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1.
Blood ; 141(4): 406-421, 2023 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-36395340

RESUMEN

Glycosylation is recognized as a key process for proper megakaryopoiesis and platelet formation. The enzyme uridine diphosphate (UDP)-galactose-4-epimerase, encoded by GALE, is involved in galactose metabolism and protein glycosylation. Here, we studied 3 patients from 2 unrelated families who showed lifelong severe thrombocytopenia, bleeding diathesis, mental retardation, mitral valve prolapse, and jaundice. Whole-exome sequencing revealed 4 variants that affect GALE, 3 of those previously unreported (Pedigree A, p.Lys78ValfsX32 and p.Thr150Met; Pedigree B, p.Val128Met; and p.Leu223Pro). Platelet phenotype analysis showed giant and/or grey platelets, impaired platelet aggregation, and severely reduced alpha and dense granule secretion. Enzymatic activity of the UDP-galactose-4-epimerase enzyme was severely decreased in all patients. Immunoblotting of platelet lysates revealed reduced GALE protein levels, a significant decrease in N-acetyl-lactosamine (LacNAc), showing a hypoglycosylation pattern, reduced surface expression of gylcoprotein Ibα-IX-V (GPIbα-IX-V) complex and mature ß1 integrin, and increased apoptosis. In vitro studies performed with patients-derived megakaryocytes showed normal ploidy and maturation but decreased proplatelet formation because of the impaired glycosylation of the GPIbα and ß1 integrin, and reduced externalization to megakaryocyte and platelet membranes. Altered distribution of filamin A and actin and delocalization of the von Willebrand factor were also shown. Overall, this study expands our knowledge of GALE-related thrombocytopenia and emphasizes the critical role of GALE in the physiological glycosylation of key proteins involved in platelet production and function.


Asunto(s)
Trombocitopenia , UDPglucosa 4-Epimerasa , Humanos , Plaquetas/metabolismo , Galactosa/metabolismo , Glicosilación , Integrina beta1/metabolismo , Megacariocitos/metabolismo , Trombocitopenia/genética , Trombocitopenia/metabolismo , Trombopoyesis/genética , UDPglucosa 4-Epimerasa/genética , UDPglucosa 4-Epimerasa/metabolismo , Uridina Difosfato/metabolismo
2.
Nat Methods ; 18(10): 1259-1264, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34608309

RESUMEN

Understanding complex biological systems requires visualizing structures and processes deep within living organisms. We developed a compact adaptive optics module and incorporated it into two- and three-photon fluorescence microscopes, to measure and correct tissue-induced aberrations. We resolved synaptic structures in deep cortical and subcortical areas of the mouse brain, and demonstrated high-resolution imaging of neuronal structures and somatosensory-evoked calcium responses in the mouse spinal cord at great depths in vivo.


Asunto(s)
Neuroimagen/métodos , Óptica y Fotónica/métodos , Animales , Proteínas Bacterianas , Embrión no Mamífero , Femenino , Proteínas Fluorescentes Verdes , Proteínas Luminiscentes , Masculino , Ratones , Pez Cebra
3.
Med Care ; 62(6): 380-387, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38728678

RESUMEN

BACKGROUND: Although federal legislation made COVID-19 vaccines free, inequities in access to medical care may affect vaccine uptake. OBJECTIVE: To assess whether health care access was associated with uptake and timeliness of COVID-19 vaccination in the United States. DESIGN: A cross-sectional study. SETTING: 2021 National Health Interview Survey (Q2-Q4). SUBJECTS: In all, 21,532 adults aged≥18 were included in the study. MEASURES: Exposures included 4 metrics of health care access: health insurance, having an established place for medical care, having a physician visit within the past year, and medical care affordability. Outcomes included receipt of 1 or more COVID-19 vaccines and receipt of a first vaccine within 6 months of vaccine availability. We examined the association between each health care access metric and outcome using logistic regression, unadjusted and adjusted for demographic, geographic, and socioeconomic covariates. RESULTS: In unadjusted analyses, each metric of health care access was associated with the uptake of COVID-19 vaccination and (among those vaccinated) early vaccination. In adjusted analyses, having health coverage (adjusted odds ratio [AOR] 1.60; 95% CI: 1.39, 1.84), a usual place of care (AOR 1.58; 95% CI: 1.42, 1.75), and a doctor visit within the past year (AOR 1.45, 95% CI: 1.31, 1.62) remained associated with higher rates of COVID-19 vaccination. Only having a usual place of care was associated with early vaccine uptake in adjusted analyses. LIMITATIONS: Receipt of COVID-19 vaccination was self-reported. CONCLUSIONS: Several metrics of health care access are associated with the uptake of COVID-19 vaccines. Policies that achieve universal coverage, and facilitate long-term relationships with trusted providers, may be an important component of pandemic responses.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Accesibilidad a los Servicios de Salud , Humanos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Estudios Transversales , Estados Unidos , Masculino , Femenino , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/epidemiología , Adulto , Vacunas contra la COVID-19/administración & dosificación , Anciano , Vacunación/estadística & datos numéricos , Adolescente , Adulto Joven , SARS-CoV-2 , Factores Socioeconómicos
4.
Pediatr Transplant ; 28(2): e14707, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38419558

