Estrogen receptor alpha gene ( ESR1) polymorphism can contribute to clinical findings in systemic lupus erythematosus patients.

Background Estrogens have a modulatory effect on several immune responses, many of which are correlated to autoimmune diseases. Estrogens act through binding to their receptors, and an overexpression of these receptors has been identified in patients with different autoimmune diseases. Here we analyzed the association of a putative functional genetic variant in the main estrogen receptor (ERα) gene ( ESR1), and the susceptibility to clinical findings and severity of SLE. Methods A total of 426 individuals (266 healthy controls and 160 SLE patients) were genotyped for the polymorphism rs2234693 in the ESR1 gene. Allele and genotype frequencies were calculated and analyzed between cases and controls using Unphased software. Results The SNP rs2234693 was not associated with SLE per se but the minor allele rs2234693-C was correlated with the presence of nephritis and discoid skin rash. On the other hand, the rs2234693-CC genotype was correlated with the absence of arthritis as well as anti-ANA and anti-RNP autoantibodies. The comprehensive clinical analysis of these patients revealed a more severe status of the disease, characterized by a younger age of onset and higher number of organs involved when compared to European populations. Conclusions Minor allele rs2234693-C was associated with renal and cutaneous involvement, as well as the absence of arthritis, anti-ANA and anti-RNP autoantibodies.

Adaptive fuzzy modeling of the hypnotic process in anesthesia.

This paper addresses the problem of patient model synthesis in anesthesia. Recent advanced drug infusion mechanisms use a patient model to establish the proper drug dose. However, due to the inherent complexity and variability of the patient dynamics, difficulty obtaining a good model is high. In this paper, a method based on fuzzy logic and genetic algorithms is proposed as an alternative to standard compartmental models. The model uses a Mamdani type fuzzy inference system developed in a two-step procedure. First, an offline model is obtained using information from real patients. Then, an adaptive strategy that uses genetic algorithms is implemented. The validation of the modeling technique was done using real data obtained from real patients in the operating room. Results show that the proposed method based on artificial intelligence appears to be an improved alternative to existing compartmental methodologies.

The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer.

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.

The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.

Contribution to the reproductive ecology of Notoscopelus resplendens (Richardson, 1845) (Myctophidae) in the Central-Eastern Atlantic.

Notoscopelus resplendens is an abundant myctophid in the region of the Central-Eastern Atlantic. As with a majority of other myctophid species, this species performs vertical migration, playing a key role in the oceanic food web and in carbon sequestration. We examined the reproductive biology of N. resplendens based on 579 specimens caught between 1997 and 2002 off the Canary Islands. We found that the maximum standard length (SL) was lower than the size reported by other authors. The sex ratio was not different from 1:1. The average size at first maturity (L50) was higher in females (60.34 mm SL) than in males (56.61 mm SL). The gonadosomatic index (GSI) at 50% sexual maturity in females was higher than that in males. The reproductive activity was observed from January to April, while from May onwards, the majority of fish caught were in the process of maturation. The macroscopic scale of maturation was validated through the histological analysis of the ovarian development. The batch fecundity was related to the standard length, with an average of 1068.69 ± 369.84 eggs/spawn. These first data obtained for N. resplendens indicated that it is a batch spawner with asynchronous ovarian development.

Admixture estimates for the population of Havana City.

