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Human and animal nutrition is mainly based on seeds. Seed size is a key factor affecting seed yield and has thus been one of the primary objectives of plant breeders since the domestication of crop plants. Seed size is coordinately regulated by signals of maternal and zygotic tissues that control the growth of the seed coat, endosperm and embryo. Here, we provide previously unreported evidence for the role of DELLA proteins, key repressors of gibberellin responses, in the maternal control of seed size. The gain-of-function della mutant gai-1 produces larger seeds as a result of an increase in the cell number in ovule integuments. This leads to an increase in ovule size and, in turn, to an increase in seed size. Moreover, DELLA activity promotes increased seed size by inducing the transcriptional activation of AINTEGUMENTA, a genetic factor that controls cell proliferation and organ growth, in the ovule integuments of gai-1. Overall, our results indicate that DELLA proteins are involved in the control of seed size and suggest that modulation of the DELLA-dependent pathway could be used to improve crop yield.
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Proteínas de Arabidopsis , Arabidopsis , Humanos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Giberelinas/metabolismo , Semillas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas/genéticaRESUMEN
The immune response is central to the pathogenesis of cutaneous leishmaniasis (CL). However, most of our current understanding of the immune response in human CL derives from the analysis of systemic responses, which only partially reflect what occurs in the skin. In this study, we characterized the transcriptional dynamics of skin lesions during the course of treatment of CL patients and identified gene signatures and pathways associated with healing and nonhealing responses. We performed a comparative transcriptome profiling of serial skin lesion biopsies obtained before, in the middle, and at the end of treatment of CL patients (eight who were cured and eight with treatment failure). Lesion transcriptomes from patients who healed revealed recovery of the stratum corneum, suppression of the T cell-mediated inflammatory response, and damping of neutrophil activation, as early as 10 d after initiation of treatment. These transcriptional programs of healing were consolidated before lesion re-epithelization. In stark contrast, downregulation of genes involved in keratinization was observed throughout treatment in patients who did not heal, indicating that in addition to uncontrolled inflammation, treatment failure of CL is mediated by impaired mechanisms of wound healing. This work provides insights into the factors that contribute to the effective resolution of skin lesions caused by Leishmania (Viannia) species, sheds light on the consolidation of transcriptional programs of healing and nonhealing responses before the clinically apparent resolution of skin lesions, and identifies inflammatory and wound healing targets for host-directed therapies for CL.
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Leishmania braziliensis , Leishmania , Leishmaniasis Cutánea , Humanos , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/genética , Piel/patología , Cicatrización de Heridas/genética , Leishmania braziliensis/fisiologíaRESUMEN
Prussian blue analogues (PBAs) are a diverse family of microporous inorganic solids, known for their gas storage ability1, metal-ion immobilization2, proton conduction3, and stimuli-dependent magnetic4,5, electronic6 and optical7 properties. This family of materials includes the double-metal cyanide catalysts8,9 and the hexacyanoferrate/hexacyanomanganate battery materials10,11. Central to the various physical properties of PBAs is their ability to reversibly transport mass, a process enabled by structural vacancies. Conventionally presumed to be random12,13, vacancy arrangements are crucial because they control micropore-network characteristics, and hence the diffusivity and adsorption profiles14,15. The long-standing obstacle to characterizing the vacancy networks of PBAs is the inaccessibility of single crystals16. Here we report the growth of single crystals of various PBAs and the measurement and interpretation of their X-ray diffuse scattering patterns. We identify a diversity of non-random vacancy arrangements that is hidden from conventional crystallographic powder analysis. Moreover, we explain this unexpected phase complexity in terms of a simple microscopic model that is based on local rules of electroneutrality and centrosymmetry. The hidden phase boundaries that emerge demarcate vacancy-network polymorphs with very different micropore characteristics. Our results establish a foundation for correlated defect engineering in PBAs as a means of controlling storage capacity, anisotropy and transport efficiency.
