Levels of microRNAs (miRNAs) within extracellular vesicles (EVs) have been shown to be useful diagnostic and prognostic biomarkers in a number of disease states 1,2,3. Strikingly, using a stepwise ...multiple regression analysis, adjusting for age, hypertension, dyslipidemia, diabetes, and D-dimer, the association between EC-EV miR-24 and CBV disease in COVID-19 patients was confirmed Wald: 17.723; Exp(B): 0.955, C.I. 95%: 0.935–0.976, P < 0.001. SEE PDF To our knowledge, this is the first study showing an association between EC-EV non-coding RNA and clinical outcome in COVID-19 patients.
We have recently demonstrated in a double-blind randomized trial the beneficial effects of L-Arginine in patients hospitalized for COVID-19. We hypothesize that one of the mechanisms underlying the ...favorable effects of L-Arginine is its action on inflammatory cytokines. To verify our hypothesis, we measured longitudinal plasma levels of pro-inflammatory and anti-inflammatory cytokines implied in the pathophysiology of COVID-19 in patients randomized to receive oral L-Arginine or placebo. The study was successfully completed by 169 patients. Patients in the L-Arginine arm had a reduced respiratory support evaluated at 10 and 20 days; moreover, the time to hospital discharge was significantly shorter in the L-Arginine group. The assessment of circulating cytokines revealed that L-Arginine significantly reduced the circulating levels of pro-inflammatory IL-2, IL-6, and IFN-γ and increased the levels of the anti-inflammatory IL-10. Taken together, these findings indicate that adding L-Arginine to standard therapy in COVID-19 patients markedly reduces the need of respiratory support and the duration of in-hospital stay; moreover, L-Arginine significantly regulates circulating levels of pro-inflammatory and anti-inflammatory cytokines.
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Objective:
In early 2020, Italy struggled with an unprecedented health emergency related to the COVID-19 pandemic. Medical care of chronic neurological diseases, such as epilepsy, is being sorely ...neglected. In this national survey, we aimed at understanding the impact of COVID-19 lockdown on the care of people with epilepsy (PwE) and identifying PwE risk factors for seizure worsening to direct telemedicine efforts.
Methods:
We administered a 48-items online survey (published on April 11, 2020) including socio-demographic, epilepsy-related, and psychometric variables (BDI-II for depression, GAD-7 for anxiety, and PSQI for sleep) to PwE and people without epilepsy (PwoE). Regression analysis identified predictors of seizure worsening.
Results:
We collected responses from 456 PwE (344 females) and 472 PwoE (347 females). Outpatient examinations of PwE were postponed in 95% of cases. One-third of PwE complained of issues with epilepsy management, but only 71% of them reached the treating physician and solved their problems. PwE had worse depressive and anxiety symptoms (higher BDI-II and GAD-7 scores;
p
< 0.001) than PwoE. Sleep quality was equally compromised in both groups (47 and 42%). Sixty-seven PwE (18%) reported seizure worsening, which was best explained by the number of anti-seizure medications (ASM) of chronic therapy and the severity of sleep disorder.
Conclusions:
During the current COVID-19 pandemic, a significant percentage of PwE experienced difficulties in follow-up and a seizure number increase, in particular those chronically taking more ASMs and with poor sleep quality. This dramatic experience outlines the urgent need for validation and implementation of telemedicine services for epileptic patients in order to provide regular follow-up.
X-Linked Epilepsies: A Narrative Review Bernardo, Pia; Cuccurullo, Claudia; Rubino, Marica ...
International journal of molecular sciences,
04/2024, Letnik:
25, Številka:
7
Journal Article
Recenzirano
Odprti dostop
X-linked epilepsies are a heterogeneous group of epileptic conditions, which often overlap with X-linked intellectual disability. To date, various X-linked genes responsible for epilepsy syndromes ...and/or developmental and epileptic encephalopathies have been recognized. The electro-clinical phenotype is well described for some genes in which epilepsy represents the core symptom, while less phenotypic details have been reported for other recently identified genes. In this review, we comprehensively describe the main features of both X-linked epileptic syndromes thoroughly characterized to date (
-related DEE,
-related DEE,
-related disorders), forms of epilepsy related to X-linked neuronal migration disorders (e.g.,
,
,
) and DEEs associated with recently recognized genes (e.g.,
,
,
,
,
,
,
,
,
,
,
,
). It is often difficult to suspect an X-linked mode of transmission in an epilepsy syndrome. Indeed, different models of X-linked inheritance and modifying factors, including epigenetic regulation and X-chromosome inactivation in females, may further complicate genotype-phenotype correlations. The purpose of this work is to provide an extensive and updated narrative review of X-linked epilepsies. This review could support clinicians in the genetic diagnosis and treatment of patients with epilepsy featuring X-linked inheritance.
