title: Systemic inflammation and oxidative stress post-lung resection: Effect of pretreatment with N-acetylcysteine.

text: BACKGROUND AND OBJECTIVE N-acetylcysteine has been used to treat a variety of lung diseases, where is it thought to have an antioxidant effect. In a randomized placebo-controlled double-blind study, the effect of N-acetylcysteine on systemic inflammation and oxidative damage was examined in patients undergoing lung resection, a human model of acute lung injury. METHODS Eligible adults were randomized to receive preoperative infusion of N-acetylcysteine (240 mg/kg over 12 h) or placebo. Plasma thiols, interleukin-6, 8-isoprostane, ischaemia-modified albumin, red blood cell glutathione and exhaled breath condensate pH were measured pre- and post-operatively as markers of local and systemic inflammation and oxidative stress. RESULTS Patients undergoing lung resection and one-lung ventilation exhibited significant postoperative inflammation and oxidative damage. Postoperative plasma thiol concentration was significantly higher in the N-acetylcysteine-treated group. However, there was no significant difference in any of the measured biomarkers of inflammation or oxidative damage, or in clinical outcomes, between N-acetylcysteine and placebo groups. CONCLUSION Preoperative administration of N-acetylcysteine did not attenuate postoperative systemic or pulmonary inflammation or oxidative damage after lung resection. CLINICAL TRIAL REGISTRATION NCT00655928 at ClinicalTrials.gov.


title: The link between maternal obesity and offspring neurobehavior: A systematic review of animal experiments.

text: Maternal obesity in pregnancy is associated with neurobehavioral problems in the offspring. Establishing causality has been challenging in existing human studies, due to confounding by genetic and postnatal environment. Animal experiments can improve our understanding of this association. This systematic review examined the effects of maternal obesity in pregnancy on offspring neurobehavior in animal models. We included 26 studies (1047 offspring animals). Meta-analyses showed that offspring of obese mothers displayed higher levels of locomotor activity (standardized mean difference (SMD) 0.34 [0.10; 0.58]) and anxiety behavior (SMD 0.47 [0.16; 0.79]) than offspring of lean mothers, but similar memory abilities (SMD -0.06 [-0.52; 0.39]). Meta-analysis of learning abilities was not sensible due to heterogeneity. Although the evidence was heterogeneous and the quality of the included studies generally unclear, this systematic review of animal studies indicates an effect of maternal obesity on increased offspring locomotor activity and anxiety, but not on offspring memory performance. These findings may be important from a public health perspective since obesity is rapidly increasing worldwide, and warrant further research.


docid: lwofdtvx

title: Radiolabeling of rituximab with (188)Re and (99m)Tc using the tricarbonyl technology.

text: INTRODUCTION The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20(+) B-cell tumors. Rituximab radiolabeled with β(-) emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the (99m)Tc- and (188)Re-tricarbonyl core (IsoLink technology). METHODS The native format of the antibody (RTX(wt)) as well as a reduced form (RTX(red)) was labeled with (99m)Tc/(188)Re(CO)(3). The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. RESULTS The radiolabeling efficiency and kinetics of RTX(red) were superior to that of RTX(wt) ((99m)Tc: 98% after 3 h for RTX(red) vs. 70% after 24 h for RTX(wt)). (99m)Tc(CO)(3)-RTX(red) was used without purification for in vitro and in vivo studies whereas (188)Re(CO)(3)-RTX(red) was purified to eliminate free (188)Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37 °C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of (99m)Tc(CO)(3)-RTX(red) but not with pre-purified (188)Re(CO)(3)-RTX(red). Both conjugates revealed high binding affinity to the CD20 antigen (K(d) = 5-6 nM). Tumor uptake of (188)Re(CO)(3)-RTX(red) was 2.5 %ID/g and 0.8 %ID/g for (99m)Tc(CO)(3)-RTX(red) 48 h after injection. The values for other organs and tissues were similar for both compounds, for example the tumor-to-blood and tumor-to-liver ratios were 0.4 and 0.3 for (99m)Tc(CO)(3)-RTX(red) and for (188)Re(CO)(3)-RTX(red) 0.5 and 0.5 (24 h pi). CONCLUSION Rituximab could be directly and stably labeled with the matched pair (99m)Tc/(188)Re using the IsoLink technology under retention of the biological activity. Labeling kinetics and yields need further improvement for potential routine application in radioimmunodiagnosis and therapy.


Single-incision laparoscopic bariatric surgery: a comprehensive review.


docid: cfdfjwdz

title: Disappearance of SARS-CoV-2 Antibodies in Infants Born to Women with COVID-19, Wuhan, China.

text: We report the detection and decline over time of severe acute respiratory syndrome coronavirus 2 antibodies in infants born to women with coronavirus disease. Among 11 infants tested at birth, all had detectable IgG and 5 had detectable IgM. IgG titers with positive IgM declined more slowly than those without.


title: Extracellular gadolinium-based contrast media: differences in diagnostic efficacy.

text: Since the introduction of the first gadolinium-based contrast agent (Gd-CA) in 1988 it has become clear that these agents significantly improve the diagnostic efficacy of MRI. Studies on single agents have shown that, in comparison to unenhanced sequences, all agents help to improve the detection and delineation of lesions which can alter diagnosis in up to 40% of patients. Doubling or tripling the standard dose of 0.1 mmol/kg body weight may be beneficial for selected indications (e.g. brain perfusion, equivocal single dose study in MRI for brain metastasis, small vessel MR angiography). A more limited number of studies have compared the various agents. These studies do not show clinically significant differences in diagnostic efficacy between the various extracellular Gd-CA. Agents with higher concentration or protein binding may be relatively better suitable for selected applications (e.g. perfusion MRI). The higher relaxivity agents may be used in somewhat lower doses than the extracellular agents.


title: Impact of point-of-care C reactive protein in ambulatory care: a systematic review and meta-analysis.

text: OBJECTIVE The aim of this review was to collate all available evidence on the impact of point-of-care C reactive protein (CRP) testing on patient-relevant outcomes in children and adults in ambulatory care. DESIGN This was a systematic review to identify controlled studies assessing the impact of point-of-care CRP in patients presenting to ambulatory care services. Ovid Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, DARE, Science Citation Index were searched from inception to March 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Controlled studies assessing the impact of point-of-care CRP in patients presenting to ambulatory care services, measuring a change in clinical care, including but not limited to antibiotic prescribing rate, reconsultation, clinical recovery, patient satisfaction, referral and additional tests. No language restrictions were applied. DATA EXTRACTION Data were extracted on setting, date of study, a description of the intervention and control group, patient characteristics and results. Methodological quality of selected studies and assessment of potential bias was assessed independently by two authors using the Cochrane Risk of Bias tool. RESULTS 11 randomised controlled trials and 8 non-randomised controlled studies met the inclusion criteria, reporting on 16 064 patients. All included studies had a high risk of performance and selection bias. Compared with usual care, point-of-care CRP reduces immediate antibiotic prescribing (pooled risk ratio 0.81; 95% CI 0.71 to 0.92), however, at considerable heterogeneity (I2=72%). This effect increased when guidance on antibiotic prescribing relative to the CRP level was provided (risk ratios of 0.68; 95% CI 0.63 to 0.74 in adults and 0.56; 95% CI 0.33 to 0.95 in children). We found no significant effect of point-of-care CRP testing on patient satisfaction, clinical recovery, reconsultation, further testing and hospital admission. CONCLUSIONS Performing a point-of-care CRP test in ambulatory care accompanied by clinical guidance on interpretation reduces the immediate antibiotic prescribing in both adults and children. As yet, available evidence does not suggest an effect on other patient outcomes or healthcare processes. PROSPERO REGISTRATION NUMBER CRD42016035426; Results.


title: The Demographics and Economics of Direct Care Staff Highlight Their Vulnerabilities Amidst the COVID-19 Pandemic.

text: An estimated 3.5 million direct care staff working in facilities and people's homes play a critical role during the COVID-19 pandemic. They allow vulnerable care recipients to stay at home and they provide necessary help in facilities. Direct care staff, on average, have decades of experience, often have certifications and licenses, and many have at least some college education to help them perform the myriad of responsibilities to properly care for care recipients. Yet, they are at heightened health and financial risks. They often receive low wages, limited benefits, and have few financial resources to fall back on when they get sick themselves and can no longer work. Furthermore, most direct care staff are parents with children in the house and almost one-fourth are single parents. If they fall ill, both they and their families are put into physical and financial risk.


title: Videolaryngoscopy With Noninvasive Ventilation in Subjects With Upper-Airway Obstruction.

text: BACKGROUND Noninvasive ventilation (NIV) titration may be difficult when dynamic airway obstruction episodes persist, even with high expiratory positive airway pressure (EPAP). We aimed to determine the usefulness of videolaryngoscopy during NIV for identifying mechanisms and sites of obstruction and for providing a guide for their resolution in difficult-to-titrate subjects. METHODS When obstructions during NIV were present in the built-in software, EPAP was raised to 12 cm H2O. If obstructions persisted, a polygraphy during NIV was performed; if the events occurred with effort, a videolaryngoscopy with nasal and oronasal masks in awake subjects was performed. RESULTS In a population of 208 subjects in whom NIV was initiated, 13 were identified as difficult to titrate with persistent obstructions during NIV despite an EPAP of 12 cm H2O. Videolaryngoscopy during NIV was able to identify the mechanism and the site of obstruction in all cases. The obstruction under oronasal mask ventilation was due to soft-palate (velum) collapse in 4 subjects, to epiglottic backward movement in 5 other subjects, and to tongue-base obstruction reducing the retroglossal space in 3 more. Videolaryngoscopy during NIV demonstrated improvement in 9 subjects (69%) upon changing to nasal mask and suggested a possible surgical approach in 2 (15%); in one of these 2 subjects, a successful uvulopalatopharyngoplasty was performed. CONCLUSIONS The use of videolaryngoscopy during NIV in difficult-to-titrate patients may help to identify the sites and mechanisms of obstruction and in some cases may improve quality of ventilation.


title: COVID-19 Emergency Reforms in Massachusetts to Support Behavioral Health Care and Reduce Mortality of People With Serious Mental Illness.

