title: Ten year retrospective evaluation of the seasonal distribution of agent viruses in childhood respiratory tract infections.

text: AIM Infections caused by respiratory viruses sometimes occur as epidemias or pandemias and are an important public health problem in the whole world. These viral agents may lead to severe respiratory diseases especially in young children and in the elderly. The aim of this study was to determine the seasonal distribution of agent viruses in childhood respiratory infections in our region. MATERIAL AND METHODS In this study, nasopharyngeal swab sample was obtained from 1 326 patients who presented to Ege University, Medical Faculty Children's Hospital between 2002 and 2012 and who were thought to have respiratory tract infection. Influenza virus type A and B, respiratory syncytial virus, adenovirus and parainfluenza virus type 1-3 were investigated using shell-vial cell culture method and direct fluorescent antibody test and/or multiplex PCR test. Parainfluenza virus type 4, human metapneumovirus, rhinovirus, coronavirus, human bocavirus were investigated using multiplex PCR test. The seasonal distributions of the viruses were determined according to the results obtained from Ege University Medical Faculty, Department of Medical Microbiology Clinical Virology Laboratory. Approval was obtained from the ethics committee (Ege University Clinical Researches Ethics Committee, 12.02.2013, number: 13-1/46). RESULTS The majority of the patients who presented were outpatients (n:888, 67%) and the remainder were hospitalized patients (33%, n:438). Respiratory viruses were found in 503 of the nasopharyngeal swab samples (38%). Parainfluenza and respiratory syncytial virus were found most frequently in December-february (58% and 59%, respectively, influenza viruses were found most frequently in November-december (72%) and adenoviruses were found most frequently in may-september (56%). CONCLUSION Although only supportive therapies are administered generally in viral infections, viral investigations are important in terms of determining the measures to be taken by determining the causes as well as in terms of establishing a general database. Another benefit of this study would be strengthening clinical approach to patients and decreasing unnecessary antibiotic use.


title: US Public Health Preparedness for Zika and Other Threats Remains Vulnerable.

text: The unanticipated global outbreak of Zika virus infection is the most current but certainly not the last emerging infectious disease challenge to confront the US public heath system. Despite a number of such threats in recent years, significant gaps remain in core areas of public health system readiness. Stable, sustained investments are required to establish a solid foundation for achieving necessary national public health emergency preparedness and response capacity.


title: Discovery of a novel bottlenose dolphin coronavirus reveals a distinct species of marine mammal coronavirus in Gammacoronavirus.

text: While gammacoronaviruses mainly comprise infectious bronchitis virus (IBV) and its closely related bird coronaviruses (CoVs), the only mammalian gammacoronavirus was discovered from a white beluga whale (beluga whale CoV [BWCoV] SW1) in 2008. In this study, we discovered a novel gammacoronavirus from fecal samples from three Indo-Pacific bottlenose dolphins (Tursiops aduncus), which we named bottlenose dolphin CoV (BdCoV) HKU22. All the three BdCoV HKU22-positive samples were collected on the same date, suggesting a cluster of infection, with viral loads of 1 × 10(3) to 1 × 10(5) copies per ml. Clearance of virus was associated with a specific antibody response against the nucleocapsid of BdCoV HKU22. Complete genome sequencing and comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 have similar genome characteristics and structures. Their genome size is about 32,000 nucleotides, the largest among all CoVs, as a result of multiple unique open reading frames (NS5a, NS5b, NS5c, NS6, NS7, NS8, NS9, and NS10) between their membrane (M) and nucleocapsid (N) protein genes. Although comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 should belong to the same species, a major difference was observed in the proteins encoded by their spike (S) genes, which showed only 74.3 to 74.7% amino acid identities. The high ratios of the number of synonymous substitutions per synonymous site (Ks) to the number of nonsynonymous substitutions per nonsynonymous site (Ka) in multiple regions of the genome, especially the S gene (Ka/Ks ratio, 2.5), indicated that BdCoV HKU22 may be evolving rapidly, supporting a recent transmission event to the bottlenose dolphins. We propose a distinct species, Cetacean coronavirus, in Gammacoronavirus, to include BdCoV HKU22 and BWCoV SW1, whereas IBV and its closely related bird CoVs represent another species, Avian coronavirus, in Gammacoronavirus.


title: Update on complications and their management during transradial cardiac catheterization.

text: Introduction: Transradial cardiac catheterization (TRA) was introduced in 1989 and has been universally used as an alternative approach to the traditional transfermoral access (TFA). Complications of TRA include asymptomatic and less likely symptomatic radial artery occlusion, nonocclusive radial artery injury, radial artery spasm, radial arterial perforation, radial artery pseudoaneurysm, arteriovenous fistula, granuloma formation, access-site bleeding, nerve damage, complex regional pain syndrome along with other rare complications. Areas covered: A literature search was performed using MedLine, PubMed, and Google Scholar (dating to 05/1/2019). Authors reviewed all articles related to transradial artery catheterization, its complications, as well as novel techniques for their management. The article provides insight on the incidence, risk factors and prevention of such complications along with a description of usual and newer techniques to decrease morbidity. Expert opinion: With increasing experience, TRA complication rate is decreasing and new very uncommon complications are being described. A "radial first" approach should be implemented in all catheterization laboratories and a physician's familiarity with minor and major complications is a must. Distal radial artery access through the snuff box might be the preferred site of accessing the radial artery and further studies will be needed to prove its superiority to the current access site.


Endovascular treatment in acute ischemic stroke: where it stands?


title: N-linked glycans on dengue viruses grown in mammalian and insect cells.

text: This study compared the ability of mosquito and mammalian cell-derived dengue virus (DENV) to infect human dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN)-expressing cells and characterized the structure of envelope (E) protein N-linked glycans on DENV derived from the two cell types. DENVs derived from both cell types were equally effective at infecting DC-SIGN-expressing human monocytes and dendritic cells. The N-linked glycans on mosquito cell-derived virus were a mix of high-mannose and paucimannose glycans. In virus derived from mammalian cells, the N-linked glycans were a mix of high-mannose and complex glycans. These results indicate that N-linked glycans are incompletely processed during DENV egress from cells, resulting in high-mannose glycans on viruses derived from both cell types. Studies with full-length and truncated E protein demonstrated that incomplete processing was most likely a result of the poor accessibility of glycans on the membrane-anchored protein.


Middle East respiratory syndrome: the need for better evidence in severe respiratory viral infections.


Tribute to a Black professor lost to COVID-19.


title: Effect of etanercept, a tumor necrosis factor-alpha inhibitor, on neuropathic pain in the rat chronic constriction injury model.

text: STUDY DESIGN The effects of a low, local dose of a tumor necrosis factor-alpha (TNF-alpha) inhibitor on neuropathic pain behaviors in a rat chronic constriction injury model were evaluated. OBJECTIVE To investigate whether a peripherally implanted polymer drug depot can deliver a dose of etanercept sufficient to reduce thermal hyperalgesia and mechanical allodynia in a rat model of neuropathic pain. SUMMARY OF BACKGROUND DATA TNF-alpha inhibitors reduce pain-associated behavior in experimental models of neuropathic pain. Moreover, systemic injections of TNF-alpha inhibitors have suggested some efficacy in treating sciatic pain in limited, off-label clinical studies. Improvements in these results may be obtained by optimal dosing via targeted, sustained delivery at the site of disc-induced inflammation. METHODS Unilateral chronic constriction injury was applied to the sciatic nerve of 56 male, Wistar rats. Four groups of animals (n = 7) received 0.5 mL phosphate-buffered saline every 3 days, 0.3 or 3 mg/kg etanercept every 3 days, or gabapentin (60 mg/kg) 1 hour before each behavioral test all via subcutaneous injection. Two groups of animals received 1.5 or 3.0 microg/h etanercept delivered by poly(lactic-co-glycolic acid) (PLGA) millicylinders (1 mm diameter x 10 mm long) implanted near the injured sciatic nerve. One group received a PLGA millicylinder implanted near the injured sciatic nerve. The final group received 3.0 microg/h etanercept via PLGA millicylinder implanted next to the uninjured, contralateral sciatic nerve. RESULTS A low, local dose of etanercept (approximately 3 microg/h) delivered by a polymer depot significantly reduced (P < 0.05) thermal hyperalgesia for 57 days as compared to polymer depot without drug or an etanercept-loaded depot implanted near the contralateral sciatic nerve, and equivalent to a 10-fold higher dose delivered by repeat subcutaneous injection. CONCLUSION This preclinical study indicates that delivering TNF-alpha inhibitors by means of a locally administered polymeric formulation provides long-lasting analgesia in an inflammatory neuropathic pain model.


title: Clinical risk predictors for cerebral hyperperfusion syndrome after carotid endarterectomy.

text: BACKGROUND Cerebral hyperperfusion syndrome (CHS) is an important complication of carotid endarterectomy (CEA), yet prior research has been limited to small cohorts and retrospective analyses, or studies using radiographic rather than clinical definitions. METHODS A prospective monitoring system was implemented to monitor CEA outcomes at a major academic medical centre. Independent, trained monitors from the neurology department examined all patients undergoing CEA preoperatively and postoperatively at 24 h and 30 days. Clinical variables were analysed to identify risk factors for CHS, which was defined as cases with postoperative development of a severe headache, new neurological deficits without infarction, seizure or intracerebral haemorrhage. RESULTS Between 2008 and 2010, 841 CEAs were monitored and CHS occurred in 14 (1.7%) subjects, including seizures in 5 (0.6%) and intracerebral haemorrhage in 4 (0.5%). Univariate analysis identified a history of dyslipidaemia, coronary artery disease, diastolic blood pressure, intraoperative shunt use and non-elective CEA (performed during hospitalisation for a symptomatic ipsilateral stroke, transient ischaemic attack or amaurosis fugax) as potential risks for CHS (all p≤0.15); other variables-including the degree of ipsilateral and contralateral stenosis, operative time, intraoperative EEG slowing, history of prior CEA or carotid stent and time from prior carotid interventions- were not significant. Logistic regression confirmed the risk association between non-elective CEA and CHS (p=0.046). CONCLUSIONS Independent, prospective monitoring of a large cohort of CEA cases identified a brief time interval between ischaemic symptoms and endarterectomy as the clearest risk factor for CHS.


