ACTN3 genotype influences skeletal muscle mass regulation and response to dexamethasone.

Homozygosity for the common ACTN3 null polymorphism (ACTN3 577X) results in α-actinin-3 deficiency in ~20% of humans worldwide and is linked to reduced sprint and power performance in both elite athletes and the general population. α-Actinin-3 deficiency is also associated with reduced muscle mass, increased risk of sarcopenia, and altered muscle wasting response induced by denervation and immobilization. Here, we show that α-actinin-3 plays a key role in the regulation of protein synthesis and breakdown signaling in skeletal muscle and influences muscle mass from early postnatal development. We also show that α-actinin-3 deficiency reduces the atrophic and anti-inflammatory response to the glucocorticoid dexamethasone in muscle and protects against dexamethasone-induced muscle wasting in female but not male mice. The effects of α-actinin-3 deficiency on muscle mass regulation and response to muscle wasting provide an additional mechanistic explanation for the positive selection of the ACTN3 577X allele in recent human history.

A Brazilian multicentre study evaluating pregnancies induced by cabergoline in patients harboring prolactinomas.

OBJECTIVE: To evaluate the maternal-fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large cohort. METHODS: The prevalence of tumor growth, miscarriage, preterm, low birth weight, congenital malformations and impairment in neuropsychological development in children among women treated with CAB were assessed in a Brazilian multicentre retrospective observational study, RESULTS: We included 194 women with a mean age of 31 (17-45) years, 43.6% presenting microadenomas and 56.4% macroadenomas, at prolactinoma diagnosis. In 233 pregnancies, CAB was withdrawn in 89%, after pregnancy confirmation. Symptoms related to tumor growth occurred in 25 cases, more frequently in macroadenomas. The overall miscarriage rate was 11%, although higher in the subgroup of patients with CAB maintainance after pregnancy confirmation (38% vs. 7.5%). Amongst the live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 4.3%. Neuropsychological development impairment was reported in 7% of cases. CONCLUSIONS: Our findings confirm previous results of safety in maternal and fetal outcomes in CAB-induced pregnancies; nevertheless, CAB maintenance after pregnancy confirmation was associated with higher miscarriage rate; result that must be further confirmed.

Gods associated with male fertility and virility.

BACKGROUND: Human fertility has always been a topic of curiosity and devotion. Many cultures consider fertility to be a necessity for the survival and perpetuation of mankind and since early times, myths were created to explain this fabulous process. Fertility gods were ubiquitous in numerous ancient human cultures and were used both to understand fertility and to cope with infertility by means of rituals and offerings. OBJECTIVES: This manuscript aims to catalog and describe the deities associated with male fertility and virility. MATERIAL AND METHODS: We conducted a comprehensive search for the terms "male fertility god" and "male virility god" on the internet using web-based search engines. Based on the information retrieved, we selected those deities directed related to male fertility and/or virility and further deepened the search using Pubmed and Medline databases for peer-reviewed articles as well as books and articles about ancient mythology. RESULTS: We identified several gods linked to male fertility and virility in various cultures from Egypt, Greece, Rome, India, Southwestern United States, France, Colombia and Buthan.. DISCUSSION: Most of these deities were depicted with an erect phallus and with other fertility symbols like snakes. Some deities were also associated with plants and/or animal fertility and their festivals were often held during the harvest period. CONCLUSION: Gods of male fertility and virility played important roles in many ancient cultures. Offerings and rituals to these gods were the only available options to deal with problems of reproduction and demonstrate the lengths to which ancient people would go seeking cures for infertility.

The Effect of ACTN3 Gene Doping on Skeletal Muscle Performance.

Loss of expression of ACTN3, due to homozygosity of the common null polymorphism (p.Arg577X), is underrepresented in elite sprint/power athletes and has been associated with reduced muscle mass and strength in humans and mice. To investigate ACTN3 gene dosage in performance and whether expression could enhance muscle force, we performed meta-analysis and expression studies. Our general meta-analysis using a Bayesian random effects model in elite sprint/power athlete cohorts demonstrated a consistent homozygous-group effect across studies (per allele OR = 1.4, 95% CI 1.3-1.6) but substantial heterogeneity in heterozygotes. In mouse muscle, rAAV-mediated gene transfer overexpressed and rescued α-actinin-3 expression. Contrary to expectation, in vivo "doping" of ACTN3 at low to moderate doses demonstrated an absence of any change in function. At high doses, ACTN3 is toxic and detrimental to force generation, to demonstrate gene doping with supposedly performance-enhancing isoforms of sarcomeric proteins can be detrimental for muscle function. Restoration of α-actinin-3 did not enhance muscle mass but highlighted the primary role of α-actinin-3 in modulating muscle metabolism with altered fatiguability. This is the first study to express a Z-disk protein in healthy skeletal muscle and measure the in vivo effect. The sensitive balance of the sarcomeric proteins and muscle function has relevant implications in areas of gene doping in performance and therapy for neuromuscular disease.

Clinical and laboratory features greatly overlap in patients with macroprolactinemia or monomeric hyperprolactinemia.

