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1.
HGG Adv ; : 100321, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38918948

RESUMEN

There is increasing evidence of the clinical utility of genetic and genomic testing (GT); however, factors influencing personal utility of GT, especially in diverse, multilingual populations, remain unclear. We explored these factors in a diverse cohort of parents/guardians (participants) whose children received clinical GT through the NYCKidSeq program. A total of 847 participants completed surveys at baseline, post-results disclosure, and 6 months (6m) post-results. The largest population groups were Hispanic/Latino(a) (48%), White/European American (24%), and Black/African American (16%). Personal utility was assessed using the Personal Utility scale (PrU), adapted for pediatric populations and included on the surveys. Three PrU subscales were identified using factor analysis: practical, educational, and parental psychological utility. Overall personal utility summary score and the three subscales significantly decreased after receiving results and over time. Hispanic/Latino(a) participants identified greater overall personal utility than European American and African American participants at all timepoints (p<0.001) as did participants whose children received positive/likely positive results compared with those with negative and uncertain results (post-results: p<0.001 and <0.001; 6m post-results: p=0.002 and <0.001, respectively). Post-results, higher utility subscale scores were associated with lower education levels (practical, parental psychological: p≤0.02) and higher levels of trust in the healthcare system (practical, parental psychological: p≤0.04). These findings help to understand the perspectives of diverse parents/guardians, which is critical to tailoring pre- and post-test counseling across a variety of populations and clinical settings.

3.
Qual Life Res ; 33(7): 1997-2009, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38743313

RESUMEN

PURPOSE: To examine associations between Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and PedsQL Infant Scales with formal health care resource utilization (HCRU) and informal caregiver burden. METHODS: We studied a pediatric cohort of 837 patients (median age: 8.4 years) with suspected genetic disorders enrolled January 2019 through July 2021 in the NYCKidSeq program for diagnostic sequencing. Using linked ~ nine-month longitudinal survey and physician claims data collected through May 2022, we modeled the association between baseline PedsQL scores and post-baseline HCRU (median follow-up: 21.1 months) and informal care. We also assessed the longitudinal change in PedsQL scores with physician services using linear mixed-effects models. RESULTS: Lower PedsQL total and physical health scores were independently associated with increases in 18-month physician services, encounters, and weekly informal care. Comparing low vs. median total scores, increases were 10.6 services (95% CI: 1.0-24.6), 3.3 encounters (95% CI: 0.5-6.8), and $668 (95% CI: $350-965), respectively. For the psychosocial domain, higher scores were associated with decreased informal care. Based on adjusted linear mixed-effects modeling, every additional ten physician services was associated with diminished improvement in longitudinal PedsQL total score trajectories by 1.1 point (95% confidence interval: 0.6-1.6) on average. Similar trends were observed in the physical and psychosocial domains. CONCLUSION: PedsQL scores were independently associated with higher utilization of physician services and informal care. Moreover, longitudinal trajectories of PedsQL scores became less favorable with increased physician services. Adding PedsQL survey instruments to conventional measures for improved risk stratification should be evaluated in further research.


The Pediatric Quality of Life Inventory (PedsQL) is widely used to measure health-related quality of life in pediatric patients; however, few studies have examined whether the PedsQL is indicative of longitudinal outcomes of morbidity and health care needs. This study captures associations between PedsQL scores with utilization of physician and informal care in children with suspected genetic disorders. We demonstrate that lower PedsQL total and physical health scores are independently associated with greater utilization of physician services and informal care. Moreover, longitudinal trajectories of PedsQL scores become less favorable with increased physician services. Results can inform future applications of PedsQL instruments.


Asunto(s)
Calidad de Vida , Humanos , Masculino , Femenino , Niño , Preescolar , Adolescente , Enfermedades Genéticas Congénitas/psicología , Encuestas y Cuestionarios , Estudios Longitudinales , Cuidadores/psicología , Lactante , Atención al Paciente , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Médicos/psicología , Médicos/estadística & datos numéricos
5.
J Exp Med ; 221(6)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38563820

RESUMEN

Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered exceedingly rare and have been identified in only four families. Here, we use forward and reverse genetics to identify 59 individuals harboring one of four heterozygous JAK1 variants. In vitro and ex vivo analysis of these variants revealed hyperactive baseline and cytokine-induced STAT phosphorylation and interferon-stimulated gene (ISG) levels compared with wild-type JAK1. A systematic review of electronic health records from the BioME Biobank revealed increased likelihood of clinical presentation with autoimmunity, atopy, colitis, and/or dermatitis in JAK1 variant-positive individuals. Finally, treatment of one affected patient with severe atopic dermatitis using the JAK1/JAK2-selective inhibitor, baricitinib, resulted in clinically significant improvement. These findings suggest that individually rare JAK1 GoF variants may underlie an emerging syndrome with more common presentations of autoimmune and inflammatory disease (JAACD syndrome). More broadly, individuals who present with such conditions may benefit from genetic testing for the presence of JAK1 GoF variants.