title: Comparison of the Xpert Flu/RSV XC and Xpress Flu/RSV Assays.

text: Molecular diagnostics for influenza and respiratory syncytial virus (RSV) have become commonplace, and various tests and systems have been cleared by the FDA for use in the United States. We performed a retrospective study to compare the Cepheid Xpress Flu/RSV assay with the Xpert Flu/RSV XC assay, using laboratory-developed tests (LDTs) as the reference method. The Xpress assay was 100% accurate compared to LDTs, whereas the Xpert Flu/RSV XC assay was 96.0% accurate. The Xpress test was determined to be faster and more sensitive than the XC assay.


title: On better estimating and normalizing the relationship between clinical parameters: comparing respiratory modulations in the photoplethysmogram and blood pressure signal (DPOP versus PPV).

text: DPOP (ΔPOP or Delta-POP) is a noninvasive parameter which measures the strength of respiratory modulations present in the pulse oximeter waveform. It has been proposed as a noninvasive alternative to pulse pressure variation (PPV) used in the prediction of the response to volume expansion in hypovolemic patients. We considered a number of simple techniques for better determining the underlying relationship between the two parameters. It was shown numerically that baseline-induced signal errors were asymmetric in nature, which corresponded to observation, and we proposed a method which combines a least-median-of-squares estimator with the requirement that the relationship passes through the origin (the LMSO method). We further developed a method of normalization of the parameters through rescaling DPOP using the inverse gradient of the linear fitted relationship. We propose that this normalization method (LMSO-N) is applicable to the matching of a wide range of clinical parameters. It is also generally applicable to the self-normalizing of parameters whose behaviour may change slightly due to algorithmic improvements.


title: Intravenous Thrombolysis in Patients Dependent on the Daily Help of Others Before Stroke.

text: BACKGROUND AND PURPOSE We compared outcome and complications in patients with stroke treated with intravenous thrombolysis (IVT) who could not live alone without help of another person before stroke (dependent patients) versus independent ones. METHODS In a multicenter IVT-register-based cohort study, we compared previously dependent (prestroke modified Rankin Scale score, 3-5) versus independent (prestroke modified Rankin Scale score, 0-2) patients. Outcome measures were poor 3-month outcome (not reaching at least prestroke modified Rankin Scale [dependent patients]; modified Rankin Scale score of 3-6 [independent patients]), death, and symptomatic intracranial hemorrhage. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (OR [95% confidence interval]) were calculated. RESULTS Among 7430 IVT-treated patients, 489 (6.6%) were dependent and 6941 (93.4%) were independent. Previous stroke, dementia, heart, and bone diseases were the most common causes of preexisting dependency. Dependent patients were more likely to die (ORunadjusted, 4.55 [3.74-5.53]; ORadjusted, 2.19 [1.70-2.84]). Symptomatic intracranial hemorrhage occurred equally frequent (4.8% versus 4.5%). Poor outcome was more frequent in dependent (60.5%) than in independent (39.6%) patients, but the adjusted ORs were similar (ORadjusted, 0.95 [0.75-1.21]). Among survivors, the proportion of patients with poor outcome did not differ (35.7% versus 31.3%). After adjustment for age and stroke severity, the odds of poor outcome were lower in dependent patients (ORadjusted, 0.64 [0.49-0.84]). CONCLUSIONS IVT-treated stroke patients who were dependent on the daily help of others before stroke carry a higher mortality risk than previously independent patients. The risk of symptomatic intracranial hemorrhage and the likelihood of poor outcome were not independently influenced by previous dependency. Among survivors, poor outcome was avoided at least as effectively in previously dependent patients. Thus, withholding IVT in previously dependent patients might not be justified.


title: Dynamic interaction of a downward plane jet and a cough jet with respect to particle transmission: An analytical and experimental study.

text: A cough jet can travel beyond the breathing zone of the source person, and thus, infectious viral- and bacterial-laden particles can be transported from the source person to others in close proximity. To reduce the interpersonal transmission of coughed particles, the objective of this study was to analytically and experimentally investigate the performance of downward plane jets with various discharge velocities. Chamber measurements were conducted to examine the interaction between a transient cough jet (discharge velocities of 12 m/sec and 16 m/sec) and a steady downward plane jet (discharge velocities from 1.0-8.5 m/sec) with respect to the transport of and human exposure to coughed particles. The results show that a relatively high-speed cough can easily penetrate a downward plane jet with a discharge velocity of less than 6 m/sec. A downward plane jet with a discharge velocity of 8.5 m/sec can bend the cough jet to a certain extent. In this study, momentum comparison of the cough jet and the downward plane jet shows that the value of personal exposure to coughed particles depends on the ratio of jet momentums. The results show that when the two momentums are equivalent or if the downward plane jet has a greater momentum, the cough jet is deflected downward and does not reach the breathing zone of the target thermal dummy. Using the ratio of the two momentums, it may be estimated whether the transmission of a cough jet can be controlled. A trajectory model was developed based on the ratio of the two momentums of a cough jet and a downward jet and was validated using the experimental data. In addition, the predicted trajectory of the cough jet agreed well with the results from smoke visualization experiments. This model can be used to guide the design of downward plane jet systems for protection of occupants from coughed particles.


title: The contribution of the cytoplasmic retrieval signal of severe acute respiratory syndrome coronavirus to intracellular accumulation of S proteins and incorporation of S protein into virus-like particles.

text: The cytoplasmic tails of some coronavirus (CoV) spike (S) proteins contain an endoplasmic reticulum retrieval signal (ERRS) that can retrieve S proteins from the Golgi to the endoplasmic reticulum (ER); this process is thought to accumulate S proteins at the CoV budding site, the ER-Golgi intermediate compartment (ERGIC), and to facilitate S protein incorporation into virions. However, we showed previously that porcine epidemic diarrhoea CoV S proteins lacking the ERRS were efficiently incorporated into virions, similar to the original virus. Thus, the precise role of the ERRS in virus assembly remains unclear. Here, the roles of the S protein ERRS in severe acute respiratory syndrome CoV (SARS-CoV) intracellular trafficking and S incorporation into virus-like particles (VLPs) are described. Intracellular trafficking and indirect immunofluorescence analysis suggested that when M protein was present, wild-type S protein (wtS) could be retained in the pre- and post-medial Golgi compartments intracellularly and co-localized with M protein in the Golgi. In contrast, mutant S protein lacking the ERRS was distributed throughout the ER and only partially co-localized with M protein. Moreover, the intracellular accumulation of mutant S protein, particularly at the post-medial Golgi compartment, was significantly reduced compared with wtS. A VLP assay suggested that wtS that reached the post-medial compartment could be returned to the ERGIC for subsequent incorporation into VLPs, while mutant S protein could not. These results suggest that the ERRS of SARS-CoV contributes to intracellular S protein accumulation specifically in the post-medial Golgi compartment and to S protein incorporation into VLPs.


title: Regulation of proinflammatory cytokine expression in primary mouse astrocytes by coronavirus infection.

text: Previous studies have shown that proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), are differentially induced in primary mouse astrocytes by mouse hepatitis virus strain A59 (MHV-A59) and MHV-2. However, the signaling events that trigger TNF-alpha and IL-6 induction in these cells upon MHV infection remain unknown. In this study, we explored the potential signaling events. We found that induction of TNF-alpha and IL-6 occurred as early as 2 h postinfection and was completely dependent on viral replication. Using inhibitors specific for three mitogen-activated protein kinases, we showed that induction of TNF-alpha and IL-6 by MHV-A59 infection was mediated through activation of the Janus N-terminal kinase signaling pathway, but not through the extracellular signal-regulated kinase or p38 signaling pathway. This finding was further confirmed with knockdown experiments using small interfering RNAs specific for Janus N-terminal kinase. Interestingly, while nuclear factor kappaB (NF-kappaB), a key transcription factor required for the expression of proinflammatory cytokines in most cell types, was activated in astrocytes during MHV-A59 infection, disruption of the NF-kappaB pathway by peptide inhibitors did not significantly inhibit TNF-alpha and IL-6 expression. Furthermore, experiments using chimeric viruses demonstrated that the viral spike and nucleocapsid proteins, which play important roles in MHV pathogenicity in mice, are not responsible for the differential induction of the cytokines. These results illustrate the complexity of the regulatory mechanism by which MHV induces proinflammatory cytokines in primary astrocytes.


title: Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial.

text: IMPORTANCE It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery. OBJECTIVE To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure <60 mm Hg or oxygen saturation [SpO2] ≤90% when breathing room air or <80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure. INTERVENTIONS Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain SpO2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain SpO2 ≥94%) (n = 148). MAIN OUTCOMES AND MEASURES The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation-free days at day 30, health care-associated infections, and 90-day mortality. RESULTS Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, -12.4%; 95% CI, -23.5% to -1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, -2.2 days; 95% CI, -0.1 to 4.6 days; P = .04), while fewer patients developed health care-associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, -17.8%; 95% CI, -30.2% to -5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, -6.5%; 95% CI, -16.0% to 3.0%; P = .15). There were no significant differences in gas exchange. CONCLUSIONS AND RELEVANCE Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01971892.


title: One-pass endovascular treatment of intracranial atherosclerotic stenosis with a novel PTA balloon and self-expanding microstent.

