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1.
Ecancermedicalscience ; 18: 1675, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38439808

RESUMEN

Haiti is a low-income country with one of the lowest human development index rankings in the world. Its childhood cancer services are provided by a single hospital with the only dedicated paediatric oncology department in the country. Our objective was to assess the cost and cost-effectiveness of all types of childhood cancer in Haiti to help prioritise investments and to support national cancer control planning. All costing data were collected from the year 2017 or 2018 hospital records. Costs were classified into 11 cost categories, and the proportion of the overall budget represented by each was calculated and converted from Haitian Gourde to United States dollars. The 5-year survival rate was retrieved from hospital records and used to calculate the cost-effectiveness of disability-adjusted life year (DALY) averted, using a healthcare costing perspective. Additional sensitivity analyses were conducted accounting for late-effect morbidity and early mortality and discounting rates of 0%, 3% and 6%. The annual cost of operating a paediatric oncology unit in Haiti treating 74 patients with newly diagnosed cancer was $803,184 overall or $10,854 per patient. The largest cost category was pharmacy, constituting 25% of the overall budget, followed by medical personnel (20%) and administration (12%). The cost per DALY averted in the base-case scenario was $1,128, which is 76% of the gross domestic product per capita, demonstrating that treating children with cancer in Haiti is very cost-effective according to the World Health Organisation Choosing Interventions that are Cost-Effective (WHO-CHOICE) threshold. In the most conservative scenario, the cost per DALY averted was cost-effective by WHO-CHOICE criteria. Our data will add to the growing body of literature illustrating a positive return on investment associated with diagnosing and treating children with cancer in even the most resource-limited environments. We anticipate that these data will aid local stakeholders and policymakers when identifying cancer control priorities and making budgetary decisions.

2.
Biomed Pharmacother ; 173: 116401, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38460363

RESUMEN

Adenosine regulates multiple physiological processes through the activation of four receptor subtypes, of which the A2B adenosine receptor (A2BAR) has the lowest affinity for adenosine. Being the adenosine receptor subtype most prominently expressed in epidermis, we recently described the antiproliferative and anti-inflammatory effect of the selective A2BAR agonist BAY60-6583 (BAY) in human keratinocytes stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), so we sought to establish the effect of topical application of BAY in a model of murine epidermal hyperplasia. Topical application of BAY (1 or 10 µg/site) prevented the inflammatory reaction and skin lesions induced by TPA, minimizing hyperproliferation and acanthosis, as well as the expression of specific markers of proliferative keratinocytes. On the other hand, pre-treatment with the selective A2BAR antagonist, PSB-1115 (PSB, 5 or 50 µg/site) reversed these beneficial effects. Additionally, BAY application normalized the expression of epidermal barrier proteins, whose integrity is altered in inflammatory skin diseases, while treatment with the antagonist alone worsened it. Our results, besides confirming the anti-inflammatory and antiproliferative effects of the A2BAR agonist, further demonstrate a role of A2BAR activation to preserve the epidermal barrier. Therefore, the activation of A2BAR may constitute a possible new pharmacological target for the treatment of skin inflammatory diseases such as psoriasis.


Asunto(s)
Adenosina , Enfermedades de la Piel , Ratones , Animales , Humanos , Adenosina/farmacología , Adenosina/metabolismo , Receptor de Adenosina A2B/metabolismo , Hiperplasia/tratamiento farmacológico , Hiperplasia/patología , Modelos Animales de Enfermedad , Epidermis , Antiinflamatorios/farmacología , Enfermedades de la Piel/patología
4.
Pediatr Blood Cancer ; 71(2): e30792, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38053237

