Evaluation of the Tasso+ blood self-collection device for quantitation of plasma cytomegalovirus (CMV) DNAemia in adult solid organ transplant recipients (SOTr).

Quantitative monitoring of cytomegalovirus (CMV) DNAemia in venous blood is standard in solid organ transplant recipients (SOTr) but is limited by the need for phlebotomy facilities and personnel. The aim of the study was to evaluate the Tasso+ capillary blood (CB) self-collection device for quantitation of plasma CMV DNAemia. Thirty adult SOTr with suspected CMV DNAemia were enrolled to have a supervised Tasso+ CB sample collection within 24 h of a venous sample. CMV DNA was quantitated in paired samples by using the Abbott M2000 Real-Time qPCR instrument. The participants were provided with a study-specific survey that measured patient acceptability of the Tasso+ device compared with venipuncture. A Tasso + CB sample was successfully collected in 28/30 (93%) patients, and 44 paired samples were analyzed. Concordance for detection of CMV DNAemia above the limit of detection (LOD) was 91% (42/44), and the Tasso + CB sample was estimated to be 95% sensitive at a viral load (VL) of 308 IU/mL. Among samples with a quantifiable DNAemia result with both methods (N = 31), there was excellent correlation between methods (Spearman R2 = 0.99). The difference in CMV VL between venous and Tasso+ CB samples was not dependent on time (P > 0.1). Of 12 who completed the survey, 11 (92%) expressed a preference for Tasso+ CB collection over venipuncture. Collection of CB with the Tasso+ device is feasible, patient-acceptable, and yields generally comparable CMV DNAemia load to standard venous samples, but with lower sensitivity. Future studies to optimize and evaluate this methodology for patient self-collected samples are warranted. IMPORTANCE: We evaluate an FDA-cleared blood self-collection device (Tasso+) and demonstrate that it is patient-acceptable and yields a liquid blood sample with quantitative CMV DNAemia results comparable to those of standard venipuncture samples. This opens up possibilities for self-blood collection to monitor for CMV and potentially other viruses in transplant and other at-risk populations.

Multi-objective ecological restoration priority in China: Cost-benefit optimization in different ecological performance regimes based on planetary boundaries.

In the context of the "United Nations Decade on Ecosystem Restoration", optimizing spatiotemporal arrangements for ecological restoration is an important approach to enhancing overall socioecological benefits for sustainable development. However, against the background of ecological degradation caused by the human use of most natural resources at levels that have approached or exceeded the safe and sustainable boundaries of ecosystems, it is key to explain how to optimize ecological restoration by classified management and optimal total benefits. In response to these issues, we combined spatial heterogeneity and temporal dynamics at the national scale in China to construct five ecological performance regimes defined by indicators that use planetary boundaries and ecological pressures which served as the basis for prioritizing ecological restoration areas and implementing zoning control. By integrating habitat conservation, biodiversity, water supply, and restoration cost constraints, seven ecological restoration scenarios were simulated to optimize the spatial layout of ecological restoration projects (ERPs). The results indicated that the provinces with unsustainable freshwater use, climate change, and land use accounted for more than 25%, 66.7%, and 25%, respectively, of the total area. Only 30% of the provinces experienced a decrease in environmental pressure. Based on the ecological performance regimes, ERP sites spanning the past 20 years were identified, and more than 50% of the priority areas were clustered in regime areas with increased ecological stress. As the restoration area targets doubled (40%) from the baseline (20%), a multi-objective scenario presents a trade-off between expanded ERPs in areas with highly beneficial effects and minimal restoration costs. In conclusion, a reasonable classification and management regime is the basis for targeted restoration. Coordinating multiple objectives and costs in ecological restoration is the key to maximizing socio-ecological benefits. Our study offered new perspectives on systematic and sustainable planning for ecological restoration.

CURTAIN-A unique web-based tool for exploration and sharing of MS-based proteomics data.

