Testicular histomorphometric patterns and spermatogenesis dynamics of Oecomys bicolor tomes, 1860 (Rodentia: Cricetidae).

Although the order Rodentia does not present a high risk of extinction compared to mammals as a whole, several families demonstrate high levels of threat and/or data deficiency, therefore highlighting the need for targeted research and the application of ecological and reproductive data to the development of conservation actions. The order Rodentia, the largest among mammals, includes 9 families, and the family Cricetidae is the most diverse of the Brazilian rodents. In Brazil, 12 of the 16 genera of Oecomys are found. Oecomys bicolor is known in Brazil as the 'arboreal rat' and is, found in dry, deciduous and tropical forests. The mean body weight of Oecomys bicolor was 35.8 g and the gonadal, tubular and epithelial somatic indexes were, 0.53%, 0.47% and 0.37%, respectively. Seminiferous tubules volume density was 89.72% and the mitotic and meiotic indexes corresponded to 8.59 and 2.45 cells, respectively, and the yield of spermatogenesis was 23.83 cells. The intertubular compartment represented 10.28% of the testis parenchyma and around 5% of the interstitial space was occupied by Leydig cells, whose number per gram of testis was 11.10 × 107 cells. By evaluating the biometric and histomorphometric characteristics of the testis, there is evidence that this species has a high investment in reproduction. Due to the high contribution of the seminiferous epithelium and the intertubular compartment in this species, compared to the others of the same family, it is possible to infer that the species Oecomys bicolor has a promiscuous reproductive behaviour.

Prevalence of urologic sequelae and bladder and bowel dysfunctions in patients with congenital Zika syndrome: A multicenter evaluation of the Zika virus bladder and bowel sequelae assistance network.

INTRODUCTION: Neurogenic bladder was first confirmed as a urological sequela of Congenital Zika Syndrome (CZS) in 2018. Further clinical-epidemiological evidence also confirmed neurogenic bowel dysfunction and cryptorchidism. To strengthen the care for these children, the Congenital Zika Virus Bladder and Bowel Sequelae Network (RASZ in Brazilian) was created, including six integrated centers in Brazil. This article represents the initial outcome of the efforts by RASZ. OBJECTIVE: To evaluate the prevalence of bladder and bowel dysfunction, cryptorchidism and other urological sequelae related to CZS in cohorts attended in six Brazilian states. STUDY DESIGN: Observational, prospective, multicenter study including children with CZS assisted in one of six RASZ collaborative centers between June 2016 and February 2023. Data were collected from patient's first assessment using the same protocols for urological and bowel evaluation. Categorical variables were analyzed by frequency of occurrence and numerical variables by mean, median, and standard deviation. The study was approved by the Research Ethics Committees of each center, all parents/caregivers provided written informed consent. RESULTS: The study included 414 children aged 2 months to 7 years (mean 2.77 years, SD 1.73), 227 (54.8 %) were male and 140 (33,8 %) referred urological and bowel symptoms on arrival. Prevalence of both urological and bowel sequelae was 66.7 %, 51 % of children aged 4 years and older had urinary incontinence (UI). UTI was confirmed in 23.4 % (two presented toxemia) and among males, 18.1 % had cryptorchidism. Renal ultrasonography, performed in 186 children, was abnormal in 25 (13.4 %), 7 had hydronephrosis. Among the 287 children who performed urodynamics, 283 (98.6 %) were altered: 232 had a lower bladder capacity, 144 a maximum bladder pressure of ≥40 cm H2O, and 127 did not satisfactorily empty their bladder. DISCUSSION: A higher prevalence of NLUTD, neurogenic bowel and cryptorchidism was confirmed in children with CZS. Early diagnosis and appropriate treatment, including a multidisciplinary approach, may reduce the risk of UTIs, UI and kidney damage. A limitation of the study was the inability of children to complete the protocol, specifically urodynamic evaluation, and ultrasonography. In both exams, the percentage of abnormal cases was higher than that expected in the normal population. CONCLUSION: A 66,7 % prevalence of combined urological sequelae and bladder-bowel dysfunction related to CZS was confirmed in patients evaluated in six Brazilian cohorts. The most frequent changes were related to NLUTD, neurogenic bowel, and cryptorchidism. Prevalence may be underestimated due to access restrictions to diagnostic tests.

The relevance of the use of plant extracts on testicular cells: A systematic review.

