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Amyotrophic lateral sclerosis (ALS) is characterized by progressive upper and lower motor neuron degeneration. A hyperintense signal on T2-weighted images along the corticospinal tract has been reported in patients with confirmed ALS. However, the specificity of this finding is under consideration, since it is also identified in healthy controls. Moreover, the correlation of this finding with disease progression has not yet been established. The purpose of our study is to evaluate the frequency with which this high signal appears in the posterior limb of the internal capsule (PLIC), compare visual with quantitative measurements, and correlate these with the progression of the disease. Our prospective clinical study included 24 patients and 51 healthy volunteers. In the ALS patient group, the diagnosis was established according to the criteria of El Escorial in the revised form of Airlee House. All patients were neurologically examined and underwent diagnostic procedures to exclude other diseases resembling ALS. The initial MRI was performed six months to two years after the onset of symptomatology. All ALS patients were clinically examined regarding their symptoms from the upper and lower motor neurons. Follow-up MRIs were performed in nine out of 24 patients over a period of six months. Signal changes in the PLIC are visually evaluated on FLAIR images, and are classified as distinct, mild or no signal change. Fractional anisotropy (FA) measurements are performed by placing a region of interest (ROI) in the PLIC bilaterally. Both findings are being compared. Mild signal changes were visualized in the PLIC in ten volunteers and seven patients. Distinct T2 FLAIR signal changes were visualized in the PLIC in seven ALS patients. No distinct signal change was visualized in the controls. Moreover this increased T2 FLAIR signal change became more accentuated with disease progress. FA measurements in patients were lower than in age-matched healthy subjects, with a further decrease with disease progression. Our findings indicate that although mild hyperintensity of the PLIC is not pathognomonic for ALS, detection of a distinct PLIC hyperintensity that gradually accentuates might actually be a sign of progressive ALS. This finding is supported by the progressively decreasing FA measurements. Larger numbers of patients need to be included and re-evaluated to obtain statistically significant results. [ABSTRACT FROM AUTHOR]

In this paper different electrostatic interdigitated comb designs for the new concept of MEMS based DC–AC capacitive power inverter for the solar photovoltaic applications has been compared and tested on the basis of different structures and materials used as a frame for the proposed model. To obtain better the performance and power conversion efficiency of the interdigitated comb drive capacitive DC/AC inverter at very low input voltage some structural parameters of the proposed model has been varied such as increase the number of comb fingers; reduced the gap between the fingers of the interdigitated comb with increase in thickness of the fingers and made uniformly tapered at its edges. As a structural material for the proposed model the polysilicon and indium antimonite has been employed, simulated, compared and tested and in COMSOL Metaphysics 5.0 environment with different comb structure to get better performances for solar photo voltaic application. The proposed MEMS DC/AC power inverter model can easily compete with the commercially available semiconductor inverters once it is implemented with efficient fabrication technology due to its certain merits over semiconductor power inverter in terms of miniaturized size, pure sinusoidal output voltage and current, regulated output frequency, ultra low power consumption, very low cost and off course very small or minimal power loss.

Abstract Background Visual dysfunction is common in Parkinson’s disease (PD). It remains, however, unknown whether it is related to structural alterations of the retina. The aim of this study is to compare visual field (VF) findings and circumpapillary retinal nerve fiber layer (RNFL) thickness in a series of PD patients and normal controls, in order to assess possible retinal anatomical changes and/or functional damage associated with PD. Methods PD patients and controls were recruited and underwent VF testing with static automated perimetry and RNFL examination with optical coherence tomography (OCT). Cognitive performance using Mini Mental State Examination (MMSE), PD staging using modified Hoehn and Yahr (H-Y) scale and duration of the disease was recorded in PD patients. Results One randomly selected eye from each of 24 patients and 24 age-matched controls was included. OCT RNFL thickness analysis revealed no difference in the inferior, superior, nasal or temporal sectors between the groups. The average peripapillary RNFL was also similar in the two groups. However, perimetric indices of generalized sensitivity loss (mean deviation) and localized scotomas (pattern standard deviation) were worse in patients with PD compared to controls (p Conclusion PD patients may demonstrate glaucomatous-like perimetric defects even in the absence of decreased RNFL thickness.

