title: Study on the public psychological states and its related factors during the outbreak of coronavirus disease 2019 (COVID-19) in some regions of China.

text: Background: As COVID-19 occurs suddenly and is highly contagious, this will inevitably cause people anxiety, depression, etc. The study on the public psychological states and its related factors during the COVID-19 outbreak is of practical significance.Methods: 600 valid questionnaires were received. The Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) were used.Results: Females' anxiety risk was 3.01 times compared to males (95% CI 1.39-6.52). Compared with people below 40 years old, the anxiety risk of people above 40 years old was 0.40 times (95% CI 0.16-0.99). SDS results indicated that the difference between education level and occupation was statistically significant (p = 0.024, 0.005). Compared to people with a master's degree or above, those with a bachelor's degree group had a depression risk of 0.39 times (95% CI 0.17-0.87). Compared with professionals, industrial service workers and other staff had a depression risk of 0.31 times (95% CI 0.15-0.65) and 0.38 times (95% CI 0.15-0.93).Conclusions: 600 questionnaire participants were psychologically stable. Non-anxiety and non-depression rates were 93.67% and 82.83%, respectively. There were anxiety in 6.33% and depression in 17.17%. Therefore, we should pay attention to the psychological states of the public.


title: Tumour eradication using synchronous thermal ablation and Hsp90 chemotherapy with protein engineered triblock biopolymer-geldanamycin conjugates.

text: PURPOSE Hepatocellular carcinoma (HCC) suffers high tumour recurrence rate after thermal ablation. Heat shock protein 90 (Hsp90) induced post-ablation is critical for tumour survival and progression. A combination therapy of thermal ablation and polymer conjugated Hsp90 chemotherapy was designed and evaluated for complete tumour eradication of HCC. MATERIALS AND METHODS A thermo-responsive, elastin-like polypeptide (ELP)-based tri-block biopolymer was developed and conjugated with a potent Hsp90 inhibitor, geldanamycin (GA). The anti-cancer efficacy of conjugates was evaluated in HCC cell cultures with and without hyperthermia (43 °C). The conjugates were also administered twice weekly in a murine HCC model as a single treatment or in combination with single electrocautery as the ablation method. RESULTS ELP-GA conjugates displayed enhanced cytotoxicity in vitro and effective heat shock inhibition under hyperthermia. The conjugates alone significantly slowed the tumour growth without systemic toxicity. Four doses of thermo-responsive ELP-GA conjugates with concomitant simple electrocautery accomplished significant Hsp90 inhibition and sustained tumour suppression. CONCLUSION Hsp90 inhibition plays a key role in preventing the recurrence of HCC, and the combination of ablation with targeted therapy holds great potential to improve prognosis and survival of HCC patients.


title: Totally Endoscopic Resection of Giant Left Atrial Myxoma Without Robotic Assistance.

text: There was no report on the application of totally endoscopic surgery for giant atrial myxoma resection. A 62-year-old female patient with giant atrial myxoma causing severe mitral stenosis and acute pulmonary edema underwent a successful operation by totally endoscopic techniques without the assistance of robotic systems using four small trocar ports (three 5-mm trocars and one 12-mm trocar). The patient recovered uneventfully and was satisfied with cosmetic results.


title: Extracorporeal Manual Morcellation of Very Large Uteri Within an Enclosed Endoscopic Bag: Our 5-Year Experience.

text: STUDY OBJECTIVES To describe a technique to manually morcellate large uteri within a polyurethane endoscopic bag at the time of laparoscopic hysterectomy, and report perioperative outcomes from our 5 years of experience. STUDY DESIGN Retrospective review of all consecutive hysterectomies with uterine weight >500 g performed between January 2010 and December 2014 in which the uterus was manually morcellated within an endoscopic bag by either an abdominal or vaginal approach (Canadian Task Force Classification Level III). SETTING Tertiary care academic medical center. PATIENTS A total of 104 women with a uterine weight >500 g who underwent laparoscopic hysterectomy using a manual morcellation technique. INTERVENTION Manual morcellation was done extracorporeally, within a partially exteriorized specimen bag, using a scalpel under direct visualization by the operating surgeon. MEASUREMENTS AND MAIN RESULTS A total of 104 laparoscopic hysterectomies were performed in women with a uterus weighing >500 g using a manual morcellation technique for specimen extraction. The median patient age was 48.1 years (range, 34-69 years), and the median body mass index was 31.0 kg/m(2) (range, 19.1-56.7 kg/m(2)). The median blood loss and specimen weight were 200 mL (range, 20-1200 mL) and 741.5 g (range, 500-1930 g), respectively. Morcellation was performed through an abdominal approach in 58.7% of the patients and through a vaginal approach in 41.3%. The median duration of morcellation was 14.8 minutes (range, 4.5-21.6 minutes) for the abdominal route and 11.7 minutes (range, 5.2-16.8 minutes) for the vaginal route. Occult malignancy was identified in 2 patients. There were no complications related to the morcellation technique or gross bag rupture. CONCLUSION Manual morcellation within an endoscopic bag allows for the extraction of large uteri without the use of a power morcellator. In our 5 years of experience, we have not experienced any incidence of gross spillage, visually noted bag rupture, or complications associated with our morcellation technique.


title: The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial.

text: RATIONALE Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-β. Exogenous IFN-β restores antiviral activity. OBJECTIVES To compare the efficacy and safety of inhaled IFN-β with placebo administered to people with asthma after onset of cold symptoms to prevent or attenuate asthma symptoms caused by respiratory viruses. METHODS A total of 147 people with asthma on inhaled corticosteroids (British Thoracic Society Steps 2-5), with a history of virus-associated exacerbations, were randomized to 14-day treatment with inhaled IFN-β (n = 72) or placebo (n = 75) within 24 hours of developing cold symptoms and were assessed clinically, with relevant samples collected to assess virus infection and antiviral responses. MEASUREMENTS AND MAIN RESULTS A total of 91% of randomized patients developed a defined cold. In this modified intention-to-treat population, asthma symptoms did not get clinically significantly worse (mean change in six-item Asthma Control Questionnaire <0.5) and IFN-β treatment had no significant effect on this primary endpoint, although it enhanced morning peak expiratory flow recovery (P = 0.033), reduced the need for additional treatment, and boosted innate immunity as assessed by blood and sputum biomarkers. In an exploratory analysis of the subset of more difficult-to-treat, Step 4-5 people with asthma (n = 27 IFN-β; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-β (P = 0.004). CONCLUSIONS Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-β is a potential treatment for virus-induced deteriorations of asthma in difficult-to-treat people with asthma and supports the need for further, adequately powered, trials in this population. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).


docid: nzhsdbqv

title: Interactions of BDNF Val66Met Polymorphism and Menstrual Pain on Brain Complexity.

text: The irregularity and uncertainty of neurophysiologic signals across different time scales can be regarded as neural complexity, which is related to the adaptability of the nervous system and the information processing between neurons. We recently reported general loss of brain complexity, as measured by multiscale sample entropy (MSE), at pain-related regions in females with primary dysmenorrhea (PDM). However, it is unclear whether this loss of brain complexity is associated with inter-subject genetic variations. Brain-derived neurotrophic factor (BDNF) is a widely expressed neurotrophin in the brain and is crucial to neural plasticity. The BDNF Val66Met single-nucleotide polymorphism (SNP) is associated with mood, stress, and pain conditions. Therefore, we aimed to examine the interactions of BDNF Val66Met polymorphism and long-term menstrual pain experience on brain complexity. We genotyped BDNF Val66Met SNP in 80 PDM females (20 Val/Val, 31 Val/Met, 29 Met/Met) and 76 healthy female controls (25 Val/Val, 36 Val/Met, 15 Met/Met). MSE analysis was applied to neural source activity estimated from resting-state magnetoencephalography (MEG) signals during pain-free state. We found that brain complexity alterations were associated with the interactions of BDNF Val66Met polymorphism and menstrual pain experience. In healthy female controls, Met carriers (Val/Met and Met/Met) demonstrated lower brain complexity than Val/Val homozygotes in extensive brain regions, suggesting a possible protective role of Val/Val homozygosity in brain complexity. However, after experiencing long-term menstrual pain, the complexity differences between different genotypes in healthy controls were greatly diminished in PDM females, especially in the limbic system, including the hippocampus and amygdala. Our results suggest that pain experience preponderantly affects the effect of BDNF Val66Met polymorphism on brain complexity. The results of the present study also highlight the potential utilization of resting-state brain complexity for the development of new therapeutic strategies in patients with chronic pain.


COVID-19 remedies.


Aspergillus endocarditis in the era of new antifungals: major role for antigen detection.


title: Battle scars and resilience at the healthcare frontline.

text: The COVID-19 pandemic has created an historic global crisis, resulting in unprecedented stressors on frontline healthcare systems. The population remains on edge, and hospitals are stretched to capacity. This is not our first pandemic. We have learned from prior outbreaks that, in addition to the sheer physical burden, there are also likely to be important but often unacknowledged behavioral and psychosocial costs.1 Frontline healthcare workers, may be particularly vulnerable to harmful psychological consequences.


title: A Comparison of China's Risk Communication in Response to SARS and H7N9 Using Principles Drawn From International Practice.

text: BACKGROUND China's emergency management of severe acute respiratory syndrome (SARS) was heavily criticized, whereas the H7N9 response was praised by the international community.AimsThe aims of this study were to examine and compare the strengths and weaknesses of risk communication conducted in response to SARS and H7N9 and their associated social impacts on affected communities in China. METHOD A qualitative comparative case study approach was employed in the present study, using a set of 8 risk communication principles selected from international literature to suit the Chinese context for the comparative analysis of emergency responses of SARS and H7N9. RESULTS The study found significant differences in the risk communication conducted in the 2 cases. The SARS outbreak fully exposed China's lack of experience in public health risk communication. By contrast, the Chinese government's risk communication strategies had improved significantly during the H7N9 outbreak.DiscussionTrust is the basis for communication. Maintaining an open and honest attitude and actively engaging stakeholders to address their risk information needs will serve to build trust and facilitate multi-sector collaborations in dealing with a public health crisis. CONCLUSIONS From SARS to H7N9, risk communication practices in China greatly improved, which, in turn, lessened adverse social impacts and improved outcomes in emergency management of public health crises. (Disaster Med Public Health Preparedness. 2018;12:587-598).


