID-19 outbreak has shown some positive impacts on the natural environment. In present work, India is taken as a case study to evaluate the effect of lockdown on air quality of three Indian cities. The variation in concentration of key air pollutants including [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] during two phases, pre-lockdown and post-lockdown phases, was analysed. The concentration of [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] reduced by 55%, 49%, 60% and 19%, and 44%, 37%, 78% and 39% for Delhi and Mumbai, respectively, during post-lockdown phase. Overall, the findings in present study may provide confidence to the stakeholders involved in air quality policy development that a significant improvement in air quality can be achieved in future if better pollution control plans are strictly executed.


title: The CDK inhibitor p57Kip2 enhances the activity of the transcriptional coactivator FHL2.

text: The eukaryotic cell cycle is negatively regulated by cyclin-dependent kinase inhibitors (CKIs). p57Kip2 is a member of the Cip/Kip family of CKIs and frequently inactivated by genomic mutations associated with human overgrowth disorders. There is increasing evidence for p57 to control cellular processes in addition to cell cycle and CDK regulation including transcription, apoptosis, migration or development. In order to obtain molecular insights to unknown functions of p57, we performed a protein interaction screen. We identified the transcription regulator four-and-a-half LIM-only protein 2 (FHL2) as a novel p57-binding protein. Co-immunoprecipitation and reporter gene assays were used to elucidate the physiological and functional relevance of p57/FHL2 interaction. We found in cancer cells that endogenous p57 and FHL2 are in a complex. We observed a substantial induction of established FHL2-regulated gene promoters by p57 in reporter gene experiments and detected strong induction of the intrinsic transactivation activity of FHL2. Treatment of cells with histone deacetylase (HDAC) inhibitors and binding of exogenous FHL2 to HDACs indicated repression of FHL2 transcription activity by HDACs. In the presence of the HDAC inhibitor sodium butyrate activation of FHL2 by p57 is abrogated suggesting that p57 shares a common pathway with HDAC inhibitors. p57 competes with HDACs for FHL2 binding which might partly explain the mechanism of FHL2 activation by p57. These results suggest a novel function of p57 in transcription regulation.


title: Video-assisted thoracoscopic surgery right upper posterior segmentectomywith systemic mediastinal lymph node dissection.

text: Video-assisted thoracoscopic surgery (VATS) segmentectomy is a promising treatment option for rigorously selected patients with earlystage non-small cell lung cancer. In the presented video, a 66-year-old male with a 1.6 cm suspicious nodule located at the posterior segment of the right upper lobe was treated with anatomic segmentectomy and systemic mediastinal lymph node (LN) dissection successfully.


title: Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study.

text: BACKGROUND The interleukin-23 pathway is implicated genetically and biologically in the pathogenesis of Crohn's disease. We aimed to assess the efficacy and safety of risankizumab (BI 655066, Boehringer Ingelheim, Ingelheim, Germany), a humanised monoclonal antibody targeting the p19 subunit of interleukin-23, in patients with moderately-to-severely active Crohn's disease. METHODS In this randomised, double-blind, placebo-controlled phase 2 study, we enrolled patients at 36 referral sites in North America, Europe, and southeast Asia. Eligible patients were aged 18-75 years, with a diagnosis of Crohn's disease for at least 3 months, assessed as moderate-to-severe Crohn's disease at screening, defined as a Crohn's Disease Activity Index (CDAI) of 220-450, with mucosal ulcers in the ileum or colon, or both, and a Crohn's Disease Endoscopic Index of Severity (CDEIS) of at least 7 (≥4 for patients with isolated ileitis) on ileocolonoscopy scored by a masked central reader. Patients were randomised 1:1:1 using an interactive response system to a double-blind investigational product, and stratified by previous exposure to TNF antagonists (yes vs no). Patients received intravenous 200 mg risankizumab, 600 mg risankizumab, or placebo, at weeks 0, 4, and 8. The primary outcome was clinical remission (CDAI <150) at week 12 (intention-to-treat population). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02031276. FINDINGS Between March, 2014, and September, 2015, 213 patients were screened, and 121 patients randomised. At baseline, 113 patients (93%) had been previously treated with at least one tumour necrosis factor (TNF) antagonist (which had failed in 96 [79%]). At week 12, 25 (31%) of 82 risankizumab patients (pooled 41 patients in 200 mg and 41 patients in 600 mg arms) had clinical remission versus six (15%) of 39 placebo patients (difference vs placebo 15·0%, 95% CI 0·1 to 30·1; p=0·0489). Ten (24%) of 41 patients who received 200 mg risankizumab had clinical remission (9·0%, -8·3 to 26·2; p=0·31) and 15 (37%) of 41 who received the 600 mg dose (20·9%, 2·6 to 39·2; p=0·0252). 95 (79%) patients had adverse events (32 in the placebo group, 32 randomised to 200 mg risankizumab, 31 randomised to 600 mg risankizumab); 18 had severe adverse events (nine, six, three); 12 discontinued (six, five, one); 24 had serious adverse events (12, nine, three). The most common adverse event was nausea and most common serious adverse event was worsening of underlying Crohn's disease. No deaths occurred. INTERPRETATION In this short-term study, risankizumab was more effective than placebo for inducing clinical remission in patients with active Crohn's disease. Therefore, selective blockade of interleukin-23 via inhibition of p19 might be a viable therapeutic approach in Crohn's disease. FUNDING Boehringer Ingelheim.


title: Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience.

text: BACKGROUND The effects of convalescent plasma (CP) infusion, one of the treatment options for severe Middle East respiratory syndrome coronavirus (MERS-CoV) infections, have not yet been evaluated. METHODS Serological responses of CP-infused MERS patients during the 2015 Korean MERS outbreak at a tertiary care centre were evaluated. Serological activity was evaluated with anti-MERS-CoV enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)G, ELISA IgA, immunofluorescence assay IgM and plaque reduction neutralization test (PRNT). Donor plasma and one or two recipient's serum samples per week of illness including one taken the day after each CP infusion were evaluated. For sensitivity and specificity analysis of ELISA IgG in predicting neutralization activity, a data set of 138 previously evaluated MERS-CoV-infected patients was used. RESULTS Three of thirteen MERS patients with respiratory failure received four CP infusions from convalesced MERS-CoV-infected patients, and only two of them showed neutralizing activity. Donor plasma with a PRNT titre 1:80 demonstrated meaningful serological response after CP infusion, while that with a PRNT titre 1:40 did not. ELISA IgG predicted neutralization activity of a PRNT titre ≥1:80 with more than 95% specificity at a cutoff optical density (OD) ratio of 1.6, and with 100% specificity at an OD ratio of 1.9. CONCLUSIONS For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used. ELISA IgG could substitute for the neutralization test in resource-limited situations.


title: Comparing endoscopic ultrasound-guided core biopsies of solid pancreatic and extrapancreatic lesions: a large single-operator experience with a new fine-needle biopsy needle.

