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1.
Pediatr Rev ; 45(4): 201-209, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38556511

RESUMEN

The incidence of diabetes in children and adolescents has increased during the past decades, with a 1.9% increase per year in type 1 diabetes mellitus (T1DM). Patients with diabetes have a greater risk of hospitalizations compared with those without diabetes. Clear evidence has emerged in the past decade that supports appropriate glycemic control in the hospital setting to improve clinical outcomes and reduce the risk of hospital complications and mortality. Determining the appropriate insulin regimen in patients with T1DM in the hospital depends on the clinical status, type of outpatient insulin regimen (multiple daily injections versus pump therapy), glycemic control before admission, nutritional status, procedures, and enteral versus parenteral nutrition. Due to the complexity of the inpatient management of diabetes, institutions should have an inpatient diabetes management team that includes dietitians, diabetes educators, nurses, pharmacists, social workers, and endocrinologists. The use of inpatient diabetes teams has been demonstrated to be beneficial in the management of patients with T1DM.


Asunto(s)
Diabetes Mellitus Tipo 1 , Niño , Adolescente , Humanos , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Hospitalización , Hospitales
2.
J Pediatr Endocrinol Metab ; 36(12): 1128-1132, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37852007

RESUMEN

OBJECTIVES: Technology use has been shown to improve diabetes control, but minority youths tend to have low rates of technology use and exhibit suboptimal glycemic control. We examined the impact of continuous glucose monitors (CGM) and continuous subcutaneous insulin infusion (CSII) on glycemic control in a racial-ethnic minority cohort of children and adolescents with type 1 diabetes (T1D). METHODS: A cross-sectional study was conducted among 140 pediatric T1D patients seen at a multidisciplinary clinic. From January to November 2022, data on demographics and glycated hemoglobin (HbA1c) levels were collected. Patients were categorized as technology (CGM, CSII, or both) or non-technology users (finger stick meter (FS) and multiple daily injections (MDI)). RESULTS: The majority identified as Hispanic (79 %) and had public health insurance (71 %). Sixty-nine percent used technology. Compared with non-technology users, technology users had significantly lower mean HbA1c levels (9.60 vs. 8.40 %, respectively) (p=0.0024), though no group (CGM + CSII, CGM + MDI, FS + CSII, and FS + MDI) achieved a mean HbA1c level of <7.0 %. Regarding minority status, no significant differences in mean HbA1c levels existed between Hispanics and Blacks in the CGM + MDI and FS + CSII groups (p=0.2232 and p=0.9224, respectively). However, there was a significant difference in mean HbA1c levels between Hispanic and Black non-technology users (9.19 vs. 11.26 %, respectively) (p=0.0385). CONCLUSIONS: Technology users demonstrated better glycemic control than non-technology users. Further research is needed to investigate factors affecting glycemic control in minority youths with T1D.


Asunto(s)
Diabetes Mellitus Tipo 1 , Humanos , Niño , Adolescente , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Minorías Étnicas y Raciales , Estudios Transversales , Etnicidad , Automonitorización de la Glucosa Sanguínea , Grupos Minoritarios , Insulina/uso terapéutico , Glucemia , Sistemas de Infusión de Insulina
3.
Pediatr Pulmonol ; 58(6): 1805-1811, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36929859

RESUMEN

BACKGROUND: The effects of elexacaftor-tezacaftor-ivacaftor (ETI) on body composition in people with CF (pwCF) are unknown. METHODS: Dual-energy X-ray absorptiometry fat-free mass and fat mass adjusted for height (FMI) as well as oral glucose tolerance test derived measures of insulin secretion and sensitivity were compared before and after ETI initiation in eight pwCF. RESULTS: Patients median age: 22 years interquartile range (IQR: 16-28), 87.5% male, median time on ETI:11 months. Weight z-score increased from -0.52 to 0.18 (p = 0.014); FMI increased from 4.12 to 6.29 (p = 0.014). Insulin secretion (C pep iAUC/Gluc iAUC) increased from 8.71 to 14.21 (p = 0.021), insulin resistance (HOMA2 IR) increased from 0.73 to 1.25 (p = 0.014) and insulin sensitivity decreased (Matsuda) 8.88 to 5.58 (p = 0.036). CONCLUSIONS: ETI resulted in increased weight and fat mass. BMI and muscle mass did not change. Both insulin secretion and insulin resistance increased. Longer-term metabolic consequences of ETI need further investigation.


