Group Of Healthy Volunteers Research Articles

Effect of exogenous ketone supplementation on cardiac energetics, function, and perfusion in type 2 diabetes, heart failure, and healthy participants- A single center, open labelled clinical study

Abstract Background Type 2 diabetes (T2D) confers loss of cardiac metabolic flexibility in fuel selection and impaired mitochondrial function. Enhanced ketone metabolism observed in T2D may represent a compensatory adaptive mechanism as ketones are a more energy efficient resource than carbohydrates or fatty acids. Favorable energetic properties of ketones may potentially mitigate the energy starved state in T2D and heart failure (HF). Purpose To test whether exogenous oral ketone supplementation would reverse cardiac energetic deficit, as well as improve cardiac function and perfusion in patients with T2D, with HF with reduced ejection fraction (HFrEF), and healthy volunteers (HV). Methods Three groups of patients were recruited: patients with T2D (n=33); patients with HFrEF (n=29, 14 with T2D); and HVs(n=25). Participants underwent cardiovascular magnetic resonance and spectroscopy to assess left ventricular (LV) function, rest and dobutamine stress perfusion and energetics (phosphocreatine/adenosine triphosphate ratio[PCr/ATP]). After the initial visit, participants had an identical second visit following 2 weeks of oral ketone supplementation (30g daily). Results Participants were matched in age and sex distribution. There were no significant differences in LV ejection fraction (LVEF) between T2D and HV groups with significantly lower LVEF in HFrEF group. Both the T2D group and the HFrEF group showed significant reductions in PCr/ATP ratio and the rest and stress GLS compared to the HV. The resting and dobutamine-stress myocardial blood flow (MBF) were only significantly reduced in patients with HFrEF compared to T2D and HV groups. Subgroup analyses of HFrEF group with and without T2D showed no significant differences in energetics, perfusion, or functional assessments. Significant increase in PCr/ATP ratio was seen only in T2D group from baseline after 2 weeks of ketone supplementation (Visit-1:1.6[1.5,1.8] vs Visit-2:1.9[1.7,2.1]; P=0.01). This significant increment was not observed in HFrEF or HV groups. Two weeks of ketone supplementation was not associated with any significant changes in LVEF, GLS, rest or dobutamine-stress myocardial blood flow, or in myocardial lipid content (Table-1). Conclusions Short-term ketone supplementation is associated with isolated significant improvements in resting cardiac energetics in patients with T2D and preserved LVEF, without changes cardiac function or perfusion. In contrast to patients with T2D and preserved LVEF, short-term ketone supplementation does not lead to any significant improvements in energetics in patients with HFrEF suggesting loss of mitochondrial plasticity with transition to HFrEF. Moreover, healthy volunteers experience no further increments of myocardial energetics from the normal range values at baseline with ketone supplementation.

Prevalence of stage B heart failure in healthy adults and people with type 2 diabetes

Abstract Introduction People with Type 2 Diabetes (T2D) are at increased risk of heart failure, and as such are classified as having Stage A Heart Failure (SAHF). Those with additional evidence of raised filling pressures, biochemical or structural cardiac changes, without heart failure symptoms, are deemed to have Stage B heart failure (SBHF). Identifying patients with SBHF may help determine those at highest risk of disease progression. Purpose The aim of this work was to assess the prevalence of SBHF in a cohort of asymptomatic healthy volunteers and people with T2D characterised according to current American Heart Association/American College Cardiology/Heart Failure Society of America. Methods A single-centre, prospectively recruited cohort of middle-aged asymptomatic adults with T2D and healthy volunteers, with no history or signs of cardiovascular disease, underwent comprehensive cardiac phenotyping with transthoracic echocardiography and circulating brain natriuretic peptide. Healthy volunteers with risk factors for heart failure, including hypertension and obesity, were excluded from analysis. Prevalence of SBHF was determined by comparing cardiovascular data to proposed standards, left ventricular ejection fraction and global longitudinal strain parameters were omitted from analysis due to data availability. Results We included 383 T2Ds (diabetes duration 9(5,15) years) and 65 healthy volunteers (Table 1); 91% of those with T2D and 65% of healthy volunteers met ≥1 criteria for SBHF (Table 2). Median number of SBHF criteria met in the T2D cohort was 3 (2,4); in particular, a large proportion of the cohort met defined cut offs for relative wall thickness (70.6%), lateral e’ (62.2%), septal e’ (54.1%) and LV wall thickness (47.4%). Of the 65 healthy volunteers, median number of SBHF criteria met was 1 (0,2.5). In healthy volunteers, SBHF was most commonly defined by lateral e’ (40.0%), septal e’ (38.3%), relative wall thickness (32.2%), left atrial volume indexed (22.4%) and serum brain natriuretic peptide (23.3%). Of note, brain natriuretic peptide levels met current SBHF parameters in 18.8% of healthy volunteers and 9.9% people with T2D, which may be attributable to the exclusion of obesity in the healthy volunteer group. Conclusion Using currently proposed standards, a high proportion of middle-aged asymptomatic people with T2D, and healthy volunteers without any risk factors for heart failure, would be categorised as having SBHF. These data strongly suggest that the majority of the proposed parameters for the definition of SBHF are not specific for a UK population and if applied will incorrectly classify many asymptomatic people at high risk of developing heart failure.

