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1.
Epilepsia ; 65(4): 984-994, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38317356

RESUMEN

OBJECTIVE: Lead time to treatment (clinical onset of epileptic spasms [ES] to initiation of appropriate treatment) is known to predict outcomes in infantile epileptic spasms syndrome (IESS). Timing the clinical onset of ES is crucial to establish lead time. We investigated how often ES onset could be established to the nearest week. We aimed to (1) ascertain the exact date or estimate the nearest week of ES onset and (2) compare clinical/demographic factors between patients where date of ES onset was determined or estimated to the nearest week and patients whose date of ES onset could not be estimated to the nearest week. Reasons for difficulties in estimating date of ES onset were explored. METHODS: Retrospective chart review of new onset IESS patients (January 2019-May 2022) extracted the date or week of the clinical onset of ES. Predictors of difficulty in date of ES onset estimation to the nearest week were examined by regression analysis. Sources contributing to difficulties determining date of ES onset were assessed after grouping into categories (provider-, caregiver-, disease-related). RESULTS: Among 100 patients, date of ES onset was estimated to the nearest week in 47%. On univariable analysis, age at diagnosis (p = .021), development delay (p = .007), developmental regression/stagnation (p = .021), ES intermixed with other seizures (p = .011), and nonclustered ES at onset (p = .005) were associated with difficulties estimating date of ES onset. On multivariable analysis, failure to establish date of ES onset was related to ES intermixed with other seizures (p = .004) and nonclustered ES at onset (p = .003). Sources contributing to difficulties determining date of ES onset included disease-related factors (ES characteristics, challenges interpreting electroencephalograms) and provider/caregiver-related factors (delayed diagnosis). SIGNIFICANCE: Difficulties with estimation of lead time (due to difficulties timing ES onset) can impact clinical care (prognostication), as even small increments in lead time duration can have adverse developmental consequences.


Asunto(s)
Espasmos Infantiles , Humanos , Lactante , Estudios Retrospectivos , Edad de Inicio , Espasmos Infantiles/diagnóstico , Espasmos Infantiles/tratamiento farmacológico , Síndrome , Electroencefalografía , Convulsiones , Espasmo
3.
Epilepsia ; 65(1): 107-114, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37953072

RESUMEN

OBJECTIVE: Non-Hispanic (NH) Black children are less likely to receive a standard treatment course for infantile epileptic spasms syndrome (IESS) than White/NH children at pediatric tertiary care epilepsy centers in the United States. However, if inequities exist in time to diagnosis is unknown. Diagnostic delays as little as 1 week can be associated with worse developmental outcomes. METHODS: Diagnostic delays were evaluated in a retrospective cohort of 100 children with new onset IESS between January 2019 and May 2022. RESULTS: Children with Black, Indigenous, and People of Color (BIPOC) caregivers were more likely to experience clinically significant delays in referral from first provider to neurologist, when compared to White/NH children, even after controlling for other demographic and clinical variables (odds ratio = 4.98, confidence interval = 1.24-19.94, p = .023). SIGNIFICANCE: Disproportionate diagnostic delays place BIPOC children at risk of adverse developmental and epilepsy outcomes. Further interventional prospective and qualitative studies are needed to address inequities in care.


Asunto(s)
Epilepsia , Espasmos Infantiles , Humanos , Niño , Estados Unidos , Estudios Retrospectivos , Estudios Prospectivos , Etnicidad , Epilepsia/diagnóstico , Síndrome , Espasmo , Espasmos Infantiles/terapia , Espasmos Infantiles/tratamiento farmacológico
4.
Neuropsychiatr Dis Treat ; 19: 733-748, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37041855

RESUMEN

Tuberous sclerosis complex (TSC) is a neurogenetic disorder that affects multiple organ systems, including the heart, kidneys, eyes, skin, and central nervous system. The neurologic manifestations have the highest morbidity and mortality, in particular in children. Clinically, patients with TSC often present with new-onset seizures within the first year of life. TSC-associated epilepsy is often difficult to treat and refractory to multiple antiseizure medications. Refractory TSC-associated epilepsy is associated with increased risk of neurodevelopmental comorbidities, including developmental delay, intellectual disability, autism spectrum disorder, and attention hyperactivity disorder. An increasing body of research suggests that early, effective treatment of TSC-associated epilepsy during critical neurodevelopmental periods can potentially improve cognitive outcomes. Therefore, it is important to treat TSC-associated epilepsy aggressively, whether it be with pharmacological therapy, surgical intervention, and/or neuromodulation. This review discusses current and future pharmacological treatments for TSC-associated epilepsy, as well as the importance of early surgical evaluation for refractory epilepsy in children with TSC and consideration of neuromodulatory interventions in young adults.

