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Spinal Cord Stimulation for Prolonged Disorders of Consciousness: A Study on Scalp Electroencephalography

CNS Neurosci Ther. 2024 Dec;30(12):e70180. doi: 10.1111/cns.70180.

ABSTRACT

BACKGROUND: Patients with disorders of consciousness (DOC) undergoing spinal cord stimulation (SCS) for arousal treatment require an assessment of their conscious state before and after the procedure. This is typically evaluated using behavioral scales (CRS-R), but this method can be influenced by the subjectivity of the physician. Event-related potentials (ERP) and EEG power spectrum are associated with the recovery of consciousness. This study aims to explore the electrophysiological and behavioral evidence of consciousness recovery in DOC patients after spinal cord stimulation (SCS) and to investigate the role of scalp EEG as a guide for preoperative assessment related to the surgery.

METHODS: For the 27 recruited patients, the CRS-R scale assessment and ERP P300 evaluation were completed before the surgery. At 3 months post-surgery, all 27 patients underwent the same assessments as preoperatively, and at 6 months post-surgery, the same evaluations were repeated for the 15 patients who could still be followed up. Between May 2023 and November 2023, resting-state EEG was collected from 13 patients using a 19-channel setup, with additional resting-state EEG recordings taken at 3 months and 6 months after the surgery. The EEG data were processed using EEGLAB to obtain P300-related metrics and EEG power spectrum. Changes in the CRS-R scale, ERP, and EEG power spectrum before and after the surgery were compared.

RESULTS: The Behavioral Scale (CRS-R) showed significant improvement at 3 months and 6 months post-surgery compared to preoperative assessments, with statistical significance (p < 0.001). The resting-state EEG power in the 5-9 Hz frequency band demonstrated statistically significant improvements at the P3 and O1 electrodes; however, this statistical result do not survive FDR correction. In the 9-13 Hz and 20-35 Hz frequency bands, the power spectrum showed statistically significant improvements across most electrodes of the brain, and these results survive FDR correction (p < 0.05). The mean amplitude, peak, and latency of P300 at the Pz electrode showed significant improvements at 3 months and 6 months post-surgery compared to preoperative values, with statistical significance (p < 0.05).

CONCLUSION: Our study shows that SCS can effectively improve the consciousness states of patients with DOC. After surgery, there were positive changes in the EEG power spectrum of the patients, transitioning from type “B” to better types “C” and “D.” The average amplitude, peak, and latency of P300 also demonstrated significant improvements postoperatively. We believe that the “ABCD” model and ERP assessment applied during the preoperative evaluation can effectively enhance the success rate of SCS surgery in promoting awakening.

PMID:39736021 | DOI:10.1111/cns.70180

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Extracting Quercetin from Different Plant Sources, Purifying It Using Different Extraction Methods (Chemical, Physical, and Enzymatic), and Measuring Its Antioxidant Activity

Front Biosci (Elite Ed). 2024 Nov 25;16(4):35. doi: 10.31083/j.fbe1604035.

ABSTRACT

BACKGROUND: Flavonoids are among the most important compounds found in plants, since laboratory studies have shown them to be a daily requirement in human diets due to their various health benefits. Therefore, this study focused on extracting, purifying, and measuring the antioxidant activity of the flavonoid quercetin, which is widely found in plants and possesses a variety of biological activities, from different plant sources.

METHODS: The extraction of quercetin was performed using several methods (chemical, physical, and enzymatic) and several extraction solutions (water, ethanol, and chloroform) from several plants (spinach, dill, Onion Skin, Pistacia eurycarpa, sumac, digalkhasab chemri, and leelwi chemri). The alcoholic extract extracted by chemical method was purified and the content of total flavonoids based on quercetin in all plant extracts was determined using adsorption chromatography on a silica gel column (100-200 mesh), followed by thin layer chromatography (TLC). TLC and high performance liquid chromatography (HPLC) were used to assess the purity of quercetin. The ability of quercetin to capture free radicals using 2,2-diphenyl-1-picrylhydrazyl (DPPH) was compared to that of butylated hydroxytoluene (BHT). Statistical analyses were performed using completely randomized designs (CRD) for factorial experiments, and the least significant difference (LSD) test was used to calculate the significant differences between the averages of the coefficients at the 0.05 probability level.

