title: Does the use of monopolar energy as the preferred mode of dissection effectively reduce seroma formation in laparoscopic total extra peritoneal hernioplasty? A prospective double-blinded randomized control trial.

text: INTRODUCTION Seroma is a commonly encountered sequela after hernia repair. Tremendous effort has been spent to investigate the effective way to prevent this "complication" including the modification of surgical technique, use of per-peritoneal drainage, etc. There were debates about the use of monopolar diathermy versus blunt dissection in laparoscopic TEP in the prevention of seroma formation. This randomized study aims to compare the effects of using 2 techniques in laparoscopic TEP on pre-peritoneal drain output and seroma formation. METHOD From 1.9.2018 to 30.9.2019, all male and female patients presented with the first occurrence, unilateral inguinal hernia anticipated for laparoscopic TEP were enrolled into the study after informed consent. Patients were randomized into "monopolar dissection preferred" (MDP) group and "blunt dissection-preferred" (BDP) group just before commencing of operation after general anesthesia. Surgeons were instructed to use monopolar energy as main dissection method for the whole operation if possible (MDP), whereas blunt dissection is the preferred choice in BDP group, but the use of monopolar energy was allowed if needed. Total energy time was measured by a specially designed homemade device attaching to the monopolar pedals as accurate as to millisecond (ms). Pre-peritoneal drains were inserted for drainage and removed 23 h after operation. Drainage output, total operating time, energy time, clinical and ultrasonic seroma sizes at day 1, day 6, 1-month post operations, recurrence are compared between 2 groups. RESULTS A total of 103 patients where included. There was no significant difference in age, gender, co-morbidities, side of hernia, mean defect size, operating time, fixation adjuncts, or postoperative stay. The drain volume in BDP group is 71.13 ± 31.42 mL while it in MDP group is 56.36 ± 21.46 mL. The MDP group had significantly fewer drain output at 23 h post operation (p = 0.007) and lower seroma incidence on days 6 (p = 0.036). Overall incidence of seroma formation was 12% on postoperative day 1, 11% on postoperative day 7. No statistically differences in postoperative pain score or complications were observed at the first week, 1- and 3-months' post operation. There was no correlation with energy time to the drain output. No recurrence was found in subsequent follow-up. CONCLUSION Pre-peritoneal drainage is clinically safe in laparoscopic totally extra-peritoneal hernioplasty and can effectively reduce the size and incidence of seroma. The seroma formation can be further reduced by appropriate use of monopolar energy as preferred dissection approach in lap TEP. Due to limitation in measuring the actual energy time, the result should be further validated by randomized multi-centers trial on its potential benefit in hernia repair by a more accurate measuring device on energy used.


title: Postendodontic pain following occlusal reduction in mandibular posterior teeth with symptomatic irreversible pulpitis and sensitivity to percussion: a single-centre randomized controlled trial.

text: AIM This randomized, prospective, controlled trial assessed the effect of occlusal reduction on postendodontic pain and medication intake following root canal treatment of mandibular posterior teeth with symptomatic irreversible pulpitis with sensitivity to percussion treated in two visits. METHODOLOGY Three hundred and eight patients were randomly assigned into two equal groups according to whether occlusal reduction was done or not (n=154). For all patients, root canal treatment was carried out in two visits without intracanal medication. Patients assessed their pain using the 0-10 numerical rating scale (NRS) 6h, 12h 24h, 48h after the first visit (Postinstrumentation) and 6h and 12h following root canal filling (Postobturation). Patients, also, recorded their medication intake (Sham or analgesic) postinstrumentation and postobturation; patients initially received a sham capsule, but, if pain persisted, an analgesic was prescribed. Data were analysed using Mann-Whitney U-test, Friedman's test, Wilcoxon's rank test and Chi2 (χ2 ) test. The Relative Risk (RR) and its 95% confidence interval (CI) were calculated for binary data. RESULTS Occlusal reduction was associated with less pain intensity than no occlusal reduction at 12h and 24h postinstrumentation (p<0.05). Pain intensity significantly and gradually decreased with both groups at all postinstrumentation and postobturation timepoints compared to preoperative pain (p<0.05). The RR of moderate-to-severe pain was 0.61 (95% CI: 0.41, 0.91) 12h postinstrumentation and the RR of pain incidence, regardless of its level, was 0.75 (95% CI: 0.61, 0.92) 24h postinstrumentation. There was no significant difference in medication intake (sham or analgesic) between groups (p>0.05). CONCLUSIONS Occlusal reduction was effective in reducing the intensity of postoperative pain 12h and 24h after root canal instrumentation in the first visit in patients with symptomatic irreversible pulpitis with sensitivity to percussion. Occlusal reduction lowered the risk of moderate-to-severe pain by about 40% 12h postinstrumentation and the overall risk of pain by 25% 24h postinstrumentation; yet, it did not affect medication intake.


title: Frequent detection of respiratory agents by multiplex PCR on oropharyngeal samples in Swedish school-attending adolescents.

text: BACKGROUND Respiratory agents may be detected in the oropharynx of healthy individuals. The extent of this condition and the reasons behind it are largely unknown. The objective of this study was to determine the factors associated with the presence of respiratory agents in the oropharynx of adolescents healthy enough to attend school activities. METHODS On a single day in December, samples from the posterior wall of the oropharynx of adolescents aged 10-15 y were obtained using cotton-tipped swabs. The samples were analyzed by real-time polymerase chain reaction (PCR) for the presence of 13 respiratory viruses and 2 bacteria (Mycoplasma pneumoniae and Chlamydophila pneumoniae). RESULTS Out of the 232 adolescents sampled, 67 (29%) had any respiratory symptom. A positive PCR result was found in 50 individuals (22%). Human rhinovirus was the most commonly found agent. Respiratory agents were significantly more frequent in the younger age group (10-13 y) than in the older age group (14-15 y): 26% (38/148) vs 14% (12/84), respectively; p = 0.04. Cough was the only symptom that was more common among individuals with a positive PCR test than among those with a negative PCR test: 8/50 (16%) vs 11/182 (6%); p = 0.02. Family size and class size were not associated with the likelihood of a positive PCR test. CONCLUSIONS The presence of respiratory agents in the oropharynx is a frequent finding among adolescents healthy enough to attend school activities. The high prevalence was found to be associated with young age, but not with the size of the family or class.


title: Economics of COVID-19: challenges and the way forward for health policy during and after the pandemic.

text: The emergence of novel coronavirus disease 2019 (COVID-19) pandemic provides unique challenges for health system. While on the one hand, the government has to struggle with the strategies for control of COVID-19, on the other hand, other routine health services also need to be managed. Second, the infrastructure needs to be augmented to meet the potential epidemic surge of cases. Third, economic welfare and household income need to be guaranteed. All of these have complicated the routine ways in which the governments have dealt with various trade-offs to determine the health and public policies. In this paper, we outline key economic principles for the government to consider for policymaking, during, and after the COVID-19 pandemic. The pandemic rightfully places long due attention of policymakers for investing in health sector. The policy entrepreneurs and public health community should not miss this once-in-a-lifetime "policy window" to raise the level of advocacy for appropriate investment in health sector.


APSDE-COVID statements: recommendations should be modified according to the prevalence of COVID infection rates.


title: Re-interventions after endovascular aortic repair for infrarenal abdominal aneurysms: a retrospective cohort study.

text: BACKGROUND Early morbidity and mortality are generally lower after endovascular aortic repair (EVAR), than after open repair but re-interventions and late complications are more common. The aim of the present study was to make a detailed description of re-interventions after EVAR-including incidence, indications, procedures, and outcome-with special reference to non-access-related re-interventions. METHODS This is a retrospective single-center cohort study of re-interventions after standard EVAR with special reference to non-access-related re-interventions. Consecutive patients (n = 405) treated with standard EVAR for non-ruptured (n = 337) or ruptured (n = 68) infrarenal aneurysms between 2005 and 2013 were analysed. Median follow-up was 29 months (range 0-108). RESULTS Eighty-nine patients (22 %) underwent 113 re-interventions during follow-up. Twenty-seven patients (7 %) had 28 access related re-intervention, 65 patients (16 %) had 85 non-access related reinterventions. Non-access related re-interventions were more common in ruptured aneurysms than in unruptured aneurysms (22 vs. 15 %, p = 0.002). The most frequent indications were endoleak type I (n = 19), type II (n = 21), or type III (n = 5); stent graft migration (n = 9); and thrombosis (n = 14). The most frequent procedures were embolization of endoleak type II (n = 21), additional iliac stent graft (n = 19), proximal extension (n = 12), thrombolysis (n = 8), iliac limb bare-metal stenting (n = 6), and stent graft relining (n = 7). Endovascular technique was used in 83 % of re-interventions. Thirty-day mortality after non-access-related re-interventions was 15 % when initiated from symptoms (rupture or infection) and 0 % when initiated from follow-up findings (p = 0.014). Cumulative survival five years after EVAR was 72 % in patients with a re-intervention and 59 % in patients without (p = 0.21). CONCLUSIONS Non-access-related re-intervention rates are still considerable after EVAR and more frequent after ruptured aneurysms. Endoleak embolization is the most frequent procedure, followed by additional iliac stent grafts. Outcomes after re-interventions are generally good, except when initiated by rupture or infection.


