Neuroprotective Effects of VGLUT1 Inhibition in HT22 Cells Overexpressing VGLUT1 Under Oxygen Glucose Deprivation Conditions.

Glutamate (Glu) is a major excitatory neurotransmitter in the brain, essential for synaptic plasticity, neuronal activity, and memory formation. However, its dysregulation leads to excitotoxicity, implicated in neurodegenerative diseases and brain ischemia. Vesicular glutamate transporters (VGLUTs) regulate Glu loading into synaptic vesicles, crucial for maintaining optimal extracellular Glu levels. This study investigates the neuroprotective effects of VGLUT1 inhibition in HT22 cells overexpressing VGLUT1 under oxygen glucose deprivation (OGD) conditions. HT22 cells, a hippocampal neuron model, were transduced with lentiviral vectors to overexpress VGLUT1. Cells were subjected to OGD, with pre-incubation of Chicago Sky Blue 6B (CSB6B), an unspecific VGLUT inhibitor. Cell viability, lactate dehydrogenase (LDH) release, mitochondrial membrane potential, and hypoxia-related protein markers (PARP1, AIF, NLRP3) were assessed. Results indicated that VGLUT1 overexpression increased vulnerability to OGD, evidenced by higher LDH release and reduced cell viability. CSB6B treatment improved cell viability and reduced LDH release in OGD conditions, particularly at 0.1 µM and 1.0 µM concentrations. Moreover, CSB6B preserved mitochondrial membrane potential and decreased levels of PARP1, AIF, and NLRP3 proteins, suggesting neuroprotective effects through mitigating excitotoxicity. This study demonstrates that VGLUT1 inhibition could be a promising therapeutic strategy for ischemic brain injury, warranting further investigation into selective VGLUT1 inhibitors.

Chicago sky blue 6B exerts neuroprotective and anti-inflammatory effects on focal cerebral ischemia.

Brain ischemia is one of the leading causes of death and long-term disability worldwide. Cessation of the blood supply to the brain directly stimulates many pathological events, including glutamate overload and neuroinflammation. Glial cell activation occurs shortly after ischemia onset, resulting in the release of proinflammatory cytokines and exacerbation of the detrimental effects of neuroinflammation. Proinflammatory signals influence the infiltration of a wide range of immune cells, including neutrophils, T cells and monocytes/macrophages. In this study, we aimed to verify the potential anti-inflammatory effect of Chicago Sky Blue 6B (CSB6B) in a rat model of focal cerebral ischemia (90-minute middle cerebral artery occlusion). CSB6B was administered 2 h before (pretreatment) or 1.5 h after reperfusion onset (posttreatment). A model of ischemic preconditioning was used as the comparator to pretreatment with CSB6B. The results of indicated that posttreatment with CSB6B had profound anti-inflammatory effects that were associated with reduced neurological deficits and a decreased infarct volume. At 24 h, 3 days and 7 days after brain ischemia, CSB6B administration reduced the protein levels of proinflammatory cytokines, such as Il1ß, Il6, Il18 and TNFα, in the cerebral cortex and the dorsal striatum. Treatment with CSB6B also limited the scope of microglia and astrocyte activation and the infiltration of immune cells. Taken together, this study shows that compounds such as CSB6B might be promising pharmacological tools; however, further studies on the improvements in the drug-like properties of these compounds must be undertaken.

The Effect of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Hereditary Spastic Paraplegia.

Background: Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited disorders affecting predominantly the motor cortex and pyramidal tract, which results in slowly progressing gait disorders, as well as spasticity and weakness of lower extremities. Repetitive transcranial magnetic stimulation (rTMS) has been previously investigated as a therapeutic tool for similar motor deficits in a number of neurologic conditions. The aim of this randomized, controlled trial was to investigate the therapeutic potential of rTMS in various forms of HSP, including pure and complicated forms, as well as adrenomyeloneuropathy. Methods: We recruited 15 patients (five women and 10 men; mean age 43.7 ± 10.6 years) with the mentioned forms of HSP. The intervention included five sessions of bilateral 10 Hz rTMS over primary motor areas of the muscles of lower extremities and five sessions of similar sham stimulation. Results: One patient dropped out due to seizure, and 14 patients completed the study protocol. After real stimulation, the strength of the proximal and distal muscles of lower extremities increased, and the spasticity of the proximal muscles decreased. Change in spasticity was still present during follow-up assessment. No effect was observed regarding gait velocity. No changes were seen after sham stimulation. A post hoc analysis revealed an inverse relation between motor threshold and the change of the strength after active rTMS. Conclusions: rTMS may have potential in improving weakness and spasticity of lower extremities in HSP, especially of proximal muscles whose motor areas are located more superficially. This trial is registered with Clinicaltrials.gov NCT03627416.

