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1.
PLoS One ; 19(6): e0300706, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38935649

RESUMEN

The Level of Personality Functioning Scale-Self-Report (LPFS-SR) operationalizes Criterion A of the DSM-5 Alternative Model for Personality Disorders. The current study aimed 1) to examine the internal consistency of the Portuguese version of the LPFS-SR in a community sample and a clinical sample, 2) to compare non-clinical participants (N = 282, Mage = 48.01, SD = 10.87) with two samples of clinical participants, one composed of patients with a personality disorder diagnosis (PD sample, n = 40, Mage = 46.18, SD = 13.59) and the other of patients with other psychiatric diagnoses (OD sample, n = 148, Mage = 49.49, SD = 11.88), with respect to LPFS-SR dimensions and total score, 3) to examine the capacity of the LPFS-SR to discriminate between samples through the ROC curve analyses, and 4) to examine the factor structure of the Portuguese version of the LPFS-SR. The Portuguese version of the LPFS-SR revealed adequate internal consistency results, akin to the original data, in the community and clinical samples. The community sample differed significantly from both clinical samples in all the LPFS-SR dimensions and total score. The ROC curve analysis indicated an optimal cut-off for the total score of 272.00, corresponding to a sensitivity of 75% and a specificity of 89%, in the PD vs. community samples. The LPFS-SR total score discriminative capacity between the PD and OD samples was lower, albeit also significant (area-under-the-curve of .63; p = .027; 95% CI: .52-.74). The current study provided evidence of the LPFS-SR's unidimensionality in both community and clinical samples. Although this study has limitations, its findings contribute to a deeper understanding of the LPFS-SR construct, as well as to its cross-cultural validation.


Asunto(s)
Manual Diagnóstico y Estadístico de los Trastornos Mentales , Trastornos de la Personalidad , Autoinforme , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Trastornos de la Personalidad/diagnóstico , Portugal , Personalidad , Psicometría/métodos , Curva ROC , Reproducibilidad de los Resultados
2.
Materials (Basel) ; 17(12)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38930181

RESUMEN

Three-dimensional printing (3DP) has emerged as a promising method for creating intricate scaffold designs. This study assessed three 3DP scaffold designs fabricated using biodegradable poly(lactic) acid (PLA) through fused deposition modelling (FDM): mesh, two channels (2C), and four channels (4C). To address the limitations of PLA, such as hydrophobic properties and poor cell attachment, a post-fabrication modification technique employing Polyelectrolyte Multilayers (PEMs) coating was implemented. The scaffolds underwent aminolysis followed by coating with SiCHA nanopowders dispersed in hyaluronic acid and collagen type I, and finally crosslinked the outermost coated layers with EDC/NHS solution to complete the hybrid scaffold production. The study employed rotating wall vessels (RWVs) to investigate how simulating microgravity affects cell proliferation and differentiation. Human mesenchymal stem cells (hMSCs) cultured on these scaffolds using proliferation medium (PM) and osteogenic media (OM), subjected to static (TCP) and dynamic (RWVs) conditions for 21 days, revealed superior performance of 4C hybrid scaffolds, particularly in OM. Compared to commercial hydroxyapatite scaffolds, these hybrid scaffolds demonstrated enhanced cell activity and survival. The pre-vascularisation concept on 4C hybrid scaffolds showed the proliferation of both HUVECs and hMSCs throughout the scaffolds, with a positive expression of osteogenic and angiogenic markers at the early stages.

