The use of activity diaries for understanding the daily lives of farmers and their livelihood choices

This paper reviews the use of activity diaries in two Australian Centre for International Agricultural Research (ACIAR) projects in PNG: a smallholder cocoa project in the East New Britain province (ASEM/2006/127) and a smallholder coffee project in Eastern Highlands province (ASEM/2008/036). Both projects were similarly concerned with identifying the production constraints on cocoa- and coffee-farming households and to better understand the range of socioeconomic and cultural factors influencing farmer decision-making and the allocation of household labour among various livelihood activities. In PNG, the household is the principal production unit underpinning livelihood activities such as commodity production. It is at the household level that decisions and negotiations are made regarding the organisation, mobilisation and management of family and extended family labour. Thus, examining in detail the daily economic and social livelihood activities of household members, through time-allocation studies, helps researchers to understand more comprehensively the factors influencing smallholder decision-making regarding livelihood choices, agricultural practices and the adoption of agricultural innovations. This paper outlines two different techniques using activity diaries employed in the projects, and discusses the methodological advantages and challenges of these techniques in smallholder studies in PNG

Tamoxifen Is Effective in the Treatment of Leishmania amazonensis Infections in Mice

Leishmaniasis is an antropozoonotic disease with a wide range of clinical manifestations. In humans, signs of disease vary from skin and mucosal ulcers to enlargement of internal organs such as the liver and spleen. The unicellular parasite Leishmania amazonensis is able to infect humans and cause localized or diffuse skin lesions. The treatment for this disease is difficult, as it requires prolonged and painful applications of toxic drugs that are poorly tolerated. Therefore, a key area in leishmaniasis research is the study of new therapeutic schemes and less toxic drugs. The present report is based on the investigation of tamoxifen's activity (a compound that has been in clinical use since the 1970s for the treatment of breast cancer) in the treatment of mice experimentally infected with L. amazonensis. We observed that infected mice treated with 20 mg/kg/day of tamoxifen for 15 days showed a significant clinical and parasitological response, with reduction in the size of lesions and ulcers and decreased numbers of parasites. These promising results pave the way for further testing of this drug as a new alternative in the chemotherapy of leishmaniasis

Predictors of Relapse in Differentiated Thyroid Carcinoma in Colombia: Multicenter Study

