Young Subjects Research Articles

Delta shock index predicts injury severity, interventions, and outcomes in trauma patients: A 10-year retrospective observational study.

Most trauma occurs among young male subjects in Qatar. We examined the predictive values of the delta shock index (DSI), defined as the change in the shock index (SI) value from the scene to the initial reading in the emergency unit (i.e., subtracting the calculated SI at admission from SI at the scene), at a Level 1 trauma center. To explore whether high DSI is associated with severe injuries, more interventions, and worse outcomes [i.e., blood transfusion, exploratory laparotomy, ventilator-associated pneumonia, hospital length of stay (HLOS), and in-hospital mortality] in trauma patients. A retrospective analysis was conducted after data were extracted from the National Trauma Registry between 2011 and 2021. Patients were grouped based on DSI as low (≤ 0.1) or high (> 0.1). Data were analyzed and compared using χ 2 and Student's t-tests. Correlations between DSI and injury severity score (ISS), revised trauma score (RTS), abbreviated injury scale (AIS), Glasgow coma scale (GCS), trauma score-ISS (TRISS), HLOS, and number of transfused blood units (NTBU), were assessed using correlation coefficient analysis. The diagnostic testing accuracy for predicting mortality was determined using the validity measures of the DSI. Logistic regression analysis was performed to identify predictors of mortality. This analysis included 13212 patients with a mean age of 33 ± 14 years, and 24% had a high DSI. Males accounted for 91% of the study population. The trauma activation level was higher in patients with a high DSI (38% vs 15%, P = 0.001). DSI correlated with RTS (r = -0.30), TRISS (r = -0.30), NTBU (r = 0.20), GCS (r = -0.24), ISS (r = 0.22), and HLOS (r = 0.14) (P = 0.001 for all). High DSI was associated with significantly higher rates of intubation, laparotomy, ventilator-associated pneumonia, massive transfusion activation, and mortality than low DSI. For mortality prediction, a high DSI had better specificity, negative predictive value, and negative likelihood ratio (77%, 99%, and 0.49%, respectively). After adjusting for age, emergency medical services time, GCS score, and ISS, multivariable regression analysis showed that DSI was an independent predictor of mortality (odds ratio = 1.9; 95% confidence interval: 1.35-2.76). In addition to sex-biased observations, almost one-quarter of the study cohort had a higher DSI and were mostly young. High DSI correlated significantly with the other injury severity scores, which require more time and imaging to be ready to use. Therefore, DSI is a practical, simple bedside tool for triaging and prognosis in young patients with trauma.

Glare at Night-Time Driving: Effect of Correlated Color Temperature of Led Lamps.

This study aims to analyze the effect of correlated color temperature from LED glare sources on driving performance. The evaluation includes assessing the effect of disability glare on visual reaction time and rating discomfort glare using a standardized scale. LED technology is widely incorporated into various lighting systems; however, the impact of glare from oncoming car headlamps on driving performance at night-time is crucial for road safety. Twenty-three healthy young subjects participated in a laboratory-based experiment simulating night driving using a two-channel Maxwellian view optical system. Two LED lamps with correlated color temperature of 2800K and 6500K were used to generate a glare of 52 lx. Disability glare was quantified in terms of foveal reaction time and discomfort glare was rated using the de Boer scale. The results show that glare-induced effect is mitigated by an increase in background luminance. The correlated color temperature of the LED lamp does not affect either reaction time or discomfort glare rating. The greater short-wavelength emission of 6500K lamp does not intensify the effect of disability or discomfort glare, probably due to the macular pigment absorption on foveal vision and the transparency of ocular media, coupled with the involvement of other contributing factors. The correlated color temperature of the lamp is not the best descriptive parameter to identify its effect on glare. It is important to consider the impact of LED technology on visual performance to enhance road safety in critical glare situations during night driving.

