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Immunization with a fusion protein vaccine candidate generated from truncated peptides of human enterovirus 71 protects mice from lethal enterovirus 71 infections

BACKGROUND: Prophylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection. Children aged less than 5 years are especially susceptible to EV71 infections. In addition to the development of vaccines containing the inactivated virus, those containing virus-like particles (VLPs) with repeated antigens also constitute an effective preventive strategy for EV71 infections, with safety and productivity advantages. We previously developed a fusion protein composed with truncated peptides of the EV71 capsid protein, which assembled into spherical particles. This study aimed to assess the immunoprotective effects of this fusion protein as a vaccine candidate in a mouse model of EV71 infection. METHODS: To evaluate the protective effect of fusion protein vaccine candidate, neonatal mice born by immunized female mice, as well as normal neonatal mice immunized twice were infected with EV71 virus. Whereafter, the survival rates, clinical scores and viral loads were measured. RESULTS: The high dosage and booster immunization helped induce specific serum antibodies with high neutralization titers, which were transferred to neonatal mice, thereby facilitating effective resistance towards EV71 infection. An active immune response was also observed in neonatal mice which generated following immunization. CONCLUSIONS: The present results suggest that this fusion protein is a suitable vaccine candidate in treating EV71 infections.

Synthesis and Bioactivity Assessment of Novel Spiro Pyrazole-Oxindole Congeners Exhibiting Potent and Selective in vitro Anticancer Effects

The present work aims to design and synthesize novel series of spiro pyrazole-3,3’-oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as antiproliferative potency against selected human cancerous cell lines (i.e., breast, MCF-7; colon, HCT-116 and liver, HepG-2) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and proapoptotic protein markers. The analytical and spectral data of the all synthesized target congeners were compatible with their structures. Synthesized compounds showed diverse moderate to powerful antimicrobial and antioxidant activities. Results of MTT assay revealed that seven synthesized compounds (i.e., 11a, 11b, 12a, 12b, 13b, 13c and 13h) particularly exhibited significant cytotoxicity against the three cancerous cell lines under investigation. Ranges of IC(50) values obtained were 5.7–21.3 and 5.8–37.4 µg/mL against HCT-116 and MCF-7, respectively; which is 3.8 and 6.5-fold (based on the least IC(50) values) more significant relative to the reference chemotherapeutic drug doxorubicin. In HepG-2 cells, the analogue 13h exhibited the highest cytotoxicity with IC(50) value of 19.2µg/mL relative to doxorubicin (IC(50) = 21.6µg/mL). The observed cytotoxicity was specific to cancerous cells, as evidenced by the minimal toxicity in the noncancerous control skin-fibroblast cells. ELISA results indicated that the observed antiproliferative effect against examined cancer cell lines is mediated via engaging the activation of apoptosis as illustrated by the significant increase in proapoptotic protein markers (p53, bax and caspase-3) and reduction in the antiapoptotic marker bcl-2. Taken together, results of the present study emphasize the potential of spiro pyrazole-oxindole analogues as valuable candidate anticancer agents against human cancer cells.

Mitteilungen des Berufsverbands der Pneumologen in Baden-Württemberg

Agenda

Deep phenotyping: Embracing complexity and temporality—Towards scalability, portability, and interoperability

Remote Treatment Delivery in Response to the COVID-19 Pandemic

Resistance of Enteric Viruses on Fomites

Human enteric viruses are associated with several clinical features, especially gastroenteritis. Large amounts of these viruses can be released in the environment and spread to people. Enteric viruses are nonenveloped viruses and have displayed good survival in the environment. They can be significantly resistant in food and water but also on fomites, and this is thought to play a role in transmission, leading to sporadic cases or outbreaks. The survival of enteric viruses on fomites relies on many factors including the virus itself, fomite properties, and extrinsic environmental factors such as temperature or relative humidity. Several reports in the literature have found an association with gastroenteritis cases or outbreaks and fomites naturally contaminated by enteric viruses. However, the study of virus survival following natural contamination is challenging, and most published studies are laboratory based, using experimental contamination. In addition, recent and detailed data on the resistance of each of the main enteric viruses on fomites are scarce. Many approaches, both physical and chemical, can be used to inactivate enteric viruses, the efficacy of which depends on the virus and the disinfection conditions.

Effects of Age on Voice Onset Time and Variability in Children with Repaired Cleft Palate

OBJECTIVE: To examine the effect of age on voice onset time (VOT) and VOT variability in children with repaired cleft palate. METHODS: Twenty-two children with repaired cleft palate were allocated into two age groups: younger children (YC: n = 13) and older children (OC: n = 9). VOT measurements from monosyllabic words (/pa/, /ta/, and /ka/) and intraspeaker VOT variability estimated by coefficients of variation (CoV) of two age groups were compared. RESULTS: Age was found to have a statistically significant effect on VOT and VOT variability. Specifically, OC had significantly longer VOT (F(1,66) = 4.196, p < 0.05) and less VOT variability (F(1,66) = 6.007, p < 0.05) for English voiceless stops than YC. No statistically significant main effect for speech sample or age by speech sample interaction was observed. CONCLUSIONS: Our data supplement the existing literature by adding VOT and VOT variability information for older children/adolescents with repaired cleft palate. Findings from the study suggest VOT patterns acquired at younger age appear to be further exaggerated and stabilized during the adolescent period among children with repaired cleft palate. A future study is necessary to determine different sources of VOT variability in children with a history of cleft palate, which may have clinical therapeutic implications.

Prognostic factors for ARDS: clinical, physiological and atypical immunodeficiency

BACKGROUND: Risk factors affecting the prognosis of acute respiratory distress syndrome (ARDS) in adults were investigated. The aim was to identify new predictors for ARDS patient prognosis, including those with clinical, pathophysiological, and atypical immunodeficiency. METHODS: ARDS patients were retrospectively included. The patients were grouped and analysed according to different oxygenation index grades and prognosis, and factors influencing prognosis and survival were examined. Adolescent patients, patients with typical immunodeficiency and patients who died within 24 h after being diagnosed with ARDS were excluded. The predictive value for mortality was determined by Cox proportional hazard analysis. RESULTS: In total, 201 patients who fulfilled the Berlin definition of ARDS were included. The severity of critical illness on the day of enrolment, as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.016), Sequential Organ Failure Assessment (SOFA) score (P = 0.027), and PaO(2)/FiO(2) (P = 0.000), worsened from mild to severe ARDS cases. Compared with survivors, non-survivors were significantly older and had higher APACHE II and SOFA scores. Moreover, significantly lower lymphocyte/neutrophil ratios and leukocyte counts were found among non-survivors than survivors (P = 0.008, P = 0.012). A moderate positive correlation between the lymphocyte/neutrophil and PaO(2)/FiO(2) ratios (P = 0.023) was observed. In predicting 100-day survival in patients with ARDS, the area under the curve (AUC) for the lymphocyte/neutrophil ratio was significantly higher than those for the PaO(2)/FiO(2) ratio alone, body mass index (BMI) alone, and the lymphocyte count alone (P = 0.0062, 0.0001, and 0.0154). Age (per log(10) years), BMI < 24, SOFA score, leukocyte count, and the lymphocyte/neutrophil ratio were independent predictors of 28-day mortality in ARDS patients. Additionally, ARDS patients with a lymphocyte/neutrophil ratio < 0.0537 had increased 28-day mortality rates (P = 0.0283). Old age affected both 28-day and 100-day mortality rates (P = 0.0064,0.0057). CONCLUSIONS: Age (per log(10) years), BMI < 24, SOFA score, lymphocytes, and the lymphocyte/neutrophil ratio were independent predictors of 100-day mortality in patients with ARDS. The lymphocyte/neutrophil ratio may represent a potential molecular marker to evaluate atypical immunosuppression or impairment in patients with ARDS.

India under COVID-19 lockdown

'We will have a lot to do when this is over'

'I do not know when I will practise again'

Online resource created to support redeployed dentists

BDJ offers support to dental companies

Alternative teaching aids

Caution with NSAIDs

Initial experience of DCTs

'We are all awaiting our call to the frontline'

Head Dental Officer appointed

Remain positive and proactive

Young colleagues need support

Out of our comfort zone

Skincare experts offer advice for those wearing face masks for long periods

Mitteilungen der Gesellschaft für Gastroenterologie in NRW

Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection

Despite being a leading cause of severe respiratory disease, there remains no licensed respiratory syncytial virus (RSV) vaccine. Neutralizing antibodies reduce the severity of RSV-associated disease, but are not sufficient for preventing reinfection. In contrast, the role of memory CD8 T cells in protecting against a secondary RSV infection is less established. We recently demonstrated that high-magnitude memory CD8 T cells efficiently reduced lung viral titers following RSV infection, but induced fatal immunopathology that was mediated by IFN-γ. To evaluate the ability of RSV-specific neutralizing antibodies to prevent memory CD8 T cell-mediated immunopathology, mice with high-magnitude memory CD8 T cell responses were treated with neutralizing antibodies prior to RSV challenge. Neutralizing antibody treatment significantly reduced morbidity and prevented mortality following RSV challenge compared with IgG-treated controls. Neutralizing antibody treatment restricted early virus replication, which caused a substantial reduction in memory CD8 T cell activation and IFN-γ production, directly resulting in survival. In contrast, therapeutic neutralizing antibody administration did not impact morbidity, mortality, or IFN-γ levels, despite significantly reducing lung viral titers. Therefore, only pre-existing neutralizing antibodies prevent memory CD8 T cell-mediated immunopathology following RSV infection. Overall, our results have important implications for the development of future RSV vaccines.

