Human Variation Research Articles

Temporal resolution relates to sensory hyperreactivity independently of stimulus detection sensitivity in individuals with autism spectrum disorder.

Researchers have been focusing on perceptual characteristics of autism spectrum disorder (ASD) in terms of sensory hyperreactivity. Previously, we demonstrated that temporal resolution, which is the accuracy to differentiate the order of two successive vibrotactile stimuli, is associated with the severity of sensory hyperreactivity. We currently examined whether an increase in the perceptual intensity of a tactile stimulus, despite its short duration, is derived from high temporal resolution and high frequency of sensory temporal summation. Twenty ASD and 22 typically developing (TD) participants conducted two psychophysical experimental tasks to evaluate detectable duration of vibrotactile stimulus with same amplitude and to evaluate temporal resolution. The sensory hyperreactivity was estimated using self-reported questionnaire. There was no relationship between the temporal resolution and the duration of detectable stimuli in both groups. However, the ASD group showed severe sensory hyperreactivity in daily life than TD group, and the ASD participants with severe sensory hyperreactivity tended to have high temporal resolution, not high sensitivity of detectable duration. Contrary to the hypothesis, there might be different processing between temporal resolution and sensitivity for stimulus detection. We suggested that the atypical temporal processing would affect to sensory reactivity in ASD.

Individual differences in color matches and cone spectral sensitivities in 51 young adults.

Forty-six young adult observers with normal color vision (plus five from an earlier study) made a series of color matches using a new LED-based, multi-wavelength visual trichromator. Thirteen LED lights of different wavelengths were combined to produce 11 triplets of lights that observers were asked to match to a white reference light of 7500 K over visual angles of either 2° or 10°. Matches were initially made by asking observers to adjust the intensities of the three lights making up each triplet. As the experiment progressed, a more intuitive matching procedure was developed. By transforming the triplet of lights into CIELAB space, observers adjusted colors using lightness (L*), redness-greenness (a*), and blueness-yellowness (b*) to make the match with white. The new procedure proved easier for observers and reduced the inter- and intra-observer variability. Given that each of the 11 matches to the reference white for a given observer (obtained by either method) should produce identical L-, M- and S-cone excitations, we were able to use the matches to infer the individual cone spectral sensitivities for each observer and thus estimate the range of individual differences across our 51 observers. By applying a model of the CIEPO06 standard LMS observer, the photopigment, macular and lens optical densities and the L- and M-cone photopigment spectral shifts that best equated the three-cone excitations across the 11 matches were found for each observer. The individual differences were consistent with the CIEPO06 observer except for a 3 nm shift of the M-cone photopigment to longer wavelengths and a slightly denser 2-deg macular pigment density.

Exome sequencing in fetuses with congenital diaphragmatic hernia in a nationwide cohort.

To evaluate the diagnostic yield of exome sequencing (ES) in fetuses and neonates with prenatally detected congenital diaphragmatic hernia (CDH) and normal copy number variant (CNV) analysis. We conducted a retrospective cohort study of prenatally diagnosed CDH cases seen between 2019 and 2022. All cases who underwent prenatal or postnatal genetic testing were reviewed. The results from the ES analysis that identified pathogenic or likely pathogenic single nucleotide variants are described. In total, 133 fetuses with CDH were seen, of whom 98 (74%) had an isolated CDH and 35 (26%) had a complex CDH (associated structural anomalies) on prenatal examination. ES was performed in 68 cases, and eight pathogenic or likely pathogenic variants were found, accounting for a 12% diagnostic yield (10% [5/50] in isolated cases and 17% [3/18] in complex CDH). In 12% of fetuses and neonates with CDH and normal CNV analysis results, pathogenic or likely pathogenic variants were identified with ES. These data indicate that there is a substantial diagnostic yield when offering ES in prenatally detected CDH, both in complex and isolated cases.