5.
J Neurosurg Pediatr ; : 1-8, 2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36905669

RESUMEN

OBJECTIVE: Posthemorrhagic hydrocephalus (PHH) remains a major morbidity of premature birth resulting from intraventricular hemorrhage (IVH). National consensus guidelines for the timing of surgical interventions are lacking, which leads to considerable variations in management among neonatal intensive care units (NICUs). Early intervention (EI) has been shown to improve outcomes, but the authors hypothesized that the timing from IVH to intervention affects the comorbidities and complications associated with PHH management. The authors used a large national inpatient care data set to characterize comorbidities and complications associated with PHH management in premature infants. METHODS: The authors used hospital discharge data from the 2006-2019 Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) to conduct a retrospective cohort study of premature pediatric patients (weight < 1500 g) with PHH. The predictor variable was the timing of the PHH intervention (EI ≤ 28 days vs late intervention [LI] > 28 days). Hospital stay data included hospital region, gestational age, birth weight (BW), length of stay (LOS), PHH treatment procedures, comorbidities, surgical complications, and death. Statistical analysis included chi-square and Wilcoxon rank-sum tests, Cox proportional hazards regression, logistic regression, and a generalized linear model with Poisson and gamma distributions. Analysis was adjusted for demographic characteristics, comorbidities, and death. RESULTS: Of the 1853 patients diagnosed with PHH, 488 (26%) had documented timing of surgical interventions during their hospital stay. More patients had LI than EI (75%). The patients in the LI group of patients had younger gestational age and lower BW. There were significant regional differences in the timing of treatment: hospitals in the West performed EI, whereas hospitals in the South performed LI, even after adjustment for gestational age and BW. The LI group was associated with longer median LOS and more total hospital charges compared with the EI group. More temporary CSF diversion procedures occurred in the EI group, whereas more permanent CSF-diverting shunts were placed in the LI group. Shunt/device replacement and complications did not differ between the two groups. The LI group had 2.5-fold higher odds of sepsis (p < 0.001) and almost 2-fold higher odds of retinopathy of prematurity (p < 0.05) than the EI group. CONCLUSIONS: The timing of PHH interventions differs by region in the United States, whereas the association of potential benefits with treatment timing suggests the importance of national consensus guidelines. Development of these guidelines can be informed by data regarding treatment timing and patient outcomes available in large national data sets, which provide insights into comorbidities and complications of PHH interventions.

6.
Epilepsia Open ; 8(2): 444-455, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36790214

RESUMEN

OBJECTIVE: To describe inpatient resource use in the 2 years following infantile epileptic spasms syndrome (IESS) diagnosis, examine the association between clinical/demographic variables and incidence of readmission, and identify risk factors/reasons for frequent readmissions. METHODS: Retrospective cohort analysis of readmissions (scheduled/unscheduled) within the first 2 years following IESS diagnosis, details of readmissions (number/time between rehospitalizations, and length of stay), demographic/clinical variables, and reasons for readmissions were collected. Negative binomial regression analysis evaluated associations between incidence of readmissions (both scheduled/unscheduled and unscheduled alone) and demographic/clinical factors. Logistic regression assessed the risk of having recurrent readmissions (≥5 readmissions). RESULTS: Among 93 (60% males) new-onset IESS patients, there were 394 readmissions (56% scheduled and 44% unscheduled) within 2-years following IESS diagnosis. Mean length of stay was 3.5 days (SD: 5.9). Readmissions occurred in 82 patients (88%) and 37 (40%) experienced ≥5 readmissions. On multivariate regression analysis, readmissions were increased with use of multiple first-line treatments for IESS (P = 0.006), technology assistance (P ≤ 0.001), and multispecialty care (P = 0.01); seizure freedom (P = 0.015) and known etiology (P = 0.011) lowered the incidence of readmissions. Examining unscheduled readmissions separately, increased readmissions occurred with public insurance (P = 0.013), technology use (P ≤ 0.0.001), and multispecialty care (P = 0.013); seizure freedom decreased unscheduled readmissions (P = 0.006). Technology assistance (G-tube, NG tube, VP shunt, and tracheostomy use) increased the odds (P = 0.007) for recurrent readmissions. Reasons for readmissions included EEG monitoring (protocol driven for verification of IESS remission/characterization of events/EEG surveillance/presurgical monitoring) (51%), acute medical issues (21%), and seizure exacerbation (15%). Protocol-driven readmissions declined an estimated 52% following protocol modification during the study. SIGNIFICANCE: In the 2 years following IESS diagnosis, there is substantial inpatient resource use with nearly 40% experiencing ≥5 readmissions (mostly epilepsy related). Since readmissions are increased by intrinsic patient characteristics such as medical complexity (technology use and multispecialty care) or epilepsy-related issues, the preventability of readmissions is uncertain, except for protocol-driven ones.


