title: Bubble bilevel ventilation facilitates gas exchange in anesthetized rabbits

text: BACKGROUND: Bubble continuous positive airway pressure is an established therapy for infants in respiratory distress. In resource-limited settings, few treatment options exist for infants requiring further respiratory support. A bubble bilevel device has been developed to provide nonelectric, time-cycled, pressure-limited respiratory support. We compared the efficacy of bubble bilevel ventilation with conventional mechanical ventilation in sedated rabbits. METHODS: Six adult rabbits under inhaled isoflurane general anesthesia were ventilated by alternating intervals of conventional and bubble bilevel ventilation for three 10−15-min periods. During each period, interval arterial blood gas (ABG) measurements were obtained after at least 10 min on the respective mode of ventilation. RESULTS: The bubble bilevel system was able to deliver the following pressures: 20/7, 15/5, 12/5, 8/5 cm H(2)O. The estimated differences in arterial blood gas values on bubble bilevel vs. ventilator were as follows (normalized values): pH 7.41 vs. 7.40, pCO(2) 37.7 vs. 40, pO(2) 97.6 vs. 80. In addition, the bubble bilevel ventilation delivered consistent pressure waveforms without interruption for over 60 min on two rabbits. CONCLUSION: This study demonstrates promising in vivo results on the efficacy of a novel bubble bilevel device, which may prove useful for infants in respiratory distress. IMPACT: Given the lack of personnel, funds or infrastructure to provide neonatal mechanical ventilation in resource-limited settings, additional low-cost, low-tech treatments are necessary to save infant lives. Bubble bilevel ventilation reliably delivers two levels of airway pressure to anesthetized rabbits resulting in normalization of blood gases comparable to those achieved on a traditional ventilator. If proven effective, simple technologies like this device have the potential to significantly impact neonatal mortality due to respiratory distress globally.


title: Streptovertimycins A–H, new fasamycin-type antibiotics produced by a soil-derived Streptomyces morookaense strain

text: Eight new fasamycin-type polyketides, streptovertimycins A–H (1−8), were isolated from soil-derived Streptomyces morookaense SC1169 cultivated on wheat grains. Their structures were established by extensive spectroscopic analysis and theoretical computations of ECD spectra. Compounds 1−8 have a fasamycin-type pentacyclic structure featuring a 15-O-methyl group. They exhibited potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) with MIC values in the range of 0.63–5.0 μg/ml. The activity profile provided new insights into the structure–activity relationships of fasamycin-type antibiotics.


title: Selecting the dosage of ceftazidime–avibactam in the perfect storm of nosocomial pneumonia

text: PURPOSE: Ceftazidime–avibactam is a novel β-lactam/β-lactamase inhibitor combination recently approved in Europe and the USA for the treatment of adults with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), among other indications. In the phase III REPROVE trial (NCT01808092), ceftazidime–avibactam demonstrated non-inferiority to meropenem for the treatment of patients with nosocomial pneumonia (NP), including VAP. As ceftazidime–avibactam was not studied in patients with NP prior to REPROVE, selecting an appropriate dosage regimen in the “perfect storm” of NP required careful consideration of potential determinants and confounders of response specific to the NP patient population. METHODS: This review describes the series of preclinical studies and pharmacokinetic/pharmacodynamic (PK/PD) analyses that supported ceftazidime–avibactam dosage selection for patients with NP/VAP (2000/500 mg by 2-h intravenous infusion every 8 h, adjusted for renal function). In parallel, important considerations for antibiotic dosage selection in patients with NP are highlighted, including adequate drug penetration into the lungs, the suitability of murine-derived plasma PK/PD targets, evaluation of MIC distributions against clinical bacterial isolates from patients with NP, and consideration of PK in patients with NP, who are often critically ill. These analyses also supported the European approval of ceftazidime–avibactam for adults with HAP, including VAP, before the completion of REPROVE. CONCLUSIONS: This work serves as a successful practical example of dosage design for a new antibacterial drug therapy in the indication of NP, including VAP, where previous drug therapies have failed, possibly as a result of evaluation of too few variables, thereby limiting the accuracy of pharmacodynamic predictions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00228-019-02804-z) contains supplementary material, which is available to authorized users.


title: Peculiarities of biofilm formation by Paracoccus denitrificans

text: Most bacteria form biofilms, which are thick multicellular communities covered in extracellular matrix. Biofilms can become thick enough to be even observed by the naked eye, and biofilm formation is a tightly regulated process. Paracoccus denitrificans is a non-motile, Gram-negative bacterium that forms a very thin, unique biofilm. A key factor in the biofilm formed by this bacterium is a large surface protein named biofilm-associated protein A (BapA), which was recently reported to be regulated by cyclic diguanosine monophosphate (cyclic-di-GMP or c-di-GMP). Cyclic-di-GMP is a major second messenger involved in biofilm formation in many bacteria. Though cyclic-di-GMP is generally reported as a positive regulatory factor in biofilm formation, it represses biofilm formation in P. denitrificans. Furthermore, quorum sensing (QS) represses biofilm formation in this bacterium, which is also reported as a positive regulator of biofilm formation in most bacteria. The QS signal used in P. denitrificans is hydrophobic and is delivered through membrane vesicles. Studies on QS show that P. denitrificans can potentially form a thick biofilm but maintains a thin biofilm under normal growth conditions. In this review, we discuss the peculiarities of biofilm formation by P. denitrificans with the aim of deepening the overall understanding of bacterial biofilm formation and functions.


title: Noninvasive respiratory support in the hypoxaemic peri-operative/periprocedural patient: a joint ESA/ESICM guideline

text: Hypoxaemia is a potential life-threatening yet common complication in the peri-operative and periprocedural patient (e.g. during an invasive procedure at risk of deterioration of gas exchange, such as bronchoscopy). The European Society of Anaesthesiology (ESA) and the European Society of Intensive Care Medicine (ESICM) developed guidelines for the use of noninvasive respiratory support techniques in the hypoxaemic patient in the peri-operative and periprocedural period. The panel outlined five clinical questions regarding treatment with noninvasive respiratory support techniques [conventional oxygen therapy (COT), high flow nasal cannula, noninvasive positive pressure ventilation (NIPPV) and continuous positive airway pressure (CPAP)] for hypoxaemic patients with acute peri-operative/periprocedural respiratory failure. The goal was to assess the available literature on the various noninvasive respiratory support techniques, specifically studies that included adult participants with hypoxaemia in the peri-operative/periprocedural period. The literature search strategy was developed by a Cochrane Anaesthesia and Intensive Care trial search specialist in close collaboration with the panel members and the ESA group methodologist. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the level of evidence and to grade recommendations. The final process was then validated by both ESA and ESICM scientific committees. Among 19 recommendations, the two grade 1B recommendations state that: in the peri-operative/periprocedural hypoxaemic patient, the use of either NIPPV or CPAP (based on local expertise) is preferred to COT for improvement of oxygenation; and that the panel suggests using NIPPV or CPAP immediately post-extubation for hypoxaemic patients at risk of developing acute respiratory failure after abdominal surgery. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-05948-0) contains supplementary material, which is available to authorized users.


docid: qvevfimk

title: 14 Years’ experience of esophageal replacement surgeries

text: BACKGROUND: Esophageal replacement is a challenge to the therapeutic skills of surgeons and a technically demanding operation in the pediatric age group. Various conduits and routes have been described in the literature, each with their specific advantages and disadvantages. We carried out this retrospective study to share our experience of esophageal replacement. METHODOLOGY: This study was conducted at the department of pediatric surgery The Children’s Hospital and The Institute of Child Health, Lahore. The records of patients treated for esophageal replacement were reviewed. The patients under follow-up were called for clinical evaluation and assessed of long terms complications if any. RESULTS: A total of 93 patients with esophageal replacement were included in the study. Esophageal replacement was done with gastric transposition in 84 cases (90%), colon interposition in 7 cases (7.5%) including one case of redo colonic interposition, and jejunal interposition in 2 cases (2%). Routes of esophageal replacement were trans-hiatal in 71 (76%), retrosternal in 13 (14%), and trans-hiatal with thoracotomy in 9 (10%) patients. Postoperatively, all of the conduits maintained viability. Wound infection was seen in 10 (11%), wound dehiscence in 5 (5%), anastomotic leak in 9 (10%), anastomotic stenosis in 12 (13%), fistula formation in 4 (4%), aortic injury 1 (1%), dumping syndrome 8 (9%), reflux 18 (19%), dysphagia 15 (16%) and death occurred in 12 patients (13%). CONCLUSION: There are problems with esophageal replacement in developing countries. In this context, gastric conduit appeared as the best conduit for esophageal replacement, using the trans-hiatal route for replacement, in the authors’ experience.


title: Treatment of Ebola-related critical illness

text: PURPOSE: To explore contemporary clincial case management of patients with Ebola virus disease. METHODS: A narrative review from a clinical perspective of clinical features, diagnostic tests, treatments and outcomes of patients with Ebola virus disease. RESULTS: Substantial advances have been made in the care of patients with Ebola virus disease (EVD), precipitated by the unprecedented extent of the 2014–2016 outbreak. There has been improved point-of-care diagnostics, improved characterization of the clinical course of EVD, improved patient-optimized standards of care, evaluation of effective anti-Ebola therapies, administration of effective vaccines, and development of innovative Ebola treatment units. A better understanding of the Ebola virus disease clinical syndrome has led to the appreciation of a central role for critical care clinicians—over 50% of patients have life-threatening complications, including hypotension, severe electrolyte imbalance, acute kidney injury, metabolic acidosis and respiratory failure. Accordingly, patients often require critical care interventions such as monitoring of vital signs, intravenous fluid resuscitation, intravenous vasoactive medications, frequent diagnostic laboratory testing, renal replacement therapy, oxygen and occasionally mechanical ventilation. CONCLUSION: With advanced training and adherence to infection prevention and control practices, clinical interventions, including critical care, are feasible and safe to perform in critically ill patients. With specific anti-Ebola medications, most patients can survive Ebola virus infection.


title: Incidence and Profile of Severe Cycling Injuries After Bikeway Infrastructure Changes

text: The objective of this study was to evaluate whether bicycling infrastructure changes in the city of Minneapolis effectively reduced the incidence or severity of traumatic bicycling related injuries sustained by patients admitted to our Level 1 Trauma Center. Data for this retrospective cohort study was obtained from the trauma database at our institution and retrospective chart review. The total number of miles of bikeway in the city on a yearly basis was used to demonstrate the change in cycling infrastructure. Adjusted regression analysis demonstrated a significant reduction in ISS when total bike lane miles increased (Coef. − 0.04, P < 0.001). Increasing bike lane miles was also associated with a significant reduction in severe head injury (OR 0.99, P < 0.001) and ICU LOS (Coef. − 0.17, P = 0.013). The miles of bike lanes were not associated with any significant changes in mortality or mechanical ventilation days when adjusted for other factors. We were able to demonstrate a reduction in the severity of injuries incurred by cyclists in the setting of a significant increase in the total number of bicycle lane miles. Our data lends credence to the existing evidence that the addition of bicycle lane miles increases cyclist safety.


