title: Detection of respiratory viruses and Legionella spp. by real-time polymerase chain reaction in patients with community acquired pneumonia.

text: We conducted a study on throat swabs obtained from a group of hospitalized patients with community acquired pneumonia (CAP). Throat swab specimens from 242 adults admitted to hospital with CAP were tested. In total, 1 or more aetiological agents were identified by real-time PCR in 55 (23%) patients. The most frequently detected pathogens were coronavirus (17%), parainfluenza virus (6%) and influenza virus (4%). Overall, viral pathogens were identified by conventional techniques in 7 (2%) patients, and real-time PCR in 50 (21%) patients (p<0.0001). The diagnostic yield increased from 137 cases (57% of patients using conventional microbiological assays) to 158 cases (65% of patients using real-time PCR assays and conventional microbiological assays; p=0.06). A significantly higher percentage of mortality was present in patients with a mixed bacterial and viral infection. L. pneumophila PCR was positive in only 3 out of 11 cases (27%) of Legionnaires' disease (LD). This study demonstrates that real-time PCR can increase the number of microbiological detections of respiratory pathogens, mainly as a result of detection of respiratory viruses.


title: Complex retrieval of fractured, embedded, and penetrating inferior vena cava filters: a prospective study with histologic and electron microscopic analysis.

text: PURPOSE To evaluate clinical outcomes, characterize adherent tissue, and analyze inferior vena cava (IVC) filter fractures in patients undergoing complex retrieval for management of filter-related complications. To elucidate mechanisms of filter fracture by radiographic and electron microscopic (EM) evaluation. MATERIALS AND METHODS Over 2.5 years, 50 consecutive patients with fractured and/or penetrating filter components were prospectively enrolled into a single-center study. There were 19 men and 31 women (mean age, 42 y; range, 15-73 y). All patients underwent complex filter retrieval after failure of standard methods, and retrieval indications along with resultant clinical outcomes were evaluated. Specimens with adherent tissue underwent histologic analysis, and all fractured components were studied with EM. RESULTS Retrieval was successful in all 50 cases (mean implantation, 815 d; range, 20-2,599 d) among the following filters: G2X (n = 23),G2 (n = 9), Eclipse (n = 3), Recovery (n = 4), ALN (n = 1), Celect (n = 7), OptEase (n = 2), and Simon Nitinol (n = 1). Mean indwell time in fractured filters (n = 31) was 1,082 days, versus 408 days in nonfractured filters (n = 19; P = .00169). Neointimal hyperplasia/fibrosis was seen in 46 of 48 specimens with adherent tissue (96%). Among 61 fractured components from conical filters, 35 had extravascular penetration whereas 26 remained intravascular (11 free-floating in IVC, 15 embolized centrally), and EM revealed fracture modes of high-cycle fatigue (n = 53), overload (n = 6), and indeterminate (n = 2). Following retrieval, previously prescribed lifelong anticoagulation was discontinued in 30 of 31 patients (97%). Filter-related symptoms from IVC occlusion, component embolization, and penetration-induced abdominal pain, duodenal injury, and/or small-bowel volvulus were alleviated in all 26 cases (100%). There were no long-term complications at a mean follow-up of 371 days (range, 67-878 d). CONCLUSIONS The risk of filter fracture increases after 408 days (ie,>1 y) of implantation and is associated with symptomatic extravascular penetration and/or intravascular embolization. Complex methods can be used to safely remove these devices, alleviate filter-related morbidity, and allow cessation of anticoagulation.


title: Forced arterial suction thrombectomy with the penumbra reperfusion catheter in acute basilar artery occlusion: a retrospective comparison study in 2 Korean university hospitals.

text: BACKGROUND AND PURPOSE A performance of forced arterial suction thrombectomy was not reported for the treatment of acute basilar artery occlusion. This study compared revascularization performance between intra-arterial fibrinolytic treatment and forced arterial suction thrombectomy with a Penumbra reperfusion catheter in patients with acute basilar artery occlusion. MATERIALS AND METHODS Fifty-seven patients with acute basilar artery occlusion were treated with intra-arterial fibrinolysis (n = 25) or forced arterial suction thrombectomy (n = 32). Baseline characteristics, successful revascularization rate, and clinical outcomes were compared between the groups. RESULTS Baseline characteristics, the frequency of patients receiving intravenous recombinant tissue plasminogen activator, and mean time interval between symptom onset and femoral puncture did not differ between groups. The forced arterial suction thrombectomy group had a shorter procedure duration (75.5 minutes versus 113.3 minutes, P = .016) and higher successful revascularization rate (88% versus 60%, P = .017) than the fibrinolysis group. Fair outcome, indicated by a modified Rankin Scale 0-3, at 3 months was achieved in 34% of patients undergoing forced arterial suction thrombectomy and 8% of patients undergoing fibrinolysis (P = .019), and the mortality rate was significantly higher in the fibrinolysis group (25% versus 68%, P = .001). Multiple logistic regression analysis identified the forced arterial suction thrombectomy method as an independent predictor of fair outcome with adjustment for age, sex, initial NIHSS score, and the use of intravenous recombinant tissue plasminogen activator (odds ratio, 7.768; 95% CI, 1.246-48.416; P = .028). CONCLUSIONS In acute basilar artery occlusion, forced arterial suction thrombectomy demonstrated a higher revascularization rate and improved clinical outcome compared with traditional intra-arterial fibrinolysis. Further clinical trials with the newer Penumbra catheter are warranted.


title: Navien catheter experience in neuroendovascular interventions.

text: Purpose Advancements in catheter technology have allowed for greater flexibility and trackability. We report 265 consecutive, single-center neurointerventional cases using the Navien guide catheter. Materials and methods Retrospective analysis was performed of consecutive intracranial endovascular procedures utilizing the Navien catheter. Data collected included procedure type, catheters, guide catheter position, cervical access artery tortuosity grade and complications. Results The 5 French catheter was used in 130 cases. The 6 French catheter was used in 135 cases. Access was via the internal carotid artery in 204, external carotid artery in 10, and vertebral artery in 51 cases. Catheter tip position was in the petrous segment of the internal carotid artery in 36.6% (97/265), distal cervical internal carotid artery in 13.9% (37/265), cavernous internal carotid artery in 10.2% (27/265), proximal or mid cervical internal carotid artery in 5.6% (15/265), supraclinoid internal carotid artery in 0.8% (2/265), and intradural vertebral artery in 0.8% (2/265) of cases. Catheter position was not determined in 18.9% (50/265) of cases. Proximal vessel tortuosity (grade B or C) was present in 98 cases (37%), and the catheter was tracked distal to the tortuosity in 93% (91/98) of these cases. The overall success rate without catheter complication was 97% (258/265). The Navien was replaced by another catheter in 1.9% (5/265) of cases. There was one cervical artery dissection (0.4%) and one severe vasospasm (0.4%) necessitating Navien removal. Conclusions The Navien guide catheter provided distal access support for neuroendovascular interventions in nearly all cases, including cases with proximal artery tortuosity, with a low rate of catheter-related complications.


Transcaval retrograde transcatheter aortic valve replacement for patients with no other access: first-in-man experience with CoreValve.


Biosafety in surgical pathology in the era of SARS-Cov2 pandemia. A statement of the Italian Society of Surgical Pathology and Cytology.


title: [EMCAM (Multiple Sclerosis Autonomous Community of Madrid) document for the management of patients with multiple sclerosis during the SARS-CoV-2 pandemic].

text: INTRODUCTION The current SARS-CoV-2 pandemic is forcing neurologists to carry out a series of adaptations in the management of multiple sclerosis. Neurologists must weigh up the need to start or continue disease-modifying treatments against the risk of infection, the risk of complications from the infection, and the risk of multiple sclerosis activity. Since this is an unprecedented situation, most decisions are being made on the basis of a theoretical approach and the criteria of each neurologist. AIMS The aim of this study is conduct a literature search to collect available evidence on the relationship between disease-modifying therapies in multiple sclerosis and SARS-CoV-2 infection. This evidence, together with the experience of the authors in the management of patients with multiple sclerosis during the pandemic, will make it possible to offer some proposals for the treatment and follow-up of patients in this epidemiological context. DEVELOPMENT After the literature search and our experience in the management of patients, a number of proposals for treatment are established for each drug, which must necessarily be individualised for each patient, since, in these exceptional circumstances, their peculiarities can affect the prognosis. CONCLUSIONS The neurologist should be aware of current evidence to assess the risk-benefit of starting, maintaining and stopping disease-modifying therapies in multiple sclerosis during the pandemic.


title: Subcutaneous Ustekinumab Provides Clinical Benefit for Two-Thirds of Patients With Crohn's Disease Refractory to Anti-Tumor Necrosis Factor Agents.

text: BACKGROUND & AIMS Ustekinumab, a human monoclonal antibody against the p40 subunit of interleukins-12 and -23, is effective in inducing and maintaining remission in patients with luminal Crohn's disease (CD). We assessed the efficacy and safety of subcutaneous ustekinumab in patients with anti-tumor necrosis factor (anti-TNF) refractory CD. METHODS We performed a retrospective observational study, collecting data from the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif on 122 consecutive patients with active CD refractory to anti-TNF therapy who received at least 1 subcutaneous injection of ustekinumab from March 2011 to December 2014, in 20 tertiary centers in Europe. Subjects were followed for at least 3 months. The primary outcome was clinical benefit, defined as reductions in symptoms and biochemical markers of CD and complete weaning from steroids, without surgery or immunosuppressant therapies. RESULTS Seventy-nine patients (65%) had a clinical benefit within 3 months of receiving ustekinumab. Concomitant immunosuppressant therapy at study inclusion increased the odds for a clinical benefit from ustekinumab (odds ratio, 5.43; 95% confidence interval, 1.14-25.77; P = .03). Over a median follow-up period of 9.8 months (interquartile range, 5.3-14.5 months), the cumulative probabilities that patients maintained the clinical benefit for 6 and 12 months after introduction of ustekinumab were 93% and 68%, respectively. CONCLUSIONS Almost two-thirds of patients with CD refractory to at least 1 anti-TNF agent receive clinical benefit from ustekinumab therapy, not requiring steroids for up to 12 months afterward. While awaiting results from ongoing trials, ustekinumab can be considered for use in these patients.


title: A critical appraisal of the quality of critical care pharmacotherapy clinical practice guidelines and their strength of recommendations.

