title: Interventions to Promote Patient Utilization of Cardiac Rehabilitation: Cochrane Systematic Review and Meta-Analysis.

text: Too few patients utilize cardiac rehabilitation (CR), despite its benefits. The Cochrane review assessing the effectiveness of interventions to increase CR utilization (enrolment, adherence, and completion) was updated. A search was performed through July 2018 of the Cochrane and MEDLINE (Medical Literature Analysis and Retrieval System Online) databases, among other sources. Randomized controlled trials in adults with myocardial infarction, angina, revascularization, or heart failure were included. Interventions had to aim to increase utilization of comprehensive phase II CR. Two authors independently performed all stages of citation processing. Following the random-effects meta-analysis, meta-regression was undertaken to explore the impact of pre-specified factors. Twenty-six trials with 5299 participants were included (35.8% women). Low-quality evidence showed an effect of interventions in increasing enrolment (risk ratio (RR) = 1.27, 95% confidence interval (CI) = 1.13⁻1.42). Meta-regression analyses suggested that the intervention deliverer (nurse or allied healthcare provider, p = 0.02) and delivery format (face-to-face, p = 0.01) were influential in increasing enrolment. There was low-quality evidence that interventions to increase adherence were effective (standardized mean difference (SMD) = 0.38, 95% CI = 0.20⁻0.55), particularly where remotely-offered (SMD = 0.56, 95% CI = 0.36⁻0.76). There was moderate-quality evidence that interventions to increase program completion were effective (RR = 1.13, 95% CI = 1.02⁻1.25). There are effective interventions to increase CR utilization, but more research is needed to establish specific, implementable materials and protocols, particularly for completion.


DILEMMAS OF A PHYSICIAN IN TIMES OF COVID-19.


title: Dynamic Respiratory Tortuosity of the Vertebral Artery Ostium.

text: PURPOSE To determine the prevalence of dynamic respiratory tortuosity (DRT) of the vertebral artery ostium (VAO) as well as to evaluate its correlation with in-stent restenosis (ISR) and stent fracture. METHODS From March 2012 to June 2015, 178 consecutive patients (mean age 65.2±5.8 years; 124 men) with symptoms of atherosclerotic vertebrobasilar ischemia underwent angiography prior to stent implantation in the vertebral, subclavian, and/or carotid arteries. In this cohort, 54 patients (mean age 67.3±5.3 years; 40 men) had VAO stent implantation. Angiography of the vertebral artery was recorded in 2 phases with breath-hold: deep inspiration (DIP) and deep expiration (DEP). Obvious VAO tortuosity was defined as any VAO angle ≤120° in DIP. Obvious VAO-DRT was defined as any VAO angle increasing ≥60° from DIP to DEP. Computed tomography angiography (CTA) or digital subtraction angiography was used in follow-up to detect ISR and stent fracture. RESULTS Of the 178 patients in this study, 21 (11.8%) had obvious VAO tortuosity and 8 (4.5%) had obvious VAO-DRT. Two of the 21 patients with obvious VAO tortuosity also had obvious VAO-DRT. Three of the 54 VAO stent patients had VAO-DRT. There were no correlations between VAO-DRT and age, sex, risk factors, body mass index, chronic obstructive pulmonary disease, asthma, or obvious VAO tortuosity (p>0.05). Over a mean follow-up of 28±10 months, there were 4 (7.4%) asymptomatic VAO ISR cases. Two (3.7%) were occlusions at 6 and 12 months, respectively; both were associated with stent fracture in patients with obvious VAO-DRT before stenting. Both stents fractured at the tortuous VAO region. VAO-DRT was correlated with stent fracture (Spearman ρ=0.81, p<0.01) and ISR (Spearman ρ=0.55, p<0.01). CONCLUSION VAO-DRT could be a risk factor for stent fracture and restenosis after VAO stent implantation. Angiography in both inspiration and expiration phases, especially the latter, should be considered before VAO stenting. Using a shorter stent to avoid crossing the tortuosity could reduce the occurrence of fracture.


title: Reducing overcrowding in an emergency department: a pilot study.

text: OBJECTIVE Exploring the use of forecasting models and simulation tools to estimate demand and reduce the waiting time of patients in Emergency Departments (EDs). METHODS The analysis was based on data collected in May 2013 in the ED of Recanto das Emas, Federal District, Brasil, which uses a Manchester Triage System. A total of 100 consecutive patients were included: 70 yellow (70%) and 30 green (30%). Flow patterns, observed waiting time, and inter-arrival times of patients were collected. Process maps, demand, and capacity data were used to build a simulation, which was calibrated against the observed flow times. What-if analysis was conducted to reduce waiting times. RESULTS Green and yellow patient arrival-time patterns were similar, but inter-arrival times were 5 and 38 minutes, respectively. Wait-time was 14 minutes for yellow patients, and 4 hours for green patients. The physician staff comprised four doctors per shift. A simulation predicted that allocating one more doctor per shift would reduce wait-time to 2.5 hours for green patients, with a small impact in yellow patients' wait-time. Maintaining four doctors and allocating one doctor exclusively for green patients would reduce the waiting time to 1.5 hours for green patients and increase it in 15 minutes for yellow patients. The best simulation scenario employed five doctors per shift, with two doctors exclusively for green patients. CONCLUSION Waiting times can be reduced by balancing the allocation of doctors to green and yellow patients and matching the availability of doctors to forecasted demand patterns. Simulations of EDs' can be used to generate and test solutions to decrease overcrowding.


title: A technical consideration when using flow diversion for recurrent aneurysms following stent-assisted coiling.

text: Flow diversion (FD) is a treatment option for recurrent aneurysms including following stent-assisted coiling (SAC), although this approach is both 'off-label' and unproven. A technical challenge of FD placement may involve the microwire catching on the tines of the previously placed stent or potentially going 'in-out-in' from the central axis of the stent. We report a case and technique that assures the wire has safely remained within the central axis of the stent. The procedure was performed in standard fashion except that the intermediate catheter was passed completely through the previously placed stent after the microwire/microcatheter had crossed. The large diameter of the intermediate catheter assured that the microwire did not go 'in-out-in'. The intermediate catheter was completely withdrawn from the stent and the FD was placed in standard fashion. This technique may help to achieve complete FD opening and prevent thromboembolic complications associated with incomplete FD opening.


title: The HIV Integrase Inhibitor Raltegravir Inhibits Felid Alphaherpesvirus 1 Replication by Targeting both DNA Replication and Late Gene Expression.

text: Alphaherpesvirus-associated ocular infections in humans caused by human alphaherpesvirus 1 (HHV-1) remain challenging to treat due to the frequency of drug application required and the potential for the selection of drug-resistant viruses. Repurposing on-the-market drugs is a viable strategy to accelerate the pace of drug development. It has been reported that the human immunodeficiency virus (HIV) integrase inhibitor raltegravir inhibits HHV-1 replication by targeting the DNA polymerase accessory factor and limits terminase-mediated genome cleavage of human betaherpesvirus 5 (HHV-5). We have previously shown, both in vitro and in vivo, that raltegravir can also inhibit the replication of felid alphaherpesvirus 1 (FeHV-1), a common ocular pathogen of cats with a pathogenesis similar to that of HHV-1 ocular disease. In contrast to what was reported for HHV-1, we were unable to select for a raltegravir-resistant FeHV-1 strain in order to define any basis for drug action. A candidate-based approach to explore the mode of action of raltegravir against FeHV-1 showed that raltegravir did not impact FeHV-1 terminase function, as described for HHV-5. Instead, raltegravir inhibited DNA replication, similarly to HHV-1, but by targeting the initiation of viral DNA replication rather than elongation. In addition, we found that raltegravir specifically repressed late gene expression independently of DNA replication, and both activities are consistent with inhibition of ICP8. Taken together, these results suggest that raltegravir could be a valuable therapeutic agent against herpesviruses.IMPORTANCE The rise of drug-resistant herpesviruses is a longstanding concern, particularly among immunocompromised patients. Therefore, therapies targeting viral proteins other than the DNA polymerase that may be less likely to lead to drug-resistant viruses are urgently needed. Using FeHV-1, an alphaherpesvirus closely related to HHV-1 that similarly causes ocular herpes in its natural host, we found that the HIV integrase inhibitor raltegravir targets different stages of the virus life cycle beyond DNA replication and that it does so without developing drug resistance under the conditions tested. This shows that the drug could provide a viable strategy for the treatment of herpesvirus infections.


title: SARS-CoV-2 infection in children - Understanding the immune responses and controlling the pandemic.

text: In December 2019, a cluster of patients with severe pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in the city of Wuhan, China. The disease is now termed coronavirus disease 2019 (COVID-19). In the early reports, the patients were mainly middle-aged and elderly men, and children appeared to be less susceptible to this infection. With modern and efficient transportation, the disease quickly spread to almost all corners of the world and the mortality far exceeds those caused by severe acute respiratory syndrome coronavirus (SARS) or Middle East respiratory syndrome coronavirus (MERS). As the number of children with COVID-19 gradually increases, the disease has been documented in premature babies, infants, children and adolescents. Severe and fatal cases in children are relatively rare. The burden of disease in children has been relatively low, but the high proportions of asymptomatic or mildly symptomatic infections in children deserve careful attention. Clear understanding of the immune responses to the virus in children and the transmission potential of asymptomatic children are of paramount importance for the development of specific treatments and vaccine in order to effectively control the ongoing pandemic.


title: The Swiss Multiple Sclerosis Cohort-Study (SMSC): A Prospective Swiss Wide Investigation of Key Phases in Disease Evolution and New Treatment Options.

text: The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects.


title: Cost-effectiveness analysis of bariatric surgery for morbid obesity in Belgium.