RESULTS: The alcoholic Pistacia extract extracted by chemical method yielded the highest concentration of quercetin (84.037 mg/g). Furthermore, it was found that quercetin purified from Pistacia possessed strong antioxidant activity, and its antioxidant activity increased with increased concentration.

CONCLUSIONS: Pistacia eurycarpa showed the highest quercetin content among the assessed plants. Moreover, solvents played a major role in extracting plant components due to the high polarity of flavonoids. Quercetin purified using a silica gel column demonstrated antioxidant activity.

PMID:39736003 | DOI:10.31083/j.fbe1604035

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Activated/Cycling Treg Deficiency and Mitochondrial Alterations in Immunological Non-Responders to Antiretroviral Therapy

Front Biosci (Landmark Ed). 2024 Dec 25;29(12):429. doi: 10.31083/j.fbl2912429.

ABSTRACT

BACKGROUND: Regulatory T-cells (Tregs) play a crucial role in maintaining immune homeostasis, but their dynamics are altered in a subset of people living with Human Immunodeficiency Virus (HIV) known as immunological non-responders (INRs). INRs fail to reconstitute CD4+ T-cell counts despite viral suppression. This study aimed to examine Treg dysregulation in INRs, comparing them to immunological responders (IRs) and healthy controls (HCs).

METHODS: The study included 40 INRs, 42 IRs, and 23 HCs. Peripheral blood mononuclear cells were isolated and analyzed by flow cytometry. Conventional CD4+ T-cells (Tconvs) were identified as CD25-/loFOXP3 cells, while Tregs were identified as CD25+CD127loFOXP3+ CD4+ T-cells. Cells were further divided into naive, central memory, effector memory, and effector memory cells re-expressing CD45RA (TEMRA) subsets. Activated/cycling cells were identified as CD71+ and quiescent cells were CD71. Mitochondrial mass and transmembrane potential were measured using MitoTracker Green and MitoTracker Orange dyes, respectively. Statistical comparisons were made using the Kruskal-Wallis test with Dunn’s post-hoc analysis and Mann-Whitney U-test.

RESULTS: INRs exhibited the highest frequencies of activated/cycling CD4+ T-cells. The proportion of activated/cycling cells was higher in Tregs compared to Tconvs in all groups. Cycling rates of Tregs and Tconvs were correlated, suggesting Tregs help control Tconv proliferation. Despite high overall Treg frequencies in INRs, they showed a Treg deficiency in activated/cycling CD4+ T-cells, specifically in naive and central memory subsets, causing an imbalance in the Tconv/Treg ratio. This deficiency was hidden by increased Treg frequencies in quiescent effector memory CD4+ T-cells. Activated/cycling naive and memory Tregs from INRs had normal forkhead box P3 (FOXP3) and CD25 expression, but activated/cycling memory Tregs showed decreased ability to regulate mitochondrial transmembrane potential, indicating impaired mitochondrial fitness. These mitochondrial abnormalities were similar to those observed in memory conventional T-cells.

CONCLUSIONS: The complex Treg dysregulation in immunological non-responders involves quantitative and functional alterations, including a Treg deficiency within activated/cycling naive and central memory CD4+ T-cells, impaired mitochondrial fitness of activated/cycling memory Tregs, and functional disorders of the parent conventional T-lymphocytes. These findings underscore the need for a nuanced understanding of Treg dynamics in suboptimal CD4+ T-cell reconstitution during HIV-infection.

PMID:39735996 | DOI:10.31083/j.fbl2912429

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Cytoprotective Effects and Intranuclear Localization of Sulfur-Containing Derivative of Buckminsterfullerene

Front Biosci (Landmark Ed). 2024 Dec 3;29(12):408. doi: 10.31083/j.fbl2912408.

