Cognitive and neuroscientific perspectives of healthy ageing.

With dementia incidence projected to escalate significantly within the next 25 years, the United Nations declared 2021-2030 the Decade of Healthy Ageing, emphasising cognition as a crucial element. As a leading discipline in cognition and ageing research, psychology is well-equipped to offer insights for translational research, clinical practice, and policy-making. In this comprehensive review, we discuss the current state of knowledge on age-related changes in cognition and psychological health. We discuss cognitive changes during ageing, including (a) heterogeneity in the rate, trajectory, and characteristics of decline experienced by older adults, (b) the role of cognitive reserve in age-related cognitive decline, and (c) the potential for cognitive training to slow this decline. We also examine ageing and cognition through multiple theoretical perspectives. We highlight critical unresolved issues, such as the disparate implications of subjective versus objective measures of cognitive decline and the insufficient evaluation of cognitive training programs. We suggest future research directions, and emphasise interdisciplinary collaboration to create a more comprehensive understanding of the factors that modulate cognitive ageing.

No Support for Two Hypotheses About the Communicative Functions of Displaying Disgust: Evidence From Turkey, Norway, Germany, and Croatia.

In recent years, researchers have discovered much about how disgust works, its neural basis, its relationship with immune function, its connection with mating, and some of its antecedents and consequents. Despite these advances in our understanding, an under-explored area is how disgust may be used to serve a communicative function, including how individuals might strategically downplay or exaggerate the disgust display in front of different audiences. Here, we generated two hypotheses about potential communicative functions of disgust, and tested these hypotheses in four countries (Turkey, Croatia, Germany, and Norway). We found no evidence in support of either hypothesis in any country. Discussion focuses on the likely falsity of the two central hypotheses, alternative interpretations of our findings, and directions for future research.

Evidence that the aesthetic preference for Hogarth's Line of Beauty is an evolutionary by-product.

In 1753, artist William Hogarth declared a specific S-shaped line to be the 'Line of Beauty' (LoB). Hogarth's assertion has had a profound impact on diverse fields over the past two and a half centuries. However, only one recent (2022) study has investigated whether Hogarth's assertion accurately captures humans' actual aesthetic preferences, and no research has explored why people find the LoB beautiful. We conducted two studies testing the hypothesis that the LoB's perceived beauty is an incidental by-product of cognitive systems that evolved to attend to fitness-relevant morphological features in people. In Study 1, we replicated the finding that female bodies whose lumbar curvature approximates the biomechanical optimum for dealing with the exigencies of pregnancy are rated as more attractive. In Study 2, we found that abstract lines extracted from these bodies were perceived as more beautiful than other lines. These results suggest that the preference for Hogarth's LoB is an incidental by-product of psychological mechanisms that evolved for other purposes. More broadly, these findings suggest that an evolutionary psychological approach - in particular the concept of evolutionary by-product - may be useful for understanding, explaining, and predicting people's aesthetic preferences for certain abstract symbols, which otherwise might seem arbitrary and inexplicable.

Lordosis in Humans.

Despite progress in attractiveness research, we have yet to identify many fitness-relevant cues in the human phenotype or humans' psychology for responding to them. Here, we test hypotheses about psychological systems that may have evolved to process distinct cues in the female lumbar region. The Fetal Load Hypothesis proposes a male preference for a morphological cue: lumbar curvature. The Lordosis Detection Hypothesis posits context-dependent male attraction to a movement: lordosis behavior. In two studies (Study 1 N: 102, Study 2 N: 231), we presented men with animated female characters that varied in their lumbar curvature and back arching (i.e., lordosis behavior). Irrespective of mating context, men's attraction increased as lumbar curvature approached the hypothesized optimum. By contrast, men experienced greater attraction to lordosis behavior in short-term than long-term mating contexts. These findings support both the Lordosis Detection and Fetal Load Hypotheses. Discussion focuses on the meaning of human lordosis and the importance of dynamic stimuli in attractiveness research.

Dysregulated long non-coding RNA in Sjögren's disease impacts both interferon and adaptive immune responses.

