The secretome from human-derived mesenchymal stem cells augments the activity of antitumor plant extracts in vitro.

Cancer is understood as a multifactorial disease that involve multiple cell types and phenotypes in the tumor microenvironment (TME). The components of the TME can interact directly or via soluble factors (cytokines, chemokines, growth factors, extracellular vesicles, etc.). Among the cells composing the TME, mesenchymal stem cells (MSCs) appear as a population with debated properties since it has been seen that they can both promote or attenuate tumor progression. For various authors, the main mechanism of interaction of MSCs is through their secretome, the set of molecules secreted into the extracellular milieu, recruiting, and influencing the behavior of other cells in inflammatory environments where they normally reside, such as wounds and tumors. Natural products have been studied as possible cancer treatments, appealing to synergisms between the molecules in their composition; thus, extracts obtained from Petiveria alliacea (Anamu-SC) and Caesalpinia spinosa (P2Et) have been produced and studied previously on different models, showing promising results. The effect of plant extracts on the MSC secretome has been poorly studied, especially in the context of the TME. Here, we studied the effect of Anamu-SC and P2Et extracts in the human adipose-derived MSC (hAMSC)-tumor cell interaction as a TME model. We also investigated the influence of the hAMSC secretome, in combination with these natural products, on tumor cell hallmarks such as viability, clonogenicity, and migration. In addition, hAMSC gene expression and protein synthesis were evaluated for some key factors in tumor progression in the presence of the extracts by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Multiplex, respectively. It was found that the presence of the hAMSC secretome did not affect the cytotoxic or clonogenicity-reducing activities of the natural extracts on cancer cells, and even this secretome can inhibit the migration of these tumor cells, in addition to the fact that the profile of molecules can be modified by natural products. Overall, our findings demonstrate that hAMSC secretome participation in TME interactions can favor the antitumor activities of natural products.

Revisiting the birth of NaCl crystals using molecular dynamics simulation.

Molecular dynamics simulations were used to investigate the initial stage of phase separation mechanisms for an oversaturated electrolytic solution. We developed a low computational cost methodology to determine the simulation frames where the first ionic clusters are formed. By discretizing the simulation box, we obtain a density profile in the moments preceding and succeeding the nuclei's formation. The growth of the clusters identified with our methodology was analyzed until the end of the simulation. Calculation of the Steinhardt parameter showed symmetry of the solid, giving indications that the classical nucleation theory explains the mechanism of the solid formation. The methodology developed was useful for identifying phase separation mechanisms in the nucleation process. At lower concentrations, there was no formation of stable clusters. At intermediate concentrations, the analyses indicate a transition of phases in one stage, from a oversaturate electrolytic solution to a crystalline solid. At high concentration, a transition of phases in two stages, initially, is the formation of a dense liquid, and only after that, crystalline solid formed inside the dense liquid. The change in phase separation mechanism due to increasing oversaturation underscores the importance of precise determination of the driving force for phase separation and concentration limits for each mechanism.

Implementation of a Brazilian Cardioprotective Nutritional (BALANCE) Program for improvement on quality of diet and secondary prevention of cardiovascular events: A randomized, multicenter trial

Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)

Comparing 3d and 2d computational modeling of an oil well blowout using MOHID platform - A case study in the Campos Basin.

The oil well blowout releases hydrocarbons into the marine environment as an oil droplets and gas bubbles dispersion. The oil trajectory is strongly influenced by physical, chemical and biological processes. In general, the ocean oil drift studies are based on a two-dimensional approach, whereas the whole oil from a well blowout can be represented by a surface oil leak in the same geographical coordinates. This work is a case study, where MOHID software is used at the Campos Basin region, in which the Lagrangian results of the surface oil leaks were confronted to their well blowout scenarios in different conditions of depth, seasonality (summer and winter), and use of dispersants at the source of the leak. The research results reinforced the importance of the three-dimensional approach to the scenario of deep and ultra-deep waters, especially for cases in which the dispersant injection into the source of the leak was considered.

Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model.