ABSTRACT

BACKGROUND: There is a growing interest in exploring the biological characteristics of nanoparticles and exploring their potential applications. However, there is still a lack of research into the potential genotoxicity of fullerene derivatives and their impact on gene expression in human cells. In this study, we investigated the effects of a water-soluble fullerene derivative, C60[C6H4SCH2COOK]5H (F1), on human embryonic lung fibroblasts (HELF).

METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to study the cytotoxicity of F1; reactive oxygen species (ROS) level was determined with 2,7-DCFH-DA; gene expression level was evaluated by reverse transcription polymerase chain reaction (RT-PCR); protein expression level was determined by flow cytofluorometry; fluorescence microscopy was used for visualization; Mann-Whitney statistical U-test was used for data processing. The differences were considered significant at p < 0.01.

RESULTS: F1 at a concentration of 0.3 mg/mL causes a short-term (up to 1 hour) increase in the number of double-strand breaks and oxidative DNA damage in HELF. Within 1 to 24 hours, F1 penetrates through the cell and nuclear membrane of HELF and localizes in the nucleus. In this case, the response of cells to DNA damage is activated: the functional activity of DNA repair genes, antioxidant and anti-apoptotic genes is increased within 24 hours. Due to the processes of activation of cell division and inhibition of apoptosis, an increase in the population of HELF cells in the presence of the fullerene derivative F1 is observed. F1 has a stabilizing effect on cell nuclei under the action of 1 Gy radiation.

CONCLUSIONS: An increase in antioxidant protection, activation of repair genes, anti-apoptotic genes, progression of the cell cycle, and a decrease in the level of oxidative damage, and DNA breaks in cells indicates the cytoprotective properties of F1.

PMID:39735985 | DOI:10.31083/j.fbl2912408

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Polymorphism in Genes Encoding HSP40 Family Proteins is Associated with Ischemic Stroke Risk and Brain Infarct Size: A Pilot Study

J Integr Neurosci. 2024 Dec 4;23(12):211. doi: 10.31083/j.jin2312211.

ABSTRACT

BACKGROUND: Heat shock proteins (HSPs) play a critical role in the molecular mechanisms of ischemic stroke (IS). A possible role for HSP40 family proteins in atherosclerosis progression has already been revealed; however, to date, molecular genetic studies on the involvement of genes encoding proteins of the HSP40 family in IS have not yet been carried out.

AIM: We sought to determine whether nine single nucleotide polymorphisms (SNPs) in genes encoding HSP40 family proteins (DNAJB1, DNAJB2, DNAJA1, DNAJA2, DNAJA3 and DNAJC7) are associated with the risk and clinical features of IS.

METHODS: Using TaqMan-based polymerase chain reaction (PCR) and the MassArray-4 system, DNA samples of 2551 Russians – 1306 IS patients and 1245 healthy individuals – were genotyped.

RESULTS: SNP rs2034598 DNAJA2 decreased the risk of IS exclusively in male patients (odds ratio = 0.81, 95% confidence interval 0.78-0.98, p = 0.028); rs7189628 DNAJA2 increased the brain infarct size (p = 0.04); and rs6500605 DNAJA3 lowered the age of onset of IS (p = 0.03). SNPs rs10448231 DNAJA1, rs7189628 DNAJA2, rs4926222 DNAJB1 and rs2034598 DNAJA2 were involved in the strongest epistatic interactions linked to IS; SNP rs10448231 DNAJA1 is characterised by the most essential mono-effect (2.96% of IS entropy); all of the top SNP-SNP interaction models included the pairwise combination rs7189628 DNAJA2×rs4926222 DNAJB1, which was found to be a key factor determining susceptibility to IS. In interactions with the studied SNPs, smoking was found to have multidirectional effects (synergism, antagonism or additive effect) and the strongest mono-effect (3.47% of IS entropy), exceeding the mono-effects of rs6500605 DNAJA3, rs10448231 DNAJA1, rs2034598 DNAJA2, rs7189628 DNAJA2 and rs4926222 DNAJB1, involved in the best G×E models and determining 0.03%-0.73% of IS entropy.

