Genetic Update and Treatment for Dystonia.

A neurological condition called dystonia results in abnormal, uncontrollable postures or movements because of sporadic or continuous muscular spasms. Several varieties of dystonia can impact people of all ages, leading to severe impairment and a decreased standard of living. The discovery of genes causing variations of single or mixed dystonia has improved our understanding of the disease's etiology. Genetic dystonias are linked to several genes, including pathogenic variations of VPS16, TOR1A, THAP1, GNAL, and ANO3. Diagnosis of dystonia is primarily based on clinical symptoms, which can be challenging due to overlapping symptoms with other neurological conditions, such as Parkinson's disease. This review aims to summarize recent advances in the genetic origins and management of focal dystonia.

Analysis of the Presence and Levels of IgG Antibodies Directed against the S1 Protein Receptor Binding Domain and the N Protein of SARS-CoV-2 in Patients with Multiple Sclerosis Treated with Immunomodulatory Therapies.

The coronavirus 2019 disease (COVID-19) course and serological statuses of patients with relapsing-remitting multiple sclerosis (RRMS), treated with disease-modifying therapies (DMTs) are generally parallel that of the general population. Over the pandemic's course, however, a notable increase in the number of RRMS patients who received vaccination against severe acute respiratory coronavirus 2 (SARS-CoV-2) and those who had COVID-19 (symptomatic and asymptomatic) was reported. This virus and/or vaccination likely influenced DMT-treated RRMS patients' serological statuses regarding the presence of SARS-CoV-2 antibodies and their quantitative expression. This investigation assesses the presence and levels of the antibody directed against the S1 protein receptor binding domain (SRBD) and against the N protein of SARS-CoV-2 in 38 DMT-treated RRMS patients. The findings indicate that people vaccinated against SARS-CoV-2 exhibited significantly higher levels of IgG antibodies against S1-RBD at both assessment points. Patients with a prior history of COVID-19 demonstrated statistically significant increases in anti-N antibodies at visit 1, whereas such statistical significance was not observed at visit 2. DMT-treated RRMS patients generated neutralizing antibodies following vaccination and/or COVID-19 infection. Nevertheless, it is noteworthy that antibody levels more accurately reflect the serological status and exhibit a stronger correlation with vaccination than just the presence of antibodies.

The Role of Selected Interleukins in the Development and Progression of Multiple Sclerosis-A Systematic Review.

Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple sclerosis remains an incurable disease, the management of MS predominantly focuses on reducing relapses and decelerating the progression of both physical and cognitive decline. The continuous autoimmune process modulated by cytokines seems to be a vital contributing factor to the development and relapse of multiple sclerosis. This review sought to summarize the role of selected interleukins in the pathogenesis and advancement of MS. Patients with MS in the active disease phase seem to exhibit an increased serum level of IL-2, IL-4, IL-6, IL-13, IL-17, IL-21, IL-22 and IL-33 compared to healthy controls and patients in remission, while IL-10 appears to have a beneficial impact in preventing the progression of the disease. Despite being usually associated with proinflammatory activity, several studies have additionally recognized a neuroprotective role of IL-13, IL-22 and IL-33. Moreover, selected gene polymorphisms of IL-2R, IL-4, IL-6, IL-13 and IL-22 were identified as a possible risk factor related to MS development. Treatment strategies of multiple sclerosis that either target or utilize these cytokines seem rather promising, but more comprehensive research is necessary to gain a clearer understanding of how these cytokines precisely affect MS development and progression.

Multiple sclerosis susceptibility may be associated with the coding rs20541 (R130Q) IL-13 gene polymorphism in the Polish population.

