Evaluation of a polymeric topical formulation of Endoxifen in an estrogen receptor positive breast cancer murine model.

Breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer and, in terms of mortality, is the fifth leading cause with 684,996 new deaths (6.7% of all cancer-related deaths) and the highest mortality amongst all cancers (15.5%) in women. Selective estrogen-receptor modulators (SERMs) have been used for the last thirty years for estrogen receptor-positive (ER+) BC prevention and treatment. Tamoxifen (TAM), the most widely used SERM, is orally administered and its long-term oral administration has been associated to toxicity and adverse side effects. Endoxifen (EDX) is one of the known active metabolites of TAM, with an affinity to ERα 100 times higher than TAM. Furthermore, EDX has shown antiproliferative activity against the ER+ BC cell line MCF-7. Alternative administration routes that avoid the metabolic processing of TAM seem an appealing alternative to its oral administration. With this aim, we have prepared a polymeric gel-like solution of Pluronic® F127 as vehicle for topical administration of EDX. In order to shed light on the potential clinical use of this formulation, we have compared it with the standard pharmaceutical form, i.e. orally administered TAM. The biodistribution, antitumor efficacy and toxic effects of topical EDX and oral TAM were evaluated in ER+ tumor xenograft athymic nu/nu mouse models. The results showed a statistically significant antitumor effect and reduced toxicity of topical EDX as compared to oral TAM or empty F127 gel. This novel administration route of SERMs could also have a strong impact in the prevention of BC at early development stages and could help to ameliorate the mortality and morbidity related to this disease.

Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity.

Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.

Do Clinical Trials Meet Current Care Needs? Views of Digestive Oncology Specialists in Galicia (Spain) Using the Delphi Method.

Background: In recent years, abundant scientific evidence has been generated based on clinical trials (CT) in the field of oncology. The general objective of this paper is to find out the extent to which decision making is based on knowledge of the most recent CT. Its specific objectives are to pinpoint difficulties with decision making based on the CT performed and find out the motivations patients and clinicians have when taking part in a CT. Methodology: Combined, prospective study, based on the Delphi method. A lack of correspondence between the people who take part in CT and patients who come for consultation has been identified. A need for training in analysing and interpreting CT has also been identified and a lack of trust in the results of CT financed by the pharmaceutical industry itself has been perceived. Conclusions: There is a difficulty in selecting oncological treatment due to the lack of correspondence between the patients included in the CT and patients seen in consultation. In this process, real world data studies may be highly useful, as they may provide this group with greater training in interpreting CT and their results.

Normalization of endometrial histopathology and endometrial NK cells concentration predict successful pregnancy in repeated implantation failure.

OBJECTIVE: The primary objective was to establish the endometrial predictors of clinical pregnancy in a population of repeated implantation failure with oocyte donation after specific endometrial treatment. The secondary one was to evaluate reproduction outcomes in terms of Implantation rate (IR), Clinical pregnancy (CP), Live birth delivery rate (LBDR) and Prematurity, in relation to normalization or no-normalization of the predictors. METHODS: 66 patients were assigned to the study. We ran a Pipelle endometrial biopsy to investigate the endometrium lymphocyte population by Flow Cytometry and abnormal/normal patterns by histopathology in pre/post-treatment. We employed the binary logistic regression model to identify the predictors for CP. For the secondary objective, we assessed the clinical outcomes in function to the normalization or no normalization in post-treatment. RESULTS: Endometrial histopathology and endometrial NK cell counts resulted in CP predictors (Wald chi2 test (p=0.044 and 0.001)), respectively. We had a higher IR, CP and LBDR when both predictors were normalized in comparison with no normalization (p<0.001). There was a high percentage of prematurity in both normalized vs. non-normalized groups (34.4% (11/32) and 71.43% (5/7), respectively) without significant differences. CONCLUSION: Endometrial histopathology and endometrial NK cell counts showed that they are valid predictors of pregnancy outcome in repeated implantation failure after treatment. In post-treatment, the pregnancy outcomes were significantly higher in the presence of both normalized predictors. Pregnancy rates were zero in the no-normalization of both predictors. There was a high percentage of prematurity in both groups.

