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El alumno deberá realizar una revisión bibliográfica de la información existente de aquellos emplazamientos seleccionados para este TFM, de dicha revisión extraerá los datos necesarios para poder realizar un análisis de riesgos tanto ecológico como para la población expuesta a la presencia de metales pesados en estos emplazamientos. Posteriormente, tendrá que estudiar los modelos matemáticos en los que se basa el análisis de riesgos y comprender como el software RISC5 integra esos modelos. Una vez conocido esto, realizará el análisis de riesgos correspondiente, definiendo los potenciales receptores como las rutas de exposición. De igual modo, tendrá que identificar aquellas variables que en mayor medida afectan los modelos anteriormente mencionados, lo cual debe de realizarlo mediante análisis de sensibilidad. Finalmente, con los resultados obtenidos deberá proponer las medidas de reducción y control de los posibles riesgos que se estén produciendo. Escuela de Ingeniería de Caminos y Minas Universidad Politécnica de Cartagena

Immune checkpoint inhibitors (ICIs) are approved for microsatellite unstable colorectal cancer (CRC), however, microsatellite stable (MSS) CRC that make up the majority of tumors in clinical practice have not seen any benefit with ICI. This is in part due to the lack of sufficient tumor infiltrating immune cells, particularly CD8+ T cells, in the milieu. Immunogenic cell death (ICD) is a particular form of cell death that elicits robust cross-priming of CD8 T cells against antigens expressed by dying cells in the absence of exogenous adjuvants. ICD-inducing drugs such as poly (ADP-ribose) polymerase inhibitors (PARPis) are poised to enhance cancer cell killing, boost tumor immunogenicity, increase in vivo immune infiltration, and thereby accelerate a tumor response to ICI treatment. Here, we tested the combinatorial therapeutic efficacy of a PARPi, olaparib (OLA), and an ICI, anti-PD-1, in in vitro and in vivo conditions. Combined treatment of OLA and anti-mouse PD-1 reduced tumor growth and increased survival in an immunocompetent, syngeneic animal model of BALB/c carrying allograft CT26 tumor that is MSS. Flow cytometry analysis revealed that the combo treatment significantly reduced percentages of anti-inflammatory macrophages and increased inflammatory monocytes. There was no significant difference in dendritic cell populations. We observed increased anti-tumor lymphocyte response via activation of CD4 and CD8 T cell populations upon combo treatment with OLA and anti-mouse PD-1. In addition, we noticed an increased association of expression of PD-L1 and its receptor PD-1 with OLA treatment in CRC cell lines and CT26 tumors. Our preliminary data suggests altered expressions of the CD8+ T cell exhaustion marker TIM-3 and its ligands galectin-9 and high mobility group protein 1 (HMGB1), an indicator of ICD. The pilot studies also revealed increased levels of STING-dependent type I interferon signaling initiator cGAS upon treatment with OLA in vivo. Mechanistically, OLA might induce DNA damage among tumor cells and trigger innate immune signaling including NF-κB activation and STING-dependent type I interferon signaling, both of which contribute to the maturation of myeloid antigen-presenting cells and subsequent activation of T cells. In conclusion, OLA potentiated the antitumor efficacy of anti-PD-1 in CT26 induced syngeneic CRC mouse model. Our findings indicate that OLA might trigger tumor immunogenicity, and enable a potential targeted-immunotherapeutic angle for exercising ICD and activating cytotoxic T lymphocytes in CT26 syngeneic CRC mouse model; however, further studies are needed to elucidate the mechanism. Despite ICD markers' identification as immuno-stimulating characteristics of dead cells, whether ICD-associated molecules can be used as a prognostic biomarker or therapeutic target, and the rational for such markers on tumor cells in eliciting antitumor immunity are still under investigation. Citation Format: Chintal Bhavsar, Peter John, Magnolia Abreu, Laura Bencosme, Radhashree Maitra, Sanjay Goel, Titto Augustine. Potentiating effect of olaparib on anti-PD-1 treatment in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1606.

