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1.
Polymers (Basel) ; 16(17)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39274059

RESUMEN

The incorporation of nanoparticles can significantly enhance the properties of polymers. However, the industrial production of nanocomposites presents a technological challenge in achieving the proper dispersion of nanoparticles within the polymer matrix. In this work, a novel device is presented that can be seamlessly integrated with standard twin-screw extruders, enabling the application of ultrasonic vibration to molten polymeric material. The primary objective of this study is to experimentally validate the effectiveness of this technology in improving the dispersion of nanoparticles. To accomplish this, a comparative analysis was carried out between nanocomposites obtained through conventional compounding extrusion and those processed with the assistance of ultrasonic vibrations. The nanocomposites under investigation consist of a polypropylene (PP) matrix reinforced with nano clays (Cloisite 20A) at a target loading ratio of 5% by weight. To comprehensively evaluate the impact of the ultrasound-assisted compounding, various key properties were assessed, such as the melt flow index (MFI) to characterize the flow behavior, mechanical properties to evaluate the structural performance, oxygen barrier properties to assess potential gas permeability, and microstructure analysis using Scanning Electron Microscopy (SEM) for detailed morphology characterization. The results suggested an improvement in nanoparticle dispersion when using the ultrasound device, particularly when the intensity was adjusted to 60%.

2.
Polymers (Basel) ; 16(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39274096

RESUMEN

This study investigates the performance of different poly(lactic acid) (PLA) composites incorporating agri-food waste additives and commercial lignin, comparing their properties with those of virgin PLA. The following composites were prepared using a single-screw extruder: PLA with 20% rice husk, PLA with 20% wheat straw and PLA with 20% olive pit. Additionally, PLA was blended with commercial lignin at the maximum feasible proportion using the same methodology. The resulting composites were injection-molded into specimens for analysis of their mechanical, thermal and morphological behavior. The primary objectives were to assess the dispersion of the additives within the PLA matrix and to evaluate the mechanical properties of the composites. The results indicate that the addition of high percentages of agricultural residues does not significantly compromise the mechanical properties of the composites. Notably, in the case of the PLA with 20% rice husk composite, the elastic modulus surpassed that of virgin PLA, despite the evident heterogeneity in filler particle sizes. It was feasible to incorporate a higher percentage of agricultural residues compared to commercial lignin, attributed to the larger volume occupied by the latter.

3.
bioRxiv ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39253496

RESUMEN

Astrocytes, a major glial cell type of the brain, regulate synapse numbers and function. However, whether astrocyte dysfunction can cause synaptic pathologies in neurological disorders such as Parkinson's Disease (PD) is unknown. Here, we investigated the impact of the most common PD-linked mutation in the leucine-rich repeat kinase 2 (LRRK2) gene (G2019S) on the synaptic functions of astrocytes. We found that both in human and mouse cortex, the LRRK2 G2019S mutation causes astrocyte morphology deficits and enhances the phosphorylation of the ERM proteins (Ezrin, Radixin, and Moesin), which are important components of perisynaptic astrocyte processes. Reducing ERM phosphorylation in LRRK2 G2019S mouse astrocytes restored astrocyte morphology and corrected excitatory synaptic deficits. Using an in vivo BioID proteomic approach, we found Ezrin, the most abundant astrocytic ERM protein, interacts with the Autophagy-Related 7 (Atg7), a master regulator of catabolic processes. The Ezrin/Atg7 interaction is inhibited by Ezrin phosphorylation, thus diminished in the LRRK2 G2019S astrocytes. Importantly, Atg7 function is required to maintain proper astrocyte morphology. These studies reveal an astrocytic molecular mechanism that could serve as a therapeutic target in PD.

4.
Front Immunol ; 15: 1447926, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267754

RESUMEN

Despite effective antiretroviral therapy (ART), 15-30% of people with HIV experience poor CD4+ T-cell recovery, termed immunologic non-responders (INR). This study aims to evaluate whether pre-ART plasma levels of interleukin-6 (IL-6), interferon gamma-induced protein-10 (IP-10), macrophage inflammatory protein-1-ß (MIP-1ß), and/or pentraxin-3 (PTX-3) could predict subsequent immunologic recovery. Seventy-four participants were enrolled and classified as INR and immunologic responders (IR) based on CD4+/CD8+ ratio increase over 24 months after starting ART. The results showed no significant differences in cytokine levels between INR and IR. Therefore, IL-6, IP-10, MIP-1ß, and PTX-3 were unsuitable as predictive markers of poor immune recovery.