Recent findings suggest that part of the anti-tumor effects of several chemotherapeutic agents require an intact immune system. This is in part due to the induction of immunogenic cell death. We have identified a gallotannin-rich fraction, obtained from Caesalpinia spinosa (P2Et) as an anti-tumor agent in both breast carcinoma and melanoma. Here, we report that P2Et treatment results in activation of caspase 3 and 9, mobilization of cytochrome c and externalization of annexin V in tumor cells, thus suggesting the induction of apoptosis. This was preceded by the onset of autophagy and the expression of immunogenic cell death markers. We further demonstrate that P2Et-treated tumor cells are highly immunogenic in vaccinated mice and induce immune system activation, clearly shown by the generation of interferon gamma (IFN-γ) producing tyrosine-related protein 2 antigen-specific CD8+ T cells. Moreover, the tumor protective effects of P2Et treatment were abolished in immunodeficient mice, and partially lost after CD4 and CD8 depletion, indicating that P2Et's anti-tumor activity is highly dependent on immune system and at least in part of T cells. Altogether, these results support the hypothesis that the gallotannin-rich fraction P2Et's anti-tumor effects are mediated to a great extent by the endogenous immune response following to the exposure to immunogenic dying tumor cells.

Genetic diversity and population structure of Synthesium pontoporiae (Digenea, Brachycladiidae) linked to its definitive host stocks, the endangered Franciscana dolphin, Pontoporia blainvillei (Pontoporiidae) off the coast of Brazil and Argentina.

Pontoporia blainvillei (Gervais and d'Orbigny, 1844) is an endangered small cetacean endemic to South America with four Franciscana Management Areas (FMA) recognized as different population stocks. The role of the intestinal parasite Synthesium pontoporiae (Digenea: Brachycladiidae) as a possible biological marker to differentiate P. blainvillei stocks was evaluated using nuclear and mitochondrial DNA markers. Internal transcribed sequence 1 and 2 (ITS1 and ITS2) regions of S. pontoporiae did not show intraspecific variability. The mitochondrial NADH dehydrogenase subunit 3 (ND3) and cytochrome oxidase subunit I (COI) gene sequences suggested lack of population structure in S. pontoporiae and population expansion. The apparent panmixia of S. pontoporiae may be due to the high mobility of one or more of its intermediary hosts. Alternatively, it may be due to the small sample size. This result is incongruent with the previously proposed FMA.

Field application of a planted fixed bed reactor (PFR) for support media and rhizosphere investigation using undisturbed samples from full-scale constructed wetlands.

This study presents a novel method for investigations on undisturbed samples from full-scale horizontal subsurface-flow constructed wetlands (HSSFCW). The planted fixed bed reactor (PFR), developed at the Helmholtz Center for Environmental Research (UFZ), is a universal test unit for planted soil filters that reproduces the operational conditions of a constructed wetland (CW) system in laboratory scale. The present research proposes modifications on the PFR original configuration in order to allow its operation in field conditions. A mobile device to obtain undisturbed samples from real-scale HSSFCW was also developed. The experimental setting is presented with two possible operational configurations. The first allows the removal and replacement of undisturbed samples in the CW bed for laboratory investigations, guaranteeing sample integrity with a mobile device. The second allows the continuous operation of the PFR and undisturbed samples as a fraction of the support media, reproducing the same environmental conditions outside the real-scale system. Investigations on the hydrodynamics of the adapted PFR were carried out with saline tracer tests, validating the proposed adaptation. Six adapted PFR units were installed next to full-scale HSSFCW beds and fed with interstitial liquid pumped from two regions of planted and unplanted support media. Fourteen points were monitored along the system, covering carbon fractions, nitrogen and sulfate. The results indicate the method as a promising tool for investigations on CW support media, rhizosphere and open space for studies on CW modeling, respirometry, kinetic parameters, microbial communities, redox potential and plant influence on HSSFCW.