Previously, the REDLINC VI study showed that the main reason for the low use of menopausal hormone therapy (MHT) was its low rate of prescription by doctors.To determine the use of MHT and perceived related risks among gynecologists.A self-administered and anonymous questionnaire was delivered to certified gynecologists in 11 Latin American countries.A total of 2154 gynecologists were contacted, of whom 85.3% responded to the survey (n = 1837). Mean age was 48.1 ± 11.4 years; 55.5% were male, 20.3% were faculty members and 85% had a partner. Overall, 85.4% of gynecologists responded that they would use MHT if they had menopausal symptoms (81.8% in the case of female gynecologists) or prescribe it to their partner (88.2% in the case of male gynecologists; p0.001). Perceived risk related to MHT use (on a scale from 0 to 10) was higher among female than among male gynecologists (4.06 ± 2.09 vs. 3.83 ± 2.11, p0.02). The top two perceived reported risks were thromboembolism (women 33.6% vs. men 41.4%, p0.009) and breast cancer (women 38.5% vs. men 33.9%, p0.03). Overall, gynecologists reported prescribing MHT to 48.9% of their symptomatic patients (women 47.3% vs. men 50.2%, p0.03) and 86.8% currently prescribed non-hormonal remedies and 83.8% alternative therapies for the management of the menopause. Gynecologists who were older and academic professionals prescribed MHT more often.Although this Latin American survey showed that gynecologists are mostly supporters of MHT use (for themselves or their partners), this is not necessarily reflected in their clinical practice.

ObjectiveTo determine the effects of the disease-modifying therapies, glatiramer acetate (GA) and dimethyl fumarate (DMF), on the gut microbiota in patients with MS.MethodsParticipants with relapsing MS who were either treatment-naive or treated with GA or DMF were recruited. Peripheral blood mononuclear cells were immunophenotyped. Bacterial DNA was extracted from stool, and amplicons targeting the V4 region of the bacterial/archaeal 16S rRNA gene were sequenced (Illumina MiSeq). Raw reads were clustered into Operational Taxonomic Units using the GreenGenes database. Differential abundance analysis was performed using linear discriminant analysis effect size. Phylogenetic investigation of communities by reconstruction of unobserved states was used to investigate changes to functional pathways resulting from differential taxon abundance.ResultsOne hundred sixty-eight participants were included (treatment-naive n = 75, DMF n = 33, and GA n = 60). Disease-modifying therapies were associated with changes in the fecal microbiota composition. Both therapies were associated with decreased relative abundance of the Lachnospiraceae and Veillonellaceae families. In addition, DMF was associated with decreased relative abundance of the phyla Firmicutes and Fusobacteria and the order Clostridiales and an increase in the phylum Bacteroidetes. Despite the different changes in bacterial taxa, there was an overlap between functional pathways affected by both therapies.InterpretationAdministration of GA or DMF is associated with differences in gut microbial composition in patients with MS. Because those changes affect critical metabolic pathways, we hypothesize that our findings may highlight mechanisms of pathophysiology and potential therapeutic intervention requiring further investigation.

The prevalence of sexual violence crimes on U.S. college campuses is prompting institutions of higher education to increasingly invest in centers to support survivors and programs to prevent the violence before it happens. Understanding bystanders to sexual violence and what may motivate them to step in and help is a promising prevention strategy. The purpose of this study was to understand how potential active bystanders’ (first-year college students) perceptions of community (including a sense of one’s influence in the community and positive peer norms for helping) and individual beliefs about self (including sense of responsibility and self-efficacy) affect their self-reports of performing bystander behavior to address sexual violence risks. Participants were 948 students at two different universities (one a rural, primarily residential campus and the other an urban, mostly commuter campus) in the northeastern United States. Regression and path analysis quantitative results suggest that individual-level characteristics may mediate some of the impact that community-level norms and perceptions have on bystander outcomes, explaining some of the mixed findings in previous research. Prevention strategies should work to change community norms and perceptions of mattering and perceptions of community influence in addition to the more traditional focus on individual-level violence specific attitudes.

The aim of the study was to evaluate the association between waist-to-height ratio (WHtR) and anxiety in middle-aged women.We carried out a secondary analysis of data from a multicenter study of women between 40 and 59 years old from 11 Latin America countries. Anxiety was assessed using the Goldberg Anxiety and Depression Scale. WHtR was calculated according to World Health Organization standards and categorized in tertiles: upper, middle, and lower using 0.45 and 0.6 as cutoff values. Prevalence ratios (PRs) and 95% CIs were calculated by generalized linear models of Poisson family with robust standard errors, both crude and adjusted models based on statistical and epidemiological criteria.Data of a total of 5,580 women were analyzed. Mean age was 49.7 ± 5.5 years, and 57.9% were postmenopausal. The 61.3% of women had anxiety and mean WHtR was 0.54 ± 0.1. In the crude model, compared with women in lower tertile, those in the middle (PR: 1.07; 95% CI, 1.01-1.13) and upper (PR: 1.23 95% CI, 1.07-1.29) WHtR tertile were significantly more likely to have anxiety. In the adjusted models, only women in upper tertile were, however, more likely of displaying anxiety than those in lower tertile (PR: 1.13; 95% CI, 1.08-1.18).In this series, WHtR was associated with anxiety in middle-aged women. It is advisable to further study this anthropometric measure in order for it to be incorporated in the routine clinical practice and evaluation of middle-aged women.