text: AIMS This study presents the cost-effectiveness analysis of bariatric surgery in Belgium from a third-party payer perspective for a lifetime and 10-year horizon. MATERIALS AND METHODS A decision analytic model incorporating Markov process was developed to compare the cost-effectiveness of gastric bypass, sleeve gastrectomy, and adjustable gastric banding against conventional medical management (CMM). In the model, patients could undergo surgery, or experience post-surgery complications, type 2 diabetes, cardiovascular diseases, or die. Transition probabilities, costs, and utilities were derived from the literature. The impact of different surgical methods on body mass index (BMI) level in the base-case analysis was informed by the Scandinavian Obesity Surgery Registry and the Swedish Obese Subject (SOS) study. Healthcare resource use and costs were obtained from Belgian sources. A base-case analysis was performed for the population, the characteristics of which were obtained from surgery candidates in Belgium. RESULTS In the base-case analysis over a 10-year time horizon, the increment in quality-adjusted life-years (QALYs) gained from bariatric surgery vs CMM was 1.4 per patient, whereas the incremental cost was €3,788, leading to an incremental cost-effectiveness ratio (ICER) of €2,809 per QALY. Over a lifetime, bariatric surgery produced savings of €9,332, an additional 1.1 life years and 5.0 QALYs. Bariatric surgery was cost-effective at 10 years post-surgery and dominant over conventional management over a lifetime horizon. LIMITATIONS The model did not include the whole scope of obesity-related complications, and also did not account for variation in surgery outcomes for different populations of diabetic patients. Also, the data about management of patients after surgery was based on assumptions and the opinion of a clinical expert. CONCLUSIONS It was demonstrated that a current mix of bariatric surgery methods was cost-effective at 10 years post-surgery and cost-saving over the lifetime of the Belgian patient cohort considered in this analysis.


title: Prospective evaluation of functional outcomes after laparoscopic sigmoidectomy with high tie of the inferior mesenteric artery for diverticular disease in consecutive male patients.

text: BACKGROUND To date, there has been no consensus concerning the vascular approach during sigmoid colectomy for diverticular disease. The aim of this study was to determine the functional impact of elective laparoscopic sigmoidectomy performed with high ligation of the inferior mesenteric artery for diverticulitis in consecutive male patients. METHODS Twenty-five consecutive patients of median age 53 years were enrolled in a prospective single-centre pilot study at a tertiary teaching hospital. Main outcome measures were functional results. Patients were asked to complete standardized, validated questionnaires to evaluate preoperative and 6 months postoperative bowel symptomatology (Jorge-Wexner Incontinence Score and KESS score), urinary function (IPSS), and sexual function (IIEF). Secondary outcomes were surgical data, morbidity, and quality of life (SF-36). RESULTS There were no significant differences between preoperative and 6 months postoperative total scores for bowel symptomatology, urinary function, and sexual function. There were no perioperative deaths. The morbidity rate was 12% including three minor and no major events. Quality of life demonstrated statistically better general health (p < 0.01) and better medical status over the prior 4 weeks at 6 months after surgery, compared to baseline. This single-centre prospective study has a limited number of patients, relatively short follow-up time, and includes only male patients. CONCLUSION Laparoscopic sigmoidectomy with high tie of the inferior mesenteric artery for diverticular disease does not induce functional disorders at 6 months after surgery. The benefit of the operation for quality of life is even greater for general health and medical status.


title: Adult bipolar diathermy circumcision and related procedures in adults - a safe and efficient technique.

text: OBJECTIVES To present our novel technique and step-by-step approach to bipolar diathermy circumcision and related procedures in adult males. METHODS We reviewed our technique of bipolar circumcision and related procedures in 54 cases over a 22-month period at our day procedure center. Bipolar diathermy cutting and hemostasis was performed using bipolar forceps with a Valleylab machine set at 15. Sleeve circumcision was used. A dorsal slit was made, followed by frenulum release and ventral slit, and was completed with bilateral circumferential cutting. Frenuloplasties released the frenulum. Preputioplasties used multiple 2-3 mm longitudinal cuts to release the constriction, with frenulum left intact. All wounds were closed with interrupted 4/0 Vicryl Rapide™. RESULTS A total of 54 nonemergency bipolar circumcision procedures were carried out from November 2010-August 2012 (42 circumcisions, eight frenuloplasties, and four preputioplasties). Patients were aged 18-72 years (mean, 34 years). There was minimal to no intraoperative bleeding in all cases, allowing for precise dissection. All patients were requested to attend outpatient reviews; three frenuloplasty and two circumcision patients failed to return. Of the remaining 49, mean interval to review was 49 days, with a range of 9-121 days. Two circumcision patients reported mild bleeding with nocturnal erections within a week postoperatively, but they did not require medical attention. Two others presented to family practitioners with possible wound infections which resolved with oral antibiotics. All 49 patients had well-healed wounds. CONCLUSION The bipolar diathermy technique is a simple procedure, easily taught, and reproducible. It is associated with minimal bleeding, is safe and efficient, uses routine operating equipment and is universally applicable to circumcision/frenuloplasty/preputioplasty. In addition, it has minimal postoperative complications, and has associated excellent cosmesis.


title: The 1-minute sit-to-stand test to detect exercise-induced oxygen desaturation in patients with interstitial lung disease.

text: BACKGROUND Although the 6-min walk test (6MWT) is the gold standard for assessing exercise-induced impairment of gas exchange, it cannot easily be performed in a clinical office environment. The aim of this study was to compare the 1-min sit-to-stand test (1STST) with the 6MWT for the ability to assess exercise-induced oxygen desaturation in patients with interstitial lung diseases (ILDs). METHODS A total of 107 patients were enrolled and classified into three groups: sarcoidosis, fibrotic idiopathic interstitial pneumonia (f-IIP), and other forms of ILD. The 6MWT and 1STST were performed on the same day, and pulmonary function tests, pulse oxygen saturation (SpO2), and dyspnea and fatigue (modified Borg scale) were assessed. SpO2 desaturation was evaluated by intraclass correlation coefficient (ICC), Bland-Altman analysis, and kappa (κ) coefficient in the whole population and the patient subgroups. RESULTS The SpO2 nadir during the 1STST and 6MWT showed good consistency [mean ± standard deviation: 92.5% ± 5% and 90% ± 7%, respectively; ICC 0.77, 95% confidence interval (CI) 0.71-0.83] and correlated strongly ( r = 0.9, p < 0.0001). The frequency of patients with oxygen desaturation ⩾4% was also consistent for the two exercise tests ( κ = 0.68, 95% CI 0.54-0.82). The number of repetitions in the 1STST correlated with the 6MWT distance ( r = 0.5, p < 0.0001), but the dyspnea scores were higher during the 1STST than the 6MWT ( p < 0.0001). These findings did not differ for the three patient subgroups. CONCLUSION The 1STST can measure exercise-induced desaturation in ILD patients and could be used as an alternative test to the 6MWT in office practice.


title: Capillary nano-immunoassay for Akt 1/2/3 and 4EBP1 phosphorylation in acute myeloid leukemia.

text: BACKGROUND Overall cure rates in acute myeloid leukemia (AML) continue to range between 60-65% with disease relapse being a major cause of mortality. The PI3K-Akt-mTOR kinase pathway plays a vital role in pro-survival signals within leukemic cells and inhibition of this pathway is being investigated to improve patient outcomes. Tracking activation of multiple signaling proteins simultaneously in patient samples can be challenging especially with limiting cell numbers within rare sub-populations. METHODS The NanoPro 1000 system (ProteinSimple) is built on an automated, capillary-based immunoassay platform and enables a rapid and quantitative analysis of specific proteins and their phosphorylation states. We have utilized this nano-immunoassay to examine activation of Akt 1/2/3 and downstream mTOR target--eukaryotic initiation factor 4E-Binding Protein 1 (4EBP1). RESULTS Assays for Akt 1/2/3 and 4EBP1 were standardized using AML cell lines (MV4-11, MOLM-14, OCI-AML3 and HL-60) prior to testing in patient samples. Target inhibition was studied using mTOR 1/2 inhibitor AZD-8055 and results were corroborated by Western blotting. The assay was able to quantify nanogram amounts of 4EBP1 and Akt 1/2/3 in AML cell lines and primary pediatric AML samples and results were quantifiable, consistent and reproducible. CONCLUSION Our data provides a strong basis for testing this platform on a larger scale and our long term aim is to utilize this nano-immunoassay prospectively in de-novo AML to be able to identify poor responders who might benefit from early introduction of targeted therapy.


title: Pneumoperitoneum deteriorates intratidal respiratory system mechanics: an observational study in lung-healthy patients.

text: BACKGROUND Pneumoperitoneum during laparoscopic surgery leads to atelectasis and impairment of oxygenation. Positive end-expiratory pressure (PEEP) is supposed to counteract atelectasis. We hypothesized that the derecruiting effects of pneumoperitoneum would deteriorate the intratidal compliance profile in patients undergoing laparoscopic surgery. METHODS In 30 adult patients scheduled for surgery with pneumoperitoneum, respiratory variables were measured during mechanical ventilation. We calculated the dynamic compliance of the respiratory system (C RS) and the intratidal volume-dependent C RS curve using the gliding-SLICE method. The C RS curve was then classified in terms of indicating intratidal recruitment/derecruitment (increasing profile) and overdistension (decreasing profile). During the surgical interventions, the PEEP level was maintained nearly constant at 7 cm H2O. Data are expressed as mean [confidence interval]. RESULTS Baseline C RS was 60 [54-67] mL cm H2O-1. Application of pneumoperitoneum decreased C RS to 40 [37-43] mL cm H2O-1 which partially recovered to 54 [50-59] mL cm H2O-1 (P < 0.001) after removal but remained below the value measured before pneumoperitoneum (P < 0.001). Baseline compliance profiles indicated intratidal recruitment/derecruitment in 48 % patients. After induction of pneumoperitoneum, intratidal recruitment/derecruitment was indicated in 93 % patients (P < 0.01), and after removal intratidal recruitment/derecruitment was indicated in 59 % patients. Compliance profiles showing overdistension were not observed. CONCLUSIONS Analyses of the intratidal compliance profiles reveal that pneumoperitoneum during laparoscopic surgery causes intratidal recruitment/derecruitment which partly persists after its removal. The analysis of the intratidal volume-dependent C RS profiles could be used to guide intraoperative PEEP adjustments during elevated intraabdominal pressure.


