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1.
Cell ; 185(20): 3789-3806.e17, 2022 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-36179670

RESUMEN

Cancer-microbe associations have been explored for centuries, but cancer-associated fungi have rarely been examined. Here, we comprehensively characterize the cancer mycobiome within 17,401 patient tissue, blood, and plasma samples across 35 cancer types in four independent cohorts. We report fungal DNA and cells at low abundances across many major human cancers, with differences in community compositions that differ among cancer types, even when accounting for technical background. Fungal histological staining of tissue microarrays supported intratumoral presence and frequent spatial association with cancer cells and macrophages. Comparing intratumoral fungal communities with matched bacteriomes and immunomes revealed co-occurring bi-domain ecologies, often with permissive, rather than competitive, microenvironments and distinct immune responses. Clinically focused assessments suggested prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers, and synergistic predictive performance with bacteriomes.


Asunto(s)
Micobioma , Neoplasias , ADN de Hongos/análisis , Hongos/genética , Humanos
2.
Nature ; 614(7946): 118-124, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36697822

RESUMEN

Diabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves1,2. Although the onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidaemia3-7, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes8-10. Serine and glycine are closely related NEAAs whose levels are consistently reduced in patients with metabolic syndrome10-14, but the mechanistic drivers and downstream consequences of this metabotype remain unclear. Low systemic serine and glycine are also emerging as a hallmark of macular and peripheral nerve disorders, correlating with impaired visual acuity and peripheral neuropathy15,16. Here we demonstrate that aberrant serine homeostasis drives serine and glycine deficiencies in diabetic mice, which can be diagnosed with a serine tolerance test that quantifies serine uptake and disposal. Mimicking these metabolic alterations in young mice by dietary serine or glycine restriction together with high fat intake markedly accelerates the onset of small fibre neuropathy while reducing adiposity. Normalization of serine by dietary supplementation and mitigation of dyslipidaemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidaemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically.


Asunto(s)
Diabetes Mellitus Experimental , Insulina , Metabolismo de los Lípidos , Enfermedades del Sistema Nervioso Periférico , Serina , Animales , Ratones , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Glicina/metabolismo , Insulina/metabolismo , Enfermedades del Sistema Nervioso Periférico/metabolismo , Serina/metabolismo , Dieta Alta en Grasa , Adiposidad , Esfingolípidos/metabolismo , Neuropatía de Fibras Pequeñas , Dislipidemias
3.
Cell ; 150(3): 470-80, 2012 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-22863002

RESUMEN

Many of the immune and metabolic changes occurring during normal pregnancy also describe metabolic syndrome. Gut microbiota can cause symptoms of metabolic syndrome in nonpregnant hosts. Here, to explore their role in pregnancy, we characterized fecal bacteria of 91 pregnant women of varying prepregnancy BMIs and gestational diabetes status and their infants. Similarities between infant-mother microbiotas increased with children's age, and the infant microbiota was unaffected by mother's health status. Gut microbiota changed dramatically from first (T1) to third (T3) trimesters, with vast expansion of diversity between mothers, an overall increase in Proteobacteria and Actinobacteria, and reduced richness. T3 stool showed strongest signs of inflammation and energy loss; however, microbiome gene repertoires were constant between trimesters. When transferred to germ-free mice, T3 microbiota induced greater adiposity and insulin insensitivity compared to T1. Our findings indicate that host-microbial interactions that impact host metabolism can occur and may be beneficial in pregnancy.


Asunto(s)
Heces/microbiología , Tracto Gastrointestinal/microbiología , Metagenoma , Embarazo , Actinobacteria/aislamiento & purificación , Animales , Femenino , Vida Libre de Gérmenes , Humanos , Lactante , Síndrome Metabólico/microbiología , Ratones , Proteobacteria/aislamiento & purificación
4.
N Engl J Med ; 386(6): 509-520, 2022 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-34914868

RESUMEN

BACKGROUND: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. RESULTS: A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, -6.8 percentage points; 95% confidence interval [CI], -11.3 to -2.4; P = 0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, -3.0 percentage points; 95% CI, -5.9 to -0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. CONCLUSIONS: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.).


Asunto(s)
Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Citidina/análogos & derivados , Hidroxilaminas/uso terapéutico , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/efectos adversos , COVID-19/virología , Citidina/efectos adversos , Citidina/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Hidroxilaminas/efectos adversos , Masculino , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación , Resultado del Tratamiento , Carga Viral , Adulto Joven
5.
Nature ; 569(7758): 655-662, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31142855

RESUMEN

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.


