Objectives: Long-term care (LTC) ombudsmen advocate for the health, safety, welfare, and rights of residents in LTC facilities. This article examines factors associated with self-rated effectiveness ...of local LTC Ombudsman Programs (LTCOPs) in California and New York across the five statutorily mandated activities under the Older Americans Act: complaint investigation, resident/family education, community education, monitoring laws, and policy advocacy. Method: Data were collected from telephone interviews with coordinators of local LTCOPs in California and New York and from the National Ombudsman Reporting System. Analyses examined factors associated with effectiveness: program size, resource adequacy, organizational autonomy, interorganizational relationships, and program outputs. Results: Resource and autonomy measures are significantly associated with different effectiveness measures in each state. Staff full-time equivalencies and coordinator hours per week in New York and the quality of training in California are significantly associated with effectiveness in most mandated activities. Discussion: Findings highlight variability within and between the local LTCOPs in California and New York.
Tamoxifen Resistance: Emerging Molecular Targets Rondón-Lagos, Milena; Villegas, Victoria E; Rangel, Nelson ...
International journal of molecular sciences,
08/2016, Letnik:
17, Številka:
8
Journal Article
Recenzirano
Odprti dostop
17β-Estradiol (E2) plays a pivotal role in the development and progression of breast cancer. As a result, blockade of the E2 signal through either tamoxifen (TAM) or aromatase inhibitors is an ...important therapeutic strategy to treat or prevent estrogen receptor (ER) positive breast cancer. However, resistance to TAM is the major obstacle in endocrine therapy. This resistance occurs either de novo or is acquired after an initial beneficial response. The underlying mechanisms for TAM resistance are probably multifactorial and remain largely unknown. Considering that breast cancer is a very heterogeneous disease and patients respond differently to treatment, the molecular analysis of TAM's biological activity could provide the necessary framework to understand the complex effects of this drug in target cells. Moreover, this could explain, at least in part, the development of resistance and indicate an optimal therapeutic option. This review highlights the implications of TAM in breast cancer as well as the role of receptors/signal pathways recently suggested to be involved in the development of TAM resistance. G protein-coupled estrogen receptor, Androgen Receptor and Hedgehog signaling pathways are emerging as novel therapeutic targets and prognostic indicators for breast cancer, based on their ability to mediate estrogenic signaling in ERα-positive or -negative breast cancer.
•We developed a methodology to construct broadband wavelength (BB) slip models suitable for strong motions and tsunami generation processes.•We estimated the BB slip model of the 1906 ...Ecuador-Colombia earthquake to fit observed tsunami waveforms and intensities.•High-frequency ground motion generation is greatly enhanced by the incorporation of short wavelength slips with strong localized stress drops.•Our methodology is an effective tool for the study of generation process of high frequency ground motions during large earthquakes.•BB slip models are appropriate to study variability in fault source process and its impact for tsunami and seismic hazard analysis.
The 1906/01/31 Ecuador-Colombia earthquake (Mw8.4–8.6), is one of the largest megathrust earthquakes that have occurred at the interface of the Nazca and South-American plates. Recently the source process of the earthquake has been re-examined using historical tsunami waveforms, yielding a slip distribution mainly near to the trench, and a smaller moment magnitude than previous estimations. Previous studies have shown that tsunami data can sufficiently constrain the long wavelength characteristics of slip during an earthquake. However to fully understand strong ground motion generation process during earthquakes in a broadband frequency range, the study of shorter wavelength slip, responsible for high frequency ground motion generation, is also necessary. In this study we use the tsunami-slip model of the 1906 earthquake, as well as comprehensive macro-seismic intensity estimations of the earthquake, to elaborate a broadband-wavelength (BB) source model appropriate for the generation of broadband frequency strong ground motions as well as tsunami modeling. Our results show that a BB slip model of the earthquake is able to satisfactorily reproduce observed intensity values as well as tsunami waveforms. Our BB slip model implies an increase in total moment magnitude to a value up to 8.6 respect to the estimation from tsunami data, which represent the contribution of short wavelength slips to seismic radiation. The methodology developed in this study is suitable to study the generation process of high frequency ground motions during large earthquakes.