Rescue renal sympathetic denervation in a patient with ventricular electrical storm refractory to endo- and epicardial catheter ablation: response to comments by Huang et al.


title: Provider-parent Communication When Discussing Vaccines: A Systematic Review.

text: PROBLEM Expert literature on communication practices with vaccine hesitant parents posits that a non-confrontational/participatory discussion with the parent would be the best approach to improve compliance. A prior literature review found limited evidence to recommend any particular face to face intervention other than to incorporate communication about vaccination effectiveness during an encounter. Hence, a systematic review was performed in an attempt to determine the most efficacious communication practices to use with parents with vaccination concerns. ELIGIBILITY CRITERIA Quantitative and qualitative studies written in English that assessed the communication framework/style of the provider-parent interaction and studies where provider communication was listed as an intervention were reviewed. SAMPLE Nine articles were included in the sample. RESULTS The majority of the studies were descriptive and qualitative in nature with only one randomized controlled trial. Five of the 9 studies utilized a descriptive cross-sectional design. Two main themes included message types recommended or given by the provider and message types that were requested by the parent. CONCLUSIONS Overall, findings showed that there is currently not enough information to definitively state the type of provider-parent communication style that should be employed to affect the parents' vaccination viewpoint. However, recurring themes of trust in the provider and a personalized provider-parent interaction were evident, which promotes a participatory type of interaction. IMPLICATIONS The literature indirectly supports providers engaging with vaccine hesitant parents in a more individualized, participatory format, though higher quality and more rigorous studies that focus specifically on provider-parent communication practices are needed.


title: Diagnostic investigation of porcine periweaning failure-to-thrive syndrome: lack of compelling evidence linking to common porcine pathogens.

text: Porcine periweaning failure-to-thrive syndrome (PFTS), an increasingly recognized syndrome in the swine industry of North America, is characterized by the anorexia of nursery pigs noticeable within 1 week of weaning, and progressive loss of body condition and lethargy during the next 1-2 weeks. Morbidity caused by PFTS is moderate, but case fatality is high. The etiology of PFTS is presently unknown and may include infectious agent(s), noninfectious factors, or both. PFTS was identified in a high health status farm with good management in early 2007. A diagnostic investigation was undertaken to identify the pathological lesions of, and infectious agents associated with, pigs demonstrating typical clinical signs. Affected (PFTS-SICK) and unaffected (PFTS-HLTHY) pigs from an affected farm, and unaffected pigs from 2 unaffected farms, were examined. The most prevalent lesions in PFTS-SICK pigs were superficial lymphocytic fundic gastritis, atrophic enteritis, superficial colitis, lymphocytic and neutrophilic rhinitis, mild nonsuppurative meningoencephalitis, and thymic atrophy. Rotavirus A and Betacoronavirus 1 (Porcine hemagglutinating encephalomyelitis virus) were identified only in PFTS-SICK pigs, but the significance of the viruses is uncertain because PFTS is not consistent with the typical presentation following infection by these pathogens. Porcine reproductive and respiratory syndrome virus, Porcine circovirus-2, Influenza A virus, Alphacoronavirus 1 (Transmissible gastroenteritis virus), Torque teno virus 1, Brachyspira hyodysenteriae, and Brachyspira pilosicoli were not identified in PFTS-SICK pigs. Suid herpesvirus 2 (Porcine cytomegalovirus), Porcine enteric calicivirus, Torque teno virus 2, pathogenic Escherichia coli, and coccidia were detected in both PFTS-SICK and PFTS-HLTHY pigs. It was concluded that there is a lack of compelling evidence that PFTS is caused by any of these pathogens.


title: ST-246 is a key antiviral to inhibit the viral F13L phospholipase, one of the essential proteins for orthopoxvirus wrapping.

text: OBJECTIVES ST-246 is one of the key antivirals being developed to fight orthopoxvirus (OPV) infections. Its exact mode of action is not completely understood, but it has been reported to interfere with the wrapping of infectious virions, for which F13L (peripheral membrane protein) and B5R (type I glycoprotein) are required. Here we monitored the appearance of ST-246 resistance to identify its molecular target. METHODS Vaccinia virus (VACV), cowpox virus (CPXV) and camelpox virus (CMLV) with reduced susceptibility to ST-246 were selected in cell culture and further characterized by antiviral assays and immunofluorescence. A panel of recombinant OPVs was engineered and a putative 3D model of F13L coupled with molecular docking was used to visualize drug-target interaction. The F13L gene of 65 CPXVs was sequenced to investigate F13L amino acid heterogeneity. RESULTS Amino acid substitutions or insertions were found in the F13L gene of six drug-resistant OPVs and production of four F13L-recombinant viruses confirmed their role(s) in the occurrence of ST-246 resistance. F13L, but not B5R, knockout OPVs showed resistance to ST-246. ST-246 treatment of WT OPVs delocalized F13L- and B5R-encoded proteins and blocked virus wrapping. Putative modelling of F13L and ST-246 revealed a probable pocket into which ST-246 penetrates. None of the identified amino acid changes occurred naturally among newly sequenced or NCBI-derived OPV F13L sequences. CONCLUSIONS Besides demonstrating that F13L is a direct target of ST-246, we also identified novel F13L residues involved in the interaction with ST-246. These findings are important for ST-246 use in the clinic and crucial for future drug-resistance surveillance programmes.


COVID-19: searching for clues among other respiratory viruses.


title: Single-trial analysis of auditory evoked potentials improves separation of normal and schizophrenia subjects.

text: OBJECTIVE In this study, we employed iterative independent component analysis of single-trial auditory evoked responses to identify features of the P50 and N100 components that provide maximum separation between normal controls and schizophrenia subjects and compared the results against classical ensemble averaging. METHOD We analyzed data from 13 schizophrenia and 20 normal control subjects. Responses were obtained in a paired-stimulus paradigm, in which an auditory stimulus S(1) is followed by an identical S(2). The amplitude and latency of the P50 and N100 components in response to the S(1) and S(2) stimuli were measured in each single trial and used as features to classify the responses into two groups. Several methods were used for classification, while their performance was quantified in a 10-fold stratified cross-validation approach. RESULTS We found that normal controls tended to respond earlier and their individual responses had significantly higher amplitude (p<0.01) and significantly less latency variability (p<0.01) compared to schizophrenia patients. The S(1) latency was the most significant discriminatory feature (p<0.01) followed by S(2) latency (p<0.01). The S(2) amplitude, though relatively larger in normal subjects (p<0.05), was the least discriminatory feature. Classification based on single-trial analysis yielded 100% accuracy, while the classical ensemble averaging yielded only a maximum of 76% accuracy. CONCLUSIONS Our results demonstrate that single-trial analysis can accurately separate schizophrenia patients from normal controls and suggest that inter-trial variability plays a significant role in information processing in the human brain. SIGNIFICANCE The proposed technique may have a significant impact as a clinical tool in the quest for identifying physiological markers of schizophrenia.


The Role of Psychotherapy During the COVID-19 Pandemic.


title: Industry 4.0 technologies and their applications in fighting COVID-19 pandemic

text: Abstract Background and aims COVID 19 (Coronavirus) pandemic has created surge demand for essential healthcare equipment, medicines along with the requirement for advance information technologies applications. Industry 4.0 is known as the fourth industrial revolution, which has the potential to fulfil customised requirement during COVID-19 crisis. This revolution has started with the applications of advance manufacturing and digital information technologies. Methods A detailed review of the literature is done on the technologies of Industry 4.0 and their applications in the COVID-19 pandemic, using appropriate search words on the databases of PubMed, SCOPUS, Google Scholar and Research Gate. Results We found several useful technologies of Industry 4.0 which help for proper control and management of COVID-19 pandemic and these have been discussed in this paper. The available technologies of Industry 4.0 could also help the detection and diagnosis of COVID-19 and other related problems and symptoms. Conclusions Industry 4.0 can fulfil the requirements of customised face masks, gloves, and collect information for healthcare systems for proper controlling and treating of COVID-19 patients. We have discussed ten major technologies of Industry 4.0 which help to solve the problems of this virus. It is useful to provide day to day update of an infected patient, area-wise, age-wise and state-wise with proper surveillance systems. We also believe that the proper implementation of these technologies would help to enhance education and communication regarding public health. These Industry 4.0 technologies could provide a lot of innovative ideas and solution for fighting local and global medical emergencies.


title: Neurally Adjusted Ventilatory Assist (NAVA) or Pressure Support Ventilation (PSV) during spontaneous breathing trials in critically ill patients: a crossover trial.

text: BACKGROUND Neurally Adjusted Ventilatory Assist (NAVA) is a proportional ventilatory mode that uses the electrical activity of the diaphragm (EAdi) to offer ventilatory assistance in proportion to patient effort. NAVA has been increasingly used for critically ill patients, but it has not been evaluated during spontaneous breathing trials (SBT). We designed a pilot trial to assess the feasibility of using NAVA during SBTs, and to compare the breathing pattern and patient-ventilator asynchrony of NAVA with Pressure Support (PSV) during SBTs. METHODS We conducted a crossover trial in the ICU of a university hospital in Brazil and included mechanically ventilated patients considered ready to undergo an SBT on the day of the study. Patients underwent two SBTs in randomized order: 30 min in PSV of 5 cmH2O or NAVA titrated to generate equivalent peak airway pressure (Paw), with a positive end-expiratory pressure of 5 cmH2O. The ICU team, blinded to ventilatory mode, evaluated whether patients passed each SBT. We captured flow, Paw and electrical activity of the diaphragm (EAdi) from the ventilator and used it to calculate respiratory rate (RR), tidal volume (VT), and EAdi. Detection of asynchrony events used waveform analysis and we calculated the asynchrony index as the number of asynchrony events divided by the number of neural cycles. RESULTS We included 20 patients in the study. All patients passed the SBT in PSV, and three failed the SBT in NAVA. Five patients were reintubated and the extubation failure rate was 25% (95% CI 9-49%). Respiratory parameters were similar in the two modes: VT = 6.1 (5.5-6.5) mL/Kg in NAVA vs. 5.5 (4.8-6.1) mL/Kg in PSV (p = 0.076) and RR = 27 (17-30) rpm in NAVA vs. 26 (20-30) rpm in PSV, p = 0.55. NAVA reduced AI, with a median of 11.5% (4.2-19.7) compared to 24.3% (6.3-34.3) in PSV (p = 0.033). CONCLUSIONS NAVA reduces patient-ventilator asynchrony index and generates a respiratory pattern similar to PSV during SBTs. Patients considered ready for mechanical ventilation liberation may be submitted to an SBT in NAVA using the same objective criteria used for SBTs in PSV. TRIAL REGISTRATION ClinicalTrials.gov ( NCT01337271 ), registered April 12, 2011.


docid: ijvitvir

title: A standardized method for in vivo mouse pancreas imaging and semiquantitative β cell mass measurement by dual isotope SPECT.

