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1.
PeerJ ; 11: e16585, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38089905

RESUMEN

Restricted movement among populations decreases genetic variation, which may be the case for the Montezuma quail (Cyrtonyx montezumae), a small game bird that rarely flies long distances. In the northern limit of its distribution, it inhabits oak-juniper-pine savannas of Arizona, New Mexico, and Texas. Understanding genetic structure can provide information about the demographic history of populations that is also important for conservation and management. The objective of this study was to determine patterns of genetic variation in Montezuma quail populations using nine DNA microsatellite loci. We genotyped 119 individuals from four study populations: Arizona, Western New Mexico, Central New Mexico, and West Texas. Compared to other quail, heterozygosity was low (H¯0 = 0.22 ± 0.04) and there were fewer alleles per locus (A = 2.41 ± 0.27). The global population genetic differentiation index RST = 0.045 suggests little genetic structure, even though a Bayesian allocation analysis suggested three genetic clusters (K = 3). This analysis also suggested admixture between clusters. Nevertheless, an isolation-by-distance analysis indicates a strong correlation (r = 0.937) and moderate evidence (P = 0.032) of non-independence between geographical and genetic distances. Climate change projections indicate an increase in aridity for this region, especially in temperate ecosystems where the species occurs. In this scenario, corridors between the populations may disappear, thus causing their complete isolation.


Asunto(s)
Ecosistema , Variación Genética , Humanos , Animales , Variación Genética/genética , Teorema de Bayes , Genética de Población , Codorniz
2.
Am J Trop Med Hyg ; 109(2): 466-470, 2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37364863

RESUMEN

It remains unclear whether a previous history of tropical infectious diseases and a second SARS-COV-2 infection may influence the likelihood of later symptoms. In this prospective cohort study, individuals infected with SARS-CoV-2 were followed up by telephone shortly after diagnosis of COVID-19 and again 12 months later. Poisson regression was used to identify the predictors of the highest number of symptoms in the post-COVID-19 syndrome. A total of 1,371 patients with COVID-19, with a mean age of 39.7 ± 11.7 years and 50% female, were followed for 12 months. Reinfection was found in 32 (2.3%) participants, and 806 (58.8%) individuals reported a previous history of dengue, malaria, Zika, chikungunya, leprosy, and visceral leishmaniasis. Eight hundred seventy-seven (63.9%) participants reported late symptoms related to COVID-19. After adjusting for multiple factors, female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection were independent predictors of higher number of symptoms in post-COVID-19 syndrome. Female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection, but not previous endemic tropical diseases, were associated with long-term symptoms.


Asunto(s)
COVID-19 , Infección por el Virus Zika , Virus Zika , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , COVID-19/epidemiología , Estudios de Cohortes , Prevalencia , SARS-CoV-2 , Síndrome Post Agudo de COVID-19 , Estudios Prospectivos , Reinfección
3.
Environ Sci Technol ; 57(13): 5149-5159, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-36939598

RESUMEN

We measured submicron aerosols (PM1) at a beachfront site in Texas in Spring 2021 to characterize the "background" aerosol chemical composition advecting into Texas and the factors controlling this composition. Observations show that marine "background" aerosols from the Gulf of Mexico were highly processed and acidic; sulfate was the most abundant component (on average 57% of total PM1 mass), followed by organic material (26%). These chemical characteristics are similar to those observed at other marine locations globally. However, Gulf "background" aerosols were much more polluted; the average non-refractory (NR-) PM1 mass concentration was 3-70 times higher than that observed in other clean marine atmospheres. Anthropogenic shipping emissions over the Gulf of Mexico explain 78.3% of the total measured "background" sulfate in the Gulf air. We frequently observed haze pollution in the air mass from the Gulf, with significantly elevated concentrations of sulfate, organosulfates, and secondary organic aerosol associated with sulfuric acid. Analysis suggests that aqueous oxidation of shipping emissions over the Gulf of Mexico by peroxides in the particles might potentially be an important pathway for the rapid production of acidic sulfate and organosulfates during the haze episodes under acidic conditions.