3.
Front Psychol ; 15: 1359695, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873509

RESUMEN

Introduction: Informal caregivers are the backbone of dementia care. iSupport is a World Health Organization digital support program for caregivers of people with dementia (PwD) that has been culturally adapted in several countries. iSupport was previously assessed for its feasibility in Portugal, and this country-specific version is now being utilized as a remote measurement tool (RMT). It constitutes the first internationally developed iSupport platform that is technically and scientifically enhanced to collect data on sociodemographic, clinical, and psychosocial variables of dementia care dyads. This paper characterizes the early adopters of iSupport-Portugal and discusses its exploration as a RMT. Methods: Cross-sectional data were collected between February and July 2023 from users registering on isupport-portugal.pt. To characterize caregivers and PwD, eligibility was limited to unpaid caregivers assisting community dwelling PwD (n = 173). Data were collected through self-administered instruments in users' accounts. Caregivers completed psychosocial measures on burden, anxiety, depression, quality of life, desire to institutionalize and usage of community services. Textual data on caregivers' needs underwent content analysis. Results: Among the early adopters of iSupport-Portugal (n = 365), 52.3% were informal caregivers, while 44.7% were health/social care professionals or others. Most caregivers were female (82.7%), middle-aged (M 51.7 years), highly educated (M 15.3 years) and supporting a parent (70.5%). Caregivers cared for a median of 24 h/week and 60.8% lived with the PwD. Neuropsychiatric symptoms were reported for 94.1% of PwD, who scored as moderately dependent (Barthel Index: M 14.0). Significant burden was reported by 88.4% of caregivers (≥21 on ZBI-22). Among caregivers scoring borderline or abnormal (≥8 on HADS) for anxiety, depression, or both (75.5%), 30.8% sought mental health counseling. Caregivers supporting a PwD not using community services scored higher on anxiety (p = 0.003), and depression (p = 0.009). Text data revealed unmet practical, emotional, and informational needs. Discussion: iSupport-Portugal has garnered fair initial interest from caregivers, particularly from those who are children, highly educated, and employed. Early adopters exhibited significant psychological distress, and both practical and emotional needs, which contrast with limited use of support services for themselves and the PwD. iSupport-Portugal shows promise for descriptive research on care dyads, particularly among newer generations of caregivers.

4.
J Environ Manage ; 365: 121391, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38905793

RESUMEN

In many industrial processes a large amount of water with high salinity is co-produced whose treatment poses considerable challenges to the available technologies. The produced water (PW) from offshore operations is currently being discharged to sea without treatment for dissolved pollutants due to space limitations. A biofilter on the seabed adjacent to a production platform would negate all size restrictions, thus reducing the environmental impact of oil and gas production offshore. The moving bed biofilm reactor (MBBR) was investigated for PW treatment from different oilfields in the North Sea at 10 °C and 40 °C, corresponding to the sea and PW temperature, respectively. The six PW samples in study were characterized by high salinity and chemical oxygen demand with ecotoxic effects on marine algae S. pseudocostatum (0.4%

5.
Epigenetics ; 19(1): 2368995, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38900099

RESUMEN

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia (SCA) caused by a polyglutamine expansion in the ataxin-3 protein, which initiates a cascade of pathogenic events, including transcriptional dysregulation. Genotype-phenotype correlations in MJD are incomplete, suggesting an influence of additional factors, such as epigenetic modifications, underlying the MJD pathogenesis. DNA methylation is known to impact the pathophysiology of neurodegenerative disorders through gene expression regulation and increased methylation has been reported for other SCAs. In this work we aimed to analyse global methylation in MJD carriers. Global 5-mC levels were quantified in blood samples of 33 MJD mutation carriers (patients and preclinical subjects) and 33 healthy controls, matched by age, sex, and smoking status. For a subset of 16 MJD subjects, a pilot follow-up analysis with two time points was also conducted. No differences were found in median global 5-mC levels between MJD mutation carriers and controls and no correlations between methylation levels and clinical or genetic variables were detected. Also, no alterations in global 5-mC levels were observed over time. Our findings do not support an increase in global blood methylation levels associated with MJD.