text: PURPOSE In order to evaluate future β cell tracers in vivo, we aimed to develop a standardized in vivo method allowing semiquantitative measurement of a prospective β cell tracer within the pancreas. PROCEDURES 2-[(123)I]Iodo-L-phenylalanine ([(123)I]IPA) and [Lys(40)([(111)In]DTPA)]exendin-3 ([(111)In]Ex3) pancreatic uptake and biodistribution were evaluated using SPECT, autoradiography, and an ex vivo biodistribution study in a controlled unilaterally nephrectomized mouse β cell depletion model. Semiquantitative measurement of the imaging results was performed using [(123)I]IPA to delineate the pancreas and [(111)In]Ex3 as a β cell tracer. RESULTS The uptake of [(123)I]IPA was highest in the pancreas. Aside from the kidneys, the uptake of [(111)In]Ex3 was highest in the pancreas and lungs. Autoradiography showed only uptake of [(111)In]Ex3 in insulin-expressing cells. Semiquantitative measurement of [(111)In]Ex3 in the SPECT images based on the delineation of the pancreas with [(123)I]IPA showed a high correlation with the [(111)In]Ex3 uptake data of the pancreas obtained by dissection. A strong positive correlation was observed between the relative insulin positive area and the pancreas-to-blood ratios of [(111)In]Ex3 uptake as determined by counting with a gamma counter and the semiquantitative analysis of the SPECT images. CONCLUSIONS [(123)I]IPA is a promising tracer to delineate pancreatic tissue on SPECT images. It shows a high uptake in the pancreas as compared to other abdominal tissues. This study also demonstrates the feasibility and accuracy to measure the β cell mass in vivo in an animal model of diabetes.


title: Elevated intrabolus pressure identifies obstructive processes when integrated relaxation pressure is normal on esophageal high-resolution manometry.

text: Elevated integrated relaxation pressure (IRP) on esophageal high-resolution manometry (HRM) identifies obstructive processes at the esophagogastric junction (EGJ). Our aim was to determine whether intrabolus pressure (IBP) can identify structural EGJ processes when IRP is normal. In this observational cohort study, adult patients with dysphagia and undergoing HRM were evaluated for endoscopic evidence of structural EGJ processes (strictures, rings, hiatus hernia) in the setting of normal IRP. HRM metrics [IRP, distal contractile integral (DCI), distal latency (DL), IBP, and EGJ contractile integral (EGJ-CI)] were compared among 74 patients with structural EGJ findings (62.8 ± 1.6 yr, 67.6% women), 27 patients with normal EGD (52.9 ± 3.2 yr, 70.3% women), and 21 healthy controls (27.6 ± 0.6 yr, 52.4% women). Findings were validated in 85 consecutive symptomatic patients to address clinical utility. In the primary cohort, mean IBP (18.4 ± 0.9 mmHg) was higher with structural EGJ findings compared with dysphagia with normal EGD (13.5 ± 1.1 mmHg, P = 0.002) and healthy controls (10.9 ± 0.9 mmHg, P < 0.001). However, mean IRP, DCI, DL, and EGJ-CI were similar across groups (P > 0.05 for each comparison). During multiple rapid swallows, IBP remained higher in the structural findings group compared with controls (P = 0.02). Similar analysis of the prospective validation cohort confirmed IBP elevation in structural EGJ processes, but correlation with dysphagia could not be demonstrated. We conclude that elevated IBP predicts the presence of structural EGJ processes even when IRP is normal, but correlation with dysphagia is suboptimal.NEW & NOTEWORTHY Integrated relaxation pressure (IRP) above the upper limit of normal defines esophageal outflow obstruction using high-resolution manometry. In patients with normal IRP, elevated intrabolus pressure (IBP) can be a surrogate marker for a structural restrictive or obstructive process at the esophagogastric junction (EGJ). This has the potential to augment the clinical value of esophageal HRM by raising suspicion for a structural EGJ process when IBP is elevated.


docid: gmwkwbld

title: Influence of human behavior on cholera dynamics.

text: This paper is devoted to studying the impact of human behavior on cholera infection. We start with a cholera ordinary differential equation (ODE) model that incorporates human behavior via modeling disease prevalence dependent contact rates for direct and indirect transmissions and infectious host shedding. Local and global dynamics of the model are analyzed with respect to the basic reproduction number. We then extend the ODE model to a reaction-convection-diffusion partial differential equation (PDE) model that accounts for the movement of both human hosts and bacteria. Particularly, we investigate the cholera spreading speed by analyzing the traveling wave solutions of the PDE model, and disease threshold dynamics by numerically evaluating the basic reproduction number of the PDE model. Our results show that human behavior can reduce (a) the endemic and epidemic levels, (b) cholera spreading speeds and (c) the risk of infection (characterized by the basic reproduction number).


Introduction of a modified double-lumen tube.


title: Role of anesthesia in endovascular stroke therapy.

text: PURPOSE OF REVIEW Recent randomized clinical trials have demonstrated strong efficacy of endovascular therapy (EVT) for acute ischemic stroke (AIS) from large vessel occlusions; in the USA alone, tens of thousands of patients annually may benefit. The impact of the type of anesthesia used during mechanical thrombectomy on patient outcomes remains controversial. This review discusses the current literature on the effects of anesthesia type on patient outcome following endovascular stroke therapy. RECENT FINDINGS EVT is the standard of treatment for intracranial large vessel occlusions. Recent studies show that general anesthesia is associated with negative clinical outcome in AIS patients undergoing EVT. Two of the possible mechanisms of this finding are systolic hypotension and hypocapnia. However, the only published randomized controlled studies to date, sedation vs. intubation for endovascular stroke treatment and anesthesia during stroke showed no difference in short-term clinical outcome between EVT patients treated with general anesthesia and conscious sedation and improved longer-term outcome in the general anesthesia group. SUMMARY Retrospective reports, and the 2015 American Heart Association/American Stroke Association Guideline (focused update of the 2013 guidelines for the early management of patients with AIS regarding endovascular treatment) based on these reports, are in favor of sedation (conscious sedation) over general anesthesia for endovascular stroke thrombectomy. However, the two randomized controlled prospective studies published provide inconclusive evidence as to the best anesthetic practice for endovascular stroke therapy. More randomized clinical trials are needed to optimize anesthetic patient care in AIS.


title: Polymicrobial acute respiratory infections in a hospital-based pediatric population.

text: BACKGROUND The clinical impact of polymicrobial respiratory infections remains uncertain. Previous reports are contradictory regarding an association with severe disease. METHODS Three hundred forty-six specimens from children with acute respiratory illness identified at the University of Iowa Hospitals and Clinics Clinical Microbiology Laboratory were evaluated by direct immunofluorescent assay and/or viral culture by Clinical Microbiology Laboratory and later by molecular study for the presence of influenza, parainfluenza, respiratory syncytial virus, adenovirus, human metapneumovirus, rhinovirus and human bocavirus. Demographic and clinical data were abstracted from medical records. RESULTS Multiple viruses were detected in 46 (21.7%) of 212 virus-positive specimens with the most frequent virus-virus combinations being HRV-respiratory syncytial virus (n = 12), HRV-human bocavirus (n = 6) and HRV-parainfluenza virus 3 (n = 4). Risk factors for coinfection included male gender (OR [odds ratio]: 1.70, 95% confidence interval [CI]: 0.83-3.46), 6 months to 1 year age (OR: 2.15, 95% CI: 0.75-6.19) and history of immunosuppression (OR: 2.05, 95% CI: 0.99-4.23). Children with viral coinfections were less likely than children with single virus infections to be admitted to an intensive care unit (OR: 0.32, 95% CI: 0.08-1.27); however, this may be explained by undetected viral-bacterial coinfections. CONCLUSIONS HRV, respiratory syncytial virus, human bocavirus, and polymicrobial infections were prevalent in this study. Although the cross-sectional design could not easily examine polymicrobial infection and disease severity, prospective, population-based research regarding the clinical impact of such infections is warranted.


title: The spread of COVID-19 in six western metropolitan regions: a false myth on the excess of mortality in Lombardy and the defense of the city of Milan.

text: We analyzed the spread of the COVID-19 epidemic in 6 metropolitan regions with similar demographic characteristics, daytime commuting population and business activities: the New York metropolitan area, the Île-de-France region, the Greater London county, Bruxelles-Capital, the Community of Madrid and the Lombardy region. The highest mortality rates 30-days after the onset of the epidemic were recorded in New York (81.2 x 100,000) and Madrid (77.1 x 100,000). Lombardy mortality rate is below average (41.4 per 100,000), and it is the only situation in which the capital of the region (Milan) has not been heavily impacted by the epidemic wave. Our study analyzed the role played by containment measures and the positive contribution offered by the hospital care system. (www.actabiomedica.it).


title: Laparoscopic ventral rectopexy with sacrocolpopexy for coexisting pelvic organ prolapse and external rectal prolapse.

text: OBJECTIVES Pelvic organ prolapse (POP) POP is defined as the protrusion of pelvic organs from the vaginal canal. POP often coexists with internal rectal prolapse or external rectal prolapse (ERP). A series of patients with coexisting POP and ERP who underwent laparoscopic ventral rectopexy (LVR) combined with laparoscopic sacrocolpopexy (LSC) are reported here. METHODS Seven patients underwent LVR and LSC together. Fecal incontinence was assessed by the Fecal Incontinence Severity Index (FISI), constipation was assessed by the Constipation Scoring System (CSS), and urinary incontinence was assessed by the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Anatomical disorders were assessed by Pelvic Organ Prolapse Quantification (POP-Q) and defecography. RESULTS The patients' median age was 81 (60-88) years. The median operative time was 380 (282-430) minutes. The median postoperative hospital stay was 3 (1-5) days. There were no postoperative complications. The FISI, CSS, POP-Q, and defecography findings improved postoperatively; however, the ICIQ-SF deteriorated in 2 of 5 patients. CONCLUSIONS LVR combined with LSC for coexisting POP and ERP is feasible.


title: A New Laparoscopic Rectal Transection Method via Umbilical Incision Using Endo GIA™ Radial Reload.

text: We have developed a new laparoscopic rectal transection method via umbilical incision using Endo GIA™ Radial Reload with a Tri-Staple™ Technology (RR) (Covidien, New Haven, CT) stapler. A 65-year-old woman with a rectal carcinoid tumor underwent a laparoscopic low anterior resection. We successfully performed a rectal transection via umbilical incision using this stapler. The postoperative course was uneventful. The possibility of a rectal transection via umbilical incision was demonstrated in the current case. However, further studies are needed to confirm the safety and feasibility of this procedure.


