title: Preventing and responding to depression, self-harm, and suicide in older people living in long term care settings: a systematic review.

text: OBJECTIVE The well documented demographic shift to an aging population means that more people will in future be in need of long term residential care. Previous research has reported an increased risk of mental health issues and suicidal ideation among older people living in residential care settings. However, there is little information on the actual prevalence of depression, self-harm, and suicidal behavior in this population, how it is measured and how care homes respond to these issues. METHOD This systematic review of international literature addressed three research questions relating to; the prevalence of mental health problems in this population; how they are identified and; how care homes try to prevent or respond to mental health issues. RESULTS Findings showed higher reported rates of depression and suicidal behavior in care home residents compared to matched age groups in the community, variation in the use of standardised measures across studies and, interventions almost exclusively focused on increasing staff knowledge about mental health but with an absence of involvement of older people themselves in these programmes. CONCLUSION We discuss the implications of these findings in the context of addressing mental health difficulties experienced by older people in residential care and future research in this area.


title: Differences between state entropy and bispectral index during analysis of identical electroencephalogram signals: a comparison with two randomised anaesthetic techniques.

text: BACKGROUND It is claimed that bispectral index (BIS) and state entropy reflect an identical clinical spectrum, the hypnotic component of anaesthesia. So far, it is not known to what extent different devices display similar index values while processing identical electroencephalogram (EEG) signals. OBJECTIVE To compare BIS and state entropy during analysis of identical EEG data. Inspection of raw EEG input to detect potential causes of erroneous index calculation. DESIGN Offline re-analysis of EEG data from a randomised, single-centre controlled trial using the Entropy Module and an Aspect A-2000 monitor. SETTING Klinikum rechts der Isar, Technische Universität München, Munich. PATIENTS Forty adult patients undergoing elective surgery under general anaesthesia. INTERVENTIONS Blocked randomisation of 20 patients per anaesthetic group (sevoflurane/remifentanil or propofol/remifentanil). Isolated forearm technique for differentiation between consciousness and unconsciousness. MAIN OUTCOME MEASURES Prediction probability (PK) of state entropy to discriminate consciousness from unconsciousness. Correlation and agreement between state entropy and BIS from deep to light hypnosis. Analysis of raw EEG compared with index values that are in conflict with clinical examination, with frequency measures (frequency bands/Spectral Edge Frequency 95) and visual inspection for physiological EEG patterns (e.g. beta or delta arousal), pathophysiological features such as high-frequency signals (electromyogram/high-frequency EEG or eye fluttering/saccades), different types of electro-oculogram or epileptiform EEG and technical artefacts. RESULTS PK of state entropy was 0.80 and of BIS 0.84; correlation coefficient of state entropy with BIS 0.78. Nine percent BIS and 14% state entropy values disagreed with clinical examination. Highest incidence of disagreement occurred after state transitions, in particular for state entropy after loss of consciousness during sevoflurane anaesthesia. EEG sequences which led to false 'conscious' index values often showed high-frequency signals and eye blinks. High-frequency EEG/electromyogram signals were pooled because a separation into EEG and fast electro-oculogram, for example eye fluttering or saccades, on the basis of a single EEG channel may not be very reliable. These signals led to higher Spectral Edge Frequency 95 and ratio of relative beta and gamma band power than EEG signals, indicating adequate unconscious classification. The frequency of other artefacts that were assignable, for example technical artefacts, movement artefacts, was negligible and they were excluded from analysis. CONCLUSION High-frequency signals and eye blinks may account for index values that falsely indicate consciousness. Compared with BIS, state entropy showed more false classifications of the clinical state at transition between consciousness and unconsciousness.


title: Augmented reality navigation system for laparoscopic splenectomy in children based on preoperative CT image using optical tracking device.

text: PURPOSE In endoscopic surgery, limited views and lack of tactile sensation restrict the surgeon's abilities and cause stress to the surgeon. Therefore, an intra-operative navigation system is strongly recommended. We developed an augmented reality (AR) navigation system based on preoperative CT imaging. The purpose of this study is to evaluate the usefulness, feasibility, and accuracy of this system using laparoscopic splenectomy in children. METHODS Volume images were reconstructed by three-dimensional (3D) viewer application. We used an optical tracking system for registration between volume image and body surface markers. The AR visualization was superimposed preoperative 3D CT images onto captured laparoscopic live images. This system was applied to six cases of laparoscopic splenectomy in children. To evaluate registration accuracy, distances from the marker position to the volume data were calculated. RESULTS The operator recognized the hidden vascular variation of the splenic artery and vein, accessory spleen, and pancreatic tail by overlaying an image onto a laparoscopic live image. The registration accuracy of six cases was 5.30 ± 0.08, 5.71 ± 1.70, 10.1 ± 0.60, 18.8 ± 3.56, 4.06 ± 1.71, and 7.05 ± 4.71. CONCLUSION This navigation system provides real-time anatomical information, which cannot be otherwise visualized without navigation. The registration accuracy was acceptable in clinical operation.


title: During exercise non-invasive ventilation in chronic restrictive respiratory failure.

text: BACKGROUND Exercise intolerance limits chronic restrictive respiratory failure (CRF) patients from participating in daily activities. The specific modalities that could improve exercise tolerance in these patients remain to be established. OBJECTIVE To investigate exercise endurance and associated physiological responses with non-invasive ventilation (NIV) during exercise in restrictive CRF patients. METHODS Eighteen patients (63+/-11 years, total lung capacity (TLC)=59+/-16% of predicted value) performed maximal exercise in spontaneous breathing conditions (MWLE) and during two constant workload exercise (CWLE) tests at 75% Pmax, with or without NIV in random order. "NIV Responders" were defined by an increase in CWLE duration of more than 50% when using NIV. RESULTS For the whole group, CWLE duration when using NIV increased from 5.6+/-4.6 to 9.6+/-8.1 min. Increase in CWLE duration correlated with reduction in heart rate and oxygen desaturation, and dyspnea relief during exercise. NIV responders (n=9) showed more severe lung restriction (TLC: 2.6+/-0.7 versus 3.5+/-1.1L; forced vital capacity: 1.0+/-0.16 versus 1.46+/-0.38 L). At the end of MWLE, responders had a lower Vt (0.60+/-0.09 versus 0.89+/-0.34 L), a higher dead-space ratio (0.51+/-0.06 versus 0.38+/-0.12) and lower oxygen pulse (4.5+/-1.2 versus 7.4+/-3.9 ml/beat). CONCLUSION In severely restrictive patients, NIV during exercise significantly improved exercise duration and tolerance and increased alveolar ventilation. TRIAL REGISTRATION The enrollment of the patients started before July 1, 2005.


title: Developmental profile of motor cortex transcallosal inhibition in children and adolescents.

text: Transcallosal fibers facilitate interhemispheric networks involved in motor tasks. Despite their clinical relevance, interhemispheric motor control systems have not been completely defined in the developing brain. The objective of this study was to examine the developmental profile of transcallosal inhibition in healthy children and adolescents. Nineteen typically developing right-handed participants were recruited. Two transcranial magnetic stimulation (TMS) paradigms assessed transcallosal inhibition: ipsilateral silent periods (iSP) and paired-pulse interhemispheric inhibition (IHI). TMS was applied to the motor hotspot of the first dorsal interosseous muscle. Resting motor threshold (RMT), iSP latency, duration and suppression strength, and paired-pulse IHI were measured from both hemispheres. The Purdue Pegboard Test assessed unimanual motor function. Hemispheric differences were evident for RMT and iSP latency and suppression strength, where the left hemisphere had a lower RMT, prolonged latency, and greater suppression strength. iSP duration showed hemispheric symmetry. RMT and iSP latency decreased with age, whereas iSP suppression strength increased. Girls showed shorter iSP latency. Children typically displayed IHI, although hemispheric differences were observed. iSP suppression strength was uniquely associated with IHI within individuals. iSP duration correlated with motor performance. TMS can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, sex, and motor performance. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy.NEW & NOTEWORTHY Here we demonstrate that transcranial magnetic stimulation can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, handedness, and motor performance. Interestingly, we also demonstrated sex effects, possibly related to the differing developmental profiles of boys and girls. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy.


title: Perioperative course and medium-term outcome of the transobturator and infracoccygeal hammock for posthysterectomy vaginal vault prolapse.

text: OBJECTIVE To describe the perioperative course and medium-term anatomic and functional outcomes of the transobturator-infracoccygeal hammock for posthysterectomy vaginal vault prolapse repair. METHODS A prospective consecutive series of 52 women with a stage 2 vaginal vault prolapse or higher that occurred after total hysterectomy who underwent surgery between 2003 and 2007. Principal outcome measures were anatomic cure (stage 1 or lower) and impact on quality of life measured using the pelvic floor distress inventory (PFDI) and pelvic floor impact self-reported questionnaire (PFIQ). Anatomical results were analyzed using chi(2) and Fisher exact tests, and PFDI and PFIQ scores were analyzed using the Wilcoxon test. RESULTS With a median follow-up of 36months, the anatomic cure rate was 96%. Significant improvements were noted in POPQ-S scores after surgery (P<0.05). Stress urinary incontinence was cured in 73% of patients and improved in 15% of patients. The PFDI and PFIQ scores were improved (P<0.05). One mesh extrusion was observed. The rates of mesh contraction and new cases of dyspareunia were 31% and 13%, respectively. CONCLUSION The transvaginal mesh hammock represents a useful treatment for recurrent and major vaginal vault prolapse, and has few complications.


title: Prevalence of endemic enteropathogens of calves in New Zealand dairy farms.