text: INTRODUCTION We present a novel endovascular technique to treat intracranial atherosclerotic stenosis (ICS) with the specific potential to reduce the procedure-related complications which so far limited safety and efficacy of endovascular ICS intervention. METHODS Six consecutive patients were included in this study with the following criteria of inclusion: (1) failure of dual antiplatelet therapy defined as recurrent TIA or ischemic stroke, (2) presence of ICS of ≥70 %, and (3) endovascular accessibility of the target lesion as judged by CTA or MRA. Technical feasibility, safety, and efficacy were observed for the first-ballon-then-stent (FBTS) technique using the percutaneous transluminal angioplasty (PTA) balloon microcatheter over which a self-expandable microstent can be directly delivered obviating the need to exchange microcatheters. RESULTS FBTS was performed in six patients (four female, median age 69, median stenosis 82.5 %) all refractory to best medical treatment: three V4, two M1, and one supraclinoid ICA stenosis. PTA and stent deployment were technically feasible in all patients and immediately effective with a median postprocedural stenosis grade of 10 %. Angiographic and clinical safety measures were met with no occult or clinically evident hemorrhage or ischemic complications (four patients discharged without alteration in mRS, two patients with significant clinical improvement). No occurrence of TIA, stroke, or death was observed during follow-up. CONCLUSION The FBTS method in this series appeared to be safe and effective for the endovascular treatment of ICS. It bears the specific potential to reduce wire perforations, which so far have been linked to major procedure-related adverse events of endovascular ICS treatment.


title: COVID-19: Real-time dissemination of scientific information to fight a public health emergency of international concern.

text: Rapidly sharing scientific information is an effective way to reduce public panic about COVID-19, and doing so is the key to providing real-time guidance to epidemiologists working to contain the outbreak, clinicians managing patients, and modelers helping to understand future developments and the possible effectiveness of various interventions. This issue has rapidly reviewed and published articles describing COVID-19, including the drug treatment options for SARS-CoV-2, its clinical characteristics, and therapies involving a combination of Chinese and Western medicine, the efficacy of chloroquine phosphate in the treatment of COVID-19 associated pneumonia according to clinical studies, and reflections on the system of reserve medical supplies for public health emergencies. As an academic journal, we will continue to quickly and transparently share data with frontline healthcare workers who need to know the epidemiological and clinical features of COVID-19.


title: Telehealth in urology after the COVID-19 pandemic

text: In response to the COVID-19 pandemic, the need to safely provide patient care meant that many health-care providers rapidly implemented and integrated telehealth into their practice. However, telehealth will continue to be an integral part of urology after the pandemic and our field should embrace telehealth and develop strategies to overcome associated challenges.


Correction: Immunodominant SARS Coronavirus Epitopes in Humans Elicited Both Enhancing and Neutralizing Effects on Infection in Non-human Primates.


title: Effect of bisoprolol on respiratory function and exercise capacity in chronic obstructive pulmonary disease.

text: Cardioselective β blockers are considered to have little impact on lung function at rest in patients with chronic obstructive pulmonary disease (COPD). However, their effects on dynamic hyperinflation, an important mechanism contributing to symptoms and exercise tolerance in patients with COPD, have not been evaluated. Twenty-seven patients with moderate to severe COPD (forced expiratory volume in 1 second 52 ± 13% predicted) completed pulmonary function tests, echocardiography, maximal exercise tests, and cycle endurance tests at baseline. Inspiratory capacity was measured at 2-minute intervals during the cycle endurance test to quantify dynamic hyperinflation. Pulmonary function and cycle endurance testing were repeated after 14 days of bisoprolol 10 mg/day and 14 days of placebo in a randomized, double-blind, placebo-controlled, crossover trial. The extent of dynamic hyperinflation at peak isotime exercise with bisoprolol and placebo was compared. Peak isotime was defined as the latest time point that was reached during the 2 cycle endurance tests. Changes in inspiratory capacity from rest to peak isotime were different with bisoprolol compared to placebo (-0.50 ± 0.35 vs -0.41 ± 0.33 L, p = 0.01). Exercise duration tended to be lower with bisoprolol compared to placebo (305 ± 125 vs 353 ± 172 seconds, p = 0.11). The magnitude of change in exercise duration between the bisoprolol and placebo conditions was correlated with the magnitude of change in inspiratory capacity (r = 0.57, p <0.01). In conclusion, bisoprolol was associated with modest worsening dynamic hyperinflation, whereas exercise duration remained unchanged in patients with moderate to severe COPD. The magnitude of these effects was small and should not contraindicate the use of bisoprolol in patients with COPD.


title: Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.

text: Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic pancreatitis decreased when the lag period was increased to 5 years (EE: 7.90; 95% CI: 4.26-14.66) or a minimum of 9 years (EE: 3.53; 95% CI: 1.69-7.38). In conclusion, chronic pancreatitis increases the risk of pancreatic cancer, but the association diminishes with long-term follow-up. Five years after diagnosis, chronic pancreatitis patients have a nearly eight-fold increased risk of pancreatic cancer. We suggest that common practice on inducing a 2-year lag period in these studies may not be sufficient. We also recommend a close follow-up in the first years following a diagnosis of chronic pancreatitis to avoid overlooking a pancreatic cancer.


title: Complete video-assisted thoracoscopic surgery anatomic segmentectomy for clinical stage I lung carcinoma - technique and feasibility.

text: This paper describes a prospective, observational, single-centre study of 20 consecutive patients with clinical stage I lung carcinoma undergoing anatomical sublobar resections using complete video-assisted thoracoscopic surgery (cVATS). Thirteen male and seven female patients with a median age of 68 (range 57-84) years and a median of four (range 0-9) relevant comorbid conditions presented with five right-sided and 15 left-sided tumours, with a median diameter of 2.3 (range 1.0-5.2) cm. Thirteen segmentectomies, three bisegmentectomies and four trisegmentectomies with lymphadenectomy of the N1 stations and the mediastinum were performed, with a median duration of 212 (range 91-397) min, a conversion rate to open surgery of 20% and conversion to lobectomy of 10%. In five patients, we noted 10 postoperative adverse events but no transfusions, no readmissions and zero mortality. Median drainage time was six days, with a median hospital stay of 8.5 days. According to the pTNM classification, 10, three, one, and six patients were staged as Ia, Ib, IIb and IIIa, respectively. The distance between the tumour and the parenchymal stapling line exceeded the tumour diameter in 56%, 0% and 0% of T1a, T1b and T2 tumours, respectively. To conclude, cVATS anatomical sublobar resections are technically feasible. We observed a favourable postoperative course in 20 multimorbid or aged patients. In patients fit for lobectomy, the tumour diameter should not exceed 2 cm.


title: Standardization of the fully stapled laparoscopic Roux-en-Y gastric bypass for obesity reduces early immediate postoperative morbidity and mortality: a single center study on 2606 patients.

text: BACKGROUND Various techniques of laparoscopic Roux-en-Y gastric bypass have been described. We completely standardized this procedure to minimize its sometimes substantial morbidity and mortality. This study describes our experience with the standardized fully stapled laparoscopic Roux-en-Y gastric bypass (FS-LRYGB) and its influence on the 30-day morbidity and mortality. METHODS We retrospectively analyzed 2,645 patients who underwent FS-LRYGB from May 2004 to August 2008. Operative time, hospital stay and readmission, re-operation, and 30-day morbidity/mortality rates were then calculated. The 30-day follow-up data were complete for 2,606 patients (98.5%). RESULTS There were 539 male and 2,067 female patients. Mean age was 39.2 years (range 14-73), mean BMI 41.44 kg/m(2) (range, 23-75.5). The mean hospital stay was 3.35 days (range 2-71). Mean total operative time was 63 min (range 35-150). One patient died of pneumonia within 30 days of surgery (0.04%). One hundred and fifty one (5.8%) patients had postoperative complications as follows: gastrointestinal hemorrhage (n = 89, 3.42%), intestinal obstruction (n = 9, 0.35%), anastomotic leak (n = 5, 0.19%) and others (n = 47, 1.80%). In 66 patients, the bleeding resolved without any surgical re-intervention. One hemorrhage resulted in hypovolemic shock with subsequent renal and hepatic failure. CONCLUSION The systematic approach and the full standardization of the FS-LRYGB procedure contribute highly to the very low mortality and the low morbidity rates in our institution. Gastrointestinal bleeding appears to be the commonest complication, but is self-limiting in the majority of cases. Our approach also significantly reduces operative time and turns the technically demanding laparoscopic Roux-en-Y gastric bypass procedure into an easy reproducible operation, effective for training.


title: Occurrence of bacteria and viruses on elementary classroom surfaces and the potential role of classroom hygiene in the spread of infectious diseases.

text: The presence of microorganisms on common classroom contact surfaces (fomites) was determined to identify the areas most likely to become contaminated. Six elementary classrooms were divided into control and intervention groups (cleaned daily with a quaternary ammonium wipe) and tested for heterotrophic bacteria. Three classrooms were also tested for norovirus and influenza A virus. Frequently used fomites were the most contaminated; water fountain toggles, pencil sharpeners, keyboards, and faucet handles were the most bacterially contaminated; desktops, faucet handles, and paper towel dispensers were the most contaminated with viruses. Influenza A virus was detected on up to 50% and norovirus on up to 22% of surfaces throughout the day. Children in the control classrooms were 2.32 times more likely to report absenteeism due to illness than children in the intervention classrooms and were absent longer (on average). Improved classroom hygiene may reduce the incidence of infection and thus student absenteeism.


title: Enrollment volume effect on risk factor control and outcomes in the SAMMPRIS trial.