This review aims to establish an association between traditional and scientific knowledge to allow the evaluation of the effectiveness of medicinal plants, as well as their risks based on the testicular microenvironment. A systematic search was performed using PRISMA guidelines. The descriptors were structured based on search filters built for three domains: Animals, Plants, and Testis. The filters on the PubMed/Medline platform were constructed using a hierarchical distribution of the MeSH Terms. Methodological quality assessments were performed using the SYRCLE risk bias tool. Data on testicular cells, hormones and biochemistry, sperm, and sexual behavior were evaluated and compared. The search came out with 2644 articles, and 36 articles met the inclusion criteria and were used in this review. The included studies analyzed testicular cells from murine models treated with crude plant extracts. Plant extracts act directly on the hypothalamic-pituitary axis and/or directly on testicular cells, inhibiting and stimulating the reproductive process, thus causing alterations in fertility rates. Apiaceae and the Cucurbitaceae families are the most used in male reproductive biology experiments, being Apiaceae described as sexual stimulants, while Cucurbitaceae are the main sources of deleterious effects on the male reproductive system.

Pfaffia glomerata polyploid accession compromises male fertility and fetal development.

ETHNOPHARMACOLOGICAL RELEVANCE: Pfaffia glomerata (Spreng.) Pedersen has traditionally been used as a tonic and a stimulant by the Brazilian population. It shows higher biomass accumulation and production of secondary compounds, such as the phytosterol 20-hydroxyecdysone. AIMS: The present study aimed to evaluate the effects of the hydroalcoholic extract of the root of tetraploid P. glomerata (BGEt) on testicular parenchyma, and its implications on fertility. MATERIAL AND METHODS: Adult Swiss mice were divided as: control (water) and sildenafil citrate (7 mg/kg), BGEt at 100, 200, and 400 mg/kg, and BGEtD 200 mg/kg (treated with BGE every three days). Males (n = 4/group) were mated with normal untreated adult females to assess fertility rates, while other animals (n = 6/group) were euthanized for testis, epididymis, and oxidative stress analyses. RESULTS: Increase in tubule diameter and epithelium height in the discontinuous group, in addition to an increase in the proportion of tubules with moderate pathologies was observed. The pre-implantation loss was lower in all treated groups. The post-implantation loss was significantly increased in all treated groups, except for the lowest BGEt dose. BGEt intake caused a decrease in daily sperm production, along with the number and quality of sperm in the epididymis. Changes were observed in protein carbonylation and hydrogen peroxide and nitric oxide levels, characterizing oxidative stress. CONCLUSIONS: The hydroalcoholic extract of P. glomerata tetraploid altered sperm and testicular parameters, compromising embryonic development after implantation.

Expression of thimet oligopeptidase (THOP) modulated by oxidative stress in human multidrug resistant (MDR) leukemia cells.

Thimet oligopeptidase (THOP) is a cytosolic metallopeptidase known to regulate the fate of post-proteasomal peptides, protein turnover and peptide selection in the antigen presentation machinery (APM) system. Oxidative stress influences THOP expression and regulates its proteolytic activity, generating variable cytosolic peptide levels, possibly affecting the immune evasion of tumor cells. In the present work, we examined the association between THOP expression/activity and stress oxidative resistance in human leukemia cells using the K562 cell line, a chronic myeloid leukemia (CML), and the multidrug-resistant (MDR) Lucena 1 (K562-derived MDR cell line) as model. The Lucena 1 phenotype was validated under vincristine treatment and the relative THOP1 mRNA levels and protein expression compared to K562 cell line. Our data demonstrated increased THOP1 gene and protein levels in K562 cells in contrast to the oxidative-resistant Lucena 1, even after H2O2 treatment, suggesting an oxidative stress dependence in THOP regulation. Further, it was observed higher basal levels of reactive oxygen species (ROS) in K562 compared to Lucena 1 cell line using DHE fluorescent probe. Since THOP activity is dependent on its oligomeric state, we also compared its proteolytic activity under reducing agent treatment, which demonstrated that its function modulation with respect to changes in redox state. Finally, the mRNA expression and FACS analyses demonstrated a reduced expression of MHC I only in K562 cell line. In conclusion, our results highlight THOP redox modulation, which could influence antigen presentation in multidrug resistant leukemia cells.

Disruption of Redox Homeostasis by Alterations in Nitric Oxide Synthase Activity and Tetrahydrobiopterin along with Melanoma Progression.

