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1.
Angiol. (Barcelona) ; 76(2): 106-108, Mar-Abr. 2024. ilus
Article in Spanish | IBECS | ID: ibc-232385

ABSTRACT

Introducción: la displasia fibromuscular (DFM) es una patología poco frecuente de la capa muscular de las arterias. El síndrome de ligamento arcuato medio (SLAM) es una entidad infrecuente causada por la compresión extrínseca del tronco celíaco por el diafragma. Caso clínico: presentamos el caso de una mujer joven con DFM diagnosticada de afectación a nivel del tronco celíaco y de la arteria hepática común. Ante clínica de dolor abdominal, se solicita angio TC, que describe un SLAM asociado a la DFM. Se decide sección quirúrgica del ligamento arcuato y descompresión del tronco celíaco mediante abordaje robótico. Discusión: en ambas entidades la angiografía es el trataminto de referencia para el diagnóstico. El tratamiento de primera línea de la DFM es el endovascular mediante angioplastia, y del SLAM, el quirúrgico, seccionando el ligamento arcuato.(AU)


Introduction: fibromuscular dysplasia (FMD) is a rare disorder that affects the muscular layer of the arteries. The medianarcuate ligament syndrome (MALS) is also a rare disorder due to the extrinsic compression of the celiac trunk by thediaphragm.Case report: we report the case of a young woman with FMD and splachnic involvement of the celiac trunk and thecommon hepatic artery level. After presenting with abdominal pain, a CCTA was performed that revealed the presenceof FMD-related MALS. The surgical section of the arcuate ligament and decompression of celiac trunk were decided andperformed through robotic approach.Discussion: the gold standard for the diagnosis of both entities is angiography. However, while the first-line therapy ofFMD is endovascular, in the case MALS the best alternative is surgical treatment sectioning the arcuate ligament.(AU)


Subject(s)
Humans , Female , Adult , Fibromuscular Dysplasia/diagnosis , Fibromuscular Dysplasia/drug therapy , Median Arcuate Ligament Syndrome , Angiography , Inpatients , Physical Examination
2.
Therap Adv Gastroenterol ; 17: 17562848241234476, 2024.
Article in English | MEDLINE | ID: mdl-38445247

ABSTRACT

Background: The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders. Objective: To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders. Design: This was a retrospective and multicentre study. Methods: We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI). Results: In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis (n = 37) or Crohn's disease of the pouch (n = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy. Conclusion: Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option.

3.
Article in English | MEDLINE | ID: mdl-38490245

ABSTRACT

OBJECTIVES: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. METHODS: A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. RESULTS: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. CONCLUSION: Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

4.
J Alzheimers Dis ; 98(2): 601-618, 2024.
Article in English | MEDLINE | ID: mdl-38427484

ABSTRACT

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPß1, a surface receptor that triggers amyloid-ß(Aß) phagocytosis via TYROBP. Objective: To analyze the impact of this copy-number variant in SIRPß1 expression and how it affects AD molecular etiology. Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPß1 isoform-specific phagocytosis assays were performed in HEK393T cells. Results: The insertion alters the SIRPß1 protein isoform landscape compromising its ability to bind oligomeric Aß and its affinity for TYROBP. SIRPß1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aß ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPß1 duplication allele correlates with higher TREM2 expression and an increased microglial activation. Conclusions: The SIRPß1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aß. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPß1 structural variant might be considered as a potential modulator of this causative pathway.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Receptors, Cell Surface , Humans , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/genetics , Amyloid beta-Peptides/metabolism , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/genetics , Cognitive Dysfunction/metabolism , Microglia/metabolism , Phagocytosis , Receptors, Cell Surface/metabolism
5.
Kidney Int ; 105(4): 824-834, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38280517