AIM: The aim of this study was to evaluate the clinical and laboratory features of 64 patients with macroprolactinemia and to compare them to those of individuals with monomeric hyperprolactinemia. METHODS: The study included 64 patients (54 women and 10 men) with macroprolactinemia and 96 patients (70 women and 26 men) with monomeric hyperprolactinemia (32 with prolactinomas). RESULTS: Symptoms related to prolactin (PRL) excess were found in about 44% of individuals from the macroprolactinemia group and in 88.5% of patients with monomeric hyperprolactinemia (P<0.0001). However, the frequency of menstrual disturbances (oligomenorrhea or amenorrhea), galactorrhea and erectile dysfunction did not differ in both groups. In contrast, the association of galactorrhea and menstrual disturbances was significantly more prevalent in women with monomeric hyperprolactinemia. Although mean PRL levels were higher in patients with monomeric hyperprolactinemia (565.9+/-2726.4 vs 113.3+/-94.5 ng/mL, P<0.001), there was a great overlap between both groups. Among macroprolactinemic patients, pituitary magnetic resonance imaging revealed an image suggestive of a microadenoma in 7 (10.9%) and a macroadenoma in 1 (1.6%). Normalization of PRL levels during therapy with dopamine agonists was significantly more frequent in patients with monomeric hyperprolactinemia than in subjects with macroprolactinemia (78.6% vs 32%, P=0.0006). CONCLUSION: Our data show that symptoms related to PRL excess are frequently found in subjects with macroprolactinemia. Moreover, no clinical or laboratory features could reliably differentiate macroprolactinemic patients from those with monomeric hyperprolactinemia. Therefore, the screening for macroprolactin should not be restricted to asymptomatic patients.

[Apical hypertrophic cardiomyopathy associated with coronary artery disease]. / Cardiomiopatia hipertrófica apical associada a doença arterial coronária.

A fifty-nine year old man, known to have hypertrophic cardiomyopathy, presented worsening of angina. Multivessel coronary artery disease was diagnosed, and he underwent myocardial revascularization (mammary and two safenous grafts were implanted) with good evolution and reduction of left atrium dimension.

Spontaneous rupture of the esophagus: report of two cases.

OBJECTIVE: To study the diagnosis, prognosis and management of spontaneous rupture of the esophagus. DESIGN: This is a retrospective study through the analysis of two cases with delayed diagnosis and subsequent treatment at the Track Surgery Service. LOCALE: The study was performed at the Thoracic Surgery Unit of the Hospital do Servidor Público Estadual Francisco Morato de Oliveira in the city of São Paulo. This is a specialized service. PARTICIPANTS: The two patients reported on had suffered spontaneous rupture of the esophagus. They were transferred to the Thoracic Surgery Unit because of the worsening of their condition in the previous institution which they had been admitted into. MEASUREMENT: The two patients with esophagus pleural fistula received similar treatment, initially advocated by Kanashin in Russia and Hauer-Santos in the United States, which consists of washing the fistula and using continuous pleural aspiration. RESULTS: Although both patients had to spend a long period of time in hospital, their evolution was satisfactory with the treatment adopted, and the fistula closed. CONCLUSION: The authors conclude that the method of lavage of the mediastinum and continuous pleural aspiration, in patients who after spontaneous rupture of the esophagus developed a pleural esophagus fistula due to belated diagnosis, is an alternative and satisfactory therapy. Furthermore, in order to have the best outcome, an early diagnosis is recommended and thoracostomy as the surgical procedure, with primary suture.

Mediastinitis after cervical suppuration.

The objective of this study is to decode the etiopathogenesis, the clinical feature, the diagnosis and the prognosis of the acute mediastinitis resulting of infectious processes of the cephalic segment. Three out of five patients studied presented focus of dental origin and two patients presented focus in the face area. One of them presented Ludwig's Angina before the suppurative process would spread over the mediastinum. In the others, there was fast expansion through the fascial spaces of the neck and, in two of them, besides the mediastinum, there was pleuropericardial involvement. Three patients died due to respiratory insufficiency and two survived with complications. The mediastinitis after cervical suppuration is a special and extremely serious kind of endothoracic infection. The pus reaches that area through the fascial spaces of the neck, taking the organism to an alarming toxemic feature. The rarity of the disease, the little is known about its physiopathology and the initial care of the patient in non-specialized services, which are not familiarized with this type of feature, are factors that can delay the diagnosis and worsen the prognosis.

[The genesis of crime according to dialectic criminology. II. Comments on the genesis of crime]. / La genesi del delitto secondo una criminologia dialettica. II. Commenti sulla genesi del delitto.

Prof. Lyra discusses in this article the basic problem of criminological sciences, stating that its essential object of study is the determination of the genesis of crime. The Author states that, before defining the crime genesis, it is necessary to outline, through a synthesis of epistemological restructurization of criminology itself. This way, we can develop a conception of Dialectic Criminology, where the term "dialectic" does not necessarily coincide with a marxist posture, but it extends along much more complex and comprehensive parameters. Dialectic Criminology is defined, in Lyra's conception, as a Classified Criminology, synthetizing both the psychological approach (clinical criminology, or micro-criminology), and the sociological approach (sociological criminology or macro-criminology), according to an anthropological basic frame of reference, which constitutes the new and original prerequisite. To this aim, according to Prof. Lyra, it is necessary to overcome merely biological or psychological theories, and the new sociologisms, which cannot explain deviant behavior without falling into dogmatism or relativism. It is necessary to give back to criminology its original ethico-philosophical roots, and to place the problem of crime within a new "praxis" concept, which takes into account the authentic freedom of man, interracting with historical evolution. This way, through Dialectic Criminology, we can overcome the conception of crime and delinquency viewed as counterparts of the concept of Law.