Asunto(s)
Fibrosis Quística , Resistencia a la Insulina , Humanos , Adolescente , Masculino , Adulto Joven , Adulto , Femenino , Fibrosis Quística/tratamiento farmacológico , Composición Corporal , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Aminofenoles/uso terapéutico , Benzodioxoles/uso terapéutico , Mutación
4.
Cell Host Microbe ; 31(2): 187-198.e3, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-36758519

RESUMEN

The human gut virome and its early life development are poorly understood. Prior studies have captured single-point assessments with the evolution of the infant virome remaining largely unexplored. We performed viral metagenomic sequencing on stool samples collected longitudinally from a cohort of 53 infants from age 2 weeks to 3 years (80.7 billion reads), and from their mothers (9.8 billion reads) to examine and compare viromes. The asymptomatic infant virome consisted of bacteriophages, nonhuman dietary/environmental viruses, and human-host viruses, predominantly picornaviruses. In contrast, human-host viruses were largely absent from the maternal virome. Previously undescribed, sequence-divergent vertebrate viruses were detected in the maternal but not infant virome. As infants aged, the phage component evolved to resemble the maternal virome, but by age 3, the human-host component remained dissimilar from the maternal virome. Thus, early life virome development is determined predominantly by dietary, infectious, and environmental factors rather than direct maternal acquisition.


Asunto(s)
Bacteriófagos , Virus , Femenino , Humanos , Viroma/genética , Virus/genética , Bacteriófagos/genética , Madres , Metagenoma , Metagenómica
5.
J Cancer Surviv ; 17(4): 1094-1110, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36367615

RESUMEN

PURPOSE: This study is to evaluate healthcare needs, preferences, and expectations in supportive cancer care as perceived by cancer survivors, family caregivers, and healthcare professionals. METHODS: Key stakeholders consisted of cancer survivors diagnosed with breast cancer, prostate cancer, or melanoma; adult family caregivers; and healthcare professionals involved in oncology. Recruitment was via several routes, and data were collected via either online surveys or telephone interviews in Greece, Spain, Sweden, and the UK. Framework analysis was applied to the dataset. RESULTS: One hundred and fifty-five stakeholders participated: 70 cancer survivors, 23 family caregivers, and 62 healthcare professionals (13 clinical roles). Cancer survivors and family caregivers' needs included information and support on practical/daily living, as frustration was apparent with the lack of follow-up services. Healthcare professionals agreed on a multidisciplinary health service with a "focus on the patient" and availability closer to home. Most healthcare professionals acknowledged that patient-reported outcomes may provide "better individualised care". Cancer survivors and family caregivers generally felt that the digital platform would be useful for timely personalised support and aided communication. Healthcare professionals were supportive of the "proactive" functionality of the platform and the expected advantages. Anticipated challenges were integration obstacles such as workload/infrastructure and training/support in using the new technology. CONCLUSIONS: Obtaining key stakeholders' insights provided a foundation for action to further co-create the LifeChamps digital platform to meet needs and priorities and deliver enhanced supportive care to "older" cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Co-creation provided insight into gaps where digital support may enhance health and well-being.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Adulto , Masculino , Humanos , Motivación , Cuidadores , Atención a la Salud
6.
Strength Cond J ; 44(1): 111-118, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35874931

RESUMEN

Cystic fibrosis (CF) is the most prevalent hereditary life-threatening disease in the Caucasian population. With the improvement in clinical care, individuals with CF are living longer, and CF-related diabetes (CFRD) has emerged as a major complication. The diagnosis of CFRD is associated with shortening survival, increasing morbidity, worsening physical capacity, and body composition. Engagement in exercise training has become a prominent nonpharmacologic intervention that aims to improve fitness and clinical outcomes in individuals with CF and CFRD. This column will specifically focus on the potential benefits of resistance training and provide recommendations for children and adolescents with CF and CFRD.