Impfen im Kontext globaler Herausforderungen


title: Oxidative stress markers in neonatal respiratory distress syndrome: advanced oxidation protein products and 8-hydroxy-2-deoxyguanosine in relation to disease severity

text: OBJECTIVE: We assessed oxidant–antioxidant status and evaluated the role of lipid peroxidation, oxidative DNA damage, and protein oxidation in the development and severity of neonatal respiratory distress syndrome (RDS). METHODS: Forty preterm neonates with RDS were compared with another 40 preterm neonates without RDS enrolled as controls. Total antioxidant capacity (TAC), malondialdehyde (MDA), advanced oxidation protein products (AOPPs), 8-hydroxy-2-deoxyguanosine (8-OHdG), and trace elements (copper and zinc) were measured in cord blood (day 0) for all neonates and repeated on day 3 for the RDS group. RESULTS: Day 0 serum levels of MDA, AOPPs, and 8-OHdG were significantly higher in neonates with RDS than controls with a further increase on day 3. Days 0 and 3 levels of TAC, copper, and zinc were significantly lower in the RDS group compared with controls. Elevated serum levels of 8-OHdG and AOPPs were associated with severe RDS, invasive mechanical ventilation, and high mortality rate. 8-OHdG and AOPPs were positively correlated with MDA, oxygenation index, duration of ventilation, and duration of hospitalization. CONCLUSIONS: Increased lipid, protein, and DNA oxidation is accompanied by alterations in the antioxidant defense status, which may play a role in the pathogenesis and severity of RDS.


title: Dexmedetomidine in Enhanced Recovery After Surgery (ERAS) Protocols for Postoperative Pain

text: PURPOSE OF REVIEW: Effective acute pain management has evolved considerably in recent years and is a primary area of focus in attempts to defend against the opioid epidemic. Persistent postsurgical pain (PPP) has an incidence of up to 30–50% and has negative outcome of quality of life and negative burden on individuals, family, and society. The 2016 American Society of Anesthesiologists (ASA) guidelines states that enhanced recovery after surgery (ERAS) forms an integral part of Perioperative Surgical Home (PSH) and is now recommended to use a multimodal opioid-sparing approach for management of postoperative pain. As such, dexmedetomidine is now being used as part of ERAS protocols along with regional nerve blocks and other medications, to create a satisfactory postoperative outcome with reduced opioid consumption in the Post anesthesia care unit (PACU). RECENT FINDINGS: Dexmedetomidine, a selective alpha(2) agonist, possesses analgesic effects and has a different mechanism of action when compared with opioids. When dexmedetomidine is initiated at the end of a procedure, it has a better hemodynamic stability and pain response than ropivacaine. Dexmedetomidine can be used as an adjuvant in epidurals with local anesthetic sparing effects. Its use during nerve blocks results in reduced postoperative pain. Also, local infiltration of IV dexmedetomidine is associated with earlier discharge from PACU. SUMMARY: Perioperative use of dexmedetomidine has significantly improved postoperative outcomes when used as part of ERAS protocols. An in-depth review of the use of dexmedetomidine in ERAS protocols is presented for clinical anesthesiologists.


title: Zooplankton invasions in the early 21st century: a global survey of recent studies and recommendations for future research

text: We present a comprehensive survey of the scientific literature pertaining to non-indigenous and invasive zooplankton published across the first decades of the twenty-first century (i.e., 2000–2018). We provide a concise summary of the manner in which the scientific community has allocated its efforts to this issue in recent decades, and to illuminate trends that emerge from the literature. Our search yielded 620 publications encompassing 139 invasive zooplankton species, with invasive zooplankton reported from every region of the planet—including the Arctic and Antarctic. Most taxa were reported in a small number of publications, with the majority being mentioned in only a single paper. In contrast, approximately half of the surveyed publications concerned just four species: Bythotrephes longimanus, Mnemioposis leidyi, Cercopagis pengoi, and Daphnia lumholtzi. Our survey reveals strong geographic patterns among the literature, with most publications arising from economically developed western nations. We found that the majority of publications pertained to holoplanktonic organisms from freshwater habitats, especially from the North American Great Lakes. Based on these results, we present several recommendations for future research topics that may hold considerable opportunity for growth in our understanding of the invasion process. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10750-019-04096-x) contains supplementary material, which is available to authorized users.


title: Photocatalytic activity and antibacterial behavior of TiO(2) coatings co-doped with copper and nitrogen via sol–gel method

text: The sol–gel process is used to prepare photocatalytic coatings with antibacterial properties. Also, doping with metallic or non-metallic elements has an impact on the antibacterial and photocatalytic activity of these coatings. Although there are many studies in this field, the effect of co-doping with Cu and N and their concentrations on the antibacterial properties of TiO(2) coatings against the E. coli and S. aureus bacteria has not been studied. In the present investigation, the sol–gel method was employed to deposit both undoped and Cu-N co-doped TiO(2) photocatalytic coatings on glass surface, which are expected to degrade bacterial and chemical contaminants in water while exposed to visible sunlight wavelengths. Before the coating process, an appropriate heat treatment was applied on the samples and the quality of coatings, band gap energy, and also photocatalytic and antibacterial properties were evaluated. Results showed that, in the presence of dopants, the band gap become narrower and the absorption spectrum is transferred from the ultraviolet to the visible light range. Also, it was demonstrated that, under the visible light radiation, all of the co-doped samples show higher photocatalytic activity than the undoped ones. Meanwhile, the antibacterial characteristics of TiO(2) coatings was enhanced by increasing the dopant concentration when exposing to sunlight. [Image: see text]


title: Capacity Building for Refugee Mental Health in Resettlement: Implementation and Evaluation of Cross-Cultural Trauma-Informed Care Training

text: Refugee mental health needs are heightened during resettlement but are often neglected due to challenges in service provision, including lack of opportunities for building capacity and partnership among providers. We developed and implemented culturally-responsive refugee mental health training, called Cross-Cultural Trauma-Informed Care (CC-TIC) training. We evaluated CC-TIC, using a free listing and semi-structured retrospective pre- and post-training evaluation with five localities in two states in the U.S. The results showed significant improvement in providers’ knowledge of trauma impacts, cultural expressions of trauma/stress-related symptoms, and culturally-responsive trauma-informed care. Trauma-informed care specific to refugee resettlement was regarded as the most helpful topic and community partnership building as the most requested area for future training. This study emphasizes that culturally-responsive trauma-informed approaches can help bridge gaps between mental health care and resettlement services and promote exchanges of knowledge and expertise to build collaborative care and community partnership.


title: The effects of weather on daily emergency ambulance service demand in Taipei: a comparison with Hong Kong

text: Numerous studies have examined the effects of weather on emergency ambulance service (EAS) demand. Given Taipei’s unique physical and social environments, empirical evidence collected from other regions may not be applicable. Collecting more information about the characteristics of vulnerable groups and the effects of weather could help the EAS managing authority in formulating cost-effective EAS policies. This study aims to look at the effects of weather on EAS demand in Taipei and to make a comparison with Hong Kong, which is also an Asian city and has a similar cultural context. The study analyzed over 370,000 EAS usage records from the Taipei City Fire Department. These records were aggregated into time series data according to patients’ characteristics and then regressed on meteorological data via multivariate forward regression. The effect size differences of the variance explained by different groups of EAS users’ regression models were compared. Afterward, the results of the regression analysis from Taipei were compared with those from a Hong Kong study. Elderly and critical patients in both cities showed significantly more sensitivity to weather than other patients. Further analysis showed that non-trauma cases were related to weather in Taipei. Although both cities had similar results, the Taipei study clearly showed that elderly and critical patients were more sensitive to weather than other patient subgroups. Health education programs should focus on the vulnerable groups identified in this study in order to increase their awareness and help them protect themselves before the onset of adverse weather conditions. By generating results that are directly applicable to Taipei, the formulation of inappropriate EAS policies can be prevented.


title: Behavioral Health Emergencies Encountered by Community Paramedics: Lessons from the Field and Opportunities for Skills Advancement

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title: Human encephalitis caused by pseudorabies virus infection: a case report

text: Pseudorabies virus (PRV) primarily infects swine but can infect cattle, dogs, and cats. Several studies have reported that PRV can cross the specie barrier and induce human encephalitis, but a definitive diagnosis of human PRV encephalitis is debatable due to the lack of PRV DNA detection. Here, we report a case of human PRV encephalitis diagnosed by the next-generation sequencing (NGS) of PRV sequences in the cerebrospinal fluid (CSF) of a patient. A male pork vendor developed fever and seizures for 6 days. NGS results showed PRV sequences in his CSF and blood. Sanger sequencing showed that PRV DNA in the CSF and PRV antibodies in both the CSF and blood were positive. MRI results revealed multiple inflammatory lesions in the bilateral hemisphere. Based on the clinical and laboratory data, we diagnosed the patient with PRV encephalitis. This case suggests that PRV can infect humans, causing severe viral encephalitis. People at risk of PRV infection should improve their self-protection awareness.


