title: Complex N-linked glycans serve as a determinant for exosome/microvesicle cargo recruitment.

text: Exosomes, also known as microvesicles (EMVs), are nano-sized membranous particles secreted from nearly all mammalian cell types. These nanoparticles play critical roles in many physiological processes including cell-cell signaling, immune activation, and suppression and are associated with disease states such as tumor progression. The biological functions of EMVs are highly dependent on their protein composition, which can dictate pathogenicity. Although some mechanisms have been proposed for the regulation of EMV protein trafficking, little attention has been paid to N-linked glycosylation as a potential sorting signal. Previous work from our laboratory found a conserved glycan signature for EMVs, which differed from that of the parent cell membranes, suggesting a potential role for glycosylation in EMV biogenesis. In this study, we further explore the role of glycosylation in EMV protein trafficking. We identify EMV glycoproteins and demonstrate alteration of their recruitment as a function of their glycosylation status upon pharmacological manipulation. Furthermore, we show that genetic manipulation of the glycosylation levels of a specific EMV glycoprotein, EWI-2, directly impacts its recruitment as a function of N-linked glycan sites. Taken together, our data provide strong evidence that N-linked glycosylation directs glycoprotein sorting into EMVs.


title: Optical inhibition of striatal neurons promotes focal neurogenesis and neurobehavioral recovery in mice after middle cerebral artery occlusion.

text: Striatal neurons regulate the activity of neural progenitor cells in the subventricular zone, but the effect of striatal neuronal activity on neurogenesis after ischemic stroke is unclear. In this study, we used optogenetic tools to investigate the impact of striatal neuronal activity on the neurogenesis and functional recovery after cerebral ischemia. We transfected striatal neurons with channelrhodopsin-2 or halorhodopsin from Natronomonas so that they can be excited by 473 nm laser or inhibited by 594 nm laser, respectively. Neural inhibition but not excitation at 4-7 days after middle cerebral artery occlusion resulted in reduced atrophy volume (6.8 ± 0.7 vs 8.5 ± 1.2 mm3, p < 0.05) and better performance represented by longer sustaining time on rotarod (99.3 ± 9 vs 80.1 ± 11 s, p < 0.01) and faster moving speed (7.7 ± 2 vs 5.7 ± 1.1 cm/s, p < 0.05) in open field tests. Furthermore, neural inhibition increased the number of nestin+, BrdU+/doublecortin+ and BrdU+/NeuN+ cells ( p < 0.001) in the subventricular zone and peri-focal region, and the expression level of axon guidance factor Netrin-1 (0.39 ± 0.16 vs 0.16 ± 0.02, p < 0.05) in the peri-focal region. These data suggest that striatal neuronal activity plays an important role in regulating neurogenesis and neural-behavioral outcomes, and that inhibiting striatal neurons by optogenetics promotes the recovery after ischemic stroke in mice.


title: Delivering non-communicable disease interventions to women and children in conflict settings: a systematic review.

text: BACKGROUND Non-communicable diseases (NCDs) are the leading cause of death worldwide. In the context of conflict settings, population displacement, disrupted treatment, infrastructure damage and other factors impose serious NCD intervention delivery challenges, but relatively little attention has been paid to addressing these challenges. Here we synthesise the available indexed and grey literature reporting on the delivery of NCD interventions to conflict-affected women and children in low- and middle-income countries (LMICs). METHODS A systematic search in MEDLINE, Embase, CINAHL and PsycINFO databases for indexed articles published between 1 January 1990 and 31 March 2018 was conducted, and publications reporting on NCD intervention delivery to conflict-affected women or children in LMICs were included. A grey literature search of 10 major humanitarian organisation websites for publications dated between 1 January 2013 and 30 November 2018 was also conducted. We extracted and synthesised information on intervention delivery characteristics and delivery barriers and facilitators. RESULTS Of 27 included publications, most reported on observational research studies, half reported on studies in the Middle East and North Africa region and 80% reported on interventions targeted to refugees. Screening and medication for cardiovascular disease and diabetes were the most commonly reported interventions, with most publications reporting facility-based delivery and very few reporting outreach or community approaches. Doctors were the most frequently reported delivery personnel. No publications reported on intervention coverage or on the effectiveness of interventions among women or children. Limited population access and logistical constraints were key delivery barriers reported, while innovative technology use, training of workforce and multidisciplinary care were reported to have facilitated NCD intervention delivery. CONCLUSION Large and persistent gaps in information and evidence make it difficult to recommend effective strategies for improving the reach of quality NCD care among conflict-affected women and children. More rigorous research and reporting on effective strategies for delivering NCD care in conflict contexts is urgently needed. PROSPERO REGISTRATION NUMBER CRD42019125221.


title: EVIDENCE trial: design of a phase 2, randomized, controlled, multicenter study comparing flow diversion and traditional endovascular strategy in unruptured saccular wide-necked intracranial aneurysms.

text: INTRODUCTION Endovascular treatment of large, wide-necked intracranial aneurysms with coils is associated with low rates of initial angiographic occlusion and high rates of recurrence. The Pipeline™ Embolization Device has shown high rates of complete occlusion in uncontrolled clinical series. METHODS The study is a prospective, controlled, randomized, multicenter, phase 2 open-label trial. Intention-to-treat population includes age ≥18, unruptured saccular aneurysm located in the intra-dural area, neck diameter ≥4 and ≤10 mm, sac diameter ≥7 mm and ≤20 mm, "dome/neck" ratio is ≥1, diameter of the parent artery ≥2 mm and ≤5 mm, and no prior treatment of the aneurysm. Site can only participate if five patients have been previously treated with the Pipeline device. The primary end point of the study is complete occlusion of the aneurysm on angiogram performed 12 months after the endovascular procedure. Complete aneurysm occlusion is defined as the absence of visible blood flow, grade 1 according to the Raymond scale for the standard procedure group and grade 4 according to the grading scale of Kamran for the flow diverter group. RESULTS The trial is currently enrolling and results of the data are pending the completion of enrollment and follow-up. CONCLUSION This paper details the trial design of the French EVIDENCE phase 2 trial, a blinded, controlled randomized trial of wide-neck intra-dural aneurysms amenable to either traditional endovascular strategy or flow diversion with Pipeline device.


Determining the impact of intraoperative smoke evacuation on the patient experience during outpatient surgery: A randomized controlled trial.


title: Thread-Traction with a Sheath of Polypectomy Snare Facilitates Endoscopic Submucosal Dissection of Early Gastric Cancers.

text: Although the thread-traction (TT) method has been found useful during endoscopic submucosal dissection (ESD) for early gastric cancers, the movement of the thread interferes with the movement of the endoscope, and the lesion can only be pulled to the mouth side. We have developed the novel TT method using a sheath of polypectomy snare (TTSPS). The TTSPS method enables free and independent movement of the thread and the endoscope and allows pulling the lesion towards the anal as well as oral side. The median dissection times, numbers of instances of arterial bleeding, and numbers of local injections into the submucosal layer were significantly lower for ESD with TTSPS than for conventional ESD. Countertraction ESD using the TTSPS method is straightforward, safe, easy, noninvasive, and cost effective, and it uses instruments readily available in most hospitals to enhance visualization of cutting lines. Therefore, the TTSPS method can be universally applied in conventional ESD.


title: Walking while resisting a perturbation: Effects on ankle dorsiflexor activation during swing and potential for rehabilitation.

text: UNLABELLED Motor control studies have shown that when walking is performed while resisting a perturbation applied to the lower limb, the muscle activation pattern can be temporarily modified. The objective of the present study is to validate if such an approach, targeting the ankle, could specifically promote an increased activation of the ankle dorsiflexor muscles that are of key importance for the rehabilitation of foot drop. METHODS 12 adults, with no gait deficit, walked on a treadmill for three periods of 5min: before, during and after exposure to a torque perturbation applied by a robotized ankle-foot orthosis that tended to plantarflex the ankle during the swing phase. Spatiotemporal gait parameters, ankle and knee kinematics, and the electromyographic activity of five lower limb muscle groups were recorded. RESULTS The perturbation initially caused a deviation of the ankle towards plantarflexion. This movement error was rapidly reduced and associated with a large increase (78.2%; p<0.001) in tibialis anterior (ankle dorsiflexor; TA) activation, specifically in the stance-to-swing burst. This increase carried over to post-perturbation walking, gradually disappearing over several strides. Interestingly, these aftereffects led to an increase in peak ankle dorsiflexion of approximately 7° during the swing phase. CONCLUSIONS Walking while resisting a torque perturbation applied at the ankle during swing promotes an increase in TA muscle activation that carries over after perturbation removal, leading to an increased ankle dorsiflexion. Training based on this approach may have the potential of improving the gait of persons with foot drop.


title: Anterior Cutaneous Nerve Entrapment Syndrome: Two Case Reports of the Forgotten Diagnosis After Bariatric Surgery.

text: Unexplained abdominal pain is an increasing phenomenon after laparoscopic bariatric surgery, with an occurrence of 7.4%. The pain could be explained by the anterior cutaneous nerve entrapment syndrome (ACNES). However, the incidence of ACNES after laparoscopic bariatric surgery is unclear. We report the cases of two patients with unexplained abdominal pain after laparoscopic bariatric surgery and a significant delay in the diagnosis of ACNES. In both cases, clinical signs of ACNES were demonstrated by a centralized trigger point in the abdominal wall and specific neuropathic aspects during examination. Both patients were temporary pain-free after a diagnostic local lidocaine injection. A neurectomy was performed in both cases, after which they remained pain-free. There was a significant delay (six months and three years, respectively) in the diagnosis of ACNES, and many additional imaging procedures including a diagnostic laparoscopy were performed. ACNES is difficult to diagnose due to its relatively unknown entity. This case report confirms that the diagnosis of ACNES is still frequently overlooked as a cause of chronic abdominal pain. Earlier diagnosis recognition can probably prevent unnecessary investigations and may improve the quality of life in bariatric patients with unexplained abdominal pain.


title: Association between circulating angiotensin-converting enzyme 2 and cardiac remodeling in hypertensive patients.

text: BACKGROUND Angiotensin-converting enzyme 2 (ACE2) plays a vital role in the pathogenesis of hypertension-induced cardiac remodeling and exhibits cardioprotective properties in hypertensive animal models. Evidence that ACE2 is an important regulator of hypertensive cardiac remodeling in humans has not been addressed directly yet. METHODS A total of 161 patients with essential hypertension and 47 age- and sex-matched normotensive healthy subjects were consecutively recruited. Serum concentration levels of ACE2 were determined by enzyme-linked immunosorbent assay. Cardiac structural and functional parameters were measured by echocardiography. RESULTS Serum ACE2 concentrations were higher in hypertensive patients compared to healthy subjects (170.31 [83.50-707.12] pg/ml in patients versus 59.28 [39.71-81.81] pg/ml in healthy subjects, P<0.001). After adjustment for confounders, including age, sex, body mass index, snoring, smoking, duration of hypertension, comorbidities, medication use, mean arterial pressure and N-terminal pro-brain natriuretic peptide, serum ACE2 concentrations were positively correlated with left atrial diameter, left ventricular end-diastolic diameter and left ventricular mass in hypertensive patients. Moreover, multiple regression analyses adjusting for covariates revealed that serum ACE2 concentrations were also independently associated with left ventricular ejection fraction and late diastolic filling velocities of the mitral inflow. CONCLUSIONS This study reveals an elevated serum concentration of ACE2 and independent associations between serum ACE2 and echocardiographic parameters in hypertensive patients.