text: AIM To conduct a country-wide prevalence study of bovine group A rotavirus, coronavirus, Cryptosporidium parvum, Salmonella spp. and enterotoxigenic K99(+) Escherichia coli (K99) in calves on New Zealand dairy farms. METHODS Faecal samples (n=1,283) were collected during the 2011 calving season from calves that were 1-5 and 9-21 days-old on 97 dairy farms, and were analysed for the presence of bovine group A rotavirus, coronavirus, Cryptosporidium and Salmonella spp., and K99. Farm-level prevalences were calculated and relationships between demographic variables and the presence of enteropathogens were examined using logistic regression models. RESULTS Of the 97 farms, 93 (96%) had at least one sample infected with enteropathogens. The standardised farm prevalences of bovine group A rotavirus, bovine coronavirus and C. parvum were 46, 14 and 18%, respectively, in calves that were 1-5 days-old, and 57, 31 and 52%, respectively, in calves that were 9-21 days-old. The farm-level prevalence of K99 was 11% in calves that were 1-5 days-old. Salmonella spp. were found in three and four samples, from calves that were 1-5 and 9-21 days-old, respectively. No associations between explanatory variables and the presence of the enteropathogens were identified at the farm level. At the calf level, the odds of C. parvum shedding and of co-infection with any combination of pathogens were greater in calves that were 9-21 than 1-5 days-old. CONCLUSIONS AND CLINICAL RELEVANCE This study provides epidemiological estimates of the prevalence of calves' enteropathogens in New Zealand, which could be used for infection risk assessment or estimation of the environmental loads of pathogens shed in cattle faeces.


title: Genomic analysis reveals pre- and postchallenge differences in a rhesus macaque AIDS vaccine trial: insights into mechanisms of vaccine efficacy.

text: We have employed global transcriptional profiling of whole blood to identify biologically relevant changes in cellular gene expression in response to alternative AIDS vaccine strategies with subsequent viral challenge in a rhesus macaque vaccine model. Samples were taken at day 0 (prechallenge), day 14 (peak viremia), and week 12 (set point) from animals immunized with replicating adenovirus type 5 host range (Ad5hr) recombinant viruses expressing human immunodeficiency virus HIV(env)(89.6P), simian immunodeficiency virus SIV(gag)(239), or SIV(nef)(239) alone or in combination with two intramuscular boosts with HIV(89.6P)gp140ΔCFI protein (L. J. Patterson et al., Virology 374:322-337, 2008), and each treatment resulted in significant control of viremia following simian-human immunodeficiency virus SHIV(89.6P) challenge (six animals per group plus six controls). At day 0, 8 weeks after the last treatment, the microarray profiles revealed significant prechallenge differences between treatment groups; data from the best-protected animals led to identification of a network of genes related to B cell development and lymphocyte survival. At peak viremia, expression profiles of the immunized groups were extremely similar, and comparisons to control animals reflected immunological differences other than effector T cell functions. Suggested protective mechanisms for vaccinated animals included upregulation of interleukin-27, a cytokine known to inhibit lentivirus replication, and increased expression of complement components, which may synergize with vaccine-induced antibodies. Divergent expression profiles at set point for the immunized groups implied distinct immunological responses despite phenotypic similarities in viral load and CD4(+) T cell levels. Data for the gp140-boosted group provided evidence for antibody-dependent, cell-mediated viral control, whereas animals immunized with only the replicating Ad5hr recombinants exhibited a different evolution of the B cell compartment even at 3 months postchallenge. This study demonstrates the sensitivity and discrimination of gene expression profiling of whole blood as an analytical tool in AIDS vaccine trials, providing unique insights into in vivo mechanisms and potential correlates of protection.


title: A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity.

text: Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections.


Acute Parotitis: A Possible Precocious Clinical Manifestation of SARS-CoV-2 Infection?


title: Re(I) and Tc(I) complexes for targeting nitric oxide synthase: influence of the chelator in the affinity for the enzyme.

text: Aiming to design (99m) Tc complexes for probing nitric oxide synthase (NOS) by SPECT, we synthesized conjugates (L4-L6) comprising a NOS-recognizing moiety connected to a diamino-propionic acid (dap) chelating unit. The conjugates led to complexes of the type fac-[M(CO)3 (ĸ(3) -L)] (M = Re/(99m) Tc; Re4/Tc4: L = L4; Re5/Tc5: L = L5; Re6/Tc6: L = L6). Enzymatic studies showed that L4 and L5, but not L6, gave complexes (Re4 and Re5) that are less potent than the conjugates. To rationalize these results, we performed docking and molecular dynamics simulations. The high affinity of L4 and L5 is due to the strong interactions between the dap chelator and polar residues of the binding cavity. These interactions are hampered by metallation resulting in complexes with lower affinity. The higher potency of Re5 compared to Re4 was assigned to the increased bulkiness of Re5 and the presence of additional anchoring groups that better fit the active site and provide more extensive contacts. In turn, Re6 is too bulky and its organometallic tail is oriented toward the peripheral pocket of iNOS, leading to loss of contacts and a lower affinity. These results were compared with our previous results obtained with analogue complexes stabilized by a pyrazolyl-diamine chelating unit.


title: Clinical and Demographic Characteristics of Cluster Cases and Sporadic Cases of Coronavirus Disease 2019 (COVID-19) in 141 Patients in the Main District of Chongqing, China, Between January and February 2020.

text: BACKGROUND In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, China. Patients with COVID-19 were also identified in Chongqing. This study aimed to investigate the clinical and demographic characteristics of cluster cases and sporadic cases of COVID-19 in 141 patients in the main district of Chongqing during one month, between January and February 2020. MATERIAL AND METHODS A retrospective study included 141 patients with a diagnosis of COVID-19. The diagnosis was confirmed using real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2. The patients were divided into cluster cases (n=90) and sporadic cases (n=51). Demographic and clinical characteristics were compared between the two study groups and included the presence of comorbidities, the presenting symptoms, chest computed tomography (CT) imaging findings, and laboratory findings. RESULTS The mean age of the 141 patients diagnosed with COVID-19 was 47.3 years, and the most common presenting symptom was a persistent cough (48.9%). The 90 cluster cases (63.8%) were older than the sporadic cases, and cross-infection from family gathering occurred in 82.2%, and cough was more common than fever, and there was an increased prevalence of asymptomatic, mild, and moderate cases. Cluster cases showed fewer typical manifestations of COVID-19 on chest CT. However, the laboratory findings between the cluster and sporadic cases showed no significant differences. CONCLUSIONS There were demographic and clinical differences between cluster cases and sporadic cases of COVID-19 in the main district of Chongqing during the month between January to February 2020.


title: Novel solution for luminal access loss into the double-layered LVIS Blue™ construct.

text: We described a novel solution for a challenging case of double-layered LVIS Blue™ (LB) stent construct retraction into a large cavernous aneurysm. The double-layered LB stent construct was used as a flow diverter for treatment of a large cavernous aneurysm. Our solution comprised a balloon angioplasty and placement of balloon-mounted cardiac-stent construct through the side wall of the LB construct, with eventual placement of a Pipeline Flex inside of the final conduit.


Temperature-dependent surface stability of SARS-CoV-2.


title: A noncanonical cysteine protease USP1 is activated through active site modulation by USP1-associated factor 1.

text: Ubiquitin-specific proteases (USPs) constitute the largest family of the human deubiquitinating enzymes. USP1 belongs to the cysteine protease family and contains a catalytic triad comprised of C90, H593, and D751. Notably, the catalytic activity of USP1 is stimulated through the formation of a tight complex with a WD40 repeat protein UAF1 (USP1-associated factor 1). Our kinetic analyses revealed a general base catalysis in USP1/UAF1, in contrast to an ion-pair mechanism as demonstrated for papain and cathepsin. The pK(a) value of the catalytic cysteine was determined to be 8.67 ± 0.07 in a pH-dependent inactivation study of USP1/UAF1 by iodoacetamide. A normal solvent kinetic isotope effect of 2.8 for k(cat) and 3.0 for k(cat)/K(m) was observed in the USP1/UAF1-catalyzed hydrolysis of ubiquitin-AMC substrate. Moreover, proton inventory analysis supported the transfer of a single solvent-derived proton in the transition state. Our study also revealed the molecular basis for the activation of USP1 by UAF1. Although the pK(a) of the catalytic cysteine in USP1 and USP1/UAF1 was almost identical, the pK(a) of the catalytic histidine in USP1/UAF1 was 0.43 pH unit lower than that in USP1, which facilitates general base catalysis at a neutral pH and contributes to the elevated catalytic efficiency. We ruled out that the higher catalytic efficiency is due to a tighter binding of ubiquitin. Our results support a regulatory mechanism in which UAF1 activates USP1 by modulating its active site conformation. This finding has a general implication for the regulation of USPs that form complex with partner proteins.


title: The Trial of Chloroquine in the Treatment of Corona Virus Disease 2019 （COVID-19） and Its Research Progress in Forensic Toxicology.

text: Abstract Chloroquine is a long-established prescription drug that is often used clinically to treat malaria and connective tissue diseases. Since December 2019, COVID-19 （corona virus disease 2019） outbreaks caused by SARS-CoV-2 （severe acute respiratory syndrome coronavirus 2） has occurred in China and many countries around the world. Due to the lack of drugs against COVID-19, the disease spreads rapidly and the mortality rate is relatively high. Therefore, specific drugs against SARS-CoV-2 need to be quickly screened. The antimalarial drug Chloroquine phosphate which has already been approved is confirmed to have an anti-SARS-CoV-2 effect and has been included in diagnostic and therapeutic guidelines. However, awareness of the risk of chloroquine phosphate causing acute poisoning or even death should be strengthened. The dosage used according to current clinical recommended dosage and course of treatment are larger than that of previous treatment of malaria. Many provinces have required close clinical monitoring of adverse reactions. This paper reviews the pharmacological effects, poisoning and toxicological mechanisms, in vivo metabolism and distribution, and forensic issues of chloroquine drugs, in order to provide help to forensic practice and clinical work.


title: Total laparoscopic distal gastrectomy with Roux-en Y reconstruction.

text: PURPOSE The aim of this study was to introduce our technique and evaluate the technical efficacy of Roux-en Y (RY) reconstruction after total laparoscopic distal gastrectomy (TLDG). METHODS We performed TLDG using our own method of RY-type anastomosis in a total of 38 consecutive patients with gastric adenocarcinomas and evaluated the techniques and postoperative outcomes. RESULTS The mean operative time was 144.5 ± 22.4 minutes, including reconstruction time, which was 26.2 ± 3.5 minutes. Most patients were of pathologic stage IA (76.3%) or IB (10.5%), 3 patients were of stage II, and 2 were of stage IIIA. The length of postoperative hospital stay was 8.3 ± 3.3 days (range, 5 to 20 d). Two cases required reoperation because of internal herniation. According to our endoscopic observation, bile reflux into the gastric remnant stump was not found. CONCLUSIONS TLDG with RY reconstruction is technically feasible in gastric cancer patients.