Protect Healthcare Workers and Patients from COVID-19: The Experience of Two Tertiary Ophthalmology Care Referral Centers in Italy

Effectiveness comparison of indocyanine green retention test with the cirrhotic severity scoring in evaluating the pathological severity of liver cirrhosis in patients with hepatocellular carcinoma and Child-Pugh grade A liver function

BACKGROUND: Evaluating cirrhotic severity is essential for individualizing surgical modalities for patients with hepatocellular carcinoma (HCC). Our previous study proposed a non-invasive method named cirrhotic severity scoring (CSS) to stage liver cirrhosis. Indocyanine green retention rate at 15 min (ICG-R15) has been widely used for the preoperative evaluation of hepatic functional reserve; however, whether ICG-R15 is well correlated with cirrhotic severity, and especially whether comparable with CSS in predicting cirrhotic severity in HCC patients with Child-Pugh grade A liver function remains unknown. METHODS: Overall, 510 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between January 2011 and December 2014 were retrospectively studied. Cirrhotic severity was pathologically assessed using the Laennec staging system. The correlations between ICG-R15, CSS, and cirrhotic severity were analyzed. Furthermore, the performance of ICG-R15 and CSS in predicting posthepatectomy liver failure (PHLF) and 90-day mortality was compared. RESULTS: Patients with no, mild, moderate, and severe cirrhosis accounted for 15.9%, 29.2%, 35.9%, and 19.0%, respectively, in the entire cohort. ICG-R15 was found to be less than 10% in 100%, 93.3%, 86.3%, and 70.1% of the patients with no, mild, moderate, and severe cirrhosis, respectively. There was only a weak correlation between ICG-R15 and the pathological severity of liver cirrhosis (r = 0.325; P < 0.001). However, CSS showed a strong correlation with the pathological severity of liver cirrhosis (r = 0.788; P < 0.001). For those with ICG-R15 in the normal range, the accuracy of CSS in diagnosing no/mild, moderate, and severe cirrhosis was 89.1%, 72.8%, and 72.1%, respectively. In addition, CSS was superior to ICG-R15 in predicting PHLF and 90-day mortality. CONCLUSIONS: CSS was more useful than ICG-R15 in the preoperative assessment of cirrhotic severity in HCC patients with Child-Pugh grade A liver function. More studies are needed to further validate CSS in patients with different Child-Pugh grades.

Pilot test of an online training module on near-infrared spectroscopy monitoring for the randomised clinical trial SafeBoosC-III

BACKGROUND: SafeBoosC-III is an international randomised clinical trial to evaluate the effect of treatment of extremely preterm infants during the first 3 days of life based on cerebral near-infrared spectroscopy (NIRS) monitoring versus treatment and monitoring as usual. To ensure high quality of the trial intervention as well as of patient care, we have developed a multilingual web-based training program to train relevant staff and test their competence. As we enter an under-explored area of e-learning, we have conducted a pilot study on the first of the five modules comprising the web-based training program to test the feasibility of developing such a program for an international trial with limited resources. METHODS: The module in this study focuses on the principles and practice of NIRS monitoring. The pedagogical idea was to integrate training and certification. One-hundred doctors and nurses from five Neonatal Intensive Care Units across China, Spain and Denmark were invited to participate in the pilot study. Upon completion of the NIRS module, participants were invited to evaluate their experience by completing an online survey. Data from closed-ended questions were analysed using descriptive statistics while data from open-ended questions underwent thematic analysis. RESULTS: In total, 81 of 100 invited staff members entered the training module and completed the online survey. The median time and the number of questions to pass the module was 15 minutes and seven questions, respectively. Most staff found the academic level of the learning material and quiz appropriate (85% and 93% of all staff members, respectively), as well as agreeing that the module was relevant to prepare them to ‘use the NIRS device’ (90%). Thematic analysis revealed issues such as a discrepancy between learning material and quiz questions, lack of clarity, and technical issues. CONCLUSION: We provide evidence of the feasibility of developing a multilingual web-based training program for an international trial, despite challenges such as low budget, language barriers and possibly differences in the clinical training of staff. Exploring the integration of training and certification for international trials, the positive results of this study motivate further developments. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03770741. Registered 10 December 2018.

Update on Ebola Treatment Center Costs and Sustainability, United States, 2019

We surveyed 56 Ebola treatment centers (ETCs) in the United States and identified costs incurred since 2014 ($1.76 million/ETC) and sustainability strategies. ETCs reported heavy reliance on federal funding. It is uncertain if, or for how long, ETCs can maintain capabilities should federal funding expire in 2020.

New trends in Manufacturing Systems Research 2020

Update to Our Reader, Reviewer, and Author Communities—April 2020

Association of early viral lower respiratory infections and subsequent development of atopy, a systematic review and meta-analysis of cohort studies

INTRODUCTION: Existing evidence on the relationship between childhood lower respiratory tract infections (LRTI) and the subsequent atopy development is controversial. We aimed to investigate an association between viral LRTI at <5 years and the development of atopy at > 2 years. METHODS: We conducted a search at Embase, Pubmed, Web of Science, and Global Index Medicus. We collected data from the included articles. We estimated the odds ratio and the 95% confidence intervals with a random effect model. We determined factors associated with atopy development after childhood LRTI using univariate and multivariate meta-regression analyses. We recorded this systematic review at PROSPERO with the number CRD42018116955. RESULTS: We included 24 studies. There was no relationship between viral LRTI at <5 years and skin prick test-diagnosed-atopy (OR = 1.2, [95% CI = 0.7–2.0]), unknown diagnosed-atopy (OR = 0.7, [95% CI = 0.4–1.3]), atopic dermatitis (OR = 1.2, [95% CI = 0.9–1.6]), hyperreactivity to pollen (OR = 0.8, [95% CI = 0.3–2.7]), food (OR = 0.8, [95% CI = 0.3–2.5]), or house dust mite (OR = 1.1, [95% CI = 0.6–2.2]). Although not confirmed in all studies with a symmetric distribution of the 23 confounding factors investigated, the overall analyses showed that there was a relationship between childhood viral LRTI at < 5 years and serum test diagnosed-atopy (OR = 2.0, [95% CI = 1.0–4.1]), allergic rhinoconjunctivitis (OR = 1.7, [95% CI = 1.1–2.9]), hyperreactivity diagnosed by serum tests with food (OR = 5.3, [1.7–16.7]) or inhaled allergens (OR = 4.2, [95% CI = 2.1–8.5]), or furred animals (OR = 0.6, [95% CI = 0.5–0.9]). CONCLUSION: These results suggest that there is no association between viral LRTI at < 5 years and the majority of categories of atopy studied during this work. These results, however, are not confirmed for the remaining categories of atopy and more particularly those diagnosed by serum tests. There is a real need to develop more accurate atopy diagnostic tools.

Comparative characterization of flavivirus production in two cell lines: Human hepatoma-derived Huh7.5.1-8 and African green monkey kidney-derived Vero

The Flaviviridae is a family of enveloped viruses with a positive-sense single-stranded RNA genome. It contains many viruses that threaten human health, such as Japanese encephalitis virus (JEV) and yellow fever virus (YFV) of the genus Flavivirus as well as hepatitis C virus of the genus Hepacivirus. Cell culture systems highly permissive for the Flaviviridae viruses are very useful for their isolation, propagation, and diagnosis, an understanding of their biology, and the development of vaccines and antiviral agents. Previously, we isolated a human hepatoma HuH-7-derived cell clone, Huh7.5.1–8, which is highly permissive to hepatitis C virus infection. Here, we have characterized flavivirus infection in the Huh7.5.1–8 cell line by comparing with that in the African green monkey kidney-derived Vero cell line, which is permissive for a wide spectrum of viruses. Upon infection with JEV, Huh7.5.1–8 cells produced a higher amount of virus particles early in infection and were more susceptible to virus-induced cell death than Vero cells. Similar outcomes were obtained when the cells were infected with another flavivirus, YFV (17D-204 strain). Quantification of cellular and extracellular viral RNA revealed that high JEV production in Huh7.5.1–8 cells can be attributed to rapid viral replication kinetics and efficient virus release early in infection. In a plaque assay, Huh7.5.1–8 cells developed JEV plaques more rapidly than Vero cells. Although this was not the case with YFV plaques, Huh7.5.1–8 cells developed higher numbers of YFV plaques than Vero cells. Sequence analysis of cDNA encoding an antiviral RNA helicase, RIG-I, showed that Huh7.5.1–8 cells expressed not only a full-length RIG-I mRNA with a known dominant-negative missense mutation but also variants without the mutation. However, the latter mRNAs lacked exon 5/6−12, indicating functional loss of RIG-I in the cells. These characteristics of the Huh7.5.1–8 cell line are helpful for flavivirus detection, titration, and propagation.

The CD1 family and T cell recognition of lipid antigens

Abstract: For many years it was thought that T lymphocytes recognized only peptide antigens presented by MHC class I or class II molecules. Recently, it has become clear that a wide variety of lipids and glycolipids are also targets of the T cell response. This novel form of cell‐mediated immune recognition is mediated by a family of lipid binding and presenting molecules known as CD1. The CD1 proteins represent a small to moderate sized family of β2‐microglobulin‐associated transmembrane proteins that are distantly related to MHC class I and class II molecules. They are conserved in most or all mammals, and control the development and function of T cell populations that participate in innate and adaptive immune responses through the recognition of self and foreign lipid antigens. Here we review the current state of our understanding of the structure and function of CD1 proteins, and the role of CD1‐restricted T cell responses in the immune system.

Detection of blood‐transmissible agents: can screening be miniaturized?

Transfusion safety relating to blood‐transmissible agents is a major public health concern, particularly when faced with the continuing emergence of new infectious agents. These include new viruses appearing alongside other known reemerging viruses (West Nile virus, Chikungunya) as well as new strains of bacteria and parasites (Plasmodium falciparum, Trypanosoma cruzi) and finally pathologic prion protein (variant Creutzfeldt‐Jakob disease). Genomic mutations of known viruses (hepatitis B virus, hepatitis C virus, human immunodeficiency virus) can also be at the origin of variants susceptible to escaping detection by diagnostic tests. New technologies that would allow the simultaneous detection of several blood‐transmissible agents are now needed for the development and improvement of screening strategies. DNA microarrays have been developed for use in immunohematology laboratories for blood group genotyping. Their application in the detection of infectious agents, however, has been hindered by additional technological hurdles. For instance, the variability among and within genomes of interest complicate target amplification and multiplex analysis. Advances in biosensor technologies based on alternative detection strategies have offered new perspectives on pathogen detection; however, whether they are adaptable to diagnostic applications testing biologic fluids is under debate. Elsewhere, current nanotechnologies now offer new tools to improve the sample preparation, target capture, and detection steps. Second‐generation devices combining micro‐ and nanotechnologies have brought us one step closer to the potential development of innovative and multiplexed approaches applicable to the screening of blood for transmissible agents.