title: A Rotavirus Virus-Like Particle Confined Palladium Nanoreactor and Its Immobilization on Graphene Oxide for Catalysis

text: ABSTRACT: In this work, a new viral protein cage based nanoreactor was successfully constructed via encapsulating Tween 80 stabilized palladium nanoparticles (NPs) into rotavirus capsid VP2 virus-like particles (i.e. Pd@VP2). The effects of stabilizers including CTAB, SDS, Tween 80 and PVP on controlling the particle size of Pd NPs were investigated. They were further immobilized on graphene oxide (i.e. Pd@VP2/GO) by a simple mixing method. Some characterizations including FT-IR and XPS were conducted to study adsorption mode of Pd@VP2 on GO sheets. Their catalytic performance was estimated in the reduction of 4-nitrophenol (4-NP). Results showed that Tween 80 stabilized Pd NPs with the molar ratio of Pd to Tween 80 at 1:0.1 possessed the smallest size and the best stability as well. They were encapsulated into viral protein cages (mean size 49 ± 0.26 nm) to assemble confined nanoreactors, most of which contained 1–2 Pd NPs (mean size 8.15 ± 0.26 nm). As-prepared Pd@VP2 indicated an enhanced activity (apparent reaction rate constant k(app) = (3.74 ± 0.10) × 10(−3) s(−1)) for the reduction of 4-NP in comparison to non-confined Pd-Tween80 colloid (k(app) = (2.20 ± 0.06) × 10(−3) s(−1)). It was logically due to confinement effects of Pd@VP2 including high dispersion of Pd NPs and high effective concentration of substrates in confined space. Pd@VP2 were further immobilized on GO surface through C-N bond. Pd@VP2/GO exhibited good reusability after recycling for four runs, confirming the strong anchoring effects of GO on Pd@VP2. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10562-020-03252-6) contains supplementary material, which is available to authorized users.


Reference guide for management of adult immune thrombocytopenia in Japan: 2019 Revision


title: B cell memory: building two walls of protection against pathogens

text: Surviving a single infection often results in lifelong immunity to the infecting pathogen. Such protection is mediated, in large part, by two main B cell memory ‘walls’ — namely, long-lived plasma cells and memory B cells. The cellular and molecular processes that drive the production of long-lived plasma cells and memory B cells are subjects of intensive research and have important implications for global health. Indeed, although nearly all vaccines in use today depend on their ability to induce B cell memory, we have not yet succeeded in developing vaccines for some of the world’s most deadly diseases, including AIDS and malaria. Here, we describe the two-phase process by which antigen drives the generation of long-lived plasma cells and memory B cells and highlight the challenges for successful vaccine development in each phase.


title: Different effects of acetyl-CoA carboxylase inhibitor TOFA on airway inflammation and airway resistance in a mice model of asthma

text: BACKGROUND AND OBJECTIVE: Acetyl CoA carboxylase (ACC) regulates the differentiation of Th1, Th2, Th17 cells and Treg cells, which play a critical role in airway inflammation of asthma. Here we investigated the role of ACC in the pathogenesis of asthma. METHODS: Chicken Ovalbumin-sensitized and -challenged mice were divided into three groups, PBS group, DMSO (solvent of TOFA) group and ACC inhibitor 5-tetradecyloxy-2-furoic acid (TOFA) + DMSO group. Airway inflammation was assessed with histology, percentages of CD4(+)T cell subsets in lung and spleen was assessed with flow cytometry, and airway responsiveness was assessed with FinePointe RC system. The expression of characteristic transcription factors of CD4(+)T cell subsets was evaluated with real-time PCR. Cytokine levels in bronchoalveolar lavage fluid (BALF) and serum was determined with ELISA. RESULTS: In asthma mice, the expression of ACC increased, while the expression of phosphorylated ACC (pACC) decreased. TOFA had no significant effect on pACC expression. TOFA reduced serum IgE, airway inflammatory cells infiltration and goblet cell hyperplasia, but dramatically increased airway responsiveness. TOFA significantly reduced the percentages of Th1, Th2, Th17 cells in lung and spleen, the expression of GATA3 and RORγt in lung, and IFN-γ, IL-4, IL-17A levels in BALF and serum. TOFA had no significant effect on the percentage of Treg cells, IL-10 level and the expression of T-bet and Foxp3. CONCLUSION: Acetyl-CoA carboxylase inhibitor TOFA might have a distinct effect on asthmatic airway inflammation and airway hyperresponsiveness.


title: Phylogenetic analysis of rabies viruses isolated from cattle in southern Brazil

text: Bats and dogs are the main reservoirs of rabies virus (RABV) in Latin America and are responsible for the maintenance of different cycles of infection. In the two neighbour and most southern Brazilian states of Rio Grande do Sul (RS) and Santa Catarina (SC), rabies in dogs has been successfully controlled for more than 30 years. However, rabies associated to the rural cycle remains endemic, with a significant, though oscillating—annual incidence of rabies in cattle. Despite the plethora of studies on genetic analyses of Brazilian RABV, isolates from southern Brazil have only scarcely been investigated. This work was performed to identify the genetic lineages of RABVs circulating in states of RS and SC. Fifty-nine RABV cattle isolates from RS and SC were selected and submitted to reverse transcription/polymerase chain reaction (RT-PCR) followed by sequencing of the nucleoprotein gene. In RS, the circulation of two sublineages (1A and 1B) of RABV was detected, both with characteristics of lineages usually detected in vampire bats (Desmodus rotundus). In SC, only one sublineage of RABV (1B) was detected. Nevertheless, the findings reported here are expected to contribute to the understanding of the biology of the virus in the region and its interactions with the natural host D. rotundus.


title: Theoretical bounds and approximation of the probability mass function of future hospital bed demand

text: Failing to match the supply of resources to the demand for resources in a hospital can cause non-clinical transfers, diversions, safety risks, and expensive under-utilized resource capacity. Forecasting bed demand helps achieve appropriate safety standards and cost management by proactively adjusting staffing levels and patient flow protocols. This paper defines the theoretical bounds on optimal bed demand prediction accuracy and develops a flexible statistical model to approximate the probability mass function of future bed demand. A case study validates the model using blinded data from a mid-sized Massachusetts community hospital. This approach expands upon similar work by forecasting multiple days in advance instead of a single day, providing a probability mass function of demand instead of a point estimate, using the exact surgery schedule instead of assuming a cyclic schedule, and using patient-level duration-varying length-of-stay distributions instead of assuming patient homogeneity and exponential length of stay distributions. The primary results of this work are an accurate and lengthy forecast, which provides managers better information and more time to optimize short-term staffing adaptations to stochastic bed demand, and a derivation of the minimum mean absolute error of an ideal forecast.


Lessons from Medicine


title: Study of Antiviral Activity of Metabolites of a New Serratia species K-57 Strain

text: The results of studies of a newly isolated Serratia species K-57 strain are presented. The strain is characterized by antiviral activity towards human influenza A/Aichi/2/68/H3N2, vaccinia, mouse smallpox, and herpes simplex-2 viruses. The detected characteristics of the strain, including the data on activities on nucleolytic enzymes, recommend it for the development of therapeutic and preventive antiviral drugs.


title: Burnout and Leadership Style in Behavioral Health Care: a Literature Review

text: Burnout among behavioral health care providers and employees is associated with poor patient and provider outcomes. Leadership style has generally been identified as a means of reducing burnout, yet it is unclear whether some leadership styles are more effective than others at mitigating burnout. Additionally, behavioral health care is provided in a variety of contexts and a leadership style employed in one context may not be effective in another. The purpose of this paper was to review the literature on leadership style and burnout in behavioral health care contexts to identify the different leadership styles and contexts in which the relationship between the two constructs was studied. Studies were categorized based on the leadership style, study design, research methods, and study context. Findings of this review provide insights into potential approaches to prevent employee burnout and its attending costs, as well as ways to improve future research in this critical area.


title: Tuberculosis vaccine development: from classic to clinical candidates

text: Bacillus Calmette-Guérin (BCG) has been in use for nearly 100 years and is the only licensed TB vaccine. While BCG provides protection against disseminated TB in infants, its protection against adult pulmonary tuberculosis (PTB) is variable. To achieve the ambitious goal of eradicating TB worldwide by 2050, there is an urgent need to develop novel TB vaccines. Currently, there are more than a dozen novel TB vaccines including prophylactic and therapeutic at different stages of clinical research. This literature review provides an overview of the clinical status of candidate TB vaccines and discusses the challenges and future development trends of novel TB vaccine research in combination with the efficacy of evaluation of TB vaccines, provides insight for the development of safer and more efficient vaccines, and may inspire new ideas for the prevention of TB.


title: Epitope-Based Vaccine Designing of Nocardia asteroides Targeting the Virulence Factor Mce-Family Protein by Immunoinformatics Approach

text: Nocardia asteroides is the main causative agent responsible for nocardiosis disease in immunocompromised patient viz. Acquired Immunodeficiency Syndrome (AIDS), malignancy, diabetic, organ recipient and genetic disorders. The virulence factor and outer membrane protein pertains immense contribution towards the designing of epitopic vaccine and limiting the robust outbreak of diseases. While epitopic based vaccine element carrying B and T cell epitope along with adjuvant is highly immunoprophylactic in nature. Present research equips immunoinformatics to figure out the suitable epitopes for effective vaccine designing. The selected epitopes VLGSSVQTA, VNIELKPEF and VVPSNLFAV amino acids sequence are identified by HLA-DRB alleles of both MHC class (MHC-I and II) molecules. Simultaneously, these also accessible to B-cell, confirmed through the ABCPred server. Antigenic property expression is validated by the Vaxijen antigenic prediction web portal. Molecular docking between the epitopes and T cell receptor delta chain authenticate the accurate interaction between epitope and receptor with significantly low binding energy. Easy access of epitopes to immune system also be concluded as transmembrane nature of the protein verified by using of TMHMM server. Appropriate structural identity of the virulence factor Mce-family protein generated through Phyre2 server and subsequently validated by ProSA and PROCHECK program suite. The structural configuration of theses epitopes also shaped using DISTILL web server. Both the structure of epitopes and protein will contribute a significant step in designing of epitopic vaccine against N. asteroides. Therefore, such immunoinformatics based computational drive definitely provides a conspicuous impel towards the development of epitopic vaccine as a promising remedy of nocardiosis


title: Parents’ acceptance and regret about end of life care for children who died due to malignancy

text: PURPOSE: To analyse the preference of end of life care place in paediatric oncology patients, and to understand the end of life care needs and regrets among the care givers. METHOD: This was an observational qualitative study. Parents of in-curable paediatric malignancy patients who died during the years 2016–2018 were interviewed using a pre-formed open-ended questionnaire. Fears during the last phase of child’s life, most disturbing symptoms, choice of end of life care plan, regret of care givers and reasons for such choices were noted and analysed. RESULT: Twenty six families were interviewed. A median of 3 months of discordance was noted between declaration of in-curability and acceptance of the same by the family. During terminal months, pain (84.62%) was described as the most bothersome symptom followed by respiratory distress (73.08%). Eighteen families (69%) opted for home-based terminal care, 8 (31%) for hospital-based terminal care. Regret of choice was noted in 62.5% families of the hospital-based care group (separation from home environment being the main reason) and 38.89% of the home-based care group (lack of access to health care personnel and pain medication being the main reasons). CONCLUSION: Home-based care is the preferred option for end of life care by the care givers. Lack of community-based terminal care support system and availability of analgesics are the main areas to work on in India.


