12 research outputs found
Role of Provocable Brugada ECG Pattern in The Correct Risk Stratification for Major Arrhythmic Events
No full textThe so-called Brugada syndrome (BS), first called precordial early repolarization syndrome (PERS), is characterized by the association of a fascinating electrocardiographic pattern, namely an aspect resembling right bundle branch block with a coved and sometime upsloping ST segment elevation in the precordial leads, and major ventricular arrhythmic events that could rarely lead to sudden death. Its electrogenesis has been related to a conduction delay mostly, but not only, located on the right ventricular outflow tract (RVOT), probably due to a progressive fibrosis of the conduction system. Many tests have been proposed to identify people at risk of sudden death and, among all, ajmaline challenge, thanks to its ability to enhance latent conduction defects, became so popular, even if its role is still controversial as it is neither specific nor sensitive enough to guide further invasive investigations and managements. Interestingly, a type 1 pattern has also been induced in many other cardiac diseases or systemic diseases with a cardiac involvement, such as long QT syndrome (LQTS), arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM) and myotonic dystrophy, without any clear arrhythmic risk profile. Evidence-based studies clearly showed that a positive ajmaline test does not provide any additional information on the risk stratification for major ventricular arrhythmic events on asymptomatic individuals with a non-diagnostic Brugada ECG pattern
Community Pharmacist's Role in Detecting Low Back Pain, and Patient Attitudes-A Cross-Sectional Observational Study in Italian Community Pharmacies
No full textBackground: Low back pain (LBP) is one of the most frequent diseases for which patients seek advice in a community pharmacy. The study aimed to evaluate the feasibility of the administration by community pharmacists of questionnaires to assess the LBP intensity and disability degree in patients entering community pharmacies and the attitudes they have toward pain management by pharmacological and non-pharmacological strategies. Methods: An explorative, cross-sectional, observational, and quantitative study was performed. Twelve Italian community pharmacists were asked to submit a questionnaire on LBP to patients visiting their pharmacies. The questionnaire included a pain intensity scale, and two validated tools: the Roland and Morris Disability Questionnaire (RMDQ) and the Start Back Screening Tool (SBST) to determine the degree and risk of patient disability, respectively. Results: 872 patients filled out the questionnaires in 6 months. No statistical dierences between genders (p > 0.30) were recorded for pain intensity (Female: median score 6, IQR 4–7; Male: median scores 5, IQR 4–7; p > 0.30) and disability associated with LBP (RMDQ high-disability level: Females, 14.7%, Males, 15.0%; p > 0.90). Most of the patients (69%) reported a low degree of disability, but the risk of disability was medium and high in 36% and 18% of them, respectively (p < 0.05). About 14% of patients declare to never seek for physician’s advice despite their medium-high degree of disability. Conclusion: The study demonstrated the feasibility of validated tools for assessing the degree and risk of disability in LBP patients administrable in community pharmacies. Moreover, the community pharmacy resulted in an important care portal for patients suering from moderate LBP and for intercepting patients who suered from severe LBP but had never reported their problem to their physician
Intermuscular Two-Incision Technique for Subcutaneous Implantable Cardioverter Defibrillator Implantation: Results from a Multicenter Registry
No full textBackground: The traditional technique for subcutaneous implantable cardioverter defibrillator (S-ICD) implantation, which involves three incisions and a subcutaneous pocket, is associated with possible complications, including inappropriate interventions. The aim of this prospective multicenter study was to evaluate the efficacy and safety of an alternative intermuscular two-incision technique for S-ICD implantation.
Methods: The study population included 36 consecutive patients (75% male, mean age 44 +/- 12 years [range 20-69]) who underwent S-ICD implantation using the intermuscular two-incision technique. This technique avoids the superior parasternal incision for the lead placement and consists of creating an intermuscular pocket between the anterior surface of the serratus anterior and the posterior surface of the latissimus dorsi muscles instead of a subcutaneous pocket.
Results: All patients were successfully implanted in the absence of any procedure-related complications with a successful 65-J standard polarity defibrillation threshold testing, except in one, who received a second successful shock after pocket revision. During a mean follow-up of 10 months (range 330), no complications requiring surgical revision were observed. At device interrogation, stable sensing without interferences was observed in all patients. Two patients (5.5%) experienced appropriate and successful shock on ventricular fibrillation and in four patients (11%), a total of seven nonsustained self-terminated ventricular tachycardias were correctly detected. No inappropriate interventions were observed.