text: OBJECTIVE Clinical practice guideline (CPG) quality assessment is important before applying their recommendations. Determining whether recommendation strength is consistent with supporting quality of evidence is also essential. We aimed to determine quality of critical care pharmacotherapy CPGs and to assess whether high quality evidence supports strong pharmacotherapy recommendations. METHODS MEDLINE (1966-February 2008), EMBASE (1980-February 2008), National Guideline Clearinghouse (February 2008) and personal files were searched to identify CPGs. Four appraisers evaluated each guideline using the appraisal of guidelines, research and evaluation (AGREE) instrument. AGREE assesses 23 items in six domains that include scope/purpose, stakeholder involvement, rigor of development, clarity, applicability and editorial independence. Standardized domain scores (0-100%) were determined to decide whether to recommend a guideline for use. One appraiser extracted strong pharmacotherapy recommendations and supporting evidence quality. RESULTS Twenty-four CPGs were included. Standardized domain scores were clarity [69% (95% confidence interval (CI) 62-76%)], scope/purpose [62% (95% CI 55-68%)], rigor of development [51% (95% CI 42-60%)], editorial independence [39% (95% CI 26-52%)], stakeholder involvement [32% (95% CI 26-37%)] and applicability [19% (95% CI 12-26%)]. The proportion of guidelines that could be strongly recommended, recommended with alterations and not recommended was 25, 37.5 and 37.5%, respectively. High quality evidence supported 36% of strong pharmacotherapy recommendations. CONCLUSION Variation in AGREE domain scores explain why one-third of critical care pharmacotherapy CPGs cannot be recommended. Only one-third of strong pharmacotherapy recommendations were supported by high quality evidence. We recommend appraisal of guideline quality and the caliber of supporting evidence prior to applying recommendations.


title: Personal Protective Equipment in the coronavirus pandemic: training with Rapid Cycle Deliberate Practice.

text: OBJECTIVE to discuss the application of Rapid Cycle Deliberate Practice for attire and unattire training in the context of COVID-19 and structure a practical guide to the application at this juncture. METHODS this methodological study described theoretical and practical aspects of the application of a simulation strategy as a technological training tool. An application guide was constructed from the search for evidence from the main health authority bodies in Brazil. RESULTS maximizing time in Deliberate Practice, feedback with evidence and psychological security are the principles of this strategy. The dynamic involves repetition and feedback. The application guide presents the sequence of actions for attire and unattire. FINAL CONSIDERATIONS coping with this pandemic requires appropriate use of personal protective equipment. The authors suggest the Rapid Cycle Deliberate Practice as a technological educational tool for attire/unattire, since it encourages mastery performance.


Dilemmas in resuscitation of COVID-19 patients based on current evidence.


title: Single-incision laparoscopic surgery and conventional laparoscopic treatment of varicocele in adolescents: Comparison between two techniques.

text: BACKGROUND Single-incision laparoscopic surgery (SILS) has gained great popularity in paediatric surgery due to its minimally invasive approach and improved cosmetic results. Notwithstanding, reports describing its adoption in children are still fragmentary and some perplexities have been raised by some surgeons. We reviewed our experience with the SILS Palomo varicocelectomy procedure (SIL-V) in children and adolescents, comparing this group with a similar series operated using conventional laparoscopic varicocelectomy (CL-V). PATIENTS AND METHODS A total of 69 Palomo laparoscopic varicocelectomies were performed in patients aged 11-17 years from January 2011 to January 2013. Indications for surgery included grades II-III varicocele or ipsilateral testicular hypotrophy. The SIL-V procedure was performed in 44 patients with roticulating and conventional 5 mm instruments. Testicular vessels were isolated "en bloc," clipped and cut. Operating time, visual analogue scale and post-operative results were compared to a similar group of 25 patients operated with CL-V. RESULTS No patient of the SIL-V group required conversion to conventional laparoscopy, none to open surgery. Mean operative time was 22 min (range: 19-28) in the SIL-V group, not significantly different compared with CL-V (mean 21 min, range: 18-25). All patients experienced a smooth recovery from surgery without any complications, and were discharged on day 1. No difficulties were found in the SIL-V group. The post-operative pain score was significantly better in SIL-V. CONCLUSION The SIL-V procedure is safe and effective and allows a fast and efficient isolation of the vascular bundle. The use of conventional instruments is technically feasible in SIL-V.


title: UV inactivation and resistance of rotavirus evaluated by integrated cell culture and real-time RT-PCR assay.

text: Rotaviruses are double-stranded RNA viruses which are among the most resistant waterborne enteric viruses to UV disinfection. An integrated cell culture and real-time RT-PCR (ICC real-time RT-PCR) assay was developed to detect the infectivity of rotaviruses in water, which uses real-time RT-PCR to detect RNA produced by infectious rotaviruses during replication in host cells. Detection of rotaviral RNA in host cells provides direct evidence of the presence of infectious rotavirus rather than just the presence of rotavirus RNA. Using this newly developed method, the inactivation and resistance of rotavirus to UV treatments at various doses was evaluated. With an initial concentration of 2 x 10(4)PFU/ml simian rotavirus (SA11), a first-order linear relationship was obtained at UV dose range of 0-120 mJ cm(-2), and the inactivation rate constant was estimated to be 0.0343 cm(2) mJ(-1) (R(2)=0.966). The dose-inactivation curve tailed off and reached plateau as the UV dose increased from 120 to 360 mJ cm(-2), indicating resistance phenomena of sub-populations of SA11 at very high UV doses. A maximal reduction of 4.8 log(10) was observed. Through parallel comparison with traditional culture assay, the ICC real-time RT-PCR method demonstrated more effective, sensitive and faster infectivity detection of rotavirus and, the results reveal that rotaviruses are more resistant to UV irradiation than previously reported with traditional cell culture assays.


title: The impact of route of anesthesia on maternal and fetal ischemia modified albumin levels at cesarean section: a prospective randomized study.

text: OBJECTIVE Ischemia modified albumin has been shown to increase in ischemic situations, and has also been shown to increase in fetal cord blood in deliveries by cesarean section. The aim of this study is to reveal whether anesthesia has an impact on maternal and fetal cord ischemia modified albumin levels. METHODS Seventy two women with uncomplicated term pregnancies were randomized to spinal (n=37) or general anesthesia (n=35) groups. The blood pressure, oxygen saturation, and pulse rate of the patients were recorded during the procedure. Maternal blood samples of ischemia modified albumin (IMA) were taken 10 min from the start of the procedure. The fetal cord blood samples of IMA were taken immediately after birth. RESULTS Maternal (0.99 ± 0.19 vs. 0.80 ± 0.27) and fetal (1.00 ± 0.21 vs. 0.70 ± 0.26) IMA levels were significantly higher in the general anesthesia group. Fetal IMA levels were positively correlated with maternal gravidity (r=0.31; P=0.008), parity (r=0.25; P=0.028), and fetal birth weight (r=0.23, P=0.045). Also, as time from incision to delivery lengthens, fetal IMA levels increase (r=0.29, P=0.012). CONCLUSION Fetal cord ischemia modified albumin levels were higher in the general anesthesia group, therefore, it is proposed that regional anesthesia should be the preferred route of anesthesia for an elective cesarean section, at least until the impact of high fetal cord IMA levels are manifested.


title: Correlation between age and weight loss after bariatric surgery.

text: BACKGROUND Conflicting evidence exists regarding age as a predictive factor in excess weight loss after bariatric surgery. The objective of this cross-sectional study is to evaluate differences in excess BMI loss (%EBMIL) 1 year after surgery in patients older and younger than 45 years. METHODS Adult obese patients fulfilling selection criteria underwent either Roux-en-Y gastric bypass or sleeve gastrectomy and were grouped according to age < and ≥45 years with follow-up at least 1 year. Both groups were compared in terms of excess BMI loss (%EBMIL) and other clinical outcomes. Possible relationship between %EBMIL, age, surgical technique, and presence of comorbidities such as diabetes mellitus, hypertension (HT), and dyslipidemia (DL) was searched. RESULTS Three hundred thirty-seven patients (72.5 % female), 196 (50.1 %) younger than 45 years and 141 (49.9 %) with age ≥45 years. There was significant difference between age group and %EBMIL 12 months after surgery (p < 0.001), showing better results in younger patients. No differences were found in terms of gender, preoperative body mass index (BMI), surgical technique, nor presence of DL. Using multiple regression, we found significant interaction effect between age group (p < 0.001), presence of HT (p = 0.001), and %EBMIL at follow-up. CONCLUSIONS Patients younger than 45 years lose greater amount of excess BMI than older patients after bariatric surgery. This tendency might be useful as a preoperative weight loss predictor in bariatric patients.


title: Patented small molecule inhibitors of p53-MDM2 interaction.

text: The interaction between p53 and murine double minute 2 (MDM2) provides an attractive drug target in oncology. Small molecule inhibitors of this interaction have not only provided strong evidence for blocking the protein-protein interaction, but are also extremely useful as biological probes and ultimately as novel therapeutics. Here, a comprehensive review of the patented small molecule inhibitors of the p53-MDM2 interaction are provided. These inhibitors are divided into eight classes of compounds that include cis-imidazolines, benzodiazepines, fused indoles, substituted piperazines, substituted piperidines, aryl boronic acids, spiro-indoles, and alpha-helix mimetic compounds. The best documented class of compounds, cis-imidazolines (e.g., Nutlins) are selective and potent inhibitors of the p53-MDM2 interaction, and selected examples exhibit potency in the nanomolar range. Nutlins induce apoptosis in p53 wild-type cells and show in vivo efficacy in mice xenograft models. Additional strategies briefly discussed in this review, and which are under current exploration in targeting the p53 pathway, include the inhibition of MDM2-mediated p53 ubiquitylation and restoration of DNA-binding activity of mutant p53 protein using small molecules.


title: Venous thromboembolism prophylaxis in patients undergoing abdominal or pelvic surgery for cancer--a real-world, prospective, observational French study: PRéOBS.

text: INTRODUCTION Data on the epidemiology and prevention of venous thromboembolism in patients undergoing abdominal or pelvic cancer surgery in real practice are limited. The primary objective of this observational study was to describe the thromboprophylactic strategy implemented in routine practice. The main secondary objective was to assess the incidence of outcomes. MATERIALS AND METHODS Patients admitted to public or private hospitals for abdominal or pelvic cancer surgery were included between November 2009 and November 2010; endoscopic route for surgery was the only exclusion criterion. Study outcomes were recorded at hospital discharge and at routine follow-up (generally 9±3weeks). RESULTS 2380 patients (mean±SD age: 66.4±11.6years, women: 36.8%) admitted to hospital for abdominal (47.8%), urological (41%), or gynaecological (11.2%) cancer surgery were included in the analysis. Of these, 2179 had data available at study end. Perioperative antithrombotic prophylaxis, consisting mainly of low-molecular-weight heparin, was given to 99.5% of patients. At hospital discharge, thromboprophylaxis was continued in 91.7% of patients, 57.4% receiving a 4-6week prophylaxis. This management strategy was associated with an overall venous thromboembolic event rate of 1.9%, 34.7% of events occurring after discharge. Incidences of fatal bleeding, bleeding in a critical organ and bleeding necessitating re-intervention were 0.1%, 0.3% and 1.7%, respectively. Overall mortality was 1.5%. CONCLUSIONS Thromboprophylaxis is routinely used in French patients undergoing major cancer surgery. For more than a third of patients, however, treatment duration did not comply with best-practice recommendations, which might explain the non-negligible rate of thromboembolic complications still observed in this patient population.