Asunto(s)
Contaminantes Atmosféricos , Sulfatos , Sulfatos/análisis , Contaminantes Atmosféricos/análisis , Golfo de México , Oxidación-Reducción , Óxidos de Azufre/análisis , Aerosoles/análisis , Material Particulado/análisis , Monitoreo del Ambiente , China
4.
Braz J Phys Ther ; 27(1): 100478, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36657216

RESUMEN

BACKGROUND: The first-line treatment consistently recommended for people with low back pain is patient education and advice. Regardless of the duration of low back pain, clinicians should provide education on the benign nature of low back pain, reassurance about the absence of a serious medical condition, and advice to remain active. There is little guidance on how best to provide this care. OBJECTIVE: This Masterclass will draw on recent evidence to explore how physical therapy clinicians could deliver person-centred education and advice to people with low back pain to refine their clinical consultation. DISCUSSION: First, we highlight the potential value of providing validation to acknowledge the distressing experience and consequences of low back pain. Second, we describe a tool to open channels of communication to provide education and advice in a patient-centred and efficient way. Clinicians could consider using the Attitude toward Education and advice for Low back pain Questionnaire to gain an insight into patient attitudes toward education and advice at the outset of a clinical encounter. Finally, we provide options for tailoring patient education and advice to promote self-management of low back pain based on patient attitudes. We present evidence that a positive attitude toward messages about causes rather than messages about physical activity predicts intention to self-manage low back pain. We combine this evidence to suggest a pathway for clinicians to provide education and advice to people with low back pain within the time constraints of a clinical consultation.


Asunto(s)
Dolor de la Región Lumbar , Automanejo , Humanos , Dolor de la Región Lumbar/terapia , Modalidades de Fisioterapia , Ejercicio Físico , Encuestas y Cuestionarios
5.
Am J Obstet Gynecol ; 228(3): 270-275.e4, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36191605

RESUMEN

The ovaries are the female gonads that are crucial for reproduction, steroid production, and overall health. Historically, the ovary was broadly divided into regions defined as the cortex, medulla, and hilum. This current nomenclature lacks specificity and fails to consider the significant anatomic variations in the ovary. Recent technological advances in imaging modalities and high-resolution omic analyses have brought about the need for revision of the existing definitions, which will facilitate the integration of generated data and enable the characterization of organ subanatomy and function at the cellular level. The creation of these high-resolution multimodal maps of the ovary will enhance collaboration and communication among disciplines and between clinicians and researchers. Beginning in March 2021, the Pediatric and Adolescent Gynecology Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited subject-matter experts to participate in a series of workshops and meetings to standardize ovarian nomenclature and define the organ's features. The goal was to develop a spatially defined and semantically consistent terminology of the ovary to support collaborative, team science-based endeavors aimed at generating reference atlases of the human ovary. The group recommended a standardized, 3-dimensional description of the ovary and an ontological approach to the subanatomy of the ovary and definition of follicles. This new greater precision in nomenclature and mapping will better reflect the ovary's heterogeneous composition and function, support the standardization of tissue collection, facilitate functional analyses, and enable clinical and research collaborations. The conceptualization process and outcomes of the effort, which spanned the better part of 2021 and early 2022, are introduced in this article. The institute and the workshop participants encourage researchers and clinicians to adopt the new systems in their everyday work to advance the overarching goal of improving human reproductive health.


Asunto(s)
Ginecología , Ovario , Adolescente , Humanos , Femenino , Niño , Ovario/diagnóstico por imagen , Pelvis
6.
Pathogens ; 11(11)2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-36365024

RESUMEN

RNA sequencing (RNA-Seq) and mass-spectrometry-based proteomics data are often integrated in proteogenomic studies to assist in the prediction of eukaryote genome features, such as genes, splicing, single-nucleotide (SNVs), and single-amino-acid variants (SAAVs). Most genomes of parasite nematodes are draft versions that lack transcript- and protein-level information and whose gene annotations rely only on computational predictions. Angiostrongylus costaricensis is a roundworm species that causes an intestinal inflammatory disease, known as abdominal angiostrongyliasis (AA). Currently, there is no drug available that acts directly on this parasite, mostly due to the sparse understanding of its molecular characteristics. The available genome of A. costaricensis, specific to the Costa Rica strain, is a draft version that is not supported by transcript- or protein-level evidence. This study used RNA-Seq and MS/MS data to perform an in-depth annotation of the A. costaricensis genome. Our prediction improved the reference annotation with (a) novel coding and non-coding genes; (b) pieces of evidence of alternative splicing generating new proteoforms; and (c) a list of SNVs between the Brazilian (Crissiumal) and the Costa Rica strain. To the best of our knowledge, this is the first time that a multi-omics approach has been used to improve the genome annotation of A. costaricensis. We hope this improved genome annotation can assist in the future development of drugs, kits, and vaccines to treat, diagnose, and prevent AA caused by either the Brazil strain (Crissiumal) or the Costa Rica strain.