To facilitate analysis and sharing of mass spectrometry (MS)-based proteomics data, we created online tools called CURTAIN (https://curtain.proteo.info) and CURTAIN-PTM (https://curtainptm.proteo.info) with an accompanying series of video tutorials (https://www.youtube.com/@CURTAIN-me6hl). These are designed to enable non-MS experts to interactively peruse volcano plots and deconvolute primary experimental data so that replicates can be visualized in bar charts or violin plots and exported in publication-ready format. They also allow assessment of overall experimental quality by correlation matrix and profile plot analysis. After making a selection of protein "hits", the user can analyze known domain structure, AlphaFold predicted structure, reported interactors, relative expression as well as disease links. CURTAIN-PTM permits analysis of all identified PTM sites on protein(s) of interest with selected databases. CURTAIN-PTM also links with the Kinase Library to predict upstream kinases that may phosphorylate sites of interest. We provide examples of the utility of CURTAIN and CURTAIN-PTM in analyzing how targeted degradation of the PPM1H Rab phosphatase that counteracts the Parkinson's LRRK2 kinase impacts cellular protein levels and phosphorylation sites. We also reanalyzed a ubiquitylation dataset, characterizing the PINK1-Parkin pathway activation in primary neurons, revealing data of interest not highlighted previously. CURTAIN and CURTAIN-PTM are free to use and open source, enabling researchers to share and maximize the impact of their proteomics data. We advocate that MS data published in volcano plot format be reported containing a shareable CURTAIN weblink, thereby allowing readers to better analyze and exploit the data.

Skin and soft tissue infection incidence before and during the COVID-19 pandemic.

Skin and Soft Tissue Infections (SSTIs) are common bacterial infections. We hypothesized that due to the COVID-19 pandemic, SSTI rates would significantly decrease due to directives to avoid unneeded care and attenuated SSTIs risk behaviours. We retrospectively examined all patients with an ICD-10 diagnosis code in the Los Angeles County Department of Health Services, the second largest U.S. safety net healthcare system between 16 March 2017 and 15 March 2022. We then compared pre-pandemic with intra-pandemic SSTI rates using an interrupted time series analysis. We found 72,118 SSTIs, 46,206 during the pre-pandemic period and 25,912 during the intra-pandemic period. Pre-pandemic SSTI rate was significantly higher than the intra-pandemic rate (3.27 vs. 2.31 cases per 1,000 empanelled patient-months, P < 0.0001). The monthly SSTI cases decreased by 1.19 SSTIs/1,000 empanelled patient-months between the pre- and intra-pandemic periods (P = 0.0003). SSTI subgroups (inpatient, observation unit, emergency department, and outpatient clinics), all had significant SSTI decreases between the two time periods (P < 0.05) except for observation unit (P = 0.50). Compared to the pre-COVID-19 pandemic period, medically attended SSTI rates in our large U.S. safety net healthcare system significantly decreased by nearly 30%. Whether findings reflect true SSTI decreases or decreased health system utilization for SSTIs requires further examination.

A spatially variant high-order variational model for Rician noise removal.

Rician noise removal is an important problem in magnetic resonance (MR) imaging. Among the existing approaches, the variational method is an essential mathematical technique for Rician noise reduction. The previous variational methods mainly employ the total variation (TV) regularizer, which is a first-order term. Although the TV regularizer is able to remove noise while preserving object edges, it suffers the staircase effect. Besides, the adaptability has received little research attention. To this end, we propose a spatially variant high-order variational model (SVHOVM) for Rician noise reduction. We introduce a spatially variant TV regularizer, which can adjust the smoothing strength for each pixel depending on its characteristics. Furthermore, SVHOVM utilizes the bounded Hessian (BH) regularizer to diminish the staircase effect generated by the TV term. We develop a split Bregman algorithm to solve the proposed minimization problem. Extensive experiments are performed to demonstrate the superiority of SVHOVM over some existing variational models for Rician noise removal.

Longitudinal analysis of SARS-CoV-2 infection and vaccination in the LA-SPARTA cohort reveals increased risk of infection in vaccinated Hispanic participants.