Asunto(s)
Biomarcadores , Proteína C-Reactiva , Quimiocina CCL4 , Quimiocina CXCL10 , Infecciones por VIH , Interleucina-6 , Componente Amiloide P Sérico , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/sangre , Componente Amiloide P Sérico/metabolismo , Masculino , Femenino , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Adulto , Quimiocina CCL4/sangre , Interleucina-6/sangre , Persona de Mediana Edad , Biomarcadores/sangre , Quimiocina CXCL10/sangre , Terapia Antirretroviral Altamente Activa , Resultado del Tratamiento , Antirretrovirales/uso terapéutico , Relación CD4-CD8 , Fármacos Anti-VIH/uso terapéutico
5.
Front Public Health ; 12: 1441786, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220460

RESUMEN

Introduction: Respiratory syncytial virus (RSV) infection is one of the main causes of morbidity and mortality from lower respiratory tract infections in children under 5 years of age worldwide. Given that, the objective of this study was estimate the effectiveness of nirsevimab (a single-dose, long-acting, human recombinant monoclonal antibody against RSV) over time for the prevention of respiratory episodes treated at different levels of care. Methods: A prospective and dynamic population-based cohort study was performed including infants born between April 1 and December 31, 2023, in the Madrid region who resided there during the follow-up period from October 1, 2023, to February 29, 2024. Infants were considered immunized from the day after receiving one dose (50 or 100 mg) of nirsevimab or nonimmunized individuals if they did not receive any dose. Results: There were 4,100 episodes of primary care, 1,954 hospital emergencies, and 509 admissions, 82 of which required intensive care in the 33,859 participants analyzed. The adjusted effectiveness of nirsevimab in preventing hospitalization due to RSV infection was 93.6% (95% CI: 89.7 to 96.1) at 30 days and 87.6% (95% CI: 67.7 to 95.3) at 150 days. The number needed to treat to prevent one hospitalization were 314.19 (95% CI: 306.22 to 327.99) at 30 days and 24.30 (95% CI: 22.31 to 31.61) at 150 days. The adjusted effectiveness of nirsevimab in avoiding admission to an intensive care unit was 94.4% (95% CI: 87.3 to 97.5) at 30 days and 92.1% (95% CI: 64.0 to 98.3) at 90 days. The adjusted effectiveness of nirsevimab for avoiding primary care consultations and hospital emergency visits was lower. Discussion: Immunization with nirsevimab is an effective measure for reducing the burden of care related to RSV at all levels of care albeit it decreases throughout follow-up. At 150 days it remained high for preventing hospital admissions. Other articles already published have also demonstrated high effectiveness although with preliminary results, short follow-up periods and wide confidence intervals. None have detected a decrease in effectiveness over time. These results can be quite useful in individual infant prevention and in the design of immunization campaigns.


Asunto(s)
Antivirales , Infecciones por Virus Sincitial Respiratorio , Humanos , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , España , Estudios Prospectivos , Lactante , Femenino , Masculino , Antivirales/uso terapéutico , Hospitalización/estadística & datos numéricos , Costo de Enfermedad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Preescolar , Recién Nacido
6.
Int J Antimicrob Agents ; : 107317, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39233214

