Insights into the Adsorption Mechanisms of the Antimicrobial Peptide CIDEM-501 on Membrane Models.

CIDEM-501 is a hybrid antimicrobial peptide rationally designed based on the structure of panusin and panulirin template peptides. The new peptide exhibits significant antibacterial activity against multidrug-resistant pathogens (MIC = 2-4 µM) while conserving no toxicity in human cell lines. We conducted molecular dynamics (MD) simulations using the CHARMM-36 force field to explore the CIDEM-501 adsorption mechanism with different membrane compositions. Several parameters that characterize these interactions were analyzed to elucidate individual residues' structural and thermodynamic contributions. The membrane models were constructed using CHARMM-GUI, mimicking the bacterial and eukaryotic phospholipid compositions. Molecular dynamics simulations were conducted over 500 ns, showing rapid and highly stable peptide adsorption to bacterial lipids components rather than the zwitterionic eucaryotic model membrane. A predominant peptide orientation was observed in all models dominated by an electric dipole. The peptide remained parallel to the membrane surface with the center loop oriented to the lipids. Our findings shed light on the antibacterial activity of CIDEM-501 on bacterial membranes and yield insights valuable for designing potent antimicrobial peptides targeting multi- and extreme drug-resistant bacteria.

Epidemiology of suicide mortality in Mexican young people (ages 15-29) from 1990 to 2020 / Epidemiología del suicidio en jóvenes mexicanos (15-29 años) de 1990 a 2020

Abstract Introduction In 2020, suicide was the third leading cause of death in Mexico among young people ages 15 and 29, accounting for 43.0% of all suicides in the country, making it a major public health issue. Objective To explore changes in the geographic distribution of suicide rates by state and to analyze the magnitude, distribution, and pattern of suicide mortality in young Mexicans ages 15 to 29 between 1990 and 2020. Method Descriptive, ecological time-series study, based on official information. Standardized mortality rates were calculated using information on deaths (INEGI) and population estimates (CONAPO). The magnitude, distribution, and patterns of suicide mortality at the national level and by state were analyzed using the Joinpoint segmented regression model. Results From 1990 to 2020, suicide mortality in young people increased by 198% and was higher in women (285%) than men (178%). The states with the highest suicide mortality rates from 2016 to 2020 were Chihuahua (18.5 suicides/100,000 young people ages 15-29), Aguascalientes (16.6), Yucatán (14.4), Guanajuato (14.1), and San Luis Potosí (12.9), accounting for 23.0% of total suicide deaths. Discussion and conclusion The study of mortality trends could contribute to the management of a national suicide prevention strategy in young Mexicans, providing support for public health decision-making, such as the identification of the states and regions that should be prioritized.

Resumen Introducción En 2020, el suicidio fue la tercera causa de muerte en México en los jóvenes de 15 a 29 años y concentró el 43.0% del total de suicidios del país. Por lo tanto, es un problema de salud pública muy relevante. Objetivo Explorar los cambios en la distribución geográfica de las tasas de suicidio por entidad federativa, así como analizar la magnitud, distribución y tendencia de la mortalidad por suicidio, en los jóvenes mexicanos de 15 a 29 años entre 1990 y 2020. Método Estudio ecológico descriptivo de series de tiempo, a partir de la información de fuentes oficiales. Se calcularon las tasas estandarizadas de mortalidad utilizando la información sobre defunciones (INEGI) y las estimaciones de población (CONAPO). Se analizó la magnitud, distribución y tendencias de la mortalidad por suicidio a nivel nacional y por entidad federativa, utilizando el modelo de regresión segmentada Joinpoint. Resultados De 1990 a 2020, la mortalidad por suicidio en jóvenes creció 198%, siendo mayor en las mujeres (285%) que en los hombres (178%). Las entidades con mayor mortalidad por suicidio, de 2016 a 2020, fueron Chihuahua (18.5 suicidios/100 mil jóvenes 15-29 años), Aguascalientes (16.6), Yucatán (14.4), Guanajuato (14.1) y San Luis Potosí (12.9), las cuales concentraron el 23.0% del total de muertes por suicidios. Discusión y conclusión El estudio de las tendencias de la mortalidad podría contribuir a la gestión de una estrategia nacional para la prevención del suicidio en jóvenes mexicanos, proporcionando sustento para la toma de decisiones en salud pública, como la identificación de las entidades federativas y regiones del país que deben recibir la máxima prioridad.