Biodegradable photoresponsive nanoparticles for chemo-, photothermal- and photodynamic therapy of ovarian cancer.

Ovarian cancer (OC) is the deadliest gynecological cancer. Standard treatment of OC is based on cytoreductive surgery followed by chemotherapy with platinum drugs and taxanes; however, innate and acquired drug-resistance is frequently observed followed by a relapse after treatment, thus, more efficient therapeutic approaches are required. Combination therapies involving phototherapies and chemotherapy (the so-called chemophototherapy) may have enhanced efficacy against cancer, by attacking cancer cells through different mechanisms, including DNA-damage and thermally driven cell membrane and cytoskeleton damage. We have designed and synthesized poly(lactic-co-glycolic) nanoparticles (PLGA NPs) containing the chemo-drug carboplatin (CP), and the near infrared (NIR) photosensitizer indocyanine green (ICG). We have evaluated the drug release profile, the photodynamic ROS generation and photothermal capacities of the NPs. Also, the antitumoral efficiency of the NPs was evaluated using the SKOV-3 cell line as an in vitro OC model, observing an enhanced cytotoxic effect when irradiating cells with an 800 nm laser. Evidence here shown supports the potential application of the biodegradable photoresponsive NPs in the clinical stage due to the biocompatibility of the materials used, the spatiotemporal control of the therapy and, also, the less likely development of resistance against the combinatorial therapy.

Characterization of comorbid conditions burdening hidradenitis suppurativa: a multicentric observational study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, disabling, inflammatory skin disorder that primarily affects the hair follicle localized at the apocrine-gland-bearing areas of the body, including axillary, inguinal, buttocks, and anogenital areas, and it may be associated with a wide array of comorbid conditions. This study aimed to described comorbid conditions affecting HS patients and to detect any correlation with disease severity. METHODS: Analyzing clinic database, we included all charts of patients visited at the HS outpatient clinic of three University Dermatologic Departments in order to describe demographic data, anthropometric measures, disease features, personal habits, clinical history, and presence of comorbidities. RESULTS: Two hundred thirty-four patients, mostly females (62%), were enrolled in this study. Based on Hurley staging classification 41% of patients were classified as Hurley Stage I, 43.0% as Hurley II, and 16% Hurley III, with a mean mSartorius Score value of 24.7 (SD: ±19.39) and a mean AISI score value of 12.5 (SD: ±11.93). The most frequently observed comorbidities were: obesity (26.1%), polycystic ovary syndrome (PCOS) (13.8% of the overall study population and 22.3% of females), hypertension (11.9%), dyslipidemia (9.9%), type II diabetes (9.5%), thyroid disorders (9.1%), nervous system disorders (7.1%), acne (6.7%), metabolic syndrome (4.4%), and Crohn's disease (3.6%). Obesity represented a key-comorbid condition increasing the likelihood of having more severe HS and PCOS (odds ratio 3.35 and 3.74, respectively). CONCLUSIONS: HS is associated with a variety of comorbid conditions that should be considered to perform targeted routine screening and to improve HS management.

Regenerative therapy by endometrial mesenchymal stem cells in thin endometrium with repeated implantation failure. A novel strategy.