RESUMEN

Epstein-Barr Virus (EBV) is a ubiquitous herpes type virus that is associated with post-transplant lymphoproliferative disorder (PTLD). Usual management includes reduction or cessation of immunosuppression and in some cases chemotherapy including rituximab. However, limited therapies are available if PTLD is refractory to rituximab. Several clinical trials have investigated the use of EBV-directed T cells in rituximab-refractory patients; however, data regarding response is scarce and inconclusive. Herein, we describe a patient with EBV-PTLD refractory to rituximab after orthotopic heart transplantation (OHT) requiring EBV-directed T-cell therapy. This article aims to highlight the unique and aggressive clinical presentation and progression of PTLD with utilization of EBV-directed T-cell therapy for management and associated pitfalls.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Trasplante de Corazón , Trasplante de Células Madre Hematopoyéticas , Trastornos Linfoproliferativos , Humanos , Preescolar , Herpesvirus Humano 4 , Rituximab/uso terapéutico , Infecciones por Virus de Epstein-Barr/terapia , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/terapia , Tratamiento Basado en Trasplante de Células y Tejidos
5.
Curr Heart Fail Rep ; 21(2): 131-138, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38363515

RESUMEN

PURPOSE OF REVIEW: Heart failure (HF) is one of the most frequent causes of hospital admission in elderly patients, especially in women, who present a high prevalence of geriatric syndromes like frailty. Studies have suggested that frailty and its impact may also differ between males and females. Understanding how frailty may differently affect HF patients depending on sex is therefore imperative for providing personalized care. The aim of this review is to summarize the role of sex in the prognostic impact of frailty in HF patients. RECENT FINDINGS: Numerous studies have identified frailty as a significant predictor of all-cause mortality and hospital readmissions. A recent study of elderly HF out-patients demonstrated that while women had a higher prevalence of frailty, it was an independent predictor of mortality and readmission only in men. Moreover, another study revealed that physical frailty was associated with time to first clinical event among men but not among women. These results raise the question about why frailty affects differently HF prognosis in men and women. Women with HF present a higher prevalence of frailty, especially when it is considered as physical decline. Nevertheless, frailty affects differently HF prognosis in men and women. Women with HF present lower mortality than men and frailty is related with prognosis only in men. The different severity of HF between men and women and other hormonal, psychosocial, and clinical factors might be involved in this fact.


Asunto(s)
Fragilidad , Insuficiencia Cardíaca , Masculino , Anciano , Humanos , Femenino , Fragilidad/epidemiología , Insuficiencia Cardíaca/complicaciones , Anciano Frágil , Hospitalización , Readmisión del Paciente , Pronóstico
6.
Health Promot Pract ; : 15248399231223744, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38293773

RESUMEN

People experiencing addiction, houselessness, or who have a history of incarceration have worse health outcomes compared with the general population. This is due, in part, to practices and policies of historically White institutions that exclude the voices, perspectives, and contributions of communities of color in leadership, socio-economic development, and decision-making that matters for their wellbeing. Community-based participatory research (CBPR) approaches hold promise for addressing health inequities. However, full engagement of people harmed by systemic injustices in CBPR partnerships is challenging due to inequities in power and access to resources. We describe how an Allentown-based CBPR partnership-the Health Equity Activation Research Team of clinicians, researchers, and persons with histories of incarceration, addiction, and houselessness-uses the Radical Welcome Engagement Restoration Model (RWERM) to facilitate full engagement by all partners. Data were collected through participatory ethnography, focus groups, and individual interviews. Analyses were performed using deductive coding in a series of iterative meaning-making processes that involved all partners. Findings highlighted six defining phases of the radical welcome framework: (a) passionate invitation, (b) radical welcome, (c) authentic sense of belonging, (d) co-creation of roles, (e) prioritization of issues, and (f) individual and collective action. A guide to assessing progression across these phases, as well as a 32-item radical welcome instrument to help CBPR partners anticipate and overcome challenges to engagement are introduced and discussed.