title: Trends in Drain Utilization in Bariatric Surgery: an Analysis of the MBSAQIP Database 2015–2017

text: BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (SG) are the two most common bariatric operations. With the implementation of enhanced recovery protocols, the use of drains should decrease. METHODS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database was queried for the years 2015–2017. Our inclusion criteria included all patients undergoing a primary LRYGB, SG, and revisions. We examined demographics, operative characteristics, the use of drains, and postoperative complications. Continuous variables were summarized using means and standard deviations (SD). Categorical variables were summarized using frequencies and proportions. Student’s T test (Wilcoxon sum rank test in the case of skewed data) and chi-squared analysis were used to assess the baseline differences in drain utilization. RESULTS: From 2015 to 2017, there were 388,239 bariatric cases performed without drains and 100,221 performed with drains. Twenty-nine percent of LRYGB patients had a drain placed but only 16.7% of SG patients. The percentage of LRYGB that had a drain dropped from 33.1 to 24.6% during the study period and that of SG dropped from 20.3 to 13.6%. Patients that had drains placed were more likely to have a provocative test at the time of surgery (prevalence ratio (PR) 2.24) and to have a postoperative swallow study (PR 1.93). CONCLUSIONS: Drains are still commonly used in bariatric patients. Over the study period, there was a decrease in the use of drains in both bypass and sleeve patients. Patients with a drain were more likely to have had a provocative test and a swallow study and have a higher rate of complications and mortality. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11695-019-04215-6) contains supplementary material, which is available to authorized users.


docid: ztagleaf

title: Assessment of the benefits of head-up preoxygenation using near-infrared spectroscopy with pulse oximetry in a swine model

text: Compared with supine positioning, head-up positioning improves preoxygenation and prolongs the time to oxygen desaturation. We reevaluated benefits of head-up positioning using near-infrared spectroscopy (NIRS) with pulse oximetry in a pig model. Six pigs (mean ± SD weight: 25.3 ± 0.6 kg) were anesthetized with isoflurane and evaluated in four positions—supine, head-up, head-down, head-up to supine—just before apnea (positions’ order after “supine” was randomized). In each position, after 5 min of preoxygenation with 100% oxygen, apnea was induced and the time to SpO(2) < 70% measured. Hemodynamic and blood-gas variables and the cerebral tissue oxygenation index (TOI) were evaluated using NIRS and recorded. Hypovolemia was induced by collecting 600 mL blood. Apnea experiment was performed again in each position. The times (seconds) ± SD to SpO(2) < 70% were 108 ± 13 (supine), 138 ± 15 (head-up; P < 0.0001 vs all other positions); 101 ± 12 (head-down) and 106 ± 15 (head-up to supine) during normovolemia, and 110 ± 29, 120 ± 7 (not significant vs all other positions), 101 ± 16, and 106 ± 11, respectively, during hypovolemia. Although the TOI was not associated with the positions during normovolemia, the head-up position during hypovolemia decreased TOI from 62% ± 6% (supine) to 50% ± 9% (head-up; P = 0.0019) before preoxygenation, and it remained low during apnea. The head-up position improves preoxygenation, but repositioning to supine negates the benefits. Head-up positioning during evident hypovolemia should be avoided because the cerebral oxygenation could decrease.


title: Care competencies in adolescents: Development of a new measure and relationships with well-being

text: Worldwide, we observe an increasing focus on fostering well-being in adolescents. This is reflected in growing research in the field of care. However, empirical research is lacking that focuses on the relationship between components of care: receiving care, self-care and extending care. This lack of research is mirrored in the lack of valid measures for assessing care competencies in educational contexts. The present research, therefore, has four goals: 1) to create a valid and reliable scale assessing levels of care competencies based on the multifaceted and multidimensional concept of care; 2) to explore the relationship between socio-demographic characteristics and care competencies in adolescents; 3) to examine the psychological outcomes associated with different levels of care competencies in adolescents; 4) to explore the interaction of the three care dimensions in predicting adolescents’ well-being. Based on data from 742 adolescents, a reliable and valid scale could be developed with six subscales: Receiving care, self-care and extending care, with each of them falling apart in care competencies and care failures. Gender, age and academic achievement were related to care competencies/failures. Findings support the link between adolescents’ well-being and care competencies/failures. These results have implications for promoting adolescents’ well-being through school-based care-cultivation programs.


title: Nanobiotechnological modules as molecular target tracker for the treatment and prevention of malaria: options and opportunity

text: Malaria is one of the major infectious diseases that remains a constant challenge to human being mainly due to the emergence of drug-resistant strains of parasite and also the availability of drugs, which are non-specific for their pharmacodynamic activity and known to be associated with multiple side effects. The disease has acquired endemic proportions in tropical countries where the hygienic conditions are not satisfactory while the environmental conditions favor the proliferation of parasite and its transmission, particularly through the female anopheles. It is obvious that to square up the problems, there is a need for designing and development of more effective drugs, which can combat the drug-resistant strains of the parasite. Molecular biology of the parasite and its homing into host cellular tropics provide multiple drug targets that could judiciously be considered for engineering and designing of new generation antimalarial drugs and also drug delivery systems. Though the recent reports document that against malaria parasite the vaccine could be developed, nevertheless, due to smart mutational change overs by the parasite, it is able to bypass the immune surveillance. The developed vaccine therefore failed to assure absolute protection against the malarial infection. In the conventional mode of treatment antimalarial drugs, the dose and dosage regimen that is followed at large crops up the contraindicative manifestations, and hence compromising the effective treatment. The emerging trends and new updates in contemporary biological sciences, material sciences, and drug delivery domain have enabled us with the availability of a multitude of mode and modules which could plunge upon the nanotechnology in particular to treat this challenging infection. The nanotechnology-based option may be tuned or customized as per the requirements to mark and target i.e. the infected RBCs, for targeted drug delivery. [Figure: see text]


title: Anti-viral activity of Zingiber officinale (Ginger) ingredients against the Chikungunya virus

text: Chikungunya is one of the highly infectious viral disease without vaccine and anti-viral. Aim of present study is to check the anti-chikungunya activities of Zingiber officinale (Ginger) in the animal cell culture model. The medicinal plant extract was prepared from Z. officinale rhizome. Median tissue culture infective dose (TCID(50)) of Chikungunya virus (CHIKV) and Maximum non-toxic dose (MNTD) of Z. officinale extract was determined in Vero cell-line on the basis of cell viability followed by MTT assay. In vitro anti-chikungunya activity was performed in Vero cell-line with MNTD and half of MNTD of Z. officinale medicinal plant extract. The anti-viral effect of Z. officinale was studied by observing the cytopathic effects and cell viability measured by MTT assay. Maximum non-toxic dose of Z. officinale plant extract was found 62.5 μg/ml. During anti-chikungunya experimentation, cell viability increased to 51.05% and 35.10%, when Vero cells were pre-treated with MNTD and half of MNTD of Z. officinale extract respectively. Similarly, in co-treatment, when MNTD, half of MNTD of Z. officinale and Median tissue culture infective dose CHIKV were inoculated simultaneously, then the viability of Vero cell-line was increases by 52.90% and 49.02% respectively. The rhizome extracts of Z. officinale have high potential to treat CHIKV. Medicinal plants and their metabolites are most important sources of antimicrobial and can be utilized for the development of new drugs. In view of the rapid expansion of CHIKV at the global level, there is an urgent need to develop newer anti-chikungunya drugs.


title: Reporting of acute pancreatitis by radiologists-time for a systematic change with structured reporting template

text: Acute pancreatitis has a wide array of imaging presentations. Various classifications have been used in the past to standardize the terminology and reduce confusing and redundant terms. We aim to review the historical and current classifications of acute pancreatitis and propose a new reporting template which can improve communication between various medical teams by use of appropriate terminology and structured radiology template. The standardized reporting template not only conveys the most important imaging findings in a simplified yet comprehensive way but also allows structured data collection for future research and teaching purposes.


title: Preclinical Evaluation of Vaccines to Treat Opioid Use Disorders: How Close are We to a Clinically Viable Therapeutic?

text: The ongoing opioid crisis, now into its second decade, represents a global public health challenge. Moreover, the opioid crisis has manifested despite clinical access to three approved opioid use disorder medications: the full opioid agonist methadone, the partial opioid agonist buprenorphine, and the opioid antagonist naltrexone. Although current opioid use disorder medications are underutilized, the ongoing opioid crisis has also identified the need for basic research to develop both safer and more effective opioid use disorder medications. Emerging preclinical evidence suggests that opioid-targeted vaccines or immunopharmacotherapies may be promising opioid use disorder therapeutics. One premise for this article is to critically examine whether vaccine effectiveness evaluated using preclinical antinociceptive endpoints is predictive of vaccine effectiveness on abuse-related endpoints such as drug self-administration, drug discrimination, and conditioned place preference. A second premise is to apply decades of knowledge in the preclinical evaluation of candidate small-molecule therapeutics for opioid use disorder to the preclinical evaluation of candidate opioid use disorder immunopharmacotherapies. We conclude with preclinical experimental design attributes to enhance preclinical-to-clinical translatability and potential future directions for immunopharmacotherapies to address the dynamic illicit opioid environment.


