title: Synthetic cathelicidin LL-37 reduces Mycobacterium avium subsp. paratuberculosis internalization and pro-inflammatory cytokines in macrophages

text: Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic diarrheic intestinal infections in domestic and wild ruminants (paratuberculosis or Johne’s disease) for which there is no effective treatment. Critical in the pathogenesis of MAP infection is the invasion and survival into macrophages, immune cells with ability to carry on phagocytosis of microbes. In a search for effective therapeutics, our objective was to determine whether human cathelicidin LL-37, a small peptide secreted by leuckocytes and epithelial cells, enhances the macrophage ability to clear MAP infection. In murine (J774A.1) macrophages, MAP was quickly internalized, as determined by confocal microscopy using green fluorescence protein expressing MAPs. Macrophages infected with MAP had increased transcriptional gene expression of pro-inflammatory TNF-α, IFN-γ, and IL-1β cytokines and the leukocyte chemoattractant IL-8. Pretreatment of macrophages with synthetic LL-37 reduced MAP load and diminished the transcriptional expression of TNF-α and IFN-γ whereas increased IL-8. Synthetic LL-37 also reduced the gene expression of Toll-like receptor (TLR)-2, key for mycobacterial invasion into macrophages. We concluded that cathelicidin LL-37 enhances MAP clearance into macrophages and suppressed production of tissue-damaging inflammatory cytokines. This cathelicidin peptide could represent a foundational molecule to develop therapeutics for controlling MAP infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00441-019-03098-4) contains supplementary material, which is available to authorized users.


title: Clinical and Environmental Surveillance of Rotavirus Common Genotypes Showed High Prevalence of Common P Genotypes in Egypt

text: The objective of this study was to compare the prevalence of human rotavirus group A common G and P genotypes in human Egyptian stool specimens and raw sewage samples to determine the most common genotypes for future vaccine development. From 1026 stool specimens of children with acute diarrhea and using nested RT-PCR, 250 samples (24.37%) were positive for human rotavirus group A. Using multiplex RT-PCR, rotavirus common P and G genotypes were detected as 89.20% and 46.40% of the positive clinical specimens respectively. This low percentage of common G genotypes frequency may affect the efficiency of the available live attenuated oral rotavirus vaccines [Rotarix® (human rotavirus G1P[8]) and RotaTeq® (reassortant bovine–human rotavirus G1-4P[5] and G6P[8])], however the percentage of clinical specimens which were negative for common G genotypes but positive for P[8] genotype was 12.00%. From 24 positive raw sewage samples for rotavirus group A VP6 collected from Zenin and El-Gabal El-Asfar wastewater treatment plants (WWTPs), 21 samples (87.50%) were typeable for common P genotypes while 13 samples (54.17%) were typeable for common G genotypes. Phylogenetic analysis of a VP8 partial gene of 45 P-typeable clinical isolates and 20 P-typeable raw sewage samples showed high similarity to reference strains and the majority of mutations were silent and showed lower to non-significant similarity with the two vaccine strains. This finding is useful for determining the most common antigens required for future vaccine development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12560-020-09426-0) contains supplementary material, which is available to authorized users.


title: Listening to the neurological teams for multiple sclerosis: the SMART project

text: OBJECTIVE: Aim of the research was to define the quality of life of Italian neurologists and nurses’ professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. MATERIAL AND METHODS: One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. RESULTS: Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. CONCLUSION: The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10072-020-04301-z) contains supplementary material, which is available to authorized users.


title: Enlightened Self-interest in Altruism (ESIA)

text: Altruism and the medical profession have been linked throughout the history of medicine. Students are drawn to the calling of medicine because of altruistic values, dedication to service, and the desire to alleviate suffering and promote healing. Despite a dedication to these values, altruism in medicine is threatened by empathy erosion that develops in the clinical years of medical school and an increasing rate of medical student burnout. Currently, there are two widespread movements in medicine aimed at addressing the dual loss of altruism and physician and student burnout—professionalism and wellness. Despite widespread recognition of the problems and programs aimed at improving them, there has been little headway, and even calls to abandon altruism in the modern marketplace of medicine. What is needed is not an abandonment of a fundamental, defining value of the profession, but a re-evaluation of the meaning of altruism in medicine and a framework that allows for students and physicians to provide altruistic care for a sustainable, rewarding career in the healing profession. This paper proposes the Enlightened Self-Interest in Altruism (ESIA) model as an ethical framework to allow medical students to synergize the interests of the self with those they serve in a mutually beneficial relationship to improve patient care and the healthcare system at large. The ESIA model acknowledges that egoism and altruism are intertwined, dynamic motivators of behavior. In the enlightened self-interest approach, the interests of the group are also the interests of the self. The physician–patient relationship is a dyad in which egoism and altruism may converge in an enlightened way that acknowledges that the interests of one are the interests of the whole. This is a paradigm shift from the historical view of egoism and altruism as opposing motivations. This paper will present the threats to altruism, explore the interface of egoism and altruism in a clinical vignette, and then present the ESIA framework as an educational approach to aligning the interests of providers and patients to prevent burnout and promote altruism.


title: Do Vaccines Trigger Neurological Diseases? Epidemiological Evaluation of Vaccination and Neurological Diseases Using Examples of Multiple Sclerosis, Guillain–Barré Syndrome and Narcolepsy

text: This article evaluates the epidemiological evidence for a relationship between vaccination and neurological disease, specifically multiple sclerosis, Guillain–Barré syndrome and narcolepsy. The statistical methods used to test vaccine safety hypotheses are described and the merits of different study designs evaluated; these include the cohort, case-control, case-coverage and the self-controlled case-series methods. For multiple sclerosis, the evidence does not support the hypothesized relationship with hepatitis B vaccine. For Guillain−Barré syndrome, the evidence suggests a small elevated risk after influenza vaccines, though considerably lower than after natural influenza infection, with no elevated risk after human papilloma virus vaccine. For narcolepsy, there is strong evidence of a causal association with one adjuvanted vaccine used in the 2009/10 influenza pandemic. Rapid investigation of vaccine safety concerns, however biologically implausible, is essential to maintain public and professional confidence in vaccination programmes.


Understanding resistance in Pseudomonas


Antibiotic prophylaxis in the ICU: to be or not to be administered for patients undergoing procedures?


title: Peripheral perfusion index as a predictor of failed weaning from mechanical ventilation

text: We hypothesized that impairment of peripheral perfusion index (PPI) during spontaneous breathing trial (SBT) might be predictive of weaning failure. We included 44 consecutive, adult, patients, who were scheduled for weaning after at least 48 h of invasive mechanical ventilation in this prospective observational study. Weaning failure was defined as failed SBT or reintubation within 48 h of extubation. PPI readings were obtained before initiation of the SBT, and every 5 min till the end of the SBT. PPI ratio was calculated at every time point as: PPI value/ baseline PPI. The primary outcome was the accuracy of PPI ratio at the end of the SBT in detecting failed weaning. Forty-three patients were available for the final analysis. Eighteen patients (42%) were considered failed weaning. PPI ratio was higher in patients with successful weaning compared to patients with failed weaning during the last 15 min of the SBT. PPI ratio at the end of SBT was higher in patients with successful weaning compared to patients with failed weaning. PPI ratio at the end of SBT had good predictive ability for weaning failure {area under receiver operating characteristic curve (95% confidence interval): 0.833(0.688–0.929), cutoff value ≤ 1.41}. The change in PPI during SBT is an independent predictor for re-intubation. PPI could be a useful tool for monitoring the patient response to SBT. Patients with successful weaning showed higher augmentation of PPI during the SBT compared to re-intubated patients. Failure of augmenting the PPI by 41% at the end of SBT could predict re-intubation with negative predictive value of 95%. Clinical trial identifier: NCT03974568. https://clinicaltrials.gov/ct2/show/NCT03974568?term=ahmed+hasanin&draw=3&rank=17


title: Hypercapnia Exacerbates the Blood–Brain Barrier Disruption Via Promoting HIF-1a Nuclear Translocation in the Astrocytes of the Hippocampus: Implication in Further Cognitive Impairment in Hypoxemic Adult Rats

text: Hypercapnia in combination with hypoxemia is usually present in severe respiratory disease in the intensive care unit (ICU) and can lead to more severe cognitive dysfunction. Increasing evidence has indicated that the compromised blood–brain barrier (BBB) in the hippocampus in hypoxemia conditions can result in cognitive dysfunction. However, the role and underlying mechanism of hypercapnia in the BBB disruption remains poorly known. A rat model of hypercapnia was first established in this study by intubation and mechanical ventilation with a small-animal ventilator. After this, the cognitive function of the experimental rats was assessed by the Morris water maze test. The BBB permeability was evaluated by the Evans Blue (EB) test and brain water content (BWC). Western blot analysis was carried out to detect the protein expressions of total and nuclear hypoxia-inducible factor-1α (HIF-1α), matrixmetalloproteinase-9 (MMP-9) and Aquaporins-4 (AQP-4) in the hippocampus tissue. Double immunofluorescence further verified the protein expression of different biomarkers was localized in the astrocytes of the hippocampus. Hypercapnia alone did not disrupt the BBB, but it could further enhance the BBB permeability in hypoxemia. Concomitantly, up-regulation of nuclear HIF-1α, AQP-4, MMP-9 protein expression along with increased degradation of the occludin and claudin-5 proteins was found in the hypercapnia rat model, while the total HIF-1α remained unchanged. Interestingly, these changes were independent of the acidosis induced by hypercapnia. Of note, after premedication of 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1α nuclear translocation), the disrupted BBB could be restored resulting in improvement of the cognitive impairment. Meanwhile, accumulation of nuclear HIF-1α, protein expression of AQP-4 and MMP-9 and protein degradation of the occludin and claudin-5 were decreased. Thus, our study demonstrated that hypercapnia can further disrupt the BBB through promoting HIF-1α nuclear translocation and up-regulation of AQP-4 and MMP-9 in hypoxemia. It is therefore suggested that the cascade of hypercapnia-induced nuclear HIF-1α protein translocation in hypoxia-activated astrocytes may be a potential target for ameliorating cognitive impairment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11064-020-03038-7) contains supplementary material, which is available to authorized users.