The coronavirus czar.


title: The Effects of Live Attenuated Influenza Vaccine on Nasopharyngeal Bacteria in Healthy 2 to 4 Year Olds. A Randomized Controlled Trial.

text: RATIONALE Viral infections of the upper respiratory tract may influence the commensal nasopharyngeal bacteria. Changes in the bacterial niche could affect transmission dynamics. Attenuated vaccine viruses can be used to investigate this empirically in humans. OBJECTIVES To study the effects of mild viral upper respiratory infections on nasopharyngeal bacterial colonization using live attenuated influenza vaccine (LAIV) as a surrogate. METHODS We used trivalent LAIV to evaluate the effects of viral infection on bacterial carriage and density of Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and Staphylococcus aureus. A total of 151 healthy children were randomized 1:1 to receive the vaccine starting either at recruitment (n = 74) or 28 days later (n = 77) in a stepped wedge fashion, allowing comparisons between recipients and nonrecipients as well as whole-group comparisons pre- and postvaccination. Bacterial carriage and density were determined using quantitative polymerase chain reaction assays. MEASUREMENTS AND MAIN RESULTS A total of 151 children were recruited, 77 in the LAIV group and 74 in the control group. LAIV recipients (n = 63 analyzed) showed an apparent transient increase in H. influenzae carriage but no further significant differences in carriage prevalence of the four bacterial species compared with controls (n = 72 analyzed). S. pneumoniae density was substantially higher in vaccine recipients (16,687 vs. 1935 gene copies per milliliter) 28 days after the first dose (P < 0.001). Whole-group multivariable analysis (prevaccine, after one dose, and after two doses) also showed increases in density of other species and H. influenzae carriage prevalence. CONCLUSIONS In the absence of any safety signals despite widespread use of the vaccine, these findings suggest that bacterial density, and thus transmission rates among children and to people in other age groups, may rise following attenuated influenza infections without associated clinical disease. LAIV could therefore be used as an experimental tool to elucidate the dynamics of transmission of nasopharyngeal bacteria.


title: Increased nutrient sensitivity and plasma concentrations of enteral hormones during duodenal nutrient infusion in functional dyspepsia.

text: OBJECTIVES Functional dyspepsia is predominantly attributed to gastric sensorimotor dysfunctions. The contribution of intestinal chemosensitivity to symptoms is not understood. We evaluated symptoms and plasma hormones during enteral nutrient infusion and the association with impaired glucose tolerance and quality-of-life (QOL) scores in patients with functional dyspepsia vs. healthy controls. METHODS Enteral hormonal responses and symptoms were measured during isocaloric and isovolumic dextrose and lipid infusions into the duodenum in 30 patients with functional dyspepsia (n=27) or nausea and vomiting (n=3) and 35 healthy controls. Infusions were administered in randomized order over 120 min each, with a 120-min washout. Cholecystokinin, glucose-dependent insulinotropic peptide, glucagon-like peptide 1 (GLP1), and peptide YY were measured during infusions. RESULTS Moderate or more severe symptoms during lipid (4 controls vs. 14 patients) and dextrose (1 control vs. 12 patients) infusions were more prevalent in patients than controls (P≤0.01), associated with higher dyspepsia symptom score (P=0.01), worse QOL (P=0.01), and greater plasma hormone concentrations (e.g., GLP1 during lipid infusion). Moderate or more severe symptoms during enteral infusion explained 18%, and depression score explained 21%, of interpatient variation in QOL. Eight patients had impaired glucose tolerance, associated with greater plasma GLP1 and peptide YY concentrations during dextrose and lipid infusions, respectively. CONCLUSIONS Increased sensitivity to enteral dextrose and lipid infusions was associated with greater plasma enteral hormone concentrations, more severe daily symptoms, and worse QOL in functional dyspepsia. These observations are consistent with the hypothesis that enteral hormones mediate increased intestinal sensitivity to nutrients in functional dyspepsia.


title: Gastric leak after laparoscopic-sleeve gastrectomy for obesity.

text: BACKGROUND One of the most serious complications after laparoscopic sleeve gastrectomy (LSG) is gastric leak. Few publications exist concerning the treatment of gastric leak. We sought to determine by way of a prospective study the clinical presentation, postoperative course, and treatment of gastric leak after LSG for obesity. METHODS From October 2005 to August 2008, 214 patients with different degrees of obesity underwent LSG. During surgery, each patient received saline with methylene blue by way of nasogastric tube and had a drain placed. All patients underwent radiologic study with liquid barium sulphate on postoperative day 3. RESULTS Seven patients developed gastric leak. Leak in two patients (28.6%) was diagnosed by upper gastrointestinal tract (UGI) study. Two patients had type I leak (28.6%), and five patients had type II leak (71.4%). Four patients underwent reoperation. Three patients were managed medically with enteral or parenteral feeding; the drain was maintained in situ; and collections were drained by percutaneous punctions guided by computed axial tomography. Mean hospital length of stay was 28.8 days, and time to leakage closure was 43 days after surgery. CONCLUSION Different ways exist to manage gastric leak, depending on the magnitude of the collection and the clinical repercussions. When treatment necessitates reintervention and is performed early, suture repair is more likely to be successful. Leakage closure time will vary.


title: An overview on upper respiratory tract infections and bacteriotherapy as innovative therapeutic strategy.

text: OBJECTIVE The aim of this review is to describe the most common recurring and chronic upper respiratory tract infections (URTI) in children and discuss the role of bacterial interference and bacteriotherapy in their prevention and treatment. MATERIALS AND METHODS A literature review has been performed on the following topics: acute otitis media, adenoiditis, tonsillitis, rhinosinusitis, microbiotics and the role of bacterial interference, and bacteriotherapy in the prevention and treatment of URTI. RESULTS Research studies into the characteristics of the microbiological flora and its role in the pathogenesis of URTI have focused on a single pathogen, on resistance to and ineffectiveness of antibiotic therapies, or on the persistence of bacterial biofilm. Recent evidence supports a central role of the existing microbial ecosystem in the pathogenesis of respiratory disease. In light of this, new therapeutic approaches include the implantation and persistence within the normal microflora of relatively innocuous "effector" bacteria that can competitively exclude or prevent the outgrowth of potentially disease-causing bacteria. Recently, a retrospective and observational study demonstrated that S. salivarius 24SMB and S. oralis 89a nasal spray could be effective in the prevention of recurrent otitis media in a real-life setting. Other studies have focused on the role of bacteriotherapy in children with beneficial effects in the prevention of URTI. CONCLUSIONS The results of previous studies on the role of bacteriotherapy in paediatric URTI suggest that the use of bacterial interference phenomena through bacteriotherapy is a feasible, safe approach and deserves proper consideration as a promising therapeutic strategy against URTI.


title: [E-health tools to overcome the gap in epilepsy care before, during and after COVID-19 pandemics].

text: INTRODUCTION Epilepsy is a common chronic neurological disorder that affects around 50 million worldwide and there is an abundance of literature on the health care gap for this sector of the population. This gap will increase with the current pandemic due to COVID-19. AIM To evaluate the current availability of digital health tools for the care of people with epilepsy according to the world medical literature and their use during said pandemic. DEVELOPMENT We reviewed the publications in scientific journals in the last decade that had as their main topic the use of digital health tools or telemedicine focused on the care of patients with epilepsy, including 4 months after the national quarantines due to the appearance of the virus SARS-CoV-2. Seventeen publications were found on the use of telemedicine focused on epilepsy. The most widely used tools internationally are online platforms, followed by mobile applications, videoconferences, epileptic seizure capture systems, checklists, algorithms for understanding medical data, phone calls, tele-encephalography and text messages. None was published during the COVID-19 current pandemic. CONCLUSIONS Although there is little literature on the use of digital health tools focused on epilepsy, there are several that can be used to fight the attention gap, especially in this global pandemic by COVID-19 that forces quarantines of people and communities for long periods. It is necessary to remove barriers and facilitate patient access to these new information technologies.


title: [Pelvic organ prolapse-surgical technique (POP-ST): a classification of techniques of mesh augmented repairs for pelvic organ prolapse by vaginal route].

text: OBJECTIVE The aim of this study was to propose a classification of surgical techniques for treatment of prolapse by vaginal route using prosthetic reinforcements and to relate the evaluation of surgeons involved in the care of surgical patients. METHODS A literature review was conducted searching for all articles relating novel technique of surgical management of patients with use of prosthetic reinforcements vaginally. The classification was made from descriptions found and then assessed by questionnaires filled out by surgeons. RESULTS The classification takes account of all the techniques available today and can integrate new. Among the surgeons, 56.5% (13/23) found that the POP-ST is adapted to reflect the reality and variety of techniques and 60.8% (14/23) will be ready for daily use. CONCLUSION A classification covering all the techniques put them at risk of a final tool too complex for routine use. The simplification would make it more usable but limited the comprehensiveness and evolutionary. Only 23 surgeons returned the questionnaire. A larger sample would be desirable. The POP-ST is the first classification of this type. We believe that it would assess the new techniques to better understand the complications.


docid: cxukpbcb

title: The in vivo tissue effect of endoscopic balloon-based radiofrequency ablation in treating esophageal squamous cell neoplasia.

text: Background Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality for early flat esophageal squamous cell neoplasms (ESCNs). However, the in vivo tissue effects of RFA on the esophageal wall are uncertain. Methods We prospectively enrolled eight patients with flat-type early ESCNs who were treated with balloon-based RFA. We evaluated the in vivo tissue effect on the esophagus using endoscopic ultrasound (EUS) and the histology of retrieved coagulum. Results The mean tumor length was 6.1 cm, and six of the eight patients achieved a complete response after primary RFA. Real-time evaluation of the tissue effect showed that the mucosa and submucosal layer were more edematous and thicker after RFA than before the procedure (mean 4.89 vs. 2.04 mm, p<.001), suggesting that the thermal effect of RFA may injure the submucosa. Histological evaluation of retrieved coagulum showed a severe cauterization (burning) effect with extensive cell necrosis; however, four cases had some residual viable neoplastic cells. Even though there were viable cells in the sloughed coagulum, half of the patients still achieved complete remission after RFA. Conclusions Our findings suggest that the thermal effect of RFA may injure the submucosal layer and enable neoplastic epithelium to slough off without "burning."