title: Antibodies to parvovirus, distemper virus and adenovirus conferred to household dogs using commercial combination vaccines containing Leptospira bacterin.

text: To examine how the inclusion (+) or exclusion (-) of inactivated Leptospira antigens in a vaccine for canine parvovirus type 2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type 2 (CAdV-2) affects antibody titres to CPV-2, CDV and CAdV-1 antigens, household dogs were vaccinated with commercially available vaccines from one of three manufacturers. CPV-2, CDV and CAdV-1 antibody titres were measured 11 to 13 months later and compared within three different age groups and three different bodyweight groups. There were significant differences between CPV-2 antibody titres in dogs vaccinated with (+) vaccine and those vaccinated with (-) vaccine for two products in the two-year-old group and for one product in the greater than seven-year-old group; no significant differences were seen that could be attributed to bodyweight. No differences in CDV antibody titres were observed within age groups, but a significant difference was seen in the 11 to 20 kg weight group for one product. Significant differences in CAdV-1 antibody titres were seen for one product in both the two-year-old group and the ≤10 kg weight group.


title: Living with PTSD amid a global pandemic.

text: The COVID-19 pandemic has demonstrated itself to be a considerable stressor, especially for those individuals coping with a preexisting mental health disorder. This article contains clinical observations and reflections from two practicing psychologists regarding the impact of the COVID-19 pandemic and associated social conditions on clients with posttraumatic stress disorder. Observations include changes in trauma-related symptom manifestations and therapeutic process issues, particularly in response to social isolation. The authors encourage specific therapeutic considerations and offer suggestions for adapting treatment with regard to these early observations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Current state of the treatment of perforating veins.

text: Perforating veins may play a role in the development of chronic venous insufficiency and ulceration. There is renewed interest in minimally invasive treatments vs historic surgical options. Current indications for treatment, technical success, and evidence for clinical efficacy are summarized. Existing recommendations include perforator closure in Clinical, Etiology, Anatomy, and Pathophysiology class 5 or class 6 disease through percutaneous thermal ablation, subfascial endoscopic perforator surgery, open surgery, or sclerotherapy. Closure rates for percutaneous thermal ablation are reported as 60% to 80% initially. More recanalization and de novo perforator formation have been reported than after thermal saphenous closure. Ultrasound-guided foam sclerotherapy has shown promise in perforator closure and wound healing, but with variable success rates. Regardless of method used, successful closure of perforators appears predictive of wound healing with minimal morbidity. However, the power and design of all studies supporting this are far from robust, and more work is needed.


title: Safety, efficacy, and short-term follow-up of the use of Pipeline Embolization Device in small (<2.5 mm) cerebral vessels for aneurysm treatment: single institution experience.

text: INTRODUCTION Flow diversion is being increasingly used to treat cerebral aneurysms. We present our experience using these stents to treat aneurysms distal to the circle of Willis with parent arteries smaller than 2.5 mm. METHODS Aneurysms treated with a Pipeline Embolization Device in vessels less than 2.5 mm between June 2012 and August 2014 were included. We evaluated risk factors, family history of aneurysms, aneurysm characteristics, National Institute of Health Stroke Scale (NIHSS), and modified Rankin scale (mRS) on admission and angiography and clinical outcome at discharge, 6 months, and 1 year. RESULTS We included seven patients with a mean age of 65 years. The parent vessel size ranged from 1.5 to 2.3 mm; mean 1.9 mm. Location of the aneurysms was as follows: two aneurysms centered along the pericallosal artery (one left, one right), one on the right angular artery, one aneurysm at the anterior communicating artery (ACom), one at the ACom-right A2 anterior cerebral artery (ACA), one at the lenticulostriate artery, and one at the A1-A2 ACA artery. Aneurysms ranged from 1 to 12 mm in diameter. All aneurysms were treated with a single Pipeline Embolization Device (PED). No peri- or post-procedural complications or mortality occurred. The patients were discharged with no change in NIHSS or mRS score. Angiographic follow-up was available in six patients. Angiography showed complete aneurysm occlusion in all. NIHSS and mRS remained unchanged at follow-up. CONCLUSION Our preliminary results show that flow diversion technology is an effective and safe therapy for aneurysms located on small cerebral arteries. Larger studies with long-term follow-up are needed to validate our promising results.


title: Analysis and Review of Automated Risk Calculators Used to Predict Postoperative Complications After Orthopedic Surgery.

text: PURPOSE OF REVIEW To discuss the automated risk calculators that have been developed and evaluated in orthopedic surgery. RECENT FINDINGS Identifying predictors of adverse outcomes following orthopedic surgery is vital in the decision-making process for surgeons and patients. Recently, automated risk calculators have been developed to quantify patient-specific preoperative risk associated with certain orthopedic procedures. Automated risk calculators may provide the orthopedic surgeon with a valuable tool for clinical decision-making, informed consent, and the shared decision-making process with the patient. Understanding how an automated risk calculator was developed is arguably as important as the performance of the calculator. Additionally, conveying and interpreting the results of these risk calculators with the patient and its influence on surgical decision-making are paramount. The most abundant research on automated risk calculators has been conducted in the spine, total hip and knee arthroplasty, and trauma literature. Currently, many risk calculators show promise, but much research is still needed to improve them. We recommend they be used only as adjuncts to clinical decision-making. Understanding how a calculator was developed, and accurate communication of results to the patient, is paramount.


title: Guidelines for the recognition and management of mixed depression.

text: A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM-5 codified a new nosological entity, the "mixed features specifier," referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.g., mixed depression, depression with mixed features, or depressive mixed states [DMX]). Current treatment guidelines, regulatory approvals, as well the current evidentiary base provide insufficient decision support to practitioners who provide care to individuals presenting with an MDE with mixed features. In addition, all existing psychotropic agents evaluated in mixed patients have largely been confined to patient populations meeting the DSM-IV definition of "mixed states" wherein the co-occurrence of threshold-level mania and threshold-level MDE was required. Toward the aim of assisting clinicians providing care to adults with MDE and mixed features, we have assembled a panel of experts on mood disorders to develop these guidelines on the recognition and treatment of mixed depression, based on the few studies that have focused specifically on DMX as well as decades of cumulated clinical experience.


The global burden of stroke, and fluoxetine for stroke recovery.


title: Frequency of post-stroke electroencephalographic epileptiform activity - a systematic review and meta-analysis of observational studies.

text: Introduction Cerebrovascular diseases are the most frequent risk factor for epilepsy in the elderly, and epileptic phenomenon following stroke is known to worsen the prognosis. Although electroencephalography is the gold standard epilepsy biomarker, it is rarely used in post-stroke studies, and the frequency of post-stroke epileptiform activity is still uncertain. Patients and methods We analysed studies indexed to MEDLINE, Embase, Web of Science, PsycINFO and OpenGrey (up to March 2015), reporting post-stroke electroencephalographic epileptiform activity frequency in adults. Epileptiform activity was classified as ictal (electrographic seizures) and interictal (non-periodic spikes and sharp waves). Data selection, extraction and appraisal were done in duplicate. Random-effects meta-analysis was used to pool frequencies. Results The pooled frequency of post-stroke ictal and interictal epileptiform activity was 7% (95% CI 3%-12%) and 8% (95% CI 4%-13%), respectively. The use of continuous electroencephalogram was not associated with an increased frequency of electrographic seizures (p = 0.05), nor did the management setting (Intensive Care Unit versus non- Intensive Care Unit, p = 0.31). However, studies with continuous electroencephalogram showed a higher frequency of interictal epileptiform activity (p = 0.01). Discussion This study provides the best available estimates of the frequency of post-stroke electroencephalographic epileptiform activity. Due to detection bias, it was not possible to correlate clinical and electrographic seizures. Conclusion The frequency of ictal and interictal epileptiform activity in the electroencephalogram was comparable with previous frequency analyses of clinical seizures. The frequency of ictal epileptiform activity did not change with continuous record or clinical setting, while the frequency of interictal epileptiform activity increased with continuous record.


title: Hepatic resection vs percutaneous radiofrequency ablation of hepatocellular carcinoma abutting right diaphragm.

text: BACKGROUND It is usually difficult to adequately conduct percutaneous ultrasound-guided radiofrequency (RF) ablation for hepatocellular carcinomas (HCCs) abutting the diaphragm. Our hypothesis was that the subphrenic location of HCC could have an effect on the long-term therapeutic outcomes after hepatic resection and RF ablation. AIM To compare the long-term therapeutic outcomes of hepatic resection and percutaneous RF ablation for HCCs abutting the diaphragm. METHODS A total of 143 Child-Pugh class A patients who had undergone hepatic resection (n = 80) or percutaneous ultrasound-guided RF ablation (n = 63) for an HCC (≤ 3 cm) abutting the right diaphragm were included. Cumulative local tumor progression (LTP), cumulative intrahepatic distant recurrence (IDR), disease-free survival (DFS), and overall survival (OS) rates were estimated. Prognostic factors for DFS and OS were analyzed. Complications were evaluated. RESULTS The cumulative IDR rate, DFS rate, and OS rate for the hepatic resection group and RF ablation group at 5 years were "35.9% vs 65.8%", "64.1% vs 18.3%", and "88.4% vs 68.7%", respectively. Hepatic resection was an independent prognostic factor for DFS (P ≤ 0.001; hazard ratio, 0.352; 95%CI: 0.205, 0.605; with RF ablation as the reference category); however, treatment modality was not an independent prognostic factor for OS. The LTP rate was 46.6% at 5 years for the RF ablation group. The major complication rate was not significantly different between the groups (P = 0.630). The rate of occurrence of peritoneal seeding was higher in the RF ablation group (1.3% vs 9.5%, P = 0.044). CONCLUSION Although OS was not significantly different between patients who had gone hepatic resection or percutaneous RF ablation for HCCs abutting the diaphragm, DFS was better in the hepatic resection group.