title: Towards common ground in the biodiversity–disease debate

text: The disease ecology community has struggled to come to consensus on whether biodiversity reduces or increases infectious disease risk, a question that directly affects policy decisions for biodiversity conservation and public health. Here, we summarize the primary points of contention regarding biodiversity–disease relationships and suggest that vector-borne, generalist wildlife and zoonotic pathogens are the types of parasites most likely to be affected by changes to biodiversity. One synthesis on this topic revealed a positive correlation between biodiversity and human disease burden across countries, but as biodiversity changed over time within these countries, this correlation became weaker and more variable. Another synthesis—a meta-analysis of generally smaller-scale experimental and field studies—revealed a negative correlation between biodiversity and infectious diseases (a dilution effect) in various host taxa. These results raise the question of whether biodiversity–disease relationships are more negative at smaller spatial scales. If so, biodiversity conservation at the appropriate scales might prevent wildlife and zoonotic diseases from increasing in prevalence or becoming problematic (general proactive approaches). Further, protecting natural areas from human incursion should reduce zoonotic disease spillover. By contrast, for some infectious diseases, managing particular species or habitats and targeted biomedical approaches (targeted reactive approaches) might outperform biodiversity conservation as a tool for disease control. Importantly, biodiversity conservation and management need to be considered alongside other disease management options. These suggested guiding principles should provide common ground that can enhance scientific and policy clarity for those interested in simultaneously improving wildlife and human health.


title: Acute respiratory distress syndrome-attributable mortality in critically ill patients with sepsis

text: PURPOSE: Previous studies assessing impact of acute respiratory distress syndrome (ARDS) on mortality have shown conflicting results. We sought to assess the independent association of ARDS with in-hospital mortality among intensive care unit (ICU) patients with sepsis. METHODS: We studied two prospective sepsis cohorts drawn from the Early Assessment of Renal and Lung Injury (EARLI; n = 474) and Validating Acute Lung Injury markers for Diagnosis (VALID; n = 337) cohorts. ARDS was defined by Berlin criteria. We used logistic regression to compare in-hospital mortality in patients with and without ARDS, controlling for baseline severity of illness. We also estimated attributable mortality, adjusted for illness severity by stratification. RESULTS: ARDS occurred in 195 EARLI patients (41%) and 99 VALID patients (29%). ARDS was independently associated with risk of hospital death in multivariate analysis, even after controlling for severity of illness, as measured by APACHE II (odds ratio [OR] 1.65 (95% confidence interval [CI] 1.02, 2.67), p = 0.04 in EARLI; OR 2.12 (CI 1.16, 3.92), p = 0.02 in VALID). Patients with severe ARDS (P/F < 100) primarily drove this relationship. The attributable mortality of ARDS was 27% (CI 14%, 37%) in EARLI and 37% (CI 10%, 51%) in VALID. ARDS was independently associated with ICU mortality, hospital length of stay (LOS), ICU LOS, and ventilator-free days. CONCLUSIONS: Development of ARDS among ICU patients with sepsis confers increased risk of ICU and in-hospital mortality in addition to other important outcomes. Clinical trials targeting patients with severe ARDS will be best poised to detect measurable differences in these outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06010-9) contains supplementary material, which is available to authorized users.


title: Ventilator-associated pneumonia and bloodstream infections in intensive care unit cancer patients: a retrospective 12-year study on 3388 prospectively monitored patients

text: PURPOSE: Some publications suggest high rates of healthcare-associated infections (HAIs) and of nosocomial pneumonia portending a poor prognosis in ICU cancer patients. A better understanding of the epidemiology of HAIs in these patients is needed. METHODS: A retrospective analysis of all the patients hospitalized for ≥ 48 h during a 12-year period in the 12-bed ICU of the Gustave Roussy hospital, monitored prospectively for ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) and for use of medical devices. RESULTS: During 3388 first stays in the ICU, 198 cases of VAP and 103 primary, 213 secondary, and 77 catheter-related BSIs were recorded. The VAP rate was 24.5/1000 ventilator days (95% confidence interval [CI] 21.2–28.0); the catheter-related BSI rate was 2.3/1000 catheter days (95% CI 1.8–2.8). The cumulative incidence during the first 25 days of exposure was 58.8% (95% CI 49.1–66.6%) for VAP, 8.9% (95% CI, 6.2–11.5%) for primary, 15.1% (95% CI 11.6–18.5%) for secondary and 5.0% (95% CI 3.2–6.8%) for catheter-related BSIs. VAP or BSIs were not associated with a higher risk of ICU mortality. CONCLUSIONS: This is the first study to report HAI rates in a large cohort of critically ill cancer patients. Although both the incidence of VAP and the rate of BSI are higher than in general ICU populations, this does not impact patient outcomes. The occurrence of device-associated infections is essentially due to severe medical conditions in patients and to the characteristics of malignancy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00520-019-04800-6) contains supplementary material, which is available to authorized users.


title: Childhood obesity, cardiovascular and liver health: a growing epidemic with age

text: BACKGROUND: The frequency of childhood obesity has increased over the last 3 decades, and the trend constitutes a worrisome epidemic worldwide. With the raising obesity risk, key aspects to consider are accurate body mass index classification, as well as metabolic and cardiovascular, and hepatic consequences. DATA SOURCES: The authors performed a systematic literature search in PubMed and EMBASE, using selected key words (obesity, childhood, cardiovascular, liver health). In particular, they focused their search on papers evaluating the impact of obesity on cardiovascular and liver health. RESULTS: We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood, as a predisposing factor to cardiovascular and hepatic alterations. We also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic consequences. CONCLUSIONS: The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and adolescence. Two key abnormalities in this context include cardiovascular diseases, and nonalcoholic fatty liver disease. Appropriate metabolic screenings and associated comorbidities should start as early as possible in obese children and adolescents. Nevertheless, improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity, cardiovascular diseases, and diabetes risk during adulthood.


title: Anti-Sarcocystis Antibodies in Lambs Deprived of Colostrum

text: INTRODUCTION: The objective of this study was to evaluate the presence of anti-Sarcocystis spp. specific IgG antibodies in serum samples from precolostral lambs to determine the occurrence of transplacental transmission of Sarcocystis spp. in sheep. METHODS: Blood samples were collected from 80 ewes and their respective lambs, immediately after lambing and before colostrum ingestion, respectively. The presence of anti-Sarcocystis spp. IgG was evaluated in serum samples using the indirect fluorescent antibody test (IFAT). Positive samples of the lambs were submitted to titration and IFAT to detect anti-T. gondii and anti-N. caninum specific IgG. RESULTS: Anti-Sarcocystis spp. IgG was detected in 62.5% of the ewes (50/80) and in 4% of the lambs of the seropositive ewes (2/50). None of the lambs from seronegative ewes were positive. The final titers of the positive lambs were 80. No cross reaction was detected among the positive samples to anti-Sarcocystis spp., anti-N. caninum, and anti-T. gondii IgG. The detection of anti-Sarcocystis spp. antibodies in serum samples of lambs deprived of colostrum suggests transplacental transmission of infection. Thus, the vertical transmission may be an alternative route of infection of Sarcocystis spp. also in sheep. Further studies are warranted to confirm transplacental transmission in sheep and to explain the importance of this infection pathway.


title: Cerebral venous volume changes and pressure autoregulation in critically ill infants

text: OBJECTIVE: To determine whether ventilator-related fluctuations in cerebral blood volume (CBV) are associated with cerebral pressure passivity. STUDY DESIGN: In a prospective study of newborns undergoing positive-pressure ventilation, we calculated coherence between continuous mean arterial pressure (MAP) and cerebral near-infrared spectroscopy hemoglobin difference (HbD). Significant HbD–MAP coherence indicated cerebral pressure passivity. CBV changes were measured as the spectral power of total hemoglobin (S(HbT)) at the ventilator frequency. A regression model tested whether S(HbT) predicts cerebral pressure passivity and/or death/brain injury, controlling for birth gestational age and other factors. RESULTS: We studied 68 subjects with prematurity (n = 19), congenital heart disease (n = 11), and hypoxic–ischemic encephalopathy (n = 38). S(HbT), sedative use, and pCO(2) were positively associated, and circulating hemoglobin negatively associated, with cerebral pressure passivity (p < 0.001), which was positively associated with brain injury (p < 0.001). CONCLUSION: In sick newborns, ventilator-related CBV fluctuations may predispose to cerebral pressure passivity, which may predispose to an adverse neonatal outcome.


title: Productive Aging in the Social Work Profession: A Comparison of Licensed Workers 60 Years and Older with Their Younger Counterparts

text: This article reports the findings of an online survey in 13 U.S. states that compared the self-described demographics, wellness factors (mental health, physical health, and substance misuse), practice factors (fields of practice and work environment issues), and feelings about being a social worker (compassion satisfaction, workplace stress, being glad one chose social work and feeling valued as a professional in society) of 870 employed licensed social workers age 60 and older to 4076 licensed social workers under age 60. The results indicate that the older social workers were more likely to be male and white, less likely to report mental health problems, and more likely to work exclusively in private practice. Although older workers reported more serious physical health problems, they rated their physical health more favorably than their younger counterparts. In both bivariate and multivariate analyses, the older social workers scored significantly higher in compassion satisfaction, being glad they chose social work as a career, and feeling valued as a professional in society. The older social workers scored lower in workplace stress at levels that were statistically significant in a bivariate analysis, but not in a multivariate analysis.