title: Totally laparoscopic Roux-en-Y gastrojejunostomy after laparoscopic distal gastrectomy: analysis of initial 50 consecutive cases of single surgeon in comparison with totally laparoscopic Billroth I reconstruction.

text: PURPOSE Roux-en-Y reconstruction (RY) in laparoscopic distal gastrectomy for gastric cancer is a more complicated procedure than Billroth-I (BI) or Billroth-II. Here, we offer a totally laparoscopic simple RY using linear staplers. MATERIALS AND METHODS Each 50 consecutive patients with totally laparoscopic distal gastrectomy with RY and BI were enrolled in this study. Technical safety and surgical outcomes of RY were evaluated in comparison with BI. RESULTS In all patients, RY gastrectomy using linear staplers was safely performed without any events during surgery. The mean operation time and anastomosis time were 177.0±37.6 min and 14.4±5.6 min for RY, respectively, which were significantly longer than those for BI (150.4±34.0 min and 5.9±2.2 min, respectively). There were no differences in amount of blood loss, time to flatus passage, diet start, length of hospital stay, and postoperative inflammatory response between the two groups. Although there was no significant difference in surgical complications between RY and BI (6.0% and 14.0%), the RY group showed no anastomosis site-related complications. CONCLUSION The double stapling method using linear staplers in totally laparoscopic RY reconstruction is a simple and safe procedure.


title: Psychological therapies for anxiety and depression in children and adolescents with long-term physical conditions.

text: BACKGROUND Long-term physical conditions affect 10% to 12% of children and adolescents worldwide. These individuals are at greater risk of developing psychological problems, particularly anxiety and depression, sometimes directly related to their illness or medical care (e.g. health-related anxiety). There is limited evidence regarding the effectiveness of psychological therapies for treating anxiety and depression in this population. Therapies designed for children and adolescents without medical issues may or may not be appropriate for use with those who have long-term physical conditions. OBJECTIVES This review was undertaken to assess the effectiveness and acceptability of psychological therapies in comparison with controls (treatment-as-usual, waiting list, attention placebo, psychological placebo, or non-psychological treatment) for treating anxiety and depression in children and adolescents with long-term physical conditions. SEARCH METHODS We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 27 September 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to May 2016). In addition we searched the Web of Science (Core Collection) (12 October 2018) and conducted a cited reference search for reports of all included trials. We handsearched relevant conference proceedings, reference lists of included articles, and grey literature. SELECTION CRITERIA Randomised controlled trials (RCTs), cluster-randomised trials and cross-over trials of psychological therapies for treating anxiety or depression in children with long-term physical conditions were included. DATA COLLECTION AND ANALYSIS Abstracts and complete articles were independently reviewed by two authors. Discrepancies were addressed by a third author. Odds ratio (OR) was used for comparing dichotomous data and standardised mean differences (SMD) for comparing continuous data. Meta-analysis was undertaken when treatments, participants, and the underlying clinical question were similar. Otherwise, narrative analysis of data was undertaken. MAIN RESULTS Twenty-eight RCTs and one cross-over trial with 1349 participants were included in the review. Most participants were recruited from community settings and hospital clinics in high-income countries. For the primary outcome of treatment efficacy, short-term depression (versus any control), there was low-quality evidence from 16 trials involving 1121 participants suggesting that psychological therapies may be more effective than control therapies (SMD -0.31, 95% CI -0.59 to -0.03; I2 = 79%). For the primary outcome of treatment efficacy, short-term anxiety (versus any control), there was inadequate evidence of moderate-quality from 13 studies involving 578 participants to determine whether psychological therapies were more effective than control conditions (SMD -0.26, CI -0.59 to 0.07, I2 = 72%). Planned sensitivity analyses could not be undertaken for risk of bias due to the small number of trials that rated high for each domain. Additional sensitivity analysis demonstrated that psychological interventions specifically designed to reduce anxiety or depression were more effective than psychological therapies designed to improve other symptoms or general coping. There was some suggestion from subgroup analyses that they type of intervention (Chi² = 14.75, df = 5 (P = 0.01), I² = 66.1%), the severity of depression (Chi² = 23.29, df = 4 (P = 0.0001), I² = 82.8%) and the type of long-term physical condition (Chi² = 10.55, df = 4 (P = 0.03), I² = 62.1%) may have an impact on the overall treatment effect.There was qualitative (reported), but not quantitative evidence confirming the acceptability of selected psychological therapies for anxiety and depression. There was low-quality evidence that psychological therapies were more effective than control conditions in improving quality of life (SMD 1.13, CI 0.44 to 1.82, I2 = 89%) and symptoms of long-term physical conditions (SMD -0.34, CI -0.6 to -0.06, I2 = 70%), but only in the short term. There was inadequate low-quality evidence to determine whether psychological therapies were more effective than control conditions at improving functioning in either the short term or long term. No trials of therapies for addressing health-related anxiety were identified and only two trials reported adverse effects; these were unrelated to psychological therapies. Overall, the evidence was of low to moderate quality, results were heterogeneous, and only one trial had an available protocol. AUTHORS' CONCLUSIONS A limited number of trials of variable quality have been undertaken to assess whether psychological therapies are effective for treating anxiety and depression in children and adolescents with long-term physical conditions. According to the available evidence, therapies specifically designed to treat anxiety or depression (especially those based on principles of cognitive behaviour therapy (CBT)) may be more likely to work in children and adolescents who have mild to moderate levels of symptoms of these disorders, at least in the short term. There is a dearth of therapies specifically designed to treat health-related anxiety in this age group.


The cause of stroke matters for secondary prevention.


title: Roux-En-Y Fistulo-Jejunostomy as a salvage procedure in patients with post-sleeve gastrectomy fistula.

text: BACKGROUND Sleeve gastrectomy (SG) is currently the most common bariatric procedure in France. It achieves both adequate excess weight loss and significant reduction of comorbidities. However, leak is still the most common complication after SG. Nevertheless, its risk of occurrence is <3% in specialized centers. Its management is difficult, long, and challenging. Although the procedure is commonly endoscopic and nonoperative, the management of post-SG fistulas could sometimes be surgical, including peritoneal lavage, abscess drainage, disrupted staple line suturing, resleeve, gastric bypass, or total gastrectomy. Roux-en-Y fistulojejunostomy (RYFJ) has been described as a salvage option. In this study, we report the early results of RYFJ for post-SG fistula, emphasizing indications, operative technique, and short-term outcome. METHODS Between January 2007 and December 2012, we treated 62 patients with post-SG fistula. Before surgery, intra-abdominal or thoracic abscesses or collections were either excluded or treated by computed tomographic scan-guided drainage or even surgery. Endoscopic stenting was then attempted. After optimization of the nutritional status in case of failure of endoscopic measures, some of the patients underwent RYFJ. RESULTS Between January 2007 and December 2012, a total of 21 patients (16 women and 5 men) had RYFJ for post-SG fistula. Mean age was 47 years (range, 22-59 years). Procedures were performed laparoscopically in all but 3 cases. The rate of secondary conversion to laparotomy was 11.1%. The was no mortality. The postoperative morbidity rate was less than 5%. The rate of fistula control was eventually 100%. CONCLUSIONS RYFJ is a safe and feasible salvage procedure for the treatment of patients with post-SG fistula. Longer outcome analysis is, however, needed especially regarding the physiological and metabolic behavior of the procedure.


Indian response to COVID-19: Expertise and transparency.


title: Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells.

text: DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C) efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions, which might be in the future exploited to tackle HIV infection.


Influence of nanostructure morphology on host capacity and kinetics of guest release.


title: Risk factors for prolonged operative time in single-incision laparoscopic cholecystectomy.

text: PURPOSE We performed 3-channel single incision laparoscopic cholecystectomy (SILC) in earlier period of this study and modified our method to 4-channel SILC using a snake retractor for better operative field in later period. This study has been designed to evaluate the risk factors for prolonged operative time in SILC. METHODS From April 2010 to August 2014, 323 cases of 3-channel SILC (Konyang standard method [KSM] group) and 399 cases of 4-channel SILC (modified KSM [mKSM] group) using a snake retractor were performed. RESULTS The clinical characteristics were not significantly different between KSM and mKSM group except preoperative percutaneous transhepatic gallbladder drainage (PTGBD) treatment (9.6% vs. 16.5%, P < 0.007). The mean operation time was longer in mKSM group than KSM group (55.8 ± 19.7 minutes vs. 51.7 ± 20.1 minutes, P = 0.006). The estimated blood loss of KSM group was more than mKSM group (24.6 ± 54.1 mL vs. 16.9 ± 27.0 mL, P = 0.013). According to the histopathologic findings, acute cholecystitis or empyema were confirmed more in mKSM group as compared with KSM group (28% vs. 14.0%, P = 0.025). In multivariate analysis, the risk factors for prolonged operation time were drainage insertion, histopathologic findings (acute cholecystitis or empyema), surgeons' technical expertise, body mass index > 30 kg/m(2) as well as the 4-channel SILC. CONCLUSION Among patients with these risk factors, conventional laparoscopic cholecystectomy could be considered as well although SILC might be safe and feasible modality for benign gallbladder disease.