RESUMEN

BACKGROUND: Data about de-escalation in sepsis associated to bloodstream caused by Enterobacterales are scarce. The objectives of this study are to identify factors associated to early de-escalation and to analyse the impact of de-escalation in mortality of patients with Enterobacterales BSI with a SOFA score ≥ 2. MATERIAL AND METHODS: A prospective, multicenter cohort study including episodes of BSI due to Enterobacterales and SOFA score ≥2 receiving an active antipseudomonal beta-lactam was performed; the isolate should be susceptible to at least one narrower-spectrum antibiotic. Variables associated to de-escalation were identified using logistic binary regression. The association of de-escalation with 30-day mortality was investigated; confounding was controlled by calculating a propensity score used as covariate, as matching variable and for inverse probability treatment weighting (IPTW). RESULTS: Of 582 cases included, de-escalation was performed in 311 (53.4%). Neutropenia (adjusted OR: 0.37; 95%CI 0.18-0.75), central venous catheter (aOR: 0.52; 95%CI 0.32-0.83) and ESBL-producing isolate (aOR: 0.28; 95%CI 0.17-0.48) were negatively associated to de-escalation, and urinary tract source was positively associated (aOR: 2.27; 95%CI 1.56-3.33). Thirty-day mortality was 6.8% (21 patients) in de-escalated patients and 14.4% (39) in not de-escalated (relative risk, 0.63; 95%CI 0.44-0.89). In multivariate analysis including the propensity score, de-escalation was not associated with mortality (aOR: 0.98; 95% CI 0.39-2.47) and was protective in urinary or biliary tract source (aOR: 0.31 95%CI: 0.09-1.06). Matched and IPWT analysis showed similar results. CONCLUSIONS: These results suggest that early de-escalation from antipseudomonal beta-lactams is safe in patients with Enterobacterales bacteremia and SOFA ≥2.

7.
Nat Prod Res ; : 1-7, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39234765

RESUMEN

Cucurbitacins are triterpene bioactive constituents of natural products, particularly in the Cucurbitaceae plant family. The presence of cucurbitacins in seeds of the Cucurbita genus (pumpkin) has been only little studied. In this work, the content of cucurbitacins B, D, and E in seed oils from three cucurbits (Cucurbita moschata Duch, Cucurbita pepo Linn, and Cucurbita maxima Linn) was studied. An analytical method based on HPLC-DAD for the detection and quantification of these three cucurbitacins in seed oils was developed and validated according to ICH guidelines. The method showed good linearity, accuracy, and precision for the simultaneous quantification of cucurbitacins B, D, and E using C.moschata seed oil as a reference. When applied to C.pepo and C.maxima seed oils, cucurbitacin B and D were quantified but to a lesser extent. This is the first report of a simple, repeatable, and reproducible analytical tool to identify cucurbitacins in oilseeds from Cucurbita spp.

8.
Chem Biodivers ; : e202401382, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235587

RESUMEN

Walnut yield and quality are often affected by beetle infestations, particularly those caused by Carpophilus truncatus (Murray) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae). Beetle damage exposes walnuts to microbial food spoilers such as Fusarium species. Insecticides currently used for beetle control are environmentally unfriendly. This work explored a green synthesis approach for copper oxide nanoparticles (CuO-NPs) in a basic medium at 30°C by hydrolates, aqueous extracts obtained from Lippia integrifolia and Pimpinella anisum, denoted as CuO-I and CuO-A, respectively. Characterization through XRD, FT-IR, Raman, UV-visible absorbance, and AFM techniques indicated that CuO-A and CuO-I have a size ranging from 2-10 nm in height. The antifungal assay showed that both have a similar efficacy (MID = 320 µg), 3-fold stronger than CuO- NPs obtained in absence of hydrolates (denoted CuO-W) (MID = 960 µg), with the broadest inhibitory halos (ID = 126-128 mm) observed for CuO-A. Insecticidal activity of CuO-NPs showed a concentration-dependent behavior, with CuO-I showing an effect comparable to that of diatomaceous earth. SEM images confirmed the adhesion of nanoparticles to insect surfaces, which could induce oxygen deprivation and disruption of metabolic processes. Both CuO-A and CuO-I are promising for their use in integrated pest control in walnut storage.