title: Gut microbiota in neonates with congenital gastrointestinal surgical conditions: a prospective study

text: BACKGROUND: There is limited information on gut microbiota of neonates with congenital gastrointestinal surgical conditions (CGISCs) available. METHODS: This study compared stool microbiota and short-chain fatty acids (SCFAs) of 37 term infants with CGISCs with 36 term healthy infants (HIs). Two stool samples were collected from each infant: as soon as possible after birth (week 1) and 10–14 days of life (week 2). RESULTS: Bacterial richness and alpha diversity were comparable between CGISCs and HIs at week 1 and week 2 (all p > 0.05). Beta diversity analysis revealed that at week 1, CGISCs had similar community structures to HIs (p = 0.415). However, by week 2, community structures of CGISCs were significantly different from HIs (p = 0.003). At week 1, there were no significant differences in the relative abundances of genera Bifidobacterium and Bacteroides between CGISCs and HIs. At week 2, the relative abundance of Bifidobacterium was significantly lower in CGISCs (mean percentage 7.21 ± 13.49 vs. 28.96 ± 19.6; p = 0.002). Bacteroides were also less abundant in the CGISC group (mean percentage 0.12 ± 0.49 vs. 6.59 ± 8.62; p = 0.039). Relative abundance of genera Pseudomonas and Escherichia–Shigella were higher in CGISCs. At week 2, stool concentrations of all SCFAs were lower in CGISCs (all p < 0.001). CONCLUSIONS: During hospitalization, neonates with CGISCs develop gut dysbiosis and deficiency of SCFAs. IMPACT: During hospitalisation, neonates with congenital gastrointestinal surgical conditions develop gut dysbiosis with deficiency of Bifidobacteria and Bacteroides and increased abundance of Escherichia-Shigella and Pseudomonas. They also have low levels of short chain fatty acids in their stools compared to healthy infants. This is the first study evaluating the gut microbiota using 16S ribosomal RNA sequencing methods and stool short chain fatty acids in neonates with congenital gastrointestinal surgical conditions and comparing them to healthy infants. The findings of this study will pave the way for randomised trials of bifidobacterial supplementation in neonates with congenital gastrointestinal surgical conditions.


title: Refeeding syndrome: multimodal monitoring and clinical manifestation of an internal severe neurotrauma

text: Refeeding syndrome (RFS) is a rare, potentially life-threatening, condition seen in malnourished patients starting refeeding. RFS may provoke seizures and acute encephalopathy and can be considered an internal severe neurotrauma in need of specific treatment. The objective was to describe course of disease, treatment and, for the first time, multimodal monitoring output in a comatose patient suffering RFS. After gastric-banding and severe weight loss, the patient initiated self-starving and was transferred to our intensive care unit (ICU) following rapid refeeding. At arrival, seizures, decrease in consciousness (GCS 7) and suspected acute encephalitis was presented. Serum albumin was 8 g/l. Intracranial pressure (ICP), invasive blood pressure and electrocardiography (ECG) were monitored. Pressure reactivity (PR(x)) and compliance (RAP) were calculated. The patient developed congestive heart failure, anuria and general oedema despite maximal neuro- and general ICU treatment. Global cerebral oedema and hypoperfusion areas with established ischemia were seen. ECG revealed massive cardiac arrhythmia and disturbed autonomic regulation. PR(x) indicated intact autoregulation (−0.06 ± 0.18, mean ± SD) and relatively normal compliance (RAP = 0.23 ± 0.13). After 15 days the clinical state was improved, and the patient returned to the primary hospital. RFS was associated with serious deviations in homeostasis, high ICP levels, ECG abnormalities, kidney and lung affections. It is of utmost importance to recognize this rare syndrome and to treat appropriately. Despite the severe clinical state, cerebral autoregulation and compensatory reserve were generally normal, questioning the applicability of indirect measurements such as PR(x) and RAP during neuro-intensive care treatment of RFS patients with cerebral engagement.


title: Sepsis and ECMO

text: Sepsis is being recognized as an important complication of extracorporeal membrane oxygenation (ECMO) and its presence is a poor prognostic marker and increases the overall mortality. The survival rate differs in the various types of cannulation techniques. Adult patients with prolonged duration of ECMO constitute the major risk population. Ventilator-associated pneumonia and bloodstream infections form the main sources of sepsis in these patients. It is important to know the most common etiological agents for sepsis in ECMO, which varies partly with the local epidemiology of the hospitals. A high index of suspicion, drawing adequate volumes for blood culture and early and timely administration of appropriate empirical antimicrobials can substantially decrease the morbidity and mortality in this high-risk population. The dosing of antimicrobials is influenced by the pharmacological variations on ECMO machine and is an important consideration. Infection control practices are of paramount importance and need to be followed meticulously to prevent sepsis in ECMO.


title: Perioperative Considerations in Endoscopic Skull Base Surgery

text: PURPOSE OF THE REVIEW: Present an overview of perioperative considerations specific to endoscopic skull base surgery necessary to maximize successful outcomes. RECENT FINDINGS: The majority of perioperative considerations for endoscopic skull base surgery lack strong supporting evidence and frequently have varied use or implementation amongst institutions. A notable exception comes from a recent randomized controlled trial demonstrating the benefit of lumbar drainage in high-risk cerebrospinal fluid leaks. SUMMARY: Skull base surgeons must consider a multitude of perioperative factors. While many components of perioperative management are extrapolated from related fields such as endoscopic sinus surgery or open cranial base surgery, additional high-quality studies are needed to delineate best practices specific to endoscopic skull base surgery.


docid: dajcwjyz

title: Surgical Options for Pulmonary Atresia with Ventricular Septal Defect in Neonates and Young Infants

text: BACKGROUND: The optimal surgical strategy for pulmonary atresia with ventricular septal defect (PA/VSD) in neonates and young infants is controversial. Staged repair may be associated with a higher risk of inter-stage mortality, while primary repair may lead to frequent post-repair re-interventions. METHODS: From 2004 to 2017, 65 patients with PA/VSD who underwent surgical intervention before 90 days of age were identified and enrolled in this retrospective study. The cohort was divided into two groups: group-SR, who underwent initial palliation with staged repair (n = 50), and group-PR who underwent primary repair (n = 15). RESULTS: There were three post-palliation in-hospital mortalities, four inter-stage mortalities, and one post-repair in-hospital mortality in group-SR. In group-PR, there was one in-hospital death and one late death. Five-year survival rates were comparable between the two groups (group-SR: 83.6%; group-PR: 86.7%; p = 0.754). During the median follow-up duration of 44.7 months (Inter-quartile range, 19–109 months), 40 post-repair re-interventions (22 in group-SR, 18 in group-PR) were performed in 26 patients (18 in group-SR, 8 in group-PR). On Cox proportional hazards model, primary repair was identified as the only risk factor for decreased time to death/1st post-repair re-intervention (Hazard ratio (HR): 2.3, p = 0.049) and death/2nd post-repair re-intervention (HR 2.91, p = 0.033). CONCLUSIONS: A staged repair strategy, compared with primary repair, was associated with comparable overall survival with less frequent re-interventions after repair in young infants with PA/VSD. Lowering the inter-stage mortality after initial palliation by vigilant outpatient care and aggressive home monitoring may be the key to better surgical outcomes in this subset. GRAPHIC ABSTRACT: Surgical outcomes of PA with VSD according to the surgical strategies. Patient 1 (birth weight: 2.7 kg) underwent primary Rastelli-type repair at post-natal day # 50 (body weight: 3.8 kg) using Contegra® 12 mm. The postoperative course was rocky, with long ventilatory support (10 days), ICU stay (14 days), and hospital stay (20 days). Cardiac CT scan at 9 months post-repair showed severe branch pulmonary artery stenosis, which necessitated LPA stenting at 12 months post-repair and RV-PA conduit replacement with extensive pulmonary artery reconstruction at 25 months post-repair. Patient 2 (birth weight: 2.5 kg) underwent RMBT at post-natal day #30 (body weight: 3.4 kg) using 4 mm PTFE vascular graft and staged Rastelli-type repair at post-natal 11 months using a hand-made Gore-Tex valved conduit (14 mm). No post-repair re-intervention has been performed. Cardiac CT scan at 90 months post-repair showed no branch pulmonary artery stenosis. [Image: see text] CT computed tomography, ICU intensive care unit, LPA left pulmonary artery, PA pulmonary atresia, PTFE polytetrafluoroethylene, RMBT right modified Blalock–Taussig shunt, RV-PA right ventricle to pulmonary artery, VSD ventricular septal defect.


title: A Comprehensive Review on Human Aichi Virus

text: Although norovirus, rotavirus, adenovirus and Astrovirus are considered the most important viral agents transmitted by food and water, in recent years other viruses, such as Aichi virus (AiV), have emerged as responsible for gastroenteritis outbreaks associated with different foods. AiV belongs to the genus Kobuvirus of the family Picornaviridae. It is a virus with icosahedral morphology that presents a single stranded RNA genome with positive sense (8280 nucleotides) and a poly (A) chain. AiV was first detected from clinical samples and in recent years has been involved in acute gastroenteritis outbreaks from different world regions. Furthermore, several studies conducted in Japan, Germany, France, Tunisia and Spain showed a high prevalence of AiV antibodies in adults (between 80% and 99%), which is indicative of a large exposure to this virus. The aim of this review is to bring together all the discovered information about the emerging pathogen human Aichi virus (AiV), discussing the possibles routes of transmission, new detection techniques and future research. Although AiV is responsible for a low percentage of gastroenteritis outbreaks, the high seroprevalence shown by human populations indicates an evident role as an enteric agent. The low percentage of AiV detection could be explained by the fact that the pathogen is more associated to subclinical infections. Further studies will be needed to clarify the real impact of AiV in human health and its importance as a causative gastroenteritis agent worldwide.