Asunto(s)
Microbioma Gastrointestinal/genética , Enfermedades Inflamatorias del Intestino/microbiología , Animales , Hongos/patogenicidad , Microbioma Gastrointestinal/inmunología , Salud , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/terapia , Enfermedades Inflamatorias del Intestino/virología , Filogenia , Especificidad de la Especie , Transcriptoma , Virus/patogenicidad
6.
Genome Res ; 31(11): 2131-2137, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34479875

RESUMEN

The number of publicly available microbiome samples is continually growing. As data set size increases, bottlenecks arise in standard analytical pipelines. Faith's phylogenetic diversity (Faith's PD) is a highly utilized phylogenetic alpha diversity metric that has thus far failed to effectively scale to trees with millions of vertices. Stacked Faith's phylogenetic diversity (SFPhD) enables calculation of this widely adopted diversity metric at a much larger scale by implementing a computationally efficient algorithm. The algorithm reduces the amount of computational resources required, resulting in more accessible software with a reduced carbon footprint, as compared to previous approaches. The new algorithm produces identical results to the previous method. We further demonstrate that the phylogenetic aspect of Faith's PD provides increased power in detecting diversity differences between younger and older populations in the FINRISK study's metagenomic data.


Asunto(s)
Microbiota , Microbiota/genética , Filogenia
8.
Int J Med Sci ; 21(2): 332-340, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38169578

RESUMEN

The aim of this study was to investigate the efficacy of physical exercise in chronic kidney disease, describing its impact on the Klotho-FGF23 axis. PubMed, Web of Science and Scopus databases, updated to January 2023, were searched. The present study employed mean difference and a 95% confidence interval (CI) to examine the efficacy of the intervention. Heterogeneity was assessed through inconsistency statistics (I2). Out of the 299 studies identified, a total of 4 randomized controlled trials (RCTs), comprising 272 participants, met the eligibility criteria. Compared with the control group, physical exercise significantly decreased the concentrations of FGF23 (MD: -102.07 Pg/mL, 95% CI: -176.23.47, -27.91 I2= 97%, p = 0.001), and a significantly increased the concentrations of Klotho protein: (MD: 158.82 Pg/mL, 95% CI: 123.33, -194.31, I2 = 0%, p = 0.001). The results of our study indicated that the exercise has a direct relationship with Klotho-FGF23 axis. We can conclude that physical exercise in patients with CKD produces beneficial effects on the pathophysiological components related to this disease, including cardiorespiratory fitness and vascular functions. As observed, both endurance and aerobic physical exercise increase Klotho production and decrease FGF23 levels. Evidence indicates that exercise attenuates the progression of CKD, improves uremic parameters and down-regulates inflammation-related markers.


Asunto(s)
Glucuronidasa , Insuficiencia Renal Crónica , Humanos , Ejercicio Físico , Factores de Crecimiento de Fibroblastos , Riñón , Insuficiencia Renal Crónica/terapia
9.
Clin Oral Implants Res ; 35(10): 1310-1323, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38940623

RESUMEN

OBJECTIVES: The aim of this study was to evaluate esthetic parameters in the anterior maxillary region by comparing single-piece zirconia versus titanium narrow-diameter implants. Additionally, clinical, radiological and patient-reported outcome measures (PROMs) were analyzed. MATERIALS AND METHODS: Thirty implants (tissue level implant) were placed in 30 patients in the maxillary esthetic sector. Depending on randomization, a zirconia (test) or titanium implant (control) was placed. Esthetic, clinical, and radiological parameters, including the implant crown esthetic index (ICAI), pink esthetic score (PES), probing pocket depth, bleeding on probing, plaque index, and marginal bone levels, were evaluated at 12, 36 and 60 months after loading. RESULTS: Sixty months after crown placement, no significant differences were found between groups. The ICAI values were 5.25 ± 4.21 and 4.50 ± 2.98 for the test and control groups, respectively. The corresponding PES values were 7.44 ± 1.93 and 7.43 ± 1.74 for the test and control groups, respectively. There were no significant intergroup differences for the rest of the parameters evaluated. CONCLUSION: It can be suggested that monotype zirconia implants may serve as a potential alternative to titanium implants in selected clinical scenarios. While the results demonstrated comparable esthetic, clinical, and radiological aspects for zirconia implants as compared to titanium implants after a 5-year follow-up period, further research with larger sample sizes and longer-term follow-up is recommended.


