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1.
Sleep Breath ; 28(1): 381-392, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37566185

ABSTRACT

BACKGROUND AND OBJECTIVE: To revise and critically summarize the available scientific evidence regarding the effect of exercise on sleep quality in patients with chronic kidney disease (CKD). METHODS: A systematic review of randomized controlled trials (RCTs) and comparative studies was conducted, searching MEDLINE/PubMed, SPORTDiscus, and Scopus using keywords "Exercise", "Physical Activity", "Chronic Kidney Disease," and "Sleep". The methodological quality of included studies was assessed using the PEDRo and MINORS scales. RESULTS: A total of 8 RCTs and 3 comparative studies were included, showing a low (n = 1), fair (n = 7), and good (n = 3) methodological quality. Most of the studies included patients undergoing hemodialysis (HD) (n = 8). Self-reported sleep quality (n = 9), sleepiness (n = 2), and objective sleep status (n = 2) were the main outcomes analyzed. The most frequent exercise interventions included aerobic training (n = 7), resistance training (n = 2), or a combination of both (n = 4). Generally, exercise induced positive effects on the reported outcomes. Data synthesis indicated that participants who exercised obtained significant improvements on their self-reported sleep quality in comparison with those included in the control groups, with a mean difference in the Pittsburgh Sleep Quality Index of - 5.27 points (95% CI - 7.76, - 2.77; p < 0.001). CONCLUSION: Preliminary scientific evidence indicates that patients with CKD, especially those undergoing HD, report improvements in self-reported sleep quality after taking part in aerobic exercise programs, while combined training interventions yielded diverse findings. The effects of exercise on sleepiness and objective sleep status were backed by few studies with mixed results.


Subject(s)
Renal Insufficiency, Chronic , Resistance Training , Humans , Quality of Life , Sleep Quality , Sleepiness , Renal Insufficiency, Chronic/therapy
2.
BMC Palliat Care ; 23(1): 157, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38907206

ABSTRACT

BACKGROUND: Cancer is a disease that transcends what is purely medical, profoundly affecting the day-to-day life of both patients and family members. Previous research has shown that the consequences of cancer are greatly aggravated in patients at the end of life, at a time when they must also grapple with numerous unmet needs. The main objective of this study was to obtain more in-depth insight into these needs, primarily in patients with end-stage cancer nearing death. METHODS: Semi-structured interviews were conducted in Spain with cancer patients at the end of life (n = 3) and their family members (n = 12). The findings from the interviews were analyzed using qualitative thematic analysis and a grounded theory approach. RESULTS: Four major themes emerged from the interviews that explored the needs and concerns of patients with cancer at the end of life: (1) physical well-being (2) emotional well-being (3) social well-being and (4), needs relating to information and autonomous decision-making. The interviews also shed light on the specific needs of family members during this period, namely the difficulties of managing increased caregiver burden and maintaining a healthy work-life balance. CONCLUSIONS: A lack of support, information and transparency during a period of immense vulnerability makes the end-of-life experience even more difficult for patients with cancer. Our findings highlight the importance of developing a more in-depth understanding of the needs of this population, so that informed efforts can be made to improve palliative healthcare and implement more comprehensive care and support at the end of life.


Subject(s)
Family , Neoplasms , Qualitative Research , Terminal Care , Humans , Neoplasms/psychology , Neoplasms/therapy , Neoplasms/complications , Male , Female , Terminal Care/psychology , Terminal Care/methods , Terminal Care/standards , Middle Aged , Aged , Family/psychology , Spain , Adult , Grounded Theory , Interviews as Topic/methods , Caregivers/psychology , Aged, 80 and over , Needs Assessment
3.
Radiology ; 306(3): e220430, 2023 03.
Article in English | MEDLINE | ID: mdl-36318030