Letter to the editor concerning “Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version)” by Zhao et al., Journal of Orthopaedic Translation, 2019, https://doi.org/10.1016/j.jot.2019.12.004

Retinopathy of prematurity in Rwanda: a prospective multi-centre study following introduction of screening and treatment services

OBJECTIVES: To investigate risk factors for retinopathy of prematurity (ROP) in a newly established ROP screening and management programme in Rwanda, Africa. METHODS: In this multi-centre prospective study 795/2222 (36%) babies fulfilled the inclusion criteria (gestational age (GA) < 35 weeks or birth weight (BW) < 1800 g or unstable clinical course), 424 (53%) of whom were screened for ROP. 270 died before the first screening. ROP and treatment-warranted ROP were classified using the revised International Classification of ROP (2005). Data on maternal and perinatal risk factors were collected from daily neonatal notes. RESULTS: 31 babies (7.3%, CI 5.0–10.2) developed any ROP, 13 of whom (41.9%, CI 24.5–60.9) required treatment. ROP was seen in six neonates with GA > 30 weeks and BW > 1500 g, one of whom required treatment. In univariate analysis the following were associated with any ROP: increasing number of days on supplemental oxygen (OR 2.1, CI 1.5–3.0, P < 0.001), low GA (OR 3.4, CI 1.8–6.4, P < 0.001), low BW (OR 2.3, CI 1.5–3.4, P < 0.001), at least one episode of hyperglycaemia ≥ 150 mg/dl (OR 6.6, CI 2.0–21.5, P < 0.001), blood transfusion (OR 3.5, CI 1.6–7.4, P < 0.001) or sepsis (OR 3.2, CI 1.2–8.6, P = 0.01). In multivariate analysis longer exposure to supplemental oxygen (OR 2.1, CI 1.2–3.6, P = 0.01) and hyperglycaemia (OR 3.5, CI 1.0–12.4, P = 0.05) remained significant. CONCLUSIONS: ROP has become an emerging health problem in Rwanda, requiring programmes for screening and treatment. ROP screening is indicated beyond the 2013 American Academy guidelines. Improved quality of neonatal care, particularly oxygen delivery and monitoring is needed.

Coronaviridae1

The family Coronavirtdae comprises a monogeneric group of 11 viruses which infect vertebrates. The main characteristics of the member viruses are: (i) Morphological: Enveloped pleomorphic particles typically 100 nm in diameter (range 60-220 nm), bearing about 20 nm long club-shaped surface projections, (ii) Structural: A single-stranded infectious molecule of genomic RNA of about (5-7) × 10(6) molecular weight. A phosphorylated nucleocapsid protein [mol.wt. (50-60) × 10(3)] complexed with the genome as a helical ribonucleoprotein; a surface (peplomer) protein, associated with one or two glycosylated polypeptides [mol.wt. (90-180) × 10(3)]; a transmembrane (matrix) protein, associated with one polypeptide which may be glycosylated to different degrees [mol.wt. (20-35) × 10(3)]. (iii) Replicative: Production in infected cells of multiple 3′ coterminal sub genomic mRNAs extending for different lengths in the 5′ direction. Virions bud intracytoplasmically. (iv) Antigenic: 3 major antigens, each corresponding to one class of virion protein, (v) Biological: Predominantly restricted to infection of natural vertebrate hosts by horizontal transmission via the fecal/oral route. Responsible mainly for respiratory and gastrointestinal disorders.

Predictive factors for successful INTELLiVENT-ASV® use: a retrospective observational study

BACKGROUND: INTELLiVENT-ASV® (I-ASV) is a closed-loop ventilation mode that automatically controls the ventilation settings. Although a number of studies have reported the usefulness of I-ASV, the clinical situations in which it may be useful have not yet been clarified. We aimed to report our initial 3 years of experience using I-ASV, particularly the clinical conditions and the technical and organizational factors associated with its use. Furthermore, we evaluated the usefulness of I-ASV and determined the predictive factors for successful management with I-ASV. METHODS: This single-center, retrospective observational study included patients who were ventilated using the Hamilton G5® ventilator (Hamilton Medical AG, Rhäzüns, Switzerland) from January 2016 to December 2018. The patients were categorized into the “I-ASV success” group and “I-ASV failure” group (those receiving mechanical ventilation with I-ASV along with any other mode). Multivariate analysis was performed to identify factors associated with successful I-ASV management. RESULTS: Of the 189 patients, 135 (71.4%) were categorized into the I-ASV success group. In the I-ASV success group, the reasons for ICU admission included post-elective surgery (94.1%), post-emergent surgery (81.5%), and other medical reasons (55.6%). I-ASV failure was associated with a low P/F ratio (278 vs. 167, P = 0.0003) and high Acute Physiology and Chronic Health Evaluation (APACHE) II score (21 vs. 26, P < 0.0001). The main reasons for not using I-ASV included strong inspiratory effort and asynchrony. The APACHE II score was an independent predictive factor for successful management with I-ASV, with an odds ratio of 0.92 (95% confidential interval 0.87–0.96, P = 0.0006). The area under the receiver operating curve for the APACHE II score was 0.722 (cut-off: 24). CONCLUSIONS: In this study, we found that 71.4% of the fully mechanically ventilated patients could be managed successfully with I-ASV. The APACHE II score was an independent factor that could help predict the successful management of I-ASV. To improve I-ASV management, it is necessary to focus on patient-ventilator interactions.

Effect of mechanical ventilation versus spontaneous breathing on abdominal edema and inflammation in ARDS: an experimental porcine model

BACKGROUND: Mechanical ventilation (MV), compared to spontaneous breathing (SB), has been found to increase abdominal edema and inflammation in experimental sepsis. Our hypothesis was that in primary acute respiratory distress syndrome (ARDS) MV would enhance inflammation and edema in the abdomen. METHODS: Thirteen piglets were randomized into two groups (SB and MV) after the induction of ARDS by lung lavage and 1 h of injurious ventilation. 1. SB: continuous positive airway pressure 15 cmH(2)O, fraction of inspired oxygen (FIO(2)) 0.5 and respiratory rate (RR) maintained at about 40 cycles min(− 1) by titrating remifentanil infusion. 2. MV: volume control, tidal volume 6 ml kg(− 1), positive end-expiratory pressure 15 cmH(2)O, RR 40 cycles min(− 1), FIO(2) 0.5. Main outcomes: abdominal edema, assessed by tissues histopathology and wet-dry weight; abdominal inflammation, assessed by cytokine concentration in tissues, blood and ascites, and tissue histopathology. RESULTS: The groups did not show significant differences in hemodynamic or respiratory parameters. Moreover, edema and inflammation in the abdominal organs were similar. However, blood IL6 increased in the MV group in all vascular beds (p < 0.001). In addition, TNFα ratio in blood increased through the lungs in MV group (+ 26% ± 3) but decreased in the SB group (− 17% ± 3). CONCLUSIONS: There were no differences between the MV and SB group for abdominal edema or inflammation. However, the systemic increase in IL6 and the TNFα increase through the lungs suggest that MV, in this model, was harmful to the lungs.

Leptospirosis as an important differential of pulmonary haemorrhage on the intensive care unit: a case managed with VV-ECMO

BACKGROUND: Leptospirosis is a potentially fatal zoonosis. It can cause a wide range of symptoms, including diffuse alveolar haemorrhage which occurs in a minority of cases but carries a mortality of over 70%. These patients may present with severe acute respiratory failure. The differential diagnosis for diffuse alveolar haemorrhage is broad whereas prompt diagnosis and treatment can be lifesaving. CASE PRESENTATION: A 20-year-old previously fit and well trout farm worker presented with a 3-day history of malaise, fevers, diarrhoea, vomiting and jaundice. He developed haemoptysis, severe headaches, neck stiffness and photophobia on the day of emergency admission. He was anaemic and thrombocytopenic. Anuric acute kidney injury (urea 32, creat 507) required immediate haemofiltration. In view of progressive respiratory failure with four-quadrant lung infiltrates on imaging, he was given broad spectrum antibiotics and pulsed methylprednisolone empirically, in case of a vasculitic pulmonary-renal presentation. He was intubated within 48 h of admission. Despite attempted protective ventilatory management, he remained hypoxaemic and developed pneumomediastinum. He was retrieved to a specialist cardiorespiratory intensive care unit on femoro-femoral mobile VV-ECMO. Three days from admission, results showed positive Leptospira IgM and real-time PCR. Serial bronchoscopies showed old and fresh clots, but not the classical progressive late red tinge of the returned lavage fluid. After eight days, VV-ECMO was weaned, he was extubated three days later, and made a full recovery. At 9 months follow-up, he was clinically better, with resolution of the CT scan findings and near normal lung function, albeit with low normal gas transfer. CONCLUSIONS: Leptospirosis is a rare but important differential to be considered in diffuse alveolar haemorrhage presenting to the ICU, especially in young males. A thorough history for occupational or recreational risk factors may offer the diagnostic clue. Most patients recover fully with antibiotics. However, resulting acute severe respiratory failure can ensue. In this situation, early consideration for respiratory ECMO support offers time for clearance of endobronchial clot, parenchymal recovery, and prevention of ventilator-induced lung injury. Steroids have no clear evidence but may be used to avoid delay in treating suspected vasculitic or autoimmune causes of diffuse alveolar haemorrhage.