7.
Artículo en Inglés | MEDLINE | ID: mdl-35409718

RESUMEN

BACKGROUND: The purpose of this pilot study was to compare body composition metrics obtained by two portable bioelectrical impedance analysis (BIA) devices with dual-energy X-ray absorptiometry (DXA) among adolescents with cystic fibrosis (CF) before and after a resistance exercise training program. METHODS: Participants with CF were assessed using DXA, single-frequency BIA (SFBIA), and multiple-frequency BIA (MFBIA) to quantify percent body fat (%Fat), fat mass (FM), and fat-free mass (FFM) at baseline and after a home-based resistance training intervention comprised of 36, 1 h sessions completed in 12-14 weeks. Repeated measures analysis of variance, paired samples t-tests, Cohen's d effect sizes, and Pearson's correlations were used to compare differences between and within methods at baseline and post-intervention. RESULTS: Ten participants (15.8 ± 2.2 yr, 60.1 ± 15.1 kg) completed the assessments. At baseline, both SFBIA and MFBIA scales significantly underestimated %Fat and FM and overestimated FFM, with small to moderate effect sizes. Post-intervention, small, non-significant differences were found between DXA and both BIA scales for all body composition metrics. Significant changes in %Fat and FFM were observed with DXA. MFBIA displayed less constant error than SFBIA when compared to DXA for pre- and post-intervention assessments for %Fat (MFBIA: pre and post -2.8 and -0.8 vs. SFBIA: -4.6 and -2.0), FM (-0.4 and -0.4 vs. -3.0 and -1.1), and FFM (+0.8 and +0.6 vs. +3.1 and +1.3). Near-perfect correlations were observed at both time points between DXA and each BIA scale. Conclusions: Portable BIA results should be interpreted with caution, and further validation studies in CF patients are needed prior to clinical use.


Asunto(s)
Fibrosis Quística , Entrenamiento de Fuerza , Absorciometría de Fotón/métodos , Adolescente , Composición Corporal , Índice de Masa Corporal , Fibrosis Quística/diagnóstico por imagen , Impedancia Eléctrica , Humanos , Proyectos Piloto
8.
Artículo en Inglés | MEDLINE | ID: mdl-35328985

RESUMEN

The aims of this study were to (1) determine the feasibility of a home-based resistance exercise training (RET) program in patients with cystic fibrosis and impaired glucose tolerance using virtual personal training and (2) observe the effects completion of the RET program had on glucose metabolism, pulmonary function, body composition, and physical fitness. The feasibility of the program was defined as 80% compliance. Ten participants (15.80 ± 2.20 yr, 25.1 ± 7.4 kg/m2) began a home-based resistance training program consisting of 36 sessions supervised via online videoconferencing. Compliance scores of 78.9% (all participants) and 81.8% (without one outlier) were observed. A significant increase was observed in 2-h C-peptide levels (2.1 ng/mL; p = 0.04), with a moderate decrease in fasting glucose (-5.2 mg/dL; p = 0.11) and a moderate increase in 2-h insulin (35.0 U/mL; p = 0.10). A small decrease in the fat percentage (-1.3%; p = 0.03) was observed in addition to increases in fat-free mass (1.5 kg; p = 0.01) and the fat-free mass index (0.4; p = 0.01). Small, yet statistically significant increases were observed in V̇O2peak (0.1 L/min p = 0.01), V̇CO2peak (0.1 L/min; p = 0.01), and ventilation (5.3 L/min; p = 0.04). Telehealth-based RET is feasible in adolescents with CF and impaired glucose tolerance and elicits small yet favorable changes in insulin secretion, body composition, and exercise capacity.


