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1.
Artículo en Inglés, Español | MEDLINE | ID: mdl-39128693

RESUMEN

Osteoporosis, and the consequences derived from it, such as fragility fractures, constitute a growing public health problem. Suffering from a fracture of this nature is the main risk factor for suffering a new fracture. It is documented that vertebral compression fractures lead to significant morbidity and mortality, in the short and long term, as well as other complications, such as sagittal imbalance and hyperkyphosis of the segment. However, we have not found documentation that analyzes the medium and long-term consequences of these injuries, assessing the type of treatment used, and the economic impact they represent. The purpose of this review is to analyze the main recent literature on the subject and make a breakdown of the consequences of these fractures in various spheres, such as economic, quality of life, sagittal balance and radiographic parameters, pain or mortality; as well as a brief analysis of epidemiology and natural history. Conclusion Osteoporotic fractures constitute an emerging problem, both in the medical and economic fields. The consequences and sequelae on the patient are multiple and although surgical options offer good long-term results, it is necessary to properly select the patient, through multidisciplinary teams, to try to minimize potential complications.

2.
Glob Chang Biol ; 30(8): e17481, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39161269

RESUMEN

Rising global temperatures present unprecedented challenges to marine ecosystems, demanding a profound understanding of their ecological dynamics for effective conservation strategies. Over a comprehensive macroalgal assessment spanning three decades, we investigated the spatiotemporal evolution of shallow-water benthic communities in the southern Bay of Biscay, uncovering climate-resilient areas amidst the ongoing phase shift in the region. Our investigation identified seven locations serving as potential climate refugia, where cold-affinity, canopy-forming macroalgal species persisted and community structure was similar to that observed in 1991. We unveiled a clear association between the emergence of these refugia, sea surface temperature (SST), and the Community Temperature Index, positioning SST as a significant driver of the observed phase shift in the region. Warming processes, defined as tropicalization (increase of warm-affinity species) and deborealization (decrease of cold-affinity species), were prominent outside refugia. In contrast, cooling processes, defined as borealization (increase of cold-affinity species) and detropicalization (decrease of warm-affinity species), prevailed inside refugia. Refugia exhibited approximately 35% lower warming processes compared to non-refuge areas. This resulted in a dominance of warm-affinity species outside refugia, contrasting with the stability observed within refugia. The persistence of canopy-forming species in refuge areas significantly contributed to maintaining ecosystem diversity and stability. These findings underscored the pivotal role of climate refugia in mitigating climate-driven impacts. Prioritizing the protection and restoration of these refugia can foster resilience and ensure the preservation of biodiversity for future generations. Our study illustrates the importance of refining our understanding of how marine ecosystems respond to climate change, offering actionable insights essential for informed conservation strategies and sustainable environmental management.


Asunto(s)
Cambio Climático , Refugio de Fauna , Algas Marinas , Temperatura , Algas Marinas/fisiología , Bahías , Ecosistema , Biodiversidad
3.
Med Oral Patol Oral Cir Bucal ; 29(5): e711-e718, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39088719

RESUMEN

BACKGROUND: The aim of this systematic review and meta-analysis was to analyze the scientific evidence about the association between osteoporosis in postmenopausal women and the prevalence of apical periodontitis, assessed radiographically. MATERIAL AND METHODS: PRISMA Guidelines have been followed. The research question was: In adult women, does the presence or absence of osteoporosis affect the prevalence of AP, radiographically diagnosed? A systematic search was performed in PubMed/MEDLINE, Web of Science, Scopus and EMBASE. The meta-analyses were calculated with the Open Meta Analyst software. Risk of bias was assessed using the Newcastle Ottawa Scale. The certainty of evidence was assessed by GRADE. RESULTS: Four studies were selected. Meta-analysis showed an overall OR = 2.2 (95% CI = 0.94 - 4.97; p = 0.07), indicating that osteoporotic women had approximately twice the probability of having periapical lesions, compared to control women, although the difference was only marginally significant. The overall risk of bias of the included studies was moderate, and the certainty of evidence was low. CONCLUSIONS: Apical periodontitis, assessed as periapical lesion, is more frequently diagnosed in osteoporotic women, who are twice as likely to have periapical radiolucent lesions.


