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Background: The burden of depressive disorder is large and new treatment approaches are required. Repurposing widely available drugs such as statins may be a time- and cost-effective solution. Statins have anti-inflammatory and anti-oxidant properties which have been shown to be relevant to the pathophysiology of depression. This study assesses the efficacy, acceptability, tolerability, and safety of statins in major depressive disorder. Methods: Our study is an update and extension of a previous meta-analysis published in 2016 by Salagre et al. We performed a systematic review (PubMed/MEDLINE, Cochrane CENTRAL, ISI Web of Science, CINAHL, and ClinicalTrials.gov until the 1st September 2020) and meta-analysis of randomized controlled trials using any statin against placebo or any other statin in the treatment of major depressive disorder. Our primary efficacy outcome measure was the mean value on any standardized scale for depressive symptoms at 8 weeks of treatment. We also calculated outcomes for efficacy, response, and remission at 2, 4, and 12 weeks, as well as acceptability (dropouts for any cause), tolerability (dropouts due to any adverse event), and safety (any adverse event) outcomes at the studies' endpoints. Furthermore, we conducted an exploratory network meta-analysis for the primary efficacy outcome to identify potential differences between statins. Results: We retrieved five randomized controlled trials meeting our inclusion criteria: four used a statin in addition to an antidepressant and compared it to placebo plus antidepressant, and one compared two statins alone. and one comparing one statin with another. Statins compared to placebo in addition to antidepressants were efficacious at 8 weeks (N = 255, SMD = -0.48, 95% CI = -0.74 to -0. 22) and 12 weeks (N = 134, SMD = -0.47, 95% CI = -0.89 to -0.05, moderate certainty) with no difference for acceptability, tolerability, and safety (low certainty). An exploratory network meta-analysis suggested that the most lipophilic statins, especially simvastatin, could be more efficacious than less lipophilic or hydrophilic molecules. Conclusions: This systematic review suggests the efficacy, acceptability, tolerability, and safety of statins in addition to antidepressants in patients with major depressive disorder. Further clinical trials in different settings are required to test this result. Trial rgistration: PROSPERO registration: CRD42020170938. [ABSTRACT FROM AUTHOR]

Fostering metacognition can be challenging within large enrollment settings, particularly within STEM fields concentrating on problem-solving skills and their underlying theories. Herein, the research problem of realizing more frequent, insightful, and explicitly-rewarded metacognition activities at significant scale is investigated via a strategy utilizing a hierarchy of assessments. Referred to as the STEM-Optimal Digitized Assessment Strategy (SODAS), this targeted approach engages frequent assessment, instructor feedback, and learner self-reflection across the hierarchy of learning mechanisms comprising Bloom's Taxonomy of Learning Domains. SODAS spans this hierarchy of learning mechanisms via a progression of (i) unregulated online assessment, (ii) proctored Computer-Based Assessment (CBA), (iii) problem-based learning activities assessed in the laboratory setting, and (iv) personalized Socratic discussions of scanned scrap sheets that accompanied each learner's machine-graded formative assessments. Results of a case study integrating SODAS within a high-enrollment Mechanical Engineering Heat Transfer course at a large state university are presented for enrollment of 118 students. Six question types were delivered with lockdown proctored testing via auto-grading within the Canvas Learning Management System (LMS), along with bi-weekly laboratory activities to address the higher layers of Bloom's Taxonomy. Sample assessment formats were validated through student use and schedules of responsibilities for instructors across four tiers of assessment levels (facts, concepts, procedures, and metacognition), two testing delivery mechanisms (electronic textbook exercises and proctored CBA), and three remediation mechanisms (self-paced, score clarification, and experiment clarification), which showed that learning achievement can increase by up to 16.9% compared to conventional assessment strategies, while utilizing comparable instructor resources and workloads. [ABSTRACT FROM AUTHOR]

The article reviews The Teaching Online Preparation Toolkit located at TOPkit.org.

Please cite this paper as: Howard et al. (2011) Report of the 'Mechanisms of lung injury and immunomodulator interventions in influenza' workshop, 21 March 2010, Ventura, California, USA*. Influenza and Other Respiratory Viruses 5(6), 453-e475. The clinical course of influenza and the extent of lung injury are determined by both viral and host factors, as well as sometimes secondary bacterial infections and exacerbations of underlying conditions. The balance between viral replication and the host immune responses is central to disease pathogenesis, and the extent of lung injury in severe influenza infections may be due in part to overly exuberant or dysregulated innate inflammatory responses or sometimes deficient responses. Acute respiratory distress syndrome (ARDS) is the principal cause of respiratory failure associated with severe influenza. ARDS can be triggered by both direct lung insults (e.g. respiratory pathogens) and systemic insults (e.g. sepsis), and the lung damage is exacerbated by the inflammatory response associated with either infectious or non-infectious insults. This workshop aimed to review the current understanding of lung injury in acute influenza and describe cellular and molecular mechanisms of lung injury that are common to influenza and infections by other respiratory pathogens. In addition, therapeutic agents that target host response proteins and pathways were identified and investigational agents in development reviewed. A logical strategy would be to combine antiviral treatment with drugs that modify excessive host responses or supplement deficient ones. However, a better understanding of common cell signalling pathways associated with acute lung injury caused by influenza and other pathogens is necessary to understand immunopathologic causes of lung injury. This will help determine which immunomodulatory interventions might be useful, and to predict the appropriate timing and consequences of their use. [ABSTRACT FROM AUTHOR]