10.
Mult Scler Relat Disord ; 91: 105861, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39265268

RESUMEN

BACKGROUND: Patients with multiple sclerosis (MS) have to deal with a variable disease trajectory often associated with disability and productivity loss. OBJECTIVE: This study aimed to assess illness-related uncertainty and associated correlates in patients with relapsing-remitting multiple sclerosis (RRMS) beyond the near diagnosis phase. METHODS: We conducted a multicenter, non-interventional study including patients diagnosed with RRMS (2017 revised McDonald criteria) and a disease duration of 3 to 8 years. Perceived uncertainty was measured using the Mishel Uncertainty of Illness Scale (MUIS). Associations between the MUIS and different patient-based outcome measures were analyzed using Spearman's rank correlation. RESULTS: A total of 201 patients were studied (mean age (standard deviation): 38.7 (8.4) years, 71.4 % female). The median disease duration (interquartile range) was 6.0 (4.0-7.0) years and the median EDSS score was 1.0 (0.0-2.0). The mean MUIS score was 38.2 (10.8). Perceived uncertainty was positively correlated with fatigue (p < 0.001), symptom severity (p < 0.001), anxiety (p < 0.001), depressive symptoms (p < 0.001), and a threatening illness perception (p < 0.001), and negatively correlated with self-management (p < 0.001), self-efficacy (p < 0.001), processing speed (p < 0.001), knowledge of MS (p = 0.006), and quality of life (p < 0.001). CONCLUSION: Illness-related uncertainty was common in a population of mid-stage RRMS. Identifying uncertainty and its associated factors may be useful for implementing preventive strategies to help patients cope with the disease throughout life.

11.
EBioMedicine ; 108: 105338, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39265504

RESUMEN

BACKGROUND: Among people living with HIV-1 (PHIV), immunological non-responders (INR) experience incomplete immune recovery despite suppressive antiretroviral treatment (ART), facing more severe non-AIDS events than immunological responders (IR) due to higher chronic immune activation and inflammation (cIA/I). We analyzed the HIV-1 reservoir and immunometabolism in monocytes as a source of cIA/I. METHODS: Cross-sectional study in which 110 participants were enrolled: 25 treatment-naïve; 35 INR; 40 IR; and 10 healthy controls. Cell-associated HIV-1-DNA (HIV-DNA) and -RNA (HIV-RNA) were measured in FACS-isolated monocytes using digital droplet PCR. Intact, 5' deleted, and 3' deleted proviruses were quantified by the intact proviral DNA assay. Systemic inflammation, monocyte immunophenotype, and immunometabolism were characterized by immunoassays, flow cytometry, and real-time cellular bioenergetics measurements, respectively. FINDINGS: Monocytes from INR harbor higher HIV-RNA and HIV-DNA levels than IR. HIV-RNA was found in 14/21 treatment-naïve [2512 copies/106 TBP (331-4666)], 17/33 INR [240 (148-589)], and 15/28 IR [144 (15-309)], correlating directly with sCD163, IP-10, GLUT1high cells and glucose uptake, and inversely with the CD4+/CD8+ ratio. HIV-DNA was identified in all participants with detectable HIV-RNA, with intact provirus in 9/12 treatment-naïve [13 copies/106 monocytes (7-44)], 8/14 INR [46 (18-67)], and 9/13 IR [9 (7-24)]. INR presented glucose metabolism alterations and mitochondrial impairment; decreased coupling efficiency and BHI, and increased mitochondrial dysfunction inversely correlating with the CD4+/CD8+ ratio. INTERPRETATION: HIV-RNA, more than HIV-DNA, in monocytes and their altered metabolism are factors associated with the higher cIA/I that characterize INR. FUNDING: This work was supported by the European Regional Development Fund, ISCIII, grant PI20/01646. Other funding sources: Instituto de Salud Carlos III through the Subprogram Miguel Servet (CP19/00159) to AGV, PFIS contracts (FI19/00304) to EMM, (FI21/00165) to ASA, and (FI19/00083) to CGC, and a mobility grant (MV21/00103) to EMM, from the Ministerio de Ciencia e Innovación, Spain. AJM was granted by a CSL Centenary Award.

