Control Participants Research Articles

Impact of statin use in head and neck cancer: a nested case-control study.

Dyslipidemia and statin use are associated with an increased risk of various cancers. However, the association in head and neck cancer (HNC) remains unclear. Therefore, this study aimed to investigate the impact of dyslipidemia and statin use on the development of HNC. Using data from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2019, we compared two groups HNC patients (n = 1006) and matched control participants (n = 4024) after propensity score overlap weighted balancing. The odds ratios (ORs) for HNC development according to dyslipidemia and statin use duration were assessed using propensity score overlap-weighted multivariable logistic regression. Individuals with untreated dyslipidemia had significantly lower odds of developing HNC than those of normal participants (OR 0.70, 95% confidence interval [CI] 0.59-0.82). Conversely, patients with dyslipidemia who received statin therapy (< 60days) showed a nearly two-fold increase in the odds of HNC (OR 1.94, 95% CI 1.29-2.90). Long-term statin use (≥ 60days) aligned the odds with those of normal participants (OR 0.89, 95% CI 0.76-1.04). The adverse effect of short-term statin use on HNC development requires further study, and long-term statin use for dyslipidemia treatment does not increase the odds of HNC.

Longitudinal accelerated brain age in mild cognitive impairment and Alzheimer's disease.

Brain age is a machine learning-derived estimate that captures lower brain volume. Previous studies have found that brain age is significantly higher in mild cognitive impairment and Alzheimer's disease (AD) compared to healthy controls. Few studies have investigated changes in brain age longitudinally in MCI and AD. We hypothesized that individuals with MCI and AD would show heightened brain age over time and across the lifespan. We also hypothesized that both MCI and AD would show faster rates of brain aging (higher slopes) over time compared to healthy controls. We utilized data from an archival dataset, mainly Alzheimer's disease Neuroimaging Initiative (ADNI) 1 with 3Tesla (3 T) data which totaled 677 scans from 183 participants. This constitutes a secondary data analysis on existing data. We included control participants (healthy controls or HC), individuals with MCI, and individuals with AD. We predicted brain age using a pre-trained model and tested for accuracy. We investigated cross-sectional differences in brain age by group [healthy controls or HC, mild cognitive impairment (MCI), and AD]. We conducted longitudinal modeling of age and brain age by group using time from baseline in one model and chronological age in another model. We predicted brain age with a mean absolute error (MAE) < 5 years. Brain age was associated with age across the study and individuals with MCI and AD had greater brain age on average. We found that the MCI group had significantly higher rates of change in brain age over time compared to the HC group regardless of individual chronologic age, while the AD group did not differ in rate of brain age change. We replicated past studies that showed that MCI and AD had greater brain age than HC. We additionally found that this was true over time, both groups showed higher brain age longitudinally. Contrary to our hypothesis, we found that the MCI, but not the AD group, showed faster rates of brain aging. We essentially found that while the MCI group was actively experiencing faster rates of brain aging, the AD group may have already experienced this acceleration (as they show higher brain age). Individuals with MCI may experience higher rates of brain aging than AD and controls. AD may represent a homeostatic endpoint after significant neurodegeneration. Future work may focus on individuals with MCI as one potential therapeutic option is to alter rates of brain aging, which ultimately may slow cognitive decline in the long-term.

Reducing Ageism and Ableism with Brief Videos Providing Education about Aging and Disabilities and Exposure to Positive Intergenerational Contact.

Older adults living with a disability (LWD) face both ageism and ableism, but there are few interventions to address this significant and growing social problem. Drawing on the PEACE (Positive Education about Aging and Contact Experiences) Model, three online studies involved participants randomly assigned to watch four brief online videos providing education about aging and disability and exposure to positive contact between younger adults and older adults/older adults LWD (experimental condition) or videos about interior design (control condition). Studies 1 (community sample) and 2 (university sample) included an immediate post-test whereas Study 3 (2 university samples) additionally included a pre-test and delayed post-test. Experimental condition (vs. control) participants reported greater agreement with older adults LWD as contributors to society (immediate post-test in Studies 1 and 2; immediate and delayed post-test in Study 3), lesser (greater) endorsement of negative (positive) stereotypes of older adults and older adults LWD, lesser agreement with older adults LWD as burdensome, lesser intergenerational tension with older adults (immediate post-test in Study 2; immediate and delayed post-test in Study 3), and greater openness to careers working with older adults and older adults LWD (immediate and delayed post-test in Study 3). Brief online interventions that involve education about aging and disabilities as well as exposure to positive intergenerational contact can be an effective means of reducing ableism and ageism toward older adults and older adults LWD.