CONCLUSIONS: We are the first to discover polymorphisms in genes encoding HSP40 family proteins as a major risk factor for IS and its clinical manifestations. The comprehensive bioinformatics analysis revealed molecular mechanisms, underscoring their significance in the pathogenesis of IS, primarily reflecting the regulation of heat stress, proteostasis and cellular signalling.

PMID:39735968 | DOI:10.31083/j.jin2312211

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Effect of Virtual Reality-Based Training on Upper Limb Dysfunction during Post-Stroke Rehabilitation: A Meta-Analysis Combined with Meta-Regression

J Integr Neurosci. 2024 Dec 27;23(12):225. doi: 10.31083/j.jin2312225.

ABSTRACT

BACKGROUND: Recently, there has been a surge in virtual reality (VR)-based training for upper limb (UL) rehabilitation, which has yielded mixed results. Therefore, we aimed to explore the effects of conventional therapy combined with VR-based training on UL dysfunction during post-stroke rehabilitation.

METHODS: Studies published in English before May 2023 were retrieved from PubMed, Embase, and the Cochrane Library. We also included randomized controlled trials that compared the use of conventional therapy and VR-based training with conventional therapy alone in post-stroke rehabilitation. The meta-analysis was performed using Review Manager Software (version 5.3; The Nordic Cochrane Centre, The Cochrane Collaboration; Copenhagen, Denmark) and Stata/MP 17.0 (StataCorp, LLC, College Station, TX, USA). Univariate and multivariate meta-regression analyses were performed to investigate the effects of stroke duration, VR characteristics, and type of conventional therapy on VR-based training.

RESULTS: In total, 27 randomized controlled trials were included, which enrolled 1354 patients. Our results showed that conventional therapy plus VR-based training is better than conventional therapy alone in UL motor impairment recovery measured using Fugl-Meyer Upper Extremity (standardized mean difference [SMD] = 0.32, 95% confidence interval [CI]: 0.07-0.57, Z = 2.52, p = 0.01). Meta-regression showed that stroke duration had independent effects on Fugl-Meyer Upper Extremity scores of VR-based training in rehabilitation (p = 0.041). Furthermore, in subgroup analysis based on stroke duration, stroke duration >6 months was statistically significant (SMD = 0.20, 95% CI: 0.01-0.39, Z = 2.06, p = 0.04). No relevant publication bias (p = 0.1303), and no significant difference in activity limitation assessed using the Box-Block Test (mean difference [MD] = 2.79, 95% CI: -0.63-6.20, Z = 1.60, p = 0.11) was observed. Regarding the functional independence measured using the Functional Independence Measure scale, studies presented no significant difference between the experimental and control groups (MD = 1.15, 95% CI: -1.84-4.14, Z = 0.76, p = 0.45).

CONCLUSIONS: Conventional therapy plus VR-based training is superior to conventional therapy alone in promoting the recovery of UL motor function after stroke. Therefore, VR-based training may be a potential option for improving UL motor function. The study was registered on PROSPERO (https://www.crd.york.ac.uk/prospero/), registration number: CRD42023472709.

PMID:39735963 | DOI:10.31083/j.jin2312225

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Using Implementation Science to Evaluate the Implementation of Patient-Reported Outcome Measures (PROMs) in a Clinical Heart Failure Care Setting

CJC Open. 2024 Oct 3;6(12):1443-1452. doi: 10.1016/j.cjco.2024.09.012. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: Patients with heart failure (HF) can experience a poor quality-of-life (QOL), recurring hospitalizations, and progressive disease symptoms. Patient-reported outcome measures (PROMs) integrate patients’ voices into clinical care, by assessing patient symptoms, function, and QOL. In 2022, PROMs were incorporated into the electronic health record system (Epic) at a large academic hospital in Toronto, Ontario, Canada. The purpose of this study was to use implementation-science frameworks to systematically evaluate the uptake and integration of PROMs into clinical HF care.

