RESUMO
We report new lipid-based, high-density, environmentally sensitive (HIDE) probes that accurately and selectively image endo-lysosomes and their dynamics at super-resolution for extended times. Treatment of live cells with the small molecules DiIC16TCO or DiIC16'TCO followed by in situ tetrazine ligation reaction with the silicon-rhodamine dye SiR-Tz generates the HIDE probes DiIC16-SiR and DiIC16'-SiR in the endo-lysosomal membrane. These new probes support the acquisition of super-resolution videos of organelle dynamics in primary cells for more than 7 min with no detectable change in endosome structure or function. Using DiIC16-SiR and DiIC16'-SiR, we describe direct evidence of endosome motility defects in cells from patients with Niemann-Pick Type-C disease. In wild-type fibroblasts, the probes reveal distinct but rare inter-endosome kiss-and-run events that cannot be observed using confocal methods. Our results shed new light on the role of NPC1 in organelle motility and cholesterol trafficking.
Assuntos
Endossomos/metabolismo , Lisossomos/metabolismo , Microscopia de Fluorescência/métodos , Transporte Biológico , Carbocianinas/química , Proteínas de Transporte/metabolismo , Colesterol/metabolismo , Fibroblastos/metabolismo , Corantes Fluorescentes , Células HeLa , Humanos , Glicoproteínas de Membrana/metabolismo , Transporte ProteicoRESUMO
BACKGROUND: The emergence of genetic and genomic sequencing approaches for pediatric patients has raised questions about the genomic health literacy levels, attitudes toward receiving genomic information, and use of this information to inform treatment decisions by pediatric patients and their parents. However, the methods to educate pediatric patients and their parents about genomic concepts through digital health interventions have not been well-established. OBJECTIVE: The primary objective of this scoping review is to investigate the current levels of genomic health literacy and the attitudes toward receiving genomic information among pediatric patients and their parents. The secondary aim is to investigate patient education interventions that aim to measure and increase genomic health literacy among pediatric patients and their parents. The findings from this review will be used to inform future digital health interventions for patient education. METHODS: A scoping review using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines and protocols was completed using the following databases: MEDLINE, Embase, CINAHL, and Scopus. Our search strategy included genomic information inclusive of all genetic and genomic terms, pediatrics, and patient education. Inclusion criteria included the following: the study included genetic, genomic, or a combination of genetic and genomic information; the study population was pediatric (children and adolescents <18 years) and parents of patients with pediatric illnesses or only parents of patients with pediatric illnesses; the study included an assessment of the knowledge, attitudes, and intervention regarding genomic information; the study was conducted in the last 12 years between 2008 and 2020; and the study was in the English language. Descriptive data regarding study design, methodology, disease population, and key findings were extracted. All the findings were collated, categorized, and reported thematically. RESULTS: Of the 4618 studies, 14 studies (n=6, 43% qualitative, n=6, 43% mixed methods, and n=2, 14% quantitative) were included. Key findings were based on the following 6 themes: knowledge of genomic concepts, use of the internet and social media for genomic information, use of genomic information for decision-making, hopes and attitudes toward receiving genomic information, experiences with genetic counseling, and interventions to improve genomic knowledge. CONCLUSIONS: This review identified that older age is related to the capacity of understanding genomic concepts, increased genomic health literacy levels, and the perceived ability to participate in decision-making related to genomic information. In addition, internet-searching plays a major role in obtaining genomic information and filling gaps in communication with health care providers. However, little is known about the capacity of pediatric patients and their parents to understand genomic information and make informed decisions based on the genomic information obtained. More research is required to inform digital health interventions and to leverage the leading best practices to educate these genomic concepts.
Assuntos
Letramento em Saúde , Pediatria , Adolescente , Idoso , Criança , Comunicação , Genômica , Humanos , PaisRESUMO
Inflammatory myofibroblastic tumors (IMT) are rare soft tissue tumors of intermediate malignant potential occurring usually in children and adolescents. Treatment options for advanced diseases are limited. A 35-year-old lady presented to us with fever, cough and decreased appetite. On evaluation, she was diagnosed with left lung IMT. She underwent surgery and developed recurrence with pleural nodules after two years. Immunohistochemistry showed positivity for ALK (diffuse). Since recent evidence suggested that crizotinib is effective in advanced IMT with 50% response rates, she was treated with crizotinib 250mg BD with which she had a complete radiological response at three months. She has completed one year of treatment thus far and continues to be in complete remission. Treatment with ALK inhibitors like crizotinib has brought about a paradigm shift in the management of advanced ALK-positive IMT's with excellent clinical responses which are durable in a majority of cases.