title: Effects of ALDH2 genotype, PPI treatment and L-cysteine on carcinogenic acetaldehyde in gastric juice and saliva after intragastric alcohol administration.

text: Acetaldehyde (ACH) associated with alcoholic beverages is Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase (ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30-50% of Eastern Asians. In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. However, there is only a limited evidence for stomach cancer. In this study we demonstrated for the first time that ALDH2 deficiency results in markedly increased exposure of the gastric mucosa to acetaldehyde after intragastric administration of alcohol. Our finding provides concrete evidence for a causal relationship between acetaldehyde and gastric carcinogenesis. A plausible explanation is the gastric first pass metabolism of ethanol. The gastric mucosa expresses alcohol dehydrogenase (ADH) enzymes catalyzing the oxidation of ethanol to acetaldehyde, especially at the high ethanol concentrations prevailing in the stomach after the consumption of alcoholic beverages. The gastric mucosa also possesses the acetaldehyde-eliminating ALDH2 enzyme. Due to decreased mucosal ALDH2 activity, the elimination of ethanol-derived acetaldehyde is decreased, which results in its accumulation in the gastric juice. We also demonstrate that ALDH2 deficiency, proton pump inhibitor (PPI) treatment, and L-cysteine cause independent changes in gastric juice and salivary acetaldehyde levels, indicating that intragastric acetaldehyde is locally regulated by gastric mucosal ADH and ALDH2 enzymes, and by oral microbes colonizing an achlorhydric stomach. Markedly elevated acetaldehyde levels were also found at low intragastric ethanol concentrations corresponding to the ethanol levels of many foodstuffs, beverages, and dairy products produced by fermentation. A capsule that slowly releases L-cysteine effectively eliminated acetaldehyde from the gastric juice of PPI-treated ALDH2-active and ALDH2-deficient subjects. These results provide entirely novel perspectives for the prevention of gastric cancer, especially in established risk groups.


title: [Suggestions for prevention of 2019 novel coronavirus infection in medical staff of otolaryngology head and neck surgery].

text: 目前2019新型冠状病毒（2019 novel coronavirus，2019-nCoV）感染的疫情进入了一个严峻而复杂的局面。截至2020年2月1日，全国已有超过11 000例新型冠状病毒感染确诊病例，给社会和经济带来极大影响，也严重影响着耳鼻咽喉头颈外科的日常医疗运行。本文针对耳鼻咽喉头颈外科的门诊及病房手术各个环节所需的医务防护措施进行讨论和建议，以期减少在2019-nCoV暴发和流行期间耳鼻咽喉头颈外科医护人员的感染。.


title: Bovine herpesvirus-1: evaluation of genetic diversity of subtypes derived from field strains of varied clinical syndromes and their relationship to vaccine strains.

text: Bovine herpesvirus-1 (BoHV-1) causes significant disease in cattle. Control programs in North America incorporate vaccination with modified live viral (MLV) or killed (KV) vaccine. BoHV-1 strains are isolated from diseased animals or fetuses after vaccination. There are markers for differentiating MLV from field strains using whole-genome sequencing and analysis identifying single nucleotide polymorphisms (SNPs). Using multiple primer sets and sequencing of products permits association of BoHV-1 isolates with vaccines. To determine association between vaccine virus and strains isolated from clinical cases following vaccination, we analyzed 12 BoHV-1 isolates from animals with various clinical syndromes; 9 corresponded to BoHV-1.1 respiratory group. The remaining three corresponded to BoHV-1.2b, typically found in genital tracts of cattle. Four BoHV-1 isolates were identical to a vaccine strain; three were from post-vaccination abortion episodes with typical herpetic lesions whose dams had received MLV vaccine during pregnancy, and one from a heifer given a related MLV vaccine; Sequences of two respiratory isolates perfectly matched mutations characterizing RLB106 strain, a temperature sensitive mutant used in intranasal and parenteral vaccines. The last three respiratory strains clearly appeared related to a group of MLV vaccines. Previously the MLV vaccines were grouped into four groups based on SNPs patterns. In contrast with above-mentioned isolates that closely matched SNP patterns of their respective MLV vaccine virus, these 3 strains both lacked some and possessed a number of additional mutations compared to a group of MLV vaccine viral genome. Finding BoHV-1.2b in respiratory cases indicates focus should be given BoHV-1.2b as an emerging virus or a virus not recognized nor fully characterized in BRD.


title: Reducing HIV-related stigma in health care settings: a randomized controlled trial in China.

text: OBJECTIVES The objective of the intervention was to reduce service providers' stigmatizing attitudes and behaviors toward people living with HIV. METHODS The randomized controlled trial was conducted in 40 county-level hospitals in 2 provinces of China between October 2008 and February 2010. Forty-four service providers were randomly selected from each hospital, yielding a total of 1760 study participants. We randomized the hospitals to either an intervention condition or a control condition. In the intervention hospitals, about 15% of the popular opinion leaders were identified and trained to disseminate stigma reduction messages. RESULTS We observed significant improvements for the intervention group in reducing prejudicial attitudes (P < .001), reducing avoidance intent towards people living with HIV (P < .001), and increasing institutional support in the hospitals (P = .003) at 6 months after controlling for service providers' background factors and clinic-level characteristics. The intervention effects were sustained and strengthened at 12 months. CONCLUSIONS The intervention reduced stigmatizing attitudes and behaviors among service providers. It has the potential to be integrated into the health care systems in China and other countries.


The complement inhibitors in COVID-19: future expectations.


title: Optimizing interpretation of the tuberculin test using an interferon-gamma release assay as a reference standard.

text: The interferon-gamma release assays have greater specificity than the tuberculin skin test (TST), and at least equal sensitivity. We analyzed the sensitivity and specificity of the TST in immunocompetent children considering QuantiFERON as the referent standard. A TST cut-off point of ≥ 5 mm indicates excellent sensitivity (100%) and specificity (93%) in children without Bacillus Calmette-Guérin. In Bacillus Calmette-Guérin-vaccinated children, the TST cut-off point of ≥ 10 mm had poorer specificity (86%), and a cut-off point of ≥ 15 mm resulted in reduced sensitivity (60%).


title: Health service psychology education and training in the time of COVID-19: Challenges and opportunities.

text: The COVID-19 pandemic has posed unprecedented challenges to health service psychology (HSP) education and training but also presents tremendous opportunities for growth that will persist well past the resolution of this public health crisis. The present article addresses three aims in understanding the challenges and opportunities faced by the HSP education and training community. First, it describes challenges to HSP education and training created by the COVID-19 pandemic, including the need to maintain the integrity of training; facilitate trainee progress; continue clinical service delivery; manage the safety and wellbeing of trainees, faculty, staff, and clients/patients; and adhere to national and local emergency orders. Second, the article summarizes guidance from training organization leadership regarding training program and clinical site responses to these challenges. Several principle-based recommendations called upon training programs to prioritize trainees and their training needs, while urging balance and flexibility in meeting the multiple demands of training programs, institutions, and the public. Third, the article discusses key opportunities for improvement in HSP education and training, including more effective use of competency evaluations; distance technologies in therapy, supervision, and admissions; and reconsideration of internship and degree timing and HSP's identity as a health care profession; and the potential for comprehensive review and redesign of HSP education and training. Embracing these opportunities may help ensure that HSP education and training is preparing its graduates to meet the psychological health care needs of the future. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Construction of Lentivirus-Based Reference Material for RT-PCR Detection of Middle East Respiratory Syndrome Coronavirus and Its Application in External Quality Assessment.

text: Nucleic acid amplification technology (NAT) has been the most used one for rapid detection of Middle East Respiratory Syndrome coronavirus (MERS-CoV) since MERS-CoV was first detected in 2012. It is important to develop stable and safe reference materials for assessing the quality of NAT kits and performing an external quality assessment (EQA) in different laboratories. In this study, the MERS-CoV RNA fragments including upE, ORF1b, and N were packed within human immunodeficiency virus type 1 (HIV-1)-like particles. The lyophilized virus-like particles (VLPs) were found to be stable at 37 °C or below and safe to be used not only as the control material for PCR detection of MERS-CoV but also as the reference material for EQA. In an EQA organized by Ningbo International Travel Healthcare Center in China, 49 participating institutions achieved 100% agreement in detecting MERS-CoV using various commercial diagnosis kits and different extraction methods. However, different Ct values reported by different sites for the same sample implied that a need exists to standardize the RNA extraction method and/or the PCR detection conditions between the laboratories.