7.
J Am Chem Soc ; 145(2): 1072-1082, 2023 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-36595477

RESUMEN

The crystal packing of organic chromophores has a profound impact on their photophysical properties. Molecular crystal engineering is generally incapable of producing precisely spaced arrays of molecules for use in photovoltaics, light-emitting diodes, and sensors. A promising alternative strategy is the incorporation of chromophores into crystalline metal-organic frameworks (MOFs), leading to matrix coordination-induced emission (MCIE) upon confinement. However, it remains unclear how the precise arrangement of chromophores and defects dictates photophysical properties in these systems, limiting the rational design of well-defined photoluminescent materials. Herein, we report new, robust Zr-based MOFs constructed from the linker tetrakis(4-carboxyphenyl)ethylene (TCPE4-) that exhibit an unexpected structural transition in combination with a prominent shift from green to blue photoluminescence (PL) as a function of the amount of acid modulator (benzoic, formic, or acetic acid) used during synthesis. Time-resolved PL (TRPL) measurements provide full spectral information and reveal that the observed hypsochromic shift arises due to a higher concentration of linker substitution defects at higher modulator concentrations, leading to broader excitation transfer-induced spectral diffusion. Spectral diffusion of this type has not been reported in a MOF to date, and its observation provides structural information that is otherwise unobtainable using traditional crystallographic techniques. Our findings suggest that defects have a profound impact on the photophysical properties of MOFs and that their presence can be readily tuned to modify energy transfer processes within these materials.


Asunto(s)
Estructuras Metalorgánicas , Ácido Acético , Ácido Benzoico , Cristalografía , Difusión
8.
Bioconjug Chem ; 34(11): 2112-2122, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37903569

RESUMEN

The encapsulation of proteins is an effective way to preserve their structure and enhance their function. One exciting possibility is adjusting the protective agent to match the specific protein's characteristics to influence its properties. In a recent study, we developed a flow cytometry-based method to quantify the encapsulation of small-molecule dyes in colloidal particles made from guanosine derivatives (supramolecular hacky sacks (SHS) particles). We aimed to determine whether this method could quantify protein encapsulation and track changes and if the particles could be tuned to bind to specific proteins. Our results showed that fluorescein isothiocyanate (FITC)-labeled proteins had apparent association constants in the micromolar range with hydrophobicity as the dominant factor enhancing the affinities. Confocal laser scanning microscopy (CLSM) imaging supported these results and provided additional information about the protein distribution within the particles. We also tested the feasibility of tuning the avidin affinity (AVI) for SHS particles with a biotin ligand. We found that increasing the amount of biotin initially enhanced AVI binding, but then reached saturation, which we hypothesize results from noncovalent cross-linking caused by strong biotin/AVI interactions. CLSM images showed that the linker also impacted the AVI distribution within the particles. Our strategy provides an advantage over other methods for quantifying protein encapsulation by being suitable for high-throughput analysis with high reproducibility. We anticipate that future efforts to use lower-affinity ligands would result in better strategies for modulating protein affinity for drug delivery applications.


Asunto(s)
Biotina , Guanosina , Biotina/química , Reproducibilidad de los Resultados , Avidina/química
9.
Microb Ecol ; 85(4): 1564-1577, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35482107

RESUMEN

Gut microbial communities provide essential functions to their hosts and are known to influence both their ecology and evolution. However, our knowledge of these complex associations is still very limited in reptiles. Here we report the 16S rRNA gene faecal microbiota profiles of two lizard species endemic to the Balearic archipelago (Podarcis lilfordi and P. pityusensis), encompassing their allopatric range of distribution through a noninvasive sampling, as an alternative to previous studies that implied killing specimens of these IUCN endangered and near-threatened species, respectively. Both lizard species showed a faecal microbiome composition consistent with their omnivorous trophic ecology, with a high representation of cellulolytic bacteria taxa. We also identified species-specific core microbiota signatures and retrieved lizard species, islet ascription, and seasonality as the main factors in explaining bacterial community composition. The different Balearic Podarcis populations are characterised by harbouring a high proportion of unique bacterial taxa, thus reinforcing their view as unique and divergent evolutionary entities.


