title: Development of Middle East Respiratory Syndrome Coronavirus vaccines - advances and challenges.

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging pathogen with the potential to pose a threat to global public health. Sporadic cases and outbreaks continue to be reported in the Middle East, and case fatality rates remain high at approximately 36% globally. No specific preventive or therapeutic countermeasures currently exist. A safe and effective vaccine could play an important role in protecting against the threat from MERS-CoV. This review discusses human vaccine candidates currently under development, and explores viral characteristics, molecular epidemiology and immunology relevant to MERS-CoV vaccine development. At present, a DNA vaccine candidate has begun a human clinical trial, while two vector-based candidates will very soon begin human trials. Protein-based vaccines are still at pre-clinical stage. Challenges to successful development include incomplete understanding of viral transmission, pathogenesis and immune response (in particular at the mucosal level), no optimal animal challenge models, lack of standardized immunological assays, and insufficient sustainable funding.


Diabetes Care at the Times of Transition and COVID-19 Pandemics (Ukrainian Experience).


title: Respiratory advice for the non-respiratory physician in the time of COVID-19.

text: COVID-19, the disease caused by the SARS-CoV-2 beta-coronavirus, has changed clinical practice in a matter of weeks. Among the physician specialties, respiratory physicians have been at the forefront of the response to this new challenge. Here we provide advice for non-respiratory physicians on the ward-based care of patients with this disease. This includes recommendations on hydration, thromboprophylaxis, nutritional support and on the importance of the early detection of deterioration, setting ceilings of care and use of anticipatory drugs where appropriate. We also discuss oxygen support modalities, proning, safe working practices and a new approach to multi-professional working. We include references to a number of important research studies.


title: The impact of the Covid-19 pandemic on domestic violence: The dark side of home isolation during quarantine.

text: Domestic violence is a global public health problem. It takes many different forms and leads to significant physical and psychological consequences for the victim and the whole family. Situations that may prompt episodes of violence in the family include stress, emotional disappointment, economic factors, bad and cramped housing, and alcohol or drug abuse. How does the government's forced home isolation to contain Covid-19 infections impact on this type of abuse? Numerous articles have reported a decrease in reports of domestic violence since quarantine began but how reliable is these data? Is it a potential wake-up call for public institutions? We discuss the risks associated with quarantine measures during the pandemic and suggest the measures to prevent and improve the reporting of abuse cases.


title: Evaluation of Chemical Protocols for Inactivating SARS-CoV-2 Infectious Samples.

text: Clinical samples collected in coronavirus disease 19 (COVID-19), patients are commonly manipulated in biosafety level 2 laboratories for molecular diagnostic purposes. Here, we tested French norm NF-EN-14476+A2 derived from European standard EN-14885 to assess the risk of manipulating infectious viruses prior to RNA extraction. SARS-CoV-2 cell-culture supernatant and nasopharyngeal samples (virus-spiked samples and clinical samples collected in COVID-19 patients) were used to measure the reduction of infectivity after 10 minute contact with lysis buffer containing various detergents and chaotropic agents. A total of thirteen protocols were evaluated. Two commercially available formulations showed the ability to reduce infectivity by at least 6 log 10, whereas others proved less effective.


title: Aberrant default mode network in patients with primary dysmenorrhea: a fMRI study.

text: Primary dysmenorrhea (PDM), characterized by cramping pain in the lower abdomen, is a common gynecological disorder in women of child-bearing age. An increasing number of neuroimaging studies have emphasized that PDM is associated with functional and structural abnormalities in the regions related to the default mode network (DMN). Based on resting-state functional magnetic resonance imaging (fMRI), the aim of this study was to use amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) to investigate changes of the intrinsic brain activity in the DMN in PDM. Pearson correlation analysis was conducted to assess relationships between the neuroimaging findings and clinical symptoms. Forty-eight PDM patients and thirty-eight matched healthy controls participated in this study. Compared to healthy controls, PDM patients had increased ALFF in the precuneus, dorsomedial prefrontal cortex (dmPFC) and anterior cingulate cortex (ACC) and decreased ALFF in the thalamus. PDM patients also had decreased connectivity between the precuneus and left dmPFC and right ACC, while increased connectivity between the precuneus and left thalamus. In addition, the ALFF in the left dmPFC in PDM patients positively correlated with disease duration. Our findings provide further evidence of the DMN-related abnormalities in PDM patients which might contribute to a better understanding of the pathophysiology of this disease.


title: Challenging a classic myth: pneumoperitoneum associated with acute diverticulitis is not an indication for open or laparoscopic emergency surgery in hemodynamically stable patients. A 10-year experience with a nonoperative treatment.

text: BACKGROUND In patients presenting with acute diverticulitis (AD) and signs of acute peritonitis, the presence of extradigestive air (EDA) on a computer tomography (CT) scan is often considered to indicate the need for emergency surgery. Although the traditional management of "perforated" AD is open sigmoidectomy, more recently, laparoscopic drainage/lavage (usually followed by delayed elective sigmoidectomy) has been reported. The aim of this retrospective study is to evaluate the results of nonoperative management of emergency patients presenting with AD and EDA. METHODS The outcomes of 39 consecutive hemodynamically stable patients (23 men, mean age = 54.7 years) who were admitted with AD and EDA and were managed nonoperatively (antibiotic and supportive treatment) at a tertiary-care university hospital between January 2001 and June 2010 were retrospectively collected and analyzed. These included morbidity (Clavien-Dindo) and treatment failure (need for emergency surgery or death). A univariate analysis of clinical, radiological, and laboratory criteria with respect to treatment failure was performed. Results of delayed elective laparoscopic sigmoidectomy were also analyzed. RESULTS There was no mortality. Thirty-six of the 39 patients (92.3%) did not need surgery (7 patients required CT-guided abscess drainage). Mean hospital stay was 8.1 days. Duration of symptoms, previous antibiotic administration, severe sepsis, PCR level, WBC concentration, and the presence of abdominal collection were associated with treatment failure, whereas "distant" location of EDA and free abdominal fluid were not. Five patients had recurrence of AD and were treated medically. Seventeen patients (47.2%) underwent elective laparoscopic sigmoidectomy for which mean operative time was 246 min (range = 100-450) and the conversion rate was 11.8%. Mortality was nil and the morbidity rate was 41.2%. Mean postoperative stay was 7.1 days (range = 4-23). CONCLUSIONS Nonoperative management is a viable option in most emergency patients presenting with AD and EDA, even in the presence of symptoms of peritonitis or altered laboratory tests. Delayed laparoscopic sigmoidectomy may be useless in certain cases and its results poorer than expected.


title: Readability and comprehensibility of over-the-counter medication labels.

text: Nonprescription medications are relatively safe, but not risk-free and can lead to serious adverse events, particularly if used contrary to directions or without attention to depicted warnings. The question arises whether the information presented on the product label is readable and comprehensible to the average lay person. We examined the product labels of nonprescription medications for readability and comprehensibility characteristics using the Flesch-Kincaid method. The Flesch-Kincaid reading ease scores and grade level scores were derived. We further validated the grade level scores using the Gunning-Fog method. Qualitative assessment of select labels found severe deficiencies such as poor organization and inundation with technical terms. By quantitative assessment the average reading ease score of 40 nonprescription medication labels (including nonsteroidal anti-inflammatory agents, antacids, laxative preparations, anti-allergy medications, H-2 blockers, proton pump inhibitors, sleep aids, an antiasthmatic, and cough and cold remedies) was 38 ± 12. The average Flesch-Kincaid grade level score was 16 ± 5. All labels except one were at reading grade level greater than the eighth grade. The average grade level of education necessary to understand the material according to the Gunning-Fog method was 17 ± 5 and all labels were above the eighth grade reading level. Nonprescription medication labels are written in a language that is not comprehensible to the average member of the general public. There is a need for considerable improvement in the readability of these labels.


COVID-19 pandemic for Pediatric Health Care: disadvantages and opportunities.


title: Study on laparoscopic spleen preserving distal pancreatectomy procedures comparing splenic vessel preservation and non-preservation.

text: BACKGROUND The purpose of this study is to investigate whether two types of laparoscopic spleen-preserving distal pancreatectomy (Lap-SPDP) techniques are being implemented safely. The study compares the clinical outcomes from laparoscopic Warshaw operation (Lap-W) with those from laparoscopic splenic vessels preserving SPDP (Lap-SPDP-VP) and considers the role of those operations. METHODS On August 2013, the Warshaw technique was introduced to our institution and 17 patients with a lesion in the distal pancreas who underwent Lap-SPDP by December 2015 were enrolled. Six patients who underwent a Lap-W and 11 patients who underwent a Lap-SPDP-VP were investigated retrospectively. RESULTS In the Lap-W and Lap-SPDP-VP patients, the sizes of the tumors were 46.5±31.2 and 25.7±14.9 mm [Probability (P) value =0.0913)]; the operative times were 287 min (range, 225-369 min) and 280 min (range, 200-496 min); the blood loss was 95 mL (range, 50-200 mL) and 60 mL (range, 0-650 mL); the length of the postoperative hospital stay was 12 days (range, 8-43 days) and 11 days (range, 7-28 days); median follow-up was 19 months (range, 13-28 months) and 23 months (range, 6-28 months), respectively. There was no case of symptomatic spleen infarction in either group. However, partial infarctions of the spleen without symptoms were observed by computed tomography in three out of six cases (50%) in the Lap-W. No patient required reoperation and the postoperative mortality was zero in both groups. All patients were alive and recurrence-free at the end of the follow-up period. Collateral veins around the spleen developed in 83.3% (five out of six patients) in the Lap-W and developed in 12.5% (one out of eight patients) in the Lap-SPDP-VP. A significant difference was observed between groups (P=0.0256). Gastric varices developed in 33.3% (two out of six patients) in the Lap-W. However, no case of rupture of varices, or other late phase complications was observed in either group. CONCLUSIONS Both the Lap-W and Lap-SPDP-VP were found to be safe and effective, and in cases in which the detachment work of the splenic vessels from the tumor or the pancreatic parenchyma is difficult, performing Lap-W, rather than Lap-SPDP-VP, is considered appropriate. While Lap-SPDP is recommended for patients with benign or low grade malignant diseases, long-term follow-up to monitor hemodynamic changes in splenogastric circulation is considered needed.


title: AFP-LSE: Antifreeze Proteins Prediction Using Latent Space Encoding of Composition of k-Spaced Amino Acid Pairs.

