GREM1 is required to maintain cellular heterogeneity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) shows pronounced epithelial and mesenchymal cancer cell populations1-4. Cellular heterogeneity in PDAC is an important feature in disease subtype specification3-5, but how distinct PDAC subpopulations interact, and the molecular mechanisms that underlie PDAC cell fate decisions, are incompletely understood. Here we identify the BMP inhibitor GREM16,7 as a key regulator of cellular heterogeneity in pancreatic cancer in human and mouse. Grem1 inactivation in established PDAC in mice resulted in a direct conversion of epithelial into mesenchymal PDAC cells within days, suggesting that persistent GREM1 activity is required to maintain the epithelial PDAC subpopulations. By contrast, Grem1 overexpression caused an almost complete 'epithelialization' of highly mesenchymal PDAC, indicating that high GREM1 activity is sufficient to revert the mesenchymal fate of PDAC cells. Mechanistically, Grem1 was highly expressed in mesenchymal PDAC cells and inhibited the expression of the epithelial-mesenchymal transition transcription factors Snai1 (also known as Snail) and Snai2 (also known as Slug) in the epithelial cell compartment, therefore restricting epithelial-mesenchymal plasticity. Thus, constant suppression of BMP activity is essential to maintain epithelial PDAC cells, indicating that the maintenance of the cellular heterogeneity of pancreatic cancer requires continuous paracrine signalling elicited by a single soluble factor.

Extensive topographic remapping and functional sharpening in the adult rat visual pathway upon first visual experience.

Understanding the dynamics of stability/plasticity balances during adulthood is pivotal for learning, disease, and recovery from injury. However, the brain-wide topography of sensory remapping remains unknown. Here, using a first-of-its-kind setup for delivering patterned visual stimuli in a rodent magnetic resonance imaging (MRI) scanner, coupled with biologically inspired computational models, we noninvasively mapped brain-wide properties-receptive fields (RFs) and spatial frequency (SF) tuning curves-that were insofar only available from invasive electrophysiology or optical imaging. We then tracked the RF dynamics in the chronic visual deprivation model (VDM) of plasticity and found that light exposure progressively promoted a large-scale topographic remapping in adult rats. Upon light exposure, the initially unspecialized visual pathway progressively evidenced sharpened RFs (smaller and more spatially selective) and enhanced SF tuning curves. Our findings reveal that visual experience following VDM reshapes both structure and function of the visual system and shifts the stability/plasticity balance in adults.

Do physical fitness and cognitive function mediate the relationship between basic activities of daily living and quality of life in older adults with dementia?

PURPOSE: Independence in activities of daily living (ADLs) is associated with quality of life (QoL) in individuals with dementia. However, the contribution of physical and cognitive functions to this relationship needs further examination. This study aims to examine the mediating effect of physical fitness and cognitive function in the relationship between independence in basic ADLs and QoL among older adults with dementia. METHODS: This cross-sectional study included 107 older adults with dementia (74.8% women; age 78.21 ± 7.70 years). Independence in basic ADL and QoL were evaluated using the Barthel Index (BI) and QoL- Alzheimer's Disease Scale, respectively. The Alzheimer's Disease Assessment Scale-Cognitive Subscale and the Mini-Mental State Examination were applied to assess cognitive function. Physical fitness was evaluated using the 30-s chair stand, 2-min step and the Timed-Up and Go tests. A structural equation modelling (SEM) with bootstrapping estimation was conducted to determine the relationship between all variables. RESULTS: Independence in basic ADL positively affected QoL and this association was mediated by physical fitness (ß = 0.242, p = 0.011). No statistically significant results were observed when testing cognitive function as a mediator between BI and QoL (ß = 0.009, p = 0.345). CONCLUSIONS: Physical fitness (i.e., lower body strength, aerobic capacity, and mobility) plays a role in the relationship between basic ADL independence and QoL of older adults with dementia, reinforcing the need to improve and monitor these parameters throughout the disease progression. Future longitudinal studies should explore the temporal relationship between physical and cognitive function and its contribution to basic ADL independence and QoL.