text: Background There has been a paradigm shift in tertiary centers from endoscopic ultrasound (EUS) fine-needle aspiration to EUS fine-needle biopsy (EUS-FNB) for tissue acquisition in solid lesions. While data exists on the use of FNB needles in solid pancreatic lesions, very few studies looked at the utility of FNB in solid extrapancreatic lesions. Our aim was to study and compare the technical success and feasibility of EUS-FNB in evaluating solid pancreatic and extrapancreatic lesions using a novel FNB needle. Methods We performed a retrospective cohort study of patients with solid masses or lesions needing EUS-guided core biopsy at the University of Utah between May 2016 and November 2017. All core biopsies were obtained using an Acquire™Fine Needle Biopsy Device (Boston Scientific Corporation, Natick MA, USA). Rapid on-site evaluation was performed by a board-certified cytopathologist in all cases. Results One hundred thirty-two patients (87 male) were included. Ninety-nine (73.3%) of the lesions were located in the pancreas. All needle sizes (19 G, 22 G and 25 G) had similar yield. The mean number of passes needed was 2.28±0.7. EUS-FNB of the pancreatic lesions had a diagnostic accuracy of 97.9%, comparable to the 97.2% for the biopsied extra-pancreatic lesions. Only 3 of 132 cases needed re-biopsy at a later date. No immediate adverse events were reported. Conclusion In this large, single-center study, EUS-FNB with a novel Franseen-design needle was proven to be an effective modality for tissue acquisition from both pancreatic and extrapancreatic solid lesions.


title: Methicillin-resistant staphylococcus aureus screening and eradication in the surgical intensive care unit: Is it worth it?

text: BACKGROUND The problem of intensive care unit methicillin-resistant Staphylococcus aureus (MRSA) infections has led to routine surveillance and eradication strategies. METHODS Our surgical intensive care unit (SICU) admissions receive MRSA nares cultures and if positive are isolated followed by eradication treatment. This strategy was retrospectively reviewed. RESULTS Our nares-positive culture rate was 21% (30/145), and the sputum positive (sputum+) rate was 18% (26/145). Positive nares culture (Nares+) was eradicated in 63%. The rate of sputum+ in Nares+ patients was 36% (9/25). The rate of sputum+ in Nares- was 10% (12/115; P = .003). The sputum+ SICU length of stay (LOS) (18 ± 12 days in 23 S+ patients) is longer than in sputum- (10 ± 9 days in 69 S-patients, P = .0002). CONCLUSIONS This SICU has high rates of both nares and sputum MRSA cultures. Our data suggest eradicating nares colonization may prevent pneumonia and might decrease SICU LOS.


title: Viral deubiquitinases: role in evasion of anti-viral innate immunity.

text: Host anti-viral innate-immune signalling pathways are regulated by a variety of post-translation modifications including ubiquitination, which is critical to regulate various signalling pathways for synthesis of anti-viral molecules. A homeostasis of host immune responses, induced due to viral infection and further ubiquitination, is maintained by the action of deubiquitinases (DUB). Infecting viruses utilize the process of deubiquitination for tricking host immune system wherein viral DUBs compete with host DUBs for inhibition of innate-immune anti-viral signalling pathways, which instead of maintaining an immune homeostasis bring about virus-mediated pathogenesis. This suggests that viruses co-evolve with their hosts to acquire similar machinery for tricking immune surveillance and establishing infection.


title: Access to Endovascular Treatment in Remote Areas: Analysis of the Reperfusion Treatment Registry of Catalonia.

text: BACKGROUND AND PURPOSE Since demonstration of the benefit of endovascular treatment (EVT) in acute ischemic stroke patients with proximal arterial occlusion, stroke care systems need to be reorganized to deliver EVT in a timely and equitable way. We analyzed differences in the access to EVT by geographical areas in Catalonia, a territory with a highly decentralized stroke model. METHODS We studied 965 patients treated with EVT from a prospective multicenter population-based registry of stroke patients treated with reperfusion therapies in Catalonia, Spain (SONIIA). Three different areas were defined: (A) health areas primarily covered by Comprehensive Stroke Centers, (B) areas primarily covered by local stroke centers located less than hour away from a Comprehensive Stroke Center, and (C) areas primarily covered by local stroke centers located more than hour away from a Comprehensive Stroke Center. We compared the number of EVT×100 000 inhabitants/year and time from stroke onset to groin puncture between groups. RESULTS Baseline characteristics were similar between groups. Throughout the study period, there were significant differences in the population rates of EVT across geographical areas. EVT rates by 100 000 in 2015 were 10.5 in A area, 3.7 in B, and 2.7 in C. Time from symptom onset to groin puncture was 82 minutes longer in group B (312 minutes [245-435]) and 120 minutes longer in group C (350 minutes [284-408]) compared with group A (230 minutes [160-407]; P<0.001). CONCLUSIONS Accessibility to EVT from remote areas is hampered by lower rate and longer time to treatment compared with areas covered directly by Comprehensive Stroke Centers.


title: Changing practice patterns: the impact of a randomized clinical trial on surgeons preference for treatment of type 3 supracondylar humerus fractures.

text: BACKGROUND A recent prospective randomized clinical trial (RCT) for comparison of medial and lateral entry pins with lateral entry pins for treatment of Gartland type 3 supracondylar humerus fractures (SCHF) was published, validating the national trend toward treatment of this injury with only lateral entry pins. But have surgeons actually changed their practice as a result of these recent data? The purpose of this study was to compare pin configuration, loss of reduction and rate of nerve injuries before and after the RCT. METHODS This was a retrospective review of patients with Gartland type 3 SCHF who were treated before the RCT (April 2000 to April 2003: 141 patients) and after the trial (April 2006 to April 2009: 126 patients). Eight surgeons were included. Patient demographic data, pin configuration, neurovascular status, and radiographic results were compared. Comparisons between the pretrial cohort and the posttrial cohort as a group as well as for each individual surgeon were performed. Comparisons included the choice of pin configuration, incidence of loss of radiographic reduction, iatrogenic nerve injuries, return to the operating room, and infection before and after the clinical trial. RESULTS There was a statistically different pin configuration in the pretrial group compared with the posttrial group (P<0.0001) with the posttrial group having a much higher percentage of bicolumnar lateral entry only pins. Five out of 8 surgeons individually had a statistically significant change in their practice pattern for pin configuration. There was no difference from pretrial to posttrial in loss of radiographic reduction, infection rate, iatrogenic nerve injuries, or return to the operating room. CONCLUSIONS Data showing change in surgeon practice have been relatively sparse. In this group of surgeons who participated in an RCT, there was a statistically significant change in pin configuration for treatment of Gartland type 3 SCHF after the results of the RCT were known. The change in clinical practice did not have an effect on outcomes. LEVEL OF EVIDENCE Level III.


title: Learning curve of transumbilical single incision laparoscopic cholecystectomy (SILS): a preliminary study of 80 selected patients with benign gallbladder diseases.