Abstract Infantile spasms are seizures manifesting within a spectrum of epileptic encephalopathies of infancy that often lead to cognitive impairment. Their current therapies, including ...adrenocorticotropic hormone (ACTH), high dose steroids, or vigabatrin, are not always effective and may be associated with serious side effects. Overactivation of the TORC1 complex of the mTOR pathway is implicated in the pathogenesis of certain genetic and acquired disorders that are linked with infantile spasms, like tuberous sclerosis. Here, we tested the therapeutic potential of rapamycin, a TORC1 inhibitor, as a potential treatment for infantile spasms in the multiple-hit rat model of ACTH-refractory symptomatic infantile spasms, which is not linked to tuberous sclerosis. Rapamycin or vehicle was given after spasms appeared. Their effects on spasms, other seizures, performance in Barnes maze, and expression of the phosphorylated S6 ribosomal protein (pS6: a TORC1 target) in the cortex, using immunofluorescence, were compared. Rapamycin suppressed spasms dose-dependently and improved visuospatial learning, although it did not reduce the frequency of other emerging seizures. High-dose pulse rapamycin effected acute and sustained suppression of spasms and improved cognitive outcome, without significant side effects. Therapeutically effective rapamycin doses normalized the pS6 expression, which was increased in perilesional cortical regions of pups with spasms. These findings support that pathological overactivation of TORC1 may be implicated in the pathogenesis of infantile spasms, including those that are not linked to tuberous sclerosis. Furthermore, a high-dose, pulse rapamycin treatment is a promising, well tolerated and disease-modifying new therapy for infantile spasms, including those refractory to ACTH.
Familial adult myoclonus Epilepsy (FAME) is a non-coding repeat expansion disorder that has been reported under different acronyms and initially linked to four main loci: FAME1 (8q23.3-q24.1), FAME 2 ...(2p11.1-q12.1), FAME3 (5p15.31-p15.1), and FAME4 (3q26.32-3q28). To date, it is known that the genetic mechanism underlying FAME consists of the expansion of similar non-coding pentanucleotide repeats, TTTCA and TTTTA, in different genes. FAME is characterized by cortical tremor and myoclonus usually manifesting within the second decade of life, and infrequent seizures by the third or fourth decade. Cortical tremor is the core feature of FAME and is considered part of a spectrum of cortical myoclonus. Neurophysiological investigations as jerk-locked back averaging (JLBA) and corticomuscular coherence analysis, giant somatosensory evoked potentials (SEPs), and the presence of long-latency reflex I (or C reflex) at rest support cortical tremor as the result of the sensorimotor cortex hyperexcitability. Furthermore, the application of transcranial magnetic stimulation (TMS) protocols in FAME patients has recently shown that inhibitory circuits are also altered within the primary somatosensory cortex and the concomitant involvement of subcortical networks. Moreover, neuroimaging studies and postmortem autoptic studies indicate cerebellar alterations and abnormal functional connectivity between the cerebellum and cerebrum in FAME. Accordingly, the pathophysiological mechanism underlying FAME has been hypothesized to reside in decreased sensorimotor cortical inhibition through dysfunction of the cerebellar-thalamic-cortical loop, secondary to primary cerebellar pathology. In this context, the non-coding pentameric expansions have been proposed to cause cerebellar damage through an RNA-mediated toxicity mechanism. The elucidation of the underlying pathological mechanisms of FAME paves the way to novel therapeutic possibilities, such as RNA-targeting treatments, possibly applicable to other neurodegenerative non-coding disorders.
Most recent studies have stressed a high risk of thromboembolism in patients with SARS-CoV-2 infection, particularly in those with severe COVID-19 pneumonia. Counterbalance between ...angiotensin-converting-enzyme (ACE) and ACE2 activities in COVID-19 disease may be crucially involved in the thrombo-inflammatory process. Currently, no study has investigated ACE I/D polymorphism involvement in COVID-19 disease complicated by pulmonary embolism, hence the aim of the present pilot study. This is a retrospective, single-center observational case-control study, conducted at the Sub-Intensive Care Unit of A.O.R.N. Ospedali dei Colli, Cotugno Hospital, Naples (Italy). We included 68 subjects with severe/critical COVID-19 pneumonia. COVID-19 patients were divided according to occurrence of PE (PE+,
= 25) or absence of thromboembolic complications (PE-,
= 43). Assessment of ACE I/D polymorphisms showed a statistically significant difference between PE+ and PE- patients (
= 0.029). Particularly, prevalence of D/D homozygous polymorphism was significantly higher in PE+ COVID-19 patients than in PE- (72 vs. 46.5%;
= 0.048), while heterozygote I/D polymorphism was significantly lower expressed in PE+ patients than in PE- (16 vs. 48.8%;
= 0.009). Computed tomographic pulmonary angiography showed predominantly mono/bilateral sub-segmental embolisms. In conclusion, our findings let us hypothesize a genetic susceptibility to thromboembolism in COVID-19 disease. ACE D/D polymorphism might represent a genetic risk factor, although studies on larger populations are needed.
Background Alpha-1 antitrypsin, also known as alpha1 proteinase inhibitor, is a protein 90% synthesized by hepatocytes. Alpha-1 antitrypsin deficiency should be suspected if patients have unexplained ...emphysema or liver disease in the absence of others recognized causes. The diagnosis is based on tests that measure the amount of the enzyme in the blood and confirm by molecular analysis. Case presentation We present the case of a man of Caucasian ethnicity, who started experiencing difficulty in breathing 20 years after liver transplantation. After about 30 years since transplantation, an intermediate alpha-1 antitrypsin deficiency is diagnosed with evidence of air trapping, pulmonary emphysema and bronchiectasis. Conclusion The presence of a Z-variant synthesized from the donor liver may have contribute to the onset of respiratory disease. Keywords: Alpha 1 antitrypsin, Liver transplant, Lung disease
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