Identifying genetic susceptibility factors for complex disorders remains a challenging task. To analyze collections of small and large pedigrees where genetic heterogeneity is likely, but biological commonalities are plausible, we have developed a weights-based pipeline to prioritize variants and genes. The Weights-based vAriant Ranking in Pedigrees (WARP) pipeline prioritizes variants using 5 weights: disease incidence rate, number of cases in a family, genome fraction shared amongst cases in a family, allele frequency and variant deleteriousness. Weights, except for the population allele frequency weight, are normalized between 0 and 1. Weights are combined multiplicatively to produce family-specific-variant weights that are then averaged across all families in which the variant is observed to generate a multifamily weight. Sorting multifamily weights in descending order creates a ranked list of variants and genes for further investigation. WARP was validated using familial melanoma sequence data from the European Genome-phenome Archive. The pipeline identified variation in known germline melanoma genes POT1, MITF and BAP1 in 4 out of 13 families (31%). Analysis of the other 9 families identified several interesting genes, some of which might have a role in melanoma. WARP provides an approach to identify disease predisposing genes in studies with small and large pedigrees., (© 2024. The Author(s).)

Introduction: Healthcare workers in anesthesiology departments often experience burnout syndrome, which may be combined with anxiety and depression., Aim: The study aimed to assess the levels of burnout among nurses and physicians working in anesthesiology departments in public hospitals in Attica and to investigate a possible correlation between burnout, anxiety, and depression., Methodology: A cross-sectional study was conducted on physicians and nurses working in anesthesiology departments in public hospitals in Attica, Greece. A questionnaire was distributed electronically using the snowball sampling method, including questions about demographic characteristics, burnout, anxiety, and depression., Results: Physicians and nurses in anesthesiology departments were found to have moderate levels of burnout, and normal/low levels of anxiety and depression. More specifically, it was found that 2% of physicians and 14.4% of nurses had extremely elevated levels of burnout. On the other hand, 6.1% of physicians and 23.7% of nurses had high anxiety, while 6.1% of physicians and 15.5% of nurses had elevated levels of depression. Females ( p = 0.008), staff aged 45-55 ( p = 0.021), lower educational level ( p = 0.025), nurses ( p = 0.001), more than 21 years of service ( p = 0.001), and having children ( p = 0.008) were determinants of greater levels of personal burnout. Work-related burnout correlated with having children ( p = 0.017), whereas client-related burnout was significantly higher for nurses ( p = 0.002). In addition, a correlation was found between anxiety, depression, and increased levels of burnout ( p = 0.000)., Conclusions: As physicians and nurses working in anesthesiology departments have stressful jobs and work long hours, it is important to further study their physical, emotional, and mental exhaustion as well as psychological resilience levels., Competing Interests: Conflicts of interest: Evangelos C. Fradelos is an editorial board member for AIMS Public Health and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 the Author(s), licensee AIMS Press.)