Using a Fluorescent Concretization Intervention Improves Hand Hygiene Training in Primary School Students: A Randomized Controlled Study

Introduction: Inadequate hand hygiene increases the rates of childhood infectious diseases and deaths, leading to the death of one child per minute. Aim: To examine the effects of an educational strategy, “using a fluorescent concretization intervention,” on the hand-washing skills of primary school students. Method: This single-center randomized controlled trial using a pretest and posttest design was conducted with 35 intervention and 35 control participants. Data were collected with Dermalux Test Lotion containing fluorescently detectable under ultraviolet light, Hand Washing Skill Checklist, Hand Washing Skill Efficacy, and Hand Hygiene Assessment Question Form in School Children. Results: After the training for both hands, the intervention group participants created a difference in the effectiveness of hand washing from dirty to clean in all areas (p &lt; 0.001). The scores regarding psychomotor skills and duration of hand washing increased in all participants. Total score percentage changes increased more in the intervention group participants when the first and final follow-ups were compared (p &lt; 0.001). Hand washing skills and durations increased after hand washing training using the fluorescent concretization method. Conclusion: Visual concretization and explanation to the students increase handwashing effectiveness. For this reason, it is highly recommended that technological devices that provide such visual feedback be used in schoolchildren's education.

Assessment of left atrial function and left atrioventricular coupling via cardiac magnetic resonance in individuals with prediabetes and diabetes.

Assessment of left atrial (LA) function and the left atrioventricular coupling index (LACI) have recently been increasingly recognized as important indices for cardiovascular diseases associated with the presence of prediabetes and diabetes. We aimed to evaluate LA function and the LACI in patients with prediabetes and diabetes via cardiac magnetic resonance (CMR). In this retrospective study, we included 35 patients with prediabetes, 32 patients with diabetes, and 84 healthy control participants. The LACI and LA total, passive, and active emptying fractions (LATEmF, LAPEmF, and LAAEmF, respectively) were calculated. The LA reservoir, conduit, and booster pump strains (εs, εe, and εa), and peak positive, peak early negative, and peak late negative strain rates (SRs, SRe, and SRa) were obtained via CMR-feature tracking (CMR-FT). For the statistical analyses, one-way analysis of variance, the Kruskal-Wallis test, and linear regression were conducted, and Pearson's and interclass correlation coefficients were calculated. Compared with healthy control participants, patients with prediabetes or diabetes presented lower εs and εe values and a relatively preserved LACI. Patients with diabetes presented considerably reduced SRs, SRe, and LAPEmF. Elevated glycated haemoglobin (HbA1c) levels were independently associated with decreased magnitudes of εs, SRs, εe, and SRe. No significant associations were found between the LACI and the HbA1c or LA deformation parameters. We observed significant correlations between LATEmF and εs, LAPEmF and εe and between LAAEmF and εa. CMR-FT provides a potential noninvasive approach for the early detection of alterations in the LA reservoir and conduit function in individuals with prediabetes and diabetes.

Protective Role of (-)-Epicatechin on Trimethylamine-N-Oxide (TMAO)-Induced Cardiac Hypertrophy via SP1/SIRT1/SUMO1 Signaling Pathway.