Cutaneous melanoma emerges from the malignant transformation of melanocytes and is the most aggressive type of skin cancer. The progression can occur in different stages: radial growth phase (RGP), vertical growth phase (VGP), and metastasis. Reactive oxygen species contribute to all phases of melanomagenesis through the modulation of oncogenic signaling pathways. Tetrahydrobiopterin (BH4) is an important cofactor for NOS coupling, and an uncoupled enzyme is a source of superoxide anion (O2•-) rather than nitric oxide (NO), altering the redox homeostasis and contributing to melanoma progression. In the present work, we showed that the BH4 amount varies between different cell lines corresponding to distinct stages of melanoma progression; however, they all presented higher O2•- levels and lower NO levels compared to melanocytes. Our results showed increased NOS expression in melanoma cells, contributing to NOS uncoupling. BH4 supplementation of RGP cells, and the DAHP treatment of metastatic melanoma cells reduced cell growth. Finally, Western blot analysis indicated that both treatments act on the PI3K/AKT and MAPK pathways of these melanoma cells in different ways. Disruption of cellular redox homeostasis by the altered BH4 concentration can be explored as a therapeutic strategy according to the stage of melanoma.

Alterations in the testicular parenchyma of Foxn1+/- and Foxn1-/- adult mice.

Nude mice carry an autosomal recessive mutation in the Foxn1 gene and therefore are homozygous recessive animals (Foxn1 -/-). The fertility rate of homozygous male (Foxn1-/- ) is low, which seems to be related to the delay in the production of gametes at the beginning of sexual maturity. The present study evaluated the structural and organizational aspects of the testicles of homozygous and heterozygous offspring related to the Foxn1 gene in mice, describing its implications on spermatogenesis. Adult males Balb/c, Foxn1+/- and Foxn1-/- mice were used. Testes and epididymis were harvested for histological, biochemical, and sperm transit analyses. Gonadal weight was significantly lower in Foxn1+/- and Foxn1-/- animals, the same behavior was noticed for the activity of antioxidant enzymes. In addition, tubular parameters such as epithelial proportion, length, and area, as well as germ and Leydig cell's populations were significantly reduced in the aforementioned groups, leading to lower sperm production. In conclusion, our results indicate the importance of the Foxn1 in Leydig cell's function, reflecting in the preservation of spermatogenesis, thus in germ cell's population and sperm cell production.

Urological outcomes in children with congenital Zika syndrome: The experience of a cohort in Campina Grande, Brazil.

OBJECTIVE: To describe the urological outcomes in children with congenital Zika syndrome (CZS) and investigate the relationship between clinical and urological findings in this population. METHODS: This cross-sectional study involved children with CZS followed up by a referral centre for children with microcephaly in the state of Paraiba in northeast Brazil. The urological evaluation included clinical history, urine culture results, ultrasonography of the urinary tract, and urodynamic evaluation, following the protocol proposed by Costa Monteiro et al. (2017). Descriptive statistical analysis was performed in addition to association and correlation tests, considering clinical and urodynamic variables. RESULTS: Among the 88 children with CZS (35.5 ± 5.5 months), 97.7% had microcephaly, and 51% presented urinary tract infection (UTI) confirmed with clinical history and lab tests. The number of confirmed UTI episodes varied from one to 14 per child. The urodynamic evaluation confirmed the presence of an overactive bladder in 78 children and incomplete voiding in 50. Urodynamic findings were associated with the number of confirmed UTI episodes, child's sex, and actual weight, in addition to the use of anticonvulsant and myorelaxant drugs. CONCLUSIONS: UTIs were confirmed in most children. Other urological outcomes observed were overactive bladder and low bladder capacity, which were associated with the number of confirmed UTI episodes, use of anticonvulsants and myorelaxants, and the child's sex and weight. These are treatable conditions, and it is paramount that paediatricians, neonatologists, and infectious disease specialists are aware of them to make clinical decisions and help reduce the risk of renal damage and other morbidities.

The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin.

Cancer development is associated with abnormal proliferation, genetic instability, cell death resistance, metabolic reprogramming, immunity evasion, and metastasis. These alterations are triggered by genetic and epigenetic alterations in genes that control cell homeostasis. Increased reactive oxygen and nitrogen species (ROS, RNS) induced by different enzymes and reactions with distinct molecules contribute to malignant transformation and tumor progression by modifying DNA, proteins, and lipids, altering their activities. Nitric oxide synthase plays a central role in oncogenic signaling modulation and redox landscape. Overexpression of the three NOS isoforms has been found in innumerous types of cancer contributing to tumor growth and development. Although the main function of NOS is the production of nitric oxide (NO), it can be a source of ROS in some pathological conditions. Decreased tetrahydrobiopterin (BH4) cofactor availability is involved in NOS dysfunction, leading to ROS production and reduced levels of NO. The regulation of NOSs by BH4 in cancer is controversial since BH4 has been reported as a pro-tumoral or an antitumoral molecule. Therefore, in this review, the role of BH4 in the control of NOS activity and its involvement in the capabilities acquired along tumor progression of different cancers was described.