text: Species living in extremely cold environments resist the freezing conditions through antifreeze proteins (AFPs). Apart from being essential proteins for various organisms living in sub-zero temperatures, AFPs have numerous applications in different industries. They possess very small resemblance to each other and cannot be easily identified using simple search algorithms such as BLAST and PSI-BLAST. Diverse AFPs found in fishes (Type I, II, III, IV and antifreeze glycoproteins (AFGPs)), are sub-types and show low sequence and structural similarity, making their accurate prediction challenging. Although several machine-learning methods have been proposed for the classification of AFPs, prediction methods that have greater reliability are required. In this paper, we propose a novel machine-learning-based approach for the prediction of AFP sequences using latent space learning through a deep auto-encoder method. For latent space pruning, we use the output of the auto-encoder with a deep neural network classifier to learn the non-linear mapping of the protein sequence descriptor and class label. The proposed method outperformed the existing methods, yielding excellent results in comparison. A comprehensive ablation study is performed, and the proposed method is evaluated in terms of widely used performance measures. In particular, the proposed method demonstrated a high Matthews correlation coefficient of 0.52, F-score of 0.49, and Youden's index of 0.81 on an independent test dataset, thereby outperforming the existing methods for AFP prediction.


title: Single incision laparoscopy for the management of postoperative hemorrhage.

text: INTRODUCTION Single incision laparoscopic surgery is being used as an access route for an increasing breadth of surgical cases. However, its use to evaluate and manage postoperative hemorrhage after laparoscopic surgery has not been reported. CASE DESCRIPTION A patient with recurrent cervical dysplasia who had undergone 2 previous cold knife conizations underwent a single incision total laparoscopic hysterectomy with right salpingectomy and left salpingo-oophorectomy. On postoperative day 1, she developed signs of intraabdominal hemorrhage. She underwent transcatheter arterial embolization of the left uterine artery and received 3U of packed red blood cells. However, on postoperative day 2, she developed signs of persistent bleeding. DISCUSSION We discuss our management of this case with single incision laparoscopy.


title: Skin Sterility After Application of a Vapocoolant Spray Part 2.

text: INTRODUCTION Refrigerant sprays have been used for pain relief at the time of minor office procedures. However, their sterility remains in question. This study investigates the microbiologic effect of this vapocoolant when sprayed after 70 % isopropyl alcohol skin preparation. MATERIALS AND METHODS In 50 healthy volunteers, three skin culture samples were collected: Group 1 prior to alcohol application; Group 2 after preparation with alcohol, and Group 3 after preparation with alcohol followed with vapocoolant spray. Samples were cultured in a blinded fashion and analyzed after 5 days of incubation. Gram staining was performed when cultures were positive. RESULTS Bacterial growth was found in 98 % of samples prior to any skin preparation. This was reduced to 54 % after alcohol use (Group 2). Spraying with the skin refrigerant further reduced bacterial growth to 46 % (Group 3). The results showed a significant reduction in the number of positive bacterial cultures following skin preparation with alcohol and when alcohol prep was followed by vapocoolant spray (p < 0.001) compared to initial cultures. No statistical difference was observed between Groups 2 and 3 (p = 0.74). CONCLUSIONS The use of the vapocoolant spray does not compromise the sterility of the skin following alcohol prep. Both 70 % isopropyl alcohol antiseptic preparation and skin preparation followed by vapocoolant spray significantly reduce skin colonization when compared to unprepared skin (p < 0.001).


title: Defining Essential Services for Deaf and Hard of Hearing Children during the COVID-19 Pandemic.

text: COVID-19 is a rapidly growing global pandemic caused by a novel coronavirus. With no vaccine or definitive treatment, public health authorities have recommended a strategy of "social distancing," reducing individual interaction, canceling elective procedures, and limiting nonessential services. Health care providers must determine what procedures are considered "elective," balancing risk of treatment delays with that of coronavirus exposure to patient, family, and providers. Given critical periods for language development and the long-term impact of auditory deprivation, some audiologic and otologic services should be considered essential. In this article, we describe the experience of a quaternary referral pediatric hospital in Seattle, the epicenter of COVID-19 in the United States, and share strategies for risk minimization employed by Seattle Children's Hospital. We hope that this work can be a reference for other centers continuing care for children who are deaf and hard of hearing during the COVID-19 and future resource-limiting crises.


title: Phenylalanine meta-hydroxylase: a single residue mediates mechanistic control of aromatic amino acid hydroxylation.

text: The rare non-proteinogenic amino acid, meta- L-tyrosine is biosynthetically intriguing. Whilst the biogenesis of tyrosine from phenylalanine is well characterised, the mechanistic basis for meta-hydroxylation is unknown. Herein, we report the analysis of 3-hydroxylase (Phe3H) from Streptomyces coeruleorbidus. Insight from kinetic analyses, of both the wild-type enzyme and key mutants, of the biocatalytic conversion of synthetic isotopically labelled substrates and fluorinated substrate analogues advances understanding of the process by which meta-hydroxylation is mediated, revealing T202 to play an important role. In contrast to the established mechanism of tyrosine biogenesis, which proceeds via NIH shift, our data support direct, enzyme catalysed deprotonation following electrophilic aromatic substitution. We demonstrate that T202 is responsible for this shift in mechanism, with mutation to alanine resulting in a switch to the NIH shift mechanism and loss of regiospecificity. Furthermore, our kinetic parameters for Phe3H show efficient regiospecific generation of meta-L-tyrosine from phenylalanine and demonstrate the enzyme's ability to regiospecifically hydroxylate unnatural fluorinated substrates.


title: Health-related regional and neighborhood correlates of sexual minority concentration: A systematic review.

text: BACKGROUND A growing literature explores spatial patterns of regional and neighborhood correlates of sexual minority (e.g., lesbian, gay, bisexual) concentration. Such patterns have implications for health and wellbeing if there are differences in health-promoting or health-hindering resources in neighborhoods or regions. We conducted a systematic review to assess sexual minority concentration in relation to area unit characteristics. METHODS We included only records published after 1973 and made no exclusions by geography or language. We searched 11 databases (Academic Search Complete, CINAHL, Embase, GeoBase, GeoRef, LGBT Life, PsycINFO, PubMed/MEDLINE, Scopus, Sociological Abstracts, Web of Science) on November 19-21, 2016. We searched reference lists of included records. We used the following inclusion criteria: (1) Record is a quantitative study (that is, it uses statistics to describe or associate two or more variables); (2) Record is about (a) migration or internal migration of, (b) area unit selection by, or (c) concentration of sexual minority people (defined by identity, behavior, or attraction); (3) Criterion 2 is linked to the characteristics of regions or neighborhoods (at any spatial scale). RESULTS Dual independent coding resulted in 51 records meeting inclusion criteria from the original pool of 5,591. From these records, we identified the 647 reported results linking sexual minority concentration with area unit characteristics. Of these, 132 were unadjusted relationships between sexual minority concentration and four theory-informed domains of neighborhood influence on health. We identified greater concentration of sexual minorities in regions with more resources and in more urban regions. A limited but troubling literature at the neighborhood level suggested potentially higher concentrations of sexual minorities in neighborhoods with fewer resources. CONCLUSIONS There are substantial gaps in the literature. We discuss the implications of our findings and gaps in relation to key theories of sexual minority health. REGISTRATION The review was not registered with PROSPERO because it was not eligible for registration at the time of the research project's initiation due to the outcome of interest.


title: Airway Management for Endoscopic Laryngotracheal Stenosis Surgery During COVID-19.

text: The novel coronavirus disease 2019 (COVID-19) pandemic presents unique challenges for surgical management of laryngotracheal stenosis. High viral concentrations in the upper aerodigestive tract, the ability of the virus to be transmitted by asymptomatic carriers and through aerosols, and the need for open airway access during laryngotracheal surgery create a high-risk situation for airway surgeons, anesthesiologists, and operating room personnel. While some surgical cases of laryngotracheal stenosis may be deferred, patients with significant airway obstruction or progressing symptoms often require urgent surgical intervention. We present best practices from our institutional experience for surgical management of laryngotracheal stenosis during this pandemic, including preoperative triage, intraoperative airway management, and personal protective measures.


title: Utility of Perioperative Lung Ultrasound in Pediatric Cardiac Surgery: A Randomized Controlled Trial.

text: BACKGROUND Pediatric cardiac patients are at risk for perioperative respiratory insufficiency. The objective of this study was to assess the utility of perioperative lung ultrasound examination in pediatric cardiac surgery. METHODS In this randomized, controlled trial, children (5 yr old or younger) undergoing cardiac surgery were allocated into a control (n = 61) or intervention (n = 61) group. The control group received only lung ultrasound examinations at the end of surgery and 6 to 12 h after surgery. The intervention group received lung ultrasound examinations and an ultrasound-guided recruitment maneuver depending on ultrasound findings after inducing anesthesia, at the end of surgery, and 6 to 12 h after surgery. Primary outcomes were incidences of intra- and postoperative desaturation, and postoperative pulmonary complications. Multiple comparisons were corrected (P ≤ 0.017) in the primary outcome analysis. RESULTS Of the 120 children included in the analysis, postoperative desaturation (64% vs. 27%; P < 0.001; odds ratio [OR], 0.210; 95% CI, 0.097 to 0.456) occurred more in the control group. The incidences of intraoperative desaturation (36% vs. 19%; P = 0.033; OR, 0.406; 95% CI, 0.176 to 0.939) and postoperative pulmonary complications (12% vs. 3%; P = 0.093; OR, 0.271; 95% CI, 0.054 to 1.361) were similar between the groups. Lung ultrasound scores were better in the intervention group than in the control group. Duration of mechanical ventilation was longer in the control group than in the intervention group (38 ± 43 vs. 26 ± 25 h; 95% CI of mean difference, 0 to 25; P = 0.048). CONCLUSIONS Perioperative lung ultrasound examination followed by ultrasound-guided recruitment maneuver helped decrease postoperative desaturation events and shorten the duration of mechanical ventilation in pediatric cardiac patients. VISUAL ABSTRACT An online visual overview is available for this article at http://links.lww.com/ALN/B682.


title: Decrease in self-esteem mediates the association between symptoms of social phobia and depression in middle adolescence in a sex-specific manner: a 2-year follow-up of a prospective population cohort study.