title: Complications, reoperations, and nutrient deficiencies two years after sleeve gastrectomy.

text: Background. The aim of this study was to investigate patient outcomes and nutritional deficiencies following sleeve gastrectomy (SG) during a follow-up of two years. Methods. Over a period of 56 months, all consecutive patients who underwent SG were documented in this prospective, single-center, observational study. The study endpoints included operative time, complication rates, nutritional deficiencies and percentage of excess weight loss (%EWL). Results. From September 26, 2005 to May 28, 2009, 82 patients (female : male = 48 : 34) with a mean age of 43.3 years (range: 22-64) and a preoperative BMI of 52.5 kg/m² (range: 36.8-77.0) underwent SG. Major complications were observed in 9.8% of the patients, with 1 death. During follow up 51.2% of patients were supplemented with iron, 36.6% with zinc, 37.8% with calcium, 26.8% with vitamin D, 46.3% with vitamin B12 and 41.5% with folic acid. %EWL was 54.3, 65.3 and 62.6% after 6, 12 and 24 months. Conclusion. SG as a single step procedure is an effective bariatric intervention. Nutritional deficiencies after SG can be detected by routine nutritional screening. Our results show that Vitamin B12 supplementation should suggest routinely after SG.


title: The course of achalasia one to four decades after initial treatment.

text: BACKGROUND Most follow-up studies of achalasia are limited to <5 years. AIM To study the long-term efficacy of pneumatic dilation (PD) and myotomy in achalasia at least 10 years after treatment. METHODS We performed a retrospective cohort study of achalasia patients with >10 years follow-up after initial myotomy or pneumatic dilation. Symptom recurrence which required repeat dilation or surgery was compared between pneumatic dilation and myotomy. RESULTS One hundred and fifty patients (112 myotomy, 38 pneumatic dilation) of similar characteristics were studied. The mean duration of follow-up after initial treatment was 17.5 ± 7.2 years (10-40 years). Symptoms recurrence rate was 60.7% (100% pneumatic dilation patients vs. 47.3% myotomy), hazard ratio 0.24 demonstrating a lower need for repeat dilation or surgery with myotomy than pneumatic dilation (P = 0.008). All pneumatic dilation patients underwent myotomy in 4 ± 4 (0-16 years). Forty of 53 myotomy patients had symptom recurrence prompting further treatment: 16 pneumatic dilation, 11 myotomy and 13 both. The mean time to repeat procedure was 6.9 years (0-40). The myotomy group required fewer dilations and/or surgeries than the pneumatic dilation group (1.6 vs. 3.6, P < 0.001). 13 patients (10.1%) progressed to end-stage achalasia (five myotomy, eight pneumatic dilation) over 40 years. At last follow-up, 57/62 (92%) patients had absent or mild dysphagia, 53/62 (85%) patients had regurgitation less than once per week and 37 (60.7%) had heartburn episodes <1/week similar for pneumatic dilation and myotomy (P = 0.27). CONCLUSION Although the majority of patients treated for achalasia do well after decades of treatment, most patients may need a series of endoscopic and/or surgical procedures to maintain effective symptom control.


title: Isolated colonic neurofibroma, a rare tumor: A case report and review of literature.

text: BACKGROUND Neurofibromas are tumors comprised of peripheral nerve sheath and connective tissue components. They can occur sporadically or as part of familial syndromes such as neurofibromatosis type 1. Isolated colonic neurofibroma without systemic manifestations is a rarely reported clinical entity. Here we present a case of a 51 years old male with an isolated colonic neurofibroma seen on a screening colonoscopy. CASE SUMMARY Fifty-one years old male who was otherwise healthy without a significant family history of cancer underwent a screening colonoscopy and was found have a 2.3 cm × 1.4 cm lesion in the colon. Tissue biopsy revealed a spindle cell tumor. Magnetic resonance imaging of the pelvis was negative for adenopathy. He underwent an endoscopic ultrasound that showed an ill-defined avascular lesion of mixed echogenicity measuring 2.8 cm × 15.2 cm in the submucosa with no communication with muscularis mucosa or propria. Immunohistochemistry staining of the tumor was strongly positive for S100, with rare penetrating axons deep within the tumor. Tumor cells were negative for c-kit and desmin and had low Ki-67 index. These findings were consistent with a solitary colonic submucosal neurofibroma. A detailed history and physical examination did not reveal any evidence of extraintestinal neurofibromatosis. He underwent transanal surgical resection of the tumor. The patient tolerated the procedure well without any complications. CONCLUSION While neurofibromas have been well described in literature, an isolated colonic neurofibroma is a rare pathological entity. Malignant transformation of neurofibromas has been reported in patients with neurofibromatosis syndromes. We report a case of isolated colonic neurofibroma and highlight the importance of resection due to the increased risk of tumorigenesis.


title: Burden, risk factors and outcomes of hyperemesis gravidarum in low-income and middle-income countries (LMICs): systematic review and meta-analysis protocol.

text: INTRODUCTION Hyperemesis gravidarum (HG) is a pregnancy condition characterised by excessive nausea and vomiting resulting in dehydration, weight loss and serious adverse pregnancy outcomes including termination of pregnancies. Even though evidence in low-income and middle-income countries (LMICs) is limited, the prevalence of HG in pregnancy ranges from 0.3% to 10.8%. With this systematic review and meta-analysis, we aim to determine the prevalence/burden, risk factors, and maternal and perinatal outcomes of HG in LMICs. METHODS PubMed, CINAHL, EMBASE, EBSCO, Ovid maternity and infant care databases, Cochrane Database of Systematic Reviews, Web of Science and SCOPUS databases will be searched. Reference lists of selected articles will be assessed in order to identify other potential studies of interest. Observational studies and (non) randomised controlled trials conducted from January 2000 to September 2018 in LMIC will be included. A weighted inverse-variance meta-analysis using fixed-effects and random-effects model will be done to generate a pooled estimate. Funnel plot and Egger's regression statistical test will be applied to check publication bias. Heterogeneity among studies will be checked using Τ2 to determine dispersion. Moreover, meta-regression analysis will be performed to investigate the source of heterogeneity. STATA V.14 will be used to analyse the data. ETHICS AND DISSEMINATION Formal ethical approval and patient consent are not required; as primary data collection will not be employed. The result will be published in a peer-reviewed scientific journal and will be presented at scientific conferences and public press. PROSPERO REGISTRATION NUMBER CRD42018096284.


title: Skin as a marker of general feline health: Cutaneous manifestations of infectious disease.

text: Practical relevance: Infectious disease in feline patients often presents a diagnostic challenge. This article reviews the most relevant viral, bacterial and protozoal diseases and their cutaneous manifestations. Many of the diseases discussed have overlapping presentations or may mimic more common noninfectious disease processes. The purpose of the article is to reinforce knowledge of common and uncommon infectious diseases, help practitioners identify possible infectious dermatoses, create a comprehensive and prioritized differential list, and provide guidance for the diagnosis of these diseases. A working knowledge of these clinical syndromes is important if what is thought to be a case of a common disease does not respond to conventional management. AUDIENCE This review is aimed at veterinarians who treat cats and especially those with an interest in feline dermatology. Tables are included to allow the reader to formulate a concise list of differential diagnoses for clinically similar presentations. The diagnostic approach to a case of ulcerative facial dermatitis is reviewed in a Case Notes quiz. Evidence base: This article includes up-to-date information regarding dermatologic manifestations of less commonly encountered feline cutaneous infectious diseases. Information has been drawn from the published, peer-reviewed literature and the most recent textbook chapters with a particular aim of describing and differentiating clinical lesions and the diagnostic approach to cutaneous disease, especially in unusual cases.


title: Intranasal treatment with poly(I•C) protects aged mice from lethal respiratory virus infections.

text: In the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, no patients under 24 years of age died, while mortality was greater than 50% in those over 65 years. Greater than 90% of all deaths from influenza A virus (IAV) occur in the elderly (>65 years of age). To address this age-related susceptibility to SARS-CoV and IAV, we infected C57BL/6 (B6) mice with mouse-adapted SARS-CoV (MA15) or IAV (PR8), both of which cause severe disease in aged mice. Intranasal pretreatment of aged mice with poly(I·C) (a TLR3 agonist) and, to a lesser extent, CpG, R848, or lipopolysaccharide (TLR9, TLR7/8, or TLR4 agonists), provided a high level of protection [90% to 100% survival rate after poly(I·C) treatment] against lethal MA15 or IAV challenge and reduced pathological changes and virus loads in the lungs at early times after infection. Poly(I·C) pretreatment upregulated beta interferon (IFN-β), IFN-γ, IL-1β, and tumor necrosis factor (TNF) gene expression in the lungs. Intranasal pretreatment with IFN-β or IFN-γ but not IL-1β or TNF also protected aged mice, consistent with the notion that poly(I·C) pretreatment functioned, at least in part, by inducing IFN-β and IFN-γ. We also identified a potential cellular target for poly(I·C) by showing that treatment inhibited virus replication in primary human airway epithelial cells. These results suggest that intranasal poly(I·C) should be evaluated as a prophylactic agent in aged individuals at high risk for contracting SARS-CoV or IAV infections.


title: Physically active lessons in schools and their impact on physical activity, educational, health and cognition outcomes: a systematic review and meta-analysis.

text: OBJECTIVE This review provides the first meta-analysis of the impact of physically active lessons on lesson-time and overall physical activity (PA), as well as health, cognition and educational outcomes. DESIGN Systematic review and meta-analysis of controlled studies. Six meta-analyses pooled effects on lesson-time PA, overall PA, in-class educational and overall educational outcomes, cognition and health outcomes. Meta-analyses were conducted using the metafor package in R. Risk of bias was assessed using the Cochrane tool for risk of bias. DATA SOURCES PubMed, Embase, PsycINFO, ERIC and Web of Science, grey literature and reference lists were searched in December 2017 and April 2019. STUDIES ELIGIBILITY CRITERIA Physically active lessons compared with a control group in a randomised or non-randomised design, within single component interventions in general school populations. RESULTS 42 studies (39 in preschool or elementary school settings, 27 randomised controlled trials) were eligible to be included in the systematic review and 37 of them were included across the six meta-analyses (n=12 663). Physically active lessons were found to produce large, significant increases in lesson-time PA (d=2.33; 95% CI 1.42 to 3.25: k=16) and small, increases on overall PA (d=0.32; 95% CI 0.18 to 0.46: k=8), large, improvement in lesson-time educational outcomes (d=0.81; 95% CI 0.47 to 1.14: k=7) and a small improvement in overall educational outcomes (d=0.36; 95% CI 0.09 to 0.63: k=25). No effects were seen on cognitive (k=3) or health outcomes (k=3). 25/42 studies had high risk of bias in at least two domains. CONCLUSION In elementary and preschool settings, when physically active lessons were added into the curriculum they had positive impact on both physical activity and educational outcomes. These findings support policy initiatives encouraging the incorporation of physically active lessons into teaching in elementary and preschool setting. TRIAL REGISTRATION NUMBER CRD42017076933.