Chromosomal instability (CIN), defined by variations in the number or structure of chromosomes from cell to cell, is recognized as a distinctive characteristic of cancer associated with the ability ...of tumors to adapt to challenging environments. CIN has been recognized as a source of genetic variation that leads to clonal heterogeneity (CH). Recent findings suggest a potential association between CIN and CH with the prognosis of BC patients, particularly in tumors expressing the epidermal growth factor receptor 2 (HER2+). In fact, information on the role of CIN in other BC subtypes, including luminal B BC, is limited. Additionally, it remains unknown whether CIN in luminal B BC tumors, above a specific threshold, could have a detrimental effect on the growth of human tumors or whether low or intermediate CIN levels could be linked to a more favorable BC patient prognosis when contrasted with elevated levels. Clarifying these relationships could have a substantial impact on risk stratification and the development of future therapeutic strategies aimed at targeting CIN in BC. This study aimed to assess CIN and CH in tumor tissue samples from ten patients with luminal B BC and compare them with established clinicopathological parameters. The results of this study reveal that luminal B BC patients exhibit intermediate CIN and stable aneuploidy, both of which correlate with lymphovascular invasion. Our results also provide valuable preliminary data that could contribute to the understanding of the implications of CIN and CH in risk stratification and the development of future therapeutic strategies in BC.
1. Climate change may increase the occurrence of droughts and fires in the Amazon. Most of our understanding on how fire affects tropical ecosystems is based on studies of nonflooded forest-savanna ...ecotones. Nonetheless, tropical floodplain forests in the Amazon can burn severely during extreme droughts. The mechanisms slowing down forest regeneration in these ecosystems remain poorly understood and have never been assessed in the field. 2. We studied the recovery of Amazonian blackwater floodplain forests after one and two fire events. We used Landsat images to map fire history and conducted field surveys to measure forest structure, tree species richness, tree seed bank and post-fire invasion of herbaceous plants. 3. Sites burnt once had on average 0% trees, 6% tree seed abundance, 23% tree seed species richness and 8% root mat thickness compared to unburnt forests. In contrast, herbaceous cover increased from 0 to 72%. Nonetheless, forest structure and diversity recovered slowly towards pre-burn levels, except for tree seed banks that remained depleted even 15 years after fire. 4. Sites burnt twice had on average 0% trees, 1% tree seed abundance, 3% tree seed species richness and 1% root mat thickness compared to unburnt forests. Herbaceous cover increased to 100%. Mean recovery of tree basal area was 50% slower and of root mat thickness 93% slower compared to recovery in sites burnt once. Tree seed banks did not recover at all, and herbaceous cover persisted close to 100% for more than 20 years after the second fire. 5. Synthesis and applications. Our results indicate that after a second fire event, Amazonian blackwater floodplain forests lose their recovery capacity, and persist in a non-forested state dominated by herbaceous vegetation. Such fragility implies that preventing human ignited fires during drought episodes is a particularly important conservation strategy for these ecosystems.
In the department of Boyacá, Colombia, agriculture stands as one of the primary economic activities. However, the escalating utilization of pesticides within this sector has sparked concern regarding ...its potential correlation with elevated risks of genotoxicity, chromosomal alterations, and carcinogenesis. Furthermore, pesticides have been associated with a broad spectrum of genetic polymorphisms that impact pivotal genes involved in pesticide metabolism and DNA repair, among other processes. Nonetheless, our understanding of the genotoxic effects of pesticides on the chromosomes (as biomarkers of effect) in exposed farmers and the impact of genetic polymorphisms (as susceptibility biomarkers) on the increased risk of chromosomal damage is still limited. The aim of our study was to evaluate chromosomal alterations, chromosomal instability, and clonal heterogeneity, as well as the presence of polymorphic variants in the
and
genes, in peripheral blood samples of farmers occupationally exposed to pesticides in Aquitania, Colombia, and in an unexposed control group. Our results showed statistically significant differences in the frequency of numerical chromosomal alterations, chromosomal instability, and clonal heterogeneity levels between the exposed and unexposed groups. In addition, we also found a higher frequency of chromosomal instability and clonal heterogeneity in exposed individuals carrying the heterozygous
AG and
(exon 10) GA genotypes. The evaluation of chromosomal alterations and chromosomal instability resulting from pesticide exposure, combined with the identification of polymorphic variants in the
and
genes, and further research involving a larger group of individuals exposed to pesticides could enable the identification of effect and susceptibility biomarkers. Such markers could prove valuable for monitoring individuals occupationally exposed to pesticides.