Background The prevalence of obesity increases during female mid-life and although many factors have been identified, data from Latin America is lacking. Objective To assess factors related to obesity among middle-aged women and determine the association with depressive symptoms, sedentary lifestyle and other factors. Methods A total of 6079 women aged 40–59 years of 11 Latin American countries were asked to fill out the Goldberg Anxiety and Depression Scale, the Menopause Rating Scale, the Athens Insomnia Scale, the Pittsburgh Sleep Quality Index and a general questionnaire containing personal socio-demographic data, anthropometric measures and lifestyle information. Obesity was defined as a body mass index (BMI) ≥30 kg/m 2 . Results Obesity was observed in 18.5% and sedentary lifestyle in 63.9%. A 55.5% presented vasomotor symptoms, 12.2% had severe menopausal symptoms and 13.2% used hormone therapy for the menopause. Prevalence of depressive symptoms was 46.5% and anxiety 59.7%. Our logistic regression model found that significant factors associated to obesity included: arterial hypertension (OR: 1.87), depressive symptoms (OR: 1.57), sedentary lifestyle (OR: 1.50) diabetes mellitus (OR: 1.34), higher number of individuals living at home (OR: 1.31), sleep problems (OR:1.22), anxiety (OR: 1.21), having a stable partner (OR: 1.20), parity (OR: 1.16) and vasomotor symptoms (OR:1.14). A lower risk for obesity was found among women using hormonal contraceptives (OR: 0.69). Conclusion Obesity in middle-aged women is the consequence of the interaction of multiple factors. It was associated to hypertension, depressive symptoms, sedentary lifestyle, climacteric symptoms and other factors.

Background Type II diabetes mellitus causes metabolic changes that may lead to early menopause and worsen climacteric symptoms. Objectives To determine the risk factors for type II diabetes mellitus and assess the impact of this disease on the age of menopause and on climacteric symptoms. Methods A total of 6079 women aged between 40 and 59 years from 11 Latin American countries were requested to answer the Menopause Rating Scale and Goldberg Anxiety-Depression Scale. Results The prevalence of diabetes was 6.7%. Diabetes mellitus was associated with arterial hypertension (odds ratio (OR) 4.49; 95% confi dence interval (CI) 3.47 – 5.31), the use of psychotropic drugs (OR 1.54; 95% CI 1.22 – 1.94), hormonal therapy (OR 1.46; 95% CI 1.11 – 1.92), 50 years of age (OR 1.48; 95% CI 1.17 – 1.86), overweight or obese (OR 1.47; 95% CI 1.15 – 1.89), and waist circumference 88 cm (OR 1.32; 95% CI 1.06 – 1.65). Factors associated with lower risk of diabetes were the use of hormonal contraceptives (OR 0.55; 95% CI 0.35 – 0.87), alcohol (OR 0.73; 95% CI 0.54 – 0.98) and living in cities 2500 meters above sea level (OR 0.70; 95% CI 0.53 – 0.91) or with high temperatures (OR 0.67; 95% CI 0.51 – 0.88). In turn, diabetes tripled the risk of menopause in women under 45 years of age. Diabetes did not increase the risk of deterioration of quality of life due to climacteric symptoms. Conclusion Menopause does not increase the risk of type II diabetes mellitus. Diabetes is associated with early menopause in women under 45 years of age.