Introduction: SARS-CoV-2 is the etiologic agent of coronavirus disease 2019 (COVID-19). Questions remain regarding correlates of risk and immune protection against COVID-19. Methods: We prospectively enrolled 200 participants with a high risk of SARS-CoV-2 occupational exposure at a U.S. medical center between December 2020 and April 2022. Participant exposure risks, vaccination/infection status, and symptoms were followed longitudinally at 3, 6, and 12 months, with blood and saliva collection. Serological response to the SARS-CoV-2 spike holoprotein (S), receptor binding domain (RBD) and nucleocapsid proteins (NP) were quantified by ELISA assay. Results: Based on serology, 40 of 200 (20%) participants were infected. Healthcare and non-healthcare occupations had equivalent infection incidence. Only 79.5% of infected participants seroconverted for NP following infection, and 11.5% were unaware they had been infected. The antibody response to S was greater than to RBD. Hispanic ethnicity was associated with 2-fold greater incidence of infection despite vaccination in this cohort. Discussion: Overall, our findings demonstrate: 1) variability in the antibody response to SARS-CoV-2 infection despite similar exposure risk; 2) the concentration of binding antibody to the SARS-CoV-2 S or RBD proteins is not directly correlated with protection against infection in vaccinated individuals; and 3) determinants of infection risk include Hispanic ethnicity despite vaccination and similar occupational exposure.

Characterization of COVID-19 Vaccine Hesitancy Among Essential Workforce Members of a Large Safety Net Urban Medical Center.

OBJECTIVES: Vaccine hesitancy among essential workers remains a significant public health challenge. We examined psychological constructs of perceived susceptibility, threat, and self-efficacy and their associations with COVID-19 vaccine hesitancy among a racially and ethnically diverse essential workforce population. METHODS: We performed a cross-sectional survey of essential workers from September-December 2020 at a large Los Angeles safety-net medical center as part of a program offering free COVID-19 serology testing. Program participants completed a standardized survey at the time of phlebotomy. Hierarchical logistic regression was utilized to determine factors independently associated with vaccine hesitancy. RESULTS: Among 1327 persons who had serology testing, 1235 (93%) completed the survey. Of these, 958 (78%) were healthcare workers. Based on expressed intent, 22% were vaccine-hesitant 78% were vaccine acceptors. In our multivariate model, vaccine hesitancy was associated with female gender [aOR = 2.09; 95% CI (1.44-3.05)], African American race [aOR = 4.32; (2.16-8.62)], LatinX ethnicity [aOR = 2.47; 95% CI (1.51-4.05)] and history of not/sometimes receiving influenza vaccination [aOR = 4.39; 95% CI (2.98-6.48)]. Compared to nurses, vaccine hesitancy was lower among physicians [aOR = 0.09; 95% CI (0.04-0.23)], non-nursing/non-physician healthcare workers [aOR = 0.55; 95% CI (0.33-0.92)], and non-healthcare care workers [aOR = 0.53; 95% CI (0.36-0.78)]. CONCLUSIONS: Among a racially/ethnically diverse group of safety net medical center essential workers, COVID-19 vaccine hesitancy was associated with racial/ethnic minority groups, employment type, and prior influenza vaccination hesitancy. Interestingly, we found no association with the Health Belief Model construct measures of perceived susceptibility, threat, and self-efficacy. Psychological constructs not assessed may be drivers of vaccine hesitancy in our population.

The Effect of Systemic Antibiotics for Suppurative Skin and Soft Tissue Infections on the Skin Microbiome.