8.
PLoS One ; 17(10): e0274406, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36191010

RESUMEN

INTRODUCTION: Although several non-pharmacological interventions have been tested in the management of Fibromyalgia (FM), there is little consensus regarding the best options for the treatment of this health condition. The purpose of this network meta-analysis (NMA) is to investigate the comparative efficacy and acceptability of non-pharmacological interventions for FM, in order to assist clinical decision making through a ranking of interventions in relation to the most important clinical outcomes in these patients. METHODS AND ANALYSIS: We will perform a systematic search to identify randomised controlled trials of non-pharmacological interventions endorsed in guidelines and systematic reviews. Information sources searched will include major bibliographic databases without language or date restrictions (MEDLINE, Cochrane Library, EMBASE, AMED, PsycINFO and PEDro). Our primary outcomes will be pain intensity, patient-reported quality of life (QoL), and acceptability of treatment will be our secondary outcome. Risk of bias of the included trials will be assessed using the Cochrane risk of bias tool (RoB2). For each pairwise comparison between the different interventions, we will present mean differences (MDs) for pain intensity and QoL outcomes and Relative Risks (RRs) for acceptability, both with respective 95% confidence intervals (CIs). Initially, standard pairwise meta-analyses will be performed using a DerSimonian-Laird random effects model for all comparisons with at least two trials and then we will perform a frequentist NMA using the methodology of multivariate meta-analysis assuming a common heterogeneity parameter, using the mvmeta command and network suite in STATA. In the NMA, two different types of control group, such as placebo/sham and no intervention/waiting list will be combined as one node called "Control". The competing interventions will be ranked using the P-score, which is the frequentist analogue of surface under the cumulative ranking curve (SUCRA) for the outcomes of interest at immediate- (intervention duration of up to 2 weeks), short- (over 2 weeks up to 12 weeks) and long-terms (over 12 weeks). The confidence in the results from NMA will be assessed using the Confidence in Network Meta-analysis (CINeMA) framework. ETHICS AND DISSEMINATION: This work synthesises evidence from previously published studies and does not require ethics review or approval. A manuscript describing the findings will be submitted for publication in a peer-reviewed scientific journal. REGISTRATION: OSF (DOI: 10.17605/OSF.IO/7MS25) and registered in the PROSPERO database (CRD42020216374).


Asunto(s)
Fibromialgia , Calidad de Vida , Fibromialgia/terapia , Humanos , Metaanálisis como Asunto , Metaanálisis en Red
9.
J Chem Inf Model ; 62(24): 6553-6573, 2022 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-35960688

RESUMEN

The worldwide COVID-19 pandemic caused by the coronavirus SARS-CoV-2 urgently demands novel direct antiviral treatments. The main protease (Mpro) and papain-like protease (PLpro) are attractive drug targets among coronaviruses due to their essential role in processing the polyproteins translated from the viral RNA. In this study, we virtually screened 688 naphthoquinoidal compounds and derivatives against Mpro of SARS-CoV-2. Twenty-four derivatives were selected and evaluated in biochemical assays against Mpro using a novel fluorogenic substrate. In parallel, these compounds were also assayed with SARS-CoV-2 PLpro. Four compounds inhibited Mpro with half-maximal inhibitory concentration (IC50) values between 0.41 µM and 9.0 µM. In addition, three compounds inhibited PLpro with IC50 ranging from 1.9 µM to 3.3 µM. To verify the specificity of Mpro and PLpro inhibitors, our experiments included an assessment of common causes of false positives such as aggregation, high compound fluorescence, and inhibition by enzyme oxidation. Altogether, we confirmed novel classes of specific Mpro and PLpro inhibitors. Molecular dynamics simulations suggest stable binding modes for Mpro inhibitors with frequent interactions with residues in the S1 and S2 pockets of the active site. For two PLpro inhibitors, interactions occur in the S3 and S4 pockets. In summary, our structure-based computational and biochemical approach identified novel naphthoquinonal scaffolds that can be further explored as SARS-CoV-2 antivirals.