12.
Anal Chim Acta ; 1328: 343187, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39266200

RESUMEN

BACKGROUND: Magnetic ionic liquids (MILs) have been explored in dispersive liquid-liquid microextraction (DLLME). Their usage allows to substitute centrifugation and/or filtration steps by a quick magnetic separation. Besides, effervescence-assisted DLLME is one of the most known options to improve the dispersion of the extractant in the sample, while allowing to avoid the consumption of external energy during dispersion. Despite these interesting features, only one study incorporates MILs containing the tetrachloroferrate anion in effervescence tablets. These MILs are highly viscous and liquid at room temperature, thus compromising the stability of the tablets when used as extraction microdevices in effervescence-assisted DLLME, and only allowing their use in the conventional MIL-DLLME mode. RESULTS: A new class of effervescence tablets containing a Ni(II)-based MIL, that is solid at room temperature, is here proposed. This type of tablets permits their use, for first time, in the in situ DLLME mode, occurring through the transformation of a water-soluble MIL into a water-insoluble MIL microdroplet. This way, the tablet formulation included: the MIL, the metathesis reagent lithium bis[(trifluoromethyl)sulfonyl]imide, NaH2PO4 and K2CO3 as effervescence precursors salts, and Na2SO4 as salting-out and desiccating agent. The method is combined with high-performance liquid-chromatography and both fluorescence and ultraviolet detection, for the determination of monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and benzophenones (BPs), as biomarkers in urine. The method simply involved the addition of the effervescence tablet to the sample, thus taken place simultaneously the effervescence process and the metathesis reaction, without requiring any external energy consumption. The method presented limits of detection down to 10 ng L-1 for OH-PAHs and to 0.60 µg L-1 for BPs, inter-day relative standard deviations lower than 17 %, and average relative recoveries of 94 % in urine. The determined OH-PAHs contents in urine were between 0.40 and 16 µg L-1, and between 17.8 and 334 µg L-1 for BPs. SIGNIFICANCE: We have developed the first MIL-based effervescence tablets that are completely solid, thus improving the stability and robustness of these microdevices with respect to previously reported tablets involving MILs, while permitting to perform into the in situ DLLME mode (thus gaining in extraction efficiency). This approach including the MIL-based effervescence tablets constitutes an alternative on-site platform for the analysis of urine, as satisfactory precision, accuracy, and sensitivity are achieved despite not involving any external energy input within the analytical sample preparation setup. This method also constitutes the first application of MIL-based effervescence tablets for bioanalysis.


Asunto(s)
Biomarcadores , Líquidos Iónicos , Microextracción en Fase Líquida , Comprimidos , Líquidos Iónicos/química , Microextracción en Fase Líquida/métodos , Comprimidos/química , Biomarcadores/orina , Biomarcadores/análisis , Humanos , Límite de Detección , Fenómenos Magnéticos
13.
J Pediatr Urol ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39218731

RESUMEN

BACKGROUND: When indicated, ureteroceles and ectopic ureters in duplicated collecting systems can be managed via upper or lower urinary tract surgical approaches, or a combination of both. Open ureteroureterostomy (UU) has been described to address these conditions in the absence of lower pole (LP) vesicoureteral reflux (VUR). We report outcomes from multiple centers worldwide with mid-term follow-up. METHODS: Our study consists of a retrospective review of records and imaging of children who underwent open distal UU via inguinal incision for duplicated collecting system without lower pole VUR in institutions from North America, South America, and the Caribbean. Descriptive statistics and univariate analysis were utilized. RESULTS: The records of 127 patients who underwent open distal UU for double collecting system between 2009 and 2022 were reviewed. Of those, 65% were female (n = 82), with a mean age at operation of 18 months (range 3-180). Main presentation at surgery included prenatal hydronephrosis (64%, n = 81), followed by febrile urinary tract infections (28%, n = 36), and urinary incontinence or other (8%, n = 10). The patients with antenatal or incidental diagnosis of hydronephrosis were classified as preoperative Society for Fetal Urology (SFU) grade 3 (n = 64) and 4 (n = 54) (96%). Those who were classified with SFU grade 0-2 (4%) had symptomatic clinical presentations including febrile urinary tract infections (UTIs) (n = 3), urinary incontinence (n = 3), and a 12-year-old patient with recurrent abdominal pain (n = 1). Mean operative time from skin incision to skin closure was 86 min (range 45-240). Mean hospital stay was estimated at 1.1 days (range 0.5-4). In our cohort of 127 patients, 3 (2%) developed Clavien-Dindo grade I (2 with ureteral stent displacement and 1 with a urine leak/managed conservatively), 6 (5%) with grade II (3 febrile and 3 non-febrile UTIs managed with oral antibiotics), and 2 (2%) with grade IIIb complications (urine leaks requiring surgical management), which were appropriately treated. None presented grade IV or V complications. A double J stent was used in 56 patients (44%), and a Penrose drain was left in 10 (8%). A total of 125 children (98%, n = 125/127) showed sonographic improvement of hydronephrosis, or resolution of symptoms with stable ultrasound findings. Successful outcome was similar for both ureterocele and ectopic ureter subgroups: 49/49 patients with ureterocele showed 100% improvement, 76/78 children with ectopic ureter showed improvement in 97% of the cases. On univariate analysis, outcomes were similar regardless of the use of ureteral stents (p = 0.11). Mean follow-up was 28.2 months (range 12-85). CONCLUSIONS: Open distal UU is a good alternative for the definitive surgical management of ectopic ureters and ureteroceles without LP VUR. This multicentric and mid-term follow-up study demonstrates that open distal UU offers high success rates, low morbidity, short operative times and hospital stays, and satisfactory aesthetic outcomes. Additionally, the surgery is performed extra-peritoneally and may not require the use of stents or drains, depending on surgeon preference. Further investigations are being conducted to determine the role of UU in the settings of double collecting systems associated with ipsilateral LP VUR.