text: People with serious mental illness are at disproportionate risk of COVID-19 morbidity and mortality because of high rates of risk factors that directly parallel those related to poor coronavirus outcomes, including smoking, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes, along with housing instability, homelessness, food insecurity, and poverty. Community-based behavioral health organizations are also at risk of adverse outcomes because of dramatic declines in revenues and a diminished workforce. The State of Massachusetts has responded to this crisis by rapidly implementing a variety of policy, regulatory, and payment reforms. This column describes some of these reforms, which are designed to enhance remote telehealth delivery of care, ensure access to needed medications and residential care staff, and support the financial livelihood of community-based behavioral health services.


title: Efficacy and safety of a single radiofrequency ablation of solid benign non-functioning thyroid nodules.

text: Objective The objective of our study is to evaluate the clinical outcomes and safety of radiofrequency thermal ablation (RFA) for benign thyroid nodules (BTNs) over a 1-year follow-up. Subjects and methods This is a monocentric retrospective study. Forty-eight patients with solid, non-functioning BTNs were treated by RFA using a 17G internally cooled electrode. We categorized thyroid nodules as small (≤ 12 mL), medium (12 to 30 mL), or large (over 30 mL). BTNs volume reduction, thyroid function, cosmetic and compressive score changes and side effect evaluation at 6 and 12 months were evaluated. Results BTN volume decreased significantly from baseline to 6 (mean percentage decrease of BTN volume was 66.8 ± 13.6%, p < 0.001). At 12 months, the mean percentage reduction of BTN volume compared to six months was 13.7 ± 17.1% (p < 0.001). At 6-month, symptom score had improved significantly (p < 0.001) while it does not change significantly between 6 and 12 months. In particular, symptom score improved significantly in the medium (p < 0.001) and large (p < 0.01) subgroups. Cosmetic score improved significantly between baseline and 6 months (p < 0.001) and between 6 and 12 months (p < 0.01). In all the subgroups, cosmetic score improved significantly between baseline and 6 months, while between 6 and 12 months it improved significantly only in the large group (p < 0.05). RFA was well tolerated. Only one patient experienced permanent right paramedian vocal cord palsy. Conclusions A single RFA treatment was effective in reducing BTNs volume, in particular small and medium nodules. Cosmetic score improved in all treated BTNs while symptom score only got better in the medium and large BTNs.


Incoming International Medical Graduates and the COVID-19 Pandemic: More Than Meets the Eye.


Blood pressure management in early ischemic stroke.


title: Recommendations for the care of patients with heart failure and COVID-19.

text: The COVID-19 pandemic decreed by the World Health Organization (WHO) since March 12, 2020 is wreaking havoc globally and it is a true economic, social and health challenge. Although the clinical manifestations of COVID-19 are respiratory symptoms, some patients also have cardiological symptoms. Among patients with cardiological conditions2 they represent a group of higher risk and, in fact, they are a particularly vulnerable group, due to their higher risk of contagion and greater severity in case of acquiring the disease1 those with heart failure (HF), including heart transplant (CT) and ventricular assists, as well as patients with pulmonary arterial hypertension (PAH). HF is the main chronic cardiovascular disease and patients in this group are the most vulnerable for the development of more serious clinical symptoms after suffering the infection, and to a greater extent cases with advanced HF3. In fact, HF is one of the most frequent complications in patients with COVID-194. Likewise, transplant patients who require immunosuppressants to avoid graft rejection, constitute a population especially susceptible to infection and to develop more serious processes. This situation has made the National Association of Cardiologists of Mexico (ANCAM) and the Mexican Society of Cardiology (SMC) together with their respective chapters, have prepared the following recommendations for medical personnel, who participate in the care of this special group of patients in the different clinical settings, who suffer or not, of COVID-19.


title: Retroperitoneoscopic laparo-endoscopic single-site radical nephrectomy (RLESS-RN): initial experience with a homemade port.

text: We successfully performed 6 LESS radical nephrectomy via the retroperitoneal approach (RLESS) using the Alexis wound retractor as a single access with conventional laparoscopic instruments. The results demonstrated that our RLESS technique of radical nephrectomy is a safe and feasible procedure for management of localized renal cancer.


title: Exposure of epitope residues on the outer face of the chikungunya virus envelope trimer determines antibody neutralizing efficacy.

text: UNLABELLED Chikungunya virus (CHIKV) is a reemerging alphavirus that causes a debilitating arthritic disease and infects millions of people and for which no specific treatment is available. Like many alphaviruses, the structural targets on CHIKV that elicit a protective humoral immune response in humans are poorly defined. Here we used phage display against virus-like particles (VLPs) to isolate seven human monoclonal antibodies (MAbs) against the CHIKV envelope glycoproteins E2 and E1. One MAb, IM-CKV063, was highly neutralizing (50% inhibitory concentration, 7.4 ng/ml), demonstrated high-affinity binding (320 pM), and was capable of therapeutic and prophylactic protection in multiple animal models up to 24 h postexposure. Epitope mapping using a comprehensive shotgun mutagenesis library of 910 mutants with E2/E1 alanine mutations demonstrated that IM-CKV063 binds to an intersubunit conformational epitope on domain A, a functionally important region of E2. MAbs against the highly conserved fusion loop have not previously been reported but were also isolated in our studies. Fusion loop MAbs were broadly cross-reactive against diverse alphaviruses but were nonneutralizing. Fusion loop MAb reactivity was affected by temperature and reactivity conditions, suggesting that the fusion loop is hidden in infectious virions. Visualization of the binding sites of 15 different MAbs on the structure of E2/E1 revealed that all epitopes are located at the membrane-distal region of the E2/E1 spike. Interestingly, epitopes on the exposed topmost and outer surfaces of the E2/E1 trimer structure were neutralizing, whereas epitopes facing the interior of the trimer were not, providing a rationale for vaccine design and therapeutic MAb development using the intact CHIKV E2/E1 trimer. IMPORTANCE CHIKV is the most important alphavirus affecting humans, resulting in a chronic arthritic condition that can persist for months or years. In recent years, millions of people have been infected globally, and the spread of CHIKV to the Americas is now beginning, with over 100,000 cases occurring in the Caribbean within 6 months of its arrival. Our study reports on seven human MAbs against the CHIKV envelope, including a highly protective MAb and rarely isolated fusion loop MAbs. Epitope mapping of these MAbs demonstrates how some E2/E1 epitopes are exposed or hidden from the human immune system and suggests a structural mechanism by which these MAbs protect (or fail to protect) against CHIKV infection. Our results suggest that the membrane-distal end of CHIKV E2/E1 is the primary target for the humoral immune response to CHIKV, and antibodies targeting the exposed topmost and outer surfaces of the E2/E1 trimer determine the neutralizing efficacy of this response.


title: Polyomaviruses KI and WU in immunocompromised patients with respiratory disease.

text: Polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified, mainly in respiratory specimens from children. Among 200 patients with respiratory disorders admitted to Saint Louis Hospital, Paris, France, KIPyV was detected in 8% and WUPyV in 1%. KIPyV was significantly more frequent among human stem cell transplant patients (17.8% vs. 5.1%; p = 0.01).


title: The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner.

text: Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an effective concentration (EC)50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. On the other hand, a significantly higher dose (EC50 around 30 mM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat's safety, make it a likely candidate drug to treat COVID-19.


title: Enablers and barriers to the implementation of socially assistive humanoid robots in health and social care: a systematic review.

text: OBJECTIVES Socially assistive humanoid robots are considered a promising technology to tackle the challenges in health and social care posed by the growth of the ageing population. The purpose of our study was to explore the current evidence on barriers and enablers for the implementation of humanoid robots in health and social care. DESIGN Systematic review of studies entailing hands-on interactions with a humanoid robot. SETTING From April 2018 to June 2018, databases were searched using a combination of the same search terms for articles published during the last decade. Data collection was conducted by using the Rayyan software, a standardised predefined grid, and a risk of bias and a quality assessment tool. PARTICIPANTS Post-experimental data were collected and analysed for a total of 420 participants. Participants comprised: older adults (n=307) aged ≥60 years, with no or some degree of age-related cognitive impairment, residing either in residential care facilities or at their home; care home staff (n=106); and informal caregivers (n=7). PRIMARY OUTCOMES Identification of enablers and barriers to the implementation of socially assistive humanoid robots in health and social care, and consequent insights and impact. Future developments to inform further research. RESULTS Twelve studies met the eligibility criteria and were included. None of the selected studies had an experimental design; hence overall quality was low, with high risks of biases. Several studies had no comparator, no baseline, small samples, and self-reported measures only. Within this limited evidence base, the enablers found were enjoyment, usability, personalisation and familiarisation. Barriers were related to technical problems, to the robots' limited capabilities and the negative preconceptions towards the use of robots in healthcare. Factors which produced mixed results were the robot's human-like attributes, previous experience with technology and views of formal and informal carers. CONCLUSIONS The available evidence related to implementation factors of socially assistive humanoid robots for older adults is limited, mainly focusing on aspects at individual level, and exploring acceptance of this technology. Investigation of elements linked to the environment, organisation, societal and cultural milieu, policy and legal framework is necessary. PROSPERO REGISTRATION NUMBER CRD42018092866.


title: Being bullied and psychosocial adjustment among middle school students in China.

text: BACKGROUND Using the Chinese version of the Global School-based Health Survey (GSHS), this article describes the prevalence of being bullied among a nationally representative sample of Chinese students in grades 6-10 and explores the relationships between being bullied and selected indicators of psychosocial adjustment. METHODS A total of 9015 students in middle schools in Beijing, Hangzhou, Wuhan, and Urumqi completed the Chinese version of the GSHS. Researchers analyzed the results from 2 questions about the frequency and form of being bullied and 11 questions about psychosocial adjustment. Descriptive statistics and logistic regression were used in the analysis. RESULTS About 25.7% of middle school students reported being bullied on 1 or more of the past 30 days. Rates of being bullied were similar for males and females, but the forms of being bullied were different. Being bullied was significantly lower in Beijing than in the other 3 cities. There were significant psychosocial differences between students who had been bullied and students who had not been bullied. Students who had been involved in a physical fight, often felt lonely, or had considered suicide in the past 30 days were more likely to report being bullied. Students who thought that other students in their school were often kind and helpful, who felt parents often understood their troubles, or who were taught in school how to handle stress were less likely to report being bullied. CONCLUSIONS Being bullied is not uncommon in Chinese middle schools. Chinese schools typically place great emphasis on academic achievement, perhaps at the expense of the social climate of the school. Results indicated schools could implement changes to the school climate to reduce the likelihood of students' being bullied.