OBJECTIVE: Our primary objective was to evaluate the endometrial changes before and after the transfer of endometrial mesenchymal stem cells (enMSCs) in a population of thinned endometrium women, with absence or hypo-responsiveness to estrogen and repeated implantation failure (RIF). The secondary objective was to evaluate the clinical outcomes of the intervention in terms of clinical pregnancy (CP), early abortions, ongoing pregnancy and live birth delivery rate (LBDR) per in vitro fertilization (IVF) cycle. METHODS: A longitudinal and experimental study. The intervention was defined as "subendometrial inoculation of enMSCs," and the post-intervention changes were evaluated by the following variables: endometrial thickness (Eth), endometrial flow cytometry (enFC), endometrial histopathology (enHP) and endometrial immunohistochemistry (enIHQ). The variables were analyzed after the intervention (Post-treatment) regarding previous values (Pretreatment). RESULTS: Eth values before and after treatment with enMSCs were 5.24±1.24 mm vs. 9.93±0.77 (p=0.000), respectively. Endometrial Flow Cytometry showed significant differences in favor of Normalized variables in the post-treatment assessment, associated with the pretreatment, LT/Li, LB/Li, NK/Li, CD8/CD3+ and CD4/CD8 (p≤0.015), respectively. Only two variables Li/PC and CD4/CD3 had NS (p=0.167 and 0.118). A similar analysis was performed on enHP with an HP increase post-treatment (p=0.007). The CP rate was 79.31% (23/29), a live birth delivery rate per embryo transfer was 45.45% (10/22) and ongoing pregnancy 7/29 (24.14%). CONCLUSION: Subendometrial enMSCs inoculation produces a significant increase in endometrial thickness; normalize the enHP, enIHQ and enFC. As a result, IVF after treatment with enMSCs yields a higher rate of CP and LBDR.

Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy.

The conventional treatment (cytoreduction combined with cisplatin/carboplatin and taxane drugs) of ovarian cancer has a high rate of failure and recurrence despite a favorable initial response. This lack of success is usually attributed to the development of multidrug resistance mechanisms by cancer cells and avoidance of the anti-growth effects of monoclonal targeted therapeutic antibodies. The disease, like other cancers, is characterized by the overexpression of molecular markers, including HER2 receptors. Preclinical and clinical studies with trastuzumab, a HER2-targeted therapeutic antibody, reveal a low improvement of the outcomes of HER2 positive ovarian cancer patients. Therefore, here, we propose a cisplatin-loaded, HER2 targeted poly(lactic-co-glycolic) nanoplatform, a system capable to escape the drug-efflux effect and to take advantage of the overexpressed HER2 receptors, using them as docks for targeted chemotherapy. The NP/trastuzumab ratio was determined after fluorescein labeling of antibodies and quantification of fluorescence in NPs. The system was also characterized in terms of size, zeta potential, drug release kinetics, cytotoxicity and cellular internalization in the epithelial ovarian cancer cell line SKOV-3, and compared with the HER2 negative breast cancer cell line HCC70. Our results show an increased cytotoxicity of NPs as compared to free cisplatin, and moreover, an enhanced internalization and cytotoxicity due to the bionfunctionalization of NPs with the monoclonal antibody.

Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells.

Estrogen receptor α (ERα) is expressed in tissues as diverse as brains and mammary glands. In breast cancer, ERα is a key regulator of tumor progression. Therefore, understanding what activates ERα is critical for cancer treatment in particular and cell biology in general. Using biochemical approaches and superresolution microscopy, we show that estrogen drives membrane ERα into endosomes in breast cancer cells and that its fate is determined by the presence of fibronectin (FN) in the extracellular matrix; it is trafficked to lysosomes in the absence of FN and avoids the lysosomal compartment in its presence. In this context, FN prolongs ERα half-life and strengthens its transcriptional activity. We show that ERα is associated with ß1-integrin at the membrane, and this integrin follows the same endocytosis and subcellular trafficking pathway triggered by estrogen. Moreover, ERα+ vesicles are present within human breast tissues, and colocalization with ß1-integrin is detected primarily in tumors. Our work unravels a key, clinically relevant mechanism of microenvironmental regulation of ERα signaling.

Preparation of PLGA/Rose Bengal colloidal particles by double emulsion and layer-by-layer for breast cancer treatment.