Asunto(s)
Lagartos , Microbiota , Animales , Lagartos/microbiología , España , ARN Ribosómico 16S/genética , Heces
10.
Platelets ; 34(1): 2176699, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36846897

RESUMEN

GALE gene encodes the uridine diphosphate [UDP]-galactose-4-epimerase, which catalyzes the bidirectional interconversion of UDP-glucose to UDP-galactose, and UDP-N-acetyl-glucosamine to UDP-N-acetyl-galactosamine. In that way, GALE balances, through reversible epimerization, the pool of four sugars that are essential during the biosynthesis of glycoproteins and glycolipids. GALE-related disorder presents an autosomal recessive inheritance pattern, and it is commonly associated with galactosemia. Peripheral galactosemia generally associates with non-generalized forms or even asymptomatic presentations, while classical galactosemia may be related to complications such as learning difficulties, developmental delay, cardiac failure, or dysmorphic features. Recently, GALE variants have been related to severe thrombocytopenia, pancytopenia, and in one patient, to myelodysplastic syndrome.


What is the context? GALE gene encodes for the UDP-Galactose 4-Epimerase, an enzyme involved in the Leloir pathway of galactose catabolism and protein glycosylation.Homozygous or compound heterozygous GALE variants associate with the disorder known as galactosemia type III.Three types of galactosemia can be distinguished: the peripheral, the intermediate, and the generalized form, which associate with different clinical symptoms and GALE genetic variants.Peripheral form is considered benign, while the intermediate and the generalized form is associated with severe and syndromic manifestations, including learning difficulties, delayed growth, sensorineural hearing loss, and early-onset cataracts, among others.What is new? In the last few years, GALE variants have been linked to hematological manifestations, such as anemia, febrile neutropenia, and severe thrombocytopenia.To date, the only GALE variants described in patients presenting hematological disorders are GALE p.Arg51Trp, p.Lys78ValfsX32, p.Val128Met, p.Thr150Met, p.Leu223Pro, and p.Gly237Asp.The thrombocytopenia observed in GALE patients is associated with reduced GPIbα and ß1 integrin glycosylation and externalization to the megakaryocyte and platelet surface, disrupting the actin cytoskeleton remodeling.What is the impact? GALE is an essential protein for the correct megakaryocyte and platelet glycosylation.


Asunto(s)
Galactosemias , Trombocitopenia , UDPglucosa 4-Epimerasa , Humanos , Galactosa , Galactosemias/genética , Hemorragia , Trombocitopenia/genética , UDPglucosa 4-Epimerasa/genética
11.
Chem Biodivers ; 20(3): e202200554, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36799136

RESUMEN

The optimized geometry of palbociclib, (PD 0332991) (8-cyclopentyl-6-ethanoyl-5-methyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one), electrostatic potential map, molecular orbitals were calculated using the density functional theory. The geometry was used in a molecular docking study of palbociclib-kinase complexes, results could be explained by the charge of the nitrogen and oxygen atoms within the palbociclib. Energy gap of HOMO-LUMO surfaces, could help to explain the reactivity of the ligand and the hydrogen bonding with three different kinases, two of CDK6 and one of CDK4 type. Docking results are similar and complementary with literature reports using molecular dynamics, were hydrogen bonding was obtained and analyzed. The promiscuity of three kinases with palbociclib was detected by the docking results, thus, palbociclib could be used in other types of cancer besides myeloid leukemia. Some similarities are found with CDK4/CDK6 kinases which allow us to determine that palbociclib could be used to control other resistant inhibitor types of cancer.


Asunto(s)
Neoplasias , Humanos , Simulación del Acoplamiento Molecular , Piperazinas/farmacología , Piridinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología
12.
Int J Mol Sci ; 24(6)2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36982178

RESUMEN

Protein glycosylation, including sialylation, involves complex and frequent post-translational modifications, which play a critical role in different biological processes. The conjugation of carbohydrate residues to specific molecules and receptors is critical for normal hematopoiesis, as it favors the proliferation and clearance of hematopoietic precursors. Through this mechanism, the circulating platelet count is controlled by the appropriate platelet production by megakaryocytes, and the kinetics of platelet clearance. Platelets have a half-life in blood ranging from 8 to 11 days, after which they lose the final sialic acid and are recognized by receptors in the liver and eliminated from the bloodstream. This favors the transduction of thrombopoietin, which induces megakaryopoiesis to produce new platelets. More than two hundred enzymes are responsible for proper glycosylation and sialylation. In recent years, novel disorders of glycosylation caused by molecular variants in multiple genes have been described. The phenotype of the patients with genetic alterations in GNE, SLC35A1, GALE and B4GALT is consistent with syndromic manifestations, severe inherited thrombocytopenia, and hemorrhagic complications.