title: Comparable Effect of Two-Step Versus Extended Infusions on the Pharmacokinetics of Imipenem in Patients with Sepsis and Septic Shock

text: INTRODUCTION: The present study aimed to compare the pharmacokinetic/pharmacodynamic (PK/PD) parameters of imipenem administered by two-step (50% delivered in a 30-min bolus, 50% for the following 90 min) or extended (administered continuously for 2 h) infusion. METHODS: Patients with sepsis and septic shock were prospectively enrolled and randomized into four groups. Subjects in the two-step or extended groups were given two doses of imipenem (0.5 g q6h and 1.0 g q8h). The plasma imipenem concentrations were measured at given time points after the fifth dose. The PK/PD target was defined as the achievement of a fractional time above the minimal inhibitory concentration (MIC) of > 40%. RESULTS: Thirty-five patients were eventually enrolled. No significant difference was observed in the percentage of patients achieving 40% T > MIC between the different infusion modes with the same dosage, although the two-step groups exhibited a significantly shorter T(max) compared with the extended groups (0.5 g q6h: 1.5 ± 0.8 vs. 2.0 ± 0.0 h; 1.0 g q8h: 1.0 ± 0.6 vs. 2.0 ± 0.0 h; both, p < 0.05). All four groups achieved 40% T > MIC when MIC was 0.5–4.0 μg/ml, but only regimens with a higher dose (1.0 g q8h) achieved target when MIC was 8 μg/ml. CONCLUSION: The two-step and extended regimens of imipenem are comparable to the PK/PD target in the treatment of sepsis and septic shock. A higher dose (1.0 g q8h) should be considered for target achievement at an MIC of > 8 μg/ml. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02616354. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12325-020-01339-5) contains supplementary material, which is available to authorized users.


title: Synergistic Activity of Ceragenins Against Carbapenem-Resistant Acinetobacter baumannii Strains in Both Checkerboard and Dynamic Time-Kill Assays

text: Acinetobacter baumannii is an emerging opportunistic pathogen that primarily infects critically ill patients in nosocomial settings and there is a need for identifying new alternative therapeutic agents against these organisms. Ceragenins are non-peptide, membrane-active agents that mimic the antimicrobial properties of antimicrobial peptides (AMPs) and affect the membrane permeability of microorganisms. The in vitro activities of CSA-8, CSA-13, CSA-44, CSA-131, CSA-138 either alone or in combination with colistin (sulphate) were determined against 25 carbapenem-resistant A. baumannii strains. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of selected ceragenins and colistin against these isolates were measured by in vitro microbroth dilution techniques. Checkerboard techniques and time-kill assays were performed to determine the activities of combinations. The MIC(50) values (mg/L) of CSA-8, CSA-13, CSA-44, CSA-131, CSA-138 and colistin were 32, 4, 8, 2, 4 and 0.5, respectively. The MIC(90) (mg/L) of CSA-8, CSA-13, CSA-44, CSA-131, CSA-138 and colistin were 128, 8, 16, 8, 16 and 16, respectively. At 6 h, 1×MIC and 2×MIC of CSA-13 were bactericidal. CSA-13 + colistin combination displayed synergistic interaction. Antagonism between antimicrobials was not observed. According to the results, CSA-13 and CSA-131 can be good alternatives for infections caused by carbapenem-resistant A. baumannii.


Impfen bei Immundefizienz: Anwendungshinweise zu den von der Ständigen Impfkommission empfohlenen Impfungen. (III) Impfen bei hämatologischen und onkologischen Erkrankungen (antineoplastische Therapie, Stammzelltransplantation), Organtransplantation und Asplenie


title: Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events

text: PURPOSE: Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction. METHODS: Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs. RESULTS: Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV). CONCLUSION: There is an urgent need for a simpler symptom- or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future.


Symposia


title: Diabetes-associated infections: development of antimicrobial resistance and possible treatment strategies

text: Diabetes mellitus is associated with various types of infections notably skin, mucous membrane, soft tissue, urinary tract, respiratory tract and surgical and/or hospital-associated infections. The reason behind this frequent association with infections is an immunocompromised state of diabetic patient because uncontrolled hyperglycemia impairs overall immunity of diabetic patient via involvement of various mechanistic pathways that lead to the diabetic patient as immunocompromised. There are specific microbes that are associated with each type of infection and their presence indicates specific type of infections. For instance, E. coli and Klebsiella are the most common causative pathogens responsible for the development of urinary tract infections. Diabetic-foot infections commonly occur in diabetic patients. In this article, we have mainly focused on the association of diabetes mellitus with various types of bacterial infections and the pattern of resistance against antimicrobial agents that are frequently used for the treatment of diabetes-associated infections. Moreover, we have also summarized the possible treatment strategies against diabetes-associated infections.


title: Influenza and antiviral resistance: an overview

text: Influenza affects approximately 1 billion individuals each year resulting in between 290,000 and 650,000 deaths. Young children and immunocompromised individuals are at a particularly high risk of severe illness attributable to influenza and these are also the groups of individuals in which reduced susceptibility to neuraminidase inhibitors is most frequently seen. High levels of resistance emerged with previous adamantane therapy for influenza A and despite no longer being used to treat influenza and therefore lack of selection pressure, high levels of adamantane resistance continue to persist in currently circulating influenza A strains. Resistance to neuraminidase inhibitors has remained at low levels to date and the majority of resistance is seen in influenza A H1N1 pdm09 infected immunocompromised individuals receiving oseltamivir but is also seen less frequently with influenza A H3N2 and B. Rarely, resistance is also seen in the immunocompetent. There is evidence to suggest that these resistant strains (particularly H1N1 pdm09) are able to maintain their replicative fitness and transmissibility, although there is no clear evidence that being infected with a resistant strain is associated with a worse clinical outcome. Should neuraminidase inhibitor resistance become more problematic in the future, there are a small number of alternative novel agents within the anti-influenza armoury with different mechanisms of action to neuraminidase inhibitors and therefore potentially effective against neuraminidase inhibitor resistant strains. Limited data from use of novel agents such as baloxavir marboxil and favipiravir, does however show that resistance variants can also emerge in the presence of these drugs.


title: Incidence of post-traumatic pneumonia in poly-traumatized patients: identifying the role of traumatic brain injury and chest trauma

text: PURPOSE: Traumatic brain injury (TBI) and chest trauma are common injuries in severely injured patients. Both entities are well known to be associated with severe post-traumatic complications, including pneumonia, a common complication with a significant impact on the further clinical course. However, the relevance of TBI, chest trauma and particularly their combination as risk factors for the development of pneumonia and its impact on outcomes are not fully elucidated. METHODS: A retrospective analysis of poly-traumatized patients treated between 2010 and 2015 at a level I trauma centre was performed. Inclusion criteria were: Injury Severity Score ≥ 16 and age ≥ 18 years. TBI and chest trauma were classified according to the Abbreviated Injury Scale. Complications (i.e. acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS) and pneumonia) were documented by a review of the medical records. The primary outcome parameter was in-hospital mortality. RESULTS: Over the clinical course, 19.9% of all patients developed pneumonia, and in-hospital mortality was 25.3%. Pneumonia (OR 5.142, p = 0.001) represented the strongest independent predictor of in-hospital mortality, followed by the combination of chest injury and TBI (OR 3.784, p = 0.008) and TBI (OR 3.028, p = 0.010). Chest injury alone, the combination of chest injury and TBI, and duration of ventilation were independent predictors of pneumonia [resp. OR 4.711 (p = 0.004), OR 4.193 (p = 0.004), OR 1.002 (p < 0.001)]. CONCLUSIONS: Chest trauma alone and especially its combination with TBI represent high-risk injury patterns for the development of pneumonia, which forms the strongest predictor of mortality in poly-traumatized patients.


title: Development and bioanalytical method validation of an LC-MS/MS assay for simultaneous quantitation of 2-alkyl-4(1H)-quinolones for application in bacterial cell culture and lung tissue

text: Pseudomonas aeruginosa is an opportunistic pathogen that produces numerous exoproducts during infection that help it evade the host immune system and procure nutrients from the host environment. Among these products are a family of secreted 2-alkyl-4(1H)-quinolone metabolites (AQs), which exhibit a range of biological activities. Here, we describe the validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method for quantifying multiple AQ congeners in complex biological matrices. The assay was validated for selectivity, sensitivity, linearity, accuracy, precision, carryover, dilution integrity, recovery, matrix effects, and various aspects of stability (freeze-thaw, bench-top, long-term storage, and autosampler/post-preparative). Using authentic standards for 6 distinct AQ congeners, we report accurate quantitation within a linear range between 25 and 1000 nmol/L for all of the validated AQ standards. This method was successfully applied to quantify AQ concentrations in P. aeruginosa cell culture and in the lungs of mice infected with P. aeruginosa. Further, we confirmed the presence of unsaturated forms of several AQ congeners in cell culture. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00216-019-02374-0) contains supplementary material, which is available to authorized users.


A glass half-full: defining ventilator-associated pneumonia in the neonatal intensive care unit


False-positive anti-NMDA receptor antibodies in severe case of Lyme neuroborreliosis


title: Comparative thermostability analysis of zoonotic and human influenza virus A and B neuraminidase

text: Neuraminidase (NA) thermostability of influenza A and B viruses isolated from birds, swine and humans was measured to evaluate its variability associated with host body temperature. The highest 50% inactivation temperature (IT(50)) was observed with H3N8 avian influenza virus (74 °C), and the lowest IT(50) was observed with the seasonal human H3N2 virus (45.5 °C). The IT(50) values of A(H1N1)pdm09 viruses 56.4-58.5 °C were statistically higher than that of the prepandemic strain A/Solomon Islands/03/06 (52.5 °C). An analysis of Ca(2+) binding sites revealed the correspondence of amino acid changes to NA thermostability. This study demonstrates that changes in NA thermostability correspond to differences in host body temperature.