14.
F1000Res ; 13: 580, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220385

RESUMEN

Background: Geopolymers are alternative materials to cement because they require less energy in their production process; hence, they contribute to the reduction in CO 2 emissions. This study aims to evaluate the possibility of using industrial residues such as silica fume (SF) to improve the physical and mechanical properties of a pumice stone (PS)-based geopolymer. Methods: Through an experimental methodology, the process starts with the extraction, grinding, and sieving of the raw material to carry out the physical and chemical characterization of the resulting material, followed by the dosage of the geopolymer mixture considering the factors that influence the resistance mechanical strength. Finally, the physical and mechanical properties of the geopolymer were characterized. This research was carried out in four stages: characterization of the pumice stone, design of the geopolymer through laboratory tests, application according to the dosage of the concrete, and analysis of the data through a multi-criteria analysis. Results: It was determined that the optimal percentage of SF replacement is 10%, which to improves the properties of the geopolymer allowing to reach a maximum resistance to compression and flexion of 14.10 MPa and 4.78 MPa respectively, showing that there is a direct relationship between the percentage of SF and the resistance. Conclusions: Geopolymer preparation involves the use of PS powder with a composition rich in silicon and aluminum. The factors influencing strength include the ratio of sodium silicate to sodium hydroxide, water content, temperature, curing time, molarity of sodium hydroxide, and binder ratio. The results showed an increase in the compression and flexural strength with 10% SF replacement. The geopolymer's maximum compressive strength indicates its non-structural use, but it can be improved by reducing the PS powder size.


Asunto(s)
Silicatos , Dióxido de Silicio , Silicatos/química , Dióxido de Silicio/química , Polímeros/química , Ensayo de Materiales , Fuerza Compresiva , Materiales de Construcción/análisis
15.
Nat Commun ; 15(1): 7848, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245746

RESUMEN

The accidental human pathogen Legionella pneumophila (Lp) is the etiological agent for a severe atypical pneumonia known as Legionnaires' disease. In human infections and animal models of disease alveolar macrophages are the primary cellular niche that supports bacterial replication within a unique intracellular membrane-bound organelle. The Dot/Icm apparatus-a type IV secretion system that translocates ~300 bacterial proteins within the cytosol of the infected cell-is a central virulence factor required for intracellular growth. Mutant strains lacking functional Dot/Icm apparatus are transported to and degraded within the lysosomes of infected macrophages. The early foundational work from Dr. Horwitz's group unequivocally established that Legionella does not replicate extracellularly during infection-a phenomenon well supported by experimental evidence for four decades. Our data challenges this paradigm by demonstrating that macrophages and monocytes provide the necessary nutrients and support robust Legionella extracellular replication. We show that the previously reported lack of Lp extracellular replication is not a bacteria intrinsic feature but rather a result of robust restriction by serum-derived nutritional immunity factors. Specifically, the host iron-sequestering protein Transferrin is identified here as a critical suppressor of Lp extracellular replication in an iron-dependent manner. In iron-overload conditions or in the absence of Transferrin, Lp bypasses growth restriction by IFNγ-primed macrophages though extracellular replication. It is well established that certain risk factors associated with development of Legionnaires' disease, such as smoking, produce a chronic pulmonary environment of iron-overload. Our work indicates that iron-overload could be an important determinant of severe infection by allowing Lp to overcome nutritional immunity and replicate extracellularly, which in turn would circumvent intracellular cell intrinsic host defenses. Thus, we provide evidence for nutritional immunity as a key underappreciated host defense mechanism in Legionella pathogenesis.