(-)-Epicatechin (EPI) is beneficial for cardiovascular health. Trimethylamine N-oxide (TMAO), a gut microbe-derived food metabolite, is strongly associated with the risk of cardiovascular diseases. However, the effects and underlying mechanisms of EPI on TMAO-induced cardiac hypertrophy remain unclear. This study aimed to determine whether EPI inhibits TMAO-induced cardiac hypertrophy. Plasma levels of TMAO in control participantsand patients with cardiac hypertrophy were measured and analyzed. Male C57BL/6 mice were randomly divided into control group, TMAO group, EPI group and TMAO + EPI group. According to the groups assignments, mice received intraperitoneal (i.p.) injection of normal saline or i.p. injection of TMAO (150mg/kg/day) for 14days. The EPI group was given intragastric (i.g.) administration of EPI alone (1mg/kg/day) for 21days, and TMAO + EPI group received i.g. administration of EPI for 7days before starting i.p. injection of TMAO, continuing until the end of the TMAO treatment. Histological analyses of the mice's hearts was accessed by H&E and Masson staining. In vitro, H9c2 cells were induced to hypertrophy by TMAO (10µM) for 24h and were pre-treated with or without EPI (10µM) for 1h. Protein level of cardiac hypertrophy markers and Sp1/SIRT1/SUMO1 pathway were determined by western blot. The plasma level of TMAO was 2.66 ± 1.59μmol/L in patients with cardiac hypertrophy and 0.62 ± 0.30μmol/L in control participants. EPI attenuated TMAO-induced hypertrophy in H9c2 cells. In vivo, TMAO induced cardiac hypertrophy and impaired the cardiac function of mice. Pathological staining showed that TMAO induced cardiac hypertrophy and collagen deposition in mice. EPI treatment improved the cardiac function, inhibited the myocardial hypertrophy induced by TMAO. EPI significantly attenuated the TMAO-induced upregulation of ANP and BNP and the downregulation of SP1, SIRT1 and SUMO1 in vivo and in vitro. EPI may suppress TMAO-induced cardiac hypertrophy by activating the Sp1/SIRT1/SUMO1 signaling pathway.

Antigen specificity of clonally-enriched CD8+ T cells in multiple sclerosis.

CD8+ T cells are the dominant lymphocyte population in multiple sclerosis (MS) lesions where they are highly clonally expanded. The clonal identity, function, and antigen specificity of CD8+ T cells in MS are not well understood. Here we report a comprehensive single-cell RNA-seq and T cell receptor (TCR)-seq analysis of the cerebrospinal fluid (CSF) and blood from a cohort of treatment-naïve MS patients and control participants. A small subset of highly expanded and activated CD8+ T cells were enriched in the CSF in MS that displayed high activation, cytotoxicity and tissue-homing transcriptional profiles. Using a combination of unbiased and targeted antigen discovery approaches, MS-derived CD8+ T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and multiple novel mimotopes were identified. These findings shed vital insight into the role of CD8+ T cells in MS and pave the way towards disease biomarkers and therapeutic targets.

Tympanostomy Tube Insertion With and Without Adenoidectomy

The benefit of adenoidectomy on otologic outcomes after tympanostomy tube (TT) insertion is unclear. Results from prior work are challenging to interpret due to small sample sizes, heterogeneous study designs, and varying outcome measures. To evaluate the association between adenoidectomy and otologic outcomes using a US population-level sample of children who received TTs, producing generalizable results for widespread clinical application. A matched cohort study was conducted using claims data from the Merative MarketScan Research Databases. The study included 601 848 children who received TTs between January 1, 2007, and December 31, 2021. Children who received adenoidectomy and TTs simultaneously (Ad+TT) were identified irrespective of the number of prior TTs. Control participants who received TTs without adenoidectomy were matched based on sex, age at the time of the procedure, and the number of prior TT procedures. Adenoidectomy without tonsillectomy was the primary exposure. The primary outcomes were repeat TT insertion and subsequent oral antibiotic prescriptions after TT insertions. Multivariable logistic regression was used to quantify the effects of adenoidectomy and covariates on each outcome. Stratified analyses were performed in children younger than 4 years and 4 years or older. Overall, 601 848 children (median [IQR] age, 2 [1-4] years; range, 0-11 years; 351 078 [58.3%] male) who received TTs were identified. The Ad+TT cohort included 201 932 children, with an equal number in the matched cohort. In children younger than 4 years, Ad+TT was common and was associated with lower odds of subsequent oral antibiotics (odds ratio [OR], 0.59; 95% CI, 0.58-0.60) but higher odds of repeat TT insertions (OR, 1.24; 95% CI, 1.22-1.27). In children 4 years or older, Ad+TT was associated with lower odds of repeat TT insertions (OR, 0.78; 95% CI, 0.75-0.81) and subsequent oral antibiotics (OR, 0.63; 95% CI, 0.62-0.65). This study found that in children younger than 4 years, Ad+TT was commonly performed and may have had a secondary benefit of reducing subsequent oral antibiotic courses; however, it was not associated with a reduction in the risks of repeat TT insertions. In children 4 years or older, Ad+TT was associated with a reduction in the risk of repeat TT insertions and subsequent oral antibiotics. Given these findings, Ad+TT may be offered in children 4 years or older to improve otologic outcomes.