Some of the multiple autoimmune diseases have been already associated with IL-13 single-nucleotide polymorphisms (SNPs). However, there are only few studies regarding multiple sclerosis (MS) risk and IL-13 rs20541 (R130Q) polymorphism, and their results are conflicting. Therefore, the aim of our study was to investigate the frequency of the IL-13 gene rs20541 (R130Q) polymorphism in MS participants and its association with MS clinical subsets in the Polish population. We conducted a case‒control study including 94 relapsing remitting MS patients and 160 healthy volunteers. We genotyped the rs20541 polymorphism in the IL-13 gene and analysed the genotype frequency, age of MS onset and clinical condition (EDSS values) of the MS participants. Fisher's exact test was used for statistical analysis, and the log-linear model was applied to test for associations. Allele A, as well as the AA and AG genotypes, was observed to be significantly more common in the MS subjects. The OR (odds ratio) for the A compared to the G allele was 1.71 (1.14-2.56), whereas OR 2.33 (0.86-6.26) and OR 1.92 (1.11-3.30) were obtained for the AA and AG genotypes, respectively. We did not identify any significant associations of the studied IL-13 SNP with the investigated clinical parameters of the MS participants. Our results suggest that the rs20541 polymorphism in the IL-13 gene may play an important role in MS predisposition but not in investigated clinical parameters in MS subjects of the Polish population.

The Levels of Leptin, Cystatin C, Neuropilin-1 and Tau Protein in Relation to Dietary Habits in Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia in older people. Its prevalence is expected to increase, and therefore it poses a serious challenge to the healthcare system. The aim of the study was to assess the concentration of leptin, cystatin C, neuropilin-1 and tau protein, as well as the influence of dietary habits on these parameters, in a group of AD patients (n = 110) compared to 60 healthy people (n = 60). It has been shown that AD patients, compared to healthy people, are characterized by significantly higher median concentrations of leptin (9.97 vs. 3.08), cystatin c (1.53 vs. 0.56) and tau protein (8.46 vs. 4.19), but significantly lower median neuropilin-1 (69.94 vs. 167.28). Multiple regression analyses showed that leptin levels could be explained by dietary habits in 27%, cystatin C in 51%, neuropilin-1 in 41% and tau protein in 25% of cases. Modification of eating habits may contribute to improving the values of the discussed parameters.

[Assessment of occupational hazards and their prevention in the work of dental technicians during the COVID-19 pandemic]. / Ocena zagrozen zawodowych oraz ich profilaktyka w pracy techników dentystycznych w czasie pandemii COVID-19.

BACKGROUND: Work of a dental technician is associated with exposure to a number of harmful factors. We can distinguish: chemical, biological, physical and psychophysical factors. They contribute to many diseases, but not all of them are classified as occupational diseases. The main aim of the study was to assess the health hazards that occur in the workplace of a dental technician and their prevention during the COVID-19 pandemic. MATERIAL AND METHODS: An epidemiological cross-sectional study was conducted. A self-created questionnaire form containing 28 questions was used. The link to the survey was shared on social groups associating dental technicians. Participation in the study did not require logging in. During the data collection, the respondents' personal data were not collected and processed. RESULTS: 148 dental technicians participated in the study. The largest group were participants aged 21-25 (32%), the smallest group were people over 50 (6%). The most frequently occupied position was acrylic and plaster. More than 1/3 of those surveyed reported having allergies, most often to acrylic or metal. More than 20% of technicians reported experience of mechanical injuries several times a week or more. 17% of technicians declared professional burnout. 80% of technicians used protective clothing. Personal protective equipment was always used by only 22% of technicians, and as many as 29% of respondents never used the listed protective equipment. CONCLUSIONS: Not all dental laboratories were equipped with the necessary personal protective equipment. The most commonly used personal protective equipment included: disposable gloves, disinfectant liquid and extract. The COVID-19 pandemic contributed to a change in disinfection procedures in more than 1/3 of the respondents. 35% of them started using disinfection only after the outbreak of the pandemic, while most of the changes concerned the improvement of existing procedures. The length of work experience of technicians had an impact on exposure to stress and occupational burnout. Med Pr Work Health Saf. 2023;74(4):289-99.

Application of 18F-PSMA-1007 PET/MR Imaging in Early Biochemical Recurrence of Prostate Cancer: Results of a Prospective Study of 60 Patients with Very Low PSA Levels ≤ 0.5 ng/mL.