Systemic manifestations of connective tissue abnormalities in patients with Mitral Valve Prolapse assessed by Cardiac Magnetic Resonance

Abstract Background Mitral valve prolapse (MVP) reflects a connective tissue abnormality of the mitral leaflets leading to myxomatous degeneration. Early echocardiography and semeiotic assessment investigations suggested that connective tissue abnormalities might be extended to heart chambers, great vessels, and the skeletal system. Cardiac Magnetic Resonance (CMR) has unique potentials in evaluating MVP, cardiac chambers, aortic dimensions, and Haller Index, an expression of the deformity of the thoracic cage, at one time. Purpose We aimed to investigate the potential phenotypic systemic expressions of connective tissue disease in patients with MVP by CMR assessment. Methods This case-control study included consecutive patients with MVP and a control group of healthy volunteers undergoing CMR at our Institution from September 2020 to November 2023. Patients with more than mild mitral or aortic regurgitation, bicuspid aortic valve, or known systemic connective diseases were excluded. The MVP, cardiac chambers, aortic dimensions, and Haller Index were assessed according to standard practice. Results 103 patients with MVP and 57 healthy volunteers (51± 17 vs. 47±18 years, p=0.2, and 5% females vs. 54.4% females, p=0.8, respectively) were enrolled. Patients with MVP showed greater left ventricular end-diastolic (91±25 vs. 78±17 ml/m2; p=0.005) and end-systolic volumes (36±12 vs. 27±6; ml/m2; p<0.001), aortic annulus (13±2 vs. 12±2 mm/m2; p<0.001), sino-tubular junction (15±3 vs. 14±3 mm/m2; p=0.03), aortic root (19±3 vs. 17±3 mm/m2; p<0.001), and descending aorta (13±2 vs. 12±2 mm/m2; p=0.03), and higher Haller Index (2.8±0.6 vs. 2.6±0.4; p=0.02) than healthy controls. No differences were found in ascending aorta (18±3 vs. 17±3 mm/m2; p=0.3), pulmonary trunk (13±2 vs. 13±2 mm/m2; p=0.5), left atrial volume (38±18 vs. 30±15 ml/m2; p=0.20), right ventricular end-diastolic-volume (86±20 vs. 81±20 ml/m2; p=0.3) were found. At ANCOVA, sex and MVP affected the Haller Index values (p = 0.005 and 0.04). The association between MVP and Haller Index persisted after controlling for sex, age, and body surface area. In multivariate regression analysis, MVP and sex had an independent impact on ventricular and aortic dimensions, with MVP and male patients showing greater values. In particular, MVP was associated with an increase in the aortic annulus (Coefficient=1.2; p< 0.001), aortic root (Coefficient=1.5, p=0.001), descending aorta (Coefficient=0.7, p = 0.026), left ventricular end-diastolic-volume (Coefficient=11.1, p=0.01) and mass (Coefficient=5.7, p=0.02) after controlling for sex, age, and body surface area. Conclusions This pivotal study assessing systemic connective tissue disorders by CMR suggests abnormalities in the aorta and the skeletal system of patients with MVP, paving the way to larger investigations exploring the clinical impact of these findings.CMR findings in the study populationBox plots showing variables distribution

Right chambers deformation after tricuspid edge-to-edge percutaneous repair

Abstract Background The development of new analysis software has allowed to broaden myocardial deformation study to right chambers. There are already reference values for right ventricle (RV) and more recently for right atrium (RA). Tricuspid edge-to-edge repair (TEER) potentially causes changes in right chambers mechanics. Purpose Our aim is to evaluate the impact of TEER in the myocardial deformation of RV and RA. Methods Observational retrospective study including all the consecutive patients undergoing TEER in our tertiary centre. Additionally, a control group of healthy volunteers was included. Baseline and 3 months postprocedural echocardiograms were analyzed with a dedicated software to obtain RV, free wall (FW-) and 4 chambers (4C-) global longitudinal strain (GLS), and RA, reservoir (SrRA), conduit (ScdRA) and centrality (SctRA) strains , deformation values. Interobserver variability was evaluated in the control group with the intraclass correlation coefficient (ICC). Differences in baseline values between cases and control group were evaluated with Mann-Whitney U test. Evolutive changes in deformation parameters were studied using paired Wilcoxon W test. Results 15 healthy controls and 29 patients undergoing TEER (79.3% female, 79 [75-82] years-old) were included. Baseline tricuspid regurgitation (TR) was severe in 21 (72.4%), whereas the others were massive or torrential, and the most frequent mechanism was functional (22, 75,9%). Interobserver agreement in the control group was excellent for FW-GLS (0.88; p <0.001), SrRA (0.99; p <0.001) y ScdRA (0.93; p <0.001), good for SctRA (0.68; p= 0.019) and insufficient for 4C-SGL (0.36; p= 0.20). RV deformation values were significantly worse in patients than in controls (Table). However, solely FW-GLS showed improvement 3 months after the procedure (-15.7 vs -20.5 %; p= 0.022). Conclusions Right chamber deformation analysis is feasible and significantly reduced in patients undergoing TEER. Nevertheless, percutaneous treatment of TR has scarce effect in mechanics at early phases. Longer follow up may be required to evaluate the impact in right strain parameters. Table. Right chambers myocardial deformation values in healthy controls and patients undergoing TEER.Figure