Metastatic Melanoma Progression Is Associated with Endothelial Nitric Oxide Synthase Uncoupling Induced by Loss of eNOS:BH4 Stoichiometry.

Melanoma is the most aggressive type of skin cancer due to its high capability of developing metastasis and acquiring chemoresistance. Altered redox homeostasis induced by increased reactive oxygen species is associated with melanomagenesis through modulation of redox signaling pathways. Dysfunctional endothelial nitric oxide synthase (eNOS) produces superoxide anion (O2-•) and contributes to the establishment of a pro-oxidant environment in melanoma. Although decreased tetrahydrobiopterin (BH4) bioavailability is associated with eNOS uncoupling in endothelial and human melanoma cells, in the present work we show that eNOS uncoupling in metastatic melanoma cells expressing the genes from de novo biopterin synthesis pathway Gch1, Pts, and Spr, and high BH4 concentration and BH4:BH2 ratio. Western blot analysis showed increased expression of Nos3, altering the stoichiometry balance between eNOS and BH4, contributing to NOS uncoupling. Both treatment with L-sepiapterin and eNOS downregulation induced increased nitric oxide (NO) and decreased O2• levels, triggering NOS coupling and reducing cell growth and resistance to anoikis and dacarbazine chemotherapy. Moreover, restoration of eNOS activity impaired tumor growth in vivo. Finally, NOS3 expression was found to be increased in human metastatic melanoma samples compared with the primary site. eNOS dysfunction may be an important mechanism supporting metastatic melanoma growth and hence a potential target for therapy.

miR-138-5p induces aggressive traits by targeting Trp53 expression in murine melanoma cells, and correlates with poor prognosis of melanoma patients.

Deregulation of miRNAs contributes to the development of distinct cancer types, including melanoma, an aggressive form of skin cancer characterized by high metastatic potential and poor prognosis. The expression of a set of 580 miRNAs was investigated in a model of murine melanoma progression, comprising non-metastatic (4C11-) and metastatic melanoma (4C11+) cells. A significant increase in miR-138-5p expression was found in the metastatic 4C11+ melanoma cells compared to 4C11-, which prompted us to investigate its role in melanoma aggressiveness. Functional assays, including anoikis resistance, colony formation, collective migration, serum-deprived growth capacity, as well as in vivo tumor growth and experimental metastasis were performed in 4C11- cells stably overexpressing miR-138-5p. miR-138-5p induced an aggressive phenotype in mouse melanoma cell lines leading to increased proliferation, migration and cell viability under stress conditions. Moreover, by overexpressing miR-138-5p, low-growing and non-metastatic 4C11- cells became highly proliferative and metastatic in vivo, similar to the metastatic 4C11+ cells. Luciferase reporter analysis identified the tumor suppressor Trp53 as a direct target of miR-138-5p. Using data sets from independent melanoma cohorts, miR-138-5p and P53 expression were also found deregulated in human melanoma samples, with their levels negatively and positively correlated with prognosis, respectively. Our data shows that the overexpression of miR-138-5p contributes to melanoma metastasis through the direct suppression of Trp53.

Testicular morphometry of rats with Walker 256 tumor supplemented with L-glutamine.

Glutamine is often used to treat metabolic changes associated with anorexia-cachexia syndrome in patients with malignant neoplasms. Walker 256 tumor is an excellent model for studying these changes associated with cancer in different organs, including injuries in testicular functions. However, the effects of supplementing glutamine on testicular morphometry in this model have not yet been investigated. Thus, the objective of this study was to evaluate the effect of L-glutamine supplementation on testicular morphometry in rats transplanted with Walker 256 tumor cells. Forty puberty Wistar rats were divided into four groups: control without L-glutamine (C); control supplemented with L-glutamine (CG); inoculated with Walker 256 tumor cells (WT) and inoculated with Walker 256 tumor cells and supplemented with L-glutamine (WTG). The testicles were removed, weighed, fixed in Bouin, and included in paraffin for histomorphometric analysis. Walker 256 tumor caused quantitative changes in the tubular and intertubular compartments and tunica albuginea, with reductions in the percentages of lumen and tunica albuginea, number of Sertoli cells per gram of testis; number of Leydig cells; percentage of blood vessels and connective tissue in intertubule. However, glutamine supplementation prevented part of these changes caused by the tumor, presenting mainly a protective effect on the tunica albuginea and percentage of blood and lymph vessels in the intertubule. These results indicate the potential of L-glutamine was able to recover for testicular dysfunction associated with cancer.