Vineyards in wine regions around the world are reservoirs of yeast with oenological potential. Saccharomyces cerevisiae ferments grape sugars to ethanol and generates flavor and aroma compounds in wine. Wineries place a high-value on identifying yeast native to their region to develop a region-specific wine program. Commercial wine strains are genetically very similar due to a population bottleneck and in-breeding compared to the diversity of S. cerevisiae from the wild and other industrial processes. We have isolated and microsatellite-typed hundreds of S. cerevisiae strains from spontaneous fermentations of grapes from the Okanagan Valley wine region in British Columbia, Canada. We chose 75 S. cerevisiae strains, based on our microsatellite clustering data, for whole genome sequencing using Illumina paired-end reads. Phylogenetic analysis shows that British Columbian S. cerevisiae strains cluster into 4 clades: Wine/European, Transpacific Oak, Beer 1/Mixed Origin, and a new clade that we have designated as Pacific West Coast Wine. The Pacific West Coast Wine clade has high nucleotide diversity and shares genomic characteristics with wild North American oak strains but also has gene flow from Wine/European and Ecuadorian clades. We analyzed gene copy number variations to find evidence of domestication and found that strains in the Wine/European and Pacific West Coast Wine clades have gene copy number variation reflective of adaptations to the wine-making environment. The "wine circle/Region B", a cluster of 5 genes acquired by horizontal gene transfer into the genome of commercial wine strains is also present in the majority of the British Columbian strains in the Wine/European clade but in a minority of the Pacific West Coast Wine clade strains. Previous studies have shown that S. cerevisiae strains isolated from Mediterranean Oak trees may be the living ancestors of European wine yeast strains. This study is the first to isolate S. cerevisiae strains with genetic similarity to nonvineyard North American Oak strains from spontaneous wine fermentations., Competing Interests: Conflicts of interest The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Genome-wide association studies have revealed common genetic variants with small effect sizes associated with diverse lymphoid cancers. Family studies have uncovered rare variants with high effect sizes. However, these variants explain only a portion of the heritability of these cancers. Some of the missing heritability may be attributable to rare variants with small effect sizes. We aim to identify rare germline variants associated with familial lymphoid cancers using exome sequencing. One case per family was selected from 39 lymphoid cancer families based on early onset of disease or rarity of subtype. Control data was from Non-Finnish Europeans in gnomAD exomes (N = 56,885) or ExAC (N = 33,370). Gene and pathway-based burden tests for rare variants were performed using TRAPD. Five putatively pathogenic germline variants were found in four genes: INTU, PEX7, EHHADH, and ASXL1. Pathway-based association tests identified the innate and adaptive immune systems, peroxisomal pathway and olfactory receptor pathway as associated with lymphoid cancers in familial cases. Our results suggest that rare inherited defects in the genes involved in immune system and peroxisomal pathway may predispose individuals to lymphoid cancers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ralli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Fahr's syndrome due to hypoparathyroidism refers to bilateral basal ganglia (BG) calcifications and manifests with movement disorders, seizures, cognitive and behavioral symptoms., Case Presentation: We report a case of a 74-year-old woman, who presented with parkinsonism due to post-surgical hypoparathyroidism and normal DaT scan, despite extensive calcifications of the BG, periventricular white matter, and cerebellum., Methods: A comprehensive literature review of all reported cases of Fahr's syndrome due to hypoparathyroidism was conducted in the electronic databases PubMed and Web of science. Moreover, demographic and clinical characteristics of the patients overall were calculated and associated with radiological findings., Results: We reviewed a total of 223 cases with Fahr's syndrome due to hypoparathyroidism (124 female, 99 male). Mean age on presentation was 44.6 ± 17.7 years. Thirty nine percent of patients had idiopathic hypoparathyroidism, 35.4 % acquired and 25.6 % pseudohypoparathyroidism. Almost half of the patients had tetany, seizures or a movement disorder and approximately 40 % neuropsychiatric symptoms. The patients with a movement disorder had a 2.23 likelihood of having neuropsychiatric symptoms as well (OR 2.23, 95 % CI 1.29-3.87). Moreover, there was a statistically significant association between the phenotype severity (i.e. the presence of more than one symptom) and the extent of brain calcifications (χ 2 = 32.383, p = 0.009)., Conclusion: Fahr's syndrome is a rare disorder, which nonetheless manifests with several neurological symptoms. A head CT should be considered for patients with hypoparathyroidism and neurological symptoms. More studies using DaT scan are needed to elucidate the effects of calcifications on the dopaminergic function of the BG., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Guillain-Barre syndrome (GBS) is the most common cause of acute flaccid paralysis and its incidence increases with age, although all age groups can be affected. The cranial subtypes of GBS account for approximately 5% of cases. Posterior reversible encephalopathy syndrome (PRES) is an acute neurological disorder, mostly reversible but with increased morbidity with permanent neurological sequelae in severe cases. The coexistence of these two syndromes is very rare and underdiagnosed. To the best of our knowledge, there are several dozen cases reported in the literature including ours with the coexistence of these two syndromes in adult patients. We present a rare case of oculopharyngeal type of GBS followed by PRES syndrome. Based on the reviewed cases we discuss various pathogenic mechanisms that support the association between these two entities. This review illustrates the importance of detecting PRES syndrome in the context of acute inflammatory immune-mediated polyneuropathies especially when the patients present early dysautonomia. We also discuss the importance of early administration of immunoglobulin (IVIG) treatment but the possible risks that poses to the occurrence of PRES syndrome as well., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A total of 178 consecutive patients with definite sALS without frontotemporal dementia (FTD) were enrolled in this study, after complete clinical evaluation. A Repeat-Primed Polymerase Chain Reaction (RP-PCR) protocol was applied to detect the G 4 C 2 repeats expansions. In the studied sALS patients, 5.06% ( n  = 9) carried the C9orf72 mutation. Among carriers, 2/3 of them were females and spinal onset accounted for 78% and bulbar for 22%, while the mean age of onset was about 60 years. Our study showed that the prevalence of C9orf72 repeat expansion in Greek sALS patients is similar to the overall frequency of the mutation in European populations. The pathogenic mutation remains a promising biomarker for genetic testing and targeted treatment.