RESUMEN

BACKGROUND/OBJECTIVES: High-risk Hodgkin lymphoma (HRHL) in children is curable with combined modality therapy. The Association of Pediatric Hematology-Oncology of Central America (AHOPCA) is a consortium of cancer centers from Central America. In 2004, AHOPCA implemented a guideline with a short course of chemotherapy (mStanfordV), strict diagnostics, and radiation guidelines, aimed at reducing abandonment and improving outcomes. METHODS: Newly diagnosed children less than 18 years of age with high-risk HL (Ann Arbor stages: IIB, IIIB, IV) from AHOPCA centers were staged with chest radiography and ultrasound or computed tomography. Therapy was a modified Stanford V (mStanfordV), substituting cyclophosphamide for mechlorethamine and involved field radiation. RESULTS: Of 219 patients with HRHL, 181 patients were eligible and evaluable; 146 (81%) were boys, 22% being less than 6 years; 43 were stage IIB, 84 IIIB, and 54 IV. Thirty-one (17%) abandoned therapy, 28 (15%) progressed, 30 (17%) relapsed, and eight (4%) died of toxicity. Radiation guidelines were not followed. Five-year abandonment-sensitive event-free survival and overall survival (AS-EFS, AS-OS ± SE) for the cohort were 46% ± 4% and 56% ± 4%; 5-year AS-OS for stages IIB, IIIB, and IV was 76% ± 7%, 59% ± 7%, and 35% ± 7% (p = .0006). CONCLUSION: Despite instituting a short treatment guideline, it did not improve the abandonment rate (17%) and did not achieve the reported outcomes of Stanford V. The cyclophosphamide dose used to replace merchlorethamine was inadequate. Despite strict guidelines, the radiation therapy application was inaccurate. Weekly chemotherapy may have adversely affected abandonment of therapy by increasing the burden of travel time. Based on these results, AHOPCA established a new abandonment strategy and a new guideline.


Asunto(s)
Antineoplásicos , Enfermedad de Hodgkin , Masculino , Niño , Humanos , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Vincristina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antineoplásicos/uso terapéutico , Ciclofosfamida , Resultado del Tratamiento , Doxorrubicina
5.
Cancer ; 130(7): 1112-1124, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38100617

RESUMEN

BACKGROUND: National cancer control plans (NCCPs) are complex public health programs that incorporate evidence-based cancer control strategies to improve health outcomes for all individuals in a country. Given the scope of NCCPs, small and vulnerable populations, such as patients with childhood cancer, are often missed. To support planning efforts, a rapid, modifiable tool was developed that estimates a context-specific national budget to fund pediatric cancer programs, provides 5-year scale-up scenarios, and calculates annual cost-effectiveness. METHODS: The tool was codeveloped by teams of policymakers, clinicians, and public health advocates in Zimbabwe, Zambia, and Uganda. The 11 costing categories included real-world data, modeled data, and data from the literature. A base-case and three 5-year scale-up scenarios were created using modifiable inputs. The cost-effectiveness of the disability-adjusted life years averted was calculated. Results were compared with each country's projected gross domestic product per capita for 2022 through 2026. RESULTS: The number of patients/total budget for year 1 was 250/$1,109,366 for Zimbabwe, 280/$1,207,555 for Zambia, and 1000/$2,277,397 for Uganda. In year 5, these values were assumed to increase to 398/$5,545,445, 446/$4,926,150, and 1594/$9,059,331, respectively. Base-case cost per disability-adjusted life year averted/ratio to gross domestic product per capita for year 1, assuming 20% survival, was: $807/0.5 for Zimbabwe, $785/0.7 for Zambia, and $420/0.5 for Uganda. CONCLUSIONS: This costing tool provided a framework to forecast a budget for childhood-specific cancer services. By leveraging minimal primary data collection with existing secondary data, local teams obtained rapid results, ensuring that childhood cancer budgeting is not neglected once in every 5 to 6 years of planning processes.


Asunto(s)
Neoplasias , Humanos , Niño , Neoplasias/terapia , Países en Desarrollo , Poblaciones Vulnerables , Análisis Costo-Beneficio , Costos de la Atención en Salud
6.
Int J Mol Sci ; 24(23)2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38069224

RESUMEN

The purinergic system has a dual role: the maintenance of energy balance and signaling within cells. Adenosine and adenosine triphosphate (ATP) are essential for maintaining these functions. Sarcopenia is characterized by alterations in the control of energy and signaling in favor of catabolic pathways. This review details the association between the purinergic system and muscle and adipose tissue homeostasis, discussing recent findings in the involvement of purinergic receptors in muscle wasting and advances in the use of the purinergic system as a novel therapeutic target in the management of sarcopenia.