ABSTRACT

In Mexico, chronic kidney disease of unknown origin is highly prevalent. Screening studies in adolescents have shown persistent microalbuminuria (pACR), adaptive podocytopathy and decreased kidney volume (KV). Here, we sought to develop normality tables of kidney dimensions by ultrasound in the Mexican state of Aguascalientes pediatric population (0 to 18y) and evaluate the relationship between the KV and pACR among the region's adolescents in a cross-sectional study. Kidney length (KL) and KV were determined by ultrasound. Our findings were compared with those in international literature of different populations where tables and graphs of normal kidney dimensions by ultrasound were reported. We compared organ dimensions in individuals above the age of 11 without albuminuria with those in patients with pACR recruited through screening studies in adolescents in Aguascalientes. This included 1068 individuals to construct percentile tables and graphs of the KL. Kidney dimensions were significantly lower when compared with all international comparisons. From a total 14,805 screen individuals, we compared 218 adolescents with pACR and 377 individuals without significant albuminuria. The Total KV adjusted to body surface (TKVBS) was significantly associated with pACR (odds ratio 1.03, 95% confidence interval 1.02-1.03). The upper quartile of TKVBS was highly associated with pACR (7.57, 4.13-13.87), hypertension (2.53, 1.66-3.86), and hyperfiltration (26 vs 11.5%). Thus, TKVBS is directly associated with pACR while greater KV, arterial hypertension, and hyperfiltration in patients with pACR suggest that the increase in volume is secondary to kidney hypertrophy. Additionally, the adaptative podocytopathy with low fibrosis seen on kidney biopsy which was performed in a subset of patients, and the smaller kidney dimensions in our population point to prenatal oligonephronia as the primary cause of the detected kidney disease.


Subject(s)
Hypertension , Renal Insufficiency, Chronic , Humans , Child , Adolescent , Albuminuria/diagnosis , Albuminuria/epidemiology , Albuminuria/etiology , Cross-Sectional Studies , Mexico/epidemiology , Glomerular Filtration Rate , Kidney/pathology , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/complications , Hypertension/pathology
6.
Rheumatology (Oxford) ; 63(1): 72-78, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-37039851

ABSTRACT

OBJECTIVES: To assess agreement between the 2021 Definition Of Remission In SLE (DORIS) and physician-judged lupus activity. METHODS: A cross-sectional analysis was conducted of data from a Spanish prospective multicentre study of SLE patients. We applied the 2021 DORIS criteria and assessed whether remission status based on this definition agreed with remission as per physician clinical judgement and reasons for disagreement between them. RESULTS: Out of 508 patients [92% women; mean age (s.d.): 50.4 years (13.7)] studied, 267 (54.4%) met the criteria for 2021 DORIS remission. Based on physicians' judgement, 277 (55.9%) patients were classified as in remission or serologically active clinically quiescent (SACQ). The overall rate of agreement between these assessments was 81.2% (95% CI: 79.9, 82.9%) with a Cohen's kappa of 0.62 (0.55-0.69). Overall, 46 (9.1%) patients were classified as in remission/SACQ by rheumatologists but did not meet the 2021 DORIS criteria for remission. The main reasons for discrepancies were a clinical SLE Disease Activity Index (cSLEDAI) score >0 in 39 patients, a Physician Global Assessment score >0.5 in five patients, and prednisone >5 mg/day in another five patients. CONCLUSIONS: The 2021 DORIS remission is an achievable target in clinical practice. There is substantial agreement between the DORIS definition and physician-judged remission. The discordance was mainly due to physicians classifying some patients with ongoing mild disease activity as in remission. Thus, the standardized DORIS definition should be used to define the target in a treat-to-target strategy for the management of SLE.


Subject(s)
Judgment , Lupus Erythematosus, Systemic , Humans , Female , Male , Prospective Studies , Cross-Sectional Studies , Rheumatologists , Lupus Erythematosus, Systemic/drug therapy , Severity of Illness Index , Remission Induction
7.
Chemistry ; 30(2): e202303041, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-37828571