Asunto(s)
Fibrosis Quística , Intolerancia a la Glucosa , Entrenamiento de Fuerza , Telemedicina , Adolescente , Fibrosis Quística/terapia , Estudios de Factibilidad , Intolerancia a la Glucosa/terapia , Humanos
9.
J Clin Transl Endocrinol ; 30: 100311, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36620757

RESUMEN

Background: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear. Methods: Twenty youth and adults with CF underwent frequently sampled oral glucose tolerance tests (fsOGTT) before and after ETI initiation. Glucose, insulin, and C-peptide were collected at 0, 10, 30, 60, 90, and 120 min after 1.75 g/kg (max 75 g) of dextrose. HbA1c and continuous glucose monitoring (CGM) were collected in a subset. Estimates of insulin secretion (C-peptide index), insulin resistance (HOMA2 IR and IS(OGTT Cpep)), and ß-cell function (C-peptide oral disposition index, oDIcoeo), were compared before and after ETI. Results: Participants were a median (IQR) of 20.4 (14.1, 28.6) years old, 75 % male. Follow-up occurred 10.5 (10.0, 12.3) months after ETI initiation. BMI z-score increased from 0.3 (-0.3, 0.8) to 0.8 (0.4, 1.5), p = 0.013 between visits. No significant differences were observed in glucose tolerance, glucose area under the curve, nor fsOGTT glucose concentrations before and after ETI. Median (IQR) C-peptide index increased from 5.7 (4.1, 8.3) to 8.8 (5.5, 10.8) p = 0.013 and HOMA2 IR increased (p < 0.001), while oDIcoeo was unchanged (p = 0.67). HbA1c decreased from 5.5 % (5.5, 5.8) to 5.4 % (5.2, 5.6) (p = 0.003) while CGM variables did not change. Conclusions: BMI z-score and measures of both insulin resistance and insulin secretion increased within the first year of ETI initiation. ß-cell function adjusted for insulin sensitivity (oDIcoeo) did not change.

10.
J Cyst Fibros ; 20(5): 796-802, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34183284

RESUMEN

BACKGROUND: Optimization of nutritional status is recommended in patients with cystic fibrosis (CF) given the association between lower body mass index (BMI) and poor clinical outcomes. However, higher BMI and body fat correlate with glucose impairment and higher leptin levels in the general population. Differences in body composition and leptin levels between the categories of glucose tolerance were assessed in youth with CF and healthy controls. METHODS: In a cross-sectional study, 59 adolescents and young adults with CF and 15 healthy controls matched by age and gender, underwent body composition analysis using dual energy X-ray absorptiometry (DXA) and a 2-hour oral glucose tolerance test (OGTT). Measures of insulin sensitivity, ß-cell insulin secretion and fasting leptin levels were obtained. RESULTS: Of the participants with CF, 62% were classified as abnormal glucose tolerant and 22% with cystic fibrosis related diabetes (CFRD). Patients with CFRD had a lower fat mass index (FMI) z-score, wt z-score and leptin levels compared to the control group (-1.86 vs. - 0.59, p=0.01; -1.86 vs 0.44, p=<0.001 and 7.9 vs vs. 27.7 µg/L, p=0.01). Leptin correlated positively with FMI z-score, BMI, weight z-score and indices of insulin secretion. FMI z-score correlated positively with higher insulin resistance (HOMA-IR), and lower insulin sensitivity (Matsuda index) (r=0.31; p =0.01 and r=-0.29; p=0.02, respectively) in the CF group. CONCLUSIONS: This study shows that despite new therapeutic strategies, youth with CF have lower body fat, weight z-score and leptin levels, particularly in subjects with early onset CFRD.