Eyes on New Product Development.


title: Immunosenescence and herd immunity: with an ever-increasing aging population do we need to rethink vaccine schedules?

text: Vaccination is a powerful public health tool that has been of tremendous benefit in protecting vulnerable populations from specific infections. Moreover, in addition to the direct benefits to vaccinated individuals, the indirect effects of protection at the community level have also been demonstrated and termed 'herd immunity'. The predicted demographic shift in the population landscape towards an ever-increasing aging population and the evidence suggesting that older individuals produce less-than-optimal vaccine responses have raised the question of rethinking vaccine schedules. This article provides evidence that even if herd immunity might be an option to indirectly protect the aging and aged adult population, the highest priorities for the near future must be to understand how vaccine responses in older individuals can be improved, to break down the public, cultural, societal and political barriers to vaccination and to counter the antivaccination movement that inhibits the worldwide spread of lifelong immunization programs.


title: Neonatal and pediatric respiratory care: what does the future hold?

text: Neonatal and pediatric respiratory care continues to move forward at a truly impressive pace. Recent technologic advances and an increasing number of randomized clinical trials are leading to improved outcomes for neonates, infants, children, and adolescents with respiratory illness. The goals of this 47th Respiratory Care Journal Conference were to review pertinent recent advances in neonatal and pediatric respiratory care and, more importantly, to offer thoughts and perspectives for the future of our field. It is important to note that of the prior 46 Journal Conferences, only 2 have been dedicated to neonatal and/or pediatric respiratory care topics. It is our hope that the publication of these proceedings will provide respiratory therapists, physicians, and other members of the clinical care team a foundation on which to ponder the future of neonatal and pediatric respiratory care.


Public Health: Our Time of Challenge.


title: Adaptation to Technology Use in Families of Children With Complex Communication Needs: An Integrative Review and Family Theory Application.

text: Families with children who have developmental disabilities and complex communication needs (CCNs) face challenging demands affecting family adaptation. Many children with CCNs use augmentative and alternative communication (AAC) devices to support communication, yet little is known about family adaptation to such technology. To fill this gap, an integrative review, guided by the Resiliency Model of Family Stress, Adjustment, and Adaptation was conducted to assess conceptual foundations and the state of the science of family adaptation among children utilizing AAC. Web-based searches were conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and the Mixed Methods Appraisal Tool. Thirty-three studies met eligibility. Findings demonstrated that to enhance the science underpinning family adaptation to AAC use, future research should be grounded conceptually and address important components of the Resiliency Model. Work in this emerging area will identify and facilitate nursing efforts to assist families as they adapt to communication technology.


title: Surgical outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma for various resection extent.

text: Although the number of laparoscopic liver resections (LRRs) has increased, studies of surgical outcomes in comparison with the conventional open approach are limited. The purpose of this study was to analyze the surgical outcomes (safety and efficacy) of LLR versus open liver resection (OLR) for hepatocellular carcinoma (HCC).We collected data on all patients who received liver resection for HCC between April 2015 and September 2016 in our institution, and retrospectively investigated the demographic and perioperative data, and also surgical outcomes.Laparoscopic liver resection was performed in 225 patients and OLR in 291. In patients who underwent minor hepatectomy, LLR associated with a shorter duration of operation time (200 vs 220 minutes; P < 0.001), less blood loss (100 vs 225 mL; P < 0.001), lower transfusion rate (3.0% vs 12.0%; P = 0.012), and shorter postoperative hospital stay (6 vs 7 days; P < 0.001) compared with OLR. Dietary recovery was relatively fast in the group of LLR, but there were no significant differences in hepatic inflow occlusion rate, complication rate, and transfusion volume. Patients who received major hepatectomy had a longer duration of operation (240 vs 230 minutes; P < 0.001), less blood loss (200 vs 400 mL; P < 0.001), lower transfusion rate (4.8% vs 16.5%; P = 0.002), lower hepatic inflow occlusion rate (68.3% vs 91.7%; P < 0.001), and shorter postoperative hospital stay (6 vs 8 days; P < 0.001). Complication rate (P = 0.366) and transfusion volume (P = 0.308) did not differ between groups.Laparoscopic liver resection is a feasible and safe alternative to OLR for HCC when performed by a surgeon experienced with the relevant surgical techniques, associated with less blood loss, lower transfusion rate, a rapid return to a normal diet, and shorter postoperative hospital stay with no compromise in complications. Further, long-term follow-up should be acquired for adequate evaluation for survival.


title: Results of a survey of blood pressure monitoring by intensivists in critically ill patients: a preliminary study.

text: OBJECTIVES Maintenance of mean arterial pressure>65 mm Hg has been associated with improved clinical outcomes in many studies of critically ill patients. Current guidelines for the management of septic shock and guidelines for managing other critical illnesses suggest intra-arterial blood pressure measurement is preferred over automated oscillometric noninvasive blood pressure measurement. Despite these recommendations, anecdotal experience suggested that the use of noninvasive blood pressure measurement in our institution and others in preference to intra-arterial blood pressure measurement remained prevalent. DESIGN We designed an online survey and sent it by e-mail. SETTING Intensive care units. PATIENTS AND SUBJECTS A randomly selected group from the membership of the Society for Critical Care Medicine. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Use of non-invasive and invasive blood pressure devices. Eight hundred eighty individuals received an invitation to complete the survey and 149 responded. We found that 71% (105 of 149) of intensivists estimated the correct cuff size rather than measuring arm circumference directly. In hypotensive patients, 73% of respondents (108 of 149) reported using noninvasive blood pressure measurement measurements for patient management. In patients on a vasopressor medication, 47% (70 of 149) of respondents reported using noninvasive blood pressure measurement for management. CONCLUSIONS The use of noninvasive blood pressure measurement measurements in critically ill patients is common despite the paucity of evidence validating its accuracy in critically ill patients. Given this widespread use, accuracy and precision validation studies comparing noninvasive blood pressure measurement with intra-arterial blood pressure measurement in critically ill patients should be performed.


title: Mefloquine for preventing malaria during travel to endemic areas.

text: BACKGROUND Mefloquine is one of four antimalarial agents commonly recommended for preventing malaria in travellers to malaria-endemic areas. Despite its high efficacy, there is controversy about its psychological side effects. OBJECTIVES To summarize the efficacy and safety of mefloquine used as prophylaxis for malaria in travellers. SEARCH METHODS We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published on the Cochrane Library; MEDLINE; Embase (OVID); TOXLINE (https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm); and LILACS. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; http://www.who.int/ictrp/en/) and ClinicalTrials.gov (https://clinicaltrials.gov/ct2/home) for trials in progress, using 'mefloquine', 'Lariam', and 'malaria' as search terms. The search date was 22 June 2017. SELECTION CRITERIA We included randomized controlled trials (for efficacy and safety) and non-randomized cohort studies (for safety). We compared prophylactic mefloquine with placebo, no treatment, or an alternative recommended antimalarial agent. Our study populations included all adults and children, including pregnant women. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the eligibility and risk of bias of trials, extracted and analysed data. We compared dichotomous outcomes using risk ratios (RR) with 95% confidence intervals (CI). Prespecified adverse outcomes are included in 'Summary of findings' tables, with the best available estimate of the absolute frequency of each outcome in short-term international travellers. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS We included 20 RCTs (11,470 participants); 35 cohort studies (198,493 participants); and four large retrospective analyses of health records (800,652 participants). Nine RCTs explicitly excluded participants with a psychiatric history, and 25 cohort studies stated that the choice of antimalarial agent was based on medical history and personal preference. Most RCTs and cohort studies collected data on self-reported or clinician-assessed symptoms, rather than formal medical diagnoses. Mefloquine efficacyOf 12 trials comparing mefloquine and placebo, none were performed in short-term international travellers, and most populations had a degree of immunity to malaria. The percentage of people developing a malaria episode in the control arm varied from 1% to 82% (median 22%) and 0% to 13% in the mefloquine group (median 1%).In four RCTs that directly compared mefloquine, atovaquone-proguanil and doxycycline in non-immune, short-term international travellers, only one clinical case of malaria occurred (4 trials, 1822 participants). Mefloquine safety versus atovaquone-proguanil Participants receiving mefloquine were more likely to discontinue their medication due to adverse effects than atovaquone-proguanil users (RR 2.86, 95% CI 1.53 to 5.31; 3 RCTs, 1438 participants; high-certainty evidence). There were few serious adverse effects reported with mefloquine (15/2651 travellers) and none with atovaquone-proguanil (940 travellers).One RCT and six cohort studies reported on our prespecified adverse effects. In the RCT with short-term travellers, mefloquine users were more likely to report abnormal dreams (RR 2.04, 95% CI 1.37 to 3.04, moderate-certainty evidence), insomnia (RR 4.42, 95% CI 2.56 to 7.64, moderate-certainty evidence), anxiety (RR 6.12, 95% CI 1.82 to 20.66, moderate-certainty evidence), and depressed mood during travel (RR 5.78, 95% CI 1.71 to 19.61, moderate-certainty evidence). The cohort studies in longer-term travellers were consistent with this finding but most had larger effect sizes. Mefloquine users were also more likely to report nausea (high-certainty evidence) and dizziness (high-certainty evidence).Based on the available evidence, our best estimates of absolute effect sizes for mefloquine versus atovaquone-proguanil are 6% versus 2% for discontinuation of the drug, 13% versus 3% for insomnia, 14% versus 7% for abnormal dreams, 6% versus 1% for anxiety, and 6% versus 1% for depressed mood. Mefloquine safety versus doxycyclineNo difference was found in numbers of serious adverse effects with mefloquine and doxycycline (low-certainty evidence) or numbers of discontinuations due to adverse effects (RR 1.08, 95% CI 0.41 to 2.87; 4 RCTs, 763 participants; low-certainty evidence).Six cohort studies in longer-term occupational travellers reported our prespecified adverse effects; one RCT in military personnel and one cohort study in short-term travellers reported adverse events. Mefloquine users were more likely to report abnormal dreams (RR 10.49, 95% CI 3.79 to 29.10; 4 cohort studies, 2588 participants, very low-certainty evidence), insomnia (RR 4.14, 95% CI 1.19 to 14.44; 4 cohort studies, 3212 participants, very low-certainty evidence), anxiety (RR 18.04, 95% CI 9.32 to 34.93; 3 cohort studies, 2559 participants, very low-certainty evidence), and depressed mood (RR 11.43, 95% CI 5.21 to 25.07; 2 cohort studies, 2445 participants, very low-certainty evidence). The findings of the single cohort study reporting adverse events in short-term international travellers were consistent with this finding but the single RCT in military personnel did not demonstrate a difference between groups in frequencies of abnormal dreams or insomnia.Mefloquine users were less likely to report dyspepsia (RR 0.26, 95% CI 0.09 to 0.74; 5 cohort studies, 5104 participants, low certainty-evidence), photosensitivity (RR 0.08, 95% CI 0.05 to 0.11; 2 cohort studies, 1875 participants, very low-certainty evidence), vomiting (RR 0.18, 95% CI 0.12 to 0.27; 4 cohort studies, 5071 participants, very low-certainty evidence), and vaginal thrush (RR 0.10, 95% CI 0.06 to 0.16; 1 cohort study, 1761 participants, very low-certainty evidence).Based on the available evidence, our best estimates of absolute effect for mefloquine versus doxycyline were: 2% versus 2% for discontinuation, 12% versus 3% for insomnia, 31% versus 3% for abnormal dreams, 18% versus 1% for anxiety, 11% versus 1% for depressed mood, 4% versus 14% for dyspepsia, 2% versus 19% for photosensitivity, 1% versus 5% for vomiting, and 2% versus 16% for vaginal thrush.Additional analyses, including comparisons of mefloquine with chloroquine, added no new information. Subgroup analysis by study design, duration of travel, and military versus non-military participants, provided no conclusive findings. AUTHORS' CONCLUSIONS The absolute risk of malaria during short-term travel appears low with all three established antimalarial agents (mefloquine, doxycycline, and atovaquone-proguanil).The choice of antimalarial agent depends on how individual travellers assess the importance of specific adverse effects, pill burden, and cost. Some travellers will prefer mefloquine for its once-weekly regimen, but this should be balanced against the increased frequency of abnormal dreams, anxiety, insomnia, and depressed mood.