The use of colloidal particles (CPs) in the transport of drugs is developing rapidly thanks to its effectiveness and biosafety, especially in the treatment of various types of cancer. In this study Rose Bengal/PLGA CPs synthesized by double emulsion (W/O/W) and by electrostatic adsorption (layer-by-layer), were characterized and evaluated as potential breast cancer treatment. CPs were evaluated in terms of size, zeta potential, drug release kinetics and cell viability inhibition efficacy with the triple negative breast cancer cell line HCC70. The results showed that both types of CPs can be an excellent alternative to conventional cancer treatment by taking advantage of the enhanced permeation and retention (EPR) effect, manifested by solid tumors; however, the double emulsion CPs showed more suitable delivery times of up to 60% within two days, while layer-by-layer showed fast release of 50% in 90 min. Both types of CPs were capable to decrease cell viability, which encourage us to further testing in in vivo models to prove their efficacy and feasible use in the treatment of triple negative breast cancer.

Challenges in the Analysis of Outcomes for Surgical Compared to Radiotherapy Treatment of Prostate Cancer.

BACKGROUND/AIM: Prostate cancer can be treated with radical prostatectomy (RP), external-beam radiotherapy (EBRT), or brachytherapy (BT). These modalities have similar cancer-related outcomes. We used an innovative method to analyze the cost of such treatment. MATERIALS AND METHODS: We queried our Institution's Insurance Division [University of Pittsburgh Medical Center (UPMC) Health Plan] beneficiaries from 2003-2008, who were diagnosed with prostate cancer and also queried the UPMC tumor registry for all patients with prostate cancer treated at our Institution. In a de-identified manner, data from the Health Plan and Tumor Registry were merged. RESULTS: A total of 354 patients with non-metastatic disease with treatment initiated within 9 months of diagnosis were included (RP=236, EBRT=55, and BT=63). Radiotherapy-treated patients tended to be older, higher-risk, and have more comorbidities. Unadjusted median total health care expenditures during the first year after diagnosis were: RP: $16,743, EBRT: $47,256, and BT: $23,237 (p<0.0005). A propensity score-matched model comparing RP and EBRT demonstrated median total health care expenditures during year one: RP: $8,189, EBRT: $10,081; p=0.48. In a propensity-matched model comparing RP and BT, the median total health care expenditures during year one were: RP: $18,143, BT: $26,531; p=0.015 and per year during years 2 through 5 from diagnosis were: RP: $5,913, BT: $6,110; p=0.68. CONCLUSION: This pilot study demonstrates the feasibility of combining healthcare costs from the payer's perspective with clinical data from a Tumor Registry within an IDFS and represents a novel approach to investigating the economic impact of cancer treatment.

DNA methylation signal has a major role in the response of human breast cancer cells to the microenvironment.

Breast cancer-associated fibroblasts (CAFs) have a crucial role in tumor initiation, metastasis and therapeutic resistance by secreting various growth factors, cytokines, protease and extracellular matrix components. Soluble factors secreted by CAFs are involved in many pathways including inflammation, metabolism, proliferation and epigenetic modulation, suggesting that CAF-dependent reprograming of cancer cells affects a large set of genes. This paracrine signaling has an important role in tumor progression, thus deciphering some of these processes could lead to relevant discoveries with subsequent clinical implications. Here, we investigated the mechanisms underlying the changes in gene expression patterns associated with the cross-talk between breast cancer cells and the stroma. From RNAseq data obtained from breast cancer cell lines grown in presence of CAF-secreted factors, we identified 372 upregulated genes, exhibiting an expression level positively correlated with the stromal content of breast cancer specimens. Furthermore, we observed that gene expression changes were not mediated through significant DNA methylation changes. Nevertheless, CAF-secreted factors but also stromal content of the tumors remarkably activated specific genes characterized by a DNA methylation pattern: hypermethylation at transcription start site and shore regions. Experimental approaches (inhibition of DNA methylation, knockdown of methyl-CpG-binding domain protein 2 and chromatin immunoprecipitation assays) indicated that this set of genes was epigenetically controlled. These data elucidate the importance of epigenetics marks in the cancer cell reprogramming induced by stromal cell and indicated that the interpreters of the DNA methylation signal have a major role in the response of the cancer cells to the microenvironment.