Alginate Microsponges as a Scaffold for Delivery of a Therapeutic Peptide against Rheumatoid Arthritis.

The quest for biocompatible drug-delivery devices that could be able to open new administration routes is at the frontier of biomedical research. In this contribution, porous polysaccharide-based microsponges based on crosslinked alginate polymers were developed and characterized by optical spectroscopy and nanoscopic microscopy techniques. We show that macropores with a size distribution ranging from 50 to 120 nm enabled efficient loading and delivery of a therapeutic peptide (CIGB814), presently under a phase 3 clinical trial for the treatment of rheumatoid arthritis. Alginate microsponges showed 80% loading capacity and sustained peptide release over a few hours through a diffusional mechanism favored by partial erosion of the polymer scaffold. The edible and biocompatible nature of alginate polymers open promising perspectives for developing a new generation of polysaccharide-based carriers for the controlled delivery of peptide drugs, exploiting alternative routes with respect to intravenous administration.

Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma.

BACKGROUND AND AIMS: A gonadotropin-releasing hormone (GnRH)-based therapeutic vaccine candidate against hormone-sensitive prostate cancer has demonstrated its safety and signs of efficacy in phase I/II trials. In this study, we characterized the isotype/subclass profiles of the anti-GnRH humoral response generated by the vaccination and analyzed its association with patients' clinical outcomes. METHODS: The immunoglobulin isotypes and IgG subclasses of the antibody responses of 34 patients included in a randomized, open, prospective phase I/II clinical trial were characterized. Every patient included in the study had a diagnosis of locally advanced prostate adenocarcinoma at stages 3 and 4 and received immunization with the vaccine candidate. Additionally, serum testosterone and prostate specific antigen (PSA) concentrations, serving as indicators of tumor response, were determined. The type of anti-GnRH antibody response was correlated to the time elapsed until the first biochemical recurrence in patients and the outcome of the disease. RESULTS: All patients developed strong and prolonged anti-GnRH antibody responses, resulting in a short- to mid-term decrease in serum testosterone and PSA levels. Following immunizations, anti-GnRH antibodies of the IgM/IgG and IgG1/IgG3 subclasses were observed. Following radiotherapy, the humoral response switched to IgG (IgG1/IgG4). Patients who experienced a short-term biochemical relapse were characterized by significantly higher levels of anti-GnRH IgG titers, particularly IgG1 and IgG4 subclasses. These characteristics, along with a high response of specific IgM antibodies at the end of immunizations and the development of anti-GnRH IgA antibody responses following radiotherapy, were observed in patients whose disease progressed, compared to those with controlled disease. CONCLUSION: The nature of the humoral response against anti-GnRH, induced by vaccination may play a key role in activating additional immunological mechanisms. Collectively, these mechanisms could contribute significantly to the regulation of tumor growth.

Migration Intentions and Alcohol Use Among Adolescents in West-Central Mexico.

This study explores the association between migration intentions and alcohol use among west-central Mexico adolescents living in high migration communities. This study used the baseline data from the Family Migration and Early Life Outcomes (FAMELO) project (N = 1286), collected in 2018. We used multiple imputations to address missingness and propensity score matching to reduce the selection bias. We also conducted subgroup analyses to compare gender difference (i.e., boys vs. girls) on the relationship between migration intention and alcohol use. The findings show that for the whole sample, youth with migration intentions had significant higher odds (OR = 1.78; p = .010) of having a lifetime drinking experience when compared to youth who reported no interest in living abroad, but this association remained significant only for boys (OR = 2.14; p = .010). This study makes an important contribution to our understanding of the etiology of migration intentions and alcohol use for adolescents living in sending migration communities. The findings have specific alcohol prevention, policy, and future research implications in Mexico and the U.S.