Introducción: El cáncer diferenciado de tiroides es una enfermedad que si bien no tiene una tasa alta de mortalidad, acarrea una carga de morbilidad importante dada principal-mente por la recurrencia. Nuestro objetivo fue determinar los factores asociados a recaída en pacientes de tres centros de referencia en Colombia. Métodos: Se realizó un estudio descriptivo retrospectivo. Las variables demográficas, clínicas e histopatológicas fue-ron recolectadas a partir de las historias clínicas de pacientes atendidos durante tres años. Resultados: Fueron incluidos 481 sujetos. El 85,7% eran mujeres y el 59,3% de la población fue mayor de 45 años. En el 97% de los casos se trató de carcinoma papilar. El promedio de seguimiento fue de 5,1±4,9 años. La recaída tumoral se do-cumentó en el 16,8% de los sujetos con una mediana de tiem-po de tres años desde la terapia inicial. Se encontró asociación entre recaída y el tamaño del tumor, extensión extratiroidea, relación ganglios comprometidos/resecados centrales y tota-les y compromiso periganglionar en el análisis univariado. El número de ganglios totales comprometidos ≥ 2 (HR 4,10, IC 95% 1,07 - 4,85) y el valor de tiroglobulina estimulada ≥ 7,29 ng/ml (HR 2,28, IC 95% 1,07-4,85, p=0,031) fueron los dos factores independientes asociados con recaída en el análisis multivariado. Autor de correspondenciaLisseth Fernanda Marín [email protected]ón de correspondencia: Centro Médico Carlos Ardila Lulle. Carrera 24 # 154 – 106 Urbanización El Bosque. Torre B, Módulo 55, consultorio 806.Teléfonos: 3188481025 - 6389303Fecha de recepción:18/06/2018Fecha de aceptación:27/02/2019 Conclusiones: Los pacientes con cáncer diferenciado de tiroides con compromiso metastásico de hasta un ganglio cer-vical y/o un nivel de tiroglobulina preablativa inferior a 7,29 ng/ml pueden ser considerados de bajo riesgo para recaída.Palabras clave: cáncer de tiroides, recurrencia, recaída, tiroglobulina, ganglios linfáticos.Artículo original92-100Background/Purpose: Differentiated thyroid cancer, de-spite not having a high mortality rate, entails an important morbidity burden, given mainly by recurrence. It was our objec-tive to determine the associated factors with relapse in patients with thyroid cancer in 3 hospitals in Colombia. Methods: A retrospective descriptive study was conducted. Demographic, clinical and histopathological characteristics were collected from medical records of patients attended dur-ing 3 years. Results: 481 patients were included. 85.7% were women and 59.3% were over 45 years. 97% of cases had papillary carci-noma. The mean time of follow-up was 5.1±4.9 years. Tumor re-lapse was documented in 16.8% of subjects with a median time of 3 years since initial therapy. Association between recurrence and tumor size, extrathyroid extension, metastatic/resected lymph node ratio (central and total) and extranodal extension was found in the univariate analysis. The total amount of meta-static lymph nodes ≥2 (HR 4.10, CI95%1.07-4.85) and a value of preablative stimulated thyroglobulin ≥7.29 ng/ml (HR 2.28, CI 95%1.07-4.85, p=0.031), were the only two significant features related to recurrence in the multivariate analysis. Conclusions: Patients with differentiated thyroid carcino-ma with ≤ 1 metastatic total lymph nodes and/or preablative stimulated thyroglobulin less than 7.29 ng/ml might be classi-fied as low recurrence risk.Keywords: thyroid cancer, recurrence, thyroglobulin, lymph nodes, lymphatic metastases

Predictores de recaída en carcinoma diferenciado de tiroides en Colombia: estudio multicéntrico

Introducción: El cáncer diferenciado de tiroides es una enfermedad que si bien no tiene una tasa alta de mortalidad, acarrea una carga de morbilidad importante dada principalmente por la recurrencia. Nuestro objetivo fue determinar los factores asociados a recaída en pacientes de tres centros de referencia en Colombia. Métodos: Se realizó un estudio descriptivo retrospectivo. Las variables demográficas, clínicas e histopatológicas fueron recolectadas a partir de las historias clínicas de pacientes atendidos durante tres años. Resultados: Fueron incluidos 481 sujetos. El 85,7% eran mujeres y el 59,3% de la población fue mayor de 45 años. En el 97% de los casos se trató de carcinoma papilar. El promedio de seguimiento fue de 5,1±4,9 años. La recaída tumoral se documentó en el 16,8% de los sujetos con una mediana de tiempo de tres años desde la terapia inicial. Se encontró asociación entre recaída y el tamaño del tumor, extensión extratiroidea, relación ganglios comprometidos/resecados centrales y totales y compromiso periganglionar en el análisis univariado. El número de ganglios totales comprometidos ? 2 (HR 4,10, IC 95% 1,07 - 4,85) y el valor de tiroglobulina estimulada ? 7,29 ng/ml (HR 2,28, IC 95% 1,07-4,85, p=0,031) fueron los dos factores independientes asociados con recaída en el análisis multivariado. Conclusiones: Los pacientes con cáncer diferenciado de tiroides con compromiso metastásico de hasta un ganglio cervical y/o un nivel de tiroglobulina preablativa inferior a 7,29 ng/ml pueden ser considerados de bajo riesgo para recaída

Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1)