title: Clinical experience with a simple retraction device in single-port laparoscopic cholecystectomy: technical description and initial results.

text: BACKGROUND Performing single-port laparoscopic cholecystectomy (SPLC) is challenging as triangulation is limited and the critical view is difficult to obtain. We present our initial experience using a simple retraction device to reduce these problems. MATERIAL AND METHODS In January 2012 a novel lifter was introduced at our department and subsequently used in SPLC for suspension of the gallbladder. Perioperative data were collected prospectively. In addition, all videos were reviewed to assess any adverse events caused by the lifter. RESULTS Thirty (20 female and 10 male) patients at a median age of 48.4 years (range: 23-83) were operated using this novel retraction device. Median BMI accounted for 26.0 kg/m(2) (median; range: 14.0-36.9). Retraction of the gallbladder using the lifter was possible in all patients. In four cases (13.3 %) spillage of bile caused by the lifter was recorded. In addition, perforation of the gallbladder was seen once (3.3 %), caused by electrocautery. No inflammation, induration or visible scars were seen in the right upper quadrant at six weeks postoperatively in any patient. CONCLUSIONS Gallbladder retraction in SPLC using this novel device is feasible and safe without leaving any apparent scar. Rate of bile spillage is (at least) comparable to that reported for conventional laparoscopic cholecystectomy.


title: Generating and Maintaining Transgenic Cryptosporidium parvum Parasites.

text: The apicomplexan parasite Cryptosporidium is a leading cause of diarrheal disease and an important contributor to overall global child mortality. We currently lack effective treatment and immune prophylaxis. Recent advances now permit genetic modification of this important pathogen. We expect this to produce rapid advances in fundamental as well as translational research on cryptosporidiosis. Here we outline genetic engineering for Cryptosporidium in sufficient detail to establish transfection in any laboratory that requires access to this key technology. This chapter details the conceptual design consideration, as well as the experimental steps required to transfect, select, and isolate transgenic parasites. We also provide detail on key in vitro and in vivo assays to detect, validate, and quantify genetically modified Cryptosporidium parasites. © 2017 by John Wiley & Sons, Inc.


title: A case series of continuous paravertebral block in minimally invasive cardiac surgery.

text: Background Minimally invasive cardiac surgery (MICS), via minithoracotomy, is thought to be a fast track to extubation and recovery after surgery. For this, good coverage analgesia is essential. Epidural anesthesia, a standard technique for thoracic surgery, has high risk of complications, such as epidural abscess and spinal hematoma in open-heart surgery. Based on the hypothesis that continuous paravertebral block (CPVB), a less invasive regional anesthetic technique, is safe and effective in open-heart surgery, we applied CPVB to MICS with thoracotomy. Findings To assess whether CPVB could be used in open-heart surgery with fewer potential complications, we investigated our medical records of the 87 adult patients who underwent MICS at Akashi Medical Center, Hyogo, Japan, between March 2009 and May 2016. We collected data of CPVB-related complications, postextubation respiratory failure, duration of intubation, and other analgesic use from hospital clinical records. We observed no severe CPVB-related complications, such as hematoma, neuropathy, or abscess. PT-INR longer than 1.1 was associated with CPVB-related minor bleeding. Forty-three patients (47.4%) were extubated within 1 h after surgery, and there were no postextubation respiratory failures in any patients. Conclusions We observed no cases of severe CPVB-related complications or postextubation respiratory failure in any of our patients who underwent MICS. Preoperative prolongation of PT-INR was associated with CPVB-related minor bleeding.


title: COVID-19, microangiopathy, hemostatic activation, and complement.

text: In COVID-19, complement activation may contribute to hemostatic activation leading to pathological features such as microvascular injury and coagulopathy.


title: Brain monitoring with electroencephalography and the electroencephalogram-derived bispectral index during cardiac surgery.

text: Cardiac surgery presents particular challenges for the anesthesiologist. In addition to standard and advanced monitors typically used during cardiac surgery, anesthesiologists may consider monitoring the brain with raw or processed electroencephalography (EEG). There is strong evidence that a protocol incorporating the processed EEG bispectral index (BIS) decreases the incidence intraoperative awareness in comparison with standard practice. However, there is conflicting evidence that incorporating the BIS into cardiac anesthesia practice improves "fast-tracking," decreases anesthetic drug use, or detects cerebral ischemia. Recent research, including many cardiac surgical patients, shows that a protocol based on BIS monitoring is not superior to a protocol based on end-tidal anesthetic concentration monitoring in preventing awareness. There has been a resurgence of interest in the anesthesia literature in limited montage EEG monitoring, including nonproprietary processed indices. This has been accompanied by research showing that with structured training, anesthesiologists can glean useful information from the raw EEG trace. In this review, we discuss both the hypothesized benefits and limitations of BIS and frontal channel EEG monitoring in the cardiac surgical population.


title: The feasibility of single-incision video-assisted thoracoscopic major pulmonary resection performed by surgeons experienced with a two-incision technique.

text: OBJECTIVES This study evaluated the safety and feasibility of a single-incision video-assisted thoracoscopic surgery (VATS) major pulmonary resection performed by surgeons experienced with the two-incision technique. METHODS Consecutive patients who underwent single-incision VATS major pulmonary resection from March 2012 to May 2013 were included. The fifth intercostal space was incised (3-5 cm) at the anterior or posterior axillary line according to the tumour location. RESULTS In total, 60 patients (39 men, 21 women; median age, 61 years; interquartile range, 53-69 years) were included in this study. Malignant lung disease was diagnosed preoperatively in 56 patients (93%) and benign disease in 4 (7%) patients. Lobectomy was performed in the majority of patients (n = 55), bilobectomy in 1, sleeve lobectomy in 1 and segmentectomy in 3. Four patients (7%) required a second incision, and conversion to thoracotomy was required in 2 (3%). In 50 lung cancer cases completed using a single-incision technique, the median surgical duration was 145 min (interquartile range, 90-182 min), and the total number of dissected lymph nodes per patient was 22 (interquartile range, 10-28 min). The chest tube was removed 5 days (interquartile range, 3-6 days) postoperatively, and there were no cases involving major perioperative morbidity or mortality. CONCLUSIONS Single-incision VATS major pulmonary resection is feasible, and following a two-incision technique learning period, may yield results similar to those obtained with conventional VATS lobectomy.


title: Do anti-embolism stockings fit our legs? Leg survey and data analysis.

text: BACKGROUND Anti-embolism stockings are commonly used worldwide to prevent the development of thrombosis in hospitalised patients. Patients are typically measured for, and fitted with, anti-embolism stockings during extended periods of non-ambulation. Anti-embolism stockings must critically fit the leg to achieve optimum blood flow and thus success of prophylaxis. Therefore, hospitals endeavour to maintain stock of anti-embolism stockings that fit the majority of their patients. OBJECTIVES The objective of this study was to establish whether popular styles/brands of anti-embolism stockings "fitted" the legs of convenience sampled volunteers. DESIGN/METHODS Volunteer's legs were measured at ankle, calf and thigh following guidance from British nurses and in accordance with brand instructions. Leg measurements were subsequently compared to the size charts of 10 anti-embolism stocking styles made by 4 different manufacturers. "Fit" is defined as a volunteer's leg measurements matching any stocking size in a range at all measurement points. SETTINGS Volunteers were measured in different settings around Scotland, including private homes, work places and shopping centres. PARTICIPANTS A convenience sample of 471 volunteers (283 female, 188 male) were recruited on the basis of willingness to participate and being over 16 years old. Volunteers ranged from 17 years to 82 years old with an average age of 35. RESULTS The 10 different styles of anti-embolism stockings, made by 4 different brands, examined for this paper had a size match coefficient ranging from 0% to 100% for our volunteer's legs. The size match coefficient is strongly influenced by the Brand's sizing policy. CONCLUSIONS The proportion of legs that "fit" a particular brand of anti-embolism stockings can be increased through: (1) the reduction of the number of leg measurement points that need to be matched to the size chart of the stockings; (2) the use of open-ended size ranges; (3) the use of increased size range width and (4) the use of increased overlap between sizes. However, all but the last of these measures can have a potentially deleterious impact on the ability of the stocking to deliver the optimum graduated pressure profile to all legs that "fit" the stocking, resulting in important implications to the efficacy of prophylaxis.


Protective Strategies in a Simulated Model When Performing Percutaneous Tracheostomies in the COVID-19 Era.


title: Interventions to improve school-based eye-care services in low- and middle-income countries: a systematic review.

text: Objective To review interventions improving eye-care services for schoolchildren in low- and middle-income countries. Methods We searched online databases (CINAHL, Embase®, ERIC, MEDLINE®, ProQuest, PubMed® and Web of ScienceTM) for articles published between January 2000 and May 2018. Eligible studies evaluated the delivery of school-based eye-care programmes, reporting results in terms of spectacle compliance rates, quality of screening or attitude changes. We considered studies to be ineligible if no follow-up data were reported. Two authors screened titles, abstracts and full-text articles, and we extracted data from eligible full-text articles using the availability, accessibility, acceptability and quality rights-based conceptual framework. Findings Of 24 559 publications screened, 48 articles from 13 countries met the inclusion criteria. Factors involved in the successful provision of school-based eye-care interventions included communication between health services and schools, the willingness of schools to schedule sufficient time, and the support of principals, staff and parents. Several studies found that where the numbers of eye-care specialists are insufficient, training teachers in vision screening enables the provision of a good-quality and cost-effective service. As well as the cost of spectacles, barriers to seeking eye-care included poor literacy, misconceptions and lack of eye health knowledge among parents. Conclusion The provision of school-based eye-care programmes has great potential to reduce ocular morbidity and developmental delays caused by childhood vision impairment and blindness. Policy-based support, while also attempting to reduce misconceptions and stigma among children and their parents, is crucial for continued access.