Asunto(s)
Hierro , Legionella pneumophila , Enfermedad de los Legionarios , Legionella pneumophila/inmunología , Enfermedad de los Legionarios/microbiología , Enfermedad de los Legionarios/inmunología , Hierro/metabolismo , Animales , Ratones , Humanos , Macrófagos/microbiología , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Transferrina/metabolismo , Monocitos/inmunología , Monocitos/metabolismo , Monocitos/microbiología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Femenino
16.
Front Psychol ; 15: 1402885, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100558

RESUMEN

Introduction: Exposure to natural environments, such as parks, forests, and green areas, is often linked to a decrease in stress, anxiety and depression, while contributing to improved emotional wellbeing. These observations are supported by well-established theories, such as the Stress Reduction Theory and Attention Restoration Theory, which highlight the psychological benefits of interacting with nature. However, the relationship between exposure to nature and emotions, and in particular, with emotional regulation, is an evolving aspect of research with no clear conclusions. Emotional regulation can be deliberate in nature, where individuals voluntarily participate in modifying various aspects of their emotions, such as their type, intensity, quality or duration. Alternatively, it may be automatic, originating from sensory perception and acting without full awareness, but significantly influencing emotional experiences. In this context, the environmental self-regulation hypothesis, suggests that people consciously or unconsciously use their physical environment to regulate their emotions. Method: To analyze the evidence of the relationship between contact with nature and emotional regulation, we conducted this review. Using the PRISMA statement as a reference, we conducted keyword searches in five databases in the period between 2013 and 2023. The databases selected were Scopus, Web of Science (WoS), PubMed, PsycINFO and ScienceDirect. Results: In addition, a manual search was carried out of journals in the research field. Initially, from which gray literature, reviews and duplicates were removed in a first step. The resulting articles were then filtered using their titles and abstracts. Subsequently, the abstracts of the 25 selected articles were reviewed and discussed by researchers to reach a final decision based on consensus about the adequacy of each paper. Finally, nine articles were included in the systematic review. Discussion: In general terms, this review suggests that research on the relationship between contact with nature and emotional regulation provides valuable insights into how natural environments can contribute to the emotional wellbeing and physical and mental health of the population.

17.
J Clin Exp Hepatol ; 14(6): 101472, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100888

RESUMEN

Background & aims: This study aims to assess the incidence and characteristics of all cancers, hepatocellular carcinoma (HCC), and extrahepatic cancers in patients with cirrhosis of various etiologies. Methods: Prospective cohort study in patients with cirrhosis but no cancer, followed every 6-9 months through the HCC early detection program. Cancer incidence was compared with Spanish population data to calculate standardized incidence ratios (SIR), and cumulative incidence was calculated separately for cancer and competing events. Longitudinal outcomes were assessed with multivariate Fine-Gray and Cox regression models. Results: A total of 215 patients (68.4% male, median age 61 years) were included. Cirrhotic etiology was alcohol (38%), hepatitis B or C virus infection (36%), alcohol plus hepatitis B or C virus infection (9%), and other causes (17%). Sixty percent were current or former smokers. Thirty-nine cancers were observed (56% liver cancer), while 3.3 were expected (SIR 11.7; 95% confidence interval [CI] 8.6-16.1). Ten (4.6%) patients were censored for liver transplantation and 34 (15.8%) for death, constituting relevant competing risks. Smoking was significantly associated with overall cancer incidence (smokers: subdistribution hazard ratio [SHR] 3.14, 95% CI 1.33-7.38; former smokers: SHR 2.54, 95% CI 1.08-5.98). In the multivariable regression analysis, viral etiology, Child-Pugh score (B or C versus A), and smoking were associated with liver cancer, and smoking with extrahepatic cancer. Conclusions: Patients with cirrhosis have an 11-fold risk of cancer compared to the general population. Risk is increased in liver and non-liver cancers. Active surveillance of any type of cancer and smoking cessation interventions are needed in these patients.