title: [Remote patient monitoring in dialysis patients: the "change of pace" for home dialysis.]

text: Lockdown and self-isolation are to date the only solution to limit the spread of recent outbreak of coronavirus disease (CoViD-19), highlighting the great advantage of home dialysis in a patient otherwise forced to travel from / to the dialysis center to receive this "life-saving" treatment. Indeed, to prevent spreading of CoViD-19 infection among extremely fragile dialysis patients, as well as among dialysis workers, hemodialysis (HD) centers are adopting specific procedures ("dedicated" dialysis facilities, portable osmosis, etc.) with a great economic and organizational commitment. Peritoneal dialysis (PD) represents a type of home dialysis therapy not yet adequately implemented to date, in spite of safe and simple practice, as well as similar dialytic efficiency vs in-center hemodialysis. Remote patient monitoring (RPM) systems have been developed in automated PD (APD) cyclers in order to improve the acceptance of this dialysis method, to increase the compliance to the prescribed therapy and to control treatment adequacy. In this review we assess the potential advantages of RPM in APD, that are the chance for patients to acquire greater independence and safety in the home treatment, to allow better access to care for residents in remote areas, faster resolution of problems, reduction in hospitalizations and mortality rates, as well as time and cost saving for both the patient and the staff. The use of medical devices (sphygmomanometer, glucometer, balance, etc.), connected by wireless to the clinician's portal, might also allow a wider diffusion of incremental dialysis, an integrated therapy that combines conservative management of ESKD patients with a soft dialysis based on the residual kidney function and symptomatology, with potential prognosis and economic benefits. Although the majority of the studies are small and observational, a wider use of RPM systems is desirable to broaden the spread of home dialysis, as we learnt from Coronavirus pandemic.


title: Safety and tolerability of an intratumorally injected DNAzyme, Dz13, in patients with nodular basal-cell carcinoma: a phase 1 first-in-human trial (DISCOVER).

text: BACKGROUND The nuclear transcription factor c-Jun is preferentially expressed in basal-cell carcinoma. Dz13 is a deoxyribozyme that targets JUN messenger RNA and has inhibited the growth of a range of tumours in mice. We did a phase 1 study to assess safety and tolerability in human beings. METHODS Adults with nodular basal-cell carcinoma were recruited from Royal Prince Alfred Hospital, Sydney, Australia, between September, 2010, and October, 2011. Patients were assigned to receive one intratumoral injected dose of 10, 30, or 100 μg Dz13, in a 50 μL volume of lipid carrier, and were assessed for adverse effects in the first 24 h then at 7, 14, and 28 days after injection. Treated tumours were surgically excised 14 days after injection and compared with the baseline biopsy samples for expression of c-Jun and tumorigenesis markers. FINDINGS Nine patients were recruited, of whom three received each dose of Dz13. All patients completed the study with no drug-related serious adverse events. No systemic Dz13 exposure was detected. c-Jun expression was reduced in the excised tumours of all nine (100%) patients, compared with baseline, and histological tumour depth had decreased in five (56%) of nine. Proportions of cells positive for caspases 3, 8, and 9 and P53 were increased, but those of cells positive for Bcl-2 and MMP-9 were decreased. Infiltration by inflammatory and immune cells was stimulated. INTERPRETATION Dz13 was safe and well tolerated after single intratumoral injections at all doses. FUNDING Cancer Institute NSW, Cancer Council Australia, and National Health and Medical Research Council.


title: Single-incision laparoscopic surgery (SILS™) versus standard laparoscopic surgery: a comparison of performance using a surgical simulator.

text: BACKGROUND Single-incision laparoscopic surgery (SILS™) is a potentially less invasive approach than standard laparoscopy (LAP). However, SILS™ may not allow the same level of manual dexterity and technical performance compared to LAP. We compared the performance of standardized tasks from the Fundamentals of Laparoscopic Surgery (FLS) program using either the LAP or the SILS™ technique. METHODS Medical students, surgical residents, and attending physicians were recruited and divided into inexperienced (IE), laparoscopy-experienced (LE), and SILS™-experienced (SE) groups. Each subject performed standardized tasks from FLS, including peg transfer, pattern cutting, placement of ligating loop, and intracorporeal suturing using a standard three-port FLS box-trainer with standard laparoscopic instruments. For SILS™, the subjects used an FLS box-trainer modified to accept a SILS Port™ with two working ports for instruments and one port for a 30° 5-mm laparoscope. SILS™ tasks were performed with instruments capable of unilateral articulation. SILS™ suturing was performed both with and without an articulating EndoStitch™ device. Task scores, including cumulative laparoscopic FLS score (LS) and cumulative SILS™ FLS score (SS), were calculated using standard time and accuracy metrics. RESULTS There were 27 participants in the study. SS was inferior to LS in all groups. LS increased with experience level, but was similar between LE and SE groups. SS increased with experience level and was different among all groups. SILS™ suturing using the articulating suturing device was superior to the use of a modified needle driver technique. CONCLUSIONS SILS™ is more technically challenging than standard laparoscopic surgery. Using currently available SILS™ platforms and instruments, even surgeons with SILS™ experience are unable to match their overall LAP performance. Specialized training curricula should be developed for inexperienced surgeons who wish to perform SILS™.


Coronavirus breakthrough: dexamethasone is first drug shown to save lives.


title: Neurophysiologic Correlates of Headache Pain in Subjects With Major Depressive Disorder.

text: BACKGROUND Headache pain is often comorbid with major depressive disorder (MDD) and is associated with greater symptom burden, disability, and suicidality. The biological correlates of headache pain in MDD, however, remain obscure. The purpose of this study was to examine the association between brain oscillatory activity and headache pain in MDD subjects. METHODS A total of 64 subjects with MDD who were free of psychoactive medications were evaluated for severity of headache pain in the past week. Brain function was assessed using resting-state quantitative electroencephalography (qEEG). We derived cordance in the theta (4-8 Hz) and alpha (8-12 Hz) frequency bands at each electrode, and examined correlations with headache pain in regions of interest while controlling for depression severity. Frontal and posterior asymmetry in alpha power was calculated in regions of interest. RESULTS Headache pain severity was associated with depression severity ( r = 0.447, P < .001). In bilateral frontal and right posterior regions, alpha cordance was significantly associated with headache intensity, including when controlling for depression severity. The direction of the correlation was positive anteriorly and negative posteriorly. Frontal left dominant alpha asymmetry correlated with severity of headache but not depression symptoms. CONCLUSION Alterations in brain oscillations identified by alpha cordance and alpha asymmetry may be associated with the pathophysiology of headache pain in depression. These findings should be prospectively confirmed.


Association between low vitamin D and COVID-19: don't forget the vitamin D binding protein.


Choices for the "New Normal".


title: Prediction of the rehabilitation duration and risk management for mild-moderate COVID-19.

text: BACKGROUND More than 80% COVID-19 cases are mild or moderate. In this study, a risk model was developed for predicting rehabilitation duration of the mild-moderate COVID-19 cases, thereby conducting refined risk management for different risk population. METHODS 90 consecutive mild-moderate COVID-19 cases were enrolled. Large-scale datasets were extracted from clinical practices. Through the multivariable linear regression analysis, the model was based on significant risk factors and was developed for predicting the rehabilitation duration of mild-moderate COVID-19. According to the local epidemic situation, risk management was conducted by weighing the risk assessment for different risk populations. RESULTS Ten risk factors from 44 high-dimensional clinical datasets were significantly correlated to rehabilitation duration (P < 0.05). Among these, five risk predictors were incorporated into a risk model. Individual rehabilitation durations were effectively calculated. Weighing the local epidemic situation, threshold probability was classified for low risk, intermediate risk, and high risk. According to this classification, risk management was based on a treatment flowchart for tailored clinical decisions-making. CONCLUSIONS The proposed model is a useful tool for the individualized risk management of mild-moderate COVID-19 cases for the first time, and it may readily facilitate dynamic clinical decision-making for different risk populations.


title: Case Report: COVID-19-Related Pneumothorax-Case Series Highlighting a Significant Complication.

text: COVID-19 is a recent outbreak in China and rapidly spread worldwide. Lung consolidation is the most common radiologic finding of COVID-19 pneumonia. Pneumothorax has been rarely reported as a complication of severe COVID-19 pneumonia. Early recognition and management are detrimental to the outcome. We here report three cases of SARS-CoV-2 infection complicated by pneumothorax. In addition, we present a brief literature review.


First antibody surveys draw fire for quality, bias.


Prevalence, risk factors and clinical outcomes of COVID-19 in patients with a history of pancreatitis in Northern California.


title: Transplant programmes during COVID-19: Unintended consequences for health inequality.

text: Transplant programmes are being scaled back as healthcare systems worldwide respond to COVID-19. Most centres are now taking only super urgent and urgent cases, if at all. Management of donor organs is also impacted. Contingency protocols may prioritise distance over equitable sharing principles. Live and deceased donation is either being selectively paused or operating under stringent criteria based on local capacity. This will inevitably lead to variable patient experience.


title: COVID-19 Pandemic: A Big Challenge in Iran and the World.

text: No abstract!


title: Unconventional roles of nonlipidated LC3 in ERAD tuning and coronavirus infection.

text: Secretory and membrane proteins attain their native structure in the endoplasmic reticulum (ER). Folding-defective polypeptides are selected for degradation by processes collectively defined as ER-associated degradation (ERAD). Enhanced ERAD activity may interfere with protein biogenesis by inappropriately targeting not-yet-native protein folding intermediates for disposal. The regulation of ERAD is therefore crucial to maintain cellular proteostasis. At steady-state, select ERAD regulators are constitutively removed from the ER in a series of processes collectively defined as ERAD tuning. This sets the ERAD activity at levels that do not interfere with completion of ongoing folding programs. Our latest work highlights a crucial, autophagy-independent role of nonlipidated LC3 (LC3-I) as part of a membrane-bound receptor that insures the vesicle-mediated clearance of at least two ERAD regulators from the ER, EDEM1 and OS9. This pathway is hijacked by coronaviruses (CoV), and silencing of LC3 substantially inhibits viral replication.