title: The predictive performance of propofol target-controlled infusion during robotic-assisted laparoscopic prostatectomy with CO2 pneumoperitoneum in the head-down position.

text: PURPOSE Propofol clearance can be reduced when cardiac output (CO) is decreased. This clearance reduction may alter the pharmacokinetics of propofol and worsen the predictive performance of target-controlled infusion (TCI) of propofol. The head-down position (HDP) and CO2 pneumoperitoneum, which are required for robotic-assisted laparoscopic prostatectomy (RALP), may cause changes in CO. We investigated the predictive performance of propofol TCI during CO2 pneumoperitoneum in patients who underwent RALP in the HDP. METHODS Fifteen male patients received propofol TCI using the Diprifusor model. Propofol concentrations were measured at seven time points: (T1) 15 min after anesthesia induction; (T2) before the insufflation; (T3, T4, and T5) 15, 60, and 90 min, respectively, after insufflation in the HDP; (T6) before the release of pneumoperitoneum in the HDP; and (T7) 15 min after the release of pneumoperitoneum in the supine position. Cardiac index (CI) was assessed using an arterial pulse contour CO monitor. The predictive performance of propofol TCI was evaluated by calculating the performance errors (PE) in propofol concentrations for each data point. The relationship between CI and PE was examined. Median PE (MDPE) and median absolute PE (MDAPE) were calculated as measures of bias and accuracy, respectively. RESULTS A total of 104 blood samples were analyzed. There was significantly negative correlation between CI and PE. The predictive performance of propofol TCI during pneumoperitoneum in the HDP was acceptable (MDPE = - 1.5% and MDAPE = 18.8%). CONCLUSION The predictive performance of propofol TCI during RALP with CO2 pneumoperitoneum in the HDP was acceptable.


title: Software tools to support title and abstract screening for systematic reviews in healthcare: an evaluation.

text: BACKGROUND Systematic reviews are vital to the pursuit of evidence-based medicine within healthcare. Screening titles and abstracts (T&Ab) for inclusion in a systematic review is an intensive, and often collaborative, step. The use of appropriate tools is therefore important. In this study, we identified and evaluated the usability of software tools that support T&Ab screening for systematic reviews within healthcare research. METHODS We identified software tools using three search methods: a web-based search; a search of the online "systematic review toolbox"; and screening of references in existing literature. We included tools that were accessible and available for testing at the time of the study (December 2018), do not require specific computing infrastructure and provide basic screening functionality for systematic reviews. Key properties of each software tool were identified using a feature analysis adapted for this purpose. This analysis included a weighting developed by a group of medical researchers, therefore prioritising the most relevant features. The highest scoring tools from the feature analysis were then included in a user survey, in which we further investigated the suitability of the tools for supporting T&Ab screening amongst systematic reviewers working in medical research. RESULTS Fifteen tools met our inclusion criteria. They vary significantly in relation to cost, scope and intended user community. Six of the identified tools (Abstrackr, Colandr, Covidence, DRAGON, EPPI-Reviewer and Rayyan) scored higher than 75% in the feature analysis and were included in the user survey. Of these, Covidence and Rayyan were the most popular with the survey respondents. Their usability scored highly across a range of metrics, with all surveyed researchers (n = 6) stating that they would be likely (or very likely) to use these tools in the future. CONCLUSIONS Based on this study, we would recommend Covidence and Rayyan to systematic reviewers looking for suitable and easy to use tools to support T&Ab screening within healthcare research. These two tools consistently demonstrated good alignment with user requirements. We acknowledge, however, the role of some of the other tools we considered in providing more specialist features that may be of great importance to many researchers.


title: Dual roles of DNA repair enzymes in RNA biology/post-transcriptional control.

text: Despite consistent research into the molecular principles of the DNA damage repair pathway for almost two decades, it has only recently been found that RNA metabolism is very tightly related to this pathway, and the two ancient biochemical mechanisms act in alliance to maintain cellular genomic integrity. The close links between these pathways are well exemplified by examining the base excision repair pathway, which is now well known for dual roles of many of its members in DNA repair and RNA surveillance, including APE1, SMUG1, and PARP1. With additional links between these pathways steadily emerging, this review aims to provide a summary of the emerging roles for DNA repair proteins in the post-transcriptional regulation of RNAs. WIREs RNA 2016, 7:604-619. doi: 10.1002/wrna.1353 For further resources related to this article, please visit the WIREs website.


title: Association between the employment status and the presence of depressive symptoms in men and women in Mexico.

text: This study aims to estimate the relationship between employment status and depressive symptoms among Mexican adults, as well as to explore its differential effect by gender. Cross-sectional study of 36,516 adults between 20 and 59 years of age taken from the 2012 Mexican National Health and Nutrition Survey. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale (CES-D), and the employment status was determined a week before the survey. Logistic regression models were stratified by gender and education level and adjusted by sociodemographic and health-related conditions to estimate the association between depressive symptoms and employment status. The prevalence of clinically depressive symptoms was 7.59% for men and 18.62% for women. In the case of men, those who were unemployed were more likely to present depressive symptoms (OR = 1.66; 95%CI: 1.08-2.55) than those who were working. For women, employment status is not associated with the presence of depressive symptoms, except in students (OR = 1.57; 95%CI: 1.02-2.43) compared with those who were working. In both genders, disability preventing one from working was associated with depressive symptoms. Although being employed has been reported to be associated with lower levels of psychiatric morbidity, the estimated effect is different for men and women. Occupational health policies should consider these conditions.


title: Laparoscopic ovariectomy in dogs: a comparison of the LigaSure™ and the SonoSurg™ systems.

text: OBJECTIVES The objective of this study was to evaluate the surgical times for removal of ovaries, and the frequency of intra-operative complications with two different instruments used for canine laparoscopic ovariectomy. METHODS A randomised prospective clinical study. Laparoscopic ovariectomy was performed under general anaesthesia on 10 healthy female dogs admitted for elective ovariectomy. Each ovary was randomly assigned to removal by use of either a SonoSurg™ ultrasonic surgical device (Olympus), or a LigaSure™ vessel-sealing system (Valleylab/Covidien). Surgical time for removal of each ovary was measured and the frequency of intra-operative complications was recorded. A follow-up was made by interview with the owners, 2·5 years after surgery. RESULTS The two techniques did not statistically differ with regard to surgical time, or frequency of complications. All owners were very satisfied with the procedure. CLINICAL RELEVANCE Both the SonoSurg™ and the LigaSure™ devices appear to be effective, safe and easy to use when performing laparoscopic ovariectomy in dogs.


title: Co-colonization by Streptococcus pneumoniae and Staphylococcus aureus in the throat during acute respiratory illnesses.

text: Pneumonia due to either Streptococcus pneumoniae (Sp) or Staphylococcus aureus (Sa) accounts for most mortality after influenza and acute respiratory illness (ARI). Because carriage precedes infection, we estimated Sp and Sa carriage to examine the co-colonization dynamics between Sp, Sa and respiratory viruses in the presence of ARI in the oropharynx. We tested oropharyngeal specimens of community subjects (aged ⩾2 years) with ARI for the presence of influenza A and B, 11 other common respiratory viruses, Sp and Sa, using real-time PCR. A total of 338 participants reported 519 ARI episodes of which 119 (35%) carried Sp, 52 (13%) carried Sa and 25 (7%) carried both. Thirty-five subjects tested positive for influenza, of which 14 (40%) carried Sp and six (17%) carried Sa, significantly more than in the influenza-negative group (P = 0·03 and P = 0·04, respectively). In subjects infected by any virus compared to those with no virus, Sp carriage (39·2% vs. 27·9%, P = 0·03) but not Sa carriage (11·6% vs. 14%, P = 0·6) was more frequent. For children, when Sa was present, Sp carriage tended to be less frequent than expected given the presence of viral infection, but not significantly [observed relative risk 1·14, 95% confidence interval (CI) 0·4-3·1; with a relative excess risk due to interaction of -0·11]. Independent of age, Sp carriers were more likely to return that season with subsequent ARI (odds ratio 2·14, 95% CI 1·1-4·3, P = 0·03). Both Sp and Sa carriage rates in the oropharynx increase during influenza infection in children. However, no negative interaction between Sp and Sa was observed. Sp carriers are more likely to suffer subsequent ARI episodes than non-carriers.


title: Comparison of multiple viral population characterization methods on a candidate cross-protection Citrus tristeza virus (CTV) source.

text: Citrus tristeza virus (CTV) is the most economically important virus found on citrus and influences production worldwide. The 3' half of the RNA genome is generally conserved amongst sources, whereas the 5' portion is more divergent, allowing for the classification of the virus into a number of genotypes based on sequence diversity. The acknowledged genotypes of CTV are continually being expanded, and thus far include T36, T30, T3, VT, B165, HA16-5, T68 and RB. The genotype composition of the CTV populations of a potential cross protection source in Mexican lime was studied whilst comparing different techniques of viral population characterization. Cloning and sequencing of an ORF 1a fragment, genotype specific RT-PCRs and Illumina sequencing of the p33 gene as well as RNA template enrichment through immuno-capture was done. Primers used in the cloning and sequencing proved to be biased towards detection of the VT genotype. RT-PCR and Illumina sequencing using the two different templates provided relatively comparable results, even though the immuno-captured enriched template provided less than expected CTV specific data, while the RT-PCRs and p33 sequencing cannot be used to make inferences about the rest of the genome; which may vary due to recombination. The source was found to contain multiple genotypes, including RB and VT. When choosing a characterization method, the features of the virus under study should be considered. It was found that Illumina sequencing offers an opportunity to gain a large amount of information regarding the entire viral genome, but challenges encountered are discussed.


title: Dynamic evaluation of near-infrared peripheral oximetry in healthy volunteers: a comparison between INVOS and EQUANOX.