METHODS: The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework guided this mixed-methods, 1-year, quality-improvement project. Data sources included the following: clinician use of PROMs; patient-level data on completed PROMs; and semistructured interviews with clinicians. The PROM was the Kansas City Cardiomyopathy Questionnaire-12, which captures 4 domains related to HF-symptom frequency, physical limitations, social limitations, and QOL (KCCQ-12 is used as an example case of PROMs in general). Quantitative data were analyzed using descriptive statistics; qualitative data were analyzed using behaviour-change frameworks and latent content analysis.

RESULTS: Over the course of 1 year, more patients were assigned to PROMs, a higher proportion of patients completed PROMs, and approximately 80% of patients had high scores on the questionnaire. Clinicians experience barriers-related to attention and decision processes, the environmental context, and their professional role-to integrating PROMs into practice. Suggested changes to improve PROM uptake include adding language licenses for PROM translations, reducing cognitive load for clinicians who are assigning and interpreting PROMs in the Epic system, and championing modelling of use of PROMs in practice.

CONCLUSIONS: This study demonstrates the benefit of using implementation science frameworks, to evaluate the implementation of PROMs in practice and provide actionable recommendations to health systems.

PMID:39735955 | PMC:PMC11681351 | DOI:10.1016/j.cjco.2024.09.012

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Immunohistochemical Detection of CD147 Expression in Adenocarcinoma of the Prostate: A Case-Control Study

Prostate Cancer. 2024 Dec 22;2024:4406057. doi: 10.1155/proc/4406057. eCollection 2024.

ABSTRACT

Prostate cancer is the most common noncutaneous malignancy among men worldwide, including in Sudan, where it represents a significant public health challenge. CD147, a transmembrane glycoprotein implicated in tumor progression, invasion, and metastasis, has shown potential as a prognostic biomarker in various cancers. This retrospective case-control study aimed to evaluate CD147 expression in prostate adenocarcinoma among Sudanese men and its association with tumor grade. A total of 80 paraffin-embedded tissue samples, including 40 cases of prostate adenocarcinoma and 40 benign prostatic hyperplasia (BPH) controls, were analyzed using immunohistochemistry. CD147 expression was observed in 22.5% of adenocarcinoma cases compared to 7% of controls; however, the association was not statistically significant (p=0.07). Low-grade tumors were predominant in the cohort, consistent with early-stage diagnoses. The findings revealed no clear link between CD147 expression and tumor grade, diverging from prior studies that associate CD147 with advanced tumor stages. The nonsignificant results may be attributed to the small sample size, emphasizing the need for future research with larger, more diverse cohorts, advanced molecular techniques, and functional studies to better elucidate the role of CD147 in prostate cancer pathogenesis and its potential as a therapeutic target.

PMID:39735939 | PMC:PMC11682863 | DOI:10.1155/proc/4406057

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Mineral composition in mussel Mytilus galloprovincialis and clam Tapes decussatus from Faro Lake of Messina: risk assessment for human health

Front Toxicol. 2024 Dec 13;6:1494977. doi: 10.3389/ftox.2024.1494977. eCollection 2024.

