Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo.

Exosomes support cell-to-cell communication in physiology and disease, including cancer. We currently lack tools, such as small chemicals, capable of modifying exosome composition and activity in a specific manner. Building on our previous understanding of how syntenin, and its PDZ partner syndecan (SDC), impact on exosome composition we optimized a small chemical compound targeting the PDZ2 domain of syntenin. In vitro , in tests on MCF-7 breast carcinoma cells, this compound is non-toxic and impairs cell proliferation, migration and primary sphere formation. It does not affect the size or the number of secreted particles, yet it decreases the amounts of exosomal syntenin, ALIX and SDC4 while leaving other exosomal markers unaffected. Interestingly, it also blocks the sorting of EpCAM, a bona fide target used for carcinoma exosome immunocapture. Our study highlights the first characterization of a small pharmacological inhibitor of the syntenin-exosomal pathway, of potential interest for exosome research and oncology.

Bismuth subsalicylate nanoparticles with anaerobic antibacterial activity for dental applications.

In recent years, nanomaterials have been used in the medical-dental field as new alternative antimicrobial agents. Bismuth subsalicylate (BSS) has been used as an antimicrobial agent, but the effect of BSS in the form of nanoparticles (BSS-nano) as a potential antimicrobial agent has not been tested, in specific against bacteria responsible for periodontal disease. The aim of this study was to evaluate the antibacterial effect of BSS-nano against oral anaerobic bacteria and to assess the safety of BSS-nano by evaluating their cytotoxicity in human gingival fibroblast (HGF-1) cells. BSS-nano were synthesized by laser ablation and were previously physico-chemically characterized using in vitro assays. The antibacterial activity was measured using the tetrazolium-based XTT assay, and cytotoxicity was determined using lactate dehydrogenase (LDH) and MTS assays in HGF-1 cells. Transmission electron microscopy of HGF-1 exposed to BSS-nano was also performed. BSS-nano was shown to have a primary size of 4-22 nm and a polygonal shape. Among the tested bacterial strains, those with a greater sensitivity to BSS-nano (highest concentration of 21.7 µg ml-1) were A. actinomycetemcomitans, C. gingivalis, and P. gingivalis. BSS-nano at a concentration of 60 µg ml-1 showed low cytotoxicity (6%) in HFG-1 cells and was mainly localized intracellularly in acidic vesicles. Our results indicate that the concentration of BSS-nano used as an effective antibacterial agent does not induce cytotoxicity in mammalian cells; thus, BSS-nano can be applied as an antibacterial agent in dental materials or antiseptic solutions.

Lead exposition by gunshot ingestion in red-legged partridge (Alectoris rufa).

Absorption of low concentrations of lead may result in a wide range of sublethal effects in birds. Although waterfowl appear the most severely affected group for this heavy metal, leadpoisoning-mortality has been observed in a wide variety of bird species, ie raptors and upland game birds. In this present work, hepatic lead levels in different red-legged partridges are presented to indicate threshold values which could help in future toxicological studies when considering the lack of information about lead poisoning of such birds in the wild.

Lesiones purpúricas acrolocalizadas y fiebre

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A de novo phe671eu mutation in the SRY gene in a patient with complete 46,XY gonadal dysgenesis.

The sex-determining region of the Y chromosome (SRY) gene initiates the process of male sex differentiation in mammalians. In humans, mutations in the SRY gene have been reported to account for 10-15% of the XY sex reversal cases. In this report we describe the clinical, endocrinological and molecular data of a patient with complete 46,XY gonadal dysgenesis caused by a de novo mutation affecting SRY amino acid phenylalanine at position 67 (F67L), located within the highly conserved high mobility group (HMG) box coding region of the gene.

Talar fractures: three case studies.

Three case studies of fractures are presented that demonstrate the potential morbidity that these injuries can cause as well as the acceptable outcomes if treated appropriately. Two of the cases are talar fracture dislocations; the third is an osteochondral fracture of the talus. The importance of early treatment with open reduction and internal fixation is demonstrated. Success following surgical intervention in a nonhealed osteochondral fracture of the talus is also demonstrated.

Clinical expression and SRY gene analysis in XY subjects lacking gonadal tissue.

In several syndromes genetic males lack gonadal tissue. A range of phenotypes are seen, which varies from complete female external genitalia to anorchic subjects with sexual infantilism. Differences in phenotypic expression depend on the stage at which testes degenerated during intrauterine development. Although most cases of these syndromes are sporadic, several instances of familial recurrence suggest a genetic origin. To help elucidate the source, we performed molecular analysis of the complete SRY gene open reading frame in two subjects with true agonadism and in two with anorchia. Our results add to previous findings indicating that molecular defects in SRY are not readily identified as a cause of these syndromes.

[Prevention of sexually transmitted diseases in women: association with socioeconomic and demographic variables]. / Prevenção de doenças sexualmente transmissíveis em mulheres: associação com variáveis sócio-econômicas e demográficas.