Asunto(s)
Sarcopenia , Humanos , Adenosina Trifosfato/metabolismo , Adenosina/metabolismo , Receptores Purinérgicos/metabolismo , Transducción de Señal
7.
Front Pharmacol ; 14: 1247664, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37771723

RESUMEN

Introduction: Sarcopenia is defined as a loss of muscle mass and strength. ATP homeostasis is crucial during myogenesis. We determined how the purinergic system modulates myogenesis using dipyridamole (blocks adenosine taken up by the cells) and tenofovir (inhibits ATP release) in a myoblast cell line. Methods: C2C12 cells were differentiated in the presence/absence of tenofovir/dipyridamole, with/without the A2B selective inhibitor PSB-603. Extra-/intracellular nucleotides were examined via HPLC. The expression of muscle differentiation proteins (Pax7, Mif5, MyoD, MyoG, and MHC), PKA/CREB, adenosine receptors (A1, A2A, A2B, and A3), ATP-channel pannexin-1 and the P2X7 receptor was analyzed via WB and RT-PCR. cAMP and AMPK activation was measured. Results: Tenofovir increased intracellular ATP and reduced extracellular adenosine, decreasing Pax7 expression and increasing MHC expression prematurely. Dipyridamole increased intracellular AMP and extracellular adenosine, counteracting the premature myogenesis promoted by tenofovir. All adenosine receptors were expressed during differentiation with dipyridamole, increasing A2B expression. Tenofovir maintained inactive AMPK and decreased cAMP levels, as well as PKAα and pCREB expression, which were recovered with dipyridamole. Discussion: Adenosine and ATP act as mediators in muscle myogenesis. The blockade of ATP release by tenofovir promotes premature myogenesis, with dipyridamole counteracting the premature differentiation promoted by tenofovir via the adenosine A2B receptor and cAMP/AMPK pathways. Therefore, dipyridamole might be of interest as a therapeutic approach in sarcopenia.

8.
Am J Obstet Gynecol MFM ; 5(11): 101143, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37669739

RESUMEN

BACKGROUND: Second-trimester ultrasound is the standard technique for fetal anatomy evaluation in the United States despite international guidelines and literature that suggest that first-trimester timing may be superior in patients with obesity. First-trimester imaging performs well in cohorts of participants with obesity. OBJECTIVE: Our aim was to compare the completion rate of a first-trimester fetal anatomy ultrasound scan with that of a second-trimester fetal anatomy ultrasound scan among pregnant people with a body mass index ≥35 kg/m2. STUDY DESIGN: This randomized controlled trial enrolled participants with a body mass index ≥35 kg/m2 with a singleton gestation and who presented before 14+0/7 weeks of gestation. Participants were randomized to receive an ultrasound assessment of anatomy at either 12+0/7 to 13+6/7 weeks or at 18+0/7 to 22+6/7 weeks. The primary outcome was completion rate (percentage of scans that optimally imaged all the required fetal structures). Secondary outcomes included the necessity of a transvaginal approach, completion rates for each individual view, number of anomalies identified and missed in each group, scan duration, and patient perspectives. A 1-year pilot sample was analyzed using Bayesian methods for the primary outcome with a neutral prior and frequentist analyses for the remaining outcomes. RESULTS: A total of 128 participants were enrolled, and 1 withdrew consent; 62 subjects underwent a first-trimester ultrasound scan and 62 underwent a second-trimester ultrasound scan. A total of 2 participants did not attend the research visits, and 1 sought termination of pregnancy. In the first-trimester group, 66% (41/62) of ultrasound scans were completed in comparison with 53% (33/62) in the second-trimester ultrasound group (Bayesian relative risk, 1.20; 95% credible interval, 0.91-1.73). When compared with a second-trimester scan plus a follow-up ultrasound, a first-trimester ultrasound plus a second-trimester ultrasound was equally successful in completing the anatomy views (76%). First-trimester anatomy ultrasound scans required a transvaginal approach in 63% (39/62) of cases and had a longer duration than a second-trimester ultrasound scan. No anomalies were missed in either group. First-trimester ultrasound participants who responded to a survey described that they were very satisfied with the technique. CONCLUSION: In pregnant subjects with a body mass index ≥35 kg/m2, a single first-trimester anatomy ultrasound scan was more likely to obtain all the recommended anatomic views than a single second-trimester ultrasound scan. An evaluation of anatomy at 12+0/7 to 13+6/7 weeks' gestation plus an evaluation at 18+0/7 to 22+6/7 led to complete anatomic evaluation 4 weeks earlier than 2 second trimester scans. Assessment of ultrasound duration in a clinical setting is needed to ensure feasibility outside of a research setting.


