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2021 ◽  
Vol 100 (6) ◽  
pp. 38-45
Author(s):  
I.V. Obraztsov ◽  
◽  
L.A. Fedorova ◽  
A.P. Prodeus ◽  
D.A. Kudlay ◽  
...  

The clinical manifestations of immunodeficiency states (IDS), whether primary or secondary, are extremely nonspecific. The consequence of this is the belated setting of the correct diagnosis and, accordingly, the late start of the necessary therapy. Early detection of IDS is a key factor in the successful treatment of patients with these diseases. Determination of the concentration of TREC and KREC in whole blood and dry blood stains by real-time PCR has already proven its effectiveness for newborns and children in the first year of life. Objective of the study: to determine the concentration reference values of TREC and KREC in peripheral blood and dry spots in children and adolescents aged 1–17 years. Materials and methods of research: 162 conditionally healthy individuals were examined, including 64 at the age of 1–5 years, 47 – 6–11 years old and 51 – 12–17 years old. The concentration of TREC and KREC DNA in peripheral whole blood and dry blood spots on neonatal screening cards was assessed by PCR. Results: reference intervals and threshold values of TREC and KREC content in dry spots and in peripheral whole blood of children and adolescents aged 1–17 years were built and substantiated. Conclusion: the obtained reference values are very convenient for identifying patients with T- and/or B-cell lymphopenia, as well as monitoring the number of naive T- and B-lymphocytes in the peripheral blood of patients with already known diseases in wide pediatric practice.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lukasz Smigielski ◽  
Sergi Papiol ◽  
Anastasia Theodoridou ◽  
Karsten Heekeren ◽  
Miriam Gerstenberg ◽  
...  

AbstractAs early detection of symptoms in the subclinical to clinical psychosis spectrum may improve health outcomes, knowing the probabilistic susceptibility of developing a disorder could guide mitigation measures and clinical intervention. In this context, polygenic risk scores (PRSs) quantifying the additive effects of multiple common genetic variants hold the potential to predict complex diseases and index severity gradients. PRSs for schizophrenia (SZ) and bipolar disorder (BD) were computed using Bayesian regression and continuous shrinkage priors based on the latest SZ and BD genome-wide association studies (Psychiatric Genomics Consortium, third release). Eight well-phenotyped groups (n = 1580; 56% males) were assessed: control (n = 305), lower (n = 117) and higher (n = 113) schizotypy (both groups of healthy individuals), at-risk for psychosis (n = 120), BD type-I (n = 359), BD type-II (n = 96), schizoaffective disorder (n = 86), and SZ groups (n = 384). PRS differences were investigated for binary traits and the quantitative Positive and Negative Syndrome Scale. Both BD-PRS and SZ-PRS significantly differentiated controls from at-risk and clinical groups (Nagelkerke’s pseudo-R2: 1.3–7.7%), except for BD type-II for SZ-PRS. Out of 28 pairwise comparisons for SZ-PRS and BD-PRS, 9 and 12, respectively, reached the Bonferroni-corrected significance. BD-PRS differed between control and at-risk groups, but not between at-risk and BD type-I groups. There was no difference between controls and schizotypy. SZ-PRSs, but not BD-PRSs, were positively associated with transdiagnostic symptomology. Overall, PRSs support the continuum model across the psychosis spectrum at the genomic level with possible irregularities for schizotypy. The at-risk state demands heightened clinical attention and research addressing symptom course specifiers. Continued efforts are needed to refine the diagnostic and prognostic accuracy of PRSs in mental healthcare.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Federica Contò ◽  
Grace Edwards ◽  
Sarah Tyler ◽  
Danielle Parrott ◽  
Emily Grossman ◽  
...  

Transcranial random noise stimulation (tRNS) can enhance vision in the healthy and diseased brain. Yet, the impact of multi-day tRNS on large-scale cortical networks is still unknown. We investigated the impact of tRNS coupled with behavioral training on resting-state functional connectivity and attention. We trained human subjects for 4 consecutive days on two attention tasks, while receiving tRNS over the intraparietal sulci, the middle temporal areas, or Sham stimulation. We measured resting-state functional connectivity of nodes of the dorsal and ventral attention network (DVAN) before and after training. We found a strong behavioral improvement and increased connectivity within the DVAN after parietal stimulation only. Crucially, behavioral improvement positively correlated with connectivity measures. We conclude changes in connectivity are a marker for the enduring effect of tRNS upon behavior. Our results suggest that tRNS has strong potential to augment cognitive capacity in healthy individuals and promote recovery in the neurological population.