OBJECTIVE: Sjögren's disease (SjD) is an autoimmune disease characterised by inflammatory destruction of exocrine glands. Patients with autoantibodies to Ro/SSA (SjDRo+) exhibit more severe disease. Long non-coding RNAs (lncRNAs) are a functionally diverse class of non-protein-coding RNAs whose role in autoimmune disease pathology has not been well characterised. METHODS: Whole blood RNA-sequencing (RNA-seq) was performed on SjD cases (n=23 Ro/SSA negative (SjDRo-); n=27 Ro/SSA positive (SjDRo+) and healthy controls (HCs; n=27). Bioinformatics and pathway analyses of differentially expressed (DE) transcripts (log2 fold change ≥2 or ≤0.5; padj<0.05) were used to predict lncRNA function. LINC01871 was characterised by RNA-seq analyses of HSB-2 cells with CRISPR-targeted LINC01871 deletion (LINC01871-/ -) and in vitro stimulation assays. RESULTS: Whole blood RNA-seq revealed autoantibody-specific transcription profiles and disproportionate downregulation of DE transcripts in SjD cases relative to HCs. Sixteen DE lncRNAs exhibited correlated expression with the interferon (IFN)-regulated gene, RSAD2, in SjDRo+ (r≥0.65 or ≤-0.6); four antisense lncRNAs exhibited IFN-regulated expression in immune cell lines. LINC01871 was upregulated in all SjD cases. RNA-seq and pathway analyses of LINC01871-/ - cells implicated roles in cytotoxic function, differentiation and IFNγ induction. LINC01871 was induced by IFNγ in a myeloid cell line and regulated by calcineurin/NFAT pathway and T cell receptor (TCR) signalling in primary human T cells. CONCLUSION: LINC01871 influences expression of many immune cell genes and growth factors, is IFNγ inducible, and regulated by calcineurin signalling and TCR ligand engagement. Altered LINC01871 expression may influence the dysregulated T cell inflammatory pathways implicated in SjD.

Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.

Sjögren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.

Why Do People (Not) Engage in Social Distancing? Proximate and Ultimate Analyses of Norm-Following During the COVID-19 Pandemic.

COVID-19 has had a profound negative effect on many aspects of human life. While pharmacological solutions are being developed and implemented, the onus of mitigating the impact of the virus falls, in part, on individual citizens and their adherence to public health guidelines. However, promoting adherence to these guidelines has proven challenging. There is a pressing need to understand the factors that influence people's adherence to these guidelines in order to improve public compliance. To this end, the current study investigated whether people's perceptions of others' adherence predict their own adherence. We also investigated whether any influence of perceived social norms was mediated by perceptions of the moral wrongness of non-adherence, anticipated shame for non-adherence, or perceptions of disease severity. One hundred fifty-two Australians participated in our study between June 6, 2020 and August 21, 2020. Findings from this preliminary investigation suggest that (1) people match their behavior to perceived social norms, and (2) this is driven, at least in part, by people using others' behavior as a cue to the severity of disease threat. Such findings provide insight into the proximate and ultimate bases of norm-following behavior, and shed preliminary light on public health-related behavior in the context of a pandemic. Although further research is needed, the results of this study-which suggest that people use others' behavior as a cue to how serious the pandemic is and as a guide for their own behavior-could have important implications for public health organizations, social movements, and political leaders and the role they play in the fight against epidemics and pandemics.

Sjögren's Syndrome Minor Salivary Gland CD4+ Memory T Cells Associate with Glandular Disease Features and have a Germinal Center T Follicular Helper Transcriptional Profile.