Asunto(s)
Diseño de Prótesis Dental , Estética Dental , Maxilar , Titanio , Circonio , Humanos , Maxilar/cirugía , Maxilar/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Adulto , Implantes Dentales , Implantación Dental Endoósea/métodos
10.
Heart Vessels ; 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39375197

RESUMEN

INTRODUCTION: Differentiation of tachycardia-induced cardiomyopathy (TIC) from dilated cardiomyopathy (DCM) in patients admitted for heart failure (HF) with left ventricular dysfunction and supraventricular tachyarrhythmia (SVT) remains challenging. The role of tissue tracking (TT) in this setting remains unknown. METHODS: Forty-three consecutive patients admitted for HF due to SVT with left ventricular ejection fraction (LVEF) < 50% undergoing CMR were retrospectively included. Those eventually evolving to LVEF > 50% at follow-up were classified as TIC and those maintaining a LVEF < 50% were classified as DCM. Clinical, echocardiography, and CMR findings, including TT, were analyzed to predict LVEF recovery. RESULTS: Twenty-five (58%) patients were classified as TIC. Late gadolinium enhancement (LGE) was more frequent in DCM group (61% vs 16%, p = 0.004). Left ventricle (LV) peak systolic radial velocity and peak diastolic radial strain rate were lower in DCM group (7.24 ± 4.44 mm/s vs 10.8 ± 4.5 mm/s; p = 0.015 and -0.12 ± 0.33 1/s vs -0.48 ± 0.51 1/s; p = 0.016, respectively). Right ventricle (RV) peak circumferential displacement was lower in patients with TIC (0.2 ± 1.3 vs 1.3 ± 0.9°; p = 0.009). In the multivariate analysis, diabetes (p = 0.046), presence of LGE (p = 0.028), LV peak systolic radial velocity < 7.5 mm/s (p = 0.034), and RV peak circumferential displacement > 0.5° (p = 0.028) were independent predictors of lack of LVEF recovery. CONCLUSION: In the setting of acute HF with LV dysfunction related to SVT, diabetes, LGE, LV peak systolic velocity, and RV peak circumferential displacement are independent predictors of lack of LVEF recovery and, therefore, represent clinically useful parameters to differentiate TIC from DCM.

11.
J Ultrasound Med ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39351866

RESUMEN

OBJECTIVES: Neuromuscular respiratory failure after cervical spinal cord injury (cSCI) can lead to dependence on an invasive mechanical ventilator. Ventilator-free breathing after cSCI is associated with improved morbidity, mortality, and quality of life. We investigated the use of diaphragm muscle ultrasound to predict ventilator weaning outcomes after cSCI. METHODS: This is a retrospective case series conducted at a university-affiliated freestanding inpatient rehabilitation facility. We identified patients with cSCI who had a tracheostomy and were dependent on an invasive mechanical ventilator at the time of admission to inpatient rehabilitation. A diaphragm muscle ultrasound was performed, which included measurements of the thickness of the diaphragm and a calculation of the thickening ratio (TR), which reflects diaphragm muscle contraction. The primary outcome measure was the need for mechanical ventilation at time of discharge from the inpatient rehabilitation facility. Successful ventilator weaning was defined as either daytime or full 24-hour ventilator-free breathing. RESULTS: Of the 21 patients enrolled, 11 (52%) were able to wean successfully (partially or fully) from the ventilator. Of the ultrasound measurements that were taken, the TR was the optimal predictor for ventilator weaning outcomes. A threshold of TR ≥ 1.2 as the maximum hemidiaphragm measurement had a sensitivity of 1.0 and specificity of 0.90 for predicting ventilator weaning. CONCLUSION: Normal diaphragm contractility (TR ≥ 1.2) as determined by diaphragm muscle ultrasound is a strong positive predictor for successful ventilator weaning in patients with cSCI. Utilizing diaphragm ultrasound, rehabilitation physicians can set precision rehabilitation goals regarding ventilator weaning for inpatients with respiratory failure after cSCI, potentially improving both outcomes and quality of life.