title: Locating stridor caused by tumor compression by using a multichannel electronic stethoscope: a case report

text: A 67-year-old male patient with chronic obstructive pulmonary disease was admitted to a hospital in northern Taiwan for progressive dyspnea and productive cough with an enlarged left upper lobe tumor (5.3 × 6.8 × 3.9 cm(3)). Previous chest auscultation on outpatient visits had yielded diffuse wheezes. A localized stridor (fundamental frequency of 125 Hz) was captured using a multichannel electronic stethoscope comprising four microelectromechanical system microphones. An energy-based localization algorithm was used to successfully locate the sound source of the stridor caused by tumor compression. The results of the algorithm were compatible with the findings obtained from computed tomography and bronchoscopy (mean radius = 9.40 mm and radial standard deviation = 14.97 mm). We demonstrated a potential diagnostic aid for pulmonary diseases through sound-source localization technology based on respiratory monitoring. The proposed technique can facilitate detection when advanced imaging tools are not immediately available. Continuing effort on the development of more precise estimation is warranted.


title: Methods for Feature Selection in Down-Selection of Vaccine Regimens Based on Multivariate Immune Response Endpoints

text: In clinical trials, it is often of interest to compare and order several candidate regimens based on multiple endpoints. For example, in HIV vaccine development, immune response profiles induced by vaccination are key for selecting vaccine regimens to advance to efficacy evaluation. Motivated by the need to rank and choose a few vaccine regimens based on their immunogenicity in phase I trials, Huang et al. (Biostatistics 18(2):230–243, 2017) proposed a ranking/filtering/selection algorithm that down-selects vaccine regimens to satisfy the superiority and non-redundancy criteria, based on multiple immune response endpoints. In practice, many candidate immune response endpoints can be correlated with each other. An important question that remains to be addressed is how to choose a parsimonious set of the available immune response endpoints to effectively compare regimens. In this paper, we propose novel algorithms for selecting immune response endpoints to be used in regimen down-selection, based on importance weights assigned to individual endpoints and their correlation structure. We show through extensive simulation studies that pre-selection of endpoints can substantially improve performance of the subsequent regimen down-selection process. The application of the proposed method is demonstrated using a real example in HIV vaccine research, although the methods are also applicable in general to clinical research for dimension reduction when comparing regimens based on multiple candidate endpoints. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12561-020-09275-2) contains supplementary material, which is available to authorized users.


title: Elimination of Staphylococcus aureus nasal carriage in intensive care patients lowers infection rates

text: This study surveys the clinical relevance of the nasal Staphylococcus aureus colonization status on intensive care unit (ICU)–acquired S. aureus infections and compares molecular characteristics of isolates from the nose and infectious sites. The 390 patients included comprised 278 non-carriers and 112 carriers. Among the carriers, 56 were decolonized with mupirocin. Decolonization was verified through a second (negative) culture. Spa typing and virulence gene profiling were performed for all isolates. Twenty six S. aureus infections were detected in the carriage group and 20 in the non-carriage group. Eighteen of these 26 (69.2%) infections were among carriers, and 8 of these 26 (30.8%) infections occurred among decolonized carriers (p = 0.02). Overall, 31/112 (27.7%) of the colonized patients and 25/46 (60.1%) of infection were due to methicillin-resistant S. aureus (MRSA). The highest frequency virulence genes were sea and hlg (both 100%) in nasal isolates and sea, hlg, fnb, and clf (100%) for infectious isolates. t030 was the most abundant spa type overall. S. aureus carriers were more likely to develop S. aureus infection compared with decolonized and non-carrying patients. The sources of ICU S. aureus infection appear to be exogenous mostly, and a predominant clone (spa type 030) plays an important role. We confirm that nasal mupirocin treatment prevents ICU infections even when there is an increased prevalence of nosocomial MRSA.


The artificial kidney induces acute kidney injury: yes


title: New Developments in Bacterial, Viral, and Fungal Cutaneous Infections

text: PURPOSE OF REVIEW: This review highlights clinically relevant updates to common and significant bacterial, viral, and fungal cutaneous infection within the past 5 years. Recent developments are presented so that the clinician may provide evidence-based, high-quality patient care. RECENT FINDINGS: New resistance patterns in cutaneous pathogens have recently emerged as a result of inappropriate antimicrobial use. Several new FDA-approved antimicrobials have been approved to treat such infections, including multi-drug resistant pathogens. Several organizational guidelines for cutaneous infection management have been updated with new recommendations for screening, diagnostic, and treatment strategies. SUMMARY: Clinicians should be aware of the most recent evidence and guidelines for the management of cutaneous infections in order to reduce the emergence of antimicrobial resistance and most effectively treat their patients.


title: ‘I’m sorry to hear that’—Empathy and Empathic Dissonance: the Perspectives of PA Students

text: CONTEXT: Our understanding of clinical empathy could be enhanced through qualitative research—research currently under-represented in the field. Physician associates within the UK undergo an intensive 2-year postgraduate medical education. As a new group of health professionals, they represent a fresh pair of eyes through which to examine clinical empathy, its nature and teaching. METHODS: Working with a constructivist paradigm, utilising grounded theory methodology, researchers studied 19 purposively sampled physician associate students in two UK medical schools. One-to-one semi-structured interviews were transcribed verbatim. Data were analysed using a grounded theory approach. RESULTS: The global themes were the pathways to empathy, empathy modifiers and empathic dissonance a novel term to describe the discomfort students experience when pressurised into making empathic statements they don’t sincerely feel. Students preferred using non-verbal over verbal expressions of empathy. A conceptual model is proposed. The more substantial empathic pathway, affective empathy, involves input from the heart. An alternative empathy, more constrained, comes from the head: cognitive empathy was considered a solution to time pressure and emotional burden. Formal teaching establishes empathic dissonance, a problem which stems from over-reliance on the empathic statement as the means to deliver clinical empathy. CONCLUSIONS: This study furthers our understanding of the construct and teaching of empathy. It identifies empathic barriers, especially time pressure. It proposes a novel concept—empathic dissonance—a concept that challenges medical educationalists to reframe future empathy teaching.


title: Melittin: a venom-derived peptide with promising anti-viral properties

text: Despite tremendous advances in the development of anti-viral therapeutics, viral infections remain a chief culprit accounting for ongoing morbidity and mortality worldwide. Natural products, in particular animal venoms, embody a veritable cornucopia of exotic constituents, suggesting an immensurable source of anti-infective drugs. In this context, melittin, the principal constituent in the venom of the European honeybee Apis mellifera, has been demonstrated to exert anti-cancer, anti-inflammatory, anti-diabetic, anti-infective, and adjuvant properties. To our knowledge, there is no review appertaining to effects of melittin against viruses, prompting us to synopsize experimental investigations on its anti-viral activity throughout the past decades. Accumulating evidence indicates that melittin curbs infectivity of a diverse array of viruses including coxsackievirus, enterovirus, influenza A viruses, human immunodeficiency virus (HIV), herpes simplex virus (HSV), Junín virus (JV), respiratory syncytial virus (RSV), vesicular stomatitis virus (VSV), and tobacco mosaic virus (TMV). However, medication safety, different routes of administrations, and molecular mechanisms behind the anti-viral activity of melittin should be scrutinized in future studies.


title: Effect of the “Recruitment” Maneuver on Respiratory Mechanics in Laparoscopic Sleeve Gastrectomy Surgery

text: PURPOSE: LSG surgery is used for surgical treatment of morbid obesity. Obesity, anesthesia, and pneumoperitoneum cause reduced pulmoner functions and a tendency for atelectasis. The alveolar “recruitment” maneuver (RM) keeps airway pressure high, opening alveoli, and increasing arterial oxygenation. The aim of our study is to research the effect on respiratory mechanics and arterial blood gases of performing the RM in LSG surgery. MATERIALS AND METHODS: Sixty patients undergoing LSG surgery were divided into two groups (n = 30) Patients in group R had the RM performed 5 min after desufflation with 100% oxygen, 40 cmH(2)O pressure for 40 s. Group C had standard mechanical ventilation. Assessments of respiratory mechanics and arterial blood gases were made in the 10th min after induction (T1), 10th min after insufflation (T2), 5th min after desufflation (T3), and 15th min after desufflation (T4). Arterial blood gases were assessed in the 30th min (T5) in the postoperative recovery unit. RESULTS: In group R, values at T5, PaO(2) were significantly high, while PaCO(2) were significantly low compared with group C. Compliance in both groups reduced with pneumoperitoneum. At T4, the compliance in the recruitment group was higher. In both groups, there was an increase in PIP with pneumoperitoneum and after desufflation this was identified to reduce to levels before pneumoperitoneum. CONCLUSION: Adding the RM to PEEP administration for morbidly obese patients undergoing LSG surgery is considered to be effective in improving respiratory mechanics and arterial blood gas values and can be used safely.


title: Measuring lung mechanics of expiratory tidal breathing with non-invasive breath occlusion

text: BACKGROUND AND OBJECTIVE: Lung mechanics measurements provide clinically useful information about disease progression and lung health. Currently, there are no commonly practiced methods to non-invasively measure both resistive and elastic lung mechanics during tidal breathing, preventing the important information provided by lung mechanics from being utilised. This study presents a novel method to easily assess lung mechanics of spontaneously breathing subjects using a dynamic elastance, single-compartment lung model. METHODS: A spirometer with a built-in shutter was used to occlude expiration during tidal breathing, creating exponentially decaying flow when the shutter re-opened. The lung mechanics measured were respiratory system elastance and resistance, separated from the exponentially decaying flow, and interrupter resistance calculated at shutter closure. Progressively increasing resistance was added to the spirometer mouthpiece to simulate upper airway obstruction. The lung mechanics of 17 healthy subjects were successfully measured through spirometry. RESULTS: N = 17 (8 female, 9 male) healthy subjects were recruited. Measured decay rates ranged from 5 to 42/s, subjects with large variation of decay rates showed higher muscular breathing effort. Lung elastance measurements ranged from 3.9 to 21.2 cmH[Formula: see text] O/L, with no clear trend between change in elastance and added resistance. Resistance calculated from decay rate and elastance ranged from 0.15 to 1.95 cmH[Formula: see text] Os/L. These very small resistance values are due to the airflow measured originating from low-resistance areas in the centre of airways. Occlusion resistance measurements were as expected for healthy subjects, and increased as expected as resistance was added. CONCLUSIONS: This test was able to identify reasonable dynamic lung elastance and occlusion resistance values, providing new insight into expiratory breathing effort. Clinically, this lung function test could impact current practice. It does not require high levels of cooperation from the subject, allowing a wider cohort of patients to be assessed more easily. Additionally, this test can be simply implemented in a small standalone device, or with standard lung function testing equipment.