Asunto(s)
Antivirales , Proteasas 3C de Coronavirus , Proteasas Similares a la Papaína de Coronavirus , Naftoquinonas , Inhibidores de Proteasas , SARS-CoV-2 , Humanos , Antivirales/farmacología , Antivirales/química , COVID-19 , Simulación del Acoplamiento Molecular , Naftoquinonas/química , Naftoquinonas/farmacología , Papaína , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/enzimología , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas Similares a la Papaína de Coronavirus/antagonistas & inhibidores
10.
Diabetes Care ; 45(4): 919-927, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35147696

RESUMEN

OBJECTIVE: To assess the association of sodium-glucose cotransporter 2 (SGLT2) inhibitors with diabetic ketoacidosis compared with dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a new-user active comparator cohort study to examine two pairwise comparisons: 1) SGLT2 inhibitors versus DPP-4 inhibitors and 2) SGLT2 inhibitors versus sulfonylureas. The main outcome was diabetic ketoacidosis present on hospital admission. We adjusted for confounders through propensity score matching. We used Cox proportional hazards regression with a robust variance estimator to estimate hazard ratios (HRs) and corresponding 95% CIs while adjusting for calendar time. RESULTS: In cohort 1 (n = 85,125 for SGLT2 inhibitors and n = 85,125 for DPP-4 inhibitors), the incidence rates of diabetic ketoacidosis per 1,000 person-years were 6.0 and 4.3 for SGLT2 inhibitors and DPP4 inhibitors, respectively. In cohort 2 (n = 72,436 for SGLT2 inhibitors and n = 72,436 for sulfonylureas), the incidence rates of diabetic ketoacidosis per 1,000 person-years were 6.3 and 4.5 for SGLT2 inhibitors and sulfonylureas, respectively. In Cox proportional hazards regression models, the use of SGLT2 inhibitors was associated with a higher rate of diabetic ketoacidosis compared with DPP-4 inhibitors (adjusted HR [aHR] 1.63; 95% CI 1.36, 1.96) and sulfonylureas (aHR 1.56; 95% CI 1.30, 1.87). CONCLUSIONS: In this comparative safety study using real-world data, patients with type 2 diabetes who were newly prescribed SGLT2 inhibitors had a higher rate of diabetic ketoacidosis compared with DPP-4 inhibitors and sulfonylureas. Clinicians should be vigilant about this association.


Asunto(s)
Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Inhibidores de la Dipeptidil-Peptidasa IV , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Cetoacidosis Diabética/inducido químicamente , Cetoacidosis Diabética/complicaciones , Cetoacidosis Diabética/epidemiología , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Glucosa , Humanos , Hipoglucemiantes/efectos adversos , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Compuestos de Sulfonilurea/efectos adversos
11.
ACG Case Rep J ; 9(1): e00714, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34977260

RESUMEN

An esophagopleural fistula (EPF) is a rare condition. EPFs are typically of spontaneous, iatrogenic, or neoplastic origin. A 50-year-old man with hepatitis C and alcoholic cirrhosis presented with a history of recurrent variceal hemorrhage requiring esophageal banding, Minnesota tube placement, and a transjugular intrahepatic portosystemic shunt. His hospital course after esophageal perforation and EPF was complicated by acute respiratory failure and empyema, necessitating intubation and thoracostomy tube placement. To the best of our knowledge, this is the first reported case of EPF secondary to Minnesota tube placement. The EPF completely healed after endoscopic repair.

12.
J Health Care Poor Underserved ; 32(4): 1798-1817, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34803044

RESUMEN

Antimicrobial resistance resulting from antibiotic overuse represents an increasing public health challenge. The purpose of this study was to investigate antibiotic self-medication practices in a rural, indigenous Guatemalan population, and to compare self-prescribing patterns in rural and semi-urban populations using a One Health integrated approach, a framework acknowledging that health arises at the interface of humans, animals, and the environment. We conducted a mixed methods study using semi-structured interviews in and around San Lucas Tolimán, Guatemala. Antibiotic self-medication was common in both rural and semi-urban populations, regardless of demographic characteristics. Antibiotic usage in animals, while less common, almost always occurred without a veterinary consult. Although subjects recognized that self-medication could be harmful to health, they face significant barriers to accessing appropriate care. These patterns of use have impacts on the rise of antimicrobial resistance locally, and have the potential to contribute to the spread of such resistance globally.