text: BACKGROUND Transumbilical single incision laparoscopic surgery (SILS) is a new laparoscopic procedure in which only one transumbilical incision is made, demonstrated as a scarless procedure. Here we report a single-center preliminary experience of transumbilical single incision laparoscopic cholecystectomy (SILC) in the treatment of benign gallbladder diseases, defining a single surgeon's learning curve. METHODS A total of 80 patients underwent SILC successfully by a single experienced laparoscopic surgeon. The operation was performed following the routine LC procedure. Then the perioperative demographics were recorded and the operative time was used to define the learning curve. RESULTS The study group included 27 male and 53 female patients with gallstones (56 cases), cholesterol polyps (16 cases), an adenomatous polyp (3 cases), adenomyomatosis (1 case), or complex diseases (4 cases), and all consented to undergo SILC. No patient was converted to normal LC or open surgery. There were no perioperative port-related or surgical complications. The average operative time was 46.9 ± 14.6 min. The average postoperative hospital stay was 1.8 ± 1.3 days. The learning curve of the SILC procedures for this series of selected patients confirmed that SILC is a feasible, safe, and effective approach to the treatment of benign gallbladder diseases. CONCLUSIONS For experienced laparoscopic surgeons, SILC is an easy and safe procedure. Patients benefit from milder pain, a lower incidence of port-related complications, better cosmesis, and fast recovery. The SILC procedure may become another option for the treatment of benign gallbladder diseases for selected patients.


Protecting society. Biological security and dual-use dilemma in the life sciences--status quo and options for the future.


title: Equid herpesvirus type 4 uses a restricted set of equine major histocompatibility complex class I proteins as entry receptors.

text: Equid herpesvirus type 1 (EHV-1) was shown to use an unusual receptor for cellular entry - MHC-I molecules. Here, we demonstrated that the closely related EHV, EHV-4, also uses this strategy for cellular invasion, both in equine cells in culture and in the heterologous, non-permissive murine mastocytoma cell line (P815) after stable transfection with horse MHC-I genes. Using a panel of P815 cell lines transfected with individual horse MHC-I genes, we provided support for the hypothesis that EHV-1 and EHV-4 target classical polymorphic MHC-I molecules as viral entry receptors. All known equine MHC-I molecules from the two principal classical polymorphic loci specify alanine at position 173 (A173), whilst other MHC-I loci encoded different amino acids at this position and did not permit viral entry. Site-directed mutagenesis of position 173 diminished or enhanced viral entry, depending upon the initial amino acid. However, there were other, as yet undefined, constraints to this process: MHC-I genes from two non-classical loci carried A173 but did not enable viral entry in P815 transfectants. Our study suggested that the capacity to bind MHC-I molecules arose in the common ancestor of EHV-1 and EHV-4. The widespread occurrence of A173 in classical polymorphic horse MHC-I molecules indicated that horses of most MHC haplotypes should be susceptible to infection via this entry portal.


title: Perceived vaccination status in ecotourists and risks of anthropozoonoses.

text: Anthropozoonotic (human to nonhuman animal) transmission of infectious disease poses a significant threat to wildlife. A large proportion of travelers to tropical regions are not protected against vaccine-preventable illnesses, and a majority of these travelers demonstrate poor recall of actual vaccination status. Here we characterize self-perceived vaccination status among a large sample of ecotourists at the Sepilok Orangutan Rehabilitation Centre, Sabah, Malaysia. Despite their recognized travel itinerary to view endangered animals, tourists at wildlife sanctuaries are not adequately protected against vaccine-preventable illnesses. Of 633 surveys, over half reported being currently vaccinated against tuberculosis, hepatitis A, hepatitis B, polio, and measles. Fewer participants reported current vaccination status for influenza, rabies, and chickenpox. Despite the fact that the majority of visitors to Sepilok are from temperate regions where influenza is relatively more prevalent, 67.1% of those surveyed with medical-related occupations reported not being currently vaccinated for influenza. Ecotourists concerned about environmental protection are themselves largely unaware of their potential contribution to the spread of diseases to animals. The risks of negatively affecting animal populations must be communicated to all concerned parties, and this may begin by urging travelers to examine their actual vaccination status, particularly as the ecotourism industry continues its rapid expansion, and is seen increasingly as a possible tool to save great ape populations from extinction.


title: Time-series analysis of the relationship of antimicrobial use and hand hygiene promotion with the incidence of healthcare-associated infections.

text: We analyzed the effect of antimicrobial use and implementation of a hand hygiene program on the incidence of healthcare-associated infections (HAIs) and healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) infections at the Chung Shan Medical University Hospital (Taichung, Taiwan). Monthly data were retrospectively reviewed from January 2004 to December 2010. Use of antimicrobials and alcohol-based hand cleaner were separately regressed against the incidences of HAIs and HA-MRSA infections. Infection incidence was expressed as persons per 1000 patient days (PDs), monthly use of i.v. antibiotics was expressed as defined daily doses per 1000 PDs and monthly alcohol-based hand cleaner use was expressed as bottle per 1000 PDs. Multivariate analysis indicated that use of hand cleaner was associated with reduced incidence of HAIs (P=0.0001) and HA-MRSA infections (P<0.0001). Time-series analysis indicated that increased use of hand cleaner was significantly associated with significant decreases in the incidences of HAIs and HA-MRSA infections. Total antibiotic use had no significant effect on HAIs, but was associated with more HA-MRSA infections. In addition, the use of J01CR01 antibiotics (combinations of penicillins, including β-lactamase inhibitors) in particular was correlated with significantly increased incidence of HA-MRSA infections. Our forecasting model demonstrates the efficacy of a hand hygiene program and the need to limit the use of certain restricted antimicrobials in order to reduce the incidence of HAIs and HA-MRSA infections.


title: P2Y6 receptor inhibition aggravates ischemic brain injury by reducing microglial phagocytosis.

text: INTRODUCTION Clearance of damaged cells and debris is beneficial for the functional recovery after ischemic brain injury. However, the specific phagocytic receptor that mediates microglial phagocytosis after ischemic stroke is unknown. AIM To investigate whether P2Y6 receptor-mediated microglial phagocytosis is beneficial for the debris clearance and functional recovery after ischemic stroke. RESULTS The expression of the P2Y6 receptor in microglia increased within 3 days after transient middle cerebral artery occlusion. Inhibition of microglial phagocytosis by the selective inhibitor MRS2578 enlarged the brain atrophy and edema volume after ischemic stroke, subsequently aggravated neurological function as measured by modified neurological severity scores and Grid walking test. MRS2578 treatment had no effect on the expression of IL-1α, IL-1β, IL-6, IL-10, TNF-α, TGF-β, and MPO after ischemic stroke. Finally, we found that the expression of myosin light chain kinase decreased after microglial phagocytosis inhibition in the ischemic mouse brain, which suggested that myosin light chain kinase was involved in P2Y6 receptor-mediated phagocytosis. CONCLUSION Our results indicate that P2Y6 receptor-mediated microglial phagocytosis plays a beneficial role during the acute stage of ischemic stroke, which can be a therapeutic target for ischemic stroke.