People with sensory processing sensitivity connect strongly to nature across five dimensions

Human connections to nature are critical to the sustainability of life on Earth. Nature connections are often linked with pro-environmental behaviors. Therefore, a better understanding of the nuances of human-nature connections can help inform policies and practices to advance sustainability. Connections to nature research has rarely investigated nuances like the nature connections of subpopulations or distinguished between types of nature connections. This article reports on an investigation of the subpopulation of highly sensitive individuals (HSPs), a group comprising about one-third of the general population thatexhibits higher levels of sensitivity to stimuli, greater depth of processing, and stronger emotional and physiological reactivity to both positive and negative stimuli than the general population, a suite of traits known as “sensory processing sensitivity” or “environmental sensitivity.” We assessed the nature connections of this group across five nature-connection types: material, experiential, cognitive, emotional, and philosophical. We found that HSPs hold deeper nature connections than less sensitive individuals with respect to all five connection types. Additionally, variability in nature-connection scores decreased as sensitivity increased, showing a significant trend. Future research can investigate links between nature connections and pro-environmental behavior in this population and the potential mediating role of specific psychological characteristics. We also recommend that researchers consider including sensitivity in future connections to nature assessments.

Effects of motor imagery using virtual reality on pain sensitivity and affect in healthy individuals: a prospective randomized crossover study.

Exercise induces a hypoalgesic response and improves affect. However, some individuals are unable to exercise for various reasons. Motor imagery, involving kinesthetic and visual imagery without physical movement, activates brain regions associated with these benefits and could be an alternative for those unable to exercise. Virtual reality also enhances motor imagery performance because of its illusion and embodiment. Therefore, we examined the effects of motor imagery combined with virtual reality on pain sensitivity and affect in healthy individuals. Randomized crossover study. Laboratory. Thirty-six participants (women: 18) were included. Each participant completed three 10-min experimental sessions, comprising actual exercise, motor imagery only, and motor imagery combined with virtual reality. Hypoalgesic responses and affective improvement were assessed using the pressure-pain threshold and the Positive and Negative Affect Schedule, respectively. All interventions significantly increased the pressure-pain threshold at the thigh (P < .001). Motor imagery combined with virtual reality increased the pressure-pain threshold more than motor imagery alone, but the threshold was similar to that of actual exercise (both P ≥ .05). All interventions significantly decreased the negative affect of the Positive and Negative Affect Schedule (all P < .05). Motor imagery combined with virtual reality exerted hypoalgesic and affective-improvement effects similar to those of actual exercise. The study was enrolled in the UMIN Clinical Trials Registry (registration number: UMIN000046095). The website for registration information is https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000052614.

Repeatability of a Virtual Reality Headset Perimeter in Glaucoma and Ocular Hypertensive Patients.

The VisuALL S is an automated, static threshold, virtual reality-based perimeter for mobile evaluation of the visual field. We examined same-day and 3-month repeatability. Adult participants with a diagnosis of glaucoma or ocular hypertension underwent two VisuALL 24-2 Normal T- Full threshold strategy tests at baseline and one additional exam at 3months for each eligible eye. Spearman, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to assess the correlation of individual point sensitivities and mean deviation (MD) among three tests. Eighty-eight eyes (44 participants) were included. Average age was 68.1 ± 14.3 years, and 60.7% were male. VisuALL MD was highly correlated between tests (intravisit: r = 0.89, intervisit: r = 0.82; P < 0.001 for both). Bland-Altman analysis showed an average difference in intravisit MD of -0.67dB (95% confidence interval [CI], -6.04 to 4.71dB) and -0.15dB (95% CI, -8.04 to 7.73dB) for intervisit exams. Eight-five percent of pointwise intravisit ICCs were above 0.75 (range, 0.63 to 0.93), and 65% of pointwise intervisit ICCs were above 0.75 (range, 0.55 to 0.91). VisuALL demonstrated high correlation of MD between tests and good repeatability for individual point sensitivities among three tests in 3months, except at the points around the blind spot and superiorly. The preliminary reproducibility results for VisuALL are encouraging. Its portable design makes it a potentially useful tool for patients with glaucoma, enabling more frequent assessments both at home and in clinical settings.