Particularidades del síndrome metabólico en una subpoblación de adultos mayores / Particularities of metabolic syndrome in an elderly subpopulation

Introducción: El síndrome metabólico (SM) se define por un conjunto de alteraciones clínicas que aumentan el riesgo de enfermedad cardiovascular. Diferentes organizaciones internacionales de salud han ajustado progresivamente los criterios que definen al SM, con el consiguiente aumento del diagnóstico del mismo. Sin embargo, ninguno de los parámetros considerados se han adaptado a la edad ni se han tomado en cuenta las modificaciones antropométricas y metabólicas características del envejecimiento. Objetivo: Caracterizar al SM en una población de adultos mayores y evaluar si existen diferencias de género. Materiales y métodos: Se realizó un estudio prospectivo en pacientes que consultaron al Servicio de Endocrinología de la U. A. Dr. César Milstein. El 68,8 % fueron mujeres y la edad de la población fue 73 ± 6 años. Para el diagnóstico de SM se utilizaron los criterios del Joint Interim Statement de 2009. Recabamos información sobre antecedentes, medicación y se realizaron análisis de laboratorio. Se midió índice cintura/talla (ICT). Se calculó media ± desvío estándar (DS) y proporciones. Para establecer comparaciones entre varones y mujeres se utilizó Test de Student y test de Chi2. Resultados: En una muestra de 77 pacientes, 42,9 % cumplió con 3 componentes de SM, 33,8 % con 4 y 23,4 % con 5, con distribución similar en hombres y mujeres. Según el índice de masa corporal (IMC), 32,5 % de la población presentó sobrepeso; 35 % obesidad grado I; 22 % grado II y 9 % grado III. Al evaluar el perímetro de cintura (PC), el 98,7 % superó los puntos de corte. El índice cintura/ talla superó el valor normal en ambos sexos, siendo significativamente superior en las mujeres (p: 0,003). Conclusiones: En la población de adultos mayores que se estudió no se observó diferencia entre ambos sexos en el número de componentes diagnósticos de SM. En cuanto al perímetro de cintura, el valor fue similar en ambos sexos, lo que podría llevar a revisar el valor de corte del mismo en este grupo etario. El ICT estuvo aumentado en toda la población y por ser un subrogante de riesgo cardiovascular, sería otro parámetro a tener en cuenta al momento del diagnóstico de SM. Rev Argent Endocrinol Metab 51:130-135, 2014 Los autores no poseen conflictos de interés.

Introduction: The metabolic syndrome (MS) denotes an association of abnormalities that increase the risk of cardiovascular disease. With the intention of decreasing this risk, international organizations have dropped the normal range for various parameters, with a consequent increase in the diagnosis of MS. Although the changes related to age are well documented, none of these parameters has been age-adapted. Aims: to characterize MS in the elderly population and to establish possible gender differences. Materials and methods: We performed a prospective study in patients who presented at the Department of Endocrinology of the Healthcare Unit Dr. Cesar Milstein. Of the total population, 68.8 % were women and the average age was 73 ± 6 years. For the diagnosis of MS, we used the 2009 Joint Interim Statement diagnostic criteria. Information was collected on previous history and medication, and laboratory analyses were performed. The waist / height ratio was also measured. Mean ± standard deviation (SD) and proportions were calculated. For comparisons between men and women, the Student test and Chi-squared test were used. Results: Of the total population, 42.9 % fulfilled 3 criteria for MS, 33.8 % fulfilled 4 criteria and 23.4 % fulfilled 5, with similar distribution in men and women. According to body mass index (BMI), 32.5 % of the population had overweight, 35 % were grade I obese, 22 % were grade II and 9 % were grade III. As regards waist circumference, 98.7 % of the total population exceeded the established cutoffs. The waist/ height ratio exceeded normal values in both genders, being significantly higher in women (p = 0.003). Conclusions: In the elderly, there are no gender differences in the number of components of MS. As for waist circumference, values were similar in both men and women. This finding could lead to redefine the cutoff value in aged woman. The waist / height ratio, a surrogate marker of cardiovascular disease, was ...

A novel nerolidol-rich essential oil from Piper claussenianum modulates Candida albicans biofilm.