The use of 18F-PSMA-1007 and the role of PET/MR in the diagnosis of prostate cancer are not conclusively confirmed. There are reports indicating the potential pros and cons of using 18F-PSMA-1007 as well as the PET/MR technique in prostate cancer recurrence, but they are not yet included in the EAU guidelines. The aim of the study was to assess the effectiveness of 18F-PSMA-1007 PET/MR in detecting BCR lesions at very low PSA levels <0.5 ng/mL. METHODS: Sixty patients with BCR after radical prostatectomy (RP) with PSA ranged 0.1-0.5 ng/mL were enrolled in a prospective study. All patients underwent simultaneous whole-body and pelvic 18F-PSMA-1007 PET/MR. The obtained results were verified by 12-month follow-up. RESULTS: Fifty-three lesions were detected in 45 patients with 75% detection rate. The mean PSA value was 0.31 ng/mL. Of all PSMA-positive foci, 91% were localized in the pelvis, and only 9% of lesions were located in the extrapelvic region. Local recurrences were detected in 29%, PSMA-positive lymph nodes were detected in 64% of patients and bone metastases lesions were detected in 7% of patients. CONCLUSIONS: 18F-PSMA-1007 PET/MR seems to be an excellent diagnostic tool in patients with early BCR with very low PSA levels, especially with dt PSA < 6 months. The synergistic effect of combining 18F-PSMA-1007 and whole-body PET/MR with precise multiparametric assessment of pelvic lesions is of particular benefit in early BCR.

COVID-19: The Course, Vaccination and Immune Response in People with Multiple Sclerosis: Systematic Review.

When the Coronavirus Disease 2019 (COVID-19) appeared, it was unknown what impact it would have on the condition of patients with autoimmunological disorders. Attention was focused on the course of infection in patients suffering from multiple sclerosis (MS), specially treated with disease-modifying therapies (DMTs) or glucocorticoids. The impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the occurrence of MS relapses or pseudo-relapses was important. This review focuses on the risk, symptoms, course, and mortality of COVID-19 as well as immune response to vaccinations against COVID-19 in patients with MS (PwMS). We searched the PubMed database according to specific criteria. PwMS have the risk of infection, hospitalization, symptoms, and mortality due to COVID-19, mostly similar to the general population. The presence of comorbidities, male sex, a higher degree of disability, and older age increase the frequency and severity of the COVID-19 course in PwMS. For example, it was reported that anti-CD20 therapy is probably associated with an increased risk of severe COVID-19 outcomes. After SARS-CoV-2 infection or vaccination, MS patients acquire humoral and cellular immunity, but the degree of immune response depends on applied DMTs. Additional studies are necessary to corroborate these findings. However, indisputably, some PwMS need special attention within the context of COVID-19.

Disturbed Ratios between Essential and Toxic Trace Elements as Potential Biomarkers of Acute Ischemic Stroke.

BACKGROUND: Cadmium (Cd) and lead (Pb) are known to be two of the metal contaminants that pose the greatest potential threat to human health. The purpose of this research study was to compare the levels of toxic metals (Cd, Pb) in patients with acute ischemic stroke (AIS), with a control group in Podlaskie Voivodeship, Poland. The study also aimed to assess the correlations between toxic metals and clinical data in AIS patients, and to assess the potential effect of smoking. MATERIALS AND METHODS: The levels of mineral components in the collected blood samples were assessed by means of atomic absorption spectrometry (AAS). RESULTS: The Cd blood concentration was significantly higher in AIS patients as compared to the control group. We found that the molar ratios of Cd/Zn and Cd/Pb were significantly higher (p < 0.001; p < 0.001, respectively), when the molar ratios of Se/Pb, Se/Cd, and Cu/Cd were significantly lower (p = 0.01; p < 0.001; p < 0.001, respectively), in AIS patients as compared to control subjects. However, there were no considerable fluctuations in relation to the blood Pb concentration or molar ratios of Zn/Pb and Cu/Pb between our AIS patients and the control group. We also found that patients with internal carotid artery (ICA) atherosclerosis, particularly those with 20-50% ICA stenosis, had higher concentrations of Cd and Cd/Zn, but lower Cu/Cd and Se/Cd molar ratios. In the course of our analysis, we observed that current smokers among AIS patients had significantly higher blood-Cd concentrations, Cd/Zn and Cd/Pb molar ratios, and hemoglobin levels, but significantly lower HDL-C concentrations, Se/Cd, and Cu/Cd molar ratios. CONCLUSIONS: Our research has shown that the disruption of the metal balance plays a crucial role in the pathogenesis of AIS. Furthermore, our results broaden those of previous studies on the exposure to Cd and Pb as risk factors for AIS. Further investigations are necessary to examine the probable mechanisms of Cd and Pb in the onset of ischemic stroke. The Cd/Zn molar ratio may be a useful biomarker of atherosclerosis in AIS patients. An accurate assessment of changes in the molar ratios of essential and toxic trace elements could serve as a valuable indicator of the nutritional status and levels of oxidative stress in AIS patients. It is critical to investigate the potential role of exposure to metal mixtures in AIS, due to its public health implications.

