Polineuropatía por amiloidosis por transtiretina de inicio tardío. Caso clínico / Late-onset hereditary transthyretin amyloidosis with polyneuropathy. Report of one case

Hereditary transthyretin amyloidosis is a multisystemic autosomal dominant genetic disorder characterized by progressive distal sensory-motor polyneuropathy or restrictive cardiomyopathy, secondary to amyloid deposits. Its pathogenesis lies in the TTR gene mutation, and the Val50Met mutation is the most frequent. Patients have significant differences in the onset and severity of clinical presentation according to their country of origin. The diagnosis of this pathology is complex, even more in countries where it is not considered endemic. However, early suspicion and management are essential to improve survival and avoid unnecessary diagnostic and therapeutic strategies. We report a 69-year-old woman who presented a sensory-motor polyneuropathy, predominantly sensory, associated with distal neuropathic pain and bilateral vitritis. The history of her Italian father with polyneuropathy of unspecified etiology stood out. A vitreous biopsy identified amyloid substance deposits (congo red positive). These were also confirmed on a superficial peroneal nerve biopsy. During the etiological study of her polyneuropathy, an increased Kappa/Lambda index of 2.55 mg/L stood out. Therefore, light chain amyloidosis was suspected, and chemotherapy treatment was indicated without favorable response. After 10 years of progressive neurological and ophthalmological involvement, a genetic study confirmed the first case of late-onset hereditary transthyretin amyloidosis Val50Met with polyneuropathy in Chile.

Advances and Perspectives for Polyploidy Breeding in Orchids.

The orchid market is a dynamic horticultural business in which novelty and beauty command high prices. The two main interests are the development of flowers, from the miniature to the large and showy, and their fragrance. Overall organ size might be modified by doubling the chromosome number, which can be accomplished by careful study of meiotic chromosome disjunction in hybrids or species. Meiosis is the process in which diploid (2n) pollen mother cells recombine their DNA sequences and then undergo two rounds of division to give rise to four haploid (n) cells. Thus, by interfering in chromosome segregation, one can induce the development of diploid recombinant cells, called unreduced gametes. These unreduced gametes may be used for breeding polyploid progenies with enhanced fertility and large flower size. This review provides an overview of developments in orchid polyploidy breeding placed in the large context of meiotic chromosome segregation in the model plants Arabidopsis thaliana and Brassica napus to facilitate molecular translational research and horticultural innovation.

[Late-onset hereditary transthyretin amyloidosis with polyneuropathy. Report of one case]. / Polineuropatía por amiloidosis por transtiretina de inicio tardío. Caso clínico.

Hereditary transthyretin amyloidosis is a multisystemic autosomal dominant genetic disorder characterized by progressive distal sensory-motor polyneuropathy or restrictive cardiomyopathy, secondary to amyloid deposits. Its pathogenesis lies in the TTR gene mutation, and the Val50Met mutation is the most frequent. Patients have significant differences in the onset and severity of clinical presentation according to their country of origin. The diagnosis of this pathology is complex, even more in countries where it is not considered endemic. However, early suspicion and management are essential to improve survival and avoid unnecessary diagnostic and therapeutic strategies. We report a 69-year-old woman who presented a sensory-motor polyneuropathy, predominantly sensory, associated with distal neuropathic pain and bilateral vitritis. The history of her Italian father with polyneuropathy of unspecified etiology stood out. A vitreous biopsy identified amyloid substance deposits (congo red positive). These were also confirmed on a superficial peroneal nerve biopsy. During the etiological study of her polyneuropathy, an increased Kappa/Lambda index of 2.55 mg/L stood out. Therefore, light chain amyloidosis was suspected, and chemotherapy treatment was indicated without favorable response. After 10 years of progressive neurological and ophthalmological involvement, a genetic study confirmed the first case of late-onset hereditary transthyretin amyloidosis Val50Met with polyneuropathy in Chile.