To assess the types of salivary gland (SG) T cells contributing to Sjögren's syndrome (SS), we evaluated SG T cell subtypes for association with disease features and compared the SG CD4+ memory T cell transcriptomes of subjects with either primary SS (pSS) or non-SS sicca (nSS). SG biopsies were evaluated for proportions and absolute numbers of CD4+ and CD8+ T cells. SG memory CD4+ T cells were evaluated for gene expression by microarray. Differentially-expressed genes were identified, and gene set enrichment and pathways analyses were performed. CD4+CD45RA- T cells were increased in pSS compared to nSS subjects (33.2% vs. 22.2%, p < 0.0001), while CD8+CD45RA- T cells were decreased (38.5% vs. 46.0%, p = 0.0014). SG fibrosis positively correlated with numbers of memory T cells. Proportions of SG CD4+CD45RA- T cells correlated with focus score (r = 0.43, p < 0.0001), corneal damage (r = 0.43, p < 0.0001), and serum Ro antibodies (r = 0.40, p < 0.0001). Differentially-expressed genes in CD4+CD45RA- cells indicated a T follicular helper (Tfh) profile, increased homing and increased cellular interactions. Predicted upstream drivers of the Tfh signature included TCR, TNF, TGF-ß1, IL-4, and IL-21. In conclusion, the proportions and numbers of SG memory CD4+ T cells associate with key SS features, consistent with a central role in disease pathogenesis.

Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized primarily by immune-mediated destruction of exocrine tissues, such as those of the salivary and lacrimal glands, resulting in the loss of saliva and tear production, respectively. This disease predominantly affects middle-aged women, often in an insidious manner with the accumulation of subtle changes in glandular function occurring over many years. Patients commonly suffer from pSS symptoms for years before receiving a diagnosis. Currently, there is no effective cure for pSS and treatment options and targeted therapy approaches are limited due to a lack of our overall understanding of the disease etiology and its underlying pathology. To better elucidate the underlying molecular nature of this disease, we have performed RNA-sequencing to generate a comprehensive global gene expression profile of minor salivary glands from an ethnically diverse cohort of patients with pSS. Gene expression analysis has identified a number of pathways and networks that are relevant in pSS pathogenesis. Moreover, our detailed integrative analysis has revealed a primary Sjögren's syndrome molecular signature that may represent important players acting as potential drivers of this disease. Finally, we have established that the global transcriptomic changes in pSS are likely to be attributed not only to various immune cell types within the salivary gland but also epithelial cells which are likely playing a contributing role. Overall, our comprehensive studies provide a database-enriched framework and resource for the identification and examination of key pathways, mediators, and new biomarkers important in the pathogenesis of this disease with the long-term goals of facilitating earlier diagnosis of pSS and to mitigate or abrogate the progression of this debilitating disease.

Sjögren Syndrome without Focal Lymphocytic Infiltration of the Salivary Glands.

OBJECTIVE: Primary Sjögren syndrome (SS) is characterized by a focal lymphocytic infiltrate in exocrine glands. We describe patients who lacked this key feature. METHODS: We evaluated patients with sicca in a comprehensive clinic at which medical, dental, and ophthalmological examinations were performed. All subjects underwent a minor salivary gland biopsy with focus score calculation. Extraglandular manifestations were also determined. We categorized subjects as high, intermediate, or low in terms of expression of interferon (IFN)-regulated genes. RESULTS: About 20% (51 of 229, 22%) of those classified as having primary SS had a focus score of zero. Compared to those with anti-Ro positivity and a focus score > 1.0, the patients with focus score of zero (who by classification criteria must be anti-Ro-positive) were statistically less likely to have anti-La (or SSB) and elevated immunoglobulin, as well as less severe corneal staining. The focus score zero patients were less likely to have elevated expression of IFN-regulated genes in peripheral blood mononuclear cells than anti-Ro-positive SS patients with a focal salivary infiltrate. CONCLUSION: There are only a few clinical differences between patients with primary SS with focus score zero and those with both anti-Ro and a focus score > 1.0. The small subset of focus score zero patients tested did not have elevated expression of IFN-regulated genes, but did have systemic disease. Thus, extraglandular manifestations are perhaps more related to the presence of anti-Ro than increased IFN. This may have relevance to pathogenesis of SS.

American Indians Have a Higher Risk of Sjögren's Syndrome and More Disease Activity Than European Americans and African Americans.