12.
Sensors (Basel) ; 24(7)2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38610443

RESUMEN

The present work proposes a comprehensive metaheuristic methodology for the development of a medical robot for the upper limb rehabilitation, which includes the topological optimization of the device, kinematic models (5 DOF), human-robot interface, control and experimental tests. This methodology applies two cutting-edge triads: (1) the three points of view in engineering design (client, designer and community) and (2) the triad formed by three pillars of Industry 4.0 (autonomous machines and systems, additive manufacturing and simulation of virtual environments). By applying the proposed procedure, a robotic mechanism was obtained with a reduction of more than 40% of its initial weight and a human-robot interface with three modes of operation and a biomechanically viable kinematic model for humans. The digital twin instance and its evaluation through therapeutic routines with and without disturbances was assessed; the average RMSEs obtained were 0.08 rad and 0.11 rad, respectively. The proposed methodology is applicable to any medical robot, providing a versatile and effective solution for optimizing the design and development of healthcare devices. It adopts an innovative and scalable approach to enhance their processes.


Asunto(s)
Dispositivo Exoesqueleto , Robótica , Humanos , Comercio , Simulación por Computador , Ingeniería
13.
Sensors (Basel) ; 24(9)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38733030

RESUMEN

This article presents a study on the neurobiological control of voluntary movements for anthropomorphic robotic systems. A corticospinal neural network model has been developed to control joint trajectories in multi-fingered robotic hands. The proposed neural network simulates cortical and spinal areas, as well as the connectivity between them, during the execution of voluntary movements similar to those performed by humans or monkeys. Furthermore, this neural connection allows for the interpretation of functional roles in the motor areas of the brain. The proposed neural control system is tested on the fingers of a robotic hand, which is driven by agonist-antagonist tendons and actuators designed to accurately emulate complex muscular functionality. The experimental results show that the corticospinal controller produces key properties of biological movement control, such as bell-shaped asymmetric velocity profiles and the ability to compensate for disturbances. Movements are dynamically compensated for through sensory feedback. Based on the experimental results, it is concluded that the proposed biologically inspired adaptive neural control system is robust, reliable, and adaptable to robotic platforms with diverse biomechanics and degrees of freedom. The corticospinal network successfully integrates biological concepts with engineering control theory for the generation of functional movement. This research significantly contributes to improving our understanding of neuromotor control in both animals and humans, thus paving the way towards a new frontier in the field of neurobiological control of anthropomorphic robotic systems.


Asunto(s)
Mano , Redes Neurales de la Computación , Robótica , Tendones , Humanos , Robótica/métodos , Mano/fisiología , Tendones/fisiología , Movimiento/fisiología , Red Nerviosa/fisiología , Fenómenos Biomecánicos/fisiología , Tractos Piramidales/fisiología , Animales
14.
Nano Lett ; 23(15): 6944-6950, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37498750

RESUMEN

The nature of superconductivity and its interplay with strong spin-orbit coupling at the KTaO3(111) interfaces remain a subject of debate. To address this problem, we grew epitaxial LaMnO3/KTaO3(111) heterostructures. We show that superconductivity is robust against the in-plane magnetic field, with the critical field of superconductivity reaching ∼25 T in optimally doped heterostructures. The superconducting order parameter is highly sensitive to the carrier density. We argue that spin-orbit coupling drives the formation of anomalous quasiparticles with vanishing magnetic moment, providing significant condensate immunity against magnetic fields beyond the Pauli paramagnetic limit. These results offer design opportunities for superconductors with extreme resilience against the applied magnetic fields.

15.
Fam Process ; 63(1): 414-427, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36747374

RESUMEN

Family functioning plays an important role in explaining the high prevalence of depressive symptoms in adolescents and it is necessary to identify the family functioning characteristics responsible for this relationship. In turn, while socioeconomic status (SES) is associated with adolescent depressive symptoms, the mechanisms that explain this relationship are largely unknown. In this study, we used the McMaster Family Assessment Device (FAD) to obtain a picture of the family functioning dimensions that genuinely contribute to explaining the relationship between family functioning and adolescent depressive symptoms and analyzed the mediating effect of family functioning on the impact of SES on depressive symptoms. Regression-based conditional process analysis was used with a sample of 636 adolescents aged 12-17 years. Pratt's measures in regression analyses showed that 95% of the variance in depressive symptoms was accounted for by three of the six FAD dimensions: the ability to experience and express emotions appropriately-Affective Responsiveness-the ability to maintain adequate involvement among family members-Affective Involvement-and the ability to set and abide by rules and standards of behavior-Behavioral Control. Results also showed that the impact of SES on depressive symptoms was mediated by the existence of clear expectations about standards of behavior and behavioral patterns for handling family tasks-Behavioral Control and Roles-and, for the boys, by experiencing and expressing emotions appropriately. The results emphasize the importance of affect and clear-cut family rules to prevent adolescent depressive symptoms and suggest that the existence of family rules and roles buffer the impact of SES on adolescent wellbeing.