Urban Violence, Migration and Alcohol, Tobacco, and Marijuana Use among Transnational Students in Northern Mexico.

This article reports on the findings of a study of the relationship between transnational experiences in the United States (US) and the use of alcohol, tobacco, and marijuana among 7th grade students (n = 1418). The study was guided by a cross-national framework for research on immigrant health and assessed the accumulation of risk factors for transnational adolescents. Data came from a survey conducted in 2017 in Nogales, Mexico. In this study, the last 30-day prevalence of use of alcohol, tobacco, and marijuana among students was 21.7%, 8.3%, and 2.4%, respectively. Most students were born in Nogales (69.6%), while 10.5% were born in the US, 7.5% attended school in the US, and 3.6% engaged in health-related risk behaviors while living in or visiting the US. Students with transnational experiences, such as attending school in the US, reported the highest 30-day prevalence of tobacco (13.3%) and marijuana (9.5%) use. After adjusting for family, school, access to substances and neighborhood violence variables, students who engaged in health-related risk behavior in the US had significantly increased odds of alcohol and marijuana use while later attending school in Mexico. The article discusses the findings from a prevention science perspective and provides implications for policy, practice, and future research on the Mexico-US border region.

Formulation matters! A spectroscopic and molecular dynamics investigation on the peptide CIGB552 as itself and in its therapeutical formulation.

Synthetic therapeutic peptides (STP) are intensively studied as new-generation drugs, characterized by high purity, biocompatibility, selectivity and stereochemical control. However, most of the studies are focussed on the bioactivity of STP without considering how the formulation actually used for therapy administration could alter the physico-chemical properties of the active principle. The aggregation properties of a 20-mer STP (Ac-His-Ala-Arg-Ile-Lys-D-Pro-Thr-Phe-Arg-Arg-D-Leu-Lys-Trp-Lys-Tyr-Lys-Gly-Lys-Phe-Trp-NH2 ), showing antitumor activity, were investigated by optical spectroscopy and atomic force microscopy imaging, as itself (CIGB552) and in its therapeutic formulation (CIGB552TF). It has found that the therapeutic formulation deeply affects the aggregation properties of the investigated peptide and the morphology of the aggregates formed on mica by deposition of CIGB552 and CIGB552TF millimolar solutions. Molecular dynamics simulations studied the first steps of CIGB552 aggregation under physiological ionic strength conditions (NaCl 150 mM), showing that peptide oligomers, from dimers to tetramers, are preferentially formed in this environment. Interestingly, cell viability assays performed on H-460 cell lines indicate a major antiproliferative activity of the peptide in its therapeutic formulation with respect to the peptide aqueous solution.

d-Amino acid substitutions and dimerization increase the biological activity and stability of an IL-15 antagonist peptide.

Interleukin (IL)-15 plays an important role in several inflammatory diseases. We have previously identified an IL-15 antagonist called P8 peptide, which binds specifically to IL-15 receptor alpha subunit. However, the P8 peptide rapidly degraded by proteases, limiting its therapeutic application. Thus, we replaced each P8 peptide l-amino acid by its corresponding d-isomers. First, we determined the biological activity of the resulting peptides in a proliferation assay by using CTLL-2 cells. The substitution of l-Ala by d-Ala ([A4a]P8 peptide) increased the inhibitory effect of the P8 peptide in CTLL-2 cells in five-fold. In addition to that, the [A4a]P8 peptide dimer showed the most inhibitory effect. To protect the [A4a]P8 peptide and its dimer against exopeptidase activity, we acetylated the N-terminal of these peptides. At least a three-fold reduction in antagonist activity of acetylated peptides was exhibited. However, the substitution of the N-terminal l-Lys residue of [A4a]P8 peptide and its dimer by d-Lys ([K1k;A4a]P8 peptide) did not affect the antagonist effect of the aforementioned peptides. The [K1k;A4a]P8 peptide dimer was stable to the degradation of trypsin, chymotrypsin, and pepsin up until 48 min. Also, the safety and immunogenicity studies in healthy BALB/c mice demonstrated that the administration of this peptide did not affect the clinical parameters of the animals nor generated antipeptide antibodies. Our findings reveal that two distinct d-amino acid substitutions and dimerization increase the biological activity and stability of P8 peptide. The resulting peptide constitutes a novel IL-15 antagonist with potential applicability in inflammatory diseases.