Case report: First manifestation of multiple sclerosis temporally correlated with COVID-19 vaccination.

There are several case reports describing a temporal correlation between the first clinical manifestation of multiple sclerosis (MS) and the occurrence of relapses with vaccination against SARS-CoV-2. Here we report a case of a 33-year-old male who developed partial right upper and lower extremities numbness 2 weeks after receiving Johnson & Johnson's Janssen COVID-19 vaccine. The brain MRI performed during diagnostics in the Department of Neurology detected several demyelinating lesions, one with enhancement. Oligoclonal bands were present in the cerebrospinal fluid. The patient was treated with high-dose glucocorticoid therapy with improvement and the diagnosis of MS was made. It seems plausible that the vaccination revealed the underlying autoimmune condition. Cases like the one we reported here are rare, and-based on current knowledge-the benefits of vaccination against SARS-CoV-2 far outweigh the potential risks.

UCHL1, besides leptin and fibronectin, also could be a sensitive marker of the relapsing-remitting type of multiple sclerosis.

Research on the markers of immunoregulatory response in multiple sclerosis (MS) is still of great importance. The aim of our study was the evaluation of leptin, fibronectin, and UCHL1 concentrations as potential biomarkers of a relapsing-remitting type of MS (RRMS). Surface Plasmon Resonance Imaging (SPRI) biosensors were used for the evaluation of proteins concentrations in 100 RRMS patients and 46 healthy volunteers. Plasma leptin, fibronectin, and UCHL1 concentrations were significantly higher in RRMS patients compared to the control group (p < 0.001, respectively). UCHL1 concentration evaluation revealed the highest diagnostic sensitivity (100%) and negative predictive value (100%) in differentiating MS patients from healthy individuals. There was no significant difference in the UCHL1 concentrations depending on the patient's sex, the presence of relapse within the last 24 months, and the EDSS value (p > 0.05, respectively). In RRMS patients UCHL1 concentration positively correlated with fibronectin levels (r = 0.3928; p < 0.001). In the current cohort of patients plasma UCHL1 concentration was independent of the time of MS relapse and the severity of neurological symptoms. Thus current study may indicate that plasma UCHL1, besides leptin and fibronectin, also could be a promising high-sensitive potential biomarker of relapsing-remitting type of MS. However, these results should be validated with a larger group of patients, taking into account neuroimaging and cerebrospinal fluid analysis data, and by comparing them to patients with other neurological diseases as a control group.

Case report: Variants in the ERCC4 gene as a rare cause of cerebellar ataxia with chorea.

Variants in the ERCC4 gene have been described to be associated with the following autosomal recessive diseases: xeroderma pigmentosum group F (XPF), xeroderma pigmentosum type F/Cockayne syndrome (XPF/CS), Fanconi anemia complementation group Q (FANCQ), and XFE progeroid syndrome (XFEPS). In this paper, we present a case of a 53-year-old Caucasian female patient with rare variants in the ERCC4 gene. When she was 42 years old, falls and loss of balance occurred. At the age of 48, involuntary, uncoordinated movements of the upper limbs and head, tongue stereotypes (licking and extending movements), speech problems (dysarthria), memory deterioration, and hearing loss occurred. Since childhood, she has shown hypersensitivity to UV radiation. The neurological examination revealed chorea syndrome, cerebellar ataxia, dysarthria, and bilateral hearing loss. She has numerous pigmented lesions on the skin. Brain MRI demonstrated massive cortico-subcortical atrophy. The neuropsychological examination revealed dysfunctions in the executive domain in terms of attention, working memory, organizing, and planning activities. The genetic diagnostics was performed which excluded spinocerebellar ataxia types 1, 2, 3, 6, and 17, Huntington's disease, and FMR1 premutation. In the genetic analysis of next-generation sequencing (NGS), two variants: c.2395C > T and c.1349G > A in the ERCC4 gene were identified in a heterozygote configuration. So far, a few cases of ERCC4 gene variants, which are associated with nucleotide excision repair pathways, have been described in connection with symptoms of cerebellar ataxia. In patients with ERCC4 biallelic variants, the adult neurological phenotype can sometimes be the first symptom and reason for access to genetic testing. The aforementioned case highlights the occurrence of rare genetic causes of progressive neurodegenerative diseases in adults, especially with the spectrum of autosomal recessive nucleotide excision repair pathway disorders (NERDs).