title: Identification and genetic characterization of a porcine hepe-astrovirus (bastrovirus) in the United States.

text: Here we describe the identification and genetic characterization of a porcine hepe-astrovirus, or bastrovirus, obtained from feces from pigs in the United States. The genome of the new bastrovirus is 5,955 nt long and contains two open reading frames (ORFs). ORF1 encodes a protein containing three domains, viral methyltransferase, RNA helicase and RNA-dependent RNA polymerase (RdRp), and is closely related to the RdRp of hepatitis E virus. The ORF2 protein shares similarities with the astrovirus capsid precursor protein. Although structural features of bastroviruses may resemble those of astroviruses, distinct characteristics of the newly identified bastrovirus include the presence of an RNA helicase domain in ORF1 and the lack of ORF1b. In addition to genetic characterization, screening of 368 porcine samples (oral fluids, oral swabs or fecal swabs) collected in the United States (US) using a porcine-bastrovirus-specific real-time PCR assay revealed that 31% of those samples were positive. These results suggest a broad distribution of bastroviruses in the swine population in the US. This represents the first description of bastrovirus in swine in the US.


title: Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

text: BACKGROUND AND PURPOSE The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. METHODS We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. RESULTS Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P < .001), parenchymal hematoma (OR 20.57; 95% CI 5.64-74.99; P < .001), and poor outcome at discharge (OR 2.35; 95% CI 1.09-5.07; P = .03). The association of BBB disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. CONCLUSIONS Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome.


title: Idiopathic pneumonia syndrome after hematopoietic cell transplantation: evidence of occult infectious etiologies.

text: Newer diagnostic methods may link more idiopathic pneumonia syndrome (IPS) cases to an infectious agent. Bronchoalveolar lavage (BAL) samples from 69 hematopoietic cell transplant (HCT) recipients with IPS diagnosed between 1992 and 2006 were tested for 28 pathogens (3 bacteria and 25 viruses) by quantitative polymerase chain reaction and for Aspergillus by galactomannan assay. Research BALs from 21 asymptomatic HCT patients served as controls. Among 69 HCT patients with IPS, 39 (56.5%) had a pathogen detected. The most frequent pathogens were human herpesvirus-6 (HHV-6) (N = 20 [29%]) followed by human rhinovirus (HRV), cytomegalovirus (CMV), and Aspergillus (N = 8 [12%] in each). HHV-6 and HRV were rarely detected in controls, whereas CMV and Aspergillus were occasionally detected with low pathogen load. Patients with pathogens had worse day-100 survival than those without (hazard ratio, 1.88; P = .03). Mortality in patients with only pathogens of "uncertain" significance in lung was similar to that in patients with pathogens of "established" significance. Metagenomic next-generation sequencing did not reveal additional significant pathogens. Our study demonstrated that approximately half of patients with IPS had pathogens detected in BAL, and pathogen detection was associated with increased mortality. Thus, an expanded infection detection panel can significantly increase the diagnostic precision for idiopathic pneumonia.


title: Up-regulation of pro-inflammatory factors by HP-PRRSV infection in microglia: implications for HP-PRRSV neuropathogenesis.

text: Atypical porcine reproductive and respiratory syndrome (PRRS) caused by a highly pathogenic PRRS virus (HP-PRRSV) is characterized by high fever, high morbidity, high mortality, and associated with severe neurological symptoms. Microglia are the resident innate immune cells in central nervous system (CNS), and their activation has been implicated as an important contributor to the pathogenesis of CNS diseases. In the present study, we successfully cultured porcine microglia and demonstrated that microglia could support PRRSV infection and replication in vitro. We further showed that HP-PRRSV infection significantly up-regulated the key inflammatory factors including IL-1β, TNF-α, IL-6, IL-12, IL-8, CXCL10, MCP-1, CCL3, CCL4, and CCL5 in cultured microglia as well as in the CNS of HP-PRRSV-infected pigs. The transcription factors NF-κB and AP-1, which are widely reported to regulate cytokine and chemokine productions, were activated by HP-PRRSV infection in microglia. Meanwhile, we found that HP-PRRSV induced cellular ROS formation in microglia and ROS scavenger was proved to significantly abolish the activation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-8), suggesting that ROS are crucial for pro-inflammatory gene production. Importantly, incubation with supernatants from HP-PRRSV-infected microglia cell culture remarkably induced SH-SY5Y neuroblastoma cell death. Collectively, these results showed that PRRSV infection induced cytokine and ROS up-regulation in microglia, which might contribute to neurotoxicity. These data have implications for us to understand the neuropathogenesis of HP-PRRSV in pigs.


title: Duty, indemnity and immunity during the COVID-19 pandemic.

text: Richard Griffith, Senior Lecturer in Health Law at Swansea University, considers arrangements for indemnifying nurses returning to practice in the pandemic, and whether nurses might be given immunity from negligence claims.


title: Hypophosphatemia, fever and prolonged length of hospital stay in seronegative PCR positive patients as compared to seropositive patients with early acute Q fever pneumonia.

text: BACKGROUND Query fever (Q fever) is a zoonotic infection, caused by the intracellular Gram-negative coccobacillus Coxiella burnetii. From 2007 until 2010, a large Q fever outbreak has occurred in the Netherlands. We studied traditional and less common inflammation markers in seronegative and seropositive patients with acute Q fever pneumonia to identify markers that distinguish different disease stages and predict disease severity. METHODS A total of 443 adult patients presenting at the Emergency Department with community-acquired pneumonia were included in a prospective etiologic study. Patients with acute Q fever pneumonia were identified by PCR and/or serology. Patient characteristics, clinical symptoms, pneumonia severity and inflammation markers were assessed upon presentation. Duration of symptoms, prior therapy and length of hospital stay were retrieved from the hospital information system. RESULTS In all, 40 patients with acute Q fever pneumonia were identified. Of these, 29 were seronegative and 11 seropositive at presentation. C-reactive protein (CRP) was the only inflammation marker increased in all seronegative and seropositive patients but no significant difference was observed between groups. In seronegative patients, hypophosphatemia was more common (p=0.01), and length of hospital stay was longer (p=0.02). However, there was no significant difference in pneumonia severity index. Furthermore, phosphate levels were inversely correlated with body temperature (p=0.003). CONCLUSIONS In acute Q fever pneumonia, CRP is the only traditional inflammation marker adequately reflecting disease activity. Patients with seronegative acute Q fever pneumonia present with hypophosphatemia and have prolonged length of hospital stay when compared to seropositive patients, suggesting an increased disease severity.


title: Biomechanical evaluation of a novel subcuticular skin stapling device for use in equine abdominal surgeries.

text: OBJECTIVE To compare the in vitro biomechanical properties of a novel subcuticular stapling device to current methods of abdominal skin closure for equine abdominal surgery. STUDY DESIGN In vitro randomized, matched design. SAMPLE POPULATION Equine ventral median abdominal skin specimens (n = 24 horses). METHODS Subcuticular absorbable staples (SAS), metallic staples (MS), polyglyconate suture (PG), and nylon monofilament (NYL) were applied to longitudinally transected portions of equine ventral midline skin. Loads that resulted in an initial failure point and the ultimate failure load and mechanism were recorded. RESULTS Mean ± SD loads at initial failure for PG (86 N ± 64 N), NYL (81 N ± 142 N), and SAS (70 N ± 20 N) were not significantly different from each other. PG and SAS were significantly higher than MS (43 N ± 17 N; P < .05). Ultimate failure load for PG (563 N ± 157 N) and NYL (558 N ± 162 N) were significantly higher than either MS (175 N ± 44 N) or SAS (96 N ± 20N; P < .001). For the suture groups, nearly all failures occurred because of skin pull through whereas all SAS staples failed because of staple fracture. Failure patterns were mixed for MS. CONCLUSIONS SAS had the lowest ultimate failure load; however, other measured variables identified characteristics of SAS that may be clinically beneficial.


title: Correlation Between Thalamus-Related Functional Connectivity and Serum BDNF Levels During the Periovulatory Phase of Primary Dysmenorrhea.