Testing a Culturally Adapted Youth Substance Use Prevention Program in a Mexican Border City: Mantente REAL.

Background: This article reports on a test of a youth substance use prevention program conducted in Nogales-Sonora, a Mexican city on the US border. Objective: The study tested the efficacy of a version of the keepin' it REAL curriculum for middle school students that was culturally adapted for Mexico and renamed Mantente REAL. Methods: Students in 7th grade classrooms in four public schools participated in the study (N = 1,418, 49% female, mean age = 11.9). Using a clustered randomized design, two schools received the intervention and two served as a treatment-as-usual control group. Regular classroom teachers were trained to deliver the twelve-lesson Mantente REAL manualized curriculum. Parents provided active consent and students gave written assent to collect pretest and posttest questionnaire data, 7 months apart, at the beginning and end of the 2017-2018 academic year. We assessed the Mantente REAL intervention with general linear models adjusted for baseline, attrition, non-linear distributions, and school-level clustering. Results: Students who participated in Mantente REAL reported relatively less frequent use of alcohol and illicit drugs other than marijuana, compared to students in control schools. Males alone reported desirable intervention effects for marijuana use. These desirable effects were especially strong among students who reported higher initial levels of involvement in risky behaviors. Among students more at risk, both females and males receiving the program reported relative reductions in the frequency of use of alcohol and illicit drugs. Conclusions: These promising results within the Mexico-US border context support a further dissemination of the intervention and additional youth prevention research in the region.

In vitro and in vivo characterization of an interleukin-15 antagonist peptide by metabolic stability, 99m Tc-labeling, and biological activity assays.

Interleukin (IL)-15 is an inflammatory cytokine that constitutes a validated therapeutic target in some immunopathologies, including rheumatoid arthritis (RA). Previously, we identified an IL-15 antagonist peptide named [K6T]P8, with potential therapeutic application in RA. In the current work, the metabolic stability of this peptide in synovial fluids from RA patients was studied. Moreover, [K6T]P8 peptide was labeled with 99m Tc to investigate its stability in human plasma and its biodistribution pattern in healthy rats. The biological activity of [K6T]P8 peptide and its dimer was evaluated in CTLL-2 cells, using 3 different additives to improve the solubility of these peptides. The half-life of [K6T]P8 in human synovial fluid was 5.88 ± 1.73 minutes, and the major chemical modifications included peptide dimerization, cysteinylation, and methionine oxidation. Radiolabeling of [K6T]P8 with 99m Tc showed a yield of approximately 99.8%. The 99m Tc-labeled peptide was stable in a 30-fold molar excess of cysteine and in human plasma, displaying a low affinity to plasma proteins. Preliminary biodistribution studies in healthy Wistar rats suggested a slow elimination of the peptide through the renal and hepatic pathways. Although citric acid, sucrose, and Tween 80 enhanced the solubility of [K6T]P8 peptide and its dimer, only the sucrose did not interfere with the in vitro proliferation assay used to assess their biological activity. The results here presented, reinforce nonclinical characterization of the [K6T]P8 peptide, a potential agent for the treatment of RA and other diseases associated with IL-15 overexpression.

The effect of pelvic pain and urinary incontinence on women's self-rated health in northern Mexico.