Effects of the economic recession on suicide mortality in Brazil: interrupted time series analysis / Efectos de la recesión económica en la mortalidad por suicidio en Brasil: análisis de series de tiempo interrumpido / Efeitos da recessão econômica na mortalidade por suicídio no Brasil: análise com séries temporais interrompidas

ABSTRACT Objectives: to analyze trends in suicide rates in Brazil in the period before and after the start of the economic recession. Methods: interrupted time series research using national suicide data recorded in the period between 2012 and 2017 with socioeconomic subgroups analyses. Quasi-Poisson regression model was employed to analyze trends in seasonally adjusted data. Results: there was an abrupt increase in the risk of suicide after economic recession in the population with less education (12.5%; RR = 1.125; 95%CI: 1.027; 1.232) and in the South Region (17.7%; 1.044; 1.328). After an abrupt reduction, there was a progressive increase in risk for the black and brown population and for those with higher education. In most other population strata, there was a progressive increase in the risk of suicide. Conclusions: the Brazilian economic recession caused different effects on suicide rates, considering social strata, which requires health strategies and policies that are sensitive to the most vulnerable populations.

RESUMEN Objetivos: analizar tendencias de tasas de suicidio en Brasil, antes y después del inicio de la recesión económica. Métodos: estudio de series de tiempo interrumpido utilizando datos nacionales de suicidio registrados entre 2012 y 2017 con análisis por subgrupos socioeconómicos. Modelo de regresión quasi-Poisson empleado para analizar tendencias de datos ajustados estacionalmente. Resultados: observado aumento abrupto en el riesgo de suicidio pos recesión económica en la población con menor escolaridad (12,5%; RR = 1,125; IC95%:1,027; 1,232) y en la Región Sur (17,7%; 1,044; 1,328). Pos reducción abrupta, ocurrió aumento progresivo en el riesgo para la población de negros y pardos y de mayor escolaridad. En la mayoría de los demás estratos poblacionales, verificado aumento progresivo en el riesgo de suicidio. Conclusiones: la recesión económica brasileña produzco efectos diferentes en las tasas de suicidio, considerando los estratos sociales, lo que demanda estrategias de salud y políticas sensibles a poblaciones más vulnerables.

RESUMO Objetivos: analisar as tendências nas taxas de suicídio no Brasil, no período antes e depois do início da recessão econômica. Métodos: estudo de séries temporais interrompidas utilizando dados nacionais de suicídio registrados no período entre 2012 e 2017 com análises por subgrupos socioeconômicos. Modelo de regressão quasi-Poisson foi empregado para analisar as tendências dos dados ajustados sazonalmente. Resultados: observou-se aumento abrupto no risco de suicídio após recessão econômica na população com menor escolaridade (12,5%; RR = 1,125; IC95%:1,027; 1,232) e na Região Sul (17,7%; 1,044; 1,328). Após redução abrupta, ocorreu aumento progressivo no risco para a população de pretos e pardos e na de maior escolaridade. Na maioria dos demais estratos populacionais, verificou-se aumento progressivo no risco de suicídio. Conclusões: a recessão econômica brasileira produziu efeitos diferentes nas taxas de suicídio, considerando os estratos sociais, o que demanda estratégias de saúde e políticas sensíveis às populações mais vulneráveis.

Geographical Variability in Mortality in Urban Areas: A Joint Analysis of 16 Causes of Death.

The geographical distribution of mortality has frequently been studied. Nevertheless, those studies often consider isolated causes of death. In this work, we aim to study the geographical distribution of mortality in urban areas, in particular, in 26 Spanish cities. We perform an overall study of 16 causes of death, considering that their geographical patterns could be dependent and estimating the dependence between the causes of death. We study the deaths in these 26 cities during the period 1996-2015 at the census tract level. A multivariate disease mapping model is used in order to solve the potential small area estimation problems that these data could show. We find that most of the geographical patterns found show positive correlations. This suggests the existence of a transversal geographical pattern, common to most causes of deaths, which determines those patterns to a higher/lower extent depending on each disease. The causes of death that exhibit that underlying pattern in a more prominent manner are chronic obstructive pulmonary disease (COPD), lung cancer, and cirrhosis for men and cardiovascular diseases and dementias for women. Such findings are quite consistent for most of the cities in the study. The high positive correlation found between geographical patterns reflects the existence of both high and low-risk areas in urban settings, in general terms for nearly all the causes of death. Moreover, the high-risk areas found often coincide with neighborhoods known for their high deprivation. Our results suggest that dependence among causes of death is a key aspect to be taken into account when mapping mortality, at least in urban contexts.