Covid-19: Government cannot say whether NHS will run out of protective gowns this weekend.


title: Thrombosed native hemodialysis fistulas: Technical and clinical outcomes of endovascular recanalization and factors influencing patency.

text: PURPOSE To evaluate the technical and clinical results of endovascular recanalization of thrombosed native hemodialysis fistula and the factors influencing patency. METHODS A retrospective study was conducted with 73 patients who had thrombosed arteriovenous fistulas and were treated with endovascular methods. Patient characteristics, arteriovenous fistula-related characteristics, and endovascular procedures were analyzed. Technical and clinical results and patency rates were evaluated. The factors influencing patency were analyzed using a univariate and multivariate Cox proportional hazards model. RESULTS Technical and clinical success rates were 93% (68/73) and 85% (62/73), respectively. At 3, 6, and 12 months, the primary patency rates were 87.9%, 73.3%, and 64.8%; assisted primary patency rates were 89.2%, 78.6%, and 70.7%; and secondary patency rates were 90.8%, 87.2%, and 83.1%, respectively. Previous intervention and cephalic arch stenosis were risk factors for lower primary and assisted primary patency ( p < 0.05 for all). Cephalic arch stenosis was the only risk factor for lower secondary patency ( p < 0.05). No major complications associated with the procedures were noticed. CONCLUSION Endovascular treatment was effective for the immediate recanalization of thrombosed arteriovenous fistula. In addition, previous intervention and cephalic arch stenosis were significantly related to lower arteriovenous fistula patency.


title: Identification of lysine acetylation sites on MERS-CoV replicase pp1ab.

text: MERS is a life-threatening disease and MERS-CoV has the potential to cause the next pandemic. Protein acetylation is known to play a crucial role in host response to viral infection. Acetylation of viral proteins encoded by other RNA viruses have been reported to affect viral replication. It is therefore of interest to see whether MERS-CoV proteins are also acetylated. Viral proteins obtained from infected cells were trypsin-digested into peptides. Acetylated peptides were enriched by immunoprecipitation and subject to nano-LC-Orbitrap analysis. Bioinformatic analysis was performed to assess the conservation level of identified acetylation sites and to predict the upstream regulatory factors. A total of 12 acetylation sites were identified from 7 peptides, which all belong to the replicase polyprotein pp1ab. All identified acetylation sites were found to be highly conserved across MERS-CoV sequences in NCBI database. Upstream factors, including deacetylases of the SIRT1 and HDAC families as well as acetyltransferases of the TIP60 family, were predicted to be responsible for regulating the acetylation events identified. Western blot confirms that acetylation events indeed occur on pp1ab protein by expressing NSP4 in HEK293 cells. Acetylation events on MERS-CoV viral protein pp1ab were identified for the first time, which indicate that MERS-CoV might use the host acetylation machinery to regulate its enzyme activity and to achieve optimal replication. Upstream factors were predicted, which might facilitate further analysis of the regulatory mechanism of MERS-CoV replication.


title: Pathogens, patterns of pneumonia, and epidemiologic risk factors associated with respiratory disease in recently weaned cattle in Ireland.

text: We examined the pathogens, morphologic patterns, and risk factors associated with bovine respiratory disease (BRD) in 136 recently weaned cattle ("weanlings"), 6-12 mo of age, that were submitted for postmortem examination to regional veterinary laboratories in Ireland. A standardized sampling protocol included routine microbiologic investigations as well as polymerase chain reaction and immunohistochemistry. Lungs with histologic lesions were categorized into 1 of 5 morphologic patterns of pneumonia. Fibrinosuppurative bronchopneumonia (49%) and interstitial pneumonia (48%) were the morphologic patterns recorded most frequently. The various morphologic patterns of pulmonary lesions suggest the involvement of variable combinations of initiating and compounding infectious agents that hindered any simple classification of the etiopathogenesis of the pneumonias. Dual infections were detected in 58% of lungs, with Mannheimia haemolytica and Histophilus somni most frequently recorded in concert. M. haemolytica (43%) was the most frequently detected respiratory pathogen; H. somni was also shown to be frequently implicated in pneumonia in this age group of cattle. Bovine parainfluenza virus 3 (BPIV-3) and Bovine respiratory syncytial virus (16% each) were the viral agents detected most frequently. Potential respiratory pathogens (particularly Pasteurella multocida, BPIV-3, and H. somni) were frequently detected (64%) in lungs that had neither gross nor histologic pulmonary lesions, raising questions regarding their role in the pathogenesis of BRD. The breadth of respiratory pathogens detected in bovine lungs by various detection methods highlights the diagnostic value of parallel analyses in respiratory disease postmortem investigation.


title: Secondary bone grafting of the cleft maxilla following reverse quad-helix expansion in 103 patients.

text: INTRODUCTION The main points to consider in secondary alveolar bone grafting (ABG) of cleft patients are age at the time of surgery, the type of bone graft, and pre/postorthodontic expansion of the upper jaw. PURPOSE The aim of this study is to evaluate the reverse quad-helix (RQH) expander device. Does RQH improve the surgical procedure before ABG? We will evaluate the outcome of the procedure, duration of the operation, hospitalization time, satisfaction of the surgeon with this procedure and the success of the bone graft in the long-term. PATIENTS AND METHODS We reviewed the medical records of 103 cleft patients who underwent secondary bone grafting at our institution between 2001 and 2012. All patients were treated presurgically with a RQH appliance to expand the cleft area. The following data were recorded for each of the patients: Unilateral/bilateral cleft, surgery time, hospital stay, success/failure, and follow-up. CONCLUSION Presurgical orthodontic application of the RQH expander in the cleft area enabled improved anterior expansion rather than posterior expansion. This technique improves access for surgery and bone grafting, the use of RQH facilitates the improved manipulation of the nasal mucosa via direct view due to the wide separation of the alveolar segments in the cleft area. Furthermore, this gap enables improved access for the bone grafting procedure, shortens the surgery time and provides stable maxillary transverse correction.


Impact of COVID-19 pandemic on Subarachnoid Hemorrhage.


title: Safe Skin Management during Open Hepatectomy in a Patient with Recessive Dystrophic Congenital Epidermolysis Bullosa.

text: Congenital epidermolysis bullosa is a rare, genetic condition in which even slight stimulation can cause blistering of the skin or mucosa. While previous reports of treatments requiring general anesthesia in these patients were focused on anesthesia-related procedures, such as endotracheal intubation, no report has described specific management required for these patients during surgery, such as preparation of the surgical site, fixation of infusion lines and other tubes, and adjustment of the operation table. This is probably the first report to address these issues. This report presents a case of recessive dystrophic congenital epidermolysis bullosa in which open hepatectomy was safely performed.


title: Indications and Outcomes of a Cross-Linked Porcine Dermal Collagen Mesh (Permacol) for Complex Abdominal Wall Reconstruction: A Multicenter Audit.

text: INTRODUCTION To reduce the occurrence of complications in the setting of high-risk patients with contaminated operative field, a wide range of biologic meshes has been developed. Yet, few series have reported outcomes after abdominal wall repair (AWR) using such meshes. Permacol is an acellular porcine dermal collagen matrix with a cross-linked pattern. This study reports short- and long-term outcomes after AWR for incisional hernia using Permacol. MATERIALS AND METHODS All consecutive patients undergoing single-stage open AWR using Permacol mesh at eight university hospitals were included. Mortality, complication and hernia recurrence rates were assessed. Independent risk factors for complications and hernia recurrence were identified with logistic regression and Fine and Gray analysis, respectively. RESULTS Overall, 250 patients underwent single-stage AWR with Permacol. Nearly 80% had a VHWG grade 3 or 4 defect. In-hospital mortality and complication rates were 4.8% (n = 12) and 61.6% (n = 154), respectively. Reintervention for complications was required for 74 patients (29.6%). Mesh explantation rate was 4% (n = 10). Independent risk factors for complications were smoking, defect size and VHWG grade. After a mean follow-up time of 16.8 months (± 18.1 months), 63 (25.2%) experienced hernia recurrence. One-, 2- and 3-year RFS were 90%, 74% and 57%, respectively. Previous AWR, mesh location and the need for reintervention were independent predictors of hernia recurrence. DISCUSSION Single-stage AWR is feasible using Permacol. Mortality and complication rates are high due to patients' comorbidities and the degree of contamination of the operative field. Given the observed recurrence rate, the benefit of biologics remains to be ascertained.


title: Neuromuscular Fatigue and Recovery after Heavy Resistance, Jump, and Sprint Training.

text: PURPOSE Training methods that require maximal intensity efforts against light and heavy resistance are commonly used for athletic development. Typically, these sessions are separated by at least 48 h recovery on the assumption that such efforts elicit marked fatigue of the central nervous system (CNS), but this posit has not been well studied. The aim of the study was to assess the etiology and recovery of fatigue after heavy-resistance (strength), jump, and sprint training methods. METHODS Ten male athletes completed three training sessions requiring maximal efforts that varied in their loading characteristics: (i) heavy-resistance exercise (10 × 5 back squats at 80% one-repetition maximum [1RM]) (STR), (ii) jumping exercise (10 × 5 jump squats) (JUMP), and (iii) maximal sprinting (15 × 30 m) (SPR). Preparticipants, postparticipants, and 24-, 48-, and 72-h postparticipants completed a battery of tests to measure neuromuscular function using electrical stimulation of the femoral nerve, and single- and paired-pulse magnetic stimulation of the motor cortex, with evoked responses recorded from the knee extensors. Fatigue was self-reported at each time point using a visual analog scale. RESULTS Each intervention elicited fatigue that resolved by 48 (JUMP) and 72 h (STR and SPR). Decrements in muscle function (reductions in the potentiated quadriceps twitch force) persisted for 48 h after all exercise. Reductions in voluntary activation were present for 24 h after JUMP and SPRINT, and 48 h after STR. No other differences in CNS function were observed as a consequence of training. CONCLUSION Strength, jump, and sprint training requiring repeated maximum efforts elicits fatigue that requires up to 72 h to fully resolve, but this fatigue is not primarily underpinned by decrements in CNS function.


title: Functional outcomes by reconstruction technique following laparoscopic proximal gastrectomy for gastric cancer: double tract versus jejunal interposition.

