Recognition of HIV-1 capsid by PQBP1 licenses an innate immune sensing of nascent HIV-1 DNA.

We have previously described polyglutamine-binding protein 1 (PQBP1) as an adapter required for the cyclic GMP-AMP synthase (cGAS)-mediated innate response to the human immunodeficiency virus 1 (HIV-1) and other lentiviruses. Cytoplasmic HIV-1 DNA is a transient and low-abundance pathogen-associated molecular pattern (PAMP), and the mechanism for its detection and verification is not fully understood. Here, we show a two-factor authentication strategy by the innate surveillance machinery to selectively respond to the low concentration of HIV-1 DNA, while distinguishing these species from extranuclear DNA molecules. We find that, upon HIV-1 infection, PQBP1 decorates the intact viral capsid, and this serves as a primary verification step for the viral nucleic acid cargo. As reverse transcription and capsid disassembly initiate, cGAS is recruited to the capsid in a PQBP1-dependent manner. This positions cGAS at the site of PAMP generation and sanctions its response to a low-abundance DNA PAMP.

Validation of a 3D Local-Scale Adaptive Solar Radiation Model by Using Pyranometer Measurements and a High-Resolution Digital Elevation Model.

The result of the multidisciplinary collaboration of researchers from different areas of knowledge to validate a solar radiation model is presented. The MAPsol is a 3D local-scale adaptive solar radiation model that allows us to estimate direct, diffuse, and reflected irradiance for clear sky conditions. The model includes the adaptation of the mesh to complex orography and albedo, and considers the shadows cast by the terrain and buildings. The surface mesh generation is based on surface refinement, smoothing and parameterization techniques and allows the generation of high-quality adapted meshes with a reasonable number of elements. Another key aspect of the paper is the generation of a high-resolution digital elevation model (DEM). This high-resolution DEM is constructed from LiDAR data, and its resolution is two times more accurate than the publicly available DEMs. The validation process uses direct and global solar irradiance data obtained from pyranometers at the University of Salamanca located in an urban area affected by systematic shading from nearby buildings. This work provides an efficient protocol for studying solar resources, with particular emphasis on areas of complex orography and dense buildings where shadows can potentially make solar energy production facilities less efficient.

Evaluation of different glycerol fed-batch strategies in a lab-scale bioreactor for the improved production of a novel engineered ß-fructofuranosidase enzyme in Pichia pastoris.

The ß-fructofuranosidase enzyme from Aspergillus niger has been extensively used to commercially produce fructooligosaccharides from sucrose. In this study, the native and an engineered version of the ß-fructofuranosidase enzyme were expressed in Pichia pastoris under control of the glyceraldehyde-3-phosphate dehydrogenase promoter, and production was evaluated in bioreactors using either dissolved oxygen (DO-stat) or constant feed fed-batch feeding strategies. The DO-stat cultivations produced lower biomass concentrations but this resulted in higher volumetric activity for both strains. The native enzyme produced the highest volumetric enzyme activity for both feeding strategies (20.8% and 13.5% higher than that achieved by the engineered enzyme, for DO-stat and constant feed, respectively). However, the constant feed cultivations produced higher biomass concentrations and higher volumetric productivity for both the native as well as engineered enzymes due to shorter process time requirements (59 h for constant feed and 155 h for DO-stat feed). Despite the DO-stat feeding strategy achieving a higher maximum enzyme activity, the constant feed strategy would be preferred for production of the ß-fructofuranosidase enzyme using glycerol due to the many industrial advantages related to its enhanced volumetric enzyme productivity.

Real-life outcomes in biotypes of psychotic disorders based on neurocognitive performance.