Do Swedish rock-climbers exhibit more eating disorder and body dissatisfaction symptoms than non-climbers? A cross-sectional study

ObjectivesThe inclusion of rock-climbing in the Olympic Games has increased participation in the sport and attention to athletes' health. In sports where the importance of low body weight is considerate,...

Impairments in Proprioceptively-Referenced Limb and Eye Movements in Chronic Stroke.

Upper limb proprioceptive impairments are common after stroke and affect daily function. Recent work has shown that stroke survivors have difficulty using visual information to improve proprioception. It is unclear how eye movements are impacted to guide action of the arm after stroke. Here, we aimed to understand how upper limb proprioceptive impairments impact eye movements in individuals with stroke. Control (N = 20) and stroke participants (N = 20) performed a proprioceptive matching task with upper limb and eye movements. A KINARM exoskeleton with eye tracking was used to assess limb and eye kinematics. The upper limb was passively moved by the robot and participants matched the location with either an arm or eye movement. Accuracy was measured as the difference between passive robot movement location and active limb matching (Hand-End Point Error) or active eye movement matching (Eye-End Point Error). We found that individuals with stroke had significantly larger Hand (2.1×) and Eye-End Point (1.5×) Errors compared to controls. Further, we found that proprioceptive errors of the hand and eye were highly correlated in stroke participants (r = .67, P = .001), a relationship not observed for controls. Eye movement accuracy declined as a function of proprioceptive impairment of the more-affected limb, which was used as a proprioceptive reference. The inability to use proprioceptive information of the arm to coordinate eye movements suggests that disordered proprioception impacts integration of sensory information across different modalities. These results have important implications for how vision is used to actively guide limb movement during rehabilitation.

Intensity dependence of auditory evoked potentials distinguish participants with unmedicated depression from non-depressed controls.

Depression is a heterogeneous syndrome that impacts an individual's emotional, social, cognitive and bodily functioning. Depression is associated with biases in emotional processing, but alterations in basic sensory processing have received less attention in depression research. Here, we measured event-related potentials (ERPs) in response to changes in the intensity of auditory stimuli and the location of somatosensory stimuli in participants with depression and in non-depressed control participants. We tested whether auditory mismatch negativity, P3a or N1 intensity dependence response or somatosensory mismatch response, P3a, P50 or N80 can dissociate depressed participants and non-depressed controls, and we also analysed the effects of depression medication and age in this sample. N1 intensity dependence response was increased in unmedicated depressed participants relative to non-depressed controls. When age was controlled for in the analysis, the effect of depression was only at a trend level. N1 intensity dependence response correlated with depression severity at the whole sample level. We did not observe any depression-related alterations in auditory mismatch negativity or P3a or somatosensory ERPs. Our results may reflect an association between the N1 intensity dependence response and altered neurotransmitter activity in depression, but this should be confirmed in future studies.

Investigating the Association between Catechol-O-Methyltransferase Gene Activity and Pain Perception in South African Patients with Different Temporomandibular Disorders Diagnoses.