title: Radiopeptide imaging and therapy in the United States.

text: Radiolabeled peptides targeted against receptors on the cell surface have been shown to be remarkably specific and effective in the diagnosis and therapy of malignant disease. Much of the early work in this field took place outside the United States, but in recent years the research effort within the United States has accelerated. Most of the initial studies in the United States focused on somatostatin receptor ligands. (111)In-pentetreotide was approved in 1994 and has been used extensively in the diagnosis and management of a wide variety of neuroendocrine tumors, particularly carcinoid. This work was extended to (99m)Tc-labeled analogs, and the most successful, (99m)Tc-depreotide, was approved in 1999. This agent was found to be accurate in the diagnosis of lung cancer, but it was not particularly successful because it was supplanted by (18)F-FDG imaging with positron tomography. More recently, studies with (68)Ga-labeled somatostatin analogs were initiated in the United States. This effort was delayed relative to that in other parts of the world because of difficulty in obtaining the necessary generators and regulatory uncertainty, both of which are less of a problem currently. Several ligands are being developed to image melanoma through targeting of the melanocyte-stimulating hormone receptor. Other ligands are being developed to use the arginine-glycine-aspartate oligopeptide to target angiogenesis and to use bombesin analogs to target the gastrin-releasing peptide receptor for the diagnosis and potential therapy of prostate cancer. Peptide dimers that target 2 receptors simultaneously are also being constructed, potentially increasing the selectivity of the approach significantly. Radiopeptide therapy has been explored with these ligands, initially with high-dose (111)In-pentetreotide. This step has been followed by U.S. participation in several trials with (90)Y-, (177)Lu-, and (188)Re-labeled analogs. Some of these agents are now available clinically outside the United States, and it is important to design and conduct the appropriate trials so that this therapy can be offered within the United States.


title: Clinical sedation and bispectral index in burn children receiving gamma-hydroxybutyrate.

text: BACKGROUND Gamma-hydroxybutyrate (GHB) may be an interesting hypnotic agent in burn patients because of its good respiratory or hemodynamic tolerance. However, its clinical and electroencephalographic (EEG) sedative effects are not yet described in children. The aim of this prospective and randomized study was to assess clinical and EEG effects of increasing intravenous (IV) doses of GHB in burn children requiring sedation for burn wound cares. METHODS Thirty six children hospitalized in a burn care unit were included and randomly assigned into three groups (G) according to the single IV dose of GHB they received before burn wound care: 10 mg · kg(-1) in G10, 25 mg · kg(-1) in G25, or 50 mg · kg(-1) in G50. All patients received oral premedication (morphine and hydroxyzine) 30 min before GHB injection. Respiratory rate, heart rate, pulse oximetry, and bispectral index (BIS) were continuously monitored. Depth of sedation was clinically assessed using Observer's Assessment of Alertness and Sedation (OAAS) Score, every 2 min until recovery (i.e., OAAS = 4). RESULTS Median age was 17.5 [12-34] months. Whatever the dose, BIS decreased after IV GHB. Nadir value of BIS was significantly lower in G25 and G50 than in G10, as was for OAAS score. Nadir values were reached after same delays in G25 and G50. Duration of sedation was dose-dependent. CONCLUSION Bispectral index decreased after GHB injection and was correlated with OAAS score. Deep sedation can be safely achieved with IV doses of 25 or 50 mg · kg(-1), but the last dose was associated with prolonged duration of clinical sedation.


title: Treatment of cervical OPLL by cervical anterior fusion using autologous vertebral bone grafts.

text: BACKGROUND In anterior fusion, we use autologous bone grafts from cervical vertebral bodies and bioabsorptive screws to prevent graft extrusion (Williams-Isu method). We report the application of and indication for the Williams-Isu method for OPLL and present our clinical and radiological results. METHODS Using the Williams-Isu method, we treated 17 patients with cervical OPLL; 15 had segmental- and 2 had continuous-type OPLL. The median follow-up term was 24 months. The patients underwent anterior decompression and fusion at a single level (n = 8) or at two levels (n = 9). As a control, 17 patients with cervical spondylosis underwent anterior single-level decompression and fusion using the Williams-Isu method. Pre- and postoperative radiographs of the cervical spine were obtained in all patients, and the alignment of the whole cervical and fused segment and the height of the fused segment were compared. RESULTS All but one patient experienced alleviation of clinical symptoms without deterioration during the follow-up period. The recovery rate on the JOA score was 71.7%. The patient with continuous-type OPLL suffered postoperative neurological deterioration because of a remnant of the upper-level OPLL. Radiological studies confirmed the absence of bone graft dislocation and fracture, and of satisfactory bone fusion in all patients. There was no significant difference between the two patient groups with respect to whole spine alignment and the alignment and height of the fused segment. CONCLUSIONS The Williams-Isu method is useful for treating not only cervical spondylosis but also cervical segmental OPLL at one or two levels.


title: Effects of Prone Sleeping on Cerebral Oxygenation in Preterm Infants.

text: OBJECTIVE To determine the effect of prone sleeping on cerebral oxygenation in preterm infants in the neonatal intensive care unit. STUDY DESIGN Preterm infants, divided into extremely preterm (gestational age 24-28 weeks; n = 23) and very preterm (gestational age 29-34 weeks; n = 33) groups, were studied weekly until discharge in prone and supine positions during active and quiet sleep. Cerebral tissue oxygenation index (TOI) and arterial oxygen saturation (SaO2) were recorded. Cerebral fractional tissue extraction (CFOE) was calculated as CFOE = (SaO2 - TOI)/SaO2. RESULTS In extremely preterm infants, CFOE increased modestly in the prone position in both sleep states at age 1 week, in no change in TOI despite higher SaO2. In contrast, the very preterm infants did not have position-related differences in CFOE until the fifth week of life. In the very preterm infants, TOI decreased and CFOE increased with active sleep compared with quiet sleep and with increasing postnatal age. CONCLUSION At 1 week of age, prone sleeping increased CFOE in extremely preterm infants, suggesting reduced cerebral blood flow. Our findings reveal important physiological insights in clinically stable preterm infants. Further studies are needed to verify our findings in unstable preterm infants regarding the potential risk of cerebral injury in the prone sleeping position in early postnatal life.


title: Evaluation of the spatter-reduction effectiveness and aerosol containment of eight dry-field isolation techniques.

text: OBJECTIVE The novel coronavirus that was first identified in Wuhan, China, in December 2019, created a pandemic that has the potential to change the paradigm of health care delivery. Of interest to the dental community is the presence of SARS-CoV-2 in the saliva of the affected patients that can potentially cause transmission of COVID-19 via droplets. The highly infectious nature of the pathogen has created a sense of urgency and a need for extra caution to prevent the spread of the disease and the potential infection of patients and the entire dental team. Spatter consists of droplets up to 50 µm in size that are effectively stopped by barriers such as gloves, masks, and gowns. Aerosols are defined as droplet particles smaller than 5 µm that can remain airborne for extended periods and that have been reported to be significant in viral respiratory infections. In this study, aerosol represented by particulate matter with a size of 2.5 µm (PM2.5) was measured. METHOD AND MATERIALS Eight dry-field isolation methods were tested in a setup that included a realistic dental manikin and a high-speed handpiece that generated air-water spray. Environmental noise generated by the suction devices, suction flow rate of each setup, and the amount of environmental spatter and aerosols, were measured. RESULTS The experimental setups showed significant variability in the suction flow rate, but this was not correlated to the level of sound generated. Some experimental setups caused a short-term level of noise that exceeded the NIOSH (National Institute for Occupational Safety and Health) guidelines and were close to the OSHA (Occupational Safety and Health Administration) recommended thresholds. It is also worth noting that the variability in the flow rate is not reflected in the efficacy of the experimental setups to mitigate spatter. All experimental setups, except the IsoVac system, provided statistically significantly better spatter mitigation compared to the control. All experimental setups also were efficient in mitigating aerosols compared with the positive control (P < .0001) and most systems yielded results similar to the negative control ambient PM (P > .05). CONCLUSION Results indicate that spatter reduction was significantly better amongst the setups in which an additional high-volume evacuator (HVE) line was used. All setups were efficient at mitigating PM2.5 aerosols in comparison to the control. The conclusions of this study should be interpreted with caution, and additional mitigation techniques consistent with the Centers for Disease Control and Prevention recommendations must be implemented in dental practices.


title: Asymptomatic COVID-19: What the Neuroradiologist Needs to Know about Pulmonary Manifestations.

text: Coronavirus disease 2019 (COVID-19) is an infectious disease with a high asymptomatic incidence. Asymptomatic infections within a population will inevitably lead to diagnosis via unrelated medical imaging. We report the case of an asymptomatic patient undergoing a spine CT examination for trauma who was incidentally found to have lung abnormalities later confirmed to be COVID-19. We aim to familiarize neuroradiologists with the spectrum of COVID-19 pulmonary manifestations that are likely to be observed on neck and spine CT imaging.


title: Stent-supported aneurysm coiling: a literature survey of treatment and follow-up.

text: BACKGROUND AND PURPOSE Stent-supported aneurysm coiling has been utilized with increasing frequency over the past few years, particularly for addressing treatment of complex and wide-neck aneurysms. A sizable body of literature describing various experiences with stent-supported coiling now exists. The purpose of this research was to carry out a comprehensive literature survey of stent-supported aneurysm coiling. MATERIALS AND METHODS A survey of papers reporting results with stent-assisted aneurysm coiling through January 2011 was conducted to identify the prevalence of stent-related and other complications, occlusion rates, and clinical and angiographic follow-up data. RESULTS Thirty-nine articles with 1517 patients met inclusion criteria for initial analysis, follow-up analysis, or both. Overall, 9% of cases were confounded by a technical stent-related issue, including 4% failure of deployment. The overall procedure complication rate was 19%, with periprocedural mortality of 2.1%. Approximately 45% of aneurysms were completely occluded at first treatment session, increasing to 61% on follow-up. Approximately 3.5% in-stent stenosis and 0.6% stent occlusion were observed at angiographic follow-up. Delayed stroke or transient ischemic attack was reported in 3% of subjects. Within a subset of articles, the incidence of stent-related issues in the first 10 patients was significantly higher than in subsequent subjects, supporting the notion of a procedural "learning curve." CONCLUSIONS In experienced hands, the morbidity of stent-supported coiling is somewhat higher compared with "traditional" coiling. As might be expected, execution of the procedure appears improved with experience. Complete occlusion rates remain somewhat low. More and longer term angiographic follow-up information is needed to understand delayed stent-related issues and to better define the durability of treatment.