Asunto(s)
Proteínas de Transporte de Nucleótidos , Trombocitopenia , Humanos , Glicosilación , Trombocitopenia/etiología , Plaquetas/metabolismo , Megacariocitos/metabolismo , Trombopoyesis , Trombopoyetina , Proteínas de Transporte de Nucleótidos/metabolismo
13.
J Sci Food Agric ; 103(11): 5201-5212, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36922737

RESUMEN

Two-dimensional nanomaterials, such as graphene, transition metal dichalcogenides, MXenes, and other layered compounds, are the subject of intense theoretical and experimental research for applications in a wide range of advanced technological solutions, given their outstanding physical, chemical, and mechanical properties. In the context of food science and technology, their contributions are starting to appear, based on the advantages that two-dimensional nanostructures offer to agricultural- and food-related key topics, such as sustainable water use, nano-agrochemicals, novel nanosensing devices, and smart packaging technologies. These application categories facilitate the grasping of the current and potential uses of such advanced nanomaterials in the field, backed by their advantageous physical, chemical, and structural properties. Developments for water cleaning and reuse, efficient nanofertilizers and pesticides, ultrasensitive sensors for food contamination, and intelligent nanoelectronic disposable food packages are among the most promising application examples reviewed here and demonstrate the tremendous impact that further developments would have in the area as the fundamental and applied research of two-dimensional nanostructures continues. We expect this work will contribute to a better understanding of the promising characteristics of two-dimensional nanomaterials that could be used for the design of novel and feasible solutions in the agriculture and food areas. © 2023 Society of Chemical Industry.


Asunto(s)
Grafito , Nanoestructuras , Nanoestructuras/química , Grafito/química , Agricultura , Tecnología de Alimentos , Agua
14.
Nat Mater ; 20(12): 1650-1656, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34413490

RESUMEN

Emergent relativistic quasiparticles in Weyl semimetals are the source of exotic electronic properties such as surface Fermi arcs, the anomalous Hall effect and negative magnetoresistance, all observed in real materials. Whereas these phenomena highlight the effect of Weyl fermions on the electronic transport properties, less is known about what collective phenomena they may support. Here, we report a Weyl semimetal, NdAlSi, that offers an example. Using neutron diffraction, we found a long-wavelength helical magnetic order in NdAlSi, the periodicity of which is linked to the nesting vector between two topologically non-trivial Fermi pockets, which we characterize using density functional theory and quantum oscillation measurements. We further show the chiral transverse component of the spin structure is promoted by bond-oriented Dzyaloshinskii-Moriya interactions associated with Weyl exchange processes. Our work provides a rare example of Weyl fermions driving collective magnetism.

15.
Eur J Neurol ; 29(3): 802-809, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34799965

RESUMEN

BACKGROUND AND PURPOSE: Optic neuritis (ON) is often the initial symptom of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). We aimed to compare the frequency and pattern of chiasmatic lesions in MOGAD-related ON (MOGAD-ON) and NMOSD-related ON (NMOSD-ON) using conventional brain imaging (magnetic resonance imaging [MRI]) in Latin America (LATAM). METHODS: We reviewed the medical records and brain MRI (≤30 days from ON onset) of patients with a first event of MOGAD-ON and NMOSD-ON. Patients from Argentina (n = 72), Chile (n = 21), Ecuador (n = 31), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 82) were included. Antibody status was tested using a cell-based assay. Demographic, clinical, imaging and prognostic (as measured by the Visual Functional System Score [VFSS] of the Expanded Disability Status Scale) data were compared. RESULTS: A total of 246 patients (208 NMOSD and 38 MOGAD) were included. No differences were found in gender and ethnicity between the groups. We observed chiasmatic lesions in 66/208 (31.7%) NMOSD-ON and in 5/38 (13.1%) MOGAD-ON patients (p = 0.01). Of these patients with chiasmatic lesions, 54/66 (81.8%) and 4/5 had associated longitudinally extensive optic nerve lesions, 45/66 (68%) and 4/5 had bilateral lesions, and 31/66 (47%) and 4/5 showed gadolinium-enhancing chiasmatic lesions, respectively. A positive correlation was observed between VFSS and presence of bilateral (r = 0,28, p < 0.0001), chiasmatic (r = 0.27, p = 0.0001) and longitudinally extensive lesions (r = 0,25, p = 0.0009) in the NMOSD-ON group, but no correlations were observed in the MOGAD-ON group. CONCLUSIONS: Chiasmatic lesions were significantly more common in NMOSD than in MOGAD during an ON attack in this LATAM cohort. Further studies are needed to assess the generalizability of these results.