Low occurrence of extended-spectrum cephalosporinase producing Enterobacteriaceae and no detection of methicillin-resistant coagulase-positive staphylococci in healthy dogs in Sweden

Sweden has a long tradition of monitoring occurrence of antibiotic resistant bacteria in both animals and humans, but there currently is no organised and harmonized monitoring on carriage of Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL), plasmid-mediated AmpC beta-lactamase (pAmpC), or methicillin-resistant coagulase positive staphylococci e.g. methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs. The aim of the current study was therefore to determine the prevalence of ESBL/pAmpC producing Enterobacteriaceae and methicillin-resistant coagulase positive staphylococci in healthy dogs in Sweden, and to phenotypically and genotypically characterize any identified isolates. It was shown that 0.9% (95% confident interval 0.3–2.7%) of the dogs (n = 325) carried multi-resistant ESBL-producing Escherichia coli, but that no methicillin-resistant coagulase positive staphylococci could be detected. In conclusion, the occurrence of multi-drug resistant bacteria remains rare among healthy dogs in Sweden. In addition, the ESBL-producing E. coli identified showed genetic characteristics related to those reported from humans.

Diagnostic Experience from an Epidemic of Canine Parvoviral Enteritis

SUMMARY: Hemagglutination (HA) test and electron microscopy (EM) were used to diagnose canine parvoviral enteritis on fecal samples from 58 hospitalized dogs of a huge epidemic. By HA‐tests the presence of the canine parvovirus (CPV) involved was shown in samples from 15 dogs (∼ 26%). A reference antiserum was used to identify the virus of each sample by hemagglutination inhibition (HI). By EM parvovirus‐like particles were seen in samples from 28 dogs (∼ 48%). Particles in six samples were identified as CPV by immunoaggregation. Sera from 17 out of 19 dogs examined showed specific HI titers during the acute stage of illness. A high incidence of concomitant infection with Campylobacter spp was found by the bacteriologists. ZUSAMMENFASSUNG: Diagnostische Erfahrungen während einer Epidemie von Parvovirus‐Enteritis der Hunde Während einer grossen Epidemie von Parvovirus‐Enteritis der Hunde (in Schweden) wurde der Nachweis von Virus in Kotproben mit Hilfe der Hëmagglutination (HA) und Elektronenmikroskopie (EM) versucht; die Kotproben stammten von 58 hospitalisierten Hunden. Mit dem HA‐Test ließ sich das ursächliche Parvovirus in den Proben von 15 Hunden nachweisen (= ∼ 26%). In jeder von diesen Proben wurde das Virus durch Hämagglutination‐Hemmung (HAH) mit einem Referenzserum identifiziert. Mit der EM waren Parvovirus‐ähnliche Partikel in den Proben von 28 Hunden zu finden (= ∼ 48%). In 6 von diesen Proben wurden die Partikel mittels der Immunaggregation als das ursächlichen Parvovirus identifiziert. In 17 Serumproben von 19 untersuchten Hunden wurden spezifische HAH‐Titer während der akuten Krankheitsphase festgestellt. Die Bakteriologen wiesen ein gehäuftes Vorkommen von gleichzeitiger Infektion mit Campylobacter spp nach. RÉSUMÉ: Expériences de diagnostic durant une épidémie d'entérite à Parvovirus chez des chiens On a recherché la mise en évidence du virus dans des matières fécales à l'aide de l'hémagglutination (HA) et de la microscopie électronique (EM) durant une forte épidémie d'entérite à Parvovirus chez des chiens en Suède. Les échantillons d'excréments provenaient de 58 chiens hospitalisés. Le Parvovirus a été mis en évidence par test HA dans les échantillons de 15 chiens (∼ 26%). Le virus a été identifié dans chacun de ces échantillons au moyen de l'inhibition de l'hémagglutination (HAH) avec un sérum de référence. On a trouvé des particules identiques au microscope électronique dans les échantillons de 28 chiens (∼ 48%). Les particules dans 6 de ces prélèvements furent identifiées comme Parvovirus au moyen de l'immunoaggrégation. Un titre HAH spécifique a été établi durant la phase aiguë de la maladie dans 17 échantillons sérologiques sur 19 chiens examinés. La bactériologie a montré la présence fréquente d'une infection simultanée à Campylobacter spp. RESUMEN: Experiencias en el diagnóstico de una epidemia de parvovirus‐enteritis en caninos Mediante pruebas de hemaglutinación y microscopía electrónica se diagnosticó parvovirus‐enteritis en caninos en muestras fecales de 58 caninos hospitalizados a raiz de una extensa epidemia. Con la prueba de hemaglutinación se detectó la presencia de virus en muestras fecales de 15 caninos (∼ 26%). Un antisuero de referencia se utilizó para la identificación del virus (prueba de inhibición de la hemaglutinación). Con microscopía electrónica se identificó parvovirus en muestras fecales de 28 caninos (∼ 48%). El virus fué identificado en seis muestras fecales utilizando la prueba de inmunoagregación. Sueros de 17 de 19 caninos examinados demostraron títulos específicos de inhibición de la hemaglutinación durante la etapa aguda de la enfermedad. Se demostró también una alta incidencia de infección concomitante con Campylobacter spp.

Telehealth’s Time Has Come

Bladder Cancer Guidelines: Let Not the Cure Be Worse than the Disease

The Wuhan COVID-19 intubation experience

Infektionsschutzrecht nach Inkrafttreten des Masernschutzgesetzes

On 1 March 2020, the amendments to the German Protection Against Infection Act that were introduced by the act to protect against measles and strengthen vaccination prevention (Measles Protection Act) entered into force. The reason for the changes is that the number of individuals with measles has significantly increased in recent years. To protect public health, the Measles Protection Act has implemented regulations requiring that persons in certain institutions must either have adequate protection against measles or have immunity to measles. In this article the current legal situation with regard to health care facilities is presented.

Safety Considerations in the Laboratory Testing of Specimens Suspected or Known to Contain the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study

Inhaltsverzeichnis

COVID-19: Keine Entwarnung im Sommer?

Hydrops fetalis and neonatal abdominal compartment syndrome continuum from immature gastric teratoma: a case report

BACKGROUND: Hydrops fetalis as well as abdominal compartment syndrome (ACS) are conditions that are associated with high mortality rates. A rare case of immature gastric teratoma causing fetal hydrops and subsequent ACS is presented. The related pathophysiologic mechanisms are discussed, and the importance of timely recognition and appropriate interventions are highlighted. CASE PRESENTATION: The male patient was born preterm, weighing 3.9 kg., by Cesarean section. Prior prenatal ultrasounds were normal, but a scan done just before delivery had findings indicating polyhydramnios, fetal ascites, and meconium peritonitis. Upon delivery, the patient had respiratory distress, anasarca and a massively distended abdomen. Resuscitation measures, including ventilatory support, were instituted. Imaging studies showed ascites as well as a large, complex intra-abdominal lesion with calcifications. In the succeeding hours, anuria persisted, anasarca worsened, the abdomen became more distended, and inotrope requirements increased. The occurrence of ACS, from what was presumed to be a retroperitoneal teratoma, was therefore considered. Laparotomy was done on the 28th hour of life, with en bloc excision of a massive tumor and attached section of the greater curvature of the stomach. Passage of urine occurred intra-operatively, and the patient was soon after weaned off inotropes and ventilator support. The histopathologic result was immature gastric teratoma. No chemotherapy was given, and the patient’s serum AFP is at normal levels 15 months following surgery. CONCLUSION: The presence of a massive intra-abdominal lesion can result in the pathophysiologic continuum of hydrops fetalis and neonatal ACS. The early recognition of such an association can enable appropriate expectant management of similarly affected neonates, including emergent decompression laparotomy.

Noninvasive oxygenation strategies in adult patients with acute respiratory failure: a protocol for a systematic review and network meta-analysis

BACKGROUND: Acute hypoxemic respiratory failure is one of the leading causes of intensive care unit admission and is associated with high mortality. Noninvasive oxygenation strategies such as high-flow nasal cannula, standard oxygen therapy, and noninvasive ventilation (delivered by either face mask or helmet interface) are widely available interventions applied in these patients. It remains unclear which of these interventions are more effective in decreasing rates of invasive mechanical ventilation and mortality. The primary objective of this network meta-analysis is to summarize the evidence and compare the effect of noninvasive oxygenation strategies on mortality and need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure. METHODS: We will search key databases for randomized controlled trials assessing the effect of noninvasive oxygenation strategies in adult patients with acute hypoxemic respiratory failure. We will exclude studies in which the primary focus is either acute exacerbations of chronic obstructive pulmonary disease or cardiogenic pulmonary edema. The primary outcome will be all-cause mortality (longest available up to 90 days). The secondary outcomes will be receipt of invasive mechanical ventilation (longest available up to 30 days). We will assess the risk of bias for each of the outcomes using the Cochrane Risk of Bias Tool. Bayesian network meta-analyses will be conducted to obtain pooled estimates of head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and 95% credible intervals. Subgroup analyses will be conducted examining key populations including immunocompromised hosts. Sensitivity analyses will be conducted by excluding those studies with high risk of bias and different etiologies of acute respiratory failure. We will assess certainty in effect estimates using GRADE methodology. DISCUSSION: This study will help to guide clinical decision-making when caring for adult patients with acute hypoxemic respiratory failure and improve our understanding of the limitations of the available literature assessing noninvasive oxygenation strategies in acute hypoxemic respiratory failure. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121755

Age Limit in Bronchiolitis Diagnosis: 6 or 12 Months?