Asunto(s)
Osteoporosis Posmenopáusica , Periodontitis Periapical , Humanos , Femenino , Periodontitis Periapical/epidemiología , Periodontitis Periapical/complicaciones , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/epidemiología , Prevalencia , Posmenopausia
4.
Rev Clin Esp (Barc) ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39216808

RESUMEN

Chronic heart failure (CHF) represents a challenge for the healthy system due to its high prevalence, high burden of morbidity and mortality, and high consumption of health resources. To address this problem, it is necessary to develop efficient management strategies that include both hospital care and outpatient care. The primary objective is to stabilize the patient and prevent decompensation, with the consequent improvement in quality of life, reduction in hospital admissions and emergency department care, and, consequently, reduction in healthcare costs. In this context, the heart failure and atrial fibrilation working group of the Spanish Society of Internal Medicine has developed a protocol for the management of outpatient CHF, that addresses, from the perspective of Internal medicine, all the problems suffered by the patient with CHF. This protocol aims to optimize pharmacological treatment, control cardiovascular risk factors and various comorbidities, educate the patient and their environment about the disease, promote adherence to treatment and stablish follow-up adapted to their condition.

5.
Biol Open ; 13(9)2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39158383

RESUMEN

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder affecting 1:3500 male births and is associated with myofiber degeneration, regeneration, and inflammation. Glucocorticoid treatments have been the standard of care due to immunomodulatory/immunosuppressive properties but novel genetic approaches, including exon skipping and gene replacement therapy, are currently being developed. The identification of additional biomarkers to assess DMD-related inflammatory responses and the potential efficacy of these therapeutic approaches are thus of critical importance. The current study uses RNA sequencing of skeletal muscle from two mdx mouse models to identify high mobility group box 1 (HMGB1) as a candidate biomarker potentially contributing to DMD-related inflammation. HMGB1 protein content was increased in a human iPSC-derived skeletal myocyte model of DMD and microdystrophin treatment decreased HMGB1 back to control levels. In vivo, HMGB1 protein levels were increased in vehicle treated B10-mdx skeletal muscle compared to B10-WT and significantly decreased in B10-mdx animals treated with adeno-associated virus (AAV)-microdystrophin. However, HMGB1 protein levels were not increased in D2-mdx skeletal muscle compared to D2-WT, demonstrating a strain-specific difference in DMD-related immunopathology.


Asunto(s)
Biomarcadores , Modelos Animales de Enfermedad , Proteína HMGB1 , Ratones Endogámicos mdx , Distrofia Muscular de Duchenne , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/genética , Animales , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Ratones , Humanos , Músculo Esquelético/metabolismo , Distrofina/metabolismo , Distrofina/genética , Células Madre Pluripotentes Inducidas/metabolismo , Masculino
6.
Trop Med Infect Dis ; 9(8)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39195606

RESUMEN

Leptospira is a bacterial genus that includes several pathogenic species related to leptospirosis. In Colombia, leptospirosis is a mandatorily reported disease, widely distributed across the country. In the Villeta municipality, leptospirosis has been identified as an important cause of febrile illness; however, to date, no studies have been performed to identify the circulating species. A genus-specific qualitative qPCR was performed on DNA extracted from febrile patients' acute-phase whole-blood samples targeting a fragment of the rrs gene. Positive qPCR samples were further amplified for the adk, icdA, LipL32, LipL41, rrs, and secY genes through conventional PCR for sequencing. All high-quality obtained sequences were further assessed through concatenated phylogenetic analysis. A total of 25% (14/56) of febrile patients' acute blood samples were positive for Leptospira spp. High-quality sequences were obtained for only five genes, and analysis through concatenated phylogeny identified that all sequences clustered within the P1/pathogenic clade; some of them formed a robustly supported clade with Leptospira santarosai, and others were closely related with other Leptospira species but exhibited considerable genetic divergence. We describe the presence of pathogenic Leptospira species among febrile patients from the Villeta municipality and identify L. santarosai and other Leptospira species as causative agents of leptospirosis in the region.