Préhypertension artérielle et hypertension artérielle : analyse comparative des facteurs sociodémographiques et comportementaux dans une population ivoirienne

IntroductionHypertension is one of the preventable causes of premature morbidity and mortality worldwide. The term "prehypertension", defined as systolic blood pressure (BP) between 120 and 139 mmHg and/or diastolic BP between 80 and 89 mmHg, was introduced in 2003 and concerns around 25% to 50% of adults worldwide. The objective of this work was to describe some sociodemographic and behavioral factors associated with prehypertension compared to hypertension in a black population. MethodA cross-sectional survey was conducted in the commune of Anyama, located about 10 km from the city of Abidjan (Côte d'Ivoire). Sociodemographic and behavioral data were collected. Body mass index and abdominal obesity were defined. BP was measured and was categorized into two modalities: prehypertension and hypertension. Data were entered with Epi data® software and analyzed with R studio® software. The existence of associations was determined using Pearson's Chi-square test at the 0.05 significance level. Univariate and multivariate logistic regression was performed. ResultsFive hundred and seven (507) people were recruited with a mean age of 35.9 ± 12.8 years, among whom 266 had prehypertension (52.5%) and 140 had hypertension (27.6%). Age, wealth index, sedentary lifestyle, obesity, and abdominal obesity were associated with blood pressure. Prehypertension was very high in younger subjects compared to older subjects with a gradually decreasing odds ratio as individuals aged (p=0.001). The determinants of prehypertension compared to hypertension were age less than 44 years; absence of sedentary lifestyle; and absence of obesity. ConclusionSome sociodemographic and behavioral factors were favorable for prehypertension compared to hypertension.

Haemorrhagic Stroke in Young People in Intensive Care: Prognostic Factors in Cote d’Ivoire

Introduction: Hemorrhagic cerebrovascular accident (HCVA) is a medical or medico- surgical emergency requiring treatment in neurovascular or intensive care units. The aim of this work was to determine the prognostic factors of hemorrhagic stroke in young subjects in intensive care in the 3 university hospitals of Abidjan. Method: This is a descriptive and analytical retrospective study covering, which extends from January 2018 to December 2022, taking into account All patients aged 18 to 50 admitted to intensive care for a hemorrhagic stroke during the study period. Results: 146 patients including 100 men were included. The average age was 43 years old. High blood pressure was the main modifiable risk factor. The average Glasgow score was 8.2 and 98% of cases presented with impaired consciousness. Grade 3 hypertension was found in 73 patients on admission. The main location of the hemorrhage on imaging was parenchymal and 45% of subjects had an ICH score greater than or equal to 3 in almost 50% of cases. Nicardipine was the antihypertensive of choice. 103 patients were intubated and ventilated. 52% underwent neurosedation 13% underwent neurosurgery. The average length of hospitalization was 8.3 days during which 72.6% of patients presented complications, mostly infectious. Mortality remains high at 66.44% of cases. We listed as prognostic factors, inaugural deep coma, inaugural grade 3 arterial hypertension, ICH severity score greater than or equal to 3, renal failure and length of stay less than 7 days. Conclusion: Hemorrhagic strokes in young subjects remain a common condition in our country. Mortality in intensive care is high and is linked to clinical and neurological severity, biological disorders, the occurrence of complications and the length of stay in intensive care.

Do conditional cash transfers improve intergenerational gains in educational achievement?: Evidence from Brazil’s Bolsa Familia Program

Conditional cash transfer programs are designed to interrupt the intergenerational cycle of poverty by improving health and educational outcomes. We evaluate the efficacy of the world’s largest CCT program utilizing educational outcomes from the complete administrative records at the intra-family level of Brazil’s Bolsa Família program (PBF). Although we find that younger siblings subject to the Bolsa Família conditionalities outperform their older, untreated siblings in educational attainment within the same household, the overall effect size remains substantively small. We consider the educational attainment of 15–17 year old beneficiaries with siblings who were above the age of 18 at the time of family enrollment. Our findings show precisely estimated positive effects due to the large sample, indicating that the program yields minimal improvements in educational outcomes for ‘treated’ children compared to their ‘untreated’ siblings. Additionally, we find modest differences across boy and girl sibling pairs, but consistent regional effects, underscoring the importance of local public goods provision for enhancing program efficacy.

Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels.

Increased dietary inorganic phosphate (Pi) intake stimulates renal Pi excretion, in part, by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) or dopamine. High dietary Pi may also stimulate sympathetic outflow. Rodent studies provided evidence for these regulatory loops, while controlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake. The effects of controlled, isolated changes in dietary Pi intake over shorter periods are unknown. We studied the effects of a low or high Pi diet on parameters of mineral metabolism in 10 healthy young men. Participants received a standardized diet (1000mg phosphorus equivalent/day) supplemented with either a phosphate binder (low Pi diet) or phosphate capsules (750mg phosphorus, high Pi diet) in a randomized cross-over trial for 5days with a 7-day washout between diets. High Pi intake increased plasma Pi levels and 24-h excretion and decreased urinary calcium excretion. High Pi intake increased intact FGF23 (iFGF23) and suppressed plasma Klotho without affecting cFGF23, PTH, calcidiol, calcitriol, Fetuin-A, dopamine, epinephrine, norepinephrine, metanephrine, or aldosterone. Higher iFGF23 correlated with lower calcitriol and higher PTH. These data support a role for iFGF23 in increasing renal Pi excretion and reducing calcitriol in healthy young men during steady-state high dietary Pi intake. High dietary Pi intake elevated blood Pi levels in healthy young subjects with normal renal function and may therefore be a health risk, as higher serum Pi levels are associated with cardiovascular risk in the general population.

Spirometry Versus Forced Oscillation to Assess Lung Function Outcome at 5 Years of Age.

Spirometry is the gold standard for assessing airway function for clinical studies; however, obtaining high-quality data in young children remains challenging. Since the forced oscillation technique (FOT) requires less subject cooperations, there has been increasing interest in FOT, particularly in young children. We evaluated whether spirometry and FOT in young children provides comparable ability to detect a treatment effect. We recently reported in a randomized controlled trial that vitamin C compared to placebo treatment of mothers who smoked during pregnancy (MSDP) results in the offspring having significantly higher forced expiratory flows (FEFs) at 5-years of age, as well as significantly less wheeze at 4-6 years of age. In these same offspring, we also measured respiratory impedance using FOT at 8-Hz impedance at 3, 4, and 5 years of age. Although spirometry demonstrated significantly increased FEFs in vitamin C compared to placebo-treatment group at 5 years of age (p < 0.001), we were not able to detect a similar treatment effect using FOT impedance. It may be challenging to obtain technically successful spirometry in preschool children; however, FEFs may provide a better outcome than single-frequency FOT impedance to assess improvements in airway function in these young subjects.

Metabolic signatures of combined exercise and fasting: an expanded perspective on previous telomere length findings.

Aging is a complex process marked by a gradual decline in physiological function and increased susceptibility to diseases. Telomere length is frequently regarded as one of the primary biomarkers of aging. Metabolic profiles are key features in longevity and have been associated with both age and age-related diseases. We previously reported an increase in the telomere length in healthy female subjects when Ramadan fasting was combined with physical training. This study aims to characterize the metabolic signature differentiating the combined effects of exercise and fasting from exercise alone and explore the correlations with the previously reported telomere length changes. Twenty-nine young, non-obese, and healthy female subjects were previously randomized into two groups: one group followed a 4-week exercise program, while the other group followed the same 4-week exercise program but also fasted during Ramadan. Metabolic profiles were assessed pre- and post-intervention using untargeted metabolomics. Our results showed a significant decrease in many lipid metabolites in the exercise-while-fasting group, particularly ceramides. Our study sheds light on the dynamic changes in lipid metabolism and its potential role in inflammation and age-related diseases, and contributes to the broader understanding of how lifestyle factors can influence cellular aging and metabolic health.