Asunto(s)
Epilepsia , Readmisión del Paciente , Masculino , Humanos , Niño , Femenino , Estudios Retrospectivos , Estudios de Cohortes , Síndrome , Espasmo
7.
iScience ; 25(11): 105384, 2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36388957

RESUMEN

Biomass conversion to fuels and chemicals is crucial to decarbonization, but choosing an advantageous upgrading pathway out of many options is challenging. Rigorously evaluating all candidate pathways (process simulation, product property testing) requires a prohibitive amount of research effort; even simple upgrading schemes have hundreds of possible permutations. We present a method enabling high-throughput screening by approximating upgrading unit operations and drop-in compatibility of products (e.g., fuel properties) and apply it to volatile fatty acid (VFA) conversion to liquid transportation fuels via a MATLAB script, VFA Upgrading to Liquid Transportation fUels Refinery Estimation (VULTURE). VULTURE selects upgrading configurations that maximize fuel blend bio-derived content. We validate VULTURE's approximations through surrogate fuel property testing and process simulation. Techno-economic and life cycle analyses suggest that VFA upgrading processes down-selected by VULTURE are profitable and have low carbon intensities, demonstrating the potential for the strategy to accelerate process development timelines at decreased costs.

8.
Sci Rep ; 12(1): 13801, 2022 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-35963878

RESUMEN

There is an urgent need to validate new drug targets and identify small molecules that possess activity against both drug-resistant and drug-sensitive bacteria. The enzymes belonging to amino acid biosynthesis have been shown to be essential for growth in vitro, in vivo and have not been exploited much for the development of anti-tubercular agents. Here, we have identified small molecule inhibitors targeting homoserine acetyl transferase (HSAT, MetX, Rv3341) from M. tuberculosis. MetX catalyses the first committed step in L-methionine and S-adenosyl methionine biosynthesis resulting in the formation of O-acetyl-homoserine. Using CRISPRi approach, we demonstrate that conditional repression of metX resulted in inhibition of M. tuberculosis growth in vitro. We have determined steady state kinetic parameters for the acetylation of L-homoserine by Rv3341. We show that the recombinant enzyme followed Michaelis-Menten kinetics and utilizes both acetyl-CoA and propionyl-CoA as acyl-donors. High-throughput screening of a 2443 compound library resulted in identification of small molecule inhibitors against MetX enzyme from M. tuberculosis. The identified lead compounds inhibited Rv3341 enzymatic activity in a dose dependent manner and were also active against HSAT homolog from S. aureus. Molecular docking of the identified primary hits predicted residues that are essential for their binding in HSAT homologs from M. tuberculosis and S. aureus. ThermoFluor assay demonstrated direct binding of the identified primary hits with HSAT proteins. Few of the identified small molecules were able to inhibit growth of M. tuberculosis and S. aureus in liquid cultures. Taken together, our findings validated HSAT as an attractive target for development of new broad-spectrum anti-bacterial agents that should be effective against drug-resistant bacteria.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Homoserina/farmacología , Humanos , Simulación del Acoplamiento Molecular , Staphylococcus aureus
9.
Annu Rev Chem Biomol Eng ; 13: 301-324, 2022 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-35320697

RESUMEN

There is an urgent need for new technologies to enable circularity for synthetic polymers, spurred by the accumulation of waste plastics in landfills and the environment and the contributions of plastics manufacturing to climate change. Chemical recycling is a promising means to convert waste plastics into molecular intermediates that can be remanufactured into new products. Given the growing interest in the development of new chemical recycling approaches, it is critical to evaluate the economics, energy use, greenhouse gas emissions, and other life cycle inventory metrics for emerging processes,relative to the incumbent, linear manufacturing practices employed today. Here we offer specific definitions for classes of chemical recycling and upcycling and describe general process concepts for the chemical recycling of mixed plastics waste. We present a framework for techno-economic analysis and life cycle assessment for both closed- and open-loop chemical recycling. Rigorous application of these process analysis tools will be required to enable impactful solutions for the plastics waste problem.