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The deubiquitinating enzyme Ataxin-3 (ATXN3) contains a polyglutamine (PolyQ) region, the expansion of which causes spinocerebellar ataxia type-3 (SCA3). ATXN3 has multiple functions, such as regulating transcription or controlling genomic stability after DNA damage. Here we report the role of ATXN3 in chromatin organization during unperturbed conditions, in a catalytic-independent manner. The lack of ATXN3 leads to abnormalities in nuclear and nucleolar morphology, alters DNA replication timing and increases transcription. Additionally, indicators of more open chromatin, such as increased mobility of histone H1, changes in epigenetic marks and higher sensitivity to micrococcal nuclease digestion were detected in the absence of ATXN3. Interestingly, the effects observed in cells lacking ATXN3 are epistatic to the inhibition or lack of the histone deacetylase 3 (HDAC3), an interaction partner of ATXN3. The absence of ATXN3 decreases the recruitment of endogenous HDAC3 to the chromatin, as well as the HDAC3 nuclear/cytoplasm ratio after HDAC3 overexpression, suggesting that ATXN3 controls the subcellular localization of HDAC3. Importantly, the overexpression of a PolyQ-expanded version of ATXN3 behaves as a null mutant, altering DNA replication parameters, epigenetic marks and the subcellular distribution of HDAC3, giving new insights into the molecular basis of the disease.
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Ataxina-3 , Cromatina , Replicación del ADN , Humanos , Ataxina-3/genética , Ataxina-3/metabolismo , Cromatina/genética , Daño del ADN , Enfermedad de Machado-Joseph/genética , Proteínas Represoras/metabolismoRESUMEN
Autophagy defects are a risk factor for inflammatory bowel diseases (IBDs) through unknown mechanisms. Whole-body conditional deletion of autophagy-related gene (Atg) Atg7 in adult mice (Atg7Δ/Δ) causes tissue damage and death within 3 mo due to neurodegeneration without substantial effect on intestine. In contrast, we report here that whole-body conditional deletion of other essential Atg genes Atg5 or Fip200/Atg17 in adult mice (Atg5Δ/Δ or Fip200Δ/Δ) caused death within 5 d due to rapid autophagy inhibition, elimination of ileum stem cells, and loss of barrier function. Atg5Δ/Δ mice lost PDGFRα+ mesenchymal cells (PMCs) and Wnt signaling essential for stem cell renewal, which were partially rescued by exogenous Wnt. Matrix-assisted laser desorption ionization coupled to mass spectrometry imaging (MALDI-MSI) of Atg5Δ/Δ ileum revealed depletion of aspartate and nucleotides, consistent with metabolic insufficiency underlying PMC loss. The difference in the autophagy gene knockout phenotypes is likely due to distinct kinetics of autophagy loss, as deletion of Atg5 more gradually extended lifespan phenocopying deletion of Atg7 or Atg12. Thus, autophagy is required for PMC metabolism and ileum stem cell and mammalian survival. Failure to maintain PMCs through autophagy may therefore contribute to IBD.
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Autofagia , Intestinos , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Células Madre , Animales , Autofagia/genética , Proteína 5 Relacionada con la Autofagia , Proteína 7 Relacionada con la Autofagia , Proteínas Relacionadas con la Autofagia , Supervivencia Celular , Ratones , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Células Madre/metabolismoRESUMEN
Graphullerene is a novel two-dimensional carbon allotrope with unique optoelectronic properties. Despite significant experimental characterization and prior density functional theory calculations, unanswered questions remain as to the nature, energy, and intensity of the electronic and optical excitations. Here, we present first-principles calculations of the quasiparticle band structure, neutral excitations, and absorption spectra of monolayer graphullerene and bulk graphullerite, employing the GW-Bethe-Salpeter equation (GW-BSE) approach. We show that strongly bound excitons dominate the absorption spectrum of monolayer graphullerene with binding energies up to 0.8 eV, while graphullerite exhibits less pronounced excitonic effects. Our calculations also reveal a strong linear polarization anisotropy, reflecting the in-plane structural anisotropy from intermolecular coupling between neighboring C60 units. We further show that the presence of Mg atoms, crucial to the synthesis process, induces structural modifications and polarizability effects, resulting in a â¼1 eV quasiparticle gap renormalization and a reduction in the exciton binding energy to â¼0.6 eV.
