The novel p.E89K mutation in the SRY gene inhibits DNA binding and causes the 46,XY disorder of sex development

Male sex determination in humans is controlled by the SRY gene, which encodes a transcriptional regulator containing a conserved high mobility group box domain (HMG-box) required for DNA binding. Mutations in the SRY HMG-box affect protein function, causing sex reversal phenotypes. In the present study, we describe a 19-year-old female presenting 46,XY karyotype with hypogonadism and primary amenorrhea that led to the diagnosis of 46,XY complete gonadal dysgenesis. The novel p.E89K missense mutation in the SRY HMG-box was identified as a de novo mutation. Electrophoretic mobility shift assays showed that p.E89K almost completely abolished SRY DNA-binding activity, suggesting that it is the cause of SRY function impairment. In addition, we report the occurrence of the p.G95R mutation in a 46,XY female with complete gonadal dysgenesis. According to the three-dimensional structure of the human SRY HMG-box, the substitution of the conserved glutamic acid residue by the basic lysine at position 89 introduces an extra positive charge adjacent to and between the positively charged residues R86 and K92, important for stabilizing the HMG-box helix 2 with DNA. Thus, we propose that an electrostatic repulsion caused by the proximity of these positive charges could destabilize the tip of helix 2, abrogating DNA interaction.

Riscos ocupacionais e acidentes de trabalho em um serviço de atendimento móvel de urgência do Rio Grande do Norte

Exploratory, descriptive and quantitative study with prospective data, performed in the Mobile Emergency Care Service in the metropolitan region of Natal/RN, in order to identify the knowledge of the multidisciplinary team about the rules of standard precautions and worker safety, to identify occupational hazards peculiar to the activities of this service; characterize work-related accidents (WRA) and know the procedures adopted after each WRA. The population consisted of 162 professionals and data were collected between the months of November and December 2010. As for personal and professional characteristics, of the 162 professional, 12,96% were physicians; 6,79%, nurses; 33,95%, nursing technicians, 46,29%, conductors; 74,70% were male; 43,21% were between 31 and 40 years old; 69,33% lived in Natal/RN, 50,00% had completed high school; 58,64% were married; 69,75% had children, 46,91% were between 1 and 4 years of training; 61,73% had improvement courses; 59,25% had 3 to 4 years of service; 54,32%, with 1-4 years experience in emergency; 44,44% received 1-2 minimum wages; 78,40% received insalubrity premium; 67,28% worked in Basic Support Unit (BSU); 83,95% had journey on SAMU Metropolitano of 31-40 hours per week; 52,47% had other employments. As for knowledge of rules of standard precautions, safety and occupational hazards, 99,38% knew what it was WRA; 62,96% gave incomplete answers; 74,07% knew the rules of prevent WRA; 46,67% acquired this knowledge in lectures; 53,09% knew Personal Protective Equipment (PPE); 71,60% gave incorrect answers about the importance of standard precautions; 45,06% never received an educational intervention on this issue; 89,51% said that educational interventions in the prevention of WRA are very important; 90,12% pointed out this as a very important issue in the workplace; 27,00% suggested guidance on the topic in the workplace; regarding the physical hazards, 34,57% considered noise as the most important; about chemical hazards, 78,40% chose the gases and smoke; for biological hazards, 48,77% reported contact with the blood; for mechanical hazards, 80,86% said that were transport accidents; about ergonomic risks, 40,12% say it is the tension/stress in the care of critically ill, psychiatric and aggressive patients; and there was an average of 4,5 to the feeling of safety in the workplace. Regarding the data on the WRAs occurred, 31,48% experienced at least one accident event; 72,55% did not notify it; 60,98% answered that there was no routine for notification; 56,86% were performing patient transportation; 49,02% were hurt in the Basic Support Unit/Rescue Unit (BSU/RH); 60,78% occurred during the day; 96,08% of professionals were in normal work schedule (24 hours on duty); 31,37% had contusion; 58.82% had damage to members/pelvic girdle; 43,14% had traffic accidents. About the evolution of the WRA, 62,75% did not have to take time away from work; 76,47% had no sequelae; 88,24% did not require rehabilitation; no professional had a change of occupation. And by means of univariate logistic regression, showed that the nurses and male sex were risk factors for the occurrence of WRA. We conclude that there were gaps in the knowledge of staff regarding WRA, emphasizing the need for continuing education in biosafety in the service.

