Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can ...therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.
Dominant intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) was associated with mutations in the
YARS
gene, encoding tyrosyl-tRNA synthetase, in two large unrelated Bulgarian and US ...pedigrees and one sporadic case. Here for the first time we describe the clinical, neurophysiological and histopathological features, and phenotypic differences between these two DI-CMTC families. Twenty-one affected individuals from the US family and 27 from the Bulgarian family were evaluated. The mean age of onset in US subjects was 10.7 years in men and 7.3 years in women, while in the Bulgarian participants it was 18.2 years in men and 33.7 years in women. The course was slowly progressive. Extensor digitorum brevis atrophy was uniform. Atrophy and/or weakness of upper and lower limb muscles were found in over 50 % of the subjects. Nerve conduction studies (NCS) were abnormal in all US adults and five of six children and all Bulgarian patients except one asymptomatic 25-year-old man. Median motor NCS were in the range of 29.5–45.6 m/s in the US family and 24.7–57.8 m/s in the Bulgarian family. Sural sensory nerve action potentials were absent in 14/21 and 4/12 NCS from adult US and Bulgarian participants, respectively. Analysis of sural nerve biopsies from US patients revealed age-dependent morphological changes of axonal degeneration, absence of onion bulbs, and <10 % fibers with segmental remyelination. Our findings provide further insights into the diagnosis and pathology of intermediate CMT. They also extend the phenotypic spectrum of peripheral neuropathies associated with aminoacyl-tRNA synthetase mutations.
Health care-associated infections (HAIs) contribute to a significant rate of morbidity, mortality, and financial burden on health systems. These infections are caused by multidrug-resistant bacteria ...that produce biofilm as the main virulence factor. This study aimed to evaluate the effect of the copper-based metallic compounds Cu(phen)(pz)NO
2
Cl (I), Cu(bpy)(pz)(NO
2
)Cl (II), and Cu(phen)(INA)NO
2
Cl (III), where phen = phenanthroline, bpy = bipyridine, pz = pyrazinamide, and INA = isonicotinic acid, against planktonic cells and biofilms formation of
Staphylococcus aureus, Staphylococcus epidermidis
, and
Escherichia coli
. The susceptibility of the microorganisms was evaluated by minimum inhibitory concentration (MIC), minimum bacterial concentration (MBC), and time-kill curve assay on planktonic cells. The biofilm formation was evaluated by biomass quantification through staining with crystal violet (CV), colony-forming units (CFUs) quantification, and biofilm metabolic activity determination by XTT assay. The compounds showed bacteriostatic and bactericidal activity on all microorganisms analyzed. Regarding the antibiofilm activity, all metallic compounds were able to reduce significantly the biofilm biomass, colony-forming units, and the metabolic activity of remaining cells, varying the efficient concentration according to the strain analyzed. Interestingly, compounds (I), (II) and (III) did not exhibit DNA degradation activity even with up to 100 µM of these metal complexes. On the other hand, complexes (I) and (III) showed a remarkable capacity to cleave DNA upon addition of glutathione, a reducing agent (Cu
II
/Cu
I
) that leads to reactive oxygen species (ROS) formation. The results presented in this study showed promising antimicrobial and antibiofilm effects.
The
cis
-Fe(cyclam)Cl
2
Cl (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex reacts with quinizarin (1,4-dihydroxy-9,10-anthraquinone, Qz), a biologically relevant molecule, yielding the binuclear ...complex (Fe(cyclam))
2
(Qz)Cl(PF
6
)
3
. This new compound was characterized by means of elemental analysis, X-ray diffraction, cyclic voltammetry and spectroscopic techniques. Crystallographic and FTIR data indicated that the bridging ligand, quinizarin, is coordinated to the Fe
III
cation
via
the oxygen atoms of the carbonyl groups in the form of quinones. The effect of ancillary (cyclam) and bridging (Qz) ligands on the properties of the complex is reflected by the stabilization of the Fe
III
-Fe
III
configuration supported by Mössbauer spectroscopy. The efficiency of ROS generation and DNA cleavage activity for this binuclear complex, as well as for the free quinizarin ligand, were investigated. This metal complex exhibited very low photochemical activity; however, it revealed a great ability to cleave the DNA molecule in the presence of glutathione, which was associated with the production of ROS species. Thereafter, the cytotoxic activity of these compounds was evaluated using the MTS assay against human tumor cells, namely lung adenocarcinoma (A549) and prostate carcinoma (LNCaP clone FGC), and against normal fibroblasts (L929). Our findings indicated low cytotoxic effects in general, where only a slight reduction in A549 and L929 cell viability was observed after light irradiation. Despite the lack of any significant biological activity, this binuclear compound validates
in vitro
the essential role of metal binding to an anthracycline-like moiety in the generation of ROS. The latter may be responsible for some of the cardiotoxicity reported for anthracycline-based drugs.
Quinizarin, an anthracyclin-like compound, was used to prepare a binuclear complex, (Fe(cyclam))
2
QzCl(PF
6
)
3
, which showed damage to DNA with glutathione. This mimic of anthracyclin drugs might explain undesired side effects of these compounds.