ABSTRACT

Bivalve are exposed to a wide range of contaminants, some of which may be toxic to human health. The aim of this study was to detect essential and non-essential elements such as Na, Ca, Mg, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd, Pb, Hg, Be and Co in water, sediments, and Mytilus galloprovincialis and Tapes decussatus from Faro Lake. It is a lake of marine origin located on the northern coast of Messina (Sicily), where shellfish farming has been practiced for many years. Metals were analysed by a single quadrupole inductively coupled plasma mass spectrometer (ICP-MS), except for Hg, which was quantified using a direct mercury analyser (DMA-80). The study evaluated the nutritional intake of elements through the ingestion of clams and mussels and the potential health risks to consumers. The lead levels found in M. galloprovincialis were below the LOQ, while in T. decussatus the concentrations were below the limit indicated by European Regulation 915/2023. Statistical analysis was carried out on M. galloprovincialis and T. decussatus samples using SPSS 27 and the data showed highly significant differences between the two species (p < 0.001). Cadmium (Cd) and mercury (Hg) concentrations were also below the legal limit in all samples analyzed. This study has shown that clams and mussels are a source of sodium (Na) with a Recommended Dietary Allowance (RDA) of 36% in M. galloprovincialis and 77% in T. decussatus. The percentages obtained for calcium (Ca) and magnesium (Mg) were 17%-19% and 18%-8%, respectively. The RDA of chromium (Cr) was of 191% for M. galloprovincialis and of 405% for T. decussatus. The Fe percentages were 92% and 169% for M. galloprovincialis and T. decussatus, respectively. The concentrations of the other metals observed in the two bivalve species of Lake Faro were generally lower than the Tolerable Weekly Intake (TWI) values estimated as a risk to human health.

PMID:39735886 | PMC:PMC11671395 | DOI:10.3389/ftox.2024.1494977

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Bone and Joint Involvement in Beta Thalassemic Patients: A Cross-sectional Study

Indian J Orthop. 2024 Nov 5;59(1):69-76. doi: 10.1007/s43465-024-01225-0. eCollection 2025 Jan.

ABSTRACT

PURPOSE: There is paucity of guidelines with inadequate data available about the extent and prevention of bone and joint disease in beta-thalassemic patients in Indian population. This study aims to determine bone and joint involvement in beta-thalassemic patients. It evaluates serum biochemical parameters of bone formation and resorption and correlates with the symptomatology in these patients. The study also determines their daily physical activity and find a correlation if any with bone mineral density.

METHODS: The study was carried out on 40 regularly transfused beta thalassemic patients between 5 and 18 years of age under regular follow-up at our centre from June 2012 to June 2014. All patients were interviewed as per a well-structured proforma for symptoms relating to bone and joint disease as described by the patient/parents in past 1 year and physical activity by QAPACE questionnaire. Venous blood samples were drawn under aseptic conditions and used for estimation of biochemical parameters (calcium, phosphorus, alkaline phosphatase, vitamin D, parathyroid hormone and serum ferritin). Enrolled subjects were scanned for bone mineral density (BMD) at femur neck, trochanter and Ward’s angle using dual-energy X-ray absorptiometry.

RESULTS: A total of 40 patients were enrolled in the study (Male:Female = 80:20). Half the patients (n = 20) had symptoms pertaining to bone and joint disease. The most common symptom was leg pain (42.50%), followed by backache (22.50%). Asymptomatic patients had greater mean serum vitamin D as compared to the symptomatic patients (22.2 vs 15.08 ng/ml) (p = 0.225). Five patients were detected to have osteopenia, all above 10 years of age. The mean BMD in symptomatic patients at femur neck, trochanter and ward’s angle was 0.781, 0.639 and 0.735 g/cm2, respectively, as compared to 0.754, 0.635 and 0.722 g/cm2 in asymptomatic patients. The difference was not statistically significant. Patients with low BMD had lower mean pre-transfusion Hb (< 9 g/dl) (p = 0.01). Eighty percent of osteopenic patients had sedentary lifestyle as compared to 44% of patients with normal BMD. Bone mineral density did not have any correlation with vitamin D levels, serum ferritin and type of chelation therapy.

CONCLUSION: Pre-transfusion hemoglobin of more than 9 gm/dL has a protective role in maintaining good bone health and bone mineral density. Engaging thalassemia patients in physical activity has a positive effect on bone mineral density. Low vitamin D levels contribute to symptoms of bone and joint involvement in thalassemia and the same needs to be determined and supplemented.

PMID:39735876 | PMC:PMC11680515 | DOI:10.1007/s43465-024-01225-0