Background: Temporomandibular disorders (TMD) affect a significant portion of the population, with profound psychological, behavioral, and social repercussions. Recent investigations have explored the genetic basis underlying pain perception in individuals with TMD, aiming to elucidate the role of specific genetic factors in modulating the condition. Notably, genetic variations have been implicated in the pathogenesis of TMD, particularly genes involved in pain perception pathways. One of the primary candidates is the Catechol-O-Methyltransferase (COMT) gene, which plays a crucial role in the catecholaminergic system and has been associated with the regulation of nociceptive processes. This study seeks to investigate the correlation between COMT gene activity and pain perception among South African patients diagnosed with varying forms of TMD. Methodology: In this study, a total of 196 participants were enrolled, comprising 97 patients diagnosed with TMD and 99 control participants. The control group was meticulously matched with the TMD group for age, gender, and ethnicity. Data collection involved clinical and radiological investigations, and saliva sampling. The English version of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I was utilized to evaluate all TMD participants, focusing on standard diagnostic measures based on clinical signs and symptoms of TMD, which primarily describe common physical manifestations of the disorder. Genomic DNA was extracted from saliva samples, enabling the analysis of single-nucleotide polymorphisms (SNPs) in the COMT gene, specifically targeting polymorphisms rs165774, rs9332377, rs6269, rs4646310, rs165656, and rs4680. Results: The current study demonstrated a pronounced gender disparity, with 80.41% of the participants being female and 19.59% male, suggesting that women in South Africa either exhibit a higher susceptibility to TMD or are more likely to seek treatment for the condition compared to men. The highest prevalence of TMD was observed in the white population (58.76%). Additionally, over 65% of TMD patients were diagnosed with at least two Axis I diagnoses, a figure that increased to 89% for those diagnosed with three Axis I diagnoses. The findings further indicated significant associations between several single-nucleotide polymorphisms (SNPs) in the Catechol-O-Methyltransferase (COMT) gene-specifically rs165656, rs9332377, rs4646310, rs6269, and rs165774-and both TMD and TMD-related pain. Myofascial pain with referral and myalgia showed a strong association with the COMT SNPs rs9332377 and rs4646310. Furthermore, COMT SNP rs4646310 was also associated with disability related to TMD. Conclusions: This study substantiates the hypothesis that pain is prevalent in a considerable proportion of patients affected by TMD. Furthermore, the findings reveal a significant association between COMT gene activity and pain perception in South African patients diagnosed with TMD.

Self-Concept in Mild Cognitive Impairment and Mild Dementia due to Alzheimer's Disease Is Affected on Tests of Self-Generated Statements.

Several studies show that Alzheimer's disease (AD) and other neurocognitive disorders have a negative impact on the self and identity formation. Most studies have included persons with mild to moderate dementia, but how AD patients in the earliest phases retrieve information about themselves has only been studied scarcely. The aim of this study was to investigate if persons with mild cognitive impairment (MCI) and mild AD would generate fewer self-related statements than healthy controls. From a memory clinic, we included 17 aMCI patients, 17 patients with mild dementia (AD; MMSE ≥ 24), and 30 healthy controls. Three Events Test and Twenty Statements Test (TST) were applied to all participants. The persons with mild dementia gave significantly fewer statements compared to the controls (p < 0.001) and the aMCI patients (p < 0.01) on TST. Fewer statements were also produced by the aMCI patients compared to the control participants (p < 0.05). Persons from both patient groups produced significantly fewer contextual details compared to the controls on the Three Events Tests. There were significant associations to lexical fluency for both the TST and Three Events Test, but only a limited amount of variance was explained, and the results cannot be explained solely by a fluency effect. The results from this study are in accordance with findings from previous studies demonstrating that mild AD leads to a decline in both autobiographical memories and a diminished sense of self. Further, this study shows that changes in self-concept may occur even in the earliest clinical stages of AD.

Preserved working memory performance along with subcortical modulation during peri-ictal phases in spontaneous migraine attacks.

To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants. Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks. In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles. The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases. During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks.

Eye movements of persons with aphasia during connected-text reading

ABSTRACT Background Eye movements reflect the cognitive-linguistic processing of neurotypical readers. Numerous reading related eye movement measures are associated with language processing, including first fixation duration, gaze duration, number of fixations, word skipping, and regressions. Eye movements have also been used to examine reading in neuro-atypical populations including persons with aphasia (PWA). Aims This study aimed to determine whether eye movement measures obtained from connected text reading differ among persons with varying types of aphasia and neurotypical individuals, as well as whether eye movement measures are associated with language processing severity and reading comprehension ability in PWA. Methods Twenty-four PWA and twenty-four age-matched control participants completed a connected text-reading eye-tracking task. The PWA also completed assessments to evaluate overall language processing severity and reading comprehension skills and to identify specific subtypes of aphasia. Results Persons with aphasia had shorter gaze duration, longer regression duration, and made more fixations than control participants, while no group differences emerged for first fixation duration or word skipping. Eye movement patterns did not differ among participants with anomic, Broca’s, or conduction/Wernicke’s. Language severity scores were a significant factor for gaze duration, while reading comprehension scores were not a significant factor for the eye movement measures examined. Conclusions The findings support previous eye tracking literature that indicate different eye movement patterns for persons with aphasia during text reading relative to neurotypical controls. The findings also highlight that the selection of eye movement measures examined, the stimuli used, and procedural considerations may impact the pattern of results. The results from this study can be used to further determine which eye movement measures may be most suited for studying language processing during reading in neuro-atypical individuals and determine whether persons with aphasia use different strategies for reading comprehension than neurotypical individuals.