Assuntos
Neoplasias Pulmonares , Adolescente , Adulto , Quinase do Linfoma Anaplásico/genética , Criança , Crizotinibe/uso terapêutico , Feminino , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
The discharge of organic dye pollutants in natural water bodies has put forward a big challenge of providing clean water to a large part of the population. As the population is increasing with time, only underground water is not sufficient to complete the water requirements of everyone everywhere. Purification of wastewater and its reuse is the only way to fulfill the water needs. Nanotechnology has been used very efficiently for wastewater treatment via photocatalytic degradation of dye molecules. In the past few years, a lot of investigations have been done to enhance the photocatalytic activity of metal oxide semiconductors for water purification. In this review, we have discussed the different methods of synthesis of various metal oxide semiconductor nanoparticles, energy band gap, their role as efficient photocatalysts, radiations used for photocatalytic reactions, and their degradation efficiency to degrade the dye pollutants. We have also discussed the nanocomposites of metal oxide with graphene. These nanocomposites have been utilized as the efficient photocatalyst due to unique characteristics of graphene such as extended range of light absorption, separation of charges, and high capacity of adsorption of the dye pollutants.
Assuntos
Poluentes Ambientais , Grafite , Óxidos , Água , Semicondutores , Corantes , CatáliseRESUMO
BACKGROUND: Infantile inflammatory myofibroblastic tumour (IMT) is rare and the majority are driven by anaplastic lymphoma kinase (ALK) rearrangements. Previous literature on the use of ALK inhibitors in paediatric IMTs is extremely limited with no published literature on the use in infants. Crizotinib and ceritinib are two ALK inhibitors which are available and have been used in IMTs; however, ceritinib is much more affordable in the low- and middle-income country (LMIC) setting than crizotinib. CASE: An 11-month-old child, who had undergone surgery for mesenteric IMT at the age of 3 months, had an unresectable recurrence with soft tissue deposits in the subdiaphragmatic location abutting the spleen and paravesical location. As surgery would have entailed splenectomy and partial cystectomy, she was treated with low-dose ceritinib (300 mg/m2/day) with which she had a near-complete response without any toxicity. DISCUSSION AND CONCLUSION: This is the first report of the use of ceritinib at a lower dose for infantile IMT having immense practical applications for the low- and middle-income setting.
RESUMO
[This corrects the article on p. 1 in vol. 15.].
RESUMO
Inflammatory myofibroblastic tumors (IMT) are rare soft tissue tumors of intermediate malignant potential with tendency for local recurrence. Although they can occur at all age groups, occurrence in infants is extremely unusual and their imaging characteristics are not well described. A 3-month-old female infant presented with gradually progressive abdominal distention without any fever or weight loss. She had a large ill-defined homogenous hypodense lesion of size 8.4 × 11.4 × 11.3 cm (APxTraxSag) in the abdomen showing mild delayed post contrast enhancement. She underwent exploratory laparotomy with gross total excision of mesenteric mass, histopathology of which was suggestive of IMT. She had recurrence within 6 months of complete resection with a well-defined heterogeneously enhancing lesion of size 1.8 × 1.8 × 2.3cm (APxTraxSag) in right paravesical region abutting the bladder without invasion with a similar lesion of size 4.4 × 2.1 × 3 cm (APxTraxSag) in left subdiaphragmatic region abutting superior surface of spleen (no invasion). Since, surgery in our patient would have entailed splenectomy and partial cystectomy, systemic therapy with ceritinib (anaplastic lymphoma kinase [ALK] inhibitor) was planned for her with which she had a near complete response after 2 months. A high index of suspicion is required to differentiate IMT from other common causes of mesenteric masses in children and role of radiologist is quintessential in this regard. Local recurrence with abutment but without invasion of surrounding structures points to the intermediate malignant pathology of IMT and may provide a clue to diagnosis. Systemic therapy is effective in patients who are ALK positive and destructive surgery should be avoided.