Increased acute blood flow induced by the aqueous extract of Euterpe oleracea Mart. fruit pulp in rats in vivo is not related to the direct activation of endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Scientific evidence supports the antioxidant, anti-inflammatory and anti-lipidemic properties of Euterpe oleracea Mart. (açaí), which all converge to reduce cardiovascular risks. Macerating the pulp of açaí fruit produces a viscous aqueous extract (AE) rich in flavonoids that is commonly used in food production. In addition to nutritional aspects, cardiovascular benefits are attributed to AE by traditional medicine. AIM OF THE STUDY: Evaluation of AE impact on blood flow in vivo in rats and investigation of the mechanism underlying this response in vitro in rat endothelial cells (RECs). MATERIALS AND METHODS: For the measurement of acute blood flow, a perivascular ultrasound probe was used in Wistar rats. The in vitro assays employed REC to evaluate: concentration (1-1000 µg/mL) and time response (2-180 min) of AE in MTT cell viability assays; nitric oxide (NO) levels measurement and intracellular calcium handling using DAF-2DA and Fluo-4-AM, respectively; cellular biopterin content by HPLC; activation of Akt pathway using western blot analysis. For the chemical analyses of AE, stock solutions of the standards (+)catechin and quercetin were used for obtaining linear calibration curves. Identification and quantification of flavonoids in AE were based on comparisons with the retention times, increase in peak area determine by co-injection of AE with standards, UV-Vis scan and standard curves of known spectra. Results were expressed as mean ± standard deviation and data were analyzed using ANOVA followed by Tukey's post-test (p < 0.05). RESULTS: Although in vivo data have revealed the participation of NO in increasing of acute blood flow on abdominal aorta, in vitro analysis demonstrated that vasodilatation AE-induced is not related to its direct action on endothelial cells inducing eNOS activation. Besides, we demonstrated in isolated endothelial cells that highest concentrations of AE caused a reduction in NO levels, effect that could be partly justified by inhibition of Akt phosphorylation which, in turn, could decrease NOS activation. The involvement of cell transduction pathways involving variations in intracellular calcium and biopterins concentration were discarded. The participation of catechin and quercetin, identified in AE, was postulated to induce the responses of AE in REC. CONCLUSIONS: Despite the responses in vitro, vasodilation prevailed in vivo, probably by activating intermediate pathways, validating a potential beneficial effect of AE in reducing cardiovascular risks.

Relevance of the Isoflavone Absorption and Testicular Function: A Systematic Review of Preclinical Evidence.

Isoflavone is a phytoestrogen found in different types of food that can act as endocrine disrupters leading to testicular dysfunction. Currently, fragmented data on the action of this compound in the testicles make it difficult to assess its effects to define a safe dose. Thus, we systematically reviewed the preclinical evidence of the impact of isoflavone on testicular function. We also determined which form (aglycones or glycosylated) was the most used, which allowed us to understand the main biological processes involved in testicular function after isoflavone exposure. This systematic review was carried out according to the PRISMA guidelines using a structured search on the biomedical databases MEDLINE (PubMed), Scopus, and Web of Science, recovering and analyzing 22 original studies. The bias analysis and the quality of the studies were assessed by the criteria described in the risk of bias tool developed by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). The aglycones and glycosylated isoflavones proved to be harmful to the reproductive health, and the glycosylates at doses of 50, 100, 146, 200, 300, 500, and 600 mg/kg, in addition to 190 and 1000 mg/L, appear to be even more harmful. The main testicular pathologies resulting from the use of isoflavones are associated with Leydig cells resulting from changes in molecular functions and cellular components. The most used isoflavone to evaluate testicular changes was the genistein/daidzein conjugate. The consumption of high doses of isoflavones promotes changes in the functioning of Leydig cells, inducing testicular changes and leading to infertility in murine models.

Different Routes of Administration Lead to Different Oxidative Damage and Tissue Disorganization Levels on the Subacute Cadmium Toxicity in the Liver.