Asunto(s)
Neuromielitis Óptica , Neuritis Óptica , Acuaporina 4 , Autoanticuerpos , Humanos , América Latina , Imagen por Resonancia Magnética , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica/diagnóstico por imagen
16.
Bioorg Med Chem Lett ; 73: 128912, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35907607

RESUMEN

We report new mitochondrial uncouplers derived from the conversion of [1,2,5]oxadiazolo[3,4-b]pyrazines to 1H-imidazo[4,5-b]pyrazines. The in situ Fe-mediated reduction of the oxadiazole fragment followed by cyclization gave access to imidazopyrazines in moderate to good yields. A selection of orthoesters also allowed functionalization on the 2-position of the imidazole ring. This method afforded a variety of imidazopyrazine derivatives with varying substitution on the 2, 5 and 6 positions. Our studies suggest that both a 2-trifluoromethyl group and N-methylation are crucial for mitochondrial uncoupling capacity.


Asunto(s)
Mitocondrias , Pirazinas , Ciclización , Mitocondrias/metabolismo , Oxadiazoles/metabolismo , Pirazinas/metabolismo
17.
BMC Infect Dis ; 22(1): 949, 2022 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-36526991

RESUMEN

BACKGROUND: In 2020, the Kingdom of Cambodia experienced a nationwide outbreak of chikungunya virus (CHIKV). Despite an increase in the frequency of outbreaks and expanding geographic range of CHIKV, diagnostic challenges remain, and limited surveillance data of sufficient granularity are available to characterize epidemiological profiles and disease dynamics of the virus. METHODS: An ongoing and long-standing cross-sectional study of acute undifferentiated febrile illness (AUFI) in Cambodia was leveraged to describe the disease epidemiology and characterize the clinical presentation of patients diagnosed with CHIKV during the 2020 outbreak. Participants presenting with AUFI symptoms at ten study locations provided acute and convalescent blood samples and were tested for CHIKV using a reverse transcription-polymerase chain reaction (RT-PCR) and serological diagnostic methods including IgM and IgG. Acute and follow-up clinical data were also collected. RESULTS: From 1194 participant blood samples tested, 331 (27.7%) positive CHIKV cases were detected. Most CHIKV positive individuals (280, 84.6%) reported having a fever 3 to 4 days prior to visiting a health facility. Symptoms including chills, joint pain, nausea, vomiting, and lesions were all statistically significant among CHIKV positive participants compared to CHIKV negative AUFI participants. Cough was negatively associated with CHIKV positive participants. Positivity proportions were significantly higher among adults compared to children. No significant difference was found in positivity proportion between rainy and dry seasons during the outbreak. Positive CHIKV cases were detected in all study site provinces, with the highest test positivity proportion recorded in the rural northeast province of Kratie. CONCLUSIONS: Surveillance data captured in this study provided a clinical and epidemiological characterization of positive CHIKV patients presenting at selected health facilities in Cambodia in 2020, and highlighted the widespread distribution of the outbreak, impacting both urban and rural locations. Findings also illustrated the importance of utilizing both RT-PCR and serological testing for effective CHIKV surveillance.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Adulto , Niño , Humanos , Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/epidemiología , Estudios Transversales , Cambodia/epidemiología , Anticuerpos Antivirales , Virus Chikungunya/genética , Brotes de Enfermedades , Fiebre/epidemiología , Fiebre/etiología
18.
J Neuropsychiatry Clin Neurosci ; 34(2): 132-140, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35040665