Surveillance for influenza virus in pigs in the United Kingdom during spring 2010 detected a novel reassortant influenza virus. This virus had genes encoding internal proteins from pandemic (H1N1) 2009 virus and hemagglutinin and neuraminidase genes from swine influenza virus (H1N2). Our results demonstrate processes contributing to influenza virus heterogeneity. [ABSTRACT FROM AUTHOR]

Surveillance for influenza virus in pigs in the United Kingdom during spring 2010 detected a novel reassortant influenza virus. This virus had genes encoding internal proteins from pandemic (H1N1) 2009 virus and hemagglutinin and neuraminidase genes from swine influenza virus (H1N2). Our results demonstrate processes contributing to influenza virus heterogeneity. [ABSTRACT FROM AUTHOR]

Young patients with myasthenia gravis (MG) frequently have ectopic GC in their thymus. We investigated these ectopic GC by microdissection of GC B cells and analysis of their Ig gene characteristics, in comparison to normal GC. CDR3 length distribution, a measure of clonal variability, and Ig gene family usage were similar in MG and normal tonsil samples. Lineage tree analysis demonstrated similar diversification and mutations per cell compared with normal control trees. Mutations were observed in the framework regions, responsible for the structural integrity of the BCR; however, these mutations were mostly conservative or neutral, confirming that a functional BCR is conserved in MG. In the CDR, responsible for Ag binding, selection against replacement mutations was revealed. This may indicate that the MG clones analyzed are already highly Ag-specific, and therefore potential affinity-reducing replacement mutations in the CDR3 are not propagated, due to Ag-driven selection. Somatic hypermutation (SHM) targeting motifs and aa substitution preferences in MG were similar to those of normal controls. Overall, these results suggest that B cells in the ectopic GC in MG appear to undergo normal diversification and selection, in spite of the chronic nature and different environment of the response. [ABSTRACT FROM AUTHOR]

The combined processes of immunoglobulin (IG) gene rearrangement and somatic hypermutation allow for the creation of an extremely diverse antibody repertoire. Knowledge of the germline sequence of the IG genes is required so that hypermutation and the affinity matured humoral response can be properly studied. Variable region genes can be arranged into subgroups; in humans, there are 11 IGLV subgroups and 6 IGKV subgroups. The rhesus macaque ( Macaca mulatta) is a relevant non-human primate model for human immunological systems. A number of macaque IGHV, IGHD and IGHJ genes have already been reported. We have also previously reported a number of macaque IGKV genes. Here we report the isolation of new macaque IGLV genes by polymerase chain reaction amplification from macaque genomic DNA using primers based on the human sequences. Nine IGLV1, 10 IGLV2, 21 IGLV3, 5 IGLV4 and 7 IGLV5 germline genes for the macaque were found, the open-reading frames of which exhibit high homology to their human counterparts (>89.3, >88.6, >89.0, >94.7 and >87.1%, respectively). [ABSTRACT FROM AUTHOR]

The combined processes of immunoglobulin (IG) gene rearrangement and somatic hypermutation allow for the creation of an extremely diverse antibody repertoire. Knowledge of the germline sequence of the IG genes is required so that hypermutation and the affinity matured humoral response can be properly studied. Variable region genes can be arranged into subgroups; in humans, there are 11IGLVsubgroups and sixIGKVsubgroups. The rhesus macaque (Macaca mulatta) is a relevant non-human primate model for human immunological systems. A number of macaqueIGHV,IGHDandIGHJgenes have already been reported, but only one light-chain germline gene has been published so far. Here we report the isolation of new macaqueIGKVgenes by polymerase chain reaction (PCR) amplification from macaque genomic DNA using primers based on the human sequences. Twenty-eightIGKV1, 22IGKV2and 12IGKV3germline genes for the macaque were found, the open reading frames of which exhibit high homology to their human counterparts (>96,>99 and>96%, respectively). [ABSTRACT FROM AUTHOR]