Asunto(s)
Colitis , Dermatitis , Hipersensibilidad , Humanos , Autoinmunidad , Colitis/genética , Inflamación , Janus Quinasa 1/genética
6.
Cureus ; 16(2): e53452, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38314383

RESUMEN

Background This study delves into the demographics and clinical characteristics of oral cavity tumors in the context of the United Arab Emirates. It further investigates the efficacy of four different treatment modalities in impacting patient survival rates. It aims to understand if any treatments significantly improve survival compared to others. Methodology To assess the survival outcomes across the different treatment groups, the study employed the log-rank test, a non-parametric statistical test widely used in survival analysis. The sample consisted of patients from the electronic medical records assigned to one of the following four treatment groups: radiotherapy only (RT), radiotherapy with surgery and chemotherapy (RT+S+C), radiotherapy with surgery (RT+S), and, finally, radiotherapy with chemotherapy including immunotherapy (RT+C). Data collection involved tracking survival times from the initiation of treatment until the last follow-up period or the occurrence of an event (e.g., death). The statistical analysis was conducted using the chi-squared statistic to determine the distribution of survival times across the groups, providing a quantitative measure of the difference between the observed and expected survival. The Kaplan-Meier curve was plotted for the cohort divided into four groups. Results The log-rank test yielded a p-value of 0.321019, suggesting no statistically significant difference in survival among the treatment groups at the 5% significance level. The chi-squared statistic was 3.498018, within the 95% acceptance region, further corroborating the null hypothesis of no significant survival difference across the groups. Despite this, an observed medium effect size of 0.59 indicates a moderate difference in survival between the groups. Conclusions The findings illustrate that while there is no statistically significant difference in survival rates among the four treatment groups, the medium effect size observed suggests a moderate difference in survival. This emphasizes the need to consider the statistical significance and effect size in clinical research, as they provide different insights into treatment efficacy.

7.
Foods ; 13(4)2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38397547

RESUMEN

Follow-on formulas are necessary for newborns that are unable to breastfeed. Thus, the development of formulas more tailored to infants' needs is highly important. Recently, using camel milk, goat milk, and sweet milk whey in the formulation of follow-on formulas has gained researchers' attention. Moreover, developing postbiotic systems to create formulas that mimic human milk, are easy to digest, improve compatibility with an infant's gut, and boost immunity is crucial. Thus, this study aimed to create and assess different formulations using fermented whey from camel and goat milks. The fermentation process involved the use of Lactobacillus helveticus as a probiotic and proteolytic lactic acid bacterium strain. The study monitored the proteolytic activity and antioxidant properties of sweet whey produced from cow, camel, and goat milks during the fermentation process with L. helveticus. Also, three different milk fat blends were recombined using edible vegetable oils (coconut oil, rice bran oil, and canola oil) and then they were used to formulate follow-on formulas with a similar fat composition to human milk. Finally, the prepared formulas were tested for their in vitro digestibility and antioxidant activity before and after digestion. The L. helveticus strain had high proteolytic activity towards whey proteins from all the types of milk used in the study. A fermentation time of 6 h produced a higher proteolytic degree and antioxidant activity than 2 and 4 h of fermentation. No significant differences were observed for proteolytic degree and antioxidant activity between 6 and 12 h of fermentation for the cow, camel, and goat whey samples. Regarding the fat blends, animal milk fat, rice bran oil, and canola oil in a fat combination were essential to provide the required amount of unsaturated fatty acids in the follow-on formulas, especially the linoleic acid-α-linolenic acid (LA:ALA) ratio. Adding coconut oil in small amounts to the follow-on formulas provided the required amounts of saturated fatty acids, especially lauric and meristic acids. The follow-on formula based on cow or goat milk whey fermented with L. helveticus released more free amino acids (mmol tyrosine equivalent mL-1) with high levels of antioxidants compared to unfermented ones. The release of free amino acids in the follow-on formula based on camel milk whey was not affected by fermentation. Our results recommend using L. helveticus in the fermentation of follow-on formulas based on camel and goat whey instead of formulas based on cow milk proteins.