Background: Α number of genetic variants have been associated with amyotrophic lateral sclerosis (ALS). A recent study supports that rs591486 across the ERCC6L2 gene and exposure to pesticides seem to have a joint effect on the development of Parkinson's disease, a disease which shares a few common characteristics with ALS., Objective: To detect a possible contribution of rs591486 ERCC6L2 to ALS., Methods: A total of 155 patients with ALS and 155 healthy controls were included in the study and genotyped for rs591486. Using logistic regression analyses (crude and adjusted for age and sex), rs591486 was tested for association with ALS risk. Subgroup analysis based on ALS site of onset was also performed. Cox regression analysis was applied in order for the effect of ERCC6L2 rs591486 on ALS age of onset to be tested., Results: Adjusted analysis showed that ERCC6L2 rs591486 was associated with an increased risk of ALS development, in dominant [odds ratio, OR (95% confidence interval, CI) 2.15 (1.04-4.46), p = 0.037] and over-dominant [OR (95%CI) = 1.91 (1.01-3.60), p = 0.043], modes. Subgroup analysis based on ALS site of onset revealed an association between ERCC6L2 rs591486 and ALS with limb onset. Results for Cox regression analysis indicated that G/A carriers had a lower age of ALS limb onset when compared to G/G carriers., Conclusions: The current study provides preliminary indication for an implication of ERCC6L2 rs591486 in ALS development, as a possible genetic risk factor. These results possibly suggest that oxidative stress may be the main contributor in the pathophysiology of ALS.

Objectives: To validate in an ethnically homogeneous Greek multiple sclerosis (MS) cohort, genetic risk factors for the disease, identified through a number of previous multi-ethnic genome-wide association studies (GWAS)., Methods: A total of 1228 MS cases and 1014 controls were recruited in the study, from 3 MS centers in Greece. We genotyped 35 susceptibility SNPs that emerged from previous GWAS or meta-analyses of GWAS. Allele and genotype single locus regression analysis, adjusted for gender and site, was performed. Permutation testing was applied to all analyses., Results: Six polymorphisms reached statistical significance (permutation p value < 0.05). In particular, rs2760524 of LOC105371664, near RGS1 (permutation p value 0.001), rs3129889 of HLA-DRA, near HLA-DRB1 (permutation p value < 1.00e-04), rs1738074 of TAGAP (permutation p value 0.007), rs703842 of METTL1/CYP27B1 (permutation p value 0.008), rs9596270 of DLEU1 (permutation p value < 1.00e-04), and rs17445836 of LincRNA, near IRF8 (permutation p value 0.001) were identified as susceptibility risk factors in our group., Conclusion: The current study replicated a number of GWAS susceptibility SNPs, which implies that some similarities between the examined Greek population and the MS genetic architecture of the GWAS populations do exist.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we adopted a next-generation sequencing approach to Greek patients suffering from sporadic ALS (together with their healthy counterparts) in order to explore further the genetic basis of sporadic ALS (sALS)., Results: Whole-genome sequencing analysis of Greek sALS patients revealed a positive association between FTO and TBC1D1 gene variants and sALS. Further, linkage disequilibrium analyses were suggestive of a specific disease-associated haplotype for FTO gene variants. Genotyping for these variants was performed in Greek, Sardinian, and Turkish sALS patients. A lack of association between FTO and TBC1D1 variants and sALS in patients of Sardinian and Turkish descent may suggest a founder effect in the Greek population. FTO was found to be highly expressed in motor neurons, while in silico analyses predicted an impact on FTO and TBC1D1 mRNA splicing for the genomic variants in question., Conclusions: To our knowledge, this is the first study to present a possible association between FTO gene variants and the genetic etiology of sALS. In addition, the next-generation sequencing-based genomics approach coupled with the two-step validation strategy described herein has the potential to be applied to other types of human complex genetic disorders in order to identify variants of clinical significance.