title: Characterization of the Interactome of the Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 2 Reveals the Hyper Variable Region as a Binding Platform for Association with 14-3-3 Proteins.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to the swine industry worldwide and hence global food security, exacerbated by a newly emerged highly pathogenic (HP-PRRSV) strain from China. PRRSV nonstructural protein 2 (nsp2) is a multifunctional polypeptide with strain-dependent influences on pathogenicity. A number of discrete functional regions have been identified on the protein. Quantitative label free proteomics was used to identify cellular binding partners of nsp2 expressed by HP-PRRSV. This allowed the identification of potential cellular interacting partners and the discrimination of nonspecific interactions. The interactome data were further investigated and validated using biological replicates and also compared with nsp2 from a low pathogenic (LP) strain of PRRSV. Validation included both forward and reverse pulldowns and confocal microscopy. The data indicated that nsp2 interacted with a number of cellular proteins including 14-3-3, CD2AP, and other components of cellular aggresomes. The hyper-variable region of nsp2 protein was identified as a binding platform for association with 14-3-3 proteins.


title: [Correlation between clinical classification of COVID-19 and imaging characteristics of MSCT volume scanning of the lungs].

text: OBJECTIVE To investigate the correlation between the clinical classification of coronavirus disease 2019 (COVID-19) and the imaging characteristics of multislice spiral computed tomography (MSCT) volume scanning of the lungs. METHODS The clinical data and thoracic MSCT volume scanning data were analyzed retrospectively for 102 patients with COVID-19 diagnosed and hospitalized in the First Affiliated Hospital of Bengbu Medical College between January 18 and February 26, 2020. According to the Fifth Edition of the Diagnosis and Treatment Guidelines by the National Health Commission, the patients were divided into common type, severe type and critical type. The imaging characteristics including the lung sides of the lesions, lung segment involved, lesion distribution, and lesion number and density were compared among the patients with different clinical types of COVID-19. RESULTS Seventy-seven of the patients had common type, 18 had severe type and 7 had critical type of COVID-19. The main clinical manifestations included fever, cough and fatigue. Severe and critical types were more frequently seen in elderly patients, who were more prone to show such symptoms as asthenia, breathing difficulty and dyspnea. Two patients presented with no obvious abnormality in the first CT examinations; in the remaining 100 patients, 89.0% had bilateral lung lesions, 16.0% had diffuse lesions, involving a mean of 6.56±4.22 lung segments. Compared with the patients with the common type, the severe and critical patients had a significantly greater number of lung segments involved (P < 0.05), and were also more likely to show diffuse lesions (P < 0.05). The lesion side, lesion number or lesion density did not differ significantly among the patients with different clinical types of COVID-19 (P > 0.05). CONCLUSIONS MSCT volume scanning not only allows early diagnosis of COVID-19 but also provides evidence for evaluating the severity of COVID-19 to assist in the clinical treatment of the patients.


title: Phages harboring specific peptides that recognize the N protein of the porcine reproductive and respiratory syndrome virus distinguish the virus from other viruses.

text: The aim of the current study was to develop a novel diagnostic test for detecting porcine reproductive and respiratory syndrome virus (PRRSV) using phage display technology. The N gene of PRRSV isolate HH08 was cloned following reverse transcription-PCR. Sequence comparison indicated that the N gene shared 96.4% homology to that of North American PRRSV (isolate VR2332) and 35.5% with that of European PRRSV (isolate LV), indicating that the PRRSV isolate was related to the North American PRRSV genotype. The bacterially expressed N protein was used as a target in a biopanning process using a phage display random peptide library. Seven phages expressing different peptides had a specific binding activity with the N protein. The putative binding motifs were identified by DNA sequencing. More importantly, the selected phages harboring specific peptides that recognize the N protein of PRRSV were able to efficiently distinguish PRRSV from other viruses in enzyme-linked immunosorbent assays.


Anti-protease Treatments Targeting Plasmin(ogen) and Neutrophil Elastase May Be Beneficial in Fighting COVID-19.


title: Mesh shrinkage and pain in laparoscopic ventral hernia repair: a randomized clinical trial comparing suture versus tack mesh fixation.

text: BACKGROUND Mesh fixation during laparoscopic ventral hernia repair can be performed using transfascial sutures or metal tacks. The aim of the present study is to compare mesh shrinkage and pain between two different techniques of mesh fixation in a prospective randomized trial. METHODS A randomized trial was performed. Patients with ventral hernia of maximal diameter 8 cm were assigned to mesh fixation using either transfascial nonabsorbable sutures or metal tacks for fixation of a parietene composite mesh. The borders of the mesh were marked using clips, and radiological images in prone position were used for assessment of mesh size and location. The primary endpoint was mesh shrinkage; secondary endpoints included postoperative pain, mesh dislocation, and surgical morbidity. RESULTS Demographic parameters were similar in both groups. A total of 40 patients were randomized, and 36 patients were available for follow-up. There was one hernia recurrence in each group. Pain was significantly higher following suture fixation after 6 weeks, but no difference was found after 6 months. Mesh shrinkage after 6 months was significantly higher using tacks for mesh fixation. CONCLUSIONS Transfascial sutures are associated with more pain within the first 6 postoperative weeks and less mesh shrinkage after 6 months compared with mesh fixation using metal tacks.


title: Anchoring BODIPY photosensitizers enable pan-microbial photoinactivation.

text: Photodynamic antimicrobial chemotherapy (PACT) is an effective strategy to inactivate pathogenic and resistant microbes. However, pan-microbial photoinactivation has hardly achieved. In this manuscript, we built anti-microbial PSs based on 2,6-diiodo-1,3,5,7-tetramethyl BODIPY (2I-BDP) using anchoring strategy through modifications on boron atom with bis-cationic moieties. With appropriate bis-cationic anchoring, we could achieve effective PACT for pan-microbial photoinactivation via straight forward modifications. Our studies suggested that integration of an efficient photosensitizer, good amphiphilicity, as well as tight interaction with microbial membrane could be essential for effective PACT.


title: Estimated cerebral oxyhemoglobin as a useful indicator of neuroprotection in patients with post-cardiac arrest syndrome: a prospective, multicenter observational study.

text: INTRODUCTION Little is known about oxyhemoglobin (oxy-Hb) levels in the cerebral tissue during the development of anoxic and ischemic brain injury. We hypothesized that the estimated cerebral oxy-Hb level, a product of Hb and regional cerebral oxygen saturation (rSO2), determined at hospital arrival may reflect the level of neuroprotection in patients with post-cardiac arrest syndrome (PCAS). METHODS The Japan Prediction of neurological Outcomes in patients with Post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurological outcomes after out-of-hospital cardiac arrest (OHCA). This study assessed a subgroup of consecutive patients who fulfilled the J-POP registry criteria and successfully achieved return of spontaneous circulation (ROSC) from OHCA. The primary outcome measure was the neurological status at 90 days. RESULTS We analyzed data from 495 consecutive comatose survivors who were successfully resuscitated from OHCA, including 119 comatose patients with prehospital return of spontaneous circulation (ROSC; 24.0%) and 376 cardiac arrests at hospital arrival. In total, 75 patients (15.1%) presented with good neurological outcomes. Univariate analysis revealed that the cerebral oxy-Hb levels were significantly higher in patients with good outcomes. Multivariate logistic regression using the backward elimination method confirmed that the oxy-Hb level was a significant predictor of good neurological outcomes (adjusted odds ratio: 1.27, 95% confidence interval (CI): 1.11 to 1.46). Analysis of the area under the receiver operating characteristic curve (AUC) revealed that an oxy-Hb cut-off of 5.5 provided optimal sensitivity and specificity for predicting good neurological outcomes (AUC: 0.87, 95% CI: 0.83 to 0.91; sensitivity: 77.3%; specificity: 85.6%). The oxy-Hb level appeared to be an excellent prognostic indicator with significant advantages over rSO2 and base excess according to AUC analysis. The significant trend for good neurological outcomes was consistent, even in the subgroup of patients who achieved return of spontaneous circulation upon hospital arrival (1st quartile: 0%; 2nd quartile: 16.7%; 3rd quartile: 29.4%; 4th quartile: 53.3%, P <0.05). CONCLUSIONS The cerebral oxy-Hb level may predict neurological outcomes and is a simple and excellent indicator of neuroprotection in patients with PCAS. TRIAL REGISTRATION UMIN Clinical Trials Registry UMIN000005065. Registered 1 April 2011.


title: Pulse oximetry-derived respiratory rate in general care floor patients.

text: Respiratory rate is recognized as a clinically important parameter for monitoring respiratory status on the general care floor (GCF). Currently, intermittent manual assessment of respiratory rate is the standard of care on the GCF. This technique has several clinically-relevant shortcomings, including the following: (1) it is not a continuous measurement, (2) it is prone to observer error, and (3) it is inefficient for the clinical staff. We report here on an algorithm designed to meet clinical needs by providing respiratory rate through a standard pulse oximeter. Finger photoplethysmograms were collected from a cohort of 63 GCF patients monitored during free breathing over a 25-min period. These were processed using a novel in-house algorithm based on continuous wavelet-transform technology within an infrastructure incorporating confidence-based averaging and logical decision-making processes. The computed oximeter respiratory rates (RRoxi) were compared to an end-tidal CO2 reference rate (RRETCO2). RRETCO2 ranged from a lowest recorded value of 4.7 breaths per minute (brpm) to a highest value of 32.0 brpm. The mean respiratory rate was 16.3 brpm with standard deviation of 4.7 brpm. Excellent agreement was found between RRoxi and RRETCO2, with a mean difference of -0.48 brpm and standard deviation of 1.77 brpm. These data demonstrate that our novel respiratory rate algorithm is a potentially viable method of monitoring respiratory rate in GCF patients. This technology provides the means to facilitate continuous monitoring of respiratory rate, coupled with arterial oxygen saturation and pulse rate, using a single non-invasive sensor in low acuity settings.


title: Association of Skin and Cartilage Variables With Composite Graft Healing in a Rabbit Model.