8.
Nat Med ; 30(2): 480-487, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38374346

RESUMEN

Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. Finally, we created a framework for regulatory compliance and developed a PRS clinical report for return to providers and for inclusion in an additional genome-informed risk assessment. The initial experience from eMERGE can inform the approach needed to implement PRS-based testing in diverse clinical settings.


Asunto(s)
Enfermedad Crónica , Puntuación de Riesgo Genético , Salud Poblacional , Adulto , Niño , Humanos , Comunicación , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Estados Unidos
9.
Genet Med ; 26(1): 101011, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37897232

RESUMEN

PURPOSE: To better understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. METHODS: Longitudinal physician claims data after diagnostic sequencing were obtained for patients aged 0 to 21 years with neurologic, cardiac, and immunologic disorders with suspected genetic etiology. We assessed specialist consultation rates prompted by primary diagnostic results, as well as marginal effects on overall 18-month physician services and costs. RESULTS: We included data on 857 patients (median age: 9.6 years) with a median follow-up of 17.3 months after disclosure of diagnostic sequencing results. The likelihood of having ≥1 recommendation for specialist consultation in 155 patients with positive findings was high (72%) vs 23% in 443 patients with uncertain findings and 21% in 259 patients with negative findings (P < .001). Follow-through consultation occurred in 30%. Increases in 18-month physician services and costs following a positive finding diminished after multivariable adjustment. Also, no significant differences between those with uncertain and negative findings were demonstrated. CONCLUSION: Our study did not provide evidence for significant increases in downstream physician services and costs after returning positive or uncertain diagnostic sequencing findings. More large-scale longitudinal studies are needed to confirm these findings.


Asunto(s)
Revelación , Médicos , Humanos , Niño , Costos y Análisis de Costo
10.
Bioorg Chem ; 143: 107062, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38150938

RESUMEN

Herein, we report the synthesis of a series of new fourteen iodoquinazoline derivatives 7a-c to 13a-e and their evaluation as potential anticancer agents via dual targeting of EGFRT790M and VEGFR-2. The new derivatives were designed according to the target receptors structural requirements. The compounds were evaluated for their cytotoxicity against HepG2, MCF-7, HCT116 and A549 cancer cell lines using MTT assay. Compound 13e showed the highest anticancer activities with IC50 = 5.70, 7.15, 5.76 and 6.50 µM against HepG2, MCF-7, HCT116 and A549 cell lines correspondingly. Compounds 7c, 9b and 13a-d exhibited very good anticancer effects against the tested cancer cell lines. The highly effective six derivatives 7c, 10, 13b, 13c, 13d and 13e were examined against VERO normal cell lines to estimate their cytotoxic capabilities. Our conclusion revealed that compounds 7c, 10, 13b, 13c, 13d and 13e possessed low toxicity against VERO normal cells with IC50 prolonging from 41.66 to 53.99 µM. Also compounds 7a-c to 13a-e were further evaluated for their inhibitory activity against EGFRT790M and VEGFR-2. Also, their ability to bind with both EGFR and VEGFR-2 receptors was examined by molecular modeling. Compounds 13e, 13d, 7c and 13c excellently inhibited VEGFR-2 activity with IC50 = 0.90, 1.00, 1.25 and 1.50 µM respectively. Moreover, Compounds 13e, 7c, 10 and 13d excellently inhibited EGFRT790M activity with IC50 = 0.30, 0.35, 0.45 and 0.47 µM respectively. Finally, our derivatives 7b, 13d and 13e showed good in silico calculated ADMET profile.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Quinazolinas , Humanos , Antineoplásicos/química , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Estructura Molecular , Mutación , Inhibidores de Proteínas Quinasas , Relación Estructura-Actividad , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Quinazolinas/química , Quinazolinas/farmacología
11.
Saudi J Gastroenterol ; 30(2): 83-88, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38099540