ABSTRACT

The "carbohydrate chemical mimicry" exhibited by sp2 -iminosugars has been utilized to develop practical syntheses for analogs of the branched high-mannose-type oligosaccharides (HMOs) Man3 and Man5 . In these compounds, the terminal nonreducing Man residues have been substituted with 5,6-oxomethylidenemannonojirimycin (OMJ) motifs. The resulting oligomannoside hemimimetic accurately reproduce the structure, configuration, and conformational behavior of the original mannooligosaccharides, as confirmed by NMR and computational techniques. Binding studies with mannose binding lectins, including concanavalin A, DC-SIGN, and langerin, by enzyme-linked lectin assay and surface plasmon resonance revealed significant variations in their ability to accommodate the OMJ unit in the mannose binding site. Intriguingly, OMJMan segments demonstrated "in line" heteromultivalent effects during binding to the three lectins. Similar to the mannobiose (Man2 ) branches in HMOs, the binding modes involving the external or internal monosaccharide unit at the carbohydrate binding-domain exist in equilibrium, facilitating sliding and recapture processes. This equilibrium, which influences the multivalent binding of HMOs, can be finely modulated upon incorporation of the OMJ sp2 -iminosugar caps. As a proof of concept, the affinity and selectivity towards DC-SIGN and langerin were adjustable by presenting the OMJMan epitope in platforms with diverse architectures and valencies.


Subject(s)
Lectins, C-Type , Mannose , Humans , Concanavalin A/metabolism , Mannose/chemistry , Lectins, C-Type/metabolism , Oligosaccharides/chemistry , Binding Sites , Mannose-Binding Lectins/chemistry
8.
J Clin Med ; 12(21)2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37959190

ABSTRACT

The present systematic review aimed to determine the chronic effects of the combination of transcranial direct current stimulation (tDCS) and exercise on motor function and performance outcomes. We performed a systematic literature review in the databases MEDLINE and Web of Science. Only randomized control trials that measured the chronic effect of combining exercise (comprising gross motor tasks) with tDCS during at least five sessions and measured any type of motor function or performance outcome were included. A total of 22 interventions met the inclusion criteria. Only outcomes related to motor function or performance were collected. Studies were divided into three groups: (a) healthy population (n = 4), (b) neurological disorder population (n = 14), and (c) musculoskeletal disorder population (n = 4). The studies exhibited considerable variability in terms of tDCS protocols, exercise programs, and outcome measures. Chronic use of tDCS in combination with strength training does not enhance motor function in healthy adults. In neurological disorders, the results suggest no additive effect if the exercise program includes the movements pretending to be improved (i.e., tested). However, although evidence is scarce, tDCS may enhance exercise-induced adaptations in musculoskeletal conditions characterized by pain as a limiting factor of motor function.

9.
Sci Data ; 10(1): 745, 2023 10 27.
Article in English | MEDLINE | ID: mdl-37891169

ABSTRACT

The United States of America has a diverse collection of freshwater mussels comprising 301 species distributed among 59 genera and two families (Margaritiferidae and Unionidae), each having a unique suite of traits. Mussels are among the most imperilled animals and are critical components of their ecosystems, and successful management, conservation and research requires a cohesive and widely accessible data source. Although trait-based analysis for mussels has increased, only a small proportion of traits reflecting mussel diversity in this region has been collated. Decentralized and non-standardized trait information impedes large-scale analysis. Assembling trait data in a synthetic dataset enables comparison across species and lineages and identification of data gaps. We collated data from the primary literature, books, state and federal reports, theses and dissertations, and museum collections into a centralized dataset covering information on taxonomy, morphology, reproductive ecology and life history, fish hosts, habitats, thermal tolerance, geographic distribution, available genetic information, and conservation status. By collating these traits, we aid researchers in assessing variation in mussel traits and modelling ecosystem change.


Subject(s)
Bivalvia , Unionidae , Animals , Ecosystem , Fresh Water , Phylogeny , Unionidae/genetics , United States
10.
Curr Opin Cell Biol ; 85: 102254, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37832167

ABSTRACT

Vessel formation and differentiation to a proper hierarchical vasculature requires a coordinated effort from endothelial and mural cells. Over the last decade Notch was identified as a key player in this process by promoting vascular arterialization and modulating endothelial tip-stalk phenotypes. Recent work has identified that Notch fine-tunes the diverse endothelial phenotypes through regulation of canonical cell-cycle and metabolism regulators, such as ERK and Myc. During arterialization, Notch signaling inhibits the cell-cycle and metabolism of endothelial cells which coincides with the acquisition of arterial identity. During angiogenesis, the same molecular machinery prevents the hypermitogenic arrest and excessive sprouting of vessels. Notch also signals in pericytes and smooth muscle cells promoting vascular coverage and maturation. Here, we will review the latest findings on how Notch signals regulate the differentiation and interactions among vascular cells during organ development and homeostasis.