Conclusions: Our experience suggests that the two-incision intermuscular technique is a safe and efficacious alternative to the current technique for S-ICD implantation that may help reducing complications including inappropriate interventions and offer a better cosmetic outcome, especially in thin individuals
Anti-Tat immunity defines CD4+ T-cell dynamics in people living with HIV on long-term cART
No full textBackground: Low-level HIV viremia originating from virus reactivation in HIV reservoirs is often present in cART treated individuals and represents a persisting source of immune stimulation associated with sub-optimal recovery of CD4(+) T cells. The HIV-1 Tat protein is released in the extracellular milieu and activates immune cells and latent HIV, leading to virus production and release. However, the relation of anti-Tat immunity with residual viremia, persistent immune activation and CD4(+) T-cell dynamics has not yet been defined.Methods: Volunteers enrolled in a 3-year longitudinal observational study were stratified by residual viremia, Tat serostatus and frequency of anti-Tat cellular immune responses. The impact of anti-Tat immunity on lowlevel viremia, persistent immune activation and CD4(+) T-cell recovery was investigated by test for partitions, longitudinal regression analysis for repeated measures and generalized estimating equations.Findings: Anti-Tat immunity is significantly associated with higher nadir CD4(+) T-cell numbers, control of lowlevel viremia and long-lasting CD4(+) T-cell recovery, but not with decreased immune activation. In adjusted analysis, the extent of CD4(+) T-cell restoration reflects the interplay among Tat immunity, residual viremia and immunological determinants including CD8(+) T cells and B cells. Anti-Env immunity was not related to CD4(+) T-cell recovery.Interpretation: Therapeutic approaches aiming at reinforcing anti-Tat immunity should be investigated to improve immune reconstitution in people living with HIV on long-term cART. (C) 2021 The Author(s). Published by Elsevier B.V
Correction to: Abolishing Tau cleavage by caspases at Aspartate421 causes memory/synaptic plasticity deficits and pre-pathological Tau alterations (Translational Psychiatry, (2017), 7, 8, (e1198), 10.1038/tp.2017.165)
No full text© 2018, The Author(s). This article was originally published under Nature Research’s License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the article have been modified accordingly
Alexandrium fundyense-Amoebophrya spp. dynamics in a semi enclosed embayment: Implications of sexual reproduction and excystment/encystment strategies on hostparasite coexistence
No full textNo abstracts are to be cited without prior reference to the author. Parasitic dinoflagellates of the genus Amoebophrya infect free-living dinoflagellates, some of which can cause harmful algal blooms (HABs). During a field study in Salt Pond (MA, USA), we found a significant influence of Amoebophrya spp. on populations of Alexandrium fundyense. Parasitism appeared to exhibit a significant top down influence on A. fundyense populations and a dramatic life-cycle transition from vegetative division to sexual fusion was recorded. Despite our intensive sampling in Salt Pond, hostparasite interactions were undersampled owing to the very short time scales relevant to host-Amoebophrya spp. dynamics. In the present work, we explored the role of sexual reproduction and excystment/encystment processes using an Individual Based Model (IBM). The model was parameterized using published data and laboratory experiments carried out to analyze Amoebophrya spp. functional response. Observed-simulated differences in host-parasite dynamics support the hypothesis of parasitehost simultaneous dormancy, and further excystment months later to propagate both species. Results suggest that coexistence of A. fundyense and Amoebophrya spp. and their annual persistence in Salt Pond might rely on a sexual response/encystment. Understanding host-parasite interactions and coexistence strategies will improve our knowledge of Alexandrium spp. blooms and assess the impact of parasites on natural plankton assemblages in coastal system
Chronicle (Paterson, NJ) Vol. 32, No. 4, Jan. 24, 1960
No full textLocal information pertaining to Paterson, N.J. and surrounding Passaic County. Issues may include events, government, business, political cartoons, engagement and marriage announcements, and birth announcements. This publication was also known as the Paterson Chronicle (1952) and the Paterson Sunday Chronicle (1951-1952)
Author response: LTP and memory impairment caused by extracellular Aβ and Tau oligomers is APP-dependent
No full textMitochondria, neurosteroids and biological rhythms : implications in health and disease states
No full textMitochondria are considered as the “powerhouses” of cells because they synthesize the universal source of energy under the form of adenosine triphosphate (ATP) molecules via oxidative phosphorylation from nutritional sources. Thus, impaired mitochondrial function, especially in neurons that have high energy requirements, lead inevitably to disease, ranging from subtle alterations in neuronal function to cell death and neurodegenerative diseases, such as Alzheimer’s disease (AD). The purpose of this PhD thesis was therefore to deepen our understanding of the regulation of mitochondrial function and to identify key factors that are critical in the control of mitochondrial bioenergetics and dynamics. To achieve this goal, the thesis was divided into two main parts:
1) Since a growing body of evidence suggests that neurosteroids have a strong neuroprotective potential, the first part is based on the hypothesis that neurosteroids may exert a determinant action against neurodegeneration by improving mitochondrial bioenergetics, (A) under “healthy” conditions as well as (B) under pathological conditions (AD);
2) In the second part (C), we determined whether the biological clock, which coordinates a whole range of daily behaviors and physiological processes, is involved in the endogenous regulation of mitochondrial dynamics and bioenergetics.