The Neuroconnective Endophenotype, A New Approach Toward Typing Functional Neurological Disorder: A Case-Control Study.

Functional neurological disorder (FND) is a core neuropsychiatric condition that includes both physical and mental symptoms. Recently, a validated clinical phenotype termed neuroconnective endophenotype (NEP), which includes several physical and psychological characteristics together with joint hypermobility (hypermobility spectrum disorders), was found at a significantly higher frequency among patients with anxiety. The purpose of the present study was to examine the presence of the NEP among patients with FND. The authors conducted a multicenter case-control study comprising 27 FND patients and 27 healthy control participants (matched by sex and age) ages 13 to 58 years. Eight questionnaires were administered. Proportional differences were examined with Student's t tests, one-way analyses of variance, and chi-square tests. Differences between FND patients and control participants were observed. FND patients had higher sensory sensitivity, increased prevalence of hypermobility features (including relevant physical signs and symptoms), greater frequency of polarized behaviors, a greater number of both psychiatric and physical comorbidities, and an increase in the characteristics and sensations typical of anxiety. Particularly striking was the presence of the hypermobility spectrum in more than 75% of FND patients compared with 15% among control participants. FND patients presented higher scores in all five dimensions included in the NEP. Thus, this phenotype, solidifying the original association between anxiety and the hypermobility spectrum, could help to identify an FND subtype when evaluating and managing FND patients, because it provides a new global view of patients' physical and mental symptoms.

Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are associated with cytokine networks and their intricate interactions with metabolic syndrome

ObjectivesTo identify alterations in the immune profiles in outpatients with major depression (MDD), and its associations with key features, such as suicidal ideation, neuroticism, cognitive symptoms, and the depression phenome while accounting for metabolic syndrome (MetS). MethodsIn this case-control study, we assayed 48 serum cytokines, chemokines, and growth factors in 67 healthy controls and 66 MDD outpatients. Around 50 % of the outpatient MDD and control participants had a diagnosis of MetS. ResultsTen differentially expressed proteins (DEPs) were upregulated in outpatient MDD (i.e., CXCL12, tumor necrosis factor [TNF]β, platelet-derived growth factor [PDGF], CCL11, interleukins [IL]9, IL4, CCL5, CCL2, CCL4, IL1 receptor antagonist [IL1RN]), indicating an immune and defense response. Six DEPs were downregulated (vascular endothelial growth factor A [VEGFA], IL12, CCL3, colony stimulating factor [CSF]1, IL1B, nerve growth factor [NGF]), indicating lowered neurogenesis and neuron death regulation. Significant interactions between outpatient MDD and MetS caused a) substantial increases in IL4, IL17, TNF, TNFB, CCL2, CCL5, PDGF, IL1RN; and b) downregulation of VEGFA and FGF. A large part of the variance in neuroticism (26 %), suicidal behaviors (23 %), and the MDD phenome (31 %) was predicted by immunological data and interactions between MetS and CCL5, TNFB or VEGFA. ConclusionOutpatient MDD is characterized by a cytokine profile with neurotoxic potential which partly explains neuroticism, suicidal behaviors, and the phenome's severity. Lowered IL-10 and activated cytokine profiles with neurotoxic potential are characteristics of outpatient MDD and other depression phenotypes, including severe first-episode inpatient MDD. The presence of MetS in outpatient MDD considerably activates immune profiles with neurotoxic potential. Consequently, immune studies in MDD should always be performed in subjects with and without MetS.