Background: Skin and soft tissue infections (SSTIs) are very common bacterial infections. There are few data on the microbiome of persons with and without SSTIs and the effects of systemic antibiotic therapy. Methods: We sampled the skin microbiome from 10 outpatients with acute suppurative SSTI before and after systemic antibiotic therapy and enrolled 10 matched controls. Samples were collected at 6 skin body sites (occipital scalp, axilla, interdigital hand web spaces, gluteal crease, inguinal creases, and popliteal fossa), 2 mucosal sites (throat, anterior nares), and the site of skin infection (for case subjects) at baseline and a week later after abscess incision, drainage, and oral antibiotics. Result: Among 10 SSTI cases, mean age was 41.5 years and 3 had diabetes mellitus. The gluteal crease at baseline had higher α-diversity in controls vs cases (P = .039); ß-diversity analysis showed significant differences in overall bacterial community composition (P = .046). However, at other body sites there were no significant differences by either α- or ß-diversity. Systemic antibiotic use did not affect body site diversity indices except at the SSTI site (α-diversity increased, P = .001). Conclusions: We surprisingly found no significant differences in microbiome comparing noninfected skin sites before and after systemic SSTI antibiotic therapy nor significant differences at noninfected skin sites between SSTI cases and uninfected controls. We also found minimal significant differences between microbiome diversity and bacterial signatures at noninfected skin sites between patients with acute skin infection and uninfected controls. Our findings challenge the dogma that systemic antibiotics impact the skin microbiome.

Two trehalase isoforms, produced from a single transcript, regulate drought stress tolerance in Arabidopsis thaliana.

KEY MESSAGE: Alternative translation initiation of the unique Arabidopsis trehalase gene allows for the production of two isoforms with different subcellular localization, providing enzyme access to both intra- and extra-cellular trehalose. The trehalose-hydrolyzing enzyme trehalase mediates drought stress tolerance in Arabidopsis thaliana by controlling ABA-induced stomatal closure. We now report the existence of two trehalase isoforms, produced from a single transcript by alternative translation initiation. The longer full-length N-glycosylated isoform (AtTRE1L) localizes in the plasma membrane with the catalytic domain in the apoplast. The shorter isoform (AtTRE1S) lacks the transmembrane domain and localizes in the cytoplasm and nucleus. The two isoforms can physically interact and this interaction affects localization of AtTRE1S. Consistent with their role in plant drought stress tolerance, both isoforms are activated by AtCPK10, a stress-induced calcium-dependent guard cell protein kinase. Transgenic plants expressing either isoform indicate that both can mediate ABA-induced stomatal closure in response to drought stress but that the short (cytoplasmic/nuclear) isoform, enriched in those conditions, is significantly more effective.

The Impact of Risk Factors on Treatment Outcomes of Nosocomial Pneumonia Due to Gram-Negative Bacteria in the Intensive Care Unit.

INTRODUCTION: Nosocomial pneumonia is a common infection associated with high mortality in hospitalized patients. Nosocomial pneumonia, caused by gram-negative bacteria, often occurs in the elderly and patients with co-morbid diseases. METHODS: Original research using a prospective cross-sectional design was conducted on 281 patients in an intensive care unit setting with nosocomial pneumonia between July 2015 and July 2019. For each nosocomial pneumonia case, data regarding comorbidities, risk factors, patient characteristics, Charlson comorbidity index (CCI), Systemic Inflammatory Response Syndrome (SIRS), and quick Sepsis-Related Organ Failure Assessment (qSOFA) points and treatment outcomes were collected. Data were analyzed by SPSS 22.0. RESULTS: Nosocomial pneumonia due to gram-negative bacteria occurred in patients with neurological disorders (34.87%), heart diseases (16.37%), chronic renal failure (7.12%), and post-surgery (10.68%). Worse outcomes attributed to nosocomial pneumonia were high at 75.8%. Mechanical ventilation, change of antibiotics, and CCI ≥ 3 and qSOFA ≥ 2 were significantly negative prognostic factors (p < 0.05) on outcomes of nosocomial pneumonia. There was no difference in treatment effects between gender, age, time of onset pneumonia, SIRS score (p > 0.05). The pathogens were significant factors that influence treatment effects, but they weren't independent risk factors for poor outcomes (p = 0.823). CONCLUSIONS: Patients with nosocomial pneumonia hospitalized in intensive care units are usually associated with many underlying diseases, including neurological diseases. Mechanical ventilation, a change in antibiotics, CCI ≥ 3, and qSOFA ≥ 2 are also associated with a worse prognosis of nosocomial pneumonia. CCI and qSOFA might be used in predicting the outcome of nosocomial pneumonia.