Subsyndromal delirium is associated with poor functional outcome after ischaemic stroke.

BACKGROUND AND PURPOSE: Subsyndromal delirium (SSD) refers to patients with delirious symptoms who do not meet the criteria for delirium. The aim was to determine the prognostic significance of SSD in stroke patients. METHODS: In all, 564 patients with ischaemic stroke (median age 71 years, 50.5% female) were included. The Confusion Assessment Method was used to assess symptoms of delirium and the Diagnostic and Statistical Manual of Mental Disorders, 5th edn, criteria were used to diagnose delirium. SSD was defined as one or more core features of delirium without fulfilling diagnostic criteria. Functional outcome was assessed using the modified Rankin Scale at 3 and 12 months after stroke. RESULTS: Delirium was diagnosed in 23.4% of patients and SSD in 10.3% of patients. SSD was associated with increased risk of poor functional outcome. The adjusted odds ratios (ORs) for unfavourable outcome at 3 and 12 months were 2.88 [95% confidence interval (CI) 1.43-5.79, P < 0.01] and 2.93 (95% CI 1.39-6.22, P < 0.01), respectively. In multivariate analysis, delirium was an independent predictor of poor functional outcome at 3 months (OR 6.41, 95% CI 3.36-12.21, P < 0.01) and 12 months (OR 6.11, 95% CI 3.05-12.27, P < 0.01) after stroke. Delirium was also independently associated with increased risk of death within 3 months (hazard ratio 3.68, 95% CI 1.69-8.02, P < 0.01) and 12 months (hazard ratio 3.76, 95% CI 2.05-6.90, P < 0.01). SSD was not associated with increased risk of death. CONCLUSIONS: In SSD patients the risk of poor functional outcome after stroke is increased and intermediate between patients with and patients without delirium.

Polymorphism in the chemokine receptor 7 gene (CCR7) is associated with previous myocardial infarction in patients undergoing elective coronary angiography.

Coronary artery disease (CAD) remains a major cause of death in developed countries. Both environmental and, less known, genetic factors contribute to progression of CAD to myocardial infarction (MI). Immune system is activated in patients with CAD through dendritic cells (DCs), which present plaque antigens to T lymphocytes. Production of proinflammatory cytokines by activated T cells contributes to plaque rupture in MI. Chemokine receptor 7 (CCR7) on DCs is required for their chemotaxis from plaque to lymph nodes. This makes possible an interaction of DCs with T lymphocytes and initiation of specific immune response. We hypothesized that single nucleotide polymorphisms (SNPs) in CCR7 gene locus are associated with previous MI in patients with CAD. To test this hypothesis, we genotyped six SNPs from the CCR7 gene locus in 300 consecutive patients, admitted for elective coronary angiography. We performed univariate-, multivariate- (including potential confounders) and haplotype-based tests of association of SNPs with previous MI and results of angiography. Allele A of rs17708087 SNP was associated with previous MI. This association remained significant after adjustment for age, sex, smoking, hypercholesterolaemia and drugs used by patients (odds ratio 2.13, 95% confidence interval: 1.13-3.86). Therefore, we conclude that CCR7 gene locus harbours a polymorphism that modifies risk of MI in patients with CAD. Replication of this association could be sought in a prospective cohort of initially healthy individuals.

Transscleral resection without hypotensive anaesthesia vs iodine-125 plaque brachytherapy in the treatment of choroidal melanoma.