Candidiasis is a major opportunistic fungal infection in humans, and its incidence has increased steadily over the last two decades. Candida albicans, the main species of the genus, has a large arsenal of virulence attributes that contribute to successful infections, such as dimorphism and biofilm formation. The adverse effects of eukaryotic antimicrobial therapies associated with an increase in resistance to the compounds presently available have boosted efforts to improve the therapeutic arsenal against candidiasis with a newer and cheaper range of drugs. In this study, a novel nerolidol-rich essential oil (EO) derived from Piper claussenianum (Miq.) C. DC., Piperaceae, was tested on the growth, transition (yeast to hyphae), formation and stability of biofilms produced by C. albicans. Both inflorescence and leaf EOs were evaluated and revealed MIC values ranging from 0.04 to 0.1 % and 0.2 to 1.26 %, respectively. Furthermore, leaf EO managed to downregulate the yeast-to-hyphae transition by 81 %, as well as reducing biofilm formation by about 30 and 50 % after incubation for 24 and 48 h, respectively. The EO was also able to reduce the viability of pre-formed biofilm by 63.9 %. Finally, the association between the leaf EO and fluconazole was evaluated and revealed an interesting synergistic effect. Taken together, these results demonstrate that this novel compound could be a promising agent and could reinforce the arsenal of therapeutic alternatives for the treatment of candidiasis. Furthermore, it may represent a novel and natural source of nerolidol, which could be of interest pharmaceutically.

Resistance exercise acutely enhances mesenteric artery insulin-induced relaxation in healthy rats.

AIMS: We evaluated the mechanisms involved in insulin-induced vasodilatation after acute resistance exercise in healthy rats. MAIN METHODS: Wistar rats were divided into 3 groups: control (CT), electrically stimulated (ES) and resistance exercise (RE). Immediately after acute RE (15 sets with 10 repetitions at 70% of maximal intensity), the animals were sacrificed and rings of mesenteric artery were mounted in an isometric system. After this, concentration-response curves to insulin were performed in control condition and in the presence of LY294002 (PI3K inhibitor), L-NAME (NOS inhibitor), L-NAME+TEA (K(+) channels inhibitor), LY294002+BQ123 (ET-A antagonist) or ouabain (Na(+)/K(+) ATPase inhibitor). KEY FINDINGS: Acute RE increased insulin-induced vasorelaxation as compared to control (CT: Rmax=7.3 ± 0.4% and RE: Rmax=15.8 ± 0.8%; p<0.001). NOS inhibition reduced (p<0.001) this vasorelaxation from both groups (CT: Rmax=2.0 ± 0.3%, and RE: Rmax=-1.2 ± 0.1%), while PI3K inhibition abolished the vasorelaxation in CT (Rmax=-0.1±0.3%, p<0.001), and caused vasoconstriction in RE (Rmax=-6.5 ± 0.6%). That insulin-induced vasoconstriction on PI3K inhibition was abolished (p<0.001) by the ET-A antagonist (Rmax=2.9 ± 0.4%). Additionally, acute RE enhanced (p<0.001) the functional activity of the ouabain-sensitive Na(+)/K(+) ATPase activity (Rmax=10.7 ± 0.4%) and of the K(+) channels (Rmax=-6.1±0.5%; p<0.001) in the insulin-induced vasorelaxation as compared to CT. SIGNIFICANCE: Such results suggest that acute RE promotes enhanced insulin-induced vasodilatation, which could act as a fine tuning to vascular tone.

Desempenho de vacas Girolando mantidas em pastejo de Tifton 85 irrigado ou sequeiro / Performance of crossbred Holstein x Zebu cows rotationally grazing in Tifton 85 pasture irrigated or rainfed