Loneliness in Old Age: An Unaddressed Health Problem


title: Characterization of 100 extended major histocompatibility complex haplotypes in Indonesian cynomolgus macaques

text: Many medical advancements—including improvements to anti-rejection therapies in transplantation and vaccine development—rely on preclinical studies conducted in cynomolgus macaques (Macaca fascicularis). Major histocompatibility complex (MHC) class I and class II genes of cynomolgus macaques are orthologous to human leukocyte antigen complex (HLA) class I and class II genes, respectively. Both encode cell-surface proteins involved in cell recognition and rejection of non-host tissues. MHC class I and class II genes are highly polymorphic, so comprehensive genotyping requires the development of complete databases of allelic variants. Our group used PacBio circular consensus sequencing of full-length cDNA amplicons to characterize MHC class I and class II transcript sequences for a cohort of 293 Indonesian cynomolgus macaques (ICM) in a large, pedigreed breeding colony. These studies allowed us to expand the existing database of Macaca fascicularis (Mafa) alleles by identifying an additional 141 MHC class I and 61 class II transcript sequences. In addition, we defined co-segregating combinations of allelic variants as regional haplotypes for 70 Mafa-A, 78 Mafa-B, and 45 Mafa-DRB gene clusters. Finally, we defined class I and class II transcripts that are associated with 100 extended MHC haplotypes in this breeding colony by combining our genotyping analyses with short tandem repeat (STR) patterns across the MHC region. Our sequencing analyses and haplotype definitions improve the utility of these ICM for transplantation studies as well as infectious disease and vaccine research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00251-020-01159-5) contains supplementary material, which is available to authorized users.


title: Voices from the Field: Addressing Job Burnout in School Psychology Training Programs

text: Job burnout among school psychologists represents a potentially serious issue given widespread shortages of practitioners. It is then important to identify effective strategies for both preventing and responding to feelings of burnout when they occur to ultimately ensure a healthy workforce. The current study examined written responses provided by 122 practicing school psychologists in the Southeastern United States to the question, “What do you think training programs can do about the issue of burnout in school psychology.” A qualitative thematic analysis of responses resulted in the identification of three main themes: develop specific personal/professional skills, modify professional/training components, and modify administrative/organizational policies and seven associated sub-themes. Resulting themes are discussed in reference to specific recommendations training programs can take in the future to better address job burnout in the field.


title: Neonatal Organ and Tissue Donation for Research: Options Following Death by Natural Causes

text: The donation of organs and tissues from neonates (birth to 28 days) for transplantation has been a relatively infrequent occurrence. Less common has been the use of neonatal organs and tissues for research. Specific ethical and legal questions beg for rational and transparent guidelines with which to evaluate referrals of potential donors. Donation of organs and tissues from a neonate can play a key role in the care and support provided to families by health care professionals around the time of a neonate’s death. We report on the recovery of neonatal organs and tissues for research. A working group made up of bioethicists, neonatologists, lawyers, obstetric practioners as well as organ procurement and tissue banking professionals evaluated legal, ethical and medical issues. Neonatal donor family members were also consulted. Our primary goals were (a) to ensure that referrals were made in compliance with all applicable federal and state laws, regulations and institutional protocols, and (b) to follow acceptable ethical standards. Algorithms and policies designed to assist in the evaluation of potential neonatal donors were developed. Neonatal donation is proving increasingly valuable for research into areas including diabetes, pulmonary, gastrointestinal, genitourinary and neurological development, rheumatoid arthritis, autism, childhood psychiatric and neurologic disorders, treatment of MRSA infection and pediatric emergency resuscitation. The development of policies and procedures will assist medical professionals who wish to offer the option of donation to family members anticipating the death of a neonate.


title: Infection and atherosclerosis: TLR-dependent pathways

text: Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is a chronic inflammatory disease, suggesting that chronic infection plays an important role in the development of atherosclerosis. Toll-like receptors (TLRs) are the most characteristic members of pattern recognition receptors (PRRs), which play an important role in innate immune mechanism. TLRs play different roles in different stages of infection of atherosclerosis-related pathogens such as Chlamydia pneumoniae (C. pneumoniae), periodontal pathogens including Porphyromonas gingivalis (P. gingivalis), Helicobacter pylori (H. pylori) and human immunodeficiency virus (HIV). Overall, activation of TLR2 and 4 seems to have a profound impact on infection-related atherosclerosis. This article reviews the role of TLRs in the process of atherosclerosis after C. pneumoniae and other infections and the current status of treatment, with a view to providing a new direction and potential therapeutic targets for the study of ASVD.


title: Evaluation of diaphragm ultrasound in predicting extubation outcome in mechanically ventilated patients with COPD

text: BACKGROUND: To explore the value of the right hemi-diaphragmatic excursion (DE) and its variation in predicting extubation outcome in mechanically ventilated patients with COPD. METHODS: All included patients with COPD received mechanical ventilation (MV) and were ready to wean from MV. After patients passed the 30 min spontaneous breathing trail (SBT), extubation was considered to be feasible, and the right DE measured by ultrasound at 0 min, 5 min, and 30 min of SBT were named as DE(0), DE(5), and DE(30), respectively. RESULTS: Twenty-five patients succeeded extubation; 12 patients failed. The area under receiver operator characteristic curve (AUC(ROC)) of DE(30) and ΔDE(30−5) (the variation between 30 and 5 min) were 0.762 and 0.835; a cutoff value of DE(30) > 1.72 cm and ΔDE(30−5) > 0.16 cm were associated with a successful extubation with a sensitivity of 76% and 84%, a specificity of 75% and 83.3%, respectively. The predictive probability equation of the DE(30) plus ∆DE(30−5) was P = 1/[1 + e(−(−5.625+17.689×∆DE)(30−5)(+1.802×DE)(30)())], a cutoff value of P > 0.626 was associated with a successful extubation with the AUC(ROC) of 0.867, a sensitivity of 92%, and a specificity of 83.3%. CONCLUSION: The combination of DE(30) and ∆DE(30−5) could improve the predictive value and could be used as the predictor of extubation outcome in mechanically ventilated patients with COPD.


title: Vibrio harveyi: a serious pathogen of fish and invertebrates in mariculture

text: Vibrio harveyi, which belongs to family Vibrionaceae of class Gammaproteobacteria, includes the species V. carchariae and V. trachuri as its junior synonyms. The organism is a well-recognized and serious bacterial pathogen of marine fish and invertebrates, including penaeid shrimp, in aquaculture. Diseased fish may exhibit a range of lesions, including eye lesions/blindness, gastro-enteritis, muscle necrosis, skin ulcers, and tail rot disease. In shrimp, V. harveyi is regarded as the etiological agent of luminous vibriosis in which affected animals glow in the dark. There is a second condition of shrimp known as Bolitas negricans where the digestive tract is filled with spheres of sloughed-off tissue. It is recognized that the pathogenicity mechanisms of V. harveyi may be different in fish and penaeid shrimp. In shrimp, the pathogenicity mechanisms involved the endotoxin lipopolysaccharide, and extracellular proteases, and interaction with bacteriophages. In fish, the pathogenicity mechanisms involved extracellular hemolysin (encoded by duplicate hemolysin genes), which was identified as a phospholipase B and could inactivate fish cells by apoptosis, via the caspase activation pathway. V. harveyi may enter the so-called viable but nonculturable (VBNC) state, and resuscitation of the VBNC cells may be an important reason for vibriosis outbreaks in aquaculture. Disease control measures center on dietary supplements (including probiotics), nonspecific immunostimulants, and vaccines and to a lesser extent antibiotics and other antimicrobial compounds.


docid: mjibquam

title: Pediatric trauma venous thromboembolism prediction algorithm outperforms current anticoagulation prophylaxis guidelines: a pilot study

text: PURPOSE: Venous thromboembolism (VTE) in injured children is rare, but sequelae can be morbid and life-threatening. Recent trauma society guidelines suggesting that all children over 15 years old should receive thromboprophylaxis may result in overtreatment. We sought to evaluate the efficacy of a previously published VTE prediction algorithm and compare it to current recommendations. METHODS: Two institutional trauma registries were queried for all pediatric (age < 18 years) patients admitted from 2007 to 2018. Clinical data were applied to the algorithm and the area under the receiver operating characteristic (AUROC) curve was calculated to test algorithm efficacy. RESULTS: A retrospective review identified 8271 patients with 30 episodes of VTE (0.36%). The VTE prediction algorithm classified 51 (0.6%) as high risk (> 5% risk), 322 (3.9%) as moderate risk (1–5% risk) and 7898 (95.5%) as low risk (< 1% risk). AUROC was 0.93 (95% CI 0.89–0.97). In our population, prophylaxis of the ‘moderate-’ and ‘high-risk’ cohorts would outperform the sensitivity (60% vs. 53%) and specificity (96% vs. 77%) of current guidelines while anticoagulating substantially fewer patients (373 vs. 1935, p < 0.001). CONCLUSION: A VTE prediction algorithm using clinical variables can identify injured children at risk for venous thromboembolic disease with more discrimination than current guidelines. Prospective studies are needed to investigate the validity of this model. LEVEL OF EVIDENCE: III—Clinical decision rule evaluated in a single population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00383-019-04613-y) contains supplementary material, which is available to authorized users.


title: Molecular and antigenic characterization of bovine herpesvirus type 1 (BoHV-1) strains from cattle with diverse clinical cases in Turkey

text: The present study reports the molecular and antigenic characterization of 13 bovine herpesvirus type 1 (BoHV-1) field viruses obtained from cattle with different clinical cases in Turkey between 1992 and 2017. We selected glycoprotein C (gC) of BoHV-1 as a target to detect and/or verify presence of the virus in suspect materials followed by virus isolation (VI) in MDBK cells. In seven out of 13 BoHV-1 positive samples, cytophatic effects (CPEs) were observed in MDBK cell cultures, although only four virus samples reached a sufficient titer to use in phylogenetic assay, restriction endonuclease analysis (REA), and virus neutralization test (VNT). According to the results of sequence analysis of the 13 BoHV-1 positive samples, nine BoHV-1 field viruses were determined as BoHV-1.1 and four as BoHV-1.2. Using REA, we demonstrated that two of our isolated viruses could be categorized as BoHV-1.1 while the other two isolates were BoHV-1.2 subtypes. Differences between the BoHV-1.1 and BoHV-1.2 isolates were also detected in the VNT results by assaying 125 suspected serum samples after testing with isolated (KY748023, KY748022, KY748020, and KY748021) and reference viruses (BoHV-1 Cooper and BoHV-5 Texas 89). These results are indicating the need to correctly identify BoHV-1 field isolates to better understand the epidemiology and pathogenesis of infection. In addition, it would be useful to identify the subtypes circulating in the specific geographical area while determining vaccination preferences.