Aiming at discerning potential biotypes within the psychotic syndrome, we have recently reported the possible existence of two clusters or biotypes across schizophrenia and bipolar disorder characterized by their cognitive performance using the Brief Assessment of Cognition in Schizophrenia (BACS) instrument and validated with independent biological and clinical indexes (Fernández-Linsenbarth et al. in Schizophr Res 229:102-111, 2021). In this previous work, the group with larger cognitive deficits (N = 93, including 69 chronic schizophrenia, 17 first episodes (FE) of schizophrenia and 7 bipolar disorder patients) showed smaller thalamus and hippocampus volume and hyper-synchronic electroencephalogram than the group with milder deficits (N = 105, including 58 chronic schizophrenia, 25 FE and 22 bipolar disorder patients). We predicted that if these biotypes indeed corresponded to different cognitive and biological substrates, their adaptation to real life would be different. To this end, in the present work we have followed up the patients' population included in that work at 1st and 3rd years after the date of inclusion in the 2021 study and we report on the statistical comparisons of each clinical and real-life outcomes between them. The first cluster, with larger cognitive deficits and more severe biological alterations, showed during that period a decreased capacity for job tenure (1st and 3rd years), more admissions to a psychiatric ward (1st year) and a higher likelihood for quitting psychiatric follow-up (3rd year). Patients in the second cluster, with moderate cognitive deficits, were less compliant with prescribed treatment at the 3rd year. The differences in real-life outcomes may give additional external validity to that yielded by biological measurements to the described biotypes based on neurocognition.

SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor (karyopherin/importin) complex and disrupt nuclear import. In addition, we show that a methionine-to-arginine substitution at residue 58 impairs Orf6 binding to the Nup98-Rae1 complex and abolishes its IFN antagonistic function. All together our data unravel a mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.

Effectiveness of nontechnical skills educational interventions in the context of emergencies: A systematic review and meta-analysis.

INTRODUCTION: In recent years, the importance of training healthcare professionals in nontechnical skills using effective methodologies has been increasingly recognised as a means of preventing clinical errors in the practice of health care. The aim of this study was to evaluate the effectiveness of educational interventions on nontechnical skills in the emergency medical services and/or critical care unit settings. METHODS: A systematic search was carried out in the PubMed, SCOPUS, CINAHL, and Web of Science databases according to predetermined inclusion and exclusion criteria. After the initial search, 7952 records were selected after duplicates removed. Finally, a selection of 38 studies was included for quantitative analysis. Separate meta-analyses of standardised mean changes were carried out for each outcome measure assuming a random-effects model. Cochran's Q-statistic and I2 index were applied to verify study heterogeneity. Weighted analyses of variance and meta-regressions were conducted to test the influence of potential moderators and funnel plots using Duval and Tweedie's trim-and-fill method, and Egger's regression test were used to examine publication bias. RESULTS: All the variables analysed had a significant effect size, with the exception of situational awareness (d+ = -0.448; 95% confidence interval [CI] = -1.034, 0.139). The highest mean effect size was found for knowledge (d+ = -0.925; 95% CI = -1.177, -0.673), followed by the mean effect sizes for global nontechnical skills (d+ = -0.642; 95% CI = -0.849, -0.434), team nontechnical skills (d+ = -0.606; 95% CI = -0.949, -0.262), and leadership nontechnical skills (d+ = -0.571; 95% CI = -0.877, -0.264). Similar mean effect sizes were found for attitude (d+ = -0.406; 95% CI = -0.769, -0.044), self-efficacy (d+ = -0.469; 95% CI = -0.874, -0.064), and communication nontechnical skills (d+ = -0.458; 95% CI = -0.818, -0.099). Large heterogeneity among the standardised mean changes was found in the meta-analyses (I2 > 75% and p < .001), except for self-efficacy where I2 = 58.17%, and there was a nonstatistical result for Cochran's Q. This great variability is also reflected in the forest plots. DISCUSSION: The use of simulation interventions to train emergency and critical care healthcare professionals in nontechnical skills significantly improves levels of knowledge, attitude, self-efficacy, and nontechnical skills performance.

The E3-ligase TRIM family of proteins regulates signaling pathways triggered by innate immune pattern-recognition receptors.

Innate immunity conferred by the type I interferon is critical for antiviral defense. To date only a limited number of tripartite motif (TRIM) proteins have been implicated in modulation of innate immunity and anti-microbial activity. Here we report the complementary DNA cloning and systematic analysis of all known 75 human TRIMs. We demonstrate that roughly half of the 75 TRIM-family members enhanced the innate immune response and that they do this at multiple levels in signaling pathways. Moreover, messenger RNA levels and localization of most of these TRIMs were found to be altered during viral infection, suggesting that their regulatory activities are highly controlled at both pre- and posttranscriptional levels. Taken together, our data demonstrate a very considerable dedication of this large protein family to the positive regulation of the antiviral response, which supports the notion that this family of proteins evolved as a component of innate immunity.