Asunto(s)
Metilación de ADN , Heterocigoto , Enfermedad de Machado-Joseph , Mutación , Humanos , Enfermedad de Machado-Joseph/genética , Enfermedad de Machado-Joseph/sangre , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios de Casos y Controles , Ataxina-3/genética , 5-Metilcitosina/metabolismo , 5-Metilcitosina/sangre , Anciano , Epigénesis Genética
6.
Foods ; 13(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38890823

RESUMEN

The nutritional composition of bovine liver, particularly in terms of vitamins E, ß-carotene, and cholesterol concentration, is significantly influenced by the cattle-rearing system and diet. This study aimed to elucidate the impact of four predominant cattle-rearing systems in the Eastern Amazon region on the vitamin E, ß-carotene content, and cholesterol levels in bovine liver during the rainy season. Liver-tissue samples were collected from 48 cattle, with twelve specimens representing each rearing system. The systems encompassed two native pastures located in flood-prone areas, cultivated pastures on upland terrain and a confinement-rearing system. Our findings indicate that, when considering all rearing systems collectively, there were no significant differences in the levels of vitamins and cholesterol in the liver tissues (p > 0.05). However, a marked disparity in cholesterol levels emerged when comparing intensive rearing systems to extensive ones, with the former demonstrating notably higher concentrations (p = 0.01). Additionally, the intensive rearing system was associated with elevated levels of ß-carotene (p < 0.01), α-tocopherol (p = 0.01), and ß-tocopherol (p = 0.01) relative to the extensive systems. No significant variations were observed amongst the different extensive systems (p > 0.05). These results suggest that, while all rearing systems yielded liver tissues with typical concentrations of vitamins and cholesterol, the intensive rearing system led to a higher accumulation of certain vitamin compounds. This study highlights the substantial nutritional implications of different cattle-rearing systems in the Eastern Amazon and provides valuable insights for developing dietary strategies to optimize the nutritional quality of bovine liver. Therefore, the generated results are groundbreaking in the Eastern Amazon, Brazil, and inspire the development of new research projects to address other demands in this field and achieve additional outcomes.

7.
Front Sociol ; 9: 1341578, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38895603

RESUMEN

The dangers and stresses of a police officer's career cause physical and psychological distress which in turn cause considerable challenges for the integration of professional, family, and personal life. This study focuses on the conditions that influence this articulation between the personal, family, and professional lives of Portuguese Police (PSP) officers. A questionnaire survey was applied to 414 police officers from 11 divisions of COMETLIS. At the empirical level, several models were tested to assess the articulation between the professional, family, and personal lives of police officers. The results highlight the influence of having young children, elderly people or other dependents living in the family home, as well as the employee's age, on the job's interaction with professional life. At a professional level, the variables shift work, professional category, years of service and working away from home were identified by the officers as conditioning factors in the work-family-personal life balance. Sex differences in the articulation of professional, family, and personal life were also observed.

8.
Sci Rep ; 14(1): 14271, 2024 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902321

RESUMEN

Understanding the neural, metabolic, and psychological mechanisms underlying human altruism and decision-making is a complex and important topic both for science and society. Here, we investigated whether transcranial Direct Current Stimulation (tDCS) applied to two prefrontal cortex regions, the ventromedial prefrontal cortex (vmPFC, anode) and the right dorsolateral prefrontal cortex (DLPFC, cathode) can induce changes in self-reported emotions and to modulate local metabolite concentrations. We employed in vivo quantitative MR Spectroscopy in healthy adult participants and quantified changes in GABA and Glx (glutamate + glutamine) before and after five sessions of tDCS delivered at 2 mA for 20 min (active group) and 1 min (sham group) while participants were engaged in a charitable donation task. In the active group, we observed increased levels of GABA in vmPFC. Glx levels decreased in both prefrontal regions and self-reported happiness increased significantly over time in the active group. Self-reported guiltiness in both active and sham groups tended to decrease. The results indicate that self-reported happiness can be modulated, possibly due to changes in Glx concentrations following repeated stimulation. Therefore, local changes may induce remote changes in the reward network through interactions with other metabolites, previously thought to be unreachable with noninvasive stimulation techniques.