docid: pemxfsgi

title: Airborne transmission of disease in hospitals.

text: Hospital-acquired infection (HAI) is an important public health issue with unacceptable levels of morbidity and mortality, over the last 5 years. Disease can be transmitted by air (over large distances), by direct/indirect contact or a combination of both routes. While contact transmission of disease forms the majority of HAI cases, transmission through the air is harder to control, but one where the engineering sciences can play an important role in limiting the spread. This forms the focus of this themed volume. In this paper, we describe the current hospital environment and review the contributions from microbiologists, mechanical and civil engineers, and mathematicians to this themed volume on the airborne transmission of infection in hospitals. The review also points out some of the outstanding scientific questions and possible approaches to mitigating transmission.


title: 'Do not resuscitate me in Barbados'.

text: New ways of encouraging discussion and education around the topic of do not attempt cardiopulmonary resuscitation (DNACPR) decisions in healthcare can prove challenging. Cardiopulmonary resuscitation is still portrayed as an intervention that is successful even in people with multiple long-term conditions. In 2020, during the first months of the COVID-19 pandemic, a letter from a palliative care doctor to his patient was read out as part of an online campaign entitled #ReadALetter, organised by the organisation Letters Live. The letter addresses misconceptions regarding DNACPR decisions and encourages thoughtful dialogue. In particular, it promotes an individualised approach for clinicians, and investigates one patient's journey: from initially rejecting the concept, to later on fully embracing it as part of his holistic care. A journey that took him to Barbados, amongst other places.


title: Suicide risk during the lockdown due to coronavirus disease (COVID-19) in Colombia.

text: The study aimed to estimate the high suicide risk during the COVID-19 lockdown in the Colombian population. A total of 700 adults aged between 18 and 76 years (M = 37.1, SD = 12.7; 68.0% women) completed an online questionnaire. Findings showed that 7.6% of participants reported a high suicide risk. High suicide risk was associated with high perceived stress related to COVID-19, risk of depressive episode, and insomnia. Our study suggests that 1 out of 13 Colombians in a non-probability sample reports a high suicide risk during COVID-19. Findings need to be corroborated in a representative sample of Colombians.


title: Targeted development of specific biomarkers of endometrial stromal cell differentiation using bioinformatics: the IFITM1 model.

text: When classifying cellular uterine mesenchymal neoplasms, histological distinction of endometrial stromal from smooth muscle neoplasms can be difficult. The only widely established marker of endometrial stromal differentiation, CD10, has marginal specificity. We took a bioinformatics approach to identify more specific markers of endometrial stromal differentiation by searching the Human Protein Atlas, a public database of protein expression profiles. After screening the database using different methods, interferon-induced transmembrane protein 1 (IFITM1) was selected for further analysis. Immunohistochemistry for IFITM1 was performed using tissue sections from the selected cases of proliferative endometrium (22), secretory endometrium (6), inactive endometrium (19), adenomyosis (10), conventional leiomyoma (11), cellular leiomyoma (16), endometrial stromal nodule (2), low-grade endometrial stromal sarcoma (16), high-grade endometrial stromal sarcoma (2) and undifferentiated uterine sarcoma (2). Stained slides were scored in terms of intensity and distribution. Normal endometrial samples uniformly showed diffuse and strong IFITM1 staining. Endometrial stromal neoplasms, particularly low-grade endometrial stromal sarcoma, showed higher IFITM1 expression compared with smooth muscle neoplasms (P<0.0001). IFITM1 immunohistochemistry has high sensitivity and specificity, particularly in the distinction between low-grade endometrial stromal sarcoma and leiomyoma (81.2 and 86.7%, respectively). Our results indicate that IFITM1 is a sensitive and specific marker of endometrial stromal differentiation across the spectrum from proliferative endometrium to metastatic stromal sarcoma. IFITM1 is a potential valuable addition to immunohistochemical panels used in the diagnosis of cellular mesenchymal uterine tumors. Further studies with larger number of cases are necessary to corroborate this impression and determine the utility of IFITM1 in routine practice. This study is a clear example of how bioinformatics, particularly tools for mining genomic and proteomic databases, can enhance and accelerate biomarker development in diagnostic pathology.


title: Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke.

text: IMPORTANCE Randomized clinical trials suggest the benefit of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke is time dependent. However, modest sample sizes have limited characterization of the extent to which onset to treatment (OTT) time influences outcome; and the generalizability of findings to clinical practice is uncertain. OBJECTIVE To evaluate the degree to which OTT time is associated with outcome among patients with acute ischemic stroke treated with intraveneous tPA. DESIGN, SETTING, AND PATIENTS Data were analyzed from 58,353 patients with acute ischemic stroke treated with tPA within 4.5 hours of symptom onset in 1395 hospitals participating in the Get With The Guidelines-Stroke Program, April 2003 to March 2012. MAIN OUTCOMES AND MEASURES Relationship between OTT time and in-hospital mortality, symptomatic intracranial hemorrhage, ambulatory status at discharge, and discharge destination. RESULTS Among the 58,353 tPA-treated patients, median age was 72 years, 50.3% were women, median OTT time was 144 minutes (interquartile range, 115-170), 9.3% (5404) had OTT time of 0 to 90 minutes, 77.2% (45,029) had OTT time of 91 to 180 minutes, and 13.6% (7920) had OTT time of 181 to 270 minutes. Median pretreatment National Institutes of Health Stroke Scale documented in 87.7% of patients was 11 (interquartile range, 6-17). Patient factors most strongly associated with shorter OTT included greater stroke severity (odds ratio [OR], 2.8; 95% CI, 2.5-3.1 per 5-point increase), arrival by ambulance (OR, 5.9; 95% CI, 4.5-7.3), and arrival during regular hours (OR, 4.6; 95% CI, 3.8-5.4). Overall, there were 5142 (8.8%) in-hospital deaths, 2873 (4.9%) patients had intracranial hemorrhage, 19,491 (33.4%) patients achieved independent ambulation at hospital discharge, and 22,541 (38.6%) patients were discharged to home. Faster OTT, in 15-minute increments, was associated with reduced in-hospital mortality (OR, 0.96; 95% CI, 0.95-0.98; P < .001), reduced symptomatic intracranial hemorrhage (OR, 0.96; 95% CI, 0.95-0.98; P < .001), increased achievement of independent ambulation at discharge (OR, 1.04; 95% CI, 1.03-1.05; P < .001), and increased discharge to home (OR, 1.03; 95% CI, 1.02-1.04; P < .001). CONCLUSIONS AND RELEVANCE In a registry representing US clinical practice, earlier thrombolytic treatment was associated with reduced mortality and symptomatic intracranial hemorrhage, and higher rates of independent ambulation at discharge and discharge to home following acute ischemic stroke. These findings support intensive efforts to accelerate hospital presentation and thrombolytic treatment in patients with stroke.


title: [Intestinal anastomoses and techniques in the lower gastrointestinal tract].

text: Surgery of the lower gastrointestinal tract includes segmental resections for benign colorectal diseases and radical resections for treating colorectal cancer performed under elective and emergency conditions. The most important part of the surgical procedure is the reconstruction of the physiological intestinal continuity by anastomosis. At present laparoscopic surgery has widened the array of different suturing and stapling techniques. The effectiveness of manual and stapled anastomoses depends on the expertise of the surgeon. However, skillful preparation of the hand-sutured technique is essential.


Should patients stop their biologic treatment during the COVID-19 pandemic.


title: The COVID-19 pandemic: is there a role for magnesium? Hypotheses and perspectives.

text: More and more studies are accumulating about COVID-19. Some aspects of the pathogenesis of the disease recall events occurring in Mg deficiency, such as a drop of T cells, increased plasma concentration of inflammatory cytokines, and endothelial dysfunction. We hypothesize that a low Mg status, which is rather common, might foment the transition from mild to critical clinical manifestations of the disease. Epidemiological, clinical, and fundamental research is needed to clarify the potential role of Mg deficiency in COVID-19.


docid: nqonweef

title: Radiolabeled cetuximab: dose optimization for epidermal growth factor receptor imaging in a head-and-neck squamous cell carcinoma model.

text: Noninvasive imaging of the epidermal growth factor receptor (EGFR) in head-and-neck squamous cell carcinoma could be of value to select patients for EGFR-targeted therapy. We assessed dose optimization of (111) Indium-DTPA-cetuximab ((111) In-cetuximab) for EGFR imaging in a head-and-neck squamous cell carcinoma xenograft model. (111) In-cetuximab slowly internalized into FaDu cells in vitro, amounting to 1.0 × 10(4) molecules cetuximab per cell after 24 hr (15.8% of added activity). In nude mice with subcutaneous FaDu xenograft tumors, a protein dose escalation study with (111) In-cetuximab showed highest specific accumulation in tumors at protein doses between 1 and 30 μg per mouse (mean tumor uptake 33.1 ± 3.1%ID/g, 3 days postinjection (p.i.)). The biodistribution of (111) In-cetuximab and (125) I-cetuximab was determined at 1, 3 and 7 days p.i. at optimal protein dose. Tumor uptake was favorable for (111) In-cetuximab compared to (125) I-cetuximab. With pixel-by-pixel analysis, good correlations were found between intratumoral distribution of (111) In-cetuximab as determined by autoradiography and EGFR expression in the same tumor sections as determined immunohistochemically (mean r = 0.74 ± 0.14; all correlations p < 0.0001). Micro Single Photon Emission Computed Tomography (MicroSPECT) scans clearly visualized FaDu tumors from 1 day p.i. onward and tumor-to-background contrast increased until 7 days p.i. (tumor-to-liver ratios 0.58 ± 0.24, 3.42 ± 0.66, 8.99 ± 4.66 and 16.33 ± 11.56, at day 0, day 1, day 3 and day 7 p.i., respectively). Our study suggests that, at optimal cetuximab imaging dose, (111) In-cetuximab can be used for visualization of EGFR expression in head-and-neck squamous cell carcinoma using SPECT.


title: Clinical Pathway for Management of Suspected or Positive Novel Coronavirus-19 Patients With ST-Segment Elevation Myocardial Infarction.

text: Novel coronavirus-19 disease (COVID-19) is an escalating, highly infectious global pandemic that is quickly overwhelming healthcare systems. This has implications on standard cardiac care for ST-elevation myocardial infarctions (STEMIs). In the setting of anticipated resource scarcity in the future, we are forced to reconsider fibrinolytic therapy in our management algorithms. We encourage clinicians to maintain a high level of suspicion for STEMI mimics, such as myopericarditis which is a known, not infrequent, complication of COVID-19 disease. Herein, we present a pathway developed by a multidisciplinary panel of stakeholders at NewYork-Presbyterian/Columbia University Irving Medical Center for the management of STEMI in suspected or confirmed COVID-19 patients.