OBJECTIVE: To describe the clinical and serologic manifestations of Sjögren's syndrome (SS) in ethnic groups of the US. METHODS: This was a cross-sectional study of 648 patients with primary SS: 20 African American (AA), 164 American Indian (AI), 426 European American (EA), and 38 patients of other races evaluated in a multidisciplinary Sjögren's International Collaborative Clinical Alliance research clinic. RESULTS: AA subjects comprised 3.1% of the SS cohort, much lower than the percentage of AA in the state of Oklahoma (P = 3.01 × E - 05), the US (P = 2.24E - 13), or a systemic lupus erythematosus (SLE) cohort at the same institution (P = 4.26 × 10E - 27). In contrast, the percentage of AI in the SS cohort (25.3%) was much higher than expected (P = 3.17E - 09 versus SLE cohort, P = 6.36 - 26 versus Oklahoma, and P = 8.14E - 96 versus US population). The SS classification criteria were similar between AA and EA, but subjects of AI ancestry had lower rates of abnormal tear and salivary flow, as well as anti-Ro/SSA and anti-La/SSB antibodies. Paradoxically, AI had higher levels of disease activity (mean ± SD European League Against Rheumatism Sjögren's Syndrome Disease Activity Index score 3.77 ± 4.78) in comparison to EA (2.90 ± 4.12; P = 0.011) and more extraglandular manifestations affecting mainly the articular and glandular domains. Meanwhile, AA patients were characterized by higher rates of hypergammaglobulinemia (odds ratio [OR] 1.39 [95% confidence interval (95% CI) 1.39-8.65]; P = 0.01), elevated erythrocyte sedimentation rate (ESR) (OR 3.95 [95% CI 1.46-9.95]; P = 0.009), and parotid enlargement (OR 4.40 [95% CI 1.49-13.07]; P = 0.02). CONCLUSION: AI are affected at high rates with SS but present with few classical features, potentially preventing timely diagnosis. In contrast to SLE, SS is infrequent and not more severe among AA, but the triad of hypergammaglobulinemia, increased ESR, and parotid enlargement warrants extra vigilance for lymphomagenesis.

Antibacterial action of functional silicon dioxide: an investigation of the attachment and separation of bacteria.

Bactericidal proteins from the Moringa oleifera seed are reported to be suitable alternatives to conventional methods of bacterial reduction in water. In this study the cationic bactericidal M. oleifera proteins were isolated by attachment onto the surface of silicon dioxide. This functionalised SiO2(ƒ-SiO2) was then exposed to Escherichia coli and Micrococcus luteus to examine whether the ƒ-SiO2 could be used to inactivate the bacteria. The effect of the non-ionic surfactant dodecyl glucoside on the attachment of these bacteria to the ƒ-SiO2 was examined with the aim of developing a method of reusable bacterial inactivation. The primary result of this study was that the E. coli could be readily separated from the ƒ-SiO2, allowing the ƒ-SiO2 to be used for further bacterial inactivation. The regeneration of the ƒ-SiO2 was demonstrated using fluorescence microscopy on bacterial cells stained with propidium iodide, and zeta potential measurements. Future applications of this work include a reusable method of removing bacteria from contaminated water.

Rates of Discontinuation and Nonpublication of Head and Neck Cancer Randomized Clinical Trials.

Importance: Randomized clinical trials (RCTs) play an important role in clinical decision-making, and discontinuation or nonpublication of these trials are causes of great concern. The extent of discontinued or unpublished RCTs about head and neck cancer remains unclear. Objective: To assess the rate of discontinuation or nonpublication of RCTs involving patients with head and neck cancer. This objective was measured by observing 3 domains: discontinuation of trial, nonpublication of trial data, and feasibility of contacting trial investigators of aforementioned trials. Evidence Review: For this study, the sample was derived using the ClinicalTrials.gov advanced search feature on March 18, 2019, to locate completed and discontinued RCTs pertaining to head and neck cancer registered before this date. Trials were analyzed to identify reasons for trial discontinuation and publication status of each trial. If publication status or reason for trial discontinuation was not allocated through the systematic search of ClinicalTrials.gov, the corresponding author was emailed to determine publication status. Findings: After exclusions, 130 RCTs were included. Of these trials, 92 (70.8%) were completed and 38 (29.2%) were discontinued for various reasons. The most common reason for discontinuation of trials was committee recommendations. Of the 130 analyzed trials, 67 (51.5%) were published in a peer-reviewed journal and 63 (48.5%) were unpublished trials. Of the 92 completed trials, 55 (59.8%) were published and 37 (40.2%) remained unpublished 3 or more years after trial completion. Trials funded by other sources (private, nonprofit, or the National Institutes of Health) were more likely to reach publication than industry-funded RCTs (unadjusted odds ratio, 4.3 [95% CI, 1.3-14.0]; adjusted odds ratio, 4.1 [95% CI, 1.2-14.3]). Conclusions and Relevance: Of RCTs in head and neck cancer, 29.2% were discontinued and 40.2% completed trials never reached publication. The findings suggest that needs exist for RCT guidance of head and neck cancer. The reporting of reasons for trial discontinuation appears to be lacking, and trial publication rates were low. This study is relevant to many physicians and researchers because it identifies potential sources of decreased research productivity and ethics.