Vascular and nerve biomarkers in thigh skin biopsies differentiate painful from painless diabetic peripheral neuropathy

BackgroundIdentifying distinct mechanisms and biomarkers for painful diabetic peripheral neuropathy (DPN) is required for advancing the treatment of this major global unmet clinical need. We previously provided evidence in calf skin biopsies that disproportion between reduced sensory small nerve fibers and increased blood vessels may distinguish painful from non-painful DPN. We proposed that overexposure of the reduced nerve fibers in DPN to increased hypoxemia-induced vasculature and related algogenic factors, e.g., nerve growth factor (NGF), leads to neuropathic pain. To further investigate this proposed mechanism, we have now studied more proximal thigh skin biopsies, to see if the same disproportion between increased vasculature and decreased nerve fibers generally differentiates painful DPN from painless DPN.MethodsA total of 28 subjects with type 2 diabetes (T2DM) and 13 healthy volunteers (HV) underwent detailed clinical and neurophysiological assessments, based on the neuropathy composite score of the lower limbs [NIS(LL)] plus 7 tests. T2DM subjects were subsequently divided into three groups: painful DPN (n = 15), painless DPN (n = 7), and no DPN (n = 6). All subjects underwent skin punch biopsy from the upper lateral thigh 20 cm below the anterior iliac spine.ResultsSkin biopsies showed decreased PGP 9.5-positive intraepidermal nerve fiber (IENF) density in both painful DPN (p < 0.0001) and painless DPN (p = 0.001). Vascular marker von Willebrand Factor (vWF) density was markedly increased in painful DPN vs. other groups, including painless DPN (p = 0.01). There was a resulting significant decrease in the ratio of intraepidermal nerve fiber density to vasculature and PGP9.5 to vWF, in painful DPN vs. painless DPN (p = 0.05). These results were similar in pattern to those observed in these HV and T2DM groups previously in distal calf biopsies; however, the increase in vWF was much higher and nerve fiber density much lower in the calf than thigh for painful DPN. Thigh skin vWF density was significantly correlated with several metabolic (waist/hip ratio, HbA1c), clinical (e.g., pain score), and neurophysiological measures.ConclusionThis study supports our proposal that increased dermal vasculature, and its disproportionate ratio to reduced nociceptors, may help differentiate painful DPN from painless DPN. This disproportion is greater in the distal calf than the proximal thigh skin; hence, neuropathic pain in DPN is length-dependent and first localized to the distal lower limbs, mainly feet.

The Correlation between Serum Cortisol Concentration in Mammals and the Level of Global Seismic Activity.

A positive correlation was found between the level of global seismic activity and dynamics of cortisol concentration in blood serum of male rabbits (r=0.33, p=0.01) and Campbell's dwarf hamsters (r=0.38, p=0.04). For a small group of healthy volunteers (n=5), we also found a positive correlation between cortisol levels and the number of major earthquakes, excluding aftershocks (r=0.36, p=0.009) and a negative correlation with IL-18 levels (r=-0.28, p=0.04). The body response to earthquakes is not delayed, and the numerous aftershocks do not seem to affect the biological indicators under study. These facts showed that the earthquakes themselves do not affect the cortisol level via the changes of the environmental parameters. In contrast, the underlying biotropic factor is an unknown trigger responsible for an increase in the number of potent earthquakes. Evidently, it is important to take into account the level of global seismicity as a marker of this trigger provoking the rise of glucocorticoid hormones.