ABSTRACT

Background The time course of cellular damage after acute ischemic stroke (IS) is currently not well known, and specific noninvasive markers of microstructural alterations linked to inflammation are lacking, which hinders the monitoring of anti-inflammatory treatment. Purpose To evaluate the temporal pattern of neuronal and glial microstructural changes after stroke using in vivo single-voxel diffusion-weighted MR spectroscopy. Materials and Methods In this prospective longitudinal study, participants with IS and healthy volunteers (HVs) underwent MRI at 3.0 T. In participants with IS, apparent diffusion coefficients (ADCs) and concentrations of total N-acetyl-aspartate (tNAA), total creatine (tCr), and total choline (tCho) were measured in volumes of interest (VOIs), including the lesion VOI (VOIles) and the contralateral VOI (VOIcl) at 2 weeks, 1 month, and 3 months after IS. HVs were examined once, with VOIs located in the same brain regions as participants with IS. Within- and between-group differences and longitudinal changes were examined using linear mixed-effects models. Results Twenty participants with IS (mean age, 61 years ± 13 [SD]; 12 women) and 20 HVs (mean age, 59 years ± 13; 12 women) were evaluated. No differences in ADCs or concentrations were observed in VOIcl between HVs and participants with IS. In participants with IS, the ADC of tCr was higher in VOIles than in VOIcl at 1 month (+14.4%, P = .004) and 3 months after IS (+19.0%, P < .001), while the ADC of tCho was higher only at 1 month (+16.7%, P = .001). No difference in the ADC of tNAA was observed between the two VOIs at any time point. tNAA and tCr concentrations were lower in VOIles than in VOIcl and were stable over time (approximately -50% and -30%, respectively; P < .001). Conclusion High diffusivity of choline-containing compounds and total creatine (tCr) in the ischemic lesion 1 month after ischemic stroke (IS) indicates glial morphologic changes, suggesting that active inflammation is still ongoing at this time point. High tCr diffusivity up to 3 months after IS likely reflects the presence of astrogliosis at the chronic stage of cerebral ischemia. Clinical trial registration no. NCT02833961 © RSNA, 2022 Online supplemental material is available for this article.


Subject(s)
Brain Ischemia , Ischemic Stroke , Humans , Female , Middle Aged , Creatine , Ischemic Stroke/diagnostic imaging , Longitudinal Studies , Prospective Studies , Magnetic Resonance Spectroscopy/methods , Brain Ischemia/diagnostic imaging , Choline , Receptors, Antigen, T-Cell
4.
Hum Mol Genet ; 28(21): 3552-3568, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31428781

ABSTRACT

Mutations in the LRRK2 kinase are the most common cause of familial Parkinson's disease, and variants increase risk for the sporadic form of the disease. LRRK2 phosphorylates multiple RAB GTPases including RAB8A and RAB10. Phosphorylated RAB10 is recruited to centrosome-localized RILPL1, which may interfere with ciliogenesis in a disease-relevant context. Our previous studies indicate that the centrosomal accumulation of phosphorylated RAB8A causes centrosomal cohesion deficits in dividing cells, including in peripheral patient-derived cells. Here, we show that both RAB8 and RAB10 contribute to the centrosomal cohesion deficits. Pathogenic LRRK2 causes the centrosomal accumulation not only of phosho-RAB8 but also of phospho-RAB10, and the effects on centrosomal cohesion are dependent on RAB8, RAB10 and RILPL1. Conversely, the pathogenic LRRK2-mediated ciliogenesis defects correlate with the centrosomal accumulation of both phospho-RAB8 and phospho-RAB10. LRRK2-mediated centrosomal cohesion and ciliogenesis alterations are observed in patient-derived peripheral cells, as well as in primary astrocytes from mutant LRRK2 mice, and are reverted upon LRRK2 kinase inhibition. These data suggest that the LRRK2-mediated centrosomal cohesion and ciliogenesis defects are distinct cellular readouts of the same underlying phospho-RAB8/RAB10/RILPL1 nexus and highlight the possibility that either centrosomal cohesion and/or ciliogenesis alterations may serve as cellular biomarkers for LRRK2-related PD.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Centrosome/metabolism , Ciliopathies/metabolism , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism , rab GTP-Binding Proteins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Ciliopathies/enzymology , Ciliopathies/genetics , Humans , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Phosphorylation , rab GTP-Binding Proteins/genetics
5.
Biochem J ; 476(19): 2797-2813, 2019 10 15.
Article in English | MEDLINE | ID: mdl-31527116