text: BACKGROUND Social phobia and depression are common, highly comorbid disorders in middle adolescence. The mechanism underlying this comorbidity, however, is unclear. Decrease in self-esteem caused by the initial disorder might play a decisive role in the development of the subsequent disorder. The present study aimed to determine whether the association between symptoms of social phobia and depression is mediated by decrease in self-esteem in mid-adolescent girls and boys. METHODS As a part of the prospective Adolescent Mental Health Cohort (AMCH), subjects of this study were 9th grade pupils (mean age, 15.5) responding to a survey conducted in 2002-2003 (T1) and to a 2-year follow-up survey in 2004-2005 (T2) (N = 2070, mean age 17.6 years, 54.5% girls). RESULTS Symptoms of social phobia without symptoms of depression at age 15 and symptoms of depression at age 17 were associated only among boys, and this association was mediated by decrease in self-esteem. Symptoms of depression without symptoms of social phobia at age 15 and symptoms of social phobia at age 17 were associated only among girls, and this association was partially mediated by decrease in self-esteem. CONCLUSIONS Decrease in self-esteem plays a decisive role in the association between social phobia and depression. Self-esteem should be a key focus in interventions for adolescents suffering from social phobia or depression. Efficient intervention for the first disorder might help to prevent the decline in self-esteem and thus the incidence of the subsequent disorder. These findings are based on a sample of Finnish adolescents and should be confirmed in other jurisdictions or in more ethnically diverse samples.


title: Host AAA+ ATPase TER94 plays critical roles in building the baculovirus viral replication factory and virion morphogenesis.

text: TER94 is a multifunctional AAA+ ATPase crucial for diverse cellular processes, especially protein quality control and chromatin dynamics in eukaryotic organisms. Many viruses, including coronavirus, herpesvirus and retrovirus, co-opt host cellular TER94 for optimal viral invasion and replication. Previous proteomics analysis identified the association of TER94 with the budded virions (BVs) of baculovirus, an enveloped insect large DNA virus. Here, the role of TER94 in the prototypic baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) life cycle was investigated. In virus-infected cells, TER94 accumulated in virogenic stroma (VS) at the early stage of infection and subsequently partially rearranged to the ring zone region. In the virions, TER94 was associated with the nucleocapsids of both BV and occlusion-derived virus (ODV). Inhibition of TER94 ATPase activity significantly reduced viral DNA replication and BV production. Electron/immunoelectron microscopy revealed that inhibition of TER94 resulted in the trapping of nucleocapsids within cytoplasmic vacuoles at the nuclear periphery for BV formation and blockage of ODV envelopment at a pre-mature stage within infected nuclei, which appeared highly consistent with its pivotal function in membrane biogenesis. Further analyses showed that TER94 was recruited to the VS or subnuclear structures through interaction with viral early proteins LEF3 and helicase, whereas inhibition of TER94 activity blocked the proper localization of replication-related viral proteins and morphogenesis of VS, providing an explanation for its role in viral DNA replication. Taken together, these data indicated the crucial functions of TER94 at multiple steps of baculovirus life cycle including genome replication, BV formation, and ODV morphogenesis.IMPORTANCE TER94 constitutes an important AAA+ ATPase that associates with diverse cellular processes including protein quality control, membrane fusion of the Golgi apparatus and endoplasmic reticulum network, nuclear envelope reformation, and DNA replication. To date, little is known regarding the role(s) of TER94 in the baculovirus life cycle. In this study, TER94 was found to play a crucial role in multiple steps of baculovirus infection including viral DNA replication and BV- and ODV formation. Further evidence showed that the membrane fission/fusion function of TER94 is likely to be exploited by baculovirus for virion morphogenesis. Moreover, TER94 could interact with the viral early proteins LEF3 and helicase to transport to and further recruit viral replication-related proteins to establish viral replication factories. This study highlights the critical roles of TER94 as an energy-supplying chaperon in the baculovirus life cycle and enriches our knowledge regarding the biological function of this important host factor.


FDA approves first RET inhibitor.


title: Acute Respiratory Distress Syndrome: Respiratory Monitoring and Pulmonary Physiology.

text: The high prevalence of acute respiratory distress syndrome (ARDS), its morbidity and mortality continue to fare a huge burden in the intensive care unit. More than 40 years ago, experimental studies have highlighted that, albeit essential, mechanical ventilation could be harmful to lungs and more recently to the diaphragm. Despite life-saving advances in mechanical ventilation (such as low tidal-volume ventilation, neuromuscular blockers agents, or prone positioning), a recent international observational study reported that most ARDS patients were not appropriately monitored. The monitoring capabilities of ventilators, in particular the simple interaction of the patient and the mechanical ventilation, are very powerful but are underutilized. This lack of monitoring may contribute to the persisting poor outcome of patients with ARDS. Providing a more careful ventilation is a priority to improve patients' outcomes. To achieve this goal, it is of paramount importance to better understand the complex relationship between the patient and the ventilator: the impact of ventilator settings on lungs during passive controlled ventilation, but also of patient's breathing efforts on lungs during assisted ventilation. In this review we present available tools to monitor respiratory mechanics at the bedside aiming at optimizing and personalizing mechanical ventilation. Hopefully, this careful management can decrease mortality of patients with ARDS in the future.


title: The SARS outbreak in a general hospital in Tianjin, China: clinical aspects and risk factors for disease outcome.

text: OBJECTIVES To describe clinical characteristics of severe acute respiratory syndrome (SARS) patients in a hospital in Tianjin, China, thereby comparing probable and suspected cases; to study risk factors associated with the death of cases; to describe the implementation of preventive interventions during the hospital outbreak. METHODS Physical and haematological information was obtained from clinical records. White blood cell counts, and percentages of neutrophilic granulocytes and neutrophilic lymphocytes were measured. The service department of the hospital provided information about daily use of protective materials. Differences in clinical symptoms between probable and suspected SARS cases were tested by Fisher's exact test. Non-linear mixed modelling was used to test for differences between the haematological patterns for probable and suspected cases. Risk factors for dying among probable SARS cases were tested by logistic regression. RESULTS The SARS outbreak started with a patient from Beijing on 15 April 2003, and spread quickly among the healthcare workers and in-patients in the hospital. In total 90 probable and 21 suspected cases were reported, with 17 deaths among them (case fatality rate 15%). Haematological patterns were significantly different between probable and suspected cases, whereas the percentages with certain clinical symptoms showed no apparent difference. Death of probable SARS cases was only significantly associated with high age and use of a respiratory machine (mainly for the most severe cases), whereas e.g. co-morbidity and steroid treatment showed no impact in multivariate analysis. Stringent control measures, including distribution of huge numbers of protective materials, started on 20 April, which soon lead to a strong decrease in the incidence of new cases. After the last SARS case left the hospital on 6 June, protective materials were dispensed at substantially lower rates, but not to zero, as was the case during the first days of the outbreak. CONCLUSION The working definition of probable SARS used during the epidemic appeared to have been fairly accurate. Many valuable lessons were learned regarding prevention of hospital spread of infection, especially the need to have sufficient protective supplies available and to implement these rigidly and at an early stage of an (threatening) epidemic.


Rheumatic disease and COVID-19.


title: Collateral grade of the Willis' circle predicts outcomes of acute intracranial internal carotid artery occlusion before thrombectomy.

text: BACKGROUND AND PURPOSE Endovascular mechanical thrombectomy (EVMT) shows significant promise in improving acute ischemic stroke (AIS) with proximal artery occlusion, but outcomes have been variable. We explored the patients treated by thrombectomy to investigate the association between a favorable clinical outcome of EVMT in intracranial internal carotid artery occlusion (iICAO) and a set of predictors. METHODS A total of 38 iICAO patients treated by EVMTs were analyzed. Primary collateral grades (PCG) at baseline based on the integrity of Willis' circle were categorized into three degrees. The favorable outcomes, measured by modified Rankin scale (mRS), were defined as ≤2 at 90 days. The reperfusion was one of the most important confounders, defined as modified thrombolysis in cerebral infarction (mTICI) ≥ 2b. The other risk factors included demographic characteristics, vascular risk factors, stroke severity, procedural EVMT, and PCG at baseline was adjusted to reveal the association with favorable outcomes. RESULTS Of 38 iICAO patients, 65.8% (25 in 38) achieved reperfusion. However, only 31.6% (12/38) achieved favorable outcomes at 90 days. With a PCG3, 61.5% of them achieved favorable outcomes, while only 37.5% of those with PCG2 and PCG1 achieved favorable outcomes (p = .003). In multivariable logistic regression, PCG was revealed as a predictor for favorable outcomes (OR 5.278, p = .019) after adjusting the reperfusion and other factors. CONCLUSIONS The PCG based on the integrity of Willis' circle might be an underlying predictor of the prognosis of AIS in patients with iICAO after EVMT. The function of intact anterior communicating artery (AcoA) and ipsilateral posterior communicating artery (PcoA) in favoring prognosis of the iICAO patients might need to be validation in future study.


title: Safety and feasibility of radiofrequency ablation for treatment of Bosniak IV renal cysts.

text: PURPOSE To describe our initial experience with radiofrequency ablation (RFA) of Bosniak IV renal cysts. MATERIALS AND METHODS From 2010 to 2014, 154 renal tumor cases were treated with percutaneous thermal ablation, of which 10 cases (6.4%) from nine patients were complex renal cysts and were treated with radiofrequency ablation. RESULTS All complex cysts were classified as Bosniak IV (four women and five men; mean age: 63.6 yrs, range: 33-83 years). One patient had a single kidney. Lesion size ranged from 1.5 to 4.1cm (mean: 2.5cm) and biopsy was performed on four cysts immediately before the procedure, all of which were malignant (two clear cell and two papillary carcinoma). Mean volume reduction of complex cysts was 25% (range: 10-40%). No patients required retreatment with RFA and no immediate or late complications were observed. The follow-up of Bosniak IV cysts had a median of 27 months (interquartile range [IQR], 23 to 38) and no recurrence or significant loss of renal function were observed. CONCLUSIONS Mid-term follow-up of the cases in our database suggests that image-guided percutaneous RFA can treat Bosniak IV cysts with very low complication rates and satisfactorily maintain renal function.


title: Corticosteroids for severe influenza pneumonia: A critical appraisal.

text: Influenza pneumonia is associated with high number of severe cases requiring hospital and intensive care unit (ICU) admissions with high mortality. Systemic steroids are proposed as a valid therapeutic option even though its effects are still controversial. Heterogeneity of published data regarding study design, population demographics, severity of illness, dosing, type and timing of corticosteroids administered constitute an important limitation for drawing robust conclusions. However, it is reasonable to admit that, as it was not found any advantage of corticosteroid therapy in so diverse conditions, such beneficial effects do not exist at all. Its administration is likely to increase overall mortality and such trend is consistent regardless of the quality as well as the sample size of studies. Moreover it was shown that corticosteroids might be associated with higher incidence of hospital-acquired pneumonia and longer duration of mechanical ventilation and ICU stay. Finally, it is reasonable to conclude that corticosteroids failed to demonstrate any beneficial effects in the treatment of patients with severe influenza infection. Thus its current use in severe influenza pneumonia should be restricted to very selected cases and in the setting of clinical trials.


title: Proteomics in China: ready for prime time.

text: Proteomics is a newborn science focusing on the comprehensive systematic analysis of all proteins in the molecule machineries, organelles, cells, tissues, organs or intact organisms. It has been becoming one of the focuses in life sciences and the cutting-edged techniques in biotechnologies in the 21st century. During last decade, proteomics in China has developed much faster than other developing fields in life sciences. This review article briefly retrospects the origin and development of proteomics in China, also provides an overview on the representative scientific progress and perspectives.