Frequency of detection of dyssynergic defecation in patients with overlap syndrome of functional disorders of the digestive organs associated with constipation

Introduction. The presence of dyssynergic defecation in a cohort of patients with overlap syndrome of functional disorders is poorly studied.Aim. To assess the motor function and sensitivity parameters of the anorectal zone, to identify dyssynergic defecation and to analyze the frequency of correlation in patients with overlap syndrome of functional gastrointestinal disorders associated with constipation.Materials and methods. A one-stage examination was conducted in four parallel groups. The study included 100 patients aged 30 to 40 years with the following diagnoses: constipation-p redominance irritable bowel syndrome (IBS-C) (group 1), IBS-C combined with functional dyspepsia (group 2), IBS-C combined with functional biliary disorder (group 3) and healthy volunteers (group 0). All patients underwent a balloon expulsion test and high-resolution anorectal manometry to determine the presence of dyssynergic defecation.Results. Based on the analysis of parameters according to anorectal manometry data, dyssynergic defecation was not detected in group 0, in group 1 dyssynergic defecation was detected in 8 people – 32.0% (95% CI 12.3–51.6), in group 2 – in 14 people – 56.0% (95% CI 35.0–76.9), in group 3 – in 16 people – 64.0% (95% CI 43.7–84.2). A negative evacuation test was detected in 8 (32%) patients in group 1, in 14 (56%) patients in group 2, and in 17 (68%) patients in group 3, which confirmed the presence of dyssynergic defecation.Conclusions. This study demonstrated the presence of dyssynergic defecation in three groups of subjects, more often with a combination of irritable bowel syndrome with predominant constipation with functional dyspepsia, and most often with a functional disorder of the gallbladder.

Sleep improves accuracy, but not speed, of generalized motor learning in young and older adults and in individuals with Parkinson's disease.

An essential aspect of motor learning is generalizing procedural knowledge to facilitate skill acquisition across diverse conditions. Here, we examined the development of generalized motor learning during initial practice-dependent learning, and how distinct components of learning are consolidated over longer timescales during wakefulness or sleep. In the first experiment, a group of young healthy volunteers engaged in a novel motor sequence task over 36 h in a two-arm experimental design (either morning-evening-morning, or evening-morning-evening) aimed at controlling for circadian confounders. The findings unveiled an immediate, rapid generalization of sequential learning, accompanied by an additional long-timescale performance gain. Sleep modulated accuracy, but not speed, above and beyond equivalent wake intervals. To further elucidate the role of sleep across ages and under neurodegenerative disorders, a second experiment utilized the same task in a group of early-stage, drug-naïve individuals with Parkinson's disease and in healthy individuals of comparable age. Participants with Parkinson's disease exhibited comparable performance to their healthy age-matched group with the exception of reduced performance in recalling motor sequences, revealing a disease-related cognitive shortfall. In line with the results found in young subjects, both groups exhibited improved accuracy, but not speed, following a night of sleep. This result emphasizes the role of sleep in skill acquisition and provides a potential framework for deeper investigation of the intricate relationship between sleep, aging, Parkinson's disease, and motor learning.

Indices of vertebral vein discirculation in workers in noise occupaions

Introduction. Occupational sensorineural hearing loss (OSNHL) is a gradual bilateral hearing loss developing over several years as a result of exposure to constant or non-constant noise (mainly high-frequency) at the workplace as one of the main causes in etiology, researchers name a violation of blood supply and vascular stenosis. The purpose of the study is to evaluate the indices of venous dyscirculation under the influence of industrial noise at the early stages of the development of OSNHL. Materials and methods. Twenty two male patients who have been working in conditions exceeding the maximum permissible noise levels for more than 5 years were examined, and the comparison group included 29 healthy male volunteers from 27 to 55 years old who do not work in the production sector. All the subjects were examined by an otorhinolaryngologist, a neurologist, and a therapist. Audiometry was performed on two axes for everyone. Air and bone conduction were performed separately for each ear. All patients underwent a triplex scan of the arteries and veins of the neck and brain in the supine and standing positions. Results. In comparison with the control group of healthy volunteers who did not work in industrial noise conditions, workers in noise occupations had a significant increase in blood flow, which averaged 25.2 cm/sec. When measuring the diameters of the vertebral veins, a tendency to vasodilation was revealed. Limitations. The limitation was the small sample size, due to the low patient turnover at the preclinical stage. Conclusion. The complex effect of noise on the body leads to changes in the wall of the venous network, a violation of venous outflow and can manifest itself not only with clinical complaints, but also in the form of episodic dizziness, cephalgia, which in turn can worsen the course of the development of OSNHL. It is necessary to perform ultrasound dopplerography of the neck veins for all workers of noise occupations at the preclinical stage to assess the risk of OSNHL occurrence.

Development of EEG Response to Unpleasant, Pleasant, and Neutral Tactile Stimuli.

The study of tactile perception during a childhood is extremely important for understanding the social and communicative aspects of the child's development. Tactile perception of stimuli with different valence can have different normative stages of development. In the present study, we examined changes in linear and nonlinear electroencephalogram (EEG) parameters during the presentation of pleasant (C-tactile optimal stroking), unpleasant (ice stroking), and neutral tactile stimuli in three groups of healthy volunteers: preschoolers 4 and 5 years, school-age children from 8 to 10 years, and adults from 20 to 40 years. According to our findings, child maturation plays a significant role in the perception of pleasant and neutral tactile stimuli. Patterns of EEG dynamics related to tactile perception showed greater similarity between adult volunteers and school-aged children than preschoolers. Non-linear EEG parameters such as fractal dimension (FD), envelope mean frequency (EMF), and power spectral density (PSD) dynamics of the theta-rhythm were particularly sensitive to developmental changes in tactile perception. Hjorth complexity and peak alpha frequency (PAF) scores may serve as indicators of mature perception of С-tactile (CT)-stimuli.