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Functionalization of metallic surfaces by molecular monolayers is a key process in fields such as nanophotonics or biotechnology. To strongly enhance light-matter interaction in such monolayers, nanoparticle-on-a-mirror (NPoM) cavities can be formed by placing metal nanoparticles on such chemically functionalized metallic monolayers. In this work, we present a novel functionalization process of gold surfaces using 5-amino-2-mercaptobenzimidazole (5-A-2MBI) molecules, which can be used for upconversion from THz to visible frequencies. The synthesized surfaces and NPoM cavities are characterized by Raman spectroscopy, atomic force microscopy (AFM), and advancing-receding contact angle measurements. Moreover, we show that NPoM cavities can be efficiently integrated on a silicon-based photonic chip performing pump injection and Raman-signal extraction via silicon nitride waveguides. Our results open the way for the use of 5-A-2MBI monolayers in different applications, showing that NPoM cavities can be effectively integrated with photonic waveguides, enabling on-chip enhanced Raman spectroscopy or detection of infrared and THz radiation.
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The Apolipoprotein E-ε4 allele (APOE-ε4) is the strongest genetic risk factor for late onset Alzheimer disease (AD). ApoE plays a critical role in amyloid-ß (Aß) accumulation in AD, and genetic deletion of the murine ApoE gene in mouse models results in a decrease or inhibition of Aß deposition. The association between the presence of ApoE and amyloid in amyloidoses suggests a more general role for ApoE in the fibrillogenesis process. However, whether decreasing levels of ApoE would attenuate amyloid pathology in different amyloidoses has not been directly addressed. Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease characterized by the presence of widespread parenchymal and vascular Danish amyloid (ADan) deposition and neurofibrillary tangles. A transgenic mouse model for FDD (Tg-FDD) is characterized by parenchymal and vascular ADan deposition. To determine the effect of decreasing ApoE levels on ADan accumulation in vivo, we generated a mouse model by crossing Tg-FDD mice with ApoE KO mice (Tg-FDD+/-/ApoE-/-). Lack of ApoE results in inhibition of ADan deposition up to 18 months of age. Additionally, our results from a genetic screen of Tg-FDD+/-/ApoE-/- mice emphasize the significant role for ApoE in neurodegeneration in FDD via glial-mediated mechanisms. Taken together, our findings suggest that the interaction between ApoE and ADan plays a key role in FDD pathogenesis, in addition to the known role for ApoE in amyloid plaque formation in AD.
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Enfermedad de Alzheimer , Amiloidosis , Enfermedades Neurodegenerativas , Ratones , Animales , Glicoproteínas de Membrana/metabolismo , Enfermedad de Alzheimer/genética , Ratones Transgénicos , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Amiloidosis/genética , Amiloidosis/patología , Amiloide , Apolipoproteínas E/genética , Encéfalo/metabolismoRESUMEN
Hepatocellular carcinoma (HCC) typically develops as a consequence of liver cirrhosis, but HCC epidemiology has evolved drastically in recent years. Metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis, has emerged as the most common chronic liver disease worldwide and a leading cause of HCC. A substantial proportion of MASLD-associated HCC (MASLD-HCC) also can develop in patients without cirrhosis. The specific pathways that trigger carcinogenesis in this context are not elucidated completely, and recommendations for HCC surveillance in MASLD patients are challenging. In the era of precision medicine, it is critical to understand the processes that define the profiles of patients at increased risk of HCC in the MASLD setting, including cardiometabolic risk factors and the molecular targets that could be tackled effectively. Ideally, defining categories that encompass key pathophysiological features, associated with tailored diagnostic and treatment strategies, should facilitate the identification of specific MASLD-HCC phenotypes. In this review, we discuss MASLD-HCC, including its epidemiology and health care burden, the mechanistic data promoting MASLD, metabolic dysfunction-associated steatohepatitis, and MASLD-HCC. Its natural history, prognosis, and treatment are addressed specifically, as the role of metabolic phenotypes of MASLD-HCC as a potential strategy for risk stratification. The challenges in identifying high-risk patients and screening strategies also are discussed, as well as the potential approaches for MASLD-HCC prevention and treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Fenotipo , Humanos , Carcinoma Hepatocelular/epidemiología , Neoplasias Hepáticas/epidemiología , Hígado Graso/complicacionesRESUMEN
Mutations in GBA1, encoding glucocerebrosidase beta 1 (GCase), are the most common genetic risk factor for Parkinson's disease (PD). GCase dysfunction leads to an accumulation of glucosylceramide (GluCer) substrates in different organs and fluids. Despite the challenges in quantifying GluCer isoforms in biological samples, their potential clinical interest as PD biomarkers justifies the development of robust assays. An extensively evaluated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for quantifying 14 GluCer and galactosylceramide (GalCer) isoforms in human cerebrospinal fluid (CSF) samples is presented. Sample pretreatment, HPLC, and MS/MS parameters were optimized. Evaluation was performed according to the recommendations of the Clinical and Laboratory Standards Institute and European Medicines Agency guidelines. Four 7-point calibration curves were generated, with a linearity interval from 2.5 to 200 nM (R2 ≥ 0.995). The limit of quantification was set at 5 nM. Between-run precision and accuracy were up to 12.5 and 9%, respectively. After method validation, we measured the levels of GluCer and GalCer isoforms in CSF human samples, including 6 healthy controls (HC), 22 idiopathic GBA1 wild-type PD (iPD) patients, and 5 GBA1-associated PD (PD-GBA) patients. GluCer/GalCer median ratios were found to be higher in the CSF of PD-GBA patients, particularly in severe GBA1 mutations, than those in iPD and HC. The observed trends in GluCer/GalCer ratios among groups provide novel information for the comprehensive analysis of sphingolipids as potential biomarkers of PD.