docid: gaziuzxf

title: Re-infection by COVID-19: a real threat for the future management of pandemia?


title: Optimizing Mask Ventilation: Literature Review and Development of a Conceptual Framework.

text: Mask ventilation is lifesaving, especially in cases of difficult intubation. Many publications have offered distinct techniques for optimizing mask ventilation. This article reviews currently available difficult mask ventilation literature and theory. We divide difficult mask ventilation into 3 broad categories based on etiology: inadequate mask seal, increased airway resistance, and decreased respiratory compliance. Published strategies for overcoming difficulty are presented and organized by etiology.


title: Diagnostic Value of Serial Measurement of C-Reactive Protein in the Detection of a Surgical Complication after Laparoscopic Bowel Resection for Endometriosis.

text: AIMS The study aimed to assess the diagnostic value of serial monitoring of biochemical inflammatory markers (C-reactive protein (CRP) and white blood cell (WBC) count) in the postoperative diagnosis of anastomotic leakage or ureteral injury after bowel resection for deep infiltrating endometriosis. METHODS This is a review of prospectively collected data from 217 patients who underwent laparoscopic bowel resection for endometriosis from January 2009 to April 2015. Patients with an anastomotic leakage or ureteral injury were identified and classified. RESULTS The frequency of anastomotic leakage requiring reoperation was 8.3%. The frequency of ureteral injury was 4.6%. Median time to diagnosis was 6 days for anastomotic leakage and 8 days for ureteral injury. The daily mean values of serum CRP were significantly higher in patients with a surgical complication starting at the second postoperative day (POD 2, p = 0.004). WBC was significantly higher (p < 0.05) on POD 2 and 3 in patients with a surgical complication. A decrease in CRP from POD 1 to 3 predicted an uncomplicated course in 92.1% of the cases. CONCLUSION A decrease in CRP from POD 1 to 3 was an indicator of uncomplicated subsequent postoperative course. The test is recommended when early discharge after rectal resection for deep infiltrating endometriosis is considered.


title: Comparing LigasureTM Exact dissector with other energy devices in total thyroidectomy: a pilot study.

text: Background Hemostasis is fundamental in thyroid surgery. The aim of this randomized active comparator-controlled study was to compare the effectiveness of LigasureTM Exact to previously existing sealing devices in patients undergoing thyroidectomy. Methods A total of 180 patients were randomly allocated into 4 groups according to the hemostatic device used: Focus Harmonic Scalpel® (FHS), LigasureTM Small Jaw (LSJ), Thunderbeat® (TB), and LigasureTM Exact (LE). We recorded epidemiologic and biochemical data, operative difficulty, postoperative vocal alteration and pain, complications, operating time, grams of gland excised per minute, and hospitalization. Results Differences (P<0.001) were observed concerning duration of surgery, operative difficulty and quantity of gland removed per minute. Concerning duration of surgery it is shorter for LE followed by TB and then by both FHS and LSJ. Concerning the quantity of thyroid removed per minute LE leads, followed by FHS and TB. The least amount of gland removed per minute is by LSJ. Finally, operative difficulty was less for LE, while it was equal for all other three devices. Conclusions Energy devices are now frequently used in thyroidectomy. Comparing these devices seems to qualify them as equal concerning post-operative complications, hemostasis, and acute inflammatory reaction. However, LigasureTM Exact Dissector seems to have better results concerning duration of surgery, quantity of thyroid tissue removed per minute and intraoperative difficulty.


title: Pre-clinical study protocol: Blood transfusion in endotoxaemic shock.

text: The Surviving Sepsis Campaign (SCC) and the American College of Critical Care Medicine (ACCM) guidelines recommend blood transfusion in sepsis when the haemoglobin concentration drops below 7.0 g/dL and 10.0 g/dL respectively, while the World Health Organisation (WHO) guideline recommends transfusion in septic shock 'if intravenous (IV) fluids do not maintain adequate circulation', as a supportive measure of last resort. Volume expansion using crystalloid and colloid fluid boluses for haemodynamic resuscitation in severe illness/sepsis, has been associated with adverse outcomes in recent literature. However, the volume expansion effect(s) following blood transfusion for haemodynamic circulatory support, in severe illness remain unclear with most previous studies having focused on evaluating effects of either different RBC storage durations (short versus long duration) or haemoglobin thresholds (low versus high threshold) pre-transfusion. •We describe the protocol for a pre-clinical randomised controlled trial designed to examine haemodynamic effect(s) of early volume expansion using packed RBCs (PRBCs) transfusion (before any crystalloids or colloids) in a validated ovine-model of hyperdynamic endotoxaemic shock.•Additional exploration of mechanisms underlying any physiological, haemodynamic, haematological, immunologic and tissue specific-effects of blood transfusion will be undertaken including comparison of effects of short (≤5 days) versus long (≥30 days) storage duration of PRBCs prior to transfusion.


title: Cloning and identification of porcine programmed death 1.

text: Programmed death 1 (PD-1) is a member of the immunoglobulin (Ig) superfamily, which is expressed on activated T cells, B cells and monocytes. Many researches have demonstrated that a high level of PD-1 expression is closely related to persistent infection and immune evasion in some human infections. In order to study the relationship between PD-1 expression and persistent infections caused by some porcine viruses, we first cloned the porcine PD-1 from porcine PBMCs based on the blast result in the EST database using the human PD-1 sequence. Sequence analysis showed that the cloned PD-1 molecule shares 63 and 54% amino acid sequence identity with human and murine PD-1, respectively. Its molecular structure is also similar to that of human and murine PD-1, containing an IgV-like domain in the extracellular region and two immune regulatory motifs in its cytoplasmic tail. The in vitro T cell proliferation assay showed that the cloned PD-1 could inhibit porcine T cell proliferation by 71% and secretion of IFN-gamma and IL-2 by 64 and 53%, respectively. These data suggest that porcine PD-1 negatively regulates the porcine immune response in a similar manner to that of its counterpart in the human and mouse immune system.


title: Bedside ultrasound to detect central venous catheter misplacement and associated iatrogenic complications: a systematic review and meta-analysis.

text: BACKGROUND Insertion of a central venous catheter (CVC) is common practice in critical care medicine. Complications arising from CVC placement are mostly due to a pneumothorax or malposition. Correct position is currently confirmed by chest x-ray, while ultrasonography might be a more suitable option. We performed a meta-analysis of the available studies with the primary aim of synthesizing information regarding detection of CVC-related complications and misplacement using ultrasound (US). METHODS This is a systematic review and meta-analysis registered at PROSPERO (CRD42016050698). PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched. Articles which reported the diagnostic accuracy of US in detecting the position of CVCs and the mechanical complications associated with insertion were included. Primary outcomes were specificity and sensitivity of US. Secondary outcomes included prevalence of malposition and pneumothorax, feasibility of US examination, and time to perform and interpret both US and chest x-ray. A qualitative assessment was performed using the QUADAS-2 tool. RESULTS We included 25 studies with a total of 2548 patients and 2602 CVC placements. Analysis yielded a pooled specificity of 98.9 (95% confidence interval (CI): 97.8-99.5) and sensitivity of 68.2 (95% CI: 54.4-79.4). US examination was feasible in 96.8% of the cases. The prevalence of CVC malposition and pneumothorax was 6.8% and 1.1%, respectively. The mean time for US performance was 2.83 min (95% CI: 2.77-2.89 min) min, while chest x-ray performance took 34.7 min (95% CI: 32.6-36.7 min). US was feasible in 97%. Further analyses were performed by defining subgroups based on the different utilized US protocols and on intra-atrial and extra-atrial misplacement. Vascular US combined with transthoracic echocardiography was most accurate. CONCLUSIONS US is an accurate and feasible diagnostic modality to detect CVC malposition and iatrogenic pneumothorax. Advantages of US over chest x-ray are that it can be performed faster and does not subject patients to radiation. Vascular US combined with transthoracic echocardiography is advised. However, the results need to be interpreted with caution since included studies were often underpowered and had methodological limitations. A large multicenter study investigating optimal US protocol, among other things, is needed.


title: Optimization of conditions for secretion of dengue virus type 2 envelope domain III using Pichia pastoris.

text: We have developed a recombinant clone of the methylotrophic yeast Pichia pastoris capable of secreting dengue virus type 2 envelope domain III (sEDIII-2). We explored various induction parameters including media composition, temperature, pH, and methanol concentration, to optimize conditions for sEDIII-2 expression in shake flask culture. Induction at 20°C in the presence of 2% (v/v) methanol in a medium buffered to pH 5.8 resulted in highest secretion of sEDIII-2. This yield could be further enhanced up to 70% by repeated induction of the same initial biomass. Using a fed-batch cultivation strategy, we observed that shake-flask yields can be scaled up ∼8-fold in a bioreactor. We obtained ∼94% purity with >70% recovery after purification. This study, which demonstrates for the first time the feasibility of secreting envelope domain III using the P. pastoris host, will be relevant to sub-unit approaches to dengue vaccine development.


title: Real-time monitoring of human blood-brain barrier disruption.

text: Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery.


title: Behavioral Correlates of Muscular Fitness in Children and Adolescents: A Systematic Review.