title: Rural–Urban Disparities in Intracerebral Hemorrhage Mortality in the USA: Preliminary Findings from the National Inpatient Sample

text: OBJECTIVES: To compare in-hospital mortality between intracerebral hemorrhage (ICH) patients in rural hospitals to those in urban hospitals of the USA. METHODS: We used the National Inpatient Sample to retrospectively identify all cases of ICH in the USA over the period 2004–2014. We used multivariable-adjusted models to compare odds of mortality between rural and urban hospitals. Joinpoint regression was used to evaluate trends in age- and sex-adjusted mortality in rural and urban hospitals over time. RESULTS: From 2004 to 2014, 5.8% of ICH patients were admitted in rural hospitals. Rural patients were older (mean [SE] 76.0 [0.44] years vs. 68.8 [0.11] years in urban), more likely to be white and have Medicare insurance. Age- and sex-adjusted mortality was greater in rural hospitals (32.2%) compared to urban patients (26.5%) (p value < 0.001). After multivariable adjustment, patients hospitalized in rural hospitals had two times the odds of in-hospital death compared to patients in urban hospitals (OR 2.07, 95% CI 1.77–2.41. p value < 0.001). After joinpoint regression, mortality declined in urban hospitals by an average of 2.8% per year (average annual percentage change, [AAPC] − 2.8%, 95% CI − 3.7 to − 1.8%), but rates in rural hospitals remained unchanged (AAPC − 0.54%, 95% CI − 1.66 to 0.58%). CONCLUSIONS: Despite current efforts to reduce disparity in stroke care, ICH patients hospitalized in rural hospitals had two times the odds of dying compared to those in urban hospitals. In addition, the ICH mortality gap between rural and urban centers is increasing. Further studies are needed to identify and reverse the causes of this disparity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-020-00950-2) contains supplementary material, which is available to authorized users.


title: C1 esterase inhibitor in pediatric cardiac surgery with cardiopulmonary bypass plays a vital role in activation of the complement system

text: Our prospective study was therefore designed to determine which part of the systemic inflammatory response after cardiac operations resulted from Cardiopulmonary bypass (CPB) in neonates and infants. After approval by the human ethical committee of the Gunma Children’s Medical Center (GCMC) and informed consent of the parents, 40 consecutive term congenital heart disease patients aged until 1 year who underwent long CPB time (> 3 h) at surgery were included in the prospective study between January 2012 and December 2014. C1 esterase inhibitor (C1-inh) drug (@Berinert) was generously provided by CSL Behring (King of Prussia, PA). The C1-inh (20 IU/kg) was given intravenously 60 min after CPB. Blood samples for complement factors were obtained before and 48 h after administration of C1-inh. Six patients did not survive and their data were not included. Of 34 patients included, median age was 6.5 months, median body weight was 6050 g, and 16 (47%) were female. According to the Mann–Whitney U test, there were no differences between the two groups concerning demographic and intraoperative data, postoperative chemical data. C1q concentration was only significant lower in patients with C1-inh non-treated group than in patients with C1-inh treated group. But, the consumption of C1q, C3, C4, CH(50), and C1-inh in patients with C1-inhibitor non-treated group was observed early postoperatively. There is a significant difference in the values before and after C1-inh treatment between the two groups. The lower value in the C1-inh-treated group is explained by the activation of the classical pathway through the replenishment of complements by C1-inh treatment. This study proposes the administration of C1-inh is an effective therapy to reduce the activation and improve the clinical capillary leak syndrome.


title: Pseudomonas syringae pv. actinidiae: Ecology, Infection Dynamics and Disease Epidemiology

text: Since 2008, the kiwifruit industry has been devastated by a pandemic outbreak of Pseudomonas syringae pv. actinidiae (Psa), the causal agent of bacterial canker. This disease has become the most significant limiting factor in kiwifruit production. Psa colonizes different organs of the host plant, causing a specific symptomatology on each of them. In addition, the systemic invasion of the plant may quickly lead to plant death. Despite the massive risk that this disease poses to the kiwifruit industry, studies focusing on Psa ecology have been sporadic, and a comprehensive description of the disease epidemiology is still missing. Optimal environmental conditions for infection, dispersal and survival in the environment, or the mechanisms of penetration and colonization of host tissues have not been fully elucidated yet. The present work aims to provide a synthesis of the current knowledge, and a deeper understanding of the epidemiology of kiwifruit bacterial canker based on new experimental data. The pathogen may survive in the environment or overwinter in dormant tissues and be dispersed by wind or rain. Psa was observed in association with several plant structures (stomata, trichomes, lenticels) and wounds, which could represent entry points for apoplast infection. Environmental conditions also affect the bacterial colonization, with lower optimum values of temperature and humidity for epiphytic than for endophytic growth, and disease incidence requiring a combination of mild temperature and leaf wetness. By providing information on Psa ecology, these data sets may contribute to plan efficient control strategies for kiwifruit bacterial canker. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00248-019-01459-8) contains supplementary material, which is available to authorized users.


title: Translational Genomics in Neurocritical Care: a Review

text: Translational genomics represents a broad field of study that combines genome and transcriptome-wide studies in humans and model systems to refine our understanding of human biology and ultimately identify new ways to treat and prevent disease. The approaches to translational genomics can be broadly grouped into two methodologies, forward and reverse genomic translation. Traditional (forward) genomic translation begins with model systems and aims at using unbiased genetic associations in these models to derive insight into biological mechanisms that may also be relevant in human disease. Reverse genomic translation begins with observations made through human genomic studies and refines these observations through follow-up studies using model systems. The ultimate goal of these approaches is to clarify intervenable processes as targets for therapeutic development. In this review, we describe some of the approaches being taken to apply translational genomics to the study of diseases commonly encountered in the neurocritical care setting, including hemorrhagic and ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and status epilepticus, utilizing both forward and reverse genomic translational techniques. Further, we highlight approaches in the field that could be applied in neurocritical care to improve our ability to identify new treatment modalities as well as to provide important information to patients about risk and prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00838-1) contains supplementary material, which is available to authorized users.


docid: cyuwuega

title: Die Urologie wird elektrisch – Elektrotherapie: Moderne Therapien zur Behandlung moderner Erkrankungen – Beispiele aus der Urologie

text: The significance of electricity for medicine in the modern industrial age should not be underestimated. Particularly in connection with neurasthenia, electrotherapeutic approaches also experienced a boom for domestic use. Thus, electrotherapy reached urology just as it was becoming established as a medical specialty. We analyzed urological manuals and textbooks and objects in the W. P. Didusch Center for Urologic History and the Museum zur Geschichte der Urologie in Berlin to present the wide range of indications for electrotherapy in the emerging field of urology from impotence to urethral strictures and try to highlight the variability of their importance over time.


title: Bacterial biopolymers: from pathogenesis to advanced materials

text: Bacteria are prime cell factories that can efficiently convert carbon and nitrogen sources into a large diversity of intracellular and extracellular biopolymers, such as polysaccharides, polyamides, polyesters, polyphosphates, extracellular DNA and proteinaceous components. Bacterial polymers have important roles in pathogenicity, and their varied chemical and material properties make them suitable for medical and industrial applications. The same biopolymers when produced by pathogenic bacteria function as major virulence factors, whereas when they are produced by non-pathogenic bacteria, they become food ingredients or biomaterials. Interdisciplinary research has shed light on the molecular mechanisms of bacterial polymer synthesis, identified new targets for antibacterial drugs and informed synthetic biology approaches to design and manufacture innovative materials. This Review summarizes the role of bacterial polymers in pathogenesis, their synthesis and their material properties as well as approaches to design cell factories for production of tailor-made bio-based materials suitable for high-value applications.


ECTES Abstracts 2020


title: Establishing Context to Build Capacity: A Qualitative Study to Determine the Feasibility, Utility, and Acceptability of a Complex Trauma Training for Psychologists Working in Urban Migrant Communities in Northern Peru

text: Across Latin America, increasing access to mental health care has become a priority. Management of common mental disorders is shifting to primary care, and community mental health centers (CMHCs) are being established to treat severe needs. In urban migrant communities on the outskirts of Trujillo, Peru, five new CMHCs have been built to treat complex mental health concerns, partially in response to high rates of domestic violence and child maltreatment. However, psychologists have no training in the treatment of interpersonal trauma. This study sought to determine the utility of such a training and identify areas for cultural adaptation. Six focus groups were conducted with CMHC psychologists. Findings revealed that, while a culturally-adapted training in trauma-focused treatment is desired, sociocultural barriers to ensuring the physical and psychological safety of the service user must be considered, as well as provider barriers including short treatment packages, insufficient physical infrastructure, and unstable work conditions.


title: A classical swine fever virus E2 fusion protein produced in plants elicits a neutralizing humoral immune response in mice and pigs

text: Classical swine fever (CSF) is one of the most important viral diseases of swine worldwide. Although live or attenuated virus vaccines have been used to control CSFV, it is difficult to distinguish vaccinated pigs from infected pigs; this leads to restrictions on import and export. Subunit vaccines based on the CSFV E2 glycoprotein have been developed using baculovirus or insect cell systems, but some weaknesses remain. Here, we describe production of an E2 recombinant protein using a Nicotiana benthamiana plant expression system. To do this, we took advantage of the ability of the swine Fc domain to increase solubility and stability of the fusion protein and to strengthen immune responses in target animals. N. benthamiana expressed high amounts of pFc2-fused E2 proteins, which were isolated and purified by affinity chromatography to yield a high pure recombinant protein in a cost-effective manner. Native-polyacrylamide gel electrophoresis and size exclusion chromatography confirmed that the pmE2:pFc2 fusion exists as a multimer rather than as a dimer. Injection of recombinant pmE2 protein into mice or piglets generated anti-pmE2 antibodies with efficient neutralizing activity against CSFV. These results suggest that a purified recombinant E2 protein produced in N. benthamiana generates high titers of neutralizing antibodies in vivo; as such, the protein could be developed as a subunit vaccine against CSFV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10529-020-02892-3) contains supplementary material, which is available to authorized users.