The Voxel-Wise Functional Connectome Can Be Efficiently Derived from Co-activations in a Sparse Spatio-Temporal Point-Process.

Large efforts are currently under way to systematically map functional connectivity between all pairs of millimeter-scale brain regions based on large neuroimaging databases. The exploratory unraveling of this "functional connectome" based on functional Magnetic Resonance Imaging (fMRI) can benefit from a better understanding of the contributors to resting state functional connectivity. In this work, we introduce a sparse representation of fMRI data in the form of a discrete point-process encoding high-amplitude events in the blood oxygenation level-dependent (BOLD) signal and we show it contains sufficient information for the estimation of functional connectivity between all pairs of voxels. We validate this method by replicating results obtained with standard whole-brain voxel-wise linear correlation matrices in two datasets. In the first one (n = 71), we study the changes in node strength (a measure of network centrality) during deep sleep. The second is a large database (n = 1147) of subjects in which we look at the age-related reorganization of the voxel-wise network of functional connections. In both cases it is shown that the proposed method compares well with standard techniques, despite requiring only data on the order of 1% of the original BOLD signal time series. Furthermore, we establish that the point-process approach does not reduce (and in one case increases) classification accuracy compared to standard linear correlations. Our results show how large fMRI datasets can be drastically simplified to include only the timings of large-amplitude events, while still allowing the recovery of all pair-wise interactions between voxels. The practical importance of this dimensionality reduction is manifest in the increasing number of collaborative efforts aiming to study large cohorts of healthy subjects as well as patients suffering from brain disease. Our method also suggests that the electrophysiological signals underlying the dynamics of fMRI time series consist of all-or-none temporally localized events, analogous to the avalanches of neural activity observed in recordings of local field potentials (LFP), an observation of potentially high neurobiological relevance.

The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action.

Little is known about the biological role of the phospholipase A2 receptor (PLA2R1) transmembrane protein. In recent years, PLA2R1 has been shown to have an important role in regulating tumor-suppressive responses via JAK2 activation, but the underlying mechanisms are largely undeciphered. In this study, we observed that PLA2R1 increases the mitochondrial content, judged by increased levels of numerous mitochondrial proteins, of the mitochondrial structural component cardiolipin, of the mitochondrial DNA content, and of the mitochondrial DNA replication and transcription factor TFAM. This effect of PLA2R1 relies on a transcriptional program controlled by the estrogen-related receptor alpha1 (ERRα) mitochondrial master regulator. Expression of ERRα and of its nucleus-encoded mitochondrial targets is upregulated upon PLA2R1 ectopic expression, and this effect is mediated by JAK2. Conversely, downregulation of PLA2R1 decreases the level of ERRα and of its nucleus-encoded mitochondrial targets. Finally, blocking the ERRα-controlled mitochondrial program largely inhibits the PLA2R1-induced tumor-suppressive response. Together, our data document ERRα and its mitochondrial program as downstream effectors of the PLA2R1-JAK2 pathway leading to oncosuppression.

Demographic and health attributes of the Nahua, initial contact population of the Peruvian Amazon / Características demográficas y de salud de la población Nahua: población en contacto inicial de la Amazonía Peruana

Abstract We present the case of the Nahua population of Santa Rosa de Serjali, Peruvian Amazon's population, considered of initial contact. This population consists of human groups that for a long time decided to live in isolation, but lately have begun living a more sedentary lifestyle and in contact with Western populations. There are two fully identified initial contact groups in Peru: the Nahua and the Nanti. The health statistics of the Nahua are scarce. This study offers an interpretation of demographic and epidemiological indicators of the Nahua people, trying to identify if a certain degree of health vulnerability exists. We performed a cross sectional study, and after analyzing their health indicators, as well as the supplemental qualitative analysis of the population, brought us to conclude that in 2006, the Nahua, remained in a state of health vulnerability.