Aim: The most frequent cause of lower respiratory tract infection in infants is bronchiolitis. Up to now there is no agreement on the upper limit age of bronchiolitis. Our aim was to identify if there are clinical differences in infants hospitalized for bronchiolitis between 0–6 months and 6–12 months of age. A secondary aim was to establish whether there was differences in terms of recurrent wheezing at 12, 24, and 36 months of follow-up. Methods: We retrospectively analyzed clinical and virological records of 824 infants hospitalized for bronchiolitis during 11 consecutive epidemic seasons. From each infant at admission to the hospital nasopharyngeal washing was collected, clinical severity was assessed and clinical data were extracted from a structured questionnaire. At 12–24–36 months after discharge, parents were interviewed seeking information on recurrent wheezing. Results: A total of 773 infants (Group1) were ≤6 months of age, while 51 were >6 months (Group 2). No differences between family history for atopy and passive smoking exposure were observed between the two groups. Respiratory syncyzial virus was detected more frequently in Group 1 and human bocavirus in Group 2. The clinical severity score (p = 0.011) and the use of intravenous fluids (p = 0.0001) were higher in Group 1 with respect to Group 2 infants. At 36 months follow-up 163/106 (39.4%) Group 1 and 9/9 Group 2 infants experienced recurrent wheezing (p = 0.149). Conclusion: We demonstrated that 0-6 months old infants bronchiolitis differs from > 6 months bronchiolitis.

Esperanza de vida al nacer. Contribuciones y desafíos de la microbiología

Immunocytochemical Localization of the Menkes Copper Transport Protein (ATP7A) to the Trans-Golgi Network

We have generated polyclonal antibodies against the amino-terminal third of the Menkes protein (ATP7A; MNK) by immunizing rabbits with a histidine-tagged MNK fusion construct containing metal-binding domains 1–4. The purified antibodies were used in Western analysis of cell lysates and in indirect immunofluorescence experiments on cultured cells. On Western blots, the antibodies recognized the ∼165 kDa MNK protein in CHO cells and human fibroblasts. No MNK signal could be detected in fibroblasts from a patient with Menkes disease or in Hep3B hepatocellular carcinoma cells, confirming the specificity of the antibodies. Immunocytochemical analysis of CHO cells and human fibroblasts showed a distinct perinuclear signal corresponding to the pattern of the Golgi complex. This staining pattern was similar to that of α-mannosidase II which is a known resident enzyme of the Golgi complex. Using brefeldin A, a fungal inhibitor of protein secretion, we further demonstrated that the MNK protein is localized to the trans-Golgi network. This data provides direct evidence for a subcellular localization of the MNK protein which is similar to the proposed vacuolar localization of Ccc2p, the yeast homolog of MNK and WND (ATP7B), the Wilson disease gene product. In light of the proposed role of MNK both in subcellular copper trafficking and in copper efflux, these data suggest a model for how these two processes are linked and represent an important step in the functional analysis of the MNK protein.

Confronting infectious diseases is a perpetual struggle, top official says

Amenity Migration and Public Lands: Rise of the Protected Areas

Rural amenity migration, or the relocation for quality of life purposes as opposed to monetary enhancement, has been occurring for decades and has been particularly pronounced in the American West where the phenomenon peaked in the 1990s. Researchers have illustrated that some places are more attractive for migrants than others and that certain regional amenities hold considerable influence on where migrants relocate. Increased migration levels typically result in increased economic growth indicators, making amenity migration an attractive rural development strategy. But comprehensive econometric analysis focused on amenity migration in the American West has been lacking. To address this, we conducted an econometric analysis of attributes that influenced migration to rural Western counties from 1980 to 2010. Over 20 potential amenity supply categories were collated for 356 rural counties from 11 Western states, with a focus on public lands. Descriptive statistics and OLS regressions were estimated and interpreted. Traditional amenities of climate, water area, and regional access were highly associated with migration levels, while designated natural amenities of Wilderness and National Monuments were the most influential public lands for migration to rural Western counties. Farming and oil and gas dependency were negatively associated with migration levels. Increasing the amount of protected areas, and branding campaigns based on natural amenities, can be a critical development strategy for rural communities.

Harnessing Cross-Reactive CD8(+) T(RM) Cells for Long-Standing Protection Against Influenza A Virus

Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN

CIRE/mDC-SIGN is a C-type lectin we originally identified as a molecule differentially expressed by mouse dendritic cell (DC) populations. Immunostaining with a CIRE/mDC-SIGN-specific mAb revealed that CIRE/mDC-SIGN is indeed on the surface of some CD4(+), CD4(−)8(−) DCs and plasmacytoid pre-DCs, but not on CD8(+) DCs. It has been proposed that CIRE/mDC-SIGN is the functional orthologue of human DC-SIGN (hDC-SIGN), a molecule that both enhances T cell responses and facilitates antigen uptake. We assessed if CIRE/mDC-SIGN and hDC-SIGN exhibit functional similarities. CIRE/mDC-SIGN is down-regulated upon activation, but unlike hDC-SIGN, incubation with IL-4 and IL-13 did not enhance CIRE/mDC-SIGN expression, indicating differences in gene regulation. Like hDC-SIGN, CIRE/mDC-SIGN bound mannosylated residues. However, we could detect no role for CIRE/mDC-SIGN in T cell–DC interactions and the protein did not bind to pathogens known to interact with hDC-SIGN, including Leishmania mexicana, cytomegalovirus, HIV and lentiviral particles bearing the Ebolavirus glycoprotein. The binding of CIRE/mDC-SIGN to hDC-SIGN ligands was not rescued when CIRE/mDC-SIGN was engineered to express the stalk region of hDC-SIGN. We conclude that there are significant differences in the fine specificity of the C-type lectin domains of hDC-SIGN and CIRE/mDC-SIGN and that these two molecules may not be functional orthologues.

Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9

Remyelination failure plays an important role in the pathophysiology of multiple sclerosis, but the underlying cellular and molecular mechanisms remain poorly understood. We now report actively demyelinating lesions in patients with multiple sclerosis are associated with increased glial expression of fibroblast growth factor 9 (FGF9), which we demonstrate inhibits myelination and remyelination in vitro. This inhibitory activity is associated with the appearance of multi-branched ‘pre-myelinating’ MBP(+)/PLP(+) oligodendrocytes that interact with axons but fail to assemble myelin sheaths; an oligodendrocyte phenotype described previously in chronically demyelinated multiple sclerosis lesions. This inhibitory activity is not due to a direct effect of FGF9 on cells of the oligodendrocyte lineage but is mediated by factors secreted by astrocytes. Transcriptional profiling and functional validation studies demonstrate that these include effects dependent on increased expression of tissue inhibitor of metalloproteinase-sensitive proteases, enzymes more commonly associated with extracellular matrix remodelling. Further, we found that FGF9 induces expression of Ccl2 and Ccl7, two pro-inflammatory chemokines that contribute to recruitment of microglia and macrophages into multiple sclerosis lesions. These data indicate glial expression of FGF9 can initiate a complex astrocyte-dependent response that contributes to two distinct pathogenic pathways involved in the development of multiple sclerosis lesions. Namely, induction of a pro-inflammatory environment and failure of remyelination; a combination of effects predicted to exacerbate axonal injury and loss in patients.

Perspectives on Fatigue from the Study of Chronic Fatigue Syndrome and Related Conditions

Fatigue is a symptom whose causes are protean and whose phenotype includes physical, mood, and behavioral components. Chronic fatigue syndrome (CFS) is an illness that has strong biological underpinnings and no definite etiology. Diagnostic criteria established by the Centers for Disease Control and Prevention have helped classify CFS as an overlap of mood, behavioral, and biological components. These include the presence of fatigue for more than 6 months associated with a diminution of functional activity and somatic symptoms, and pain not attributable to a specific diagnosis or disease. Four of the following criteria need to be present: sore throat, impaired memory or cognition, unrefreshing sleep, postexertional fatigue, tender glands, aching stiff muscles, joint pain, and headaches. Many researchers have observed that CFS shares features in common with other somatic syndromes, including irritable bowel syndrome, fibromyalgia, and temporomandibular joint dysfunction. Correlations between inflammation and infection, augmented sensory processing, abnormalities of neurotransmitters, nerve growth factors, low levels of serotonin and norepinephrine, abnormalities of homeostasis of the stress system, and autonomic dysfunction may be hallmarks of CFS. The relative contributions of each of these abnormalities to the profound fatigue associated with CFS need to be explored further to better evaluate and treat the syndrome.

Pediatric Patient Safety in the Ambulatory Setting

LRRK2 Expression in Normal and Pathologic Human Brain and in Human Cell Lines

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been recently identified in families with autosomal-dominant late-onset Parkinson disease. We report that by reverse transcriptase-polymerase chain reaction, the mRNA of LRRK2 is expressed in soluble extracts of human brain, liver, and heart and in cultured human astrocytes, microglia, and oligodendroglia as well as in human neuroblastoma cell lines. We find by Western blotting using a polyclonal antibody of the leucine-rich repeat kinase 2 protein (Lrrk2) specific for C-terminal residues 2511-2527 that an apparent full-length protein and several of its fractions are expressed in soluble extracts of normal human brain. By immunocytochemistry, the antibody recognizes neurons, and more weakly astrocytes and microglia, in normal brain tissue. It intensely labels Lewy bodies in Parkinson disease and related neurodegenerative disorders. It also labels a subset of neurofibrillary tangles in Alzheimer disease and the Parkinsonism dementia complex of Guam (PDCG). It labels thorn-shaped astrocytes and oligodendroglial coiled bodies in PDCG; oligodendroglial inclusions in multiple system atrophy; Pick bodies in Pick disease; nuclear and cytoplasmic inclusions in Huntington disease; and intraneuronal and glial inclusions in amyotrophic lateral sclerosis. In summary, LRRK2 is constitutively expressed in neurons and also in glial cells of human brain. It strongly associates with pathological inclusions in several neurodegenerative disorders.