AimsThe aim of this study was to compare transscleral resection technique performed without hypotensive anaesthesia (TSRWH) with iodine-125 brachytherapy (IBT) in the treatment of choroidal melanoma.Patients and methodsThis was a retrospective surgical cohort study. Nineteen eyes treated with TSRWH were matched with 53 eyes treated with IBT according to: tumour size, distance to fovea, distance to optic nerve, and follow-up time. Best-corrected visual acuity (BCVA), local recurrence, secondary enucleation, metastasis, overall and specific survival, and complications were evaluated.ResultsPatients treated with TSRWH had significantly better BCVA than those treated with IBT. The local recurrence risk was significantly higher when ciliary body was involved (HR=11.4, 95% CI 2.24-49.7, P=0.04). Metastatic disease was observed in 14 of 53 patients (26.4%) in the IBT group vs 3 patients (15.8%) in the TSRWH group (P=0.531). Multivariate analysis showed that iris involvement (HR=16.0, 95% CI 4.2-170.2, P=0.033) and large tumour (HR=2.3, 95% CI 1.2-4.8, P=0.04) increased the probability of metastasis. During follow-up, six patients (11.3%) in IBT group died vs two (10.5%) in the TSRWH group (P≥0.999). Nine patients required secondary enucleation: 5 (9.4%) in the IBT group vs 4 (21.1%) in the TSRWH group (P=0.231). The most common complications in IBT group were radiation-induced retinopathy (45.3%), neovascular glaucoma (28.3%), and macular oedema (24.5%), whereas rhegmatogenous retinal detachment (21.1%), ocular hypertension (21.1%), and submacular haemorrhage (15.8%) were the most frequent complications after TSRWH.ConclusionTSRWH is a technically challenging procedure. However, when performed successfully, this technique achieves better preservation of visual acuity than IBT and without the limitations inherent in hypotensive anaesthesia.

Interleukin 6-174G>C polymorphism and risk of aneurysmal subarachnoid hemorrhage: case-control study and meta-analysis.

OBJECTIVES: Vascular inflammation contributes to the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH). Interleukin 6 (IL6) is a proinflammatory cytokine involved in many vascular pathologies. Two studies analyzing an association of the functional IL6 gene -174G>C promoter polymorphism with aSAH provided inconsistent results. The aim of this study was to investigate whether this IL6 polymorphism is associated with aSAH in a Polish population. MATERIAL AND METHODS: We genotyped 276 aSAH patients and 581 unrelated control subjects. All were of Caucasian origin. In addition, a meta-analysis combining results of the current and previously published studies was conducted. RESULTS: The distribution of IL6 genotypes and alleles did not differ significantly between aSAH (GG - 29.7%, GC - 50.0%, CC - 20.2%, G - 54.7%) and control subjects (GG - 32.0%, GC - 47.3%, CC - 20.7%, G - 44.3%). In the meta-analysis, the IL6-174G>C polymorphism was not associated with aSAH risk either. CONCLUSIONS: We failed to find an association between the IL6 -174G>C polymorphism and aSAH in analyzed European populations.

Twenty-year experience in the management of squamous cell anal canal carcinoma with interstitial brachytherapy

OBJECTIVES: The aim of this study was to retrospectively evaluate clinical characteristics, local control, acute and late toxicity, and prognostic factors of patients with anal canal carcinoma treated with brachytherapy. METHODS: From 1989 to 2009, 38 patients were treated with iridium 192 low-dose-rate (N = 26) or pulsed-dose-rate (N = 12) interstitial brachytherapy at a single institution. The median age was 62 years (range, 38-86 years). The TNM classification was as follows: 10 T1, 22 T2, 5 T3 and 1 T4; 32 N0, 3 N1 and 3 N2. Most patients (32/38) received either a first course of radiochemotherapy (N = 22) or radiotherapy alone (N=10) consisting of a total delivered dose of 45 Gy to the pelvis (range, 32-50) followed by a boost a median of 18 days later of 15-35 Gy (median 20 Gy) to the anal canal. The remaining 6 cases were treated with brachytherapy alone (dose range, 60-65 Gy). RESULTS: With a median follow-up of 30 months (range, 4-200), 2- and 5-year local control rates were 91% and 87%, respectively. Preservation of the anal sphincter was achieved in 32 patients (84%). Three patients experienced incontinence after brachytherapy. Only 2 patients showed chronic mucositis grade 3/4. Age proved to be a statistically significant prognostic factor for overall survival in the univariate (p = 0.033) and multivariate analyses (p = 0.018). Concurrent chemotherapy with external beam radiotherapy was a statistically significant prognostic factor for disease-free survival in the univariate and multivariate analyses (p = 0.007 and p = 0.044, respectively). CONCLUSIONS: Interstitial brachytherapy appears to be an effective and well tolerated treatment for anal carcinoma offering both high local tumour control and anal sphincter preservation (AU)

Quality of life two years after radical prostatectomy, prostate brachytherapy or external beam radiotherapy for clinically localised prostate cancer: the Catalan Institute of Oncology/Bellvitge Hospital experience.