2021 ◽  
Vol 1 (1) ◽  
pp. 30-49
Author(s):  
Annel Koomen ◽  
◽  
Daniel Keeser ◽  
Verhagen Sonja ◽  
◽  
...  

Electroencephalography-Neurofeedbacktraining (E-NFT) is a method to support subjects in learning to self-regulate their own brain activity. Besides that E-NFT may improve cognitive functions in healthy people, it may improve symptoms in different disorders, such as Attention Deficit and Hyperactivity Disorder (ADHD) and insomnia. The evidence of E-NFT for the treatment of attention problems in ADHD is still under debate just as the suggested efficacy of E-NFT for reducing sleep problems in individuals suffering from insomnia and for improving attention and sleep in the general population. Therefore, this review examines the efficacy of E-NFT on attention and sleep in patients and healthy individuals. The reviewed literature provides evidence that standard E-NFT protocols may have a positive long-lasting effect on the inattention and hyperactivity/impulsivity symptoms in children with ADHD. In healthy children and young adults, E-NFT has been found to improve different aspects of attention and to reduce impulsivity. In addition, positive effects of E-NFT have been documented on sleep onset latency and on tiredness in healthy individuals. Sleep improvements have also been found in insomnia patients after standard E-NFT, although these subjective sleep improvements may likely depend on unspecific E-NFT training effects.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Mohamed A Badawy ◽  
Basma A Yasseen ◽  
Riem M El-Messiery ◽  
Engy A Abdel-Rahman ◽  
Aya A Elkhodiry ◽  
...  

Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1-35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance (EPR) spectra of spin labelled fatty acids (SLFA) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10-11). Non-survivor' HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA we show that transport function of HSA maybe impaired in severe patients. Stratified at the means, Kaplan–Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H2O2]>8.6 mM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (< 0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), logrank c2 = 12.1, p=4.9x10-4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.


2021 ◽  
Vol 67 (3) ◽  
pp. 85-91
Author(s):  
Al Essa M

In an assessment of risk for differentiated thyroid cancer (DTC) in individuals with human papillary thyroid cancer (PTC) and thyroid nodules a cohort prospective study was undertaken to establish the significance of preoperative thyroid-stimulating hormone (TSH) levels. Confirmed histologically PTC cases in one tertiary care center, and matched healthy individuals were tested for TSH, T3, T4 and T4 free total. The ORs and 95% confidence intervals have been calculated using conditional logistic regression models (CI). The blood TSH levels were related to the higher risk of PTC for men (OR,0,09; 95% Ci, 04–0,21, 95% CI and women) compared with the middle tertile of the TSH levels in the normal range (OR,0,07; 95 percent CI, 0,04–0,1). Over the normal range of TSH levels, an elevated PTC risks were connected amongst women (OR 0,09; 95% CI, 0,04–0,21) but not amongst men (OR,0,07; 95% CI, 0,04–0,1). With an increase in TSH level in the normal range between men and women, the risk for PTC reduced (Ptrend=0.041 and 0.0001). The risk of PTC related to TSH levels has been dramatically elevated above  the normal range for men  and TSH values below the normal range for women.


Author(s):  
Rishya Manikam ◽  
Wang Seok Mui ◽  
Yong Yean Kong ◽  
Chandramathi Samudi Raju ◽  
Shamala Devi Sekaran

Insights into the molecular pathogenesis of respiratory viral infections were investigated using serum and peripheral blood from patients with clinical syndromes. Signatures of expression of cytokines, genes and apoptotic proteins that discriminate symptomatic individuals from healthy individuals were determined among 21 patients. In symptomatic patients, significant upregulation of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-12, IL-15, TNF-a and IFN-g (P<0.05) was noted, while IL-10 was significantly downregulated (P<0.05). This is accompanied by either up or down-regulation of various pro-apoptotic and anti-apoptotic markers, suggesting a protective role of immune responses against viral infection and the capacity of viruses to subvert host cell apoptosis. Gene expression analysis for both T and B cells were categorized according to their functional status of activation, proliferation, and differentiation. Of note, genes SH2D1A and TCL1A were upregulated only in rhinovirus samples, while PSMB7, CD4, CD8A, HLA-DMA, HLA-DRA and CD69 were upregulated in samples of Flu A and RSV but were not significant in samples of rhinovirus as compared to healthy individuals. These results demonstrated Flu A and RSV elicit different alterations in human peripheral blood gene expression as compared to rhinovirus. Overall, despite the small number of study subjects, the current study for the first time has recognized signature genes, cytokines and proteins that are used by some respiratory viruses that may serve as candidates for rapid diagnosis as well as targets for therapeutic interventions.