7.
Acta Trop ; : 107370, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39216810

RESUMEN

Bartonella is a bacterial genus that comprises arthropod-borne microorganisms. Several Bartonella isolates have been detected from bats worldwide, which are thought to be undescribed species. We aimed to test the presence of Bartonella spp. among bats from Colombia, and evaluate the genetic diversity of bat-associated Bartonella spp. through phylogenetic analyses. A total of 108 bat blood samples were collected from three bat species (Carollia perspicillata, Mormoops megalophylla, and Natalus tumidirostris) that inhabit the Macaregua cave. The Bartonella ssrA gene was targeted through real-time and end-point PCR; additionally, the gltA and rpoB genes were detected by end-point PCR. All obtained amplicons were purified and bidirectionally sequenced for phylogenetic analysis using a concatenated supermatrix and a supertree approaches. A detection frequency of 49.1% (53/108) for Bartonella spp. was evidenced among bat blood samples, of which 59.1% (26/44), 54.3% (19/35) and 27.6% (8/29) were identified in Carollia perspicillata, Natalus tumidirostris and Mormoops megalophylla respectively. A total of 35 ssrA, 5 gltA and 4 rpoB good-quality sequences were obtained which were used for phylogenetic analysis. All obtained bat sequences clustered together with sequences obtained from Neotropical bat species into two bat-restricted clades namely clade A and clade N. We detected the presence of Bartonella spp. that clustered within two different bat-associated Bartonella clades, giving the first data of the genetic diversity of these bacteria among bats from Colombia.

8.
Sci Rep ; 14(1): 15157, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956353

RESUMEN

Affiliated athletes are frequently subject to higher levels of anxiety due to the intensity of training, competition and many other factors. This anxiety can cause alterations in their health, both physically and mentally, such as menstrual irregularities, eating disorders, etc. In this work we have analysed the anxiety levels of a population of female affiliated paddlers and the possible consequences for their health. The results showed that a third of the female paddlers analysed have a moderate/high risk of suffering from anxiety; and within this group, the less sporting experience the athlete has, the greater the probability is of suffering from anxiety. Moreover, almost half the total of the female paddlers suffers from menstrual dysfunction before an important competition, with this number rising among high performance athletes, even though three out of every four adjust their training schedule to their menstrual cycle. Less-experienced female athletes, who show higher anxiety levels, also present a greater risk of suffering from eating disorders.


Asunto(s)
Ansiedad , Atletas , Trastornos de Alimentación y de la Ingestión de Alimentos , Trastornos de la Menstruación , Humanos , Femenino , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Atletas/psicología , Trastornos de la Menstruación/epidemiología , Trastornos de la Menstruación/etiología , Adulto , España/epidemiología , Adulto Joven , Factores de Riesgo , Deportes , Adolescente
9.
Sci Rep ; 14(1): 15378, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965295

RESUMEN

The possibility of inducing new polar and/or magnetic transient states through the pumping of optical phonons towards the non-linear regime has renewed the scientific interest in orthoferrites. Nonetheless, to perform these studies it is fundamental to have a deep knowledge of the lattice excitations at equilibrium conditions. In this work, we present a complete characterization of the optically-active zone-center phonons in NdFeO3 single crystals at room temperature by means of polarized Raman and infrared spectroscopies. The study is complemented with polarized infrared spectroscopy at 4 K and unpolarized Raman scattering at 10 K. The predicted polar phonons were successfully observed together with some of the crystal-field excitations. First-principles simulations further allow the eigenmode and symmetry assignments of the optical phonons. The calculated atomic motions of each mode are of significant interest, as they are common for all orthoferrites and to most of the large family of orthorhombic Pbnm perovskites.