Asunto(s)
Composición Corporal , Fibrosis Quística/metabolismo , Fibrosis Quística/fisiopatología , Intolerancia a la Glucosa/metabolismo , Intolerancia a la Glucosa/fisiopatología , Leptina/metabolismo , Absorciometría de Fotón , Adolescente , Adulto , Niño , Estudios Transversales , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Adulto Joven
11.
Cyberpsychol Behav Soc Netw ; 24(10): 673-682, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33761276

RESUMEN

Alcohol use disorder (AUD) is a major global problem. Neuropsychological studies have shown that AUD causes deficits in executive functions (EFs), a set of higher order cognitive skills that govern individual behavior in everyday situations. Many standardized neuropsychological tests are used to evaluate EF. These are reliable and valid but have limitations in predicting real-life performance. To address this, we present a preliminary study to test the virtual cooking task (VCT) as an alternative to standardized neuropsychological tests. The VCT includes four subtasks developed to assess attentional, planning, and cognitive shifting abilities; it was tested in an immersive three-dimensional environment. To evaluate the VCT performance and standardized neuropsychological tests, data were gathered from a sample of healthy subjects (control group [CG]; n = 23) and AUD patients (n = 18). The standardized neuropsychological measures used consisted of questionnaires (Attentional Control Scale, Barratt Impulsiveness Scale, and Cognitive Flexibility Scale) and specific tests (Dot-probe task, Go/No-go test, Stroop test, the trail making test, and Tower of London test). The results showed significant higher correlations for AUD patients than for the CG for the VCT, questionnaires, and specific tests, mainly related to planning and cognitive shifting abilities. Furthermore, comparative analyses of the VCT performance showed that the AUD patients made more errors and had higher latency times than the CG. The present study provides initial evidence that a more ecologically valid assessment can be a useful tool to detect cognitive impairments in many neuropsychological and mental disorders, affecting daily activities.


Asunto(s)
Alcoholismo , Realidad Virtual , Culinaria , Función Ejecutiva , Humanos , Pruebas Neuropsicológicas , Encuestas y Cuestionarios
12.
Nat Commun ; 12(1): 1660, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33712587

RESUMEN

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin-angiotensin-aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies.


Asunto(s)
COVID-19/genética , COVID-19/virología , SARS-CoV-2/genética , Adulto , Anciano , Antagonistas de Receptores de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antivirales/farmacología , COVID-19/epidemiología , Prueba de Ácido Nucleico para COVID-19 , Interacciones Farmacológicas , Femenino , Perfilación de la Expresión Génica , Genoma Viral , Antígenos HLA/genética , Interacciones Microbiota-Huesped/efectos de los fármacos , Interacciones Microbiota-Huesped/genética , Humanos , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Ciudad de Nueva York/epidemiología , Técnicas de Amplificación de Ácido Nucleico , Pandemias , RNA-Seq , SARS-CoV-2/clasificación , SARS-CoV-2/efectos de los fármacos , Tratamiento Farmacológico de COVID-19
13.
Sci Adv ; 7(6)2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33536218

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has emerged as the cause of a global pandemic. We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. Overall, a muted immune response was observed in COVID-19 relative to other infections (influenza, other seasonal coronaviruses, and bacterial sepsis), with paradoxical down-regulation of several key differentially expressed genes. Hospitalized patients and outpatients exhibited up-regulation of interferon-associated pathways, although heightened and more robust inflammatory responses were observed in hospitalized patients with more clinically severe illness. Two-layer machine learning-based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 85.1-86.5% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for COVID-19 diagnosis.