2021 ◽  
pp. 00493-2021
Author(s):  
M. Westhoff ◽  
M. Friedrich ◽  
J. I. Baumbach

The high sensitivity of methods, which are applied in breath analysis, entails a high risk of detecting analytes which do not derive from endogenous production. Consequentially, it appears useful to have knowledge about the composition of inhaled air and to include alveolar gradients into interpretation.The current study aimed to standardise sampling procedures in breath analysis, especially with multicapillary column ion-mobility spectrometry (MCC-IMS), by applying a simultaneous registration of inhaled air and exhaled breath.A “Double MCC-IMS” device, which for the first time allows simultaneous analysis of inhaled air and exhaled breath, was developed and tested in 18 healthy individuals. For this two BreathDiscoverys® (BDs) were coupled with each other.Measurements of inhaled air and exhaled breath in 18 healthy individuals (mean age 46±10.9 years; 9 men, 9 women) identified 35 different volatile organic compounds (VOCs) for further analysis. Not all out of these had positive alveolar gradients and could be regarded as endogenous VOCs; 16 VOCs had a positive alveolar gradient in mean, 19 VOCs a negative one. 12 VOCs were positive in more than 12 of the healthy subjects.For the first time in our understanding a method is described, which enables simultaneous measurement of inhaled air and exhaled breath. This facilitates the calculation of alveolar gradients and selection of endogenous VOCs for exhaled breath analysis. Only a part of VOCs in exhaled breath are truly endogenous VOCs. The observation of different and varying polarities of the alveolar gradients needs further analysis.


2021 ◽  
Author(s):  
Gabriela Assis-de-Lemos ◽  
Jamila Monteiro ◽  
Viviane Medeiros Oliveira-Valença ◽  
Guilherme A Melo ◽  
Ricardo Augusto de Melo Reis ◽  
...  

Dopamine signaling has numerous roles during brain development. In addition, alterations in dopamine signaling may be also involved in the pathophysiology of psychiatric disorders. Neurodevelopment is modulated in multiple steps by reactive oxygen species (ROS), byproducts of oxidative metabolism which are signaling factors involved in proliferation, differentiation, and migration. Hexokinase (HK), when associated with the mitochondria (mt-HK), is a potent modulator of the generation of mitochondrial ROS in the brain. In this study we investigated whether dopamine could affect both the activity and redox function of mt-HK in human neural progenitor cells (NPCs). We found that dopamine signaling via D1R decreases mt-HK activity and impairs ROS modulation, which is followed by an expressive release of H2O2 and impairment in calcium handling by the mitochondria. Nevertheless, mitochondrial respiration is not affected, suggesting specificity for dopamine on mt-HK function. In neural stem cells (NSCs) derived from iPSCs of schizophrenia patients, mt-HK is unable to decrease mitochondrial ROS, in contrast to NSCs derived from healthy individuals. Our data point to mitochondrial hexokinase as a novel target of dopaminergic signaling, as well as a redox modulator in human neural progenitor cells, which may be relevant to the pathophysiology of neurodevelopmental disorders such as schizophrenia.


2021 ◽  
pp. 155982762110491
Author(s):  
Monica Kazlausky Esquivel

The digestive system is involved in providing both regulatory and biochemical signaling to the nervous system via the gut–brain axis. Major brain neurotransmitters within the enteric nervous system include acetylcholine, serotonin, and norepinephrine, which are triggered by various stimuli within the digestive system, including the microbiota. Associations between the gut microbiome and activation of neuroreceptors and neurotransmitters are related to factors such as appetite control, mood, and memory. This column presents the results of a brief review of recently published clinical trials related to gut microbiome interventions (n = 11) that aimed to address a variety of mental health outcomes. The impacts of probiotics on mental health and other clinical outcomes vary by the health of study participants. Continuing research on the mental health benefits of probiotics in healthy individuals is necessary.


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