EEG-Based Emotion Recognition by Convolutional Neural Network with Multi-Scale Kernels.

Besides facial or gesture-based emotion recognition, Electroencephalogram (EEG) data have been drawing attention thanks to their capability in countering the effect of deceptive external expressions of humans, like faces or speeches. Emotion recognition based on EEG signals heavily relies on the features and their delineation, which requires the selection of feature categories converted from the raw signals and types of expressions that could display the intrinsic properties of an individual signal or a group of them. Moreover, the correlation or interaction among channels and frequency bands also contain crucial information for emotional state prediction, and it is commonly disregarded in conventional approaches. Therefore, in our method, the correlation between 32 channels and frequency bands were put into use to enhance the emotion prediction performance. The extracted features chosen from the time domain were arranged into feature-homogeneous matrices, with their positions following the corresponding electrodes placed on the scalp. Based on this 3D representation of EEG signals, the model must have the ability to learn the local and global patterns that describe the short and long-range relations of EEG channels, along with the embedded features. To deal with this problem, we proposed the 2D CNN with different kernel-size of convolutional layers assembled into a convolution block, combining features that were distributed in small and large regions. Ten-fold cross validation was conducted on the DEAP dataset to prove the effectiveness of our approach. We achieved the average accuracies of 98.27% and 98.36% for arousal and valence binary classification, respectively.

Silicon in mitigation of abiotic stress-induced oxidative damage in plants.

Accumulation of reactive oxygen species (ROS), and their destructive effects on cellular organelles are the hallmark features of plants exposed to abiotic stresses. Plants are well-equipped with defensive mechanisms like antioxidant systems to deal with ROS-induced oxidative stress. Silicon has been emerged as an important regulator of plant protective mechanisms under environmental stresses, which can be up-taken from soil through a system of various silicon-transporters. In plants, silicon is deposited underneath of cuticles and in the cell wall, and help plant cells reduce deleterious effects of stresses. Furthermore, silicon can provide resistance to ROS-toxicity, which often accounts for silicon-mediated improvement of plant tolerance to different abiotic constraints, including salinity, drought, and metal toxicity. Silicon enhances the ROS-detoxification ability of treated plants by modulating the antioxidant defense systems, and the expression of key genes associated with oxidative stress mitigation and hormone metabolism. Silicon also displays additive roles in ROS-elimination when supplied with other external stimuli. Here, we discuss recent findings on how silicon is able to modulate antioxidant defense of plants in response to oxidative stress triggered by different abiotic constraints. We also review interactions of silicon with other signaling molecules, including nitric oxide, ROS, polyamines, and phytohormones in the mediation of plant protection against abiotic stress-induced oxidative damage.

Different strategies of strigolactone and karrikin signals in regulating the resistance of Arabidopsis thaliana to water-deficit stress.

Strigolactone and karrikin receptors, DWARF14 (D14) and KARRIKIN INSENSITIVE 2 (KAI2), respectively, have been shown to positively regulate drought resistance in Arabidopsis thaliana by modulating abscisic acid responsiveness, anthocyanin accumulation, stomatal closure, cell membrane integrity and cuticle formation. Here, we aim to identify genes specifically or commonly regulated by D14 and KAI2 under water scarcity, using comparative analysis of the transcriptome data of the A. thaliana d14-1 and kai2-2 mutants under dehydration conditions. In comparison with wild-type, under dehydration conditions, the expression levels of genes related to photosynthesis and the metabolism of glucosinolates and trehalose were significantly changed in both d14-1 and kai2-2 mutant plants, whereas the transcript levels of genes related to the metabolism of cytokinins and brassinosteroids were significantly altered in the d14-1 mutant plants only. These results suggest that cytokinin and brassinosteroid metabolism might be specifically regulated by the D14 pathway, whereas photosynthesis and metabolism of glucosinolates and trehalose are potentially regulated by both D14 and KAI2 pathways in plant response to water scarcity.