Asunto(s)
COVID-19/diagnóstico , Nasofaringe/virología , ARN Viral/metabolismo , SARS-CoV-2/genética , Área Bajo la Curva , COVID-19/metabolismo , COVID-19/patología , COVID-19/virología , Biblioteca de Genes , Humanos , Aprendizaje Automático , ARN Viral/sangre , Curva ROC , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2/aislamiento & purificación , Sensibilidad y Especificidad , Transcriptoma
14.
Nat Commun ; 11(1): 4698, 2020 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-32943630

RESUMEN

Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seroreactivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors in early April 2020. We additionally describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3-11.0 days for these 3 assays. Neutralizing antibodies rose in tandem with immunoglobulin titers following symptom onset, and positive percent agreement between detection of IgG and neutralizing titers was >93%. These findings emphasize the importance of using highly accurate tests for surveillance studies in low-prevalence populations, and provide evidence that seroreactivity using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Betacoronavirus/inmunología , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Anticuerpos Antivirales/inmunología , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/inmunología , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Pandemias , Neumonía Viral/sangre , Neumonía Viral/inmunología , SARS-CoV-2 , San Francisco/epidemiología , Sensibilidad y Especificidad , Estudios Seroepidemiológicos , Pruebas Serológicas/métodos
15.
Sci Rep ; 10(1): 15392, 2020 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-32958861

RESUMEN

The potential role of enteric viral infections and the developing infant virome in affecting immune responses to the oral poliovirus vaccine (OPV) is unknown. Here we performed viral metagenomic sequencing on 3 serially collected stool samples from 30 Bangladeshi infants following OPV vaccination and compared findings to stool samples from 16 age-matched infants in the United States (US). In 14 Bangladeshi infants, available post-vaccination serum samples were tested for polio-neutralizing antibodies. The abundance (p = 0.006) and richness (p = 0.013) of the eukaryotic virome increased with age and were higher than seen in age-matched US infants (p < 0.001). In contrast, phage diversity metrics remained stable and were similar to those in US infants. Non-poliovirus eukaryotic virus abundance (3.68 log10 vs. 2.25 log10, p = 0.002), particularly from potential viral pathogens (2.78log10 vs. 0.83log10, p = 0.002), and richness (p = 0.016) were inversely associated with poliovirus shedding. Following vaccination, 28.6% of 14 infants tested developed neutralizing antibodies to all three Sabin types and also exhibited higher rates of poliovirus shedding (p = 0.020). No vaccine-derived poliovirus variants were detected. These results reveal an inverse association between eukaryotic virome abundance and poliovirus shedding. Overall gut virome ecology and concurrent viral infections may impact oral vaccine responsiveness in Bangladeshi infants.


Asunto(s)
Vacuna Antipolio Oral/inmunología , Poliovirus/genética , Esparcimiento de Virus/genética , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Bangladesh/epidemiología , Heces/virología , Femenino , Humanos , Esquemas de Inmunización , Lactante , Masculino , Metagenoma/genética , Metagenómica/métodos , Poliomielitis/virología , Poliovirus/inmunología , Vacuna Antipolio de Virus Inactivados/inmunología , Vacunación , Viroma/genética
16.
medRxiv ; 2020 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-32511449

RESUMEN

An outbreak of novel betacoronavirus, SARS-CoV-2 (formerly named 2019-nCoV), began in Wuhan, China in December 2019 and the COVID-19 disease associated with infection has since spread rapidly to multiple countries. Here we report the development of SARS-CoV-2 DETECTR, a rapid (~30 min), low-cost, and accurate CRISPR-Cas12 based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated this method using contrived reference samples and clinical samples from infected US patients and demonstrated comparable performance to the US CDC SARS-CoV-2 real-time RT-PCR assay.

17.
medRxiv ; 2020 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-32511477

RESUMEN

We report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seropositivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors. We additionally describe the longitudinal dynamics of immunoglobulin-G, immunoglobulin-M, and in vitro neutralizing antibody titers in COVID-19 patients. Neutralizing antibodies rise in tandem with immunoglobulin levels following symptom onset, exhibiting median time to seroconversion within one day of each other, and there is >93% positive percent agreement between detection of immunoglobulin-G and neutralizing titers.