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Galactosilceramidas , Glucosilceramidas , Enfermedad de Parkinson , Espectrometría de Masas en Tándem , Humanos , Enfermedad de Parkinson/líquido cefalorraquídeo , Glucosilceramidas/líquido cefalorraquídeo , Galactosilceramidas/líquido cefalorraquídeo , Cromatografía Líquida de Alta Presión , Biomarcadores/líquido cefalorraquídeo , Glucosilceramidasa/líquido cefalorraquídeo , Glucosilceramidasa/genéticaRESUMEN
Memory CD8+ T cells are indispensable for maintaining long-term immunity against intracellular pathogens and tumors. Despite their presence at oxygen-deprived infected tissue sites or in tumors, the impact of local oxygen pressure on memory CD8+ T cells remains largely unclear. We sought to elucidate how oxygen pressure impacts memory CD8+ T cells arising after infection with Listeria monocytogenes-OVA. Our data revealed that reduced oxygen pressure during in vitro culture switched CD8+ T cell metabolism from oxidative phosphorylation to a glycolytic phenotype. Quantitative proteomic analysis showed that limiting oxygen conditions increased the expression of glucose transporters and components of the glycolytic pathway, while decreasing TCA cycle and mitochondrial respiratory chain proteins. The altered CD8+ T cell metabolism did not affect the expansion potential, but enhanced the granzyme B and IFN-γ production capacity. In vivo, memory CD8+ T cells cultured under low oxygen pressure provided protection against bacterial rechallenge. Taken together, our study indicates that strategies of cellular immune therapy may benefit from reducing oxygen during culture to develop memory CD8+ T cells with superior effector functions.
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Listeria monocytogenes , Listeriosis , Neoplasias , Animales , Ratones , Linfocitos T CD8-positivos , Proteómica , Neoplasias/patología , Oxígeno/metabolismo , Glucólisis , Memoria Inmunológica , Ratones Endogámicos C57BLRESUMEN
Members of the mammalian gut microbiota metabolize diverse complex carbohydrates that are not digested by the host, which are collectively labeled "dietary fiber." While the enzymes and transporters that each strain uses to establish a nutrient niche in the gut are often exquisitely specific, the relationship between carbohydrate structure and microbial ecology is imperfectly understood. The present study takes advantage of recent advances in complex carbohydrate structure determination to test the effects of fiber monosaccharide composition on microbial fermentation. Fifty-five fibers with varied monosaccharide composition were fermented by a pooled feline fecal inoculum in a modified MiniBioReactor array system over a period of 72 hours. The content of the monosaccharides glucose and xylose was significantly associated with the reduction of pH during fermentation, which was also predictable from the concentrations of the short-chain fatty acids lactic acid, propionic acid, and the signaling molecule indole-3-acetic acid. Microbiome diversity and composition were also predictable from monosaccharide content and SCFA concentration. In particular, the concentrations of lactic acid and propionic acid correlated with final alpha diversity and were significantly associated with the relative abundance of several of the genera, including Lactobacillus and Dubosiella. Our results suggest that monosaccharide composition offers a generalizable method to compare any dietary fiber of interest and uncover links between diet, gut microbiota, and metabolite production. IMPORTANCE: The survival of a microbial species in the gut depends on the availability of the nutrients necessary for that species to survive. Carbohydrates in the form of non-host digestible fiber are of particular importance, and the set of genes possessed by each species for carbohydrate consumption can vary considerably. Here, differences in the monosaccharides that are the building blocks of fiber are considered for their impact on both the survival of different species of microbes and on the levels of microbial fermentation products produced. This work demonstrates that foods with similar monosaccharide content will have consistent effects on the survival of microbial species and on the production of microbial fermentation products.