Objective: To evaluate associations between anxiety and severe impairment of quality of life (QoL) in Latin American postmenopausal women. Methods: This was a secondary analysis of a multicenter cross-sectional study among postmenopausal women aged 40 to 59 from 11 Latin American countries. We evaluated anxiety (The Goldberg Depression and Anxiety Scale), and QoL (Menopause Rating Scale [MRS]), and included sociodemographic, clinical, lifestyle, and anthropometric variables in the analysis. Poisson family generalized linear models with robust standard errors were used to estimate prevalence ratios (PRs) and 95% CIs. There were two adjusted models: a statistical model that included variables associated with the outcomes in bivariate analyses, and an epidemiologic model that included potentially confounding variables from literature review. Results: Data from 3,503 women were included; 61.9% had anxiety (Goldberg). Severe QoL impairment (total MRS score >=17) was present in 13.7% of women, as well as severe symptoms (MRS subscales): urogenital (25.5%), psychological (18.5%), and somatic (4.5%). Anxiety was independently associated with severe QoL impairment and severe symptoms in the epidemiological (MRS total score: PR 3.6, 95% CI, 2.6-5.0; somatic: 5.1, 95% CI, 2.6-10.1; psychological: 2.8, 95% CI, 2.2-3.6; and urogenital: 1.4, 95% CI, 1.2-1.6) and the statistical model (MRS total score: PR 3.5, 95% CI, 2.6-4.9; somatic: 5.0, 95% CI, 2.5-9.9; psychological: 2.9, 95% CI, 2.2-3.7; and urogenital: 1.4; 95% CI, 1.2-1.6). Conclusions: In this postmenopausal Latin American sample, anxiety was independently associated with severe QoL impairment. Hence, screening for anxiety in this population is important. Revisión por pares

Musculoskeletal pain (MSP) has been recently linked with high plasma leptin levels. Our objective was to study if obese women, who have higher leptin levels, could have a higher frequency of MSP. We studied 6079 Latin-American women, 40-59 years old. Their epidemiological data were recorded and the Menopause Rating Scale (MRS), Golberg Anxiety and Depression Scale and Insomnia Scale were applied. MSP was defined as a score ≥2 on MRS11. Women with MSP were slightly older, had fewer years of schooling and were more sedentary. They also complained of more severe menopausal symptoms (29.2% versus. 4.4%, p 0.0001). Furthermore, they had a higher abdominal perimeter (87.2 ± 12.0 cm versus 84.6 ± 11.6 cm, p 0.0001) and a higher prevalence of obesity (23.1% versus 15.2%, p 0.0001). Compared to normal weight women, those with low body weight (IMC 18.5) showed a lower risk of MSP (OR 0.71; 95%CI, 0.42-1.17), overweight women had a higher risk (OR 1.64; 95%CI, 1.44-1.87) and obese women the highest risk (OR 2.06; 95%CI, 1.76-2.40). Logistic regression analysis showed that obesity is independently associated to MSP (OR 1.34; 95%CI, 1.16-1.55). We conclude that obesity is one identifiable risk factor for MSP in middle-aged women.

Item does not contain fulltext BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS: At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P/=70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of >/=100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P

To evaluate whether menopausal status and symptoms among female gynecologists would influence their clinical behavior related to menopausal hormone therapy (MHT).Female gynecologists of 11 Latin American countries were requested to fill out the Menopause Rating Scale and a questionnaire containing personal information and that related to MHT use.A total of 818 gynecologists accepted to participate (86.4%). Overall, the mean age was 45.0 ± 10.7 years, 32.2% were postmenopausal, and 17.6% worked in an academic position; 81.8% reported that they would use MHT if they have symptoms, regardless of menopausal status. Academic gynecologists favor personal MHT use at a higher rate (p = 0.04) and have a higher MHT prescription rate as compared to non-academic ones (p = 0.0001). The same trend was observed among post- as compared to premenopausal ones (p = 0.01) and among those who had hysterectomy alone as compared to those experiencing natural menopause (p = 0.002). The presence of menopausal symptoms did not influence their MHT prescription. Current use of MHT and alternative therapy was higher among post- than premenopausal gynecologists (both, p = 0.0001) and among those who had undergone hysterectomy than those experiencing natural menopause. A 38.5% perceived breast cancer as the main risk related to MHT, and a high proportion prescribed non-hormonal drugs (86.4%) or alternative therapies (84.5%).Most female gynecologists in this survey would use MHT if menopausal symptoms were present. Postmenopausal physicians use MHT and prescribe it to their symptomatic patients at a higher rate than premenopausal physicians.