10.
Dev Cogn Neurosci ; 69: 101397, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-39029330

RESUMEN

Measures of physical growth, such as weight and height have long been the predominant outcomes for monitoring child health and evaluating interventional outcomes in public health studies, including those that may impact neurodevelopment. While physical growth generally reflects overall health and nutritional status, it lacks sensitivity and specificity to brain growth and developing cognitive skills and abilities. Psychometric tools, e.g., the Bayley Scales of Infant and Toddler Development, may afford more direct assessment of cognitive development but they require language translation, cultural adaptation, and population norming. Further, they are not always reliable predictors of future outcomes when assessed within the first 12-18 months of a child's life. Neuroimaging may provide more objective, sensitive, and predictive measures of neurodevelopment but tools such as magnetic resonance (MR) imaging are not readily available in many low and middle-income countries (LMICs). MRI systems that operate at lower magnetic fields (< 100mT) may offer increased accessibility, but their use for global health studies remains nascent. The UNITY project is envisaged as a global partnership to advance neuroimaging in global health studies. Here we describe the UNITY project, its goals, methods, operating procedures, and expected outcomes in characterizing neurodevelopment in sub-Saharan Africa and South Asia.

11.
J Hosp Infect ; 152: 13-20, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39032565

RESUMEN

BACKGROUND: Peripheral venous catheter-associated Staphylococcus aureus bacteraemia (PVC-SAB) is a potentially life-threatening nosocomial infection. AIM: This cohort study aims to identify the risk factors associated with its mortality and complications. METHODS: Retrospective analysis of a prospective cohort study conducted at two tertiary-care hospitals in Spain. Adult patients admitted between January 2011 and July 2019 which developed PVC-SAB during their hospital stay were included. Primary outcome was all-cause 30- and 90-day mortality. Secondary outcomes were sepsis or septic shock at the onset of bacteraemia, metastatic infection and length of hospital stay. Univariate and multivariate analyses were performed. FINDINGS: A total of 256 PVC-SAB were diagnosed in 243 patients between 2011 and 2019. Thirty-day and 90-day all-cause mortality were 18.3% and 24.2%, respectively. Lack of susceptible antibiotic administration the day after blood culture collection (odds ratio: 4.14; 95% confidence interval: 1.55-11.03; P = 0.005), sepsis and complicated bacteraemia were identified as independent risk factors for 30- and 90-day mortality; meticillin-resistant S. aureus bacteraemia was identified as an independent risk factor only for 30-day mortality and functional dependence only for 90-day mortality. Persistent bacteraemia and sepsis were associated with septic metastases, which significantly increased hospital stay, and endocarditis. A greater proportion of patients experiencing septic shock were subsequently institutionalized compared to those without. CONCLUSION: PVC-SAB remains linked to high mortality rates. Prompt administration of appropriate antibiotics is crucial for lowering mortality. A comprehensive diagnostic approach is essential, especially in patients with persistent bacteraemia and implanted cardiovascular devices, to rule out metastatic complications and endocarditis.