The toxic effects of cadmium (Cd) on hepatic parameters are widely described in the literature. Experimental models often make use of the intraperitoneal route (i.p.) because it is easier to apply, while in the oral route, Cd poisoning in humans is best represented by allowing the metal to pass through the digestive system and be absorbed into the bloodstream. Thus, this study investigated the Cd exposure impact on the liver, by comparing both i.p. and oral routes, both in single dose, in addition to the oral route in fractional doses. Swiss adult male mice received CdCl2 1.5 mg/kg i.p., 30 mg/kg oral single dose, and 4.28 mg/kg oral route in fractional doses for 7 consecutive days. Cd bioaccumulation was observed in all animals exposed to Cd. Hepatic concentrations of Ca and Fe increased only in the fractionated oral route. Liver activities of SOD and CAT increased only by oral single dose. GST decreased in all forms of oral administration, while MDA decreased only in i.p. route. Liver weight and HSI increased in the i.p. route, while organ volume increased in all forms of oral administration, and liver density increased in all animals exposed to Cd. In hepatic histomorphometry, the changes were more evident in oral administration, mainly in exposure to metal in a single dose. Thus, the subacute administration of Cd in different routes of administration leads to different changes in liver poisoning.

Anatomy of the dura mater venous sinus of Alouatta belzebul.

The anatomy of the dura mater's venous sinuses is important in the veterinary clinical and surgical area, for cranial procedures and interventions of wild animals, in addition to assisting in the management of neurological diseases, which can prevent serious complications. The macroscopic anatomy of the venous sinuses of the dura mater of Alouatta belzebul was studied. Five adult specimens, males and females, were dissected and fixed in 10% formaldehyde solution. In the dura mater of the Alouatta belzebul, nine venous sinuses were observed, being them dorsal sagittal sinus, ventral sagittal sinus, transverse sinus, straight sinus, sigmoid sinus, temporal sinus, parietal sinus, basilar sinus and cavernous sinus, with morphological similarities in origin, path and destination of blood flow to the internal jugular vein, assisting in the venous drainage function of the brain in this species. These data are similar to those found in other species of non-human and human primates such as Saimiri sciureus, Sapajus libidinosus and Homo sapiens. Of the venous sinuses observed, the cavernous sinus was of considerable clinical and surgical importance in Alouatta belzebul due to its topographic arrangement next to the internal carotid artery and pituitary gland, data that corroborate Sapajus libidinosus, Macaca fascicularis, Macaca mulatta, Papio ursinus, Cercopithecus pygerithrus and Galago senegalensis. In this context, the knowledge of the macroscopic anatomy of the venous sinuses of the dura mater may contribute to the role of veterinarians in less invasive surgical procedures in non-human primates such as Alouatta belzebul and other mammals.

Cadmium Exposure and Testis Susceptibility: a Systematic Review in Murine Models.

It is known that cadmium induces damage to the testis. However, the significant cadmium impact on the testicular architecture and the mechanisms involved in this process are not clear. Besides, the relationship between dose, route, and time of exposure and injuries remains poorly understood. Thus, we aimed to assess whether cadmium exposure in any dose, route, and time of exposure causes significant alteration in the testicular tissue of murine models, as well as the main mechanisms involved. We performed a structured search on the Medline/PubMed and Scopus databases to retrieve studies published until September 2018. The results were organized into an Adverse Outcome Pathway (AOP) framework. Also, a bias analysis of included studies was performed. We included 37 studies, and most of them identified significant histopathologies in both tubule and intertubule regarding routes, in a dose- and time-dependent manner. The damages were observed after the first hours of exposure, mainly vascular damages suggesting that vasculature failure is the primary mechanism. The AOP showed that potential molecular initiating events may mimic and interfere with essential elements disrupting proteins (structural and antioxidants), change in the oxidative phosphorylation enzyme activities, and gene expression alteration, which lead to reproductive failure (adverse outcome). Analysis of methodological quality showed that the current evidence is at high risk of bias. Despite the high risk of bias, cadmium triggers significant lesions in the testis of murine models, regarding routes, in a dose- and time-dependent manner, mainly due to vascular changes. Therefore, cadmium is a risk factor for male reproductive health.

Descriptive morphometry and stereology in accessing the testis structure and function of the marsupial Philander frenatus (Olfers, 1818) (Didelphimorphia: Didelphidae).

Philander frenatus is an important marsupial for the maintenance and conservation of the Atlantic Rainforest, however, it has biological characteristics that are still little explored. The study of the reproductive biology is an important key to understand the species reproductive strategies and to improve the development of conservation and management activities. The present study aimed to conduct a histological and morphometric investigation of the testis structure and function of P. frenatus. The average body and testicular weight were 445 g and 0.74 g, respectively, with a gonadosomatic index of 0.17%. The seminiferous tubules occupying 64.95% of the organ, totalising 9.26 m per gram of testis. The tubulesomatic and epitheliumsomatic indexes were 0.10% and 0.07%, respectively. Philander frenatus showed cell loss of approximately 98% during the proliferative phase and the spermatogenic yield was 10.3 cells. The high loss during the mitotic phase contributed to the low spermatogenic yield. The testicular parenchyma was composed of 35% of intertubular components, one of the highest proportions observed in mammals. Leydig cells were responsible for approximately 25% of the testes, followed by lymphatic space (6.44%), blood vessels and connective tissue (4% together). The organisation of the intertubular components resembles the Fawcett III category. The volume and number of Leydig cell per gram of testis were 2,627.12 µm3 and 91.28 × 106 cells, respectively. High investment in the intertubular compartment, specifically number and volume of Leydig cells in P. frenatus is consistent with territorial behaviour and polygynic mating system, which have greater androgenic capacity.