Vascular ageing in relation to chronological and self-perceived age in the general Swedish population

Background. Aortic stiffness is a marker of vascular ageing. Non-conventional risk markers reflecting vascular ageing are largely unexplored. We aimed to investigate the relationship between self-perceived age (SPA) and self-rated health (SRH) with aortic stiffness in the general population. Methods. Cross-sectional assessment of 3760 participants from two Swedish population-based cohorts (mean age 43.5 ± 14.5 years, 53.4% women). Participants completed two self-administered questions about SPA (SPA-self referring to SPA perceived by oneself, and SPA-others referring to SPA perceived by others) graded as: younger, no difference, or older than same-aged/sex peers. SRH was graded as poor versus good. Aortic stiffness (vascular ageing) was assessed by carotid–femoral pulse wave velocity (PWV). Linear regression was performed stratified by the median age of 45 years. Results. Chronologically younger men and women ≤45 years with older SPA-others had unexpectedly lower PWV (β − 0.39, p < .001 and β − 0.40, p < .001, respectively), independently of cardiovascular risk factors and social health determinants, compared with subjects with younger SPA-others. Lower PWV was also observed in women ≤45 years with older SPA-self (β − 0.24 m/s, p = .005) compared with younger SPA-self, but not in men. A similar pattern between SPA-self, SPA-others and PWV was found in chronologically younger subjects ≤45 years reporting good SRH. On the contrary, chronologically older subjects >45 years reporting poor SRH, with older SPA-others had increased vascular ageing (PWV β 2.57, p = .03). Conclusions. Self-perceived age is a subjective cognitive variable inversely associated with vascular ageing particularly among chronologically younger adults ≤45 years.

Palovarotene (Sohonos), a synthetic retinoid for reducing new heterotopic ossification in fibrodysplasia ossificans progressiva: history, present, and future.

Retinoids are metabolic derivatives of vitamin A and play crucial roles in the regulation of various tissues and organs during prenatal and postnatal development. Active retinoids, like all-trans-retinoic acid, are synthesized in the cytoplasm and subsequently interact with nuclear retinoic acid receptors (RARα, RARβ, and RARγ) to enhance transcription of specific genes. In the absence of retinoids, RARs can still bind to response elements of target genes but repress their transcription. Chondrogenic cell differentiation and cartilage maturation in the growth plate require the absence of retinoid signaling and transcriptional repression by unliganded RARs. This led to the hypothesis that synthetic retinoid agonists may be pharmacological agents to inhibit those cellular processes and counter the excessive formation of cartilage and bone in conditions like heterotopic ossification (HO). HO can be instigated by diverse culprits including trauma, invasive surgeries, inflammatory disorders, or genetic conditions. One such genetic disease is fibrodysplasia ossificans progressiva (FOP), a rare disorder driven by activating mutations in the ACVR1 gene. Patients with FOP have severe and progressive HO formation in soft tissues, leading to extensive permanent loss of mobility and increased mortality. Synthetic retinoid agonists selective for RARα or RARγ showed efficacy against injury-induced and genetic HO in mouse models. The RARγ agonists showed the highest effectiveness, with palovarotene being selected for clinical trials in patients with FOP. Post hoc analyses of phase II and phase III clinical trials showed that palovarotene has significant disease-modifying effects for FOP, but with significant risks such as premature growth plate closure in some younger subjects. This review provides an overview of retinoid and RAR roles in skeletal development and discusses the identification of palovarotene as a potential FOP therapy, the clinical data supporting its regulatory approval in some countries, and the potential applications of this drug for other relevant disorders besides FOP.

Relationship Between Serum Levels of Oxidized Lipoproteins, Circulating Levels of Myeloperoxidase and Paraoxonase 1, and Diet in Young Subjects with Insulin Resistance.