Infrared spectroscopy as a new approach for early fabry disease screening: a pilot study

BackgroundFabry disease (FD) is a rare X-linked lysosomal storage disorder marked by alpha-galactosidase-A (α-Gal A) deficiency, caused by pathogenic mutations in the GLA gene, resulting in the accumulation of glycosphingolipids within lysosomes. The current screening test relies on measuring α-Gal A activity. However, this approach is limited to males. Infrared (IR) spectroscopy is a technique that can generate fingerprint spectra of a biofluid’s molecular composition and has been successfully applied to screen numerous diseases. Herein, we investigate the discriminating vibration profile of plasma chemical bonds in patients with FD using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy.ResultsThe Fabry disease group (n = 47) and the healthy control group (n = 52) recruited were age-matched (39.2 ± 16.9 and 36.7 ± 10.9 years, respectively), and females were predominant in both groups (59.6% and 65.4%, respectively). All patients had the classic phenotype (100%), and no late-onset phenotype was detected. A generated partial least squares discriminant analysis (PLS-DA) classification model, independent of gender, allowed differentiation of samples from FD vs. control groups, reaching 100% sensitivity, specificity and accuracy.ConclusionATR-FTIR spectroscopy harnessed to pattern recognition algorithms can distinguish between FD patients and healthy control participants, offering the potential of a fast and inexpensive screening test.

The illusion of information adequacy.

How individuals navigate perspectives and attitudes that diverge from their own affects an array of interpersonal outcomes from the health of marriages to the unfolding of international conflicts. The finesse with which people negotiate these differing perceptions depends critically upon their tacit assumptions-e.g., in the bias of naïve realism people assume that their subjective construal of a situation represents objective truth. The present study adds an important assumption to this list of biases: the illusion of information adequacy. Specifically, because individuals rarely pause to consider what information they may be missing, they assume that the cross-section of relevant information to which they are privy is sufficient to adequately understand the situation. Participants in our preregistered study (N = 1261) responded to a hypothetical scenario in which control participants received full information and treatment participants received approximately half of that same information. We found that treatment participants assumed that they possessed comparably adequate information and presumed that they were just as competent to make thoughtful decisions based on that information. Participants' decisions were heavily influenced by which cross-section of information they received. Finally, participants believed that most other people would make a similar decision to the one they made. We discuss the implications in the context of naïve realism and other biases that implicate how people navigate differences of perspective.

Association of Polygenic Risk Score With Lifetime Risk of Developing Multiple Sclerosis in a Population-Based Birth-Year Cohort.

More than 200 genetic variants have been associated with multiple sclerosis (MS) susceptibility. However, it is unclear to what extent genetic factors influence lifetime risk of MS. Using a population-based birth-year cohort, we investigate the effect of genetics on lifetime risk of MS. In the Project Y study, we tracked down almost all persons with MS (pwMS) from birth year 1966 in the Netherlands. As control participants, we included non-MS participants from the Project Y cohort (born 1965-1967 in the Netherlands) and non-MS participants from the Amsterdam Dementia Cohort born between 1963 and 1969. Genetic variants associated with MS were determined in pwMS and control participants using genotyping or imputation methods. Polygenic risk scores (PRSs) based on variants and weights from the largest genetic study in MS were calculated for each participant and assigned into deciles based on the PRS distribution in the control participants. We examined the lifetime risk for each decile and the association between PRS and MS disease variables, including age at onset and time to secondary progression. MS-PRS was calculated for 285 pwMS (mean age 53.0 ± 0.9 years, 72.3% female) and 267 control participants (mean age 51.8 ± 3.2 years, 58.1% female). Based on the lifetime risk estimation, we observed that 1:2,739 of the women with the lowest 30% genetic risk developed MS, whereas 1:92 of the women with the top 10% highest risk developed MS. For men, only 1:7,900 developed MS in the lowest 30% genetic risk group, compared with 1:293 men with the top 10% genetic risk. The PRS was not significantly associated with age at onset and time to secondary progression in both sexes. Our results show that the lifetime risk of MS is strongly influenced by genetic factors. Our findings have the potential to support diagnostic certainty in individuals with suspected MS: a high PRS could strengthen a diagnosis, but especially a PRS from the lowest tail of the PRS distribution should be considered a red flag and could prevent misdiagnosing conditions that mimic MS.