ABSTRACT

Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for the treatment of Parkinson's disease (PD), and orally bioavailable, brain penetrant and highly potent LRRK2 kinase inhibitors are in early stages of clinical testing. Detection of LRRK2 phosphorylation, as well as phosphorylation of Rab10, a LRRK2 kinase substrate, have been proposed as target engagement biomarkers for LRRK2 inhibitor clinical trials. However, these readouts do not seem able to stratify patients based on enhanced LRRK2 kinase activity. Here, we describe a robust cell biological assay based on centrosomal cohesion alterations which were observed in peripheral blood mononuclear cell-derived lymphoblastoid cell lines (LCLs) from patients with G2019S LRRK2 mutations as compared with healthy controls, and could also be detected in a subset of sporadic PD patient samples. We suggest that LCLs may be a valuable resource for LRRK2 research, and that determination of centrosomal cohesion deficits may assist in the stratification of a subset of sporadic PD patients.


Subject(s)
Centrosome/metabolism , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism , Leukocytes, Mononuclear/metabolism , Parkinson Disease/metabolism , Adult , Aged , Biomarkers/metabolism , Cell Line, Tumor , Female , Humans , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/antagonists & inhibitors , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Leukocytes, Mononuclear/pathology , Male , Middle Aged , Phosphorylation
6.
Int J Mol Sci ; 21(9)2020 Apr 29.
Article in English | MEDLINE | ID: mdl-32365648

ABSTRACT

We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we determined the cytotoxicity and the anti-inflammatory potential of the cobalt compounds and ind and bum ligands in RAW 264.7 cells. Indomethacin-based metal complex was able to inhibit the NO production up to 35% in a concentration-dependent manner without showing cytotoxicity, showing around 6-37 times more effective than indomethacin. Cell cycle analysis showed that the inhibition of NO production was accompanied by a reversion of the differentiation processes in LPS-stimulated RAW 264.7 cells, due to a decreased of cell percentage in G0/G1 phase, with the corresponding increase in the number of cells in S phase. These two materials have mononuclear structures and show slow relaxation of magnetization. Moreover, both compounds show anti-diabetic activity with low in vitro cell toxicities. The formation of metal complexes with bioactive ligands is a new and promising strategy to find new compounds with high and enhanced biochemical properties and promises to be a field of great interest.


Subject(s)
Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Drug Design , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Algorithms , Animals , Cell Cycle Checkpoints , Cell Survival/drug effects , Dose-Response Relationship, Drug , Magnets , Mice , Models, Chemical , Models, Molecular , Molecular Conformation , Nitric Oxide/metabolism , RAW 264.7 Cells , Solubility , Structure-Activity Relationship
7.
Nitric Oxide ; 85: 17-27, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30703499

ABSTRACT

Nitric oxide (NO) is an essential signal molecule to maintain cellular homeostasis in uni and pluricellular organisms. Conceptually, NO intervenes as much in sustaining basal metabolic processes, as in firing cellular responses to changes in internal and external conditions, and also in guiding the return to basal conditions. Behind these unusual capabilities of NO is the chemistry of this molecule, an unstable, reactive, free radical and short half-life gas. It is a lipophilic molecule that crosses all the barriers that biological membranes can impose. The extraordinary impact that the elucidation of physiological processes regulated by NO has had on plants, is comparable to the consequences of the discovery in 1986 that NO is present in animal tissues, and the following deep studies that demonstrated its biological activity regulating blood pressure. In this review, we have summarized and discuss the main discoveries that have emerged at Mar del Plata University over the past 20 years, and that have contributed to understand part of the biology of NO in plants. Besides, these findings are put in context with the progress made by other research groups, and in perspective, emphasizing that the history of NO in plants has just begun.