Subject(s)
Endothelial Cells , Receptors, Notch , Endothelial Cells/metabolism , Receptors, Notch/metabolism , Cell Communication , Signal Transduction/physiology , Cell Differentiation , Neovascularization, Physiologic/physiology
11.
Int J Mol Sci ; 24(15)2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37569459

ABSTRACT

Genome-wide association studies (GWAS) constitute a powerful tool to identify the different biochemical pathways associated with disease. This knowledge can be used to prioritize drugs targeting these routes, paving the road to clinical application. Here, we describe DAGGER (Drug Repositioning by Analysis of GWAS and Gene Expression in R), a straightforward pipeline to find currently approved drugs with repurposing potential. As a proof of concept, we analyzed a meta-GWAS of 1.6 × 107 single-nucleotide polymorphisms performed on Alzheimer's disease (AD). Our pipeline uses the Genotype-Tissue Expression (GTEx) and Drug Gene Interaction (DGI) databases for a rational prioritization of 22 druggable targets. Next, we performed a two-stage in vivo functional assay. We used a C. elegans humanized model over-expressing the Aß1-42 peptide. We assayed the five top-scoring candidate drugs, finding midostaurin, a multitarget protein kinase inhibitor, to be a protective drug. Next, 3xTg AD transgenic mice were used for a final evaluation of midostaurin's effect. Behavioral testing after three weeks of 20 mg/kg intraperitoneal treatment revealed a significant improvement in behavior, including locomotion, anxiety-like behavior, and new-place recognition. Altogether, we consider that our pipeline might be a useful tool for drug repurposing in complex diseases.


Subject(s)
Alzheimer Disease , Animals , Mice , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Genome-Wide Association Study , Caenorhabditis elegans/genetics , Staurosporine/therapeutic use , Drug Repositioning
12.
Virol J ; 20(1): 153, 2023 07 18.
Article in English | MEDLINE | ID: mdl-37464399

ABSTRACT

Resistant CMV infections are challenging complications after SOT and HSCT. Prompt recognition of ARMs is imperative for appropriate therapy. 108 plasma samples from 96 CMV + transplant recipients with suspected resistance were analysed in CNM in a retrospective nationwide study from January 2018 to July 2022 for resistance genotyping. ARMs in UL97 and UL54 were found in 26.87% (18/67) and 10.60% (7/66) of patients, respectively. Patients' ARM distribution in UL97 was as follows: L595S n = 3; L595S/M460I n = 1; L595S/N510S n = 1; L595W n = 1; C603W n = 4; A594V n = 3; A594E n = 1; C607Y n = 1; L397R/T409M/H411L/M460I n = 1; L397I n = 1; H520Q n = 1; four patients showed ARMs in UL54 as well (F412C n = 1; T503I n = 2; P522S n = 1), whereas three patients exhibited ARMs in UL54 only (L501I/T503I/L516R/A834P n = 1; A987G n = 2). L516R in UL54 and L397R/I and H411L in UL97 have been found for the first time in a clinical sample. L595S/W was the most prevalent ARM found to lend resistance to GCV. In UL54 all ARMs lent resistance to GCV and CDV. In addition, A834P, found in one patient, also lent resistance to FOS. CMV load did not differ significantly in patients with or without ARMs, and no differences were found either between patients with ARMs in UL97 or in UL97 and UL54. Despite extensive use of classical antivirals for the treatment of CMV infection after HSCT and SOT, ARMs occurred mainly in viral UL97 kinase, which suggests that CDV and mostly FOS continue to be useful alternatives to nucleoside analogues after genotypic detection of ARMs.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Humans , Cytomegalovirus/genetics , Ganciclovir/therapeutic use , Transplant Recipients , Retrospective Studies , Phosphotransferases (Alcohol Group Acceptor)/genetics , Phosphotransferases (Alcohol Group Acceptor)/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cytomegalovirus Infections/drug therapy , Mutation , Drug Resistance, Viral/genetics
13.
Nat Commun ; 14(1): 3372, 2023 06 08.
Article in English | MEDLINE | ID: mdl-37291151