Similarity relations of DNA and RNA polymerases investigated by the principal component analysis of amino acid sequences

The principal component analysis based on the physicochemical properties of amino acid residues is applied to DNA and RNA polymerases to assign the sequence motifs for the polymerization activities of these proteins. After the reconfirmation of the sequence motifs of families A and B of DNA polymerases indicated previously, it elucidates the sequence motifs for the polymerization activity of DNA polymerase III (family C) by the similarity to the polymerization center of multimeric DNA dependent RNA polymerases. This identification proceeds to clarify the sequence motifs for polymerization activities of primases; eukaryotic and archaebacterial primases carry motifs similar to those of family C, while the motifs of eubacterial primase fall into the category of the motifs in family B DNA polymerases such as α, δ, ϵ and II. This finding means that DNA dependent RNA polymerases are also divided into groups corresponding to three families, A, B and C, because the monomeric DNA dependent RNA polymerases in phages are reconfirmed to carry sequence motifs similar to those of family A DNA polymerases. Furthermore, the three families of polymerization motifs are found to fall within the variation range of polymerization motifs displayed by many RNA dependent RNA polymerases, suggesting a close evolutionary relation between them. The sequence motifs for polymerization activities of reverse transcriptase and telomerase seem to be the intermediate between family A DNA polymerase and some RNA dependent RNA polymerases, e.g., from Leviviridae. On the contrary, the sequence fragments similar to the nucleotidyltransferase superfamily including DNA polymerase β are not found in any RNA dependent RNA polymerase, suggesting their other lineage of polymerization motifs.

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Editorial statement

Regional Lung Perfusion as Determined by Electrical Impedance Tomography in Comparison With Electron Beam CT Imaging

The aim of the experiments was to check the feasibility of pulmonary perfusion imaging by functional electrical impedance tomography (EIT) and to compare the EIT findings with electron beam computed tomography (EBCT) scans. In three pigs, a Swan-Ganz catheter was positioned in a pulmonary artery branch and hypertonic saline solution or a radiographic contrast agent were administered as boli through the distal or proximal openings of the catheter. During the administration through the proximal opening, the balloon at the tip of the catheter was either deflated or inflated. The latter case represented a perfusion defect. The series of EIT scans of the momentary distribution of electrical impedance within the chest were obtained during each saline bolus administration at a rate of 13/s. EBCT scans were acquired at a rate of 3.3/s during bolus administrations of the radiopaque contrast material under the same steady-state conditions. The EIT data were used to generate local time-impedance curves and functional EIT images showing the perfusion of a small lung region, both lungs with a perfusion defect and complete both lungs during bolus administration through the distal and proximal catheter opening with an inflated or deflated balloon, respectively. The results indicate that EIT imaging of lung perfusion is feasible when an electrical impedance contrast agent is used.

Reassortment Networks and the Evolution of Pandemic H1N1 Swine-Origin Influenza

Prior research developed Reassortment Networks to reconstruct the evolution of segmented viruses under both reassortment and mutation. We report their application to the swine-origin pandemic H1N1 virus (S-OIV). A database of all influenza A viruses, for which complete genome sequences were available in Genbank by October 2009, was created and dynamic programming was used to compute distances between all corresponding segments. A reassortment network was created to obtain the minimum cost evolutionary paths from all viruses to the exemplar S-OIV A/California/04/2009. This analysis took 35 hours on the Cray Extreme Multithreading (XMT) supercomputer, which has special hardware to permit efficient parallelization. Six specific H1N1/H1N2 bottleneck viruses were identified that almost always lie on minimum cost paths to S-OIV. We conjecture that these viruses are crucial to S-OIV evolution and worthy of careful study from a molecular biology viewpoint. In phylogenetics, ancestors are typically medians that have no functional constraints. In our method, ancestors are not inferred, but rather chosen from previously observed viruses along a path of mutation and reassortment leading to the target virus. This specificity and functional constraint render our results actionable for further experiments in vitro and in vivo.

System for Infectious Disease Information Sharing and Analysis: Design and Evaluation

Motivated by the importance of infectious disease informatics (IDI) and the challenges to IDI system development and data sharing, we design and implement BioPortal, a Web-based IDI system that integrates cross-jurisdictional data to support information sharing, analysis, and visualization in public health. In this paper, we discuss general challenges in IDI, describe BioPortal's architecture and functionalities, and highlight encouraging evaluation results obtained from a controlled experiment that focused on analysis accuracy, task performance efficiency, user information satisfaction, system usability, usefulness, and ease of use.

Design and Control of a Mechatronic Tracheostomy Tube for Automated Tracheal Suctioning

Goal: Mechanical ventilation is required to aid patients with breathing difficulty to breathe more comfortably. A tracheostomy tube inserted through an opening in the patient neck into the trachea is connected to a ventilator for suctioning. Currently, nurses spend millions of person-hours yearly to perform this task. To save significant person-hours, an automated mechatronic tracheostomy system is needed. This system allows for relieving nurses and other carers from the millions of person-hours spent yearly on tracheal suctioning. In addition, it will result in huge healthcare cost savings. Methods: We introduce a novel mechatronic tracheostomy system including the development of a long suction catheter, automatic suctioning mechanisms, and relevant control approaches to perform tracheal suctioning automatically. To stop the catheter at a desired position, two approaches are introduced: 1) Based on the known travel length of the catheter tip; 2) Based on a new sensing device integrated at the catheter tip. It is known that backlash nonlinearity between the suction catheter and its conduit as well as in the gear system of the actuator are unavoidable. They cause difficulties to control the exact position of the catheter tip. For the former case, we develop an approximate model of backlash and a direct inverse scheme to enhance the system performances. The scheme does not require any complex inversions of the backlash model and allows easy implementations. For the latter case, a new sensing device integrated into the suction catheter tip is developed and backlash compensation controls are avoided. Results: Automated suctioning validations are successfully carried out on the proposed experimental system. Comparisons and discussions are also introduced. Significance: The results demonstrate a significant contribution and potential benefits to the mechanical ventilation areas.

Automatic Control of Arterial Carbon Dioxide Tension in Mechanically Ventilated Patients

This paper presents a method of controlling the arterial carbon dioxide tension of patients receiving mechanical ventilation. Controlling of the CO(2) tension is achieved by regulating the ventilator initiated breath frequency and also volume per breath.

Temporal and Spatial Monitoring and Prediction of Epidemic Outbreaks

This paper introduces a nonlinear dynamic model to study spatial and temporal dynamics of epidemics of susceptible-infected-removed type. It involves modeling the respective collections of epidemic states and syndromic observations as random finite sets. Each epidemic state consists of the number of infected individuals in an isolated population system and the corresponding partially known parameters of the epidemic model. The infectious disease could spread between population systems with known probabilities based on prior knowledge of ecological and biological features of the environment. The problem is then formulated in the context of Bayesian framework and estimated via a probability hypothesis density filter. Each population system under surveillance is assumed to be homogenous and fixed, with daily reports on the number of infected people available for monitoring and prediction. When model parameters are partially known, results of numerical studies indicate that the proposed approach can help early prediction of the epidemic in terms of peak and duration.

Characterization and Use of a Fiber Optic Sensor Based on PAH/SiO(2) Film for Humidity Sensing in Ventilator Care Equipment

Objective: To develop a compact probe that can be used to monitor humidity in ventilator care equipment. A mesoporous film of alternate layers of Poly(allylamine hydrochloride) (PAH) and silica (SiO2) nanoparticles (bilayers), deposited onto an optical fibre was used. The sensing film behaves as a Fabry-Perot cavity of low-finesse where the absorption of water vapour changes the optical thickness and produces a change in reflection proportional to humidity. Methods: The mesoporous film was deposited upon the cleaved tip of an optical fibre using the layer-by-layer method. The sensor was calibrated in a bench model against a commercially available capacitive sensor. The sensitivity and response time were assessed in the range from 5 % relative humidity (RH) to 95%RH for different numbers of bilayers up to a maximum of nine. Results: The sensitivity increases with the number of bilayers deposited; sensitivity of 2.28 mV/%RH was obtained for nine bilayers. The time constant of the response was 1.13 s ± 0.30 s which is faster than the commercial device (measured as 158 s). After calibration, the optical fibre humidity sensor was utilised in a bench top study employing a mechanical ventilator. The fast response time enabled changes in humidity in individual breaths to be resolved. Conclusion: Optical fibre sensors have the potential to be used to monitor breath to breath humidity during ventilator care. Significance: Control of humidity is an essential part of critical respiratory care and the developed sensor provides a sensitive, compact and fast method of humidity monitoring.

A Strategic Plan for Strengthening America’s Families: A Brief from the Coalition of Behavioral Science Organizations

Despite significant progress in research on the treatment and prevention of psychological, behavioral, and health problems, the translation of this knowledge into population-wide benefit remains limited. This paper reviews the state of America’s children and families, highlighting the influence of stressful contextual and social conditions on child and family well-being and the concentration of disadvantage in numerous neighborhoods and communities throughout the nation. It then briefly reviews the progress that has been made in pinpointing policies that can reduce stressful contextual conditions such as poverty, discrimination, and the marketing of unhealthful foods and substances. It also describes numerous family and school interventions that have proven benefit in preventing psychological and behavioral problems as diverse as tobacco, alcohol, and other drug use; depression; antisocial behavior; academic failure; obesity prevention; and early childbearing. We argue that progress in translating existing knowledge into widespread benefit will require a nationwide effort to intervene comprehensively in neighborhoods and communities of concentrated disadvantage. We present a strategic plan for how such an effort could be organized. The first step in this organizing would be the creation of a broad and diverse coalition of organizations concerned with advancing public health and well-being. Such a coalition could increase public support both for the policies needed to focus on these disadvantaged areas and the research needed to incrementally improve our ability to help these areas.

Revue de presse

Defining trained immunity and its role in health and disease

Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed ‘trained immunity’, a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define ‘trained immunity’ as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.

The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route

BACKGROUND: Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions. RESULTS: Fifty-two healthy, community dwelling elderly adults (65–82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alum-adjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ≥10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21–34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%, p = 0.008). The low seroconversion rate in the IM group progressively declined with increasing age, and responders had significantly lower HBsAb titers and limited isotype responses. Moreover, T-CMI (proliferation and cytokine production) were significantly reduced in both percentage of responders and intensity of the response for both Th1 and Th2 subsets in the elderly. CONCLUSIONS: Our data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B- and T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04162223. Registered 14 November 2019. Retrospectively registered.