Celebrating a momentous milestone.


title: Presence of bacteria in failed anterior cruciate ligament reconstructions.

text: BACKGROUND Novel microbial detection technologies have revealed that chronic bacterial biofilms, which are recalcitrant to antibiotic treatment, are common in failed orthopedic procedures. QUESTIONS Are bacteria present on failed anterior cruciate ligament (ACL) reconstructions? Is there a difference in the presence or nature of bacteria in failed ACL reconstructions relative to a control set of healthy ACL's? METHODS We used a case-control study design, where we analyzed the bacterial composition of 10 failed ACL reconstructions and compared it to 10 native ACL's harvested during total knee arthroplasty. The IBIS Universal Biosensor was used to determine the nature of bacteria on ACL specimens, and fluorescent in situ hybridization (FISH) was used to visualize bacteria in a subset of cases. RESULTS Bacteria are present in failed ACL reconstructions. Bacteria are present in ACL's harvested during total knee arthroplasty, but the nature of the species differs significantly between experimental and control sets. Twelve genera were detected in the experimental set (in both allografts and autografts), and in four samples multiple species were detected. In contrast, the control group was characterized by presence of Propionibacterium acnes. CONCLUSIONS We demonstrate the presence of bacteria on failed ACLs surgeries, and open the door to investigate whether and how bacteria and the associated immune responses could possibly contribute to graft failure. CLINICAL RELEVANCE If microbial pathogens can be linked to failed grafts, it could provide: (1) markers for early diagnosis of abnormal healing in ACL surgeries, and (2) targets for early treatment to prevent additional reconstruction surgeries.


title: Antibiotic Use in Hospitalized Children With Respiratory Viruses Detected by Multiplex Polymerase Chain Reaction.

text: BACKGROUND Multiplex polymerase chain reaction-based methods are increasingly used to detect respiratory pathogens in children. While rapid identification of viruses has been shown to reduce antibiotic use, the impact of detecting specific viruses on antibiotic utilization has not been ascertained. This study compared antibiotic utilization among hospitalized children who tested positive for different respiratory viruses at admission. METHODS A single-center study of hospitalized children under 21 years of age who tested positive at admission for at least 1 respiratory virus by multiplex polymerase chain reaction from October 1, 2012 to October 1, 2015 was performed. Multivariable logistic regression was used to determine the association of testing positive for specific viruses with the use of antibiotics for ≥ 2 days, adjusted for demographic and clinical characteristics. RESULTS The study included 1416 patients with a median age of 2.1 years (interquartile range: 0.6-6.2 years). Patients positive for influenza (odds ratio: 2.0, 95% confidence interval: 1.1-3.4) and human metapneumovirus (odds ratio: 2.0, 95% confidence interval: 1.1-3.7) were more likely to receive ≥ 2 days of treatment compared with patients positive for respiratory syncytial virus (RSV). Other variables affecting prolonged use of antibiotics included respiratory support, primary nonrespiratory diagnosis, complex comorbid conditions and admission to the intensive care unit. CONCLUSIONS Providers are more likely to use antibiotics in non-RSV-infected patients compared with RSV. These trends likely represent concern about bacterial superinfection and may reflect lack of familiarity with these pathogens.


title: Fibrin Glue Increases the Tensile Strength of Conduit-Assisted Primary Digital Nerve Repair.

text: BACKGROUND An ideal peripheral nerve repair construct does not currently exist. Our primary goal was to determine whether fibrin glue adds to the tensile strength of conduit-assisted primary digital nerve repairs. Our secondary goal was to evaluate the impact of varying suture number and location on the tensile strength. METHODS Ninety cadaveric digital nerves were harvested and divided equally into the following repair groups: A (4/4), B (2/2), C (0/2), D (0/1), and E (0/0) with the first number referring to the number of sutures at the coaptation and the second number referring to the number of sutures at each proximal and distal end of the nerve-conduit junction. When fibrin glue was added, the group was labeled prime. The nerve specimens were transected and then repaired with 8-0 nylon suture and conduit. The tensile strength of the repairs was tested, and maximum failure load was determined. The results were analyzed with a 2-way analysis of variance. The Tukey post hoc test compared repair groups if the 2-way analysis of variance showed significance. RESULTS Both suture group and glue presence significantly affected the maximum failure load. Increasing the number of sutures increased the maximum failure load, and the presence of fibrin glue also increased the failure load. CONCLUSIONS Fibrin glue was found to increase the strength of conduit-assisted primary digital nerve repairs. Furthermore, the number of sutures correlated to the strength of the repair. Fibrin glue may be added to a conduit-assisted primary digital nerve repair to maintain strength and allow fewer sutures at the primary coaptation site.


title: Early Endovascular Treatment in Intravenous Tissue Plasminogen Activator-Ineligible Patients.

text: BACKGROUND AND PURPOSE Intravenous tissue-type plasminogen activator (tPA) treatment in acute stroke has many exclusion criteria. We aimed to assess the safety and efficacy of endovascular therapy (ET) in intravenous (IV) tPA-ineligible patients. METHODS Retrospective analysis of a prospectively collected database of consecutive patients treated with ET within 6 hours of stroke onset between September 2010 and April 2015. Patients treated with IV-tPA followed by ET were compared with those treated with ET alone because of IV-tPA ineligibility. Efficacy and safety end points included the rates of good outcome (90-day modified Rankin scale score ≤2), successful reperfusion (modified Treatment in Cerebral Ischemia 2b-3), parenchymal hematoma (PH-1 and PH-2), and 90-day mortality. Univariate and logistic regression were performed to identify the predictors of outcomes. RESULTS A total of 422 patients were included. Two hundred and fifty-three (59%) patients received IV-tPA+ET, and 169 (41%), ET alone. Combined IV-tPA+ET patients were slightly younger (64.9±15.2 versus 67.9±14.9 years; P=0.05), more often males (56% versus 44%; P=0.01), and had less hypertension (70% versus 81%; P=0.02) and vertebrobasilar occlusions (3% versus 8%; P=0.02). The remaining baseline characteristics, including National Institutes of Health Stroke Scale score (20 [15-23] versus 19 [15-24]; P=0.85), Alberta Stroke Program Early CT Score (ASPECTS; 8 [7-9] versus 8 [7-9]; P=0.24), and stroke onset to puncture times (235±70 versus 240±81 minutes; P=0.27), were similar across both groups. There were no significant differences in the rates of modified Treatment in Cerebral Ischemia 2b-3 (83% versus 80%; P=0.52), 90-day modified Rankin scale score ≤2 (45% versus 38%; P=0.21), or any PH (3% versus 5%; P=0.21). Unadjusted 90-day mortality was higher with ET alone (21% versus 34%; P<0.01); however, IV-tPA ineligibility was not associated with modified Treatment in Cerebral Ischemia 2b-3, any PH, good outcome, or 90-day mortality on logistic regression. CONCLUSIONS IV-tPA-eligible and -ineligible patients seem to have similar outcomes after early ET.


title: Aggregated COVID-19 suicide incidences in India: Fear of COVID-19 infection is the prominent causative factor.

text: Many Indian COVID-19 suicide cases are turning the press-media attention and flooding in the social media platforms although, no particular studies assessed the COVID-19 suicide causative factors to a large extent. Therefore, the present study presents 69 COVID-19 suicide cases (aged 19 to 65 years; 63 cases were males). The suicide causalities are included as follows - fear of COVID-19 infection (n=21), followed by financial crisis (n=19), loneliness, social boycott and pressure to be quarantine, COVID-19 positive, COVID-19 work-related stress, unable to come back home due to lockdown, unavailability of alcohol etc. Considering the extreme psychological impacts related to COVID-19, there emerges a need for countrywide extensive tele-mental health care services.


title: Effects of Acute Salbutamol Intake on Peripheral and Central Fatigue in Trained Men.

text: PURPOSE Ergogenic effect in physically active subjects has been reported after acute salbutamol (SAL) intake. β2-Agonists have potential stimulant effects within the central nervous system that could be involved in this ergogenic effect. We hypothesized that acute SAL intake would induce changes in cerebral responses during exercise, with significant improvement in cerebral oxygenation and voluntary activation (VA) contributing to an increase in muscle performance. METHODS Fourteen trained male subjects (25 ± 5 yr) performed repeated isometric knee extensions until task failure (TF) after 4 mg (oral) SAL, 800 μg (inhaled) SAL, or placebo intake. VA, corticospinal excitability, and inhibition assessed by transcranial magnetic stimulation and changes in hemoglobin concentrations assessed by near-infrared spectroscopy were measured before and during the fatiguing task. RESULTS SAL had no significant effect both at rest and during exercise on prefrontal cortex oxygenation (e.g., changes in oxyhemoglobin concentration at TF: 11.4 ± 11.1 (4 mg SAL) vs 10.4 ± 10.6 (800 μg SAL) vs 10.8 ± 8.1 μmol (placebo); P = 0.314) and neuromuscular function (e.g., VA measured by TMS at TF: 90.2% ± 6.6% vs 92.6% ± 5.0% vs 90.1% ± 7.0%; P = 0.760). SAL had no effect on the number of contractions until TF (95 ± 51 vs 100 ± 52 vs 93 ± 47; P = 0.629). CONCLUSIONS These results indicate that acute SAL intake had no effect on central and peripheral mechanisms of neuromuscular fatigue and did not improve quadriceps endurance.


title: COVID-19 and the otolaryngologist - preliminary evidence-based review.

text: The SARS-CoV-2 virus which causes coronavirus disease 2019 (COVID-19) has rapidly swept across the world since its identification in December 2019. Otolaryngologists are at unique risk due to the close contact with mucus membranes of the upper respiratory tract and have been among the most affected healthcare workers in Wuhan, China. We present information on COVID-19 management relevant to otolaryngologists on the frontlines of this pandemic and provide preliminary guidance based on practices implemented in China and other countries and practical strategies deployed at Stanford University. This article is protected by copyright. All rights reserved.