Madagascar's mysterious, murderous cats identified.


A Case Series of the 2019 Novel Coronavirus (SARS-CoV-2) in Three Febrile Infants in New York.


title: Population pharmacokinetic-pharmacodynamic model of propofol in adolescents undergoing scoliosis surgery with intraoperative wake-up test: a study using Bispectral index and composite auditory evoked potentials as pharmacodynamic endpoints.

text: BACKGROUND In adolescents limited data are available on the pharmacokinetics (PK) and pharmacodynamics (PD) of propofol. In this study we derived a PK-PD model for propofol in adolescents undergoing idiopathic scoliosis surgery with an intraoperative wake-up test with reinduction of anesthesia using both Bispectral Index (BIS) and composite A-line ARX index (cAAI) as endpoints. METHODS Fourteen adolescents (9.8-20.1 years) were evaluated during standardized propofol-remifentanil anesthesia for idiopathic scoliosis surgery with an intraoperative wake-up test with reinduction of anesthesia. BIS and cAAI were continuously measured and blood samples collected. A propofol PKPD model was developed using NONMEM. RESULTS The time courses of propofol concentrations, BIS and cAAI values during anesthesia, intra-operative wakeup and reduction of anesthesia were best described by a two-compartment PK model linked to an inhibitory sigmoidal Emax PD model. For the sigmoidal Emax model, the propofol concentration at half maximum effect (EC50) was 3.51 and 2.14 mg/L and Hill coefficient 1.43 and 6.85 for BIS and cAAI, respectively. The delay in PD effect in relation to plasma concentration was best described by a two compartment effect-site model with a keo of 0.102 min- 1, ke12 of 0.121 min- 1 and ke21 of 0.172 min- 1. CONCLUSIONS A population PKPD model for propofol in adolescents was developed that successfully described the time course of propofol concentration, BIS and cAAI in individuals upon undergoing scoliosis surgery with intraoperative wake-up test and reinduction of anesthesia. Large differences were demonstrated between both monitors. This may imply that BIS and cAAI measure fundamentally different endpoints in the brain.


title: Prognostic significance of cardiac injury in COVID-19 patients with and without coronary artery disease.

text: OBJECTIVE COVID-19 is a disease with high mortality, and risk factors for worse clinical outcome have not been well-defined yet. The aim of this study is to delineate the prognostic importance of presence of concomitant cardiac injury on admission in patients with COVID-19. METHODS For this multi-center retrospective study, data of consecutive patients who were treated for COVID-19 between 20 March and 20 April 2020 were collected. Clinical characteristics, laboratory findings and outcomes data were obtained from electronic medical records. In-hospital clinical outcome was compared between patients with and without cardiac injury. RESULTS A total of 607 hospitalized patients with COVID-19 were included in the study; the median age was 62.5 ± 14.3 years, and 334 (55%) were male. Cardiac injury was detected in 150 (24.7%) of patients included in the study. Mortality rate was higher in patients with cardiac injury (42% vs. 8%; P < 0.01). The frequency of patients who required ICU (72% vs. 19%), who developed acute kidney injury (14% vs. 1%) and acute respiratory distress syndrome (71%vs. 18%) were also higher in patients with cardiac injury. In multivariate analysis, age, coronary artery disease (CAD), elevated CRP levels, and presence of cardiac injury [odds ratio (OR) 10.58, 95% confidence interval (CI) 2.42-46.27; P < 0.001) were found to be independent predictors of mortality. In subgroup analysis, including patients free of history of CAD, presence of cardiac injury on admission also predicted mortality (OR 2.52, 95% CI 1.17-5.45; P = 0.018). CONCLUSION Cardiac injury on admission is associated with worse clinical outcome and higher mortality risk in COVID-19 patients including patients free of previous CAD diagnosis.


docid: lyorqurb

title: Clinical Research of the Application of Bone Turnover Markers in Monitoring the Short-Term Therapeutic Efficacy of Vitamin D in Postmenopausal Osteoporotic women in Harbin, China.

text: BACKGROUND The incidence of osteoporosis (OP) is increasing year by year. researches have shown that there was an intense link between the vitamin D (VitD) status and the efficacy of zoledronate (ZOL) in patients with osteoporosis. Since VitD is related to the geogen, its promotion effect on zoledronate has regional specificity. AIM Combining dual-energy X-ray and bone turnover markers (BTM) to explore the VitD level in postmenopausal osteoporosis patients in Harbin and monitor its effect on the anti-osteoporosis effect of ZOL. METHODS A total of 120 patients with postmenopausal osteoporosis (PMO) were enrolled .These patients were divided into two groups with 25(OH)D levels = 10ng/ml as a critical point, and each group was randomly divided into experimental groups and control groups). All of the patients were conducted 5 mg ZOL. Then the experimental group was given calcitriol and calcium carbonate, and the control group was only given calcium carbonate. BTM were measured at baseline, 24h, 3 months and 6 months. We also measured bone mineral density (BMD) of bilateral hips (TH BMD) and lumbar spine (LS BMD) at baseline and 6 months. RESULTS The VitD deficiency rates of the patients enrolled were 84.1%. There was an inverse relationship between the baseline level of VitD and the serum levels of P1NP / β-CTX, (r=-0.452,p=0.00; r=-0.225, p=0.01). Comparing with baseline, the level of serum P1NP,β-CTX in each group declined significantly after the treatment (P<0.05). The mean decreasing rates of P1NP and β-CTX in the both experimental groups were significantly higher than that of the corresponding control groups at the same time point (P<0.05), after 6 months of medication. Both TH BMD and LS BMD at 6 months increased significantly. The increase rate of LS BMD in the high VitD experimental group was significantly higher than the other three groups (P<0.05), the increase rates of TH BMD in the low VitD control group were significantly lower than the other three groups (P<0.05). CONCLUSIONS The levels of serum VitD in the patients enrolled in this study were generally low. VitD could increase the therapeutic effect of ZOL on osteoporosis.


title: Validated methods to identify patients with asthma-COPD overlap in healthcare databases: a systematic review protocol.

text: INTRODUCTION Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is characterised by patients presenting symptoms of both asthma and COPD. Many efforts have been made to validate different methods of identifying asthma-COPD overlap cases based on symptoms, spirometry and medical history in epidemiological studies using healthcare databases. There are various coding algorithm strategies that can be used and selection depends on targeted validation. The primary objectives of this systematic review are to identify validated methods (or algorithms) that identify patients with ACO from healthcare databases and summarise the reported validity measures of these methods. METHODS MEDLINE, EMBASE databases and the Web of Science will be systematically searched by using appropriate search strategies that are able to identify studies containing validated codes and algorithms for the diagnosis of ACO in healthcare databases published, in English, before October 2018. For each selected study, we require the presence of at least one test measure (eg, sensitivity, specificity etc). We will also include studies, in which the validated algorithm is compared with an external reference standard such as questionnaires completed by patients or physicians, medical charts review, manual review or an independent second database. For all selected studies, a uniform table will be created to summarise the following vital information: name of author, publication year, country, data source, population, clinical outcome, algorithms, reference standard method of validation and characteristics of the test measure used to determine validity. PROSPERO REGISTRATION NUMBER CRD42018087472.


title: Methemoglobinemia in Patient with G6PD Deficiency and SARS-CoV-2 Infection.

text: We report a case of intravascular hemolysis and methemoglobinemia, precipitated by severe acute respiratory syndrome coronavirus 2 infection, in a patient with undiagnosed glucose-6-phosphate dehydrogenase deficiency. Clinicians should be aware of this complication of coronavirus disease as a cause of error in pulse oximetry and a potential risk for drug-induced hemolysis.


title: Is behavioural plasticity consistent across different environmental gradients and through time?

text: Despite accumulating evidence for individual variation in behavioural plasticity, there is currently little understanding of the causes and consequences of this variation. An outstanding question is whether individual reaction norm (RN) slopes are consistent across different environmental variables-that is, whether an individual that is highly responsive to one environmental variable will be equally responsive to a second variable. Another important and related question is whether RNs are themselves consistently expressed through time or whether they are simply state dependent. Here, we quantified individual activity rates of zebrafish in response to independent manipulations of temperature and food availability that were repeated in discrete 'bursts' of sampling through time. Individuals that were thermally responsive were not more responsive to food deprivation, but they did exhibit greater unexplained variation. Individual RN slopes were consistent (repeatable) over time for both temperature (Rslope = 0.92) and food deprivation responses (Rslope = 0.4), as were mean activity rates in the standard environment (Rintercept = 0.83). Despite the high potential lability of behaviour, we have demonstrated consistency of behavioural RN components and identified potential energetic constraints leading to high consistency of thermal RNs and low consistency of food deprivation RNs.


Religious cliché and COVID-19 management: a barrier for physicians.


A novel tourniquet technique for transient pulmonary artery occlusion during video-assisted thoracoscopic surgery.


title: Hemostasis and other benefits of fibrin sealants/glues in spine surgery beyond cerebrospinal fluid leak repairs.

text: BACKGROUND Fibrin sealants (FS)/glues (FG) are primarily utilized in spinal surgery to either strengthen repairs of elective (e.g., intradural tumors/pathology) or traumatic cerebrospinal fluid (CSF) fistulas. Here, additional roles/benefits of FS/FG in spine surgery are explored; these include increased hemostasis, reduction of scar, reduction of the risk of infection if impregnated with antibiotics, and its application to restrict diffusion and limit some of the major complications attributed to the controversial "off-label" use of bone morphogeneitc protein (rhBMP-2/INFUSE). METHODS We reviewed multiple studies, focusing not just on the utility of FS/FG in the treatment of CSF fistulas, but on its other applications. RESULTS FS/FG have been primarily used to supplement elective/traumatic dural closure in spinal surgery. However, FS/FG also contribute to; hemostasis, reducing intraoperative/postoperative bleeding/transfusion requirements, length of stay (LOS)/costs, reduced postoperative scar/radiculitis, and infection when impregnated with antibiotics. Nevertheless, one should seriously question whether FS/FG should be applied to prevent diffusion and limit major complications attributed to the "off-label" use of BMP/INFUSE (e.g., limit/prevent heterotopic ossification, dysphagia/respiratory decompensation, and new neurological deficits). CONCLUSIONS FS/FG successfully supplement watertight dural closure following elective (e.g., intradural tumor) or traumatic CSF fistulas occurring during spinal surgery. Additional benefits include: intraoperative hemostasis with reduced postoperative drainage, reduced transfusion requirements, reduced LOS, cost, scar, and prophylaxis against infection (e.g., impregnated with antibiotics). However, one should seriously question whether FS/FG should be used to contain the diffusion of BMP/INFUSE and limit its complications when utilized "off-label".