text: The thalamus is a key region for the transmission of nociceptive information in the central modulation of pain and has been studied in the setting of numerous chronic pain conditions. Brain-derived neurotrophic factor (BDNF) is considered an important modulator for mediating nociceptive pathways in chronic pain. The present study aimed to investigate whether there was thalamus-related abnormal functional connectivity or relevant serum BDNF level alterations during periovulation in long-term primary dysmenorrhea (PDM). Thalamic subregions were defined according to the Human Brainnetome Atlas. Functional connectivity analyses were performed in 36 patients in the periovulatory phase and 29 age-, education-, and gender-matched healthy controls. Serum BDNF levels were evaluated by enzyme-linked immunosorbent assay and a significantly higher BDNF level was detected in PDM patients. Compared with HCs, PDM patients had abnormal functional connectivity of thalamic-subregions, mainly involving with prefrontal cortex, sensorimotor cortex, and temporal cortex. In addition, the functional connectivity of thalamic-subregions showed significant interactive effect correlated with serum BDNF level between PDM and HCs. It has been suggested that there were maladaptive or adoptive alteration associated with chronic menstrual pain even without the ongoing menstrual pain. BDNF might play a role in the development and chronicity of central nervous system dysfunction. These findings provided more accurate information about the involvement of the thalamus in the pathophysiology of PDM.


title: Robust Conditional Independence maps of single-voxel Magnetic Resonance Spectra to elucidate associations between brain tumours and metabolites.

text: The aim of the paper is two-fold. First, we show that structure finding with the PC algorithm can be inherently unstable and requires further operational constraints in order to consistently obtain models that are faithful to the data. We propose a methodology to stabilise the structure finding process, minimising both false positive and false negative error rates. This is demonstrated with synthetic data. Second, to apply the proposed structure finding methodology to a data set comprising single-voxel Magnetic Resonance Spectra of normal brain and three classes of brain tumours, to elucidate the associations between brain tumour types and a range of observed metabolites that are known to be relevant for their characterisation. The data set is bootstrapped in order to maximise the robustness of feature selection for nominated target variables. Specifically, Conditional Independence maps (CI-maps) built from the data and their derived Bayesian networks have been used. A Directed Acyclic Graph (DAG) is built from CI-maps, being a major challenge the minimization of errors in the graph structure. This work presents empirical evidence on how to reduce false positive errors via the False Discovery Rate, and how to identify appropriate parameter settings to improve the False Negative Reduction. In addition, several node ordering policies are investigated that transform the graph into a DAG. The obtained results show that ordering nodes by strength of mutual information can recover a representative DAG in a reasonable time, although a more accurate graph can be recovered using a random order of samples at the expense of increasing the computation time.


title: Measles outbreak from Hong Kong International Airport to the hospital due to secondary vaccine failure in healthcare workers.

text: OBJECTIVE To report an outbreak of measles with epidemiological link between Hong Kong International Airport (HKIA) and a hospital. METHODS Epidemiological investigations, patients' measles serology, and phylogenetic analysis of the hemagglutinin (H) and nucleoprotein (N) genes of measles virus isolates were conducted. RESULTS In total, 29 HKIA staff of diverse ranks and working locations were infected with measles within 1 month. Significantly fewer affected staff had history of travel than non-HKIA-related measles patients [10 of 29 (34.5%) vs 28 of 35 (80%); P < .01]. Of 9 airport staff who could recall detailed exposure history, 6 (66.7%) had visited self-service food premises at HKIA during the incubation period, where food trays, as observed during the epidemiological field investigation, were not washed after use. Furthermore, 1 airport baggage handler who was admitted to hospital A before rash onset infected 2 healthcare workers (HCWs) known to have 2 doses of MMR vaccination with positive measles IgG and lower viral loads in respiratory specimens. Infections in these 2 HCWs warranted contact tracing of another 168 persons (97 patients and 71 HCWs). Phylogenetic comparison of H and N gene sequences confirmed the clonality of outbreak strains. CONCLUSION Despite good herd immunity with overall seroprevalence of >95% against measles, major outbreaks of measles occurred among HKIA staff having daily contact with many international pssengers. Lessons from severe acute respiratory syndrome (SARS) and measles outbreaks suggested that an airport can be a strategic epidemic center. Pre-exanthem transmission of measles from airport staff to HCWs with secondary vaccine failure poses a grave challenge to hospital infection control.


title: Acupoint herbal plaster for patients with primary dysmenorrhea: study protocol for a randomized controlled trial.

text: BACKGROUND Primary dysmenorrhea (PD), is one of main gynecological complaints in women of child-bearing age. Common medications for PD do not always achieve satisfactory outcome of pain relief. Hence, both health professionals and patients are seeking help from complementary and alternative medicine. The acupoint herbal plaster (AHP), which appears to be a safe and effective way to alleviate menstrual pain, as well as to improve other PD-related symptoms. Despite similar clinical studies for this condition in the past, no high-quality methodology-based clinical trial has been reported to date. The current study aims to assess the efficacy of the AHP compared with the acupoint placebo plaster (APP) and being placed on a waiting-list control group in patients with primary dysmenorrhea. METHODS/DESIGN This study is a randomized, single-center, placebo-controlled clinical trial. A total of 180 women with PD will be included and randomly allocated to the AHP, APP and waiting-list (WL) groups in a 1:1:1 ratio. Patients in the AHP group will be provided with herbal plasters (Shaofuzhuyu decoction) on various acupoints: Shenque (CV8), Guanyuan (CV4), Qihai (CV5), Ciliao (BL32) and Zigong (EX-CA1). Women in the APP group will receive placebo plasters on the same acupoints, and no intervention will be given to the WL group until completion of the study. The primary outcome will be pain intensity reduction measured by a Visual Analog Scale (VAS), with other outcome measurements including the Cox Menstrual Symptom Scale (CMSS), the 12-Item Short Form Health Survey (SF-12) and the Participant Global Impression of Change (PGIC). All assessments will be performed at baseline, each menstrual cycle during the treatment course and the follow-up course. Any adverse events will be recorded throughout the study. DISCUSSION This is the first study to compare the changes in menstrual pain after three different interventions: the active intervention (AHP), the placebo intervention (APP), and a period of no intervention (WL). This three-arm randomized controlled trial (RCT) aims to investigate the relative contributions of the specific (AHP vs. APP) and non-specific (APP vs. WL) effects to the overall clinical effects of the active AHP on women with PDM. The scientific and rigorous methodology design of this trial should gather good evidence to assess the curative effects and safety of the AHP on PD. Moreover, the results of this study may provide evidence-based references for the treatment of menstrual pain in future. TRIAL REGISTRATION Chinese Clinical Trial Registry, ID: ChiCTR-TRC-16008701. Registered on 22 July 2016.


title: ELL Protein-associated Factor 2 (EAF2) Inhibits Transforming Growth Factor β Signaling through a Direct Interaction with Smad3.

text: A series of in vitro and in vivo studies has shown that EAF2 can affect multiple signaling pathways involved in cellular processes. However, the molecular mechanisms underlying its effects have remained elusive. Here we report the discovery of a new functional link between EAF2 and TGF-β signaling. Promoter reporter assays indicated that EAF2 suppresses Smad3 transcriptional activity, resulting in inhibition of TGF-β signaling. Coimmunoprecipitation assays showed that EAF2 specifically interacts with Smad3 in vitro and in vivo but not with other Smad proteins. In addition, we observed that EAF2 binding does not alter Smad3 phosphorylation but causes Smad3 cytoplasmic retention, competes with Smad4 for binding to Smad3, and prevents p300-Smad3 complex formation. Furthermore, we demonstrated that EAF2 suppresses both TGF-β-induced G1 cell cycle arrest and TGF-β-induced cell migration. This study identifies and characterizes a novel repressor of TGF-β signaling.


title: Pension reforms in Hong Kong: using residual and collaborative strategies to deal with the government's financial responsibility in providing retirement protection.

text: In 2000, the Hong Kong government introduced the first compulsory retirement saving scheme intended to protect the entire workforce, the Mandatory Provident Fund (MPF). Prior to the introduction of this scheme, the government's main measure for giving financial protection to retirees was the Comprehensive Social Security Assistance (CSSA) scheme, which is a noncontributory, means-tested financial assistance scheme. This paper studies the government's attempt to introduce the MPF on top of the CSSA scheme as a means to illustrate how governments might address their financial responsibilities in providing pension schemes by adopting both the residual strategy-centered reform approach and the collaborative strategy-centered reform approach. The former approach is concerned with developing noncontributory schemes using residual strategies, and the latter is concerned with developing contributory schemes using collaborative strategies. The paper shows the difficulties involved in carrying out these two reform approaches simultaneously.


title: Communication skills in the training of psychiatrists: A systematic review of current approaches.

text: OBJECTIVES A range of communication skills training programmes have been developed targeting trainees in various medical specialties, predominantly in oncology but to a lesser extent in psychiatry. Effective communication is fundamental to the assessment and treatment of psychiatric conditions, but there has been less attention to this in clinical practice for psychiatrists in training. This review examines the outcomes of communication skills training interventions in psychiatric specialty training. METHODS The published English-language literature was examined using multiple online databases, grey literature and hand searches. The review was conducted and reported using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies examining the efficacy of communication skills training were included. Randomised controlled trials, pseudo-randomised studies and quasi-experimental studies, as well as observational analytical studies and qualitative studies that met criteria, were selected and critically appraised. No limits were applied for date of publication up until 16 July 2016. RESULTS Total search results yielded 2574 records. Of these, 12 studies were identified and reviewed. Two were randomised controlled trials and the remaining 10 were one-group pretest/posttest designs or posttest-only designs, including self-report evaluations of communication skills training and objective evaluations of trainee skills. There were no studies with outcomes related to behaviour change or patient outcomes. Two randomised controlled trials reported an improvement in clinician empathy and psychotherapeutic interviewing skills due to specific training protocols focused on those areas. Non-randomised studies showed varying levels of skills gains and self-reported trainee satisfaction ratings with programmes, with the intervention being some form of communication skills training. CONCLUSION The heterogeneity of communication skills training is a barrier to evaluating the efficacy of different communication skills training programmes. Further validation studies examining specific models and frameworks would support a stronger evidence base for communication skills training in psychiatry. It remains a challenge to develop research to investigate behaviour change over time in clinical practice or to measure patient outcomes due to the effects of communication skills training.