title: How Did the Dengue Fever Outbreak Progress in Yoyogi Park, Tokyo, in 2014?-Evaluation Based on a Mathematical Model.

text: OBJECTIVES In the summer of 2014, an outbreak of autochthonous dengue fever occurred in Yoyogi Park and its vicinity, Tokyo, Japan. In this study, we investigated how the dengue fever outbreak progressed in Yoyogi Park using a mathematical model. METHODS This study was limited to the transmission of the dengue virus in Yoyogi Park and its vicinity. We estimated the distributions of the intrinsic incubation period and infection dates on the basis of epidemiological information on the dengue outbreak in 2014. We searched for an assumption that satisfactorily explains the outbreak in 2014 using rough estimates of secondary and tertiary infection cases. We constructed a mathematical model for the transmission of the dengue virus between humans and Aedes albopictus. RESULTS We carried out 1,000-trial stochastic simulations for all combinations of three kinds of assumption about Ae. albopictus and asymptomatic infection with each of three levels. Simulation results showed that the scale of the outbreak was markedly affected by the daily survival rate of Ae. albopictus. The outbreak involved a small number of secondary infection cases, reached a peak at tertiary infection, and transformed to termination at the fourth infection. Under some assumptions, the daily progress of onset cases was within a range between the 1st-3rd quartiles of 1,000 trials for 87% of dates and within a range between the minimum and maximum for all dates. CONCLUSIONS It is important to execute plans to detect asymptomatic cases and reduce the survival rate of Ae. albopictus to prevent the spread of tertiary infections unless an outbreak is suppressed at the secondary infection stage.


Covid-19: International staff are considered vital to NHS's efforts, survey finds.


title: Structure of a conserved Golgi complex-targeting signal in coronavirus envelope proteins.

text: Coronavirus envelope (CoV E) proteins are ∼100-residue polypeptides with at least one channel-forming α-helical transmembrane (TM) domain. The extramembrane C-terminal tail contains a completely conserved proline, at the center of a predicted β-coil-β motif. This hydrophobic motif has been reported to constitute a Golgi-targeting signal or a second TM domain. However, no structural data for this or other extramembrane domains in CoV E proteins is available. Herein, we show that the E protein in the severe acute respiratory syndrome virus has only one TM domain in micelles, whereas the predicted β-coil-β motif forms a short membrane-bound α-helix connected by a disordered loop to the TM domain. However, complementary results suggest that this motif is potentially poised for conformational change or in dynamic exchange with other conformations.


title: Comparison of five media for detection of extended-spectrum Beta-lactamase by use of the wasp instrument for automated specimen processing.

text: Overall, 2,337 rectal screening samples (RSSs) were seeded by using the Wasp instrument for automated microbiological processing with five media for detection of extended-spectrum β-lactamase (ESBL): CHROMagar, ChromID, Brilliance, BD Drigalski, and HEGP media. Of 354 RSSs harboring ESBL-producing isolates, 89.3% were found to be positive on all media. Sensitivity and specificity ranged from 95.5 to 98.3% and from 57.9 to 72.3%, respectively. No medium was perfectly ESBL selective, and non-ESBL-producing strains were mainly Enterobacteriaceae overproducing AmpC β-lactamase and nonfermenting Gram-negative bacilli, mostly Pseudomonas aeruginosa.


title: Lack of evidence of avian adenovirus infection among turkey workers.

text: Zoonotic infections constitute a major public health concern. Outbreaks of the SARS (severe acute respiratory syndrome) and avian influenza viruses are but recent examples. Although there are many animal-specific adenoviruses and occasionally they have been noted to infect man, rarely have they been studied as potential zoonotic pathogens. In this study, the authors hypothesized that the hemorrhagic enteritis virus (HEV), an avian adenovirus that causes illness among turkeys, might infect humans. Using an enzyme immunosorbent assay, the authors compared sera from 95 turkey-exposed individuals with sera from 82 nonexposed controls for serologic evidence of infection with HEV. Multivariate modeling revealed no statistical difference in elevated antibody titers against HEV between the two groups. These data do not support the hypothesis that avian adenoviruses cross the species barrier to infect humans.


Rapid mobilisation of research in response to covid-19: a paradigm for the future.


title: Nitinol self-expanding stents vs. balloon angioplasty for very long femoropopliteal lesions.

text: PURPOSE To compare the patency rates and clinical outcomes of balloon angioplasty vs. nitinol stent placement for patients with short (≤150 mm) as compared to long (>150 mm) femoropopliteal (FP) occlusive lesions. METHODS Between 2006 and 2011, 254 patients (134 men; mean age 68 years) underwent FP angioplasty. The majority of patients (64%) were treated for critical limb ischemia. One hundred thirty-nine (55%) patients had short FP lesions ≤150 mm, while 115 patients had long FP lesions >150 mm. The mean lesion length was 78±43 mm in the short FP lesion group and 254±58 mm in the long FP lesion group. Duplex ultrasound follow-up with a peak systolic velocity ratio ≥2.0 was used to define restenosis. RESULTS The overall procedure success rate was 98%. One hundred forty-eight (58%) patients underwent stent placement. The mean number of stents deployed for treatment of short FP lesions was 1.0±0.4 vs. 2.0±0.7 for long FP lesions (p<0.001). The primary patency rate of short FP lesions treated with balloon angioplasty vs. stenting was 66% vs. 63% at 1 year (p=0.7). For long FP lesions, the 1-year primary patency rates of balloon angioplasty vs. stenting were 34% vs. 49% (p=0.006). Balloon angioplasty of long FP lesions was also associated with significantly lower assisted primary and secondary patency compared to stenting (p<0.05 for all comparisons). Sustained clinical improvement was >90% at 30 days but declined to 62% to 75% at 1 year. CONCLUSION Balloon angioplasty and stent placement result in similar patency rates and clinical outcomes for shorter to medium-length FP lesions. In comparison, stent placement in long FP lesions is associated with superior outcomes to balloon angioplasty, even when multiple stents are required. Procedure success and clinical improvement can be achieved in the majority of patients, but rates of restenosis remain high.


title: The link between neurosteroids and syndromic/syndromal components of the mood spectrum disorders in women during the premenstrual phase.

text: OBJECTIVES Females with a lifetime diagnosis of major mood disorder (Bipolar Disorder BD, Major Depressive Disorder MMD) investigated during the luteal phase of their menstrual cycle and in a condition of clinical well-being showed higher blood serum concentrations of progesterone and allopregnanolone compared to healthy controls. Women with BD presented even higher levels than those affected by MDD. This study attempted to verify, in line with a dimensional approach, if the possible differences in neurohormonal levels may be directly linked to some syndromal clusters (dimensions) of the mood spectrum disorders indipendently of diagnosis. METHODS Premenstrual concentrations of allopregnanolone, THDOC, progesterone, and cortisol were measured in 3 groups of women: 17 BD and 14 MDD outpatients, and 16 control subjects. Psychiatric evaluation was performed with the SCID-I interview and the SCI-MOODS-SR questionnaire. The correlation between steroid levels and mood disorder syndromal cluster (SCI-MOODS-SR domains and sub-domains) was evaluated by means of analysis of main components with Varimax rotation and Kaiser's normalization (which provided for inclusion of all components with an Eigen value >1). RESULTS Analysis of the main components evidenced the presence of 3 components: 1) mania, 2) depression both with mixed component 3) steroid + manic cognitivity and suicidal ideas. CONCLUSION Levels of allopregnanolone and progesterone do not correlate with the association of the depressive and manic syndromes, but rather with mixed symptomatological aspects, and in particular with cognitive manic and depressive (with suicidal thoughts) dimensions. Further studies should be carried out to confirm these findings.


title: Microbiology of otitis media in Indigenous Australian children: review.

text: OBJECTIVES To review research addressing the polymicrobial aetiology of otitis media in Indigenous Australian children in order to identify research gaps and inform best practice in effective prevention strategies and therapeutic interventions. METHODS Literature review. RESULTS Studies of aspirated middle-ear fluid represented a minor component of the literature reviewed. Most studies relied upon specimens from middle-ear discharge or the nasopharynx. Culture-based middle-ear discharge studies have found that non-typeable Haemophilus influenzae and Streptococcus pneumoniae predominate, with Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pyogenes isolated in a lower proportion of samples. Alloiococcus otitidis was detected in a number of studies; however, its role in otitis media pathogenesis remains controversial. Nasopharyngeal colonisation is a risk factor for otitis media in Indigenous infants, and bacterial load of otopathogens in the nasopharynx can predict the ear state of Indigenous children. CONCLUSION Most studies have used culture-based methods and specimens from middle-ear discharge or the nasopharynx. Findings from these studies are consistent with international literature, but reliance on culture may incorrectly characterise the microbiology of this condition. Advances in genomic technologies are now providing microbiologists with the ability to analyse the entire mixed bacterial communities ('microbiomes') of samples obtained from Indigenous children with otitis media.


title: Monopolar cautery and adverse effects on cochlear implants.

text: IMPORTANCE The use of monopolar cautery has been widely regarded as a contraindication in the setting of a cochlear implant because of presumed risk to the implant device. There are very limited data to support this contraindication. OBJECTIVES (1) To evaluate the effects of monopolar cautery on cochlear implant devices. (2) To determine whether monopolar cautery changes the endocochlear temperature in an implanted cochlea. DESIGN Sixteen cochlear implants from 3 manufacturers (Advanced Bionics LLC, Cochlear Americas Ltd, and Med-El Ltd) were implanted into 2 unembalmed, fresh cadavers. Monopolar cautery was applied to either the tongue or abdomen at coagulation settings of 10 W or 50 W for 30 minutes. Impedance and integrity testing were performed before, during, and after 30 minutes of cautery. The temperature in the endocochlear perilymph was measured during cautery. After explantation, devices were returned to the manufacturer for an in-depth "failure" analysis according to each manufacturer's current protocol evaluating explanted devices. SETTING Basic science laboratory, tertiary medical center. PARTICIPANTS Cadaveric study. INTERVENTION Application of monopolar cautery to implanted cochlear implants in a cadaveric model. MAIN OUTCOME AND MEASURE (1) Changes to the implanted devices either during electrocautery or following failure analysis. (2) Changes in the intracochlear temperature. RESULTS No change in impedance, integrity testing, or failure analysis occurred at any cautery setting when applied to either the oral cavity or abdomen. The temperature of the cochlea did not increase with up to 30 minutes of cautery at a setting of 50 W. Comprehensive device analysis did not show any evidence of device damage at the conclusion of the study. CONCLUSIONS AND RELEVANCE Monopolar cautery did not produce detectible damage to any of the cochlear implant devices or produce detectible temperature change in the cochlea at low or high levels of cautery in the oral cavity in this experimental model.