OBJECTIVE: The objective was to compare the short- and long-term impact of 3 different treatment modalities on health-related quality of life (HRQOL) in patients treated for localised prostate cancer at a single centre in Catalonia, Spain. MATERIAL AND METHODS: This was a longitudinal, prospective study of 304 patients from a single centre in Catalonia, Spain. Patients underwent 1 of 3 treatment procedures: radical prostatectomy (114 patients), external beam radiation (134) or interstitial brachytherapy (56). HRQOL was assessed by both general and specific questionnaires, including the SF-36 health survey and the Expanded Prostate Cancer Index Composite (EPIC). Interviews were administered prior to treatment and at months 1, 3, 6, 12 and 24. One-way analysis of variance and generalised estimating equations models were constructed to assess between group differences in HRQOL. RESULTS: After initial deterioration, HRQOL scores partially recovered, although significant differences between treatment groups persisted at two years. Worsening of urinary incontinence was especially marked for the radical prostatectomy group (11.45, p=0.005), while deterioration in the urinary irritative/obstructive domain was worse following brachytherapy treatment (4.76, p=0.025). Decline in sexual function was significantly greater for the radical prostatectomy group than for the brachytherapy group (18.74, p<0.001). No significant between-group differences were observed in bowel domain scores. CONCLUSIONS: Quality of life 2 years after treatment for prostate cancer shows wide variability. Radical prostatectomy had the largest negative impact on the sexual and urinary incontinence domains. Differences between external radiation and brachytherapy were relatively small. Brachytherapy led to a moderate increase in urinary irritation compared to the other 2 groups.

Quality of life two years after radical prostatectomy, prostate brachytherapy or external beam radiotherapy for clinically localised prostate cancer: the Catalan Institute of Oncology/Bellvitge Hospital experience

OBJECTIVE: The objective was to compare the short- and long-term impact of 3 different treatment modalities on health-related quality of life (HRQOL) in patients treated for localised prostate cancer at a single centre in Catalonia, Spain. MATERIAL AND METHODS: This was a longitudinal, prospective study of 304 patients from a single centre in Catalonia, Spain. Patients underwent 1 of 3 treatment procedures: radical prostatectomy (114 patients), external beam radiation (134) or interstitial brachytherapy (56). HRQOL was assessed by both general and specific questionnaires, including the SF-36 health survey and the Expanded Prostate Cancer Index Composite (EPIC). Interviews were administered prior to treatment and at months 1, 3, 6, 12 and 24. One-way analysis of variance and generalised estimating equations models were constructed to assess between group differences in HRQOL. RESULTS: After initial deterioration, HRQOL scores partially recovered, although significant differences between treatment groups persisted at two years. Worsening of urinary incontinence was especially marked for the radical prostatectomy group (11.45, p=0.005), while deterioration in the urinary irritative/obstructive domain was worse following brachytherapy treatment (4.76, p=0.025). Decline in sexual function was significantly greater for the radical prostatectomy group than for the brachytherapy group (18.74, p<0.001). No significant between-group differences were observed in bowel domain scores. CONCLUSIONS: Quality of life 2 years after treatment for prostate cancer shows wide variability. Radical prostatectomy had the largest negative impact on the sexual and urinary incontinence domains. Differences between external radiation and brachytherapy were relatively small. Brachytherapy led to a moderate increase in urinary irritation compared to the other 2 groups (AU)

Association between hyperglycemia, heart failure and mortality in stroke patients.