Antibodies against SARS-CoV-2 S and N proteins in relapsing-remitting multiple sclerosis patients treated with disease-modifying therapies.

CLINICAL RATIONALE FOR THE STUDY: The course of COVID-19 in people with multiple sclerosis (PwMS) has been described, while the serological status after SARS-CoV-2 infection or vaccination, especially in patients treated with disease-modifying therapies (DMT), is still under investigation. This is a significant clinical problem, as certain DMTs may predispose to a severe course of viral infections. AIM OF THE STUDY: We analyzed the presence of antibodies against spike (S) and nucleocapsid (N) proteins of SARS-CoV-2 in relapsing-remitting PwMS treated with DMT, especially dimethyl fumarate, interferon beta, and glatiramer acetate, in a single multiple sclerosis (MS) centre in north-eastern Poland (the Department of Neurology, Medical University of Bialystok). MATERIAL AND METHODS: The presence of antibodies against S and N proteins in PwMS was assessed twice: on visit one (between May and June 2020) (n = 186) and on visit two (between May and June 2021) (n = 88). Samples were taken from 68 individuals on both visits. Demographic and clinical data was collected: duration of MS, Expanded Disability Status Scale Score (EDSS), type of DMT, history of COVID-19 (positive PCR or antigen test in the past), vaccination status, and the type of vaccine. RESULTS: It was shown that on visit one: 3.7% (n = 7) PwMS were positive for IgA against S protein (IgA-S), 3.2% (n = 6) for IgG against S (IgG-S) protein, and none of those examined was positive for IgG against N protein (IgG-N). On visit two, the most common detected antibodies were IgG-S (71.3%; n = 62), then IgA-S (65.1%; n = 55), and the least common was IgG-N (18.2%; n = 16). On visit two: 20.45% of PwMS had a history of a positive SARS-CoV-2 PCR or antigen test during the last year. By the time of visit two, 42.05% (n = 37) of patients who participated in visit two had been full-course vaccinated against COVID-19. It was demonstrated that vaccination against SARS-CoV-2 significantly induces the production of IgG-S and IgA-S (p < 0.0001), while no difference between vaccinated and unvaccinated patients was shown in the detection of IgG-N. There was no correlation between COVID-19 infection and antibodies against proteins S and N in the study group. Moreover, the presented study did not show any relationship between the ability to produce antibodies against the S protein with any of the used DMTs. CONCLUSIONS AND CLINICAL IMPLICATIONS: According to our study, PwMS treated with dimethyl fumarate, interferon beta, or glatiramer acetate can efficiently produce antibodies against SARS-CoV-2 both after infection and after vaccination.

Visualization of human optic nerve by diffusion tensor mapping and degree of neuropathy.

Diffusion-weighted magnetic resonance imaging of the human optic nerve and tract is technically difficult because of its small size, the inherent strong signal generated by the surrounding fat and the cerebrospinal fluid, and due to eddy current-induced distortions and subject movement artifacts. The effects of the bone canal through which the optic nerve passes, and the proximity of blood vessels, muscles and tendons are generally unknown. Also, the limited technical capabilities of the scanners and the minimization of acquisition times result in poor quality diffusion-weighted images. It is challenging for current tractography methods to accurately track optic pathway fibers that correspond to known anatomy. Despite these technical limitations and low image resolution, here we show how to visualize the optic nerve and tract and quantify nerve atrophy. Our visualization method based on the analysis of the diffusion tensor shows marked differences between a healthy male subject and a male subject with progressive optic nerve neuropathy. These differences coincide with diffusion scalar metrics and are not visible on standard morphological images. A quantification of the degree of optic nerve atrophy in a systematic way is provided and it is tested on 9 subjects from the Human Connectome Project.