text: OBJECTIVE The role of physician experience and patient volumes on the outcome of surgical or endovascular procedures has been well-studied but there are limited data on how these factors affect the outcome of medical therapy. METHODS In the stenting and medical cohorts of the Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial, we compared Kaplan-Meier (K-M) curves for the primary endpoint (any stroke or death within 30 days of enrollment or ischemic stroke in the territory beyond 30 days) using the log-rank test and the percentages of patients achieving target levels for primary and secondary risk factors during the study using Fisher exact test between patients at high-enrolling (≥12 patients) vs low-enrolling (<12 patients) sites. RESULTS In the stenting group, the K-M curves for the primary endpoint were similar at high-enrolling sites and low-enrolling sites (p = 0.93) with rates of 13.5% vs 14.7% at 30 days and 19.0% vs 20.6% at 2 years. In the medical group, the K-M curves differed between high-enrolling sites and low-enrolling sites (p = 0.0005) with rates of 1.8% vs 9.8% at 30 days and 7.3% vs 20.9% at 2 years. The percentages of patients who achieved targets for low-density lipoprotein cholesterol and systolic blood pressure at high- vs low-enrolling sites in both treatment groups combined were 64% vs 49% (p = 0.003) and 70% vs 59% (p = 0.026), respectively. CONCLUSIONS High-enrolling sites in SAMMPRIS achieved better control of primary risk factors and much lower rates of the primary endpoint than low-enrolling sites in the medical group, suggesting that experience with medical management is an important determinant of patient outcome.


title: Back pain in physically inactive students compared to physical education students with a high and average level of physical activity studying in Poland.

text: BACKGROUND The aim of the study was (1) to characterise back pain in physically inactive students as well as in trained (with a high level of physical activity) and untrained (with an average level of physical activity) physical education (PE) students and (2) to find out whether there exist differences regarding the declared incidence of back pain (within the last 12 months) between physically inactive students and PE students as well as between trained (with a high level of physical activity) and untrained (with an average level of physical activity) PE students. METHODS The study included 1321 1st-, 2nd- and 3rd-year students (full-time bachelor degree course) of Physical Education, Physiotherapy, Pedagogy as well as Tourism and Recreation from 4 universities in Poland. A questionnaire prepared by the authors was applied as a research tool. The 10-point Visual Analogue Scale (VAS) was used to assess pain intensity. Prior to the study, the reliability of the questionnaire was assessed by conducting it on the group of 20 participants twice with a shorter interval. No significant differences between the results obtained in the two surveys were revealed (p < 0.05). RESULTS In the group of 1311 study participants, 927 (70.7%) respondents declared having experienced back pain within the last 12 months. Physically inactive students declared back pain frequency similar to the frequency declared by their counterparts studying physical education (p > 0.05). Back pain was more common in the group of trained students than among untrained individuals (p < 0.05). Back pain was mainly located in the lumbar spine. CONCLUSIONS A frequent occurrence of back pain (70.7%) was noted in the examined groups of students. The percentage of students declaring back pain increased in the course of studies (p < 0.05) and, according to the students' declarations, it was located mainly in the lumbar spine. No significant differences regarding the incidence of back pain were found between physically inactive students and physical education students (p > 0.05). The trained students declared back pain more often than their untrained counterparts (p < 0.05).


title: Injection therapy for base of thumb osteoarthritis: a systematic review and meta-analysis.

text: OBJECTIVE To evaluate the effectiveness of injection-based therapy in base of thumb osteoarthritis. DESIGN Systematic review and meta-analysis. DATA SOURCES MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO were searched from inception to 22 May 2018. STUDY SELECTION Randomised controlled trials (RCTs) and non-RCTs of adults with base of thumb osteoarthritis investigating an injection-based intervention with any comparator/s. DATA EXTRACTION AND ANALYSIS Data were extracted and checked for accuracy and completeness by pairs of reviewers. Primary outcomes were pain and function. Comparative treatment effects were analysed by random-effects model for short-term and medium-term follow-up. RESULTS In total, 9 RCTs involving 504 patients were identified for inclusion. All compared different injection-based therapies with each other, no studies compared an injection-based therapy with a non-injection-based intervention. Twenty injection-based intervention groups were present within these nine trials, consisting of hyaluronic acid (n=9), corticosteroid (n=7), saline placebo (n=3) and dextrose (n=1). Limited meta-analysis was possible due to the heterogeneity in the injections and outcomes used, as well as incomplete outcome data. Meta-analysis of two RCTs (92 patients) demonstrated reduced Visual Analogue Scale pain on activity with corticosteroid versus hyaluronic acid (mean difference (MD) -1.32, 95% CI -2.23 to -0.41) in the medium term, but no differences in other measures of pain or function in the short term and medium term. Overall, the available evidence does not suggest that any of the commonly used injection therapies are superior to placebo, one another or a non-injection-based comparator. CONCLUSION Current evidence is equivocal regarding the use of injection therapy in base of thumb osteoarthritis, both in terms of which injection-based therapy is the most effective and in terms of whether any injection-based therapy is more effective than other non-injection-based interventions. Given limited understanding of both the short-term and long-term effects, there is a need for a large, methodologically robust RCT investigating the commonly used injection therapies and comparing them with other therapeutic options and placebo. PROSPERO REGISTRATION NUMBER CRD42018095384.


title: Minimally invasive treatment of intracerebral hemorrhage.

text: Intracerebral hemorrhages (ICH) cause high levels of morbidity and mortality. Secondary neuronal injury from perihematomal edema is thought to contribute to poor outcomes. Surgical evacuation of ICH is a theoretically promising approach, yet clinical data on the efficacy of standard craniotomy approaches is limited. Recent exploration of minimally invasive techniques for ICH removal includes stereotactic surgery combined with intra-clot thrombolysis, as well as endoscopic hematoma evacuation. Ongoing trials have demonstrated the safety of such minimally invasive approaches, and pending efficacy data from these studies is likely to change the standard management of ICH.


Middle East Respiratory Syndrome Coronavirus Patients in the ICU.


title: Reinstating elective orthopaedic surgery in the age of COVID-19.

text: The transition from shutdown of elective orthopaedic services to the resumption of pre-COVID-19 activity presents many challenges. These include concerns about patient safety, staff safety, and the viability of health economies. Careful planning is necessary to allow patients to benefit from orthopaedic care in a safe and sustainable manner. Cite this article: Bone Joint J 2020;102-B(7):1-4.


title: Thoracoscopic subphrenic pericardectomy using double-lumen endobronchial intubation for alternating one-lung ventilation.

text: OBJECTIVE To report the technique, complications, and effectiveness of thoracoscopic subphrenic pericardectomy (SPP) using double-lumen endobronchial intubation for alternating 1-lung (OLV) in healthy dogs. STUDY DESIGN Prospective cohort study. ANIMALS Mature purpose-bred dogs (n=7). METHODS Bronchoscope-assisted placement of a left-sided double-lumen endobronchial tube, immediately before surgery, allowed intraoperative alternation of ventilation between lung fields. A camera portal was established in a subxyphoid location. Two instrument portals were established at the 4th-6th intercostal spaces on the right and left sides. A vessel-sealing device was used to create the subphrenic pericardectomy. After termination of the procedure, dogs were humanely euthanatized under anesthesia and necropsy performed. In each dog, the extent of pericardectomy and any complications were evaluated. RESULTS Technical difficulties with tube placement occurred in 4 dogs, but alternating OLV was achieved in all dogs and SPP completed successfully. Median surgical time was 87.5 minutes (range, 80-105 minutes). At necropsy, 0.5-2 cm of pericardial tissue remained ventral to the intact phrenic nerve in 6 dogs; in 1 dog, the phrenic nerve was transected on the left side only. CONCLUSIONS Thoracoscopic subphrenic pericardectomy is a technically feasible procedure in healthy dogs. Double-lumen endobronchial intubation allowed alternating OLV without intraoperative bronchoscopically guided tube manipulation in all but 1 dog. CLINICAL RELEVANCE Thoracoscopic subphrenic pericardectomy could potentially be used for management of conditions where relief of pericardial constriction or access to intrapericardial structures is desired.


title: Apolipoprotein D subcellular distribution pattern in neuronal cells during oxidative stress.

text: Apolipoprotein D (Apo D) is a secreted glycoprotein, member of the lipocalin superfamily, with a related beneficial role in metabolism and lipid transport due to the presence of a binding pocket that allows its interaction with several lipids. Nowadays, it has been clearly demonstrated that Apo D expression is induced and its subcellular location undergoes modifications in stressful and pathological conditions that characterize aging processes and neurodegenerative diseases. The aim of the present work was to study in detail the effect of H2O2 on the subcellular location of Apo D, in the hippocampal cell line HT22, by structural, ultrastructural, immunocytochemical, and molecular techniques in order to characterize the Apo D distribution pattern in neurons during oxidative stress. Our results indicate that Apo D is located in the cytoplasm under physiological conditions but treatment with H2O2 induces apoptosis and causes a displacement of Apo D location to the nucleus, coinciding with DNA fragmentation. In addition, we demonstrated that Apo D tends to accumulate around the nuclear envelope in neurons and glial cells of different brain areas in some neurodegenerative diseases and during human aging, but never inside the nucleus. These data suggest that the presence of Apo D in the nucleus, which some authors related with a specific transport, is a consequence of structural and functional alterations during oxidative stress and not the result of a specific role in the regulation of nuclear processes.


title: Single-port laparoscopic right hemicolectomy: the first 100 resections.