Asunto(s)
Antibacterianos , Salud Única , Antibacterianos/uso terapéutico , Guatemala , Humanos , Población Rural , Población Urbana
13.
Commun Biol ; 4(1): 1168, 2021 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-34621007

RESUMEN

Knowledge of associations between fungal hosts and their bacterial associates has steadily grown in recent years as the number and diversity of examinations have increased, but current knowledge is predominantly limited to a small number of fungal taxa and bacterial partners. Here, we screened for potential bacterial associates in over 700 phylogenetically diverse fungal isolates, representing 366 genera, or a tenfold increase compared with previously examined fungal genera, including isolates from several previously unexplored phyla. Both a 16 S rDNA-based exploration of fungal isolates from four distinct culture collections spanning North America, South America and Europe, and a bioinformatic screen for bacterial-specific sequences within fungal genome sequencing projects, revealed that a surprisingly diverse array of bacterial associates are frequently found in otherwise axenic fungal cultures. We demonstrate that bacterial associations with diverse fungal hosts appear to be the rule, rather than the exception, and deserve increased consideration in microbiome studies and in examinations of microbial interactions.


Asunto(s)
Bacterias/aislamiento & purificación , Hongos , Interacciones Microbianas , Microbiota , Biología Computacional , ADN Bacteriano/análisis , ADN Ribosómico/análisis , Europa (Continente) , América del Norte , América del Sur
14.
ACG Case Rep J ; 8(5): e00610, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34549071

RESUMEN

Hirschsprung disease (HD) is a congenital bowel innervation disorder characterized by the absence of ganglion cells in the neural plexus of the colorectal wall. Variant HD describes a heterogeneous group of intestinal innervation disorders in which clinical presentation resembles HD despite the presence of ganglion cells seen in rectal biopsies. We present the first reported case of a rare variant HD, hypoganglionosis isolated in the anorectal canal, diagnosed in an adult who presented with a long history of constipation and treated with proctosigmoidectomy with coloanal anastomosis. Histopathology showed rare ganglion cells isolated in the anorectal canal.

15.
Emerg Infect Dis ; 27(9): 2462-2465, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34424171

RESUMEN

Disseminated cutaneous leishmaniasis (DCL) is an uncommon form of Leishmania braziliensis infection. It remains unknown why some people develop this clinical condition. We describe 14 DCL patients in Northeast Brazil during 2015-2018. These patients regularly drank large amounts of alcohol, possibly increasing their risk for DCL.


Asunto(s)
Alcoholismo , Leishmania braziliensis , Leishmaniasis Cutánea , Brasil/epidemiología , Etanol , Humanos , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/epidemiología
16.
Schizophr Res ; 235: 102-108, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34340062

RESUMEN

INTRODUCTION: Little is known about predictors of clinical response to clozapine treatment in treatment-resistant psychosis. Most published cohorts are small, providing inconsistent results. We aimed to identify baseline clinical predictors of future clinical response in patients who initiate clozapine treatment, mainly focusing on the effect of age, duration of illness, baseline clinical symptoms and homelessness. METHODOLOGY: Retrospective cohort of patients with treatment-resistant schizophrenia, aged between 15 and 60 years, that initiated clozapine between 2014 and 2017. Sociodemographic characteristics, years from illness diagnosis, and clinical presentation before the initiation of clozapine were collected and analyzed. All-cause discontinuation at two years follow-up was used as the primary measure of clozapine response. RESULTS: 261 patients were included with a median age at illness diagnosis of 23 years old (IQR 19-29) and a median age at clozapine initiation of 25 (IQR: 21-33). 72.33% (183/253) continued clozapine after two years follow-up. Being homeless was associated to higher clozapine non-adherence, with an OR of 2.78 (95%CI 1.051-7.38) (p = 0.039, controlled by gender). Older age at clozapine initiation and longer delay from first schizophrenia diagnosis to clozapine initiation were also associated with higher clozapine non-adherence, with each year increasing the odds of discontinuation by 1.043 (95%CI 1.02-1.07; p = 0.001) and OR 1.092 (95%CI 1.01-1.18;p = 0.032) respectively. CONCLUSION: Starting clozapine in younger patients or shortly after schizophrenia diagnosis were associated with better adherence.