Asunto(s)
Emociones , Corteza Prefrontal , Estimulación Transcraneal de Corriente Directa , Ácido gamma-Aminobutírico , Humanos , Masculino , Femenino , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiología , Adulto , Emociones/fisiología , Adulto Joven , Ácido gamma-Aminobutírico/metabolismo , Ácido Glutámico/metabolismo , Altruismo , Glutamina/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Corteza Prefontal Dorsolateral/metabolismo , Corteza Prefontal Dorsolateral/fisiología
9.
Science ; 384(6703): eadl0370, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38935708

RESUMEN

Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood. Using CRISPR screens in ILCs we identified previously unappreciated myocyte-specific enhancer factor 2d (Mef2d)-mediated regulation of GATA3-dependent type-2 lymphocyte differentiation. Mef2d-deletion from ILC2s and/or T cells specifically protected against an allergen lung challenge. Mef2d repressed Regnase-1 endonuclease expression to enhance IL-33 receptor production and IL-33 signaling and acted downstream of calcium-mediated signaling to translocate NFAT1 to the nucleus to promote type-2 cytokine-mediated immunity.


Asunto(s)
Factor de Transcripción GATA3 , Inmunidad Innata , Interleucina-33 , Factores de Transcripción MEF2 , Factores de Transcripción NFATC , Neumonía , Células Th2 , Animales , Ratones , Factores de Transcripción MEF2/metabolismo , Factores de Transcripción MEF2/genética , Células Th2/inmunología , Interleucina-33/metabolismo , Factores de Transcripción NFATC/metabolismo , Neumonía/inmunología , Factor de Transcripción GATA3/metabolismo , Factor de Transcripción GATA3/genética , Ratones Endogámicos C57BL , Diferenciación Celular , Señalización del Calcio , Hipersensibilidad/inmunología , Pulmón/inmunología , Alérgenos/inmunología , Linfocitos/inmunología , Proteína 1 Similar al Receptor de Interleucina-1
10.
Sci Rep ; 14(1): 14815, 2024 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937573

RESUMEN

The association of postpartum cardiac reverse remodeling (RR) with urinary proteome, particularly in pregnant women with cardiovascular (CV) risk factors who show long-term increased risk of cardiovascular disease and mortality is unknown. We aim to profile the urinary proteome in pregnant women with/without CV risk factors to identify proteins associated with postpartum RR. Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6 months postpartum. Shotgun HPLC-MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. An increase in arterial stiffness was documented from 3rd trimester to 6 months after delivery, being significantly elevated in women with CV risk factors. In addition, the presence of at least one CV risk factor was associated with worse LVM RR. We identified 6 and 11 proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system's activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Urinary proteome showed a predicting potential for identifying pregnant women with incomplete postpartum RR.


Asunto(s)
Periodo Posparto , Proteoma , Remodelación Ventricular , Humanos , Femenino , Embarazo , Adulto , Proteoma/análisis , Periodo Posparto/orina , Estudios Prospectivos , Biomarcadores/orina , Rigidez Vascular , Ecocardiografía , Factores de Riesgo
11.
Cureus ; 16(5): e60277, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38872649

RESUMEN

The purpose of this clinical report is to describe a 10-year clinical outcome of advanced surface ablation with photorefractive keratectomy (PRK) in a patient who had been previously incorrectly diagnosed with keratoconus (KC). Corneal ectasia is a rare but extremely relevant complication of laser vision correction, and KC represents a major contraindication for these procedures. Nonetheless, some surface ablation procedures, such as PRK, might be a valid option for particular patients with atypical corneal topography or subclinical or mild forms of KC. Patient education and complete preoperative refractive multimodal imaging are essential for a more conscious therapeutic decision, minimizing iatrogenic ectasia, as well as decreasing the number of patients who are incorrectly denied refractive surgery, as was the patient presented in this study.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38822989