Asunto(s)
Feto , Obesidad , Embarazo , Femenino , Humanos , Primer Trimestre del Embarazo , Teorema de Bayes , Segundo Trimestre del Embarazo , Feto/anomalías , Obesidad/diagnóstico por imagen , Obesidad/epidemiología
9.
Pediatr Blood Cancer ; 70(12): e30657, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37690982

RESUMEN

BACKGROUND: Survival from pediatric cancers in low middle-income countries is often very low compared to that of high-income countries due to multifactorial etiologies, including late presentation, delayed diagnosis, difficulty with accessing healthcare, drug unavailability, and treatment abandonment. The St. Jude Pediatric Oncology Facility Integrated Local Evaluation Tool (PrOFILE) was developed to map and evaluate childhood cancer healthcare delivery in individual institutions and entire countries, identifying the strengths and weaknesses, as well as opportunities for advancement of care. PROCEDURE: Using the PrOFILE self-assessment tool, selected Kenyan pediatric oncology facilities entered data into 12 modules: national context, facility and local context, finances and resources, personnel, service capacity, service integration, diagnostics, chemotherapy, supportive care, surgery, radiation therapy, and patients and outcomes. These modules are grouped into five specific components, including Context, Workforce, Diagnostics, Therapy, and Patients and Outcomes. The St. Jude PrOFILE team analyzed the data and organized the first hybrid workshop, containing both in-person and virtual components. RESULTS: Multidisciplinary stakeholders prioritized recommendations for improving care and developed smart objectives to accomplish identified goals over the following 2 years. Strengths and weaknesses of conducting a hybrid global workshop were identified. CONCLUSIONS: We demonstrated successful use of the PrOFILE tool to conduct a hybrid workshop and identify strategies to improve pediatric oncology care in Kenya. The voluntarily structured work groups will methodically aim to achieve outcome-oriented goals moving forward.

10.
Sci Rep ; 13(1): 9064, 2023 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-37271755

RESUMEN

Prognostic scales may help to optimize the use of hospital resources, which may be of prime interest in the context of a fast spreading pandemics. Nonetheless, such tools are underdeveloped in the context of COVID-19. In the present article we asked whether accurate prognostic scales could be developed to optimize the use of hospital resources. We retrospectively studied 467 files of hospitalized patients after COVID-19. The odds ratios for 16 different biomarkers were calculated, those that were significantly associated were screened by a Pearson's correlation, and such index was used to establish the mathematical function for each marker. The scales to predict the need for hospitalization, intensive-care requirement and mortality had enhanced sensitivities (0.91 CI 0.87-0.94; 0.96 CI 0.94-0.98; 0.96 CI 0.94-0.98; all with p < 0.0001) and specificities (0.74 CI 0.62-0.83; 0.92 CI 0.87-0.96 and 0.91 CI 0.86-0.94; all with p < 0.0001). Interestingly, when a different population was assayed, these parameters did not change considerably. These results show a novel approach to establish the mathematical function of a marker in the development of highly sensitive prognostic tools, which in this case, may aid in the optimization of hospital resources. An online version of the three algorithms can be found at: http://benepachuca.no-ip.org/covid/index.php.


Asunto(s)
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estudios Retrospectivos , Unidades de Cuidados Intensivos , Hospitalización , Cuidados Críticos , Biomarcadores , Probabilidad
11.
Sci Rep ; 11(1): 19728, 2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-34611251

RESUMEN

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Proteína C-Reactiva/análisis , COVID-19/mortalidad , COVID-19/patología , Relación Dosis-Respuesta a Droga , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Oportunidad Relativa , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tasa de Supervivencia
12.
Purinergic Signal ; 17(4): 591-605, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34392490

RESUMEN

Extracellular adenosine triphosphate (ATP) plays a central role in a wide variety of joint diseases. ATP is generated intracellularly, and the concentration of the extracellular ATP pool is determined by the regulation of its transport out of the cell. A variety of ATP transporters have been described, with connexins and pannexins the most commonly cited. Both form intercellular channels, known as gap junctions, that facilitate the transport of various small molecules between cells and mediate cell-cell communication. Connexins and pannexins also form pores, or hemichannels, that are permeable to certain molecules, including ATP. All joint tissues express one or more connexins and pannexins, and their expression is altered in some pathological conditions, such as osteoarthritis (OA) and rheumatoid arthritis (RA), indicating that they may be involved in the onset and progression of these pathologies. The aging of the global population, along with increases in the prevalence of obesity and metabolic dysfunction, is associated with a rising frequency of joint diseases along with the increased costs and burden of related illness. The modulation of connexins and pannexins represents an attractive therapeutic target in joint disease, but their complex regulation, their combination of gap-junction-dependent and -independent functions, and their interplay between gap junction and hemichannel formation are not yet fully elucidated. In this review, we try to shed light on the regulation of these proteins and their roles in ATP transport to the extracellular space in the context of joint disease, and specifically OA and RA.