Vascular endothelial dysfunction improvements in patients with uraemia using pentoxifylline-suppressing NLRP3 expressions and HMGB1 release.

This study aimed to investigate the protective effect of pentoxifylline (PTX) on vascular endothelial dysfunction in uraemia. The human aortic endothelial cells (HAECs) required for the experiments were all obtained from the National Collection of Authenticated Cell Cultures (Salisbury, UK). The permeability of HAECs was assessed. Each group had six samples. Compared with the healthy volunteer group, HAEC proliferation in the 20% uraemia group was significantly inhibited after 72 h (p < 0.001), co-localisation of nucleotide-binding domain, leucine-rich repeat-containing receptor family pyrin domain-containing 3 (NLRP3) and apoptosis-associated speck-like (ASC) protein induced by uremic serum was enhanced (p < 0.01) and high mobility group box 1 (HMGB1) release was increased (0.594 ± 0.057, p = 0.03). The co-immunoprecipitation of NLRP3, ASC and HMGB1 induced by uremic toxin was also enhanced (p < 0.01), and PTX inhibited this phenomenon. The expression of NLRP3 (0.810 ± 0.032, p = 0.02) and caspase-1 (0.580 ± 0.041, p = 0.03) was increased, whereas the expression of ZO-1 (0.255 ± 0.038, p = 0.03) and VE-cadherin (0.0546 ± 0.053, p = 0.02) was decreased in the uraemia group; compared with the healthy volunteer group, treated with PTX (NLRP3, 0.298 ± 0.042, p = 0.03; caspase-1, 0.310 ± 0.021, p = 0.03; ZO-1, 0.412 ± 0.028, p = 0.02; VE-cadherin, 0.150 ± 0.034, p = 0.02) and MCC950 (NLRP3, 0.432 ± 0.022, p = 0.03; caspase-1, 0.067 ± 0.031, p > 0.05; ZO-1, 0.457 ± 0.026, p = 0.03; VE-cadherin, 0.286 ± 0.017, p = 0.03) lessened this trend. Pentoxifylline promoted the HAEC permeability mediated by uremic toxins (1.507 ± 0.012, p = 0.02). In conclusion, PTX enhances the release of HMGB1, which is dependent on NLRP3 activation, and consequently exerts positive effects on interconnecting proteins, ultimately leading to an improvement in vascular permeability.

Comparacão dos Parâmetros Ecocardiográficos Convencionais e com Speckle Tracking entre Indivíduos Saudáveis e Transplantados Cardíacos sem Rejeição

Abstract Background Echocardiography is essential for the assessment of patients with heart transplants. However, normal values in such individuals are not clearly defined. Objectives To compare conventional echocardiographic and speckle tracking variables between patients with unrejected heart transplants and healthy individuals. Methods : A prospective study was conducted with adult patients having undergone heart transplantation at least one year earlier and submitted to endomyocardial biopsy followed by transthoracic echocardiogram (TTE). Conventional TTE measures and mechanical heart strain assessments using speckle tracking were performed and the results were compared to those of a group of healthy volunteers. Statistical significance was set at 5% (p &lt; 0.05). Results Thirty-six transplant patients without rejection were analyzed and compared to 30 healthy individuals. Chagas disease was the main reason for transplantation. Lower left ventricular global longitudinal strain expressed in absolute values was found (11.99% in transplant patients vs. 20.60% in controls; p &lt;0.0001), right ventricular free wall longitudinal strain (16.67% in transplant patients vs. 25.50% in controls; p &lt;0.0001) and myocardial work indices (p &lt; 0.0001) as well as a larger size of the left atrium (38.17 ml/m2 in transplant patients vs. 18.98 ml/m2 in controls; p &lt;0.0001) and greater mass and relative wall thickness (p &lt;0.0001). Conclusion Stable patients having undergone heart transplants without rejection have differences concerning echocardiographic variables compared to healthy individuals. These findings indicate that conventional echocardiographic measures and heart mechanics are altered in transplant patients even in the absence of rejection. Such findings are relevant to the clinical context and follow-up of the patient.

Evaluation of microstructural brain changes in post-coronavirus disease 2019 (COVID-19) patients with neurological symptoms: a cross-sectional study.