12.
Acta Crystallogr C Struct Chem ; 80(Pt 8): 357-365, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39051727

RESUMEN

A series of organotin heterocycles of general formula [{Me2C(C6H3CH2)2O}SnR2] [R = methyl (Me, 4), n-butyl (n-Bu, 5), benzyl (Bn, 6) and phenyl (Ph, 7)] was easily synthesized by a Barbier-type reaction assisted by the sonochemical activation of metallic magnesium. The 119Sn{1H} NMR data for all four compounds confirm the presence of a central Sn atom in a four-coordinated environment in solution. Single-crystal X-ray diffraction studies for 17,17-dimethyl-7,7-diphenyl-15-oxa-7-stannatetracyclo[11.3.1.05,16.09,14]heptadeca-1,3,5(16),9(14),10,12-hexaene, [Sn(C6H5)2(C17H16O)], 7, at 100 and 295 K confirmed the formation of a mononuclear eight-membered heterocycle, with a conformation depicted as boat-chair, resulting in a weak Sn...O interaction. The Sn and O atoms are surrounded by hydrophobic C-H bonds. A Hirshfeld surface analysis of 7 showed that the eight-membered heterocycles are linked by weak C-H...π, π-π and H...H noncovalent interactions. The pairwise interaction energies showed that the cohesion between the heterocycles are mainly due to dispersion forces.

13.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39078239

RESUMEN

Ion temperature, rotation, and density are key parameters to evaluate the performance of present and future fusion reactors. These parameters are critical for understanding ion heat, momentum, and particle transport, making it mandatory to properly diagnose them. A common technique to measure these properties is charge exchange recombination spectroscopy (CXRS). For characterizing positive and negative triangularity plasmas at the small aspect ratio tokamak, a poloidal array of gas puff based CXRS diagnostics will be measuring the ion properties in different poloidal positions. In this work, the modeling of the expected signal and spatial coverage using the FIDASIM code is presented. Furthermore, the design and characterization of the low field side midplane CXRS diagnostic are described. Each diagnostic is composed of a gas injection system, an optical system that collects the light emitted by the plasma, and a spectrometer. These systems will provide ion temperature, rotation, and density with a radial resolution of 3.75 mm and a temporal resolution of 2.2 ms.

14.
Actas Dermosifiliogr ; 2024 Jul 18.
Artículo en Inglés, Español | MEDLINE | ID: mdl-39032773

RESUMEN

BACKGROUND: Functional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents. OBJECTIVE: To evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used. PATIENTS AND METHODS: The Spanish Infantile Hemangioma Nationwide Prospective Cohort (2016-2022) recruited all consecutive patients diagnosed with IH in 12 Spanish hospitals. The children included had two photos of the IH lesion (at both baseline and at the end of the study). A panel of parents blindly assessed all available photos using a scale from 0 (worst cosmetic outcomes) to 10 (best cosmetic outcomes). The different scores - both before and after treatment - as well as the outcomes percent considered excellent (>9) were described and compared. We analyzed the effect of receiving different therapies and performed causal model analyses estimating the mean treatment effect of parents' assessments. RESULTS: The median follow-up was 3.1 years. A total of 824 photos were evaluated. Baseline aesthetic impact was higher in the propranolol group vs the topical timolol and observation treatment groups (1.85 vs 3.14 vs 3.66 respectively; p<0.001). After treatment, the aesthetic impact was similar between both treatment groups (7.59 vs 7.93 vs 7.90; p>0.2). The causal model could only be applied to the comparison between topical timolol and observation, revealing no differences whatsoever. CONCLUSION: This is the first prospective cohort to analyze the aesthetic outcome of IH. The final aesthetic results of the three therapies were similar, with nearly 40% of patients achieving excellent aesthetic outcomes.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38937197

RESUMEN

OBJECTIVE: Analyze the usefulness of the midline catheter in terms of efficacy and safety for treatments lasting more than 3 days in the neonatal population requiring admission to the NICU. DESIGN: Analytical and observational of a prospective cohort (December 2021-November 2023) compared to a historical cohort (January 2020-November 2021). SETTING: 9-bed Neonatal Intensive Care Unit (NICU, level III hospital. PATIENTS OR PARTICIPANTS: 288, 66 midline group and 222 control group. INCLUSION CRITERIA: newborns from 24 to 42 weeks of gestation who required short peripheral or midline cannulation and treatment longer than 3 days. INTERVENTIONS: Follow-up during NICU stay and comparison with retrospective data from a historical cohort. MAIN VARIABLES OF INTEREST: Sociodemographics, success rate (permanence of the same vascular catheter without complications until finish the prescribed treatment), number of catheters, cannulation rate per patient, indwell time, complications. RESULTS: The midline group showed a higher success rate (54.2% vs 5.6%, p < 0.001), a lower number of canalizations per patient (p < 0.001), a longer indwell time (p < 0.001) and a lower number of extravasations (p < 0.001). CONCLUSIONS: The midline catheter has advantages over short peripheral catheters, being a useful alternative in terms of efficacy and safety for treatments lasting more than 3 days in the neonatal population that requires admission to the NICU.