INTRODUCTION AND HYPOTHESIS: This study was designed to assess the effect of gynecological morbidities on Mexican women's self-rated health status and emotional health. METHODS: A cross-sectional population-based study was conducted among Mexican women aged 25-54. We analyzed information on 1,303 participants living in Hermosillo, Mexico. Multiple logistic regression was used to assess the effect of having any one of three kinds of pelvic pain, urinary incontinence or both of these conditions on women's self-rated health. Additionally, we conducted analysis of variance and multiple linear regression to test the effect of these gynecological morbidities on women's self-reported emotional health. RESULTS: Nearly one-third (31.2%) of participants rated their health as fair to very poor. Women reporting of at least one gynecological morbidity were more likely to rate their health as fair to very poor. In adjusted analyses, in addition to older age, low educational attainment, marital status other than single, lack of access to medical care, recurrent kidney infection, asthma, diabetes, and, reporting one or concurrent gynecological morbidities were associated with increased odds (adjusted odds ratios = 1.53-3.91) of reporting fair to very poor self-rated health. Women who did not report any gynecological morbidity had significantly lower mean scores for anxiety/fear 0.30 (±0.30) than women with two to four conditions (anxiety/fear 0.45 ± 0.31). CONCLUSION: Pelvic pain, urinary incontinence, and the co-occurrence of these conditions have a negative impact on women's perception of their health status and their emotional health.

The influence of different peptide combinations to increase the immunogenicity of the Gonadotrophin Releasing Hormone Vaccine for prostate cancer treatment.

PURPOSE: Therapeutic vaccines, specifically the Gonadotrophin Releasing Hormone (GnRH) vaccine, are considered an additional therapeutic option for advanced stage prostate cancer. Our work showed amplification of the immune response when combining two peptides with and without the Very Small Size Proteoliposomes (VSSP). VSSP is a potent adjuvant for dendritic cells activation and Th1 differentiation. as enhanced immune response. METHODS: The test was carried out in Copenhagen rats as animal model. RESULTST: The use of both peptides and their combination with VSSP generated a potentiation of the immune response statistically superior, in term of generating anti GnRH antibody and effects on target organs, when it was compared with the effects which occurs with independent peptides and with and without the VSSP. These results can find application in the development of GnRH vaccine candidates and in peptide based vaccine strategies. CONCLUSIONS: Immunization with the peptide combination enhances the immune response when mixed with the VSSPs.

[Analysis of HIV/AIDS mortality in Mexico from 1990 to 2013: An assessment of the feasibility of millennium development goals by 2015]. / Análisis de la mortalidad por VIH/SIDA en México en el periodo 1990-2013: ¿se cumplirá la meta establecida en los Objetivos de Desarrollo del Milenio (ODM) para el año 2015?

OBJECTIVE: We aimed to assess the feasibility of achieving the goal of Mexican AIDS mortality in the Millennium Development Goals, nationally and by state. METHODS: For the period 1990-2013, we estimated annual rates of decline/increase in AIDS mortality according to five-year interval, using published data from the Mexican Instituto Nacional de Estadística y Geografía and Consejo Nacional de Población. Subsequently, we analyzed the feasibility of achieving the Millennium Development Goals target by 2015 by estimating the year in which the country and each state could achieve them. RESULTS: We estimated that only 13/32 states (40%) would achieve the goal established for AIDS mortality by Millennium Development Goals. Mexico, as a country, and the remaining 19 states (60%) did not will attain it. It is important to emphasize that seven states, rather than decrease, had an upward trend in mortality in the last five years analyzed. CONCLUSIONS: The free and universal access to antiretroviral treatment against HIV/AIDS has failed to reduce mortality as expected in Mexico. It is urgent to improve access to HIV testing by using more aggressive strategies. Also, it is necessary to apply interventions to link and retain persons in care until they are virologically suppressed.