New views on three-dimensional imaging technologies for glaucoma: an overview.

PURPOSE OF REVIEW: To summarize the literature on three-dimensional (3D) technological advances in ophthalmology, the quantitative methods associated with this, and their improved ability to help detect glaucoma disease progression. RECENT FINDINGS: Improvements in measuring glaucomatous structural changes are the result of dual innovations in optical coherence tomography (OCT) imaging technology and in associated quantitative software. SUMMARY: Compared with two-dimensional (2D) OCT parameters, newer 3D parameters provide more data and fewer artifacts.

Adaptation of Saccharomyces cerevisiae in a concentrated spent sulphite liquor waste stream for increased inhibitor resistance.

The fermentation of spent sulphite liquor (SSL) from the pulping of hardwoods is limited by the combination of xylose, the primary fermentable sugar and high concentrations of microbial inhibitors that decrease the yeast fermentation ability. The inhibitor resistance phenotypes of xylose-capable Saccharomyces cerevisiae strains were therefore enhanced by combining rational engineering for multi-inhibitor tolerance, with adaptation in concentrated hardwood SSL as selective pressure. The adapted strains were assessed in fermentations with 60-80% v/v concentrated SSL under industrially relevant fermentation conditions. During adaptation, strains produced ethanol concentrations between 11.0 and 15.4 g/L in the range of that reported in literature. The adapted TFA40 and TP50 strains displayed enhanced inhibitor resistance phenotypes and were able to ferment xylose-rich SSL at pH below 5, exhibiting improved ethanol yields relative to the reference strain. Using yeast extract and peptone as nitrogen source in concentrated SSL fermentations further improved ethanol yields. However, strains exhibited a trade-off between resistance and ethanol productivity, indicating a carbon/energy cost for the expression of this inhibitor tolerance phenotype. KEY POINTS : • Achieved fermentation of xylose-rich hardwood spent sulphite liquor at pH below 5.0 • Adaptation of xylose-capable S. cerevisiae in concentrated spent sulphite liquor • Adapted strains exhibited enhanced inhibitor resistance phenotypes.

Use of a Meter With Color-Range Indicators and a Mobile Diabetes Management App Improved Glycemic Control and Patient Satisfaction in an Underserved Hispanic Population: "Tu Salud"-A Randomized Controlled Partial Cross-Over Clinical Study.

Objective: To demonstrate the clinical value of OneTouch (OT) Verio Flex glucose meter used in combination with a Spanish-language version of the OT Reveal mobile application (app) to support diabetes care and improve glycemic control in an underserved Hispanic population with type 2 diabetes. Research Design and Methods: Test subjects (n = 81) used the meter and app for 12 weeks, while a randomized control group (n = 39) used their own glucose meters without connection to an app. Thereafter, test subjects continued the same regimen for an additional 12 weeks to determine the durability of effect, and control subjects crossed over to use the new meter and app. Results: Test subjects experienced a mean reduction in A1C of 1.0% after 12 weeks (P <0.001), a statistically significant greater reduction than in control subjects (P = 0.045). The improvement in A1C in test subjects was sustained over the next 12 weeks. Crossed-over subjects also demonstrated significant improvements in A1C (P <0.001). Mean blood glucose was reduced significantly without an increase in hypoglycemia, and results in range increased over 12 weeks of meter and mobile app use. Results were independent of subjects' numeracy skills. Subjects using the new meter and app reacted favorably to the tools and expressed improvements in their diabetes treatment satisfaction based on Diabetes Treatment Satisfaction Questionnaire-Change scores. Conclusion: Use of the OT meter and a Spanish-language version of its diabetes management app in an underserved population helped participants achieve a sustained improvement in glycemic control. The tools were well received by the subjects and may have important utility in other low-numeracy, low-literacy populations.

Palliative Professionals' Experiences of Receiving Gratitude: A Transformative and Protective Resource.