title: Imaging investigation of intracranial arterial dissecting aneurysms by using 3 T high-resolution MRI and DSA: from the interventional neuroradiologists' view.

text: OBJECTIVES The purpose of this study was to investigate vessel wall imaging features combined with the luminal shapes of intracranial dissecting aneurysms (IDAs) by using 3 Tesla (3T) high-resolution magnetic resonance imaging (MRI) and digital subtraction angiography (DSA). METHODS Sixty-seven patients with 76 IDAs were consecutively enrolled in the study from December 2011 to May 2013. DSA was performed to diagnose an IDA and to categorize its angiography patterns into either aneurysmal dilation, steno-occlusive, combined, or unclassifiable. Images of 3T high-resolution MRI were used to evaluate arterial wall imaging features of each lesion. Chi-squared tests were used for statistical analyses. RESULTS Aneurysmal dilation (51 of 76, [67%]) was the most common angiography pattern of IDAs, followed by the combined pattern (20 of 76, [26%]). Seven percent (five of 76) of IDAs showed steno-occlusive (n = 3) and unclassifiable (n = 2) angiography patterns, in which intramural hematomas were detected in the arterial wall without luminal connection. Intimal flaps (32 of 76, [42%]), double-lumen sign (38 of 76, [50%]) and intramural hematomas (46 of 76, [61%]) were recognized as the characteristic features of dissection by high-resolution MRI. Intramural hematomas occurred more frequently in the combined patterns group (16 of 20, [80 %]) than in the aneurysmal dilation group (25 of 51, [49%]) (P = .017), while the occurrence of intimal flaps and double-lumen sign did not differ between angiographic patterns (P > .05). CONCLUSIONS 3T high-resolution MRI combined with DSA offered clear visualization of vessel wall features and accurate assessment of the vessel lumen in IDAs. This combined approach would be highly useful for understanding the underlying pathological status of IDAs and in guiding treatment choices.


title: Interleukin-12 (IL-12), but not IL-23, deficiency ameliorates viral encephalitis without affecting viral control.

text: The relative contributions of interleukin-12 (IL-12) and IL-23 to viral pathogenesis have not been extensively studied. IL-12p40 mRNA rapidly increases after neurotropic coronavirus infection. Infection of mice defective in both IL-12 and IL-23 (p40(-/-)), in IL-12 alone (p35(-/-)), and in IL-23 alone (p19(-/-)) revealed that the symptoms of coronavirus-induced encephalitis are regulated by IL-12. IL-17-producing cells never exceeded background levels, supporting a redundant role of IL-23 in pathogenesis. Viral control, tropism, and demyelination were all similar in p35(-/-), p19(-/-), and wild-type mice. Reduced morbidity in infected IL-12 deficient mice was also not associated with altered recruitment or composition of inflammatory cells. However, gamma interferon (IFN-gamma) levels and virus-specific IFN-gamma-secreting CD4 and CD8 T cells were all reduced in the central nervous systems (CNS) of infected p35(-/-) mice. Transcription of the proinflammatory cytokines IL-1beta and IL-6, but not tumor necrosis factor, were initially reduced in infected p35(-/-) mice but increased to wild-type levels during peak inflammation. Furthermore, although transforming growth factor beta mRNA was not affected, IL-10 was increased in the CNS in the absence of IL-12. These data suggest that IL-12 does not contribute to antiviral function within the CNS but enhances morbidity associated with viral encephalitis by increasing the ratio of IFN-gamma to protective IL-10.


Phylogenetic analysis of avian infectious bronchitis virus isolates from Morocco: a retrospective study (1983 to 2014).


title: [Membranes in pre-implantation surgery].

text: The use of membranes in pre-implantation surgery is part of the guided bone regeneration (GBR) concept, one of the usual bone augmentation techniques. Membranes for GBR procedures have two main uses: a mechanical function to maintain bone regeneration space and a physical function as cellular barrier. The goal is to promote colonization of the regeneration space located under the membrane, by osteogenic cells from the residual bone walls. GBR was the subject of numerous publications and protocols since its first use in the 1980s. These protocols are mainly supported by team experience and the level of evidence is poor. Few indications are truly validated. The goal of our study was to review the recent literature on membrane use for pre-implantations surgery, and, in the absence of any consensus, to provide some arguments for their rational use.


title: Midterm Outcomes of Gastric Pouch Resizing for Weight Regain After Roux-en-Y Gastric Bypass.

text: PURPOSE Resizing of the gastric pouch, with eventually resizing of the gastrojejunal anastomosis, has been proposed as revisional procedure to treat weight regain after Roux-en-Y gastric bypass (RYGB), in patients with large gastric pouch and/or large gastrojejunal (GJ) anastomosis. The aim of this study is to determine the midterm results and the safety of laparoscopic resizing of the gastric pouch after RYGB in cases where gastric pouch is > 200 ml and/or GJ anastomosis > 20 mm. MATERIALS AND METHODS All patients who underwent gastric pouch resizing between January 2009 and December 2016 were retrospectively reviewed from a prospective database. The gastric pouch was resized to a volume of 30-40 ml. RESULTS A total of 48 patients had gastric pouch resizing after RYGB. The mean initial BMI was 42.9 ± 4.8 kg/m2. Perioperative morbidity was 8.3% in this series. Mean follow-up was 5.4 years. The mean BMI was 30.0 ± 7.3 kg/m2 at 1 year, 30.0 ± 6.0 kg/m2 at 3 years, and 30.9 ± 5.7 kg/m2 at 5 years. Mean %EBMIL at 1-, 3-, and 5-year follow-up was 51.9%, 55.1%, and 39%, respectively, in 48% follow-up rate. The obesity-related comorbidities disappeared in 67.3% of cases at maximum follow-up. CONCLUSIONS In carefully selected patients with gastric pouch size > 200 ml and/or GJ anastomosis > 20 mm, and after extensive preoperative evaluation, gastric pouch resizing is a potentially effective option to treat weight regain due to anatomical factors after RYGB, with complication rate of 8%.


docid: ivvouuvg

title: Influence of type of mesh fixation in endoscopic totally extraperitoneal hernia repair (TEP) on long-term quality of life.

text: INTRODUCTION Laparoscopic total extraperitoneal mesh repair (TEP) of inguinal hernia has become well accepted with low recurrence and high patient satisfaction rates. However, inguinal pain has also been reported. Source of this pain has been suggested to be the fixation method, especially the use of tacks. Introduction of fibrin glue and absorbable tacks were suggested to lower chronic pain and inguinal discomfort rates. This study analyses the different methods of fixation. PATIENTS AND METHODS 201 patients were analysed. Primary end-points were patients' satisfaction, health-related quality of life, and specific inguinal conditions (e.g. pulling, swelling, troubles at coughing). Secondary endpoints were duration of operation, length of hospital stay, and material costs. RESULTS Fibrin glue was used in 101 patients and tacks in 100 patients, in 21 of those absorbable tacks. Patients were fully satisfied with the results in more than 90%, irrespective of the fixation method. Health-related quality of life along the SF-12(®) questionnaire attested no differences. Inguinal pulling occurred significantly more often after fibrin glue (25.7 %) than after tack fixation (11 %; p = 0.026), whereas no differences in the other specific inguinal sensations occurred. CONCLUSION Mesh fixation in TEP can be performed either by tacks or by fibrin glue with similar long-term results concerning satisfaction, health-related quality of life, and pain. No advantage of fibrin glue could be found, in fact, a higher percentage of patients had inguinal pulling and burning sensations after the use of fibrin glue. The use of absorbable tacks showed no advantage.


Topic: Mesh and Prosthesis.


docid: zlrkcntg

title: Glibenclamide and Therapeutic Hypothermia Have Comparable Effect on Attenuating Global Cerebral Edema Following Experimental Cardiac Arrest.

text: BACKGROUND Cerebral edema is one of the major causes of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). A subunit of the sulfonylurea receptor 1-transient receptor potential M4 (Sur1-TRPM4) channel has been implicated in the pathogenesis of ischemia-evoked cerebral edema. In this study, we examined whether glibenclamide (GBC), a Sur1-TRPM4 channel inhibitor, attenuates cerebral edema following CA/CPR and further examined the efficacy of GBC combined with therapeutic hypothermia. METHODS Isoflurane-anesthetized adult male wild-type C57Bl/6 mice subjected to 7-min CA/CPR were randomized into five groups: sham operation, control with normothermia, GBC with normothermia, control with hypothermia, and GBC with hypothermia. The primary outcome was to evaluate regional brain water content; the secondary outcome was to measure blood glucose level, Sur1-TRPM4 expression, and pro-inflammatory factor expression. RESULTS Compared with normothermia, GBC treatment or hypothermia significantly attenuated brain water content in mice subjected to CA/CPR. GBC combined with hypothermia had no additional effects on attenuating cerebral edema. Pro-inflammatory factor messenger RNA expression (TNF-α and IL-6), NFκβ activation, and SUR1-TRPM4 levels were upregulated after CA/CPR. Compared with normothermia, hypothermia, but not GBC, partly suppressed these factors' expression. CONCLUSIONS GBC attenuated cerebral edema following CA/CPR by blocking Sur1-TRPM4 channels upregulated by CA insult. The effect of GBC was comparable with that of therapeutic hypothermia alone. These results suggest that GBC is an alternative approach for treating CA-evoked cerebral edema.


title: EML4-ALK fusion variant V3 is a high-risk feature conferring accelerated metastatic spread, early treatment failure and worse overall survival in ALK+ non-small cell lung cancer.

text: In order to identify anaplastic lymphoma kinase-driven non-small cell lung cancer (ALK+ NSCLC) patients with a worse outcome, who might require alternative therapeutic approaches, we retrospectively analyzed all stage IV cases treated at our institutions with one of the main echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variants V1, V2 and V3 as detected by next-generation sequencing or reverse transcription-polymerase chain reaction (n = 67). Progression under tyrosine kinase inhibitor (TKI) treatment was evaluated both according to Response Evaluation Criteria in Solid Tumors (RECIST) and by the need to change systemic therapy. EML4-ALK fusion variants V1, V2 and V3 were found in 39%, 10% and 51% of cases, respectively. Patients with V3-driven tumors had more metastatic sites at diagnosis than cases with the V1 and V2 variants (mean 3.3 vs. 1.9 and 1.6, p = 0.005), which suggests increased disease aggressiveness. Furthermore, V3-positive status was associated with earlier failure after treatment with first and second-generation ALK TKI (median progression-free survival [PFS] by RECIST in the first line 7.3 vs. 39.3 months, p = 0.01), platinum-based combination chemotherapy (median PFS 5.4 vs. 15.2 months for the first line, p = 0.008) and cerebral radiotherapy (median brain PFS 6.1 months vs. not reached for cerebral radiotherapy during first-line treatment, p = 0.028), and with inferior overall survival (39.8 vs. 59.6 months in median, p = 0.017). Thus, EML4-ALK fusion variant V3 is a high-risk feature for ALK+ NSCLC. Determination of V3 status should be considered as part of the initial workup for this entity in order to select patients for more aggressive surveillance and treatment strategies.