text: PURPOSE The present study aimed to compare peripheral regional tissue oxygen saturation (rSO2) values and desaturation/resaturation rates given by INVOS and EQUANOX devices. MATERIALS AND METHODS Twenty healthy volunteers were investigated during 4 experimental steps: baseline, hyperoxia, ischemia, and reperfusion. For each volunteer, 2 sensors INVOS and 2 sensors EQUANOX were placed on both left and right calves. Blood pressure, heart rate, and peripheral pulse oximetry were monitored. RESULTS Peripheral rSO2 ranged from 40% to 95% (INVOS) and from 47% to 100% (EQUANOX): 81±12 vs 82±9 (P=.469). A significant relationship was found at baseline between absolute values of INVOS and EQUANOX (n=40; R2=0.159; P=.011). Bias was -0.4%, and limits of agreement were ±15.1%. The percent maximum differences vs baseline values during dynamic maneuvers were 33%±19% (95% confidence interval, 24-42) and 21%±14% (95% confidence interval, 15-28) for INVOS and EQUANOX, respectively. No significant relationship was observed between percent maximum differences in INVOS and EQUANOX (n=20; R2=0.128; P=.122). Rates of desaturation/resaturation during occlusive vascular tests were 3.65% per minute vs 2.36% per minute (P=.027) and 30.42% per minute vs 16.28% per minute (P=.004) for INVOS and EQUANOX, respectively. CONCLUSIONS INVOS and EQUANOX are not comparable in measuring both absolute values and dynamic changes of peripheral rSO2 and near-infrared spectroscopy-derived parameters during occlusion vascular tests.


title: Open mini-flank partial nephrectomy: an essential contemporary operation.

text: Secondary to the widespread use of the modern imaging techniques of computed tomography, magnetic resonance imaging, and ultrasound, 70% of renal tumors today are detected incidentally with a median tumor size of less than 4 cm. Twenty years ago, all renal tumors, regardless of size were treated with radical nephrectomy (RN). Elective partial nephrectomy (PN) has emerged as the treatment of choice for small renal tumors. The basis of this paradigm shift is three major factors: (1) cancer specific survival is equivalent for T1 tumors (7 cm or less) whether treated by PN or RN; (2) approximately 45% of renal tumors have indolent or benign pathology; and (3) PN prevents or delays the onset of chronic kidney disease, a condition associated with increased cardiovascular morbidity and mortality. Although PN can be technically demanding and associated with potential complications of bleeding, infection, and urinary fistula, the patient derived benefits of this operation far outweigh the risks. We have developed a "mini-flank" open surgical approach that is highly effective and, coupled with rapid recovery postoperative care pathways associated with a 2-day length of hospital stay.


title: Probing the metastable state of influenza hemagglutinin.

text: Viral entry into host cells is mediated by membrane proteins in a metastable state that transition to a more stable state upon a stimulus. For example, in the influenza envelope protein hemagglutinin (HA), the low pH in the endosome triggers a transition from the metastable prefusion conformation to the stable fusion conformation. To identify probes that interfere with HA function, here we screened a library of H7 HA peptides for inhibition of H7 HA-mediated entry. We discovered a peptide, PEP87 (WSYNAELLVAMENQHTI), that inhibited H7 and H5 HA-mediated entry. PEP87 corresponds to a highly conserved helical region of the HA2 subunit of HA that self-interacts in the neutral pH conformation. Mutagenesis experiments indicated that PEP87 binds to its native region in the HA trimer. We also found that PEP87 is unstructured in isolation but tends to form a helix as evidenced by CD and NMR studies. Fluorescence, chemical cross-linking, and saturation transfer difference NMR data suggested that PEP87 binds to the neutral pH conformation of HA and disrupts the HA structure without affecting its oligomerization state. Together, this work provides support for a model in which PEP87 disrupts HA function by displacing native interactions of the neutral pH conformation. Moreover, our observations indicate that the HA prefusion structure (and perhaps the metastable states of other viral entry proteins) is more dynamic with transient motions being larger than generally appreciated. These findings also suggest that the ensemble of prefusion structures presents many potential sites for targeting in therapeutic interventions.


title: Laparoscopic hand-assisted liver resection for tumours in the left lateral section.

text: Context The role of the laparoscopic left lateral sectionectomy (LLLS) is debatable, and Level-1 data are lacking. Aims The aim of the study is to evaluate the feasibility and safety of this approach. Settings and Design This was a retrospective study. Subjects and Methods From 2007 to 2014, patients undergoing LLLS were identified from two institutions. Statistical Analysis Used Continuous variables were compared between groups with Student's t-test or Mann-Whitney test, as appropriate by type of distribution. Categorical variables were compared with Chi-square or Fisher's exact test, depending on the number of observations. Results Thirty-eight patients were included in the study. The mean age was 63.5 + 13 years (range, 31-89), and the mean number of tumours was 1.7 + 1.5. Eleven (29%) patients underwent LLS combined with an additional liver resection (combined resections group). The mean duration of the operation and the mean estimated blood loss were significantly decreased in the LLS group compared to the combined resection group (101 + 71 min vs. 208 + 98 min and 216 + 217 ml vs. 450 + 223 ml; P < 0.05 for both, respectively). The major complications rate was 8% and no mortality occurred. Conclusions In a subset of carefully selected cases, LLLS may provide the benefits of laparoscopy. This does not appear to compromise perioperative morbidity rates. We believe that this approach may serve as a training platform for surgical trainees.


title: A Network Pharmacology Approach to Explore the Potential Mechanisms of Huangqin-Baishao Herb Pair in Treatment of Cancer.

text: BACKGROUND The aim of this study was to identify the bioactive ingredients of Huangqin-Baishao herb pair and to reveal its anti-cancer mechanisms through a pharmacology approach. MATERIAL AND METHODS Detailed information on compounds in the HQ-BS herb pair was obtained from the Traditional Chinese medicine systems pharmacology (TCMSP) and screened by the criteria of OB ≥30% and DL ≥0.18. A systematic drug targeting model (SysDT) was used for compound targets prediction, and then the targets were analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The protein-protein interaction (PPI) network of HQ-BS targets was constructed, after identifying core networks through Cytoscape plugins. RESULTS We found 47 bioactive compounds of HQ-BS and 107 human-derived targets. A compound target network and a target signal pathway network were constructed and used for topological analysis. Kaempferol, beta-sitosterol, stigmasterol, wogonin, and oroxylin-a were identified as core compounds and pathways in cancer. The calcium signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, chemical carcinogenesis, estrogen signaling pathway, proteoglycans in cancer, HIF-1 signaling pathway, thyroid hormone signaling pathway, VEGF signaling pathway, small cell lung cancer, prostate cancer, colorectal cancer, NOD-like receptor signaling pathway, and T cell receptor signaling pathway were found to be potential signals of HQ-BS in treating cancer. Through PPI network analysis, TNF signaling pathway, tryptophan metabolism, proteoglycans in cancer, cell cycle, and chemical carcinogenesis sub-networks were obtained. CONCLUSIONS HQ-BS contains various bioactive compounds, including flavonoids, phytosterols, and other compounds, and these compounds can inhibit or activate multiple targets and pathways against cancer.


Challenges of pancreatic cancer chemotherapy in the COVID-19 era.


title: Viral mutation rates.

text: Accurate estimates of virus mutation rates are important to understand the evolution of the viruses and to combat them. However, methods of estimation are varied and often complex. Here, we critically review over 40 original studies and establish criteria to facilitate comparative analyses. The mutation rates of 23 viruses are presented as substitutions per nucleotide per cell infection (s/n/c) and corrected for selection bias where necessary, using a new statistical method. The resulting rates range from 10(-8) to 10(-6) s/n/c for DNA viruses and from 10(-6) to 10(-4) s/n/c for RNA viruses. Similar to what has been shown previously for DNA viruses, there appears to be a negative correlation between mutation rate and genome size among RNA viruses, but this result requires further experimental testing. Contrary to some suggestions, the mutation rate of retroviruses is not lower than that of other RNA viruses. We also show that nucleotide substitutions are on average four times more common than insertions/deletions (indels). Finally, we provide estimates of the mutation rate per nucleotide per strand copying, which tends to be lower than that per cell infection because some viruses undergo several rounds of copying per cell, particularly double-stranded DNA viruses. A regularly updated virus mutation rate data set will be available at www.uv.es/rsanjuan/virmut.


Helen Salisbury: Practising in the dark.


title: Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex.

text: Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.


title: Use of ferrets for electrophysiologic monitoring of ion transport.

text: Limited success achieved in translating basic science discoveries into clinical applications for chronic airway diseases is attributed to differences in respiratory anatomy and physiology, poor approximation of pathologic processes, and lack of correlative clinical endpoints between humans and laboratory animal models. Here, we discuss advantages of using ferrets (Mustela putorus furo) as a model for improved understanding of human airway physiology and demonstrate assays for quantifying airway epithelial ion transport in vivo and ex vivo, and establish air-liquid interface cultures of ferret airway epithelial cells as a complementary in vitro model for mechanistic studies. We present data here that establishes the feasibility of measuring these human disease endpoints in ferrets. Briefly, potential difference across the nasal and the lower airway epithelium in ferrets could be consistently assessed, were highly reproducible, and responsive to experimental interventions. Additionally, ferret airway epithelial cells were amenable to primary cell culture methods for in vitro experiments as was the use of ferret tracheal explants as an ex vivo system for assessing ion transport. The feasibility of conducting multiple assessments of disease outcomes supports the adoption of ferrets as a highly relevant model for research in obstructive airway diseases.


title: The era of genomic epidemiology.

text: The recent revolution in genomics is already having a profound impact on the practice of epidemiology. The purpose of this commentary is to demonstrate how genomics and epidemiology will continue to rely heavily on each other, now and in the future, by illustrating a number of interaction points between these 2 disciplines: (1) the use of genomics to estimate disease heritability; (2) the impact of genomics on analytical study design; (3) how genome-wide data can be employed to effectively overcome residual population stratification arising from selection bias; (4) the importance of genomics as a tool in epidemiological investigation; (5) the importance of epidemiology in the collection of adequately phenotyped samples for genomics studies, and (6) for unraveling the clinical and therapeutic relevance of genetic variants once they are discovered.


title: Measles-vectored vaccine approaches against viral infections: a focus on Chikungunya.