[Toxic epidermal necrolysis during a hemophagocytic syndrome secondary to Hodgkin lymphoma. Report of one case]. / Necrolisis epidérmica tóxica en el curso de un síndrome hemofagocítico secundario a linfoma de Hodgkin. Caso clínico.

Toxic epidermal necrolysis (TEN) is a lethal entity, characterized by extensive epidermal necrosis and multiorgan failure. Hemophagocytic syndrome (HFS) is also a rare and lethal syndrome characterized by hyperinflammation that leads to the appearance of fever, pancytopenia, organomegaly and hemophagocytosis. The concomitance of these diseases is extremely uncommon. We report a 38 years old female, who during the course of a HFS secondary to Hodgkin Lymphoma (HL), presented a TEN secondary to antibiotics. She was admitted due to a consumptive syndrome, lymphadenopathy, visceromegaly and severe pancytopenia. Laboratory and bone marrow tests confirmed HFS. Due to constant fever, imipenem was indicated. On the third day she started with pain and skin rash. She evolved with positive Nikolsky sign. Cutaneous biopsy was concordant with extensive TEN, which was managed with intravenous immunoglobulin and dexamethasone. A complete response and normalization of the blood count were achieved. Finally, the lymph node biopsy showed HL of mixed cellularity type, which was managed with 8 cycles of ABVD chemotherapy, achieving complete remission.

Necrolisis epidérmica tóxica en el curso de un síndrome hemofagocítico secundario a linfoma de Hodgkin: caso clínico / Toxic epidermal necrolysis during a hemophagocytic syndrome secondary to Hodgkin lymphoma: report of one case

Toxic epidermal necrolysis (TEN) is a lethal entity, characterized by extensive epidermal necrosis and multiorgan failure. Hemophagocytic syndrome (HFS) is also a rare and lethal syndrome characterized by hyperinflammation that leads to the appearance of fever, pancytopenia, organomegaly and hemophagocytosis. The concomitance of these diseases is extremely uncommon. We report a 38 years old female, who during the course of a HFS secondary to Hodgkin Lymphoma (HL), presented a TEN secondary to antibiotics. She was admitted due to a consumptive syndrome, lymphadenopathy, visceromegaly and severe pancytopenia. Laboratory and bone marrow tests confirmed HFS. Due to constant fever, imipenem was indicated. On the third day she started with pain and skin rash. She evolved with positive Nikolsky sign. Cutaneous biopsy was concordant with extensive TEN, which was managed with intravenous immunoglobulin and dexamethasone. A complete response and normalization of the blood count were achieved. Finally, the lymph node biopsy showed HL of mixed cellularity type, which was managed with 8 cycles of ABVD chemotherapy, achieving complete remission.

High CD8+ and absence of Foxp3+ T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival.

BACKGROUND: Gallbladder cancer (GBC), although infrequent in industrialized countries, has high incidence rates in certain world regions, being a leading cause of death among elderly Chilean women. Surgery is the only effective treatment, and a five-year survival rate of advanced-stage patients is less than 10%. Hence, exploring immunotherapy is relevant, although GBC immunogenicity is poorly understood. This study examined the relationship between the host immune response and GBC patient survival based on the presence of tumor-infiltrating lymphocytes at different disease stages. METHODS: Tumor tissues from 80 GBC patients were analyzed by immunohistochemistry for the presence of CD3+, CD4+, CD8+, and Foxp3+ T cell populations, and the results were associated with clinical stage and patient survival. RESULTS: The majority of tumor samples showed CD3+ T cell infiltration, which correlated with better prognosis, particularly in advanced disease stages. CD8+, but not CD4+, T cell infiltration correlated with improved survival, particularly in advanced disease stages. Interestingly, a < 1 CD4+/CD8+ T cell ratio was related with increased survival. Additionally, the presence of Foxp3+ T cells correlated with decreased patient survival, whereas a ≤ 1 Foxp3+/CD8+ T cell ratio was associated with improved patient survival. CONCLUSIONS: Depending on the disease stage, the presence of CD8+ and absence of Foxp3+ T cell populations in tumor tissues correlated with improved GBC patient survival, and thus represent potential markers for prognosis and management of advanced disease, and supports testing of immunotherapy.