Subject(s)
Nitric Oxide/metabolism , Plants/metabolism , Animals , Humans
8.
Acta Radiol ; 59(6): 649-656, 2018 Jun.
Article in English | MEDLINE | ID: mdl-28870087

ABSTRACT

Background In 2014, Siemens developed a new software-based scatter correction (Progressive Reconstruction Intelligently Minimizing Exposure [PRIME]), enabling grid-less digital mammography. Purpose To compare doses and image quality between PRIME (grid-less) and standard (with anti-scatter grid) modes. Material and Methods Contrast-to-noise ratio (CNR) was measured for various polymethylmethacrylate (PMMA) thicknesses and dose values provided by the mammograph were recorded. CDMAM phantom images were acquired for various PMMA thicknesses and inverse Image Quality Figure (IQFinv) was calculated. Values of incident entrance surface air kerma (ESAK) and average glandular dose (AGD) were obtained from the DICOM header for a total of 1088 pairs of clinical cases. Two experienced radiologists compared subjectively the image quality of a total of 149 pairs of clinical cases. Results CNR values were higher and doses were lower in PRIME mode for all thicknesses. IQFinv values in PRIME mode were lower for all thicknesses except for 40 mm of PMMA equivalent, in which IQFinv was slightly greater in PRIME mode. A mean reduction of 10% in ESAK and 12% in AGD in PRIME mode with respect to standard mode was obtained. The clinical image quality in PRIME and standard acquisitions resulted to be similar in most of the cases (84% for the first radiologist and 67% for the second one). Conclusion The use of PRIME software reduces, in average, the dose of radiation to the breast without affecting image quality. This reduction is greater for thinner and denser breasts.


Subject(s)
Breast/diagnostic imaging , Mammography/methods , Radiographic Image Enhancement , Software , Breast Density , Female , Humans , Phantoms, Imaging , Radiation Dosage , Retrospective Studies
9.
Contemp Oncol (Pozn) ; 22(2): 118-123, 2018.
Article in English | MEDLINE | ID: mdl-30150890

ABSTRACT

Epithelioid haemangioendothelioma (EHE) is a rare low-grade vascular neoplasm that is composed of mostly epithelioid cells. EHE may arise as a solitary tumour or in the form of multiple body lesions, and commonly occurs in soft tissues, liver, pleura, lung, peritoneum, lymph nodes, breast, and many other sites. EHE in the cranionasal region is extremely rare. There are very few reports of cases of skull-base EHE. We discuss an extremely rare presentation of an aggressive EHE that originated from the sellar region. Based on literature review, our patient is the first reported case of a giant solitary EHE with prepontine cistern invasion and abducens nerve encroachment mimicking a chondrosarcoma. We treated this rare tumour by near subtotal surgical excision with subsequent radiotherapy, considering that complete tumour resection with free margins in both cavernous sinus and clival region avoiding neural and vascular structure encroachment becomes technically difficult.

10.
Biochem Soc Trans ; 45(1): 147-154, 2017 02 08.
Article in English | MEDLINE | ID: mdl-28202668

ABSTRACT

Leucine-rich repeat kinase 2 (LRRK2) is a key player in the pathogenesis of Parkinson's disease. Mutations in LRRK2 are associated with increased kinase activity that correlates with cytotoxicity, indicating that kinase inhibitors may comprise promising disease-modifying compounds. However, before embarking on such strategies, detailed knowledge of the cellular deficits mediated by pathogenic LRRK2 in the context of defined and pathologically relevant kinase substrates is essential. LRRK2 has been consistently shown to impair various intracellular vesicular trafficking events, and recent studies have shown that LRRK2 can phosphorylate a subset of proteins that are intricately implicated in those processes. In light of these findings, we here review the link between cellular deficits in intracellular trafficking pathways and the LRRK2-mediated phosphorylation of those newly identified substrates.