text: BACKGROUND Muscular fitness (MF) is considered a powerful marker of health, but the extent to which common health behaviors are associated with MF during childhood and adolescence is currently unclear. OBJECTIVE We conducted a systematic review of studies investigating associations between MF (i.e., strength/power, local muscular endurance) and physical activity, sedentary behaviors, and sleep in children and adolescents. METHODS A systematic search of six electronic databases was performed on 8 March, 2017. Search results were screened for relevance and studies conducted with children and adolescents (3-18 years) that explored associations between MF and physical activity, sedentary behavior, or sleep were considered eligible. Data were extracted and checked by a second author. The proportion of studies reporting a statistically significant association between each MF component and behavioral variables was calculated, and additional coding was conducted to account for risk of bias. RESULTS There was consistent evidence for a positive association between MF and physical activity. For both MF components, there was support for objectively measured physical activity, particularly for activity of vigorous intensity. Sports participation was also consistently linked with both MF components, whereas the association with active transport was inconsistent. For both MF components, associations with sedentary behaviors were inconsistent irrespective of measurement method, and the association between MF and sleep was considered uncertain. CONCLUSIONS The available evidence supports a link between MF and physical activity, particularly for vigorous intensity activity and organized sports participation. Conversely, there is limited support for an association with sedentary behaviors, and more research exploring MF and sleep is required.


title: Fear of COVID-19 scale: Psychometric characteristics, reliability and validity in the Israeli population.

text: Mental health clinicians worldwide have been expressing concerns regarding the broad psychological effects of the COVID-19 pandemic. Nonetheless, only a few studies have thus far evaluated the degree of fear of COVID-19, partially due to the lack of validated measures. In this study we evaluated the psychometric properties of the Hebrew version of the Fear of COVID-19 scale (FCV-19S), recently developed to assess different aspects of the fear of the pandemic, in a normative population of participants in Israel. Participants (n = 639) were asked to complete the FCV-19S scale, as well as to report anxiety, depression, and stress levels using validated scales. The results a unidimensional factor structure of the FCV-19S which explained 53.71% of the variance. When forcing a two-factor structure model, the analysis revealed two factors pertaining to emotional fear reactions and symptomatic expressions of fear. Gender, sociodemographic status, chronic illness, being in an at-risk group, and having a family member dying of COVID-19 were positively associated with fear of COVID-19. The measure was associated with anxiety, stress and depression. These results suggest that the FCV-19S has good psychometric properties, and can be utilized in studies assessing the effects of the pandemic on the population's mental health.


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title: Cosmetic surgeries amidst pandemic area of COVID-19: suggested protocol.


title: The Past, Present and Future of Endovascular Aneurysm Treatment.

text: The technology available for the endovascular treatment of intracranial aneurysms is rapidly evolving. Both current and future devices are described. This includes, among others, UNO for parent vessel occlusion, the Medina device for saccular filling, the Comaneci device for remodeling, pCONus for assisted coil occlusion, and WEB and pCANvas for intrasaccular flow disruption. Perspectives of further development such as surface coating for increased radioopacity and decreased thrombogenicity are explained.


title: Generation of Xeno-Free, cGMP-Compliant Patient-Specific iPSCs from Skin Biopsy.

text: This unit describes protocols for the generation of clinical-grade patient-specific induced pluripotent stem cell (iPSC)-derived retinal cells from patients with inherited retinal degenerative blindness. Specifically, we describe how, using xeno-free reagents in an ISO class 5 environment, one can isolate and culture dermal fibroblasts, generate iPSCs, and derive autologous retinal cells via 3-D differentiation. The universal methods described herein for the isolation of dermal fibroblasts and generation of iPSCs can be employed regardless of disease, tissue, or cell type of interest. © 2017 by John Wiley & Sons, Inc.


title: A microwave-assisted diastereoselective multicomponent reaction to access dibenzo[c,e]azepinones: synthesis and biological evaluation.

text: An unprecedented microwave-assisted multicomponent strategy has been elaborated for the fast, efficient, and diastereoselective generation of the dibenzo[c,e]azepinone scaffold. The generated compounds were evaluated for their bioactivity.


Appearance deceives: unusual pneumothorax: traumatic phrenic nerve paralysis.


title: Detection of 11 common viral and bacterial pathogens causing community-acquired pneumonia or sepsis in asymptomatic patients by using a multiplex reverse transcription-PCR assay with manual (enzyme hybridization) or automated (electronic microarray) detection.

text: Community-acquired pneumonia (CAP) and sepsis are important causes of morbidity and mortality. We describe the development of two molecular assays for the detection of 11 common viral and bacterial agents of CAP and sepsis: influenza virus A, influenza virus B, respiratory syncytial virus A (RSV A), RSV B, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, Legionella micdadei, Bordetella pertussis, Staphylococcus aureus, and Streptococcus pneumoniae. Further, we report the prevalence of carriage of these pathogens in respiratory, skin, and serum specimens from 243 asymptomatic children and adults. The detection of pathogens was done using both a manual enzyme hybridization assay and an automated electronic microarray following reverse transcription and PCR amplification. The analytical sensitivities ranged between 0.01 and 100 50% tissue culture infective doses, cells, or CFU per ml for both detection methods. Analytical specificity testing demonstrated no significant cross-reactivity among 19 other common respiratory organisms. One hundred spiked "surrogate" clinical specimens were all correctly identified with 100% specificity (95% confidence interval, 100%). Overall, 28 (21.7%) of 129 nasopharyngeal specimens, 11 of 100 skin specimens, and 2 of 100 serum specimens from asymptomatic subjects tested positive for one or more pathogens, with S. pneumoniae and S. aureus giving 89% of the positive results. Our data suggest that asymptomatic carriage makes the use of molecular assays problematic for the detection of S. pneumoniae or S. aureus in upper respiratory tract secretions; however, the specimens tested showed virtually no carriage of the other nine viral and bacterial pathogens, and the detection of these pathogens should not be a significant diagnostic problem. In addition, slightly less sensitive molecular assays may have better correlation with clinical disease in the case of CAP.


title: GENETIC RELATEDNESS OF EPIZOOTIC HEMORRHAGIC DISEASE VIRUS SEROTYPE 2 FROM 2012 OUTBREAK IN THE USA.

text: During summer and early fall of 2012, the US experienced the largest outbreak of hemorrhagic disease (HD) on record; deer (both Odocoileus virginianus and Odocoileus hemionus) in 35 states were affected, including many northern states where HD typically does not occur. Epizootic hemorrhagic disease virus (EHDV) was the predominant virus isolated, with serotype 2 (EHDV-2) representing 66% (135/205) of all isolated viruses. Viruses within the EHDV serogroup are genetically similar, but we hypothesized that subtle genetic distinctions between viruses would exist across the geographic range of the outbreak if multiple EHDV-2 strains were responsible. We examined viral relatedness and molecular epidemiology of the outbreak by sequencing the mammalian binding protein (VP2) gene and the insect vector binding protein (VP7) gene of 34 EHDV-2 isolates from 2012 across 21 states. Nucleotide sequences of VP2 had 99.0% pairwise identity; VP7 nucleotide sequences had 99.1% pairwise identity. Very few changes were observed in either protein at the amino acid level. Despite the high genetic similarity between isolates, subtle nucleotide differences existed. Both VP2 and VP7 gene sequences separated into two distinct clades based on patterns of single-nucleotide polymorphisms after phylogenetic analysis. The clades were divided geographically into eastern and western clades, although those divisions were not identical between VP2 and VP7. There was also an association between percent sequence identity and geographic distance between isolates. We concluded that multiple EHDV-2 strains contributed to this outbreak.


Risky Business: lessons from covid-19.


title: Human pathogenic bacteria, fungi, and viruses in Drosophila: disease modeling, lessons, and shortcomings.

text: Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila-microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection.


title: Systematic Review and Meta-Analysis on the Value of Chest CT in the Diagnosis of Coronavirus Disease (COVID-19): Sol Scientiae, Illustra Nos.

text: OBJECTIVE. The purpose of this article is to systematically review and meta-analyze the diagnostic accuracy of chest CT in detecting coronavirus disease (COVID-19). MATERIALS AND METHODS. MEDLINE was systematically searched for publications on the diagnostic performance of chest CT in detecting COVID-19. Methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Meta-analysis was performed using a bivariate random-effects model. RESULTS. Six studies were included, comprising 1431 patients. All six studies included patients at high risk of COVID-19, and five studies explicitly reported that they included only symptomatic patients. Mean prevalence of COVID-19 was 47.9% (range, 27.6-85.4%). High or potential risk of bias was present throughout all QUADAS-2 domains in all six studies. Sensitivity ranged from 92.9% to 97.0%, and specificity ranged from 25.0% to 71.9%, with pooled estimates of 94.6% (95% CI, 91.9-96.4%) and 46.0% (95% CI, 31.9-60.7%), respectively. The included studies were statistically homogeneous in their estimates of sensitivity (p = 0.578) and statistically heterogeneous in their estimates of specificity (p < 0.001). CONCLUSION. Diagnostic accuracy studies on chest CT in COVID-19 suffer from methodologic quality issues. Chest CT appears to have a relatively high sensitivity in symptomatic patients at high risk of COVID-19, but it cannot exclude COVID-19. Specificity is poor. These data, along with other local factors such as COVID-19 prevalence, available real-time reverse transcriptase-polymerase chain reaction tests, staff, hospital, and CT scanning capacity, can be useful to healthcare professionals and policy makers to decide on the utility of chest CT for COVID-19 detection in the hospital setting.


title: High Prevalence of Middle East Respiratory Coronavirus in Young Dromedary Camels in Jordan.

text: Prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) was determined in 45 dromedary camels from two geographically separated herds in Jordan. Virus shedding was only detected in swabs obtained from the respiratory tract and primarily observed in camels younger than 3 years. MERS-CoV seroprevalence increased with age of camels. Bovine and sheep sera were seronegative. Phylogenetic analysis of partial S2 clustered the Jordanian MERS-CoV strains with contemporary MERS-CoV strains associated with nosocomial outbreaks.


title: Technique and Patient Selection Criteria of Right Anterior Mini-Thoracotomy for Minimal Access Aortic Valve Replacement.