Hipercalcemia, peak monoclonal y leucemización como presentación de un linfoma de células B de alto grado, con reordenamiento de MYC, BCL-2 y BCL-6 (Triple Hit). Caso clínico / Hypercalcemia, monoclonal peak and leukemic presentation of a High-grade B-cell lymphoma with MYC, BCL-2 and BCL-6 translocations (triple hit). Report of one case

High-grade B-cell lymphomas with rearrangement of MYC, BCL-2 and/or BCL-6 were introduced by the update of the WHO classification of lymphoid neoplasms. They usually present unique morphological and molecular characteristics, with an aggressive clinical outcome and worse prognosis. We report a 48 year-old female patient presenting with B symptoms and enlarged lymph nodes. Blood count showed pancytopenia and peripheral blood smears showed large lymphoid cells, some with nuclei and vacuoles. LDH was 3524 g/L and serum calcium was 11.5 mg/dL. Flow cytometry immunophenotyping showed pathological mature B lymphocytes. Protein electrophoresis showed a slight monoclonal peak. The biopsy disclosed a triple expressor diffuse large B-cell lymphoma, arising from germinal center. FISH was positive for MYC, BCL-2 and BCL-6 (triple hit) with a clonal evolution. Conventional cytogenetics showed a complex karyotype. Chemotherapy was started with R-CHOP (Rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone). She developed impaired consciousness; the brain CT scan showed a large brain mass. The patient died within 3 weeks.

[Differential diagnosis of bone marrow and lung granulomas: Report of one case]. / Granulomas pulmonares y en médula ósea: más allá de la tuberculosis. A propósito de un caso.

The differential diagnosis of pulmonary tuberculosis and lymphoma with pulmonary infiltration is very difficult, given their similar clinical characteristics. We report a 59 year old female with weight loss, fever, dyspnea and cough of several months of duration. She had a cavitated mass in lung imaging. A positive conventional PCR lead to the diagnosis of tuberculosis, but she had negative smears and cultures for Mycobacterium tuberculosis. The patient did not respond to treatment and her clinical condition worsened. A peripheral lymph node biopsy confirmed the presence of a diffuse large B cell non-Hodgkin lymphoma. Bone marrow pathology showed non caseating granulomas, again with negative microbiological tests for M. tuberculosis. Findings in the bone marrow were interpreted as a secondary sarcoid reaction to cancer and PCR results as a false positive. The lymphoma was treated, achieving complete remission. This case highlights the importance of the differential diagnosis between these two entities.

In Favor of Establishment: Regulation of Chromatid Cohesion in Plants.

In eukaryotic organisms, the correct regulation of sister chromatid cohesion, whereby sister chromatids are paired and held together, is essential for accurate segregation of the sister chromatids and homologous chromosomes into daughter cells during mitosis and meiosis, respectively. Sister chromatid cohesion requires a cohesin complex comprised of structural maintenance of chromosome adenosine triphosphatases and accessory proteins that regulate the association of the complex with chromosomes or that are involved in the establishment or release of cohesion. The cohesin complex also plays important roles in the repair of DNA double-strand breaks, regulation of gene expression and chromosome condensation. In this review, we summarize progress in understanding cohesion dynamics in plants, with the aim of uncovering differences at specific stages. We also highlight dissimilarities between plants and other eukaryotes with respect to the key players involved in the achievement of cohesion, pointing out areas that require further study.