Asunto(s)
Antipsicóticos , Clozapina , Trastornos Psicóticos , Esquizofrenia , Adolescente , Adulto , Anciano , Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Humanos , Persona de Mediana Edad , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/epidemiología , Estudios Retrospectivos , Esquizofrenia/tratamiento farmacológico , Adulto Joven
17.
J Acquir Immune Defic Syndr ; 88(4): 399-405, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34326283

RESUMEN

BACKGROUND: We have previously shown that the initiation of antiretroviral therapy (ART) is associated with a decrease in skeletal muscle density (greater fat accumulation), suggesting that gains in lean body mass seen in many ART studies may reflect gains in low quality, fatty muscle. Here, we explore whether skeletal muscle density and area are associated with markers of inflammation and immune activation. METHODS: ART-naïve people with HIV were randomized to raltegravir or ritonavir-boosted atazanavir or darunavir, each with tenofovir disoproxil fumarate/emtricitabine. Abdominal computed tomography scans from baseline and week 96 were reanalyzed for psoas density and area and correlations explored with inflammation [interleukin-6 (IL-6) and high-sensitivity C-reactive protein] and immune activation [soluble CD14 (sCD14), soluble CD163 (sCD163), and %CD38+HLADR+ on CD4+ or CD8+ T cells]. RESULTS: Two hundred twenty-two participants had available inflammation/immune activation markers and paired computed tomography scans. At baseline, lower psoas density (greater fat) correlated with higher IL-6 (r = -0.26, P < 0.001) and sCD163 (r -0.15, P = 0.03) and lower lean psoas area correlated with higher IL-6, high-sensitivity C-reactive protein, sCD14, sCD163, and %CD38+HLADR+ on CD4+ T cells (r = -0.30-0.13; all P ≤ 0.05). From baseline to week 96, greater percent decrease in total psoas density (more fat) correlated with greater increase in IL-6 (r = -0.14; P = 0.04); greater % decrease in lean psoas area correlated greater increases in IL-6, sCD14, sCD163, and %CD38+HLADR+ on CD8+ T cells (r = -0.15 to -0.18; all P < 0.04). CONCLUSIONS: Greater fat infiltration within the psoas muscle (lower density) and greater loss in lean psoas muscle area were associated with higher inflammation and immune activation, which may portend important effects on muscle function and cardiometabolic risk.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Inflamación , Músculo Esquelético , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/métodos , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Sistema Inmunológico/efectos de los fármacos , Interleucina-6/sangre , Receptores de Lipopolisacáridos , Resultado del Tratamiento
18.
Bioorg Med Chem ; 41: 116213, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33992862

RESUMEN

Chagas disease and Human African Trypanosomiasis (HAT) are caused by Trypanosoma cruzi and T. brucei parasites, respectively. Cruzain (CRZ) and Rhodesain (RhD) are cysteine proteases that share 70% of identity and play vital functions in these parasites. These macromolecules represent promising targets for designing new inhibitors. In this context, 26 CRZ and 5 RhD 3D-structures were evaluated by molecular redocking to identify the most accurate one to be utilized as a target. Posteriorly, a virtual screening of a library containing 120 small natural and nature-based compounds was performed on both of them. In total, 14 naphthoquinone-based analogs were identified, synthesized, and biologically evaluated. In total, five compounds were active against RhD, being three of them also active on CRZ. A derivative of 1,4-naphthoquinonepyridin-2-ylsulfonamide was found to be the most active molecule, exhibiting IC50 values of 6.3 and 1.8 µM for CRZ and RhD, respectively. Dynamic simulations at 100 ns demonstrated good stability and do not alter the targets' structures. MM-PBSA calculations revealed that it presents a higher affinity for RhD (-25.3 Kcal mol-1) than CRZ, in which van der Waals interactions were more relevant. A mechanistic hypothesis (via C3-Michael-addition reaction) involving a covalent mode of inhibition for this compound towards RhD was investigated by covalent molecular docking and DFT B3LYP/6-31 + G* calculations, exhibiting a low activation energy (ΔG‡) and providing a stable product (ΔG), with values of 7.78 and - 39.72 Kcal mol-1, respectively; similar to data found in the literature. Nevertheless, a reversibility assay by dilution revealed that JN-11 is a time-dependent and reversible inhibitor. Finally, this study applies modern computer-aided techniques to identify promising inhibitors from a well-known chemical class of natural products. Then, this work could inspire other future studies in the field, being useful for designing potent naphthoquinones as RhD inhibitors.