RESUMEN

BACKGROUND: Lower gastrointestinal bleeding (LGIB) is an urgent presentation with increasing prevalence and remains a common cause of hospitalization. The clinical outcome can vary based on several factors, including the cause of bleeding, its severity, and the effectiveness of management strategies. The aim of this study is to provide a comprehensive report on the clinical outcomes observed in patients with LGIB who underwent lower endoscopy. METHODS: All patients who underwent emergency lower endoscopy for fresh bleeding per rectum, from May 2015 to December 2021, were included. The primary outcome was to identify the rate of rebleeding after initial control of bleeding. The second was to measure the clinical outcomes and the potential predictors leading to intervention and readmission. RESULTS: A total of 84 patients were included. Active bleeding was found in 20% at the time of endoscopy. Rebleeding within 90 days occurred in 6% of the total patients; two of which (2.38%) were within the same admission. Ninety-day readmission was reported in 19% of the cases. Upper endoscopy was performed in 32.5% of the total cases and was found to be a significant predictor for intervention (OR 4.1, P = 0.013). Personal history of inflammatory bowel disease (IBD) and initial use of sigmoidoscopy were found to be significant predictors of readmission [(OR 5.09, P = 0.008) and (OR 5.08, P = 0.019)]. CONCLUSIONS: LGIB is an emergency that must be identified and managed using an agreed protocol between all associated services to determine who needs upper GI endoscopy, ICU admission, or emergency endoscopy within 12 hours.


Asunto(s)
Endoscopía Gastrointestinal , Enfermedades Inflamatorias del Intestino , Humanos , Hemorragia Gastrointestinal/terapia , Hospitalización
12.
Hum Mutat ; 20232023.
Artículo en Inglés | MEDLINE | ID: mdl-38084291

RESUMEN

Germline pathogenic variants in DICER1 predispose individuals to develop a variety of benign and malignant tumors. Accurate variant curation and classification is essential for reliable diagnosis of DICER1-related tumor predisposition and identification of individuals who may benefit from surveillance. Since 2015, most labs have followed the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) sequence variant classification guidelines for DICER1 germline variant curation. However, these general guidelines lack gene-specific nuances and leave room for subjectivity. Consequently, a group of DICER1 experts joined ClinGen to form the DICER1 and miRNA-Processing Genes Variant Curation Expert Panel (VCEP), to create DICER1- specific ACMG/AMP guidelines for germline variant curation. The VCEP followed the FDA-approved ClinGen protocol for adapting and piloting these guidelines. A diverse set of 40 DICER1 variants were selected for piloting, including 14 known Pathogenic/Likely Pathogenic (P/LP) variants, 12 known Benign/Likely Benign (B/LB) variants, and 14 variants classified as variants of uncertain significance (VUS) or with conflicting interpretations in ClinVar. Clinically meaningful classifications (i.e., P, LP, LB, or B) were achieved for 82.5% (33/40) of the pilot variants, with 100% concordance among the known P/LP and known B/LB variants. Half of the VUS or conflicting variants were resolved with four variants classified as LB and three as LP. These results demonstrate that the DICER1-specific guidelines for germline variant curation effectively classify known pathogenic and benign variants while reducing the frequency of uncertain classifications. Individuals and labs curating DICER1 variants should consider adopting this classification framework to encourage consistency and improve objectivity.


Asunto(s)
Pruebas Genéticas , Neoplasias , Humanos , Pruebas Genéticas/métodos , Variación Genética , Genoma Humano , Genómica/métodos , Neoplasias/genética , Células Germinativas , Ribonucleasa III/genética , ARN Helicasas DEAD-box/genética
13.
Pharmacogenomics ; 24(18): 921-930, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38054855

RESUMEN

We developed novel electronic phenotyping algorithms for the BioMe biobank data, which accurately identified angiotensin converting enzyme inhibitor (ACEi)-induced angioedema cases and controls. A survey was mailed to all 1075 patients and 91 were returned. Over a third reported that prescribing physicians had not discussed with them the concepts of interindividual drug response variability or adverse event risk, and 73% of patients were previously unaware of pharmacogenomics; however, most patients were interested in having pharmacogenomic testing. Moreover, 67% of patients indicated that pharmacogenomic testing would positively influence their medication compliance. In addition to identifying an innovative approach to define biobank cohorts for pharmacogenomic studies, these results indicate that patients are interested in pharmacogenomic testing, which could translate to improved adherence.