Granulomas pulmonares y en médula ósea: más allá de la tuberculosis. A propósito de un caso / Differential diagnosis of bone marrow and lung granulomas: Report of one case

The differential diagnosis of pulmonary tuberculosis and lymphoma with pulmonary infiltration is very difficult, given their similar clinical characteristics. We report a 59 year old female with weight loss, fever, dyspnea and cough of several months of duration. She had a cavitated mass in lung imaging. A positive conventional PCR lead to the diagnosis of tuberculosis, but she had negative smears and cultures for Mycobacterium tuberculosis. The patient did not respond to treatment and her clinical condition worsened. A peripheral lymph node biopsy confirmed the presence of a diffuse large B cell non-Hodgkin lymphoma. Bone marrow pathology showed non caseating granulomas, again with negative microbiological tests for M. tuberculosis. Findings in the bone marrow were interpreted as a secondary sarcoid reaction to cancer and PCR results as a false positive. The lymphoma was treated, achieving complete remission. This case highlights the importance of the differential diagnosis between these two entities.

Phenolic composition, antioxidant and anti-proliferative activities of edible and medicinal plants from the Peruvian Amazon

ABSTRACT Among 23 extracts of medicinal and edible plants tested, Mauritia flexuosa L.f., Arecaceae, showed significant antioxidant ability (DPPH and ORAC = 1062.9 and 645.9 ± 51.4 µg TE/mg extract, respectively), while Annona montana Macfad., Annonaceae, demonstrated the most promising anti-proliferative effect (IC50 for Hep-G2 and HT-29 = 2.7 and 9.0 µg/ml, respectively). However, combinatory antioxidant/anti-proliferative effect was only detected in Oenocarpus bataua Mart., Arecaceae (DPPH = 903.8 and ORAC = 1024 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 102.6 and 38.8 µg/ml, respectively) and Inga edulis Mart., Fabaceae (DPPH = 337.0 and ORAC = 795.7 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 36.3 and 57.9 µg/ml, respectively). Phenolic content was positively correlated with antioxidant potential, however not with anti-proliferative effect. None of these extracts possessed toxicity towards normal foetal lung cells, suggesting their possible use in development of novel plant-based agents with preventive and/or therapeutic action against oxidative stress-related diseases.

Trends in socioeconomic inequalities in preventable mortality in urban areas of 33 Spanish cities, 1996-2007 (MEDEA project).

BACKGROUND: Preventable mortality is a good indicator of possible problems to be investigated in the primary prevention chain, making it also a useful tool with which to evaluate health policies particularly public health policies. This study describes inequalities in preventable avoidable mortality in relation to socioeconomic status in small urban areas of thirty three Spanish cities, and analyses their evolution over the course of the periods 1996-2001 and 2002-2007. METHODS: We analysed census tracts and all deaths occurring in the population residing in these cities from 1996 to 2007 were taken into account. The causes included in the study were lung cancer, cirrhosis, AIDS/HIV, motor vehicle traffic accidents injuries, suicide and homicide. The census tracts were classified into three groups, according their socioeconomic level. To analyse inequalities in mortality risks between the highest and lowest socioeconomic levels and over different periods, for each city and separating by sex, Poisson regression were used. RESULTS: Preventable avoidable mortality made a significant contribution to general mortality (around 7.5%, higher among men), having decreased over time in men (12.7 in 1996-2001 and 10.9 in 2002-2007), though not so clearly among women (3.3% in 1996-2001 and 2.9% in 2002-2007). It has been observed in men that the risks of death are higher in areas of greater deprivation, and that these excesses have not modified over time. The result in women is different and differences in mortality risks by socioeconomic level could not be established in many cities. CONCLUSIONS: Preventable mortality decreased between the 1996-2001 and 2002-2007 periods, more markedly in men than in women. There were socioeconomic inequalities in mortality in most cities analysed, associating a higher risk of death with higher levels of deprivation. Inequalities have remained over the two periods analysed. This study makes it possible to identify those areas where excess preventable mortality was associated with more deprived zones. It is in these deprived zones where actions to reduce and monitor health inequalities should be put into place. Primary healthcare may play an important role in this process.