title: Structural and Mechanistic Insights into Protein Translocation.

text: Many proteins are translocated across the endoplasmic reticulum (ER) membrane in eukaryotes or the plasma membrane in prokaryotes. These proteins use hydrophobic signal sequences or transmembrane (TM) segments to trigger their translocation through the protein-conducting Sec61/SecY channel. Substrates are first directed to the channel by cytosolic targeting factors, which use hydrophobic pockets to bind diverse signal and TM sequences. Subsequently, these hydrophobic sequences insert into the channel, docking into a groove on the outside of the lateral gate of the channel, where they also interact with lipids. Structural data and biochemical experiments have elucidated how channel partners, the ribosome in cotranslational translocation, and the eukaryotic ER chaperone BiP or the prokaryotic cytosolic SecA ATPase in posttranslational translocation move polypeptides unidirectionally across the membrane. Structures of auxiliary components of the bacterial translocon, YidC and SecD/F, provide additional insight. Taken together, these recent advances result in mechanistic models of protein translocation.


title: Perspective on COVID-19: Finally, Telemedicine at Center Stage.

text: The new world order caused by COVID-19 virus, associated with severe acute respiratory syndrome, multiple organ failure, and very high mortality, has brought about many changes to our world. Suddenly, the medical community, and those who finance the health care sector, realized that telemedicine and telepresence are applicable, desirable, acceptable, and much sought after by our patients and we can manage just about every disease and condition. Although, by and large, telemedicine has faced challenges and perhaps some resistance, despite its great potential, it has become evident that telemedicine can provide rapid, safe, and high-quality care remotely during this pandemic, the largest one since 1918. Perhaps one benefit of suffering through the COVID-19 pandemic will be the establishment of a new virtual medical world order, and that telemedicine has taken its deserving place in health care: prime time and a center stage.


title: COVID-19, Australia: Epidemiology Report 3 (Reporting week ending 19:00 AEDT 15 February 2020).

text: This is the third epidemiological report for coronavirus disease 2019 (COVID-19), previously known as novel coronavirus (2019-nCoV), from the virus now known as SARS-CoV-2, reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 15 February 2020. It includes data on the COVID-19 Australian cases, the international situation and current information on the severity, transmission and spread.


title: The impact of COVID-19 related lockdown on ophthalmology training programs in India - Outcomes of a survey.

text: Purpose In 2020, in response to the emergence and global spread of the disease COVID-19, caused by a new variant of coronavirus 2019-nCoV, the government of India ordered a nationwide lockdown for 21 days, which was then extended to a total of over 50 days. The aim of this study is to assess the effect of the lockdown on ophthalmic training programs across India. Methods An online survey was sent across to trainee ophthalmologists across India through various social media platforms. Results In all, 716 trainees responded; the average age was 29.1 years. Results showed that majority of the respondents were enrolled in residency programs (95.6%; 685/716) and the others were in fellowship programs. About 24.6% (176/716) of the trainees had been deployed on 'COVID-19 screening' duties. Nearly 80.7% (578/716) of the trainees felt that the COVID-19 lockdown had negatively impacted their surgical training. Furthermore, 54.8% (392/716) of the trainees perceived an increase in stress levels during the COVID-19 lockdown and 77.4% (554/716) reported that their family members had expressed an increased concern for their safety and wellbeing since the lockdown began. In all, 75.7% (542/716) of the respondents felt that online classes and webinars were useful during the lockdown period. Conclusion Our survey showed that majority ophthalmology trainees across the country felt that the COVID-19 lockdown adversely affected their learning, especially surgical training. While most found online classes and webinars useful, the trainees' perceived stress levels were higher than normal during the lockdown. Training hospitals should take cognizance of this and reassure trainees; formulate guidelines to augment training to compensate for the lost time as well as mitigate the stress levels upon resumption of regular hospital services and training. Going ahead, permanent changes such as virtual classrooms and simulation-based training should be considered.


What If I Told You the COVID-19 Pandemic Is Not Entirely Bad?


title: In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses.

text: Background/Aims As the coronavirus disease-2019 global pandemic progresses, screening of antiviral agents effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed. In addition, considering the viral load kinetics of SARS-CoV-2, which peaks early in the illness, and the massive burden of the disease, which may increase in the near future, identifying well-tolerated oral antivirals becomes increasingly important. We examined the in vitro activity of lopinavir/ritonavir and hydroxychloroquine on SARS-CoV-2, at concentrations which can be used to treat coronavirus-19 patients with little concern of toxicity. Methods Lopinavir/ritonavir (7/1.75 μg/mL), hydroxychloroquine base (1 or 2 μg/mL), or a combination thereof were administered 1 hour after the inoculation of SARS-CoV-2 to Vero cells at a multiplicity of infection of 0.05. We examined cytopathic effects of virus 48 hours after administration of the respective treatments and measured viral loads at three time points (0, 24, and 48 hours post-treatment) by quantitative real-time reverse-transcription polymerase chain reaction, and compared the results obtained from the different antiviral regimens tested. Results The severity of cytopathic effects was lower in lopinavir/ritonavir-treated cells, and viral load was significantly reduced in this group compared with the control group (p < 0.001). However, hydroxychloroquine did not show significant inhibitory effects on anti-SARS-CoV-2-mediated cytotoxicity or on viral load at either concentration. Conclusions Lopinavir/ritonavir showed significant inhibitory effects on SARS-CoV-2 in vitro at its usual plasma concentration. However, the in vitro antiviral activity of hydroxychloroquine at concentrations commonly used in humans was minimal, whether used alone or in combination with lopinavir/ritonavir.


title: Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells.

text: TRAIL (TNF-related apoptosis inducing ligand) is a promising anti-cancer drug target that selectively induces apoptosis in cancer cells. However, many cancer cells are resistant to TRAIL-induced apoptosis. Therefore, reversing TRAIL resistance is an important step for the development of effective TRAIL-based anti-cancer therapies. We previously reported that knockdown of the TOR signaling pathway regulator-like (TIPRL) protein caused TRAIL-induced apoptosis by activation of the MKK7-c-Jun N-terminal Kinase (JNK) pathway through disruption of the MKK7-TIPRL interaction. Here, we identified Taraxacum officinale F.H. Wigg (TO) as a novel TRAIL sensitizer from a set of 500 natural products using an ELISA system and validated its activity by GST pull-down analysis. Furthermore, combination treatment of Huh7 cells with TRAIL and TO resulted in TRAIL-induced apoptosis mediated through inhibition of the MKK7-TIPRL interaction and subsequent activation of MKK7-JNK phosphorylation. Interestingly, HPLC analysis identified chicoric acid as a major component of the TO extract, and combination treatment with chicoric acid and TRAIL induced TRAIL-induced cell apoptosis via JNK activation due to inhibition of the MKK7-TIPRL interaction. Our results suggest that TO plays an important role in TRAIL-induced apoptosis, and further functional studies are warranted to confirm the importance of TO as a novel TRAIL sensitizer for cancer therapy. © 2015 Wiley Periodicals, Inc.


title: Mind and Brain: Consciousness in Unresponsive Subjects.

text: A new study shows that subjects rendered unresponsive with sedatives do not exhibit a stereotypic 'unconscious' response to direct cortical stimulation; instead, agent-specific effects are seen that can distinguish between unresponsiveness with and without consciousness.