text: BACKGROUND For early gastric cancer located in the upper third of the stomach, we have adopted laparoscopic 1/2-proximal gastrectomy (PG) with two types of reconstruction: double tract reconstruction (L-DT) and jejunal interposition reconstruction with crimping of the jejunum on the anal side of the jejunogastrostomy with a knifeless linear stapler (L-JIP). METHODS Functional outcomes were prospectively compared between these two types of reconstruction following laparoscopic PG. Resection and reconstruction were performed using L-DT (n = 10) and L-JIP (n = 10) alternately. Quality of life was evaluated through a questionnaire and endoscopic examination of the ten patients in each group, and functional evaluations were carried out in five patients of each group. RESULTS The postoperative/preoperative body weight ratio was significantly higher in the L-JIP group than in the L-DT group. While the incidence of reflux esophagitis was 10% in both groups, the endoscope could reach the remnant stomach in all patients. In the L-DT group, the plasma acetaminophen concentration at 15 minutes and the insulin level at 30 minutes were markedly increased after oral administration, while the increases in the blood sugar level at 30 and 60 minutes were more gradual than in the L-JIP group. CONCLUSIONS While L-JIP may be thought of as the ideal method for function-preserving gastrectomy, L-DT may be suitable for gastric cancer patients with impaired glucose tolerance. These results raise the possibility of individualized selection of reconstruction for gastric cancer patients with various kinds of preoperative complications.


title: Hydroxychloroquine in systemic lupus erythematosus and rheumatoid arthritis and its safety in pregnancy.

text: INTRODUCTION The antimalarial drug hydroxychloroquine (HCQ) is widely used to treat various rheumatic diseases. Many autoimmune diseases occur in women of child-bearing age who may become pregnant while on therapy, which raises concerns regarding the teratogenicity of HCQ and its effect on the outcome of the pregnancy. There is a lack of data regarding the safety of HCQ during pregnancy. AREAS COVERED In this review, the authors attempt to identify relevant publications by searching MEDLINE, Cochrane database, Ovid-Currents Clinical Medicine, Ovid-Embase:Drugs and Pharmacology, EBSCO, Web of Science and SCOPUS using the search terms HCQ and/or pregnancy. A basis for the mechanism of action of HCQ is provided. EXPERT OPINION HCQ has been shown by numerous studies over the past 15 years to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus, discoid lupus erythematosus and rheumatoid arthritis. HCQ does not appear to be associated with any increased risk of congenital defects, spontaneous abortions, fetal death, prematurity or decreased numbers of live births in patients with autoimmune diseases. Therefore, in the author's opinion, HCQ is safe for the treatment of autoimmune diseases during pregnancy.


title: Preoperative cerebral oxygen saturation and clinical outcomes in cardiac surgery.

text: BACKGROUND The current study was designed to determine the relation between preoperative cerebral oxygen saturation (Sco2), variables of cardiopulmonary function, mortality, and morbidity in a heterogeneous cohort of cardiac surgery patients. METHODS In this study, 1,178 consecutive patients scheduled for on-pump surgery were prospectively studied. Preoperative Sco2, demographics, N-terminal pro-B-type natriuretic peptide, high-sensitive troponin T, clinical outcomes, and 30-day and 1-yr mortality were recorded. RESULTS Median additive EuroSCORE was 5 (range: 0-19). Thirty-day and 1-yr mortality and major morbidity (at least two major complications and/or a high-dependency unit stay of at least 10 days) were 3.5%, 7.7%, and 13.3%, respectively. Median minimal preoperative oxygen supplemented Sco2 (Sco2min-ox) was 64% (range: 15-92%). Sco2min-ox was correlated (all: P value <0.0001) with N-terminal pro-B-type natriuretic peptide (ρ: -0.35), high-sensitive troponin T (ρ: -0.28), hematocrit (ρ: 0.34), glomerular filtration rate (ρ: 0.19), EuroSCORE (τ: 0.20), and left ventricular ejection fraction class (τ: 0.12). Thirty-day nonsurvivors had a lower Sco2min-ox than survivors (median 58% [95% CI, 50.7-62%] vs. 64% [95% CI, 64-65%]; P < 0.0001). Receiver-operating curve analysis of Sco2min-ox and 30-day mortality revealed an area-under-the-curve of 0.71 (95% CI, 0.68-0.73%; P < 0.0001) in the total cohort and an area-under-the-curve of 0.77 (95% CI, 0.69-0.86%; P < 0.0001) in patients with a EuroSCORE more than 10. Logistic regression based on different EuroSCORE categories (0-2; 3-5, 6-10, >10), Sco2min-ox, and duration of cardiopulmonary bypass showed that a Sco2min-ox equal or less than 50% is an independent risk factor for 30-day and 1-yr mortality. CONCLUSIONS Preoperative Sco2 levels are reflective of the severity of cardiopulmonary dysfunction, associated with short- and long-term mortality and morbidity, and may add to preoperative risk stratification in patients undergoing cardiac surgery.


Conservative surgical treatment for caesarean scar pregnancy.


title: Banding the Sleeve Improves Weight Loss in Midterm Follow-up.

text: INTRODUCTION Laparoscopic sleeve gastrectomy (LSG) can achieve excellent weight loss, yet sleeve dilatation with concomitant weight regain proves to be a relevant issue. Hence, additional restriction might improve results after LSG. METHODS In a retrospective matched-pair analysis, 42 patients who underwent banded LSG (BLSG) using a MiniMizer® ring between January 2012 and October 2014 were analysed regarding weight loss, complications and comorbidity. Median follow-up was 3 years. Forty-two patients who had undergone conventional LSG were selected as matched pairs. RESULTS Mean preoperative BMI was 54.93 ± 7.42 kg/m2 for BLSG and 53.46 ± 6.69 kg/m2 for LSG (Mann-Whitney P = 0.540). Total weight loss (%TWL) was significantly greater in the BLSG group 3 years after surgery (BLSG 38.22% ± 7.26; n = 26 vs. LSG 32.69 ± 9.47; n = 26; P = 0.0154). Ring placement had no relevant impact on new-onset reflux (Fisher's exact test P = 1.0) but a tendency towards reflux improvement when reflux pre-existed (odds ratio 1.96). The major side effect of ring implantation was regurgitation with over 44% of patients presenting with regurgitation >1 per week (Fisher's exact test P = 0.0019, odds ratio 18.07). CONCLUSION BLSG is a safe procedure showing similar comorbidity to conventional LSG. However, BLSG leads to a higher rate of postoperative regurgitation. Weight loss is significantly improved 3 years after surgery. Hence, additional ring implantation might be an option for increased restriction in LSG surgery.


title: [Immunocompetent adults hospitalized for a community-acquired pneumonia: Serum C-reactive protein as a prognostic marker].

text: BACKGROUND C-reactive protein (CRP) is used to monitor patients' response during treatment of infectious diseases. Morbidity and mortality associated with community-acquired pneumonia (CAP) is high, particularly in hospitalized patients. Better risk prediction during hospitalization could improve management and ultimately reduce mortality rates. AIM To evaluate CRP measured at admission and the third day of hospitalization as a predictor for adverse events in CAP. MATERIAL AND METHODS A prospective cohort study of adult patients hospitalized with CAP at an academic hospital. Major adverse outcomes were admission to ICU, mechanical ventilation, prolonged hospital length of stay, hospital complications and 30-day mortality. Predictive associations between CRP (as absolute levels and relative decline at third day) and adverse events were analyzed. RESULTS Eight hundred and twenty-three patients were assessed, 19% were admitted to ICU and 10.6% required mechanical ventilation. The average hospital stay was 8.8 ± 8.2 days, 42% had nosocomial complications and 8.1% died within 30 days. Ninety eight percent of patients had elevated serum CRP on admission to the hospital (18.1 ± 14.1 mg/dL). C-reactive protein measured at admission was associated with the risk of bacterial pneumonia, bacteremic pneumonia, septic shock and use of mechanical ventilation. Lack of CRP decline within three days of hospitalization was associated with high risk of complications, septic shock, mechanical ventilation and prolonged hospital stay. CONCLUSIONS CRP responses at third day of hospital admission was a valuable predictor of adverse events in hospitalized CAP adult patients.


title: Trapped in a Double Bind: Chinese Overseas Student Anxiety during the COVID-19 Pandemic.

text: The severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the COVID-19 disease cases stemming from it, and the resulting pandemic have imposed severe, distressing, physical, and psychological challenges on communities worldwide. The stressful situation faced by Chinese overseas students (COSs) has been particularly acute. With this population as the focus, the current study evaluated the psychological state of COSs abroad during the initial phases of the pandemic. Participants (N = 182) were recruited to complete an online survey (during April 7-14, 2020) assessing their physical and social circumstances, and sense of wellbeing. Results showed COSs experienced high levels of anxiety primarily stemming from discrimination from the media, fear of COVID-19, and mixed messages from their social connections. Feeling entrapped in a double bind (DbB) situation with their close relations significantly increased anxiety. Perceived social support negatively correlated with anxiety, and those experiencing a DbB felt the greatest stress, particularly those unable to effectively differentiate the opposing messages. Findings of the study, limitations, and implications are discussed.


title: Synthesis and evaluation of a new 99mTc(I)-tricarbonyl complex bearing the 5-nitroimidazol-1-yl moiety as potential hypoxia imaging agent.

text: The objective of this work was to develop a novel (99m) Tc complex bearing the 5-nitroimidazol-1-yl moiety with recognised selectivity towards hypoxic tissue, as a potential radiopharmaceutical for imaging tumour hypoxia. The new metronidazole derivative (2-amine-3-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylthio]propanoic acid) (L) containing adequate groups to coordinate technetium through the formation of a Tc(I)-tricarbonyl complex was synthesised with adequate yield (33%) and characterised by spectroscopy. Labelling was performed by substitution of three labile water molecules of the technetium tricarbonyl precursor, fac-[(99m)Tc(CO)3 (H2O)3](+) with the ligand. A radiochemical purity higher than 90% was achieved and remained unchanged for more than 4 h. The complex has a high stability in plasma, a moderate plasma protein binding and a moderate hydrophilicity. In vitro cell uptake studies showed a ratio between the activity taken up by cells in hypoxia/normoxia of 1.6 ± 0.4 (p < 0.5). Biodistribution in normal mice showed rapid depuration and low uptake in all organs and tissues except liver. Biodistribution in mice bearing induced tumours showed a low tumour uptake, but tumour/muscle ratio was favourable thanks to depuration. Comparison with biological results of other metronidazole derivatives clearly shows that modifications of the chelator are very important and contribute to improve the biological behaviour.


title: Why is influenza vaccine uptake so low among Aboriginal adults?

text: OBJECTIVES Determine major barriers to, and facilitators of, influenza vaccination of Aboriginal adults, in order to improve coverage from the current level of 30%. METHODS i) A focus group with 13 Aboriginal Immunisation Healthcare Workers; and ii) a cross-sectional survey of Aboriginal people aged ≥18 years at the 2017 New South Wales Koori Knockout (29 September-2 October). RESULTS The focus group nominated poor identification of Aboriginality in general practice. Of 273 survey respondents, a substantial minority (30%) were unaware of their eligibility for free influenza vaccination. More than half (52%) believed the vaccine could cause influenza, 40% reported there were better ways than vaccination for avoiding infection and 30% said they would not have the vaccine if it was offered to them. Regarding health service access, few reported experiencing difficulty (17%), feeling uncomfortable (15%) or being discriminated against (8%), but 53% reported not receiving a reminder from a health professional. CONCLUSIONS Misconceptions about influenza disease and vaccine among Aboriginal people and inadequate identification of Aboriginality in general practice appear to be the greatest barriers to vaccination, rather than health service access in general. Implications for public health: More active communication to and targeting of Aboriginal adults is required; this is even more urgent following the arrival of COVID-19.