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Bacterias , Fibras de la Dieta , Fermentación , Microbioma Gastrointestinal , Monosacáridos , Fibras de la Dieta/metabolismo , Monosacáridos/metabolismo , Monosacáridos/análisis , Animales , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/genética , Heces/microbiología , Heces/química , Ácidos Grasos Volátiles/metabolismoRESUMEN
Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.
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COVID-19 , Mitocondrias , SARS-CoV-2 , Proteínas Virales , Humanos , Células A549 , COVID-19/metabolismo , COVID-19/virología , COVID-19/patología , Mitocondrias/metabolismo , Sistemas de Lectura Abierta , SARS-CoV-2/genética , Transcriptoma , Proteínas Virales/genética , Proteínas Virales/metabolismo , Proteínas Reguladoras y Accesorias Virales/metabolismo , Proteínas Reguladoras y Accesorias Virales/genética , Proteínas Viroporinas/metabolismoRESUMEN
BACKGROUND: The most common mode of ovarian cancer (OC) spread is intraperitoneal dissemination, with the peritoneum as the primary site of metastasis. Cytoreductive surgery (CRS) with chemotherapy is the primary treatment. When necessary, a digestive resection can be performed, but the role of mesenteric lymph nodes (MLNs) in advanced OC remains unclear, and its significance in treatment and follow-up evaluation remains to be determined. This study aimed to evaluate the prevalence of MLN involvement in patients who underwent digestive resection for OC peritoneal metastases (PM) and to investigate its potential prognostic value. METHODS: This retrospective, descriptive study included patients who underwent CRS with curative intent for OC with PM between 1 January 2007 and 31 December 2020. The study assessed MLN status and other clinicopathologic features to determine their prognostic value in relation to overall survival (OS) and progression-free survival (PFS). RESULTS: The study enrolled 159 women with advanced OC, 77 (48.4%) of whom had a digestive resection. For 61.1% of the patients who underwent digestive resection, MLNs were examined and found to be positive in 56.8%. No statistically significant associations were found between MLN status and OS (p = 0.497) or PFS ((p = 0.659). CONCLUSIONS: In anatomopathologic studies, MLNs are not systematically investigated but are frequently involved. In the current study, no statistically significant associations were found between MLN status and OS or PFS. Further prospective studies with a systematic and standardized approach should be performed to confirm these findings.
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Hipertermia Inducida , Neoplasias Ováricas , Neoplasias Peritoneales , Humanos , Femenino , Pronóstico , Peritoneo/patología , Estudios Retrospectivos , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Peritoneales/secundario , Estudios Prospectivos , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Neoplasias Ováricas/patología , Carcinoma Epitelial de Ovario/cirugía , Tasa de SupervivenciaRESUMEN
IL-13 signaling polarizes macrophages to an M2 alternatively activated phenotype, which regulates tissue repair and anti-inflammatory responses. However, an excessive activation of this pathway leads to severe pathologies, such as allergic airway inflammation and asthma. In this work, we identified NOTCH4 receptor as an important modulator of M2 macrophage activation. We show that the expression of NOTCH4 is induced by IL-13, mediated by Janus kinases and AP1 activity, probably mediated by the IL-13Rα1 and IL-13Rα2 signaling pathway. Furthermore, we demonstrate an important role for NOTCH4 signaling in the IL-13 induced gene expression program in macrophages, including various genes that contribute to pathogenesis of the airways in asthma, such as ARG1, YM1, CCL24, IL-10, or CD-163. We also demonstrate that NOTCH4 signaling modulates IL-13-induced gene expression by increasing IRF4 activity, mediated, at least in part, by the expression of the histone H3K27me3 demethylase JMJD3, and by increasing AP1-dependent transcription. In summary, our results provide evidence for an important role of NOTCH4 signaling in alternative activation of macrophages by IL-13 and suggest that NOTCH4 may contribute to the increased severity of lesions in M2 inflammatory responses, such as allergic asthma, which points to NOTCH4 as a potential new target for the treatment of these pathologies.