Asunto(s)
Adenosina Trifosfato/metabolismo , Artritis Reumatoide/metabolismo , Cartílago Articular/metabolismo , Conexinas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Osteoartritis/metabolismo , Uniones Comunicantes/metabolismo , Humanos
14.
Pediatr Blood Cancer ; 67(12): e28760, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33049116

RESUMEN

PURPOSE: A considerable barrier to global pediatric oncology efforts has been the scarcity and even absence of trained professionals in many low- and middle-income countries, where the majority of children with cancer reside. In 2013, no dedicated pediatric hematology-oncology (PHO) programs existed in Ethiopia despite the estimated annual incidence of 6000-12000 cases. The Aslan Project initiative was established to fill this gap in order to improve pediatric cancer care in Ethiopia. A major objective was to increase subspecialty PHO-trained physicians who were committed to practicing locally and empowered to lead programmatic development. METHODS: We designed and implemented a PHO training curriculum to provide a robust educational and clinical experience within the existing resource-constrained environment in Ethiopia. Education relied on visiting PHO faculty, a training attachment abroad, and extraordinary initiative from trainees. RESULTS: Four physicians have completed comprehensive PHO subspecialty training based primarily in Ethiopia, and all have remained local. Former fellows are now leading two PHO centers in Ethiopia with a combined capacity of 64 inpatient beds and over 800 new diagnoses per year; an additional former fellow is developing a pediatric cancer program in Nairobi, Kenya. Two fellows currently are in training. Program leadership, teaching, and advocacy are being transitioned to these physicians. CONCLUSIONS: Despite myriad challenges, a subspecialty PHO training program was successfully implemented in a low-income country. PHO training in Ethiopia is approaching sustainability through human resource development, and is accelerating the growth of dedicated PHO services where none existed 7 years ago.


Asunto(s)
Educación de Postgrado en Medicina/normas , Becas/normas , Hematología/educación , Oncología Médica/educación , Neoplasias/terapia , Pediatría/educación , Médicos/estadística & datos numéricos , Niño , Etiopía/epidemiología , Humanos , Neoplasias/epidemiología
15.
Rep Pract Oncol Radiother ; 23(5): 392-397, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30127680

RESUMEN

AIM: To identify clinical and dosimetric factors associated with the development of hematologic toxicity (HT) for cervical cancer (CC) treated with chemotherapy and 3D conformal radiotherapy. BACKGROUND: Chemoradiotherapy is the standard of care management for CC patients with IB2-IVA clinical stages (CS). This treatment carries toxicities, standing out the one that occurs at the hematologic level. SUBJECTS AND METHODS: CC patients with IB2-IVA CS treated with chemotherapy and 3D conformal radiotherapy (50 Gy) plus Brachyterapy (7 Gy x3 or 9 Gy x2) at our institution between March 2016 and March 2017. Clinical and dosimetric factors were studied as was their probable association with the development of HT. RESULTS: 59 patients were analyzed. 89.8% of the subjects developed some grade of HT and 50.2% developed ≥grade 2 toxicity. No statistical relationship was found for the dosimetric factors: V10 > 90% (p = 0.47) and V20 > 80% (p = 0.17). Regarding clinical factors: neither age >50 years (p = 0.88) nor diabetes mellitus (DM) showed statistical relationship with development of ≥grade 2 HT (p = 0.88 and p = 0.61, respectively). On the contrary, obesity showed a significant association (p = 0.02). For other factors analyzed, we found statistical correlation for epidermoid histology and ≥III A CS (p = 0.01 and p = 0.02, respectively). CONCLUSIONS: We did not find statistical relationship between HT and the clinical factors of age >50 years and DM. Statistical relationship for the dosimetric factors V10 > 90% and V20 > 80% was not found as well. On the contrary, obesity, epidermoid histology and ≥IIIA CS, showed statistical significance for development of HT ≥grade 2.