18.
Nat Biotechnol ; 38(7): 870-874, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32300245

RESUMEN

An outbreak of betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 began in Wuhan, China in December 2019. COVID-19, the disease associated with SARS-CoV-2 infection, rapidly spread to produce a global pandemic. We report development of a rapid (<40 min), easy-to-implement and accurate CRISPR-Cas12-based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated our method using contrived reference samples and clinical samples from patients in the United States, including 36 patients with COVID-19 infection and 42 patients with other viral respiratory infections. Our CRISPR-based DETECTR assay provides a visual and faster alternative to the US Centers for Disease Control and Prevention SARS-CoV-2 real-time RT-PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Sistemas CRISPR-Cas , Técnicas de Laboratorio Clínico , Técnicas de Amplificación de Ácido Nucleico/métodos , Betacoronavirus/genética , COVID-19 , Prueba de COVID-19 , Vacunas contra la COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/virología , ARN Guía de Kinetoplastida/genética , SARS-CoV-2 , Factores de Tiempo
19.
Acta Inform Med ; 28(1): 58-64, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32210517

RESUMEN

INTRODUCTION: NCDs (non-communicable diseases) are considered an important social issue and a financial burden to the health care systems in the EU which can be decreased if cost-effective policies are implemented, along with proactive interventions. The CrowdHEALTH project recognizes that NCD poses a burden for the healthcare sector and society and aims at focusing on NCDs' public health policies. AIM: The aim of this paper is to present the concept of Public Health Policy (PHP), elaborate on the state-of-the-art of PHPs development, and propose a first approach to the modeling and evaluation of PHPs used in a toolkit that is going to support decision making, the Policy Development Toolkit (PDT). METHODS: The policy creation module is a part of the PDT aiming to integrate the results of the rest of the health analytics and policy components. It is the module that selects, filters, and aggregates all relevant information to help policy-makers with the decision making process. The policies creation component is connected to the visualization component to provide the final users with data visualization on different PHPs, including outcomes from data-driven models, such as risk stratification, clinical pathways mining, forecasting or causal analysis models, outcomes from cost-benefit analysis, and suggestions and recommendations from the results of different measured KPIs, using data from the Holistic Health Records (HHRs). RESULTS: In the context of CrowdHEALTH project, PHP can be defined as the decisions taken for actions by those responsible in the public sector that covers a set of actions or inactions that affect a group of public and private actors of the health care system. In the CrowdHEALTH project, the Policy Development Toolkit works as the main interface between the final users and the whole system in the CrowdHEALTH platform. The three components related to policy creation are: (i) the policy modeling component, (ii) the population identification component and (iii) the policy evaluation component. In policy evaluation, KPIs are used as measurable indicators to help prevent ambiguity problems in the interpretation of the model and the structure. CONCLUSIONS: This initial Policy creation component design might be modified during the project life circle according to the concept complexity.

20.
J Cyst Fibros ; 18 Suppl 2: S10-S18, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31679720

RESUMEN

Cystic Fibrosis Related Diabetes Mellitus (CFRD) drives excess pulmonary morbidity and mortality in patients with cystic fibrosis (CF). The recommended treatment is insulin therapy. Insulin therapy in CF should be customized to the specific patient. CF patients typically require intensive insulin regimens such as multiple daily injections or insulin pump therapy, but frequently require lower doses than in type 1 diabetes mellitus. Patients with CF may also need insulin to cover intravenous or enteral feedings. Pre-diabetic glycaemic abnormalities are also associated with clinical decline in cystic fibrosis prior to the diagnosis of CFRD, however, whether and how this should be treated is not fully determined. There is also interest, but inadequate data regarding other treatments besides insulin (i.e., oral medications) for treatment of pre-diabetes or CFRD. CFTR potentiator and corrector therapy has yet to demonstrate an effect on the rate of CFRD, but may improve insulin secretion. There is great opportunity for further research to better understand when and how best to treat glycaemic abnormalities in cystic fibrosis.


Asunto(s)
Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Diabetes Mellitus/etiología , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Fibrosis Quística/terapia , Humanos
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