text: Importance Composite grafting in nasal reconstruction involves transplanting auricular chondrocutaneous grafts, but the optimal design of these grafts is unknown. Objectives To investigate the ideal ratio of skin to cartilage as well as study the importance of the perichondrial attachment for graft survival. Design, Setting, and Participants A New England white rabbit model was used in this study, performed at the Laboratory for Animal Research at University of Kansas Medical Center from January 25 to March 18, 2016. Four varying designs of chondrocutaneous auricular grafts were transplanted to dorsal back defects, with a total of 10 grafts per treatment arm completed. The following 4 chondrocutaneous circular grafts were designed: group A, 1.5-cm diameter graft of equal skin to cartilage ratio; group B, 2.0-cm diameter skin and 1.5-cm diameter cartilage; group C, 1.5-cm diameter skin and 2.0-cm diameter cartilage; and group D, 1.5-cm diameter skin and cartilage separated and placed back together in a layered fashion. Grafts were observed until postoperative day 21, harvested, and evaluated with visual observation as well as histopathologic assessment. Main Outcomes and Measures Visually graded areas of survival were marked by 2 blinded academic facial plastic surgeons and calculated for approximate survival. Hematoxylin-eosin-stained, paraffin-embedded 5-μm slides were evaluated for overall survival rate, rate of cartilage necrosis, and mean vessel density per high-power field. In both cases, observers were blinded as to the study group. Results Visual assessments of the 5 female rabbits showed significant agreement between surgeons and consistency, with a Spearman coefficient of 0.84 and an intraclass correlation of 0.98. Group D (skin and cartilage separation) was visually graded to have significantly decreased mean survival (45.4%; 95% CI, 23.3%-67.4%) compared with group A (mean survival, 97.4%; 95% CI, 94.8%-99.9%; P < .001), group B (mean survival, 87.6%; 95% CI, 69.9%-100%; P = .004), and group C (mean survival, 82.1%; 95% CI, 66.0%-98.1%; P = .008). Histopathologic assessment revealed that group D again showed significantly inferior overall survival, increased cartilage necrosis, and decreased mean vessel density compared with group A. Group C additionally showed significantly decreased cartilage survival compared with group A (65% vs 0%; P < .001) and group B (65% vs 35%; P = .02). Conclusions and Relevance These results represent preliminary evidence that the attachment of skin to perichondrium in a composite graft plays an important role for graft survival. Clinicians performing nasal reconstruction with chondrocutaneous composite grafts should consider preserving attachments at this junction to improve graft survival. Levels of Evidence NA.


title: Review of frequency of dysmenorrhea and some associated factors and evaluation of the relationship between dysmenorrhea and sleep quality in university students.

text: OBJECTIVE To determine the frequency of dysmenorrhea in university students, review some associated factors and evaluate the relationship between dysmenorrhea and sleep quality. MATERIAL AND METHODS The study group included 520 students. Survey forms prepared previously in line with the study objective were completed by the students under supervision. The severity of dysmenorrhea was rated with Visual Analogue Scale. Pittsburgh Sleep Quality Index was used to evaluate the sleep quality. The χ(2) test, Mann-Whitney U test and Kruskal-Wallis test were used for the analyses. Statistical significance level was accepted at p < 0.05. RESULTS Mean age of the students was 20.23 ± 1.59 years (range 17-25). Frequency of dysmenorrhea was determined to be 69.0% (n = 359). Frequency of dysmenorrhea was higher in smokers, those with menstrual irregularity, those who use drugs for menstrual regulation and those having a family history (p < 0.05 for each). The most frequent symptoms in those having dysmenorrhea history were weakness (59.6%), fatigue (58.5%) and breast tenderness (45.4%), respectively. Sleep quality was found to be poorer in the students having a history of dysmenorrhea (p < 0.05). CONCLUSIONS Dysmenorrhea is an important health problem in young women. Dysmenorrhea affects the sleep quality negatively.


title: TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS.

text: The host response to RNA virus infection consists of an intrinsic innate immune response and the induction of apoptosis as mechanisms to restrict viral replication. The mitochondrial adaptor molecule MAVS plays critical roles in coordinating both virus-induced type I interferon production and apoptosis; however, the regulation of MAVS-mediated apoptosis is poorly understood. Here, we show that the adaptor protein TAX1BP1 functions as a negative regulator of virus-induced apoptosis. TAX1BP1-deficient cells are highly sensitive to apoptosis in response to infection with the RNA viruses vesicular stomatitis virus and Sendai virus and to transfection with poly(I·C). TAX1BP1 undergoes degradation during RNA virus infection, and loss of TAX1BP1 is associated with apoptotic cell death. TAX1BP1 deficiency augments virus-induced activation of proapoptotic c-Jun N-terminal kinase (JNK) signaling. Virus infection promotes the mitochondrial localization of TAX1BP1 and concomitant interaction with the mitochondrial adaptor MAVS. TAX1BP1 recruits the E3 ligase Itch to MAVS to trigger its ubiquitination and degradation, and loss of TAX1BP1 or Itch results in increased MAVS protein expression. Together, these results indicate that TAX1BP1 functions as an adaptor molecule for Itch to target MAVS during RNA virus infection and thus restrict virus-induced apoptosis.


title: MAGNAMOSIS IV: magnetic compression anastomosis for minimally invasive colorectal surgery.

text: BACKGROUND AND STUDY AIMS MAGNAMOSIS forms a compression anastomosis using self-assembling magnetic rings that can be delivered via flexible endoscopy. The system has proven to be effective in full-thickness porcine small-bowel anastomoses. The aim of this study was to show the feasibility of the MAGNAMOSIS system in hybrid endoscopic colorectal surgery and to compare magnetic and conventional stapled anastomoses. METHODS A total of 16 swine weighing 35 - 50 kg were used following animal ethical committee approval. The first animal was an acute model to establish the feasibility of the procedure. The subsequent 15 animals were survival models, 10 of which underwent side-to-side anastomoses (SSA) and 5 of which underwent end-to-side (ESA) procedures. Time to patency, surveillance endoscopy, burst pressure, compression force, and histology were assessed. Histology was compared with conventional stapled anastomoses. Magnetic compression forces were measured in various anastomosis configurations. RESULTS Colorectal anastomoses were performed in all cases using a hybrid NOTES technique. The mean operating time was 71 minutes. Mean time to completion of the anastomosis was similar between the SSA and ESA groups. Burst pressure at 10 days was greater than 95 mmHg in both groups. One complication occurred in the ESA group. Compression force among various configurations of the magnetic rings was significantly different (P < 0.05). Inflammation and fibrosis were similar between magnetic SSA and conventional stapled anastomoses. CONCLUSION MAGNAMOSIS was feasible in performing a hybrid NOTES colorectal anastomosis. It has the advantage over circular staplers of precise endoscopic delivery throughout the entire colon. SSA was reliable and effective. A minimum initial compression force of 4 N appears to be required for reliable magnetic anastomoses.


title: Safety and accuracy of semirigid pleuroscopy performed by pulmonary fellows at a major university hospital: our initial experience.

text: BACKGROUND Pleuroscopy is considered a safe procedure with a high diagnostic accuracy but this record is based on studies published by pulmonologists experienced in performing the procedure. METHODS Review of 40 consecutive patients who underwent semirigid pleuroscopy by a pulmonary fellow under the supervision of a pulmonologist. RESULTS Pleuroscopy was performed for diagnosis of pleural effusion (n=33), or treatment of pleural effusion (n=4) or pneumothorax (n=3). The mean age±SD of the patients was 58.23±12.98 years and 23 patients were male. Pleuroscopy was performed with a flex-rigid pleuroscope under local anesthesia and conscious sedation. An ultrasound was used to choose the entry site. The dose of midazolam and fentanyl used was 6.45±2.87 mg and 173.39±77.17 mcg, respectively. The duration of the procedure was 69.3±25.3 minutes. The amount of pleural fluid removed was 1.5±0.94 L. The overall diagnostic accuracy of pleuroscopy was 87.8%, and the sensitivity, specificity, negative and positive predictive value for malignancy was 93.9%, 100%, 92.3% and 100%, respectively. There were a few complications: desaturation (n=2), hypotension (n=5), extensive subcutaneous emphysema (n=3), and persistent air leak (n=1). There was no case of significant bleeding or death from the procedure. Six of the 7 cardiopulmonary complications occurred during the first 4 procedures performed by the fellows. CONCLUSIONS The diagnostic accuracy of pleuroscopy remains high in the hands of pulmonary fellows. However, the procedure can be associated with a slightly higher rate of complications when performed by fellows in training, especially in the early part of their learning curve. Most of the few complications observed were not caused by the procedure per se and resulted from over-zealous use of medications for conscious sedation.


title: Dysphagia in the intensive care unit: epidemiology, mechanisms, and clinical management.

text: Dysphagia may present in all critically ill patients and large-scale clinical data show that e.g. post-extubation dysphagia (PED) is commonly observed in intensive care unit (ICU) patients. Recent data demonstrate that dysphagia is mostly persisting and that its presence is independently associated with adverse patient-centered clinical outcomes. Although several risk factors possibly contributing to dysphagia development were proposed, the underlying exact mechanisms in ICU patients remain incompletely understood and no current consensus exists on how to best approach ICU patients at risk.From a clinical perspective, dysphagia is well-known to be associated with an increased risk of aspiration and aspiration-induced pneumonia, delayed resumption of oral intake/malnutrition, decreased quality of life, prolonged ICU and hospital length of stay, and increased morbidity and mortality. Moreover, the economic burden on public health care systems is high.In light of high mortality rates associated with the presence of dysphagia and the observation that dysphagia is not systematically screened for on most ICUs, this review describes epidemiology, terminology, and potential mechanisms of dysphagia on the ICU. Furthermore, the impact of dysphagia on affected individuals, health care systems, and society is discussed in addition to current and future potential therapeutic approaches.


title: Computational fluid dynamics analysis of flow reduction induced by flow-diverting stents in intracranial aneurysms: a patient-unspecific hemodynamics change perspective.