Changes in both the vascular system and brain tissues can occur after a prior episode of coronavirus disease 2019 (COVID-19), detectable through modifications in diffusion parameters using magnetic resonance imaging (MRI) techniques. These changes in diffusion parameters may be particularly prominent in highly organized structures such as the corpus callosum (CC), including its major components, which have not been adequately studied following COVID-19 infection. Therefore, the study aimed to evaluate microstructural changes in whole-brain (WB) diffusion, with a specific focus on the CC. A total of 101 probands (age range from 18 to 69 years) participated in this retrospective study, consisting of 55 volunteers and 46 post-COVID-19 patients experiencing neurological symptoms. The participants were recruited from April 2022 to September 2023 at the Institute for Clinical and Experimental Medicine in Prague, Czech Republic. All participants underwent MRI examinations on a 3T MR scanner with a diffusion protocol, complemented by additional MRI techniques. Two volunteers and five patients were excluded from the study due to motion artefacts, severe hypoperfusion or the presence of lesions. Participants were selected by a neurologist based on clinical examination and a serological test for COVID-19 antibodies. They were then divided into three groups: a control group of healthy volunteers (n=28), an asymptomatic group (n=25) with a history of infection but no symptoms, and a symptomatic group (n=41) with a history of COVID-19 and neurological symptoms. Symptomatic patients did not exhibit neurological symptoms before contracting COVID-19. Diffusion data underwent eddy current and susceptibility distortion corrections, and fiber tracking was performed using default parameters in DSI studio. Subsequently, various diffusion metrics, were computed within the reconstructed tracts of the WB and CC. To assess the impact of COVID-19 and its associated symptoms on diffusion indices within the white matter of the WB and CC regions, while considering age, we employed a statistical analysis using a linear mixed-effects model within the R framework. Statistical analysis revealed a significant difference in mean diffusivity (MD) between the symptomatic and control groups in the forceps minor (P=0.001) and CC body (P=0.003). In addition to changes in diffusion, alterations in brain perfusion were observed in two post-COVID-19 patients who experienced a severe course. Furthermore, hyperintense lesions were identified in subcortical and deep white matter areas in the vast majority of symptomatic patients. The main finding of our study was that post-COVID-19 patients exhibit increased MD in the forceps minor and body of the CC. This finding suggests a potential association between microstructural brain changes in post-COVID-19 patients and reported neurological symptoms, with significant implications for research and clinical applications.

Association of cell-free DNA with the length of ulcerated plaque in the infarct-related artery and the myocardial infarct size among patients with ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention

Aim. To evaluate the changes of cell-free DNA (cfDNA) levels before and after percutaneous coronary intervention (PCI) in patients with ST-segment elevation acute coronary syndrome (STE-ACS). To identify associations of cfDNA concentration before and after PCI with complications and length of ulcerated plaque in patients with STE-ACS.Material and methods. This prospective single-center observational pilot study included 44 patients with STE-ACS admitted to the cardiac intensive care unit during the period of May-August 2023. In all patients, along with standard laboratory tests, cfDNA level was measured upon admission and 24 hours after PCI. Assessment of cfDNA associations before and after PCI was carried out in relation to following significant complications and conditions in STE-ACS patients: death, acute left ventricular failure (ALVF), acute heart failure (AHF), arrhythmia, number of stents implanted, number of segments with impaired local contractility, total stent length.Results. The mean age of the patients was 60,6±9,6 years, of which 74,6% were men. TIMI 0-1 flow was recorded in 93,2% of the subjects. The most common complications were cardiogenic shock (18,4%), arrhythmia (16,9%), AHF (13,6%), ALV (11,9%). Death was recorded in 8,5%. Implantation of 1 stent in PCI was performed in 75% of cases, while in the rest, 2 or more stents were implanted. The proportion of patients with impaired local contractility was 90%, the median stent length was 24,0 (20,0-50,0) mm. CfDNA level on admission did not differ from level after PCI 94,5 (78,3-155,5) ng/ml vs 115,0 (71,0-152,0), p=0,46. However, it signi­ficantly exceeded the cfDNA concentration from a group of healthy volunteers (78,0 (59,7-106,0), p=0,017). Characteristic curve showed significant relationships both for the concentration of cfDNA before (with implantation of 2 or more stents (AUC 0,71 with 95% confidence interval (CI) 0,56-0,86, p=0,039), stent length &gt;24 mm (AUC 0,73 with 95% CI 0,58-0,89, p=0,009)) and after PCI (with the number of impaired local contractility segments (AUC 0,73 with 95% CI 0,57-0,89, p=0,014)). If the cfDNA level before PCI was &gt;90 ng/ml, the risk of implantation of 2 or more stents per procedure increased by 5,4 times (odds ratio (OR) 5,4, 95% CI 1,11-28,93, p=0,044). The risk of a stent length &gt;24 mm with pre-PCI cfDNA &gt;107 ng/ml increased 9-fold (OR 9,0 with 95% CI 2,2-36,9, p=0,001), and the cfDNA level after PCI &gt;105 ng/ml increased the risk of impaired local left ventricular (LV) contractility in 2 or more segments by 5 times (OR 5,0, 95% CI 1,23-20,3).Conclusion. In the studied group of patients with STE-ACS subject to intervention, the cfDNA concentration before PCI was associated with the implantation of ≥2 stents and the stent length (&gt;24 mm). CfDNA level before PCI was associated with the number of segments of impaired local LV contractility (≥2).