Subject(s)
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism , Parkinson Disease/enzymology , Transport Vesicles/metabolism , rab GTP-Binding Proteins/metabolism , Amino Acid Sequence , Animals , Humans , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Models, Biological , Mutation , Parkinson Disease/genetics , Parkinson Disease/metabolism , Phosphorylation , Sequence Homology, Amino Acid , Substrate Specificity , rab GTP-Binding Proteins/genetics
11.
Water Sci Technol ; 74(11): 2515-2522, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27973356

ABSTRACT

Production of biogas from different organic materials is a most interesting source of renewable energy. The biomethane potential (BMP) of these materials has to be determined to get insight in design parameters for anaerobic digesters. Although several norms and guidelines for BMP tests exist, inter-laboratory tests regularly show high variability of BMPs for the same substrate. A workshop was held in June 2015, in Leysin, Switzerland, with over 40 attendees from 30 laboratories around the world, to agree on common solutions to the conundrum of inconsistent BMP test results. This paper presents the consensus of the intense roundtable discussions and cross-comparison of methodologies used in respective laboratories. Compulsory elements for the validation of BMP results were defined. They include the minimal number of replicates, the request to carry out blank and positive control assays, a criterion for the test duration, details on BMP calculation, and last but not least criteria for rejection of the BMP tests. Finally, recommendations on items that strongly influence the outcome of BMP tests such as inoculum characteristics, substrate preparation, test setup, and data analysis are presented to increase the probability of obtaining validated and reproducible results.


Subject(s)
Biofuels/analysis , Methane/analysis , Anaerobiosis , Biotechnology/standards , Laboratories/standards , Reproducibility of Results
12.
Biochem Soc Trans ; 43(3): 390-5, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26009181

ABSTRACT

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene comprise the most common cause of familial Parkinson's disease (PD), and variants increase the risk for sporadic PD. LRRK2 displays kinase and GTPase activity, and altered catalytic activity correlates with neurotoxicity, making LRRK2 a promising therapeutic target. Despite the importance of LRRK2 for disease pathogenesis, its normal cellular function, and the mechanism(s) by which pathogenic mutations cause neurodegeneration remain unclear. LRRK2 seems to regulate a variety of intracellular vesicular trafficking events to and from the late endosome in a manner dependent on various Rab proteins. At least some of those events are further regulated by LRRK2 in a manner dependent on two-pore channels (TPCs). TPCs are ionic channels localized to distinct endosomal structures and can cause localized calcium release from those acidic stores, with downstream effects on vesicular trafficking. Here, we review current knowledge about the link between LRRK2, TPC- and Rab-mediated vesicular trafficking to and from the late endosome, highlighting a possible cross-talk between endolysosomal calcium stores and Rab proteins underlying pathomechanism(s) in LRRK2-related PD.


Subject(s)
Calcium Channels/genetics , Endocytosis/genetics , Nerve Degeneration/genetics , Parkinson Disease/genetics , Protein Serine-Threonine Kinases/metabolism , Calcium Channels/chemistry , Calcium Channels/metabolism , Endosomes/metabolism , Endosomes/pathology , Humans , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 , Lysosomes/metabolism , Lysosomes/pathology , Mutation , Nerve Degeneration/pathology , Parkinson Disease/pathology , Protein Serine-Threonine Kinases/genetics , Protein Transport/genetics , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism
13.
Am J Med Genet A ; 164A(2): 338-45, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24311462

ABSTRACT

In 2005, we reported on a family as having Frías syndrome (OMIM: 609640), with four affected members displaying a pattern of congenital defects nearly identical to those observed in a mother and son described by Frias [Frías et al. (1975). Birth Defects Orig Artic Ser 11:30-33]. These defects included growth deficiency, facial anomalies, and hand and foot alterations. We had the opportunity to study this family again due to the birth of another affected girl, who presented with similar facial characteristics to those of her elder half-sister and the rest of affected relatives, which consisted of mild exophthalmia, bilateral palpebral ptosis, downslanting palpebral fissures, and hypertelorism. We performed array-CGH, which identified an identical interstitial deletion of chromosome 14q22.1-q22.3 in the mother and two daughters. The deletion is 4.06 Mb in length and includes the BMP4 gene, a member of the bone morphogenetic protein (BMP) family of secreted proteins. A review of the literature showed that deletions or mutations of this gene underlie congenital defects affecting brain, eye, teeth, and digit development. Although the clinical manifestations of the current family correlate with the defects observed in patients having either 14q22-q23 deletions or mutations of BMP4, they show a milder phenotype. In order to understand the clinical variability, we evaluated the already known functional characteristics of the BMP gene members. This gene family plays an important role during early embryogenesis, and the complex synergistic functions and redundancies of the BMPs led us to conclude that haploinsufficiency of BMP4 is likely to be responsible for the clinical expression of Frías syndrome.