Sexually transmitted diseases (STDs) have been a subject of discussion both among scientists and in the mass media, especially because of their association with the human immunodeficiency virus (HIV). We studied the adoption of specific protective behaviors for the prevention of STDs among women, as well as the associations between these behaviors and socioeconomic and demographic variables. This was a descriptive study based on secondary data from a previous study carried out in Campinas, São Paulo State, Brazil. A total of 635 women were selected using the social network ("snowball") technique. Subjects were classified into four groups: adolescents and adults of upper middle and lower socioeconomic status, respectively. Condoms were the STD prevention method most frequently mentioned by interviewees. A negative association was observed between having a steady partner and condom use in all the groups. The main reason mentioned for not using condoms was "having a single partner and trusting him". Among adolescents, a positive association was observed between schooling above the 8th grade and condom use, and a negative association was observed between age and condom use. Among adults, only condom use in general was also positively associated with socioeconomic status.

Partially deleted SRY gene confined to testicular tissue in a 46,XX true hermaphrodite without SRY in leukocytic DNA.

True hermaphroditism is an uncommon form of intersexuality in which testicular and ovarian tissue develop in the same individual. Most true hermaphrodites are 46,XX and lack SRY, the testis-determining gene. We describe results of molecular studies performed in a 46,XX true hermaphrodite SRY-negative in DNA from blood leukocytes but SRY-positive in DNA obtained from the testicular portion of the ovotestis. Surprisingly, the SRY identified in gonadal DNA carries a partial deletion at the 5' end of the gene. Our patient is the first case of a naturally occurring deletion within the SRY ORF (with a normal HMG box) and provides a new explanation for the abnormal gonadal development observed in 46,XX true hermaphrodites.

Women's preferences for vaginal antimicrobial contraceptives. I. Methodology.

Sexually transmitted diseases, including AIDS, and unplanned pregnancies continue to be a serious worldwide problem. A number of organizations are developing woman-controlled vaginal formulations to prevent these problems. However, little information is available regarding the types of products women prefer even though such knowledge is essential to obtain widespread use. This is the first of several articles that describe the results of a consumer preference study for such vaginal formulations performed in Campinas, São Paulo State, Brazil. Because no published methodology was available, the instruments and interview techniques were developed first and procedures established for the identification and participation of research subjects. After preparation of a questionnaire, a pilot study was performed to evaluate it, to establish the interview technique, and to determine the optimal method for subject recruitment. Based on the results, the approach was selected and applied to 635 subjects from different age and socioeconomic groups. The developed methodology and questionnaire, the advantages and the problems encountered, are presented.

Women's preferences for vaginal antimicrobial contraceptives. II. Preferred characteristics according to women's age and socioeconomic status.

A study was carried out to identify characteristics that women would want for an idealized vaginal contraceptive, and the possible association of these characteristics with age and socioeconomic status. The study was done in Campinas, São Paulo State, Brazil. A total of 635 women were selected by age and socioeconomic status, using the "social network" technique. Almost half were adolescents (15-19 years old) and the rest were adults (20-45 years old). Half were of low socioeconomic status and the rest of medium-high status. The data were analyzed with SPSS-PC and EPI-INFO 6.0. Logistic regression and chi 2 were used for the analysis. Despite some differences found between age and socioeconomic status in regard to the characteristics desired for the idealized method, most of the participants expressed the same preferences. The results indicate that women would like the idealized method to be a cream, rather than a suppository, with no odor or flavor, to be colorless, to be placed in the vagina with an applicator well before coitus, and to offer protection against sexually transmitted diseases including AIDS.

Women's preferences for vaginal antimicrobial contraceptives. III. Choice of a formulation, applicator, and packaging.

Novel vaginal formulations are under development to combat the increasing incidence of sexually transmitted diseases, including AIDS, and also unplanned pregnancies. A study was performed to determine women's preferences for different dosage forms (gel, cream, ovule/suppository, film, foam, tablet), width, length, and color of an applicator, and various types of packages. The study was conducted in Campinas, Brazil. A total of 635 women were interviewed, including both adolescents and adults and low and middle-high socioeconomic groups. The large majority of the women preferred a gel over a cream; both were preferred over the other methods. When asked which method they would not use, the film was most frequently identified, followed by the tablet and ovule. The primary reasons for selecting a particular dosage form were ease of use, absence of odor or the presence of a pleasant one, absence of color, and insertion with an applicator. The major reasons for not using a method were discomfort, "plastic" appearance, distrust of effectiveness, difficulty with insertion, messiness, and rigidity/hardness. The majority of the women liked the applicator shown. The prefilled single dose applicator was by far the preferred packaging. This information should aid in the development of consumer-friendly, vaginal formulations.

Women's preferences for vaginal antimicrobial contraceptives. IV. Attributes of a formulation that would protect from STD/AIDS.