Resumen Presentamos el caso de la población Nahua de Santa Rosa de Serjali, una población de la región Amazonica del Perú, considerada en contacto inicial. Esta población está compuesta por grupos humanos que durante mucho tiempo han decidido vivir en aislamiento, pero últimamente han comenzado a vivir un estilo de vida más sedentario y en contacto con la población occidental. Hay dos grupos de contacto iniciales plenamente identificados en el Perú: Los Nahuas y los Nantis . Las estadísticas de salud de los nahuas son escasas. Este estudio ofrece una interpretación de los indicadores demográficos y epidemiológicos del pueblo Nahua, tratando de identificar si existe un cierto grado de vulnerabilidad de la salud . Se realizó un estudio transversal, y después de analizar sus indicadores de salud, así como el análisis cualitativo complementario de la población, nos llevó a la conclusión de que en el año 2006, los nahuas, aún presentaban un estado de vulnerabilidad en salud.

A novel two-step genome editing strategy with CRISPR-Cas9 provides new insights into telomerase action and TERT gene expression.

BACKGROUND: To facilitate indefinite proliferation, stem cells and most cancer cells require the activity of telomerase, which counteracts the successive shortening of telomeres caused by incomplete DNA replication at the very end of each chromosome. Human telomerase activity is often determined by the expression level of telomerase reverse transcriptase (TERT), the catalytic subunit of the ribonucleoprotein complex. The low expression level of TERT and the lack of adequate antibodies have made it difficult to study telomerase-related processes in human cells. RESULTS: To overcome the low CRISPR-Cas9 editing efficiency at the TERT locus, we develop a two-step "pop-in/pop-out" strategy to enrich cells that underwent homologous recombination (HR). Using this technique, we fuse an N-terminal FLAG-SNAP-tag to TERT, which allows us to reliably detect TERT in western blots, immunopurify it for biochemical analysis, and determine its subcellular localization by fluorescence microscopy. TERT co-localizes detectably with only 5-7 % of the telomeres at a time in S-phase HeLa cells; no nucleolar localization is detected. Furthermore, we extend this approach to perform single base-pair modifications in the TERT promoter; reverting a recurrent cancer-associated TERT promoter mutation in a urothelial cancer cell line results in decreased telomerase activity, indicating the mutation is causal for telomerase reactivation. CONCLUSIONS: We develop a two-step CRISPR-Cas9 genome editing strategy to introduce precise modifications at the endogenous TERT locus in human cell lines. This method provides a useful tool for studying telomerase biology, and suggests a general approach to edit loci with low targeting efficiency and to purify and visualize low abundance proteins.

Repeated implantation failure in oocyte donation. What to do to improve the endometrial receptivity?

OBJECTIVE: To determine the role of polyvalent endometrial treatment in patients undergoing IVF-ET who had recurrent implantation failure (RIF) in a program of oocyte donation (OD). The results were expressed in terms of live birth rate (LBR). Secondly analyze changes of endometrial leukocyte population evaluated by flow cytometer (FC) and histopathology. METHODS: Prospective study of a model-based control with analog abductive methodology. Over initial population of 75 patients with RIF in ovodonation, thirty cycles / patient of IVF/ET were selected in this study. A control group of 12 patients was established to variables FC. All patients were transferred to day 5-6 with a maximum of 2 expanded blastocysts with at least one of optimum quality. A versatile treatment was applied in all cases with both assessments in pre and postreatment. RESULTS: Chronic endometritis was diagnosed in 14/30 (46.7%) with endometrial identifying germs in 12/30 (40%) and 6/30 (20%) was associated with endometrial thinning. A significant increase in endometrial thickness associated with a decrease in abnormal histopathology and Li/PC was observed at postreatment in relation with a pretreatment (P=0.047 and P=0.002) respectively. An increase of uterine killer cells (Nku) was observed in postreatment in absence of pregnancy. CD4/CD3 was established with prognostic value when their values are close to those of the control group. CONCLUSION: Our findings demonstrate the reversibility of endometrial histological changes, both sonographics as immunological in RIF group under a polyvalent therapeutic; which is capable of modifying the immunology and endometrial histopathology and to obtain live birth.