RESUMEN

PURPOSE: There are no clinical treatments to prevent/revert age-related alterations associated with oocyte competence decline in the context of advanced maternal age. Those alterations have been attributed to oxidative stress and mitochondrial dysfunction. Our study aimed to test the hypothesis that in vitro maturation (IVM) medium supplementation with antioxidants (resveratrol or phloretin) may revert age-related oocyte competence decline. METHODS: Bovine immature oocytes were matured in vitro for 23 h (young) and 30 h (aged). Postovulatory aged oocytes (control group) and embryos obtained after fertilization were examined and compared with oocytes supplemented with either 2 µM of resveratrol or 6 µM phloretin (treatment groups) during IVM. RESULTS: Aged oocytes had a significantly lower mitochondrial mass and proportion of mitochondrial clustered pattern, lower ooplasmic volume, higher ROS, lower sirtuin-1 protein level, and a lower blastocyst rate in comparison to young oocytes, indicating that postovulatory oocytes have a lower quality and developmental competence, thus validating our experimental model. Supplementation of IVM medium with antioxidants prevented the generation of ROS and restored the active mitochondrial mass and pattern characteristic of younger oocytes. Moreover, sirtuin-1 protein levels were also restored but only following incubation with resveratrol. Despite these findings, the blastocyst rate of treatment groups was not significantly different from the control group, indicating that resveratrol and phloretin could not restore the oocyte competence of postovulatory aged oocytes. CONCLUSION: Resveratrol and phloretin can both revert the age-related oxidative stress and mitochondrial dysfunction during postovulatory aging but were insufficient to enhance embryo developmental rates under our experimental conditions.

13.
Eur J Heart Fail ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38837573

RESUMEN

Cardiovascular disease (CVD) is the leading cause of morbimortality in Europe and worldwide. CVD imposes a heterogeneous spectrum of cardiac remodelling, depending on the insult nature, that is, pressure or volume overload, ischaemia, arrhythmias, infection, pathogenic gene variant, or cardiotoxicity. Moreover, the progression of CVD-induced remodelling is influenced by sex, age, genetic background and comorbidities, impacting patients' outcomes and prognosis. Cardiac reverse remodelling (RR) is defined as any normative improvement in cardiac geometry and function, driven by therapeutic interventions and rarely occurring spontaneously. While RR is the outcome desired for most CVD treatments, they often only slow/halt its progression or modify risk factors, calling for novel and more timely RR approaches. Interventions triggering RR depend on the myocardial insult and include drugs (renin-angiotensin-aldosterone system inhibitors, beta-blockers, diuretics and sodium-glucose cotransporter 2 inhibitors), devices (cardiac resynchronization therapy, ventricular assist devices), surgeries (valve replacement, coronary artery bypass graft), or physiological responses (deconditioning, postpartum). Subsequently, cardiac RR is inferred from the degree of normalization of left ventricular mass, ejection fraction and end-diastolic/end-systolic volumes, whose extent often correlates with patients' prognosis. However, strategies aimed at achieving sustained cardiac improvement, predictive models assessing the extent of RR, or even clinical endpoints that allow for distinguishing complete from incomplete RR or adverse remodelling objectively, remain limited and controversial. This scientific statement aims to define RR, clarify its underlying (patho)physiologic mechanisms and address (non)pharmacological options and promising strategies to promote RR, focusing on the left heart. We highlight the predictors of the extent of RR and review the prognostic significance/impact of incomplete RR/adverse remodelling. Lastly, we present an overview of RR animal models and potential future strategies under pre-clinical evaluation.

14.
J Clin Invest ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38833311

RESUMEN

BACKGROUND: Clinical trials have suggested antitumor activity from PARP inhibition beyond homologous recombination deficiency (HRD). RNASEH2B loss is unrelated to HRD and preclinically sensitizes to PARP inhibition. The current study reports on RNASEH2B protein loss in advanced prostate cancer and its association with RB1 protein loss, clinical outcome and clonal dynamics during treatment with PARP inhibition in a prospective clinical trial. METHODS: Whole tumor biopsies from multiple cohorts of patients with advanced prostate cancer were interrogated using whole-exome sequencing (WES), RNA sequencing (bulk and single nucleus) and immunohistochemistry (IHC) for RNASEH2B and RB1. Biopsies from patients treated with olaparib in the TOPARP-A and TOPARP-B clinical trials were used to evaluate RNASEH2B clonal selection during olaparib treatment. RESULTS: Shallow co-deletion of RNASEH2B and adjacent RB1, co-located at chromosome 13q14, was common, deep co-deletion infrequent, and gene loss associated with lower mRNA expression. In castration-resistant PC (CRPC) biopsies, RNASEH2B and RB1 mRNA expression correlated, but single nucleus RNA sequencing indicated discordant loss of expression. IHC studies showed that loss of the two proteins often occurred independently, arguably due to stochastic second allele loss. Pre- and post-treatment metastatic CRPC (mCRPC) biopsy studies from BRCA1/2 wildtype tumors, treated on the TOPARP phase II trial, indicated that olaparib eradicates RNASEH2B-loss tumor subclones. CONCLUSION: PARP inhibition may benefit men suffering from mCRPC by eradicating tumor subclones with RNASEH2B loss. CLINICALTRIALS: gov NCT01682772FUNDING. AstraZeneca; Cancer Research UK; Medical Research Council; Cancer Research UK; Prostate Cancer UK; Movember Foundation; Prostate Cancer Foundation.