ABSTRACT

Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells - astrocytes and mature myelin-forming oligodendrocytes - is a determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models, unbiased RNA sequencing, functional manipulation, and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation in focally-lesioned male mice yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.


Subject(s)
Astrocytes , NF-E2-Related Factor 2 , Male , Mice , Animals , Humans , Astrocytes/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Central Nervous System/metabolism , Oligodendroglia/metabolism , Myelin Sheath/metabolism , Nerve Regeneration/physiology , Cholesterol/metabolism
14.
Commun Biol ; 6(1): 623, 2023 06 09.
Article in English | MEDLINE | ID: mdl-37296226

ABSTRACT

Recent advances in long-read sequencing technologies have allowed the generation and curation of more complete genome assemblies, enabling the analysis of traditionally neglected chromosomes, such as the human Y chromosome (chrY). Native DNA was sequenced on a MinION Oxford Nanopore Technologies sequencing device to generate genome assemblies for seven major chrY human haplogroups. We analyzed and compared the chrY enrichment of sequencing data obtained using two different selective sequencing approaches: adaptive sampling and flow cytometry chromosome sorting. We show that adaptive sampling can produce data to create assemblies comparable to chromosome sorting while being a less expensive and time-consuming technique. We also assessed haplogroup-specific structural variants, which would be otherwise difficult to study using short-read sequencing data only. Finally, we took advantage of this technology to detect and profile epigenetic modifications among the considered haplogroups. Altogether, we provide a framework to study complex genomic regions with a simple, fast, and affordable methodology that could be applied to larger population genomics datasets.


Subject(s)
Epigenomics , High-Throughput Nucleotide Sequencing , Humans , Sequence Analysis, DNA/methods , High-Throughput Nucleotide Sequencing/methods , Genomics/methods , Y Chromosome
15.
Rev Esp Enferm Dig ; 115(6): 344-345, 2023 06.
Article in English | MEDLINE | ID: mdl-37170538

ABSTRACT

We present the case of an 83-year-old male, with a past medical history of benign pneumoperitoneum secondary to pneumatosis intestinalis which evolved for a number of years with periodic follow-ups. The patient comes to the Emergency Room with sintomatology of intestinal obstruction. Urgent surgical management is decided, an exploratory laparotomy is performed where an intestinal obstruction secondary to pneumatosis intestinalis, with loss of structure of the intestinal wall as visualized in the images, is determined; therefore resection of the affected small intestine segment and primary anastomosis are performed. The pathology report confirms the diagnosis. The patient progresses favorably during the postoperative period and is currently asymptomatic after 12 months.


Subject(s)
Intestinal Obstruction , Pneumatosis Cystoides Intestinalis , Male , Humans , Aged, 80 and over , Pneumatosis Cystoides Intestinalis/complications , Pneumatosis Cystoides Intestinalis/diagnostic imaging , Pneumatosis Cystoides Intestinalis/surgery , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Intestine, Small , Intestines , Tomography, X-Ray Computed
16.
Healthcare (Basel) ; 11(10)2023 May 11.
Article in English | MEDLINE | ID: mdl-37239676