Detection of short-lasting and ictal spike-and-wave discharges in around-the-ears EEG recordings in children with absence epilepsy

PurposeLong-term ambulatory EEG recordings can improve the monitoring of absence epilepsy in children, but signal quality and increased review workload are a concern. We evaluated the feasibility of around-the-ears EEG arrays (cEEGrids) to capture 3-Hz short-lasting and ictal spike-and-wave discharges and assessed the performance of automated detection software in cEEGrids data. We compared patterns of bilateral synchronisation between short-lasting and ictal spike-and-wave discharges. MethodsWe recruited children with suspected generalised epilepsy undergoing routine video-EEG monitoring and performed simultaneous cEEGrids recordings. We used ASSYST software to detect short-lasting 3-Hz spike-and-wave discharges (1–3 s) and ictal spike-and-wave discharges in the cEEGrids data. We assessed data quality and sensitivity of cEEGrids for spike-and-wave discharges in routine EEG. We determined the sensitivity and false detection rate for automated spike-and-wave discharge detection in cEEGrids data. We compared bihemispheric synchrony across the onset of short-lasting and ictal spike-and-wave discharges using the mean phase coherence in the 2–4 Hz frequency band. ResultsWe included nine children with absence epilepsy (median age = 11 y, range 8–15 y, nine females) and recorded 4 h and 27 min of cEEGrids data. The recordings from seven participants were suitable for quantitative analysis, containing 82 spike-and-wave discharges. The cEEGrids captured 58 % of all spike-and-wave discharges (median individual sensitivity: 100 %, range: 47–100 %). ASSYST detected 82 % of all spike-and-wave discharges (median: 100 %, range: 41–100 %) with a false detection rate of 48/h (median: 6/h, range: 0–154/h). The mean phase coherence significantly increased during short-lasting and ictal spike-and-wave discharges in the 500-ms pre-onset to 1-s post-onset interval. ConclusionscEEGrids are of variable quality for monitoring spike-and-wave discharges in children with absence epilepsy. ASSYST could facilitate the detection of short-lasting and ictal spike-and-wave discharges with clear periodic structures but with low specificity. A similar course of bihemispheric synchrony between short-lasting and ictal spike-and-wave discharges indicates that cortico-thalamic driving may be relevant for both types of spike-and-wave discharges.

The Buford Complex Redefined: A Pathologic Morphology in Sheep's Clothing.

Considered a normal anatomic variant, the Buford complex has not been studied in children. A Buford complex is not a normal anatomic variant and would, therefore, be present at a lower rate than that seen in the adult population. Cross-sectional study; Level of evidence, 3. Measurements were recorded from magnetic resonance imaging performed over 13 years in children aged ≤11 years for various pathologies unrelated to glenohumeral instability. Interrater reliability was determined to identify Buford complexes, sublabral foramens and tears, and normal shoulders via 16 preadolescent and adolescent patients with confirmed arthroscopic correlation. The Buford complex and labral foramen rates were then compared with a published rate in adults using a binomial probability test. A total of 122 children (62 girls; mean age, 6.4 years [age range, 2 months-10.9 years]) were evaluated. Interrater reliability was 0.846 (95% CI, 0.56-1) to identify anterosuperior labral variants. The expected sublabral foramen count was 23 children, but only 1 was identified (P < .001). The expected Buford complex count was 8 children, but none could be identified (P < .001). The absence of Buford complexes and the significant reduction in sublabral foramen abundance in younger children suggest that these anatomic variants are more likely to be developmental than congenital. The distinct possibility that these previously considered normal variants are truly pathologic findings cannot be ignored. Evidence of a Buford complex could potentially signify an underlying, long-term shoulder instability issue to the treating provider that warrants further investigation or management.

Myofiber-specific lipidomics unveil differential contributions to insulin sensitivity in individuals of African and European ancestry