15.
J Phys Chem A ; 128(23): 4674-4684, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38815182

RESUMEN

This work presents a comprehensive study exploring the thermodynamics of the solid phase of a series of phenylimidazoles, encompassing experimental measurements of heat capacity, volatility, and thermal behavior. The influence of successive phenyl group insertions on the imidazole ring on thermodynamic properties and supramolecular behavior was thoroughly examined through the evaluation of 2-phenylimidazole (2-PhI), 4-phenylimidazole (4-PhI), 4,5-diphenylimidazole (4,5-DPhI), and 2,4,5-triphenylimidazole (2,4,5-TPhI). Structural correlations between molecular structure and thermodynamic properties were established. Furthermore, the investigation employed UV-vis spectroscopy and quantum chemical calculations. Additive effects arising from the introduction of phenyl groups were found through the analysis of the solid-liquid and solid-gas equilibria, as well as heat capacities. A good correlation emerged between the thermodynamic properties of sublimation and the molar volume of the unit cell, evident across 2-PhI, 4,5-DPhI, and 2,4,5-TPhI. In contrast to its isomer 2-PhI, 4-PhI exhibited greater cohesive energy due to the stronger N-H···N intermolecular interactions, leading to the disruption of coplanar geometry in the 4-PhI molecules. The observed higher entropies of phase transition (fusion and sublimation) are consistent with the higher structural order observed in the crystalline lattice of 4-PhI.

16.
ACS Appl Bio Mater ; 7(5): 2872-2886, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38721671

RESUMEN

Antimicrobial coatings provide protection against microbes colonization on surfaces. This can prevent the stabilization and proliferation of microorganisms. The ever-increasing levels of microbial resistance to antimicrobials are urging the development of alternative types of compounds that are potent across broad spectra of microorganisms and target different pathways. This will help to slow down the development of resistance and ideally halt it. The development of composite antimicrobial coatings (CACs) that can host and protect various antimicrobial agents and release them on demand is an approach to address this urgent need. In this work, new CACs based on microsized hybrids of calcium carbonate (CaCO3) and silver nanoparticles (AgNPs) were designed using a drop-casting technique. Polyvinylpyrrolidone and mucin were used as additives. The CaCO3/AgNPs hybrids contributed to endowing colloidal stability to the AgNPs and controlling their release, thereby ensuring the antibacterial activity of the coatings. Moreover, the additives PVP and mucin served as a matrix to (i) control the distribution of the hybrids, (ii) ensure mechanical integrity, and (iii) prevent the undesired release of AgNPs. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) techniques were used to characterize the 15 µm thick CAC. The antibacterial activity was determined against Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa, three bacteria responsible for many healthcare infections. Antibacterial performance of the hybrids was demonstrated at concentrations between 15 and 30 µg/cm2. Unloaded CaCO3 also presented bactericidal properties against MRSA. In vitro cytotoxicity tests demonstrated that the hybrids at bactericidal concentrations did not affect human dermal fibroblasts and human mesenchymal stem cell viability. In conclusion, this work presents a simple approach for the design and testing of advanced multicomponent and functional antimicrobial coatings that can protect active agents and release them on demand.