RESUMEN: Introducción: En estadios de ERC (estadios 4-5) existen alteraciones del magnesio sérico que han motivado diferentes estudios buscando la relación con la insuficiencia renal y los cambios séricos de magnesio. Este estudio busca analizar los niveles de magnesio en pacientes con Enfermedad Renal Crónica (ERC) tomando en cuenta las variables que podrían afectarlos. Métodos: Es un estudio observacional descriptivo. Se revisaron los expedientes de 509 pacientes en diferentes estadios de la ERC para obtener datos sociodemográficos, niveles de Magnesio, PTH, el uso de Acetato de calcio/Carbonato de magnesio o de IBP. Resultados: La media del magnesio sérico obtenida fue de 2,04±0,39 mg/dL (rango = 0,6-3,6 mg/dL). Por subgrupos se destacaron niveles menores de magnesio en los pacientes trasplantados (n=301, =1,89±0,37 mg/dL) en comparación a los pacientes en prediálisis (n=117, =2,17±0,38 mg/dL), en hemodiálisis (n=60, =2,41±0,44 mg/dL) y en diálisis peritoneal (n=31, =2,27±0,34 mg/dL). Se encontró una relación inversa entre el magnesio y los niveles de PTH (Exp B -69,9, 95%CI -129,0 – 10,8, p = 0,02) en el análisis multivariante y otra relación inversa entre la filtración glomerular y los niveles de magnesio (r=-0,44, p

Spermatogenesis in all animal species occurs within a syncytium. Only at the very end of spermatogenesis are individual sperm cells resolved from this syncytium in a process known as individualization. Individualization in Drosophila begins as a membrane-cytoskeletal complex known as the individualization complex (IC) assembles around the sperm heads and proceeds down the flagella, removing cytoplasm from between the sperm tails and shrink-wrapping each spermatid into its own plasma membrane as it travels. The mulet (mlt) mutation results in severely disrupted ICs, indicating that the mlt gene product is required for individualization. Inverse PCR followed by cycle sequencing maps all known P-insertion alleles of mlt to two overlapping genes, CG12214 (the Drosophila tubulin-binding cofactor E-like homolog) and KCNQ (a large voltage-gated potassium channel). However, since the alleles of mlt map to the 5′-UTR of CG12214 and since CG12214 is contained within an intron of KCNQ, it was hypothesized that mlt and CG12214 are allelic. Indeed, CG12214 mutant testes exhibited severely disrupted ICs and were indistinguishable from mlt mutant testes, thus further suggesting allelism. To test this hypothesis, alleles of mlt were crossed to CG12214 in order to generate trans-heterozygous males. Testes from all trans-heterozygous combinations revealed severely disrupted ICs and were also indistinguishable from mlt mutant testes, indicating that mlt and CG12214 fail to complement one another and are thus allelic. In addition, complementation testing against null alleles of KCNQ verified that the observed individualization defect is not caused by a disruption of KCNQ. Finally, since a population of spermatid-associated microtubules known to disappear prior to movement of the IC abnormally persists during individualization in CG12214 mutant testes, this work implicates TBCE-like in the removal of these microtubules prior to IC movement. Taken together, these results identify mlt as CG12214 and suggest that the removal of microtubules by TBCE-like is a necessary pre-requisite for proper coordinated movement of the IC.

Although sleep disturbances are common during female mid-life, few studies have described in detail the prevalence of this problem and related risk factors.To determine the prevalence of sleep disturbances in mid-aged women using validated tools. Assessment of determinants capable of influencing the prevalence of insomnia and poor sleep quality was also performed.A total of 6079 women aged 40-59 of 11 Latin American countries were invited to fill out the Athens Insomnia Scale (AIS), the Pittsburgh Sleep Quality Index (PSQI), the Goldberg Anxiety and Depression Scale, the Menopause Rating Scale (MRS), the Brief Scale of Abnormal Drinking and a general socio-demographic questionnaire.Overall, 56.6% of surveyed women suffered of either insomnia, poor sleep quality, or both. Specifically, 43.6% and 46.2% presented insomnia and poor sleep quality in accordance to the AIS and the PSQI respectively. The prevalence of insomnia increased with female age (from 39.7% in those aged 40-44 to 45.2% in those aged 55-59, p0.0001) and menopausal stage (from 39.5% in premenopausal aged 40-44 to 46.3% in late postmenopausal ones, p0.0001). "Awakening during the night" (AIS: Item 2) was the most highly rated of all items and contributing in a higher degree (mean 16%) to the total score of the scale in all menopausal phases. Sleep quality also worsened with age and menopausal status, impairment particularly affecting sleep efficiency and latency and the increased use of hypnotics. Vasomotor symptoms (VMS), depressive mood and anxiety were associated to sleep disturbances. Women presenting sleep disturbances displayed a 2-fold increase in the severity of menopausal symptoms (higher total MRS scores) which was translated into a 6-8 times higher risk of impaired quality of life. Logistic regression analysis determined that female age, the presence of chronic disease, troublesome drinking, anxiety, depression, VMS, drug use (hypnotics and hormone therapy) were significant risk factors related to the presence of sleep disturbances. Higher educational level related to less insomnia and better sleep quality.Insomnia and poor sleep quality were highly prevalent in this mid-aged female sample in which the influence of age and the menopause was only modest and rather linked to menopausal symptoms already occurring since the premenopause.