text: BACKGROUND Single-port laparoscopy remains a novel technique in the field of colorectal surgery. Several small series have examined its safety for colon resection. OBJECTIVE Our aim was to analyze our entire experience and short-term outcomes with single-port laparoscopic right hemicolectomy since its introduction at our institution. We assert that this approach is feasible and safe for the wide array of patients and indications encountered by a colorectal surgeon. DESIGN This is a retrospective analysis of prospectively gathered data for all patients who underwent single-port laparoscopic right hemicolectomy with the use of standard laparoscopic instrumentation, for malignant or benign disease, between July 2009 and November 2010 in a high-volume, academic, colorectal surgery practice. MAIN OUTCOME MEASURES Demographic, clinical, operative, and pathologic factors were reviewed and analyzed. All conversions to conventional laparoscopic or open operations were considered in this analysis. RESULTS One hundred patients underwent single-port laparoscopic right hemicolectomy during the study period. Mean age was 63 years, and 61% of the patients were men. Forty-three percent had undergone previous abdominal surgery, and the median body mass index was 26 (range, 18-46). Median ASA classification was 3 (range, 1-4). Five percent of the operations were performed urgently, and 56% were performed for carcinoma, of which half were T3 or T4 tumor stage. Median operative duration was 105 (range, 64-270) minutes. Mean and median blood loss was 106 and 50 mL. Two percent required conversion to multiport laparoscopy, and 4% converted to the open approach. Median postoperative stay was 4 (range, 2-48) days. Median lymph node number was 18 (range, 11-42). There was one mortality in this series. Morbidity, including wound infection, was 13%. CONCLUSIONS This represents the largest experience with single-port laparoscopic right hemicolectomy to date. This technique was used with acceptable morbidity and mortality and without compromise of conventional oncologic parameters by colorectal surgeons experienced in minimally invasive technique. These findings support the use of a single-port approach for patients requiring right hemicolectomy.


title: Prognostic Value of Preoperative Systemic Immunoinflammatory Measures in Patients with Esophageal Cancer.

text: BACKGROUND It is reported that several systemic immunoinflammatory measures, including systemic immune-inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and C-reactive protein (CRP)-to-albumin ratio (CAR), are associated with survival in patients with various types of cancer. OBJECTIVE The aim of the present study was to clear which systemic immunoinflammatory measures had the greatest prognostic values. In addition, we examined which component had the greatest prognostic power in patients with esophageal cancer. METHODS Preoperative systemic immunoinflammatory measures were evaluated in 143 patients undergoing esophageal resection for esophageal cancer from 2009 to 2014. Univariate and multivariate analyses were performed to determine the prognostic significance of these markers. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curves (AUROCs) were compared to verify the accuracy of each measure in predicting overall survival (OS). RESULTS In univariate analysis, preoperative SII, NLR, and CAR were the predictors of OS in patients who underwent esophagectomy for esophageal cancer (p < 0.05, respectively), whereas in multivariate analysis, CAR and pathological tumor depth were the significant predictors of OS (hazard ratio [HR] 1.994, p = 0.03 vs. HR 1.967, p = 0.02, respectively). According to AUROC, the CRP (0.66) and albumin levels (0.66) were more important systemic immunoinflammatory measures than neutrophil (0.58), lymphocyte (0.63), and platelet (0.56) levels. CONCLUSION Among systemic immunoinflammatory measures, CAR was the most significant predictor of OS in patients with esophageal cancer. CRP and albumin levels were more important components of systemic immunoinflammatory measures.


title: Evaluation of cotton rats as a model for severe acute respiratory syndrome.

text: Experimental studies were conducted to evaluate two species of cotton rats, Sigmodon hispidus and Sigmodon fulviventer, as a model for severe acute respiratory syndrome (SARS). Blood and turbinate wash samples, and lung tissue were collected from each animal at different time points after SARS coronavirus (CoV) infection for determining the growth curve of virus, if any, by the standard infectivity assay in Vero E6 cells. In addition, sections of the lung, liver, spleen, and kidney were taken and used for histology analysis. All animals were observed daily for signs of illness, and in some experiments, animals were weighed on the day when they were sacrificed. The results indicated that the cotton rat species, S. hispidus and S. fulviventer, were not a useful model for either SARS-CoV infection or disease. This observation was supported by the absence of any signs of illness, the failure to consistently demonstrate virus in the blood and tissues, and the absent of any notable histopathology. However, infected animals were capable of producing neutralizing antibodies against SARS-CoV, suggesting the seroconversion did occur. Further studies are warranted to consider other animal species in efforts to find better animal models for the evaluation of SARS-CoV vaccines and antiviral drugs.


title: Humidity and Inspired Oxygen Concentration During High-Flow Nasal Cannula Therapy in Neonatal and Infant Lung Models.

text: BACKGROUND High-flow nasal cannula therapy (HFNC) for neonate/infants can deliver up to 10 L/min of heated and humidified gas, and FIO2 can be adjusted to between 0.21 and 1.0. With adults, humidification and actual FIO2 are known to vary according to inspiratory and HFNC gas flow, tidal volume (VT), and ambient temperature. There have been few studies focused on humidification and FIO2 in HFNC settings for neonates/infants, so we performed a bench study to investigate the influence of gas flow, ambient temperature, and respiratory parameters on humidification and actual FIO2 in a neonate/infant simulation. METHODS HFNC gas flow was set at 3, 5, and 7 L/min, and FIO2 was set at 0.3, 0.5, and 0.7. Spontaneous breathing was simulated using a 2-bellows-in-a-box model of a neonate lung. Tests were conducted with VT settings of 20, 30, and 40 mL and breathing frequencies of 20 and 30 breaths/min. Inspiratory time was 0.8 s with decelerating flow waveform. The HFNC tube was placed in an incubator, which was either set at 37°C or turned off. Absolute humidity (AH) and actual FIO2 were measured for 1 min using a hygrometer and an oxygen analyzer, and data for the final 3 breaths were extracted. RESULTS At all settings, when the incubator was turned on, AH was greater than when it was turned off (P < .001). When the incubator was turned off, as gas flow increased, AH increased (P < .001); however, VT did not affect AH (P = .16). As gas flow increased, actual FIO2 more closely corresponded to set FIO2 . When gas flow was 3 L/min, measured FIO2 decreased proportionally more at each FIO2 setting increment (P < .001). CONCLUSIONS AH was affected by ambient temperature and HFNC gas flow. Actual FIO2 depended on VT when gas flow was 3 L/min.


title: Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.

text: Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.


title: Coronavirus-induced demyelination of neural pathways triggers neurogenic bladder overactivity in a mouse model of multiple sclerosis.

text: In the present study, we aimed to determine whether mice with coronavirus-induced encephalomyelitis (CIE) develop neurogenic bladder dysfunction that is comparable with the neurogenic detrusor overactivity observed in patients with multiple sclerosis. Adult mice (C57BL/6J, 8 wk of age, n = 146) were inoculated with a neurotropic strain of mouse hepatitis virus (A59 strain) and followed for 4 wk. Inoculation with the virus caused a significant neural deficit in mice with an average clinical symptom score of 2.6 ± 0.5 at 2 wk. These changes were accompanied by 25 ± 5% weight loss at 1 and 2 wk postinoculation (P ≤ 0.001 vs. baseline) followed by a recovery phase. Histological analysis of spinal cord sections revealed multifocal sites of demyelinated lesions. Assessment of micturition patterns by filter paper assay determined an increase in the number of small and large urine spots in CIE mice starting from the second week after inoculation. Cystometric recordings in unrestrained awake animals confirmed neurogenic bladder overactivity at 4 wk postinoculation. One week after inoculation with the A59 strain of mouse hepatitis virus, mice became increasingly sensitive to von Frey filament testing with responses enhanced by 45% (n = 8, P ≤ 0.05 vs. baseline at 4 g); however, this initial increase in sensitivity was followed by gradual and significant diminution of abdominal sensitivity to mechanical stimulation by 4 wk postinoculation. Our results provide direct evidence showing that coronavirus-induced demyelination of the central nervous system causes the development of a neurogenic bladder that is comparable with neurogenic detrusor overactivity observed in patients with multiple sclerosis.


A call to arms: a perspective of safe general surgery in Singapore during the COVID-19 pandemic.


title: Reduced mortality and severe disability rates in the SENTIS trial.

text: BACKGROUND AND PURPOSE The Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke trial showed a trend for reduced all-cause mortality and positive secondary safety end point outcomes. We present further analyses of the mortality and severe disability data from the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke trial. MATERIALS AND METHODS The Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke trial was a multicenter, randomized, controlled trial that evaluated the safety and effectiveness of the NeuroFlo catheter in patients with stroke. The current analysis was performed on the as-treated population. All-cause and stroke-related mortality rates at 90 days were compared between groups, and logistic regression models were fit to obtain ORs and 95% CIs for the treated versus not-treated groups. We categorized death-associated serious adverse events as neurologic versus non-neurologic events and performed multiple logistic regression analyses. We analyzed severe disability and mortality by outcomes of the mRS. Patient allocation was gathered by use of a poststudy survey. RESULTS All-cause mortality trended in favor of treated patients (11.5% versus 16.1%; P = .079) and stroke-related mortality was significantly reduced in treated patients (7.5% versus 14.2%; P = .009). Logistic regression analysis for freedom from stroke-related mortality favored treatment (OR, 2.41; 95% CI, 1.22, 4.77; P = .012). Treated patients had numerically fewer neurologic causes of stroke-related deaths (52.9% versus 73.0%; P = .214). Among the 90-day survivors, nominally fewer treated patients were severely disabled (mRS 5) (5.6% versus 7.5%; OR, 1.72; 95% CI, 0.72, 4.14; P = .223). Differences in allocation of care did not account for the reduced mortality rates. CONCLUSIONS There were consistent reductions in all-cause and stroke-related mortality in the NeuroFlo-treated patients. This reduction in mortality did not result in an increase in severe disability.


title: Does prior antiplatelet treatment improve functional outcome after intra-arterial treatment for acute ischemic stroke?

text: Background and purpose In patients with acute ischemic stroke who receive antiplatelet treatment, uncertainty exists about the effect and safety of intra-arterial treatment. Our aim was to study whether intra-arterial treatment in patients with prior antiplatelet treatment is safe and whether prior antiplatelet treatment modifies treatment effect. Methods All 500 MR CLEAN patients were included. We estimated the effect of intra-arterial treatment with ordinal logistic regression analysis, and tested for interaction of antiplatelet treatment with intra-arterial treatment on outcome. Furthermore, safety parameters and serious adverse events were analyzed. Results The 144 patients (29%) on antiplatelet treatment were older, more often male, and had more vascular comorbidity. Intra-arterial treatment effect size after adjustments in antiplatelet treatment patients was 1.7 (95% confidence interval 0.9-3.2), and in no antiplatelet treatment patients 1.8 (95% confidence interval: 1.2-2.6). There was no statistically or clinically significant interaction between prior antiplatelet treatment and the relative effect of intra-arterial treatment ( p = 0.78). However, in patients on antiplatelet treatment, the effect of successful reperfusion on functional outcome in the intervention arm of the trial was doubled: the absolute risk difference for favorable outcome after successful reperfusion in patients on prior antiplatelet treatment was 39% versus 18% in patients not on prior antiplatelet treatment (Pinteraction = 0.025). Patients on antiplatelet treatment more frequently had a symptomatic intracranial hemorrhage (15%) compared to patients without antiplatelet treatment (4%), without differences between the control and intervention arm. Conclusions Prior treatment with antiplatelet agents did not modify the effect of intra-arterial treatment in patients with acute ischemic stroke presenting with an intracranial large vessel occlusion. There were no safety concerns. In patients with reperfusion, antiplatelet agents may improve functional outcome.