Factors associated with poor outcomes in SLE patients with COVID-19: Data from ReumaCoV-Brazil register.

OBJECTIVES: To evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study-"The ReumaCoV Brazil"-designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K). RESULTS: 604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post-COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04-5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12-96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10-16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97-15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12-0.88], p = 0.02). CONCLUSION: Hypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19.

Automatic attention to sexual stimuli: exploring the role of neuroticism and sexual excitation/inhibition through event-related potentials.

BACKGROUND: Previous findings have shown that neuroticism is a higher-order vulnerability factor in the development and maintenance of sexual dysfunctions and can have an impact on the attentional processing of sexual stimuli; however, the influence of psychosexual dimensions on the early automatic phases of such cognitive processes has not been established yet. AIM: To examine the mediating role of sexual inhibition/excitation propensity in the relationship between neuroticism and automatic attention to visual erotica and to identify the neuroelectric correlates of such a process. METHODS: We analyzed the answers provided by 58 individuals on the Neuroticism subscale of the NEO Personality Inventory-Revised and the Sexual Inhibition/Excitation Scales. Event-related potentials (ERPs) were recorded during a modified oddball paradigm containing romantic and sexually explicit pictures. Parallel mediations were performed to simultaneously test the mediating role of sexual inhibition/excitation in the relationship between neuroticism and each ERP. OUTCOMES: Three early attention ERP components (P1, P2, and N2) were assessed. RESULTS: Findings revealed an indirect effect of neuroticism on automatic attention, via sexual inhibition due to threat of performance failure (SIS1), for romantic and sexually explicit stimuli. This effect was significant only for component N2, which showed increased amplitudes and earlier latencies in participants with high SIS1. CLINICAL IMPLICATIONS: Sexual stimuli, due to their emotional valence and arousal potential, might be perceived as virtually threatening by individuals with neuroticism, who may benefit from strategies that decrease hyperarousal and sympathetic activation. STRENGTHS AND LIMITATIONS: This was one of the first studies to analyze neuroelectric activity associated with automatic attention toward sexual stimuli in relation to personality and sexual excitation/inhibition propensity. Nevertheless, the limited number of participants demands caution in generalizing the results. CONCLUSION: These results provide a better understanding of the relationship between personality and sexual cognition and open new avenues of research in relation to other automatic cognitive phenomena related to human sexual behavior.

Sexual boredom and sexual desire in long-term relationships: a latent profile analysis.

BACKGROUND: Research suggests a general link between sexual boredom and sexual desire, but its understanding is currently very limited. AIM: To identify distinct (latent) groups of women and men in long-term relationships based on their reported levels of sexual boredom and sexual desire. METHODS: Latent profile analysis (LPA) was conducted in an online sample of 1223 Portuguese participants aged 18 and 66 years (mean ± SD, 32.75 ± 6.11), using indicators of sexual boredom and partner-related, attractive other-related, and solitary sexual desire to categorize participants. Multinomial logistic regression analysis was carried out to explore predictors and correlates of the latent profiles. OUTCOMES: Sexual boredom was assessed by the Sexual Boredom Scale, while sexual desire was measured with the Sexual Desire Inventory. RESULTS: As compared with women, men reported higher levels of sexual boredom and sexual desire. LPA indicated 3 profiles in women and 2 profiles in men. Among women, P1 was characterized by above-average sexual boredom, below-average partner- and attractive other-related sexual desire, and very low solitary sexual desire; P2 by below-average sexual boredom, attractive other-related sexual desire, and solitary sexual desire and above-average partner-related sexual desire; and P3 by above-average sexual boredom, attractive other-related sexual desire, and solitary sexual desire and below-average partner-related sexual desire. In men, P1 was characterized by high sexual boredom, above-average partner-related sexual desire, and high attractive other-related and solitary sexual desire and P2 by below-average sexual boredom and above-average partner-related, attractive other-related, and solitary sexual desire. The latent profiles did not differ according to relationship duration. Overall, the sole consistent correlate of the latent categorization was sexual satisfaction. CLINICAL IMPLICATIONS: In women, above-average levels of sexual boredom were linked to below-average levels of partner-related desire, which suggests likely benefits of helping the couple to minimize or cope better with their sexual routines. In men, participants in the 2 profiles did not differ in partner-related sexual desire, suggesting that clinical interventions dealing with male sexual boredom should investigate factors beyond the current relationship. STRENGTHS AND LIMITATIONS: This study explored different facets of sexual desire and used LPA, rendering advantages over previous research. The male sample has lower statistical power than the female sample. CONCLUSION: Patterns of sexual boredom and sexual desire among individuals in long-term monogamous relationships are distinct and consistently related to sexual satisfaction in women and men and to relationship satisfaction among only women, which have important clinical ramifications.