AimsIndividuals of African ancestry (AA) present with lower insulin sensitivity compared to their European counterparts (EA). Studies show ethnic differences in skeletal muscle fiber type (lower type I fibers in AA), muscle fat oxidation capacity (lower in AA), whilst no differences in total skeletal muscle lipids. However, skeletal muscle lipid subtypes have not been examined in this context. We hypothesize that lower insulin sensitivity in AA is due to a greater proportion of type II (non-oxidative) muscle fibers, and that this would result in an ancestry-specific association between muscle lipid subtypes and peripheral insulin sensitivity. To test this hypothesis, we examined the association between insulin sensitivity and muscle lipids in AA and EA adults, and in an animal model of insulin resistance with muscle-specific fiber types. MethodsIn this cross-sectional study, muscle biopsies were obtained from individuals with a BMI ranging from normal to overweight with AA (N = 24) and EA (N = 19). Ancestry was assigned via genetic admixture analysis; peripheral insulin sensitivity via hyperinsulinaemic–euglycemic clamp; and myofiber content via myosin heavy chain immunohistochemistry. Further, muscle types with high (soleus) and low (vastus lateralis) type I fiber content were obtained from high-fat diet-induced insulin resistant F1 mice and littermate controls. Insulin sensitivity in mice was assessed via intraperitoneal glucose tolerance test. Mass spectrometry (MS)-based lipidomics was used to measure skeletal muscle lipid. ResultsCompared to EA, AA had lower peripheral insulin sensitivity and lower oxidative type 1 myofiber content, with no differences in total skeletal muscle lipid content. Muscles with lower type I fiber content (AA and vastus from mice) showed lower levels of lipids associated with fat oxidation capacity, i.e., cardiolipins, triacylglycerols with low saturation degree and phospholipids, compared to muscles with a higher type 1 fiber content (EA and soleus from mice). Further, we found that muscle diacylglycerol content was inversely associated with insulin sensitivity in EA, who have more type I fiber, whereas no association was found in AA. Similarly, we found that insulin sensitivity in mice was associated with diacylglycerol content in the soleus (high in type I fiber), not in vastus (low in type I fiber).Conclusions; Our data suggest that the lipid contribution to altered insulin sensitivity differs by ethnicity due to myofiber composition, and that this needs to be considered to increase our understanding of underlying mechanisms of altered insulin sensitivity in different ethnic populations.

Meaning and Clinical Interest of Minor Malformations and Normal Variants in Neonatology.

Congenital malformations can be found in all organ systems of a newborn. Almost two-thirds of congenital malformations have an unknown cause. There are minor (mM) and major (MM) congenital malformations. Searching for minor malformations has its vital place in everyday neonatology practice. Minor malformations are defined as physical variants that have no medical consequences and are mostly located on the face and distal parts of the extremities and are easily noticed. Minor malformations occur in approximately 15% of newborns. Minor congenital malformations are of great importance because they can be an indicator of the existence of major congenital malformations and syndromes. In a one-year retrospective study that analyzed the occurrence of 38 minor malformations through the year 2023 at the University Clinical Hospital of Mostar, there was an incidence of 10.59% of minor malformations. The most frequently recorded minor malformation was deep a sacral dimple at 44.72%, then poorly modeled ears at 15.08%, and moderate rectal diastasis at 14.58%. Three or more minor congenital malformations indicate one or more major congenital malformations. Major congenital malformations are severe structural defects of tissues and organs that endanger life, create serious functional disturbances and hinder the development of the child. In our country, there is currently a recorded incidence of 8.04%. The search for minor malformations in the newborn period is of great importance to children and the whole family, and the search must not be neglected.

Beta2-agonist impairs muscle insulin sensitivity in persons with insulin resistance.

Given the promising effects of prolonged treatment with beta2-agonist on insulin sensitivity in animals and non-diabetic individuals, the beta2-adrenergic receptor has been proposed as a target to counter peripheral insulin resistance. On the other hand, rodent studies also reveal that beta2-agonists acutely impair insulin action, posing a potential caveat for their use in treating insulin resistance. To assess the impact of beta2-agonist on muscle insulin action and glucose metabolism and identify the underlying mechanism(s) in 10 insulin-resistant subjects. In a cross-over design, we assessed the effect of beta2-agonist on insulin-stimulated muscle glucose uptake during a 3-h hyperinsulinemic isoglycemic clamp with and without intralipid infusion in 10 insulin-resistant overweight subjects. Two hours into the clamp, we infused beta2-agonist. We collected muscle biopsies before, two hours into and by the end of the clamp and analyzed them using metabolomic and lipidomic techniques. We establish that beta2-agonist, independently from and additively to intralipid, impairs insulin-stimulated muscle glucose uptake via different mechanisms. In combination, beta2-agonist and intralipid nearly eliminates insulin-dependent muscle glucose uptake. While both beta2-agonist and intralipid elevated muscle glucose-6-phosphate, only intralipid caused accumulation of downstream muscle glycolytic intermediates, whereas beta2-agonist attenuated incorporation of glucose into glycogen. Our findings suggest that beta2-agonist inhibits glycogenesis while intralipid inhibits glycolysis in skeletal muscle of insulin-resistant individuals. These results should be addressed in future treatment of insulin resistance with beta2-agonist.