text: Aortic valve stenosis has become the most prevalent valvular heart disease in developed countries, and is due to the aging of these populations. The incidence of the pathology increases with growing age after 65 years. Conventional surgical aortic valve replacement through median sternotomy has been the gold standard of patient care for symptomatic aortic valve stenosis. However, as the risk profile of patients worsens, other therapeutic strategies have been introduced in an attempt to maintain the excellent results obtained by the established surgical treatment. One of these approaches is represented by transcatheter aortic valve implantation. Although the outcomes of high-risk patients undergoing treatment for symptomatic aortic valve stenosis have improved with transcatheter aortic valve replacement, many patients with this condition remain candidates for surgical aortic valve replacement. In order to reduce the surgical trauma in patients who are candidates for surgical aortic valve replacement, minimally invasive approaches have garnered interest during the past decade. Since the introduction of right anterior thoracotomy for aortic valve replacement in 1993, right anterior mini-thoracotomy and upper hemi-sternotomy have become the predominant incisional approaches among cardiac surgeons performing minimal access aortic valve replacement. Beside the location of the incision, the arterial cannulation site represents the second major landmark of minimal access techniques for aortic valve replacement. The two most frequently used arterial cannulation sites include central aortic and peripheral femoral approaches. With the purpose of reducing surgical trauma in these patients, we have opted for a right anterior mini-thoracotomy approach with a central aortic cannulation site. This protocol describes in detail a technique for minimally invasive aortic valve replacement and provides recommendations for patient selection criteria, including cardiac computer tomography measurements. The indications and limitations of this technique, as well as its alternatives, are discussed.


title: Heat shock protein 70 enhances mucosal immunity against human norovirus when coexpressed from a vesicular stomatitis virus vector.

text: UNLABELLED Human norovirus (NoV) accounts for 95% of nonbacterial gastroenteritis worldwide. Currently, there is no vaccine available to combat human NoV as it is not cultivable and lacks a small-animal model. Recently, we demonstrated that recombinant vesicular stomatitis virus (rVSV) expressing human NoV capsid protein (rVSV-VP1) induced strong immunities in mice (Y. Ma and J. Li, J. Virol. 85:2942-2952, 2011). To further improve the safety and efficacy of the vaccine candidate, heat shock protein 70 (HSP70) was inserted into the rVSV-VP1 backbone vector. A second construct was generated in which the firefly luciferase (Luc) gene was inserted in place of HSP70 as a control for the double insertion. The resultant recombinant viruses (rVSV-HSP70-VP1 and rVSV-Luc-VP1) were significantly more attenuated in cell culture and viral spread in mice than rVSV-VP1. At the inoculation dose of 1.0 × 10(6) PFU, rVSV-HSP70-VP1 triggered significantly higher vaginal IgA than rVSV-VP1 and significantly higher fecal and vaginal IgA responses than rVSV-Luc-VP1, although serum IgG and T cell responses were similar. At the inoculation dose of 5.0 × 10(6) PFU, rVSV-HSP70-VP1 stimulated significantly higher T cell, fecal, and vaginal IgA responses than rVSV-VP1. Fecal and vaginal IgA responses were also significantly increased when combined vaccination of rVSV-VP1 and rVSV-HSP70 was used. Collectively, these data indicate that (i) insertion of an additional gene (HSP70 or Luc) into the rVSV-VP1 backbone further attenuates the VSV-based vaccine in vitro and in vivo, thus improving the safety of the vaccine candidate, and (ii) HSP70 enhances the human NoV-specific mucosal and T cell immunities triggered by a VSV-based human NoV vaccine. IMPORTANCE Human norovirus (NoV) is responsible for more than 95% of acute nonbacterial gastroenteritis worldwide. Currently, there is no vaccine for this virus. Development of a live attenuated vaccine for human NoV has not been possible because it is uncultivable. Thus, a live vector-based vaccine may provide an alternative vaccine strategy. In this study, we developed a vesicular stomatitis virus (VSV)-based human NoV vaccine candidate. We constructed rVSV-HSP70-VP1, coexpressing heat shock protein (HSP70) and capsid (VP1) genes of human NoV, and rVSV-Luc-VP1, coexpressing firefly luciferase (Luc) and VP1 genes. We found that VSVs with a double gene insertion were significantly more attenuated than VSV with a single VP1 insertion (rVSV-VP1). Furthermore, we found that coexpression or coadministration of HSP70 from VSV vector significantly enhanced human NoV-specific mucosal immunity. Collectively, we developed an improved live vectored vaccine candidate for human NoV which will be useful for future clinical studies.


title: Integrative Physiological Aspects of Brain RAS in Hypertension.

text: PURPOSE OF REVIEW The renin-angiotensin system (RAS) plays an important role in modulating cardiovascular function and fluid homeostasis. While the systemic actions of the RAS are widely accepted, the role of the RAS in the brain, its regulation of cardiovascular function, and sympathetic outflow remain controversial. In this report, we discuss the current understanding of central RAS on blood pressure (BP) regulation, in light of recent literature and new experimental techniques. RECENT FINDINGS Studies using neuronal or glial-specifc mouse models have allowed for greater understanding into the site-specific expression and role centrally expressed RAS proteins have on BP regulation. While all components of the RAS have been identified in cardiovascular regulatory regions of the brain, their actions may be site specific. In a number of animal models of hypertension, reduction in Ang II-mediated signaling, or upregulation of the central ACE2/Ang 1-7 pathway, has been shown to reduce BP, via a reduction in sympathetic signaling and increase parasympathetic tone, respectively. Emerging evidence also suggests that, in part, the female protective phenotype against hypertension may be due to inceased ACE2 activity within cardiovascular regulatory regions of the brain, potentially mediated by estrogen. Increasing evidence suggests the importance of a central renin-angiotensin pathway, although its localization and the mechanisms involved in its expression and regulation still need to be clarified and more precisely defined. All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).


title: What to do about fibrin rich 'tough clots'? Comparing the Solitaire stent retriever with a novel geometric clot extractor in an in vitro stroke model.

text: BACKGROUND Despite advances in revascularization tools for large vessel occlusion presenting as acute ischemic stroke, a significant subset of clots remain recalcitrant to current strategies. We assessed the effectiveness of a novel thrombectomy device that was specifically designed to retrieve resistant fibrin rich clots, the geometric clot extractor (GCE; Neuravi, Galway, Ireland), in an in vitro cerebrovascular occlusion stroke model. METHODS After introducing fibrin rich clot analogues into the middle cerebral artery of the model, we compared the rates of recanalization between GCE and Solitaire flow restoration stent retriever (SR; Medtronic, Minneapolis, Minnesota, USA; control group) cases. A maximum of three passes of each device was allowed. If the SR failed to recanalize the vessel after three passes, one pass of the GCE was allowed (rescue cases). RESULTS In a total of 26 thrombectomy cases (13 GCE, 13 SR), successful recanalization (Thrombolysis in Cerebral Infarction score of 2b or 3) was achieved 100% of the time in the GCE cases with an average of 2.13 passes per case. This rate was significantly higher compared with the Solitaire recanalization rate (7.7%, P<0.0001) with an average of three passes per case. After SR failure (in 92% of cases), successful one pass GCE rescue recanalization was achieved 66% of the time (P<0.005). CONCLUSION Application of the GCE in this experimental stroke model to retrieve typically recalcitrant fibrin rich clots resulted in higher successful recanalization rates than the SR.


title: COVID-19: Hygiene and Public Health to the front.

text: Public Health professionals and academics have been on the frontline of Italian history during the COVID-19 response like they never did before. Ancient professors of Hygiene such as Celli, Pagliani, Sclavo, Petragnani, Seppilli and Giovanardi flanked politicians in other critical moments. They helped them to manage healthcare reforms, earthquakes response, Seveso Dioxin disaster, cholera and poliomielitis epidemics and other health threats. The ongoing COVID-19 epidemic has highlighted the paramount importance of the practical application of basic concepts of public health, which were considered so far became obsolete, such as personal hygiene, quarantine, individual protective devices or basic epidemiological measures. Hygiene and Public Health used to have a targeted audience in professionals and lecturers. Nowadays, these topics are critical and of concern of a much larger audience. Public Health women and men are now asked to act in task forces, media broadcasts, webinars and consulting activities. In phase 2 of this epidemic - which is about to begin when this volume is to be published - the role of Public Health professionals could become even more relevant. However, this unexpected season must be managed with seriousness and intelligence, capitalizing it also for the future. If our Post-Graduate Schools of Public Health ("Igiene e Medicina Preventiva"), our scientific associations, our academic lecturers and our officers do not prove to be up to the situation, a dull future for the discipline might very well be. On the contrary, if as we all hope, we will be able to ride the wave of a dramatic health crisis, transforming it into a relevant scientific and professional opportunity, then we will be able to build on the post-COVID-19 a cutting-edge, a more attractive, relevant and modern discipline. This Supplement of Acta Biomedica, planned before the onset of the epidemic emergency in Italy, but already successful in presenting two papers on COVID-19, is further proof of how current and lively our discipline is.


title: Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques.

text: The transplantation of pancreatic islet cells could restore glycaemic control in patients with type-I diabetes. Microspheres for islet encapsulation have enabled long-term glycaemic control in diabetic rodent models; yet human patients transplanted with equivalent microsphere formulations have experienced only transient islet-graft function, owing to a vigorous foreign-body reaction (FBR), to pericapsular fibrotic overgrowth (PFO) and, in upright bipedal species, to the sedimentation of the microspheres within the peritoneal cavity. Here, we report the results of the testing, in non-human primate (NHP) models, of seven alginate formulations that were efficacious in rodents, including three that led to transient islet-graft function in clinical trials. Although one month post-implantation all formulations elicited significant FBR and PFO, three chemically modified, immune-modulating alginate formulations elicited reduced FBR. In conjunction with a minimally invasive transplantation technique into the bursa omentalis of NHPs, the most promising chemically modified alginate derivative (Z1-Y15) protected viable and glucose-responsive allogeneic islets for 4 months without the need for immunosuppression. Chemically modified alginate formulations may enable the long-term transplantation of islets for the correction of insulin deficiency.


Covid-19: are face masks a good long term strategy?


title: Hyperglycemia management in the critically ill patient with COVID-19.

text: Hyperglycemia is common in critically ill patients and is associated with worse outcomes in those admitted to an intensive care unit. Glucose control helps prevent and control infections and their complications. For critically ill patients with COVID-19, management of hyperglycemia must consider caregiver protection and the frequency of monitoring glucose based on patient safety and the use of personal protective equipment. If steroids are used in the management plan, be aware of steroid-induced hyperglycemia. An endocrinology consult may be beneficial to help manage drip rate and frequency of glucose checks.