16.
Plant Cell Environ ; 41(8): 1776-1790, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29486055

RESUMEN

Protein breakdown and mobilization are some of the major metabolic features associated with abiotic stresses, essential for nutrient recycling and plant survival. Genetic manipulation of protease and/or protease inhibitors may contribute to modulate proteolytic processes and plant responses. The expression analysis of the whole cystatin family, inhibitors of C1A cysteine proteases, after water deprivation in barley leaves highlighted the involvement of Icy-2 and Icy-4 cystatin genes. Artificial microRNA lines independently silencing the two drought-induced cystatins were generated to assess their function in planta. Phenotype alterations at the final stages of the plant life cycle are represented by the stay-green phenotype of silenced cystatin 2 lines. Besides, the enhanced tolerance to drought and differential responses to water deprivation at the initial growing stages are observed. The mutual compensating expression of Icy-2 and Icy-4 genes in the silencing lines pointed to their cooperative role. Proteolytic patterns by silencing these cystatins were concomitant with modifications in the expression of potential target proteases, in particular, HvPap-1, HvPap-12, and HvPap-16 C1A proteases. Metabolomics analysis lines also revealed specific modifications in the accumulation of several metabolites. These findings support the use of plants with altered proteolytic regulation in crop improvement in the face of climate change.


Asunto(s)
Cistatinas/metabolismo , Hordeum/metabolismo , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Cistatinas/fisiología , Deshidratación , Regulación de la Expresión Génica de las Plantas , Silenciador del Gen , Genes de Plantas/fisiología , Hordeum/fisiología , Metabolómica , MicroARNs/metabolismo , Hojas de la Planta/fisiología , Proteínas de Plantas/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa
17.
J Psychosoc Oncol ; 36(3): 319-332, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29452054

RESUMEN

OBJECTIVE: In order to reduce nonadherence and treatment abandonment of children with cancer in El Salvador, institutions located nearby the patients' homes were involved to provide support. Methodological approach: Health clinics and municipality offices in the patients' communities were asked to assist families who were not promptly located after missing hospital appointments, or those whose financial limitations were likely to impede continuation of treatment. Data was collected about the number of contacted institutions, the nature of help provided, staff's time investments, and parents' perceptions about the intervention. FINDINGS: Local institutions (133 from 206 contacts) conducted home visits (83), and/or provided parents with money (55) or transportation (60). Parents found this support essential for continuing the treatment but they also encountered challenges regarding local institutions' inconsistencies. Nonadherence and abandonment decreased. IMPLICATIONS: Economic burden was reduced on both the families and the hospital. Involvement of external institutions might become regular practice to support families of children with cancer.


Asunto(s)
Servicios de Salud del Niño/organización & administración , Agentes Comunitarios de Salud , Neoplasias/terapia , Cumplimiento y Adherencia al Tratamiento/estadística & datos numéricos , Niño , El Salvador , Femenino , Humanos , Masculino , Padres/psicología , Factores Socioeconómicos
18.
Expert Rev Hematol ; 8(5): 627-45, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26211675

RESUMEN

Infections are the most important cause of morbidity and mortality in children treated for acute lymphoblastic leukemia (ALL). The rates of infection-associated mortality are up to 10-times higher in low- and middle-income countries (LMIC) than in high-income countries. The prevention, early recognition and management of infectious complications is especially challenging in LMIC because of disease and poverty-related factors, as well as the shortage of trained personnel, supplies, diagnostic tools and adequate organizational infrastructure. Children in LMIC with ALL, who are frequently underweight, are at increased risk of community-acquired pathogens, nosocomial multidrug-resistant pathogens and opportunistic microorganisms. This review summarizes the challenges of managing the major categories of infections in children receiving treatment for ALL and provides updated practical recommendations for preventing and managing these infections in LMIC.