(A) In the first part of this thesis, we aimed to characterize the bioenergetic modulating profile of a panel of seven structurally diverse neurosteroids (progesterone, estradiol, estrone, testosterone, 3alpha-androstanediol, DHEA and allopregnanolone), known to be involved in brain function regulation. Our key findings were that: i) the majority of these steroids increased energy metabolism, mainly via an up-regulation of the mitochondrial activity and at least in part via receptor activation, and ii) neurosteroids regulated redox homeostasis by increasing the antioxidant activity as a compensatory mechanism to the reactive oxygen species (ROS) level enhancement which might result from the acceleration in oxygen consumption accompanied by a greater electron leakage from the electron transport chain. Additionally, each neurosteroid seems to have a specific bioenergetic profile.
Together, these first data indicated that neurosteroids were indeed able to boost mitochondrial function in a delicate balance, possibly by regulating the expression of genes involved in glycolysis and oxidative phosphorylation, but also the content and activity of mitochondrial respiratory complexes. Further investigations are required to determine the underlying molecular mechanisms.
(B) Based on these findings, we investigated in the next step whether neurosteroids were able to alleviate AD-related bioenergetic deficits. We distinguished the effects of several neurosteroids on ATP synthesis, mitochondrial membrane potential (MMP), mitochondrial respiration and glycolysis in two AD cellular models overexpressing either the amyloid precursor protein and amyloid-beta peptide (APP/Abeta) or the mutant form of tau producing abnormally hyperphosphorylated tau proteins, respectively. Key findings were that: i) APP/Abeta and mutant tau-overexpressing cells present distinct bioenergetic impairments, with APP/Abeta having the strongest deleterious effect on mitochondrial function; ii) the male steroid hormone, testosterone, was more efficient to alleviate mitochondrial deficits induced by APP/Abeta, whereas female steroid hormones, progesterone and estrogen, were more efficient to increase bioenergetic outcomes in our model of AD-related tauopathies. Together, our findings lend further evidence to the neuroprotective effects of neurosteroids in AD pathology and indicate that these molecules represent promising tools able to increase mitochondrial bioenergetics via enhanced mitochondrial respiration, in healthy and pathological conditions, respectively. Our results may open new avenues for drug development with regard to targeting mitochondria in neurodegeneration.
(C) The aim of the second part of this thesis was to investigate more closely how mitochondrial function is endogenously regulated within the cells. Since a growing body of evidences shows that the circadian clock and metabolic homeostasis are connected in numerous ways via reciprocal regulation, we asked whether mitochondrial bioenergetics and dynamics may exhibit circadian oscillations and whether mitochondria themselves may be able to influence the circadian clock. We found that mitochondrial bioenergetics, including mitochondrial respiration and, consequently, generation of the byproducts ATP and ROS, is directly coupled to mitochondrial network which is, at least in part, regulated by clock-controlled phosphorylation of Drp1, the main factor involved in mitochondrial fission. The time-dependent reorganization of mitochondrial architecture in turn regulates the clock through circadian oscillation of mitochondrial ATP which can act as input signal through activation of AMP-activated protein kinase (AMPK). Our findings highlight new insights in the understanding of the reciprocal temporal crosstalk that governs the molecular interplay between the coupling of mitochondrial dynamics and metabolism and circadian rhythms.
Overall, the studies performed in the present thesis importantly helped to deepen our knowledge about the modulation of mitochondrial function in health and disease states. Our findings could have multiple implications with regard to the regulation of metabolic homeostasis in health and disease states associated with mitochondrial impairments and / or circadian disruption