text: BACKGROUND AND PURPOSE Flow-diverter stents (FDSs) have been used effectively to treat large neck and complex saccular aneurysms on the anterior carotid circulation. Intra-aneurysmal flow reduction induces progressive aneurysm thrombosis in most patients. Understanding the degree of flow modification necessary to induce complete aneurysm occlusion among patients with considerable hemodynamics variability may be important for treatment planning. MATERIALS AND METHODS Patients with incidental intracranial saccular aneurysms who underwent FDS endovascular procedures were included and studied for a 12 months' follow-up period. We used computational fluid dynamics on patient-specific geometries from 3D rotational angiography without and with virtual stent placement and thus compared intra-aneurysmal hemodynamic problems. Receiver operating characteristic analysis was used to estimate the stent:no-stent minimum hemodynamic ratio thresholds that significantly (p≤0.05) determined the condition necessary for long-term (12 months) aneurysm occlusion. RESULTS We included 12 consecutive patients with sidewall aneurysms located in the internal carotid or vertebral artery. The measured porosity of the 12 deployed virtual FDSs was 83±3% (mean±SD). Nine aneurysms were occluded during the 12 months' follow-up, whereas three were not. A significant (p=0.05) area under the curve (AUC) was found for spatiotemporal mean velocity reduction in the aneurysms: AUC=0.889±0.113 (mean±SD) corresponding to a minimum velocity reduction threshold of 0.353 for occlusion to occur. The 95% CI of the AUC was 0.66 to 1.00. The sensitivity and specificity of the method were ∼99% and ∼67%, respectively. For both wall shear stress and pressure reductions in aneurysms no thresholds could be determined: AUC=0.63±0.16 (p=0.518) and 0.67±0.165 (p=0.405), respectively. CONCLUSIONS For successful FDS treatment the post-stent average velocity in sidewall intracranial aneurysms must be reduced by at least one-third from the initial pre-stent conditions.


title: Prevalence of Self-Reported Hypertension and Antihypertensive Medication Use by County and Rural-Urban Classification - United States, 2017.

text: In 2017, approximately one in three U.S. adults reported having been told by a health care professional that they had high blood pressure (hypertension) (1). Although hypertension prevalence is well documented at national and state levels, less is known about rural-urban variation and county-level prevalence. To examine prevalence of self-reported hypertension and antihypertensive medication use by rural-urban classification and county, CDC analyzed data reported by 442,641 adults aged ≥18 years who participated in the 2017 Behavioral Risk Factor Surveillance System (BRFSS). In rural (noncore) areas, 40.0% (unadjusted prevalence) of adults reported having hypertension, whereas in the most urban (large central metro) areas, 29.4% reported having hypertension. Age-standardized hypertension prevalence was significantly higher in the most rural areas, compared with the most urban areas within nearly all categories of age, sex, and other demographic characteristics. Model-based hypertension prevalence across counties ranged from 18.0% to 55.0% and was highest in Southeastern* and Appalachian† counties. Model-based county-level prevalence of antihypertensive medication use among adults with hypertension ranged from 54.3% to 84.7%. Medication use also was higher in rural areas compared with use in most urban areas, with prevalence highest in Southeastern and Appalachian counties as well as counties in the Dakotas and Nebraska. CDC is working with states to enhance hypertension awareness and management through a strategy of team-based care that involves physicians, nurses, pharmacists, dietitians, and community health workers. The increased use of telemedicine to support this strategy might improve access to care among underserved populations.


title: COVID-19 and diabetes mellitus: implications for prognosis and clinical management.

text: INTRODUCTION COVID-19 is a novel coronavirus that emerged from Wuhan, China in December 2019, and within 3 months became a global pandemic. AREAS COVERED PubMed search of published data on COVID-19, respiratory infections, and diabetes mellitus (DM). DM associates with impairments of both cellular and humoral immunity. Early emergent global data reveal that severity of clinical outcome from COVID-19 infection (including hospitalization and admission to Intensive Care Unit [ICU]), associate with co-morbidities, prominently DM. The key principles of management of COVID-19 in patients with DM include ongoing focused outpatient management (remotely where necessary) and maintenance of good glycemic control. EXPERT OPINION We will remember the dawn of the third decade of the twenty-first century as a time when the world changed, the true scale and impact of which is hard for us to imagine. Like a phoenix from the ashes though, COVID-19 provides us with a great learning opportunity to renew insights into ourselves as individuals, our clinical teams, and the optimized provision of care for our patients. COVID-19 has re-shaped and re-focused our collective societal values, with a sea-changed shift from materialistic to human-centric, from self-centredness to altruism, ultimately for the betterment of patient care and the whole of society.


title: Mechanical Thrombectomy for M2 Occlusions: A Single-Centre Experience.

text: Background The recent success of several mechanical thrombectomy trials has resulted in a significant change in the management of patients presenting with stroke. However, questions still remain as to whether certain groups will benefit from mechanical thrombectomy. In particular, it is still uncertain whether mechanical thrombectomy should be performed in the M2 branches and, more generally, in the distal vasculature. Methods We retrospectively analysed our prospectively maintained database of all patients undergoing mechanical thrombectomy between January 2008 and August 2016. We collected demographic, radiological, procedural and outcome data. Results We identified 106 patients that met our inclusion criteria. The mean age of the patients was 68 ± 13.8 years, and there were 58 (54.7%) male patients. Associated medical conditions were common with hypertension seen in 71% of the patients. The average Alberta Stroke Program Early CT (ASPECT) score on admission was 8.5 ± 1.7. The mean National Institutes of Health Stroke Scale score was 11.8 ± 7.02. The mean duration of the procedure was 103 ± 3.4 min, and the average number of thrombectomy attempts required was 1.8 (range 1-8). Angiographically, Thrombolysis in Cerebral Infarction Scale (TICI) ≥2b was obtained in 90.5% of the patients. Five patients (4.7%) had symptomatic intracranial haemorrhage on follow-up. At 90-day follow-up, 54.6% of the patients had a modified Rankin Scale (mRS) score 0-2, and 71.5% had an mRS score ≤3. There were 15 deaths at 90 days (14.1%). Conclusion Mechanical thrombectomy in patients with solitary M2 clots is technically possible and carries a high degree of success with a good safety profile. Patients with confirmed M2 occlusion should be considered for mechanical thrombectomy.


Physical Activity And Reducing Sedentary Behavior During The Coronavirus Pandemic.


title: The Clinical Picture of Severe Systemic Capillary-Leak Syndrome Episodes Requiring ICU Admission.

text: OBJECTIVE Systemic capillary-leak syndrome is a very rare cause of recurrent hypovolemic shock. Few data are available on its clinical manifestations, laboratory findings, and outcomes of those patients requiring ICU admission. This study was undertaken to describe the clinical pictures and ICU management of severe systemic capillary-leak syndrome episodes. DESIGN, SETTING, PATIENTS This multicenter retrospective analysis concerned patients entered in the European Clarkson's disease (EurêClark) Registry and admitted to ICUs between May 1992 and February 2016. MEASUREMENTS AND MAIN RESULTS Fifty-nine attacks occurring in 37 patients (male-to-female sex ratio, 1.05; mean ± SD age, 51 ± 11.4 yr) were included. Among 34 patients (91.9%) with monoclonal immunoglobulin G gammopathy, 20 (58.8%) had kappa light chains. ICU-admission hemoglobin and proteinemia were respectively median (interquartile range) 20.2 g/dL (17.9-22 g/dL) and 50 g/L (36.5-58.5 g/L). IV immunoglobulins were infused (IV immunoglobulin) during 15 episodes (25.4%). A compartment syndrome developed during 12 episodes (20.3%). Eleven (18.6%) in-ICU deaths occurred. Bivariable analyses (the 37 patients' last episodes) retained Sequential Organ-Failure Assessment score greater than 10 (odds ratio, 12.9 [95% CI, 1.2-140]; p = 0.04) and cumulated fluid-therapy volume greater than 10.7 L (odds ratio, 16.8 [1.6-180]; p = 0.02) as independent predictors of hospital mortality. CONCLUSIONS We described the largest cohort of severe systemic capillary-leak syndrome flares requiring ICU admission. High-volume fluid therapy was independently associated with poorer outcomes. IV immunoglobulin use was not associated with improved survival; hence, their use should be considered prudently and needs further evaluation in future studies.


title: Differential reactivity of serum immunoglobulins from Brazilian wild mammals to staphylococcal A and streptococcal G proteins.

text: Human pathogens have evolved to infect vertebrate hosts other than human beings without causing symptoms of the disease, thus permitting them to complete their life cycle and to develop into infectious forms. The identification and management of infected animals are alternatives to control dissemination of the disease and to prevent human illness. In the current study, the potential use of staphylococcal A or streptococcal G proteins was evaluated with enzyme-linked immunosorbent assays (ELISAs) for seroepidemiological studies. Sera were collected from animals that were representative of 23 different Brazilian wild mammals. A high protein A binding rate was observed in all animals, except for the orders Didelphimorphia, Artiodactyla, and Rodentia, in which affinity was medium or low. Affinity for streptococcal G protein was higher in animals of the order Artiodactyla, whereas no streptococcal G protein binding was observed in samples obtained from felines (order Carnivora). Bacterial protein binding to mammalian immunoglobulins was confirmed by immunoblotting. The results suggest that secondary detection systems should be better investigated in ELISA protocols before their implementation in seroepidemiological studies involving wild mammals.