Genome-wide association studies (GWAS) have been shown to be a powerful approach to identify risk loci for neurodegenerative diseases. Recent GWAS in Parkinson's disease (PD) have been successful in identifying numerous risk variants pointing to novel pathways potentially implicated in the pathogenesis of PD. Contributing to these GWAS efforts, we performed genotyping of previously identified risk alleles in PD patients and control subjects from Greece. We showed that previously published risk profiles for Northern European and American populations are also applicable to the Greek population. In addition, although our study was largely underpowered to detect individual associations, we replicated 5 of 32 previously published risk variants with nominal p values <0.05. Genome-wide complex trait analysis revealed that known risk loci explain disease risk in 1.27% of Greek PD patients. Collectively, these results indicate that there is likely a substantial genetic component to PD in Greece, similarly to other worldwide populations, that remains to be discovered., (Published by Elsevier Inc.)

We investigated the association of specific polymorphisms of the interleukin IL-1b (AvaI -511 and TaqI +3,953) and IL-1 receptor antagonist (IL-1RN) (a variable number of tandem repeats; VNTR) genes with both the susceptibility to and the clinical characteristics in Greek multiple sclerosis (MS) patients cohort with bout-onset. Genotypes were determined from 351 patients with clinically definite MS and 375 age- and sex-matched healthy controls. Our results showed no significant differences in the distribution of these polymorphisms between MS patients and controls. Furthermore, stratification for clinical characteristics, such as age at disease onset, clinical course, sex, and severity did not provide significant differences between patients and controls. Together, our findings suggest that IL-1B and IL-1RN gene polymorphisms may not be relevant to the susceptibility to MS or the clinical characteristics of Greek MS patients.

This study was performed to compare the anesthetic efficacy and safety of three local anesthetic agents: racemic bupivacaine and its two isomers: ropivacaine and levobupivacaine, in patients undergoing lower abdominal surgery. One hundred-twenty patients, ASA I-III, were randomized to receive an intrathecal injection of one of three local anesthetic solutions. Group A (n = 40) received 3 ml of isobaric bupivacaine 5 mg/ml (15 mg). Group B (n = 40) received 3 ml of isobaric ropivacaine 5 mg/ml (15 mg). Group C (n = 40) received 3 ml of isobaric levobupivacaine 5 mg/ml (15 mg). The onset and duration of sensory block at dermatome level T8, maximum upper spread of sensory block, time for 2-segment regression of sensory block as well as the onset, intensity and duration of motor block were recorded, as were any adverse effects, such as bradycardia, hypotension, hypoxia, tremor, nausea and/or vomiting. Time to unassisted standing up and voluntary micturition was also recorded. The onset of motor block was significantly faster in the bupivacaine group compared with that in the ropivacaine group and almost the same of that in the levobupivacaine group (P < 0.05). Ropivacaine presented a shorter duration of both motor and sensory block than bupivacaine and levobupivacaine (P < 0.05). Bupivacaine required more often the use of a vasoactive drug (ephedrine) compared to both ropivacaine and levobupivacaine and of a sympathomimetic drug (atropine) compared to the ropivacaine group.