Asunto(s)
Infecciones/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Factores de Edad , Profilaxis Antibiótica , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Países en Desarrollo , Manejo de la Enfermedad , Neutropenia Febril/diagnóstico , Neutropenia Febril/tratamiento farmacológico , Neutropenia Febril/etiología , Neutropenia Febril/prevención & control , Humanos , Infecciones/diagnóstico , Infecciones/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Vacunas/administración & dosificación
19.
Pediatr Blood Cancer ; 62(9): 1609-15, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25925227

RESUMEN

BACKGROUND: In El Salvador, about 200 new cases of pediatric cancer are diagnosed each year, and survival rates approach 70%. Although treatment is available at no cost, abandonment of therapy has remained at a steady yearly rate of 13% during the past decade. A time sensitive adherence tracking procedure (TS-ATP) was recently implemented to detect missed appointments, identify their causes, and intervene promptly. Procedure The study team was informed daily of patient/family failure to attend medical appointments in the pediatric oncology unit; the families were contacted and interviewed to ascertain and address the reasons. Patients who did not return after this initial contact were contacted again through local health clinics and municipalities. Law enforcement was a last resort for patients undergoing frontline treatment with a good prognosis., The system was adapted to clinical urgency: families of patients undergoing induction therapy were contacted within 24 hr, those in other therapy phases, within 48 hr, and those who had completed treatment, within one week. Reasons for absence were obtained by telephone or in person. RESULTS: The annual rate of abandonment was reduced from 13-3% during the 2 years period. There were 1,111 absences reported and 1,472 contacts with caregivers and institutions. The three main reasons for absences were financial needs (165, 23%), unforeseen barriers (116, 16%), and domestic needs (86, 12%). CONCLUSIONS: Use of the treatment adherence tracking system to locate and communicate with patients/families after missed appointments and the allocated aid stemming from these interviews substantially reduced abandonment and non-adherence.


Asunto(s)
Neoplasias/psicología , Pacientes Desistentes del Tratamiento/psicología , Negativa del Paciente al Tratamiento/psicología , Adolescente , Instituciones Oncológicas/organización & administración , Cuidadores/psicología , Niño , Preescolar , El Salvador/epidemiología , Registros Electrónicos de Salud , Femenino , Hospitales Pediátricos/organización & administración , Humanos , Lactante , Aplicación de la Ley , Masculino , Motivación , Neoplasias/epidemiología , Neoplasias/terapia , Servicio de Oncología en Hospital/organización & administración , Cooperación del Paciente , Pacientes Desistentes del Tratamiento/legislación & jurisprudencia , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Educación del Paciente como Asunto , Comunicación Persuasiva , Pobreza , Relaciones Profesional-Familia , Servicio de Asistencia Social en Hospital/organización & administración , Teléfono , Centros de Atención Terciaria/organización & administración , Factores de Tiempo , Negativa del Paciente al Tratamiento/legislación & jurisprudencia , Negativa del Paciente al Tratamiento/estadística & datos numéricos
20.
Pediatr Blood Cancer ; 61(7): 1222-6, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24443303

RESUMEN

BACKGROUND: Relapsed childhood acute myeloid leukemia (AML) outcomes have not been documented in resource-limited settings. We examined survival after relapse for children with AML (non-APML) and acute promyelocytic leukemia (APML) in Central America. PROCEDURE: We retrospectively evaluated outcomes of children with first relapse of AML (non-APML) and APML in Guatemala, Honduras, or El Salvador diagnosed between 1997 and 2011. Predictors of subsequent event-free survival (EFS) and overall survival (OS) were examined. RESULTS: We identified 140 children with relapsed AML (non-APML), and 24 with relapsed APML. Two-year subsequent EFS and OS (±SE) were 7.0 ± 2.5% and 9.1 ± 2.8%, respectively. Worse outcomes were associated with Hispanic or Indigenous heritage, white blood cell count at diagnosis ≥50 × 10(9) /L, and time to relapse <18 months. For those with relapsed APML, subsequent 2-year EFS and OS were 36.7 ± 10.8% and 43.4 ± 12.1%, although few patients survived beyond 3 years. 15.2% of all patients were managed solely with palliative intent following first relapse. CONCLUSIONS: Children with relapsed AML in Central America rarely survive, so palliative strategies should be considered following relapse in this population. However, children with late relapse or with APML may have a prolonged period of remission with second treatment, and consideration of re-treatment may be appropriate.


Asunto(s)
Leucemia Promielocítica Aguda/mortalidad , Leucemia Promielocítica Aguda/prevención & control , Adolescente , América Central/epidemiología , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Promielocítica Aguda/patología , Masculino , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo
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