title: The Use of Catheter Mount Will Result in More Reliable Carbon Dioxide Monitoring under Fluid Exposing Conditions.

text: Introduction Capnometer can be readily malfunctioned by fluid exposure during treatment of critically ill patients. This study aimed to determine whether placing capnometer distant from the endotracheal tube by connecting direct connect catheter mount (DCCM) is effective in yielding reliable end-tidal carbon dioxide (ETCO2) by reducing capnometer malfunctioning caused by water exposure. Methods In 25 healthy adults, a prospective, open label, crossover study was conducted to examine the effect of DCCM in mainstream and microstream capnometers under water exposing conditions. The primary endpoint was the comparison of ETCO2 between proximal DCCM (pDCCM) and distal DCCM (dDCCM). Results For mainstream capnometers, mean ETCO2 was significantly (p < 0.001) higher in dDCCM compared to pDCCM under water exposing conditions (29.5 vs. 19.0 with 5 ml; 33.8 vs. 21.2 with 10 ml; mmHg). Likewise, for microstream capnometers, ETCO2 was greatly higher (p < 0.001) in dDCCM compared to pDCCM (30.5 vs. 13.9 with 5 ml; 29.9 vs.11.4 with 10 mL; mmHg). ETCO2 measured by dDCCM was reliable in microstream settings, whereas it was unreliable in mainstream (correlation coefficient 0.88 vs. 0.27). Conclusions Application of DCCM onto the capnometer setting seems to be effective in reducing capnometer malfunctioning under fluid exposing conditions, which is obvious in microstream capnometer by producing more reliable ETCO2.


title: Watertight dural closure in brain surgery: a simple model for training.

text: BACKGROUND To avoid cerebrospinal fluid leaks and related possible complications, the dura mater should be meticulously closed after craniotomy procedures. Several techniques for duraplasty and different material for watertight closure have been described. OBJECTIVE To describe a device to be used for the training of neurosurgical procedures of duraplasty. TECHNICAL REPORT A plastic dummy with a balloon was developed to test the efficacy of the watertight closure of the dura. The technical notes to reproduce the method have been described. CONCLUSION The described model represents a new, simple, effective and affordable device to be used for neurosurgical training in the procedures of duraplasty and to test the efficacy of watertight closures.


title: Potential for international spread of wild poliovirus via travelers.

text: BACKGROUND The endgame of polio eradication is hampered by the international spread of poliovirus via travelers. In response to ongoing importations of poliovirus into polio-free countries, on 5 May 2014, WHO's Director-General declared the international spread of wild poliovirus a public health emergency of international concern. Our objective was to develop a mathematical model to estimate the international spread of polio infections. METHODS Our model took into account polio endemicity in polio-infected countries, population size, polio immunization coverage rates, infectious period, the asymptomatic-to-symptomatic ratio, and also the probability of a traveler being infectious at the time of travel. We applied our model to three scenarios: (1) number of exportations of both symptomatic and asymptomatic polio infections out of currently polio-infected countries, (2) the risk of spread of poliovirus to Saudi Arabia via Hajj pilgrims, and (3) the importation risk of poliovirus into India. RESULTS Our model estimated 665 polio exportations (>99 % of which were asymptomatic) from nine polio-infected countries in 2014, of which 78.3 % originated from Pakistan. Our model also estimated 21 importations of poliovirus into Saudi Arabia via Hajj pilgrims and 20 poliovirus infections imported to India in the same year. CONCLUSION The extent of importations of asymptomatic and symptomatic polio infections is substantial. For countries that are vulnerable to polio outbreaks due to poor national polio immunization coverage rates, our newly developed model may help guide policy-makers to decide whether imposing an entry requirement in terms of proof of vaccination against polio would be justified.


title: Trends of Hospitalization for Acute Alcohol Intoxication in Slovenian Children and Adolescents with and without Dual Disorder. Implications for a Correct Intervention.

text: BACKGROUND Binge drinking and other forms of ethanol abuse are, when present, a serious problem in preteens and adolescents worldwide. AIM The present study has analyzed the trend in alcohol-related intoxications requiring the hospitalization of children, adolescents and young adults aged less than 21 years in Slovenia in the 1999-2018 period. METHODS We performed a retrospective study on patients discharged after hospitalizations due to mental and behavioral disorders due to acute alcohol intoxication (MBDAAI) or hospitalizations due to the toxic effects of alcohol (TEA We considered three groups: children (aged 10-14), adolescents (aged 15-19) and young adults (20-21 years old). Hospitalization rates and time trends were analyzed using joinpoint regression to obtain the annually calculated age- and sex-specific rates and the annual percentage of change (APC). RESULTS Considering a total of 2912 MBDAAI-hospitalizations, 15-19-year-old subjects showed a significantly higher hospitalization rate compared to the immediately younger and older age groups and a significant increase in hospitalization rates in the period 1999-2011, followed by a significant decrease. Considering 1143 TEA-hospitalizations, we observed a continuous decrease in the hospitalization rates for children and young adults and, conversely, a continuous even if less than significant increase for adolescents aged 15-19. CONCLUSIONS Alcohol consumption in Slovenian children and adolescents is a highly important health concern. Special attention to public health problem of severe alcohol abuse requiring hospitalization in children and adolescents is needed, especially with possible crisis of SARS-CoV-2/Covid-19 situation.


title: A multicenter, randomized, observation-controlled clinical trial to evaluate the efficacy and safety of thymalfasin adjuvant therapy in patients with HBV-related HCC after curative resection - first announcement of the protocol.

text: Hepatocellular carcinoma (HCC), the third leading cause of cancer-related death worldwide, is a disease of immune microenvironment. Chronic Hepatitis B virus (HBV) infection, also an immune-related disease, is the major etiological factor for HCC especially in Asia. As an immune regulator, which has pleiotropic activities on T cells, nature killer cells and dendritic cells and so on, the efficacy of thymalfasin on HCC patients has been proven by several pilot studies as an adjuvant therapy. Combination of thymalfasin significantly improved survival and prolonged the time to tumor recurrence in patients who received transcatheter arterial chemoembolization after tumor resection. An improvement in patients' immunity has also been demonstrated. However, there is no large-scale randomized controlled study so far in resectable HCC patients. To confirm the role of thymalfasin adjuvant therapy in patients with HBV-related HCC after curative resection, a large-scale multicenter randomized controlled trial has been planned in China to investigate the effect of thymalfasin (1.6 mg twice a week for 12 months) on 2-year recurrence-free survival rate and tumor immune microenvironment. Here is the first announcement of the study protocol (ClinialTrials.gov Identifier: NCT02281266).


title: Ex vivo evaluation of canine lung biopsy techniques.

text: OBJECTIVE An ex vivo comparison of thoracoscopic lung biopsy techniques in dogs. STUDY DESIGN Experimental. SAMPLE POPULATION Cadaveric canine lung lobes. METHODS Lungs were inflated to 10 cmH2 O. After collecting biopsies 3 cm from the edge of lung lobes, leak pressures were recorded as inflation pressure was increased to 40 cmH2 O. Pre-tied loop ligature, square knot (SQ), modified 4S Roeder knot (M4SR) with glycomer 631 and polyglactin 910 size 0 and 2-0 were used in addition to EndoGIA 45-2.5 mm (Covidien, Norwalk, CT) and a vessel sealant device (VSDS single and VSDD double seal). Six biopsies were performed with each of these modalities. RESULTS Median airway pressure at which leakage occurred was 28 (20-34)cmH2 O for EndoGIA 45; 33 (14-40) for VSDD; and 33 (10-40) for VSDS while other groups reached a median pressure of 40 cmH2 O (P < .0001). Leakage occurred at 20 cmH2 O in 1 sample with the EndoGIA and the VSDS, and in 2 with the VSDD while leakage did not occur in any other group (P = .36). Leakage occurred at 30 cmH2 O in 1 specimen each of the 0-polyglactin SQ, 2-0 glycomer 631 M4SR, 2-0 polyglactin M4SR, and 2-0 Surgitie (Covidien, Norwalk, CT); 2 with the VSDS; and 3 with the EndoGIA and the VSDD while leakage did not occur in any other group (P = .26). CONCLUSIONS All tested techniques seemed safe except the vessel sealant device since it did not consistently seal every biopsy and leaked at pressures <20 cmH2 O.


title: Reducing food waste in residential complexes using a pilot-scale on-site system.

text: A pilot-scale on-site system combining biological treatment and a drying stage was applied to achieve mass reduction of food waste (FW) at an urban residential complex. The effectiveness of biodegrading the organic portion of FW via microorganisms existing in FW improved by 38.80% by controlling rates of FW loading and air-flow. In one stage of the on-site biological treatment, the major bacterial community was identified to be mesophilic and facultative; Lactobacillus was the most dominant genus, accounting for 78.1% of bacterial community. Total mass reduction of FW approached 90.15% by increasing removal of both moisture and the organic portion of FW. In addition, the solids and liquids of the final by-products have the potential to be recycled into resources such as fertilizer, a bio-solid refuse fuel or external carbon sources for wastewater treatment plants. The proposed decentralized system offers practical and environmental approaches for FW management in residential complexes.


title: Rotaviruses reach late endosomes and require the cation-dependent mannose-6-phosphate receptor and the activity of cathepsin proteases to enter the cell.