In addition to seven known alkaloids (2, 6–11) and 1,2,4-trimethoxybenzene (1), three isoquinoline-derived alkaloids (3–5), namely, duguetinine (3), a compound based on an unprecedented ...oxahomoaporphine scaffold, and two new 8-oxohomoaporphine alkaloids, duguesuramine (4) and 11-methoxyduguesuramine (5), and a new asarone-derived phenylpropanoid (10) were isolated from the bark of Duguetia surinamensis. The isolation workflow was guided by HPLC-HRESIMS/MS and molecular networking-based analyses. Twenty-four known alkaloids were dereplicated from the D. surinamensis alkaloid-rich fraction network and were assigned by manual MS/MS interpretation. Their cytotoxic potential was evaluated.
amplification represents the leading oncogenic pathway and diagnostic hallmark of liposarcoma, whose assessment is based on Fluorescence In Situ Hybridization (FISH) analysis. Despite its diagnostic ...relevance, no univocal interpretation criteria regarding FISH assessments of
amplification have been established so far, leading to several different approaches and potential diagnostic misinterpretations. This study aims to address the most common issues and proposes troubleshooting guidelines for
amplification assessments by FISH. We retrospectively retrieved 51 liposarcomas, 25 Lipomas, 5 Spindle Cell Lipoma/Pleomorphic Lipomas, and 2 Atypical Spindle Cell Lipomatous Tumors and the corresponding
FISH analysis. We observed
amplification in liposarcomas cases only (43 out of 51 cases) and identified three
-amplified patterns (scattered (50% of cases), clustered (14% of cases), and mixed (36% of cases)) and two nonamplified patterns (low number of signals (82% of cases) and polysomic (18% of cases)). Based on these data and published evidence in the literature, we propose a set of criteria to guide
amplification analysis in liposarcoma. Kindled by the compelling importance of
assessments to improve diagnostic and therapeutic liposarcoma management, these suggestions could represent the first step to develop a univocal interpretation model and consensus guidelines.
Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon form of non-Hodgkin lymphoma (cancer of the immune system) that can develop around breast implants. Breast implants ...are among the most commonly used medical devices for cosmetic or reconstructive purposes. In the past few years, the number of women with breast implants diagnosed with anaplastic large cell lymphoma (ALCL) has increased, and several studies have suggested a direct association between breast implants and an increased risk of this disease. Although it has been hypothesized that chronic stimulation of the immune system caused by implant materials and biofilms as well as a possible genetic predisposition play an important role in this disease, the cellular and molecular causes of BIA-ALCL are not fully understood. This review aims to describe the current understanding around the environmental and molecular drivers of BIA-ALCL as well as the genetic and chromosomal abnormalities identified in this disease to date.
Obesity is an increasing health challenge and is recognized as a breast cancer risk factor. Although obesity-related breast cancer mechanisms are not fully understood, this association has been ...linked to impaired hormone secretion by the dysfunctional obese adipose tissue (hyperplasic and hypertrophic adipocytes). Among these hormones, altered production of androgens and adipokines is observed, and both, are independently associated with breast cancer development. In this review, we describe and comment on the relationships reported between these factors and breast cancer, focusing on the biological associations that have helped to unveil the mechanisms by which signaling from androgens and adipokines modifies the behavior of mammary epithelial cells. Furthermore, we discuss the potential crosstalk between the two most abundant adipokines produced by the adipose tissue (adiponectin and leptin) and the androgen receptor, an emerging marker in breast cancer. The identification and understanding of interactions among adipokines and the androgen receptor in cancer cells are necessary to guide the development of new therapeutic approaches in order to prevent and cure obesity and breast cancer.
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