Oxidized low-density lipoproteins (ox-LDLs) are involved in atherosclerotic plaque formation and progression and have been linked to insulin resistance (IR). Myeloperoxidase is a potent oxidant of lipoproteins related to atherogenic risk. High-density lipoproteins (HDLs) are considered antioxidants due to their association with paraoxonase 1 (PON1). However, HDL can also be oxidized (ox-HDL), and its relationship with IR has not been described. This study evaluated the relationship between circulating levels of myeloperoxidase and paraoxonase 1, diet, and serum levels of ox-LDL and ox-HDL in young people with IR. This cross-sectional study examined 136 young subjects (67 and 69 with and without insulin resistance, respectively). Serum levels of ox-LDL, ox-HDL, myeloperoxidase, and PON1 were quantified using an enzyme-linked immunosorbent assay. The nutritional dietary content of the foods was determined with a food frequency questionnaire, which was analyzed with Nutrimind 2013 software. Serum ox-HDL levels were higher in young subjects without IR than those with IR (p = 0.031). Women with IR presented increased ox-LDL levels compared with women without IR (p = 0.012) and men with IR (p < 0.001). In the IR group, serum ox-LDL levels were negatively correlated with total cholesterol, triglycerides, and LDL-C, whereas the correlation was positive in the insulin-sensitive group. Consumption of vitamins B1 and B2 was related to increased HDL-C levels, while higher ox-LDL levels were related to vitamin K intake. In addition, low energy consumption and phosphorus increased PON1 levels. The results suggest that insulin resistance in young women may promote lipoprotein oxidation, and the intake of B complex vitamins may have an antiatherogenic effect.

The Combination of Topological Data Analysis and Mathematical Modeling Improves Sleep Stage Prediction From Consumer-Grade Wearables.

Wearable devices have become commonplace tools for tracking behavioral and physiological parameters in real-world settings. Nonetheless, the practical utility of these data for clinical and research applications, such as sleep analysis, is hindered by their noisy, large-scale, and multidimensional characteristics. Here, we develop a neural network algorithm that predicts sleep stages by tracking topological features (TFs) of wearable data and model-driven clock proxies (CPs) reflecting the circadian propensity for sleep. To evaluate its accuracy, we apply it to motion and heart rate data from the Apple Watch worn by young subjects undergoing polysomnography (PSG) and compare the predicted sleep stages with the corresponding ground truth PSG records. The neural network that includes TFs and CPs along with raw wearable data as inputs shows improved performance in classifying Wake/REM/NREM sleep. For example, it shows significant improvements in identifying REM and NREM sleep (AUROC/AUPRC improvements >13% and REM/NREM accuracy improvement of 12%) compared with the neural network using only raw data inputs. We find that this improvement is mainly attributed to the heart rate TFs. To further validate our algorithm on a different population, we test it on elderly subjects from the Multi-ethnic Study of Atherosclerosis cohort. This confirms that TFs and CPs contribute to the improvements in Wake/REM/NREM classification. We next compare the performance of our algorithm with previous state-of-the-art wearable-based sleep scoring algorithms and find that our algorithm outperforms them within and across different populations. This study demonstrates the benefits of combining topological data analysis and mathematical modeling to extract hidden inputs of neural networks from puzzling wearable data.

Abstract PR004: Age-induced chronic accumulation of glucocorticoids drives therapy resistance in lung cancer

Abstract Non-small cell lung cancer (NSCLC), a highly aggressive cancer, is the leading cause of cancer- related deaths in the U.S. While chemotherapy and targeted therapy are the main treatment modalities in the clinic, many patients do not respond to these treatments. Strikingly, the median age for lung cancer diagnosis is 71. Yet, preclinical and clinical research have largely been skewed towards young mice and patients. Here, we address this gap in knowledge and evaluate if old age affects the response to standard of care NSCLC therapies in KRAS-driven NSCLC. Using human sera from young and old healthy subjects to treat NSCLC cell lines, we show that age-driven circulatory changes are sufficient to drive a state of profound resistance to both chemotherapies as well as KRASG12C targeted therapies. We confirmed the relevance of our findings in vivo, by transplanting cancer cells derived from the K-rasLSL-G12D/+; p53fl/fl genetically engineered mouse model of lung cancer into young and old C57BL/6 mice. Using this model we showed that unlike young lung tumor-bearing mice on chemotherapy, old tumor-bearing mice do not respond to treatment and have a poor prognosis. Mechanistically, we found that old age drives a transcriptional reprogramming that favors drug resistance and identified the glucocorticoid receptor as a major driver of these transcriptional changes. We traced this to an age-induced chronic accumulation of glucocorticoids in circulation and within the tumor interstitial fluid. Chronic treatment with age-relevant concentrations of cortisol alone was sufficient to drive glucocorticoid receptor activation and induce resistance to therapies mirroring the effects of old age. Further supporting a driving role for glucocorticoids in driving age- induced drug resistance, blocking the glucocorticoid receptor genetically or pharmacologically rescues the drug resistance state imposed by old age in NSCLC cells. Lastly, using TCGA patient data we show an inverse correlation between glucocorticoid receptor activation (GR score) and progression-free survival of lung cancer patients. Together, our work demonstrates a role for age-induced glucocorticoids in circulation in promoting therapy-resistance in NSCLC patients and supports the use of therapeutic agents that block the glucocorticoid receptor as a strategy to increase therapy efficacy in NSCLC patients. Citation Format: Devesh Raizada, Felicia Lazure, Stanislav Drapela, Nadir Sarigul, Joanne Tejero, Didem Ilter, Ana Da Silva Gomes. Age-induced chronic accumulation of glucocorticoids drives therapy resistance in lung cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR004.