text: UNLABELLED Rotaviruses (RVs) enter cells through different endocytic pathways. Bovine rotavirus (BRV) UK uses clathrin-mediated endocytosis, while rhesus rotavirus (RRV) employs an endocytic process independent of clathrin and caveolin. Given the differences in the cell internalization pathway used by these viruses, we tested if the intracellular trafficking of BRV UK was the same as that of RRV, which is known to reach maturing endosomes (MEs) to infect the cell. We found that BRV UK also reaches MEs, since its infectivity depends on the function of Rab5, the endosomal sorting complex required for transport (ESCRT), and the formation of endosomal intraluminal vesicles (ILVs). However, unlike RRV, the infectivity of BRV UK was inhibited by knocking down the expression of Rab7, indicating that it has to traffic to late endosomes (LEs) to infect the cell. The requirement for Rab7 was also shared by other RV strains of human and porcine origin. Of interest, most RV strains that reach LEs were also found to depend on the activities of Rab9, the cation-dependent mannose-6-phosphate receptor (CD-M6PR), and cathepsins B, L, and S, suggesting that cellular factors from the trans-Golgi network (TGN) need to be transported by the CD-M6PR to LEs to facilitate RV cell infection. Furthermore, using a collection of UK × RRV reassortant viruses, we found that the dependence of BRV UK on Rab7, Rab9, and CD-M6PR is associated with the spike protein VP4. These findings illustrate the elaborate pathway of RV entry and reveal a new process (Rab9/CD-M6PR/cathepsins) that could be targeted for drug intervention. IMPORTANCE Rotavirus is an important etiological agent of severe gastroenteritis in children. In most instances, viruses enter cells through an endocytic pathway that delivers the viral particle to vesicular organelles known as early endosomes (EEs). Some viruses reach the cytoplasm from EEs, where they start to replicate their genome. However, other viruses go deeper into the cell, trafficking from EEs to late endosomes (LEs) to disassemble and reach the cytoplasm. In this work, we show that most RV strains have to traffic to LEs, and the transport of endolysosomal proteases from the Golgi complex to LEs, mediated by the mannose-6-phosphate receptor, is necessary for the virus to exit the vesicular compartment and efficiently start viral replication. We also show that this deep journey into the cell is associated with the virus spike protein VP4. These findings illustrate the elaborate pathway of RV entry that could be used for drug intervention.


title: COVID-19 in Refractory Myasthenia Gravis- A Case Report of Successful Outcome.

text: This is a brief report of a patient who has refractory Myasthenia Gravis, on multiple long-term immunosuppressive therapies and contracted COVID-19 during this 2020 pandemic. She was quarantined for total of 14 days and recovered successfully without any complications (no myasthenia exacerbation or crisis, no COVID-19 related complications), with no changes to her immunosuppressive therapy. Treatment of MG patients with COVID-19 needs to be tailored to individual patient.


title: Effect of audit and feedback on physicians' intraoperative temperature management and patient outcomes: a three-arm cluster randomized-controlled trial comparing benchmarked and ranked feedback.

text: PURPOSE Audit and feedback can improve physicians' practice; however, the most effective type of feedback is unknown. Inadvertent perioperative hypothermia is associated with postoperative complications and remains common despite the use of effective and safe warming devices. This study aimed to measure the impact of targeted audit and feedback on anesthesiologists' intraoperative temperature management and subsequent patient outcomes. METHODS This study was a three-arm cluster randomized-controlled trial. Anesthesiologists' intraoperative temperature management performance was analyzed in two phases. The first was a baseline phase with audit but no feedback for eight months, followed by an intervention phase over the next seven-month period after participants had received interventions according to their randomized group allocation of no feedback (control), benchmarked feedback, or ranked feedback. Anesthesiologists' percentage of hypothermic patients at the end of surgery (primary endpoint) and use of a warming device were compared among the groups. RESULTS Forty-five attending anesthesiologists who took care of 7,846 patients over 15 months were included. The odds of hypothermia (temperature < 36°C at the end of surgery) increased significantly from pre- to post-intervention in the control and ranked groups (control odds ratio [OR], 1.27; 95% confidence interval [CI], 1.03 to 1.56; P = 0.02; ranked OR, 1.26; 95% CI, 1.01 to 1.56; P = 0.04) but not in the benchmarked group (OR, 1.05; 95% CI, 0.87 to 1.28; P = 0.58). Between-arm differences in pre- to post-intervention changes were not significant (benchmark vs control OR, 0.83; 95% CI, 0.62 to 1.10; P = 0.19; ranked vs control OR, 0.99; 95% CI, 0.73 to 1.33, P = 0.94). No significant overall effect on intraoperative warmer use change was detected. CONCLUSION We found no evidence to suggest that audit and feedback, using benchmarked or ranked feedback, is more effective than no feedback at all to change anesthesiologists' intraoperative temperature management performance. Feedback may need to be included in a bundle to produce its effect. TRIALS REGISTRATION www.clinicaltrials.gov (NCT02414191). Registered 19 March 2015.


title: Generalized anxiety disorder in China: prevalence, sociodemographic correlates, comorbidity, and suicide attempts.

text: PURPOSE This study aims to determine the 12-month and lifetime prevalence of generalized anxiety disorder (GAD) and its sociodemographic correlates. DESIGN AND METHODS A total of 5,926 subjects were randomly selected and interviewed. FINDINGS The overall 12-month and lifetime prevalence of GAD was 0.8%, and 1.2%, respectively. Being older than 25 years and female, lower education level, unemployed status, and lower (RMB2000/month) monthly income were associated with increased risk of GAD. PRACTICE IMPLICATIONS The low percentage of subjects treated for GAD indicates a major public health problem that should be addressed.


title: Identifying Factors Associated with Risk Assessment Competencies of Public Health Emergency Responders.

text: This study aimed to better understand the current situation of risk assessment and identify the factors associated with competence of emergency responders in public health risk assessment. The participants were selected by a multi-stage, stratified cluster sampling method in Heilongjiang Centers for Disease Control and Prevention (CDC). The questionnaires that measured their perceptions on risk assessment competences were administered through the face-to-face survey. A final sample of 1889 staff was obtained. Of this sample, 78.6% of respondents rated their own risk assessment competences as "relatively low", contrasting with 21.4% rated as "relatively high". Most of the respondents (62.7%) did not participate in any risk assessment work. Only 13.7% and 42.7% of respondents reported participating in risk assessment training and were familiar with risk assessment tools. There existed statistical significance between risk assessment-related characteristics of respondents and their self-rated competences scores. Financial support from the government and administrative attention were regarded as the important factors contributing to risk assessment competences of CDC responders. Higher attention should be given to risk assessment training and enhancing the availability of surveillance data. Continuous efforts should be made to remove the financial and technical obstacles to improve the competences of risk assessment for public health emergency responders.


title: Self-inflicted oral penetration injury: An intravenous drip pole advanced from the mouth to the retroperitoneum.

text: INTRODUCTION Patients with oral penetration injuries require a systematic physical examination. These patients should be managed by a multidisciplinary medical team. Airway management, operative procedures, and transfusion needs of the patient with an oral penetration injury should be discussed before surgery. PRESENTATION OF CASE A 63-year-old man with a history of recurrent hepatic duct cancer attempted suicide by advancing an intravenous pole through his mouth, neck, and thorax, ultimately penetrating into the right retroperitoneal space. A multidisciplinary team assembled by code blue emergently treated the patient, initially with fiberoptic intubation. The injured right lower lung was resected under one lung ventilation via a double lumen tube after tracheostomy. Fortunately, the pole did not injure any other organs or major vessels. Despite successful removal of the pole after lung resection, the patient died 14 days postoperatively due to his primary hepatic duct cancer. DISCUSSION We highlight the need for a multidisciplinary approach to this patient's management and discuss particular aspects of airway and transfusion management. CONCLUSION A systematic and multidisciplinary approach allowed successful removal of the drip pole and stabilization of the patient's respiratory and hemodynamic status.


title: Endoscopic endonasal approach for resection of ventral skull base keratinaceous cysts.

text: BACKGROUND Epidermoid and dermoid cysts are uncommon entities that belong in the differential diagnosis of ventral skull base lesions. The endoscopic endonasal approach is an attractive option for management of these lesions with limited morbidity. The clinical characteristics and management course from our experience is reviewed along with the relevant literature. METHODS A prospective database of endoscopic endonasal skull base cases performed since 2003 at a tertiary referral center was reviewed for cases involving keratinaceous lesions. Data on the pathology, radiology and management of the disease was reviewed. A search of pertinent literature using Medline was performed to complement the discussion. RESULTS Three cases of intracranial keratinaceous cysts successfully managed with the endoscopic endonasal approach. All cases presented with headache, and 1 case presented with bitemporal hemianopsia. Characteristic appearance on magnetic resonance imaging was seen in each case. All lesions were intradural with variable involvement of the suprasellar, prepontine, and premedullary cisterns. Total resection was achieved in 2 cases and near total resection in 1 case. Postoperative cerebrospinal fluid leak occurred in one case, which was controlled after revision surgery using the "gasket-seal" technique. There were no cranial nerve palsies or vascular events. CONCLUSION The endoscopic endonasal approach allows the rhinologic surgeon to access the ventral midline skull base for the successful management of keratinaceous cysts without major complications.


title: Neurofilaments: neurobiological foundations for biomarker applications.

text: Interest in neurofilaments has risen sharply in recent years with recognition of their potential as biomarkers of brain injury or neurodegeneration in CSF and blood. This is in the context of a growing appreciation for the complexity of the neurobiology of neurofilaments, new recognition of specialized roles for neurofilaments in synapses and a developing understanding of mechanisms responsible for their turnover. Here we will review the neurobiology of neurofilament proteins, describing current understanding of their structure and function, including recently discovered evidence for their roles in synapses. We will explore emerging understanding of the mechanisms of neurofilament degradation and clearance and review new methods for future elucidation of the kinetics of their turnover in humans. Primary roles of neurofilaments in the pathogenesis of human diseases will be described. With this background, we then will review critically evidence supporting use of neurofilament concentration measures as biomarkers of neuronal injury or degeneration. Finally, we will reflect on major challenges for studies of the neurobiology of intermediate filaments with specific attention to identifying what needs to be learned for more precise use and confident interpretation of neurofilament measures as biomarkers of neurodegeneration.


title: Less social emergency departments: implementation of workplace contact reduction during COVID-19.

text: The COVID-19 pandemic has led to rapid changes in community and healthcare delivery policies creating new and unique challenges to managing ED pandemic response efforts. One example is the practice of social distancing in the workplace as an internationally recommended non-pharmaceutical intervention to reduce transmission. While attention has been focused on public health measures, healthcare workers cannot overlook the transmission risk they present to their colleagues and patients. Our network of three EDs are all high traffic areas for both patients and staff, which makes the limitation of close person-to-person contact particularly difficult to achieve. To design, implement and communicate contact reduction changes in the ED workplace, our COVID-19 task force formalised a set of multidisciplinary recommendations that enumerated concrete ways to reduce healthcare worker transmission to coworkers and to patients from ED patient arrival to discharge. We also addressed staff-to-staff contact reduction strategies when not performing direct patient care. We describe our conceptual approach and successful implementation of workplace distancing.


title: Evaluating the effects of a 532-nm fiber-based KTP laser on transoral laser surgery supplies.

text: OBJECTIVE The KTP laser has become commonplace in transoral head and neck surgery. The interactions of this laser with commonly used supplies in transoral surgery have not been formally examined. This study evaluates the effects of the KTP laser on surgical supplies. STUDY DESIGN Experimental study. SETTING The study was conducted in an empty operating room at a university-affiliated medical center. METHODS An Aura XP 532-nm KTP laser with a 600-nm fiber was used in pulsed and continuous modes. The beam was focused at the shaft and balloon of 3 "laser-safe" endotracheal tubes (ETTs), a polyvinyl chloride (PVC) ETT, and a Codman surgical patty. Time to penetrate was recorded. Results The KTP laser beam was unable to penetrate any of the laser-resistant ETTs. It did react with the black number markings on the PVC ETT by producing sparks but was unable to penetrate the shaft of the ETT. The KTP laser was nonreactive with all ETT cuffs except in 1 of 3 trials with the outer balloon cuff of a Rusch Lasertubus ETT when the laser was used in a continuous mode. The KTP laser caused the production of a flame upon contact with the blue radiopaque strip of the surgical patty, even when the patty was wet. CONCLUSION This study demonstrates that a number of safe ETT options may be used during transoral laser microsurgery with a KTP laser. In addition, Codman surgical patties are shown to be a significant fire risk in KTP laser surgery.