Few Latin American studies have described menopausal symptoms in detail by means of a standardized assessment tool. The objective of this study was to assess the prevalence and severity of menopausal symptoms and their impact over quality of life among mid-aged Latin American women.In this cross-sectional study, 8373 otherwise healthy women aged 40-59 years from 12 Latin American countries were asked to fill out the Menopause Rating Scale (MRS) and a questionnaire containing personal sociodemographic data. Menopause status (pre-, peri- and postmenopausal) was defined according to the criteria of the Stages of Reproductive Aging Workshop.Of all the studied women, 90.9% had at least one menopausal symptom (complaint) that they rated. Muscle and joint discomfort, physical and mental exhaustion and depressive mood were highly prevalent and rated as severe-very severe (scores of 3 and 4), at a higher rate than vasomotor symptoms (15.6%, 13.8% and 13.7% vs. 9.6%, respectively). Of premenopausal women (40-44 years), 77.0% reported at least one rated complaint, with 12.9% displaying MRS scores defined as severe (16). The latter rate increased to 26.4% in perimenopausal, 31.6% in early postmenopausal and 29.9% among late postmenopausal women. As measured with the MRS, the presence of hot flushes increased the risk of impairment of overall quality of life in both premenopausal (odds ratio 12.67; 95% confidence interval 9.53-16.83) and peri/postmenopausal women (odds ratio 9.37; 95% confidence interval 7.85-11.19).In this large, mid-aged, female Latin American series, muscle/joint discomfort and psychological symptoms were the most prevalent and severely rated menopausal symptoms. The symptoms appear early in the premenopause, significantly impair quality of life and persist 5 years beyond the menopause.

Resumen Si bien la neumonitis por hipersensibilidad es la complicacion pulmonar mas frecuentemente descrita durante el tratamiento con metotrexato, existen otras complicaciones de tipo linfoproliferativo e infeccioso que hay que tener en cuenta dentro del diagnostico diferencial ante una neumopatia en el contexto de dicho tratamiento. La existencia de un riesgo incrementado de desarrollar procesos infecciosos o reactivaciones de microorganismos latentes puede ser similar al observado a lo largo del tratamiento con antagonistas del factor de necrosis tumoral y corticoides. Dentro de ellas, la neumonia por citomegalovirus es una complicacion muy severa a tener en cuenta, ya que el diagnostico acertado y el tratamiento oportuno evitaran un desenlace potencialmente mortal.

e18838Background: Intracranial metastases occur in more than 50% of patients with small cell lung cancer (SCLC). Cranial irradiation (PCI) is effective in decreasing the incidence of cerebral metas...