BACKGROUND: Acute hyperglycemia predicts increased mortality after stroke. The aim of our study was to determine if acute stroke patients with hyperglycemia suffer from increased rate of in-hospital adverse events which could influence survival such as pneumonia, heart failure and myocardial infarction. METHODS: In a retrospective study with prospective follow-up, 689 patients with first-ever ischaemic stroke and high frequency of cardiovascular diseases were eligible. Follow-up period was 1-7 years (14 308 person-months). RESULTS: The frequency of in-hospital heart failure and nosocomial pneumonia was the highest in patients without pre-hospital diagnosis of diabetes mellitus and with fasting glucose >or=7 mmol/l (50% and 20.2%, respectively) and the lowest in patients without pre-hospital diagnosis of diabetes and fasting glucose

Valorization of phosphogypsum as hydraulic binder.

Phosphogypsum (calcium sulfate) is a naturally occurring part of the process of creating phosphoric acid (H(3)PO(4)), an essential component of many modern fertilizers. For every tonne of phosphoric acid made, from the reaction of phosphate rock with acid, commonly sulfuric acid, about 3t of phosphogypsum are created. There are three options for managing phosphogypsum: (i) disposal or dumping, (ii) stacking, (iii) use-in, for example, agriculture, construction, or landfill. This paper presents the valorization of two Tunisian phosphogypsums (referred as G and S) in calcium sulfoaluminate cement in the following proportions: 70% phosphogypsum-30% calcium sulfoaluminate clinker. The use of sample G leads to the production of a hydraulic binder which means that it is not destroyed when immersed in water. The binder including sample S performs very well when cured in air but is not resistant in water. Formation of massive ettringite in a rigid body leads to cracking and strength loss.

Immobilization of calcium sulfate contained in demolition waste.

This paper presents the results of a laboratory study undertaken to examine the treatment of demolition waste containing calcium sulfate by means of calcium sulfoaluminate clinker (CSA). The quantity of CSA necessary to entirely consume calcium sulfate was determined. Using infrared spectrometry analysis and X-ray diffraction, it was shown that calcium sulfate was entirely consumed when the ratio between CSA and calcium sulfate was 4. Standard sand was polluted by 4% calcium sulfate. Two solutions were investigated: *either global treatment of sand by CSA, *or immobilization of calcium sulfate by CSA, followed by the introduction of this milled mixture in standard sand. Regardless of the type of treatment, swelling was almost stabilized after 28 days of immersion in water.

Hypoalbuminemia in acute ischemic stroke patients: frequency and correlates.

OBJECTIVE: Hypoalbuminemia in acute stroke patients is associated with increased mortality and morbidity. The aim of our study was to determine the frequency and correlates of hypoalbuminemia in unselected cohort of patients with acute cerebral infarction. DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Seven hundred and five consecutive ischemic stroke patients. METHODS: Albumin and other serum protein fractions were measured within 36 h after stroke using electrophoresis. RESULTS: Hypoalbuminemia defined as serum albumin level <35 g/l was found in 45.5% of patients. Serum albumin level correlates significantly with age (r=-0.13, P<0.01), Scandinavian Stroke Scale score (r=0.14, P<0.01), body temperature on admission (r=0.14, P<0.01), leukocyte count (r=-0.17, P<0.01), fasting glucose (r=-0.16, P<0.01), total cholesterol (r=0.14, P<0.01), alpha1-globulin (r=-0.48, P<0.01), alpha2-globulin (r=-0.49, P<0.01), beta-globulin (r=-0.26, P<0.01) and gamma-globulin (r=-0.35, P<0.01). CONCLUSIONS: Hypoalbuminemia is a frequent finding in acute stroke patients and it is associated with more severe stroke and pro-inflammatory pattern of serum protein electrophoresis.

Quantitative detection of Lactarius deliciosus extraradical soil mycelium by real-time PCR and its application in the study of fungal persistence and interspecific competition.

Real-Time PCR has been applied to quantify extraradical soil mycelium of the edible ectomycorrhizal fungus Lactarius deliciosus in an interspecific competition experiment under greenhouse conditions. Couples of Pinus pinea seedlings inoculated with either L. deliciosus, Rhizopogon roseolus, or non-inoculated (control) were transplanted into pots filled with two types of soil in all the possible combinations. Total DNA was extracted from soil samples at 3 and 6 months after transplantation to perform real-time PCR analysis. DNA extractions from soil mixed with known amounts of mycelium of L. deliciosus were used as standards. Six months after transplantation, the percentage of mycorrhizas of L. deliciosus and seedling growth were significantly affected by the soil type. Extraradical soil mycelium of L. deliciosus was positively correlated with the final percentage of mycorrhizas and significantly affected by the sampling time and soil depth. The competition effect of R. roseolus was not significant for any of the measured parameters, probably due to the sharp decrease of the mycorrhizal colonization by this fungus. We conclude that real-time PCR is a powerful technique for extraradical mycelium quantification in studies aimed at evaluating the persistence of introduced strains of L. deliciosus in field plantations.