Efeitos dos esteroides anabólicos androgênicos sobre funções cognitivas de ratos

The use and the demand for substances that enhance masculinity, strength and sexual power are not novel. Over the years, this search has assisted the research directions in this area, leading to the discovery of the primary male sex hormone testosterone in 1935. Since then, numerous testosterone analogue compounds were synthesized, which are generically called Anabolic Androgenic Steroids (AAS). The AAS were produced for therapeutic purposes, but an increase in the use of these compounds for other purposes occurred over time. Initially they were used mainly to improve performance in athletes. However, recent studies have shown that the use of AAS by non-athletes with aesthetical purposes have been increasing as well. The abuse of AAS with non-clinical purposes can promote a number of physiological alterations, such as heart, liver, respiratory and psychological problems such as changes in mood, levels of anxiety and aggression. Exposure to supraphysiological doses of AAS is associated with behavioral changes, however, little is known about the effects of AAS on cognitive functions. In this work, we aimed to mimic the AAS abuse in humans with intramuscular administration of a supraphysiological dose of testosterone propionate (TP) in rats. We investigated the effects of this treatment on different aspects of cognitive function, specifically learning, memory and anxiety. Adult male Wistar rats were tested in the spontaneous alternation, novel object recognition and plus-maze discriminative avoidance tasks. The control group received intramuscular injections of vegetable oil (vehicle), and the TP group received injections of TP (10 mg/kg, i.m.). The injections were administered for 40 days, with intervals of 48 hours (chronic treatment) or in a single injection (acute treatment). In addition to the behavioral assessments, we performed biochemical analyzes as indicators of the endocrine effects of the treatment. Our results show that chronic treatment with a supraphysiological dose of TP caused memory impairments in the novel object recognition and the discriminative avoidance tasks. The spatial working memory (evaluated by spontaneous alternation task) was not affected. Also, we did not observe changes in anxiety levels. Regarding the biochemical parameters, chronic treatment increased serum levels of glutamicpyruvic transaminase, an indicator of hepatic and pancreatic lesions (as those observed after chronic use of these substances in humans). On the other hand, acute treatment with PT did not promote significant changes in any of these parameters when compared to the control group. In summary, we conclude that chronic treatment with a supraphysiological dose of testosterone propionate produces memory deficits in novel object recognition and retrieval of the discriminative avoidance task in adult male rats

Elaboração e avaliação de indicadores comportamentais de aderência ao tratamento hemodialítico

Introduction: This work intents to characterize behavioral indicators of tack to the hemodialysis treatment in a sample of carrying patients of chronic kidney failure (CKF) in the great Natal/RN. The therapeutical adherence represents the agreement degree between the patient behavior and the health team lapsings. The CKF is the gradual and irreversible loss of the renal function, being the hemodialysis treatment an important alternative to assist or to substitute the kidneys. Method: The sample consisted in 80 chronic kidney patients in hemodialysis treatment in two located clinical centers in the region of the great Natal, RN. It was used as instruments (a) a protocol of clinical data collection, (b) the Millon Index of Personality Styles (MIPS) and (c) a script of halfstructuralized interview. Results: The results show a balance between the genders (51% of female and 48.8% of the male sex), average age and equal average time of dialysis respectively to the 43,4 years (±13,25 years) and 22,04 years (±4,24 years). The marital status of half of the sample is married, predominating basic education (43.6%) and a familiar income until a minimum wage (43.8%). It had been defined six physicianlaboratorial indicators to evaluate the therapeutical adherence, further the use of the evaluation of the health team and the patient themselves. Thus, there was an average adherence around 55.97% of the sample ±18.37%). However only between selfassessment of the patients about the adherence and the assessment made by blood pressure post-dialysis indicated a significant association (p=0,029, qui-square test). On the other hand, there was a significant association (p <0.05, chi-square test) among the criteria for treatment adherence and issues investigated in the interview - the perception on the quality of the health services provided to patients, the difficulties following the prescribed diet, the characterization of the days between dialysis sessions and the perception of patients about the dialysis sessions. It was also noted a significant association (p <0.05, Levene test) between adherence to therapy and scales that constitute the MIPS. The health team characterized the patients more adherent behavior as an attitude of acceptance of the treatment, looking actively for their implementation, for more information and knowledge, and establishing a positive communication with the team and with other patients. Similar results were confirmed by the MIPS evaluation. According to that assessment the more compliant patients adopt a more optimistic attitude, trying to act or adapt themselves to their environment, processing cognitively both concrete and objective information, such as more speculative and symbolic information. In addition they establish a gregarious, cooperative, submissive and flexibly pattern of interpersonal relationships to social demands. These characteristics managed to explain 55.7% of the adherence variation according the health team and 23.3% of the variation according the CaxP laboratory indicator. Conclusions: The MIPS shown to be able to identify the most and least adherent to therapy patients. The use of different adherence indicators is important for an evaluation covering the different facets of this process. The adhesion levels are observed within registered by the relevant literature. There is need for further studies with a larger sample to deepen the data findings in this work