Covid-19: how a virus is turning the world upside down.


NS1 is the fluid for "flu-transmission".


title: Impact of procedural time on clinical and angiographic outcomes in patients with acute ischemic stroke receiving endovascular treatment.

text: BACKGROUND Procedural time in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy may affect clinical outcomes. We performed a pooled analysis of the effect of procedural time on clinical outcomes using data from three prospective endovascular treatment trials. OBJECTIVE To examine the relationship between endovascular procedural time and clinical outcomes of patients with AIS following endovascular treatment. METHODS We analyzed data from SWIFT, STAR, and SWIFT PRIME studies, including baseline characteristics: National Institutes of Health Stroke Scale (NIHSS) score on admission, intracranial hemorrhage rates, and modified Rankin Scale score at 3 months. The Thrombolysis in Cerebral Infarction (TICI) scale was used to grade postprocedure recanalization. We recorded two procedural time intervals: (1) symptom onset to groin puncture and (2) groin puncture to angiographic recanalization. A multivariate analysis was performed using a logistic regression model to analyze predictors of unfavorable outcome. RESULTS We analyzed 301 patients who had undergone endovascular treatment and had near-complete or complete recanalization (TICI 2b or 3). At 3 months, 122 patients (40.5%) had unfavorable outcomes. The rate of favorable outcomes was significantly higher when the procedural time was <60 min compared with ≥60 min (62% vs 45%, p=0.020). Predictors of unfavorable outcome at 3 months were age (unit 10 years, OR=0.62, 95% CI 0.46 to 0.82, p<0.001), onset to groin puncture time (unit hour, OR=0.61, 95% CI 0.48 to 0.77, p<0.001), groin puncture to recanalization (unit 10 min, OR=0.89, 95% CI 0.80 to 0.99, p=0.032), baseline NIHSS score (20-28 vs 8-10, OR=0.17, 95% CI 0.05 to 0.62, p=0.018), and collaterals (OR=1.48, 95% CI 1.04 to 2.10, p=0.029). CONCLUSION Procedural time in patients with stroke undergoing mechanical thrombectomy may be an important determinant of favorable outcomes in those with recanalization.


title: Evaluation of a new energy device for parenchymal transection in laparoscopic liver resection.

text: INTRODUCTION THUNDERBEAT (TB) is a novel device that uses both ultrasonic and advanced bipolar energies for hemostasis. Several recent human studies have proved the safety and efficacy of TB in different surgical procedures, but there have been no similar studies about its efficacy in hepatic parenchymal transection. Therefore, the aim of the study was to assess the safety and efficacy of the TB device in laparoscopic liver resection. METHODS This retrospective study compared TB and ultrasonic Harmonic devices in 80 patients who underwent laparoscopic liver resection from 2010 to 2016 in our institution. To reduce the selection bias, the two groups were matched in a 1-to-2 ratio on the basis of propensity scores. RESULTS There were no differences in the preoperative patient characteristics between the two groups. The extent of liver resection was comparable between the groups. Although the Harmonic group's intraoperative blood loss and operative time were less than that of the TB group, the differences were not statistically significant (P = 0.08, P = 0.32, respectively). Postoperative complications, mortality within 90 days, and hospital stay were comparable between the two groups. CONCLUSION TB is as safe and effective for parenchymal transection in laparoscopic hepatectomy as ultrasonic devices, but it is not a superior alternative.


title: Revival of the identification of cytotoxic T-lymphocyte epitopes for immunological diagnosis, therapy and vaccine development.

text: Immunogenic T-cell epitopes have a central role in the cellular immunity against pathogens and tumors. However, in the early stage of cellular immunity studies, it was complicated and time-consuming to identify and characterize T-cell epitopes. Currently, the epitope screening is experiencing renewed enthusiasm due to advances in novel techniques and theories. Moreover, the application of T-cell epitope-based diagnoses for tuberculosis and new data on epitope-based vaccine development have also revived the field. There is a growing knowledge on the emphasis of epitope-stimulated T-cell immune responses in the elimination of pathogens and tumors. In this review, we outline the significance of the identification and characterization of T-cell epitopes. We also summarize the methods and strategies for epitope definition and, more importantly, address the relevance of cytotoxic T-lymphocyte epitopes to clinical diagnoses, therapy and vaccine development.


title: Initial experience with a new distal intermediate and aspiration catheter in the treatment of acute ischemic stroke: clinical safety and efficacy.

text: PURPOSE To describe our initial experience with the novel 5 F SOFIA (Soft Torqueable catheter Optimized For Intracranial Access) intermediate and aspiration catheter for endovascular treatment of patients with acute ischemic stroke. METHODS A retrospective review was performed in three centers of prospectively collected data of all stroke patients who underwent endovascular therapy using the SOFIA catheter. Patients were enrolled between November 2013 and December 2014. The primary endpoint of the study was accessibility of the thrombus with the SOFIA catheter. As a secondary endpoint, the study assessed recanalization success (Thrombolysis In Cerebral Infarction (TICI) ≥2b). Clinical presentation on admission and discharge was also documented. In addition, catheter- and procedure-related complications (particularly thromboembolic complications) were recorded. RESULTS The SOFIA catheter was used in 115 acute stroke procedures. In 110 cases (96%) the catheter could be advanced to the occlusion site. After mechanical thrombectomy, successful recanalization (TICI ≥2b) was documented in 86.9%. There were no complications related to positioning of the catheter. Distal thrombus migration into a new vascular territory occurred in three patients following thrombectomy with a stent retriever (2.6%). The mean NIH Stroke Scale (NIHSS) score on admission was 16.8±6 and at discharge the mean NIHSS score was 8.2±7.7. Sixteen patients died. CONCLUSIONS The SOFIA catheter is a safe and efficient catheter for endovascular stroke therapy.


title: Are we fully utilizing the functionalities of modern operating room ventilators?

text: PURPOSE OF REVIEW The modern operating room ventilators have become very sophisticated and many of their features are comparable with those of an ICU ventilator. To fully utilize the functionality of modern operating room ventilators, it is important for clinicians to understand in depth the working principle of these ventilators and their functionalities. RECENT FINDINGS Piston ventilators have the advantages of delivering accurate tidal volume and certain flow compensation functions. Turbine ventilators have great ability of flow compensation. Ventilation modes are mainly volume-based or pressure-based. Pressure-based ventilation modes provide better leak compensation than volume-based. The integration of advanced flow generation systems and ventilation modes of the modern operating room ventilators enables clinicians to provide both invasive and noninvasive ventilation in perioperative settings. Ventilator waveforms can be used for intraoperative neuromonitoring during cervical spine surgery. SUMMARY The increase in number of new features of modern operating room ventilators clearly creates the opportunity for clinicians to optimize ventilatory care. However, improving the quality of ventilator care relies on a complete understanding and correct use of these new features. VIDEO ABSTRACT: http://links.lww.com/COAN/A47.