Asunto(s)
Plásticos , Reciclaje , Plásticos/química , Polímeros
10.
Nutrients ; 13(10)2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34684427

RESUMEN

Cow's milk allergy (CMA) is the most common food allergy in early childhood, and its prevalence continues to rise. Exclusive breastfeeding is recommended for infants in the first 6 months of life, but this recommendation is poorly adhered to in many parts of the world, including the Middle East, North Africa, and Pakistan (MENAP) region. If the infant is affected by CMA, current guidelines recommend extensively hydrolyzed formulas (eHFs) or amino acid-based formulas (AAFs) in the case of severe symptoms, and hydrolyzed rice formulas (HRFs) where available. In recent years, HRFs have been proposed as a plant-based alternative to cow's milk protein-based eHFs, and updates to current guidelines have been recommended. In 2014, a consensus statement and guidelines were published for the Middle East region on the prevention, diagnosis, and management of CMA. As new advances have been made in the extensively hydrolyzed hypoallergenic infant formula space, along with updated scientific evidence, a workshop of experts from the MENAP region focused on HRF was convened in 2021. This publication summarizes the insights from this meeting. During the consensus part of the meeting, a new approach was discussed and approved by all participants, and agreement was reached that HRF can be recommended as a first-line alternative to cow's milk-based eHF in the dietary management of CMA.


Asunto(s)
Fórmulas Infantiles , Hipersensibilidad a la Leche/epidemiología , Hipersensibilidad a la Leche/etiología , Oryza , África del Norte/epidemiología , Animales , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Medio Oriente/epidemiología , Hipersensibilidad a la Leche/diagnóstico , Hipersensibilidad a la Leche/terapia , Pakistán/epidemiología , Vigilancia en Salud Pública
11.
Ann Neurol ; 89(2): 327-340, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33201535

RESUMEN

OBJECTIVE: In the absence of controlled trials, treatment of neonatal seizures has changed minimally despite poor drug efficacy. We tested bumetanide added to phenobarbital to treat neonatal seizures in the first trial to include a standard-therapy control group. METHODS: A randomized, double-blind, dose-escalation design was employed. Neonates with postmenstrual age 33 to 44 weeks at risk of or with seizures were eligible. Subjects with electroencephalography (EEG)-confirmed seizures after ≥20 and <40mg/kg phenobarbital were randomized to receive additional phenobarbital with either placebo (control) or 0.1, 0.2, or 0.3mg/kg bumetanide (treatment). Continuous EEG monitoring data from ≥2 hours before to ≥48 hours after study drug administration (SDA) were analyzed for seizures. RESULTS: Subjects were randomized to treatment (n = 27) and control (n = 16) groups. Pharmacokinetics were highly variable among subjects and altered by hypothermia. The only statistically significant adverse event was diuresis in treated subjects (48% vs 13%, p = 0.02). One treated (4%) and 3 control subjects died (19%, p = 0.14). Among survivors, 2 of 26 treated subjects (8%) and 0 of 13 control subjects had hearing impairment, as did 1 nonrandomized subject. Total seizure burden varied widely, with much higher seizure burden in treatment versus control groups (median = 3.1 vs 1.2 min/h, p = 0.006). There was significantly greater reduction in seizure burden 0 to 4 hours and 2 to 4 hours post-SDA (both p < 0.01) compared with 2-hour baseline in treatment versus control groups with adjustment for seizure burden. INTERPRETATION: Although definitive proof of efficacy awaits an appropriately powered phase 3 trial, this randomized, controlled, multicenter trial demonstrated an additional reduction in seizure burden attributable to bumetanide over phenobarbital without increased serious adverse effects. Future trials of bumetanide and other drugs should include a control group and balance seizure severity. ANN NEUROL 2021;89:327-340.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Bumetanida/uso terapéutico , Fenobarbital/uso terapéutico , Convulsiones/tratamiento farmacológico , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Electroencefalografía , Femenino , Moduladores del GABA/uso terapéutico , Enfermedades Genéticas Congénitas/complicaciones , Humanos , Hipoxia-Isquemia Encefálica/complicaciones , Recién Nacido , Hemorragias Intracraneales/complicaciones , Masculino , Meningoencefalitis/complicaciones , Malformaciones del Sistema Nervioso/complicaciones , Proyectos Piloto , Convulsiones/etiología , Accidente Cerebrovascular/complicaciones
12.
Clin Infect Dis ; 71(10): 2752-2756, 2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-32463076