title: Coronavirus nsp10/nsp16 Methyltransferase Can Be Targeted by nsp10-Derived Peptide In Vitro and In Vivo To Reduce Replication and Pathogenesis.

text: UNLABELLED The 5' cap structures of eukaryotic mRNAs are important for RNA stability and protein translation. Many viruses that replicate in the cytoplasm of eukaryotes have evolved 2'-O-methyltransferases (2'-O-MTase) to autonomously modify their mRNAs and carry a cap-1 structure (m7GpppNm) at the 5' end, thereby facilitating viral replication and escaping innate immune recognition in host cells. Previous studies showed that the 2'-O-MTase activity of severe acute respiratory syndrome coronavirus (SARS-CoV) nonstructural protein 16 (nsp16) needs to be activated by nsp10, whereas nsp16 of feline coronavirus (FCoV) alone possesses 2'-O-MTase activity (E. Decroly et al., J Virol 82:8071-8084, 2008, http://dx.doi.org/10.1128/JVI.00407-08; M. Bouvet et al., PLoS Pathog 6:e1000863, 2010, http://dx.doi.org/10.1371/journal.ppat.1000863; E. Decroly et al., PLoS Pathog 7:e1002059, 2011, http://dx.doi.org/10.1371/journal.ppat.1002059; Y. Chen et al., PLoS Pathog 7:e1002294, 2011, http://dx.doi.org/10.1371/journal.ppat.1002294) . In this study, we demonstrate that stimulation of nsp16 2'-O-MTase activity by nsp10 is a universal and conserved mechanism in coronaviruses, including FCoV, and that nsp10 is functionally interchangeable in the stimulation of nsp16 of different coronaviruses. Based on our current and previous studies, we designed a peptide (TP29) from the sequence of the interaction interface of mouse hepatitis virus (MHV) nsp10 and demonstrated that the peptide inhibits the 2'-O-MTase activity of different coronaviruses in biochemical assays and the viral replication in MHV infection and SARS-CoV replicon models. Interestingly, the peptide TP29 exerted robust inhibitory effects in vivo in MHV-infected mice by impairing MHV virulence and pathogenesis through suppressing virus replication and enhancing type I interferon production at an early stage of infection. Therefore, as a proof of principle, the current results indicate that coronavirus 2'-O-MTase activity can be targeted in vitro and in vivo. IMPORTANCE Coronaviruses are important pathogens of animals and human with high zoonotic potential. SARS-CoV encodes the 2'-O-MTase that is composed of the catalytic subunit nsp16 and the stimulatory subunit nsp10 and plays an important role in virus genome replication and evasion from innate immunity. Our current results demonstrate that stimulation of nsp16 2'-O-MTase activity by nsp10 is a common mechanism for coronaviruses, and nsp10 is functionally interchangeable in the stimulation of nsp16 among different coronaviruses, which underlies the rationale for developing inhibitory peptides. We demonstrate that a peptide derived from the nsp16-interacting domain of MHV nsp10 could inhibit 2'-O-MTase activity of different coronaviruses in vitro and viral replication of MHV and SARS-CoV replicon in cell culture, and it could strongly inhibit virus replication and pathogenesis in MHV-infected mice. This work makes it possible to develop broad-spectrum peptide inhibitors by targeting the nsp16/nsp10 2'-O-MTase of coronaviruses.


COVID-19 pandemic: palliative care for elderly and frail patients at home and in residential and nursing homes.


title: Treatment of experimental aneurysms with a new liquid embolic agent and a retrievable stent: proof of concept and feasibility study.

text: BACKGROUND Occlusion of canine bifurcation and sidewall aneurysms was undertaken with a new liquid embolic agent (PHIL 35) assisted by a high-density partially retrievable stent (FRED) with preservation of the carotid artery. METHODS Three dogs were used as acute preparations for development of the technique and two were used for chronic studies lasting 90 days. In one animal we intentionally did not completely fill the aneurysm to determine the long-term results of incomplete treatment. The degree of occlusion, carotid artery compromise, and dislodgement and/or migration of embolic material in treated aneurysms were assessed. RESULTS All aneurysms planned for complete obliteration were totally occluded successfully. By design, we partially occluded one aneurysm. In this aneurysm, angiography performed at 30 days revealed less filling, but at 90 days it had persistent small residual filling. We did not detect any distal embolization during the injection and no angiographic occlusions, change in configuration, or delayed migration of the embolic material were found. In the inspected stent, no foreign material was noted. In four animals we successfully removed the stent with preservation of the integrity of the carotid artery. In the fifth we intentionally left both stents deployed. CONCLUSIONS We have developed a new treatment for cerebral aneurysms using a combination of a retrievable stent and a new liquid embolic agent.


title: Appendectomy in Germany-an analysis of a nationwide survey 2011/2012.

text: INTRODUCTION Although appendectomies are frequently performed and new procedural techniques have emerged, no nationwide analysis exists after the cessation of the German quality control in 2004. METHODS One thousand eight hundred seventy surgical hospitals in Germany were asked to answer questions anonymously concerning the size of the department, applied procedural techniques, various technical details, as well as the approach to the intraoperative finding of an inconspicuous appendix. RESULTS We received 643 questionnaires (34.4 %) for evaluation. Almost all hospitals (95.5 %) offer laparoscopic appendectomy (LA), 15.4 % offer single-port (SPA), and 2.2 % (hybrid-) NOTES technique (NA). LA is the standard procedure in 85.2 % of male and in 89.1 % for female patients. In an open procedure (OA), the appendix and mesoappendix are mostly ligated (93.8 and 91.5 %). A Veress needle and open access are employed equally for LA. In 66.6 % of LA, the appendix is divided using an Endo-GIA, the mesoappendix in 45.5 % with bipolar coagulation. Almost half of the hospitals routinely flush the site in OA and LA. In open surgery with an inconspicuous appendix but a pathological finding elsewhere in the abdomen, it is resected "en principe" in 64.7 % and in the absence of any pathological finding in 91.2 %. For laparoscopic procedures, the numbers are 54.8 and 88.4 %. CONCLUSIONS Most German hospitals perform appendectomies laparoscopically regardless of patients' gender. Usage of an Endo-GIA is widely established. SPA has not gained much acceptance, nor is NA widely used yet. In the absence of any pathological findings in particular, the macroscopically inconspicuous appendix results in an appendectomy "en principe" in most German hospitals.


title: Prognostic value of perioperative near-infrared spectroscopy during neonatal and infant congenital heart surgery for adverse in-hospital clinical events.

text: BACKGROUND Perioperative monitoring with multisite near-infrared spectroscopy (NIRS) for congenital cardiac surgery with cardiopulmonary bypass may aid in predicting adverse clinical outcomes. METHODS Forty-one consecutive neonates and infants undergoing bypass were monitored with right + left cerebral and renal NIRS. Near-infrared spectroscopy and lactate were measured at 20 time points, from baseline 1 day preoperatively, during bypass and modified ultrafiltration (MUF; 10 minutes), until 24 hours postoperatively. Adverse events were extracorporeal membrane oxygenation (ECMO)/death, prolonged intensive care unit (ICU) or length of hospital stay. RESULTS Perioperative mean renal NIRS remained higher than baseline (n = 41) as did cerebral NIRS in all undergoing biventricular repair. During bypass (n = 41), mean right and left cerebral NIRS were equal. During MUF, cerebral and renal NIRS values increased (P < .001). Cerebral NIRS and lactate inversely correlated during the first six postoperative hours. Extracorporeal membrane oxygenation /death occurred in four patients, correlating with cerebral and renal NIRS below 45% (P = .030) and 40% (P = .019) at anytime, respectively, and with mean lactate levels >9.3 mmol/L in the first postoperative 24 hours (P < .001). Among survivors, renal NIRS below 30% at any time predicted a longer ICU stay. CONCLUSIONS At bypass conclusion, 10 minutes of MUF does not adversely affect cerebral or renal NIRS. Left and right cerebral NIRS are equal, so that biparietal cerebral NIRS monitoring is probably not warranted. Perioperative cerebral and renal NIRS readings, respectively, below 45% and 40% correlate with ECMO/death and renal NIRS below 30% with prolonged ICU stay. Cerebral NIRS and lactate levels showed a strong inverse correlation during the first six postoperative hours.


title: Season of birth and primary central nervous system tumors: a systematic review of the literature with critical appraisal of underlying mechanisms.

text: PURPOSE Season of birth has been considered a proxy of seasonally varying exposures around perinatal period, potentially implicated in the etiology of several health outcomes, including malignancies. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we have systematically reviewed published literature on the association of birth seasonality with risk of central nervous system tumors in children and adults. RESULTS Seventeen eligible studies using various methodologies were identified, encompassing 20,523 cases. Eight of 10 studies in children versus four of eight in adults showed some statistically significant associations between birth seasonality and central nervous system tumor or tumor subtype occurrence, pointing to a clustering of births mostly in fall and winter months, albeit no consistent pattern was identified by histologic subtype. A plethora of perinatal factors might underlie or confound the associations, such as variations in birth weight, maternal diet during pregnancy, perinatal vitamin D levels, pesticides, infectious agents, immune system maturity, and epigenetic modifications. CONCLUSIONS Inherent methodological weaknesses of to-date published individual investigations, including mainly underpowered size to explore the hypothesis by histological subtype, call for more elegant concerted actions using primary data of large datasets taking also into account the interplay between the potential underlying etiologic factors.


title: Genetic and Pathologic Characterization of a Novel Recombinant TC07-2-Type Avian Infectious Bronchitis Virus.

text: Avian infectious bronchitis viruses (IBVs) with the TC07-2 genotype have spread rapidly in East Asia since they were first reported in China in 2007. In 2015, an IBV with the TC07-2 genotype (designated KrD1515) was isolated from layer chickens with severe respiratory symptoms in Korea. In the present study, the full-length open reading frames of the spike (S) and nucleocapsid (N) genes of the virus were sequenced and analyzed. S1 gene phylogenetic analysis revealed that the KrD1515 virus clustered with viruses with the TC07-2 genotype, whereas N gene phylogenetic analysis revealed that the KrD1515 virus clustered with Korean IBVs, but not with Chinese TC07-2 IBV. When 7-day-old specific-pathogen-free chickens were inoculated with the KrD1515 virus, they developed severe respiratory symptoms and tracheal lesions. However, there were no other clinical symptoms or pathologic lesions in other tissues. The virus was shed from the trachea for at least a week and from the cloaca for only a day. Our findings suggest that the KrD1515 virus is a recombinant virus between a Chinese TC07-2 IBV and a non-TC07-2 Korean IBV and engages in respiratory tropism in chickens.


title: Generation of cubic membranes by controlled homotypic interaction of membrane proteins in the endoplasmic reticulum.

text: Cell membranes predominantly consist of lamellar lipid bilayers. When studied in vitro, however, many membrane lipids can exhibit non-lamellar morphologies, often with cubic symmetries. An open issue is how lipid polymorphisms influence organelle and cell shape. Here, we used controlled dimerization of artificial membrane proteins in mammalian tissue culture cells to induce an expansion of the endoplasmic reticulum (ER) with cubic symmetry. Although this observation emphasizes ER architectural plasticity, we found that the changed ER membrane became sequestered into large autophagic vacuoles, positive for the autophagy protein LC3. Autophagy may be targeting irregular membrane shapes and/or aggregated protein. We suggest that membrane morphology can be controlled in cells.