Does Multicomponent Physical Exercise Training Work for Dementia? Exploring the Effects on Cognition, Neuropsychiatric Symptoms, and Quality of Life.

OBJECTIVE: To explore the effects of a multicomponent training (MT) physical exercise intervention in the cognitive function, neuropsychiatric symptoms, and quality of life of older adults with major neurocognitive disorder (NCD). METHODS: Quasi-experimental controlled trial. Thirty-six individuals (25 female) were equally distributed to an exercise group (aged 74.33 ± 5.87 years) or a control group (aged 81.83 ± 6.18 years). The Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog), the Neuropsychiatric Inventory (NPI) and the Quality of Life - Alzheimer's Disease (QoL-AD) tests were performed before and after the intervention. RESULTS: There was no clear interaction effect factor of intervention on ADAS-Cog (B = 1.33, 95% CI: -2.61 - 5.28, P = .513), NPI (B = -8.35, 95% CI: -18.48 - 1.72, P = .115), and QoL-AD (B = 2.87, 95% CI: .01 - 5.73, P = .058). CONCLUSIONS: The 6-month MT physical exercise intervention did not present evidence of slowing down cognitive decline neither improving neuropsychiatric symptomatology, and quality of life of older adults with major NCD. Future studies with larger samples are needed to better understand the impact of physical exercise interventions using MT methodology on specific cognitive abilities, neuropsychiatric symptoms, and quality of life domains.

Measuring Sexual Motivation as a Trait Dimension: A multisample study of the Portuguese (European) Version of the Trait Sexual Motivation Questionnaire.

The current study aimed at translating and validating the TSMQ into Portuguese-European (TSMQ-PT) and to investigate its psychometric properties. Three online studies were conducted with independent samples collected between September 2020 and March 2022. Study 1 tested the exploratory factorial structure (N = 325; 206 women); Study 2 explored the confirmatory factorial structure and construct validity (N = 450; 230 women); and Study 3 examined the temporal stability of the TSMQ-PT (N = 30; 15 women). Participants completed the TSMQ-PT for all three studies. In study 2, further completed the Sexual Compulsivity Scale, the Sexual Sensation Seeking Scale, and the Sexual Desire Inventory. Data revealed that the TSMQ-PT yielded a four-structure model, (i.e., Sexually Oriented, Comparison with Others, Seeking for Sexual Encounters, and Importance of Sex) comprising 13 items, with seven additional items for assessing existence and number of sexual partners, and frequency of sexual behaviors. The TSMQ-PT achieved good internal consistency levels (McDonald's omega ranged from .71 to .89) and construct validity, and temporal stability over 10-11 months (values ranged from .80 to .87) supporting the trait-dimension of sexual motivation. Current findings support a brief, valid, and reliable self-report instrument for assessing sexual motivation in the Portuguese context.