Management of Melanoma in Elderly Patients over 80 Years.

Melanoma is a malignant tumour with a poorer prognosis in stage III and IV patients. Development of effective therapies for the treatment of advanced melanoma has led to an improvement in survival. Furthermore, the French population is ageing, and treatment of melanoma in this population has several specific limitations. This descriptive, retrospective, single-centre study collected data on the diagnostic and therapeutic management of patients with melanoma of Breslow ≥ 1 mm or of unknown primary and metastatic spread, at Limoges University Hospital, between 2018 and 2022, and compared the results obtained between 2 groups: under 80 and over 80 years of age; 344 patients were included. The extension work-up was more frequently complete and the sentinel lymph node technique more frequently performed in patients under 80. Wide excision was more frequently in accordance with guidelines in patients over 80. Adjuvant or first-line metastatic treat-ment was more frequently instituted in patients under 80, but no difference was found as regards the second and third lines, the frequency of adverse events, and the reason for stopping treatment. Our study supports similar management of elderly and young subjects, given the safety profile and efficacy of treatments.

Development of a cerebellar ataxia diagnosis model using conditional GAN-based synthetic data generation for visuomotor adaptation task

This study proposes a synthetic data generation model to create a classification framework for cerebellar ataxia patients using trajectory data from the visuomotor adaptation task. The classification objectives include patients with cerebellar ataxia, age-matched normal individuals, and young healthy subjects. Synthetic data for the three classes is generated based on class conditions and random noise by leveraging a combination of conditional adversarial generative neural networks and reconstruction networks. This synthetic data, alongside real data, is utilized as training data for the patient classification model to enhance classification accuracy. The fidelity of the synthetic data is assessed visually to measure the validity and diversity of the generated data qualitatively while quantitatively evaluating distribution similarity to real data. Furthermore, the clinical efficacy of the patient classification model employing synthetic data is demonstrated by showcasing improved classification accuracy through a comparative analysis between results obtained using solely real data and those obtained when both real and synthetic data are utilized. This methodological approach holds promise in addressing data insufficiency in the digital healthcare domain, employing deep learning methodologies, and developing early disease diagnosis tools.

Abstract 4117657: Targeting GPR39 for Hypoxia-induced Pulmonary Hypertension in Mice