Análisis de la distribución geográfica de médicos especialistas en la República Argentina / Analysis of the geographical distribution of medical specialists in the Argentine Republic

A lo largo de las tres últimas décadas, muchos países de Latinoamérica y el Caribe (LAC) han reconocido la salud como un derecho humano y han actuado de acuerdo a ese reconocimiento. En consecuencia las exigencias a los sistemas de salud han aumentado de forma sostenida con el objetivo de responder mejor a la prestación de servicios. De ahí que se hayan promovido y puesto en marcha políticas y programas encaminados a lograr la cobertura universal de salud(1). En este contexto las políticas de Recursos Humanos han adquirido, si cabe, una mayor relevancia.

Arabidopsis CHROMOSOME TRANSMISSION FIDELITY 7 (AtCTF7/ECO1) is required for DNA repair, mitosis and meiosis.

The proper transmission of DNA in dividing cells is crucial for the survival of eukaryotic organisms. During cell division, faithful segregation of replicated chromosomes requires their tight attachment, known as sister chromatid cohesion, until anaphase. Sister chromatid cohesion is established during S-phase in a process requiring an acetyltransferase that in yeast is known as Establishment of cohesion 1 (Eco1). Inactivation of Eco1 typically disrupts chromosome segregation and homologous recombination-dependent DNA repair in dividing cells, ultimately resulting in lethality. We report here the isolation and detailed characterization of two homozygous T-DNA insertion mutants for the Arabidopsis thaliana Eco1 homolog, CHROMOSOME TRANSMISSION FIDELITY 7/ESTABLISHMENT OF COHESION 1 (CTF7/ECO1), called ctf7-1 and ctf7-2. Mutants exhibited dwarfism, poor anther development and sterility. Analysis of somatic tissues by flow cytometry, scanning electron microscopy and quantitative real-time PCR identified defects in DNA repair and cell division, including an increase in the area of leaf epidermal cells, an increase in DNA content and the upregulation of genes involved in DNA repair including BRCA1 and PARP2. No significant change was observed in the expression of genes that influence entry into the endocycle. Analysis of meiocytes identified changes in chromosome morphology and defective segregation; the abundance of chromosomal-bound cohesion subunits was also reduced. Transcript levels for several meiotic genes, including the recombinase genes DMC1 and RAD51C and the S-phase licensing factor CDC45 were elevated in mutant anthers. Taken together our results demonstrate that Arabidopsis CTF7/ECO1 plays important roles in the preservation of genome integrity and meiosis.

Do socioeconomic inequalities in mortality vary between different Spanish cities? a pooled cross-sectional analysis.

BACKGROUND: The relationship between deprivation and mortality in urban settings is well established. This relationship has been found for several causes of death in Spanish cities in independent analyses (the MEDEA project). However, no joint analysis which pools the strength of this relationship across several cities has ever been undertaken. Such an analysis would determine, if appropriate, a joint relationship by linking the associations found. METHODS: A pooled cross-sectional analysis of the data from the MEDEA project has been carried out for each of the causes of death studied. Specifically, a meta-analysis has been carried out to pool the relative risks in eleven Spanish cities. Different deprivation-mortality relationships across the cities are considered in the analysis (fixed and random effects models). The size of the cities is also considered as a possible factor explaining differences between cities. RESULTS: Twenty studies have been carried out for different combinations of sex and causes of death. For nine of them (men: prostate cancer, diabetes, mental illnesses, Alzheimer's disease, cerebrovascular disease; women: diabetes, mental illnesses, respiratory diseases, cirrhosis) no differences were found between cities in the effect of deprivation on mortality; in four cases (men: respiratory diseases, all causes of mortality; women: breast cancer, Alzheimer's disease) differences not associated with the size of the city have been determined; in two cases (men: cirrhosis; women: lung cancer) differences strictly linked to the size of the city have been determined, and in five cases (men: lung cancer, ischaemic heart disease; women: ischaemic heart disease, cerebrovascular diseases, all causes of mortality) both kinds of differences have been found. Except for lung cancer in women, every significant relationship between deprivation and mortality goes in the same direction: deprivation increases mortality. Variability in the relative risks across cities was found for general mortality for both sexes. CONCLUSIONS: This study provides a general overview of the relationship between deprivation and mortality for a sample of large Spanish cities combined. This joint study allows the exploration of and, if appropriate, the quantification of the variability in that relationship for the set of cities considered.