Disrupted functional connectivity of the pain network in fibromyalgia.

OBJECTIVE: To investigate the impact of chronic pain on brain dynamics at rest. METHODS: Functional connectivity was examined in patients with fibromyalgia (FM) (n = 9) and healthy controls (n = 11) by calculating partial correlations between low-frequency blood oxygen level-dependent fluctuations extracted from 15 brain regions. RESULTS: Patients with FM had more positive and negative correlations within the pain network than healthy controls. Patients with FM displayed enhanced functional connectivity of the anterior cingulate cortex (ACC) with the insula (INS) and basal ganglia (p values between .01 and .05), the secondary somatosensory area with the caudate (CAU) (p = .012), the primary motor cortex with the supplementary motor area (p = .007), the globus pallidus with the amygdala and superior temporal sulcus (both p values < .05), and the medial prefrontal cortex with the posterior cingulate cortex (PCC) and CAU (both p values < .05). Functional connectivity of the ACC with the amygdala and periaqueductal gray (PAG) matter (p values between .001 and .05), the thalamus with the INS and PAG (both p values < .01), the INS with the putamen (p = .038), the PAG with the CAU (p = .038), the secondary somatosensory area with the motor cortex and PCC (both p values < .05), and the PCC with the superior temporal sulcus (p = .002) was also reduced in FM. In addition, significant negative correlations were observed between depression and PAG connectivity strength with the thalamus (r = -0.64, p = .003) and ACC (r = -0.60, p = .004). CONCLUSIONS: These findings demonstrate that patients with FM display a substantial imbalance of the connectivity within the pain network during rest, suggesting that chronic pain may also lead to changes in brain activity during internally generated thought processes such as occur at rest.

Tuberculosis en la población indígena del Perú 2008 / Tuberculosis in the indigenous population of Peru 2008

Objetivos. Identificar a los pobladores indígenas afectados por tuberculosis (TB) en el Perú durante el año 2008. Materiales y métodos. Estudio observacional, descriptivo, realizado de agosto a diciembre de 2009, que incluyó a los pacientes indígenas afectados por tuberculosis que ingresaron al programa durante el año 2008, de las 25 regiones delPerú; los cuales se presentan en tablas y gráficos elaborados en SPSS 16.0 y Excell 2007. Resultados. Se identificó a 702 indígenas con tuberculosis. El grupo étnico que presenta la mayor cantidad de pacientes con TB son los quechuas(417/702; 59,4 por ciento), los indígenas amazónicos (201/702; 28,6 por ciento) de los cuales los grupos étnicos que presenta más del 60 por ciento de indígenas con TB, son los Ashaninka (Campas), Shipibo y Matsiguenga. En tercer lugar se encuentran los indígenas aymaras quienes presentaron (84/702; 11,97 por ciento de todos los pacientes diagnosticados con TB). Es importante mencionar que la distribución de los casos de tuberculosis multidrogoresistente involucra a cinco departamentos (nueve casos con TB MDR), siendo mayor el número de casos de TB MDR antes tratado 6/9, encontrándose sólo tres casos de TB MDR nuevos, pertenecientes al grupo indígena quechua. Conclusiones. Se han reportado altas tasas de incidenciaen población indígena, lo que hace necesario investigaciones más profundas que garanticen la adecuada recolección de información por grupos étnicos a fin de contar con una evidencia de mayor jerarquía acerca de la situación de la tuberculosis en población indígena del Perú.