The "Interest Game": A Ludic Application to Improve Apathy Assessment in Patients with Neurocognitive Disorders.

BACKGROUND: Apathy, a highly prevalent behavioral disorder in Alzheimer's disease and other related disorders, is currently assessed using clinical scales as it is for all neuropsychiatric disorders. OBJECTIVE: The aim of this study is to propose a new type of assessment using new technologies designed to assess loss of interest by a more implicit and indirect method. METHODS: The Interest Game is a form of interactive self-report, where categories of interests are presented in order to quantify them and identify the activities that constitute them. Two indices can be extracted, the number of categories and the number of activities selected. We compared the scores between three groups: Apathetic (A) and Non-Apathetic (NA) subjects (according to the Apathy Diagnostic Criteria) and controls with no objective cognitive impairment. RESULTS: 95 subjects were included. Results showed that subjects from the A group had significantly less interests (both categories and images selected) than the NA group. As expected, the control group selected a higher number of categories than the other groups. The diagnosis (minor or major neurocognitive disorder) and level of education had also a significant effect on the number of categories selected. Furthermore, subjects with major neurocognitive disorder (NCD) had significantly less interests than minor NCD group. The number of categories measure was more sensitive than the number of images selected. CONCLUSION: The Interest Game is a promising tool to quantify and identify subject interests and differentiate between apathetic and non-apathetic subjects. Future studies should focus on including more apathetic subjects in the minor NCD group and validating this tool with the general population.

Functional Characterization of Class I Trehalose Biosynthesis Genes in Physcomitrella patens.

The function of trehalose metabolism in plants during growth and development has been extensively studied, mostly in the eudicot Arabidopsis thaliana. So far, however, not much is known about trehalose metabolism in the moss Physcomitrella patens. Here, we show that in P. patens, two active trehalose-6-phosphate synthase enzymes exist, PpTPS1 and PpTPS2. Expression of both enzymes in Saccharomyces cerevisiae can complement the glucose-growth defect of the yeast tps1∆ mutant. Truncation of N-terminal extension in PpTPS1 and PpTPS2 resulted in higher TPS activity and high trehalose levels, upon expression in yeast. Physcomitrella knockout plants were generated and analyzed in various conditions to functionally characterize these proteins. tps1∆ and tps2∆ knockouts displayed a lower amount of caulonema filaments and were significantly reduced in size of gametophores as compared to the wild type. These phenotypes were more pronounced in the tps1∆ tps2∆ mutant. Caulonema formation is induced by factors such as high energy and auxins. Only high amounts of supplied energy were able to induce caulonema filaments in the tps1∆ tps2∆ mutant. Furthermore, this mutant was less sensitive to auxins as NAA-induced caulonema development was arrested in the tps1∆ tps2∆ mutant. In contrast, formation of caulonema filaments is repressed by cytokinins. This effect was more severe in the tps1∆ and tps1∆ tps2∆ mutants. Our results demonstrate that PpTPS1 and PpTPS2 are essential for sensing and signaling sugars and plant hormones to monitor the balance between caulonema and chloronema development.

Association of N-acetyltransferase-2 and glutathione S-transferase polymorphisms with idiopathic male infertility in Vietnam male subjects.

N-acetyltransferase-2 (NAT2) and Glutathione S-transferases (GSTs) are phase-II xenobiotic metabolizing enzymes participating in detoxification of toxic arylamines, aromatic amines, hydrazines and reactive oxygen species (ROS), which are produced under oxidative and electrophile stresses. The purpose of this research was to investigate whether two common single-nucleotide polymorphisms (SNP) of NAT2 (rs1799929, rs1799930) and GSTP1 (rs1138272, rs1695) associated with susceptibility to idiopathic male infertility. A total 300 DNA samples (150 infertile patients and 150 healthy control) were genotyped for the polymorphisms by ARMS - PCR. We revealed a significant association between the NAT2 variant genotypes (CT + TT (rs1799929), (OR: 3.74; p < 0.001)) and (GA + AA (rs1799930), (OR: 3.75; p < 0.001)) or GSTP1 variant genotypes (GA + AA (rs1695), (OR: 5.11; p < 0,001)) and (CT + TT (rs1138272), (OR: 7.42; p < 0,001) with idiopathic infertility risk. Our findings rate the effect of single-nucleotide polymorphisms of GSTP1 and/or NAT2 in modulation of the risk of male infertility in subjects from Vietnam. This pilot study is the first (as far as we know) to reveal that polymorphisms of NAT2 (rs1799929, rs1799930) and GSTP1 (rs1138272, rs1695) are some novel genetic markers for susceptibility to idiopathic male infertility.