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Asma , Interleucina-13 , Humanos , Macrófagos/metabolismo , Inflamación/metabolismo , Transducción de Señal/genética , Receptor Notch4/metabolismoRESUMEN
In the first two experiments an empty tube open at one end was placed in different locations. Male hamsters, tested one at a time, tended to stay close to the tube or in it. During the first minute of the first 4 sessions of Experiment 3, the hamster was unrestrained. If it entered the tube, it was locked within the tube. If it did not enter the tube during the first min, it was placed in it, and the tube was locked. Fifteen min later, the tube was opened, and the hamster was unrestrained for a further 20 min. The tube remained open during Session 5. Hamsters spent more time near the tube than predicted by chance and continued to enter the tube although tube-occupancy duration did not differ from chance levels. In Experiment 4, male rats were tested in two groups: rats in one group had been previously trapped in a tube and rats in the other group allowed to freely explore the test space. For the first two min of each of four 20-min sessions, trapped-group subjects were permitted to move about the chamber unless they entered the tube. In that case, they were locked in for the remainder of the session. If, after two min, they did not enter the tube, they were locked in it for the remaining 18 min. Free rats were unrestricted in all sessions. In Session 5, when both groups were permitted to move freely in the chamber, trapped and free rats spent more time in and near the tube than predicted by chance. These data show tube restraint does not seem to distress either hamsters or rats.
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Empatía , Roedores , Humanos , Ratas , Masculino , AnimalesRESUMEN
INTRODUCTION: The frequency of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in Latin America has decreased considerably. However, new infections continue to be recorded, and the pediatric population remains one of the most vulnerable groups in this region. The main objective of the study was to describe the clinical, epidemiological and psychosocial characteristics of new diagnoses of HIV MTCT in 2018 in the PLANTAIDS network (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children) during the 3 years following diagnosis. METHODOLOGY: Retrospective, multicenter, descriptive study based on a 3-year follow-up of patients diagnosed with HIV infection due to MTCT in 2018 in 10 hospitals in 8 Latin American countries (Costa Rica, Ecuador, Mexico, Honduras, El Salvador, Panama, Guatemala and Venezuela). The hospitals belonged to the PLANTAIDS network, which is included in CYTED (Ibero-American Programme of Science and Technology for Development). RESULTS: The study population comprised 72 pediatric patients (38.9% male). The median age at diagnosis was 2.4 years (IQR: 0.8-5.4). There were 35 cases of opportunistic infections corresponding to 25 patients (34.7%), with tuberculosis being the most common. Adequate childhood vaccination coverage was achieved in 80.5%. There were 3 cases of acute SARS-CoV-2 infection, and these were asymptomatic or mildly symptomatic. According to the Centers for Disease Control and Prevention (CDC) classification, the most frequent clinical-immunological stage at all check-ups was C1. Three patients died from opportunistic infections and/or advanced HIV infection. CONCLUSIONS: It is important to diagnose HIV infection early in pediatrics, since early initiation of ART is associated with a decrease in mortality. Despite this, HIV infection has a poor prognosis in children, necessitating adequate follow-up to ensure adherence to health care and ART, although it can sometimes prove difficult in children.
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Infecciones por VIH , Infecciones Oportunistas , Niño , Humanos , Masculino , Femenino , Lactante , Preescolar , América Latina/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , VIH , Estudios Retrospectivos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Estudios de SeguimientoRESUMEN
Inhaled tobramycin treatment has been associated with nephrotoxicity in some case reports, but limited data are available about serum levels and its possible systemic absorption in lung transplant recipients (LTR). We conducted a single-center, observational and retrospective study of all adult (>18 years old) LTR treated with inhaled tobramycin for at least 3 days between June 2019 and February 2022. Trough serum levels were collected and >2 µg/mL was considered a high drug level. The primary outcome assessed the presence of detectable trough levels, while the secondary outcome focused on the occurrence of acute kidney injury (AKI) in individuals with detectable trough levels. Thirty-four patients, with a median age of 60 years, were enrolled. The primary indications for treatment were donor bronchial aspirate bacterial isolation (18 patients) and tracheobronchitis (15 patients). In total, 28 patients (82%) exhibited detectable serum levels, with 9 (26%) presenting high levels (>2 µg/mL). Furthermore, 9 patients (26%) developed acute kidney injury during the treatment course. Median trough tobramycin levels were significantly elevated in invasively mechanically ventilated patients compared to non-ventilated individuals (2.5 µg/mL vs. 0.48 µg/mL) (p < 0.001). Inhaled tobramycin administration in LTRs, particularly in those requiring invasive mechanical ventilation, may result in substantial systemic absorption.