Detecção precoce do câncer de mama em Unidades Básicas de Saúde / Detección precoz de cáncer de mama en unidades básicas de salud / Early detection of breast cancer in primary care center

Resumo Objetivo: Analisar as ações para detecção precoce do câncer de mama realizadas por enfermeiros da atenção primária, de acordo com as diferentes configurações de unidades básicas de saúde. Métodos: Estudo de corte transversal, desenvolvido em 38 unidades básicas de saúde. As unidades foram selecionadas mediante cálculo de amostra aleatória simples; os critérios de inclusão foram os enfermeiros de ambos os sexos, com tempo mínimo de um ano de atuação na unidade. As diferentes hipóteses cogitadas foram avaliadas por meio de análise bivariada na tabela de contingência, utilizando o teste de qui-quadrado ou teste exato de Fischer; todos os testes realizados levaram em consideração um α bidirecional de 0,05 e intervalo de confiança (IC) de 95%. Resultados: Dos 133 enfermeiros do estudo, 46,6% atuavam em unidades básicas da Estratégia Saúde da Família, 31,6% em unidades mistas e 21,8% em unidades tradicionais. Houve melhor desempenho para o modelo Estratégia Saúde da Família, com resultados estatisticamente significativos para as seguintes ações: investigação dos fatores de risco (p=<0,001); orientação da idade ideal para exame clínico das mamas e a importância de sua realização (p=0,002 e p=<0,001 respectivamente); reunião educativa sobre câncer de mama (p=<0,001); busca ativa de mulheres com laudo suspeito (p=0,002) e encaminhamento à unidade de referência (p=<0,001). Conclusão: As ações para a detecção precoce do câncer de mama realizadas pelos enfermeiros diferenciam-se em relação à configuração da Unidade Básica de Saúde, sendo que as do modelo Estratégia Saúde da Família se aproximam mais das recomendações do Ministério da Saúde.

Resumen Objetivo: Analizar las acciones para la detección precoz de cáncer de mama realizadas por enfermeros de atención primaria, de acuerdo con las diferentes configuraciones de las unidades básicas de salud. Métodos: Estudio de corte transversal, llevado a cabo en 38 unidades básicas de salud. Las unidades fueron seleccionadas mediante cálculo de muestra aleatoria simple. Los criterios de inclusión fueron enfermeros de ambos sexos, con un tiempo mínimo de un año de actuación en la unidad. Las diferentes hipótesis consideradas fueron evaluadas mediante el análisis bivariado en la tabla de contingencia, utilizando la prueba χ² de Pearson o prueba exacta de Fisher. Todas las pruebas realizadas tuvieron en consideración un α bidireccional de 0,05 e intervalo de confianza (IC) de 95 %. Resultados: De los 133 enfermeros del estudio, el 46,6 % actuaba en unidades básicas de Estrategia Salud de la Familia, el 31,6 % en unidades mixtas y el 21,8 % en unidades tradicionales. Se observó un mejor desempeño en el modelo Estrategia Salud de la Familia, con resultados estadísticamente significativos en las siguientes acciones: investigación de los factores de riesgo (p=<0,001), orientación sobre la edad ideal para examen clínico de las mamas y la importancia de su realización (p=0,002 y p=<0,001 respectivamente), reunión educativa sobre cáncer de mama (p=<0,001), búsqueda activa de mujeres con resultados sospechosos (p=0,002) y derivación a la unidad de referencia (p=<0,001). Conclusión: Las acciones para la detección precoz de cáncer de mama realizadas por los enfermeros se diferencian según la configuración de la unidad básica de salud, entre las cuales el modelo Estrategia Salud de la Familia está más cerca de las recomendaciones del Ministerio de Salud.