Background: Primary pulmonary arterial hypertension (PAH) is a disease affecting young subjects. It has very poor prognosis and optimal treatment is not available. 15-hydroxyeicosatetraenoic acid (15-HETE), a potent vasoconstrictor, has been implicated in the pathogenesis of PAH. Elevated levels of 15-HETE have been shown to be associated with worse prognosis in patients with PAH. Oral ingestion of 15-HETE leads to development of PAH in rodents. We recently showed that 15-HETE is the endogenous agonist for the G-protein coupled receptor 39 (GPR39) present in vascular smooth muscle cells. Hypothesis: We, therefore, hypothesized that global deletion of GPR39 (knock-out [KO] mice) would protect from PAH by removing the receptor through which 15-HETE causes vasoconstriction. Methods: Accordingly, 13 wild-type (WT) and 16 KO mice were placed in a hypoxia chamber (10% O 2 ). Litter-mate controls (7 WT and 13 KO) were subjected to normoxia (room air, 21% O 2 ). At the end of 4 weeks heart rate as well as aortic and right ventricular (RV) pressures were measured (latter using micromanometer-tipped catheter), and the animals were then euthanized for measurement of RV wall thickness and RV size from which RV wall stress was calculated. Results: Heart rate and systolic blood pressure were not different between the 4 groups . WT hypoxic animals developed PAH with peak RV systolic pressures (RVSP) being significantly higher than normoxic WT and hypoxic WT and hypoxic KO mice. (Figure 1) Similar results were noted for RV end-diastolic pressure (Figure 2) and RV wall stress (Figure 3). Conclusions: By deleting GPR39, the target for 15-HETE, we were able to prevent hypoxia induced PAH and RV dysfunction. Pharmacological inhibition of GPR39 may open new frontiers in the treatment of PAH.

Effect of STIN2VNTR polymorphism of the serotonin transporter gene on background EEG in aged subjects depends on the intellectual environment of professional activity

Previously, we found that associations between the STin2VNTR polymorphism of the serotonin transporter gene and cognitive characteristics during aging depend on the intellectual environment of professional activity. In this regard, the present study was aimed to investigate the age-related characteristics of the electrical activity of the brain depending on this polymorphism and long-term intellectual training. We examined EEG power indicators in subjects of the younger (YG, 18–35 years, N = 261) and older (OG, 55–80 years, N = 142) age groups. According to the intellectual richness of the professional activity environment, the subjects were divided into scientists (SA) and those engaged in non-scientific activities (NSA). All subjects were genotyped for the STin2VNTR polymorphism of the serotonin transporter gene. It was found that the power of delta-beta1 rhythms in older carriers of the 10/10 and 12/12 genotypes was opposite in SA and NSA groups (in the SA group 10/10 12/12, in the NSA 12/12 10/10) while similar effects in young subjects were absent. In the absence of cognitive training, genetic differences were determined by an age-related decrease in the power of delta-alpha3 rhythms in carriers of the 10/10 genotype with no age-related differences in carriers of the 12/12 genotype, suggesting the resistance of the 12/12 genotype to age-related changes. In contrast, under cognitive training conditions, there were no age differences in the 10/10 genotype, and a decrease in power was observed in the 12/12 genotype, suggesting an effect of cognitive training on both homozygous genotypes. The decrease in power observed for the 10/10 NSA and 12/12 SA genotypes appears to have different physiological significance, since it was accompanied by changes in attentional efficiency only in the NSA group. The work shows for the first time that the background EEG features associated with the STin2VNTR polymorphism of the serotonin transporter gene in elderly people are under the modulating influence of long-term cognitive training, determined by the specificity of professional activity.

Cannabis smoke and oral Δ9THC enhance working memory in aged but not young adult subjects.

With increased legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis use can impair cognition in young adults, it is critically important to understand how consumption interacts with the cognitive profile of aged individuals, who are already at increased risk of decline. The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration. Acute exposure to cannabis smoke enhanced prefrontal cortex-dependent working memory accuracy in aged males, but impaired accuracy in aged females, while having no effects in young adults of either sex. In contrast, the same cannabis smoke exposure regimen had minimal effects on a hippocampus-dependent trial-unique non-matching to location mnemonic task, irrespective of age or sex. In a second set of experiments, chronic oral consumption of Δ9-tetrahydrocannabinol (Δ9THC) enhanced working memory in aged rats of both sexes, while having no effects in young adults. In contrast, the same oral Δ9THC regimen did not affect spatial learning and memory in either age group. Minimal age differences were observed in Δ9THC pharmacokinetics with either route of administration. Together, these results show that cannabis and Δ9THC can attenuate working memory impairments that emerge in aging. While these enhancing effects do not extend to hippocampus-dependent cognition, cannabis does not appear to exacerbate age-associated impairments in this cognitive domain.