Asunto(s)
Angioedema , Inhibidores de la Enzima Convertidora de Angiotensina , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Farmacogenética , Angioedema/inducido químicamente
14.
Ann Saudi Med ; 43(6): 386-393, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38071440

RESUMEN

BACKGROUND: The prevalence of inflammatory bowel diseases (IBD), Crohn's (C) and ulcerative colitis (UC) has increased in Saudi Arabia during the past decade. Even though medical treatment is first-line therapy, most patients require surgery during the course of the disease. Stoma creation complications in IBD are underreported in the literature of the Middle East and especially in Saudi Arabia. OBJECTIVES: Report the postoperative, stoma and peristomal complications following stoma creation in (C) versus UC. DESIGN: Retrospective cohort study. SETTINGS: Tertiary care center. PATIENTS AND METHODS: Patients with IBD who underwent stoma creation for either UC or CD between August 2015 and July 2020 were included. The diseases were compared to assess their characteristics and association to postoperative, stoma and peristomal complications. All complications were reported over a 90-day duration from the surgery. Patients younger than 14 years of age were excluded. MAIN OUTCOME MEASURES: Postoperative complications, stoma and peristomal complications in IBD patients who underwent stoma creation. SAMPLE SIZE: 50. RESULTS: Of 50 IBD patients underwent stoma creation, 32 patients (64%) were diagnosed with CD and 18 patients (36%) with UC. Most of the procedures in both groups were laparoscopic and elective. Low BMI and serum albumin were more prevalent in the CD group. Postoperative complications were higher in the CD patients compared to the UC patients (CD 40.6% vs UC 11.1%, P=.028) with the most common complication being abdominal collection[a]. Stoma complications were comparable between the two groups (UC 16.7% vs CD 15.6%). However, peristomal complications were higher clinically in UC patients in comparison with the CD patients (UC 61.1% vs CD 37.5% P=.095) with the most common complication being skin excoriation (UC 44.4% vs CD 37.5%). CONCLUSIONS: CD has significantly higher postoperative complications compared to UC. Peristomal complications were high in both groups and had a negative impact on quality of life. Therefore, comprehensive stoma education and regular outpatient follow ups are recommended to improve the overall outcomes. LIMITATIONS: Retrospective and conducted in one academic institution with a small sample size.


Asunto(s)
Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Humanos , Estudios Retrospectivos , Arabia Saudita/epidemiología , Calidad de Vida , Enfermedades Inflamatorias del Intestino/cirugía , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Colitis Ulcerosa/cirugía , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento
15.
RSC Adv ; 13(50): 35321-35338, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38053688

RESUMEN

Novel azobenzene scaffold-joined heterocyclic isoxazole, pyrazole, triazole, and/or triazine moieties have been developed and synthesized utilizing microwave and traditional methods. Our compounds were tested for growth inhibition of A549, MCF-7, HCT-116, and HepG2 tumors by dual targeting the VEGFR-2 and EGFRT790M enzymes. The suggested compound's manner of binding with EGFRT790M and VEGFR-2 active sites was explored through molecular design and MD modeling. The information from the results of the biological screening and the docking studies was highly correlated. The A549 cell line was the one that responded to the novel compound's effects most effectively. Having IC50 values of 5.15, 6.37, 8.44 and 6.23 µM, respectively, 14 was the most effective derivative on the four A549, MCF-7, HCT116 and HepG2 cancer cells. It had greater activity than erlotinib and slightly inferior activities on the tested cell lines than sorafenib, respectively. The cytotoxicity of the most effective derivatives, 5, 6, 10 and 14, was evaluated against typical VERO cell lines. Having IC50 values ranging from 42.32 to 55.20 µM, the results showed that the investigated drugs have modest toxicity against VERO normal cells. Additionally all derivatives were assessed for their dual VEGFR-2 and EGFRT790M inhibitory effects. Among them, derivatives 14, 5 and 10 were established as the greatest inhibitors of VEGFR-2 at IC50 values of 0.95, 1.25 and 1.50 µM correspondingly. As well, derivatives 14, 6, 5 and 10 could inhibit EGFRT790M activity demonstrating strongest effects with IC50 = 0.25, 0.35, 0.40 and 0.50 µM respectively. Furthermore, the ADMET profile was evaluated for compounds 5, 6, 10 and 14 in contrast to reference drugs sorafenib and erlotinib.