BACKGROUND: The Cuban population is essentially a result of the admixture between Spanish, West African and, to a lesser degree, Amerindian tribes that inhabited the island. AIM: The study analysed the genetic structure of the three principal ethnic groups from Havana City, and the contribution of parental populations to its genetic pool. SUBJECTS AND METHODS: According to genealogical information and anthropological traits, 206 subjects were classified as Mulatto, of Spanish decent or of African descent. Seventeen Ancestry Informative Markers, with high difference in frequency between parental populations, were selected to estimate individual and group admixture proportions. The statistical analyses were performed using the ADMIX, ADMIX95 and STRUCTURE 2.1 packages. RESULTS: The results demonstrate a high level of European and African admixture in Mulattos (57-59% European; 41-43% West African). The European contribution was higher in those of Spanish descent (85%) while in those of African descent, the West African contribution ranged between 74% and 76%. Genetic structure was only detected in Mulattos and those of African descent. An Amerindian contribution was not detectable in the studied sample. CONCLUSION: Our findings indicate the existence of admixture and genetic structure in the population of Havana City. This study represents one of the first steps towards understanding Cuban population admixture in order to produce successful experimental designs for admixture mapping.

The chemistry of marine pulmonate gastropods.

Secondary metabolites from pulmonate molluscs of the genera Siphonaria, Onchidium, and Trimusculus are described. Siphonaria and Onchidium biosynthesize mostly propionate-based metabolites whereas Trimusculus yields diterpene derivatives with a single type of labdane skeleton. The 42 regular polypropionates reported to date from Siphonaria are divided into two classes (class I, class II), based on their observed structural and stereochemical analogy. The strong resemblance between class I and cephalaspidean metabolites and between class II and onchidiid metabolites as well as the structural features of Trimusculus, in relation to the other pulmonates, encourage speculation about their biosynthetic and phylogenetic relationship. Class I metabolites could be suitable material to evidence that type I PKS modules are perhaps used iteratively in their biosynthesis.

Frequency of CCR5delta32 in Brazilian populations.

A sample of 103 randomly chosen healthy individuals from Alegrete, RS, Brazil, was tested for the CCR5delta32 allele, which is known to influence susceptibility to HIV-1 infection. The CCR5delta32 allele was identified by PCR amplification using specific primers flanking the region of deletion, followed by electrophoresis on a 3% agarose gel. The data obtained were compared to those reported for other populations and interpreted in terms of Brazilian history. The individuals studied came from a highly admixed population. Most of them were identified as white (N = 59), while blacks and browns (mulattoes) were N = 13 and N = 31, respectively. The observed frequencies, considering the white, black and brown samples (6.8, 3.8, and 6.4%, respectively), suggest an important European parental contribution, even in populations identified as black and brown. However, in Brazil as a whole, this allele shows gradients indicating a relatively good correlation with the classification based on skin color and other physical traits, used here to define major Brazilian population groups.

Inferior vena cava filters in cancer patients: indications and outcome.

PURPOSE: Our experience with inferior vena cava (IVC) filter placement to prevent pulmonary emboli (PE) in cancer patients with deep vein thromboses (DVT) was reviewed to identify indications, patient characteristics, complications, and long-term outcome. METHODS: Charts of 182 patients with cancer were retrospectively analyzed. All patients had received an IVC filter in our institution between January 1980 and April 1992. RESULTS: Of 182 patients, 103 were men and 79 were women. Median age was 59 years (range, 15 to 88). Eight patients (4%) had stage I disease, 22 patients (12%) stage II, 37 patients (20%) stage III, and 115 patients (63%) stage IV. A DVT was diagnosed in 97 patients (53%), a PE in 46 patients (25%), and a combination in 39 patients (21%). Indications for IVC filter placement were DVT or PE in the presence of contraindications to anticoagulation therapy (perioperative, n = 58; CNS metastases, n = 20; thrombocytopenia, n = 7; bleeding, n = 61; others, n = 24; total, N = 170) or anticoagulation failure (recurrent PE, n = 6; recurrent DVT; n = 6; total N = 12). Filter placement complications (n = 6, 3%) included malposition (n = 3), migration (n = 1), arrhythmia (n = 1), and wound infection (n = 1), but no deaths. After filter placement, four patients developed a recurrent PE, and 11 patients developed a recurrent DVT. No significant postthrombotic complications were observed. CONCLUSION: IVC filter placement patients with advanced cancer and thrombotic complications is safe, well tolerated, and can offer effective therapy/prophylaxis with a low incidence of treatment failure.