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly in a few months despite global public health strategies to curb transmission by testing symptomatic patients and social distancing. This review summarizes evidence that highlights transmission by asymptomatic and presymptomatic individuals. Viral load of asymptomatic and symptomatic cases is comparable. Viral shedding is highest before symptom onset, suggesting high transmissibility before symptoms. Within universally tested subgroups, high percentages of SARS-CoV-2 infected asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters, including a Wuhan study showing an alarming rate of intrahospital transmission. Several countries reported higher prevalence among healthcare workers than general population raising concern that healthcare workers could act as silent vectors. Therefore, current strategies that rely solely on "symptom onset" for infection identification need urgent reassessment. Extensive universal testing irrespective of symptoms may be considered, with priority placed on groups with high frequency exposure to positive patients.


Asunto(s)
COVID-19 , Pandemias , Humanos , Salud Pública , SARS-CoV-2 , Esparcimiento de Virus
13.
CNS Drugs ; 34(1): 47-63, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31879852

RESUMEN

Convulsive status epilepticus (CSE) is one of the most common pediatric neurological emergencies. Ongoing seizure activity is a dynamic process and may be associated with progressive impairment of gamma-aminobutyric acid (GABA)-mediated inhibition due to rapid internalization of GABAA receptors. Further hyperexcitability may be caused by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors moving from subsynaptic sites to the synaptic membrane. Receptor trafficking during prolonged seizures may contribute to difficulties treating seizures of longer duration and may provide some of the pathophysiological underpinnings of established and refractory SE (RSE). Simultaneously, a practice change toward more rapid initiation of first-line benzodiazepine (BZD) treatment and faster escalation to second-line non-BZD treatment for established SE is in progress. Early administration of the recommended BZD dose is suggested. For second-line treatment, non-BZD anti-seizure medications (ASMs) include valproate, fosphenytoin, or levetiracetam, among others, and at this point there is no clear evidence that any one of these options is better than the others. If seizures continue after second-line ASMs, RSE is manifested. RSE treatment consists of bolus doses and titration of continuous infusions under continuous electro-encephalography (EEG) guidance until electrographic seizure cessation or burst-suppression. Ultimately, etiological workup and related treatment of CSE, including broad spectrum immunotherapies as clinically indicated, is crucial. A potential therapeutic approach for future studies may entail consideration of interventions that may accelerate diagnosis and treatment of SE, as well as rational and early polytherapy based on synergism between ASMs by utilizing medications targeting different mechanisms of epileptogenesis and epileptogenicity.


Asunto(s)
Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Animales , Niño , Humanos , Convulsiones/tratamiento farmacológico
14.
J Crohns Colitis ; 13(12): 1518-1526, 2019 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-31120524

RESUMEN

BACKGROUND AND AIM: Acute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC. METHODS: This retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged <18 years, admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥65) between 2009 and 2011, were collected at discharge and 1, 3 and 5 years after admission. The primary outcome was colectomy-free rates at each time point. RESULTS: Of the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate >70 mm/h, and albumin <2.5 g/dL, were significantly associated with 5-year colectomy risk. CONCLUSIONS: High colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome.