Comparison of a Novel Head-Mounted Objective Auto-perimetry (Gaze Analyzing Perimeter) and Humphrey Field Analyzer

To evaluate the agreement between 24-2 visual field (VF) test results obtained using the gaze analyzing perimeter (GAP; FINDEX, Tokyo, Japan) and the Humphrey field analyzer (HFA; Carl Zeiss Meditec, Dublin, CA, USA). Cross-sectional study PARTICIPANTS: Patients who underwent HFA 24-2 for suspected or confirmed VF loss and were treated at the Kyoto University Hospital between December 2022 and July 2023. Patients underwent consecutive VF tests on the same eye using HFA and GAP 24-2 tests. Bland-Altman analysis was used to compare GAP and HFA results. Examination points where the sensitivity measured using GAP was ≥10 dB higher than that measured using HFA were reevaluated by referring back to the original gaze data; two ophthalmologists assessed whether the gaze moved linearly toward the new test target. Mean deviation (MD) and elapsed time on an individual basis and sensitivity on an examination point basis. Forty-seven eyes of 47 patients were analyzed. The correlation coefficient of the MD using HFA and GAP was 0.811 (95% confidence interval [CI]: 0.683-0.891). Bland-Altman analysis showed good agreement between HFA and GAP tests. The mean difference (95% limits of agreement [LOA]) in MD between HFA and GAP results was -0.63 dB (-5.81 to 4.54 dB). Although no statistically significant differences were observed in the elapsed time (P = 0.99), measurements completed within 200 s were observed only in the GAP group (11 cases, 23.4%), who had significantly better HFA MD value than others (P=0.001). On an examination point basis for sensitivity, the correlation coefficient between HFA and GAP was 0.691 (95% LOA, 0.670-0.711). Original gaze data assessment revealed that the gaze moved linearly toward the new test target for 70.2% of the examination points with a sensitivity discrepancy. The results indicate that the GAP provides VF assessment outcomes comparable to those of the HFA. The GAP exhibited advantages in terms of testing time, particularly in patients with minimal VF impairment. Furthermore, the GAP records all eye movements, enabling the objective determination of VF abnormalities based on gaze patterns and facilitating easy post-hoc verification.

Reduced contrast sensitivity, pattern electroretinogram ratio, and diminished a-wave amplitude in patients with major depressive disorder.

The electroretinogram (ERG), a non-invasive electrophysiological tool used in ophthalmology, is increasingly applied to investigate neural correlates of depression. The present study aimed to reconsider previous findings in major depressive disorder (MDD) reporting (1) a diminished contrast sensitivity and (2) a reduced patten ERG (PERG) amplitude ratio, and additionally, to assess (3) the photopic negative response (PhNR) from the flash ERG (fERG), with the RETeval® device, a more practical option for clinical routine use. We examined 30 patients with a MDD and 42 healthy controls (HC), assessing individual contrast sensitivity thresholds with an optotype-based contrast test. Moreover, we compared the PERG ratio, an established method for early glaucoma detection, between both groups. The handheld ERG device was used to measure amplitudes and peak times of the fERG components including a-wave, b-wave and PhNR in both MDD patients and HCs. MDD patients exhibited diminished contrast sensitivity together with a reduced PERG ratio, compared to HC. With the handheld ERG device, we found reduced a-wave amplitudes in MDD, whereas no significant differences were observed in the fERG b-wave or PhNR between patients and controls. The reduced contrast sensitivity and PERG ratio in MDD patients supports the hypothesis that depression is associated with altered visual processing. The findings underscore the PERG's potential as a possible objective marker for depression. The reduced a-wave amplitude recorded with the RETeval® system in MDD patients might open new avenues for using handheld ERG devices as simplified approaches for advancing depression research compared to the PERG.

Lipid Profile and Triglyceride-Glucose Index (TyG) Alterations in a Single-Center Cohort of Children Diagnosed with Central Precocious Puberty.