TRIP4 is one of the subunits of the transcriptional coregulator ASC-1, a ribonucleoprotein complex that participates in transcriptional coactivation and RNA processing events. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy. Here we present the diagnostic journey of a patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures. Initial exome sequencing analysis revealed no candidate variants. Reanalysis of the exome data by inclusion in the Solve-RD project resulted in the identification of a homozygous stop-gain variant in the TRIP4 gene, previously reported as disease-causing. This highlights the importance of analysis reiteration and improved and updated bioinformatic pipelines. Proteomic profile of the patient’s fibroblasts showed altered RNA-processing and impaired exosome activity supporting the pathogenicity of the detected variant. In addition, we identified a novel genetic form of PCH1, further strengthening the link of this characteristic phenotype with altered RNA metabolism

Germline mutations in mitochondrial complex I reveal genetic and targetable vulnerability in IDH1-mutant acute myeloid leukaemia

The interaction of germline variation and somatic cancer driver mutations is underinvestigated. Here we describe the genomic mitochondrial landscape in adult acute myeloid leukaemia (AML) and show that rare variants affecting the nuclear- and mitochondriallyencoded complex I genes show near-mutual exclusivity with somatic driver mutations affecting isocitrate dehydrogenase 1 (IDH1), but not IDH2 suggesting a unique epistatic relationship. Whereas AML cells with rare complex I variants or mutations in IDH1 or IDH2 all display attenuated mitochondrial respiration, heightened sensitivity to complex I inhibitors including the clinical-grade inhibitor, IACS-010759, is observed only for IDH1-mutant AML. Furthermore, IDH1 mutant blasts that are resistant to the IDH1-mutant inhibitor, ivosidenib, retain sensitivity to complex I inhibition. We propose that the IDH1 mutation limits the flexibility for citrate utilization in the presence of impaired complex I activity to a degree that is not apparent in IDH2 mutant cells, exposing a mutation-specific metabolic vulnerability. This reduced metabolic plasticity explains the epistatic relationship between the germline complex I variants and oncogenic IDH1 mutation underscoring the utility of genomic data in revealing metabolic vulnerabilities with implications for therapy.Mahmoud A. Bassal, Saumya E. Samaraweera, Kelly Lim, Brooks A. Bernard, Sheree Bailey, Satinder Kaur, Paul Leo, John Toubia, Chloe Thompson-Peach, Tran Nguyen, Kyaw Ze Ya Maung, Debora A. Casolari, Diana G. Iarossi, Ilaria S. Pagani, Jason Powell, Stuart Pitson, Siria Natera, Ute Roessner, Ian D. Lewis, Anna L. Brown, Daniel G. Tenen, Nirmal Robinson, David M. Ross, Ravindra Majeti, Thomas J. Gonda, Daniel Thomas, Richard J. D, Andre

A highly conserved protein of unknown function in Sinorhizobium meliloti affects sRNA regulation similar to Hfq

The SMc01113/YbeY protein, belonging to the UPF0054 family, is highly conserved in nearly every bacterium. However, the function of these proteins still remains elusive. Our results show that SMc01113/YbeY proteins share structural similarities with the MID domain of the Argonaute (AGO) proteins, and might similarly bind to a small-RNA (sRNA) seed, making a special interaction with the phosphate on the 5′-side of the seed, suggesting they may form a component of the bacterial sRNA pathway. Indeed, eliminating SMc01113/YbeY expression in Sinorhizobium meliloti produces symbiotic and physiological phenotypes strikingly similar to those of the hfq mutant. Hfq, an RNA chaperone, is central to bacterial sRNA-pathway. We evaluated the expression of 13 target genes in the smc01113 and hfq mutants. Further, we predicted the sRNAs that may potentially target these genes, and evaluated the accumulation of nine sRNAs in WT and smc01113 and hfq mutants. Similar to hfq, smc01113 regulates the accumulation of sRNAs as well as the target mRNAs. AGOs are central components of the eukaryotic sRNA machinery and conceptual parallels between the prokaryotic and eukaryotic sRNA pathways have long been drawn. Our study provides the first line of evidence for such conceptual parallels. Furthermore, our investigation gives insights into the sRNA-mediated regulation of stress adaptation in S. meliloti