ACE I/D polymorphism in different etiologies of ischemic stroke.

OBJECTIVES: Data concerning an association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and ischemic stroke (IS) remain inconsistent. Results of some studies suggest that DD genotype may be a risk factor for small vessel disease (SVD) stroke. Here, we investigated whether this polymorphism is associated with IS of different etiologies in a Polish population. SUBJECTS AND METHODS: Ischemic stroke etiology was established according to the TOAST criteria. We studied 92 stroke patients with large vessel disease and their 184 matched controls; 96 stroke patients with SVD and 192 controls; 180 patients with cardioembolic stroke (CE) and 180 controls. ACE I/D polymorphism was determined using the polymerase chain reaction method. RESULTS: The distribution of ACE genotypes and alleles was essentially the same in all analyzed IS subtypes and their matched controls. CONCLUSIONS: We failed to find an association between ACE polymorphism and etiological subtypes of IS in a Polish population.

Irradiación parcial de la mama con braquiterapia: un nuevo enfoque terapéutico / No disponible

La irradiación parcial de la mama es un tratamiento de recienteaparición que consiste en la irradiación del cuadrante mamariodonde se encuentra el tumor inicial. Este tipo de tratamientose basa en las pocas recidivas locales que existen despuésde la cirugía fuera del cuadrante donde se encontraba el tumorinicial, sobretodo en lesiones pequeñas y sin factores de mal pronósticolocal. Existen en la literatura numerosos autores que hanpublicado resultados prometedores con dicho tratamiento y actualmenteexisten 2 ensayos fase III, uno en EE.UU. y otro enEuropa, que comparan el tratamiento conservador estándar detumorectomía y radioterapia de toda la mama versus la irradiaciónparcial de la mama.En este artículo se revisan las bases clínicas y bibliográficasde la irradiación parcial de la mama(AU)

Partial breast irradiation is a new treatment which consists inthe irradiation of the quadrant where the initial tumour was located.The basis of such a treatment is that patients with a smalltumour and without bad local prognostic factors have a very lowrate of local relapses out of the involved quadrant. In the literature,a number of authors have published promising results withpartial breast radiotherapy and nowadays 2 phase III trials, onein USA and the other in Europe, are comparing conservativetreatment with partial breast irradiation.In this article we review the clinical and bibliographical basisfor partial breast irradiation(AU)

Paraoxonase gene polymorphisms and sporadic ALS.

BACKGROUND: The human paraoxonase (PON) gene family consists of three members, PON1, PON2, and PON3, located adjacent to each other on chromosome 7. PON catalytic activity may be influenced by frequent amino acid variants. Chronic exposure to certain chemicals or to environmental factors causing enhanced lipid peroxidation metabolized by paraoxonases may be a risk factor for sporadic ALS (sALS). OBJECTIVE: The aim of this study was to examine the association between PON1 Q192R, PON1 L55M, and PON2 C311S functional polymorphisms and the risk of sALS in a Polish population. METHODS: The authors included 185 patients with a definite or probable diagnosis of sALS (El Escorial Criteria) and 437 healthy controls of similar age and gender. The paraoxonase polymorphisms were studied by PCR and restriction enzyme digestion. RESULTS: Using logistic regression analyses, the C allele of the C311S polymorphism was associated with sALS in dominant and additive models, whereas the R allele of the Q192R polymorphism was associated with sALS in recessive, additive, and dominant models. The authors compared the distribution of haplotypes between cases and controls. The R-C haplotype was overrepresented among cases (odds ratio 3.44, 95% CI: 1.55 to 7.62, p = 0.002). CONCLUSIONS: Frequent amino acid variants in the paraoxonase 1 and paraoxonase 2 genes are associated with sporadic ALS in a Polish population.