Providing palliative care can be both challenging and rewarding. It involves emotionally demanding work and yet research shows that burnout is lower than in other fields of health care. Spontaneous expressions of gratitude from patients and family members are not uncommon and are highly valued. This study explored the experience of Spanish palliative professionals who received expressions of gratitude from their patients and families. A phenomenological approach was used to better understand the role of receiving gratitude in participants' lives. Interviews were transcribed verbatim and a phenomenological approach to analysis was undertaken using macro-thematic and micro-thematic reflection. Two team members independently engaged in this reflection with an inductive approach. The analysis was shared and discussed at periodic meetings to identify the key themes and sub-themes of the gratitude experience. Ten palliative professionals were interviewed. Participants engaged in a process of recognizing, internalizing, and treasuring the expressions of gratitude which they then used for reflection and growth. These expressions were a powerful and deeply meaningful resource that the palliative professionals revisited over time. Receiving expressions of gratitude invited a stronger sense of the value of one's self and one's work that was motivational and protective, particularly during challenging times.

A meta-review of transparency and reproducibility-related reporting practices in published meta-analyses on clinical psychological interventions (2000-2020).

Meta-analysis is a powerful and important tool to synthesize the literature about a research topic. Like other kinds of research, meta-analyses must be reproducible to be compliant with the principles of the scientific method. Furthermore, reproducible meta-analyses can be easily updated with new data and reanalysed applying new and more refined analysis techniques. We attempted to empirically assess the prevalence of transparency and reproducibility-related reporting practices in published meta-analyses from clinical psychology by examining a random sample of 100 meta-analyses. Our purpose was to identify the key points that could be improved, with the aim of providing some recommendations for carrying out reproducible meta-analyses. We conducted a meta-review of meta-analyses of psychological interventions published between 2000 and 2020. We searched PubMed, PsycInfo and Web of Science databases. A structured coding form to assess transparency indicators was created based on previous studies and existing meta-analysis guidelines. We found major issues concerning: completely reproducible search procedures report, specification of the exact method to compute effect sizes, choice of weighting factors and estimators, lack of availability of the raw statistics used to compute the effect size and of interoperability of available data, and practically total absence of analysis script code sharing. Based on our findings, we conclude with recommendations intended to improve the transparency, openness, and reproducibility-related reporting practices of meta-analyses in clinical psychology and related areas.

Preventing microalbuminuria with benazepril, valsartan, and benazepril-valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy. METHODS AND FINDINGS: VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion. CONCLUSIONS: Risk/benefit profile of study treatments was similar. Dual renin-angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients. TRIAL REGISTRATION: EudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.

Innate immune sensor LGP2 is cleaved by the Leader protease of foot-and-mouth disease virus.

The RNA helicase LGP2 (Laboratory of Genetics and Physiology 2) is a non-signaling member of the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), whose pivotal role on innate immune responses against RNA viruses is being increasingly uncovered. LGP2 is known to work in synergy with melanoma differentiation-associated gene 5 (MDA5) to promote the antiviral response induced by picornavirus infection. Here, we describe the activity of the foot-and-mouth disease virus (FMDV) Leader protease (Lpro) targeting LGP2 for cleavage. When LGP2 and Lpro were co-expressed, cleavage products were observed in an Lpro dose-dependent manner while co-expression with a catalytically inactive Lpro mutant had no effect on LGP2 levels or pattern. We further show that Lpro localizes and immunoprecipitates with LGP2 in transfected cells supporting their interaction within the cytoplasm. Evidence of LGP2 proteolysis was also detected during FMDV infection. Moreover, the inhibitory effect of LGP2 overexpression on FMDV growth observed was reverted when Lpro was co-expressed, concomitant with lower levels of IFN-ß mRNA and antiviral activity in those cells. The Lpro target site in LGP2 was identified as an RGRAR sequence in a conserved helicase motif whose replacement to EGEAE abrogated LGP2 cleavage by Lpro. Taken together, these data suggest that LGP2 cleavage by the Leader protease of aphthoviruses may represent a novel antagonistic mechanism for immune evasion.