Liver resection for colorectal metastases.

PURPOSE: More than 50,000 patients in the United States will present each year with liver metastases from colorectal cancers. The current study was performed to determine if liver resection for colorectal metastases is safe and effective and to evaluate predictors of outcome. MATERIALS AND METHODS: Data for 456 consecutive resections performed between July 1985 and December 1991 in a tertiary referral center were analyzed. RESULTS: The perioperative mortality rate was 2.8%, with a mortality rate of 4.6% for resections that involved a lobectomy or more. The median hospital stay was 12 days and only 9% of patients were admitted to the intensive care unit. The 5-year survival rate is 38%, with a median survival duration of 46 months. By univariate analysis, nodal status of the primary lesion, short disease-free interval before detection of liver metastases, carcinoembryonic antigen (CEA) level greater than 200 ng/mL, multiple liver tumors, extrahepatic disease, large tumors, or positive resection margin was predictive of poorer outcome. Sex, age greater than 70 years, site of primary tumor, or perioperative transfusion was not predictive of outcome. By multivariate analysis, positive margin, size greater than 10 cm, disease-free interval less than 12 months, multiple tumors, and extrahepatic disease were independent predictors of poorer outcome. Short disease-free interval or multiple tumors were nevertheless associated with a 5-year survival rate greater than 24%. CONCLUSION: Liver resection for colorectal metastases is safe and effective therapy and currently represents the only potentially curative therapy for metastatic colorectal cancer. The only absolute contraindication to resection is extrahepatic disease. A randomized trial to examine efficacy of surgical resection cannot ethically be performed. Liver resection should be considered standard therapy for all fit patients with colorectal metastases isolated to the liver.

Sex differences in pain perception and cardiovascular responses in persons with parental history for hypertension.

We investigated gender differences in cardiovascular and pain responses to the cold pressor (CP) test in persons with positive (PH+) or negative parental history (PH-) for hypertension. Previous work has suggested an attenuated sensitivity to painful stimulation in hypertensive men and more recently in men with parental disposition for hypertension. It is not known whether this hypoalgesic effect is present in PH+ women. In this study, we evaluated differences in pain perception between men and women with PH+ or PH- using an assessment method to measure current as well as delayed pain. Participants rated their pain every 15 s during a 90-s hand CP (0-4 degrees C) and a 90-s post-CP rest period. Systolic and diastolic blood pressures (SBP, DBP) and heart rate (HR) were measured before, during, and after the CP. PH+ and PH- groups did not differ in age, height, weight, education, resting SBP, DBP, or HR. PH+ men showed greater DBP responses to the CP than PH- men, while female groups did not differ in cardiovascular responses to the CP. Although pain ratings during the CP did not differ between groups, post-CP reported pain receded faster in the PH+ men than in the PH- men. PH+ women, on the other hand, tended to report greater pain than PH- women. These findings question the generalizability of the hypoalgesic effects in hypertension-prone women.

Immunoreactive neurotensin in gonadotrophs and thyrotrophs is regulated by sex steroid hormones in the female rat.