ABSTRACT

We investigated the influence of post-traumatic growth (PTG) and mental health (MH) on multiple sclerosis (MS) caregivers' uses of coping strategies and identified biopsychosocial predictors of proactive or reactive coping. The Short Form Health Survey (SF-12), General Health Questionnaire (GHQ-28), Post-Traumatic Growth Inventory (PGI-21), Brief COPE Questionnaire (COPE-28), and Multidimensional Scale of Perceived Social Support (MSPSS) were used to evaluate 209 caregivers. Higher PTG was related to greater use of emotional support, positive reframing, religion, active coping, instrumental support, planning, denial, self-distraction, self-blaming, and venting. Better MH was associated with greater use of acceptance, while behavioral disengagement and self-distraction were associated with poorer MH. The PTG dimensions relating to others and new possibilities, SF-12 dimensions of physical and emotional roles as well as partnership, not living with the patient, and significant others' social support were predictors of proactive coping. Reactive coping was positively predicted by the PTG dimension relating to others, depression, vitality, other than partner relation, and physical role, and negatively predicted by mental health level and emotional role. In summary, higher MH was associated with proactive coping strategies, whereas post-traumatic growth was related to the use of a wide range of proactive coping as well as reactive coping strategies.

17.
Mol Ecol ; 32(22): 5894-5912, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37203688

ABSTRACT

Understanding patterns of diversity across macro (e.g. species-level) and micro (e.g. molecular-level) scales can shed light on community function and stability by elucidating the abiotic and biotic drivers of diversity within ecological communities. We examined the relationships among taxonomic and genetic metrics of diversity in freshwater mussels (Bivalvia: Unionidae), an ecologically important and species-rich group in the southeastern United States. Using quantitative community surveys and reduced-representation genome sequencing across 22 sites in seven rivers and two river basins, we surveyed 68 mussel species and sequenced 23 of these species to characterize intrapopulation genetic variation. We tested for the presence of species diversity-abundance correlations (i.e. the more-individuals hypothesis, MIH), species-genetic diversity correlations (SGDCs) and abundance-genetic diversity correlations (AGDCs) across all sites to evaluate relationships between different metrics of diversity. Sites with greater cumulative multispecies density (a standardized metric of abundance) had a greater number of species, consistent with the MIH hypothesis. Intrapopulation genetic diversity was strongly associated with the density of most species, indicating the presence of AGDCs. However, there was no consistent evidence for SGDCs. Although sites with greater overall densities of mussels had greater species richness, sites with higher genetic diversity did not always exhibit positive correlations with species richness, suggesting that there are spatial and evolutionary scales at which the processes influencing community-level diversity and intraspecific diversity differ. Our work reveals the importance of local abundance as indicator (and possibly a driver) of intrapopulation genetic diversity.


Subject(s)
Bivalvia , Unionidae , Humans , Animals , Metagenomics , Biodiversity , Fresh Water , Rivers , Bivalvia/genetics , Ecosystem
18.
Acta Neuropathol Commun ; 11(1): 49, 2023 03 22.
Article in English | MEDLINE | ID: mdl-36949514

ABSTRACT

Myelination of neuronal axons is a critical aspect of central nervous system development and function. However, the fundamental cellular and molecular mechanisms influencing human developmental myelination and its failure are not fully understood. Here, we used digital spatial transcriptomics of a rare bank of human developing white matter to uncover that a localized dysregulated innate immune response is associated with impeded myelination. We identified that poorly myelinating areas have a distinct signature of Type II interferon signalling in microglia/macrophages, relative to adjacent myelinating areas. This is associated with a surprising increase in mature oligodendrocytes, which fail to form myelin processes appropriately. We functionally link these findings by showing that conditioned media from interferon-stimulated microglia is sufficient to dysregulate myelin process formation by oligodendrocytes in culture. We identify the Type II interferon inducer, Osteopontin (SPP1), as being upregulated in poorly myelinating brains, indicating a potential biomarker. Our results reveal the importance of microglia-mature oligodendrocyte interaction and interferon signaling in regulating myelination of the developing human brain.