title: First assessment of interferon gamma release assay results among healthcare workers at a general hospital in China.

text: INTRODUCTION China has a very high tuberculosis (TB) burden. The interferon-gamma release assay (IGRA) is more specific for the diagnosis of latent tuberculosis infection (LTBI) than the tuberculin skin test, especially among populations with a high degree of coverage by the BCG vaccine. OBJECTIVES To evaluate the first screening of healthcare workers (HCW) for LTBI using the IGRA at a general hospital in Beijing. METHODS A pilot screening program for LTBI was triggered by accidental contact between HCW and two patients with active TB in the emergency department (ED). Given the necessity of estimating the overall LTBI prevalence in the institution, a sample of 518 HCW was enrolled in our cross-sectional study. The second IGRA was repeated with 43 of the 121 HCW in the ED after exposure to index TB cases. Data on putative risk factors were collected with a self-administered questionnaire. RESULTS The prevalence of LTBI in the targeted population was 21.8%. Differences in the prevalence of LTBI were significantly related to age, employment duration, and history of occupational exposure. A lack of childhood BCG vaccination was independently associated with the prevalence of LTBI (adjusted OR: 1.686, 95% CI: 1.045-2.723, P = .0325). No new LTBI was diagnosed 12 weeks postexposure. No HCW adopted the preventive treatment for LTBI. CONCLUSIONS Considering the high morbidity of LTBI among HCW even in general hospitals, it is essential to formulate government policies and institutional operation protocols for the systematic screening, registration, and administration of prophylaxes for the control of LTBI.


Saline vs contrast infusion during optical coherence tomography imaging of peripheral percutaneous intervention.


title: Efficacy evaluation of a protocol for safe hip surgery (total hip arthroplasty).

text: OBJECTIVE To propose a multidisciplinary protocol to standardize the care of patients undergoing total hip arthroplasty (THA) and evaluate it effectiveness after implementation. METHODS Retrospective evaluation of 95 consecutive patients undergoing THA divided into two groups, one group of 47 patients operated before the protocol implementation and 48 after. RESULTS Assessing the re-admission rate, among 47 patients evaluated prior to implementation of the protocol, seven (14.9%) were re-admitted, and when observing the 48 patients evaluated after implementation, one (2.1%) was re-admitted, showing statistical significance (p < 0.05). The chance of re-admission before the protocol was eight times the chance of hospitalization after implementation (95% CI: 1.01 to 377.7). By comparing the clinical complications among the groups, it was observed that there was a lower rate of complications following implementation of the protocol (p = 0.006). CONCLUSION The introduction of a multidisciplinary protocol to standardize the management of patients undergoing THA decreased the rates of rehospitalization and clinical complications after the procedure.


title: Regionalization of the stretch reflex in the human vastus medialis.

text: KEY POINTS Regionalization of the stretch reflex, i.e. the notion that the activation of 1a afferents from a muscle region influences only the activation of motor units in the same region, has been demonstrated previously in animals but not in humans. Mechanical stretches applied to regions of vastus medialis as close as 10 mm apart resulted in recruitment of motor units localized topographically with respect to the location of the mechanical stretch. Stretch reflexes are regionalized in the human vastus medialis. The human spinal cord has the neuromuscular circuitry to preferentially activate motoneurones innervating muscle fibres located in different regions of the vastus medialis. ABSTRACT The localization of motor unit territories provides an anatomical basis to suggest that the CNS may have more independence in motor unit recruitment and control strategies than what was previously thought. In this study, we investigated whether the human spinal cord has the neuromuscular circuitry to independently activate motor units located in different regions of the vastus medialis. Mechanical taps were applied to multiple locations in the vastus medialis (VM) in nine healthy individuals. Regional responses within the muscle were observed using a grid of 5 × 13 surface EMG electrodes. The EMG amplitude was quantified for each channel, and a cluster of channels showing the largest activation was identified. The spatial location of the EMG response was quantified as the position of the channels in the cluster. In a subset of three participants, intramuscular recordings were performed simultaneously with the surface EMG recordings. Mechanical taps resulted in localized, discrete responses for each participant. The spatial location of the elicited responses was dependent on the location of the tap (P < 0.001). Recordings with intramuscular electrodes confirmed the regional activation of the VM for different tap locations. Selective stimulation of 1a afferents localized in a region of the VM results in reflex recruitment of motor units in the same region. These findings suggest that the human spinal cord has the neuromuscular circuitry to modulate spatially the motoneuronal output to vastus medialis regions, which is a neuroanatomical prerequisite for regional activation.


title: Superficial dermal melanocytosis of the elderly: an exceptional occurrence?

text: The development of flat pigmented lesions on chronically sun-damaged (CSD) skin of the face may represent the clinical manifestation of a wide variety of hyperplastic/neoplastic melanocytic proliferations. We report the exceptional case of an acquired pigmented patch occurring on CSD skin, histopathologically characterized by diffuse hyperplasia of dendritic/spindled melanocytes in the superficial dermis within a widened band of actinic elastosis. This lesion was associated with a small focus of early invasive lentigo maligna melanoma (LMM). We demonstrate the melanocytic nature of the population of dermal pigmented cells by means of single and double immunohistochemical staining for melanocytic and histiocytic markers. The biologic significance of the focus of LMM within the hyperpigmented lesion (whether random collision phenomenon or causally related occurrence), as well as the pathogenesis of the whole dermal lesion are difficult to elucidate. Our case emphasizes the need for a better understanding of the pathophysiology of so-called dermal melanocytes.


title: SILS: Is It Cost- and Time-Effective Compared to Standard Pediatric Laparoscopic Surgery?

text: The aim of the study was to review our experience with single-incision laparoscopic surgery (SILS) and to compare costs and operative time to standard laparoscopic surgery (SLS). A prospectively collected database of operative times and costs was analysed for the years 2008-2011. SILS cases were compared to standard laparoscopy on a procedure-matched basis. Patient demographics, on-table time and consumable costs were collated. Descriptive statistics and Mann-Whitney U-test were utilized with SPSS for windows. Analysis of the data demonstrate that neither consumable costs nor operative time were significantly different in each group. Comparing operative costs, SILS appendicectomy, nephrectomy/heminephrectomy, and ovarian cystectomy/oophorectomy showed cost benefit over SLS (£397 versus £467; £942 versus £1127; £394 versus £495). A trend toward higher cost for SILS Palomo procedure is noted (£734 versus £400). Operative time for SILS appendicectomy, nephrectomy/heminephrectomy, and Palomo was lower compared to SLS (60 versus 103 minutes[mins.]; 130 versus 60 mins.; 60 versus 80 mins.). In conclusion, SILS appears to be cost-effective for the common pediatric surgical operations. There is no significant difference in operating time in this series, but small sample size is a limiting factor. Studies with larger numbers will be necessary to validate these initial observations.


title: Alterations in gut hormones after laparoscopic sleeve gastrectomy: a prospective clinical and laboratory investigational study.

text: OBJECTIVE To evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on fasting and meal-stimulated release of the gut hormones ghrelin, pancreatic polypeptide (PP), peptide-YY (PYY), glucagon-like peptide-1 (GLP-1), and amylin and of the adipocytokine leptin. BACKGROUND Mounting evidence suggests that the mechanisms of weight loss and the improvement in glucose metabolism seen after LSG are related not only to gastric restriction but also to neurohormonal changes. METHODS : Fasting and postprandial levels at 60 and 120 minutes after a standard test meal of the above peptides and glucose metabolism indices were evaluated in 15 consecutive morbidly obese (MO) subjects before and 6 and 12 months after LSG. As study controls, 15 lean subjects matched for age and sex were also assessed. RESULTS Body mass index values notably decreased at 6 and 12 months (P < 0.01), postoperatively. In addition, an overall improvement of the glycemic profile of MO patients was noted. After LSG, markedly decreased fasting and postprandial levels of ghrelin, amylin, and leptin were observed. A significant postprandial increase of PYY and GLP-1 levels was also noted postoperatively. Interestingly, significantly increased levels of PP were noted only at 60 minutes postprandially after LSG. CONCLUSIONS LSG markedly improved glucose homeostasis and generated significant changes in ghrelin, PP, PYY, GLP-1, amylin, and leptin levels. These multiple hormonal actions may have several beneficial effects on the underlying mechanism of weight loss, demonstrating that LSG could be more than just a restrictive bariatric operation.


title: Dose-dependent reversal of KCC2 hypofunction and phenobarbital-resistant neonatal seizures by ANA12.

text: Neonatal seizures have an incidence of 3.5 per 1000 newborns; while hypoxic-ischemic encephalopathy (HIE) accounts for 50-60% of cases, half are resistant to 1st-line anti-seizure drugs such as phenobarbital (PB). Tyrosine receptor kinase B (TrkB) activation following ischemic injury is known to increase neuronal excitability by downregulation of K-Cl co-transporter 2 (KCC2); a neuronal chloride (Cl-) co-transporter. In this study, three graded doses of ANA12, a small-molecule selective TrkB antagonist, were tested in CD1 mice at P7 and P10 following induction of neonatal ischemia by a unilateral carotid ligation. The PB loading dose remained the same in all treatment groups at both ages. Evaluation criteria for the anti-seizure efficacy of ANA12 were: (1) quantitative electroencephalographic (EEG) seizure burden and power, (2) rescue of post-ischemic KCC2 and pKCC2-S940 downregulation and (3) reversal of TrkB pathway activation following ischemia. ANA12 significantly rescued PB resistant seizures in a dose-dependent manner at P7 and improved PB efficacy at P10. Additionally, female pups responded better to lower doses of ANA12 compared to males. ANA12 significantly reversed post-ischemic KCC2 downregulation and TrkB pathway activation at P7 when PB alone was inefficacious. Rescuing KCC2 hypofunction may be critical for preventing emergence of refractory seizures.


title: Evaluation of a Safety Awareness Group Program for Adults With Intellectual Disability.

text: Using a participatory research approach, we enlisted 12 U.S. Centers for Independent Living (CILs) to recruit and enroll 170 adults with intellectual disability (ID) to be randomized to either The Safety Class, an abuse prevention group program, or usual care. Participants were asked to complete pre, post, and 3-month follow-up questionnaires. CIL staff members facilitated the eight-session, interactive program. Quantitative and qualitative findings suggest that participation in a brief safety program may improve safety protective factors among men and women with ID. The Safety Class serves as one model for delivering an abuse prevention and education intervention to adults with significant safety needs but extremely limited access to relevant community resources.