Psychometric properties of the Alcohol Use Disorders Identification Test (AUDIT) across cross-cultural subgroups, genders, and sexual orientations: Findings from the International Sex Survey (ISS).

INTRODUCTION: Despite being a widely used screening questionnaire, there is no consensus on the most appropriate measurement model for the Alcohol Use Disorders Identification Test (AUDIT). Furthermore, there have been limited studies on its measurement invariance across cross-cultural subgroups, genders, and sexual orientations. AIMS: The present study aimed to examine the fit of different measurement models for the AUDIT and its measurement invariance across a wide range of subgroups by country, language, gender, and sexual orientation. METHODS: Responses concerning past-year alcohol use from the participants of the cross-sectional International Sex Survey were considered (N = 62,943; Mage: 32.73; SD = 12.59). Confirmatory factor analysis, as well as measurement invariance tests were performed for 21 countries, 14 languages, three genders, and four sexual-orientation subgroups that met the minimum sample size requirement for inclusion in these analyses. RESULTS: A two-factor model with factors describing 'alcohol use' (items 1-3) and 'alcohol problems' (items 4-10) showed the best model fit across countries, languages, genders, and sexual orientations. For the former two, scalar and latent mean levels of invariance were reached considering different criteria. For gender and sexual orientation, a latent mean level of invariance was reached. CONCLUSIONS: In line with the two-factor model, the calculation of separate alcohol-use and alcohol-problem scores is recommended when using the AUDIT. The high levels of measurement invariance achieved for the AUDIT support its use in cross-cultural research, capable also of meaningful comparisons among genders and sexual orientations.

NGS Data Repurposing Allows Detection of tRNA Fragments as Gastric Cancer Biomarkers in Patient-Derived Extracellular Vesicles.

Transfer RNA fragments (tRFs) have gene silencing effects similarly to miRNAs, can be sorted into extracellular vesicles (EVs) and are emerging as potential circulating biomarkers for cancer diagnoses. We aimed at analyzing the expression of tRFs in gastric cancer (GC) and understanding their potential as biomarkers. We explored miRNA datasets from gastric tumors and normal adjacent tissues (NATs) from TCGA repository, as well as proprietary 3D-cultured GC cell lines and corresponding EVs, in order to identify differentially represented tRFs using MINTmap and R/Bioconductor packages. Selected tRFs were validated in patient-derived EVs. We found 613 Differentially Expressed (DE)-tRFs in the TCGA dataset, of which 19 were concomitantly upregulated in TCGA gastric tumors and present in 3D cells and EVs, but barely expressed in NATs. Moreover, 20 tRFs were expressed in 3D cells and EVs and downregulated in TCGA gastric tumors. Of these 39 DE-tRFs, 9 tRFs were also detected in patient-derived EVs. Interestingly, the targets of these 9 tRFs affect neutrophil activation and degranulation, cadherin binding, focal adhesion and the cell-substrate junction, highlighting these pathways as major targets of EV-mediated crosstalk with the tumor microenvironment. Furthermore, as they are present in four distinct GC datasets and can be detected even in low quality patient-derived EV samples, they hold promise as GC biomarkers. By repurposing already available NGS data, we could identify and cross-validate a set of tRFs holding potential as GC diagnosis biomarkers.

Soma and Neurite Density MRI (SANDI) of the in-vivo mouse brain and comparison with the Allen Brain Atlas.