Oat polar lipids and sunflower lecithin similarly improve cardiometabolic risk markers and appetite controlling hormone responses after breakfast and a subsequent lunch. A randomized crossover study in healthy adults.

The alarming global increase in lifestyle-related disorders such as obesity and type 2 diabetes mellitus (T2DM) has increased during the last several decades. Poor dietary choices significantly contribute to this increase and prevention measures are urgently needed. Dietary intake of bioactive compounds found in foods are linked to a decrease likelihood of these disorders. For this purpose, a randomized crossover meal study was performed to compare the postprandial metabolic effects of lecithin and oat polar lipids in healthy subjects. Eighteen young healthy subjects ingested test meals enriched with lecithin, oat polar lipids (PLs) or rapeseed oil. There were four test meals (i) 15 g oat polar lipids: OPL, (ii) 18 g sunflower lecithin (of which 15 g were polar lipids): LPL, (iii) 18 g rapeseed oil: RSO, and (iv) reference white wheat bread: WWB. Lipid-enriched test meals contained equivalent amounts of total fat (18 g), and all breakfast meals contained 50 g available carbohydrates. The meals were served as breakfast followed by a standardised lunch (white wheat bread and meat balls) after 3.5 h. Test variables were measured at fasting and repeatedly during 5.5 h after ingestion of the breakfast. Our study demonstrated that both LPL and OPL had beneficial effects on postprandial glucose and insulin responses, and appetite regulating gut hormones, as compared to RSO and WWB. Significant increase in GLP-1, GIP, and PYY concentrations were seen after consuming breakfast meals with LPL and OPL, and ghrelin concentration was reduced compared to meals with RSO and WWB (p < 0.05). Furthermore, triglycerides (TG) concentration was significantly reduced after OPL compared to RSO (p < 0.05). Our data show that there were no significant variations in glycaemic and insulin responses, TG, and gut hormone concentrations between LPL and OPL during breakfast (0-210 min) or over the whole study period (0-330 min). Our study revealed that the consumption of both lecithin and oat PLs included in breakfast meal may similarly enhance postprandial glucose tolerance, reduce TG, and enhance the secretion of incretins and appetite regulating hormones in healthy young adults. ClinicalTrials.gov, identifier NCT05139355.

Optical and retinal changes influenced by different lighting conditions

Retinal morphology, specifically in its curvature, and ocular aberrations change when the eye adapts to different lighting conditions, including photopic, scotopic, mesopic, blue light, and red light. Sixty healthy young subjects with refractive error less than ±4.00 D of sphere and 3.00 D of cylinder, not suffering from accommodative problems, ocular or systemic pathology, and not having used electronic devices half an hour before or having taken substances that alter the retina during the 2 h prior to the study were included. The subjects adapted to five lighting conditions, each for 5 min, in a controlled environment. Ocular aberrometry and Optical Coherence Tomography (OCT) were taken to capture images of the central and peripheral retina before (baseline measurements) and after adaptation to each lighting condition. The OCT images were exported and processed to analyze retinal curvature, obtaining parameters such as eccentricity, asphericity and shape factor. The results showed that the shape of the retina was hyperbolic prolate, becoming flatter in scotopic and blue light conditions, and more curved in mesopic conditions. Retinal curvature was closest to baseline under red light and photopic conditions. Aberrometric differences, particularly in the C(2,0) polynomial for defocus, showed higher values in mesopic, baseline, and scotopic conditions, and lower values in photopic, blue light, and red light. Significant differences were also observed in spherical aberrations C(4,0) and C(6,0), vertical coma C(3,-1), and trefoil C(3,-3). The spherical equivalent indicated more myopic values in mesopic, baseline, and scotopic conditions, and more hyperopic values in blue, photopic, and red light, suggesting a link between myopia and lower luminosity. This study concludes that illumination affects retinal curvature and ocular refraction, influencing myopia.