Presence and morphology of the molar tubercle according to dentition, hemi-arch and sex

The purpose of this study was to assess the presence and the degree of expression of the molar tubercle according to sex, dentition and hemi-arches. Study casts of 126 patients were assessed, and those were under orthodontic treatment at the University of Franca, UNIFRAN; they were from both sexs, from 4 to 13 years old. The upper second primary molars and the upper first permanent molars, from both sides, were evaluated regarding the presence and the degree of expression of the molar tubercle. For an association study, the qui-square test was utilized. The concordance about the presence or absence of the molar tubercle according to dentition, hemi-arch and sex, was estimated by the Kappa Statistics. There was a sexual dimorphism concerning the presence/absence of the molar tubercle (p=0.009), however there was no significant association between the degree of expression of the tubercle and the sex (p=0.791). The molar tubercle was more frequently observed in the male sex, in upper second primary molars and in the form of depression. There was a significant and "moderate" concordance between the left and right sides in primary dentition (k=0.596), there was a "good" concordance in permanent dentition (k=0.708) and a "weak" and significant concordance between the presence of the molar tubercle and dentition (k=0.207).

THE HYPOPHYSEAL-TESTICULAR AXIS AND SEX ACCESSORY-GLANDS FOLLOWING CHEMICAL SYMPATHECTOMY WITH GUANETHIDINE OF PRE-PUBERTAL TO MATURE RATS

Selective chemical sympathectomy of the internal sex organs of prepubertal to mature male Wistar rats was performed by chronic treatment with low doses of guanethidine. Plasma testosterone and luteinizing hormone and the intratesticular level of testosterone were determined. The weight and fructose content of seminal vesicle and ventral prostate were also investigated. The results showed that sympathetic innervation is related to the control of the hypophyseal-testicular axis as well as to the growth and potential secretory activity of the male sex accessory glands.

Cytogenetic analysis of Epicauta atomaria (Meloidae) and Palembus dermestoides (Tenebrionidae) with Xyp sex determination system using standard staining, C-bands, NOR and synaptonemal complex microspreading techniques

The mitotic and meiotic chromosomes of the beetles Epicauta atomaria (Meloidae) and Palembus dermestoides (Tenebrionidae) were analysed using standard staining, C-banding and silver impregnation techniques. We determine the diploid and haploid chromosome numbers, the sex determination system and describe the chromosomal morphology, the C-banding pattern and the chromosome(s) bearing NORs (nucleolar organizer regions). Both species shown 2n = 20 chromosomes, the chromosomal meioformula 9 + Xyp, and regular chromosome segregation during anaphases I and II. The chromosomes of E. atomaria are basically metacentric or submetacentric and P. dermestoides chromosomes are submetacentric or subtelocentric. In both beetles the constitutive heterochromatin is located in the pericentromeric region in all autosomes and in the Xp chromosome; additional C-bands were observed in telomeric region of the short arm in some autosomes in P. dermestoides. The yp chromosome did not show typical C-bands in these species. As for the synaptonemal complex, the nucleolar material is associated to the 7th bivalent in E. atomaria and 3rd and 7th bivalents in P. dermestoides. Strong silver impregnated material was observed in association with Xyp in light and electron microscopy preparations in these species and this material was interpreted to be related to nucleolar material.

Morphologically differentiated sex chromosomes in neotropical freshwater fish

A general survey of the occurrence of morphologically differentiated sex chromosomes in the neotropical freshwater fishes is presented. The total number of 32 occurrences involving simple XX-XY and ZZ-ZW, and multiple X1X2Y, XY1Y2 and ZW1W2 sex chromosome systems is described, with comments on the aspects of sex chromosome evolution in this fish fauna. The occurrence of different sex chromosome systems in related species of the same genus, or in different populations of the same nominal species, involving male and sometimes female heterogamety, and differences in the molecular composition of sex-linked heterochromatin, are considered as indicative of the early stage of sex chromosomes evolution in fish.

Chronic renal failure in male and female rats

Gender influences the progression of chronic renal failure (CRF). We studied male (M) and female (F) Wistar rats for 90 days: castrated (CMc, n=7; CFc, n=6) and non castrated controls (CM, n=9; CF, n=6); castrated (CRFMc, n=8; CRFFc, n=6) and non castrated animals submitted to 5/6 nephrectomy (CRFM, n=13; CRFF, n=6). Data are expressed as mean ± SEM. Proteinuria (PTN) was higher in CRFM (554 ± 69mg/24h) compared to CRFMc (277 ± 85 mg/24h), but not in females (CRFF=193 ± 20mg/24h, CRFFc=164 ± 71mg/24h). Mesangial fractional volume increased in all CRF animals. CRF animals showed an increase of glomerular sclerosis index (GSI) and tubulointerstitial damage (TID) but in a smaller proportion in male castrated animals; the opposite occurred with females: castration induced an increase of these parameters. CRF animals showed increased cortical and glomerular fibronectin (FN) rates. Castration decreased glomerular and cortical FN rates in CRFM but not in females. In conclusion, proteinuria was higher in CRFM and probably led to glomerular and interstitial damage, as well as to FN accumulation, castration seems to protect against development of PTN, TID and FN accumulation in males. Castrated female rats presented mesangial expansion, with no changes in PTN, TID and FN rates. It seems that female sex hormones do not protect against renal disease progression, instead, we suggest that male sex hormones lead to acceleration of CRF.