Subject(s)
Microglia , Myelin Sheath , Humans , Myelin Sheath/physiology , Oligodendroglia/physiology , Axons/physiology , Brain
19.
Rev. cient. cienc. salud ; 5(1): 1-10, 26-01-2023.
Article in Spanish | LILACS, BDNPAR | ID: biblio-1512809

ABSTRACT

Introducción. El síndrome metabólico (SM) constituye una serie de desórdenes metabólicos que en conjunto son considerados factor de riesgo para desarrollar diabetes y enfermedad cardiovascular. Objetivo. Determinar la prevalencia del SM y sus componentes en estudiantes del campus San Lorenzo dela Universidad Nacional de Asunción en el periodo 2015-2016. Materiales y métodos. Estudio observacional descriptivo de corte transverso con un muestreo por conglomerados. Se incluyeron a 163 estudiantes de facultades o institutos seleccionados. Se aplicó un cuestionario para datos sociodemográficos y actividad física, y se realizaron mediciones de circunferencia de cintura(CC), peso y altura, además de niveles séricos en ayunas de glucosa, colesterol-HDLc y triglicéridos, conjuntamente con medición de presión arterial para determinar la presencia de SM según los criterios del Panel III (NCEP-ATP-III). Los datos fueron resguardados con estricta confidencialidad. Resultados.El50,92% de los participantes era del sexo masculino, con edad promedio de 21,6± 2,4 años. El 49,7% fueron considerados sedentarios,25,16% presentó sobrepeso, 8,59% obesidad,6,75% CCelevaday16,56% hipertensión. El 2,45% y 4,9% presenta ronglicemia basal y triglicérido elevados, respectivamente, y 37,42%HDL-c bajo. La prevalencia del SM fue del 4,91%,el 52,15 % presentó al menos un factor del NCEP-ATP-III para SM Conclusión. Alrededor de la mitad de los participantes presentó al menos un factor de riesgo de SM, y los componentes más frecuentes fueron la baja concentración de HDLc, y la hipertensión arterial. Se recomienda acciones preventivas en la población juvenil basadas en actividad física y alimentación saludable. Palabras Clave: síndrome metabólico; hipertensión; sobrepeso; adulto joven


Introduction: The metabolic syndrome (MS) constitutes of a series of metabolic disorders that together are considered a risk factor to develop diabetes and cardiovascular disease.Objective.To determine the prevalence of MS and its components in students of the National University of Asunción ­San Lorenzo Campusin the 2015-2016 period. Materials and Methods.Observational descriptive cross-sectional study with a cluster sampling. A total of 163 students from selected faculties or instituteswas included. A questionnaire was applied for sociodemographic data and physical activityandwaist circumference(WC), weight and height were measured, as well as fasting serum levels of Glucose, HDLc cholesterol and triglycerides, together with blood pressure to determine the presence of MS according to the Panel III criteria (NCEP-ATP-III). All data were kept strictly confidential. Results. 50,92% of participants were male, with a mean age of 21,6± 2,4 years.49.7% were considered sedentary,25,16% presented overweight, and 8,59% obesity, 16,56%hypertension. 6,75% presentedan elevated abdominal circumference,2,45% elevated basal glycemia, 4,9% elevated Triglycerides, 37,42% low HDLc.The prevalence of MS was 4,91%and52,15% presented at least one NCEP-ATP-III factor for MS. Conclusion. Aroundhalf of the participantspresented at least one risk factor for MS, the most frequent components were low HDLc concentration and arterial hypertension.It is recommendedpreventive actions in the youth population based on physical activity and healthy eating. Key words: metabolic syndrome; hypertension; overweight; young adult


Subject(s)
Humans , Male , Female , Metabolic Syndrome , Hypertension , Overweight , Young Adult
20.
Nature ; 613(7942): 120-129, 2023 01.
Article in English | MEDLINE | ID: mdl-36517604

ABSTRACT

Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health1, it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFß1-TGFßR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease2,3.


Subject(s)
Central Nervous System , Microglia , Myelin Sheath , Adult , Animals , Humans , Mice , Axons/metabolism , Central Nervous System/cytology , Central Nervous System/metabolism , Central Nervous System/pathology , Microglia/cytology , Microglia/metabolism , Microglia/pathology , Myelin Sheath/metabolism , Myelin Sheath/pathology , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Oligodendroglia/metabolism , Oligodendroglia/pathology , Cognition , Transforming Growth Factor beta1/metabolism , Receptor, Transforming Growth Factor-beta Type I/metabolism , Lipid Metabolism , Aging/metabolism , Aging/pathology
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