Charcot-Marie-Tooth (CMT) neuropathies are common disorders of the peripheral nervous system caused by demyelination or axonal degeneration, or a combination of both features. We previously assigned ...the locus for autosomal dominant intermediate CMT neuropathy type C (DI-CMTC) to chromosome 1p34-p35. Here we identify two heterozygous missense mutations (G41R and E196K) and one de novo deletion (153-156delVKQV) in tyrosyl-tRNA synthetase (YARS) in three unrelated families affected with DI-CMTC. Biochemical experiments and genetic complementation in yeast show partial loss of aminoacylation activity of the mutant proteins, and mutations in YARS, or in its yeast ortholog TYS1, reduce yeast growth. YARS localizes to axonal termini in differentiating primary motor neuron and neuroblastoma cultures. This specific distribution is significantly reduced in cells expressing mutant YARS proteins. YARS is the second aminoacyl-tRNA synthetase found to be involved in CMT, thereby linking protein-synthesizing complexes with neurodegeneration.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform ...treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a potential noninvasive and reliable tool for diagnosing and predicting outcomes in meningioma patients. This approach can improve personalized management strategies for these patients.
Background
Peripheral neuropathies (PN) and primary headaches (PH) are common comorbidities in inflammatory bowel disease (IBD) patients. We aimed to evaluate whether PN and PH affect the same ...subgroups of IBD patients.
Methods
Since 2004, we established a cohort study to evaluate neurological diseases in IBD patients. Over 2 years, all consecutive (
N
= 155) IBD patients (either Crohn’s disease (CD) or ulcerative colitis (UC) were evaluated for the presence of PN and PH. PH were also evaluated in dyspeptic patients (
N
= 84) and IBD relatives (controls,
N
= 101). After neurological evaluation, symptomatic patients underwent skin wrinkling test to evaluate small fiber function and/or electromyography.
Results
Headaches and migraine were more prevalent in IBD than control patients: 52.3 and 34.2% vs. 40.6 and 20.8% (
P
< 0.05). Migraine was 2.6 times more common in CD patients than controls (CI = 1.34–5.129) and 8.6 times (13.3 times in the CD group) more common in men with IBD (
P
< 0.05). Headache and migraine were also more common in dyspeptic patients (
P
< 0.05). Chi-square, univariate, and multivariate regression analysis did not disclose any association between PN, headache, or PH (
P
> 0.05). Multivariate regression analysis disclosed that headaches were more prevalent in women, co-existing psychiatric disease, IBD, CD, and UC. After age, gender distribution, and prevalence of hypertension and psychiatric diseases were matched among the groups, there were still differences in the prevalence of headaches and migraine among IBD, CD, and UC versus control patients.
Conclusion
In summary, PH and PN are common in IBD and do not affect the same subgroups of patients.
Highlights • A cohort study was established in 2004, to evaluate the prevalence of neurological diseases in IBD patients. • Two patients with myasthenia gravis and IBD were diagnosed over a 9-year ...period. • MG started abruptly over a few weeks and in one patient it followed discontinuation of immunosuppression. • The prevalence of MG in patients with IBD was 0.9% over 9 years. • The clinical course of MG was not significantly altered by IBD relapses.
Despite reports in the literature that both leisure-time physical activity (LTPA) and commuting physical activity (CPA) can promote health benefits, the literature lacks studies comparing the ...associations of these domains of physical activity with cardiovascular risk scores.
To investigate the association between LTPA and CPA with different cardiovascular risk scores in the cohort of the Longitudinal Study of Adult Health ELSA-Brasil.
Cross-sectional study with data from 13,721 participants of both genders, aged 35-74 years, free of cardiovascular disease, from ELSA Brazil. Physical activity was measured using the International Physical Activity Questionnaire (IPAQ). Five cardiovascular risk scores were used: Framingham score - coronary heart disease (cholesterol); Framingham score - coronary heart disease (LDL-C); Framingham score - cardiovascular disease (cholesterol); Framingham score - cardiovascular disease (body mass index, BMI); and pooled cohort equations for atherosclerotic cardiovascular disease (ASCVD). Associations adjusted for confounding variables between physical activity and different cardiovascular risk scores were analyzed by logistic regression. Confidence interval of 95% (95%CI) was considered.
LTPA is inversely associated with almost all cardiovascular risk scores analyzed, while CPA shows no statistically significant association with any of them. Dose-response effect in association between LTPA and cardiovascular risk scores was also found, especially in men.
LTPA was shown to be associated with the cardiovascular risk scores analyzed, but CPA not. The amount of physical activity (duration and intensity) was more significantly associated, especially in men, with cardiovascular risk scores in ELSA-Brasil.
Several neurological diseases, especially different types of peripheral neuropathy (PN) are common in inflammatory bowel disease (IBD).
We prospectively evaluated the presence of PN in 121 patients ...with IBD (51 with Crohn's disease CD and 70 with ulcerative colitis UC) and 50 controls (gastritis and dyspepsia) over 3.5 years.
A total of 15 patients (12.4%) with small-fiber neuropathy and IBD (7 CD and 8 UC) and 24 patients (19.8%) with large-fiber PN (12 CD and 12 UC) were diagnosed. Small-fiber neuropathy affected 6% and large-fiber PN affected 4% of the control patients. Patients with CD with PN were older, had more metabolic complications and more severe motor involvement than patients with UC with PN. Carpal tunnel syndrome was more common in patients with UC. Sural and median sensory nerves were the most commonly and severely affected sensory responses. Tibial, peroneal, median, and ulnar compound muscle action potential amplitudes were also significantly decreased in patients with CD and UC. In general, sensory and motor amplitudes were a more sensitive marker for PN in patients with IBD than conduction velocities.
In summary, PN is common in patients with IBD. It may be primarily related to IBD, phenotypically modified by metabolic complications. Its phenotype is diverse (most commonly small to predominantly axonal sensory large-fiber), but usually more severe in CD. It also includes ataxic and demyelinating forms. Results from our 10-year follow-up will elucidate the PN clinical course and the real impact of the comorbidities and new therapies.
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