Comparative study of spirometry parameters in chronic smokers with and without Type 2 Diabetes Mellitus (T2DM).

The study aimed to know the changes in spirometry parameters in chronic smokers and evaluate how the presence of type 2 diabetes mellitus (T2DM) affects their lung function. A prospective, cross-sectional, observational study was done for 12 months at a tertiary care hospital in the western region of Maharashtra State in India. Two groups of patients and one group of healthy volunteers aged 18 years or more were studied (with 50 in each group, n = 150). Group A consisted of smokers with T2DM, Group B- smokers without T2DM and Group 3- healthy controls who were non-smokers and non-diabetic. Spirometry was done for the following parameters: forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio, and peak expiratory flow (PEF) and results compared between the three groups. The mean age of the participants was 51.13 ± 10.74 years. There were 137 (91.3%) males and 13 (8.6%) females. Among the enrolled subjects, 66% had smoked for more than ten years. All spirometry parameters were significantly different across all three groups. When the spirometry parameters were compared between smokers with and without T2DM, all the parameters were significantly decreased (P < 0.05). FEV1 and FEV1/FVC were significantly decreased in T2DM patients with HbA1c >7%. The presence of T2DM in smokers significantly affects their pulmonary function tests. Uncontrolled T2DM (HbA1c >7%) can result in increased abnormality in the spirometry parameters studied. Thus, adequate glycemic control and cessation of smoking can be beneficial for the improvement of lung functions in smokers.

Evaluation of Triglyceride-Glucose Index Elevation as a Biomarker and Risk Factor in Laryngeal Squamous Cell Carcinoma.

Insulin resistance is associated with increased levels of IGF-1. IGF-1 has been shown to increase the risk of laryngeal squamous cell carcinoma. The Triglyceride-glucose index (TyG index) is a marker of insulin resistance. Our study aimed to investigate the relationship between the TyG index and laryngeal squamous cell carcinoma. Retrospective cohort study. Two tertiary care academic hospitals. The study included 53 patients with laryngeal squamous cell carcinoma (Group 1) and 48 healthy volunteers (Group 2). Laryngeal cancer patients were divided into two groups according to their stage. Stages I and II were named Group 1A, and Stages III and IV were called Group 1B. The TyG index was calculated as ln [fasting Triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The effect of the TyG index on laryngeal cancer was investigated on the parameters of sex, age, body mass index, and stage of the disease. There were no significant differences in age, sex, and BMI between the groups. The TyG index of group 1 (4.75 ± 0.33) was significantly higher than that of group 2 (4.59 ± 0.15). The TyG index value of group 1B (4.84 ± 0.31) was significantly higher than both group 1A (4.61 ± 0.32) and group 2 (4.59 ± 0.15). There was no significant difference between the TyG index values of group 1A (4.61 ± 0.32) and group 2 (4.59 ± 0.15). The TyG index may be a promising laryngeal squamous cell carcinoma biomarker. People with a higher TyG index may have a higher incidence of laryngeal squamous cell carcinoma and a higher risk of progression.

Feasibility study on the use of peripheral blood differentially expressed genes for objective classification of chronic subjective tinnitus: a case study on high-frequency tinnitus

Objective: To explore the feasibility of constructing an objective tinnitus subtype model based on peripheral blood differentially expressed genes (DEGs) using a combination of Weighted Gene Co-expression Network Analysis (WGCNA) and Random Forest algorithm (RF). Methods: From October 2019 to June 2020, peripheral blood DEGs were obtained from 37 patients (from the Third Affiliated Hospital of Sun Yat-sen University)with chronic subjective high-frequency tinnitus (21 unbothersome type, 16 bothersome type) and 20 healthy volunteers through high-throughput sequencing. WGCNA was used to construct gene modules with different expression patterns and analyze their relationships with tinnitus characteristics. Subsequently, RF was employed to build subtype models, which were evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, and F1-score. Results: A total of 12 351 intergroup DEGs were divided into 9 gene modules. Among them, MEblue, MEgreen, and MEbrown showed significant negative correlations with the healthy volunteer group, while MEpink showed a significant positive correlation with the tinnitus distress group. The "Tinnitus vs. Normal" and "Compensatory vs. Decompensatory" subtype models, based on MEblue and MEpink respectively, both had AUCs greater than 0.80, accuracies above 90%, and F1-scores above 0.90, indicating good performance. Conclusions: Peripheral blood DEGs are potential biological indicators for objective classification of subjective tinnitus. The combined application of WGCNA and the Random Forest algorithm should be a viable approach to constructing an objective tinnitus subtype model. However, further exploration and refinement are needed to validate the model's generalizability, cross-dataset performance, and algorithm optimization.