Diffusion MRI (dMRI) provides unique insights into the neural tissue milieu by probing interactions between diffusing molecules and tissue microstructure. Most dMRI techniques focus on white matter (WM) tissues, nevertheless, interest in gray matter characterizations is growing. The Soma and Neurite Density MRI (SANDI) methodology harnesses a model incorporating water diffusion in spherical objects (assumed to be associated with cell bodies) and in impermeable "sticks" (assumed to represent neurites), which potentially enables the characterization of cellular and neurite densities. Recognising the importance of rodents in animal models of development, aging, plasticity, and disease, we here employ SANDI for in-vivo preclinical imaging and provide a first validation of the methodology by comparing SANDI metrics with cellular density reflected by the Allen mouse brain atlas. SANDI was implemented on a 9.4T scanner equipped with a cryogenic coil, and in-vivo experiments were carried out on N = 6 mice. Pixelwise, ROI-based, and atlas comparisons were performed, magnitude vs. real-valued analyses were compared, and shorter acquisitions with reduced the number of b-value shells were investigated. Our findings reveal good reproducibility of the SANDI parameters, including the sphere and stick fractions, as well as sphere size (CoV < 7%, 12% and 3%, respectively). Additionally, we find a very good rank correlation between SANDI-driven sphere fraction and Allen mouse brain atlas contrast that represents cellular density. We conclude that SANDI is a viable preclinical MRI technique that can greatly contribute to research on brain tissue microstructure.

Bayesian connective field modeling using a Markov Chain Monte Carlo approach.

The majority of neurons in the human brain process signals from neurons elsewhere in the brain. Connective Field (CF) modelling is a biologically-grounded method to describe this essential aspect of the brain's circuitry. It allows characterizing the response of a population of neurons in terms of the activity in another part of the brain. CF modelling translates the concept of the receptive field (RF) into the domain of connectivity by assessing, at the voxel level, the spatial dependency between signals in distinct cortical visual field areas. Thus, the approach enables to characterize the functional cortical circuitry of the human cortex. While already very useful, the present CF modelling approach has some intrinsic limitations due to the fact that it only estimates the model's explained variance and not the probability distribution associated with the estimated parameters. If we could resolve this, CF modelling would lend itself much better for statistical comparisons at the level of single voxels and individuals. This is important when trying to gain a detailed understanding of the neurobiology and pathophysiology of the visual cortex, notably in rare cases. To enable this, we present a Bayesian approach to CF modeling (bCF). Using a Markov Chain Monte Carlo (MCMC) procedure, it estimates the posterior probability distribution underlying the CF parameters. Based on this, bCF quantifies, at the voxel level, the uncertainty associated with each parameter estimate. This information can be used in various ways to increase confidence in the CF model predictions. We applied bCF to BOLD responses recorded in the early human visual cortex using 3T fMRI. We estimated both the CF parameters and their associated uncertainties and show they are only weakly correlated. Moreover, we show how bCF facilitates the use of effect size (beta) as a data-driven parameter that can be used to select the most reliable voxels for further analysis. Finally, to further illustrate the functionality gained by bCF, we apply it to perform a voxel-level comparison of a single, circular symmetric, Gaussian versus a Difference-of-Gaussian model. We conclude that our bCF framework provides a comprehensive tool to study human functional cortical circuitry in health and disease.

Mutant KRAS modulates colorectal cancer cells invasive response to fibroblast-secreted factors through the HGF/C-MET axis.

Genetic alterations influence the malignant potential of cancer cells, and so does the tumor microenvironment. Herein, we combined the study of KRAS oncogenic effects in colorectal cancer cells with the influence of fibroblast-derived factors. Results revealed that mutant KRAS regulates cell fate through both autonomous and nonautonomous signaling mechanisms. Specifically, processes such as proliferation and cell-cell aggregation were autonomously controlled by mutant KRAS independently of the stimulation with fibroblasts conditioned media. However, cancer cell invasion revealed to be a KRAS-dependent nonautonomous effect, resulting from the cooperation between fibroblast-derived HGF and mutant KRAS regulation of C-MET expression. C-MET downregulation upon KRAS silencing rendered cells less responsive to HGF and thus less invasive. Yet, in one cell line, KRAS inhibition triggered invasion upon stimulation with fibroblasts conditioned media. Inhibition of PIK3CA oncogene did not promote invasion, thus showing a KRAS-specific effect. Moreover, the invasive capacity also depended on the HGF-C-MET axis. Overall, our study awards oncogenic KRAS an important role in modulating the response to fibroblast-secreted factors either by promoting or impairing invasion, and depicts the HGF-C-MET axis as a putative therapeutic target to impair the invasive properties of mutant KRAS cancer cells.