The Concentration of Fibronectin and MMP-1 in Patients with Alzheimer's Disease in Relation to the Selected Antioxidant Elements and Eating Habits.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common form of dementia in the elderly. In recent years, markers of this disease have been researched, with an emphasis on prophylaxis. The aim of this study is to evaluate the concentration of fibronectin and MMP-1 in serums in relation to levels of antioxidant elements, as well as eating habits in the group of patients with AD (n = 110). The control group consisted of 60 healthy people. The conducted studies showed that patients with AD are characterized by a significantly higher median concentration of fibronectin compared to healthy subjects (652.06 vs. 268.31 µg/mL), but a significantly lower median of MMP-1 (4.62 vs. 18.09 ng/mL). Significant inverse correlations between MMP-1 and the concentration of antioxidant elements, as well as positive correlations between MMP-1 vs. Total Antioxidant Status (TAS) and MMSE, were observed. Multiple regressions showed that the concentration of fibronectin can be explained in 28% cases by eating habits, and by MMP-1 in 25%. Nutritional modifications to reduce the consumption of fruit, meat and processed products can be part of AD prevention.

Relationship between Selected Micronutrient Concentrations, Total Antioxidant Status, Pain Severity, and the Image of 1H MR Spectroscopy in Degenerative Spine Disease: A Case-Control Study.

Osteoarthritis of the spine is a common disease and constitutes a significant problem in highly developed countries. Due to the aging of the population, the number of patients with advanced degenerative changes continues to grow. Trace elements and antioxidant status may play an active role in the pathogenesis of osteoarthritis of the spine. The aim of this study was to assess the relationship between total antioxidant status (TAS), the concentration of selected elements (Zn, Cu, Se, Mn) in the serum, nutritional and environmental factors, the severity of pain, and images of degenerative changes in the spine demonstrated in proton magnetic resonance spectroscopy (1H MRS). The study included 90 patients with degenerative spine disease and 40 healthy people. Serum Zn, Cu, Se, and Mn concentrations were determined by atomic absorption spectrometry. The Cu/Zn molar ratio was calculated. TAS was determined spectrophotometrically using a ready-made Randox kit. The severity of spine pain was assessed using the visual analogue scale VAS. In the 1H MRS study, the fat/water ratio was determined in L1 and L5 vertebral bodies and in the L4/5 intervertebral disc. In patients with osteoarthritis of the spine, there was a reduced concentration of Zn and Cu in the serum (0.77 ± 0.22 mg/L, 1.1 ± 0.35 mg/L) compared to the control group (0.83 ± 0.13 mg/L, 1.25 ± 0.41 mg/L, respectively). In the study group, we also observed a significantly lower Cu concentration in smokers (1.07 ± 0.35 mg/L) compared to non-smokers (1.17 ± 0.34 mg/L). A relationship between the female sex and a decreased concentration of TAS in the serum, both in people with degenerative spine disease and in healthy people, has been demonstrated. In patients with serum TAS levels below the reference values, the fat/water ratio was higher in the L5 spine shaft, while in those with elevated Mn levels, the value was higher in the L4/L5 intervertebral disc, which indicates a greater degree of degeneration in both cases. Patients with normal serum Cu concentration experienced lower pain intensity assessed in the VAS scale. The study showed some abnormalities in serum trace element levels and TAS in patients with osteoarthritis of the spine.

Concentration of Selected Macronutrients and Toxic Elements in the Blood in Relation to Pain Severity and Hydrogen Magnetic Resonance Spectroscopy in People with Osteoarthritis of the Spine.

Macronutrients and toxic elements may play an important role in the pathogenesis of osteoarthritis of the spine. The objective of this study was to evaluate the relationship between the concentrations of Ca, Mg, Pb, Cd and Hg in blood with the results of hydrogen magnetic resonance spectroscopy and the severity of pain. Patients with osteoarthritis of the spine (n = 90) and control subjects (n = 40) were studied. The concentrations of mineral components in blood were determined by atomic absorption spectrometry (ASA). Spinal pain severity was assessed using the Visual Analog Scale (VAS). Hydrogen magnetic resonance spectroscopy (1H-MRS) was used to determine the fat/water ratio in the bodies of L1, L5 and the L4/5 intervertebral disc. The median concentration of Mg in the serum of subjects with spinal degenerative disease was significantly lower (p < 0.001) than that in healthy subjects. The median concentration of Cd in the blood of subjects with osteoarthritis of the spine was significantly higher (p < 0.05) than that in the control group. Significantly lower (p < 0.05) median molar ratios of Ca to Cd and Pb as well as Mg to Pb and Cd were observed among patients with osteoarthritis of the spine. Significant differences (p < 0.05) were observed in the value of the fat/water ratio in selected spinal structures, depending on normal or abnormal serum Ca and Mg concentrations. The study showed some abnormal macronutrient concentrations, as well as disturbed ratios of beneficial elements to toxic elements in the blood of people with osteoarthritis of the spine.