Articles of Significant Interest Selected from This Issue by the Editors.


title: Single-surgeon experience with robot-assisted ureteroneocystostomy for distal ureteral pathologies in adults.

text: PURPOSE To demonstrate our technical approach for robot-assisted ureteroneocystostomy (R-UNC) for benign and malignant distal ureteral pathologies. MATERIALS AND METHODS Between January 2009 and January 2013, a total of 10 patients underwent R-UNC in the distal ureter by a single surgeon. Indications for R-UNC were as follows: idiopathic (3), fistula (2), iatrogenic (2), malignancy (2), and chronic vesicoureteral reflux (1). RESULTS Tension-free anastomosis was attained in all 10 R-UNC procedures. A psoas hitch was performed in 6/10 cases (60%). Intravesical and extravesical reimplantations were completed in 5/10 (50%) and 5/10 cases (50%), respectively. A nonrefluxing ureter was constructed in 2/10 cases (20%). The patients' mean age was 52.9±16.6 years, their mean body mass index was 30.8±6.3 kg/m(2), the mean operative time was 211.7±69.3 minutes, mean estimated blood loss was 102.5±110.8 mL, and mean length of stay was 2.8±2.3 days. There were no intraoperative complications. There was one Clavien-Dindo grade I and one Clavien-Dindo grade II postoperative complication. The mean postoperative follow-up duration was 28.5±15.5 months. Two patients had recurrence of ureteral strictures at 3 months postoperatively and were managed successfully with balloon dilation. CONCLUSIONS Our technique for R-UNC demonstrates good perioperative outcomes. However, underlying periureteral inflammation and pelvic adhesions may predispose patients for stricture recurrence after R-UNC.


title: Should coronavirus disease 2019 concern rheumatologists?

text: Coronavirus disease 2019 (COVID-19) is an infectious disease that became a global health emergency. The paper reviews aspects of COVID-19 that pertain to rheumatology, including symptoms and signs akin to those observed in rheumatic disorders, risk of infection or severe course of the disease in patients with a pre-existing rheumatic disease and those receiving antirheumatic or immunosuppressive medication as well as potential applications of antirheumatic or anticytokine therapeutic strategies that are already applied in rheumatology (including chloroquine, hydroxychloroquine, tocilizumab, baricitinib, and others) for patients with COVID-19.


title: Single cannula versus double cannula tracheostomy tubes in major oral and oropharyngeal resections.

text: OBJECTIVE To compare the outcomes of two types of tracheostomy tubes used in major head and neck surgery. METHODS A retrospective study was conducted of prospectively collected data. The post-operative safety and adequacy of a single cannula tracheostomy tube was compared to a double cannula tracheostomy tube in patients undergoing tracheostomy during major oral and oropharyngeal resections. RESULTS Out of 46 patients with the single cannula tube, 7 (15 per cent) experienced significant obstruction warranting immediate tube removal, while another 9 (20 per cent) needed a change of tube or tube re-insertion for continued airway protection. In contrast, out of 50 patients with the double cannula tube, the corresponding numbers were 0 (p = 0.004) and 1 (2 per cent; p = 0.007) respectively. CONCLUSION Insertion of a double cannula (instead of a single cannula) tracheostomy tube in the course of major oral and oropharyngeal resections offers better airway protection during the post-operative period.


title: Laparoscopic inguinal hernioplasty in a ram.

text: CASE DESCRIPTION A 4-month-old Hampshire ram underwent open right inguinal herniorrhaphy and unilateral castration following herniation that developed after a kick injury. Seven months later, the ram was reevaluated because of scrotal swelling of 1 month's duration as well as suspected left inguinal hernia. CLINICAL FINDINGS The ram had marked scrotal swelling. Palpation of the left testicle revealed no abnormalities. Ultrasonographic examination revealed heterogenous tissue within the cranial and medial portions of the scrotum with pronounced accumulation of hypoechoic fluid at the scrotal apex. Examination findings indicated left-sided indirect inguinal herniation of omentum. TREATMENT AND OUTCOME To preserve fertility, left inguinal hernioplasty without castration was performed. The ram was anesthetized and placed in dorsal recumbency, and laparoscopic abdominal evaluation revealed omental entrapment within the left inguinal ring. The omentum was removed, and a polypropylene mesh was secured over the internal inguinal ring with an articulating hernia stapler. Following mesh placement, a dorsally based peritoneal flap was elevated and secured over the mesh repair. The ram recovered well from surgery; there was no repeated herniation following the surgical correction, and the ram was able to breed successfully without complication. CLINICAL RELEVANCE Laparoscopic mesh hernioplasty can be successful in rams with inguinal hernias when preservation of fertility is preferred.


title: Computed Tomography-Guided Tumor Ablation: Analysis and Optimization of Computed Tomography Technique With Various Ablation Devices.

text: PURPOSE Ablation device-associated computed tomography beam hardening artifacts can make tumor margin visualization and its relationship to the ablation applicator tip challenging. Determine optimal scanning conditions for currently-used applicators. MATERIALS AND METHODS Eleven applicators were placed in ex vivo cow livers with implanted mock tumors, surrounded by bolus gel. Various computed tomography scans were performed at 440 mA with 5 mm thickness changing kVp (80, 100, 120, 140), scan time (0.5, 0.7, 1.0, 2.0 seconds), adaptive statistical iterative reconstruction (ASiR) (30, 60, 90), scan type (helical, axial), pitch (0.5, 0.94, 1.37, 1.75), and reconstruction algorithm (soft, standard, lung). Two radiologists blindly scored the images for image quality and artifact quantitatively. RESULTS Cool-tip single (CTS) RF electrode (Covidien) performed significantly better than all other devices in both perceived image quality and artifact while Boston Scientific 4.0 RF electrode (Boston Scientific) underperformed (all P < 0.001), when not controlling for any other factors. An effect for artifact (P < 0.001) was found for kVp and device: for most conditions, 80 kVp was rated significantly lower than all other levels, whereas 120 and 140 performed significantly better than 100 and 80. No significant effect with ASiR level and device was found for the artifact. There was an effect observed for artifact (P < 0.001) between scan time and probe: for most devices, 0.5 seconds was rated significantly lower than all other scan times, but CTS was resilient-showing no difference from other scan times. Algorithm did not show any significant effects. Taking into account ASiR, kVp, and time, CTS outperformed all other devices. CONCLUSIONS Higher kVp and scan times reduce device artifacts. It appears that CTS performs the best, even when considering ASiR, kVp, pitch, scan type, and scan time.


title: The ethics of biosafety considerations in gain-of-function research resulting in the creation of potential pandemic pathogens.

text: This paper proposes an ethical framework for evaluating biosafety risks of gain-of-function (GOF) experiments that create novel strains of influenza expected to be virulent and transmissible in humans, so-called potential pandemic pathogens (PPPs). Such research raises ethical concerns because of the risk that accidental release from a laboratory could lead to extensive or even global spread of a virulent pathogen. Biomedical research ethics has focused largely on human subjects research, while biosafety concerns about accidental infections, seen largely as a problem of occupational health, have been ignored. GOF/PPP research is an example of a small but important class of research where biosafety risks threaten public health, well beyond the small number of persons conducting the research.We argue that bioethical principles that ordinarily apply only to human subjects research should also apply to research that threatens public health, even if, as in GOF/PPP studies, the research involves no human subjects. Specifically we highlight the Nuremberg Code's requirements of 'fruitful results for the good of society, unprocurable by other methods', and proportionality of risk and humanitarian benefit, as broad ethical principles that recur in later documents on research ethics and should also apply to certain types of research not involving human subjects. We address several potential objections to this view, and conclude with recommendations for bringing these ethical considerations into policy development.


title: Single-incision pediatric endosurgery-assisted ileocecectomy for resection of a NEC stricture.

text: A single-incision pediatric endosurgery (SIPES) has not been typically used for operations in premature infants yet. We report a case of a 3-month-old 25-week premature infant who underwent SIPES-assisted ileocecal resection for a stricture after medically treated necrotizing enterocolitis. The patient recovered uneventfully, and was discharged on full feeds 15 postoperatively with virtually no appreciable scar. SIPES is a reasonable alternative for NEC stricture resection in premature infants. Prematurity should not be considered a contraindication to single-incision endosurgery.