Asunto(s)
Diseño Asistido por Computadora , Cisteína Endopeptidasas/metabolismo , Inhibidores de Cisteína Proteinasa/farmacología , Diseño de Fármacos , Proteínas Protozoarias/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas , 1-Naftilamina/análogos & derivados , Aminoquinolinas , Inhibidores de Cisteína Proteinasa/química , Descubrimiento de Drogas , Modelos Moleculares , Simulación del Acoplamiento Molecular , Estructura Molecular , Conformación Proteica , Relación Estructura-Actividad , Tripanocidas/química , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/enzimología
19.
Nanomedicine ; 34: 102383, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33722692

RESUMEN

Calcium phosphosilicate nanoparticles (CPSNPs) are bioresorbable nanoparticles that can be bioconjugated with targeting molecules and encapsulate active agents and deliver them to tumor cells without causing damage to adjacent healthy tissue. Data obtained in this study demonstrated that an anti-CD71 antibody on CPSNPs targets these nanoparticles and enhances their internalization by triple negative breast cancer cells in-vitro. Caspase 3,7 activation, DNA damage, and fluorescent microscopy confirmed the apoptotic breast cancer response caused by targeted anti-CD71-CPSNPs encapsulated with gemcitabine monophosphate, the active metabolite of the chemotherapeutic gemcitabine used to treat cancers including breast and ovarian. Targeted anti-CD71-CPSNPs encapsulated with the fluorophore, Rhodamine WT, were preferentially internalized by breast cancer cells in co-cultures with osteoblasts. While osteoblasts partially internalized anti-CD71-GemMP-CPSNPs, their cell growth was not affected. These results suggest that CPSNPs may be used as imaging tools and selective drug delivery systems for breast cancer that has metastasized to bone.


Asunto(s)
Anticuerpos/metabolismo , Compuestos de Calcio/metabolismo , Nanopartículas , Metástasis de la Neoplasia , Osteoblastos/citología , Silicatos/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Células 3T3 , Animales , Técnicas de Cocultivo , Femenino , Humanos , Ratones , Neoplasias de la Mama Triple Negativas/patología
20.
PLoS One ; 16(1): e0246084, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33503071

RESUMEN

The Nicaraguan COVID-19 situation is exceptional for Central America. The government restricts testing and testing supplies, and the true extent of the coronavirus crisis remains unknown. Dozens of deaths have been reported among health-care workers. However, statistics on the crisis' effect on health-care workers and their risk of being infected with SARS-CoV-2 are lacking. We aimed to estimate the prevalence of SARS-CoV-2 infection in health-care workers and to examine correlations with risk factors such as age, sex and comorbidities. Study participants (N = 402, median age 38.48 years) included physicians, nurses and medical assistants, from public and private hospitals, independent of symptom presentation. SARS-CoV-2 was detected on saliva samples using the loop-mediated isothermal amplification assay. A questionnaire was employed to determine subjects' COVID-19-associated symptoms and their vulnerability to complications from risk factors such as age, sex, professional role and comorbidities. The study was performed five weeks into the exponential growth period in Nicaragua. We discovered that 30.35% of health-care workers participating in our study had been infected with SARS-CoV-2. A large percentage (54.92%) of those who tested positive were asymptomatic and were still treating patients. Nearly 50% of health-care workers who tested positive were under 40, an astonishing 30.33% reported having at least one comorbidity. In our study, sex and age are important risk factors for the probability of testing positive for SARS-CoV-2 with significance being greatest among those between 30 and 40 years of age. In general, being male resulted in higher risk. Our data are the first non-governmental data obtained in Nicaragua. They shed light on several important aspects of COVID-19 in an underdeveloped nation whose government has implemented a herd-immunity strategy, while lacking an adequate healthcare system and sufficient PPE for health-care workers. These data are important for creating policies for containing the spread of SARS-CoV-2.


Asunto(s)
COVID-19/epidemiología , Personal de Salud/estadística & datos numéricos , Adulto , Anciano , Enfermedades Asintomáticas/epidemiología , COVID-19/transmisión , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Femenino , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Nicaragua/epidemiología , Prevalencia , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación , Saliva/virología
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