A Single-Copy IS5-Like Transposon in the Genome of a Bdelloid Rotifer

In the course of sequencing telomeric chromosomal regions of the bdelloid rotifer Adineta vaga, we encountered an unusual DNA transposon. Unlike other bdelloid and, more generally, eukaryotic transposable elements (TEs), it exhibits similarity to prokaryotic insertion sequences (ISs). Phylogenetic analysis indicates that this transposon, named IS5_Av, is related to the ISL2 group of the IS5 family of bacterial IS elements. Despite the apparent intactness of the single open reading frame coding for a DDE transposase and the perfect identity of its 213-bp terminal inverted repeats (TIRs), the element is present in only one copy per diploid genome. It does not exhibit any detectable levels of transcription, so that its transposase gene appears to be silent in the bdelloid host. Although horizontal transfers of TEs between kingdoms are not known to happen in nature, it appears likely that IS5_Av underwent integration into the A. vaga genome relatively recently, but was not successful in adapting to the new host and failed to increase in copy number. Alternatively, it might be the only known member of a novel eukaryotic DNA TE superfamily which is so rare that its other members, if any, have not yet been identified in eukaryotic genomes sequenced to date.

Alternative Regimens of Neuraminidase Inhibitors for Therapy of Hospitalized Adults with Influenza: A Systematic Review of Randomized Controlled Trials

INTRODUCTION: Influenza in hospitalized intensive care unit (ICU) patients with respiratory failure is associated with 25% mortality, despite timely oseltamivir treatment. A systematic review of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of alternative neuraminidase inhibitor (NAI) regimens compared to standard of care in patients hospitalized for H1N1, H3N2, or B influenza. METHODS: The Cochrane collaboration searching methods were followed in Cochrane Library, PubMed, and Web of Science databases (2009–2019). Eligibility criteria were RCTs comparing different regimens of NAIs in hospitalized patients (at least 1 year old) for clinically diagnosed influenza (H1N1, H3N2, or B). Pre-defined endpoints were time to clinical resolution (TTCR), overall mortality, hospital discharge, viral clearance, drug-related adverse events (AEs), and serious adverse events. RESULTS: Seven trials (1579 patients) were included. Two trials compared two regimens of oral oseltamivir therapy, and one trial compared two regimens of intravenous zanamivir therapy vs oral oseltamivir therapy. Four trials focused on intravenous peramivir therapy: two trials compared two different regimens and two trials compared two different regimens vs oral oseltamivir therapy. Overall, the different regimens were well tolerated, with no significant differences in AEs; nonetheless non-significant differences were reported among different regimens regarding TTCR, mortality, and viral clearance. CONCLUSION: Higher compared to standard doses of NAIs or systemic peramivir therapy compared to oral oseltamivir therapy did not demonstrate benefit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12325-020-01347-5) contains supplementary material, which is available to authorized users.

Toxigenic type D Pasteurella multocida in New South Wales pig herds—prevalence and factors associated with infection

Between March and July 1987, a study was undertaken to determine the prevalence of and factors associated with toxigenic type D Pasteurella multocida infection in New South Wales pig herds. Toxigenic type D P. multocida was isolated from the nasal cavities of pigs in one (2%) of 50 randomly selected herds. Toxigenic isolates were also recovered from 2 (8%) of a separate group of 25 herds that had purchased pigs from a known infected piggery in South Australia (herd SA). Snout abnormalities were present in 9.4%, 3.2% and 1.8% of grower pigs in the 3 affected herds. Isolation of toxigenic P. multocida was significantly associated (p < 0.0001) with the occurrence of clinically affected pigs in the herd. Purchase of at least 5 pigs from herd SA was associated with an elevated risk (p < 0.05) of isolation of toxigenic P. multocida.

Investigations of an enteric infection of cockatoos caused by an enterovirus‐like agent

An enteric infection in cockatoos associated with a 30nm diameter enterovirus‐like agent seen in faeces and intestinal epithelial cells is described. The disease is characterised by intractable, profuse, mucoid diarrhoea, weight loss, dehydration and death. Lesions in the intestine consist of villous atrophy, villous fusion, enterocyte hyperplasia and, in some cases, chronic inflammation. Affected birds so far examined have concurrent psittacine beak and feather disease.

Characteristics and prognosis of hospital‐treated obstructive bronchitis in children aged less than two years

In a prospective study 101 children aged less than 2 years (median age 10 months), were examined the first time they were admitted to a paediatric ward for asthmatic symptoms. Two‐thirds were boys and 58 had parents or siblings with allergic symptoms. During winter‐spring, respiratory syncytial (RS) virus was verified in 50% of children. Other viral agents were adenovirus, parainfluenza 3, coxsackie B 2, ECHO 6 and rotavirus. At the acute stage, 54% of the children displayed changes on pulmonary X‐ray. The total IgE value was + 2 SD score units in 14 children. At reinvestigation after 3–4.5 years, when the children were aged 3.3–6.3 years, 53% were free from asthmatic symptoms; the median age for the last episode was 2 years. A total of 33% had mild asthma, 8% moderate and 6% severe asthma. The factors which correlated significantly with persistent asthma were: (1) The need for daily medication for at least 6 months. (2) A young age in conjunction with the first wheezing episode and on the first admission to a paediatric ward because of asthmatic symptoms. (3) Other past or present atopic symptoms. Heredity, tobacco smoking at home, having a furry pet, RS virus infection, or high total IgE at the time of the first admission did not correlate significantly with the persistence of asthma 3–4.5 years later. The results emphasize the good overall prognosis of wheezing in early childhood, even when the wheezing is severe enough to lead to inpatient treatment.

UNEXPECTED ISOLATION OF A NEWCASTLE DISEASE VIRUS

ω-3 vs. ω-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation

OBJECTIVE: To compare the effects of a conventional ω-6 lipid infusion and a fish oil based (ω-3) lipid infusion for parenteral nutrition on neutrophil function, lipid mediators, and plasma free fatty acids. DESIGN AND SETTING: Open-label, randomized, pilot study in a university hospital medical intensive care unit and experimental laboratory. PATIENTS AND PARTICIPANTS: Ten patients with septic shock and eight healthy controls. INTERVENTIONS: Patients (five per group) requiring parenteral nutrition received intravenously either a ω-3 or a ω-6 lipid emulsion for a 10-day period. MEASUREMENTS AND RESULTS: At baseline levels of plasma free fatty acids were elevated several-fold, including high concentrations of the ω-6 lipid precursor arachidonic acid (AA). Neutrophils isolated from septic patients displayed markedly reduced responsiveness to ex vivo stimulation, including lipid mediator generation [leukotrienes (LT), PAF], respiratory burst, and phosphoinositide hydrolysis signaling. Under the ω-6 lipid infusion regimen abnormalities in plasma free fatty acids and impairment of neutrophil functions persisted or worsened. In contrast, a rapid switch in the plasma free fatty acid fraction to predominance of the ω-3 acids eicosapentaenoic acid and docosahexaenoic acid over AA occurred in response to ω-3 lipid infusion. LTB(5), in addition to LTB(4), appeared upon neutrophil stimulation originating from these patients, and neutrophil function was significantly improved in the ω-3 lipid group. CONCLUSIONS: ω-3 vs. ω-6 lipid emulsions differentially influence the plasma free fatty acid profile with impact on neutrophil functions. Lipid-based parenteral nutrition in septic patients may thus exert profound influence on sequelae and status of immunocompetence and inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-003-1900-2.

Modeling the helicase domain of Brome mosaic virus 1a replicase

Brome mosaic virus (BMV) is a representative member of positive-strand RNA viruses. The 1a replicase from BMV is a membrane protein of unknown structure with a methyltransferase N-terminal domain and a putative helicase activity in the C-terminal domain. In order to make a functional prediction of the helicase activity of the BMV 1a C-terminal domain, we have built a model of its structure. The use of fold recognition servers hinted at two different superfamilies of helicases [superfamily 1 (SF1) and superfamily 2 (SF2)] as putative templates for the C-terminal fragment of BMV 1a. A structural model of BMV 1a in SF2 was obtained by means of a fold recognition server (3D-PSSM). On the other hand, we used the helicase motifs described in the literature to construct a model of the structure of the BMV 1a C-terminal domain as a member of the SF1. The biological functionality and statistic potentials were used to discriminate between the two models. The results illustrate that the use of sequence profiles and patterns helps modeling. Accordingly, the C-terminal domain of BMV 1a is a potential member of the SF1 of helicases, and it can be modeled with the structure of a member of the UvrD family of helicases. The helicase mechanism was corroborated by the model and this supports the hypothesis that BMV 1a should have helicase activity.

Images in Clinical ECT: Immediate impact of COVID-19 on ECT Practice

Nurses transforming systems of care: The bicentennial of Florence Nightingale's legacy

Lessons from Florence Nightingale are just as relevant today as they were more than 150 years ago. Learn how nurse leaders can follow her lead and embrace the importance of nurturing highly motivated nurses who are critical thinkers.

Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial

OBJECTIVE: To assess the efficacy and safety of ultra-low dose 0.005% estriol vaginal gel in women with breast cancer receiving nonsteroidal aromatase inhibitors (NSAIs) and experiencing treatment-related vulvovaginal symptoms and signs. METHODS: Women with hormone receptor-positive early breast cancer receiving NSAIs were randomized to either estriol vaginal gel or placebo for 12 weeks. Vaginal maturation, vaginal pH, and total and individual scores of symptoms and signs of vulvovaginal atrophy were assessed at baseline and at weeks 3 and 12; sexual functioning was also evaluated using the Female Sexual Functioning Index (FSFI) questionnaire, as well as circulating estrogens, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). RESULTS: Sixty-one women with a mean age of 59 years were included: 50 received 0.005% estriol vaginal gel and 11 received placebo. Active treatment significantly improved maturation value and pH, vaginal dryness and global scores of symptoms and signs. Active treatment also increased the total FSFI score and all the FSFI domains, with the exception of pain. Small oscillations were observed in FSH and LH, which remained within the postmenopausal range. Estriol levels increased initially and normalized by week 12, and estradiol and estrone remained mostly undetectable throughout the study. CONCLUSIONS: Ultra-low dose 0.005% estriol vaginal gel showed efficacy in improving the symptoms and signs of vulvovaginal atrophy. These results, together with minimal oscillations in hormonal levels throughout the treatment, support the use of ultra-low dose 0.005% estriol vaginal gel as a treatment option for vulvovaginal atrophy in women with breast cancer receiving NSAIs with an indication for treatment with vaginal estrogens.