Subject(s)
Bone Morphogenetic Protein 4/genetics , Face/abnormalities , Foot Deformities, Congenital/diagnosis , Foot Deformities, Congenital/genetics , Growth Disorders/diagnosis , Growth Disorders/genetics , Haploinsufficiency , Child , Child, Preschool , Chromosome Banding , Chromosome Deletion , Chromosomes, Human, Pair 14 , Comparative Genomic Hybridization , Facies , Female , Gene Deletion , Humans , Infant, Newborn , Pedigree , Phenotype
14.
Front Microbiol ; 15: 1388895, 2024.
Article in English | MEDLINE | ID: mdl-38903785

ABSTRACT

Given the increasing pressure on water bodies, it is imperative to explore sustainable methodologies for wastewater treatment and reuse. The simultaneous presence of multiples contaminants in complex wastewater, such as the liquid effluents from biogas plants, can compromise biological treatment effectiveness for reclaiming water. Vertical subsurface flow constructed wetlands were established as low-cost decentralized wastewater treatment technologies to treat the liquid fraction of digestate from municipal organic waste with metals, antibiotics, and antibiotic resistance genes, to allow its reuse in irrigation. Twelve lab-scale planted constructed wetlands were assembled with gravel, light expanded clay aggregate and sand, testing four different treating conditions (liquid digestate spiked with oxytetracycline, sulfadiazine, or ofloxacin, at 100 µg/ L, or without dosing) during 3 months. Physicochemical parameters (pH, chemical oxygen demand (COD), nutrients, metals, and antibiotics), the microbial communities dynamics (through 16S high-throughput sequencing) and antibiotic resistance genes removal (qPCR) were monitored in influents and effluents. Systems removed 85.8%-96.9% of organic matter (as COD), over 98.1% of ammonium and phosphate ions, and 69.3%-99.4% of nitrate and nitrite ions, with no significant differences between the presence or absence of antibiotics. Removal of Fe, Mn, Zn, Cu, Pb and Cr exceeded 82% in all treatment cycles. The treatment also removed oxytetracycline, sulfadiazine and ofloxacin over 99%, and decreased intl1, tetA, tetW, sul1 and qnrS gene copies. Nonetheless, after 3 months of ofloxacin dosing, qnrS gene started being detected. Removal processes relied on high HRT (14 days) and various mechanisms including sorption, biodegradation, and precipitation. Microbial community diversity in liquid digestate changed significantly after treatment in constructed wetlands with a decrease in the initial Firmicutes dominance, but with no clear effect of antibiotics on the microbial community structure. Removals above 85% and 94% were observed for Streptococcus and Clostridium, respectively. Results suggest that vertical subsurface flow constructed wetlands were a suitable technology for treating the liquid digestate to reuse it in irrigation agricultural systems, contributing to the circular bioeconomy concept. However, a more profound understanding of effective wastewater treatment strategies is needed to avoid antibiotic resistance genes dissemination.