Prevalence and molecular characterization of G6PD deficiency in two Plasmodium vivax endemic areas in Venezuela: predominance of the African A-(202A/376G) variant.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency causes acute haemolytic anaemia triggered by oxidative drugs such as primaquine (PQ), used for Plasmodium vivax malaria radical cure. However, in many endemic areas of vivax malaria, patients are treated with PQ without any evaluation of their G6PD status. METHODS: G6PD deficiency and its genetic heterogeneity were evaluated in northeastern and southeastern areas from Venezuela, Cajigal (Sucre state) and Sifontes (Bolívar state) municipalities, respectively. Blood samples from 664 randomly recruited unrelated individuals were screened for G6PD activity by a quantitative method. Mutation analysis for exons 4-8 of G6PD gen was performed on DNA isolated from G6PD-deficient (G6PDd) subjects through PCR-RFLP and direct DNA sequencing. RESULTS: Quantitative biochemical characterization revealed that overall 24 (3.6%) subjects were G6PDd (average G6PD enzyme activity 4.5 ± 1.2 U/g Hb, moderately deficient, class III), while DNA analysis showed one or two mutated alleles in 19 of them (79.2%). The G6PD A-(202A/376G) variant was the only detected in 17 (70.8%) individuals, 13 of them hemizygous males and four heterozygous females. Two males carried only the 376A → G mutation. No other mutation was found in the analysed exons. CONCLUSIONS: The G6PDd prevalence was as low as that one shown by nearby countries. This study contributes to the knowledge of the genetic background of Venezuelan population, especially of those living in malaria-endemic areas. Despite the high degree of genetic mixing described for Venezuelan population, a net predominance of the mild African G6PD A-(202A/376G) variant was observed among G6PDd subjects, suggesting a significant flow of G6PD genes from Africa to Americas, almost certainly introduced through African and/or Spanish immigrants during and after the colonization. The data suggest that 1:27 individuals of the studied population could be G6PDd and therefore at risk of haemolysis under precipitating factors. Information about PQ effect on G6PDd individuals carrying mild variant is limited, but since the regimen of 45 mg weekly dose for prevention of malaria relapse does not seem to be causing clinically significant haemolysis in people having the G6PD A-variant, a reasoned weighing of risk-benefit for its use in Venezuela should be done, when implementing public health strategies of control and elimination.

Contenido nutricional de los alimentos promovidos por el Canal 5 de la televisión mexicana dirigidos a la población infantil / Nutritional content of foods promoted by Channel 5 of mexican television focused on child population

The aim of this study was to analyze the nutritional content of processed foods announced by Channel 5 of Mexican television. TV programs were recorded from February 6 to 10, 2012, at the times of greatest child audience. Five independent teams recorded and validated the duration of each advertisement, product or service advertised, advertising strategy its nutritional content and the additives they contain. 135 advertisements of unhealthy processed foods were transmitted. In contrast, none of natural and nutritious food aired. 74.0% of the time was occupied by products with high carbohydrate and sugar content 17.5% for foods high in fat and sodium; and 8.5% were dairy products with high sugar content. The results indicate that the Mexican television strongly promotes the consumption of unhealthy food to children. It is urgent that the government of Mexico to regulate the advertising of unhealthy food in children's programming schedules.

El objetivo de este estudio fue analizar el contenido nutricional de los alimentos industrializados anunciados por el canal 5 de la televisión mexicana con mayor audiencia infantil y como puede asociarse con obesidad infantil. Se grabaron los programas de TV del 6 al 10 de febrero de 2012, en los horarios de mayor audiencia infantil. Cinco equipos independientes registraron y validaron la duración de cada anuncio, producto o servicio anunciado, la estrategia publicitaria, su contenido nutricional y los aditivos que contienen. Se trasmitieron 135 anuncios de alimentos industrializados no saludables. En contraste, no se trasmitió ninguno de alimentos naturales o nutritivos. El 74,0% del tiempo fue ocupado por productos con alto contenido de carbohidratos y azúcar; 17,5% por alimentos con alto contenido de grasa y sodio; y 8,5% correspondió a lácteos con alto contenido de azúcar. Los resultados muestran que la televisión mexicana promueve intensamente el consumo de alimentos no saludables en la población infantil. Es urgente que el gobierno de México regule la publicidad de alimentos no saludables en los horarios de programación infantil.