title: A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease

text: In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared with IM alone in CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two patients were randomly assigned to either arm. Treatment ‘successes’ was the primary end point, defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end points were 24-month treatment ‘successes’, molecular response and progression at 12 and 24 months, comparison of IM levels, and achievement of blood HCQ levels >2000 ng/ml. At 12 months, there was no difference in ‘success’ rate (p = 0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p = 0.21). At 24 months, the ‘success’ rate was 20.8% higher with IM/HCQ (p = 0.059). No patients progressed. Seventeen serious adverse events, including four serious adverse reactions, were reported; diarrhoea occurred more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.


title: Protective cellular immune response against hepatitis C virus elicited by chimeric protein formulations in BALB/c mice

text: The eradication of hepatitis C virus (HCV) infection is a public health priority. Despite the efficiency of treatment with direct-acting antivirals, the high cost of the therapy and the lack of accurate data about the HCV-infected population worldwide constitute important factors hampering this task. Hence, an affordable preventive vaccine is still necessary for reducing transmission and the future disease burden globally. In this work, chimeric proteins (EnvCNS3 and NS3EnvCo) encompassing conserved and immunogenic epitopes from the HCV core, E1, E2 and NS3 proteins were produced in Escherichia coli, and their immunogenicity was evaluated in BALB/c mice. The impact of recombinant HCV E2.680 protein and oligodeoxynucleotide 39M (ODN39M) on the immune response to chimeric proteins was also assessed. Immunization with chimeric proteins mixed with E2.680 enhanced the antibody and cellular response against HCV antigens and chimeric proteins. Interestingly, the combination of NS3EnvCo with E2.680 and ODN39M as adjuvant elicited a potent antibody response characterized by an increase in antibodies of the IgG2a subclass against E2.680, NS3 and chimeric proteins, suggesting the induction of a Th1-type response. Moreover, a cytotoxic T lymphocyte response and a broad response of IFN-γ-secreting cells against HCV antigens were induced with this formulation as well. This T cell response was able to protect vaccinated mice against challenge with a surrogate model based on HCV recombinant vaccinia virus. Overall, the vaccine candidate NS3EnvCo/E2.680/ODN39M might constitute an effective immunogen against HCV with potential for reducing the likelihood of viral persistence.


title: Medical Ethics in Extreme and Austere Environments

text: American society has a history of turning to physicians during times of extreme need, from plagues in the past to recent outbreaks of communicable diseases. This public instinct comes from a deep seated trust in physician duty that has been earned over the centuries through dedicated and selfless care, often in the face of personal risks. As dangers facing our communities include terroristic events physicians must be adequately prepared to respond, both medically and ethically. While the ethical principles that govern physician behavior—beneficence, nonmaleficence, autonomy, and social justice—are unchanging, fundamental doctrines must change with the new risks inherent to terroristic events. Responding to mass casualty disasters caused by terrorists, natural calamities, and combat continue to be challenging frontiers in medicine. Preparing physicians to deal with the consequences of a terroristic disease must include understanding the ethical challenges that can occur.


title: Megaprosthesis in distal femur nonunions in elderly patients—experience from twenty four cases

text: PURPOSE OF THE STUDY: To evaluate the outcomes and complications using cemented megaprosthesis in elderly patients with distal femur nonunions (DFN). MATERIALS AND METHODS: Between 2012 and 2016, 24 patients of DFN with an average age of 71.8 years (66–83) and an average 1.9(1–3) prior surgery was managed with distal femur replacement using cemented modular endoprosthesis. Outcomes were analysed on the following criteria: implant status, complications, knee range of motion, Knee Society Score (KSS) and Musculoskeletal Tumor Society (MSTS) score. RESULTS: All patients were extremely satisfied with their outcomes. At an average 22.1 months (10–43) follow-up, patients had an average 69.5° (40°-110°) knee flexion, an average KSS of 75.7 (63–88) and an average MSTS score of 19.3 (17–25). Four patients died at an average 21.3 months after surgery due to causes unrelated to the fracture. One patient (4.1%) had implant-related complication; deep infection which required debridement and intravenous antibiotics. There were no late amputations or peri-operative deaths and no patient had aseptic loosening of components. CONCLUSION: By permitting immediate full weight-bearing ambulation and with most patients returning to an acceptable functional status, cemented megaprosthesis is a viable and useful single-stage management option in elderly patients with DFN.


title: The Spectrophotometric Characteristic of Immunoglobulin Conjugates for Diagnostics of Causative Agents of Especially Dangerous Infections

text: The possibility of characterizing fluorescent immunoglobulins using spectrophotometric analysis as a testing method is considered. The comparative analysis of optical properties of fluorescent immunoglobulin preparations and their components—immunoglobulins and fluorochrome—is carried out. The obtained results testify that the proposed methodological approach of optical detection of labeled immunoglobulin molecules can be promising for tests on obtaining conjugates used in immunological tests on revealing specific antigens of causative agents of especially dangerous infections.


title: Practical approach to respiratory emergencies in neurological diseases

text: Many neurological diseases may cause acute respiratory failure (ARF) due to involvement of bulbar respiratory center, spinal cord, motoneurons, peripheral nerves, neuromuscular junction, or skeletal muscles. In this context, respiratory emergencies are often a challenge at home, in a neurology ward, or even in an intensive care unit, influencing morbidity and mortality. More commonly, patients develop primarily ventilatory impairment causing hypercapnia. Moreover, inadequate bulbar and expiratory muscle function may cause retained secretions, frequently complicated by pneumonia, atelectasis, and, ultimately, hypoxemic ARF. On the basis of the clinical onset, two main categories of ARF can be identified: (i) acute exacerbation of chronic respiratory failure, which is common in slowly progressive neurological diseases, such as movement disorders and most neuromuscular diseases, and (ii) sudden-onset respiratory failure which may develop in rapidly progressive neurological disorders including stroke, convulsive status epilepticus, traumatic brain injury, spinal cord injury, phrenic neuropathy, myasthenia gravis, and Guillain–Barré syndrome. A tailored assistance may include manual and mechanical cough assistance, noninvasive ventilation, endotracheal intubation, invasive mechanical ventilation, or tracheotomy. This review provides practical recommendations for prevention, recognition, management, and treatment of respiratory emergencies in neurological diseases, mostly in teenagers and adults, according to type and severity of baseline disease.


Cyclosporine A prevents cardiac arrest-induced acute respiratory failure: a post-hoc analysis of the CYRUS trial


title: Contemporary strategies to improve clinical trial design for critical care research: insights from the First Critical Care Clinical Trialists Workshop

text: BACKGROUND: Conducting research in critically-ill patient populations is challenging, and most randomized trials of critically-ill patients have not achieved pre-specified statistical thresholds to conclude that the intervention being investigated was beneficial. METHODS: In 2019, a diverse group of patient representatives, regulators from the USA and European Union, federal grant managers, industry representatives, clinical trialists, epidemiologists, and clinicians convened the First Critical Care Clinical Trialists (3CT) Workshop to discuss challenges and opportunities in conducting and assessing critical care trials. Herein, we present the advantages and disadvantages of available methodologies for clinical trial design, conduct, and analysis, and a series of recommendations to potentially improve future trials in critical care. CONCLUSION: The 3CT Workshop participants identified opportunities to improve critical care trials using strategies to optimize sample size calculations, account for patient and disease heterogeneity, increase the efficiency of trial conduct, maximize the use of trial data, and to refine and standardize the collection of patient-centered and patient-informed outcome measures beyond mortality. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-05934-6) contains supplementary material, which is available to authorized users.


title: Burn injury

text: Burn injuries are under-appreciated injuries that are associated with substantial morbidity and mortality. Burn injuries, particularly severe burns, are accompanied by an immune and inflammatory response, metabolic changes and distributive shock that can be challenging to manage and can lead to multiple organ failure. Of great importance is that the injury affects not only the physical health, but also the mental health and quality of life of the patient. Accordingly, patients with burn injury cannot be considered recovered when the wounds have healed; instead, burn injury leads to long-term profound alterations that must be addressed to optimize quality of life. Burn care providers are, therefore, faced with a plethora of challenges including acute and critical care management, long-term care and rehabilitation. The aim of this Primer is not only to give an overview and update about burn care, but also to raise awareness of the ongoing challenges and stigmata associated with burn injuries.


title: Comparison of Conventional Intensive Care Scoring Systems and Prognostic Scores Specific for Intracerebral Hemorrhage in Predicting One-Year Mortality

text: BACKGROUND: Specific prognostic models for intracerebral hemorrhage (ICH) have short and simple features, whereas intensive care unit (ICU) severity scales include more complicated parameters. Even though newly developed ICU severity scales have disease-specific properties, they still lack radiologic parameters, which is crucial for ICH. AIMS: To compare the performance of the Simplified Acute Physiology Score (SAPS) III, Acute Physiology and Chronic Health Evaluation (APACHE) IV, Logistic Organ Dysfunction Score (LODS), ICH, max-ICH, ICH functional outcome score (ICH-FOS), and Essen-ICH for prediction of in-hospital and one-year mortality of patients with ICH. METHODS: A single-center analysis of 137 patients with ICH was conducted over 5 years. The performance of scoring systems was evaluated with receiver operating characteristic analysis. The independent predictors of one-year mortality were investigated with a multivariate logistic regression analysis. The SAPS-III score was calculated both in the emergency department (ED) and ICU. RESULTS: Among the independent variables, the need for mechanical ventilation, hematoma volume, the presence of intraventricular hemorrhage, and hematoma originating from both lobar and nonlobar regions were found as the strongest predictor of one-year mortality. For in-hospital mortality, the discriminative power of SAPS-II, APACHE-IV, and LODS was excellent, and for SAPS-III-ICU and SAPS-III-ED, it was good. For one-year mortality, the discriminative power of SAPS-II, APACHE-IV, LODS, and SAPS-III-ICU was good, and for SAPS-III-ED, Essen-ICH, ICH, max-ICH, and ICH-FOS, it was fair. CONCLUSIONS: Although all three ICH-specific prognostic scales performed satisfactory results for predicting one-year mortality, the common intensive care severity scoring showed better performance. SAPS-III scores may be recommended for use in EDs after proper customization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-020-00987-3) contains supplementary material, which is available to authorized users.