Telemedicine Home-Based Cardiac Rehabilitation: A CASE SERIES

In this case series report, we review 2 patients who were among the first to participate in the Henry Ford telemedicine home-based cardiac rehabilitation (TM-HBCR) program. These patients had barriers to full participation in a facility-based cardiac rehabilitation (CR) program due to return to work and access to transportation. However, they were willing and able to participate in the TM-HBCR program. DISCUSSION: The two cases discussed herein are examples of individuals who likely would not have fully participated in CR if the only option available was a facility-based program. While HBCR is not an option for all patients, it does address several barriers that are known to limit participation in facility-based CR for some individuals. SUMMARY: Technology has made it possible to provide the key components of a facility-based CR program through a TM-HBCR model using a secure connection to the patients via their personal mobile device.

Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial

OBJECTIVES: To evaluate the safety, pharmacokinetics, and preliminary efficacy of NT-814, a dual neurokinin 1,3 antagonist, in postmenopausal women with vasomotor symptoms (hot flashes). METHODS: We completed a double-blind, randomized, placebo-controlled trial in three US clinical research units in 76 postmenopausal women with moderate/severe hot flashes. Participants were randomized to 14 days of once-daily NT-814 or placebo within each of four sequential dose cohorts; 50, 100, 150, and 300 mg. Participants completed diaries of hot flash frequency and severity and waking due to night sweats before (baseline) and during treatment. RESULTS: All prespecified efficacy parameters (24-h hot flash frequency and severity, frequency of waking due to night sweats) decreased in all groups (including placebo). Mean reduction from baseline at week 2 in moderate/severe hot flash frequency was 37% in the placebo group and, respectively, 24% (P = 0.048 vs placebo), 59% (P = 0.155), 84% (P < 0.001) and 66% (P = 0.022) in the 50 mg, 100 mg, 150 mg, and 300 mg NT-814 groups; in waking due to night sweats reduction was 20% (P = 0.059), 55% (P = 0.135), 81% (P < 0.001), and 63% (P = 0.031) in the NT-814 groups and 32% in the placebo group. The improvement with NT-814 ≥150 mg was also evident in the first week of treatment. The most common treatment-related adverse events were mild somnolence and headache, more frequently in the 300 mg group. Safety monitoring identified no concerns. CONCLUSIONS: Once-daily NT-814 (≥150 mg/d) resulted in a rapid, marked improvement in hot flashes and waking due to night sweats. No safety concerns were identified. Doses up to 300 mg were well tolerated.

ECT during COVID-19: An Essential Medical Procedure – Maintaining Service Viability and Accessibility

The association between hormone therapy and sarcopenia in postmenopausal women: the Korea National Health and Nutrition Examination Survey, 2008-2011

OBJECTIVE: Menopausal transition contributes to sarcopenia, but the effects of hormone therapy (HT) on sarcopenia in postmenopausal women have not been determined. This study assessed the effect of HT on sarcopenia in postmenopausal women. METHODS: The present study included 4,254 postmenopausal women who participated in the Korea National Health and Nutritional Examination Surveys from 2008 to 2011. Appendicular skeletal muscle mass divided by weight (ASM/Wt) and the prevalence of sarcopenia were analyzed in groups of women stratified by duration of HT use. RESULTS: ASM/Wt was higher and the prevalence of sarcopenia was lower in participants with a history of prolonged (≥13 mo) HT use than in participants with a shorter duration of HT use or no HT use. After adjusting for multiple confounding factors, prolonged use of HT remained significantly associated with estimated mean ASM/Wt and the prevalence of sarcopenia (odds ratio: 0.60; 95% confidence interval: 0.41-0.88; P = 0.01). In addition, the prevalence of sarcopenia was linearly associated with history of hypertension, duration of hypertension, physical activity, and duration of HT use. Subgroup analysis showed that the association between duration of HT use and the prevalence of sarcopenia was maintained in younger (<65 y old) and leaner (body mass index <25 kg/m(2)) postmenopausal women. CONCLUSIONS: The present study showed that the prolonged use of HT was associated with high muscle mass and a low prevalence of sarcopenia in postmenopausal women.

ECT in a time of COVID-19

Double-Edged Spike: Are SARS-CoV-2 Serologic Tests Safe Right Now?

Knowledge, awareness and practices towards seasonal influenza and its vaccine: implications for future vaccination campaigns in Jordan

BACKGROUND. Influenza is an underestimated contributor to morbidity and mortality. Population knowledge regarding influenza and its vaccination has a key role in enhancing vaccination coverage. OBJECTIVES. This study aimed to identify the gaps of knowledge among Jordanian population towards influenza and its vaccine, and to identify the major determinants of accepting seasonal influenza vaccine in adults and children in Jordan. METHODS. This was a cross-sectional study that enrolled 941 randomly selected adults in Amman, Jordan. A four-section questionnaire was used which included questions about the sociodemographic characteristics, knowledge about influenza and the factors that affect seasonal influenza vaccine acceptance and refusal. RESULTS. Only 47.3% of the participants were considered knowledgeable. About half of the participants (51.9%) correctly identified the main influenza preventative measures. Lack of knowledge about the important role of seasonal influenza vaccine in disease prevention was observed. Low vaccination rate (20% of adults) was reported. The most critical barrier against vaccination in adults and children was the concern about the safety and the efficacy of the vaccine, while the most important predictors for future vaccination in adults and children were physician recommendation and government role. In children, the inclusion of the vaccine within the national immunization program was an important determinant of vaccine acceptance. CONCLUSION. Formulating new strategies to improve the population’s level of knowledge, assuring the population about the safety and the efficacy of the vaccine and the inclusion of the vaccine within the national immunization program are the essential factors to enhance vaccination coverage in Jordan.

Compliance in teenagers with coeliac disease—a Swedish follow‐up study

A group of 47 children with coeliac disease, born between 1973 and 1978 in the Swedish county of Västmanland, participated in a controlled questionnaire study. Health, self‐esteem, knowledge of the disease and dietary compliance were investigated. The children with coeliac disease were otherwise just as healthy as the control children. Growth and self‐esteem were normal. Good knowledge of coeliac disease and dietary treatment was found in 87% of children and dietary compliance was 81%. Girls and younger children (12–14 years) were more compliant than boys and older children (15–17 years). Compliance correlated positively to knowledge.

Mixed Infection Is Common in Children with Respiratory Adenovirus Infection

ABSTRACT. The presence of concomitant viral or bacterial infection was evaluated in 20 patients hospitalized for adenovirus infection of the middle or lower airways by using new serological methods for detection of both antigens and antibodies. Adenovirus infection was identified by measurement of antibodies with complement fixation test or by direct detection of viral antigen in nasopharyngeal aspirates. Mixed infection was present in 11 (55%) of the 20 patients. Viral coinfection was demonstrated in five (25%) and bacterial in nine (45%) patients. Bacterial coinfection was common, 67%, in children with an infection focus, pneumonia or acute otitis media, but rare, 13%, in those without it. Seroconversion to nontypable Haemophilus influenzae was indicated in six children; four of them were infants, four had pneumonia and three acute otitis media. Pneumococcal infection was indicated in two patients with pneumonia, both aged over two years. Chlamydia trachomatis was involved in one case. The results indicate that bacterial coinfection is common in respiratory adenovirus infection affecting lower airways, especially if pneumonia is present.

Multiple sclerosis in the Faroe Islands

Detailed questionnaires were completed in 1978–79 by 23 of the 28 then known resident Faroese multiple sclerosis (MS) patients and 127 controls. These controls were divided into 69 Group A (patient sibs and other relatives), 37 Group B (matched neighbor controls, their spouses and sibs, plus patient's spouse), and 21 Group C (distant matched controls, spouses, relatives living where MS patients never resided and British troops were not encamped during the war). No differences between cases and controls were found for education, occupation, types of residence, bathing, sanitary or drinking facilities, and nature of house construction or heating. Detailed dietary histories, available for half the subjects, revealed no difference, cases versus controls, for four age periods between age 0 and 30 years, and for 16 specified foodstuffs. Animal exposures showed overall no consistent differences by location or type of animal. There was a tendency to greater exposure to British troops during the war for cases versus Groups A and B, but this did not attain statistical significance. Vaccinations for smallpox, tetanus and diphtheria were less common in the MS; no difference was found for other vaccinations. Except for a relative deficit in the cases for rubella and (insignificantly) for measles, mumps and chicken pox, reported illnesses were equally common among all groups. Operations, hospitalizations and injuries did not differentiate the groups, nor did age at menarche for women. Neurologic symptoms were significantly more common in the cases than in the controls.

Endemism in Tasmanian cool temperate rainforest: alternative hypotheses

Endemism in Tasmanian cool temperate rainforest: alternative hypotheseS. Evidence is presented which suggests that hypotheses presented by Kirkpatrick & Brown relating to endemic species in Tasmania are either invalid or of limited importance for woody rainforest species. In their place three hypotheses are presented to account for the presence of endemic species in Tasmanian cool temperate rainforest on the basis of the fossil record and the distribution of species which are closely related to the endemics. The first two hypotheses relate to the presence of the endemic species in the general Tasmanian region. They are: 1.. Some species evolved in southeastern Australia during the Tertiary in response to the changing climate. Some of the ancestral species still occur in temperate rainforest at lower latitudes in Australia. 2.. Some species have remained essentially unchanged in Tasmania during the Tertiary and Quaternary climatic changes. The third hypothesis relates to the restriction of these cool temperate rainforest species to Tasmania: 1.. Post‐glacial climatic changes (especially a decrease in rainfall) and the human influence (especially land clearing and fire) may have combined to eliminate some cool temperate rainforest species from mainland Australia.