In addition to regulating anterior pituitary function by being released from the median eminence, mammalian neurotensin (NT) may also exert an autocrine or a paracrine action within the anterior pituitary. In this study, using double immunostaining with elution restaining, we identified the specific anterior pituitary cells which express NT immunoreactivity (NT-IR) during the rat oestrous cycle. In the normal cycling rat, NT-IR was present in both gonadotrophs and thyrotrophs and displayed plastic changes along the oestrous cycle. Both the number of TSH-NT positive cells and the intensity of immunological reaction were elevated during dioestrus, and decreased through pro-oestrus and early oestrus. NT-IR was also high in both follicle stimulating hormone (FSH)- or luteinizing hormone (LH)-positive cells during early pro-oestrus, and decreased during late pro-oestrus. Treatment of intact rats with either the anti-oestrogens Tamoxifen or LY117018, or the anti-progestagen RU486 prevented the normal expression of NT-IR in thyroid-stimulating hormone (TSH)-, FSH-, and LH-positive cells during pro-oestrus. Bilateral ovariectomy induced a dramatic reduction in the number of NT-IR cells. This effect was completely prevented by treatment of ovariectomized rats with oestradiol and progesterone, and was unaffected by the concurrent administration of a GnRH antagonist. Furthermore, administration of an anti-oestrogen together with an anti-progestagen to ovariectomized-oestrogen, progesterone-treated rats, blocked the stimulatory effect of ovarian hormones on NT-IR in anterior pituitary cells. These findings demonstrate that, in female rats, NT is specifically localized in gonadotrophs or thyrotrophs. In addition, they strongly suggest that changes in circulating concentrations of ovarian steroids may control both NT synthesis in, and release from, these cells.

Molecular epidemiology of tuberculosis in Cuba outside of Havana, July 1994-June 1995: utility of spoligotyping versus IS6110 restriction fragment length polymorphism.

SETTING: Molecular typing has become an important tool for examining the extent of active transmission of tuberculosis. OBJECTIVES: To examine transmission of tuberculosis in Cuba using IS6110 restriction fragment length polymorphism (RFLP) typing and to evaluate the utility of spoligotyping. DESIGN: One hundred and sixty Mycobacterium tuberculosis strains isolated over a one year period in Cuba were subjected to RFLP and spoligotyping. RESULTS: Forty-eight percent of the isolates were found in 19 clusters of strains with identical RFLP patterns. In general, cluster sizes were limited, except for two large institutional outbreaks. Age was strongly inversely correlated to clustering. Most streptomycin-resistant isolates were found in clusters. Fifteen spoligotype clusters comprised 78% of the isolates. Significantly different IS6110 RFLP types subdivided 11 spoligotype clusters, whereas none of the IS6110 clusters were subdivided by spoligotyping. CONCLUSIONS: Considering the short study period, 48% clustering is high, indicating that recent transmission plays an important role in Cuba. Although resistance is still a minor problem, transmission of streptomycin-resistant strains occurs. The high polymorphism observed with IS6110 RFLP indicates that this marker is useful for future molecular epidemiological studies in Cuba. Spoligotyping appeared less suitable for population-based studies.

Early primary tissue failure of a Labcor bioprosthesis.

A 78-year-old woman underwent re-replacement of a 19mm Labcor bioprosthesis implanted in aortic position eighteen months earlier. The rupture of the free margin of one leaflet was found at reoperation. There was no apparent cause of this rupture.

Heparin-coated circuit in coronary surgery. A clinical study.

We performed a randomized study in 101 patients who underwent routine isolated coronary bypass graft surgery. In 50 cases an entire coated Carmeda circuit was used (coated group), and an uncoated circuit in the remaining 51 (uncoated group). A Medtronic Maxima oxygenator and a Biomedicus Biohead were used in all cases. Patients with coated circuits received low systemic heparinization with a heparin loading dose of 200 IU/kg, and 300 IU/kg for the control. Activated coagulation time was maintained at more than 275 s for the coated group versus more than 400 s for the uncoated one. The mean age of patients was 64.1 +/- 9.6 for coated and 63.5 +/- 9.7 for the uncoated group. The number of coronary grafts was 3.1 +/- 0.7 for the coated group and 3.1 +/- 0.1 for the uncoated one. Cross-clamp and bypass times were 53 +/- 14 and 98 +/- 24 min for the coated, versus 57 +/- 15 and 104 +/- 24 for the uncoated, group. Chest drainage was 989.4 +/- 509.5 ml for the coated group versus 1435 +/- 1027 for the uncoated one (P < 0.02). The amount of transfused homologous blood was 723 +/- 597 ml for the coated group versus 1071 +/- 831 ml for the uncoated one (P < 0.03). Postoperative endotracheal intubation time was 12.1 +/- 3.6 h for the coated and 14.6 +/- 4.5 h for the uncoated group (P < 0.05). Bleeding required rethoracotomy in 1/50 of the coated group, and in 4/51 of the uncoated one. Hospital mortality was 1/50 in the coated, and 4/51 in the uncoated, group. In our preliminary experience, heparin coating of an extracorporeal circuit reduces post-operative blood loss and blood transfusions in routine coronary bypass operations.