Coinfection of SARS-CoV-2 and multiple respiratory pathogens in children.


title: Strengthening Local Food Systems in Times of Concomitant Global Crises: Reflections From Chile.

text: The COVID-19 pandemic is superimposed on the existing challenges of obesity, undernutrition, and climate change. Currently, Chile is still facing the worst drought on record, which will continue to negatively affect agriculture. In Chile, COVID-19 also comes on top of a social crisis that began on October 18, 2019, and was driven by the cumulative effects of an economic system established by former dictator Augusto Pinochet that deregulated markets and privatized social security.1 As of March 26, 2020, Chile, already in a state of catastrophe, had reached 1300 confirmed cases of COVID-19, which catalyzed a total lockdown for the counties with the greatest concentration of cases. As in the rest of the world, in Chile COVID-19 has affected the national food system-which has been observed but mostly not yet documented. (Am J Public Health. Published online ahead of print May 14, 2020: e1-e3. doi:10.2105/AJPH.2020.305711).


title: Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients.

text: RATIONALE Measured at intensive care unit admission (ICU), the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) for severe acute kidney injury (AKI) is unclear. OBJECTIVES To assess the ability of plasma and urine NGAL to predict severe AKI in adult critically ill patients. METHODS Prospective-cohort study consisting of 632 consecutive patients. MEASUREMENTS AND MAIN RESULTS Samples were analyzed by Triage immunoassay for NGAL expression. The primary outcome measure was occurrence of AKI based on Risk-Injury-Failure (RIFLE) classification during the first week of ICU stay. A total of 171 (27%) patients developed AKI. Of these 67, 48, and 56 were classified as RIFLE R, I, and F, respectively. Plasma and urine NGAL values at ICU admission were significantly related to AKI severity. The areas under the receiver operating characteristic curves for plasma and urine NGAL were for RIFLE R (0.77 ± 0.05 and 0.80 ± 0.04, respectively), RIFLE I (0.80 ± 0.06 and 0.85 ± 0.04, respectively), and RIFLE F (0.86 ± 0.06 and 0.88 ± 0.04, respectively) and comparable with those of admission estimated glomerular filtration rate (eGFR) (0.84 ± 0.04, 0.87 ± 0.04, and 0.92 ± 0.04, respectively). Plasma and urine NGAL significantly contributed to the accuracy of the "most efficient clinical model" with the best four variables including eGFR, improving the area under the curve for RIFLE F prediction to 0.96 ± 0.02 and 0.95 ± 0.01. Serial NGAL measurements did not provide additional information for the prediction of RIFLE F. CONCLUSIONS NGAL measured at ICU admission predicts the development of severe AKI similarly to serum creatinine-derived eGFR. However, NGAL adds significant accuracy to this prediction in combination with eGFR alone or with other clinical parameters and has an interesting predictive value in patients with normal serum creatinine.


title: The roles of transportation and transportation hubs in the propagation of influenza and coronaviruses: a systematic review.

text: BACKGROUND Respiratory viruses spread in humans across wide geographical areas in short periods of time, resulting in high levels of morbidity and mortality. We undertook a systematic review to assess the evidence that air, ground and sea mass transportation systems or hubs are associated with propagating influenza and coronaviruses. METHODS Healthcare databases and sources of grey literature were searched using pre-defined criteria between April and June 2014. Two reviewers screened all identified records against the protocol, undertook risk of bias assessments and extracted data using a piloted form. Results were analysed using a narrative synthesis. RESULTS Forty-one studies met the eligibility criteria. Risk of bias was high in the observational studies, moderate to high in the reviews and moderate to low in the modelling studies. In-flight influenza transmission was identified substantively on five flights with up to four confirmed and six suspected secondary cases per affected flight. Five studies highlighted the role of air travel in accelerating influenza spread to new areas. Influenza outbreaks aboard cruise ships affect 2-7% of passengers. Influenza transmission events have been observed aboard ground transport vehicles. High heterogeneity between studies and the inability to exclude other sources of infection means that the risk of influenza transmission from an index case to other passengers cannot be accurately quantified. A paucity of evidence was identified describing severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus transmission events associated with transportation systems or hubs. CONCLUSION Air transportation appears important in accelerating and amplifying influenza propagation. Transmission occurs aboard aeroplanes, at the destination and possibly at airports. Control measures to prevent influenza transmission on cruise ships are needed to reduce morbidity and mortality. There is no recent evidence of sea transport accelerating influenza or coronavirus spread to new areas. Further investigation is required regarding the roles of ground transportation systems and transport hubs in pandemic situations.


title: Laparoscopic pylorus-preserving pancreatic head resection and hybrid open reconstruction via pancreatogastrostomy.

text: INTRODUCTION Laparoscopic pancreatic surgery is ambitious and should only be performed in institutions with expert knowledge in pancreatic surgery. METHODS Whereas pancreatic tail resection is routinely and safely performed in several institutions, the laparoscopic resection of the pancreatic head is only performed by a handful of surgeons. RESULTS In this article, we present our hybrid approach with complete laparoscopic pylorus-preserving pancreatic head resection and successive reconstruction via a small retrieval incision, which might combine the advantages of the laparoscopic resection with the safety of an open and routine pancreatic anastomosis.


title: Incidence of mortality due to rebound toxicity after 'treat and release' practices in prehospital opioid overdose care: a systematic review.

text: INTRODUCTION Death due to opioid overdose was declared a public health crisis in Canada in 2015. Traditionally, patients who have overdosed on opioids that are managed by emergency medical services (EMS) are treated with the opioid antagonist naloxone, provided ventilatory support and subsequently transported to hospital. However, certain EMS agencies have permitted patients who have been reversed from opioid overdose to refuse transport, if the patient exhibits capacity to do so. Evidence on the safety of this practice is limited. Therefore, our intent was to examine the available literature to determine mortality and serious adverse events within 48 hours of EMS treat and release due to suspected rebound opioid toxicity after naloxone administration. METHODS A systematic search was performed on 11 May 2017 in PubMed, Cochrane Central, Embase and CINHAL. Studies that reported on the outcome of patients treated with prehospital naloxone and released at the scene were included. Analyses for incidence of mortality and adverse events at the scene were conducted. Risk of bias and assessment of publication bias was also done. RESULTS 1401 records were screened after duplicate removal. Eighteen full-text studies were reviewed with seven selected for inclusion. None were found to be high risk of bias. In most studies, heroin was the source of the overdose. Mortality within 48 hours was infrequent with only four deaths among 4912 patients ﴾0.081%﴿ in the seven studies. Only one study reported on adverse events and found no incidence of adverse events from their sample of 71 released patients. CONCLUSION Mortality or serious adverse events due to suspected rebound toxicity in patients released on scene post-EMS treatment with naloxone were rare. However, studies involving longer-acting opioids were rare and no study involved fentanyl.


title: KLF5 is involved in regulation of IFITM1, 2, and 3 genes during H5N1 virus infection in A549 cells.

text: The interferon-induced transmembrane (IFITM) proteins usually protect cells from many virus infections by viral entry and replication. Thus, the present study aimed to identification novel regulation factors of IFITM genes. Our data showed up-regulation of IFITM1, IFITM2, and IFITM3 genes in A549 by H5N1 virus infection. However, IFITM1 was not affected, IFITM2 and IFITM3 increases expression following different concentration H5N1 virus infection in HEK293T cells. This is the first time to find differences of IFITM1 transcription in different cells with the H5N1 virus infection. Moreover, experiments showed that H5N1 virus promotes expression of KLF4 and KLF5 in both A549 and HEK293T cells, but H5N1 virus NS1, M1, NP or PB2 alone has no obvious effect on transcription of KLF5. Overexpression of KLF5 increases transcription of IFITM1, IFITM2, and IFITM3 in A549 cells, however, it does not affect transcription of IFITM1, IFITM2, and IFITM3 in HEK293T cells. In addition, results for the first time displayed that KLF4 can up-regulate expression of IFITM5 in both A549 and HEK293T cells. In conclusion, we revealed KLF5 is involved in transcription of IFITM1, 2, and 3 thus making it a potential therapeutic activator in the future to treat viral infections through promoting the innate immune response.


Maintaining stereotactic radiosurgical treatments during Covid-19 outbreak: the case of the Gamma Knife Unit in Brescia - Italy.


Learning the lessons from 1000 robot-assisted radical prostatectomy procedures.


title: Viral Acute Respiratory Illnesses in Young Infants Increase the Risk of Respiratory Readmission.

text: BACKGROUND Respiratory viruses cause acute respiratory illness (ARI) in early childhood, but their effect on subsequent ARI admissions is not fully understood. This study aimed to determine the association between initial ARI admission because of viruses including human rhinovirus (HRV), respiratory syncytial virus (RSV), human adenovirus (HAdV) and human metapneumovirus (hMPV) and the risk of ARI readmission in children. METHODS Clinical information and nasopharyngeal swab samples were collected from children <2 years old at their initial ARI admission in Nha Trang, Vietnam, from January 2007 to April 2012. The incidence of ARI readmission during the follow-up period (initial admission to 5 years of age) was compared between children with and without 1 of 13 respiratory viruses (influenza virus A, influenza virus B, RSV, hMPV, parainfluenza virus-1, parainfluenza virus-2, parainfluenza virus-3 and parainfluenza virus-4, HRV, human coronavirus-229E, human coronavirus-OC43, HAdV and human bocavirus) at initial admission. RESULTS A total of 1941 children were enrolled in the study. Viruses were detected in 1254 (64.6%) children at enrollment; HRV, RSV, HAdV and hMPV were detected in 499 (25.7%), 439 (22.6%), 156 (8.0%) and 47 (2.4%) children, respectively. During the follow-up period (4572.7 person-years), 277 children were readmitted with ARI. Virus-related ARI initial admission was associated with an increased risk of ARI readmission for children who were initially admitted before 6 months of age (adjusted rate ratio, 1.6; 95% confidence interval: 1.1-2.5). HAdV (4.6; 1.8-11.9), hMPV (20.4; 6.2-66.9) and HRV (1.6; 1.0-2.4) were independently associated with the outcome. These associations were not observed for children whose initial admission occurred after 6 months of age. CONCLUSIONS HAdV-, hMPV- and HRV-related initial ARI admissions, when occurring during early infancy, increased the risk of subsequent ARI-related readmission.


title: Phase I trial of 90Y-DOTATOC therapy in children and young adults with refractory solid tumors that express somatostatin receptors.