16.
Meat Sci ; 216: 109558, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38850887

RESUMEN

Pale, Soft, and Exudative (PSE)-like pork defects are associated with fiber destruction and pale discoloration and have become a severe economic burden for the European meat sector. However, robust detection of PSE-like pork and its diverse features is challenging and makes studies into defect causation difficult. Implementation of histological examination may improve our knowledge about less-known features linked to PSE-like defects. Here we evaluate if a new histological protocol can reveal how myopathy in ham may be associated with visual and traditional physicochemical anomalies of PSE-like pork. We first created a list of pathological features, quantified them, and integrated them into a myodegeneration scoring scheme (MYO) for semimembranosus muscle sections. We then explored potential associations between overall MYO scoring and individual histology features with visual PSE-like defect scoring (DES) and with individual meat quality variables [pHu, color: L*, a*, b* (CIELAB), bioimpedance, and near-infrared spectroscopy (NIR)]. As the primary finding of this study, we show a significant association between overall myopathy (MYO) scoring and PSE-like defect (DES) scores. We also found associations of specific myopathy features with DES scores, and of overall MYO scoring with specific quality variables. In all, our data suggest links between signs of acute myodegeneration and PSE-like defects. Our data, hence, supports the implementation of semi-quantitative histopathological approaches for diagnosing PSE-like pork features and may help identify the underlying mechanisms behind these defects.


Asunto(s)
Color , Enfermedades Musculares , Carne de Cerdo , Animales , Enfermedades Musculares/patología , Carne de Cerdo/análisis , Porcinos , Músculo Esquelético/patología , Enfermedades de los Porcinos/patología , Músculos Isquiosurales/patología
17.
Aliment Pharmacol Ther ; 59(12): 1604-1615, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38690746

RESUMEN

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.


Asunto(s)
Fosfatasa Alcalina , Ácido Quenodesoxicólico , Colagogos y Coleréticos , Quimioterapia Combinada , Cirrosis Hepática Biliar , Ácido Ursodesoxicólico , Humanos , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Ácido Ursodesoxicólico/uso terapéutico , Estudios Longitudinales , Cirrosis Hepática Biliar/tratamiento farmacológico , Anciano , Resultado del Tratamiento , Fosfatasa Alcalina/sangre , Colagogos y Coleréticos/uso terapéutico , Ácidos Fíbricos/uso terapéutico , España , Bilirrubina/sangre , Adulto
18.
Int J Biol Macromol ; 272(Pt 2): 132705, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38810850

RESUMEN

Trypanosoma cruzi is the causative agent of Chagas disease, as well as a trypanosomatid parasite with a complex biological cycle that requires precise mechanisms for regulating gene expression. In Trypanosomatidae, gene regulation occurs mainly at the mRNA level through the recognition of cis elements by RNA-binding proteins (RBPs). Alba family members are ubiquitous DNA/RNA-binding proteins with representatives in trypanosomatid parasites functionally related to gene expression regulation. Although T. cruzi possesses two groups of Alba proteins (Alba1/2 and Alba30/40), their functional role remains poorly understood. Thus, herein, a characterization of T. cruzi Alba (TcAlba) proteins was undertaken. Physicochemical, structural, and phylogenetic analysis of TcAlba showed features compatible with RBPs, such as hydrophilicity, RBP domains/motifs, and evolutionary conservation of the Alba-domain, mainly regarding other trypanosomatid Alba. However, in silico RNA interaction analysis of T. cruzi Alba proteins showed that TcAlba30/40 proteins, but not TcAlba1/2, would directly interact with the assayed RNA molecules, suggesting that these two groups of TcAlba proteins have different targets. Given the marked differences existing between both T. cruzi Alba groups (TcAlba1/2 and TcAlba30/40), regarding sequence divergence, RNA binding potential, and life-cycle expression patterns, we suggest that they would be involved in different biological processes.