Objective: The purpose of this study was to assess the prevalence of sexual dysfunction (SD) and associated risk factors among middle-aged Latin American women using one validated instrument. Methods: The Female Sexual Function Index (FSFI) was applied to 7,243 healthy women aged 40 to 59 years who were users of 19 healthcare systems from 11 Latin American countries. An itemized questionnaire containing personal and partner sociodemographic data was also filled out. Results: Mean T SD age of surveyed women was 49.0 T 5.7 years, with 11.6 years of schooling on average. There were 55.1% of women who were married, 46.8% who were postmenopausal, 14.1% who used hormonal therapy (HT), and 25.6% who were sexually inactive. Among those who were active (n = 5,391), the mean T SD total FSFI score was 25.2 T 5.9 and 56.8% of them presented SD (FSFI total score e26.55), with a prevalence varying from 21.0% to 98.5% depending on the center. Centers were grouped in terciles (according to mean T SD prevalence). The tercile with higher SD prevalence (86.4%) compared with that with lower SD prevalence (32.2%) had significantly older women (49.5 T 5.3 vs 48.0 T 5.6 y) with a higher rate of vaginal dryness (60.4% vs 40.8%) and older partners (53.0 T 6.9 vs 50.2 T 7.5 y). Similarly, there was a significantly higher rate of married (68.5% vs 63.1%), postmenopausal (49.7% vs 39.3%), and HT-using women (23% vs 9.2%). There were no differences in regard to their health perception, history of oophorectomy, rape, and partner SD rate (27% vs 26.2%). The total FSFI score was significantly lower in the tercile with higher SD prevalence (22.0 T 5.0 vs 27.5 T 5.4). Logistic regression analysis was used to determine the odds ratios (95% CIs) for the main risk factors associated with SD among those who were sexually active: bad lubrication, 3.86 (3.37-4.43); use of alternative menopausal therapies, 2.13 (1.60-2.84); partner SD, 1.89 (1.63-2.20); older women (948 y), 1.84 (1.61-2.09); bladder problems, 1.47 (1.28-1.69); HT use, 1.39 (1.15-1.68); negative perception of female health status, 1.31 (1.05-1.64); and being married, 1.22 (1.07-1.40). Protective factors were higher educational level (women), partner faithfulness, and access to private healthcare. Conclusions: The prevalence of SD in this middle-aged Latin American series was found to be high, varying widely in different populations. A decrease in vaginal lubrication was the most important associated risk factor. Differences in the prevalence of risk factors among the studied groups, several of which are modifiable, could explain the variation of SD prevalence observed in this study.

Background Several studies indicate that quality of life (QoL) is impaired in middle aged women. Assessment of QoL using a single validated tool in Latin American climacteric women has not been reported to date at large scale. Objective The Menopause Rating Scale (MRS) was used to assess QoL among middle aged Latin American women and determine factors associated with severe menopausal symptoms (QoL impairment). Methods In this cross-sectional study, 8373 healthy women aged 40–59 years, accompanying patients to healthcare centres in 18 cities of 12 Latin American countries, were asked to fill out the MRS and a questionnaire containing socio-demographic, female and partner data. Results Mean age of the entire sample was 49.1 ± 5.7 years (median 49), a 62.5% had 12 or less years of schooling, 48.8% were postmenopausal and 14.7% were on hormonal therapy (HT). Mean total MRS score (n = 8373) was 11.3 ± 8.5 (median 10); for the somatic subscale, 4.1 ± 3.4; the psychological subscale, 4.6 ± 3.8 and the urogenital subscale, 2.5 ± 2.7. The prevalence of women presenting moderate to severe total MRS scorings was high (>50%) in all countries, Chile and Uruguay being the ones with the highest percentages (80.8% and 67.4%, respectively). Logistic regression determined that impaired QoL (severe total MRS score ≥17) was associated with the use of alternatives therapies for menopause (OR: 1.47, 95% CI [1.22–1.76], p = 0.0001), the use of psychiatric drugs (OR: 1.57, 95% CI [1.29–1.90], p = 0.0001), attending a psychiatrist (OR: 1.66, 95% CI [1.41–1.96], p = 0.0001), being postmenopausal (OR: 1.48, 95% CI [1.29–1.69, p = 0.0001]), having 49 years or more (OR: 1.24, 95% CI [1.08–1.42], p = 0.001), living at high altitude (OR: 1.43, 95% CI [1.25–1.62, p = 0.0001]) and having a partner with erectile dysfunction (OR: 1.69, 95% CI [1.47–1.94, p = 0.0001]) or premature ejaculation (OR: 1.34, 95% CI [1.16–1.55, p = 0.0001]). Lower risk for impaired QoL was related to living in a country with a lower income (OR: 0.77, 95% CI [0.68–0.88], p = 0.0002), using HT (OR: 0.65, 95% CI [0.56–0.76], p = 0.0001) and engaging in healthy habits (OR: 0.59, 95% CI [0.50–0.69], p = 0.0001). Conclusion To the best of our knowledge this is the first and largest study assessing QoL in a Latin American climacteric series with a high prevalence of impairment related to individual female and male characteristics and the demography of the studied population.