title: From feedback loop transitions to biomarkers in the psycho-immune-neuroendocrine network: Detecting the critical transition from health to major depression.

text: BACKGROUND Biological pathways underlying major depressive disorder (MDD) can be viewed as systems biology networks. The psycho-immune-neuroendocrine (PINE) network comprises central nervous, immune, endocrine and autonomic systems, integrating biological mechanisms of MDD. Such networks exhibit recurrent motifs with specific functions, including positive and negative feedback loops, and are subject to critical transitions, influenced by feedback loop transitions (FLTs). AIMS We aim to identify critical feedback loops and their FLTs, as well sentinel network nodes (SNNs), key network nodes that drive FLTs, within the PINE network. Examples of biomarkers are provided which may reflect early warning signs of impending critical transition to MDD. RESULTS Disruption of homeostatic feedback loops reflects the physiological transition to MDD. Putative FLTs are identified within hypothalamic-pituitary-adrenal (HPA) and sympathetic-parasympathetic axes, the kynurenine pathway, gut function and dysbiosis. CONCLUSIONS Progression from health to disease is driven by FLTs in the PINE network, which is likely to undergo changes characteristic of system instability. Biomarkers of system instability may effectively predict the critical transition to MDD.


title: Expert Opinion on the Management and Follow-up of Uveitis Patients during SARS-CoV-2 Outbreak.

text: INTRODUCTION Routine medical and ophthalmic care is being drastically curtailed in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Uveitis patients require particular attention because of their theoretical risk of viral infection, in the context of therapeutic immunosuppression. AREAS COVERED This collaborative work proposes practical management and follow-up criteria for uveitis patients in the context of the ongoing SARS-CoV-2 pandemic. EXPERT OPINION Management should proceed as usual when access to healthcare is possible in patients who do not belong to a group at high risk of severe SARS-CoV-2 infection; and in uncontrolled uveitis cases. In case of reduced access to eye clinics or high risk of SARS-CoV-2 infection, patients' management should be stratified based on their clinical presentation. In non-severe uveitis cases, the use of systemic steroids should be avoided, and local steroids preferred whenever possible. In uncontrolled situations where there is real risk of permanent visual loss, high-dose intravenous steroids and/or systemic immunosuppressants and/or biotherapies can be administered depending on the severity of eye disease. Immunosuppressive therapy should not be withheld, unless the patient develops SARS-CoV2 infection.


Concerns about injectable naltrexone for opioid dependence.


title: Video. Laparoscopic distal pancreatectomy and splenectomy for splenic artery aneurysm.

text: BACKGROUND Large splenic artery aneurysms are rare but comprise 60% of all visceral artery aneurysms. Most are found incidentally and rupture in the nonpregnant patient has an approximate 25 to 36% mortality rate. Historically these have been managed with an open surgical approach for resection. METHODS We present the case of a 43-year-old man with a recent episode of bacterial endocarditis with an incidental finding of a large 6-cm splenic artery aneurysm. There was noted to be splenic vein occlusion and multiple splenic infarcts versus abscesses on preoperative imaging. There were concerns that this represented a mycotic aneurysm. He underwent laparoscopic en bloc splenic artery aneurysm resection with splenectomy and distal pancreatectomy with preoperative prophylactic balloon catheter placement. RESULTS His large splenic artery aneurysm was adjacent to the splenic hilum. Due to the splenic vein occlusion, there were large collateral vessels complicating the dissection. Additionally, the aneurysm had dense adhesions to the tail of the pancreas from a desmoplastic reaction. To safely remove the aneurysm, a distal pancreatectomy was included with resection of the spleen. The specimen was successfully removed intact using the laparoscopic approach. The patient had an uneventful recovery and was discharged home on postoperative day 2. Final pathology revealed no evidence of bacterial etiology. CONCLUSIONS Laparoscopic distal pancreatectomy with splenectomy is an appropriate minimally invasive option for the treatment of splenic artery aneurysms. This video demonstrates the technical challenges and management options for successfully completing a distal pancreatectomy and splenectomy in the face of a splenic artery aneurysm.


title: Business Intelligence applied to Emergency Medical Services in the Lombardy region during SARS-CoV-2 epidemic.

text: BACKGROUND AND AIM OF THE WORK On the 21st of February, the first patient was tested positive for SARS-CoV-2 at Codogno hospital in the Lombardy region. From that date, the Regional Emergency Medical Services (EMS) Trust (AREU) of the Lombardy region decided to apply Business Intelligence (BI) to the management of EMS during the epidemic. The aim of the study is to assess in this context the impact of BI on EMS management outcomes. METHODS Since the beginning of the COVID-19 outbreak, AREU is using BI daily to track the number of first aid requests received from 112. BI analyses the number of requests that have been classified as respiratory and/or infectious episodes during the telephone dispatch interview. Moreover, BI allows identifying the numerical trend of episodes in each municipality (increasing, stable, decreasing). RESULTS AREU decides to reallocate in the territory the resources based on real-time data recorded and elaborated by BI. Indeed, based on that data, the numbers of vehicles and personnel have been implemented in the municipalities that registered more episodes and where the clusters are supposed to be. BI has been of paramount importance in taking timely decisions on the management of EMS during COVID-19 outbreak. Conclusions: Even if there is little evidence-based literature focused on BI impact within the health care, this study suggests that BI can be usefully applied to promptly identify clusters and patterns of the SARS-CoV-2 epidemic and, consequently, make informed decisions that can improve the EMS management response to the outbreak.