Endovascular management of a giant symptomatic gluteal artery aneurysm with selective arterial embolization.


title: Development of a standardized laparoscopic caecum resection model to simulate laparoscopic appendectomy in rats.

text: BACKGROUND Laparoscopic appendectomy (LA) has become one of the most common surgical procedures to date. To improve and standardize this technique further, cost-effective and reliable animal models are needed. METHODS In a pilot study, 30 Wistar rats underwent laparoscopic caecum resection (as rats do not have an appendix vermiformis), to optimize the instrumental and surgical parameters. A subsequent test study was performed in another 30 rats to compare three different techniques for caecum resection and bowel closure. RESULTS Bipolar coagulation led to an insufficiency of caecal stump closure in all operated rats (Group 1, n = 10). Endoloop ligation followed by bipolar coagulation and resection (Group 2, n = 10) or resection with a LigaSure™ device (Group 3, n = 10) resulted in sufficient caecal stump closure. CONCLUSIONS We developed a LA model enabling us to compare three different caecum resection techniques in rats. In conclusion, only endoloop closure followed by bipolar coagulation proved to be a secure and cost-effective surgical approach.


The Ebola emergency--immediate action, ongoing strategy.


title: Clinical features, pathogenesis and immunobiology of severe acute respiratory syndrome.

text: PURPOSE OF REVIEW Severe acute respiratory syndrome coronavirus is a novel virus responsible for the major pandemic in 2003, and it re-emerged in China in late 2003 and 2004 following resumption of wild animal trading activities. Over the past few years, research work has looked into factors that may lead to super-spreading events, clinical/laboratory parameters that may differentiate severe acute respiratory syndrome from other causes of community-acquired pneumonia, the origin of severe acute respiratory syndrome, reservoir host distribution and transmission routes. A better understanding of these issues may help prevent and control future outbreaks of severe acute respiratory syndrome. RECENT FINDINGS Bats are natural reservoirs of severe acute respiratory syndrome like coronaviruses. The human and civet isolates of severe acute respiratory syndrome coronavirus nestle phylogenetically within the spectrum of severe acute respiratory syndrome like coronaviruses. Severe acute respiratory syndrome has the potential of being converted from droplet to airborne transmission. When evaluating epidemiologically high-risk patients with community-acquired pneumonia and no immediate alternative diagnosis, a low absolute neutrophil count on presentation, along with poor responses after 72 h of antibiotic treatment, may raise the index of suspicion for severe acute respiratory syndrome. SUMMARY The presence of severe acute respiratory syndrome like coronaviruses in horseshoe bats raises the possible role of bats in previous and potentially future severe acute respiratory syndrome outbreaks in human. Healthcare workers should take adequate respiratory protection in addition to strict contact and droplet precautions when managing patients with severe acute respiratory syndrome.


Home Care and Use of Telehealth Amidst the COVID-19 Pandemic.


title: A risk balancing act - tourism competition using health leverage in the COVID-19 era.

text: The world is currently in the throes of the COVID-19 pandemic which has halted the tourism sector and created an unprecedented global economic crisis. This paper will outline economics pertaining to COVID-19 lockdown, recovery and the inevitable competition that will occur between countries for tourists who will be scarcer and therefore more valuable. Countries are competing with a variety of incentives in order to lure visitors. However, persistent first waves that extend into July will put off tourists, further reducing tourism revenues and accelerate job losses and bankruptcies in affected countries. The example of Sweden's response to COVID-19 in this regard will be described. Countries that have COVID-19 relatively under control but experience second waves will also manifest negative tourism effects. Governments and public health must act in unison so as to exit lockdown as speedily and as safely as feasible, with COVID-19 rises that are as low and brief as possible in order to better compete in the tourism sector with other countries. Websites are already online comparing not only safety for travellers vis-à-vis COVID-19 but also the incentives offered by different countries in their attempts to woo tourists in this difficult market.


title: Esophageal epiphrenic diverticulum associated with diffuse esophageal spasm.

text: INTRODUCTION Esophageal diverticulum, a relatively rare condition, has been considered to be associated with motor abnormalities such as conditions that cause a lack of coordination between the distal esophagus and lower esophageal sphincter. PRESENTATION OF CASE We herein report a case of esophageal epiphrenic diverticulum associated with diffuse esophageal spasm. A 73-year-old woman presented with dysphagia and regurgitation. Imaging examinations revealed a right-sided esophageal diverticulum located about 10cm above the esophagogastric junction. High-resolution manometry revealed normal esophageal motility. However, 24-h pH monitoring revealed continuous acidity due to pooling of residue in the diverticulum. An esophageal epiphrenic diverticulum was diagnosed and resected thoracoscopically. Her dysphagia recurred 2 years later. High-resolution manometry revealed diffuse esophageal spasm. DISCUSSION The diverticulum in the present case was considered to have been associated with diffuse esophageal spasm. The motility disorder was likely not identified at the first evaluation. CONCLUSION In this case, the patient's symptoms spontaneously resolved without any treatment; however, longer-term follow-up is needed.


title: Colectomies in children with inflammatory bowel disease: a national referral centre experience.

text: OBJECTIVES Few studies have reported on the utility and efficacy of laparoscopic colectomy in the paediatric population. We aim to compare the characteristics and outcomes of children with inflammatory bowel disease (IBD) who underwent open vs laparoscopic treatment at our centre. METHODS A 10-year retrospective review was performed. Collected data included demographics, indication for surgery, operative characteristics, histopathology results, post-operative course and peri-operative complications. RESULTS A total of 58 patients underwent subtotal colectomy for IBD, with 38 laparoscopic procedures. The cohort included 33 males and 25 females with a mean age at surgery of 12.9 ± 3.3 years. The pre-operative diagnosis was ulcerative colitis in n = 41, Crohn's disease in n = 5 and indeterminate colitis in n = 11. There was an 84.2% concordance between the pre-operative and the post-operative histological diagnoses. Overall, 34 (58.6%) patients had complications, of which 19 (32.7%) patients required return to theatre. The complication rate was significantly smaller for laparoscopic compared to open procedures (42.1% vs 75%) as well as for elective compared with emergency colectomies (38.4% vs 75%). Four patients (10.5%) required conversion to open approach. CONCLUSIONS Laparoscopic approach is feasible and safe in most paediatric patients with IBD and has a lower complication rate and better recovery than open procedures, especially when performed in an elective setting.


title: Adaptive support ventilation: an appropriate mechanical ventilation strategy for acute respiratory distress syndrome?

text: BACKGROUND Adaptive support ventilation (ASV) allows the clinician to set a maximum plateau pressure (PP) and automatically adjusts tidal volume to keep PP below the set maximum. METHODS ASV was compared to a fixed tidal volume of 6 ml/kg. ASV determined the respiratory rate and tidal volume based on its algorithms. Maximum airway pressure limit was 28 cm H2O in ASV. Six sets of lung mechanics were simulated for two ideal body weights: 60 kg, Group I; 80 kg, Group II. Positive end expiratory pressure was 8, 12, and 16 cm H2O, and target minute volume 120%, 150%, and 200% of predicted minute volume. RESULTS ASV "sacrificed" tidal volume and minute ventilation to maintain PP in 9 (17%) of 54 scenarios in Group I and 20 (37%) of 54 scenarios in Group II. In Group I, the number of scenarios with PP of 28 cm H2O or more was 14 for ASV (26%) and 19 for 6 ml/kg (35%). In these scenarios, mean PP were ASV 28.8 +/- 0.86 cm H2O (min 28, max 30.3) and 6 ml/kg 33.01 +/- 3.48 cm H2O (min 28, max 37.8) (P = 0.000). In group II, the number of scenarios PP of 28 cm H2O or more was 10 for ASV (19%) and 21 for 6 ml/kg (39%). In these cases, mean PP values were ASV 28.78 +/- 0.54 cm H2O (min 28, max 29.6) and 6 ml/kg 32.66 +/- 3.37 cm H2O (min 28.2, max 38.2) (P = 0.000). CONCLUSION In a lung model with varying mechanics, ASV is better able to prevent the potential damaging effects of excessive PP (greater than 28 cm H2O) than a fixed tidal volume of 6 ml/kg by automatically adjusting airway pressure, resulting in a decreased tidal volume.


title: Circular economy and the matter of integrated resources.

text: A circular economy offers solutions for global sustainability challenges through the transition from the linear take-make-use-dispose economy to a better organisation of resources. However, realising a circular economy has ran into various biophysical constraints. Circular economy implementation is shaped by the Ellen MacArthur Foundation's butterfly diagram that depicts 'biological' and 'technical' flows as separate cycles, subsequently interpreted as organic materials circulating in open loop systems via the environment and inorganic materials circulating in closed loop systems within society. Conversely, in our view, resource flows often contain tightly bound combinations of organic and inorganic materials either due to their natural composition or due to their technical design. Building on this observation, a new diagram is proposed that broadens the scope of the circular economy to cover extractive sectors and the return of materials from anthropogenic use to natural reserves, thereby reshaping the conceptual space within which solutions such as effective zero-waste-residue technologies, business models, and policies can be developed for the optimal management of integrated resources from a whole-system perspective. The diagram offers a realistic outlook on the biophysical limitations of circularity and endeavours to inspire discussion that supports the transition towards a sustainable circular economy.


title: Impact of Human Disasters and COVID-19 Pandemic on Mental Health: Potential of Digital Psychiatry.

text: Deep emotional traumas in societies overwhelmed by large-scale human disasters, like, global pandemic diseases, natural disasters, man-made tragedies, war conflicts, social crises, etc., can cause massive stress-related disorders. Motivated by the ongoing global coronavirus pandemic, the article provides an overview of scientific evidence regarding adverse impact of diverse human disasters on mental health in afflicted groups and societies. Following this broader context, psychosocial impact of COVID-19 as a specific global human disaster is presented, with an emphasis on disturbing mental health aspects of the ongoing pandemic. Limited resources of mental health services in a number of countries around the world are illustrated, which will be further stretched by the forthcoming increase in demand for mental health services due to the global COVID-19 pandemic. Mental health challenges are particularly important for the Republic of Croatia in the current situation, due to disturbing stress of the 2020 Zagreb earthquake and the high pre-pandemic prevalence of chronic Homeland-War-related posttraumatic stress disorders. Comprehensive approach based on digital psychiatry is proposed to address the lack of access to psychiatric services, which includes artificial intelligence, telepsychiatry and an array of new technologies, like internet-based computer-aided mental health tools and services. These tools and means should be utilized as an important part of the whole package of measures to mitigate negative mental health effects of the global coronavirus pandemic. Our scientific and engineering experiences in the design and development of digital tools and means in mitigation of stress-related disorders and assessment of stress resilience are presented. Croatian initiative on enhancement of interdisciplinary research of psychiatrists, psychologists and computer scientists on the national and EU level is important in addressing pressing mental health concerns related to the ongoing pandemic and similar human disasters.