text: UNLABELLED The purpose of this study was to conduct a phase I trial of (90)Y-DOTATOC to determine the dose-toxicity profile in children and young adults with somatostatin receptor-positive tumors. METHODS A 3 × 3 design was used to determine the highest tolerable dose of (90)Y-DOTATOC, with administered activities of 1.11, 1.48, and 1.85 GBq/m(2)/cycle given in 3 cycles at 6-wk intervals. An amino acid infusion was coadministered with the radiopharmaceutical for renal protection. Eligibility criteria included an age of 2-25 y, progressive disease, a positive lesion on (111)In-diethylenetriaminepentaacetic acid-D-Phe(1)-octreotide scanning, a glomerular filtration rate of 80 mL/min/1.73 m(2) or more, bone marrow cellularity of 40% or more or stored autologous hematopoietic stem cells, 60% or more on the Lansky Play Scale, and informed consent. RESULTS Seventeen subjects (age, 2-24 y) received at least 1 dose of (90)Y-DOTATOC; diagnoses included neuroblastoma, embryonal and astrocytic brain tumors, paraganglioma, multiple endocrine neoplasia IIB, and neuroendocrine tumors. No dose-limiting toxicities and no individual dose reductions due to renal or hematologic toxicity were noted. No complete responses were observed; 2 subjects experienced partial response, 5 had minor responses, 6 experienced stable disease, 2 had progressive disease, and 2 withdrew. CONCLUSION Peptide receptor radionuclide therapy with (90)Y-DOTATOC is safe in children and young adults and demonstrated a 12% partial response plus 29% minor response rate in patients with somatostatin receptor-positive tumors. No dose-limiting toxicities were observed. The recommended phase II dosing is 3 cycles of 1.85 GBq/m(2)/dose of (90)Y-DOTATOC coadministered with amino acids.


title: Advanced esophageal cancer in patients who underwent radiofrequency ablation for barrett esophagus with high-grade dysplasia.

text: OBJECTIVE We sought to evaluate clinicopathologic features of patients who underwent esophageal surgery after radiofrequency ablation (RFA) treatment using the HALO system for Barrett esophagus (BE) with high-grade dysplasia (HGD). METHODS We evaluated patients from our hospital database who underwent esophagectomy from August 2006 to January 2012 after previously receiving RFA for BE. Information on demographics, time between RFA and surgery, indications for surgery, and final esophageal pathology was collected. RESULTS In our study, we selected 102 patients who underwent esophagectomy. Five patients had a history of RFA for BE with HGD. Three patients were referred because of persistent HGD despite RFA, and all three patients had HGD in the esophagectomy specimen. Two patients presented with a benign diagnosis (esophageal perforation and leiomyoma), and both of these patients had pathologic stage T3N2M0 adenocarcinoma of the esophagus in the resected specimen. One of these patients had normal mucosa overlying carcinoma in the muscularis propria and adventitia. The patients with stage T3N2M0 cancer did not have pre-RFA endoscopic ultrasound, first treatment of RFA with HALO, or surveillance endoscopic biopsy every 3 months. CONCLUSIONS Radiofrequency ablation for BE with HGD may mask underlying esophageal cancer. Patients who are counseled to undergo RFA for HGD should be aware that RFA could lead to delayed diagnosis and delayed treatment of invasive esophageal cancer without careful patient selection, appropriate RFA use, and close surveillance.


title: Optimal care and design of the tracheal cuff in the critically ill patient.

text: Despite the increasing use of non-invasive ventilation and high-flow nasal-oxygen therapy, intubation is still performed in a large proportion of critically ill patients. The aim of this narrative review is to discuss recent data on long-term intubation-related complications, such as microaspiration, and tracheal ischemic lesions. These complications are common in critically ill patients, and are associated with substantial morbidity and mortality. Recent data suggest beneficial effects of tapered cuffed tracheal tubes in reducing aspiration. However, clinical data are needed in critically ill patients to confirm this hypothesis. Polyurethane-cuffed tracheal tubes and continuous control of cuff pressure could be beneficial in preventing microaspiration and ventilator-associated pneumonia (VAP). However, large multicenter studies are needed before recommending their routine use. Cuff pressure should be maintained between 20 and 30 cmH2O to prevent intubation-related complications. Tracheal ischemia could be prevented by manual or continuous control of cuff pressure.


title: Role of Changes in State of Bound Water and Tissue Stiffness in Development of Age-Related Diseases.

text: An essential effect of environmental stiffness on biological processes in cells at present is generally accepted. An increase in arterial stiffness with advanced age has been reported in many publications. The aim of the present review is to summarize current information about possible chemical reactions and physical processes that lead to tissue stiffening and result in age-related diseases in order to find methods that can prevent or retard time-dependent tissue stiffening. The analysis of published data shows that bound water acts as a plasticizer of biological tissues, a decrease in bound water content results in an increase in biological tissue stiffness, and increased tissue stiffness leads to NF-kB activation and triggered actin polymerization-NF-kB activation is associated with age-related diseases. It can be suggested that changes in bound water content through changing tissue stiffness can affect cellular processes and the development of pathologies related to aging. Both age-related diseases and COVID-19 may be associated with tight-junction disruption and increased tissue stiffness and permeability.


title: In-vitro examination of the biocompatibility of fibroblast cell lines on alloplastic meshes and sterilized polyester mosquito mesh.

text: INTRODUCTION The use of alloplastic implants for tissue strengthening when treating hernias is an established therapy worldwide. Despite the high incidence of hernias in Africa and Asia, the implantation of costly mesh netting is not financially feasible. Because of that various investigative groups have examined the use of sterilized mosquito netting. The animal experiments as well as the clinical trials have both shown equivalent short- and long-term results. The goal of this paper is the comparison of biocompatibility of human fibroblasts on the established commercially available nets and on sterilized polyester mosquito mesh over a period of 12 weeks. MATERIALS AND METHODS Three commercially available plastic mesh types and a gas-sterilized mosquito polyethylenterephtalate (polyester) mesh were examined. Human fibroblasts from subcutaneous healthy tissue were used. Various tests for evaluating the growth behavior and the cell morphology of human fibroblasts were conducted. The semi-quantitative (light microscopy) and qualitative (scanning electron microscopy) analyses were performed after 1 week and then again after 12 weeks. The cell proliferation and cytotoxicity of the implants were investigated with the help of the 5'-bromo-2'-deoxyuridine (BrdU)-cell proliferation test and the LDH-cytotoxicity test. The number of live cells per ml was determined with the Bürker counting chamber. In addition, analyses were made of the cell metabolism (oxidative stress) by measuring the pH value, hydrogen peroxide, and glycolysis. RESULTS After 12 weeks, a proliferation of fibroblasts on all mesh is documented. No mesh showed a complete apoptosis of the cells. This qualitative observation could be confirmed quantitatively in a biochemical assay by marking the proliferating cells with BrdU. The biochemical analysis brought the proof that the materials used, including the polyester of the mosquito mesh, are not cytotoxic for the fibroblasts. The vitality of the cells was between 94 and 98%. The glucose metabolism as well as the pH value of the fibroblasts showed no significant differences between the tested meshes. The examination of the oxidative stress via measurement of the H2O2 concentration showed values in the normal range for the commercially alloplastic meshes and the mosquito mesh. CONCLUSIONS Our examination showed no significant difference with regard to biocompatibility between the officially approved and cost-intensive meshes and the sterilized (autoclaved) mosquito mesh. Due to the proven strength and stability of the mosquito mesh and their proven compatibility, the implantation of the sterilized mosquito mesh in additional in vivo studies must be considered. A wide-scale and cost-effective treatment of hernias could thus be guaranteed, not only in Third World countries.


title: A survey of rodent-borne pathogens carried by wild-caught Norway rats: a potential threat to laboratory rodent colonies.

text: Unintentional infection of laboratory rodents can compromise scientific research as well as the health of the animals and animal handlers. The source of contamination often is unknown, but may be introduced by wild rats from surrounding environments. To determine whether rats in Baltimore, Maryland, USA carry infectious agents commonly found in laboratory rodent colonies, we live-trapped 162 rats during 2005 to 2006 and screened them for a panel of viruses, bacteria and parasites. Antibodies against rat coronavirus/sialodacryoadenitis virus (91.7%), Mycoplasma pulmonis (72.9%), cilia-associated respiratory bacillus (52.1%), rat parvovirus/rat minute virus (29.2%), Kilham rat virus (10.4%), Toolan's H-1 virus (10.4%), Sendai virus (4.2%) and Theiler's mouse encephalomyelitis virus (4.2%), were detected in wild-caught Norway rats. Antibodies against reovirus and pneumonia virus of mice were not detected in wild Norway rats. Endoparasites, including Nippostrongylus braziliensis (71.6%), Rodentolepis nana or Hymenolepis diminuta (34.4%), Hetarakis spumosa (24.1%) and Trichuris muris (14.8%), as well as ectoparasites (14.8%), were identified in wild-caught rats. The risk of pathogen transmission from wild-caught rats to laboratory colonies needs to be mitigated by minimizing exposures rather than assuming wild animals represent a minimal hazard.


title: Single-incision laparoscopic inguinal herniorraphy with telescopic extraperitoneal dissection: technical aspects and potential benefits.

text: INTRODUCTION Our recent prospective randomized controlled trial (NCT01660048) comparing single-incision laparoscopic (SIL) totally extraperitoneal (TEP) and multi-incision inguinal herniorraphy confirmed safety, efficacy and benefits of single-incision approach. This study (NCT01883115) aimed to assess safety, efficacy and cost effectiveness of telescopic extraperitoneal dissection. METHODS Patients with inguinal/femoral hernias from February 2013 to February 2014 undergoing SILTEP herniorraphy with telescopic dissection were compared with patients who had previously undergone SILTEP herniorraphy with balloon dissection. Costs of different ports/trocars were analysed. RESULTS There were 102 patients in telescopic compared to 51 in balloon dissection group; these had no significant differences in age, sex, body mass index, American Society of Anesthesiologists and pre-op visual analogue scores. Telescopic vs. balloon showed: post-operative pain-day one 2.5 vs. 2.5; p = 0.90, day seven 0 vs. 0; p = 0.02 (0 vs. 1; p < 0.01 for bilateral hernias); operation times-unilateral 48.0 vs. 48.0 min; p = 0.88 and bilateral 70.0 vs. 65.0 min; p = 0.66, length of hospital stay 1.0 vs. 1.0 day, analgesic intake (dextropropoxyphene) 6.0 vs. 6.0 tablets; p = 0.95, return to work/normal physical activities 7.0 vs. 7.0 days; p = 0.46 and cosmetic scar scores 24.0 vs. 24.0, respectively. There was no conversion to open surgery/need for additional ports in either group. Median scar length for telescopic group was 13.0 mm. Costs of disposable ports/trocars for telescopic and balloon groups were US$480 and $720, respectively. There were no morbidities/recurrences with follow-up of 2-36 months. CONCLUSIONS Telescopic extraperitoneal dissection during SILTEP inguinal herniorraphy represents a safe and efficient alternative with potential cost savings compared to balloon dissection.