Novel treatment targets for COVID-19: Contribution from molecular psychiatry.


title: The Amyloid-beta rich CNS environment alters myeloid cell functionality independent of their origin.

text: Microglia, the innate immune cells of the central nervous system (CNS) survey their surroundings with their cytoplasmic processes, phagocytose debris and rapidly respond to injury. These functions are affected by the presence of beta-Amyloid (Aβ) deposits, hallmark lesions of Alzheimer's disease (AD). We recently demonstrated that exchanging functionally altered endogenous microglia with peripheral myeloid cells did not change Aβ-burden in a mouse model mimicking aspects of AD at baseline, and only mildly reduced Aβ plaques upon stimulation. To better characterize these different myeloid cell populations, we used long-term in vivo 2-photon microscopy to compare morphology and basic functional parameters of brain populating peripherally-derived myeloid cells and endogenous microglia. While peripherally-derived myeloid cells exhibited increased process movement in the non-diseased brain, the Aβ rich environment in an AD-like mouse model, which induced an alteration of surveillance functions in endogenous microglia, also restricted functional characteristics and response to CNS injury of newly recruited peripherally-derived myeloid cells. Our data demonstrate that the Aβ rich brain environment alters the functional characteristics of endogenous microglia as well as newly recruited peripheral myeloid cells, which has implications for the role of myeloid cells in disease and the utilization of these cells in Alzheimer's disease therapy.


title: Endotracheal bioimpedance cardiography improves immediate postoperative outcome: a case-control study in off-pump coronary surgery.

text: The feasibility and clinical utility of the endotracheal cardiac output monitor (ECOM) to optimize intraoperative hemodynamics and improve short-term outcome in off-pump coronary artery bypass grafting (OPCAB) is unknown. We aimed to compare ECOM with a standard of care in that specific surgical setting. Twenty consecutive adult ECOM-monitored patients undergoing OPCAB were prospectively included (ECOM group) and retrospectively compared to 42 patients scheduled for similar surgery without ECOM monitoring (Control group). The primary endpoint was the global rate of postoperative admission to the intensive care unit (ICU). Secondary endpoints were the time to extubation, the length of stay in ICU and in hospital, the postoperative levels of lactate and troponin and the feasibility of ECOM. The rate of postoperative admission to the ICU was 38/42 (90%) in the Control group versus 11/20 (55%) in the ECOM group, P = 0.008. None unexpected admission for hemodynamic instability was observed in the ECOM group. The time to extubation, the length of stay in ICU, and both troponin level at admission and lactate level at H6 were all significantly decreased in the ECOM group. On a scale ranging from 0 to 5, convenience and satisfaction regarding ECOM were 4.30 ± 1.17 and 3.45 ± 0.68, respectively. The systematic use of ECOM is associated with a significant reduction in the rate of admission to the ICU and an improvement in immediate outcome in OPCAB.


title: Enhancing a sedation score to include truly noxious stimulation: the Extended Observer's Assessment of Alertness and Sedation (EOAA/S).

text: BACKGROUND Although the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) is frequently used in sedation-related drug and device studies, a major shortcoming is that it does not differentiate between lighter and deeper levels of general anaesthesia because the only noxious stimulus of the MOAA/S is a trapezius squeeze. The primary aim of this investigation was to expand the MOAA/S score to include truly noxious stimulation, thereby extending the dynamic range of the assessment to include sedation states consistent with deeper levels of general anaesthesia. METHODS Twenty healthy volunteers received target controlled infusions of fentanyl (target=0.8 ng ml(-1)) and propofol (starting at 0.5 µg ml(-1) and gradually increasing to 5 µg ml(-1)). At each propofol concentration, a MOAA/S score was obtained before and after tetanic electrical stimulation. The tetanic electrical stimulation current was gradually increased until the subject responded or until 50 mA was delivered without a response. A pharmacodynamic model was constructed to characterize the concentration-effect relationship between propofol and the MOAA/S scores. RESULTS All subjects required a significantly higher propofol concentration to produce unresponsiveness to tetanic electrical stimulation at 50 mA compared with a standardized trapezius squeeze. The pharmacodynamic model adequately characterized the concentration-effect relationship. CONCLUSIONS The Extended Observer's Assessment of Alertness and Sedation (or EOAA/S) extends the range of the widely used MOAA/S score to include truly noxious stimulation, thereby enabling the identification of drug-induced central nervous system depression representative of surgical anaesthesia.


title: Disruption of Inferior Longitudinal Fasciculus Microstructure in Parkinson's Disease: A Systematic Review of Diffusion Tensor Imaging Studies.

text: Parkinson's disease (PD) is a neurodegenerative disorder accompanied by a series of pathological mechanisms which contribute to a variety of motor and non-motor symptoms. Recently, there has been an increasing interest in structural diffusion tensor imaging (DTI) in PD which has shed light on our understanding of structural abnormalities underlying PD symptoms or its associations with pathological mechanisms. One of the white matter tracts shown to be disrupted in PD with a possible contribution to some PD symptoms is the inferior longitudinal fasciculus (ILF). On the whole, lower ILF integrity contributes to thought disorders, impaired visual emotions, cognitive impairments such as semantic fluency deficits, and mood disorders. This review outlines the microstructural changes in ILF associated with systemic inflammation and various PD symptoms like cognitive decline, facial emotion recognition deficit, depression, color discrimination deficit, olfactory dysfunction, and tremor genesis. However, few studies have investigated DTI correlates of each symptom and larger studies with standardized imaging protocols are required to extend these preliminary findings and lead to more promising results.


title: High respiratory virus oropharyngeal carriage rate during Kingella kingae osteoarticular infections in children.

text: AIM Kingella kingae osteoarticular (KKO) infections are frequently associated with upper respiratory tract infections. However, no comparative studies detecting respiratory viruses had ever been performed between KKO and non-KKO (NKO). PATIENTS & METHODS Eighteen viruses were searched by FilmArray(®) Respiratory Panel (BioFire Diagnostics, UT, USA) in the oropharynx of 6-to-48-month-children admitted for KKO and NKO in 2013. RESULTS At least one virus was detected in the oropharynx of 19/21 (90.5%) KKO and 3/8 (37.5%) NKO cases (p = 0.008). In KKO group, human rhinovirus was predominant (12/21; 57.1%), especially during winter (7/11; 63.6%) despite its low concomitant circulation (<10%). Human rhinovirus was found in 2/8 (25%) in NKO group. CONCLUSION Higher prevalence of respiratory virus in oropharynx was observed in KKO than NKO, strengthening their putative role in KKO pathophysiology.


title: Morphologic characteristics of macroscopic peritoneal finding in patients with peritoneal dialysis.

text: Peritoneal dialysis (PD) has been an attractive treatment for end-stage kidney disease. Long-term exposure to the PD solution creates functional and morphological alterations, and these alterations diminish the efficacy of PD. It is important to establish an evaluation of the changes in PD patients and strategies for the prevention of PD damage and encapsulating peritoneal sclerosis (EPS). We determined the relationship between clinical findings and macroscopic morphological findings by laparoscopy in patients receiving PD. Macroscopic intraperitoneal findings were recorded at the PD catheter removal in 23 PD patients. We examined macroscopic morphological findings such as fibrin deposition, peritoneal turbidity, vasculopathy, adhesion and calcification in both parietal and visceral peritoneum of upper and lower peritoneal cavities, and assessed the score semi-quantitatively. We then evaluated the relationship between the morphological score and clinical findings, especially observational parts and findings in EPS patients. The total macroscopic score increased with PD duration. Peritoneal turbidity, fibrin deposition, and calcification were observed in the whole peritoneal cavity. Scores of fibrin deposition, turbidity, and calcification increased with PD duration. Vasculopathy in the parietal peritoneum was more serious compared with that in the visceral peritoneum, but there was no difference in the vasculopathy between the upper and lower areas. A characteristic of the macroscopic findings in EPS patients was peritoneal calcification in this study. It appears that macroscopic findings using laparoscopy is significant in evaluating the degree of the peritoneum damage and predicting EPS development.