Asunto(s)
Colectomía , Colitis Ulcerosa , Glucocorticoides/uso terapéutico , Infliximab/uso terapéutico , Efectos Adversos a Largo Plazo/epidemiología , Niño , Colectomía/efectos adversos , Colectomía/métodos , Colectomía/estadística & datos numéricos , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/terapia , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , América del Norte/epidemiología , Evaluación de Procesos y Resultados en Atención de Salud , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico
15.
Dev Genes Evol ; 229(2-3): 43-52, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30825002

RESUMEN

One of the earliest patterning events in the vertebrate neural plate is the specification of mes/r1, the territory comprising the prospective mesencephalon and the first hindbrain rhombomere. Within mes/r1, an interface of gene expression defines the midbrain-hindbrain boundary (MHB), a lineage restriction that separates the mesencephalon and rhombencephalon. wnt1 is critical to mes/r1 development and functions within the MHB as a component of the MHB gene regulatory network (GRN). Despite its importance to these critical and early steps of vertebrate neurogenesis, little is known about the factors responsible for wnt1 transcriptional regulation. In the zebrafish, wnt1 and its neighboring paralog, wnt10b, are expressed in largely overlapping patterns, suggesting co-regulation. To understand wnt1 and wnt10b transcriptional control, we used a comparative genomics approach to identify relevant enhancers. We show that the wnt1-wnt10b locus contains multiple cis-regulatory elements that likely interact to generate the wnt1 and wnt10b expression patterns. Two of 11 conserved enhancers tested show activity restricted to the midbrain and MHB, an activity that is conserved in the distantly related spotted gar orthologous elements. Three non-conserved elements also play a likely role in wnt1 regulation. The identified enhancers display dynamic modes of chromatin accessibility, suggesting controlled deployment during embryogenesis. Our results suggest that the control of wnt1 and wnt10b expression is under complex regulation involving the interaction of multiple enhancers.


Asunto(s)
Encéfalo/embriología , Elementos Reguladores de la Transcripción , Proteínas Wnt/genética , Proteína Wnt1/genética , Proteínas de Pez Cebra/genética , Pez Cebra/embriología , Animales , Cromatina , Embrión no Mamífero/metabolismo , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Peces/embriología , Peces/genética , Regulación del Desarrollo de la Expresión Génica , Genómica , Ratones , Regiones Promotoras Genéticas , Proteínas Wnt/metabolismo , Proteína Wnt1/metabolismo , Pez Cebra/metabolismo , Proteínas de Pez Cebra/metabolismo
16.
J Pediatr Gastroenterol Nutr ; 68(6): 824-828, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30664563

RESUMEN

BACKGROUND: Caustic ingestion with concentrated detergent pods (CDPs) is a common problem encountered in pediatric population. There is insufficient literature about endoscopic findings in CDP ingestion and hence no current consensus or guidelines regarding the need for endoscopic evaluation. OBJECTIVES: To review cases of children with exposure to CDPs from 2010 to 2016 at a tertiary care children's hospital and to identifying the possibility of a correlation between clinical presentation and the endoscopic findings. METHODS: A retrospective review identified pediatric patients with accidental caustic exposure to CDPs. Data on demographics, type of exposure, clinical symptoms, physical examination, details of the hospital course were collected. Esophagogastroduodenoscopy (EGD) findings and direct laryngoscopy-bronchoscopy findings were also collected. Descriptive statistics were computed for all demographic and clinical variables. The association between EGD findings and clinical presentation were tested using Fisher exact test. RESULTS: A total of 23 (28%) cases of CDP ingestion were identified out of 83 total cases of caustic ingestion between January 2010 and June 2016. Median age was 15 months. gastrointestinal symptoms were present in 21 (91%) patients. Examination findings were present in 8 of 23 (35%) patients. EGD (done by gastroenterologists) evaluation was done in 21 (91%) patients and positive findings were seen in 5 of 21 (24%). The proportion of patients with positive examination findings was significantly higher in patients with positive EGD findings (80% vs 20%, respectively; P = 0.0307). Direct laryngoscopy-bronchoscopy (done by otolaryngologists) evaluation was done in 6 (26%) patients and positive findings were seen in 4 of 6 (67%). CONCLUSIONS: Our results suggest that oropharyngeal examination findings increase the likelihood of endoscopy findings; hence, we recommend endoscopic evaluation of patients who have examination findings secondary to exposure to CDPs. In other patients, it will be reasonable to evaluate the need for endoscopy on a case-by-case basis.