Objetivou-se com este trabalho avaliar a taxa de lotação e a produção de leite de vacas mestiças Holandês x Zebu em pastagens de Tifton 85 irrigadas e em sequeiro, em Uberaba-MG. Os dados foram analisados em um delineamento de blocos inteiramente ao acaso, com três repetições por tratamento, num esquema fatorial 2x10 (dois tratamentos e 10 épocas). Foi utilizado um lote de 11 vacas em lactação por tratamento para avaliação do desempenho animal. As médias foram comparadas por meio do teste de Scott-Knott ao nível de 5% de probabilidade (P<0,05). A pastagem foi manejada em sistema de pastejo rotacionado com três e cinco dias de ocupação e 21 e 35 dias de descanso no período das águas e da seca, respectivamente. A taxa de lotação média do sistema irrigado, no período avaliado, foi de 4,6 UA.ha-1, valor superior (P<0,05) à taxa média de 2,2 UA.ha-1 observada para o sistema de sequeiro. Não houve diferenças nas produções diárias de leite das vacas (P<0,05). A produção de leite média obtida no sistema irrigado foi de 51,7 litros. ha-1.dia-1. A irrigação possibilitou uma considerável intensificação do sistema, na medida em que proporcionou uma taxa de lotação bastante superior ao sistema de sequeiro.

The aim of this study was to determine the stocking rates and milk production of crossbred Holstein x Zebu cows managed under irrigated or rainfed Tifton 85 pastures in Uberaba- MG. The statistical design adopted was completely randomized blocks with three repetitions per treatment, in a 2 x 10 factorial arrangement (2 treatments and 10 seasons). The average was compared using the Scott-Knott test with 5% probability (P<0.05). To evaluate animal performance, 11 lactating cows per treatment were used. The pasture was managed in a rotational grazing system with 21 and 35 days of grazing interval and 3 and 5 days of grazing in each paddock, in the rainy and dry seasons respectively. The stocking rate of the irrigated system was 4.6 UA.ha-1 and was superior (p<0.05) to the stocking rate of the rainfed system that was 2.2 UA.ha-1. There were no differences among the systems (p>0.05) for the average daily milk yield of the cows. In the irrigated system the average milk yield was 51.7 liters.ha-1.dia-1. With irrigation, a considerable intensification of the system was possible because it provided a superior stocking rate capacity compared to the rainfed system.

Desempenho de vacas Girolando mantidas em pastejo de Tifton 85 irrigado ou sequeiro / Performance of crossbred Holstein x Zebu cows rotationally grazing in Tifton 85 pasture irrigated or rainfed

Objetivou-se com este trabalho avaliar a taxa de lotação e a produção de leite de vacas mestiças Holandês x Zebu em pastagens de Tifton 85 irrigadas e em sequeiro, em Uberaba-MG. Os dados foram analisados em um delineamento de blocos inteiramente ao acaso, com três repetições por tratamento, num esquema fatorial 2x10 (dois tratamentos e 10 épocas). Foi utilizado um lote de 11 vacas em lactação por tratamento para avaliação do desempenho animal. As médias foram comparadas por meio do teste de Scott-Knott ao nível de 5% de probabilidade (P<0,05). A pastagem foi manejada em sistema de pastejo rotacionado com três e cinco dias de ocupação e 21 e 35 dias de descanso no período das águas e da seca, respectivamente. A taxa de lotação média do sistema irrigado, no período avaliado, foi de 4,6 UA.ha-1, valor superior (P<0,05) à taxa média de 2,2 UA.ha-1 observada para o sistema de sequeiro. Não houve diferenças nas produções diárias de leite das vacas (P<0,05). A produção de leite média obtida no sistema irrigado foi de 51,7 litros. ha-1.dia-1. A irrigação possibilitou uma considerável intensificação do sistema, na medida em que proporcionou uma taxa de lotação bastante superior ao sistema de sequeiro.(AU)

The aim of this study was to determine the stocking rates and milk production of crossbred Holstein x Zebu cows managed under irrigated or rainfed Tifton 85 pastures in Uberaba- MG. The statistical design adopted was completely randomized blocks with three repetitions per treatment, in a 2 x 10 factorial arrangement (2 treatments and 10 seasons). The average was compared using the Scott-Knott test with 5% probability (P<0.05). To evaluate animal performance, 11 lactating cows per treatment were used. The pasture was managed in a rotational grazing system with 21 and 35 days of grazing interval and 3 and 5 days of grazing in each paddock, in the rainy and dry seasons respectively. The stocking rate of the irrigated system was 4.6 UA.ha-1 and was superior (p<0.05) to the stocking rate of the rainfed system that was 2.2 UA.ha-1. There were no differences among the systems (p>0.05) for the average daily milk yield of the cows. In the irrigated system the average milk yield was 51.7 liters.ha-1.dia-1. With irrigation, a considerable intensification of the system was possible because it provided a superior stocking rate capacity compared to the rainfed system.(AU)

Recombinant streptokinase suppositories in the treatment of acute haemorrhoidal disease. Multicentre randomized double-blind placebo-controlled trial (THERESA-2).