title: Management of hospital wastewaters: the case of the effluent of a large hospital situated in a small town.

text: Hospitals are the main source of pharmaceutical compounds (PhCs) released into the environment. Generally, their discharges are co-treated with domestic wastewaters, resulting in a decrement of the recalcitrant compound concentrations in the final effluent due to water dilution. However, as many PhCs resist normal treatments, pollutant load does not change. This paper compares the chemical characteristics of hospital and domestic wastewaters on the basis of an experimental investigation for macro-pollutants and literature data for PhCs. A membrane biological reactor pilot plant fed by a hospital effluent is tested in order to evaluate the feasibility of treating these kinds of wastewaters with membrane systems. The paper then presents the possible scenarios in the management of the effluent of a large hospital situated in a small town. In particular, it reports on a case study of designing a (new) treatment plant for the effluent of the 900 bed hospital in Ferrara, Northern Italy, located on the outskirts of the town. Finally, costs for the intervention are given.


title: Indirect skin sign of COVID-19 days: striae rubrae.

text: During COVID-19 pandemic, an increase was observed in stress-related dermatological diseases and COVID-19 related rash, while a significant decrease was observed in cosmetological outpatient applications. However, one month after the COVID-19 outbreak began, we observed a rapid increase especially individuals under 20 years of age diagnosed with stria rubrae in dermatology outpatient clinics. The number of patients diagnosed with striae rubrae was four times higher than last month (0.1% vs 0.4%). In order to prevent the rapid spread of the COVID-19 epidemic, the closure of schools, the transition to online education and the curfew imposed under the age of 20 caused a change in lifestyle and diet in young people. The incidence of striae rubrae due to rapid weight gain increased. If not heeded, COVID-19 pandemic can cause striae rubrae pandemic.


title: Genome engineering.

text: For more than 50 years, those engineering genetic material have pursued increasingly challenging targets. During that time, the tools and resources available to the genetic engineer have grown to encompass new extremes of both scale and precision, opening up new opportunities in genome engineering. Today, our capacity to generate larger de novo assemblies of DNA is increasing at a rapid pace (with concomitant decreases in manufacturing cost). We are also witnessing potent demonstrations of the power of merging randomness and selection with engineering approaches targeting large numbers of specific sites within genomes. These developments promise genetic engineering with unprecedented levels of design originality and offer new avenues to expand both our understanding of the biological world and the diversity of applications for societal benefit.


title: Olfactory Dysfunction in COVID-19 Patients: Prevalence and Prognosis for Recovering Sense of Smell.

text: While olfactory dysfunction associated with coronavirus disease 2019 (COVID-19) has attracted considerable interest, few studies have tracked outcomes at serial time points or beyond 2 weeks. Furthermore, data are conflicting regarding whether COVID-19 severity correlates with degree of olfactory dysfunction. This prospective case-control study analyzed prevalence and severity of subjective loss of smell in outpatients (n = 23) and inpatients (n = 20) with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vs healthy controls (n = 25). Olfactory dysfunction was reported more commonly in COVID-19 patients than in healthy controls (P < .001), and outpatients paradoxically reported loss of smell more commonly than inpatients (P = .02). Headaches were present in 52% of patients with olfactory dysfunction. Anosmia or hyposmia persisted beyond 5 days but most of the patients recovered by 30 days, suggesting favorable prognosis for olfaction. Differences between inpatients and outpatients are potentially reflective of timeline of olfactory symptoms and contextual factors, underscoring the importance of corroborative objective testing, coupled with careful tracking of temporal relationships.


title: Chronic rhinosinusitis: pathogenesis, therapy options, and more.

text: INTRODUCTION When rhinosinusitis - the inflammation of the nasal cavity and paranasal sinuses - persists for over 12 weeks, it is termed 'chronic rhinosinusitis' (CRS). Both innate and adaptive immunity contribute to the heterogeneous inflammatory pathogenesis of CRS, which is driven by genetic and environmental factors and the microbiome. CRS is classified by the presence of polyps. Molecular mechanisms in CRS with nasal polyps are similar to those in atopic diseases. AREAS COVERED This review focuses on the immune pathogenesis of CRS, differences between the two CRS subtypes, and latest treatments that may aid in the provision of personalized medicine. EXPERT OPINION Basic research in the last decade has helped significantly in enhancing our knowledge of the pathophysiologic processes of CRS, due to which there is now a better understanding of the associated natural history, physiopathology, novel treatments, and prevention strategies. Treatment success depends on the clarification of the underlying pathogenesis and disease-contributing factors. The exploration of disease endotypes and introduction of novel agents are important advancements. Prior studies performed without disease-endotyping resulted in the inefficiency of certain drugs and insignificant results. The identification of biomarkers, development of personalized approaches, and utilization of disease algorithms are required for CRS therapy success.


title: Persistent Smell Loss Following Undetectable SARS-CoV-2.

text: The association of smell and taste loss with COVID-19 has been well demonstrated with high prevalence rates. In certain cases, chemosensory loss may be the only symptom of COVID-19 and may linger while other symptoms have resolved. The significance of persistent smell and taste loss and its relationship to ongoing viral shedding has yet to be investigated. In this cross-sectional study, of the 316 laboratory test-confirmed COVID-19 cases at our institution, 46 had subsequent test-based confirmation of viral clearance with 2 consecutive negative RT-PCR test results (reverse transcriptase polymerase chain reaction). Olfactory dysfunction was reported by 50% of the patients (23 of 46), with 78% (18 of 23) having subjective persistent smell loss despite negative RT-PCR test results. These preliminary data demonstrate the persistence of self-reported smell loss despite otherwise clinical resolution and undetectable nasal viral RNA.


title: The Trevo XP 3×20 mm retriever ('Baby Trevo') for the treatment of distal intracranial occlusions.

text: OBJECTIVE To report our single-center initial experience using the Trevo XP ProVue Retriever 3×20 mm ('Baby Trevo') for distal intracranial occlusions. METHODS We performed a retrospective review of our interventional database for consecutive patients who underwent treatment for acute ischemic stroke with the Baby Trevo device between February and December 2014. RESULTS Of 134 patients treated during the study period, 8 underwent treatment with the Baby Trevo for distal occlusions. Their mean age was 51±20 years, 5 (62.5%) were male, mean baseline National Institutes of Health Stroke Scale was 19±5. The mean interval between the time the patient was last-known normal to groin puncture was 527±285 min, and the overall procedural length was 110±26 min. Intra-arterial tissue plasminogen activator was used in 5 (62.5%) cases. The device was used for a total of 10 branches: five middle cerebral artery (four superior M3 and one inferior M3), three anterior cerebral arteries (two pericallosal and one callosomarginal), and two posterior cerebral arteries (one P2 and one P3) occlusions. All patients achieved complete recanalization of the artery targeted by the Baby Trevo (arterial occlusive lesion 3). Good capillary reperfusion (TICI 2b-3) was noted in 6 (75%) cases. One pass was performed in 7 vessels and 2 passes in three branches. Vasospasm was noted in 5 (62.5%) of the vessels and fully responded to intra-arterial vasodilator infusion. Follow-up MRI revealed no infarct within the territory vascularized by the artery targeted by the Baby Trevo in 4 cases, partial infarct in 5, and complete infarct in 1. Two patients had parenchymal hematomas (one PH1 and one PH2). No vessel perforations, dissections, or subarachnoid hemorrhage were noted. CONCLUSIONS Our initial data suggest that treatment of distal cerebrovascular occlusions with the Trevo XP 3×20 mm Retriever is feasible. Although this device emerges as a promising technology for small and tortuous distal intracranial vessels, larger studies are still necessary to establish its safety and clinical benefit.


Tuberculosis: progress and challenges in product development and delivery.


Is extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest superior compared with conventional resuscitation?


title: Exploitation of reverse vaccinology and immunoinformatics as promising platform for genome-wide screening of new effective vaccine candidates against Plasmodium falciparum.

text: BACKGROUND In the current scenario, designing of world-wide effective malaria vaccine against Plasmodium falciparum remain challenging despite the significant progress has been made in last few decades. Conventional vaccinology (isolate, inactivate and inject) approaches are time consuming, laborious and expensive; therefore, the use of computational vaccinology tools are imperative, which can facilitate the design of new and promising vaccine candidates. RESULTS In current investigation, initially 5548 proteins of P. falciparum genome were carefully chosen for the incidence of signal peptide/ anchor using SignalP4.0 tool that resulted into 640 surface linked proteins (SLP). Out of these SLP, only 17 were predicted to contain GPI-anchors using PredGPI tool in which further 5 proteins were considered as malarial antigenic adhesins by MAAP and VaxiJen programs, respectively. In the subsequent step, T cell epitopes of 5 genome derived predicted antigenic adhesins (GDPAA) and 5 randomly selected known malarial adhesins (RSKMA) were analysed employing MHC class I and II tools of IEDB analysis resource. Finally, VaxiJen scored T cell epitopes from each antigen were considered for prediction of population coverage (PPC) analysis in the world-wide population including malaria endemic regions. The validation of the present in silico strategy was carried out by comparing the PPC of combined (MHC class I and II) predicted epitope ensemble among GDPAA (99.97%), RSKMA (99.90%) and experimentally known epitopes (EKE) of P. falciparum (97.72%) pertaining to world-wide human population. CONCLUSIONS The present study systematically screened 5 potential protective antigens from P. falciparum genome using bioinformatics tools. Interestingly, these GDPAA, RSKMA and EKE of P. falciparum epitope ensembles forecasted to contain highly promiscuous T cell epitopes, which are potentially effective for most of the world-wide human population with malaria endemic regions. Therefore, these epitope ensembles could be considered in near future for novel and significantly effective vaccine candidate against malaria.


title: Porcine Deltacoronavirus Accessory Protein NS6 Antagonizes Interferon Beta Production by Interfering with the Binding of RIG-I/MDA5 to Double-Stranded RNA.