RESUMO
CONTEXT: Dental fluorosis is caused by successive exposure to high concentrations of fluoride during tooth development leading to enamel with lower mineral content and increased porosity. AIMS: The aim of the study was to evaluate and compare the effectiveness of minimally invasive techniques for the removal of dental fluorosis stains in children in vivo. DESIGN: Ninety children in the age group of 10-17 years were selected. MATERIALS AND METHODS: The study sample was equally and randomly divided into three groups; Group 1: In-office bleaching with 35% hydrogen peroxide (HP) activated by light-emitting diode (LED) bleaching unit (35% HP), Group 2: Enamel microabrasion (EM) followed by in-office bleaching with 44% carbamide peroxide gel (EM), Group 3: In-office bleaching with 5% sodium hypochlorite (5% NaOCl). Statistical analysis was done using one-way ANOVA test. RESULTS: Bleaching with 35% HP activated by LED bleaching unit and EM followed by bleaching with 44% carbamide peroxide were equally effective for the removal of dental fluorosis stains in children in vivo. However, bleaching with 5% NaOCl could not completely remove moderate to severe stains. It was effective in removing only mild stains. Bleaching and microabrasion procedures caused slight decrease in tooth sensitivity readings by electric pulp vitality tester which continued to increase over time. However, none of the patients reported sensitivity in their teeth at any point of time. Patients were highly satisfied with the treatment outcome postoperatively but reported slight relapse of color in the three groups. CONCLUSIONS: Bleaching and microabrasion techniques can consider as an interesting alternatives to conventional operative treatment options.
Assuntos
Microabrasão do Esmalte/métodos , Fluorose Dentária/terapia , Clareadores Dentários/farmacologia , Clareamento Dental/métodos , Descoloração de Dente/terapia , Adolescente , Peróxido de Carbamida , Criança , Feminino , Humanos , Peróxido de Hidrogênio/farmacologia , Índia , Masculino , Satisfação do Paciente , Peróxidos/farmacologia , Hipoclorito de Sódio/farmacologia , Descoloração de Dente/etiologia , Resultado do Tratamento , Ureia/análogos & derivados , Ureia/farmacologiaRESUMO
INTRODUCTION: Dental care is often overlooked by the parents of children receiving treatment for cancer including chemotherapy who are in a phase of severe immunosuppression. AIM: (i) To study dental attitudes of parents of children receiving chemotherapy towards importance of dental care. (ii) To evaluate oral hygiene status and compare it with healthy controls. MATERIALS AND METHODS: A questionnaire assessing the awareness towards dental care was given to the parents of 47 paediatric patients suffering from cancer receiving chemotherapy and to parents of 47 paediatric patients reporting to outpatient Department of Pedodontics at SGT Dental College. Oral examination was also carried out for both the groups and DMFT/dmft, plaque and gingival index were noted. RESULTS: Parents had a varying opinion regarding dental health of their child. The caries status of children in the control group was greater than children in the study group. The mean plaque index of children in the control group (1.40) was greater than children in the study group (1.34) which was statistically significant according to Mann-Whitney U test. The gingival health of children in the study group was better than children in the control group which was also not statistically significant. CONCLUSION: This study highlights need for a periodic referral of the child cancer patients to the paediatric dental clinic in hospitals for the timely dental care.
RESUMO
Microbial fatty acid biosynthetic enzymes are important targets for areas as diverse as antibiotic development to biofuel production. Elucidating the molecular basis of chain length control during fatty acid biosynthesis is crucial for the understanding of regulatory processes of this fundamental metabolic pathway. In Escherichia coli, the acyl carrier protein (AcpP) plays a central role by sequestering and shuttling the growing acyl chain between fatty acid biosynthetic enzymes. FabA, a ß-hydroxyacyl-AcpP dehydratase, is an important enzyme in controlling fatty acid chain length and saturation levels. FabA-AcpP interactions are transient in nature and thus difficult to visualize. In this study, four mechanistic crosslinking probes mimicking varying acyl chain lengths were synthesized to systematically probe for modified chain length specificity of 14 FabA mutants. These studies provide evidence for the AcpP-interacting "positive patch," FabA mutations that alter substrate specificity, and the roles that the FabA "gating residues" play in chain length control.