Objective. To identify the indigenous inhabitants affected by tuberculosis (TB) in Peru during the year 2008. Material and methods. Descriptive observational study, performed from August to December 2009, including all indigenous patients affected by tuberculosis that were including in the Control Program during the year 2008 in the 25 regions of Peru. Results. We identified 702 indigenous patients with tuberculosis. The ethnical groups that have most patients were the Quechua group (417/702; 59.4 per cent) and the Amazonic indigenous (201/702, 28.6 per cent). Out of the Amazonic, more than 60 per cent belonged to the Ashaninka (Campas), Shipibo and Matsiguenga groups. In third place, we found the Aymara natives, who had 84/702 (11.97 per cent) of cases of tuberculosis. It is important to mention that the distribution of the cases of multidrugresistant tuberculosis (MDR TB) involves five departments (nine cases of MDR TB), being the greater number of cases of MDR TB in patients previously treated (6/9), and only 3 cases were primary MDR TB, belonging to the quechua group. Conclusions. High incidence rates of tuberculosis in indigenous population have been found, which raises the need offurther research in order to guarantee the correct gathering of information in ethnic groups in order to have more and better evidence about the situation of tuberculosis in the indigenous population of Peru.

El chacho (alcanzo, hapiruzqa), Síndrome cultural andino: características y tratamiento tradicional en Ayacucho, Perú / Chacho (Alcanzo, Hapiruzqa), Andean cultural syndrome: frequency, characteristics and traditional treatments in Ayacucho, Peru

Objetivos. Conocer el cuadro clínico, formas de diagnóstico y tratamiento de los pacientes que presentan el síndrome conocido como chacho y cuál es su prevalencia sentida en cinco distritos de Ayacucho. Materiales y métodos. Estudio cuali-cuantitativo, que incluyó dos grupos de participantes, el primero (95) fueron pobladores o familiares de éstos, que alguna vez en su vida presentaron chacho, el segundo grupo (11) constituido por curanderos de cada comunidad. Resultados. El chacho (alcanzo, hapiruzqa en quechua), se considera como una enfermedad de origen mágico, caracterizada por presentar fiebre, malestar general, rechazo a algunos derivados lácteos y carne de chancho; en la mayoría de los pacientes se menciona el antecedente de descanso cercano a un cerro o dormir en el suelo (tierra). El tiempo de duración de la enfermedad fue menor de una semana en promedio y se evidenció que el tratamiento incluye, el consumo de gasolina, creso, kerosene, así como el pagapo (pago a la tierra). El consumo de medicamentos agrava la condición de salud del paciente. La prevalencia sentida varió entre 9,1 a 38,0 casos por mil habitantes y la mortalidad sentida entre 3,8 a 16,8 por diez mil habitantes. Conclusiones. El chacho es un síndrome cultural vigente, que debeser reconocido y abordado por el personal de salud, brindándonos así la oportunidad, de armonizar los conocimientos ancestrales de la medicina tradicional con los biomédicos actuales.

Objectives. Knowing the clinical features, diagnose and treatment for patients with the syndrome mean as chacho and what is its perceived prevalence in five districts of Ayacucho (Peruvian Central Andes). Material and methods. Qualiquantitative study, which included two groups of participants, the first (95) were residents or relatives of those who have ever had in your life chacho, the second group (11) formed by traditional healers of every community. Resultados. Chacho (alcanzo, hapiruzqa in quechua), is regarded as a disease of magical origin, characterized by fever, malaise, rejection of some dairy products and pork, in most patients referred the antecedent of a to rest near hill or sleep on the floor (ground ). The duration of the disease was less than a week on average and it was shown that treatment includes the consumption of gasoline, creso (disinfectant), kerosene, as well as the pagapo (Andean ritual of payment to the ground). The consumption of drugs worsens the health condition of patients. Perceived prevalence ranged between 9.1 to 38.0 cases per thousand people habitants, and perceived mortality from 3.8 to 16.8 per ten thousand habitants. Conclusions. Chacho is a present cutlural syndrome, which must be recognized and addressed by health personnel, thus giving them the opportunity to bring the ancestral knowledge of traditional medicine with the current biomedical.