15.
NPJ Parkinsons Dis ; 10(1): 12, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38191886

ABSTRACT

Parkinson´s disease (PD) is a common neurodegenerative movement disorder and leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for disease intervention. However, the ability to stratify patients who will benefit from such treatment modalities based on shared etiology is critical for the success of disease-modifying therapies. Ciliary and centrosomal alterations are commonly associated with pathogenic LRRK2 kinase activity and can be detected in many cell types. We previously found centrosomal deficits in immortalized lymphocytes from G2019S-LRRK2 PD patients. Here, to investigate whether such deficits may serve as a potential blood biomarker for PD which is susceptible to LRKK2 inhibitor treatment, we characterized patient-derived cells from distinct PD cohorts. We report centrosomal alterations in peripheral cells from a subset of early-stage idiopathic PD patients which is mitigated by LRRK2 kinase inhibition, supporting a role for aberrant LRRK2 activity in idiopathic PD. Centrosomal defects are detected in R1441G-LRRK2 and G2019S-LRRK2 PD patients and in non-manifesting LRRK2 mutation carriers, indicating that they accumulate prior to a clinical PD diagnosis. They are present in immortalized cells as well as in primary lymphocytes from peripheral blood. These findings indicate that analysis of centrosomal defects as a blood-based patient stratification biomarker may help nominate idiopathic PD patients who will benefit from LRRK2-related therapeutics.

16.
Sci Rep ; 14(1): 353, 2024 01 03.
Article in English | MEDLINE | ID: mdl-38172152

ABSTRACT

SARS-CoV-2 reinfections have been frequent, even among those vaccinated. The aim of this study is to know if hybrid immunity (infection + vaccination) is affected by the moment of vaccination and number of doses received. We conducted a retrospective study in 746 patients with a history of COVID-19 reinfection and recovered the dates of infection and reinfection and vaccination status (date and number of doses). To assess differences in the time to reinfection(tRI) between unvaccinated, vaccinated before 6 months, and later; and comparing one, two or three doses (incomplete, complete and booster regime) we performed the log-rank test of the cumulative incidence calculated as 1 minus the Kaplan-Meier estimator. Also, an adjusted Cox-regression was performed to evaluate the risk of reinfection in all groups. The tRI was significantly higher in those vaccinated vs. non-vaccinated (p < 0.001). However, an early incomplete regime protects similar time than not receiving a vaccine. Vaccination before 6 months after infection showed a lower tRI compared to those vaccinated later with the same regime (adj-p < 0.001). Actually, early vaccination with complete and booster regimes provided lower length of protection compared to vaccinating later with incomplete and complete regime, respectively. Vaccination with complete and booster regimes significantly increases the tRI (adj-p < 0.001). Vaccination increases the time it takes for a person to become reinfected with SARS-CoV-2. Increasing the time from infection to vaccination increases the time in which a person could be reinfected and reduces the risk of reinfection, especially in complete and booster regimes. Those results emphasize the role of vaccines and boosters during the pandemic and can guide strategies on future vaccination policy.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Reinfection/epidemiology , Reinfection/prevention & control , Retrospective Studies , Vaccination
17.
Inorg Chem ; 52(2): 546-8, 2013 Jan 18.
Article in English | MEDLINE | ID: mdl-23286441

ABSTRACT

We report the synthesis of a novel ligand, 3,3'-(1,2,4,5-tetrazine-3,6-diyl)dibenzoic acid (1). In this fragment, we have introduced two carboxylate groups with the aim of using this ligand as a linker to construct three-dimensional metal-organic frameworks (MOFs). We have been successful in the formation of zinc (2) and lanthanum (3) MOFs. The zinc compound is a two-dimensional structure, while the lanthanum material is a three-dimensional MOF with interesting channels. We include the luminescence and adsorption studies of these materials. Moreover, we have evaluated the in vitro toxicity of this novel ligand, concluding that it can be considered negligible.


Subject(s)
Benzoates/chemical synthesis , Heterocyclic Compounds/chemical synthesis , Organometallic Compounds/chemical synthesis , Adsorption , Animals , Benzoates/chemistry , Cell Survival , Cells, Cultured , Crystallography, X-Ray , Heterocyclic Compounds/chemistry , Humans , Lanthanum/chemistry , Luminescence , Organometallic Compounds/chemistry , Organometallic Compounds/metabolism , Zinc/chemistry
18.
Waste Manag Res ; 31(12): 1195-202, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24163377