title: Pathophysiological approach to bowel dysfunction after segmental colorectal resection for deep endometriosis infiltrating the rectum: a preliminary study.

text: BACKGROUND Colorectal segmental resection is performed worldwide in a majority of women presenting with symptomatic deep endometriosis infiltrating the rectum. The aim of the present study was to investigate the pathophysiological mechanisms involved in post-operative digestive dysfunction. METHODS We selected patients managed by colorectal resection for rectal endometriosis, who had developed post-operative severe constipation and whose follow up was superior to 24 months. To assess the mechanisms involved in the pathogenesis of this complaint, we performed a step-by-step work up including: low digestive tract endoscopy, colonic transit time measurement and when appropriate anorectal manometry, electromyography and defecographic evaluation. RESULTS Five out of 25 (20%) patients, whose age ranged from 27 to 41 years, were investigated for severe post-operative terminal constipation. Four different mechanisms responsible for terminal constipation were identified: tight stenosis of the colorectal anastomosis, post-operative neurological sequelae, colonic intussusception through the colorectal anastomosis and transit constipation that developed post surgery. CONCLUSIONS Post-operative constipation is a frequent complaint in women managed by colorectal resection for rectal endometriosis. A multidisciplinary approach is mandatory as pathophysiologic mechanisms may vary and prove difficult to understand. The risk of post-operative bowel dysfunction following colorectal endometriosis must be taken into account whenever this technique is proposed in young women presenting with a benign disease such as deep endometriosis.


title: Preclinical Testing of a Novel Thin Film Nitinol Flow-Diversion Stent in a Rabbit Elastase Aneurysm Model.

text: BACKGROUND AND PURPOSE Thin film nitinol can be processed to produce a thin microporous sheet with a low percentage of metal coverage (<20%) and high pore attenuation (∼70 pores/mm(2)) for flow diversion. We present in vivo results from the treatment of experimental rabbit aneurysms by using a thin film nitinol-based flow-diversion device. MATERIALS AND METHODS Nineteen aneurysms in the rabbit elastase aneurysm model were treated with a single thin film nitinol flow diverter. Devices were also placed over 17 lumbar arteries to model perianeurysmal branch arteries of the intracranial circulation. Angiography was performed at 2 weeks (n = 7), 1 month (n = 8), and 3 months (n = 4) immediately before sacrifice. Aneurysm occlusion was graded on a 3-point scale (grade I, complete occlusion; grade II, near-complete occlusion; grade III, incomplete occlusion). Toluidine blue staining was used for histologic evaluation. En face CD31 immunofluorescent staining was performed to quantify neck endothelialization. RESULTS Markedly reduced intra-aneurysmal flow was observed on angiography immediately after device placement in all aneurysms. Grade I or II occlusion was noted in 4 (57%) aneurysms at 2-week, in 6 (75%) aneurysms at 4-week, and in 3 (75%) aneurysms at 12-week follow-up. All 17 lumbar arteries were patent. CD31 staining showed that 75% ± 16% of the aneurysm neck region was endothelialized. Histopathology demonstrated incorporation of the thin film nitinol flow diverter into the vessel wall and no evidence of excessive neointimal hyperplasia. CONCLUSIONS In this rabbit model, the thin film nitinol flow diverter achieved high rates of aneurysm occlusion and promoted tissue in-growth and aneurysm neck healing, even early after implantation.


title: Cumulative effect of indoor temperature on cardiovascular disease-related emergency department visits among older adults in Taiwan.

text: Studies have demonstrated that exposure to extreme outdoor temperatures increases cardiovascular disease mortality and morbidity. However, people spend 80%-90% of their time indoors, and the cumulative effects of exposure to high or low temperature on the risk of cardiovascular diseases had not been considered. This study investigated the cumulative effects of high or low indoor temperature exposure on the risk of cardiovascular diseases. We estimated indoor temperatures by using a prediction model of indoor temperature from a previous study and further calculated the cumulative degree hours at different indoor temperature ranges. Samples of emergency department visits due to cardiovascular diseases were collected from the Longitudinal Health Insurance Database (LHID) from 2000 to 2014 in Taiwan. We used a distributed lag nonlinear model to analyze the data. Our data demonstrated a significant risk of emergency department visits due to cardiovascular diseases at 27, 28, 29, 30, and 31 °C when cooling cumulative degree hours exceeded 62, 43, 16, 1, and 1 during the hot season (May to October), respectively, and at 19, 20, 21, 22, and 23 °C when heating cumulative degree hours exceeded 1, 1, 1, 11, and 33 during the cold season (November to April), respectively. Cumulative degree hours were different according to gender and age groups. Policymakers should further consider the cumulative effects to prevent hot- or cold-related cardiovascular diseases for populations.


COVID Blindness.


title: Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis.

text: OBJECTIVE It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. The findings from the available observational studies varied, and summary estimates are urgently needed to elucidate whether these drugs should be suspended during the pandemic, or patients and physicians should be definitely reassured. This meta-analysis of adjusted observational data aimed to summarise the existing evidence on the association between these medications and severe/lethal COVID-19. METHODS We searched MedLine, Scopus and preprint repositories up to 8 June 2020 to retrieve cohort or case-control studies comparing the risk of severe/fatal COVID-19 (either mechanical ventilation, intensive care unit admission or death), among hypertensive subjects treated with: (1) ACE inhibitors, (2) ARBs and (3) both, versus untreated subjects. Data were combined using a random-effect generic inverse variance approach. RESULTS Ten studies, enrolling 9890 hypertensive subjects were included in the analyses. Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95% CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs). The results did not change when both drugs were considered together, when death was the outcome and excluding the studies with significant, divergent results. CONCLUSION The present meta-analysis strongly supports the recommendation of several scientific societies to continue ARBs or ACE inhibitors for all patients, unless otherwise advised by their physicians who should thus be reassured.


Clinical and health policy challenges in responding to the COVID-19 pandemic.


Coronavirus: limit short-term economic damage.


title: Telomere- and telomerase-interacting protein that unfolds telomere G-quadruplex and promotes telomere extension in mammalian cells.

text: Telomere extension by telomerase is essential for chromosome stability and cell vitality. Here, we report the identification of a splice variant of mammalian heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2), hnRNP A2*, which binds telomeric DNA and telomerase in vitro. hnRNP A2* colocalizes with telomerase in Cajal bodies and at telomeres. In vitro assays show that hnRNP A2* actively unfolds telomeric G-quadruplex DNA, exposes 5 nt of the 3' telomere tail and substantially enhances the catalytic activity and processivity of telomerase. The expression level of hnRNP A2* in tissues positively correlates with telomerase activity, and overexpression of hnRNP A2* leads to telomere elongation in vivo. Thus, hnRNP A2* plays a positive role in unfolding telomere G-quadruplexes and in enhancing telomere extension by telomerase.