Abstract Objective: To analyze the actions for early detection of breast cancer performed by primary care nurses, according to the different configurations of primary care center. Method: Cross-sectional study, carried out in a total of 38 primary care center. The centers were selected by calculating a simple random sample; the inclusion criteria were nurses of both genders, with at least one year working in the health center. The different hypotheses considered were evaluated by a bivariate analysis in the contingency table, using the chi-square test or Fisher's exact test; all tests performed considered a bidirectional α of 0.05 and a 95% confidence interval (CI). Result: Out of the 133 nurses in the study, 46.6% worked in primary care center of the Family Health Strategy, 31.6% in mixed centers and 21.8% in traditional ones. There was a better performance for the Family Health Strategy model, with statistically significant results for the following actions: investigation of risk factors (p=<0.001); orientation of the ideal age for clinical breast examination and the importance of its performance (p=0.002 and p=<0.001 respectively); educational meeting on breast cancer (p=<0.001); active search for women with suspicious medical reports (p=0.002) and referral to the health center (p=<0.001). Conclusion: The actions for early detection of breast cancer performed by nurses differ in relation to the configuration of the Primary care center, and those from the Family Health Strategy model are closer to the recommendations of the Ministry of Health.

Perfil de ocorrência no atendimento aos idosos pelo serviço de atendimento pré-hospitalar móvel / Profile of occurrence in the service to elderly people by the mobile pre-hospital care service / Perfil de ocurrencia en el servicio a personas mayores por el servicio móvil de atención prehospitalaria

Objetivo: analisar o perfil das ocorrências clínicas e traumatológicas em idosos atendidos pelo Serviço de Atendimento Móvel de Urgências. Métodos: estudo descritivo, transversal, documental retrospectivo, realizado em 359 registros do Serviço de Atendimento Móvel de Urgência em um município da Paraíba, entre julho de 2017 e julho de 2018. Utilizou-se um instrumento com questões sociodemográfica, natureza da ocorrência e intervenções realizadas. Analisou-se os dados com estatística descritiva e inferencial. Resultados: a maioria das ocorrências acometeram homens de 80 anos ou mais. Os agravos clínicos predominaram em ambos os sexos (79,9%), seguido pelas ocorrências traumáticas (19,4%). Destas, 84,2% foram quedas, 14,3% acidentes e 1,5% afogamento. A Unidade de Suporte Avançado de Vida foi utilizada em 77,2% das ocorrências. As intervenções prevalentes foram a instalação do acesso venoso periférico e a oxigenoterapia. Conclusão: enfatiza-se a necessidade do reconhecimento dos grupos vulneráveis para compreender os aspectos relacionados as ocorrências e implementar medidas preventivas

Objective: to analyze the profile of clinical and traumatological occurrences in elderly assisted by the Mobile Emergency Care Service. Methods: descriptive, cross-sectional, retrospective documentary study, carried out on 359 records of the Mobile Emergency Care Service in a municipality in Paraíba, between July 2017 and July 2018. It was used an instrument involving sociodemographic questions, nature of the occurrence and interventions performed. Data were analyzed using descriptive and inferential statistics. Results: most occurrences involved men aged 80 years or more. Clinical problems predominated in both genders (79.9%), followed by traumatic events (19.4%). Among these, 84.2% were falls, 14.3% accidents and 1.5% drowning. The Advanced Life Support Unit was used in 77.2% of the cases. The prevalent interventions were the installation of peripheral venous access and oxygen therapy. Conclusion: it emphasizes the need to recognize vulnerable groups to understand the aspects related to the occurrences and implement preventive measures

Objetivo: analizar el perfil de las ocurrencias clínicas y traumatológicas en ancianos atendidos por el Servicio de Atención móvil de Urgencia. Métodos: estudio descriptivo, transversal, documental retrospectivo, realizado en 359 registros del Servicio de Atención móvil de Urgencia en una ciudad de Paraíba, entre junio del 2017 y julio del 2018. Se utilizó un instrumento con preguntas sociodemográficas, naturaleza de la ocurrencia e intervenciones realizadas. Los datos se analizaron con estadística descriptiva e inferencial. Resultados: la mayoría de las ocurrencias acometieron hombres de 80 años o más. Los agravios clinicos predominaron en ambos sexos (79,9%), seguido por las ocurrencias traumáticas (19,4%). De estas, 84,2% fueron caídas, 14,3% accidentes y 1,5% ahogamiento. La Unidad Avanzada de Soporte de Vida fue utilizada en 77,2% de las ocurrencias. Las intervenciones predominantes fueron la instalación de acceso venoso periférico y la oxigenoterapia. Conclusión: Se enfatiza la necesidad de reconocer los grupos vulnerables para comprender los aspectos relacionados con las ocurrencias e implementar medidas preventivas