A fully human anti-BMP6 antibody reduces the need for erythropoietin in rodent models of the anemia of chronic disease.

Recombinant erythropoietin (EPO) and iron substitution are a standard of care for treatment of anemias associated with chronic inflammation, including anemia of chronic kidney disease. A black box warning for EPO therapy and concerns about negative side effects related to high-dose iron supplementation as well as the significant proportion of patients becoming EPO resistant over time explains the medical need to define novel strategies to ameliorate anemia of chronic disease (ACD). As hepcidin is central to the iron-restrictive phenotype in ACD, therapeutic approaches targeting hepcidin were recently developed. We herein report the therapeutic effects of a fully human anti-BMP6 antibody (KY1070) either as monotherapy or in combination with Darbepoetin alfa on iron metabolism and anemia resolution in 2 different, well-established, and clinically relevant rodent models of ACD. In addition to counteracting hepcidin-driven iron limitation for erythropoiesis, we found that the combination of KY1070 and recombinant human EPO improved the erythroid response compared with either monotherapy in a qualitative and quantitative manner. Consequently, the combination of KY1070 and Darbepoetin alfa resulted in an EPO-sparing effect. Moreover, we found that suppression of hepcidin via KY1070 modulates ferroportin expression on erythroid precursor cells, thereby lowering potentially toxic-free intracellular iron levels and by accelerating erythroid output as reflected by increased maturation of erythrocyte progenitors. In summary, we conclude that treatment of ACD, as a highly complex disease, becomes more effective by a multifactorial therapeutic approach upon mobilization of endogenous iron deposits and stimulation of erythropoiesis.

Spatio-temporal changes in chimpanzee density and abundance in the Greater Mahale Ecosystem, Tanzania.

Species conservation and management require reliable information about animal distribution and population size. Better management actions within a species' range can be achieved by identifying the location and timing of population changes. In the Greater Mahale Ecosystem (GME), western Tanzania, deforestation due to the expansion of human settlements and agriculture, annual burning, and logging are known threats to wildlife. For one of the most charismatic species, the endangered eastern chimpanzee (Pan troglodytes schweinfurthii), approximately 75% of the individuals are distributed outside national park boundaries, requiring monitoring and protection efforts over a vast landscape of various protection statuses. These efforts are especially challenging when we lack data on trends in density and population size. To predict spatio-temporal chimpanzee density and abundance across the GME, we used density surface modeling, fitting a generalized additive model to a 10-year time-series data set of nest counts based on line-transect surveys. The chimpanzee population declined at an annual rate of 2.41%, including declines of 1.72% in riparian forests (from this point forward, forests), 2.05% in miombo woodlands (from this point forward, woodlands) and 3.45% in nonforests. These population declines were accompanied by ecosystem-wide declines in vegetation types of 1.36% and 0.32% per year for forests and woodlands, respectively; we estimated an annual increase of 1.35% for nonforests. Our model predicted the highest chimpanzee density in forests (0.86 chimpanzees/km2 , 95% confidence intervals (CIs) 0.60-1.23; as of 2020), followed by woodlands (0.19, 95% CI 0.12-0.30) and nonforests (0.18, 95% CI 0.10-1.33). Although forests represent only 6% of the landscape, they support nearly one-quarter of the chimpanzee population (769 chimpanzees, 95% CI 536-1103). Woodlands dominate the landscape (71%) and therefore support more than a half of the chimpanzee population (2294; 95% CI 1420-3707). The remaining quarter of the landscape is represented by nonforests and supports another quarter of the chimpanzee population (750; 95% CI 408-1381). Given the pressures on the remaining suitable habitat in Tanzania, and the need of chimpanzees to access both forest and woodland vegetation to survive, we urge future management actions to increase resources and expand the efforts to protect critical forest and woodland habitat and promote strategies and policies that more effectively prevent irreversible losses. We suggest that regular monitoring programs implement a systematic random design to effectively inform and allocate conservation actions and facilitate interannual comparisons for trend monitoring, measuring conservation success, and guiding adaptive management.