AIM: A four-arm multicentre randomized double-blind placebo-controlled trial was undertaken to assess the effect and safety of suppositories containing recombinant streptokinase (rSK) at two dose levels (100,000 IU and 200,000 IU) with sodium salicylate (SS) compared with placebo and SS for the treatment of acute haemorrhoidal disease. METHOD: Patients with acute symptoms of haemorrhoids were randomized to four treatment groups: (I) placebo, (II) SS, (III) SS + rSK 100,000 IU and (IV) SS + rSK 200,000 IU per suppository. Inpatient treatment was by four suppositories given every 6 h to discharge at 24 h. Evaluations were made at the time of discharge (24 h) and at 3, 5 and 20 days later. The main end-point was the degree of relief of pain, oedema and reduction in the size of the lesion by 90% on day 5. Adverse events and the occurrence of anti-SK antibodies were also determined. RESULTS: Eighty patients were included. Respective response rates in the four groups were 16%, 30%, 25% and 52%. In the last group there was a significant difference (36.8%) compared with control (95% CI 7.0-58.4%). The time to response was significantly shorter (median 5 days) in the 200,000 IU rSK group with respect to the others. There were no adverse events attributable to the treatment. No increase in anti-SK antibodies was detected 20 days after treatment. CONCLUSION: Suppositories with 200,000 IU rSK showed a significant improvement in symptoms of acute haemorrhoids, with an adequate safety profile.

Comparative analysis of the complications of 5347 endomyocardial biopsies applied to patients after heart transplantation and with cardiomyopathies: a single-center study.

INTRODUCTION: Endomyocardial biopsy (EMB) plays an important role in allograft surveillance to screen an acute rejection episode after heart transplantation (HT), to diagnose an unknown cause of cardiomyopathies (CMP) or to reveal a cardiac tumor. However, the procedure is not risk free. OBJECTIVE: The main objective of this research was to describe our experience with EMB during the last 33 years comparing surgical risk between HT versus no-HT patients. METHOD: We analyzed retrospectively the data of 5347 EMBs performed from 1978 to 2011 (33 years). For surveillance of acute rejection episodes after HT we performed 3564 (66.7%), whereas 1777 (33.2%) for CMP diagnosis, and 6 (1.0%) for cardiac tumor identification. RESULTS: The main complications due to EMB were divided into 2 groups to facilitate analysis: major complications associated with potential death risk, and minor complications. The variables that showed a significant difference in the HT group were as follows: tricuspid injury (.0490) and coronary fistula (.0000). Among the no-HT cohort they were insufficient fragment (.0000), major complications (.0000) and total complications (.0000). CONCLUSIONS: EMB can be accomplished with a low risk of complications and high effectiveness to diagnose CMP and rejection after HT. However, the risk is great among patients with CMP due to their anatomic characteristics. Children also constitute a risk group for EMB due to their small size in addition to the heart disease. The risk of injury to the tricuspid valve was higher among the HT group.

Extensive Mycobacterium tuberculosis circulation in a highly endemic prison and the need for urgent environmental interventions.

Aimed at assessing the circulation of Mycobacterium tuberculosis in a highly endemic prison, this 13-month prospective study was performed on strains isolated from tuberculosis (TB) cases detected passively and actively. We used X-ray screening of newly admitted inmates and mass screening at the beginning of the study and again 1 year later. Of the 94 strains genotyped by restriction fragment-length polymorphism, 79 (84·0%) belonged to one of the 12 identified clusters (2-21 strains each), including two main clusters (18 and 21 cases, respectively). A history of TB treatment was reported in 22/79 (27·8%) clustered cases. Time-space distribution of clustered cases was predominantly consistent with transmission, in micro-epidemics. Given the dominant pattern of exogenous infection and the extensive strain circulation, effective TB control should emphasize reduction of overcrowding and improvement of environmental measures as a complement to detection and treatment of cases.

Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease

Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17) was prospectively followed for 0.7 to 4.0 years (median 3.6 years). Plasma levels of von Willebrand factor antigen (VWF:Ag), tissue plasminogen activator (t-PA) and its inhibitor (PAI-1), P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106 percent increase, P < 0.003). Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response). Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6) correlated with disease severity indices (P < 0.05). Seven patients died during follow-up. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was independently associated with a high risk of death (hazard ratio = 6.56, 95 percentCI = 1.46 to 29.4, P = 0.014). Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival.

Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease.

Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17) was prospectively followed for 0.7 to 4.0 years (median 3.6 years). Plasma levels of von Willebrand factor antigen (VWF:Ag), tissue plasminogen activator (t-PA) and its inhibitor (PAI-1), P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106% increase, P < 0.003). Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response). Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6) correlated with disease severity indices (P < 0.05). Seven patients died during follow-up. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was independently associated with a high risk of death (hazard ratio = 6.56, 95%CI = 1.46 to 29.4, P = 0.014). Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival.

A clinical follow-up study of the periodontal conditions of RPD abutment and non-abutment teeth.

The purpose of this study was to evaluate the periodontal conditions of removable partial denture (RPD) wearers, comparing direct and indirect abutment teeth, and the teeth not involved in the denture design before denture placement and 1 year later. Fifty patients (32 women and 18 men), average age 45, were assessed by the same examiner at the moment of denture insertion and 3, 6, 9 and 12 months later. The following items were verified in each assessment: probing depth (PD), plaque index (PI) and gingival index (GI). PD and PI data were evaluated by anova test for linear trend followed by Tukey-Kramer post-test, while GI data were analysed by Friedman's test. Results showed that the teeth not involved in the denture design were the least affected for all variables studied. It was also verified that PD and GI mean values increased from the initial assessment to 1 year of RPD wearing in every group, but that only PI showed a significant increase. This study indicated that direct and indirect retainer elements tend to undergo more damaging periodontal effects associated with RPD wearing when compared with non-abutment elements. Plaque index values were significantly higher after 1 year of denture use.

Rosuvastatin and vascular dysfunction markers in pulmonary arterial hypertension: a placebo-controlled study.

We investigated whether chronic rosuvastatin administration could improve the abnormalities of the circulating levels of vascular dysfunction markers in pulmonary arterial hypertension (PAH). Sixty patients, aged 13 to 60 years, with idiopathic (N = 14) or congenital heart disease-associated PAH (N = 46) were equally but randomly assigned to rosuvastatin treatment (10 mg a day, orally) or placebo for 6 months in a blind fashion. Plasma levels of P-selectin, tissue-plasminogen activator and its inhibitor as well as von Willebrand factor antigen were measured by enzyme-linked immunoassay before and after 1, 3, and 6 months of treatment. Baseline levels of biomarkers were elevated (68, 16, 45 and 46% increase relative to controls, for P-selectin, von Willebrand factor antigen, tissue-plasminogen activator and its inhibitor, respectively; P < 0.001). P-selectin values at baseline, 1, 3, and 6 months were 39.9 +/- 18.5, 37.6 +/- 14.6, 34.8 +/- 14.6, and 35.4 +/- 13.9 ng/mL, respectively, for the rosuvastatin group and 45.7 +/- 26.8, 48.0 +/- 26.9, 48.1 +/- 25.7, and 45.7 +/- 25.6 ng/mL for the placebo group. The P-selectin level was lower in the rosuvastatin group compared with placebo throughout treatment (P = 0.037, general linear model). A trend was observed towards a decrease in tissue-plasminogen activator in the statin group (16% reduction, P = 0.094), with no significant changes in the other markers. Since P-selectin is crucial in inflammation and thrombosis, its reduction by rosuvastatin is potentially relevant in the pathophysiological scenario of PAH.