text: INTRODUCTION The large global burden of viral infections and especially the rapidly spreading vector-borne diseases and other emerging viral diseases show the need for new approaches in vaccine development. Several new vaccine technology platforms have been developed and are under evaluation. Areas covered: This article discusses the measles vector platform technology derived from the safe and highly efficacious measles virus vaccine. The pipeline of measles-vectored vaccine candidates against viral diseases is reviewed. Particular focus is given to the Chikungunya vaccine candidate as the first measles-vectored vaccine that demonstrated safety, immunogenicity, and functionality of the technology in humans even in the presence of pre-existing anti-measles immunity and thus achieved proof of concept for the technology. Expert commentary: Demonstrating no impact of pre-existing anti-measles immunity in humans on the response to the transgene was fundamental for the technology and indicates that the technology is suitable for large-scale immunization in measles pre-immune populations. The proof of concept in humans combined with a large preclinical track record of safety, immunogenicity, and efficacy for a variety of pathogens suggest the measles vector platform as promising plug-and-play vaccine platform technology for rapid development of effective preventive vaccines against viral and other infectious diseases.


title: Early results of endovascular treatment of patients with bilateral stenoses of the internal carotid arteries using proximal protection systems at 30-day follow-up.

text: BACKGROUND Although surgical endarterectomy remains the treatment of choice for carotid artery stenosis, carotid artery stenting (CAS) with use of proximal protection systems (PPS) plays an very important role as alternative treatment modality, especially in patients with critical, symptomatic lesions. This study was single-centre study to evaluate the technical and clinical success of proximal protection devices as the first choice for embolic protection in symptomatic and asymptomatic carotid stenosis in patients with bilateral, advanced lesions of carotid arteries (bilateral stenoses or stenosis and occlusion). METHODS This was a post hoc analysis, with 30-day follow up. We analyzed results of treatment of 38 patients who underwent 38 CAS with PPS, 17 such procedures in asymptomatic (group A), and 21 in symptomatic individuals (group B). The GORE® Flow Reversal System (W.L. Gore, Flagstaff, AZ, USA) was used in 2 patients, and the Mo.Ma Ultra device (Medtronic, Minneapolis, MN, USA) in 36 patients. Mean age was 68±7 years, 65% percent of patient were male. RESULTS There were no procedural and during 30-day follow-up neurologic events. Intolerance of occlusion system occurred in 4 patients (11%) in both groups with any later symptoms. Risk factors of this adverse event comprised: lesions of the left internal carotid lesion and coexisiting diabetes mellitus. CONCLUSIONS CAS in high risk patients with bilateral lesions of carotid arteries with the use of PPS seems to be a relatively very safe procedure.


title: Silk flow-diverter stent for the treatment of complex intracranial aneurysms: A one-year follow-up multicenter study.

text: Background Flow-diverter stents have been successfully used in the treatment of complex aneurysms with limited therapeutic alternatives. We report our experience using the Silk flow diverter (SFD; Balt Extrusion, Montmorency, France) for the treatment of complex aneurysms in four Argentine centers. Methods We conducted a retrospective review of 246 consecutive patients who were treated with the SFD at four Argentine centers between January 2009 and January 2017. The patient and aneurysm characteristics, as well as the details of the procedure, were analyzed. The angiographic and clinical findings were recorded during and immediately after the procedure and at 12-month follow-up. Results Angiography follow-up at 12 months was possible in 235 patients (95.5%) with 282 aneurysms. A total of 265 aneurysms (93.9%) presented with complete occlusion of the aneurysmal sac (class 1) and 17 aneurysms (6.1%) presented with partial occlusion (class 2). The 12-month clinical follow-up showed 11 patients with major events (seven, scale 2; five, scale 3; and two, scale 4). The morbidity and mortality rates were 4.2% (11/289) and 2.1% (5/289), respectively. Conclusions The treatment of aneurysms with the SFD was associated with a low rate of complications and a high percentage of aneurysmal occlusion. These findings suggest that SFD is an effective and safe alternative in the endovascular treatment of complex aneurysms.


title: Clinical characteristics of human bocavirus infections compared with other respiratory viruses in Spanish children.

text: BACKGROUND Human bocavirus (HBoV) can be found in a substantial proportion of children with respiratory tract diseases. The relative importance of HBoV in viral respiratory tract illnesses is not yet well known. OBJECTIVE In this study, we looked for HBoV in pediatric patients to determine the incidence of HBoV as single infection and compared it with other commonly found respiratory viruses to describe the clinical differences associated with HBoV infections in children. PATIENTS AND METHODS A prospective study was conducted on children less than 14 years old, admitted with respiratory infection from September 2005 to August 2007 to the Pediatrics Department of the Severo Ochoa Hospital, Madrid, Spain. We studied the frequency of HBoV and 15 other respiratory viruses in nasopharyngeal aspirates and compared the clinical course of the infections caused by HBoV with those caused by other common respiratory viruses. RESULTS Positive results were confirmed in 435 (61.2%) of the 710 children studied. A single virus was detected in 308 patients. HBoV was found in 99 (13.9%) samples, but it was recovered as a single virus in only 35. Most of patients with HBoV infection (75%) were aged < or =26 months. The most common clinical diagnosis was recurrent wheezing (53%), followed by bronchiolitis (32%). Clinical differences were observed between HBoV and respiratory syncytial virus (RSV) infections (children were older and bronchiolitis less frequent), adenovirus (fever less frequent in HBoV group), and rhinovirus-associated infections (less hypoxia in HBoV group). CONCLUSIONS HBoV was the fourth most frequent single virus after RSV, rhinovirus, and adenovirus in children hospitalized because of respiratory infection. It was associated with recurrent wheezing and bronchiolitis showing a different clinical course from other virus in terms of diagnosis, fever, and age.


title: The role of single-incision laparoscopic surgery in abdominal and pelvic surgery: a systematic review.

text: OBJECTIVE This review aimed to determine the role of single-incision laparoscopic surgery (SILS) in abdominal and pelvic operations. DATA SOURCES The Medline, EMBASE, and PsycINFO databases were systematically searched until October 2009 using "single-incision laparoscopic surgery" and related terms as keywords. References from retrieved articles were reviewed to broaden the search STUDY SELECTION The study included case reports, case series, and empirical studies that reported SILS in abdominal and pelvic operations. DATA EXTRACTION Number of patients, type of instruments, operative time, blood loss, conversion rate, length of hospital stay, length of follow-up evaluation, and complications were extracted from the reviewed items DATA SYNTHESIS The review included 102 studies classified as level 4 evidence. Most of these studies investigated SILS in cholecystectomy (n=34), appendectomy (n=24), and nephrectomy (n=17). For these procedures, operative time, hospital stay, and complications were comparable with those of conventional laparoscopy. Conversion to conventional laparoscopy was seldom performed in cholecystectomy (range, 0-24%) and more frequent in appendectomy (range, 0-41%) and nephrectomy (range, 0-33%). CONCLUSION The potential benefits of SILS include superior cosmesis and possibly shorter operative time, lower costs, and a shortened time to full physical recovery. Careful case selection and a low threshold of conversion to conventional laparoscopic surgery are essential. Multicenter, randomized, prospective studies are needed to compare short- and long-term outcome measures against those of conventional laparoscopic surgery.


title: Median infectious dose of human norovirus GII.4 in gnotobiotic pigs is decreased by simvastatin treatment and increased by age.

text: Human noroviruses (NoVs), a major cause of viral gastroenteritis, are difficult to study due to the lack of a cell-culture and a small-animal model. Pigs share with humans the types A and H histo-blood group antigens on the intestinal epithelium and have been suggested as a potential model for studies of NoV pathogenesis, immunity and vaccines. In this study, the effects of age and a cholesterol-lowering drug, simvastatin, on the susceptibility of pigs to NoV infection were evaluated. The median infectious dose (ID50) of a genogroup II, genotype 4 (GII.4) 2006b variant was determined. The ID50 in neonatal (4-5 days of age) pigs was ≤2.74×10(3) viral RNA copies. In older pigs (33-34 days of age), the ID50 was 6.43×10(4) but decreased to <2.74×10(3) in simvastatin-fed older pigs. Evidence of NoV infection was obtained by increased virus load in the intestinal contents, cytopathological changes in the small intestine, including irregular microvilli, necrosis and apoptosis, and detection of viral antigen in the tip of villi in duodenum. This GII.4 variant was isolated in 2008 from a patient from whom a large volume of stool was collected. GII.4 NoVs are continuously subjected to selective pressure by human immunity, and antigenically different GII.4 NoV variants emerge every 1-2 years. The determination of the ID50 of this challenge virus is valuable for evaluation of protection against different GII.4 variants conferred by NoV vaccines in concurrence with other GII.4 variants in the gnotobiotic pig model.


title: Development of a lateral flow immunoassay strip for rapid detection of IgG antibody against SARS-CoV-2 virus.

text: The ongoing worldwide SARS-CoV-2 epidemic clearly has a tremendous influence on public health. Molecular detection based on oral swabs was used for confirmation of SARS-CoV-2 infection. However, high false negative rates were reported. We describe here the development of a point-of-care (POC) serological assay for the detection of IgG antibody against SARS-CoV-2. The principle of a lateral flow immunoassay strip (LFIAs) consists of fixing SARS-CoV-2 nucleocapsid protein to the surface of the strip and coupling anti-human IgG with colloidal gold nanoparticles (Au NPs). A series of parameters of this method were optimized, including the concentration of coating antigen, BSA blocking concentration and pH value for conjugation. The entire detection process took 15-20 min with a volume of 80 μL of the analyte solution containing 10 μL of serum and 70 μL sample diluent. The performance of the established assay was evaluated using serum samples of the clinically diagnosed cases of Coronavirus Disease 2019 (COVID-19). Our results indicated that the LFIAs for SARS-CoV-2 had satisfactory stability and reproducibility. As a result, our fast and easy LFIAs could provide a preliminary test result for physicians to make the correct diagnosis of SARS-CoV-2 infections along with alternative testing methods and clinical findings, as well as seroprevalence determination, especially in low-resource countries.