16.
Molecules ; 28(21)2023 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-37959750

RESUMEN

Echinacea purpurea (L.) Moench is a medicinal plant commonly used for the treatment of upper respiratory tract infections, the common cold, sore throat, migraine, colic, stomach cramps, and toothaches and the promotion of wound healing. Based on the known pharmacological properties of essential oils (EOs), we hypothesized that E. purpurea EOs may contribute to these medicinal properties. In this work, EOs from the flowers of E. purpurea were steam-distilled and analyzed by gas chromatography-mass spectrometry (GC-MS), GC with flame-ionization detection (GC-FID), and chiral GC-MS. The EOs were also evaluated for in vitro antimicrobial and innate immunomodulatory activity. About 87 compounds were identified in five samples of the steam-distilled E. purpurea EO. The major components of the E. purpurea EO were germacrene D (42.0 ± 4.61%), α-phellandrene (10.09 ± 1.59%), ß-caryophyllene (5.75 ± 1.72%), γ-curcumene (5.03 ± 1.96%), α-pinene (4.44 ± 1.78%), δ-cadinene (3.31 ± 0.61%), and ß-pinene (2.43 ± 0.98%). Eleven chiral compounds were identified in the E. purpurea EO, including α-pinene, sabinene, ß-pinene, α-phellandrene, limonene, ß-phellandrene, α-copaene, ß-elemene, ß-caryophyllene, germacrene D, and δ-cadinene. Analysis of E. purpurea EO antimicrobial activity showed that they inhibited the growth of several bacterial species, although the EO did not seem to be effective for Staphylococcus aureus. The E. purpurea EO and its major components induced intracellular calcium mobilization in human neutrophils. Additionally, pretreatment of human neutrophils with the E. purpurea EO or (+)-δ-cadinene suppressed agonist-induced neutrophil calcium mobilization and chemotaxis. Moreover, pharmacophore mapping studies predicted two potential MAPK targets for (+)-δ-cadinene. Our results are consistent with previous reports on the innate immunomodulatory activities of ß-caryophyllene, α-phellandrene, and germacrene D. Thus, this study identified δ-cadinene as a novel neutrophil agonist and suggests that δ-cadinene may contribute to the reported immunomodulatory activity of E. purpurea.


Asunto(s)
Antiinfecciosos , Echinacea , Aceites Volátiles , Humanos , Aceites Volátiles/química , Calcio , Vapor , Cromatografía de Gases y Espectrometría de Masas , Antiinfecciosos/química
17.
Am J Hum Genet ; 110(12): 2029-2041, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38006881

RESUMEN

Digital solutions are needed to support rapid increases in the application of genetic/genomic tests (GTs) in diverse clinical settings and patient populations. We developed GUÍA, a bilingual digital application that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GTs. The trial evaluated GUÍA's impact on understanding the GT results by randomizing families to results disclosure genetic counseling with GUÍA (intervention) or standard of care (SOC). Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6 months later. Survey measures assessed the primary study outcomes of participants' perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. The analysis included 551 diverse participants, 270 in the GUÍA arm and 281 in SOC. Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR = 2.8, CI[1.004, 7.617], p = 0.049) and maintained higher objective understanding over time (OR = 1.1, CI[1.004, 1.127], p = 0.038) compared to SOC. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR = 3.9, CI[1.603, 9.254], p = 0.003), confidence (OR = 2.7, CI[1.021, 7.277], p = 0.046), and objective understanding (OR = 1.1, CI[1.009, 1.212], p = 0.032) compared to SOC. This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions and builds a case for utilizing GUÍA to deliver complex results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics.


Asunto(s)
Revelación , Asesoramiento Genético , Niño , Humanos , Pruebas Genéticas , Padres , Genómica
18.
Cureus ; 15(9): e45781, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37872898

RESUMEN

BACKGROUND: Palliative care in Saudi Arabia has witnessed significant recent progress through the establishment of the Saudi Society for Palliative Care and the National Palliative Care Program. The objective of this study was to assess knowledge and attitudes regarding palliative care and end-of-life decision-making in Saudi Arabia's Eastern and Central provinces among individuals residing in these regions. METHODS: Utilizing a cross-sectional survey-based research design, we assessed knowledge and attitudes regarding palliative care and end-of-life decision-making in Saudi Arabia's Eastern and Central provinces. Participants were recruited through purposive sampling via social media. Data collection included demographic information, palliative care knowledge, attitudes toward palliative care, and cultural influences on end-of-life decisions. RESULTS: A total of 710 participants completed the survey, resulting in a response rate of 85%, with a balanced gender distribution, predominantly aged 25-54. Over half were healthcare providers, many possessing more than 15 years of healthcare experience. A substantial proportion had received formal palliative care training and had personal involvement in end-of-life decisions. While most participants demonstrated a good understanding of palliative care, knowledge gaps, especially regarding its timing, persisted. Generally, participants felt at ease discussing end-of-life care and believed in palliative care's effectiveness. Cultural influences on end-of-life decisions were perceived both positively and negatively, with some facing cultural challenges in palliative care. CONCLUSIONS: This study underscores a promising understanding of palliative care in Saudi Arabia alongside persistent misconceptions. It highlights the necessity for targeted education to rectify misperceptions, particularly concerning the initiation timing of palliative care. Cultural factors strongly impact end-of-life decisions, emphasizing the need for culturally sensitive healthcare discussions and provider training.