Pearls and Pitfalls in Multimodality Imaging of Colonic Volvulus.


title: Laryngeal mask airway reduces incidence of post-operative sore throat after thyroid surgery compared with endotracheal tube: a single-blinded randomized controlled trial.

text: BACKGROUND Sore throat is a remarkable complication after thyroid surgery with endotracheal tube (ETT). Many studies revealed that laryngeal mask airway (LMA) might reduce the incidence and severity of postoperative sore throat. However, little is known about the use of a flexible reinforced LMA (FLMA) in thyroid surgery. The purpose of this study was to explore the potential benefits of FLMA compared with ETT on postoperative sore throat. METHODS In this prospective, single-blinded, randomized, controlled trial, ninety-six patients aged 20-80 years, scheduled for elective radical thyroidectomy under general anesthesia were enrolled. They were randomly divided into ETT group and FLMA group. All the included patients received total intravenous anesthesia (with propofol, fentanyl and rocuronium) and controlled mechanical ventilation during the surgery. Cuff pressure of ETT and FLMA were strictly controlled. Incidence and severity of postoperative sore throat, numbness and hoarseness at 1, 24, and 48 h after surgery was evaluated and compared between the two groups. Incidence and severity of buckling during extubation and the hemodynamic profile during intubation were also recorded and compared. RESULTS The incidence of sore throat and hoarseness was significantly lower in FLMA group than those in ETT group at 1 h, 24 h and 48 h postoperatively, as well as the severity of sore throat. Compared to ETT group, there was a significantly lower incidence of buckling during extubation and less fluctuation of HR and BP at 1 min and 3 min after intubation in FLMA group. CONCLUSIONS Patients undergoing thyroid surgery with FLMA had less postoperative laryngopharyngeal symptoms when compared with ETT. The use of FLMA also achieved less buckling during extubation and better hemodynamic profiles during intubation. TRIAL REGISTRATION The research was registered in Chinese Clinical Trial Registry (ChiCTR-IOR-15006602) on May 23th, 2015.


title: Lower socioeconomic status is associated with an increased prevalence of comorbid anxiety and depression among patients with irritable bowel syndrome: results from a multicenter cohort.

text: Background/Aims: Anxiety and depression are common comorbid psychiatric disorders in IBS patients, but the population-level determinants influencing these comorbidities in IBS patients are poorly understood. We sought to determine whether there was an association between comorbid affective disorders and socioeconomic status among irritable bowel syndrome (IBS) patients. Methods: We assembled a retrospective cohort of 1074 IBS patients with comorbid Generalized Anxiety Disorder (GAD) and/or Major Depressive Disorder (MDD) seen at two tertiary referral centers between 2007 and 2015. IBS patients with comorbid GAD and/or MDD were matched 3:1 by age, sex, and race to controls with IBS and no history of comorbid GAD and/or MDD. Socioeconomic status was approximated by patient zip codes. Results: IBS patients in the lowest socioeconomic group were more likely to be diagnosed with GAD and/or MDD compared to controls (OR = 1.38, p = .0004). The median average per capita income for comorbid GAD/MDD IBS patient cohort was also significantly lower than the control IBS patient cohort ($39,880.50 vs. $41,277.00, p = .02). Conclusions: Among IBS patients, the presence of comorbid Generalized Anxiety Disorder and/or Major Depressive Disorder is associated with lower socioeconomic status and lower average per capita income. These findings speak to a biopsychosocial model of illness, which should be considered by clinicians in the care of IBS patients.


title: A Systematic Review of Psychosocial Barriers and Facilitators to Smoking Cessation in People Living With Schizophrenia.

text: Background: People living with schizophrenia are less likely to quit smoking compared with the general population and people living with other psychiatric disorders. Understanding the schizophrenia-specific psychosocial barriers and facilitators to smoking cessation is important for designing effective smoking cessation interventions. We aimed to systematically review research examining psychosocial barriers and facilitators to smoking cessation in people living with schizophrenia. Methods: We followed the PRISMA statement to conduct a systematic literature review examining psychosocial barriers and facilitators to smoking cessation in people living with schizophrenia. We searched EMBASE, Medline, PsycINFO, and CINAHL databases from inception to 14 June 2018 to identify relevant articles. We included peer-reviewed original research articles that examined psychosocial barriers and facilitators to smoking cessation, as well as factors associated with maintenance of smoking habits in people living with schizophrenia spectrum disorders. Qualitative, quantitative, or mixed-methods study designs were included. Three authors screened titles, abstracts, and full-texts using the eligibility criteria. We conducted a narrative synthesis of the data to account for the heterogeneity of study designs. We analyzed qualitative and quantitative studies separately. Results: We identified 685 studies from our systematic search and screened the full-text of 134 articles. The final set of 23 articles included 20 quantitative studies and 3 qualitative studies. The most commonly cited barrier to smoking cessation in people living with schizophrenia was cravings and addiction, followed by a perceived increased risk of negative affect associated with quitting smoking. People living with schizophrenia reported smoking to manage stress and to maintain social relationships. People living with schizophrenia were found to be less likely to receive cessation support from health professionals than smokers without schizophrenia. Health concerns were the most commonly mentioned facilitator to quit smoking. Conclusions: People living with schizophrenia experience a wide range of barriers to smoking cessation. The influence of these barriers on smoking cessation likelihood may be greater among people living with schizophrenia than people without psychiatric disorders. Health professionals play an important role in smoking cessation for people living with schizophrenia and should consider barriers and facilitators identified in this review to support quitting in this vulnerable population.


title: Reovirus nonstructural protein sigma1s is required for establishment of viremia and systemic dissemination.

text: Serotype-specific patterns of reovirus disease in the CNS of newborn mice segregate with the viral S1 gene segment, which encodes attachment protein sigma1 and nonstructural protein sigma1s. The importance of receptor recognition in target cell selection by reovirus implicates the sigma1 protein as the primary effector of disease outcome. However, the contribution of sigma1s to reovirus disease is unknown. To define the function of sigma1s in reovirus pathogenesis, we generated a sigma1s-deficient virus by altering a single nucleotide to disrupt the sigma1s translational start site. Viruses were recovered that contain nine gene segments from strain type 3 Dearing and either the wild-type or sigma1s-null S1 gene segment from strain type 1 Lang. Following peroral inoculation of newborn mice, both viruses replicated in the intestine, although the wild-type virus achieved higher yields than the sigma1s-null virus. However, unlike the wild-type virus, the sigma1s-deficient virus failed to disseminate to sites of secondary viral replication, including the brain, heart, and liver. Within the small intestine, both viruses were detected in Peyer's patches, but only the wild-type virus reached the mesenteric lymph node. Concordantly, wild-type virus, but not sigma1s-deficient virus, was detected in the blood of infected animals. Wild-type and sigma1s-null viruses produced equivalent titers following intracranial inoculation, indicating that sigma1s is dispensable for viral growth in the murine CNS. These results suggest a key role for sigma1s in virus spread from intestinal lymphatics to the bloodstream, thereby allowing the establishment of viremia and dissemination to sites of secondary replication within the infected host.


title: Protection of chickens vaccinated with combinations of commercial live infectious bronchitis vaccines containing Massachusetts, Dutch and QX-like serotypes against challenge with virulent infectious bronchitis viruses 793B and IS/1494/06 Israel variant 2.

text: Infectious bronchitis virus (IBV) is a coronavirus which affects chickens of all ages. IBV mainly causes respiratory disease but can also result in reduced weight gain, reduced egg production, increased frequency of abnormal eggs and increased rates of mortality. Vaccination is the most important way to control the disease. Nevertheless, novel strains of infectious bronchitis (IB) continue to emerge in the field. In order to respond promptly, combinations of existing IB vaccines are frequently tested to see whether they can provide cross-protection. The efficacy of a combination of vaccines based on Massachusetts, Dutch and QX-like IB strains against emerging IB Israel variant 2 and IB 793B strains was assessed by means of four challenge studies. At least 80% of the birds vaccinated with IB H120 (Mass type) combined with IB D274 (Dutch type) followed by a QX-like IB vaccine booster or vaccinated with a combination of IB H120, IB D274 and QX-like IB were protected against a challenge with IB 793B. In addition, IB 1263 (Mass type) boosted by QX-like IB showed an 85% protection following challenge with IB 793B. A combination of IB H120 and IB D274 boosted by QX-like IB vaccine conferred 70% protection whilst H120 and IB D274 combination on its own showed 61.1% protection against Israel variant 2 challenge. IB 1263 boosted by a QX-like IB vaccine showed 50% protection against IB Israel variant 2. Therefore, it can be concluded that a combination of the IB H120, IB D274 and QX-like IB confers broad protection against different non-related virulent IB strains.


title: One-Year Prospective Study of Community Acquired Influenza and Parainfluenza Viral Infections in Hospitalized Egyptian Children with Malignancy: Single Center Experience.

text: BACKGROUND Respiratory viruses are widespread in the community and easily transmitted to immunocompromised patients. AIMS Assess the prevalence of community-acquired respiratory viral infections among children with cancer presenting with clinical picture suggestive of lower respiratory tract infections (LRTIs), and evaluate its risk factors and prognosis. METHODS Over a year, 90 hospitalized children with malignancy and LRTIs recruited, subjected to clinical assessment, investigated through hematology panel, blood culture, chest x-ray, CT chest and PCR for influenza A and B, parainfluenza (PIV) types 1 and 3 viruses, and respiratory syncytial virus (RSV), and prospectively followed up for the clinical outcome. RESULTS Viral pathogens were identified in 34 patients (37.7%), with a seasonal peak from April to May. The most frequently detected virus was influenza virus [type A (16 cases; 47%), type B (4 cases; 12%)] followed by parainfluenza virus [PIV1 (9 cases; 26%), PIV3 (3 cases; 15%)], and none had RSV. Bacteria were identified in 26 patients, fungi in four, mixed infections [bacterial/viral and bacterial/fungal] in 13, and 36 cases had unidentified etiology. The majority of patients with influenza and parainfluenza infections had hematological malignancy, presented with fever, and had mild self-limited respiratory illness. Five patients with mixed viral and bacterial infection had severe symptoms necessitating ICU admission. Six patients died from infection-related sequelae; two had mixed PIV and Staphylococcal infections. CONCLUSIONS Community acquired influenza and parainfluenza infections are common in pediatrics patients with malignancy, either as isolated or mixed viral/bacterial infections. Clinical suspicion is essential as hematological and radiological manifestations are nonspecific. Rapid diagnosis and management are mandatory to improve patients' outcome.


title: Internal Herniation After Laparoscopic Roux-en-Y Gastric Bypass Surgery: Pitfalls in Diagnosing and the Introduction of the AMSTERDAM Classification.

text: INTRODUCTION Internal herniation (IH) probably is the most elusive complication of laparoscopic Roux- en-Y gastric bypass (LRYGB) surgery. This study provides a definition for IH, a diagnosing algorithm, and information on several factors influencing IH formation. METHOD Baseline characteristics, laboratory findings, imaging studies, operative findings, and follow up data of 1583 patients that underwent LRYGB at our bariatric facility between 2007 and 2013 were recorded. Follow up varied between 3 and 76 months, and 85 % of the data was available for analysis at 12 months. Our surgical technique was standardized. Intermesenteric spaces were not closed until July 2012, where after they were closed. To facilitate comparison, IH cases were matched with controls. RESULTS Forty patients (2.5 %) had an IH during re-laparoscopy. The modal clinical presentation is acute onset epigastric discomfort, often crampy/colicky in nature. Additional examinations included laboratory testing, abdominal X-ray, abdominal ultrasound, and abdominal CT scanning. Patients who developed an IH lost a significantly higher percentage of their total body weight than their matched controls at every time point. IH incidence was higher in the non-closure group than the closure group. CONCLUSION The large variation in reported IH incidence is due to the large variation in IH definition. To gain more uniformity in reporting IH prevalence, we propose the use of the AMSTERDAM classification. Post-LRYGB patients with acute onset crampy/colicky epigastric pain should undergo abdominal ultrasound to rule out gallbladder pathology and offered re-laparoscopy with a low threshold. IH incidence is highest among patients with rapid weight loss and non-closure of intermesenteric defects.