Vaginal formulations may have "dual" protective activity, against sexually transmitted diseases/AIDS and unplanned pregnancy. The attributes that women find acceptable or unacceptable for such dual protective methods were investigated. More than 50% of the women would not accept messiness, but it was more accepted for dual protective methods than for contraceptives. Very few women would use a dual protective method if it caused vaginal irritation, itching, swelling, or burning, problems associated with presently marketed methods. More than half of the women would use it if it appeared on the penis of their partner or required refrigeration. Use of an applicator to insert the formulation was generally preferred over a manual method. Most women preferred the formulation to be colorless or white, about 16% liked light colors, and about 10% liked darker colors. Almost half of the women were willing to pay up to $5.00 per application of a dual protective formulation, about 15% $3.00, and 30% $1.00. Dual protective methods seem highly acceptable and women would pay much more for them than for condoms. However, these methods should be free of problems usually associated with presently marketed formulations.

Handwashing practices in a tertiary-care, pediatric hospital and the effect on an educational program.

OBJECTIVE: To study the frequency of handwashing and the effects of an educational program. DESIGN: A prospective study. SETTING: A tertiary-care, pediatric hospital. PARTICIPANTS: Three divisions (two general pediatric wards and one infectious disease ward). The personnel observed included 60 medical staff (interns, residents, and attending, including consulting, physicians), 37 nurses, and 15 paramedical staff. INTERVENTIONS: The study was carried out in 5 phases: (1) unobtrusive observation to obtain a baseline handwashing rate; (2) observation after written notification; (3) observation after providing motivating devices: movies, brochures, posters; (4) discontinuation of observation and motivation; (5) unobtrusive observation, to obtain a residual handwashing rate. RESULTS: During this study, 1,123 patient contacts were observed. The baseline handwashing rates before and after patient contact were 52% and 49%, respectively. During phase 2, handwashing rates before and after patient contact increased slightly to 56% and 52%, respectively. During phase 3, rates increased to 74% and 69% (P < .01). However, rates fell during the final phases to 49% and 52%, respectively (P < .01). There were no significant differences among hospital staff in any phase of this study (P > .05). CONCLUSIONS: Constant motivation, using movies, brochures, and posters, transiently increased the frequency of handwashing among the house staff of a tertiary-care facility; however, to be effective, this motivation needs to be sustained.

Mental health utilization in women with symptoms of depression.

This paper examines the help-seeking process of mental health services in women with high depressive symptoms. The data are based on an island wide probabilistic sample (n = 1,062) of 18- to 64-year-old women living in low socioeconomic areas in Puerto Rico. Symptoms of depression were measured by the Center for Epidemiological Studies Depression Scale (CES-D). Results show that one out of three women living in poor residential areas report high depressive symptoms. Of these women with high depressive symptoms, only 12% seek help from a mental health specialist and 14.5% from a general health care provider to deal with their emotional problems. Some factors related to the use of mental health services are: presence of an occupational disability, head of household status, having private insurance, and having a regular source of care. These data suggest that women underutilize mental health services and overutilize physical health services to deal with their emotional problems. The lack of recognition of emotional problems by these women may explain the low utilization of mental health services.

Burkitt's lymphoma presenting as Tolosa-Hunt syndrome.

An 11-year-old girl presented with acute, severe symptoms resembling Tolosa-Hunt syndrome. Response to corticosteroids was rapid and satisfactory, but of short duration. Cranial magnetic resonance imaging demonstrated a supra- and parasellar mass and the abdominal ultrasound demonstrated a round tumor. Histopathologic study of the abdominal mass revealed Burkitt's lymphoma.

A receiver operating characteristic (ROC) curve analysis of a model of mental health services use by Puerto Rican poor.

In this study, the contribution of four distinct domains of the Help Seeking-Decision Making model to predicting the use of mental health services is examined. Using a proposed methodology the authors assess the relevance of this model and its domains to mental services planning. The methodology combines logistic regression analysis and receiver operating characteristic (ROC) curves. Logistic regression analysis allows us to examine the individual variables of the model and generate predictions about use. ROC curves allow us to compare and interpret the relative contribution of a predisposing domain, a physical and mental health domain, an enabling-restrictive domain, and an organizational domain in correctly classifying users and nonusers of mental health services. The physical and mental health domain yielded a Somer's D-statistic of 0.7, which corresponds to an 85% correct classification of randomly selected pairs of users and nonusers. The study findings suggest that comparing ROC curves helps to describe and interpret the domains of the model that are relevant for making predictions about who will or will not use mental health services during a 1-year period.

[Evaluation of vesico-ureteral reflux in infants under 6 months of age]. / Evolución del reflujo vesicoureteral en lactantes menores de seis meses.

Forty-five infants less than 6 months old with vesicoureteral reflux have been evaluated in the Neonatology Unit of Niño Jesus Hospital. All of them have received medical treatment. We found bilateral vesicoureteral reflux in 55.6%, predominantly degree II (70%). Clinical symptoms were not specific, but it was evident that urine cultures were negative in 31.12%. After a mean follow-up of 31.5 months, kidney status was evaluated with echographic procedures. We found good growth in all but one case which was initially hypoplastic. New lesions were not demonstrated in the kidneys. We report a good prognosis for vesicoureteral reflux in infants of less than 6 months of age that have received only medical treatments. Therefore, we emphasize the importance of recognizing this pathology in infants, including those with negative urine cultures.