title: Male gender is an independent risk factor for patients undergoing laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass: an MBSAQIP® database analysis

text: BACKGROUND: Male patients undergoing bariatric surgery have (historically) been considered higher risk than females. The aim of this study was to examine the disparity between genders undergoing laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) procedures and assess gender as an independent risk factor. METHODS: The MBSAQIP® Data Registry Participant User Files for 2015–2017 was reviewed for patients having primary SG and RYGB. Patients were divided into groups based on gender and procedure. Variables for major complications were grouped together, including but not limited to PE, stroke, and MI. Univariate and propensity matching analyses were performed. RESULTS: Of 429,664 cases, 20.58% were male. Univariate analysis demonstrated males were older (46.48 ± 11.96 vs. 43.71 ± 11.89 years, p < 0.0001), had higher BMI (46.58 ± 8.46 vs. 45.05 ± 7.75 kg/m(2), p < 0.0001), and had higher incidence of comorbidities. Males had higher rates of major complications (1.72 vs. 1.05%; p < 0.0001) and 30-day mortality (0.18 vs. 0.07%, p < 0.0001). Significance was maintained after subgroup analysis of SG and RYGB. Propensity matched analysis demonstrated male gender was an independent risk factor for RYGB and SG, major complications [2.21 vs. 1.7%, p < 0.0001 (RYGB), 1.12 vs. 0.89%, p < 0.0001 (SG)], and mortality [0.23 vs. 0.12%, p < 0.0001 (RYGB), 0.10 vs. 0.05%; p < 0.0001 (SG)]. CONCLUSION: Males continue to represent a disproportionately small percentage of bariatric surgery patients despite having no difference in obesity rates compared to females. Male gender is an independent risk factor for major post-operative complications and 30-day mortality, even after controlling for comorbidities.


title: Design, synthesis and evaluation of 3-hydroxypyridin-4-ones as inhibitors of catechol-O-methyltransferase

text: ABSTRACT: The most effective treatment of Parkinson’s disease is restoring central dopamine levels with levodopa, the metabolic precursor of dopamine. However, due to extensive peripheral metabolism by aromatic l-amino acid decarboxylase and catechol-O-methyltransferase (COMT), only a fraction of the levodopa dose reaches the brain unchanged. Thus, by preventing levodopa metabolism and increasing the availability of levodopa for uptake into the brain, the inhibition of COMT would be beneficial in Parkinson’s disease. Although nitrocatechol COMT inhibitors have been used in the treatment of Parkinson’s disease, efforts have been made to discover non-nitrocatechol inhibitors. In the present study, the 3-hydroxypyridin-4-one scaffold was selected for the design and synthesis of non-nitrocatechol COMT inhibitors since the COMT inhibitory potential of this class has been illustrated. Using COMT obtained from porcine liver, it was shown that a synthetic series of ten 3-hydroxypyridin-4-ones are in vitro inhibitors with IC(50) values ranging from 4.55 to 19.8 µM. Although these compounds are not highly potent inhibitors, they may act as leads for the development of non-nitrocatechol COMT inhibitors. Such compounds would be appropriate for the treatment of Parkinson’s disease. GRAPHIC ABSTRACT: 3-Hydroxypyridin-4-ones have been synthesised and evaluated as non-nitrocatechol COMT inhibitors. In vitro, the IC(50) values ranged from 4.55 to 19.8 μM. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11030-020-10053-x) contains supplementary material, which is available to authorized users.


title: The immunology of other mycobacteria: M. ulcerans, M. leprae

text: Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing leprosy, and atypical mycobacteria, or non-tuberculous mycobacteria (NTM), responsible for a wide range of diseases. Among the NTMs, M. ulcerans is responsible for the neglected tropical skin disease Buruli ulcer (BU). Most pathogenic mycobacteria, including M. leprae, evade effector mechanisms of the humoral immune system by hiding and replicating inside host cells and are furthermore excellent modulators of host immune responses. In contrast, M. ulcerans replicates predominantly extracellularly, sheltered from host immune responses through the cytotoxic and immunosuppressive effects of mycolactone, a macrolide produced by the bacteria. In the year 2018, 208,613 new cases of leprosy and 2713 new cases of BU were reported to WHO, figures which are notoriously skewed by vast underreporting of these diseases.


title: Antimicrobial de-escalation as part of antimicrobial stewardship in intensive care: no simple answers to simple questions—a viewpoint of experts

text: Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more components of combination empirical therapy, and/or the change from a broad-spectrum to a narrower spectrum antimicrobial. It is most commonly recommended in the intensive care unit (ICU) patient who is treated with broad-spectrum antibiotics as a strategy to reduce antimicrobial pressure of empirical broad-spectrum therapy and prevent antimicrobial resistance, yet this has not been convincingly demonstrated in a clinical setting. Even if it appears beneficial, ADE may have some unwanted side effects: it has been associated with prolongation of antimicrobial therapy and could inappropriately be used as a justification for unrestricted broadness of empirical therapy. Also, exposing a patient to multiple, sequential antimicrobials could have unwanted effects on the microbiome. For these reasons, ADE has important shortcomings to be promoted as a quality indicator for appropriate antimicrobial use in the ICU. Despite this, ADE clearly has a role in the management of infections in the ICU. The most appropriate use of ADE is in patients with microbiologically confirmed infections requiring longer antimicrobial therapy. ADE should be used as an integral part of an ICU antimicrobial stewardship approach in which it is guided by optimal specimen quality and relevance. Rapid diagnostics may further assist in avoiding unnecessary initiation of broad-spectrum therapy, which in turn will decrease the need for subsequent ADE.


title: Preoperative miRNA-208a as a Predictor of Postoperative Complications in Children with Congenital Heart Disease Undergoing Heart Surgery

text: Major perioperative cardiovascular events are important causes of morbidity in pediatric patients with congenital heart disease who undergo reparative surgery. Current preoperative clinical risk assessment strategies have poor accuracy for identifying patients who will sustain adverse events following heart surgery. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome following pediatric heart surgery. We tested whether preoperative levels of miRNAs-208a can serve as such a biomarker. Serum samples were obtained from pediatric patients immediately before heart surgery. MiRNA-208a was quantified by RQ-PCR. Correlations between the patient’s clinical variables and miRNA levels were tested. Lower levels of preoperative miRNA-208a correlated with and could predict the appearance of postoperative cardiac and inflammatory complications. MiRNA-208a may serve as a biomarker for the prediction of patients who are at risk to develop complications following surgery for the repair of congenital heart defects.


title: Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model

text: Acute lung injury is an inflammatory condition developed after severe sepsis in response to excessive secretion of pro-inflammatory cytokines. Doxycycline is widely reported to possess immunomodulatory activity through inhibition of various inflammatory pathways. Considering the broad spectrum of anti-inflammatory activity, protective effect of doxycycline was evaluated in clinically relevant murine polymicrobial sepsis model induced by caecal ligation and puncture (CLP). In this model, sepsis is accompanied with infection and therefore ceftriaxone at sub-protective dose was combined to retard the bacterial growth. Three hours after CLP challenge, mice were administered vehicle, ceftriaxone (100 mg/kg subcutaneously) alone and in combination with immunomodulatory dose of doxycycline (50 mg/kg, intraperitoneal) and survival were monitored for 5 days. Bacterial count in blood and peritoneal fluid along with cytokines [interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α] and myeloperoxidase (MPO) in plasma and lung homogenate were measured at 18 h post-CLP. Plasma glutathione (GSH) was also determined. Doxycycline in presence of ceftriaxone improved survival of septic mice by significantly reducing the plasma and lung pro-inflammatory cytokines and MPO levels. It also increased plasma GSH levels. Doxycycline did not improve antibacterial effect of ceftriaxone in combination, suggesting that the protective effect of doxycycline was due to its immunomodulatory activity. Doxycycline in the presence of ceftriaxone demonstrated improved survival of septic mice by modulating the immune response.


title: Development of a measure of stigma towards occupational stress for mental health professionals

text: PURPOSE: Stigma is a common barrier to mental health professionals (MHPs) seeking help for occupational stress and burnout, although there is a lack of psychometrically sound tools to measure this construct. The current study aimed to develop and validate a scale (the Mental Health Professional Stigma Scale; MHPSS) for this purpose. METHODS: The MHPSS and related measures were completed by 221 Australian MHPs via online survey, with a subsample completing the MHPSS again 2 weeks after initial completion. RESULTS: Exploratory factor analysis revealed a four-factor solution, comprising of 13 items and accounting for 50.16% of variance. Factors were Perceived Other Stigma, Perceived Structural Stigma, Personal Stigma, and Self stigma. The internal consistency, test–retest reliability, and validity of the scale were supported. CONCLUSIONS: The MHPSS has utility to capture stigmatising attitudes and beliefs related to occupational stress and burnout among MHPs. It may be used to assist in the development and evaluation of initiatives to reduce stigma and increase help-seeking among MHPs.