title: Viral etiology of mumps-like illnesses in suspected mumps cases reported in Catalonia, Spain.

text: We investigated the etiology of reported sporadic suspected mumps cases with a negative RT-PCR result for the mumps virus in the Barcelona-South region in 2007-2011. Samples from mumps virus-negative patients presenting unilateral or bilateral parotitis or other salivary gland swelling were tested for Epstein-Barr virus (EBV) by real-time PCR and for respiratory viruses by two multiplex-PCR-based assays to detect parainfluenza virus (PIV) 1-4, influenza virus (InV) A, B and C, respiratory syncytial virus (RSV), enterovirus, coronavirus 229E, coronavirus OC43, and rhinovirus. 101 samples were analyzed in persons aged 8 months to 50 years. Oral samples were collected on the first day of glandular swelling in 53 patients (52.5%), and on the first two days in 74 patients (73.3%). Viruses were detected in 52 (51.5%) of samples: one virus (25 EBV, 8 PIV3, 4 adenovirus, 4 PIV2, 1 PIV1, 1 InVA, and 1 enterovirus) was detected in 44 patients (84.6%), two viruses in 7 patients, and three viruses in one patient. In 58 patients (57.5%) whose sample was collected in the first 2 days after onset of parotitis and had received two doses of MMR vaccine and in 15 patients (14.8%) whose sample was collected on the first day, it is very likely that the cause was not the mumps virus. This would mean that 72.3% (73/101) of the reported sporadic suspected mumps cases were not mumps cases. The timing of oral-sample collection is crucial to correctly interpret the negative results for mumps virus RNA, especially when suspected cases occur in vaccinated persons.


title: Neuraminidase of Influenza A Virus Binds Lysosome-Associated Membrane Proteins Directly and Induces Lysosome Rupture.

text: UNLABELLED As a recycling center, lysosomes are filled with numerous acid hydrolase enzymes that break down waste materials and invading pathogens. Recently, lysosomal cell death has been defined as "lysosomal membrane permeabilization and the consequent leakage of lysosome contents into cytosol." Here, we show that the neuraminidase (NA) of H5N1 influenza A virus markedly deglycosylates and degrades lysosome-associated membrane proteins (LAMPs; the most abundant membrane proteins of lysosome), which induces lysosomal rupture, and finally leads to cell death of alveolar epithelial carcinoma A549 cells and human tracheal epithelial cells. The NA inhibitors peramivir and zanamivir could effectively block the deglycosylation of LAMPs, inhibit the virus cell entry, and prevent cell death induced by the H5N1 influenza virus. The NA of seasonal H1N1 virus, however, does not share these characteristics. Our findings not only reveal a novel role of NA in the early stage of the H5N1 influenza virus life cycle but also elucidate the molecular mechanism of lysosomal rupture crucial for influenza virus induced cell death. IMPORTANCE The integrity of lysosomes is vital for maintaining cell homeostasis, cellular defense and clearance of invading pathogens. This study shows that the H5N1 influenza virus could induce lysosomal rupture through deglycosylating lysosome-associated membrane proteins (LAMPs) mediated by the neuraminidase activity of NA protein. NA inhibitors such as peramivir and zanamivir could inhibit the deglycosylation of LAMPs and protect lysosomes, which also further interferes with the H5N1 influenza virus infection at early stage of life cycle. This work is significant because it presents new concepts for NA's function, as well as for influenza inhibitors' mechanism of action, and could partially explain the high mortality and high viral load after H5N1 virus infection in human beings and why NA inhibitors have more potent therapeutic effects for lethal avian influenza virus infections at early stage.


title: Functional Results after Repair of Large Hiatal Hernia by Use of a Biologic Mesh.

text: BACKGROUND The aim of this observational study is to analyze the results of patients with large hiatal hernia and upside-down stomach after surgical closure with a biological mesh (Permacol(®), Covidien, Neustadt an der Donau, Germany). Biological mesh is used to prevent long-term detrimental effects of artificial meshes and to reduce recurrence rates. METHODS A total of 13 patients with a large hiatal hernia and endothoracic stomach, who underwent surgery between 2010 and 2014, were included. Interviews and upper endoscopy were conducted to determine recurrences, lifestyle restrictions, and current complaints. RESULTS After a mean follow-up of 26 ± 18 months (range: 3-58 months), 10 patients (3 men, mean age 73 ± 13, range: 26-81 years) were evaluated. A small recurrent axial hernia was found in one patient postoperatively. Dysphagia was the most common complaint (four cases); while in one case, the problem was solved after endoscopic dilatation. In three cases, bloat and postprandial pain were documented. In one case, an explantation of the mesh was necessary due to mesh migration and painful adhesions. In one further case with gastroparesis, pyloroplasty was performed without success. The data are compared to the available literature. It was found that dysphagia and recurrence rates are unrelated both in biological and in synthetic meshes if the esophagus is encircled. In series preserving the esophagus at least partially uncoated, recurrences after the use of biological meshes relieve dysphagia. After the application of synthetic meshes, dysphagia is aggravated by recurrences. CONCLUSION Recurrence is rare after encircling hiatal hernia repair with the biological mesh Permacol(®). Dysphagia, gas bloat, and intra-abdominal pain are frequent complaints. Despite the small number of patients, it can be concluded that a biological mesh may be an alternative to synthetic meshes to reduce recurrences at least for up to 2 years. Our study demonstrates that local fibrosis and thickening of the mesh can affect the outcome being associated with abdominal discomfort despite a successful repair. The review of the literature indicates comparable results after 2 years with both biologic and synthetic meshes embracing the esophagus. At the same point in time, reconstruction with synthetic and biologic materials differs when the esophagus is not or only partially encircled in the repair. This is important since encircling artificial meshes can erode the esophagus after 5-10 years.


title: Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.

text: The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.


title: Pneumothorax secondary to pulmonary thromboembolism in a dog.

text: OBJECTIVE To describe a case of spontaneous pneumothorax secondary to pulmonary thromboembolism possibly associated with pituitary dependent hyperadrenocorticism. CASE SUMMARY A 7-year-old spayed female Collie weighing 26 kg was referred for evaluation of spontaneous pneumothorax. An exploratory thoracotomy was performed and revealed 2 lung lobes to be diffusely hemorrhagic and they were resected. Histologic examination of multiple sections documented diffuse thromboembolism. A 2-3 cm thrombus was visualized distal to the bifurcation of the pulmonary artery during an echocardiographic examination postoperatively. The dog was discharged to the owner after recovery from surgery. The thrombus had resolved at the 4-week recheck examination. Diagnosis of pituitary dependent hyperadrenocorticism was confirmed based on follow-up endocrine testing. NEW OR UNIQUE INFORMATION PROVIDED This is the first report of pulmonary thromboembolism causing spontaneous pneumothorax in the dog.


title: Resting-state networks in the macaque at 7 T.

text: Assessment of brain connectivity has revealed that the structure and dynamics of large-scale network organization are altered in multiple disease states suggesting their use as diagnostic or prognostic indicators. Further investigation into the underlying mechanisms, organization, and alteration of large-scale brain networks requires a homologous animal model that would allow neurophysiological recordings and experimental manipulations. The current study presents a comprehensive assessment of macaque resting-state networks based on evaluation of intrinsic low-frequency fluctuations of the blood oxygen-level-dependent signal using group independent component analysis. Networks were found underlying multiple levels of sensory, motor, and cognitive processing. The results demonstrate that macaques share remarkable homologous network organization with humans, thereby providing strong support for their use as an animal model in the study of normal and abnormal brain connectivity as well as aiding the interpretation of electrophysiological recordings within the context of large-scale brain networks.


title: Preliminary Experience with the TransForm Occlusion Balloon Catheter: Safety and Potential Advantages.

text: PURPOSE Balloon-assisted coiling (BAC) has made the treatment of aneurysms with complex shape and broad neck possible, especially during the acute phase of hemorrhage. The authors present a prospective series of their preliminary experience with the TransForm occlusion balloon catheter (TOBC). METHODS Between September 2015 to February 2016 a total of 20 patients underwent endovascular treatment assisted by TOBC of which 19 had 20 untreated aneurysms and 1 patient harboring a meningioma was submitted to balloon test occlusion (BTO). The TOBC was used to perform BAC and BTO for the treatment of vasospasms and to cross the neck of giant aneurysms (anchor technique). All data regarding the feasibility and safety of treatment with the device were collected prospectively. RESULTS All patients completed treatment according to the modality previously chosen. The balloon was employed solely for remodeling in 17 patients, for anchor technique in 2, for both remodeling and vasospasm angioplasty in 1 and for BTO in 1 patient. The balloon could be navigated to the target aneurysm in all cases. Evaluation of postoperative anatomical results indicated total occlusion in 13 (72.2 %) aneurysms, neck remnants in 4 (22.2 %) and residual sac filling in 1 (5.5 %). There were two (9.5 %) complications related to treatment, all thromboembolic. No technical complications were observed. CONCLUSION The TOBC was shown to be safe and effective for the treatment of intracranial aneurysms with BAC. In addition, it was successfully employed to perform angioplasty for vasospasm and BTO. Finally, it was used in the balloon anchor technique for the first time.


title: [Clinical features of 2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing].

text: Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte, and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.