The diversity of the antibody response is achieved, in part, by rearrangement of different immunoglobulin (Ig) genes. The Ig heavy chain is made up of a variable region (IGHV), a diversity region (IGHD) and a joining region (IGHJ). Human germline IGHV genes have been grouped into seven multigene subgroups. Size and usage of these subgroups is not equal, the IGHV3 subgroup is the most commonly used (36%), followed by IGHV1/7 (26%), then IGHV4, IGHV5, IGHV2, IGHV6 (15%, 12%, 4%, 3% respectively). The rhesus macaque (Macaca mulatta) is a useful non-human primate model for studies of infection and the database of germline Ig genes for the macaque is gradually growing to become a useful tool in the study of B-cell responses. The proportions of IGHV subgroup usage in the macaque are similar to those in man. Representatives from IGHV3 and IGHV4 subgroups for the macaque have been published, as have germline sequences of the IGHD and IGHJ genes. However, to date there have been no sequences published from the second largest IGHV subgroup, IGHV1. We report the isolation and sequencing of a genomic fragment containing an IGHV1 gene from the macaque. Polymerase chain reaction (PCR) primers designed from this sequence enabled us to amplify and sequence 25 new IGHV1 germline genes. We also isolated two IGHV7 genes, using the same primers, and two IGHV5 genes, using human IGHV5 primers. [ABSTRACT FROM AUTHOR]

We evaluated the differential effect of platelet count in platelet-rich plasma (PRP) on the level of ex vivo inhibition of platelet aggregation provided by abciximab, eptifibatide, and tirofiban as part of a randomized, comparative trial of these agents on platelet function in patients with unstable angina pectoris undergoing percutaneous coronary intervention. Platelet count <350 K/µL in PRP reduced measured platelet inhibition by abciximab, but not eptifibatide nor tirofiban. This observation suggests the need for standardized, uniform platelet counts in PRP during future comparisons of the degree of platelet inhibition by these agents. [ABSTRACT FROM AUTHOR]

Anciximab provides potent, but variable degrees of platelet inhibition both during the duration of intravenous administration and at 12 hours following therapy. Platelet function was assessed using the PC-RPFA system in 78 patients scheduled for percutaneous coronary revascularization who were administered the standard abciximab weight-adjusted bolus and 12-hour infusion. The PC-RPFA system is a cartridge-based, semiautomated point-of-care whole-blood assay that incorporates fibrinogen-coated polystyrene beads, buffers, and a modified thrombin receptor activating peptide (Isotrap) in lyophilized form. The instrument detects the agglutination rate between the stimulated platelets and the fibrinogen-coated beads, and provides a quantitative digital display in less than 2 minutes. No differences in the level of platelet inhibition were observed in these abciximab-treated patients by diabetic status, gender, smoking, diagnosis (unstable angina, chronic stable angina, recent myocardial infarction), or abciximab treatment status (first time vs. retreatment). Nocorrelation of the PC-RPFA rate of platelet aggregation with clinical demographic factors was observed, with the exception of baseline hematocrit (r2 = 0.4556). The relationship between the PC-RPFA rate of aggregation and hematocrit reflects light absorbance by erythrocytes and is specific to the PC-RPFA system. The absolute rate of platelet aggregation (slope) reported by the PC-RPFA is correlated with percent aggregation, thus making it potentially possible to predict the level of aggregation without reference to a baseline (pretreatment) measure of platelet function. This correlation was closest for patients having <40% baseline aggregation (r2 = 0.55). Thus, PC-RPFA provides a rapid point-of-care assessment of platelet function that could allow for adjustment of abciximab dosing to achieve targeted levels of platelet inhibition. The utility of this device to optimize therapy with platelet glycoprotein IIb/IIIa inhibitors is currently being evaluated. [ABSTRACT FROM AUTHOR]

Outbreaks of highly pathogenic avian influenza virus (HPAIV) often result in the infection of millions of poultry, causing up to 100% mortality. HPAIV has been shown to emerge from low pathogenicity avian influenza virus (LPAIV) in field outbreaks. Direct evidence for the emergence of H7N7 HPAIV from a LPAIV precursor with a rare di-basic cleavage site (DBCS) was identified in the UK in 2008. The DBCS contained an additional basic amino acid compared to commonly circulating LPAIVs that harbor a single-basic amino acid at the cleavage site (SBCS). Using reverse genetics, outbreak HPAIVs were rescued with a DBCS (H7N7DB), as seen in the LPAIV precursor or an SBCS representative of common H7 LPAIVs (H7N7SB). Passage of H7N7DB in chicken embryo tissues showed spontaneous evolution to a HPAIV. In contrast, deep sequencing of extracts from embryo tissues in which H7N7SB was serially passaged showed retention of the LPAIV genotype. Thus, in chicken embryos, an H7N7 virus containing a DBCS appears naturally unstable, enabling rapid evolution to HPAIV. Evaluation in embryo tissue presents a useful approach to study AIV evolution and allows a laboratory-based dissection of molecular mechanisms behind the emergence of HPAIV. [ABSTRACT FROM AUTHOR]

The article presents a correction to the article "Immunoglobulin light-chain genes in the rhesus macaque I: kappa light-chain germline sequences for subgroups IGKV1, IGKV2 and IGKV3," that was published in a 2005 issue of "Immunogenetics."