MERS-CoV 4b protein interferes with the NF-κB-dependent innate immune response during infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that emerged in 2012, causing severe pneumonia and acute respiratory distress syndrome (ARDS), with a case fatality rate of ~36%. When expressed in isolation, CoV accessory proteins have been shown to interfere with innate antiviral signaling pathways. However, there is limited information on the specific contribution of MERS-CoV accessory protein 4b to the repression of the innate antiviral response in the context of infection. We found that MERS-CoV 4b was required to prevent a robust NF-κB dependent response during infection. In wild-type virus infected cells, 4b localized to the nucleus, while NF-κB was retained in the cytoplasm. In contrast, in the absence of 4b or in the presence of cytoplasmic 4b mutants lacking a nuclear localization signal (NLS), NF-κB was translocated to the nucleus leading to the expression of pro-inflammatory cytokines. This indicates that NF-κB repression required the nuclear import of 4b mediated by a specific NLS. Interestingly, we also found that both in isolation and during infection, 4b interacted with α-karyopherin proteins in an NLS-dependent manner. In particular, 4b had a strong preference for binding karyopherin-α4 (KPNA4), which is known to translocate the NF-κB protein complex into the nucleus. Binding of 4b to KPNA4 during infection inhibited its interaction with NF-κB-p65 subunit. Thereby we propose a model where 4b outcompetes NF-κB for KPNA4 binding and translocation into the nucleus as a mechanism of interference with the NF-κB-mediated innate immune response.

The Medical Outcome Study-HIV Health Survey: A systematic review and reliability generalization meta-analysis.

The Medical Outcome Study-HIV Health Survey (MOS-HIV) is one of the most used questionnaires for the evaluation of the health-related quality of life (HRQoL) in people living with HIV (PLWHIV) in both medical settings and research studies. This study aimed to estimate the average reliability of the MOS-HIV scores and to evaluate the characteristics of the studies that could explain the variability between reliability estimates. Furthermore, the study aimed to estimate the induction rate of the reliability of the MOS-HIV. A systematic review of the previous literature, including studies that reported α and/or test-retest coefficients with the data at hand for the total score of the MOS-HIV and the subscales, was conducted. Fifty studies (52 samples; N = 14,132) were included in the reliability generalization meta-analysis. The average α coefficient for the total score of MOS-HIV was .91 and above .80 for all of the subscales, except for role functioning, which had an average coefficient of .76. Different study dimensions were related to the heterogeneity of reliability between studies. Reliability induction was found to be 76.1%. The results obtained in the present study indicate that the MOS-HIV is a reliable instrument for HRQoL evaluation in PLWHIV, for clinical and research purposes. In the clinical practice of health services, nurses could employ this gold standard for reliable evaluations of HRQoL in PLWHIV.

The Padua Inventory-Washington State University Revision of Obsessions and Compulsions: A Reliability Generalization Meta-Analysis.

The Padua Inventory-Washington State University Revision (PI-WSUR) is a frequently used test to assess obsessive-compulsive symptoms in screening and clinical contexts. A reliability generalization meta-analysis was carried out to estimate the average reliability of the PI-WSUR scores and its subscales and to search for characteristics of the studies that can explain the heterogeneity among reliability coefficients. A total of 124 independent samples reported some coefficient alpha or test-retest correlation with the data at hand for the PI-WSUR scores. The average internal consistency reliability of the PI-WSUR total scores was .929 (95% CI [.922, .936]), and for the subscales, the means ranged from .792 to .900. The test-retest reliability for PI-WSUR total scores was .767 (95% CI [.700, .820]), with the subscales ranging from .540 to .790. Moderator analyses revealed a positive relationship between the standard deviation of PI-WSUR total scores and alpha coefficients, as well as higher reliability estimates for the original version of the test and for studies from North America. The reliability induction rate for the PI-WSUR was 53.7%. Regarding reliability, the PI-WSUR ranks among the best scales for assessing obsessive-compulsive symptoms. Internal consistency reliability was excellent for the PI-WSUR total score and good for the subscales.

Results after the application of tranexamic acid intravenous or intra-articular in the control of postsurgical bleeding after total hip arthroplasty: a randomized controlled trial.