Substrate viscosity impairs temozolomide-mediated inhibition of glioblastoma cells' growth.

BACKGROUND: The mechanical state of the extracellular environment of the brain cells considerably affects their phenotype during the development of central nervous system (CNS) pathologies, and when the cells respond to drugs. The reports on the evaluation of the viscoelastic properties of different brain tumors have shown that both tissue stiffness and viscosity can be altered during cancer development. Although a compelling number of reports established the role of substrate stiffness on the proliferation, motility, and drug sensitivity of brain cancer cells, there is a lack of parallel data in terms of alterations in substrate viscosity. METHODS: Based on viscoelasticity measurements of rat brain samples using strain rheometry, polyacrylamide (PAA) hydrogels mimicking elastic and viscous parameters of the tissues were prepared. Optical microscopy and flow cytometry were employed to assess the differences in glioblastoma cells morphology, proliferation, and cytotoxicity of anticancer drug temozolomide (TMZ) due to increased substrate viscosity. RESULTS: Our results indicate that changes in substrate viscosity affect the proliferation of untreated glioma cells to a lesser extent, but have a significant impact on the apoptosis-associated depolarization of mitochondria and level of DNA fragmentation. This suggests that viscosity sensing and stiffness sensing machinery can activate different signaling pathways in glioma cells. CONCLUSION: Collected data indicate that viscosity should be considered an important parameter in in vitro polymer-based cell culture systems used for drug screening.

Levels of Trace Elements in the Lens, Aqueous Humour, and Plasma of Cataractous Patients-A Narrative Review.

Cataracts are one of the most common causes of effective vision loss. Although most cases of cataracts are related to the ageing process, identifying modifiable risk factors can prevent their onset or progression. Many studies have suggested that micro and macroelement levels, not only in blood serum but also in the lens and aqueous humour, may affect the risk of the occurrence and severity of cataracts. This systematic review aims to summarise existing scientific reports concerning the importance of trace elements in cataractogenesis. Many authors have pointed out elevated or decreased levels of particular elements in distinct ocular compartments. However, it is not known if these alterations directly affect the increased risk of cataract occurrence. Further studies are needed to show whether changes in the levels of these elements are correlated with cataract severity and type. Such information would be useful for determining specific recommendations for micronutrient supplementation in preventing cataractogenesis.

Comparative Analysis of Neurodegeneration and Axonal Dysfunction Biomarkers in the Cerebrospinal Fluid of Patients with Multiple Sclerosis.

BACKGROUND: Given the significant role of neurodegeneration in the progression of multiple sclerosis (MS) and insufficient therapies, there is an urgent need to better understand this pathology and to find new biomarkers that could provide important insight into the biological mechanisms of the disease. Thus, the present study aimed to compare different neurodegeneration and axonal dysfunction biomarkers in MS and verify their potential clinical usefulness. METHODS: A total of 59 patients, who underwent CSF analysis during their diagnostics, were enrolled in the study. Quantitative analysis of neurodegeneration biomarkers was performed through immunological tests. Oligoclonal bands were detected by isoelectric focusing on agarose gel, whereas the concentrations of immunoglobulins and albumin were measured using nephelometry. RESULTS: Our studies showed that NfL, RTN4, and tau protein enabled the differentiation of MS patients from the control group. Additionally, the baseline CSF NfL levels positively correlated with the tau and MRI results, whereas the RTN4 concentrations were associated with the immunoglobulin quotients. The AUC for NfL was the highest among the tested proteins, although the DeLong test of the ROC curves showed no significant difference between the AUCs for NfL and RTN4. CONCLUSION: The CSF NfL, RTN-4, and tau levels at the time of diagnosis could be potential diagnostic markers of multiple sclerosis, although NfL seems to have the best clinical value.