Mechanisms of acute coronary syndromes.


title: [Suture materials in urology].

text: Since ancient times, sutures have been a fundamental part of the surgeon's practice. Beside the vegetable and animal origin materials, in the last decades different refined synthetic materials have been introduced in the clinical practice. More recently, different devices, such as staplers and tissue sealers have been developed. Thus, more than ever, urologists are faced with a multitude of suture materials, and research of safe, effective materials and devices seems to be continuously growing. The introduction and widespread diffusion of laparoscopic and robotic surgery has further boosted this research. Given there is no single material that is ideal for all situations, the surgeon must choose the best material for each particular case. The aim of this non-systematic review is to summarize the more innovative suture materials and devices and to describe the different surgical methods to utilize them both in general and in urologic surgery.


title: On the Design of an Efficient Cardiac Health Monitoring System Through Combined Analysis of ECG and SCG Signals.

text: Cardiovascular disease (CVD) is a major public concern and socioeconomic problem across the globe. The popular high-end cardiac health monitoring systems such as magnetic resonance imaging (MRI), computerized tomography scan (CT scan), and echocardiography (Echo) are highly expensive and do not support long-term continuous monitoring of patients without disrupting their activities of daily living (ADL). In this paper, the continuous and non-invasive cardiac health monitoring using unobtrusive sensors is explored aiming to provide a feasible and low-cost alternative to foresee possible cardiac anomalies in an early stage. It is learned that cardiac health monitoring based on sole usage of electrocardiogram (ECG) signals may not provide powerful insights as ECG provides shallow information on various cardiac activities in the form of electrical impulses only. Hence, a novel low-cost, non-invasive seismocardiogram (SCG) signal along with ECG signals are jointly investigated for the robust cardiac health monitoring. For this purpose, the in-laboratory data collection model is designed for simultaneous acquisition of ECG and SCG signals followed by mechanisms for the automatic delineation of relevant feature points in acquired ECG and SCG signals. In addition, separate feature points based novel approach is adopted to distinguish between normal and abnormal morphology in each ECG and SCG cardiac cycle. Finally, a combined analysis of ECG and SCG is carried out by designing a Naïve Bayes conditional probability model. Experiments on Institutional Review Board (IRB) approved licensed ECG/SCG signals acquired from real subjects containing 12,000 cardiac cycles show that the proposed feature point delineation mechanisms and abnormal morphology detection methods consistently perform well and give promising results. In addition, experimental results show that the combined analysis of ECG and SCG signals provide more reliable cardiac health monitoring compared to the standalone use of ECG and SCG.


title: Novel dimeric DOTA-coupled peptidic Y1-receptor antagonists for targeting of neuropeptide Y receptor-expressing cancers.

text: BACKGROUND Several peptide hormone receptors were identified that are specifically over-expressed on the cell surface of certain human tumors. For example, high incidence and density of the Y1 subtype of neuropeptide Y (NPY) receptors are found in breast tumors. Recently, we demonstrated that the use of potent radiolabeled somatostatin or bombesin receptor antagonists considerably improved the sensitivity of in vivo imaging when compared to agonists. We report here on the first DOTA-coupled peptidic Y1 receptor affine dimer antagonists. METHODS Based on a Y1 affine dimeric peptide scaffold previously reported to competitively antagonize NPY-mediated processes, we have developed new dimeric DOTA-coupled Y1 receptor affine antagonists for scintigraphy and radiotherapy. These dimeric peptides were tested for their specific binding to Y1 expressed in SK-N-MC cells and Y2 expressed in SH-SY5Y as well as for their ability to mediate cAMP production in SK-N-MC cells. RESULTS Introduction of two DOTA moieties at the N-termini of the dimeric NPY analogs as well as the double Asn29 replacement by Dpr(DOTA) or Lys(DOTA) (6 and 10) moiety dramatically reduced binding affinity. However, asymmetric introduction of the DOTA moiety in one segment of the peptidic heterodimer (8 and 11) resulted in suitable antagonists for receptor targeting with high binding affinity for Y1. All compounds were devoid of Y2 binding affinity. CONCLUSIONS The design and the in vitro characterization of the first DOTA-coupled dimeric NPY receptor antagonist with high affinity and selectivity for Y1 over Y2 are described. This compound may be an excellent candidate for the imaging of Y1-positive tumors and their treatment.


title: Early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection.

text: Several respiratory viruses, including influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV), produce more severe disease in the elderly, yet the molecular mechanisms governing age-related susceptibility remain poorly studied. Advanced age was significantly associated with increased SARS-related deaths, primarily due to the onset of early- and late-stage acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Infection of aged, but not young, mice with recombinant viruses bearing spike glycoproteins derived from early human or palm civet isolates resulted in death accompanied by pathological changes associated with ARDS. In aged mice, a greater number of differentially expressed genes were observed than in young mice, whose responses were significantly delayed. Differences between lethal and nonlethal virus phenotypes in aged mice could be attributed to differences in host response kinetics rather than virus kinetics. SARS-CoV infection induced a range of interferon, cytokine, and pulmonary wound-healing genes, as well as several genes associated with the onset of ARDS. Mice that died also showed unique transcriptional profiles of immune response, apoptosis, cell cycle control, and stress. Cytokines associated with ARDS were significantly upregulated in animals experiencing lung pathology and lethal disease, while the same animals experienced downregulation of the ACE2 receptor. These data suggest that the magnitude and kinetics of a disproportionately strong host innate immune response contributed to severe respiratory stress and lethality. Although the molecular mechanisms governing ARDS pathophysiology remain unknown in aged animals, these studies reveal a strategy for dissecting the genetic pathways by which SARS-CoV infection induces changes in the host response, leading to death.


title: Investigating the Usability and Acute Effects of a Bedside Video Console to Prefrontal Cortical Activity Alterations: A Preclinical Study in Healthy Elderly.

text: Elderly people at risk of developing cognitive decline; e.g., following surgery, may benefit from structured, challenging, and repetitive cognitive video training. This study assessed usability and acute effects of a newly developed bedside console (COPHYCON). Fifteen healthy elderly individuals performed a one-time 80-min intervention, including cognitive video games aimed at improving awareness and selective attention. Perceived usefulness and perceived ease of use (Technology Acceptance Model) were assessed together with measures of the achieved game level, reaction times, (in-) correct responses during ALERT and SELECT game play. Further, prefrontal cortical involvement of the regional cerebral hemoglobin saturation (rS02%) assessed with functional near infrared spectroscopy (fNIRS) (n = 5) and EEG power (n = 10) was analyzed. All participants completed the study without any adverse events. Perceived usefulness and perceived ease of use (TAM scores range 1-7) of the system varied between 3.9 and 6.3. The game levels reached for awareness varied between 9 and 11 (initial score 8-10), for reaction speed between 439 and 469 ms, and for correct responses between 74.1 and 78.8%. The highest level for the selective attention games was 2 (initial score 1), where reaction speed varied between 439 and 469 ms, correct responses between 96.2 and 98.5%, respectively. The decrease of rS02% in the right prefrontal cortex during gameplay was significantly (p < 0.001) lower, compared to the left prefrontal cortex. Four participants yielded significant lower rS02% measures after exergaming with the ALERT games (p < 0.000), but not with the SELECT games. EEG recordings of theta power significantly decreased in the averaged ~0.25-0.75 time interval for the left prefrontal cortex sensor across the cognitive game levels between the ALERT 1 and SELECT 1, as well as between SELECT 1 and 2 games. Participants rated the usability of the COPHYCON training positively. Further results indicate that video gaming may be an effective measure to affect prefrontal cortical functioning in elderly. The results warrant a clinical explorative study investigating the feasibility of the COPHYCON in a clinical setting.


title: A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer.

text: Several natural products have been suggested as effective agents for the treatment of cancer. Given the important role of CSCs (Cancer Stem Cells) in cancer, which is a trendy hypothesis, it is worth investigating the effects of pristimerin on CSCs as well as on the other malignant cells (MCF-7 and MDA-MB-231) of breast cancer. The anti-growth activity of pristimerin against MCF-7 and MCF-7s (cancer stem cell enriched population) cells was investigated by real time viability monitorization (xCELLigence System®) and ATP assay, respectively. Mode of cell death was evaluated using electron and fluorescence microscopies, western blotting (autophagy, apoptosis and ER-stress related markers) and flow cytometry (annexin-V staining, caspase 3/7 activity, BCL-2 and PI3K expressions). Pristimerin showed an anti-growth effect on cancer cells and cancer stem cells with IC50 values ranging at 0.38-1.75μM. It inhibited sphere formation at relatively lower doses (<1.56μM). Apoptosis was induced in MCF-7 and MCF-7s cells. In addition, extensive cytoplasmic vacuolation was observed, implying an incompleted autophagy as evidenced by the increase of autophagy-related proteins (p62 and LC3-II) with an unfolded protein response (UPR). Pristimerin inhibited the growth of MCF-7 and MDA-MB-231-originated xenografts in NOD.CB17-Prkdcscid/J mice. In mice, apoptosis was further confirmed by cleavage of PARP, activation of caspase 3 and/or 7 and TUNEL staining. Taken together, pristimerin shows cytotoxic activity on breast cancer both in vitro and in vivo. It seems to represent a robust promising agent for the treatment of breast cancer. Pristimerin's itself or synthetic novel derivatives should be taken into consideration for novel potent anticancer agent(s).