Dealing With the CARDS of COVID-19.


title: Biannual birth pulses allow filoviruses to persist in bat populations.

text: Filoviruses Ebolavirus (EBOV) and Marburgvirus (MARV) cause haemorrhagic fevers with high mortality rates, posing significant threats to public health. To understand transmission into human populations, filovirus dynamics within reservoir host populations must be understood. Studies have directly linked filoviruses to bats, but the mechanisms allowing viral persistence within bat populations are poorly understood. Theory suggests seasonal birthing may decrease the probability of pathogen persistence within populations, but data suggest MARV may persist within colonies of seasonally breeding Egyptian fruit bats, Rousettus aegyptiacus. I synthesize available filovirus and bat data in a stochastic compartmental model to explore fundamental questions relating to filovirus ecology: can filoviruses persist within isolated bat colonies; do critical community sizes exist; and how do host-pathogen relationships affect spillover transmission potential? Synchronous annual breeding and shorter incubation periods did not allow filovirus persistence, whereas bi-annual breeding and longer incubation periods, such as reported for Egyptian fruit bats and EBOV in experimental studies, allowed persistence in colony sizes often found in nature. Serological data support the findings, with bats from species with two annual birth pulses more likely to be seropositive (odds ratio (OR) 4.4, 95% confidence interval (CI) 2.5-8.7) than those with one, suggesting that biannual birthing is necessary for filovirus persistence.


title: Emerging indications of endoscopic radiofrequency ablation.

text: INTRODUCTION Radiofrequency ablation (RFA) is a well-validated treatment of dysplastic Barrett's esophagus. Other indications of endoscopic RFA are under evaluation. RESULTS Four prospective studies (total 69 patients) have shown that RFA achieved complete remission of early esophageal squamous intra-epithelial neoplasia at a rate of 80%, but with a substantial risk of stricture. In the setting of gastric antral vascular ectasia, two prospective monocenter studies, and a retrospective multicenter study, (total 51 patients), suggest that RFA is efficacious in terms of reducing transfusion dependency. In the setting of chronic hemorrhagic radiation proctopathy, a prospective monocenter study and a retrospective multicenter study (total 56 patients) suggest that RFA is an efficient treatment. A retrospective comparative study (64 patients) suggests that RFA improves stents patency in malignant biliary strictures. CONCLUSIONS Endoscopic RFA is an upcoming treatment modality in early esophageal squamous intra-epithelial neoplasia, as well as in gastric, rectal, and biliary diseases.


title: Antiviral Compounds Against Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus.

text: Porcine epidemic diarrhea (PED) is a severe diarrhea disease in swine that is caused by porcine epidemic diarrhea virus (PEDV). Nucleocapsid (N) protein is the RNA-binding protein of PEDV, which plays an important role for virus life cycle. The aim of this research was to screen and characterize the compounds that could inhibit the activity of PEDV N protein. The gene encoding PEDV N protein obtained from PEDV Thai isolate was cloned and expressed in E. coli. Its amino acid sequence was employed to generate the three dimensional structure by homology modeling. There were 1,286 compounds of FDA-approved drug database that could virtually bind to the RNA-binding region of N protein. Three compounds, trichlormethiazide, D-(+) biotin, and glutathione successfully bound to the N protein, in vitro, with the IC50 at 8.754 mg/mL, 0.925 mg/mL, and 2.722 mg/mL. Antiviral activity in PEDV-infected Vero cells demonstrated that the effective concentration of trichlormethiazide, D-(+) biotin, and glutathione in inhibiting PEDV replication were 0.094, 0.094 and 1.5 mg/mL. This study demonstrated a strategy applied for discovery of antiviral agents capable of inhibiting PEDV N protein and PEDV replication. The compounds identified here exhibited a potential use as therapeutic agents for controlling PEDV infection.


title: Intraoperative fluorescence-based enhanced reality laparoscopic real-time imaging to assess bowel perfusion at the anastomotic site in an experimental model.

text: BACKGROUND Fluorescence videography is a promising technique for assessing bowel perfusion. Fluorescence-based enhanced reality (FLER) is a novel concept, in which a dynamic perfusion cartogram, generated by computer analysis, is superimposed on to real-time laparoscopic images. The aim of this experimental study was to assess the accuracy of FLER in detecting differences in perfusion in a small bowel resection-anastomosis model. METHODS A small bowel ischaemic segment was created laparoscopically in 13 pigs. Animals were allocated to having anastomoses performed at either low perfusion (25 per cent; n = 7) or high perfusion (75 per cent; n = 6), as determined by FLER analysis. Capillary lactate levels were measured in blood samples obtained by serosal puncturing in the ischaemic area, resection lines and vascularized areas. Pathological inflammation scoring of the anastomosis was carried out. RESULTS Lactate levels in the ischaemic area (mean(s.d.) 5·6(2·8) mmol/l) were higher than those in resection lines at 25 per cent perfusion (3·7(1·7) mmol/l; P = 0·010) and 75 per cent perfusion (2·9(1·3) mmol/l; P < 0·001), and higher than levels in vascular zones (2·5(1·0) mmol/l; P < 0·001). Lactate levels in resection lines with 75 per cent perfusion were lower than those in lines with 25 per cent perfusion (P < 0·001), and similar to those in vascular zones (P = 0·188). Levels at resection lines with 25 per cent perfusion were higher than those in vascular zones (P = 0·001). Mean(s.d.) global inflammation scores were higher in the 25 per cent perfusion group compared with the 75 per cent perfusion group for mucosa/submucosa (2·1(0·4) versus 1·2(0·4); P = 0·003) and serosa (1·8(0·4) versus 0·8(0·8); P = 0·014). A ratio of preanastomotic lactate levels in the ischaemic area relative to the resection lines of 2 or less was predictive of a more severe inflammation score. CONCLUSION In an experimental model, FLER appeared accurate in discriminating bowel perfusion levels. Surgical relevance Clinical assessment has limited accuracy in evaluating bowel perfusion before anastomosis. Fluorescence videography estimates intestinal perfusion based on the fluorescence intensity of injected fluorophores, which is proportional to bowel vascularization. However, evaluation of fluorescence intensity remains a static and subjective measure. Fluorescence-based enhanced reality (FLER) is a dynamic fluorescence videography technique integrating near-infrared endoscopy and specific software. The software generates a virtual perfusion cartogram based on time to peak fluorescence, which can be superimposed on to real-time laparoscopic images. This experimental study demonstrates the accuracy of FLER in detecting differences in bowel perfusion in a survival model of laparoscopic small bowel resection-anastomosis, based on biochemical and histopathological data. It is concluded that real-time imaging of bowel perfusion is easy to use and accurate, and should be translated into clinical use.


title: The short-term outcomes of robotic sphincter-preserving surgery for rectal cancer: comparison with open and laparoscopic surgery using a propensity score analysis.

text: PURPOSE The aim of this study is to clarify the short-term outcomes of robotic sphincter-preserving surgery for rectal cancer in a retrospective study. METHODS The short-term outcomes of robotic sphincter-preserving surgery (n = 130) were retrospectively compared to open (n = 234) and laparoscopic surgery (n = 318) by a propensity score analysis. RESULTS Robotic surgery was performed more frequently for patients with lower rectal cancer (55%) than open (30%, p < 0.0001) or laparoscopic surgery (36%, p < 0.0001). None of the robotic surgery cases were converted to open surgery. After propensity score matching, robotic surgery was found to be associated with a longer operation time (342 vs. 230 min, p < 0.0001) and less blood loss (7 vs. 420 mL, p < 0.0001) than open surgery. The overall complication rate of robotic surgery was lower than that of open surgery (13 vs. 28%, p = 0.032). Robotic surgery was associated with a lower incidence of surgical site infections (SSIs) than laparoscopic surgery (0 vs. 7%, p = 0.028). There were no cases of anastomotic leakage after robotic surgery. The circumferential resection margin was involved in 0.8% of the patients who underwent robotic surgery; the incidence did not differ among the treatment groups. CONCLUSIONS Although robotic surgery for rectal cancer was associated with a longer operation time, it was associated with a very low incidence of SSIs. The degree of safety was comparable to both open and laparoscopic surgery.


title: Automatic inference model construction for computer-aided diagnosis of lung nodule: Explanation adequacy, inference accuracy, and experts' knowledge.

text: We aimed to describe the development of an inference model for computer-aided diagnosis of lung nodules that could provide valid reasoning for any inferences, thereby improving the interpretability and performance of the system. An automatic construction method was used that considered explanation adequacy and inference accuracy. In addition, we evaluated the usefulness of prior experts' (radiologists') knowledge while constructing the models. In total, 179 patients with lung nodules were included and divided into 79 and 100 cases for training and test data, respectively. F-measure and accuracy were used to assess explanation adequacy and inference accuracy, respectively. For F-measure, reasons were defined as proper subsets of Evidence that had a strong influence on the inference result. The inference models were automatically constructed using the Bayesian network and Markov chain Monte Carlo methods, selecting only those models that met the predefined criteria. During model constructions, we examined the effect of including radiologist's knowledge in the initial Bayesian network models. Performance of the best models in terms of F-measure, accuracy, and evaluation metric were as follows: 0.411, 72.0%, and 0.566, respectively, with prior knowledge, and 0.274, 65.0%, and 0.462, respectively, without prior knowledge. The best models with prior knowledge were then subjectively and independently evaluated by two radiologists using a 5-point scale, with 5, 3, and 1 representing beneficial, appropriate, and detrimental, respectively. The average scores by the two radiologists were 3.97 and 3.76 for the test data, indicating that the proposed computer-aided diagnosis system was acceptable to them. In conclusion, the proposed method incorporating radiologists' knowledge could help in eliminating radiologists' distrust of computer-aided diagnosis and improving its performance.