Asunto(s)
Antibacterianos , Carbonato de Calcio , Ensayo de Materiales , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Plata , Carbonato de Calcio/química , Carbonato de Calcio/farmacología , Plata/química , Plata/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Nanopartículas del Metal/química , Humanos , Supervivencia Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Escherichia coli/efectos de los fármacos , Propiedades de Superficie , Staphylococcus aureus/efectos de los fármacos
17.
Eur J Cancer ; 205: 114103, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38729054

RESUMEN

BACKGROUND: PTEN loss and aberrations in PI3K/AKT signaling kinases associate with poorer response to abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC). In this study, we assessed antitumor activity of the AKT inhibitor capivasertib combined with enzalutamide in mCRPC with prior progression on AA and docetaxel. METHODS: This double-blind, placebo-controlled, randomized phase 2 trial, recruited men ≥ 18 years with progressing mCRPC and performance status 0-2 from 15 UK centers. Randomized participants (1:1) received enzalutamide (160 mg orally, once daily) with capivasertib (400 mg)/ placebo orally, twice daily on an intermittent (4 days on, 3 days off) schedule. Primary endpoint was composite response rate (RR): RECIST 1.1 objective response, ≥ 50 % PSA decrease from baseline, or circulating tumor cell count conversion (from ≥ 5 at baseline to < 5 cells/7.5 mL). Subgroup analyses by PTENIHC status were pre-planned. RESULTS: Overall, 100 participants were randomized (50:50); 95 were evaluable for primary endpoint (47:48); median follow-up was 43 months. RR were 9/47 (19.1 %) enzalutamide/capivasertib and 9/48 (18.8 %) enzalutamide/placebo (absolute difference 0.4 % 90 %CI -12.8 to 13.6, p = 0.58), with similar results in the PTENIHC loss subgroup. Irrespective of treatment, OS was significantly worse for PTENIHC loss (10.1 months [95 %CI: 4.6-13.9] vs 14.8 months [95 %CI: 10.8-18]; p = 0.02). Most common treatment-emergent grade ≥ 3 adverse events for the combination were diarrhea (13 % vs 2 %) and fatigue (10 % vs 6 %). CONCLUSIONS: Combined capivasertib/enzalutamide was well tolerated but didn't significantly improve outcomes from abiraterone pre-treated mCRPC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Docetaxel , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración , Pirimidinas , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Feniltiohidantoína/administración & dosificación , Feniltiohidantoína/uso terapéutico , Feniltiohidantoína/efectos adversos , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Persona de Mediana Edad , Método Doble Ciego , Pirimidinas/uso terapéutico , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Androstenos/uso terapéutico , Androstenos/administración & dosificación , Anciano de 80 o más Años , Pirroles
18.
Ultrasound ; 32(2): 103-113, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38694827

RESUMEN

Background: Novel ultrasound technology and software processing allow offline evaluation of tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements. We wished to compare both novel 4D matrix (eM6C) and conventional (RAB6-D) transducers with variable settings (electronic spatiotemporal image correlation, spatiotemporal image correlation and four-dimensional real time) to determine if there was a significant difference in absolute value, quality and repeatability of the resultant reconstructed image and M-mode trace. Methods: A blinded prospective cross-sectional study of normal fetuses from 23 to 38 weeks' gestation were recruited. After routine sonography, four-dimensional volumes were stored and analysed using GE 4DView™ software. Statistical analysis explored variability, correlations and repeatability of the measurements with chi-square analysis, intraclass correlations and the Bland-Altman comparison plots. A scoring system was devised for image quality. Results: Eighteen participants generated 282 data volumes. Absolute values demonstrated some inconsistencies for both tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements with variations between transducers: the highest for the RAB6-D/spatiotemporal image correlation setting and the lowest for the four-dimensional real-time settings. The RAB6-D/spatiotemporal image correlation setting was the most repeatable combination (intraclass correlation coefficient = 0.85). Poorest image quality (M-mode trace, four-chamber view, annuli) came from the RAB6-D/four-dimensional real-time combination with the eM6C/electronic spatiotemporal image correlation and RAB6-D/spatiotemporal image correlation settings being nearly identical. Conclusion: We show that transducer and setting combinations influence absolute tricuspid annular plane systolic excursion/mitral annular plane systolic excursion measurements, so need to be articulated in future research. The transducer setting (electronic spatiotemporal image correlation/spatiotemporal image correlation/four-dimensional real time) was a more significant factor than the type of transducer (conventional vs matrix). Subjective image evaluation does not correlate well with repeatability of image acquisition. Further studies are needed to compare measurements using four-dimensional post-processing tools against conventional real-time measurements.