title: Tidal Volume Lowering by Instrumental Dead Space Reduction in Brain-Injured ARDS Patients: Effects on Respiratory Mechanics, Gas Exchange, and Cerebral Hemodynamics

text: BACKGROUND: Limiting tidal volume (V(T)), plateau pressure, and driving pressure is essential during the acute respiratory distress syndrome (ARDS), but may be challenging when brain injury coexists due to the risk of hypercapnia. Because lowering dead space enhances CO(2) clearance, we conducted a study to determine whether and to what extent replacing heat and moisture exchangers (HME) with heated humidifiers (HH) facilitate safe V(T) lowering in brain-injured patients with ARDS. METHODS: Brain-injured patients (head trauma or spontaneous cerebral hemorrhage with Glasgow Coma Scale at admission < 9) with mild and moderate ARDS received three ventilatory strategies in a sequential order during continuous paralysis: (1) HME with V(T) to obtain a PaCO(2) within 30–35 mmHg (HME1); (2) HH with V(T) titrated to obtain the same PaCO(2) (HH); and (3) HME1 settings resumed (HME2). Arterial blood gases, static and quasi-static respiratory mechanics, alveolar recruitment by multiple pressure–volume curves, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and mean flow velocity in the middle cerebral artery by transcranial Doppler were recorded. Dead space was measured and partitioned by volumetric capnography. RESULTS: Eighteen brain-injured patients were studied: 7 (39%) had mild and 11 (61%) had moderate ARDS. At inclusion, median [interquartile range] PaO(2)/FiO(2) was 173 [146–213] and median PEEP was 8 cmH(2)O [5–9]. HH allowed to reduce V(T) by 120 ml [95% CI: 98–144], V(T)/kg predicted body weight by 1.8 ml/kg [95% CI: 1.5–2.1], plateau pressure and driving pressure by 3.7 cmH(2)O [2.9–4.3], without affecting PaCO(2), alveolar recruitment, and oxygenation. This was permitted by lower airway (− 84 ml [95% CI: − 79 to − 89]) and total dead space (− 86 ml [95% CI: − 73 to − 98]). Sixteen patients (89%) showed driving pressure equal or lower than 14 cmH(2)O while on HH, as compared to 7 (39%) and 8 (44%) during HME1 and HME2 (p < 0.001). No changes in mean arterial pressure, cerebral perfusion pressure, intracranial pressure, and middle cerebral artery mean flow velocity were documented during HH. CONCLUSION: The dead space reduction provided by HH allows to safely reduce V(T) without modifying PaCO(2) nor cerebral perfusion. This permits to provide a wider proportion of brain-injured ARDS patients with less injurious ventilation.


title: Small steps forward for HIV vaccine development

text: A trial of a therapeutic vaccine against HIV induces cellular immunity and, although it provides hope, it highlights the hurdles for the development of such strategies.


title: The role of physical exercise and rehabilitation in delirium

text: PURPOSE: This article aims to analyze the intersections between delirium, physical exercise and rehabilitation, to better understand their interrelation and to visualize future lines of research. METHODS: In this narrative review, after an overview of brain neurophysiology and function, as common substrates to understand the relationship between delirium and physical function, we explore the scientific evidence in: (1) physical dysfunction as a risk factor for delirium; (2) physical dysfunction as a symptom of delirium and (3) functional consequences related to delirium. Later, we analyze the physical therapy as one of the main strategies in multicomponent interventions to prevent delirium, by examining intervention studies including rehabilitation, which have shown to be effective in managing delirium. Finally, we analyze how frailty, delirium and physical exercise interact with each other. RESULTS: This review confirms the close relationship between delirium and physical dysfunction; therefore, it is not surprising that physical exercise is widely used in delirium preventive strategies. Although delirium is catalogued as a neurocognitive disorder, scientific evidence shows that it is also a motor disorder, which is to be expected, since a vast body of literature already supports an interaction between motor and cognitive function. CONCLUSION: The motor component of delirium should be taken into account when designing interventions or strategies to address delirium. These interventions may have a special importance in frail older adults.


Infektionsschutzrecht nach Inkrafttreten des Masernschutzgesetzes


title: ICU-acquired weakness

text: Critically ill patients often acquire neuropathy and/or myopathy labeled ICU-acquired weakness. The current insights into incidence, pathophysiology, diagnostic tools, risk factors, short- and long-term consequences and management of ICU-acquired weakness are narratively reviewed. PubMed was searched for combinations of “neuropathy”, “myopathy”, “neuromyopathy”, or “weakness” with “critical illness”, “critically ill”, “ICU”, “PICU”, “sepsis” or “burn”. ICU-acquired weakness affects limb and respiratory muscles with a widely varying prevalence depending on the study population. Pathophysiology remains incompletely understood but comprises complex structural/functional alterations within myofibers and neurons. Clinical and electrophysiological tools are used for diagnosis, each with advantages and limitations. Risk factors include age, weight, comorbidities, illness severity, organ failure, exposure to drugs negatively affecting myofibers and neurons, immobility and other intensive care-related factors. ICU-acquired weakness increases risk of in-ICU, in-hospital and long-term mortality, duration of mechanical ventilation and of hospitalization and augments healthcare-related costs, increases likelihood of prolonged care in rehabilitation centers and reduces physical function and quality of life in the long term. RCTs have shown preventive impact of avoiding hyperglycemia, of omitting early parenteral nutrition use and of minimizing sedation. Results of studies investigating the impact of early mobilization, neuromuscular electrical stimulation and of pharmacological interventions were inconsistent, with recent systematic reviews/meta-analyses revealing no or only low-quality evidence for benefit. ICU-acquired weakness predisposes to adverse short- and long-term outcomes. Only a few preventive, but no therapeutic, strategies exist. Further mechanistic research is needed to identify new targets for interventions to be tested in adequately powered RCTs.


title: Neuroprotective Role of Oral Vitamin D Supplementation on Consciousness and Inflammatory Biomarkers in Determining Severity Outcome in Acute Traumatic Brain Injury Patients: A Double-Blind Randomized Clinical Trial

text: BACKGROUND AND OBJECTIVE: Early management of traumatic brain injury (TBI) is essential. We aimed to evaluate the efficacy of vitamin D over early clinical outcome and serum cytokine levels in patients with moderate to severe brain injury. METHODS: Thirty-five patients with moderate to severe traumatic brain injury who were admitted to the ICU unit were recruited into the study. Subjects were randomly allocated to a treatment regimen comprising either a one-time oral dose of 120,000 IU (two tablets of 60,000 IU each) of vitamin D (n = 20) or 8 mg of saccharide (two tablets of 4 g each) as placebo (n = 15). The main parameters evaluated included duration of mechanical ventilation and ICU stay, Glasgow Coma Scale (GCS) and cytokine levels (interleukin (IL)-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, IL-2). RESULTS: The results indicated an improvement in the level of consciousness after 7 days in the vitamin D-treated group compared with placebo. An elevation in GCS score by 3.86 units in the vitamin D-treated group with a 0.19-unit descent in the control group was recorded. Duration of mechanical ventilation was reduced in the vitamin D-treated group compared with the control group (4.7 days vs. 8.2 days, p value 0.0001). A noticeable reduction was recorded in inflammatory biomarkers (cytokines) in the vitamin D-treated group (IL-6 p = 0.08, TNF-α p = 0.02, IL-2 p = 0.36) with notable elevation in IFN-γ (p = 0.65) compared to the control group. CONCLUSION: In the acute phase of moderate to severe traumatic brain injury, vitamin D supplementation plays a vital role and has a favourable effect on the consciousness level of patients. Clinical trial Registry (CTRI) No. CTRI/2019/05/019259.


title: Respiratory drive in the acute respiratory distress syndrome: pathophysiology, monitoring, and therapeutic interventions

text: Neural respiratory drive, i.e., the activity of respiratory centres controlling breathing, is an overlooked physiologic variable which affects the pathophysiology and the clinical outcome of acute respiratory distress syndrome (ARDS). Spontaneous breathing may offer multiple physiologic benefits in these patients, including decreased need for sedation, preserved diaphragm activity and improved cardiovascular function. However, excessive effort to breathe due to high respiratory drive may lead to patient self-inflicted lung injury (P-SILI), even in the absence of mechanical ventilation. In the present review, we focus on the physiological and clinical implications of control of respiratory drive in ARDS patients. We summarize the main determinants of neural respiratory drive and the mechanisms involved in its potentiation, in health and ARDS. We also describe potential and pitfalls of the available bedside methods for drive assessment and explore classical and more “futuristic” interventions to control drive in ARDS patients.


title: Dengue vaccine development: status and future

text: Dengue, the most common arbovirus, represents an increasingly significant cause of morbidity worldwide, including in travelers. After decades of research, the first dengue vaccine was licensed in 2015: CYD-TDV, a tetravalent live attenuated vaccine with a yellow fever vaccine backbone. Recent analyses have shown that vaccine performance is dependent on serostatus. In those who have had a previous dengue infection, i.e., who are seropositive, the efficacy is high and the vaccine is safe. However, in seronegative vaccinees, approximately 3 years after vaccination the vaccine increases the risk of developing severe dengue when the individual experiences a natural dengue infection. The World Health Organization recommends that this vaccine be administered only to seropositive individuals. Current efforts are underway to develop rapid diagnostic tests to facilitate prevaccination screening. Two second-generation dengue vaccine candidates, both also live attenuated recombinant vaccines in late-stage development, may not present the same limitations because of differences in the backbone used, but results of phase 3 trials need to be available before firm conclusions can be drawn. Dengue is increasingly frequent in travelers, but the only licensed dengue vaccine to date can be used only in seropositive individuals. However, the vast majority of travelers are seronegative. Furthermore, the primary series of three doses given 6 months apart renders this vaccine difficult in the travel medicine context.