Asunto(s)
Quemaduras Químicas/patología , Cáusticos/toxicidad , Detergentes/toxicidad , Endoscopía del Sistema Digestivo , Tracto Gastrointestinal/lesiones , Adolescente , Quemaduras Químicas/etiología , Niño , Preescolar , Ingestión de Alimentos , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Tracto Gastrointestinal/cirugía , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos
17.
Soft Matter ; 12(29): 6196-205, 2016 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-27383924

RESUMEN

Fluorescence spectroscopy was employed to characterize the kinetics of guest exchange in diblock copolymer micelles composed of poly(ethylene oxide-b-ε-caprolactone) (PEO-PCL) diblock copolymers in water/tetrahydrofuran (THF) mixtures which encapsulated fluorophores. The solvent composition (THF content) of the micelle solution was varied as a means of modulating the strength of interactions between the fluorophore and solvent as well as between the micelle core and solvent. A donor-acceptor fluorophore pair was employed consisting of 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO, the donor) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI, the acceptor). Through the process of Förster resonance energy transfer (FRET), energy was transferred from the donor to acceptor when the fluorophores were in close proximity. A micelle solution containing DiO was mixed with a micelle solution containing DiI at t = 0, and the emission spectra of the mixed solution were monitored over time (at an excitation wavelength optimized for the donor). In micelle solutions containing 5 and 10 vol% THF in the bulk solvent, an increase in the acceptor peak intensity maximum occurred over time in the post-mixed solution, accompanied by a decrease in the donor peak intensity maximum, indicating the presence of energy transfer from the donor to the acceptor. At long times, the FRET ratios (acceptor peak intensity divided by the sum of the acceptor and donor peak intensities) were indistinguishable from that determined from pre-mixed micelle solutions of the same THF content (in pre-mixed solutions, DiO and DiI were encapsulated within the same micelle cores). In the micelle solution containing 20 vol% THF, the fluorophore exchange process occurred too quickly to be observed (the FRET ratios measured from the solutions mixed at t = 0 were commensurate to that measured from the pre-mixed solution). A time constant describing the guest exchange process was extracted from the time-dependence of the FRET ratio through fit of an exponential decay. An increase in the THF content in the micelle solution resulted in a decrease in the time constant, and the time constant varied over five orders of magnitude as the THF content was varied from 5-20 vol%.

18.
J Indian Soc Pedod Prev Dent ; 32(3): 242-5, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25001445

RESUMEN

Variations in dental anatomy and canal morphology are found in all teeth. Knowledge of these variations, particularly the location and treatment of all canals, plays a key role in the success of endodontic therapy. The presence of extra canals, apical ramification, or lateral canals is commonly encountered, and their incidence and significance have been well-documented. However, the clinician should also be aware of the possibility of the existence of fewer root and/or canal numbers. Here is a case report of left maxillary first permanent molar with a single root and single canal. The goal of this clinical article is to report a maxillary molar with single root and single canal and to highlight the role of spiral computed tomography (SCT) as a method to confirm the three-dimensional (3D) anatomy of teeth.


Asunto(s)
Diente Molar/diagnóstico por imagen , Niño , Femenino , Humanos , Tomografía Computarizada por Rayos X
19.
Indian J Pediatr ; 81(1): 24-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23949869

RESUMEN

OBJECTIVE: To evaluate the factors associated with low birth weight (LBW) and to formulate a scale to predict the probability of having a LBW infant. METHODS: This hospital based case-control study was conducted in a tertiary care university hospital in North India. The study included 250 LBW neonates and 250 neonates with birth weight ≥2,500 g. Data were collected by interviewing mothers using pre-designed structured questionnaire and from hospital records. RESULTS: Factors significantly associated with LBW were inadequate weight gain by the mother during pregnancy (<8.9 kg), inadequate proteins in diet (<47 g/d), previous preterm baby, previous LBW baby, anemic mother and passive smoking. The prediction model made on these six variables has a sensitivity of 71.6 %, specificity 67.0 %, positive LR 2.17 and negative LR of 0.42 for a cut-off score of ≥29.25. On validation, it has a sensitivity of 72 % and specificity of 64 %. CONCLUSIONS: It is possible to predict LBW using a prediction model based on significant risk factors associated with LBW.


Asunto(s)
Recién Nacido de Bajo Peso , Modelos Estadísticos , Estudios de Casos y Controles , Femenino , Predicción , Humanos , Recién Nacido , Masculino , Medición de Riesgo
20.
Ann Indian Acad Neurol ; 15(2): 137-8, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22566730

RESUMEN

Neurological complications following honey bee sting are rare. We report a case of a 3-year-old girl who developed acute polyradiculoneuropathy following honey bee sting, which was diagnosed by nerve conduction studies.

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