19.
Clin Ophthalmol ; 18: 1381-1390, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38770398

RESUMEN

Purpose: To evaluate the progression of chorioretinal atrophic areas associated with myopic choroidal neovascularization (CNV) in high myopic patients followed by a minimum period of 10 years. Patients and Methods: Patients with myopic CNV lesions that achieved clinical and structural remissions over 10 years of follow-up were included. Medical records were reviewed for CNV characterization and treatment, best-corrected visual acuity at baseline (BCVA0), immediately after the last treatment (BCVA1) and at the latest visit (BCVA2). Fundus autofluorescence (FAF) was used to quantify the amount of atrophic area increase per year associated with the treated myopic CNV lesion. The first FAF performed after treatment suspension (FAF1) was compared with the most recent exam (FAF2). Results: Thirty-six eyes from 36 patients were included. Mean total follow-up was 12.38 ± 2.68 years. Mean number of intravitreal injections (IVI) was 12.50 ± 12.40 and 25% of the eyes had previous treatment with photodynamic therapy (PDT). Mean improvement between BCVA0 and BCVA1 was 5.58 ± 15.98 letters (p < 0.001). However, a drop of 8.03 ± 12.25 letters was noticed between BCVA1 and BCVA2. FAF1 was 6.34 ± 4.92mm2 and increased to 9.88 ± 7.56mm2 (3.54 ± 3.79mm2 variation p < 0.001). The mean growth rate of the atrophic area was 0.89 ± 0.84mm2 per year. BCVA2 negatively correlated with FAF2 (k = -0.498, p = 0.002) being worse in patients with higher atrophic area growth rate (k = -0.341, p = 0.042). Eyes treated with PDT needed less IVI (5.89 ± 5.21 vs 14.70 ± 13.36, p = 0.008) but had larger FAF1 (9.80 ± 5.33 vs 5.19 ± 4.27, p = 0.013) and FAF2 (16.05 ± 7.10 vs 7.83 ± 6.63, p = 0.003). Hypothyroidism was associated with higher atrophy growth rate (1.55 ± 1.15 vs 0.73 ± 0.67, p = 0.016). Conclusion: This research demonstrates the importance of chorioretinal atrophy progression after myopic CNV lesions regression and its impact on visual prognosis, reporting a mean yearly growth of 0.89 mm2 in atrophic areas. Previous treatment with PDT and hypothyroidism were identified as risk factors associated with larger atrophic areas and worse visual outcomes.

20.
Artículo en Inglés | MEDLINE | ID: mdl-38805572

RESUMEN

INTRODUCTION: The PID-5 is a tool used to assess maladaptive personality traits according to the DSM-5 Alternative Model. Objective: The objective is to seek evidence of the validity and reliability of the Personality Inventory for DMS-5 (PID-5-SRF) admin-istered online and assess its measurement invariance compared to the paper-and-pencil administration. METHODS: A sample of 274 individuals from the general population (73.4% of women; 34.76 years old ±11.6) completed the instrument online after the study was dissemi-nated on social media and among the authors' contacts. RESULTS: Internal consistency (facets α≥0.70; domains α≥0.89) and test-retest reliability (15 to 30 days: facets ICC≥0.63; domains ICC≥0.82) were satisfactory, but a floor effect was found in almost all the items. A large number of facets (N=9) showed better fit to a bifactorial structure, and the Exploratory Factor Analysis suggested that a six-factor model better fits the data. Measurement invariance between the online and paper-and-pencil administrations was not attested at a configural level. CONCLUSION: The results revealed satisfactory psychometric indicators when the instrument was applied online, confirming its feasibility in collecting data. However, the in-strument's structure is not invariant, and caution must be adopted when compar-ing and interpreting data collected through different formats.

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