19.
Molecules ; 28(20)2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37894493

RESUMEN

Blue lotus, also known as Nymphaea caerulea (Nymphaeaceae), is a water lily found globally in lakes and rivers. With its long history of use in Egyptian culture, blue lotus has been associated with spiritual rituals and health benefits. Nowadays, blue lotus is still consumed as a tea or tincture to induce relaxation and heightened spiritual awareness. In this study, six authentic N. caerulea extracts from trusted sources and eleven commercial products were analyzed using gas chromatography-mass spectrometry (GC-MS). Authentic blue lotus extracts were produced in industrial settings. Overall, the extracts were a mixture of aliphatic hydrocarbons, aromatic alcohols, fatty acids, phenyl derivatives, diterpenoids, phytosterols, and stigmastanes. Apomorphine and nuciferine, which are responsible for psychoactive effects of the blue lotus flower, were virtually absent from the authentic blue lotus extract. Although blue lotus has a long history of use, the safety data on the plant and its extracts is limited; however, together with the analytical data, the available information does not indicate major safety concerns for the topical application of authentic blue lotus flower concrete or absolute when diluted as a fragrance ingredient.


Asunto(s)
Nymphaea , Fitosteroles , Nymphaea/química , Apomorfina , Cromatografía de Gases y Espectrometría de Masas , Egipto , Extractos Vegetales/química
20.
Sci Rep ; 13(1): 16270, 2023 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-37758773

RESUMEN

Human pathogenic fungi and bacteria pose a huge threat to human life, accounting for high rates of mortality every year. Unfortunately, the past few years have seen an upsurge in multidrug resistance pathogens. Consequently, finding an effective alternative antimicrobial agent is of utmost importance. Hence, this study aimed to phytofabricate silver nanoparticles (AgNPs) using aqueous extracts of the solid endosperm of Cocos nucifera L, also known as coconut meat (Cm). Green synthesis is a facile, cost-effective and eco-friendly methods which has several benefits over other physical and chemical methods. The synthesized nanoparticles were characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The Cm-AgNPs showed a UV-Vis peak at 435 nm and were crystalline and quasi-spherical, with an average size of 15 nm. The FTIR spectrum displayed functional groups of phenols, alkaloids, sugars, amines, and carbonyl compounds, which are vital in the reduction and capping of NPs. The antibacterial and anticandidal efficacy of the Cm-AgNPs was assessed by the agar-well diffusion method and expressed as a zone of inhibition (ZOI). Amongst all the test isolates, Staphylococcus epidermidis, Candida auris, and methicillin-resistant Staphylococcus epidermidis were more susceptible to the NPs with a ZOI of 26.33 ± 0.57 mm, 19.33 ± 0.57 mm, and 18 ± 0.76 mm. The MIC and MFC values for Candida spp. were higher than the bacterial test isolates. Scanning electron microscopic studies of all the test isolates at their MIC concentrations showed drastically altered cell morphology, indicating that the NPs could successfully cross the cell barrier and damage the cell integrity, causing cell death. This study reports the efficacy of Cm-AgNPs against several Candida and bacterial strains, which had not been reported in earlier studies. Furthermore, the synthesized AgNPs exhibited significant antioxidant activity. Thus, the findings of this study strongly imply that the Cm-AgNPs can serve as promising candidates for therapeutic applications, especially against multidrug-resistant isolates of Candida and bacteria. However, further investigation is needed to understand the mode of action and biosafety.


Asunto(s)
Antiinfecciosos , Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina , Humanos , Cocos , Antioxidantes/farmacología , Plata/farmacología , Antiinfecciosos/farmacología , Candida , Carne
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