MicroRNAs as Biomarkers in CS-resistant/Neutrophilic Asthma: Still a Long Way to Go!


title: Assessing the impact of a 2-day laparoscopic intestinal workshop.

text: BACKGROUND Surgical educators have responded to the demand for increased skills in minimally invasive surgery by offering short technique-focused workshops at academic centres. The purpose of this study was to determine the impact of a comprehensive laparoscopic intestinal workshop for the adoption of laparoscopic colonic surgery. METHODS A 2-day comprehensive laparoscopic intestinal surgery workshop included didactic teaching and supervised hands-on practice of numerous laparoscopic colon resections on a cadaveric model. Participants completed pre-, post- and 6-month postcourse questionnaires. RESULTS The participants (n = 39) had been in practice for a mean of 10 (interquartile range 3-18) years. Fifty-one percent (n = 20) were already performing laparoscopic colectomies as part of their practices prior to the course. Regardless of whether they were performing laparoscopic colectomies prior to the course or not, attending the 2-day workshop improved their self-assessed preparedness to perform laparoscopic colectomies. Six months after the intestinal workshop, 10 of 16 respondents who were not performing laparoscopic colectomies prior to the course had performed at least 1 since the course. Seven of these individuals had a preceptor for their first case. Reasons cited for not performing a laparoscopic colectomy since the workshop included perceived inadequate surgical skill set, a lack of preceptor and the lack of an appropriate patient. CONCLUSION A comprehensive laparoscopic intestinal workshop contributed to the perceived acquisition of advanced laparoscopic surgical skills. Local laparoscopic preceptorship was an important adjunct to the workshop for the incorporation of laparoscopic colorectal surgery into practice.


title: A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties.

text: This report describes the design, generation and testing of Ylanthia, a fully synthetic human Fab antibody library with 1.3E+11 clones. Ylanthia comprises 36 fixed immunoglobulin (Ig) variable heavy (VH)/variable light (VL) chain pairs, which cover a broad range of canonical complementarity-determining region (CDR) structures. The variable Ig heavy and Ig light (VH/VL) chain pairs were selected for biophysical characteristics favorable to manufacturing and development. The selection process included multiple parameters, e.g., assessment of protein expression yield, thermal stability and aggregation propensity in fragment antigen binding (Fab) and IgG1 formats, and relative Fab display rate on phage. The framework regions are fixed and the diversified CDRs were designed based on a systematic analysis of a large set of rearranged human antibody sequences. Care was taken to minimize the occurrence of potential posttranslational modification sites within the CDRs. Phage selection was performed against various antigens and unique antibodies with excellent biophysical properties were isolated. Our results confirm that quality can be built into an antibody library by prudent selection of unmodified, fully human VH/VL pairs as scaffolds.


Appearance of an electrocardiogram tracing on a bispectral index monitor with plausible BIS values.


title: Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement.

text: Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the routine acquisition of quantitative measures of myocardial and blood T1 which are key tissue characteristics. These capabilities introduce a new frontier in cardiology, enabling the practitioner/investigator to quantify biologically important myocardial properties that otherwise can be difficult to ascertain clinically. CMR may be able to track biologically important changes in the myocardium by: a) native T1 that reflects myocardial disease involving the myocyte and interstitium without use of gadolinium based contrast agents (GBCA), or b) the extracellular volume fraction (ECV)-a direct GBCA-based measurement of the size of the extracellular space, reflecting interstitial disease. The latter technique attempts to dichotomize the myocardium into its cellular and interstitial components with estimates expressed as volume fractions. This document provides recommendations for clinical and research T1 and ECV measurement, based on published evidence when available and expert consensus when not. We address site preparation, scan type, scan planning and acquisition, quality control, visualisation and analysis, technical development. We also address controversies in the field. While ECV and native T1 mapping appear destined to affect clinical decision making, they lack multi-centre application and face significant challenges, which demand a community-wide approach among stakeholders. At present, ECV and native T1 mapping appear sufficiently robust for many diseases; yet more research is required before a large-scale application for clinical decision-making can be recommended.


title: Child Development Outcomes of DIR/Floortime TM-based Programs: A Systematic Review.

text: BACKGROUND. Occupational therapy is often part of the multi-disciplinary approach within the Developmental, Individual-differences, Relationship-based (DIR) FloortimeTM Model. The model addresses the emotional development of children, which is considered to be critical for the other child developmental areas. PURPOSE. This review serves to inform practitioner decision-making about the use of this model, as no systematic reviews exist on child development outcomes. METHODS. The systematic search included Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Cochrane. For critical appraisal, the McMaster Critical Review was utilized. FINDINGS. Nine studies were identified with varying quality levels. Outcomes were mostly reported for increased socio-emotional development. IMPLICATIONS. The evidence base for this model is emerging from a published research perspective. It is recommended that the use of this model be supported by sound clinical reasoning processes, intervention fidelity, use of valid outcome measures, and regular monitoring. Higher quality research is urgently needed to progress the research base for this intervention.


title: Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysis.

text: OBJECTIVE To investigate the efficacy and safety of prostate-specific antigen (PSA) testing to screen for prostate cancer. DESIGN Systematic review and meta-analysis. DATA SOURCES Electronic search of Cochrane Central Register of Controlled Trials, Web of Science, Embase, Scopus, OpenGrey, LILACS, and Medline, and search of scientific meeting abstracts and trial registers to April 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials comparing PSA screening with usual care in men without a diagnosis of prostate cancer. DATA EXTRACTION At least two reviewers screened studies, extracted data, and assessed the quality of eligible studies. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including selection of outcomes important to patients. We used a random effects model to obtain pooled incidence rate ratios (IRR) and, when feasible, conducted subgroup analyses (defined a priori) based on age, frequency of screening, family history, ethnicity, and socioeconomic level, as well as a sensitivity analysis based on the risk of bias. The quality of the evidence was assessed with the GRADE approach. RESULTS Five randomised controlled trials, enrolling 721 718 men, were included. Studies varied with respect to screening frequency and intervals, PSA thresholds for biopsy, and risk of bias. When considering the whole body of evidence, screening probably has no effect on all-cause mortality (IRR 0.99, 95% CI 0.98 to 1.01; moderate certainty) and may have no effect on prostate-specific mortality (IRR 0.96, 0.85 to 1.08; low certainty). Sensitivity analysis of studies at lower risk of bias (n=1) also demonstrates that screening seems to have no effect on all-cause mortality (IRR 1.0, 0.98 to 1.02; moderate certainty) but may have a small effect on prostate-specific mortality (IRR 0.79, 0.69 to 0.91; moderate certainty). This corresponds to one less death from prostate cancer per 1000 men screened over 10 years. Direct comparative data on biopsy and treatment related complications from the included trials were limited. Using modelling, we estimated that for every 1000 men screened, approximately 1, 3, and 25 more men would be hospitalised for sepsis, require pads for urinary incontinence, and report erectile dysfunction, respectively. CONCLUSIONS At best, screening for prostate cancer leads to a small reduction in disease-specific mortality over 10 years but has does not affect overall mortality. Clinicians and patients considering PSA based screening need to weigh these benefits against the potential short and long term harms of screening, including complications from biopsies and subsequent treatment, as well as the risk of overdiagnosis and overtreatment. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42016042347.


title: REPLY: Factors Other Than Climate Are Likely to Influence Alcohol Consumption.

text: We would like to thank Selck et al. for their letter. The issue they raise has both methodological and scientific interest. We clearly acknowledge in our discussion the limitations of our approach to estimate the causal impact of cold weather on alcoholic cirrhosis at a population level. In addition, as highlighted in the accompanying editorial, these associations at a population level might not hold at an individual level, and the causes of differences in alcohol intake between populations and individuals might not be the same.


title: Avian coronavirus isolated from a pigeon sample induced clinical disease, tracheal ciliostasis, and a high humoral response in day-old chicks.

text: The detection of avian coronaviruses (AvCoV) in wild birds and the emergence of new AvCoV have increased in the past few years. In the present study, the pathogenicity of three AvCoV isolates was investigated in day-old chicks. One AvCoV isolated from a pigeon, which clustered with the Massachusetts vaccine serotype, and two AvCoV isolated from chickens, which grouped with a Brazilian genotype lineage, were used. Clinical signs, gross lesions, histopathological changes, ciliary activity, viral RNA detection, and serology were evaluated during 42 days post infection. All AvCoV isolates induced clinical signs, gross lesions in the trachea, moderate histopathological changes in the respiratory tract, and mild changes in other tissues. AvCoV isolated from the pigeon sample caused complete tracheal ciliostasis over a longer time span. Specific viral RNA was detected in all tissues, but the highest RNA loads were detected in the digestive tract (cloacal swabs and ileum). The highest antibody levels were also detected in the group infected with an isolate from the pigeon. These results confirm the pathogenicity of Brazilian variants, which can cause disease and induce gross lesions and histopathological changes in chickens. Our results suggest that non-Galliformes birds can also play a role in the ecology of AvCoV.


title: Health problems and healthcare service utilisation amongst homeless adults in Africa- a scoping review.

text: BACKGROUND Homelessness is a growing concern as it affects a large number of people worldwide. Individuals and families experiencing homelessness are vulnerable in terms of health and underutilise health services. Despite being a global problem, not much is known about the range and breath of literature exploring health problems and health care service utilisation among homeless adults in Africa. OBJECTIVES To identify the nature and scope of existing evidence on physical and mental health, and health service utilisation among homeless adults in Africa. The review aimed to examine how research is conducted, identify gaps, guide future research, and make recommendations for development and implementation of policies and practices. METHODS A search of articles and reports involving six databases: Scopus, MEDLINE, CINAHL, PubMed, African Journal Online, and Google Scholar was conducted from June 2018 to February 2019. Studies published between 1980 and 2019 that examined the health problems and health service utilisation among homeless adults in Africa were considered. Manual search in reference lists and grey literature was also done to add reports. Data was extracted manually using a charting developed. A descriptive analysis and narrative synthesis were performed. RESULTS Of 761 records found, 14 satisfied the pre-determined inclusion and exclusion criteria. Three themes emerged from the studies: Physical health problems, mental health problems; and healthcare services utilisation. Of the 14 included studies, nine studied and reported physical health problems such as sexually transmitted infections, injuries and disabilities, respiratory and cardiac diseases. Five studies explored mental health problems such as psychotic disorders, mood disorders, self-harm and suicidal behaviour. Only five studies investigated utilisation of different types of health care services among homeless people. CONCLUSIONS Evidence shows that homeless adults suffered from a range of physical and mental health problems, and underutilisation of health care services. However, there is lack of information on the complex interrelationship between homelessness and health, as well as differences in prevalence of health problems among the various sub-groups of homeless. There is also lack of information regarding utilisation other important healthcare services such as mental health services, alcohol and drugs services, and accident and emergency service, and future researches should address that. Also, attention should be given to intervention models for complex and effective physical and psychiatric care as well as social support to address the homeless people's health vulnerabilities.