Dual colorimetric strategy for specific DNA detection by nicking endonuclease-assisted gold nanoparticle signal amplification.

The continuous spread of invasive alien species, as zebra mussel (Dreissena polymorpha), is a major global concern and it is urgent to stop it. Early stages of an invasion are crucial and challenging; however, detection tools based on environmental DNA analysis are promising alternatives. We present an alternative DNA target amplification strategy for signal enhancement followed by dual-mode colorimetric naked eye and optical smartphone analysis for the early detection of zebra mussel environmental DNA. Target amplification was designed based on the nicking endonuclease probe cleavage upon probe and complementary target hybridization. The cleaved/intact probe interacts with DNA-modified nanoparticles for colorimetric detection. We have demonstrated that enzyme amplification strategy enhanced 12-fold the sensitivity by naked eye detection, achieving a detection limit of ~8 nM (4.48×1010 copies) in controlled conditions, whereas target in complex environmental samples allowed the detection of 22.5 nM (1.26×1011 copies). Competitive assays also showed that the system can discriminate specific zebra mussel DNA sequences from other DNA sequences. Additionally, smartphone analysis for DNA quantification further improved the sensitivity of its detection by 130-fold, more than 2 orders of magnitude, when applied to environmental samples. The limit of detection to 0.17 nM (9.52×108 copies) is based on RGB coordinates, which is especially relevant to monitor early aggregation stages, being more accurate and reducing naked eye detection subjectivity. DNA extracted from zebra mussel meat, zebra mussel contaminated river water, and non-contaminated river water samples were successfully tested. Dual-mode colorimetric detection is useful in field analysis without the need for expensive laboratory equipment.

Women's Cognitive and Emotional Appraisal of Sex Pictures: The Predictive Role of Age, Exposure Time, and Sexual Beliefs.

This study researched how age predicts women's cognitive and emotional appraisal of sex pictures. One hundred and fifty five women were exposed to romantic, sexually moderate and sexually explicit pictures. Women reported on the emotional valence, subjective sexual arousal, and level of sexual content attributed to the pictures; women's sexual beliefs were further evaluated. Findings revealed that age predicted increased pleasantness to sexually moderate and explicit pictures, as well as higher subjective sexual arousal to all type of pictures. Some predictions were moderated by sexual beliefs and exposure time, pointing the role of contextual factors in women's appraisal of erotica.

Sexual Health and the Pandemic Crisis: Testing the Role of Psychological Vulnerability/Protective Factors on Sexual Functioning and Sexual Distress During a Critical Life Period in Portugal.

Recent findings suggest that the current COVID-19 pandemic has a potential negative impact in several areas of life, including sexual health. However, less is known about the psychological dimensions that may work as vulnerability/protective factors for the development of sexual problems in the current pandemic. The current study used a longitudinal design to examine the role played by personality trait factors (neuroticism, extraversion) as well as psychosexual factors (sexual beliefs) in predicting sexual functioning and sexual distress across time during the current pandemic crisis. A total of 528 individuals (337 women) completed a web survey assessing sexual health indicators and psychological factors. The first wave was conducted during the confinement period in Portugal (N = 528) between May and June 2020 and the second four months later (N = 146), when strict confinement rules were over. Generalized estimating equations (GEE) were used to examine the ability of psychological factors to predict sexual functioning and distress across time, while controlling for age and gender. Results indicated that sexual distress at time point 2 was lower than during confinement, and men had lower levels of sexual functioning post-confinement while no significant difference was observed for women. Moreover, higher levels of neuroticism and age-related beliefs significantly predicted lower sexual functioning as well as higher sexual distress, whereas lower levels of extraversion predicted lower sexual functioning after controlling for age and gender effects. Findings support the role of psychological vulnerability factors to predict sexual problems across time and may have important implications in the prevention and treatment of sexual dysfunctions.