Covid-19 and Namaste.


title: Effect of neck extension on the advancement of tracheal tubes from the nasal cavity to the oropharynx in nasotracheal intubation: a randomized controlled trial.

text: BACKGROUND Clinicians sometimes encounter resistance in advancing a tracheal tube, which is inserted via a nostril, from the nasal cavity into the oropharynx during nasotracheal intubation. The purpose of this study was to investigate the effect of neck extension on the advancement of tracheal tubes from the nasal cavity into the oropharynx during nasotracheal intubation. METHODS Patients were randomized to the 'neck extension group (E group)' or 'neutral position group (N group)' for this randomized controlled trial. After induction of anesthesia, a nasal RAE tube was inserted via a nostril. For the E group, an anesthesiologist advanced the tube from the nasal cavity into the oropharynx with the patient's neck extended. For the N group, an anesthesiologist advanced the tube without neck extension. If the tube was successfully advanced into the oropharynx within two attempts by the same maneuver according to the assigned group, the case was defined as 'success.' We compared the success rate of tube advancement between the two groups. RESULTS Thirty-two patients in the E group and 33 in the N group completed the trial. The success rate of tube passage during the first two attempts was significantly higher in the E group than in the N group (93.8% vs. 60.6%; odds ratio = 9.75, 95% CI = [1.98, 47.94], p = 0.002). CONCLUSION Neck extension during tube advancement from the nasal cavity to the oropharynx before laryngoscopy could be helpful in nasotracheal intubation. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT03377114 , registered on 13 December 2017.


Time for coordinated action in waste management under lockdown challenges.


title: Interferon-λs: special immunomodulatory agents and potential therapeutic targets.

text: Interferon (IFN)-λs are a new addition to the old IFN family and share many similarities, such as antiviral and antiproliferative characteristics, with type I IFNs. IFN-λs also exhibit unique characteristics in immunomodulation. Accumulating studies have indicated the interactions between IFN-λs and immune cells, which lead to the regulation of the latter. IFN-λs can influence dendritic cells (DCs) and their product, IFN-λs-DCs, can then regulate the function of T cells. On the other hand, IFN-λs can also directly affect T cells through inhibition of the T helper 2 cell (Th2) responses. IFN-λs have varying immunomodulatory functions under different physiological conditions or in different organs and can inhibit tumor growth via regulation of the immune system. Diseases associated with IFN-λs include asthma, allergy, and systemic lupus erythematosus. In this review, we summarize the current knowledge of the biology of IFN-λs and their immunomodulatory function in relevant human diseases.


title: Porcine Epidemic Diarrhea Virus 3C-Like Protease Regulates Its Interferon Antagonism by Cleaving NEMO.

text: UNLABELLED Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus causing lethal watery diarrhea in piglets. Since 2010, a PEDV variant has spread rapidly in China, and it emerged in the United States in 2013, posing significant economic and public health concerns. The ability to circumvent the interferon (IFN) antiviral response, as suggested for PEDV, promotes viral survival and regulates pathogenesis of PEDV infections, but the underlying mechanisms remain obscure. Here, we show that PEDV-encoded 3C-like protease, nsp5, is an IFN antagonist that proteolytically cleaves the nuclear transcription factor kappa B (NF-κB) essential modulator (NEMO), an essential adaptor bridging interferon-regulatory factor and NF-κB activation. NEMO is cleaved at glutamine 231 (Q231) by PEDV, and this cleavage impaired the ability of NEMO to activate downstream IFN production and to act as a signaling adaptor of the RIG-I/MDA5 pathway. Mutations specifically disrupting the cysteine protease activity of PEDV nsp5 abrogated NEMO cleavage and the inhibition of IFN induction. Structural analysis suggests that several key residues outside the catalytic sites of PEDV nsp5 probably impact NEMO cleavage by modulating potential interactions of nsp5 with their substrates. These data show that PEDV nsp5 disrupts type I IFN signaling by cleaving NEMO. Previously, we and others demonstrated that NEMO is also cleaved by 3C or 3C-like proteinases of picornavirus and artertivirus. Thus, NEMO probably represents a prime target for 3C or 3C-like proteinases of different viruses. IMPORTANCE The continued emergence and reemergence of porcine epidemic diarrhea virus (PEDV) underscore the importance of studying how this virus manipulates the immune responses of its hosts. During coevolution with its hosts, PEDV has acquired mechanisms to subvert host innate immune responses for its survival advantage. At least two proteins encoded by PEDV have been identified as interferon (IFN) antagonists, papain-like protease (PLP) and N protein. Here, we report that the PEDV nsp5 gene, which encodes the 3C-like protease of PEDV, is another IFN antagonist. Mechanistically, the cysteine protease activity of PEDV nsp5 mediates proteolysis of NEMO, the key adaptor for IFN synthesis, and NEMO is cleaved at glutamine 231 (Q231). The new molecular details and determinants impacting NEMO scission by PEDV nsp5 delineated in this study are fundamental to our understanding of critical virus-host interactions that determine PEDV pathogenesis.


title: The landscape of viral proteomics and its potential to impact human health.

text: INTRODUCTION Advances in mass spectrometry-based proteomic technologies are enhancing studies of viral pathogenesis. Identification and quantification of host and viral proteins and modifications in cells and extracellular fluids during infection provides useful information about pathogenesis, and will be critical for directing clinical interventions and diagnostics. AREAS COVERED Herein we review and discuss a broad range of global proteomic studies conducted during viral infection, including those of cellular responses, protein modifications, virion packaging, and serum proteomics. We focus on viruses that impact human health and focus on experimental designs that reveal disease processes and surrogate markers. Expert commentary: Global proteomics is an important component of systems-level studies that aim to define how the interaction of humans and viruses leads to disease. Viral-community resource centers and strategies from other fields (e.g., cancer) will facilitate data sharing and platform-integration for systems-level analyses, and should provide recommended standards and assays for experimental designs and validation.


title: Clinical Practice Guidelines for the Use of Video Capsule Endoscopy.

text: BACKGROUND & AIMS Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. METHODS A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. RESULTS The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. CONCLUSIONS CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.


title: Features of cerebral oxygenation detects brain injury in premature infants.

text: Babies born prematurely can develop brain injury within days after birth. Early identification of high-risk infants enables appropriate clinical care to mitigate potential lifelong disabilities. Near infra-red spectroscopy is an established technology that can provide continuous measurements of cerebral oxygen saturation (rcSO2) over this critical period. We develop a feature set of the rcSO2 signal for the purpose of detecting brain injury. Our feature set contains amplitude, spectral, and fractal dimension features within 5 frequency bands. Features are combined in a support vector machine (SVM) and performance is assessed within a cross-validation procedure. Using a cohort of 47 infants of <;32 weeks of gestation, we find significant (p <; 0.05) features of amplitude in the frequency band 0.9-3.6 mHz and a fractal dimension measure in the frequency band 1.8-3.6 mHz. The SVM has an area-under the receiver operator characteristic (AUC) of 0.75 with sensitivity-specificity values of 67-77%. These moderate results highlight the potential for quantitative analysis of rcSO2 to detect brain injury and thus enable early identification of high-risk infants.


Long-Term Hemodialysis during the COVID-19 Pandemic.


title: Carotid I's, L's and T's: collaterals shape the outcome of intracranial carotid occlusion in acute ischemic stroke.

text: BACKGROUND Collaterals may affect revascularization, ischemic severity, and clinical outcomes in acute stroke owing to internal carotid artery (ICA) occlusion. OBJECTIVE To examine the hypothesis that morphology of occlusive thrombus and collateral flow patterns may influence the outcome of ICA occlusions after mechanical thrombectomy. METHODS Pooled analyses of ICA occlusions in the MERCI and Multi-MERCI trials employed central angiography review readings to categorize lesions as I, L, or T clots and functional lesions based on collateral flow patterns. Demographic variables, procedural details, and clinical outcomes were compared across ICA lesion types. RESULTS A total of 72 subjects (mean age 67 years (SD 16), 51% female, median National Institutes of Health Stroke Scale 20 (range 8-35)) were included, with 90-day modified Rankin score ≤2 in 28% and 51% mortality. Clots were categorized as an I lesion in 9/72 (12.5%), L lesion in 12/72 (16.7%), and T lesion in 51/72 (70.8%). Based on collateral flow patterns, cases were categorized as having a functional I lesion in 7/72 (9.7%), functional L in 38/72 (52.8%), and functional T in only 27/72 (37.5%). Multivariate analyses showed that a functional T lesion, with insufficient collateral flow to ipsilateral anterior cerebral arteries via the contralateral ICA, was a strong predictor of both revascularization success and subsequent clinical outcomes. CONCLUSIONS Collateral flow patterns distinguish the nature and impact of ICA occlusions on expected revascularization and subsequent clinical outcomes in acute ischemic stroke. The nomenclature of terminal ICA occlusions introduced here (carotid I's, L's, and T's) may enhance future endovascular trials targeting such proximal occlusions. TRIAL REGISTRATION NUMBER NCT00318071 (http://clinicaltrials.gov). MERCI was not registered because enrollment began before July 1, 2005.