title: Evaluating use cases for human challenge trials in accelerating SARS-CoV-2 vaccine development.

text: Human challenge trials (HCTs) have been proposed as a means to accelerate SARS-CoV-2 vaccine development. We identify and discuss three potential use cases of HCTs in the current pandemic: evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. We outline the limitations of HCTs and find that HCTs are likely to be most useful for vaccine candidates currently in preclinical stages of development. We conclude that, while currently limited in their application, there are scenarios in which HCTs would be extremely beneficial. Therefore, the option of conducting HCTs to accelerate SARS-CoV-2 vaccine development should be preserved. As HCTs require many months of preparation, we recommend an immediate effort to (1) establish guidelines for HCTs for COVID-19; (2) take the first steps toward HCTs, including preparing challenge virus and making preliminary logistical arrangements; and (3) commit to periodically re-evaluating the utility of HCTs.


title: Unexpected interference of baby wash products with a cannabinoid (THC) immunoassay.

text: OBJECTIVES The results of newborn drug screening have far-reaching impact not only in healthcare, but also in the legal domain. Therefore, the accuracy of these results cannot be undervalued. When false positive cannabinoid (THC) screening results for this population were suspected at our institution, a multidisciplinary approach was initiated to evaluate the screening process for any pre-analytical or analytical sources of error or interference. DESIGN AND METHODS Mixtures of drug-free urine with various commercial products and materials that commonly contact newborns in our nursery were prepared and tested using the immunoassay screening methods in our laboratory. Additional commercial products were similarly tested; and when available, individual surfactants common to the interfering products were also evaluated. RESULTS Addition of Head-to-Toe Baby Wash to drug-free urine produced a dose dependent measureable response in the THC immunoassay. Addition of other commercially available baby soaps gave similar results, and subsequent testing identified specific chemical surfactants that reacted with the THC immunoassay. CONCLUSION We have identified commonly used soap and wash products used for newborn and infant care as potential causes of false positive THC screening results. Such results in this population can lead to involvement by social services or false child abuse allegations. Given these consequences, it is important for laboratories and providers to be aware of this potential source for false positive screening results and to consider confirmation before initiating interventions. Most importantly, we demonstrate the need for active involvement in the "total testing process," as sources of error are not confined to the laboratory walls.


title: Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 protein has unique biological functions that have not been described in the viral proteins of any RNA viruses; expressed SARS-CoV nsp1 protein has been found to suppress host gene expression by promoting host mRNA degradation and inhibiting translation. We generated an nsp1 mutant (nsp1-mt) that neither promoted host mRNA degradation nor suppressed host protein synthesis in expressing cells. Both a SARS-CoV mutant virus, encoding the nsp1-mt protein (SARS-CoV-mt), and a wild-type virus (SARS-CoV-WT) replicated efficiently and exhibited similar one-step growth kinetics in susceptible cells. Both viruses accumulated similar amounts of virus-specific mRNAs and nsp1 protein in infected cells, whereas the amounts of endogenous host mRNAs were clearly higher in SARS-CoV-mt-infected cells than in SARS-CoV-WT-infected cells, in both the presence and absence of actinomycin D. Further, SARS-CoV-WT replication strongly inhibited host protein synthesis, whereas host protein synthesis inhibition in SARS-CoV-mt-infected cells was not as efficient as in SARS-CoV-WT-infected cells. These data revealed that nsp1 indeed promoted host mRNA degradation and contributed to host protein translation inhibition in infected cells. Notably, SARS-CoV-mt infection, but not SARS-CoV-WT infection, induced high levels of beta interferon (IFN) mRNA accumulation and high titers of type I IFN production. These data demonstrated that SARS-CoV nsp1 suppressed host innate immune functions, including type I IFN expression, in infected cells and suggested that SARS-CoV nsp1 most probably plays a critical role in SARS-CoV virulence.


title: Committee opinion no. 555: hospital disaster preparedness for obstetricians and facilities providing maternity care.

text: Numerous occurrences in the past decade have brought the issue of disaster preparedness, and specifically hospital preparedness, to the national forefront. Much of the work in this area has focused on large hospital system preparedness for various disaster scenarios. Many unique features of the obstetric population warrant additional consideration in order to optimize the care received by expectant mothers and their fetuses or newborns in the face of future natural or biologic disasters.


title: Clinical Outcomes of Comparing Soft Tissue Alternatives to Free Gingival Graft: A Systematic Review and Meta-Analysis .

text: OBJECTIVES This systematic review and meta-analysis aimed to compare clinical outcomes and width of keratinized tissue (KT) around teeth, following the soft tissue alter- natives and free gingival graft (FGG) procedures. The specific graft materials that were explored were extracellular matrix membrane, bilayer collagen membrane, living cellular construct, and acellular dermal matrix. METHODS Four different databases were queried to identify human controlled clinical trials and randomized controlled clinical trials that fulfilled the eligibility criteria. Relevant studies were identified by 3 independent reviewers, compiling the results of the electronic and handsearches. Studies identified through electronic and handsearches were reviewed by title, abstract, and full text using Covidence Software. Primary outcome in the present study was change in the width of KT. Results of the included studies were pooled to estimate the effect size, expressed as weighted mean differences and 95% confidence interval. A random-effects model was used to perform the meta-analyses. RESULTS Six hundred thirty-eight articles were screened by title, 55 articles were screened by abstracts, and 34 full-text articles were reviewed. Data on quantitative changes in width of KT were provided in 7 studies. Quantitative analyses revealed a significant difference in changes in width of KT between patients treated with soft tissue alternatives and patients treated with FGGs (P < .001). The weighted mean difference of changes in the width of KT was 21.39 (95% confidence interval: 21.82 to 20.96; heterogeneity I 5 70.89%), indicating patients who were treated with soft tissue alternatives gained 1.39 mm less KT width compared with the patients who received free gingival graft. CONCLUSIONS Based on the clinical outcomes, the results of this systematic review and meta-analysis showed that soft tissue alternatives result in an increased width of KT. Patients in the soft tissue alternatives group obtained 1.39 mm less KT compared with those in the FGGs group.


docid: hnzzersh

title: An Ethnographic Manifestation of Religious Life of Gadaba Tribe in Its Changing Dimensions.

text: The captivating tribal communities living across the length and breadth of the state of Central India and mostly in Odisha have enriched the cultural heritage of the region by their cultural diversities. Gadaba's religious life reflected through their rich folk traditions of songs, dance, music, rituals and festivals celebrated round the year adds colourful dimensions to their very existence. The amazing conglomeration of traditions, beliefs, sorrows and philosophies that together constitute and vitalize the religion of tribes has descended from antiquity and has been preserved unimpaired to the present day. Every dimension of their life covering round the year activities is intimately connected with religion and the world view associated with it. It is these aspects of their culture that give meaning and depth to their lives and solidarity to their social structure. However, in recent days many changes have been taken place in traditional religious life of Gadaba tribe. Against this backdrop, this paper has tried to explore some of that core structure of Gadaba's religious life as well as the changing dimensions of their religious manifestation.


title: FiY101: A quick guide for newly qualified doctors.

text: Final-year medical students in the UK have been allowed to voluntarily apply for early provisional registration in response to the COVID-19 pandemic, allowing these foundation interim year-1 (FiY1) doctors to assist in service provision in hospitals where resources and staffing may be strained. The authors, as recently qualified foundation year-1 (FY1) doctors, use this article to draw on their own experiences, and those of their colleagues, to provide advice on key topics that may not have been covered, or not covered sufficiently, in medical education, such as prescribing, rotas, wellbeing, and useful apps and websites.


title: New suture materials for midline laparotomy closure: an experimental study.

text: BACKGROUND Midline laparotomy closure carries a significant risk of incisional hernia. This study examines the behavior of two new suture materials, an elastic material, polyurethane (PUe), and a barbed polydioxanone (PDXb) suture thread in a rabbit model of midline incision closure. METHODS Three 2-cm midline incisions were made in 68 New Zealand White rabbits. The incisions were closed by running suture using four 3/0 threads: polypropylene (PP) (Surgipro®, Covidien), PUe (Assuplus®, Assut Europe), PDX (Assufil®, Assut Europe) or PDXb (Filbloc®, Assut Europe). Animals in each suture group were euthanized 3 weeks and 6 months after surgery. Histological sections of the tissue-embedded sutures were subjected to morphological, collagen expression, macrophage response and uniaxial tensiometry studies. RESULTS No signs of wound dehiscence or complications were observed. At 3 weeks, all sutures were surrounded by connective tissue composed mainly of collagen III. PUe showed greater collagen I expression than the other sutures. All sutures elicited a macrophage response that diminished from 3 weeks to 6 months (p < 0.001). This response was similar for the non-reabsorbable sutures (PP and PUe) yet PDXb showed a significantly greater response than the other reabsorbable suture (PDX) at 3 weeks (p < 0.01). At this early time point, the tensile strength of PUe was similar to that of control intact tissue (p > 0.05). CONCLUSION Three weeks after surgery, PUe revealed more collagen I deposition than the remaining materials and this translated to a similar biomechanical behavior to linea alba, that could avoid the appearance of short term dehiscences and thus reduce the incidence of incisional hernia. PDXb provides no additional advantages in their behavior regarding PDX suture.


COVID-19 Research in Brief: 16 May to 22 May, 2020.