title: Ethics as a Non-technical Skill for Surgical Education in Sub-Saharan Africa

text: BACKGROUND: In recent years, surgical education has increased its focus on the non-technical skills such as communication and interpersonal relationships while continuing to strive for technical excellence of procedures and patient care. An awareness of the ethical aspects of surgical practice that involve non-technical skills and judgment is of vital concern to surgical educators and encompasses disparate issues ranging from adequate supervision of trainees to surgical care access. METHODS: This bibliographical research effort seeks to report on ethical challenges from a sub-Saharan Africa (SSA) perspective as found in the peer-reviewed literature employing African Journals Online, Bioline, and other sources with African information as well as PubMed and PubMed Central. The principles of autonomy, non-maleficence, beneficence, and justice offer a framework for a study of issues including: access to care (socioeconomic issues and distance from health facilities); resource utilization and decision making based on availability and cost of resources, including ICU and terminal extubation; informed consent (both communication about reasonable expectations post-procedure and research participation); research ethics, including local projects and international collaboration; quality and safety including supervision of less experienced professionals; and those religious and cultural issues that may affect any ethical decision making. The religious and cultural environment receives attention because beliefs and traditions affect medical choices ranging from acceptance of procedures, amputations, to end-of-life decisions. RESULTS AND CONCLUSIONS: Ethics awareness and ethics education should be a vital component of non-technical skills training in surgical education and medical practice in SSA for trainees. Continuing professional development of faculty should include an awareness of ethical issues.


title: Neurally adjusted ventilatory assist versus pressure support ventilation: a randomized controlled feasibility trial performed in patients at risk of prolonged mechanical ventilation

text: BACKGROUND: The clinical effectiveness of neurally adjusted ventilatory assist (NAVA) has yet to be demonstrated, and preliminary studies are required. The study aim was to assess the feasibility of a randomized controlled trial (RCT) of NAVA versus pressure support ventilation (PSV) in critically ill adults at risk of prolonged mechanical ventilation (MV). METHODS: An open-label, parallel, feasibility RCT (n = 78) in four ICUs of one university-affiliated hospital. The primary outcome was mode adherence (percentage of time adherent to assigned mode), and protocol compliance (binary—≥ 65% mode adherence). Secondary exploratory outcomes included ventilator-free days (VFDs), sedation, and mortality. RESULTS: In the 72 participants who commenced weaning, median (95% CI) mode adherence was 83.1% (64.0–97.1%) and 100% (100–100%), and protocol compliance was 66.7% (50.3–80.0%) and 100% (89.0–100.0%) in the NAVA and PSV groups respectively. Secondary outcomes indicated more VFDs to D28 (median difference 3.0 days, 95% CI 0.0–11.0; p = 0.04) and fewer in-hospital deaths (relative risk 0.5, 95% CI 0.2–0.9; p = 0.032) for NAVA. Although overall sedation was similar, Richmond Agitation and Sedation Scale (RASS) scores were closer to zero in NAVA compared to PSV (p = 0.020). No significant differences were observed in duration of MV, ICU or hospital stay, or ICU, D28, and D90 mortality. CONCLUSIONS: This feasibility trial demonstrated good adherence to assigned ventilation mode and the ability to meet a priori protocol compliance criteria. Exploratory outcomes suggest some clinical benefit for NAVA compared to PSV. Clinical effectiveness trials of NAVA are potentially feasible and warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01826890. Registered 9 April 2013.


Focus on infection


title: Exploring the Experiences of Child Welfare-Focused Therapeutic Service Providers

text: The importance of mental and behavioral health for child welfare clients is well-documented; yet, little is known about the challenges therapeutic service providers (TSPs) experience working in child welfare practice. To explore this topic, five focus groups were conducted with 40 TSPs in a contracted mental and behavioral health agency and data were analyzed following an inductive thematic process. Eleven primary challenges were identified, including the difficulty of navigating numerous involved parties, an overwhelmed work environment, legal intersections common to child welfare cases, unrealistic agency expectations, and heighten case complexity when working with child welfare populations. Findings are organized across system, agency, and client levels and add to the understanding of TSP perspectives working with child welfare. Targeted interventions are discussed, such as efforts to promote realistic expectations and training strategies, as well as directions for future research to improve the intersection between child welfare and mental and behavioral health.


title: Association between anemia and hematological indices with mortality among cardiac intensive care unit patients

text: BACKGROUND: Anemia and elevated red cell distribution width (RDW) or mean corpuscular volume (MCV) are associated with an adverse prognosis in patients with cardiovascular disease and critical illness. Limited data exist regarding these associations in unselected cardiac intensive care unit (CICU) patients. METHODS: Retrospective cohort study of CICU patients between January 1, 2007, and December 31, 2015, with a hemoglobin (Hb) level measured at admission. Multivariable regression was performed to determine predictors of hospital mortality, and Kaplan–Meier analysis was used to determine post-discharge survival. RESULTS: We included 9644 patients with a mean age of 67.5 ± 15.1 years, including 3604 (37.4%) females. The median (IQR) values of Hb, MCV and RDW were 12.2 g/dL (10.6, 13.7), 90.7 fL (87.3, 94.2) fL, and 14.1% (13.3, 15.8), respectively. Anemia (admission Hb < 12 g/dL) was present in 4434 (46%) patients. A total of 845 (8.8%) patients died in the hospital. Patients with anemia had higher hospital mortality (11.3% vs. 6.6%, unadjusted OR 1.82, 95% CI 1.58–2.10, p < 0.001). After multivariable regression, admission Hb and MCV were not significantly associated with hospital mortality (both p > 0.1), while admission RDW (adjusted OR 1.12 per 1%, 95% CI 1.07–1.18, p < 0.001) was significantly associated with hospital mortality. Hospital survivors with lower Hb, higher MCV, or higher RDW had lower post-discharge survival. CONCLUSION: Elevated RDW on admission was independently associated with higher hospital mortality in CICU patients. These data emphasize the importance of hematologic abnormalities for mortality risk stratification in CICU populations. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00392-019-01549-0) contains supplementary material, which is available to authorized users.


title: Does Partisanship Affect Compliance with Government Recommendations?

text: This article studies the role of partisanship in American’s willingness to follow government recommendations. I combine survey and behavioral data to examine partisans’ vaccination rates during the Bush and Obama administrations. I find that presidential co-partisans are more likely to believe that vaccines are safe and more likely to vaccinate themselves and their children than presidential out-partisans. Depending on the vaccine, presidential co-partisans are 4–10 percentage points more likely to vaccinate than presidential out-partisans. Using causal mediation analysis, I find that this effect is the result of partisans’ differing levels of trust in government. This finding sheds light on the far-reaching role of partisanship in Americans’ interactions with the federal government. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11109-020-09613-6) contains supplementary material, which is available to authorized users.


title: Atmospheric Plasma Supported by TiO(2) Catalyst for Decolourisation of Reactive Orange 16 Dye in Water

text: PURPOSE: Every advanced oxidation process (AOP) has its limitations in water purification. Novel designs with simultaneous application of different AOPs can offer better solutions for cleaner water. METHODS: We have comparatively studied two advanced oxidation processes (AOPs) on decolourisation of Reactive Orange 16 (RO 16) azo dye pollutant from water: gas plasma treatment by low power atmospheric pressure plasma using novel plasma needle configuration, and semiconductor heterogeneous photocatalysis using titanium dioxide (TiO(2)) nanopowders. Additionally, simultaneous application of two advanced oxidation processes on azo dye decolourisation was studied. RESULTS: It was found that plasma treatment is very efficient system for the dye removal even for low flow rates (1 slm) of the Ar as feed gas. The presence of 10% of O(2) in Ar flow intensified dye oxidation process and shortened required time for total decolourisation. When plasma and catalyst were simultaneously applied, TiO(2) was activated with a few Watts plasma source as well as 300 W UV lamp source. The synergic effect of two AOPs was more pronounced for higher feed gas flow rates, resulting in improved decolourisation efficiency. CONCLUSION: Plasma needle can efficiently remove Reactive Orange 16 azo dye from water with a power consumption of only few Watts. With the addition of TiO(2) the removal efficiency is significantly improved. GRAPHIC ABSTRACT: [Image: see text]


title: The spread and control of rumors in a multilingual environment

text: This paper studies the rumor propagation model with heterogeneous networks in a multilingual environment. Firstly, a rumor propagation model with two language spreaders, in which the immunologic mechanism is considered in the ignorant, is proposed on heterogeneous networks. Secondly, the basic reproduction number and the dynamic behaviors are analyzed by using the next-generation matrix method and Lyapunov stability theory, respectively. Moreover, two control strategies are designed to effectively suppress the spread of the rumor. The one is continuous control strategy. By applying real-time control to the spreaders, the rumor spreading time can be greatly reduced and the rumor can die out in a short time. The other is event-triggered impulsive control strategy, which can effectively reduce the consumption of resources and ensure the extinction of the rumor. Finally, the correctness of theoretical analysis and the feasibility of control methods are verified by numerical simulations.


title: A summary of second systemic pulmonary shunt for congenital heart disease with pulmonary hypoxemia

text: BACKGROUND: There has been an increasing number of children with congenital heart disease that undergo primary or second systemic-pulmonary shunt, while there are few reports on the second systemic-pulmonary shunt. Therefore, this study summarizes the experience of second systemic-pulmonary shunt for congenital heart disease in our hospital. METHODS AND RESULTS: Sixty-five children with congenital heart disease who underwent systemic-pulmonary shunt for the second time in our hospital were analyzed. At the early stage after the operation, cyanosis improved and SpO(2) significantly increased. One patient died in hospital (1.54%) and the causes of death were aggravated atrioventricular regurgitation, low cardiac output syndrome, and liver failure. Early complications occurred in 18 patients (27.7%). All the children were rechecked in our hospital every 3–6 months and the McGoon index significantly increased. CONCLUSION: Systemic-pulmonary artery shunt can promote pulmonary vascular development, improve cyanosis symptoms, and increase the chance of radical treatment in children with pulmonary vascular dysplasia.


title: Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination

text: Viral escape from CD8(+) cytotoxic T lymphocyte responses correlates with disease progression and represents a significant challenge for vaccination. Here, we demonstrate that CD8(+) T cell recognition of the naturally occurring MHC-I-restricted LCMV-associated immune escape variant Y4F is restored following vaccination with a proline-altered peptide ligand (APL). The APL increases MHC/peptide (pMHC) complex stability, rigidifies the peptide and facilitates T cell receptor (TCR) recognition through reduced entropy costs. Structural analyses of pMHC complexes before and after TCR binding, combined with biophysical analyses, revealed that although the TCR binds similarly to all complexes, the p3P modification alters the conformations of a very limited amount of specific MHC and peptide residues, facilitating efficient TCR recognition. This approach can be easily introduced in peptides restricted to other MHC alleles, and can be combined with currently available and future vaccination protocols in order to prevent viral immune escape.


title: Digital exercise interventions for improving measures of central obesity: a systematic review

text: OBJECTIVES: We aimed to systematically review the potential benefits of digital exercise interventions for improving measures of central obesity including visceral adipose tissue (VAT) and anthropometric surrogates for VAT in overweight or centrally obese adults aged 18 or over. METHODS: A systematic literature search was conducted in three databases up until March 2020 (PROSPERO registration nr CRD42019126764). RESULTS: N = 5 studies including 438 participants (age 48–80) with body mass index ≥ 25 kg/m(2) met the eligibility criteria and were included. The duration of the interventions ranged from 8 to 24 weeks. No study measured the primary outcome VAT, although in N = 4 studies, waist circumference (WC) decreased by between 1.3 and 5.6 cm in the intervention groups. CONCLUSIONS: This systematic review shows that there is no evidence for the effects of digital exercise on VAT, although digital exercise may decrease WC. These findings highlight the need for additional randomized controlled trials to confirm the findings with respect to WC, and to further investigate the effects of digital exercise on VAT. Together, this may have important implications for reducing the burden of physical inactivity and obesity.