Innovative Use of Denver Shunt in a Child with Generalized Lymphatic Anomaly.

BACKGROUND: Denver® shunts have traditionally been used for palliation of refractory malignant and chylous peritoneal and pleural collections. We describe an innovative use of the Denver shunt in a child with generalized lymphatic anomaly. MATERIALS AND METHODS: Retrospective chart review of a 6-year-old girl with generalized lymphatic anomaly, who presented with refractory lymphorrhea from the labium majus, was performed. This was managed with innovative placement of the Denver shunt between a large abdominal wall cyst and the peritoneal cavity. RESULTS: There was progressive reduction in lymphorrhea with complete cessation at 11 months post shunt placement. At 33-month follow-up, the shunt remains patent with no further lymphorrhea. CONCLUSION: Denver shunts can be utilized for the creation of internal drainage pathways besides its traditional uses for draining peritoneal and pleural fluids.

Recommendations for the Use of Serious Games in Neurodegenerative Disorders: 2016 Delphi Panel.

The use of Serious Games (SG) in the health domain is expanding. In the field of neurodegenerative disorders (ND) such as Alzheimer's disease, SG are currently employed both to support and improve the assessment of different functional and cognitive abilities, and to provide alternative solutions for patients' treatment, stimulation, and rehabilitation. As the field is quite young, recommendations on the use of SG in people with ND are still rare. In 2014 we proposed some initial recommendations (Robert et al., 2014). The aim of the present work was to update them, thanks to opinions gathered by experts in the field during an expert Delphi panel. Results confirmed that SG are adapted to elderly people with mild cognitive impairment (MCI) and dementia, and can be employed for several purposes, including assessment, stimulation, and improving wellbeing, with some differences depending on the population (e.g., physical stimulation may be better suited for people with MCI). SG are more adapted for use with trained caregivers (both at home and in clinical settings), with a frequency ranging from 2 to 4 times a week. Importantly, the target of SG, their frequency of use and the context in which they are played depend on the SG typology (e.g., Exergame, cognitive game), and should be personalized with the help of a clinician.

Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects.

Diverse Ab effector functions mediated by the Fc domain have been commonly associated with reduced risk of infection in a growing number of nonhuman primate and human clinical studies. This study evaluated the anti-HIV Ab effector activities in polyclonal serum samples from HIV-infected donors, VAX004 vaccine recipients, and healthy HIV-negative subjects using a variety of primary and cell line-based assays, including Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cell-mediated viral inhibition, and Ab-dependent cellular phagocytosis. Additional assay characterization was performed with a panel of Fc-engineered variants of mAb b12. The goal of this study was to characterize different effector functions in the study samples and identify assays that might most comprehensively and dependably capture Fc-mediated Ab functions mediated by different effector cell types and against different viral targets. Deployment of such assays may facilitate assessment of functionally unique humoral responses and contribute to identification of correlates of protection with potential mechanistic significance in future HIV vaccine studies. Multivariate and correlative comparisons identified a set of Ab-dependent cell-mediated viral inhibition and phagocytosis assays that captured different Ab activities and were distinct from a group of ADCC assays that showed a more similar response profile across polyclonal serum samples. The activities of a panel of b12 monoclonal Fc variants further identified distinctions among the ADCC assays. These results reveal the natural diversity of Fc-mediated Ab effector responses among vaccine recipients in the VAX004 trial and in HIV-infected subjects, and they point to the potential importance of polyfunctional Ab responses.