Medical Education during the health contingency by COVID-19: Lessons for the future.


title: Increases in Health-Related Workplace Absenteeism Among Workers in Essential Critical Infrastructure Occupations During the COVID-19 Pandemic - United States, March-April 2020.

text: During a pandemic, syndromic methods for monitoring illness outside of health care settings, such as tracking absenteeism trends in schools and workplaces, can be useful adjuncts to conventional disease reporting (1,2). Each month, CDC's National Institute for Occupational Safety and Health (NIOSH) monitors the prevalence of health-related workplace absenteeism among currently employed full-time workers in the United States, overall and by demographic and occupational subgroups, using data from the Current Population Survey (CPS).* This report describes trends in absenteeism during October 2019-April 2020, including March and April 2020, the period of rapidly accelerating transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Overall, the prevalence of health-related workplace absenteeism in March and April 2020 were similar to their 5-year baselines. However, compared with occupation-specific baselines, absenteeism among workers in several occupational groups that define or contain essential critical infrastructure workforce† categories was significantly higher than expected in April. Significant increases in absenteeism were observed in personal care and service§ (includes child care workers and personal care aides); healthcare support¶; and production** (includes meat, poultry, and fish processing workers). Although health-related workplace absenteeism remained relatively unchanged or decreased in other groups, the increase in absenteeism among workers in occupational groups less able to avoid exposure to SARS-CoV-2 (3) highlights the potential impact of COVID-19 on the essential critical infrastructure workforce because of the risks and concerns of occupational transmission of SARS-CoV-2. More widespread and complete collection of occupational data in COVID-19 surveillance is required to fully understand workers' occupational risks and inform intervention strategies. Employers should follow available recommendations to protect workers' health.


title: H7N9 Incident, immune status, the elderly and a warning of an influenza pandemic.

text: The novel re-assortment A influenza H7N9 (nrH7N9) emerged in humans in the Shanghai and surrounding provinces of China in late February and early March. Three infected index patients developed severe viral pneumonia with acute respiratory distress syndrome (ARDS) and resulted in fatal outcome. As of 15 April 2013 there were reported 60 confirmed nrH7N9 infections with 13 fatalities. Human-to-human transmission has not been observed, but zoonotic infections of nrH7N9 from birds to humans appear to be associated with live poultry markets. Elderly patients greater than 60 years of age accounted for 61% of the cases, indicating that the elderly may be at high risk for severe disease.


title: Real-world stent retriever thrombectomy for acute ischemic stroke beyond 6 hours of onset: analysis of the NASA and TRACK registries.

text: BACKGROUND The DEFUSE 3 and DAWN trials have shown the benefit of thrombectomy beyond 6 hours of stroke symptom onset in carefully selected patients. OBJECTIVE To evaluate the real-world outcomes of stent retriever thrombectomy beyond 6 hours of stroke onset using combined individual patient data from the North American Solitaire Stent Retriever Acute Stroke (NASA) and Trevo Stent-Retriever Acute Stroke (TRACK) registries. METHODS Pooled analysis of individual patient data of all cases of anterior circulation acute ischemic stroke (AIS) from NASA and TRACK was performed to compare outcomes of patients presenting within the first hours 6 or beyond 6 hours of stroke symptom onset. RESULTS Of 830 patients with anterior circulation AIS from the NASA and TRACK registries, 32.7% (271 patients) underwent thrombectomy beyond the first 6 hours of symptom onset. The rates of good clinical outcome (modified Rankin scale score of 0-2 at 90 days), mortality, and symptomatic intracranial hemorrhage were similar: 48.1%, 20.6%, and 8.0% within 0-6 hours, 46.2%, 21.6%, and 10.9% within 6-16 hours, and 38.9%, 33.3%, and 5% within 16-24 hours (p=0.8, 0.6, and 0.5, respectively). The rates of successful recanalization (Thrombolysis in Cerebral Infarction 2b/3) were 79.4% in patients with stroke within 0-6 hours, 72.6% within 6-16 hours, and 85.0% within 16-24 hours (p=0.04). CONCLUSIONS Real-world experience with patients with anterior circulation AIS treated with the Solitaire and Trevo thrombectomy devices beyond the first 6 hours of symptom onset proved to be equally safe and effective as for patients with symptom onset within the first 6 hours.


[The impact of the COVID-19 pandemic on surgery for malignant diseases].


title: Endovascular treatment with flow diverters may fail to occlude experimental bifurcation aneurysms.

text: INTRODUCTION Animal models may explain how stents and flow diverters (FDs) may succeed or fail to treat bifurcation aneurysms. METHODS In vitro studies were designed to anticipate device deformations in bifurcations. Large, wide-necked bifurcation aneurysms were constructed in 21 animals and treated 4-8 weeks later using stents and FDs in various combinations, forming four main groups: parent artery to right branch flow diversion (RBFD, n = 6), parent artery to left branch flow diversion (LBFD, n = 6), Y flow diversion (YFD, n = 4), and compared with high-porosity Y-stenting (YHPS, n = 4). The results include immediate and follow-up angiography at 3 months, followed by grading of the extent of neointimal coverage of devices at pathology. RESULTS In vitro, all braided devices showed varying porosities according to characteristic zones. FDs can be compacted to decrease porosities, but a limiting factor is the constant presence of a more porous transition zone. In vivo, 3/6 RBFD, 4/6 LBFD, and 2/4 YFD treated aneurysms had decreased in size by 3 months, while those treated with YHPS increased in size (P = 0.15). There was a significant correlation between device porosities and extent of neointimal coverage (r = 0.639, P = 0.002), and between porosities and angiographic evolution (r = -0.655, P = 0.002), but not between neointima formation and angiographic evolution (r = -0.278, P = 0.235). Failures could be explained in all cases by the presence of leaks or holes in the neointima at the level of the transition zones. CONCLUSION FDs did not successfully treat most bifurcation aneurysms, at least in this animal model.


title: Buying Time: Using OMM to Potentially Reduce the Demand for Mechanical Ventilation in Patients With COVID-19.

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic is causing an increased need for mechanical ventilation for a significant percentage of people who present to the hospital for treatment. This increase in demand could surpass the supply of ventilators and lead to an increase in mortality due to a lack of ventilator vacancies. There is significant evidence that osteopathic manipulative medicine (OMM) can alleviate pulmonary symptoms and aid in quicker recoveries from various respiratory ailments. OMM has the potential to play a significant role in helping reduce a patient's need for mechanical ventilation by delaying the onset of acute respiratory distress syndrome stemming from SARS-Cov2 infections.


docid: qnyepwxt

title: Emergent endovascular recanalization for cervical internal carotid artery occlusion in patients presenting with acute stroke.

text: BACKGROUND Acute proximal (cervical) internal carotid artery (ICA) occlusion may cause ischemia of an entire hemisphere or no ischemia at all, depending on the presence of intracranial collaterals. OBJECTIVE To retrospectively analyze the clinical results for emergent endovascular carotid recanalization in patients with acute proximal (cervical) ICA occlusion and to assess predictors of recanalization and clinical, neurological, and functional outcome. METHODS Emergent endovascular revascularization was attempted in 22 patients presenting with acute stroke secondary to complete cervical ICA occlusion. Patients with pseudo-occlusion were excluded. Recanalization was assessed with the Thrombolysis in Myocardial Ischemia (TIMI) system: grade 0 (no flow) to grade 3 (normal flow). RESULTS The median age of the patients was 65 years; mean admission National Institutes of Health Stroke Scale (NIHSS) score was 14. Recanalization (TIMI grade 2/3) occurred in 17 patients (77.3%). Ten patients (45.5%) demonstrated significant clinical improvement during hospitalization (NIHSS improved ≥4 points). Fifty percent of patients had good outcomes (modified Rankin Scale ≤2) after a median follow-up of 3 months. Patient age <70 years and successful recanalization (TIMI grade 2/3) predicted a good outcome (P ≤ .01). Presence of atrial fibrillation, admission NIHSS score ≥20, and complete ICA occlusion at all levels (cervical, petrocavernous, and intracranial) were associated with poor outcomes (P ≤ .05). Patients with complete cervical ICA occlusion but partial distal preservation of the vessel were most likely to benefit from the intervention (recanalization in 88.2%; good outcome in 64.7%). CONCLUSION Attempts at emergent endovascular carotid recanalization for acute stroke are encouraged, particularly in younger patients with partial distal preservation of the ICA.


title: SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms.

text: Among the multiple organ disorders caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), acute lung failure following atypical pneumonia is the most serious and often fatal event. We hypothesized that two of the hydrophilic structural coronoviral proteins (S and E) would regulate alveolar fluid clearance by decreasing the cell surface expression and activity of amiloride-sensitive epithelial sodium (Na(+)) channels (ENaC), the rate-limiting protein in transepithelial Na(+) vectorial transport across distal lung epithelial cells. Coexpression of either S or E protein with human alpha-, beta-, and gamma-ENaC in Xenopus oocytes led to significant decreases of both amiloride-sensitive Na(+) currents and gamma-ENaC protein levels at their plasma membranes. S and E proteins decreased the rate of ENaC exocytosis and either had no effect (S) or decreased (E) rates of endocytosis. No direct interactions among SARS-CoV E protein with either alpha- or gamma-ENaC were indentified. Instead, the downregulation of ENaC activity by SARS proteins was partially or completely restored by administration of inhibitors of PKCalpha/beta1 and PKCzeta. Consistent with the whole cell data, expression of S and E proteins decreased ENaC single-channel activity in oocytes, and these effects were partially abrogated by PKCalpha/beta1 inhibitors. Finally, transfection of human airway epithelial (H441) cells with SARS E protein decreased whole cell amiloride-sensitive currents. These findings indicate that lung edema in SARS infection may be due at least in part to activation of PKC by SARS proteins, leading to decreasing levels and activity of ENaC at the apical surfaces of lung epithelial cells.


title: Conserved residues in the UL24 protein of herpes simplex virus 1 are important for dispersal of the nucleolar protein nucleolin.

text: The UL24 family of proteins is widely conserved among herpesviruses. We demonstrated previously that UL24 of herpes simplex virus 1 (HSV-1) is important for the dispersal of nucleolin from nucleolar foci throughout the nuclei of infected cells. Furthermore, the N-terminal portion of UL24 localizes to nuclei and can disperse nucleolin in the absence of any other viral proteins. In this study, we tested the hypothesis that highly conserved residues in UL24 are important for the ability of the protein to modify the nuclear distribution of nucleolin. We constructed a panel of substitution mutations in UL24 and tested their effects on nucleolin staining patterns. We found that modified UL24 proteins exhibited a range of subcellular distributions. Mutations associated with a wild-type localization pattern for UL24 correlated with high levels of nucleolin dispersal. Interestingly, mutations targeting two regions, namely, within the first homology domain and overlapping or near the previously identified PD-(D/E)XK endonuclease motif, caused the most altered UL24 localization pattern and the most drastic reduction in its ability to disperse nucleolin. Viral mutants corresponding to the substitutions G121A and E99A/K101A both exhibited a syncytial plaque phenotype at 39 degrees C. vUL24-E99A/K101A replicated to lower titers than did vUL24-G121A or KOS. Furthermore, the E99A/K101A mutation caused the greatest impairment of HSV-1-induced dispersal of nucleolin. Our results identified residues in UL24 that are critical for the ability of UL24 to alter nucleoli and further support the notion that the endonuclease motif is important for the function of UL24 during infection.


title: Optimized on-line enantioselective capillary electrophoretic method for kinetic and inhibition studies of drug metabolism mediated by cytochrome P450 enzymes.

text: Pharmacokinetic and pharmacodynamic properties of a chiral drug can significantly differ between application of the racemate and single enantiomers. During drug development, the characteristics of candidate compounds have to be assessed prior to clinical testing. Since biotransformation significantly influences drug actions in an organism, metabolism studies represent a crucial part of such tests. Hence, an optimized and economical capillary electrophoretic method for on-line studies of the enantioselective drug metabolism mediated by cytochrome P450 enzymes was developed. It comprises a diffusion-based procedure, which enables mixing of the enzyme with virtually any compound inside the nanoliter-scale capillary reactor and without the need of additional optimization of mixing conditions. For CYP3A4, ketamine as probe substrate and highly sulfated γ-cyclodextrin as chiral selector, improved separation conditions for ketamine and norketamine enantiomers compared to a previously published electrophoretically mediated microanalysis method were elucidated. The new approach was thoroughly validated for the CYP3A4-mediated N-demethylation pathway of ketamine and applied to the determination of its kinetic parameters and the inhibition characteristics in presence of ketoconazole and dexmedetomidine. The determined parameters were found to be comparable to literature data obtained with different techniques. The presented method constitutes a miniaturized and cost-effective tool, which should be suitable for the assessment of the stereoselective aspects of kinetic and inhibition studies of cytochrome P450-mediated metabolic steps within early stages of the development of a new drug.