COVID 19


Transmission electron microscopy imaging of SARS-CoV-2.


Trauma Does not Quarantine: Violence During the COVID-19 Pandemic


What’s Important: Hoping to Help: An Orthopaedic Perspective


Trail Blazers Without Blades: Surgeons as Palliative Care Physicians in Response to COVID-19


Thoughts on Dermatology Residents who are New Parents


title: Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice

text: Mechanisms regulating the turnover of synaptic vesicle (SV) proteins are not well understood. They are thought to require poly-ubiquitination and degradation through proteasome, endo-lysosomal or autophagy-related pathways. Bassoon was shown to negatively regulate presynaptic autophagy in part by scaffolding Atg5. Here, we show that increased autophagy in Bassoon knockout neurons depends on poly-ubiquitination and that the loss of Bassoon leads to elevated levels of ubiquitinated synaptic proteins per se. Our data show that Bassoon knockout neurons have a smaller SV pool size and a higher turnover rate as indicated by a younger pool of SV2. The E3 ligase Parkin is required for increased autophagy in Bassoon-deficient neurons as the knockdown of Parkin normalized autophagy and SV protein levels and rescued impaired SV recycling. These data indicate that Bassoon is a key regulator of SV proteostasis and that Parkin is a key E3 ligase in the autophagy-mediated clearance of SV proteins.


title: Combined ultrasound–CT approach to monitor acute exacerbation of interstitial lung disease

text: BACKGROUND: Lung ultrasound is a bedside non-irradiating tool for assessment and monitoring of lung diseases. A lung ultrasound score based on visualized artefacts allows reliable quantification of lung aeration, and is useful to monitor mechanical ventilation setting, fluid resuscitation and antibiotic response in critical care. In the context of interstitial lung diseases associated to connective tissue disorders, lung ultrasound has been integrated to computed tomography for diagnosis and follow-up monitoring of chronic lung disease progression. CASE PRESENTATION: This case describes a severe acute exacerbation of interstitial lung disease associated to dermatomyositis–polymyositis requiring prolonged extra-corporeal life support. Lung ultrasound score was performed daily and allowed monitoring and guiding both the need of advanced imaging as computed tomography and immunosuppressive therapy. CONCLUSIONS: This case suggests lung ultrasound may be a useful monitoring tool for the response to immunosuppressive therapy in acute severe rheumatic interstitial lung disease, where chest X-ray is poorly informative, and transportation is at high risk.


title: Association of Burnout with Emotional Coping Strategies, Friendship, and Institutional Support Among Internal Medicine Physicians

text: Physician burnout influences physician mental health, staff stress, safety events, and patient outcomes. The association of burnout with compassion satisfaction, secondary stress, emotional coping strategies and many psychosocial variables, such as institutional support, friendship, and spirituality, have not been well studied. A convenience sample of internal medicine physicians was emailed a survey using validated instruments to explore these associations. The response rate was 337/1021 (33%), with a burnout prevalence of 175/337 (52%). Grit, acceptance, active coping, positive reframing, and strategy planning were associated with lower burnout domains and greater compassion satisfaction. Certain emotional coping strategies such as denial, disengagement, self-blame, substance abuse, and venting were associated with greater burnout and lower compassion satisfaction. Greater institutional support was associated with lower burnout (r = − .35, p < .001), secondary stress (r = − .14, p < .05), and compassion satisfaction (r = .28, p < .0001). Friendship was associated with lower burnout (r = − .25, p < .0001) and greater compassion satisfaction (r = .28, p < .0001). This study suggests that amelioration of burnout requires both intrinsic strategies that emphasize physician coping skills as well as extrinsic strategies that address institutional support.


title: Multiple arboviral infections during a DENV-2 outbreak in Solomon Islands

text: BACKGROUND: Solomon Islands, a country made up of tropical islands, has suffered cyclic dengue fever (DF) outbreaks in the past three decades. An outbreak of dengue-like illness (DLI) that occurred in April 2016 prompted this study, which aimed to determine the population’s immunity status and identify the arboviruses circulating in the country. METHODS: A household survey, involving 188 participants in two urban areas (Honiara and Gizo), and a parallel hospital-based clinical survey were conducted in April 2016. The latter was repeated in December after a surge in DLI cases. Arbovirus IgG ELISA were performed on the household blood samples to determine the prevalence of arboviruses in the community, while qPCR testing of the clinical samples was used to identify the circulating arboviruses. Dengue virus (DENV)-positive samples were further characterized by amplifying and sequencing the envelope gene. RESULTS: The overall prevalence rates of DENV, Zika virus, and chikungunya virus were 83.4%, 7.6%, and 0.9%, respectively. The qPCR positivity rates of the clinical samples collected in April 2016 were as follows: DENV 39.6%, Zika virus 16.7%, and chikungunya virus 6.3%, which increased to 74%, 48%, and 20% respectively in December 2016. The displacement of the circulating serotype-3, genotype-1, with DENV serotype 2, genotype cosmopolitan was responsible for the outbreak in 2016. CONCLUSIONS: A DENV outbreak in Solomon Islands was caused by the introduction of a single serotype. The high prevalence of DENV provided transient cross-protection, which prevented the introduction of a new serotype from the hyperendemic region for at least 3 years. The severe outcomes seen in the recent outbreak probably resulted from changes in the causative viruses and the effects of population immunity and changes in the outbreak pattern. Solomon Islands needs to step up surveillance to include molecular tools, increase regional communication, and perform timely interventions.


title: P1′ Residue-Oriented Virtual Screening for Potent and Selective Phosphinic (Dehydro) Dipeptide Inhibitors of Metallo-Aminopeptidases

text: Designing side chain substituents complementary to enzyme binding pockets is of great importance in the construction of potent and selective phosphinic dipeptide inhibitors of metallo-aminopeptidases. Proper structure selection makes inhibitor construction more economic, as the development process typically consists of multiple iterative preparation/bioassay steps. On the basis of these principles, using noncomplex computation and modeling methodologies, we comprehensively screened 900 commercial precursors of the P1′ residues of phosphinic dipeptide and dehydrodipeptide analogs to identify the most promising ligands of 52 metallo-dependent aminopeptidases with known crystal structures. The results revealed several nonproteinogenic residues with an improved energy of binding compared with the best known inhibitors. The data are discussed taking into account the selectivity and stereochemical implications of the enzymes. Using this approach, we were able to identify nontrivial structural elements substituting the recognized phosphinic peptidomimetic scaffold of metallo-aminopeptidase inhibitors.


title: A High-Throughput Single-Clone Phage Fluorescence Microwell Immunoassay and Laser-Driven Clonal Retrieval System

text: Phage display is one of the most frequently used platform technologies utilized to screen and select therapeutic antibodies, and has contributed to the development of more than 10 therapeutic antibodies used in the clinic. Despite advantages like efficiency and low cost, it has intrinsic technical limitations, such as the asymmetrical amplification of the library after each round of biopanning, which is regarded as a reason for it yielding a very limited number of antigen binders. In this study, we developed a high-throughput single-clonal screening system comprised of fluorescence immunoassays and a laser-driven clonal DNA retrieval system using microchip technology. Using this system, from a single-chain variable fragment (scFv) library displayed on phages with a complexity of 5.21 × 10(5) harboring random mutations at five amino acid residues, more than 70,000 clones—corresponding to ~14% of the library complexity—were screened, resulting in 78 antigen-reactive scFv sequences with mutations restricted to the randomized residues. Our results demonstrate that this system can significantly reduce the number of biopanning rounds, or even eliminate the need for this process for libraries with lower complexity, providing an opportunity to obtain more diverse clones from the library.


title: Novel Abs targeting the N‐terminus of fibroblast growth factor 19 inhibit hepatocellular carcinoma growth without bile‐acid‐related side‐effects

text: Hepatocellular carcinoma (HCC) is a common and particularly fatal form of cancer for which very few drugs are effective. The fibroblast growth factor 19 (FGF19) has been viewed as a driver of HCC development and a potential Ab target for developing novel HCC therapy. However, a previously developed anti‐FGF19 Ab disrupted FGF19’s normal regulatory function and caused severe bile‐acid‐related side‐effects despite of having potent antitumor effects in preclinical models. Here, we developed novel human Abs (G1A8 and HS29) that specifically target the N‐terminus of FGF19. Both Abs inhibited FGF19‐induced HCC cell proliferation in vitro and significantly suppressed HCC tumor growth in mouse models. Importantly, no bile‐acid‐related side effects were observed in preclinical cynomolgus monkeys. Fundamentally, our study demonstrates that it is possible to target FGF19 for anti‐HCC therapies without adversely affecting its normal bile acid regulatory function, and highlights the exciting promise of G1A8 or HS29 as potential therapy for HCC.