title: Understanding the unfavorable result after otoplasty: an integrated approach to correction.

text: The correction of an unfavorable outcome after otoplasty requires a thorough understanding of the anatomy of prominent ear and recognition of the spectrum of secondary deformities and their origin. The goal of this article is to describe the causes of postotoplasty deformity, including both undercorrection and overcorrection. The latter presents the more complicated reconstructive problem, as both skin shortage and permanent cartilage disruption need to be addressed. The authors propose an algorithm for revision otoplasty based on clinical findings and patient concerns. Finally, a case with overcorrection secondary to both skin deficiency and cartilage disruption is illustrated showing the sequential steps needed for optimal correction.


title: An Integrative Review of Nurse-Authored Research to Improve Health Equity and Human Rights for Criminal-Justice-Involved People.

text: BACKGROUND An estimated 10 million people are incarcerated internationally, including 2.1 million people in the United States. Criminal justice involvement is a social determinant of individual and family health disparities. Health care in correctional and forensic psychiatric facilities is nurse driven. The unique contributions of nurse authors to the research literature on health equity and humane conditions for this population have not been aggregated, nor have the nursing research gaps in this area been systematically identified. This article determines the volume and country location of nurse-authored research in this area and analyzes the research by population (prisons, jails, community supervision, forensic psychiatry), clinical foci, and research methods. METHODS We conducted an integrative review of research literature published in English between 1990 and 2017. RESULTS Our search revealed 283 data-based articles written by 349 nurse authors, representing Asia, Australia, Europe, and North and South Americas. Most research occurred in prisons (53.3%) and focused on mental health/substance use (32.5%), infectious disease (21.6%), or correctional health services (15.6%). Almost one third of articles across clinical foci sampled nurses, not patients. IMPLICATIONS Although there is clearly a cadre of nurse researchers working in this area, it remains a relatively small group focused most closely on mental health, infectious disease, and the correctional nursing experience. Gaps and opportunities for important nursing contributions remain, especially in reproductive health, meeting the needs of community-supervised people, and explicitly connecting this work with its human rights implications.


title: Age is not associated with increased surgical complications in patients after laparoscopic sleeve gastrectomy.

text: Introduction Age is considered as a risk factor in bariatric surgery. The observation was made on the basis of results from studies where patients underwent different type of surgery, but laparoscopic sleeve gastrectomy (LSG) was not among them. It is necessary to reevaluate the association of age with adverse events in the group of patients after LSG. Aim To investigate the association of age with surgery-related adverse events in patients after LSG. Material and methods Retrospective analysis of medical data was performed. The study involved 345 patients who underwent LSG in our institution between January 2013 and December 2014. The patients were subdivided by age into four groups according to quartiles. In 30-day follow-up adverse events were evaluated. We considered the presence of the following events as the endpoint of our study: death, medical events and surgical events. Results In general, we observed adverse events in 36 (10.4%) patients. The mortality rate in our study was 0.59%. Nineteen events were surgical and 18 medical. In 1 patient a surgical event was associated with a medical event. Bleeding was the most common surgical event and was observed in 17 (4.9%) cases. Age was not associated with surgical events (OR = 1.032, 95% CI: 0.991-1.075, p = 0.33) or medical events (OR = 0.997, 95% CI: 0.956-1.039, p = 0.89). Conclusions The LSG is a safe bariatric procedure with low mortality. Bleeding is the most frequent surgical complication. Our findings suggest that age is not associated with increased risk of surgical or medical adverse events after LSG.


title: Progression from laparoscopic-assisted to totally laparoscopic distal gastrectomy: comparison of circular stapler (i-DST) and linear stapler (BBT) for intracorporeal anastomosis.

text: BACKGROUND Billroth I (B-I) gastroduodenostomy is an anastomotic procedure that is widely performed after gastric resection for distal gastric cancer. A circular stapler often is used for B-I gastroduodenostomy in open and laparoscopic-assisted distal gastrectomy. Recently, totally laparoscopic distal gastrectomy (TLDG) has been considered less invasive than laparoscopic-assisted gastrectomy, and many institutions performing laparoscopic-assisted distal gastrectomy are trying to progress to TLDG without markedly changing the anastomosis method. The purpose of this report is to introduce the technical details of new methods of intracorporeal gastroduodenostomy using either a circular or linear stapler and to evaluate their technical feasibility and safety. METHODS Seventeen patients who underwent TLDG with the intracorporeal double-stapling technique using a circular stapler (n = 7) or the book-binding technique (BBT) using a linear stapler (n = 10) between February 2010 and April 2011 were enrolled in the study. Clinicopathological data, surgical data, and postoperative outcomes were analyzed. RESULTS There were no intraoperative complications or conversions to open surgery in any of the 17 patients. The usual postoperative complications following gastroduodenostomy, such as anastomotic leakage and stenosis, were not observed. Anastomosis took significantly longer to complete with DST (64 ± 24 min) than with BBT (34 ± 7 min), but more stapler cartridges were needed with BBT than with DST. CONCLUSIONS TLDG using a circular or linear stapler is feasible and safe to perform. DST will enable institutions performing laparoscopic-assisted distal gastrectomy with circular staplers to progress to TLDG without problems, and this progression may be more economical because fewer stapler cartridges are used during surgery. However, if an institution has already been performing δ anastomosis in TLDG but has been experiencing certain issues with δ anastomosis, converting from δ anastomosis to BBT should be beneficial.


title: Faecal virome of cats in an animal shelter.

text: We describe the metagenomics-derived feline enteric virome in the faeces of 25 cats from a single shelter in California. More than 90 % of the recognizable viral reads were related to mammalian viruses and the rest to bacterial viruses. Eight viral families were detected: Astroviridae, Coronaviridae, Parvoviridae, Circoviridae, Herpesviridae, Anelloviridae, Caliciviridae and Picobirnaviridae. Six previously known viruses were also identified: feline coronavirus type 1, felid herpes 1, feline calicivirus, feline norovirus, feline panleukopenia virus and picobirnavirus. Novel species of astroviruses and bocaviruses, and the first genome of a cyclovirus in a feline were characterized. The RNA-dependent RNA polymerase region from four highly divergent partial viral genomes in the order Picornavirales were sequenced. The detection of such a diverse collection of viruses shed within a single shelter suggested that such animals experience robust viral exposures. This study increases our understanding of the viral diversity in cats, facilitating future evaluation of their pathogenic and zoonotic potentials.


Vaccination strategies.


title: Refusal of viral testing during the SARS-CoV-2 pandemic.

text: Widespread testing for the respiratory syndrome coronavirus-2 (SARS-CoV-2) will represent an important part of any strategy designed to safely reopen societies from lockdown. Healthcare settings have the potential to become reservoirs of infectivity, and therefore many hospital trusts are beginning to carry out routine screening of staff and patients. This could promote the effective cohorting of patients and reduce the rate of nosocomial infection. However, for various reasons, some individuals may refuse this testing. Here we highlight this as an emergent ethicolegal issue which we expect to become increasingly relevant as testing becomes ubiquitous. We explore this position from an ethical and legal perspective, determining whether refusal of testing is acceptable under UK law. Individual patients refusing testing could undermine a hospital's testing strategy; therefore clinicians and policy makers must prospectively determine the best course of action if this were to occur.


title: Acute Bacterial Meningitis.

text: PURPOSE OF REVIEW While acute bacterial meningitis is becoming less common in developed countries because of the widespread use of vaccines against Streptococcus pneumoniae, Neisseria meningitides, and Haemophilus influenzae, bacterial meningitis still occurs worldwide, with peak incidence in young children and the elderly. Bacterial meningitis is usually lethal unless appropriate antibiotics that cross the blood-brain barrier are given. Clinical suspicion of bacterial meningitis begins when patients present with the abrupt onset of fever, headache, and meningismus. RECENT FINDINGS New technologies are being developed for more rapid identification of the bacterial species causing meningitis. When appropriate, administration of adjunctive dexamethasone with the antibiotics often lessens neurologic sequelae in survivors, which may include aphasia, ataxia, paresis, hearing loss, and cognitive impairment. SUMMARY Confirmation of the diagnosis of bacterial meningitis comes mainly from examination and culture of CSF obtained from a lumbar puncture. Typically, the CSF shows an elevated neutrophil count, elevated protein, depressed glucose, positive Gram stain, and growth of the bacteria on appropriate culture media. Antibiotic sensitivities of the bacteria determine the appropriate antibiotics, although an educated guess of the best antibiotics to be given promptly must be made until the antibiotic sensitivities return, usually in a few days.


title: Identification of bacterial plant pathogens using multilocus polymerase chain reaction/electrospray ionization-mass spectrometry.

text: Polymerase chain reaction/electrospray ionization-mass spectrometry (PCR/ESI-MS, previously known as "TIGER") utilizes PCR with broad-range primers to amplify products from a wide array of organisms within a taxonomic group, followed by analysis of PCR amplicons using mass spectrometry. Computer analysis of precise masses allows for calculations of base compositions for the broad-range PCR products, which can then be compared to a database for identification. PCR/ESI-MS has the benefits of PCR in sensitivity and high-throughput capacity, but also has the distinct advantage of being able to detect and identify organisms with no prior characterization or sequence data. Existing broad range PCR primers, designed with an emphasis on human pathogens, were tested for their ability to amplify DNA of well characterized phytobacterial strains, as well as to populate the existing PCR/ESI-MS bacterial database with base counts. In a blinded panel study, PCR/ESI-MS successfully identified 93% of unknown bacterial DNAs to the genus level and 73% to the species/subspecies level. Additionally, PCR/ESI-MS was capable of detecting and identifying multiple bacteria within the same sample. The sensitivity of PCR/ESI-MS was consistent with other PCR based assays, and the specificity varied depending on the bacterial species. Preliminary tests with real life samples demonstrate a high potential for using PCR/ESI-MS systems for agricultural diagnostic applications.