Men at risk for hypertension show elevated vascular resistance at rest and during mental stress.

Men at risk for development of hypertension may show elevated blood pressure at rest and during work on mental stressors. We examined which component of blood pressure, vascular resistance or cardiac output, accounted for raised blood pressures seen in a high-risk, normotensive sample. Parental history of hypertension and resting systolic blood pressures were used to categorize subjects into high (n = 19) and low (n = 14) risk groups. Blood pressure, heart rate, cardiac output, stroke volume, and vascular resistance were measured during rest, mental arithmetic, and reaction time. Compared to low risk subjects, the high risk men had significantly higher blood pressures accompanied by higher vascular resistances at rest and during mental stress. The groups had negligible differences in heart rate, stroke volume, and cardiac output. This pattern of results implicates vascular resistance as the dominant element in altered blood pressure control in these young men at high risk for hypertension.

[Coronary revascularization surgery with arterial grafts]. / Cirugía de revascularización coronaria con injertos arteriales.

Coronary artery revascularization surgery is well established procedure throughout the world. The benefits are based on the blood perfusion through the implanted grafts distal to the coronary occlusions and continue as long as the grafts remains patent. The immediate success of this procedure is related to the surgical technique and the anatomical characteristics of the grafted coronary arteries. However, the long term results are mainly dependent on the type of grafts used. The modern era of myocardial revascularization started in the sixties with the use of saphenous vein grafts by Johnson and Favaloro. Alternative vascular conduits to the saphenous vein have been tried, and the internal mammary artery has become the first choice. In recent years, various publications have demonstrated the supremacy of the internal mammary artery over the saphenous vein when used as a single, bilateral, sequential of free graft. In order to obtain full myocardial revascularization, the use of alternatives to the internal mammary artery is required. The gastroepiploic artery, the inferior epigastric artery and the radial artery have been used as alternatives to the saphenous vein with the hope of obtaining long term results similar to the internal mammary artery.

Effects of clonality on the genetic variability of rare, insular species: the case of Ruta microcarpa from the Canary Islands.

Many plant species combine sexual and clonal reproduction. Clonal propagation has ecological costs mainly related to inbreeding depression and pollen discounting; at the same time, species able to reproduce clonally have ecological and evolutionary advantages being able to persist when conditions are not favorable for sexual reproduction. The presence of clonality has profound consequences on the genetic structure of populations, especially when it represents the predominant reproductive strategy in a population. Theoretical studies suggest that high rate of clonal propagation should increase the effective number of alleles and heterozygosity in a population, while an opposite effect is expected on genetic differentiation among populations and on genotypic diversity. In this study, we ask how clonal propagation affects the genetic diversity of rare insular species, which are often characterized by low levels of genetic diversity, hence at risk of extinction. We used eight polymorphic microsatellite markers to study the genetic structure of the critically endangered insular endemic Ruta microcarpa. We found that clonality appears to positively affect the genetic diversity of R. microcarpa by increasing allelic diversity, polymorphism, and heterozygosity. Moreover, clonal propagation seems to be a more successful reproductive strategy in small, isolated population subjected to environmental stress. Our results suggest that clonal propagation may benefit rare species. However, the advantage of clonal growth may be only short-lived for prolonged clonal growth could ultimately lead to monoclonal populations. Some degree of sexual reproduction may be needed in a predominantly clonal species to ensure long-term viability.