text: Porcine deltacoronavirus (PDCoV) has recently emerged as an enteric pathogen that can cause serious vomiting and diarrhea in suckling piglets. The first outbreak of PDCoV occurred in the United States in 2014 and was followed by reports of PDCoV in South Korea, China, Thailand, Lao People's Democratic Republic, and Vietnam, leading to economic losses for pig farms and posing a considerable threat to the swine industry worldwide. Our previous studies have shown that PDCoV encodes three accessory proteins, NS6, NS7, and NS7a, but the functions of these proteins in viral replication, pathogenesis, and immune regulation remain unclear. Here, we found that ectopic expression of accessory protein NS6 significantly inhibits Sendai virus-induced interferon beta (IFN-β) production as well as the activation of transcription factors IRF3 and NF-κB. Interestingly, NS6 does not impede the IFN-β promoter activation mediated via key molecules in the RIG-I-like receptor (RLR) signaling pathway, specifically RIG-I, MDA5, and their downstream molecules MAVS, TBK1, IKKε, and IRF3. Further analyses revealed that NS6 is not an RNA-binding protein; however, it interacts with RIG-I/MDA5. This interaction attenuates the binding of double-stranded RNA by RIG-I/MDA5, resulting in the reduction of RLR-mediated IFN-β production. Taken together, our results demonstrate that ectopic expression of NS6 antagonizes IFN-β production by interfering with the binding of RIG-I/MDA5 to double-stranded RNA, revealing a new strategy employed by PDCoV accessory proteins to counteract the host innate antiviral immune response.IMPORTANCE Coronavirus accessory proteins are species specific, and they perform multiple functions in viral pathogenicity and immunity, such as acting as IFN antagonists and cell death inducers. Our previous studies have shown that PDCoV encodes three accessory proteins. Here, we demonstrated for the first time that PDCoV accessory protein NS6 antagonizes IFN-β production by interacting with RIG-I and MDA5 to impede their association with double-stranded RNA. This is an efficient strategy of antagonizing type I IFN production by disrupting the binding of host pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs). These findings deepen our understanding of the function of accessory protein NS6, and they may direct us toward novel therapeutic targets and lead to the development of more effective vaccines against PDCoV infection.


title: Oral care and pulmonary infection - the importance of plaque scoring.

text: Improving the quality of oral hygiene is recognised as an important counter measure for reducing the incidence of ventilator-associated pneumonia amongst critically ill patients. Toothbrushing physically disrupts the dental plaque that acts as a reservoir for pulmonary infection and therefore has the potential to reduce the incidence of ventilator-associated pneumonia. Gu and colleagues performed a systematic review and meta-analysis of oral hygiene with and without a toothbrush and found no difference in the incidence of pneumonia in mechanically ventilated patients. The diagnosis of ventilator-associated pneumonia is prone to bias and future studies of oral care interventions should focus on measures of oral cleanliness such as plaque and gingival scores. Once the optimal strategy for oral hygiene is defined in the critically ill, larger studies focussing on ventilator-associated pneumonia or mortality can be conducted.


title: The host immune dynamics of pneumococcal colonization: implications for novel vaccine development.

text: The human nasopharynx (NP) microbiota is complex and diverse and Streptococcus pneumoniae (pneumococcus) is a frequent member. In the first few years of life, children experience maturation of their immune system thereby conferring homeostatic balance in which pneumococci are typically rendered as harmless colonizers in the upper respiratory environment. Pneumococcal carriage declines in many children before they acquire capsular-specific antibodies, suggesting a capsule antibody-independent mechanism of natural protection against pneumococcal carriage in early childhood. A child's immune system in the first few years of life is Th2-skewed so as to avoid inflammation-induced immunopathology. Understanding Th1/Th2 and Th17 ontogeny in early life and how adjuvant vaccine formulations shift the balance of T helper-cell differentiation, may facilitate the development of new protein-based pneumococcal vaccines. This article will discuss the immune dynamics of pneumococcal colonization in infants. The discussion aims to benefit the design and improvement of protein subunit-based next-generation pneumococcal vaccines.


title: Impact of the defect size, the mesh overlap and the fixation depth on ventral hernia repairs: a combined experimental and numerical approach.

text: BACKGROUND Ventral hernia repairs (VHRs) still exhibit clinical complications in terms of recurrence, pain, and discomfort. Factors such as surgical technique or mesh features are thought to be highly influent. The aim was to evaluate the impact of the defect size, the mesh overlap and the fixation depth on VHR using both physical and numerical models. METHODS The physical model was developed to mimic a passive abdominal wall. Healthy, damaged, and repaired configurations were evaluated using a spherical plunger. The associated numerical (Finite Elements) model was first loaded by a plunger for validation. A parametric study was then conducted with the numerical model loaded by a uniform pressure. Two defect sizes (3.5 × 5 cm and 8.25 × 12 cm elliptic shape), two overlaps (2 and 5 cm), and two fixation depths (peritoneum or muscle) were investigated for both passive and active abdominal walls. RESULTS With the physical model, the repaired configuration was 22 % stiffer than the damaged configuration. The statistical analysis of the parametric study showed that the defect size was the most influential parameter regarding the stress in the mesh, the bulging and the pull-out force at the fixation points. The overlap was influential in terms of stress in the mesh. The fixation depth was not influential. These trends increased with the abdominal wall activity. CONCLUSION Increase of the defect size and decrease of the overlap affected significantly the VHR mechanical performances. Such numerical models could help to better understand the behavior of the repaired abdominal wall and finally to reduce the clinical complications.


title: Coronavirus Disease 2019 and Transplantation: a view from the inside.

text: Since December 2019, world healthcare community faced with Coronavirus Disease 2019 (COVID-19) outbreak caused by SARS-CoV-2. Due to the high viral contagiousness and the possible transmission during the pre-symptomatic phase, COVID-19 progressively spread to several countries. Currently, Italy is the third Country for number of confirmed cases after mainland China and South Chorea, and the first western nation with a well-established deceased transplant program to tackle a COVID-19 outbreak1 .


Corrigendum: Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction.


Intraoperative airway obstruction from a whole dissection of the inner wall of a reinforced endotracheal tube.


title: The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities.

text: The pulmonary endothelium is a dynamic, metabolically active layer of squamous endothelial cells ideally placed to mediate key processes involved in lung homoeostasis. Many of these are disrupted in acute respiratory distress syndrome (ARDS), a syndrome with appreciable mortality and no effective pharmacotherapy. In this review, we consider the role of the pulmonary endothelium as a key modulator and orchestrator of ARDS, highlighting advances in our understanding of endothelial pathobiology and their implications for the development of endothelial-targeted therapeutics including cell-based therapies. We also discuss mechanisms to facilitate the translation of preclinical data into effective therapies including the application of biomarkers to phenotype patients with ARDS with a predominance of endothelial injury and emerging biotechnologies that could enhance delivery, discovery and testing of lung endothelial-specific therapeutics.


title: Gasless robotic perineal radical prostatectomy: An initial experience.

text: Radical prostatectomy (RP) is the gold standard treatment method of localized prostate cancer. Today, this surgery is performed with open or minimally invasive methods. The history of open perineal RP (RPP) is very old, but it is not often preferred by urologists. The use of robot-assisted laparoscopic RP (RALP) is very frequently applied today. Robotic perineal RP (r-RPP) by using a Gel-Point and insufflating CO2 into the perineal region was first described in 2014. In this case report, we report a 68-year-old patient with localized prostate cancer in whom we successfully performed gasless r-RPP, and according to our knowledge, this is the first case of gasless r-RPP to be reported.


title: [Noninvasive Respiratory Support for Novel Coronavirus Pneumonia: Enough is Enough].

text: 新型冠状病毒易导致急性呼吸窘迫综合征(ARDS)，已对生命安全构成极大的威胁。无创呼吸辅助治疗是新型冠状病毒肺炎引起ARDS的常规治疗手段，但在新型冠状病毒肺炎治疗中，往往存在过度使用无创呼吸功能支持治疗而导致气管插管延迟进而影响患者的临床预后，因此，了解无创通气使用的指征和禁忌，早期识别无创通气治疗失败的危险因素，适时终止无创通气转为有创通气是目前临床医师治疗新型冠状病毒肺炎亟需关注的问题。.


title: Virus infection cycle events coupled to RNA replication.

text: Replication, the process by which the genetic material of a virus is copied to generate multiple progeny genomes, is the central part of the virus infection cycle. For an infection to be productive, it is essential that this process is coordinated with other aspects of the cycle, such as translation of the viral genome, encapsidation, and movement of the genome between cells. In the case of positive-strand RNA viruses, this represents a particular challenge, as the infecting genome must not only be replicated but also serve as an mRNA for the production of the replication-associated proteins. In recent years, it has become apparent that in positive-strand RNA plant viruses all the aspects of the infection cycle are intertwined. This article reviews the current state of knowledge regarding replication-associated events in such viruses.


Is Sensitivity the Key Measure to Predict Acute Liver Failure in Drug-Induced Liver Injury Patients?


Isolationist Policies Threaten Public Health.


title: Nonneoplastic and neoplastic Barrett's esophagus: the European perspective.

text: The cancer risk of nondysplastic Barrett's esophagus is very low (0.33-0.5 per year). Therefore, any endoscopic ablation technique is an overtreatment. Patients with low-grade intraepithelial neoplasia confirmed by a specialized GI pathologist seem to have a significant risk for developing high-grade intraepithelial neoplasia (HGIN) or cancer. Therefore, endoscopic treatment in this case seems to be justified. However, up to now there has been no prospective study supporting this. In recent years, endoscopic treatment of HGIN and mucosal Barrett's cancer has become a widely accepted treatment approach and even the therapy of choice in many countries. Endoscopic resection (ER) is the best validated treatment method in patients with HGIN and mucosal Barrett's cancer, and is widely used all over the world. In contrast to ablative treatment methods like argon plasma coagulation and radiofrequency ablation, ER allows histological assessment of the resected specimen in order to assess the depth of infiltration of the tumor. However, ER of the neoplastic lesions should always be followed by ablation of the nondysplastic remaining Barrett's esophagus in order to reduce the risk of recurrence or metachronous neoplasia. The long-time complete remission rate with this two-step strategy is ≥95%. A matter of continuing debate is whether patients with Barrett's cancer infiltrating the upper third of the mucosal layer (pT1sm1) can be treated by ER. Data from our and other centers indicate that a subgroup of patients with pT1sm1 adenocarcinomas without the presence of risk factors (poor differentiation grade, lymph or blood vessel infiltration, size >20 mm, ulcerated lesion) have a very low risk for lymph node metastasis (<2%) and endoscopic therapy can be an alternative to radical surgery.


title: Fingolimod treatment abrogates chikungunya virus-induced arthralgia.

text: Chikungunya virus (CHIKV) is one of the many rheumatic arthropod-borne alphaviruses responsible for debilitating joint inflammation in humans. Despite the severity in many endemic regions, clinically approved intervention targeting the virus remains unavailable. CD4+ T cells have been shown to mediate CHIKV-induced joint inflammation in mice. We demonstrate here that transfer of splenic CD4+ T cells from virus-infected C57BL/6 mice into virus-infected T cell receptor-deficient (TCR-/-) mice recapitulated severe joint pathology including inflammation, vascular leakages, subcutaneous edema, and skeletal muscle necrosis. Proteome-wide screening identified dominant CD4+ T cell epitopes in nsP1 and E2 viral antigens. Transfer of nsP1- or E2-specific primary CD4+ T cell lines into CHIKV-infected TCR-/- recipients led to severe joint inflammation and vascular leakage. This pathogenic role of virus-specific CD4+ T cells in CHIKV infections led to the assessment of clinically approved T cell-suppressive drugs for disease intervention. Although drugs targeting interleukin-2 pathway were ineffective, treatment with fingolimod, an agonist of sphingosine 1-phosphate receptor, successfully abrogated joint pathology in CHIKV-infected animals by blocking the migration of CD4+ T cells into the joints without any effect on viral replication. These results set the stage for further clinical evaluation of fingolimod in the treatment of CHIKV-induced joint pathologies.