Background: Anemia has been associated with worse symptoms and increased mortality in patients with advanced HF. The association between anemia and biomarkers of increased HF risk is unknown. This study aimed to evaluate the relationship between hemoglobin (Hb), cardiac troponin I (cTnI), B-type natriuretic peptide (BNP), and mortality in patients with advanced heart failure (HF)., Methods: A cohort of 264 patients with advanced HF referred to a single university HF center was analyzed. Hb, cTnI, and BNP levels were drawn at time of initial evaluation. Patients were divided into groups based on the presence or absence of anemia, detectable cTnI (> or = 0.04 ng/mL), and elevated BNP (> or = 485 pg/mL)., Results: Mean Hb was 13.0 and the values ranged from 7.7 to 17.9 g/dL. Anemic patients were more likely to have elevated BNP (65.7% vs 47.4%, P = .002). Cardiac troponin I levels were detectable in 50.9% and 46.8% of anemic and non-anemic patients, respectively (P = .3). Anemic patients were at 2.3-fold increased risk of mortality (P = .04). Low Hb, detectable cTnI, and elevated BNP remained independent predictors of mortality on multivariate analysis. Anemia in the setting of detectable cTnI, elevated BNP, or both, was associated with markedly increased mortality., Conclusions: Anemia is associated with elevated BNP and increased mortality in HF. Furthermore, elevation of the cardiac biomarkers, BNP and cTnI, in patients with HF and anemia identifies patients at particularly high risk of future events.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that frequently metastasizes and that overexpresses transforming growth factor-beta s (TGF-beta s). To determine whether TGF-beta s can act to enhance the metastatic potential of PDAC, PANC-1 human pancreatic cancer cells were transfected with an expression construct encoding a soluble type II TGF-beta receptor (sT beta RII) that blocks cellular responsiveness to TGF-beta 1. When injected s.c. in athymic mice, PANC-1 clones expressing sT beta RII exhibited decreased tumor growth in comparison with sham-transfected cells and attenuated expression of plasminogen activator inhibitor 1 (PAI-1), a gene associated with tumor growth. When tested in an orthotopic mouse model, these clones formed small intrapancreatic tumors that exhibited a suppressed metastatic capacity and decreased expression of plasminogen activator inhibitor 1 and the metastasis-associated urokinase plasminogen activator. These results indicate that TGF-beta s act in vivo to enhance the expression of genes that promote the growth and metastasis of pancreatic cancer cells and suggest that sT beta RII may ultimately have a therapeutic benefit in PDAC.

Unlabelled: Human pancreatic ductal adenocarcinomas overexpress transforming growth factor-betas (TGF-betas). This overexpression has been correlated with decreased patient survival. TGF-betas bind to a type II TGF-beta receptor (TbetaRII) dimer, which heterotetramerizes with a type I TGF-beta receptor (TbetaRI) dimer, thereby activating downstream signaling., Purpose and Experimental Design: To determine whether blocking TGF-beta actions would suppress pancreatic cancer cell growth in vivo, we expressed a soluble TbetaRII, encoding amino acids 1-159 of the extracellular domain in COLO-357 human pancreatic cancer cells. This cell line expresses all of the three mammalian TGF-beta isoforms and is growth inhibited by TGF-beta in vitro., Results: COLO-357 clones expressing soluble TbetaRII were no longer growth inhibited by exogenous TGF-beta1 and exhibited a marked decrease in their invasive capacity in vitro. When injected s.c. into athymic mice, these clones exhibited attenuated growth rates and angiogenesis and decreased levels of plasminogen activator inhibitor-1 mRNA as compared with tumors formed by sham-transfected cells., Conclusions: These results indicate that endogenous TGF-betas can confer a growth advantage in vivo to a pancreatic cancer cell line that is growth inhibited in vitro and suggest that a soluble receptor approach can be used to block these tumorigenic effects of TGF-betas.