Wastewater monitoring and public health surveillance of SARS-CoV-2.


title: Percutaneous mechanical thrombectomy in the treatment of acute iliofemoral deep vein thrombosis: a systematic review.

text: BACKGROUND Conventional treatment of deep vein thrombosis (DVT) of the lower extremities by anticoagulation alone has been proven to be insufficient to prevent recurrence and post-thrombotic syndrome (PTS). Early restoration of venous patency and preservation of valvular function by endovascular surgery has been advocated. The aim of this study was to review the efficacy and safety of percutaneous mechanical thrombectomy (PMT) against catheter-directed thrombolysis (CDT) in the treatment of acute iliofemoral DVT. METHODS Three hundred sixty-nine articles were identified through screening of the PubMed, EMBASE, and Cochrane databases from January 2006 to December 2016. RESULTS Fifteen retrospective studies and one prospective registry, totalling 1170 patients, were recruited for qualitative synthesis. The venous patency rate ranged from 75% to 100% with mean follow-up of 12.3 months. The rates of PTS and recurrent DVT were less than 17% and 15%, respectively. The overall mortality rate was 0.26%. Compared with CDT, PMT was shown to reduce PTS at 1 year (Villalta score: 2.1 ± 3.0 in the PMT group and 5.1 ± 4.1 in the CDT group, P=0.03) and bleeding complications (packed cells transfused: 0.2 ± 0.3 units in the pharmacomechanical thrombectomy group and 1.2 ± 0.7 units in the CDT group, P<0.05). CONCLUSION Percutaneous mechanical thrombectomy is a safe and effective treatment for acute iliofemoral DVT in terms of restoration of venous patency, prevention of DVT recurrence, and PTS. Compared with CDT alone, PMT offers a lower risk of PTS and bleeding complications.


Sterile Technique.


Supporting children with autism spectrum disorder in the face of the COVID-19 pandemic.


title: Healthcare costs and outcomes for patients undergoing tracheostomy in an Australian tertiary level referral hospital.

text: Objective Patients undergoing tracheostomy represent a unique cohort, as often they have prolonged hospital stay, require multi-disciplinary, resource-intensive care, and may have poor outcomes. Currently, there is a lack of data around overall healthcare cost for these patients and their outcomes in terms of morbidity and mortality. The objective of the study was to estimate healthcare costs and outcomes associated in tracheostomy patients at a tertiary level hospital in South Australia. Design Retrospective review of prospectively collected data in patients who underwent tracheostomy between July 2009 and May 2015. Methods Overall healthcare-associated costs, length of mechanical ventilation, length of intensive care unit stay, and mortality rates were assessed. Results A total of 454 patients with tracheostomies were examined. Majority of the tracheostomies (n = 386 (85%)) were performed in intensive care unit patients, predominantly using bedside percutaneous approach (85%). The median length of hospital stay was 44 (29-63) days and the in-hospital mortality rate was 20%. Overall total cost of managing a patient with tracheostomy was median $192,184 (inter-quartile range $122560-$295553); mean 225,200 (range $5942-$1046675) Australian dollars. There were no statistically significant differences in any of the measured outcomes, including costs, between patients who underwent percutaneous versus surgical tracheostomy and patients who underwent early versus late tracheostomy in their intensive care unit stay. Factors that predicted (adjusted R 2 = 0.53) the cost per patient were intensive care unit length of stay and hospital length of stay. Conclusion Hospitalised patients undergoing tracheostomy experience high morbidity and mortality and typically experience highly resource-intensive and costly healthcare.


title: Inhibition of USP10 induces degradation of oncogenic FLT3.

text: Oncogenic forms of the kinase FLT3 are important therapeutic targets in acute myeloid leukemia (AML); however, clinical responses to small-molecule kinase inhibitors are short-lived as a result of the rapid emergence of resistance due to point mutations or compensatory increases in FLT3 expression. We sought to develop a complementary pharmacological approach whereby proteasome-mediated FLT3 degradation could be promoted by inhibitors of the deubiquitinating enzymes (DUBs) responsible for cleaving ubiquitin from FLT3. Because the relevant DUBs for FLT3 are not known, we assembled a focused library of most reported small-molecule DUB inhibitors and carried out a cellular phenotypic screen to identify compounds that could induce the degradation of oncogenic FLT3. Subsequent target deconvolution efforts allowed us to identify USP10 as the critical DUB required to stabilize FLT3. Targeting of USP10 showed efficacy in preclinical models of mutant-FLT3 AML, including cell lines, primary patient specimens and mouse models of oncogenic-FLT3-driven leukemia.


title: 3CL Hydrolase Based Multi Epitope Peptide Vaccine Against Sars-CoV-2 Using Immunoinformatics.

text: The present study provides the first multi-epitope vaccine construct using 3CL hydrolase protein of SARS-CoV-2. The coronavirus 3CL hydrolase (Mpro) enzyme is essential for proteolytic maturation of the virus. This research was based on immunoinformatics and structural vaccinology strategies. The design of the multi epitope vaccine was built using HTLs and CTLs epitopes from 3CL hydrolase protein along with adjuvant to enhance immune response; these are joined to each other by short peptide linkers. The vaccine also carries potential B-cell linear epitope regions, B-cell discontinuous epitopes, and Interferon-γ inducing epitopes. Epitopes of the constructed multi epitope vaccine was found to be antigenic, nonallergic, nontoxic, and cover large human population worldwide. The vaccine construct was modeled, validated and refined by different programs to achieve high-quality 3D structure. The resulting high-quality model was applied for conformational B cell epitope selection and docking analyses with toll-like receptor-3 for understanding the capability of vaccine to elicit an immune response. Insilico cloning and Codon adaptation were also performed into the pET-19b plasmid vector. The designed multi-epitope peptide vaccine may prompt the development of a vaccine to control SARS-CoV-2 infection. This article is protected by copyright. All rights reserved.


title: Laparoscopic umbilical hernia repair is the preferred approach in obese patients.

text: INTRODUCTION The optimal method of umbilical hernia repair (UHR) in the obese population, laparoscopic vs open, is not standardized. The purpose of this study was to determine the optimal surgical option for UHR in the obese population. METHODS A retrospective chart review was conducted on 123 obese patients (body mass index [BMI] >30) who underwent UHR from 2003 to 2009 at a single institution. Patients were grouped by surgical approach (open vs laparoscopic). Intraoperative and postoperative courses were compared. Follow-up in the postoperative period was obtained from patient records and telephone interviews. RESULTS Of the 123 patients undergoing UHR, 40 and 83 patients were operated on with the laparoscopic and open approach, respectively. Patients were well matched by demographics as well as comorbidities. No difference in the mean BMI was shown between the laparoscopic and open groups (37 vs 35, P = not significant, respectively). The operative time was significantly prolonged in the laparoscopic group (106 vs 71 minutes, P < .01). Intraoperatively, no complications occurred in either group. In the immediate postoperative period, 1 patient who underwent laparoscopic UHR was readmitted for small bowel obstruction, and 2 patients in the open group were readmitted, 1 for pain control and 1 for wound infection. Follow-up was achieved in 63% of the laparoscopic group and 58% of the open group with a mean follow-up of 15 months in the laparoscopic group and 20 months in the open group (P = not significant). A significant increase in wound infection was reported in the open group with mesh insertion when compared with the laparoscopic procedure (26% vs 4%, P < .05, respectively). No hernia recurrence was shown in the laparoscopic vs the open group with mesh insertion (0% vs 4%, P = not significant, respectively). CONCLUSIONS In obese patients, the laparoscopic approach was associated with a significantly lower rate of postoperative infection and no hernia recurrence. Laparoscopic hernia repair may be the preferred option in the obese patient.


title: Evaluation of 99mTc-Z IGF1R:4551-GGGC affibody molecule, a new probe for imaging of insulin-like growth factor type 1 receptor expression.

text: Overexpression of insulin-like growth factor-1 receptor (IGF-1R) in several cancers is associated with resistance to therapy. Radionuclide molecular imaging of IGF-1R expression in tumors may help in selecting the patients that will potentially respond to IGF-1R-targeted therapy. Affibody molecules are small (7 kDa) non-immunoglobulin-based scaffold proteins that are well-suited probes for radionuclide imaging. The aim of this study was the evaluation of an anti-IGF-1R affibody molecule labeled with technetium-99m using cysteine-containing peptide-based chelator GGGC at C-terminus. ZIGF1R:4551-GGGC was efficiently and stably labeled with technetium-99m (radiochemical yield 97 ± 3%). (99m)Tc-ZIGF1R:4551-GGGC demonstrated specific binding to IGF-1R-expressing DU-145 (prostate cancer) and MCF-7 (breast cancer) cell lines and slow internalization in vitro. The tumor-targeting properties were studied in BALB/c nu/nu mice bearing DU-145 and MCF-7 xenografts. [(99m)Tc(CO)3](+)-(HE)3-ZIGF1R:4551 was used for comparison. The biodistribution study demonstrated high tumor-to-blood ratios (6.2 ± 0.9 and 6.9 ± 1.0, for DU-145 and MCF-7, respectively, at 4 h after injection). Renal radioactivity concentration was 16-fold lower for (99m)Tc-ZIGF1R:4551-GGGC than for [(99m)Tc(CO)3](+)-(HE)3-ZIGF1R:4551 at 4 h after injection. However, the liver uptake of (99m)Tc-ZIGF1R:4551-GGGC was 1.2- to 2-fold higher in comparison with [(99m)Tc(CO)3](+)-(HE)3-ZIGF1R:4551. A possible reason for the elevated hepatic uptake of (99m)Tc-ZIGF1R:4551-GGGC is a high lipophilicity of amino acids in the binding site of ZIGF1R:4551, which is not compensated in (99m)Tc-ZIGF1R:4551-GGGC. In conclusion, (99m)Tc-ZIGF1R:4551-GGGC can visualize the IGF-1R expression in human tumor xenografts and provides low retention of radioactivity in kidneys. Further development of this imaging agent should include molecular design aimed at reducing the hepatic uptake.


docid: jfpkyxyk

title: Obstetric anesthesia and COVID 19 times.