RESUMEN

OBJECTIVE: According to DSM-5, catatonia and delirium are mutually exclusive clinical syndromes. The investigators explored the co-occurrence of delirium and catatonia (i.e., catatonic delirium) and the clinical significance of this syndrome with a sample of neurological patients. METHODS: This prospective study with consecutive sampling included patients diagnosed with delirium at the National Institute of Neurology and Neurosurgery of Mexico. DSM-5 criteria for delirium, the Confusion Assessment Method, and the Delirium Rating Scale-Revised-98 were used to select and characterize patients. Catatonia was assessed using the Bush-Francis Catatonia Rating Scale and DSM-5 diagnostic criteria. Logistic regression analysis was performed to identify etiological factors associated with catatonic delirium. RESULTS: A total of 264 patients with delirium were included, 61 (23%) of whom fulfilled the criteria for catatonia and delirium simultaneously. Brain tumors, subarachnoid hemorrhage, acute hydrocephalus, and ischemic stroke were associated with delirium without catatonic signs. Catatonic delirium was observed among patients with encephalitis, epilepsy, brain neoplasms, and brain tuberculosis. After multivariate analysis, the association between catatonic delirium and encephalitis (both viral and anti-N-methyl-d-aspartate receptor [NMDAR]) was confirmed. CONCLUSIONS: Delirium is a common complication of neurological diseases, and it can coexist with catatonia. The recognition of catatonic delirium has clinical significance in terms of etiology, as it was significantly associated with viral and anti-NMDAR encephalitis.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Catatonia , Delirio , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Catatonia/complicaciones , Catatonia/etiología , Delirio/complicaciones , Delirio/etiología , Humanos , Estudios Prospectivos
19.
Platelets ; 33(1): 27-34, 2022 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-34423718

RESUMEN

Platelet transfusion, both prophylactic and therapeutic, is a key element in modern medicine. Currently, the standard platelet product for clinical use is platelet concentrates at room temperature (20-24°C) under gentle agitation. As this temperature favors bacterial growth, storage is limited to 5-7 days, which result in high wastage rate, and complicates inventory and product availability at remote areas. Frozen and/or cold storage would ameliorate those disadvantages by reducing the risk of bacterial contamination and by extending the product shelf-life to weeks or even years. Consequently, the usefulness in transfusion medicine of platelet cryopreservation and refrigeration, two old and scarcely used platelet storage approaches, is reemerging. Indeed, there have been substantial recent research efforts to characterize both cold and cryopreserved platelets. Most recent studies indicate that cryopreserved and cold platelets display a pro-coagulant profile that may produce the rapid hemostatic response which is needed in bleeding patients. Thus, it seems appropriate that blood banks and blood transfusion centers explore the possibility of split platelet inventories consisting of platelets stored at room temperature and cryopreserved and cold-stored platelets.


Asunto(s)
Plaquetas/metabolismo , Criopreservación/métodos , Humanos
20.
Molecules ; 27(18)2022 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-36144505

RESUMEN

The temperature dependence of the electrical properties of composites formed by biphasic sodium titanate and poly(o-methoxyaniline) (Na2Ti3O7/Na2Ti6O13/POMA) with different concentrations of POMA (0%, 1%, 10%, 15%, 35% and 50%) in the ceramic matrix was determined from measurements of complex impedance. The structural details were studied by means of X-ray diffraction, confirming the formation of the Na2Ti3O7/Na2Ti6O13/POMA composites. The displacement of the (200) reflection from 2θ = 10.45° to 11.15° in the composites with 10 and 15% of POMA suggested the partial replacement of H+ for Na+ in the Na2Ti3O7 structure. The thermal properties were investigated by Thermogravimetry and Differential Thermal Analysis. The Thermogravimetry curves of the composites with POMA content of 1, 10 and 15% presented profiles similar to that of pure sodium titanate sample. The composites with 35 and 50% of POMA showed a process at temperatures around 60-70 °C, which was associated with water absorbed by the polymer. The analysis of the complex impedance spectroscopy measurements revealed that the electrical resistivity of the composites in the range from 0 to 35% increased by two orders of magnitude, with different values for each concentration. This positive temperature coefficient of resistivity was less noticeable in the composite with highest POMA mass content (50%). The rapid increase in resistivity caused an increase in the relaxation time calculated from the time domain. The electrical response of the 50% of POMA compound changes in relation to what was observed in the other compounds, which suggests that there is a saturation limit in the increase in resistivity with POMA content.


Asunto(s)
Polímeros , Titanio , Óxidos , Polímeros/química , Ácidos Polimetacrílicos , Temperatura , Agua
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