Background: A correlation between plasma lipids and timing of pubertal development has been hypothesized, though lipid influence remains unclear in central precocious puberty (CPP). Aim: To assess any possible alterations in the lipid profile and triglyceride glucose index (TyG) in children diagnosed with CPP. Patients and Methods: Retrospective single-center study conducted on children (aged 6.3 ± 2.1 years) evaluated for the suspicion of CPP. Results: Based on the results of the gonadotropin releasing hormone (GnRH) test, considering 5 IU/L as cut-off of the luteinizing hormone peak, CPP was confirmed in 43 patients (57.3%). Sixteen (37.2%) had a pathologic body mass index (BMI), with 9 (20.9%) being overweight and 7 (16.27%) obese. High total cholesterol was found in 3 patients with CPP (6.97%), high triglycerides were found in 11 patients with CPP (25.58%), high LDL cholesterol was found in 5 patients with CPP (11.62%), low HDL cholesterol was found in 12/43 patients with CPP (27.9%), a pathologic TyG was found in 13/43 patients with CPP (30.23%). No significant association was observed in the lipid profile for patients with or without CPP, except for HDL cholesterol, which was lower in the CPP group (47.1 ± 10.9; p = 0.033). However, the association between serum HDL cholesterol and CPP was not confirmed at the multivariate logistic regression analysis adjusted for patients' sex and age (p = 0.1; OR: 1.035; 95% CI: 0.993-1.078). Conclusion: The overall lipid profile of our pediatric patients diagnosed with CPP did not differ from patients having idiopathic precocious thelarche or normal variants of puberty development.

Molecular characterization, clinical value, and cancer–immune interactions of genes related to disulfidptosis and ferroptosis in colorectal cancer

BackgroundThis research strived to construct a new signature utilizing disulfidptosis-related ferroptosis (SRF) genes to anticipate response to immunotherapy, prognosis, and drug sensitivity in individuals with colorectal cancer (CRC).MethodsThe data for RNA sequencing as well as corresponding clinical information of individuals with CRC, were extracted from The Cancer Genome Atlas (TCGA) dataset. SRF were constructed with the help of the random forest (RF), least absolute shrinkage and selection operator (LASSO), and stepwise regression algorithms. To validate the SRF model, we applied it to an external cohort, GSE38832. Prognosis, immunotherapy response, drug sensitivity, molecular functions of genes, and somatic mutations of genes were compared across the high- and low-risk groups (categories). Following this, all statistical analyses were conducted with the aid of the R (version 4.23) software and various packages of the Cytoscape (version 3.8.0) tool.ResultsSRF was developed based on five genes (ATG7, USP7, MMD, PLIN4, and THDC2). Both univariate and multivariate Cox regression analyses established SRF as an independent, prognosis-related risk factor. Individuals from the high-risk category had a more unfavorable prognosis, elevated tumor mutational burden (TMB), and significant immunosuppressive status. Hence, they might have better outcomes post-immunotherapy and might benefit from the administration of pazopanib, lapatinib, and sunitinib.ConclusionIn conclusion, SRF can act as a new biomarker for prognosis assessment. Moreover, it is also a good predictor of drug sensitivity and immunotherapy response in CRC but should undergo optimization before implementation in clinical settings.

Resting energy expenditure differs among individuals with different levels of perceived thermal sensitivity: A cross-sectional study.

Metabolic rate has been used in thermophysiological models for predicting the thermal response of humans. However, only a few studies have investigated the association between an individual's trait-like thermal sensitivity and resting energy expenditure (REE), which resulted in inconsistent results. This study aimed to explore the association between REE and perceived thermal sensitivity. The REE of healthy adults was measured using an indirect calorimeter, and perceived thermal intolerance and sensation in the body were evaluated using a self-administered questionnaire. In total, 1567 individuals were included in the analysis (women = 68.9%, age = 41.1 ± 13.2 years, body mass index = 23.3 ± 3.3 kg/m2, REE = 1532.1 ± 362.4 kcal/d). More women had high cold intolerance (31.8%) than men (12.7%), and more men had high heat intolerance (23.6%) than women (16.1%). In contrast, more women experienced both cold (53.8%) and heat (40.6%) sensations in the body than men (cold, 29.1%; heat, 27.9%). After adjusting for age, fat-free mass, and fat mass, lower cold intolerance, higher heat intolerance, and heat sensation were associated with increased REE only in men (cold intolerance, P for trend = .001; heat intolerance, P for trend = .037; heat sensation, P = .046), whereas cold sensation was associated with decreased REE only in women (P = .023). These findings suggest a link between the perceived thermal sensitivity and REE levels in healthy individuals.