Asunto(s)
Filogenia , Proteínas Protozoarias , Proteínas de Unión al ARN , Trypanosoma cruzi , Trypanosoma cruzi/metabolismo , Trypanosoma cruzi/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/química , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/química , Unión Proteica , Secuencia de Aminoácidos , Secuencia Conservada
19.
Nat Plants ; 10(6): 1018-1026, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38806655

RESUMEN

The endosperm is a reproductive tissue supporting embryo development. In most flowering plants, the initial divisions of endosperm nuclei are not succeeded by cellularization; this process occurs only after a specific number of mitotic cycles have taken place. The timing of cellularization significantly influences seed viability and size. Previous research implicated auxin as a key factor in initiating nuclear divisions and determining the timing of cellularization. Here we uncover the involvement of a family of clustered auxin response factors (cARFs) as dosage-sensitive regulators of endosperm cellularization. cARFs, maternally expressed and paternally silenced, are shown to induce cellularization, thereby restricting seed growth. Our findings align with the predictions of the parental conflict theory, suggesting that cARFs represent major molecular targets in this conflict. We further demonstrate a recurring amplification of cARFs in the Brassicaceae, suggesting an evolutionary response to parental conflict by reinforcing maternal control over endosperm cellularization. Our study highlights that antagonistic parental control on endosperm cellularization converges on auxin biosynthesis and signalling.


Asunto(s)
Arabidopsis , Endospermo , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos , Endospermo/metabolismo , Endospermo/genética , Ácidos Indolacéticos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Brassicaceae/genética , Brassicaceae/metabolismo , Brassicaceae/fisiología , Reguladores del Crecimiento de las Plantas/metabolismo
20.
Pharmaceuticals (Basel) ; 17(5)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38794218

RESUMEN

Astrocytes play a pivotal role in maintaining brain homeostasis. Recent research has highlighted the significance of palmitic acid (PA) in triggering pro-inflammatory pathways contributing to neurotoxicity. Furthermore, Genomic-scale metabolic models and control theory have revealed that metabolic switches (MSs) are metabolic pathway regulators by potentially exacerbating neurotoxicity, thereby offering promising therapeutic targets. Herein, we characterized these enzymatic MSs in silico as potential therapeutic targets, employing protein-protein and drug-protein interaction networks alongside structural characterization techniques. Our findings indicate that five MSs (P00558, P04406, Q08426, P09110, and O76062) were functionally linked to nervous system drug targets and may be indirectly regulated by specific neurological drugs, some of which exhibit polypharmacological potential (e.g., Trifluperidol, Trifluoperazine, Disulfiram, and Haloperidol). Furthermore, four MSs (P00558, P04406, Q08426, and P09110) feature ligand-binding or allosteric cavities with druggable potential. Our results advocate for a focused exploration of P00558 (phosphoglycerate kinase 1), P04406 (glyceraldehyde-3-phosphate dehydrogenase), Q08426 (peroxisomal bifunctional enzyme, enoyl-CoA hydratase, and 3-hydroxyacyl CoA dehydrogenase), P09110 (peroxisomal 3-ketoacyl-CoA thiolase), and O76062 (Delta(14)-sterol reductase) as promising targets for the development or repurposing of pharmacological compounds, which could have the potential to modulate lipotoxic-altered metabolic pathways, offering new avenues for the treatment of related human diseases such as neurological diseases.

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