Reproducibility of Ocular Surface Staining in the Assessment of Sjögren Syndrome-Related Keratoconjunctivitis Sicca: Implications on Disease Classification.

OBJECTIVE: The objective of this study was to assess the performance and reproducibility of the two currently used ocular surface staining scores in the assessment of keratoconjunctivitis sicca in Sjögren syndrome (SS) research classification. METHODS: In a multidisciplinary clinic for the evaluation of sicca, we performed all tests for the American European Consensus Group (AECG) and the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, including the van Bijsterveld score (vBS) and the Ocular Staining Score (OSS), in 994 participants with SS or with non-SS sicca. We analyzed the concordance between the scores, the diagnostic accuracy and correlation with clinical variables, and interrater and intrasubject reproducibility. RESULTS: A total of 308 (31.1%) participants had a discordant vBS and OSS that was due to extra corneal staining points in the OSS. The presence of one or more of the additional points was highly predictive of SS classification (odds ratio = 3.66; P = 1.65 × 10e-20) and was associated with abnormal results of all measures of autoimmunity and glandular dysfunction. Receiver operating characteristic curves showed optimal cutoff values of four for the vBS (sensitivity = 0.62; specificity = 0.71; Youden's J = 0.33) and five for the OSS (sensitivity = 0.56; specificity = 0.75; Youden's J = 0.31). Notably, there was very poor consistency in interobserver mean scores and distributions (P < 0.0001) and in intrasubject scores after a median of 5.5 years (35% changed status of the ocular criterion). CONCLUSION: Ocular surface staining scores are useful for SS research classification; however, they are subject to significant interrater and intrasubject variability, which could result in changes in classification in 5%-10% of all subjects. These results highlight the need for objective and reproducible markers of disease that have thus far remained elusive for SS.

Study of the impacts of process changes of a pulp and paper mill on aerated stabilization basin (ASB) performance.

A laboratory scale (LS) and a field-based pilot plant (PP), designed to simulate aerobic stabilization basin (ASB) operation, were utilized to assess the potential impacts of changes in pulp and paper (P&P) mill operations on full-scale (FS) ASB performance. Two stages of investigation were conducted. The first was undertaken to determine the potential of pre-alum treatment of pulp mill wastewaters on ASB performance. The second investigation was conducted to assess ASB performance where wastewaters transitioned from being coagulated pulp and paper mill wastewaters to paper mill wastewaters only. Simulation ASB performance was assessed based on removals of BOD5, colour, UV@254 nm and nutrients [total phosphorus (TP) and nitrogen compounds (TN)]. Pre-alum treatment of pulp mill wastewaters with subsequent ASB treatment following mixing with paper mill wastewaters showed high percentage removals of BOD5. Despite low TP concentrations (≤0.05 mg/L) and low nutrient to BOD5 ratios of wastewaters in the LS-ASB trial, the high % BOD5 removal indicated recycling of nutrients from sludge [sourced from the FS-ASB]. Despite coagulation of pulp mill wastewater being performed using a very high alum dose (∼2000 mg/L) to remove colour and its precursors, colour formation remained high throughout the simulated ASB trials. Simulation of discontinuation of pulping indicated that colour would reduce rapidly to low levels in ASB wastewaters, but that TP and TN concentrations would persist for longer periods of time and decline slowly. Survey data of water qualities of the FS-ASB system obtained before, during and 2 years after discontinuation of pulping are presented.