MiR-486-5p-rich extracellular vesicles derived from patients with olanzapine-induced insulin resistance negatively affect glucose-regulating function

A high risk of glucometabolic disorder severely disturbs compliance and limits the clinical application of olanzapine. MicroRNAs (miRNAs) in extracellular vesicles (EVs) have been reported as emerging biomarkers in glucolipid metabolic disorders. A total of 81 individuals with continuous olanzapine treatment over 3 months were recruited in this study, and plasma EVs from these individuals were isolated and injected into rats via the tail vein to investigate the glucose-regulating function in vivo. Moreover, we performed a miRNA profiling assay by high through-put sequencing to clarify the differentiated miRNA profiles between two groups of patients who were either susceptible or not susceptible to olanzapine-induced insulin resistance (IR). Finally, we administered antagomir and cocultured them with adipocytes to explore the mechanism in vitro. The results showed that individual insulin sensitivity varied in those patients and in olanzapine-administered rats. Furthermore, treatment with circulating EVs from patients with olanzapine-induced IR led to the development of metabolic abnormalities in rats and adipocytes in vitro through the AKT-GLUT4 pathway. Deep sequencing illustrated that the miRNAs of plasma EVs from patients showed a clear difference based on susceptibility to olanzapine-induced IR, and miR-486-5p was identified as a notable gene. The adipocyte data indicated that miR-486-5p silencing partially reversed the impaired cellular insulin sensitivity. Collectively, this study confirmed the function of plasma EVs in the interindividual differences in olanzapine-induced insulin sensitivity.

Insulin-related traits and prostate cancer: A Mendelian randomization study

Investigating the causal relationship between insulin secretion and prostate cancer (PCa) development is challenging due to the multifactorial nature of PCa, which complicates the isolation of the specific impact of insulin-related factors. We conducted a Mendelian randomization (MR) study to investigate the associations between insulin secretion-related traits and PCa. We used 36, 60, 56, 23, 48, and 49 single nucleotide polymorphisms (SNPs) as instrumental variables for fasting insulin, insulin sensitivity, proinsulin, and proinsulin in nondiabetic individuals, individuals with diabetes, and individuals receiving exogenous insulin, respectively. These SNPs were selected from various genome-wide association studies. To clarify the causal relationship between insulin-related traits and PCa, we utilized a multivariable MR analysis to adjust for obesity and body fat percentage. Additionally, two-step Mendelian randomization was conducted to assess the role of insulin-like growth factor 1 (IGF-1) in the relationship between proinsulin and PCa. Two-sample MR analysis revealed strong associations between genetically predicted fasting insulin, insulin sensitivity, proinsulin, and proinsulin in nondiabetic individuals and the development of PCa. After adjustment for obesity and body fat percentage using multivariable MR analysis, proinsulin remained significantly associated with PCa, whereas other factors were not. Furthermore, two-step MR analysis demonstrated that proinsulin acts as a negative factor in prostate carcinogenesis, largely independent of IGF-1. This study provides evidence suggesting that proinsulin may act as a negative factor contributing to the development of PCa. Novel therapies targeting proinsulin may have potential benefits for PCa patients, potentially reducing the need for unnecessary surgical treatments.

Homophily in opinion networks affects collective risk perception in heterogeneous populations

Understanding how to accurately inform the population about the risks of disasters is key for the well-functioning of our societies. Risk communication is also an essential feature of the disaster cycle, fundamentally contributing to preparedness but also to management. Here, we use an agent-based model (ABM) to investigate such an important problem. Specifically, we study the emergent behavior of a population of individuals who revise their opinion on therisk of a certain event, based on information received from an institution, processed through individual sensitivity, and discussed with peers. Such a complex process may include several biases, e.g., due to heterogeneous risk perception across the population, and homophily, i.e., tendency of individuals to interact with like-minded people.Our ABM, which encapsulates these crucial features, allows us to perform a campaign of numerical simulations towards gaining mathematically-grounded insights into their impact on the emergent behavior of the population and, ultimately, on how accurately institutional information is received and processed by a population. Such insights can be useful to design empirical studies to test them and, in case of empirical support, to use them to design recommendations for policy decision makers.

Pseudolesions involving bone and soft tissue regarding orthopedic oncology.

Pseudolesions in bone and muscle are encountered mostly incidentally in routine imaging studies, especially due to the recent advancements on many different imaging modalities. These lesions can be categorized into the following categories: normal variants; congenital; iatrogenic; degenerative; and postoperative. In this review, we discuss the many different radiological characteristics of musculoskeletal pseudolesions that appear on imaging, which can prevent non-essential additional studies.