In search of work. International migration of women in Latin America and the Caribbean. Selected bibliography

Includes bibliography

Estresse, qualidade de vida e percepção de suporte familiar em porteiros

Pós-graduação em Psicologia do Desenvolvimento e Aprendizagem - FC

Avaliação da qualidade de vida de pacients tratados e em tratamento para hanseníase: uso do Dermatology Life Quality Index e do Whoqol-bref

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Differential expression of IGF-I mRNA and peptide in the male and female gonad during early development of a bony fish, the tilapia Oreochromis niloticus

Insulin-like growth factor I (IGF-I) plays a key role in the complex system that regulates bony fish growth, differentiation, and reproduction. The major source of circulating IGF-I is liver, but IGF-I-producing cells also occur in other organs, including the gonads. Because no data are available on the potential production sites of IGF-I in gonad development, developmental stages of monosex breedings of male and female tilapia from 0 day postfertilization (DPF) to 90 DPF were investigated for the production sites of IGF-I at the peptide (immunohistochemistry) and mRNA (in situ hybridization) level. IGF-I mRNA first appeared in somatic cells of the male and female gonad anlage at 7 DPF followed by IGF-I peptide around 9-10 DPF. Gonad anlagen were detected from 7 DPF. Starting at 7 DPF, IGF-I peptide but no IGF-I mRNA was observed in male and female primordial germ cells (PGCs) provided that IGF-I mRNA was not under the detection level, this observation may suggest that IGF-I originates from the somatic cells and is transferred to the PGCs or is of maternal origin. While in female germ cells IGF-I mRNA and peptide appeared at 29 DPF, in male germ cells both were detected as late as at 51-53 DPF. It is assumed that the production of IGF-I in the germ cells is linked to the onset of meiosis that in tilapia ovary starts at around 28 DPF and in testes at around 52-53 DPF. In adult testis, IGF-I mRNA and peptide occurred in the majority of spermatogonia and spermatocytes as well as in Leydig cells, the latter indicating a role of IGF-I in the synthesis of male sex steroids. In adult ovary, IGF-I mRNA and IGF-I peptide were always present in small and previtellogenic oocytes but only IGF-I peptide infrequently occurred in oocytes at the later stages. IGF-I expression appeared in numerous granulosa and some theca cells of follicles at the lipid stage and persisted in follicles with mature oocytes. The results suggest a crucial role of local IGF-I in the formation, differentiation and function of tilapia gonads.

Sex differences in cryptogenic stroke with patent foramen ovale

BACKGROUND: Sex differences in patients with patent foramen ovale (PFO) and cryptogenic stroke have not been systematically analyzed. We aimed to determine sex influences on demographics, vascular risk factors, clinical manifestations, stroke location, and clinical outcome. METHODS: One thousand two hundred eighty-eight consecutive patients with ischemic stroke or transient ischemic attack (TIA) were admitted to a single stroke center. All patients underwent a complete stroke workup including clinical examination, standard blood tests, cerebral and vascular imaging, transesophageal echocardiography, and 24-hour electrocardiography. In 500 patients, no definite etiology could be established (cryptogenic stroke/TIA). Of them, 167 patients (107 men and 60 women, mean age 52 +/- 13 years) had an PFO. RESULTS: The prevalence of PFO in patients with cryptogenic stroke or TIA was higher in men than in women (38% vs 28%, P = .014). Stroke severity and the prevalence of risk factors did not differ between the 2 sexes. There was an independent association between male sex and stroke location in the posterior cerebral circulation (OR 3.0, 95% CI 1.4-6.5, P = .006). Men and women did not differ in respect to PFO grade, prevalence of right-to-left shunt at rest, or coexistence of atrial septal aneurysm. Clinical outcome at 3 months was similar in both sexes. CONCLUSION: Patent foramen ovale was more prevalent in men than in women with cryptogenic stroke. There were no sex influences on age, risk factors, echocardiographic characteristics of PFO, or clinical outcome. Male sex was independently associated with stroke in the posterior cerebral circulation.