COVID-19 Pandemic: Saudi Arabia's Role at National and International Levels.


title: Extended left pneumonectomy and left atrial reconstruction with autogenous graft in patient with T4 lung cancer.

text: In selective patients with T4 non-small cell lung cancer with the primary tumor invading the mediastinal organs, extended lung resection may contribute to long-term survival. Adequate patients should be given a chance for surgery if complete resection and required reconstruction can be achieved. In this article, we report a 63-year-old male patient with T4 non-small cell lung cancer invading the left atrium. In the patient, we performed an extended left pneumonectomy with en bloc partial resection of the left atrium wall (4×2.5 cm) where the defect was repaired with pericardial patch via cardiopulmonary bypass. No severe complication developed postoperatively. The patient who was given adjuvant chemotherapy has been living for more than 10 years without disease.


title: Management of the mother-infant dyad with suspected or confirmed SARS-CoV-2 infection in a highly epidemic context.

text: addresses a number of aspects of the mother-infant dyad management during SARS-CoV-2 epidemic. Networking among maternity centers and anticipatory planning is essential to organise the assistance to mothers and neonates in maternity and neonatal wards. Early identification of SARS-CoV-2 infected mothers, before delivery, allows their management through dedicated protocols and minimizes the risk of contagion for other patients and healthcare providers. Vertical transmission of SARS-CoV-2 cannot be excluded at present, and should be ruled out as soon as possible after birth. Rooming in of infected mothers and neonates, provided their good clinical conditions, is not contraindicated based on current knowledge. The choice of breastfeeding should be carefully discussed with parents based on current, evolving scientific evidence.


title: Comparative Retrospective Study of Tension-Free Vaginal Mesh Surgery, Native Tissue Repair, and Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse Repair.

text: Methods We identified that 308 women who had undergone surgical repair of POP were followed up for at least 6 months. Recurrence rates of POP after tension-free vaginal mesh (TVM) surgery (n = 243), native tissue repair (NTR) (vaginal hysterectomy with colpopexy, anterior and posterior colpoplasty, or circumferential suturing of the levator ani muscles and apical repair by transvaginal sacrospinous ligament fixation (SSLF)) (NTR; n = 31), and laparoscopic sacrocolpopexy after subtotal hysterectomy (LSC; n = 34) were compared. Presence of mesh erosion was also recorded. Results Patients who underwent LSC were significantly younger (65.32 ± 3.23 years) than those who underwent TVM surgery (69.61 ± 8.31 years). After TVM surgery, the rate of recurrence (over POP-Q stage II) was 6.17% (15/243) and was highest in patients with advanced POP. The recurrence rate in patients who underwent NTR procedure was 3.23% (1/34) and that in patients who underwent LSC was 11.76% (4/11). There was no statistically significant difference in the recurrence rate between the three types of surgery. There were 13 cases (5.35%) of mesh erosion after TVM surgery and none after LSC surgery. The risk of mesh erosion was correlated with having had total TVM surgery but not with patient age or POP stage. Repeat procedures were performed in 5 women (2.14%) who underwent TVM surgery and 1 (2.94%) who underwent LSC. No patient underwent repeat surgery after NTR. There was no statistically significant difference in the reoperation rate between the three types of surgery. Conclusion Our study suggested that TVM surgery, NTR, and LSC have comparable outcomes as for the postoperative recurrence rate and mesh erosion. However, the outcomes of each technique need to be carefully evaluated over a long period of time.


title: Avian bornavirus associated with fatal disease in psittacine birds.

text: Thanks to new technologies which enable rapid and unbiased screening for viral nucleic acids in clinical specimens, an impressive number of previously unknown viruses have recently been discovered. Two research groups independently identified a novel negative-strand RNA virus, now designated avian bornavirus (ABV), in parrots with proventricular dilatation disease (PDD), a severe lymphoplasmacytic ganglioneuritis of the gastrointestinal tract of psittacine birds that is frequently accompanied by encephalomyelitis. Since its discovery, ABV has been detected worldwide in many captive parrots and in one canary with PDD. ABV induced a PDD-like disease in experimentally infected cockatiels, strongly suggesting that ABV is highly pathogenic in psittacine birds. Until the discovery of ABV, the Bornaviridae family consisted of a single species, classical Borna disease virus (BDV), which is the causative agent of a progressive neurological disorder that affects primarily horses, sheep, and some other farm animals in central Europe. Although ABV and BDV share many biological features, there exist several interesting differences, which are discussed in this review.


title: In silico virtual screening approaches for anti-viral drug discovery

text: Despite the considerable advances in medical and pharmaceutical research during the past years, diseases caused by viruses have remained a major burden to public health. Virtual in silico screening has repeatedly proven to be useful to meet the special challenges of antiviral drug discovery. Large virtual compound libraries are filtered by different computational screening methods such as docking, ligand-based similarity searches or pharmacophore-based screening, reducing the number of candidate molecules to a smaller set of promising candidates that are then tested biologically. This rational approach makes the drug discovery process more goal-oriented and saves resources in terms of time and money. In this review we discuss how different virtual screening techniques can be applied to antiviral drug discovery, present recent success stories in this field and finally address the main differences between the methods.


title: Virus-infected alveolar epithelial cells direct neutrophil chemotaxis and inhibit their apoptosis.

text: The alveolar epithelium is a critical target for pulmonary viruses and can produce proinflammatory cytokines and chemokines upon viral infection. However, the molecular interactions between virus-infected alveolar epithelial cells and inflammatory cells, including polymorphonuclear leukocytes (PMNs), have not been thoroughly characterized. Rat coronavirus (RCoV) is used as a model to study the immune response to viral infection in the lung of the natural host. We have developed an in vitro model to characterize the response of PMNs to RCoV-infected type I-like alveolar epithelial (AT1) cells, the primary target for RCoV infection in the alveoli. Multiple CXC chemokines that signal through CXCR2 were required for PMN chemotaxis toward medium from RCoV-infected AT1-like cells (RCoV-AT1). Furthermore, RCoV-AT1 inhibited spontaneous PMN apoptosis, including activation of effector caspase 3 and initiator caspases 8 and 9. Use of a selective inhibitor of CXCR2, SB265610, demonstrated that CXCR2 signaling was required for RCoV-AT1-mediated inhibition of PMN apoptosis. These data suggest that CXC chemokines produced by RCoV-infected AT1-like cells inhibit PMN apoptosis during infection. These studies provide new insight into the molecular mechanisms whereby alveolar epithelial cells direct the functions of PMNs during viral infection of the lung.


title: Symptoms and responses to critical incidents in paramedics who have experienced childhood abuse and neglect.

text: BACKGROUND Mental and physical symptoms are common in paramedics, which may relate to high work stress, including critical incidents. As previous trauma is a risk factor for psychological symptoms after exposure to critical incidents, the prevalence of childhood experiences with abuse and neglect and paramedics' adaptation to critical incidents may be important. METHODS 635 paramedics were surveyed regarding childhood experiences of physical, sexual or emotional abuse as well an index critical incident from the past, acute stress responses to that event and current mental and physical symptoms. A comparison group of 159 female hospital-based healthcare workers completed the same survey of childhood abuse and neglect in a separate study. RESULTS 232 paramedics (36.5%) responded. Among these, physical, sexual or emotional childhood abuse was reported by 38.4%. Female paramedics reported significantly more emotional and physical abuse and neglect than female hospital workers. Paramedics who reported childhood abuse or neglect more frequently experienced signs of acute stress immediately following the index critical incident and for the following 2 weeks. Childhood abuse and neglect were associated with significantly higher scores for depressive symptoms, physical symptoms and burnout, and a higher prevalence of 'cases' scoring above thresholds of clinical significance. CONCLUSION Childhood abuse may be more common in paramedics than in other healthcare workers, at least in women. Childhood abuse and neglect is associated with acute stress responses to critical incidents and to current physical and mental symptoms. These results are based on a low response rate and may not be generalisable.


docid: lngrasqt

title: A novel running annuloplasty suture technique for robotically assisted mitral valve repair.


title: Cerebellar degeneration in adult spinal muscular atrophy patients.

text: BACKGROUND Spinal muscular atrophy (SMA) is a genetic motor neuron disease related to deletions in the SMN1 gene. There is mounting evidence that the disease is not restricted to motor neurons. In this neuroimaging study, we aimed to investigate the presence of in-vivo cerebellar damage in adult SMA patients not treated with disease-modifying treatment. METHODS Twenty-five molecularly confirmed patients with SMA type III or IV and 25 healthy controls underwent MRI with cerebellar focused structural analysis by the CERES automated pipeline. Volumetry (total and gray matter-GM) as well as cortical thickness of the cerebellar lobules were compared in both groups. Full clinical and demographic data were then assessed for correlations with cerebellar imaging findings. RESULTS Volumes of cerebellar lobules VIIIB (right), IX and X were significantly smaller in patients with SMA. Lobule IX also had GM atrophy in comparison to controls. We found no significant correlation between clinical findings and cerebellar damage. CONCLUSIONS Neuroimaging detects cerebellar structural changes in adult SMA patients, suggesting that neurodegeneration is not confined to the lower motor neurons in the disease.