Redefinition of familial intestinal gastric cancer: clinical and genetic perspectives.

BACKGROUND: Familial intestinal gastric cancer (FIGC) remains genetically unexplained and without testing/clinical criteria. Herein, we characterised the age of onset and disease spectrum of 50 FIGC families and searched for genetic causes potentially underlying a monogenic or an oligogenic/polygenic inheritance pattern. METHODS: Normal and tumour DNA from 50 FIGC probands were sequenced using Illumina custom panels on MiSeq, and their respective germline and somatic landscapes were compared with corresponding landscapes from sporadic intestinal gastric cancer (SIGC) and hereditary diffuse gastric cancer cohorts. RESULTS: The most prevalent phenotype in FIGC families was gastric cancer, detected in 138 of 208 patients (50 intestinal gastric cancer probands and 88 unknown gastric cancer histology relatives), followed by colorectal and breast cancers. After excluding benign and intronic variants lacking impact in splicing, 12 rare high-quality variants were found exclusively in 11 FIGC probands. Only two probands carried potentially deleterious variants, but lacked somatic second-hits, weakly supporting the monogenic hypothesis for FIGC. However, FIGC probands developed gastric cancer at least 10 years earlier and carried more TP53 germline common variants than SIGC (p=4.5E-03); FIGC and SIGC could be distinguished by specific germline and somatic variant profiles; there was an excess of FIGC tumours presenting microsatellite instability (38%); and FIGC tumours displayed significantly more somatic common variants than SIGC tumours (p=4.2E-06). CONCLUSION: This study proposed the first data-driven testing criteria for FIGC families, and supported FIGC as a genetically determined, likely polygenic, gastric cancer-predisposing disease, with earlier onset and distinct from patients with SIGC at the germline and somatic levels.

Can two multimodal psychomotor exercise programs improve attention, affordance perception, and balance in community dwellings at risk of falling? A randomized controlled trial.

BACKGROUND: Falls are associated with cognitive and physical function deterioration. Attention decline, inaccurate affordance perception, and balance impairment are considered to be risk factors for falls. Furthermore, few studies have reported psychomotor intervention as a fall prevention program. This study aimed to investigate the effects of two multimodal programs on attention, perceptual and stepping-forward boundaries, and balance in community-dwelling older adults at risk of falling. METHODS: Fifty-one community-dwelling older adults were recruited to participate in a 24-week randomized controlled trial. Participants (75.4 ± 5.6 years) were randomly assigned to one of three groups: the 1) multimodal psychomotor program [EG1], 2) combined program (multimodal psychomotor program + whole-body vibration program) [EG2], and 3) control group. Participants were assessed at baseline, at post-intervention, and after a 12-week no-intervention follow-up period. RESULTS: The within-group comparisons showed significant improvements in attention and balance in EG1 and EG2 after the intervention (p <  0.05). The magnitudes of the treatment effects were similar in both EGs, ranging from medium to large. Decreases in the fall rate were also observed in EG1 (- 44.2%) and EG2 (- 63.0%) (p <  0.05). During the follow-up period, these improvements in attention were maintained, while those in balance were reversed in both EGs. No significant differences between groups were found. CONCLUSIONS: These study results suggest that both multimodal exercise programs were effective for fall prevention and were well tolerated by the participants. Specifically, EG1 and EG2 showed identical improvements in attention, and EG2 presented a slightly larger enhancement in balance and a larger decrease in the fall rate. Our findings demonstrate the benefits of maintaining the psychomotor intervention program by itself or in combination with the whole-body vibration program to prevent cognitive and physical function deterioration. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03446352 . Date of registration: February 26, 2018.