18.
Cureus ; 16(7): e64074, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39114232

RESUMEN

This study provides a comprehensive overview of hereditary hemochromatosis (HH), a genetic condition characterized by iron overload due to excessive iron absorption. It elucidates diverse inheritance patterns and clinical manifestations by exploring mutations in critical genes such as HFE (hemochromatosis), HJV (hemojuvelin), HAMP (hepcidin antimicrobial peptide), TfR2 (transferrin receptor 2), and FP (ferroportin). The significance of early screening, diagnosis, and personalized management strategies based on genetic classification is emphasized, particularly in terms of high-income vs. low-income countries. Addressing challenges in diagnosis, genetic testing accessibility, and healthcare disparities, the study highlights the importance of early detection, cost-effective screening strategies, and enhancing healthcare outcomes globally. Advanced genetic testing in high-income countries facilitates early diagnosis and management, reducing complications such as liver disease and cardiomyopathy. In contrast, low-income populations face several barriers, including limited access to genetic testing, high costs, and inadequate healthcare infrastructure. Cost-effective serum ferritin (SF) and transferrin saturation (TS) tests and emerging point-of-care (POC) tests offer affordable diagnostic options for low-resource settings. Additionally, the ongoing development of hepcidin measurement methods holds promise for enhancing diagnostic capabilities. Implementing these strategies can aid healthcare providers in improving global HH management and reducing the burden of iron overload complications. Furthermore, the study underscores the need for public health initiatives to raise awareness about HH, promote routine screenings, and advocate for equitable healthcare policies. Collaborative efforts between governments, healthcare organizations, and research institutions are crucial in addressing the global burden of HH. By fostering international cooperation and resource-sharing, it is possible to bridge the gap between high-income and low-income countries, ensuring all individuals have access to the necessary diagnostic and treatment options. This holistic approach can ultimately lead to better health outcomes and improved quality of life for individuals affected by HH worldwide. This comprehensive examination of HH not only illuminates the genetic and clinical aspects of the condition but also provides a roadmap for addressing the multifaceted challenges associated with its diagnosis and management.

19.
Gac Sanit ; 38: 102416, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39098171

RESUMEN

OBJECTIVE: To assess the self-perceived quality of life of institutionalized adults with cerebral palsy and to identify factors that influence their well-being, including sociodemographic, clinical, and diagnostic characteristics, as well as the degree of institutionalization. METHOD: A descriptive cross-sectional study was conducted using the San Martin Quality of Life Scale among adults with cerebral palsy. Data were collected in 2021 and 2022 in a sample of adults with cerebral palsy in Navarra, Spain. Multivariate regression was used to explore the relationship between quality of life and various influential factors. RESULTS: The self-determination dimension positively influenced quality of life scores, whereas the social inclusion dimension had the opposite effect. Descriptive and regression analyses revealed that factors such as residing outside the city and a high degree of dependency had a negative influence on quality of life, while the degree of institutionalization had a positive impact. CONCLUSIONS: It is important to highlight the positive effects of the degree of institutionalization on rehabilitation and well-being, as it seeks to enhance autonomy and social integration when talking about patient-centered models of institutionalization.

20.
iScience ; 27(8): 110560, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39184436

RESUMEN

Individual complexes of the mitochondrial oxidative phosphorylation system (OXPHOS) are not linked solely by their function; they also share dependencies at the maintenance/assembly level, where one complex depends on the presence of a different individual complex. Despite the relevance of this "interdependence" behavior for mitochondrial diseases, its true nature remains elusive. To understand the mechanism that can explain this phenomenon, we examined the consequences of the aberration of different OXPHOS complexes in human cells. We demonstrate here that the complete disruption of each of the OXPHOS complexes resulted in a decrease in the complex I (cI) level and that the major reason for this is linked to the downregulation of mitochondrial ribosomal proteins. We conclude that the secondary cI defect is due to mitochondrial protein synthesis attenuation, while the responsible signaling pathways could differ based on the origin of the OXPHOS defect.

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