INTRODUCTION: A frequent complication after total hip arthroplasty is bleeding; to reduce it, intravenous or intra-articular tranexamic acid (TXA) is used. There is no evidence yet on which route of administration is better. MATERIALS AND METHOD: This was a prospective, controlled, randomized study in 2 arms between February 2017 and February 2019. In group A, 15 mg/kg intravenous TXA was administered and in group B 2 g intra-articular TXA. Haemoglobin and haematocrit values were evaluated at 24-72 h, also volume of drained blood, volume of blood lost, transfusions and complications. RESULTS: A total of 195 patients were included: 110 in group A and 85 group B. Haemoglobin dropped 3.10 ± 1.32 g/dl in 24 h and 3.63 ± 1.41 g/dl at 72 h in group A; the haematocrit dropped 8.38 ± 4.67% in 24 h and 15.40 ± 4.39% in 72 h. In group B, haemoglobin dropped 3.09 ± 1.40 g/dl in 24 h and 3.34 ± 1.23 g/dl in 72 h and haematocrit 9.75 ± 3.95% and 10.40 ± 3.72% in 24 and 72 h. No significant differences were found for haemoglobin values at 24 and 72 h and haematocrit at 24 h (p > 0.05); we did not obtain statistically significant differences in drainage, blood loss between groups or in the proportion of transfused. When stratifying the results by age, we obtained significant differences in the decrease in haemoglobin (p = 0.021) and haematocrit (p = 0.025) in patients > 65 years. CONCLUSIONS: The different routes of administration of TXA in PTC have a similar effect in reducing post-operative bleeding without evidencing an increase in complications. LEVEL OF EVIDENCE: I.

Paramyxovirus V Proteins Interact with the RIG-I/TRIM25 Regulatory Complex and Inhibit RIG-I Signaling.

Paramyxovirus V proteins are known antagonists of the RIG-I-like receptor (RLR)-mediated interferon induction pathway, interacting with and inhibiting the RLR MDA5. We report interactions between the Nipah virus V protein and both RIG-I regulatory protein TRIM25 and RIG-I. We also observed interactions between these host proteins and the V proteins of measles virus, Sendai virus, and parainfluenza virus. These interactions are mediated by the conserved C-terminal domain of the V protein, which binds to the tandem caspase activation and recruitment domains (CARDs) of RIG-I (the region of TRIM25 ubiquitination) and to the SPRY domain of TRIM25, which mediates TRIM25 interaction with the RIG-I CARDs. Furthermore, we show that V interaction with TRIM25 and RIG-I prevents TRIM25-mediated ubiquitination of RIG-I and disrupts downstream RIG-I signaling to the mitochondrial antiviral signaling protein. This is a novel mechanism for innate immune inhibition by paramyxovirus V proteins, distinct from other known V protein functions such as MDA5 and STAT1 antagonism.IMPORTANCE The host RIG-I signaling pathway is a key early obstacle to paramyxovirus infection, as it results in rapid induction of an antiviral response. This study shows that paramyxovirus V proteins interact with and inhibit the activation of RIG-I, thereby interrupting the antiviral signaling pathway and facilitating virus replication.

Psychological treatment for family members of children with cancer: A systematic review and meta-analysis.

OBJECTIVE: This meta-analytical study examined the effects of psychological treatments applied to family members of children and adolescents with cancer, as well as the characteristics of the studies that can be associated with their effects. METHODS: Four databases were searched between January 1980 and January 2017; the references of the located studies were reviewed, and emails were sent to experts in this topic. Forty articles fulfilled the selection criteria. The standardized mean pretest-posttest (or pretest-follow-up) change was used as the effect-size index for the treatment and control groups. RESULTS: The 40 articles included 40 treatment groups and 21 control groups. When treatment and control pretest-posttest mean effects were compared, psychological interventions revealed positive, statistically significant results for anxiety (dadj  = 0.339) and problem-solving skills (dadj  = 0.385) and, to a lesser extent, for posttraumatic stress (dadj  = 0.224). No statistically significant differences were found for mood (dadj  = 0.147), acute stress (dadj  = -0.010), coping skills (dadj  = 0.123), social support (dadj  = 0.245), or quality of life (dadj  = 0.538). CONCLUSIONS: Positive effects of mild to moderate magnitude were found in the posttests for some outcome measures. Behavioral interventions seem to be the most promising. Interventions achieved the best results when they were long in duration and low in intensity and when they were applied to family members with young children who were undergoing medical treatment. At follow-up, the intervention benefits were diminished. The application of psychological interventions is recommended to mitigate the negative psychological repercussions in this population.