ABSTRACT

Thermogravimetric analysis coupled to mass spectrometry (TGA-MS) and Fourier-transform infrared spectroscopy (FTIR) were used to describe the effect of pasteurization as a hygienic pre-treatment of animal by-products over biogas production. Piggery and poultry meat wastes were used as substrates for assessing the anaerobic digestion under batch conditions at mesophilic range. Poultry waste was characterized by high protein and carbohydrate content, while piggery waste presented a major fraction of fat and lower carbohydrate content. Results from anaerobic digestion tests showed a lower methane yield for the pre-treated poultry sample. TGA-MS and FTIR spectroscopy allowed the qualitative identification of recalcitrant nitrogen-containing compounds in the pre-treated poultry sample, produced by Maillard reactions. In the case of piggery waste, the recalcitrant compounds were not detected and its biodegradability test reported higher methane yield and production rates. TGA-MS and FTIR spectroscopy were demonstrated to be useful tools for explaining results obtained by anaerobic biodegradability test and in describing the presence of inhibitory problems.


Subject(s)
Abattoirs , Biodegradation, Environmental , Industrial Waste , Pasteurization , Waste Management/methods , Anaerobiosis , Animals , Biofuels/analysis , Mass Spectrometry , Meat , Methane/analysis , Poultry , Spectroscopy, Fourier Transform Infrared , Swine , Thermogravimetry
19.
STAR Protoc ; 4(1): 102024, 2023 03 17.
Article in English | MEDLINE | ID: mdl-36856766

ABSTRACT

The present protocol allows for quantification of inter-centrosome distances in G2 phase cells by confocal fluorescence microscopy to determine centrosome cohesion deficits. We describe transfection and immunofluorescence approaches followed by image acquisition and analysis of inter-centrosome distances. This protocol is for adherent A549 cells transiently overexpressing pathogenic LRRK2 and for immortalized murine embryonic fibroblasts endogenously expressing LRRK2 but is amenable to any other cultured cell type as well. For complete details on the use and execution of this protocol, please refer to Fdez et al.1 and Lara Ordóñez et al.2.


Subject(s)
Centrosome , Coleoptera , Animals , Mice , Humans , Cell Line , A549 Cells , Microscopy, Confocal
20.
Chemosphere ; 313: 137502, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36495981

ABSTRACT

About 13% and 7% of monitored groundwater stations in Europe exceed the permitted levels of nitrates (50 mg NO3- L-1) or pesticides (0.1 µg L-1), respectively. Although slow sand filtration can remove nitrates via denitrification when oxygen is limited, it requires an organic carbon source. The present study evaluates the performance of the use of wood pellets and granulated cork as carbon sources in bench-scale biofilters operated under water-saturated and water-unsaturated conditions for more than 400 days. The biofilters were monitored for nitrate (200 mg L-1) and pesticide (mecoprop, diuron, atrazine, and bromacil, each at a concentration of 5 µg L-1) attenuation, as well as for the formation of nitrite and pesticide transformation products. Microbiological characterization of each biofilter was also performed. The water-saturated wood biofilter achieved the best nitrate removal (>99%), while the cork biofilters lost all denitrification power over time (from 38% to no removal). The unsaturated biofilter columns were not effective for removing nitrates (20-30% removal). As for pesticides, all the biofilters achieved high removal rates of mecoprop and diuron (>99% and >75%, respectively). Atrazine removal was better in the wood-pellet biofilters than the cork ones (68-96% vs. 31-38%). Bromacil was only removed in the water-unsaturated cork biofilter (67%). However, a bromacil transformation product was formed there. The water-saturated wood biofilter contained the highest number of denitrifying microorganisms, with Methyloversatilis as the characteristic genus. Microbial composition could explain the high removal of pesticides and nitrates achieved in the wood-pellet biofilter. Overall, the results indicate that wood-pellet biofilters operated under water-saturated conditions are a good solution for treating groundwater contaminated with nitrates and pesticides.


Subject(s)
Atrazine , Groundwater , Pesticides , Nitrates , Wood , Diuron , Filtration/methods , Carbon , Denitrification
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