Techniques used in lung metastasectomy.


title: Measles vaccination: Threat from related veterinary viruses and need for continued vaccination post measles eradication.

text: Measles virus (MV) is the only human virus within the morbillivirus genus of the Paramyxoviridae. The veterinary members are canine distemper virus (CDV), peste des petits ruminants virus (PPRV), Rinderpest Virus (RPV) as well as the marine morbilliviruses phocine distemper virus (PDV), dolphin morbillivirus (DMV) and porpoise morbillivirus (PMV). Morbilliviruses have a severe impact on humans and animal species. They confer diseases which have contributed to morbidity and mortality of the population on a global scale. There is substantial evidence from both natural and experimental infections that morbilliviruses can readily cross species barriers. Of most concern with regard to zoonosis is the more recently reported fatal infection of primates in Japan and China with strains of CDV which have adapted to this host. The close genetic relationship, shared cell entry receptors and similar pathogenesis between the morbilliviruses highlights the potential consequences of complete withdrawal of MV vaccination after eradication. Therefore, it would be prudent to continue the current MV vaccination. Ultimately development of novel, safe vaccines which have higher efficacy against the veterinary morbilliviruses is a priority. These would to protect the human population long term against the threat of zoonosis by these veterinary viruses.


title: Long-term recurrence and complication rates after incisional hernia repair with the open onlay technique.

text: BACKGROUND Incisional hernia after abdominal surgery is a well-known complication. Controversy still exists with respect to the choice of hernia repair technique. The objective of this study was to evaluate the long-term recurrence rate as well as surgical complications in a consecutive group of patients undergoing open repair using an onlay mesh technique. METHODS Consecutive patients undergoing open incisional hernia repair with onlay-technique between 01/05/1995 and 01/09/2007 at a single institution were included in the study. For follow-up patients were contacted by telephone, and answered a questionnaire containing questions related to the primary operation, the hernia and general risk factors. Patients were examined by a consultant surgeon in the outpatient clinic or in the patient's home if there was suspicion of an incisional hernia recurrence. RESULTS The study included 56 patients with 100% follow-up. The median follow-up was 35 months (range 4-151). Recurrent incisional hernia was found in 8 of 56 patients (15%, 95% CI: 6-24). The overall complication rate was 13% (95% CI, 4-22). All complications were minor and needed no hospital admission. CONCLUSION This study with a long follow-up showed low recurrence and complication rates in patients undergoing incisional hernia repair with the open onlay technique.


title: Comparison of simultaneous dual-isotope multipinhole SPECT with rotational SPECT in a group of patients with coronary artery disease.

text: UNLABELLED A triple-detector, multipinhole SPECT system was optimally configured to perform simultaneous (201)Tl (stress)/(99m)Tc (rest) myocardial perfusion imaging (MPI) using a protocol that permitted direct diagnostic comparison of this multipinhole SPECT system with conventional rotational SPECT. METHODS Both the rotational and the multipinhole SPECT systems used the same model gamma-detectors. The 2 systems were applied in tandem to study 26 patients with documented coronary status. Visual image evaluation of the MPI together with quantitative analysis using circumferential profile curves (CPC) were used for interpretation of stress/rest myocardial flow differences. A dual-peak attenuation compensation (DPAC) technique was applied to the stress (201)Tl multipinhole SPECT images by weighted combination of the images from the upper and lower peaks. RESULTS Detection of myocardial infarction by location and extent correlated closely, and correlation of differential flow changes between stress and rest indicated similar accuracy in terms of location and extent of myocardial blood flow differences as well. In addition, the application of DPAC clarified the multipinhole stress (201)Tl images through reduced background and increased statistics and also improved the relative superposition of the normalized CPC, especially for the inferior and more basal reconstructed regions. CONCLUSION The prototype 3-detector multipinhole SPECT system achieved diagnostic results comparable to those for rotational SPECT and required only a single image-acquisition session to generate stress/rest MPI and 16-segment poststress gated studies. This reduction in acquisition time significantly improves productivity without compromising diagnostic accuracy. In addition, DPAC is a useful adjunct to the multipinhole SPECT modality because it improves both the visual clarity of the stress images and the stress/rest quantitative comparability.


title: Progression of kidney injury and cardiac remodeling in obese spontaneously hypertensive rats: the role of renal sympathetic innervation.

text: BACKGROUND Hypertension and metabolic syndrome (MetS) are associated with increased sympathetic activation possibly contributing to the progression of renal damage and cardiac remodeling. Renal sympathetic denervation (RDN) decreases sympathetic renal efferent and afferent nerve activity. METHODS Obese spontaneously hypertensive rats (SHRs-ob) were subjected to RDN at the age of 34 weeks (SHRs-ob + RDN) and were compared with sham-operated SHRs-ob and their normotensive lean controls (Ctrs). Blood pressure was measured by telemetry. Kidney and heart function were determined by magnetic resonance imaging (MRI). Renal and cardiac remodeling were characterized by immunohistochemical analyses. Animals were killed at the age of 48 weeks. RESULTS In SHRs-ob, RDN attenuated the progressive increase in blood pressure and preserved a mean blood pressure of 156±7mm Hg compared with 220±8mm Hg in sham-operated SHRs-ob at 100 days after RDN, whereas heart rate, body weight, and metabolic parameters remained unchanged. Renal catecholamine and tyrosine hydroxylase levels were significantly reduced after RDN, suggesting effective renal denervation. Progression of renal dysfunction as characterized by increased urinary albumin/creatinine ratio and reduced glomerular filtration rate were attenuated by RDN. In SHRs-ob, renal perfusion was significantly reduced and normalized by RDN. Cardiac fibrosis and cardiac diastolic dysfunction measured by MRI and invasive pressure measurements were significantly attenuated by RDN. CONCLUSIONS In SHRs-ob, progressive increase in blood pressure and progression of renal injury and cardiac remodelling are mediated by renal sympathetic activation as they were attenuated by RDN.


title: Stereotactic radiosurgery for central nervous system hemangioblastoma: systematic review and meta-analysis.

text: Hemangioblastomas are rare, benign, vascular tumors of the central nervous system (CNS), often associated with von-hippel lindau (VHL) disease. Current therapeutic options include microsurgical resection or stereotactic radiosurgery (SRS). With no randomized controlled studies and minimal data beyond single-institution reviews, the optimal management approach for patients with CNS hemangioblastomas is unclear. We completed a Pubmed/SCOPUS literature search from January 1990 to January 2017 for eligible studies on SRS for CNS hemangioblastomas. Relevant articles were identified and reviewed in accordance to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. 26 studies met eligibility criteria for qualitative synthesis, representing 596 subjects and 1535 tumors. The Gamma Knife was the most published SRS method for CNS hemangioblastomas. After critical study appraisal for intra-study bias, 14 studies were used for quantitative meta-analysis of 5-year progression free survival (PFS). The pooled 5-year PFS across all eligible studies was 88.4%. No difference was observed between spine versus intracranial studies. Individual patient data (IPD) was extracted from 14 studies, representing 322 tumors. Univariate analysis of IPD revealed that VHL patients were younger, and had smaller tumors compared to those with sporadic disease. Adverse events were associated with increasing marginal dose, independent of tumor volume. VHL status, sex, radiosurgical method, tumor location, and tumor volume were not found to be significantly associated with tumor progression. Multiple studies show excellent tumor control at 5-year follow up, however, the long-term efficacy of SRS for CNS hemangioblastomas still needs to be investigated, and the studies exploring the role of SRS for early treatment of asymptomatic lesions is wanting.


title: First documentation of persistent SARS-CoV-2 infection presenting with late acute severe myocarditis.

text: A 64 year-old man presented with severe myocarditis 6 weeks after an initial almost asymptomatic SARS-CoV2 infection. He was found to have a persistent positive swab. Mechanisms explaining myocardial injury in patients with COVID-19 remains unclear, but this case suggests that severe acute myocarditis can develop in the late phase of COVID-19 infection, even after a symptom-free interval.


title: Response to Covid-19: An ethical imperative to build a resilient health system in India.

text: China reported cases of a severe form of pneumonia in December 2019 from Wuhan city, Hubei province. The virus causing this illness was identified as the novel Coronavirus 2019, which has now been christened Covid-19. The illness is characterised by fever, cough, body pain and in a few cases, progression to acute respiratory distress syndrome (ARDS) which marks very serious damage to the lungs (1-4). Apart from Wuhan, China, the virus has spread to 26 other countries as on February 18, 2020. Of these 26 countries, the cases of Covid-19 have been exported directly from China in 23 of them. As on February 23, 2020, a total of 78,811 confirmed cases, 2445 deaths have been reported globally. The World Health Organization declared this as a Public Health Emergency of International Concern (PHEIC) on January 30, 2020 (5).


title: Gaussian position weighted center of gravity algorithm for multiplexed readout.

text: Readout signal multiplexing is a commonly used method to reduce the electronics cost in PET systems, and calculation of the scintillation coordinates typically is done by using a Center of Gravity (CoG) technique due to its simplicity and ease of implementation. This comes with a drawback, since CoG has a non-linear response at the periphery of the detector due to the lack of weights beyond the detector. Detectors with multiplexed readout that are based on finely segmented scintillators and coarsely segmented photosensors are known to suffer from the so called edge effect where a pile-up of the reconstructed coordinates from the edge crystals is observed. This may lead to incorrect assignment of the events to crystal pixels and result in formation of erroneous lines of response causing a degradation of spatial resolution and reduction of image contrast. To overcome abovementioned limitations in gamma ray detectors with multiplexed photosensor readout, we propose to use modified Gaussian Position Weighted Center of Gravity technique for calculation of gamma ray interaction position. Here the proposed method is applied to PET detectors with 24×24 LYSO crystals read out by 8 × 8 SiPM array with 64:16 row/column multiplexing. Furthermore, we compared the modified Gaussian Position Weighted Center of Gravity (PW-CoG) and Truncated Center of Gravity (TCoG) coordinate reconstruction methods. It was observed that both algorithms resolve peaks corresponding to events registered in the crystal pixels on the periphery of the crystal array, however peak-to-valley ratios and crystal resolvability metrics for PW-CoG algorithm are generally greater.