title: Advances in Telemedicine in Ophthalmology.

text: Telemedicine is the provision of healthcare-related services from a distance and is poised to move healthcare from the physician's office back into the patient's home. The field of ophthalmology is often at the forefront of technological advances in medicine including telemedicine and the use of artificial intelligence. Multiple studies have demonstrated the reliability of tele-ophthalmology for use in screening and diagnostics and have demonstrated benefits to patients, physicians, as well as payors. There remain obstacles to widespread implementation, but recent legislation and regulation passed due to the devastating COVID-19 pandemic have helped to reduce some of these barriers. This review describes the current status of tele-ophthalmology in the United States including benefits, hurdles, current programs, technology, and developments in artificial intelligence. With ongoing advances patients may benefit from improved detection and earlier treatment of eye diseases, resulting in better care and improved visual outcomes.


title: The future of antivirals: broad-spectrum inhibitors.

text: PURPOSE OF REVIEW Potent antivirals are successfully used for the treatment of infections with herpesviruses, hepatitis B and C viruses, HIV, and with some success for influenza viruses. However, no selective inhibitors are available for a multitude of medically important viruses, most of which are (re-)emerging RNA viruses. As it is impossible to develop drugs against each of these viruses, broad-spectrum antiviral agents (BSAA) are a prime strategy to cope with this challenge. RECENT FINDINGS We propose four categories of antiviral molecules that hold promise as BSAA. Several nucleoside analogues with broad antiviral activity have been described and given the relatively conserved nature of viral polymerases, it may be possible to develop more broad-spectrum nucleoside analogues. A number of viral proteins are relatively conserved between families and may also be interesting targets. Host-targeting antiviral drugs such as modulators of lipid metabolism and cyclophilin inhibitors can be explored as well. Finally, the potent and broad antiviral function of the immune system can be exploited by the development of immune-modulating BSAA. SUMMARY Despite the recent advances, the BSAA field is still in its infancy. Nevertheless, the discovery and development of such molecules will be a key aim of antiviral research in the coming decades.


title: Febrile respiratory illnesses in infancy and atopy are risk factors for persistent asthma and wheeze.

text: Severe viral respiratory illnesses and atopy are risk factors for childhood wheezing and asthma. The aim of this study was to explore associations between severe respiratory infections and atopy in early childhood with wheeze and asthma persisting into later childhood. 147 children at high atopic risk were followed from birth to age 10 yrs. Data on all respiratory infections occurring in infancy were collected prospectively and viral aetiology ascertained. Atopy was measured by skin prick tests at 6 months, and 2 and 5 yrs. History of wheeze and doctor-diagnosed eczema and asthma was collected regularly until 10 yrs of age. At 10 yrs, 60% of the cohort was atopic, 25.9% had current eczema, 18.4% current asthma and 20.4% persistent wheeze. 35.8% experienced at least one lower respiratory infection (LRI) associated with fever and/or wheeze in first year of life. Children who had wheezy or, in particular, febrile LRI in infancy and were atopic by 2 yrs, were significantly more likely to have persistent wheeze (RR 3.51, 95% CI 1.83-6.70; p<0.001) and current asthma (RR 4.92, 95% CI 2.59-9.36; p<0.001) at 10 yrs. Severe viral respiratory infections in infancy and early atopy are risk factors for persistent wheeze and asthma. The strongest marker of the asthmatogenic potential of early life infections was concurrent fever. The occurrence of fever during respiratory illnesses is an important marker of risk for wheeze and asthma later in childhood, suggesting it should be measured in prospective studies of asthma aetiology.


title: A direct endoscopic approach for left-sided infrarenal para-aortic lymphadenectomy immediately after hysterectomy for endometrial cancer treatment: left dome formation (LDF).

text: BACKGROUND Endoscopic surgery for infrarenal para-aortic lymphadenectomy has been widely accepted. Two major approaches, "transperitoneal" and "extraperitoneal", are generally used; however, they have several disadvantages. A "transperitoneal" approach to the left para-aortic region is usually indirect, often performed after wide extension of the right para-aortic region. An "extraperitoneal" approach is unsuitable when a peritoneal tear exists after a prior surgical procedure such as hysterectomy. Here, we propose a modified transperitoneal technique, "Left dome formation (LDF)," which directly provides a surgical field for left infrarenal para-aortic lymphadenectomy even after hysterectomy. METHODS The LDF procedure comprised three processes: (1) setting, (2) dissection of inframesenteric lymph nodes (step 1), and (3) dissection of infrarenal lymph nodes (step 2). SETTING two trocars were added 4 cm bilateral to the low-mid abdominal trocar that was used in prior hysterectomy. Step 1: The posterior layer of the renal fascia along with the left ureter and left ovarian vessel were separated from the left common iliac artery and iliopsoas. Left inframesentric nodes were removed from the surgical field. Step 2: The left ureter was isolated from the posterior renal fascia, and the dome was expanded cranially to the left renal vein, with the ovarian vein always visualizable at the dome ceiling. Left infrarenal nodes were removed. RESULTS We applied LDF to ten endometrial cancer patients, recommended for additional dissection of para-aortic nodes based on intraoperative evaluation using the laparoscopically removed uterus. The operative time and number of removed lymph nodes in Step 1 and Step 2 were 28.8 (20-49) min and 5.3 (2-10) and 54.6 (52-70) min and 6.5 (1-11), respectively. Blood loss was below 50 ml. No serious organ injury occurred during procedures. CONCLUSION Since the left ureter is always observable, LDF procedure facilitates effective surgery to overcome the anatomical complexity of the left para-aortic region and is potentially useful for sentinel node sampling.


Obesity and covid-19: the role of the food industry.


title: Benchmarking the in vitro toxicity and chemical composition of plastic consumer products.

text: Plastics are known sources of chemical exposure and few, prominent plastic-associated chemicals, such as bisphenol A and phthalates, have been thoroughly studied. However, a comprehensive characterization of the complex chemical mixtures present in plastics is missing. In this study, we benchmark plastic consumer products, covering eight major polymer types, according to their toxicological and chemical signatures using in vitro bioassays and non-target high resolution mass spectrometry. Most (74 %) of the 34 plastic extracts contained chemicals triggering at least one endpoint, including baseline toxicity (62 %), oxidative stress (41 %), cytotoxicity (32 %), estrogenicity (12 %) and antiandrogenicity (27 %). In total, we detected 1,411 features, tentatively identified 213, including monomers, additives and non-intentionally added substances, and prioritized 25 chemicals. Extracts of polyvinyl chloride (PVC) and polyurethane (PUR) induced the highest toxicity whereas polyethylene terephthalate (PET) and high-density polyethylene (HDPE) caused no or low toxicity. High baseline toxicity was detected in all "bioplastics" made of polylactic acid (PLA). The toxicities of low-density polyethylene (LDPE), polystyrene (PS) and polypropylene (PP) varied. Our study demonstrates that consumer plastics contain compounds that are toxic in vitro but remain largely unidentified. Since the risk of unknown compounds cannot be assessed, this poses a challenge to manufacturers, public health authorities and researchers alike. However, we also demonstrate that products not inducing toxicity are already on the market.


title: Results of primary stent therapy for femoropopliteal peripheral arterial disease at 7 years.

text: OBJECTIVE Primary stenting is a well-established treatment option for femoropopliteal arterial disease. However, there is a paucity of data concerning the performance of this modality at ≥5 years. This study evaluated the long-term clinical and radiologic outcomes of primary stent therapy in patients with femoropopliteal arterial disease. METHODS A prospective data collection and analysis was conducted in patients undergoing primary stent placement in femoropopliteal lesions between September 2006 and September 2007. The EverFlex (Medtronic/Covidien, Plymouth, Minn) bare-metal stent was used. The primary outcome of this study was the primary patency rate. Secondary outcomes were secondary patency rate, amputation-free-survival (AFS), and freedom from target lesion revascularization (TLR). A Cox regression analysis identified risk factors for the primary and the secondary measure outcomes. RESULTS Included were 89 patients (102 stents). The prevalence of critical limb ischemia was 34% (n = 30). The initial angiography revealed a TransAtlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease C/D lesion in 31 patients (35%). Occlusions were present in 49 patients (55%), and the mean lesion length was 116 ± 33 mm. Popliteal artery disease was present in 39 treated limbs (35%). The primary patency rate at 1, 3, 5, and 7 years was 73%, 64%, 47%, and 33% respectively. At 7 years, secondary patency rate was 67%, freedom from TLR was 47%, and the AFS was 73%. Cox regression analysis revealed a decreased AFS among diabetic patients (hazard ratio [HR], 2.6; 95% confidence interval [CI], 1.08-6.28; P = .03), whereas secondary endovascular interventions showed a protective effect for AFS (HR, 0.14; 95% CI, 0.03-0.65; P = .01). Popliteal artery disease was identified as independent risk factor for secondary interventions (HR, 2.07; 95% CI, 1.05-4.06; P = .04) and TLR (HR, 1.99; 95% CI, 1.03-3.83; P = .04). Critical limb ischemia was associated with an increased incidence of surgical conversion owing to endovascular treatment failure (HR, 5.46; 95% CI, 2.44-12.17; P < .001). CONCLUSIONS This study found primary stenting was associated with acceptable clinical and radiologic long-term outcomes. Diabetes was associated with poor AFS, and popliteal artery involvement correlated with an increased need for reinterventions. AFS was better among patients undergoing secondary procedures.