Asunto(s)
Depresión , Familia , Masculino , Humanos , Adolescente , Depresión/psicología , Familia/psicología , Emociones , Composición Familiar , Clase Social
16.
Environ Microbiol ; 25(9): 1747-1761, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37186411

RESUMEN

Quercus pyrenaica is a woody species of high landscape value, however, its forests show an advanced state of degradation in the Iberian Peninsula. Afforestation typically has low success, thus, it is necessary to improve the fitness of oaks plantlets to be transplanted, for instance, by inoculating beneficial microorganisms. In adding microorganisms to ecosystems, there must be balanced efficacy with potential effects on native microbial communities. We addressed changes in diversity, richness, composition and co-occurrence networks of prokaryotic communities in the rhizosphere of inoculated and control trees outplanted to three different sites located in the Sierra Nevada National and Natural Park (Spain). After 18 months in wild conditions, we did not detect changes due to the inoculation in the richness, diversity and structure in none of the sites. However, we observed an increase in the complexity of the co-occurrence networks in two experimental areas. Modularization of the networks changed as a result of the inoculation, although the sense of the change depended on the site. Although it was impossible to unravel the effect of bacterial inoculation, our results highlighted that inoculation alters the association of rhizosphere bacteria without entailing other changes, so networks should be analysed prior to inoculating the plantlets.


Asunto(s)
Microbiota , Quercus , Rizosfera , Árboles , Bosques , Microbiología del Suelo
17.
Chemistry ; 29(70): e202302847, 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-37743257

RESUMEN

The study of halogen bonds (XBs) has been a subject of great interest in recent years due to its clear application in catalysis, liquid crystals, and crystal engineering. In this study, we analyzed the intermolecular interactions, in particular halogen bonds in BODIPYs with an increasing number of bromine atoms. The computational study included analyses through three different methods: the first approach of close contacts provided by mercury, then the expanded approach of the electron density partition of the molecules in the crystals provided by the analysis of Hirshfeld surfaces, and finally, the approach of the Quantum Theory of Atoms in Molecules (QT-AIM) to characterize the non-covalent interactions through finding electron density critical points between atoms and between neighboring molecules. The use of different computational methods allowed to gain insight into the interactions directing the crystal packing as the number of bromine atoms increased in the BODIPY moiety. Monocoordinated and bifurcated halogen bonds involving halide/halide were found. The penta-brominated BODIPY showed four-center cyclic nodes where each node is linked via XBs. This kind of motif can be useful in supramolecular chemistry and self-assembly.

18.
J Nutr ; 153(7): 2004-2015, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36828255

RESUMEN

BACKGROUND: The Dietary Guidelines for Americans advises on dietary intake to meet nutritional needs, promote health, and prevent diseases. Diet affects the intestinal microbiota and is increasingly linked to health. It is vital to investigate the relationships between diet quality and the microbiota to better understand the impact of nutrition on human health. OBJECTIVES: This study aimed to investigate the differences in fecal microbiota composition in adults from the American Gut Project based on their adherence to the Dietary Guidelines for Americans. METHODS: This study was a cross-sectional analysis of the 16S sequencing and food frequency data of a subset of adults (n = 432; age = 18-60 y; 65% female, 89% white) participating in the crowdsourced American Gut Project. The Healthy Eating Index-2015 assessed the compliance with Dietary Guideline recommendations. The cohort was divided into tertiles based on Healthy Eating Index-2015 scores, and differences in taxonomic abundances and diversity were compared between high and low scorers. RESULTS: The mean Total Score for low-scoring adults (58.1 ± 5.4) was comparable with the reported score of the average American adult (56.7). High scorers for the Total Score and components related to vegetables, grains, and dairy had greater alpha diversity than low scorers. High scorers in the fatty acid component had a lower alpha diversity than low scorers (95% CI: 0.35, 1.85). A positive log-fold difference in abundance of plant carbohydrate-metabolizing taxa in the families Lachnospiraceae and Ruminococcaceae was observed in high-scoring tertiles for Total Score, vegetable, fruit, and grain components (Benjamini-Hochberg; q < 0.05). CONCLUSIONS: Adults with greater compliance to the Dietary Guidelines demonstrated higher diversity in their fecal microbiota and greater abundance of bacteria capable of metabolizing complex carbohydrates, providing evidence on how Dietary Guidelines support the gut microbiota.