An Observational Study: Association Between Atopic Dermatitis and Bacterial Colony of the Skin Based on 16S rRNA Gene Sequencing.

Atopic dermatitis (AD) often accompanies skin infections, and bacterial skin infections often cause persistent and worsening symptoms. In this study, we explored the key changes in the microbiota of AD patients, as well as the effects of different ages and the severity of rash on changes in the microbiota. A total of 95 AD patients and 77 healthy volunteers were recruited. The AD patients were divided into three groups based age and three groups according to the EASI score. Microorganisms collected from the skin were analyzed through 16S rRNA gene sequencing, revealing species diversity via α and β diversity analyses. Species compositions were compared at the phylum and genus levels. The significance of skin microbiota at the genus level was assessed using the random forest algorithm. Finally, the impact of relationships between different microbial communities on the microbial community composition and the pathogenesis of AD was explored using Pearson correlation coefficients. The species diversity of the skin microbiota in the AD group significantly decreased. Compared with that in the healthy volunteers (HV) group, the bacterial diversity in the two groups of samples significantly differed. Staphylococcus dominated the bacterial communities, and as AD symptoms gradually worsened, the abundance of Staphylococcus gradually increased. Among all bacterial genera with a relative abundance greater than 1%, Staphylococcus showed a negative correlation with other genera, and showed significant consistency in specimens from different age groups. Changes in the abundance of Staphylococcus in the skin bacterial colonies are the main cause of AD. Brevundimonas, Paracoccus, Corynebacterium, and Veillonella may serve as characteristic biomarkers for AD. These results indicate that altering the microbiota composition of the skin may aid in the treatment of AD.

Comparative Analysis of Conventional and Speckle Tracking Echocardiographic Variables between Patients with Unrejected Heart Transplants and Healthy Individuals.

Echocardiography is essential for the assessment of patients with heart transplants. However, normal values in such individuals are not clearly defined. To compare conventional echocardiographic and speckle tracking variables between patients with unrejected heart transplants and healthy individuals. :A prospective study was conducted with adult patients having undergone heart transplantation at least one year earlier and submitted to endomyocardial biopsy followed by transthoracic echocardiogram (TTE). Conventional TTE measures and mechanical heart strain assessments using speckle tracking were performed and the results were compared to those of a group of healthy volunteers. Statistical significance was set at 5% (p < 0.05). Thirty-six transplant patients without rejection were analyzed and compared to 30 healthy individuals. Chagas disease was the main reason for transplantation. Lower left ventricular global longitudinal strain expressed in absolute values was found (11.99% in transplant patients vs. 20.60% in controls; p <0.0001), right ventricular free wall longitudinal strain (16.67% in transplant patients vs. 25.50% in controls; p <0.0001) and myocardial work indices (p < 0.0001) as well as a larger size of the left atrium (38.17 ml/m2 in transplant patients vs. 18.98 ml/m2 in controls; p <0.0001) and greater mass and relative wall thickness (p <0.0001). Stable patients having undergone heart transplants without rejection have differences concerning echocardiographic variables compared to healthy individuals. These findings indicate that conventional echocardiographic measures and heart mechanics are altered in transplant patients even in the absence of rejection. Such findings are relevant to the clinical context and follow-up of the patient.

Comparative Evaluation of Calibrated and Non-calibrated Infrared Thermometer Versus Calibrated Digital Thermometer in Healthy Volunteers and Febrile Patients in a Tertiary Care Center in Central India

ABSTRACT Body temperature is a crucial indicator in assessing human physiological activity and health, particularly in pediatric and critically ill patients. This study aimed to compare temperature recordings obtained from digital calibrated thermometers with calibrated infrared thermometers and non-calibrated infrared thermometers against calibrated ones. An observational prospective study was conducted at AIIMS Bhopal, involving volunteers and febrile patients who consented to participate. Approval was obtained from the Institutional Human Ethics Committee, and 200 participants meeting inclusion/exclusion criteria were included. Data were collected and analyzed using Microsoft Excel. Mean and variance values were computed for both volunteer and febrile patient groups. The P values in both groups were less than 0.05, indicating a significant difference between non-calibrated handheld infrared thermometers (T1), calibrated digital thermometers (T2), and their individual comparison with calibrated infrared thermometers (T3). Variance was higher in non-calibrated infrared thermometers (T1) compared to calibrated ones (T2) in both healthy volunteers and febrile patients. Pearson’s correlation coefficient analysis within the febrile patient group demonstrated a robust positive correlation among all three thermometers compared to the healthy volunteers group. The study highlights variations in temperature readings when using different thermometers, irrespective of whether the assessment is conducted on healthy volunteers or febrile patients. Notably, the strength of association is lower in healthy volunteers than in febrile patients, suggesting that the interchangeability of thermometers may be more reliable and sufficient when assessing individuals with fever. These findings underscore the importance of careful consideration and validation of thermometer choices, especially in clinical settings where accurate temperature measurement is critical.