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Lesión Renal Aguda , Tobramicina , Humanos , Persona de Mediana Edad , Lesión Renal Aguda/inducido químicamente , Administración por Inhalación , Antibacterianos/efectos adversos , Estudios de Cohortes , Pulmón , Estudios Retrospectivos , Tobramicina/efectos adversos , Receptores de TrasplantesRESUMEN
The use of a new nanomaterial in the feed chain requires a risk assessment that involves in vitro gastrointestinal digestions to predict its degradation and oral exposure to nanoparticles. In this study, a nanosilver-based material was incorporated into pig and chicken feed as a growth-promoting additive and subjected to the corresponding in vitro gastrointestinal digestions. An inductively coupled plasma mass spectroscopy (ICP-MS) analytical platform was used to obtain information about the silver released in the different digestion phases. It included conventional ICP-MS for total silver determination, but also single particle ICP-MS and coupling to hydrodynamic chromatography for detection of dissolved and particulate silver. The bioaccessible fraction in the intestinal phase accounted for 8-13% of the total silver, mainly in the form of dissolved Ag(I) species, with less than 0.1% as silver-containing particles. Despite the additive behaving differently in pig and chicken digestions, the feed matrix played a relevant role in the fate of the silver.
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Digestión , Tracto Gastrointestinal , Nanopartículas del Metal , Alimentación Animal , Pollos , Tracto Gastrointestinal/metabolismo , Caolín/química , Espectrometría de Masas , Nanopartículas del Metal/química , Plata/química , Porcinos , AnimalesRESUMEN
Developmental dysplasia of the hip (DDH) is the most common musculoskeletal anomaly of childhood. This study analyses paediatrician's concordance performing hip ultrasound according to Graf's method. An analytical cross-sectional study is designed. Patients' hips are evaluated by Graf's ultrasound method at 4-6 and 12-16 weeks of age. Demographic characteristics, pregnancy history, factors related to DDH, hip type, and α and ß angles are collected. To assess the agreement degree of hip diagnosis and hip types Kappa index (I. kappa) is used. Intraclass correlation coefficient (ICC) evaluates the concordance of α and ß angles. A p value < 0.05 is considered statistically significant. All results are represented with their 95% confidence interval (95% CI). Four hundred sixty-seven neonates are recruited and meet the inclusion criteria. A total of 3182 images were analysed. Agreement between paediatricians according to hip diagnosis and different types ranges from moderate to almost perfect I. kappa 0.6-1.0 (95% CI 0.5-0.7; 95% CI 1.0-1.0). α angle ICC for paediatricians is between 0.75 and 0.88 (95% CI 0.61-0.86; 95% CI 0.80-0.92). ß angle value agreement degree among paediatricians at both visits is moderate. The Graf method is the most popular ultrasound technique for hip assessment. In our setting, paediatricians carry out children follow-up; therefore, they should perform universal screening. In this study agreement degree between paediatricians varies between substantial and almost perfect. Conclusion: The Graf ultrasound procedure performed by paediatricians is a reliable test and can be used for DDH screening. What is Known ⢠Developmental dysplasia of the hip (DDH) is the most common congenital musculoskeletal anomaly of childhood. Early diagnosis and treatment improve DDH prognosis. Lack of detection can cause complications such as lameness, early osteoarthritis and need for hip replacement at an early age. What is New ⢠Today, the best screening method is still subject of debate. But it seems that with selective screening many pathological hips go unnoticed. Universal screening implementation may be a challenge in some countries. But the question is if this could be carried out by paediatricians as part of healthy child follow-up.