Asunto(s)
Promoción de la Salud , Microbiota , Humanos , Adulto , Estados Unidos , Adolescente , Adulto Joven , Persona de Mediana Edad , Estudios Transversales , Dieta , Verduras , ARN Ribosómico 16S
19.
Nat Chem Biol ; 17(2): 146-151, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33199911

RESUMEN

Untargeted mass spectrometry is employed to detect small molecules in complex biospecimens, generating data that are difficult to interpret. We developed Qemistree, a data exploration strategy based on the hierarchical organization of molecular fingerprints predicted from fragmentation spectra. Qemistree allows mass spectrometry data to be represented in the context of sample metadata and chemical ontologies. By expressing molecular relationships as a tree, we can apply ecological tools that are designed to analyze and visualize the relatedness of DNA sequences to metabolomics data. Here we demonstrate the use of tree-guided data exploration tools to compare metabolomics samples across different experimental conditions such as chromatographic shifts. Additionally, we leverage a tree representation to visualize chemical diversity in a heterogeneous collection of samples. The Qemistree software pipeline is freely available to the microbiome and metabolomics communities in the form of a QIIME2 plugin, and a global natural products social molecular networking workflow.


Asunto(s)
Espectrometría de Masas/métodos , Metabolómica , Algoritmos , Análisis por Conglomerados , ADN/química , Dermatoglifia del ADN , Bases de Datos Factuales , Ecología , Análisis de los Alimentos , Microbiota , Análisis Multivariante , Programas Informáticos , Espectrometría de Masas en Tándem , Flujo de Trabajo
20.
Lupus ; 32(12): 1409-1417, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37840528

RESUMEN

BACKGROUND: Pregnancy in SLE continues to be a challenge. The neutrophil-to-lymphocyte ratio (NLR) and chemerin are predictors of preeclampsia in the general population; however, their role as predictors of maternal-fetal complications in pregnant SLE patients has not been analyzed. OBJECTIVE: To investigate the prognostic value of NLR and serum chemerin, to predict maternal-fetal complications in pregnant SLE patients, and compare both biomarkers among three study groups. METHODS: Design: Analytical cross-sectional study of cases and controls with the following study groups: systemic lupus erythematosus (SLE), preeclampsia, and healthy. NLR and chemerin serum were determined between 20 and 25 weeks of gestation. Patients were evaluated every 4-6 weeks until pregnancy resolution. Maternal and fetal outcomes were registered. We employed Receiver Operating Characteristic (ROC) curves to validate prognostic values. RESULTS: Seventy pregnant patients were included: 20 with SLE, 20 with preeclampsia, and 30 healthy pregnant women; NLR values were 4 (2.3-5.6) in SLE, 6 (4.6-9.2) in preeclampsia, and 2.8 (2.1-2.9) in the group of healthy women (p = .0001). Chemerin levels were: 26 (15.3-56.2) in SLE, 96 (37.3-146.2) in preeclampsia, and 24.6 ng/mL (15.3-47.4) in the healthy group (p = .007) Maternal complications were observed in 11 (55%), 20 (100%), and 8 (26%) per group, respectively. Thrombocytopenia was the most frequent complication in all pregnant women, followed by hypertensive disorders. Fetal complications were registered in 12 (60%), 16 (80%), and 2 (6.7%), respectively. Congenital malformations and prematurity were the most frequent fetal complications. NLR had good diagnostic accuracy in predicting maternal-fetal complications (AUROC 0.715) p = .015, CI 95% 0.56-0.86, cut-off point level: 2.9, sensitivity 61%, specificity 78%, positive predictive value (PPV) 65%, negative predictive value (NPV) 75%. Regarding chemerin, a cut-off point level >43 ng/mL had a sensitivity of 75%, specificity of 72% AUROC 0.75, p = .001, CI 95% 0.61-0.89, PPV 51.7% NPV 87.8%, meaning that 51.7% of patients with chemerin levels >43 ng/mL have or will have preeclampsia. CONCLUSION: The NLR may help predict maternal-fetal complications in SLE pregnancy, constituting a marker of subclinical inflammation. Chemerin levels may be associated with preeclampsia. These biomarkers could improve the care of SLE patients with timely intervention of potential complications during pregnancy.


Asunto(s)
Lupus Eritematoso Sistémico , Preeclampsia , Complicaciones del Embarazo , Humanos , Embarazo , Femenino , Lupus Eritematoso Sistémico/diagnóstico , Resultado del Embarazo/epidemiología , Pronóstico , Neutrófilos , Estudios Transversales , Complicaciones del Embarazo/diagnóstico , Biomarcadores , Linfocitos , Estudios Retrospectivos
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