Objective: The aim of the study was to evaluate the association between sedentary lifestyle and the severity of menopausal symptoms and obesity in middle-aged women. Methods: The Menopause Rating Scale, the Goldberg Anxiety and Depression Scale, and the Athens Insomnia Scale were administered to 6,079 Latin American women aged 40 to 59 years. Sedentary lifestyle was defined as fewer than three weekly, 30-minute periods of physical activity. Results: Sedentary women had more severe menopausal symptoms (total Menopause Rating Scale score: 9.576.71 vs 8.01-6.27 points, P

The investigation of cortical gray matter (GM), deep GM nuclei, and spinal cord damage in patients with primary progressive multiple sclerosis (PP-MS) provides insights into the neurodegenerative process responsible for clinical progression of MS.To investigate the association of magnetic resonance imaging measures of cortical, deep GM, and spinal cord damage and their effect on clinical disability.Cross-sectional analysis of 26 patients with PP-MS (mean age, 50.9 years; range, 31-65 years; including 14 women) and 20 healthy control participants (mean age, 51.1 years; range, 34-63 years; including 11 women) enrolled at a single US institution. Clinical disability was measured with the Expanded Disability Status Scale, 9-Hole Peg Test, and 25-Foot Walking Test. We collected data from January 1, 2012, through December 31, 2013. Data analysis was performed from January 21 to April 10, 2015.Cortical lesion burden, brain and deep GM volumes, spinal cord area and volume, and scores on the Expanded Disability Status Scale (score range, 0 to 10; higher scores indicate greater disability), 9-Hole Peg Test (measured in seconds; longer performance time indicates greater disability), and 25-Foot Walking Test (test covers 7.5 m; measured in seconds; longer performance time indicates greater disability).The 26 patients with PP-MS showed significantly smaller mean (SD) brain and spinal cord volumes than the 20 control group patients (normalized brain volume, 1377.81 [65.48] vs 1434.06 [53.67] cm3 [P = .003]; normalized white matter volume, 650.61 [46.38] vs 676.75 [37.02] cm3 [P = .045]; normalized gray matter volume, 727.20 [40.74] vs 757.31 [38.95] cm3 [P = .02]; normalized neocortical volume, 567.88 [85.55] vs 645.00 [42.84] cm3 [P = .001]; normalized spinal cord volume for C2-C5, 72.71 [7.89] vs 82.70 [7.83] mm3 [P.001]; and normalized spinal cord volume for C2-C3, 64.86 [7.78] vs 72.26 [7.79] mm3 [P =.002]). The amount of damage in deep GM structures, especially with respect to the thalamus, was correlated with the number and volume of cortical lesions (mean [SD] thalamus volume, 8.89 [1.10] cm3; cortical lesion number, 12.6 [11.7]; cortical lesion volume, 0.65 [0.58] cm3; r = -0.52; P.01). Thalamic atrophy also showed an association with cortical lesion count in the frontal cortex (mean [SD] thalamus volume, 8.89 [1.1] cm3; cortical lesion count in the frontal lobe, 5.0 [5.7]; r = -0.60; P.01). No association was identified between magnetic resonance imaging measures of the brain and spinal cord damage.In this study, the neurodegenerative process occurring in PP-MS appeared to spread across connected structures in the brain while proceeding independently in the spinal cord. These results support the relevance of anatomical connectivity for the propagation of MS damage in the PP phenotype.

OBJECTIVE: To assess the age at menopause (AM) in Latin America urban areas. DESIGN: A total of 17,150 healthy women, aged 40 to 59 years, accompanying patients to healthcare centers in 47 cities of 15 Latin American countries, were surveyed regarding their age, educational level, healthcare coverage, history of gynecological surgery, smoking habit, presence of menses, and the use of contraception or hormone therapy at menopause. The AM was calculated using logit analysis. RESULTS: The mean age of the entire sample was 49.4 ± 5.5 years. Mean educational level was 9.9 ± 4.5 years, and the use of hormone therapy and oral contraception was 22.1% and 7.9%, respectively. The median AM of women in all centers was 48.6 years, ranging from 43.8 years in Asuncion (Paraguay) to 53 years in Cartagena de Indias (Colombia). Logistic regression analysis determined that women aged 49 living in cities at 2,000 meters or more above sea level (OR = 2.0, 95% CI: 1.4-2.9, P less than 0.001) and those with lower educational level (OR = 1.9, 95% CI: 1.3-2.8, P less than 0.001) or living in countries with low gross national product (OR = 2.1, 95% CI: 1.5-2.9, P less than 0.001) were more prone to an earlier onset of menopause. CONCLUSIONS: The AM varies widely in Latin America. Lower income and related poverty conditions influence the onset of menopause. © 2006 by The North American Menopause Society.