Response to: 'Concerns and needs of patients with systemic lupus erythematosus regarding hydroxychloroquine supplies during the COVID-19 pandemic: results from a patient-centred survey' by Plüß et al.


Audio Interview: New Research on Possible Treatments for Covid-19.


title: Genetic evidence of a long-range RNA-RNA interaction between the genomic 5' untranslated region and the nonstructural protein 1 coding region in murine and bovine coronaviruses.

text: Higher-order RNA structures in the 5' untranslated regions (UTRs) of the mouse hepatitis coronavirus (MHV) and bovine coronavirus (BCoV), separate species in the betacoronavirus genus, appear to be largely conserved despite an ∼36% nucleotide sequence divergence. In a previous study, each of three 5'-end-proximal cis-acting stem-loop domains in the BCoV genome, I/II, III, and IV, yielded near-wild-type (wt) MHV phenotypes when used by reverse genetics to replace its counterpart in the MHV genome. Replacement with the BCoV 32-nucleotide (nt) inter-stem-loop fourth domain between stem-loops III and IV, however, required blind cell passaging for virus recovery. Here, we describe suppressor mutations within the transplanted BCoV 32-nt domain that along with appearance of potential base pairings identify an RNA-RNA interaction between this domain and a 32-nt region ∼200 nt downstream within the nonstructural protein 1 (Nsp1)-coding region. Mfold and phylogenetic covariation patterns among similarly grouped betacoronaviruses support this interaction, as does cotransplantation of the BCoV 5' UTR and its downstream base-pairing domain. Interestingly, cotransplantation of the BCoV 5' UTR and BCoV Nsp1 coding region directly yielded an MHV wt-like phenotype, which demonstrates a cognate interaction between these two BCoV regions, which in the MHV genome act in a fully interspecies-compliant manner. Surprisingly, the 30-nt inter-stem-loop domain in the MHV genome can be deleted and viral progeny, although debilitated, are still produced. These results together identify a previously undescribed long-range RNA-RNA interaction between the 5' UTR and Nsp1 coding region in MHV-like and BCoV-like betacoronaviruses that is cis acting for viral fitness but is not absolutely required for viral replication in cell culture.


title: Optimal blood pressure during cardiopulmonary bypass defined by cerebral autoregulation monitoring.

text: OBJECTIVES We sought to define the lower and upper limits of cerebral blood flow autoregulation and the optimal blood pressure during cardiopulmonary bypass. We further sought to identify variables predictive of these autoregulation end points. METHODS Cerebral autoregulation was monitored continuously with transcranial Doppler in 614 patients during cardiopulmonary bypass enrolled in 3 investigations. A moving Pearson's correlation coefficient was calculated between cerebral blood flow velocity and mean arterial pressure to generate the variable mean velocity index. Optimal mean arterial pressure was defined as the mean arterial pressure with the lowest mean velocity index indicating the best autoregulation. The lower and upper limits of cerebral blood flow autoregulation were defined as the mean arterial pressure at which mean velocity index was increasingly pressure passive (ie, mean velocity index ≥0.4) with declining or increasing blood pressure, respectively. RESULTS The mean (± standard deviation) lower and upper limits of cerebral blood flow autoregulation, and optimal mean arterial pressure were 65 ± 12 mm Hg, 84 ± 11 mm Hg, and 78 ± 11 mm Hg, respectively, after adjusting for study enrollment. In 17% of patients, though, the lower limit of cerebral autoregulation was above this optimal mean arterial pressure, whereas in 29% of patients the upper limit of autoregulation was below the population optimal mean arterial pressure. Variables associated with optimal mean arterial pressure based on multivariate regression analysis were nonwhite race (increased 2.7 mm Hg; P = .034), diuretics use (decreased 1.9 mm Hg; P = .049), prior carotid endarterectomy (decreased 5.5 mm Hg; P = .019), and duration of cardiopulmonary bypass (decreased 1.28 per 60 minutes of cardiopulmonary bypass). The product of the duration and magnitude that mean arterial pressure during cardiopulmonary bypass was below the lower limit of cerebral autoregulation was associated with the risk for stroke (P = .02). CONCLUSIONS Real-time monitoring of autoregulation may improve individualizing mean arterial pressure during cardiopulmonary bypass and improving patient outcomes.


title: Cerebral oxygenation and echocardiographic parameters in preterm neonates with a patent ductus arteriosus: an observational study.

text: BACKGROUND A haemodynamically significant patent ductus arteriosus (hsPDA) is clinically suspected and confirmed by echocardiographic examination. A hsPDA decreases cerebral blood flow and oxygen saturation by the ductal steal phenomenon. AIM To determine the relationship between echocardiographic parameters, cerebral oxygenation and a hsPDA in preterm infants. METHODS 380 preterm infants (<32 weeks gestational age) born between 2008 and 2010 were included. Blinded echocardiographic examination was performed on the second, fourth and sixth day after birth. Examinations were deblinded when hsPDA was clinically suspected. Regional cerebral oxygen saturation (rScO2) was continuously monitored by near-infrared spectroscopy during 72 h after birth, and afterwards for at least 1 h before echocardiography. Echocardiographic parameters included ductal diameter, end-diastolic flow in the left pulmonary artery, left atrium/aorta ratio and ductal flow pattern. RESULTS rScO2 was significantly related only to ductal diameter over time. Mixed modelling analysed the course of rScO2 over time, where infants were divided into four groups: a closed duct, an open haemodynamically insignificant duct (non-sPDA), a hsPDA, which was successfully closed during study period (SC hsPDA) or a hsPDA, which was unsuccessfully closed during study period (UC hsPDA). SC hsPDA infants showed the highest rScO2 on day 6, while UC hsPDA infants had the lowest rScO2 values. CONCLUSIONS Ductal diameter is the only echocardiographic parameter significantly related to cerebral oxygenation over time. Cerebral oxygenation takes a different course over time depending on the status of the duct. Low cerebral oxygenation may be suggestive of a hsPDA.


title: Consensus statement on definitions and nomenclature for robotic thoracic surgery.

text: OBJECTIVES Robotic thoracic operations are increasing, and new robotic systems are imminent. A definition of what constitutes a robotic thoracic operation and a nomenclature to detail the technique used is needed to accurately compare outcomes. METHODS The American Association of Thoracic Surgeons Guideline Committee appointed an expert consensus writing committee to construct definitions and nomenclature for robotic thoracic surgery. A PubMed search was generated and after vetting and review of the literature a consensus statement was reached. RESULTS The proposed definition is: "A robotic thoracic operation is a minimally invasive surgical procedure that does not spread, lift or remove any part of the chest or abdominal wall and is characterized by: the surgeon and the assistant's vision of the operative field is via a monitor only and the patient's tissue is manipulated by robotic instruments that follow a slave like mimic of human hands or thoughts via a computerized system." In addition, a flexible nomenclature is proposed that should be applicable to current and future robotic systems that details the number of robotic arms used, the types of ports and/or incisions made, the use of insufflation, and the operation performed. CONCLUSIONS The American Association of Thoracic Surgeons writing committee proposes a definition and nomenclature for robotic thoracic surgery. Definitions are needed to ensure that future studies accurately compare results and outcomes and nomenclatures allow surgeons and scientists from diverse countries and cultures to use the same language to allow accurate communication.


title: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia].

text: Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients, serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased (15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mild group. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.


title: Charge dependent substrate activity of C3' and N3 functionalized, organometallic technetium and rhenium-labeled thymidine derivatives toward human thymidine kinase 1.

text: Human cytosolic thymidine kinase (hTK1) has proven to be a suitable target for the noninvasive imaging of cancer cell proliferation using radiolabeled thymidine analogues such as [(18)F]3'-fluoro-3'-deoxythymidine ([(18)F]FLT). A thymidine analogue for single photon emission computed tomography (SPECT), which incorporates the readily available and inexpensive nuclide technetium-99m, would be of considerable practical interest. hTK1 is known to accommodate modification of the structure of the natural substrate thymidine at the positions N3 and C3' and, to a lesser extent, C5. In this work, we used the copper-catalyzed azide-alkyne cycloaddition to synthesize two series of derivatives in which thymidine is functionalized at either the C3' or N3 position with chelating systems suitable for the M(CO)(3) core (M = (99m)Tc, Re). The click chemistry approach enabled complexes with different structures and overall charges to be synthesized from a common precursor. Using this strategy, the first organometallic hTK1 substrates in which thymidine is modified at the C3' position were identified. Phosphorylation of the organometallic derivatives was measured relative to thymidine. We have shown that the influence of the overall charge of the derivatives is dependent on the position of functionalization. In the case of the C3'-functionalized derivatives, neutral and anionic substrates were most readily phosphorylated (20-28% of the value for the parent ligand thymidine), whereas for the N3-functionalized derivatives, cationic and neutral complexes were apparently better substrates for the enzyme (14-18%) than anionic derivatives (9%).