Glucosa 6 fosfato deshidrogenasa: características bioquímicas y moleculares. Prevalencia de la deficiencia / Glucose-6-phosphate dehydrogenase: biochemical and molecular characteristics. Prevalence of deficiency

La glucosa-6-fosfato deshidrogenasa (G6PD) es una enzima citoplasmática que se encuentra distribuida en todas las células del organismo y que cataliza el primer paso de la vía de las pentosas en el cual la glucosa 6 fosfato (G6P) es convertida a 6-fosfogluconato(6FG) y el NADP reducido a NADPH, proceso indispensable para proteger a los eritrocitos del daño oxidativo. La deficiencia de la enzima G6PD es la eritroenzimopatía más común, es recesiva y ligada al cromosoma X, con amplia distribución mundial y elevada heterogeneidad genética y bioquímica. Se realizó una revisión sobre aspectos bioquímicos, estructura, genética, bases moleculares, defecto enzimático, prevalencia de la deficiencia en el mundo y en Venezuela, y el papel de la deficiencia de G6PD en el tratamiento de la malaria por el incremento en el riesgo de hemolisis que lleva consigo la tendencia de aumentar la dosis total de Primaquina en sujetos paludismo,particularmente en las regiones donde predomina la infección por Plasmodium vivax.

Measuring urinary incontinence in a population of women in northern Mexico: prevalence and severity.

INTRODUCTION AND HYPOTHESIS: This study was designed to estimate the prevalence of urinary incontinence and its associated risk factors among women in northern Mexico. The type and severity of incontinence were also assessed. METHODS: This cross-sectional population-based study assessed self-reported urinary incontinence in a random sample of 1,307 women aged 25-54 years. Logistic regression was used to estimate the association of urinary incontinence with sociodemographic and reproductive characteristics and other medical conditions. RESULTS: Overall, 18.4% of participants reported having involuntary loss of urine at some time within the last 12 months (95% CI, 16.4-20.7%). Among women reporting urinary incontinence, stress incontinence was the most common form (56.8%), followed by mixed (31.1%) and urge incontinence (10.0%). Approximately half of the women with urinary incontinence symptoms reported a severity index of moderate (25.8%) to severe (26.2%), with 30% stating that their leakage was extremely bothersome. Forty percent of incontinent women reported use of some sort of protection, although only 28% had ever talked to a physician about their symptoms. In adjusted analyses, high body mass index (BMI) ≥ 25 kg/m(2), chronic urinary tract infections, and a history of a hysterectomy or uterine leiomyomata were associated with increased odds of reporting incontinence symptoms. Increased odds of reporting severe urinary incontinence was associated with chronic urinary tract infections, current smoking and high BMI. CONCLUSION: Our results suggest that there might be a need to develop a culturally sensitive screening questionnaire in order to identify and counsel women with mild incontinence symptoms in the primary care setting.

Very small size proteoliposomes (VSSP) and Montanide combination enhance the humoral immuno response in a GnRH based vaccine directed to prostate cancer.

Very small size proteoliposomes (VSSP) constitute a complex of very small size proteoliposomes that includes proteins, lipids, CpG and gangliosides tumor-associated that provides a potential target for cancer immunotherapy. This compound has been described to stimulate the humoral and cellular response, dendritic cells (DC) activation and differentiation of T-helper cells, specially, in immunocompromised patients with cancer status. This work deals with the stimulating capacity of the VSSP to reach a humoral response when they are used as a component in a peptidic vaccine based on the gonadotrophin releasing hormone (GnRH). This study was carried out in male Copenhagen rats, which were immunized with 750µg of the GnRH mimetic peptide (GnRHm1-TT) with or without the VSSP. The mixtures were always emulsified with the oil adjuvant Montanide ISA 51. The anti GnRH seroconversion analysis revealed that the group immunized with the peptide GnRHm1-TT/VSSP developed a strong anti GnRH seroconversion. These antibody levels proved to be significant superior to those reached by the use of the GnRHm1-TT peptide solely emulsified in Montanide. Post-mortem analysis on the Testosterone ablation target organs (prostate and testicles) yielded a sudden decrease in their size and weight in respect to the control group. On the other hand, the group submitted to the use of GnRHm1-TT/VSSP, showed a significant difference in the reduction of these target organs in comparison with the group only immunized with GnRHm1-TT adjuvated in Montanide ISA 51. These values turned to be of p=0.023 and p=0.009 in the prostate and testicles respectively. These findings foreground the VSSP as a useful immunopotentiator to be used as part of a GnRH based vaccine to treat prostate cancer.