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The incorporation of titanium dioxide nanoparticles into concrete blocks for paving adds photocatalytic functionality to the cementitious matrix, providing self-cleaning and pollutant-degrading properties. However, wear and leaching from these pavements can release potentially toxic compounds into water bodies, affecting aquatic organisms. In this context, this study evaluated the toxicological effects of leachates from photocatalytic concrete containing nano-TiO 2 with an average size of 10 nm and anatase crystallinity on Daphnia magna . Acute and chronic toxicity tests on neonates were conducted with two leachate extracts: one from reference concrete and one from photocatalytic concrete (with 9% nano-TiO 2 added by mass of cement). In terms of acute toxicity, the reference concrete extract had an EC 50 of 104.0 mL/L at 48 h, whereas the concrete with TiO 2 had an EC 50 of 64.6 mL/L at 48 h. For chronic toxicity, the leachate from reference concrete had a significant effect ( p < 0.05) on the size parameter with an LOEC of 4 mL/L, whereas the leachate from concrete with 9% nano-TiO 2 did not have significant toxicological effects on any of the analyzed parameters (longevity, size, reproduction, and age of first posture) (LOEC > 6.5 mL/L). Furthermore, FTIR analysis indicated that TiO 2 nanoparticles were not detected in the leachates, suggesting efficient anchoring within the cementitious matrix. The results indicate that there was no increase in the chronic toxicity of the leachate from the cementitious matrix when nanoparticles were added at a 9% mass ratio of cement.

This research evaluated the rheological behavior of conventional asphalt binders modified with TiO 2 and ZnO nanoparticles and proposed mathematical equations for performance prediction. First, composites were evaluated at high temperatures to investigate the Performance Grade (PG), non-recoverable creep compliance, and Aging Index (AI). Subsequently, the fatigue damage tolerance was determined at a temperature of 20 °C through the Linear Amplitude Sweep (LAS) test. At high temperatures, for both nanoparticles, stiffness gain was observed as the nanomaterial content increased, evidenced by the increase in the dynamic shear modulus. This resulted in an increase in the Performance Grade and reduction in non-recoverable creep compliance, leading to greater resistance to permanent deformations. Furthermore, it was found that nanoparticles were able to reduce the effects of oxidation of the asphalt matrix, corroborated by the reduction of the Aging Index (AI). Regarding the fatigue damage tolerance, for both nanoparticles, an increase in performance was observed at low deformation amplitudes and a decrease at high deformation amplitudes. Finally, the analysis of each rheological parameter allowed to define the mathematical equations capable of predicting the performance of conventional asphalt binders when modified with nano-TiO 2 or nano-ZnO.

Titanium and its alloys are used as biomaterials for medical and dental applications, due to their mechanical and physical properties. Surface modifications of titanium with bioactive molecules can increase the osseointegration by improving the interface between the bone and implant. In this work, titanium dioxide nanotubes (TiO 2 NTs) were functionalized with a lectin from the plasma of the fish Oreochromis niloticus aiming to favor the adhesion and proliferation of osteoblast-like cells, improving its biocompatibility. The TiO 2 NTs were obtained by anodization of titanium and annealed at 400 °C for 3 h. The resulting TiO 2 NTs were characterized by high-resolution scanning electron microscopy. The successful incorporation of OniL on the surface of TiO 2 NTs, by spin coating, was demonstrated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIE), and attenuated total reflection-Fourier transform infrared spectrum (ATR-FTIR). Our results showed that TiO 2 NTs were successfully synthesized in a regular and well-distributed way. The modification of TiO 2 NTs with OniL favored adhesion, proliferation, and the osteogenic activity of osteoblast-like cells, suggesting its use to improve the quality and biocompatibility of titanium-based biomaterials.

3D printing is presented as an auspicious additive manufacturing technique for diverse interesting applications coupling electrochemistry and spectroscopy techniques, proposing as utilities: a general-purpose module for specular spectroscopy and spectroelectrochemical (SEC) cells for in situ UV-VIS and Raman measures capable of acting in flux or a stationary regime. As a proof of concept, UV-VIS absorption and middle-infrared spectra of an azo dye thin film were collected with the specular module showing characteristic bands according to the literature data. SEC investigations related to the Prussian Blue (PB) film growth on the platinum electrode surface were also investigated. By applying appropriate potentials, the PB film growth was accompanied by a proportional increase in the absorption signal at 700 nm in the UV-VIS region. This signal was related to the intervalence charge transfer from the Fe(II)-C to Fe(III)-N. Moreover, the Raman SEC experiment presented scattering intensity at 2092 and 2156 cm -1 , related to the (CN) mode associated with the Fe(II) and Fe(III) cations, which was observed during the thin film growth. In addition, the conversion to the Berlin Green (BG) and Prussian White (PB) forms was monitored while applying the suitable potential and in situ spectroscopic observations of structural changes during the redox processes were also detected as described in the literature. Thus, it is possible to state that the accessories successfully validated in situ spectroelectrochemical dynamic investigations unlocking many other applications in this research field., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: The prognostic importance of non-traditional risk factors for peripheral artery disease (PAD) development/progression is scarcely studied in diabetes. We investigated if carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (cf-PWV) added prognostic information beyond traditional cardiovascular risk markers for PAD outcomes., Methods: Ankle-brachial index (ABI) was measured at baseline and after a median of 91 months of follow-up in 681 individuals with type 2 diabetes. Multivariate Cox regressions examined the associations between the candidate variables and the outcome. PAD development/progression was defined by a reduction in ABI ≥ 0.15 (to a level < 0.9) or limb revascularization procedures, lower-extremity amputations or death due to PAD. The improvement in risk discrimination was assessed by increases in C-statistics of the models., Results: Seventy-seven patients developed/progressed PAD: 50 reduced ABI to < 0.9, seven had lower-limb revascularizations, and 20 had amputations or death. Age, male sex, diabetes duration, presence of microvascular complications (peripheral neuropathy and diabetic kidney disease), baseline HbA 1c , 24-h systolic BP (SBP) and mean cumulative office SBP and LDL-cholesterol were associated with PAD development/progression in several models. CIMT and cf-PWV were additionally associated with PAD outcomes, and their inclusion further improved risk discrimination (with C-statistic increases between 0.025 and 0.030). The inclusion of ambulatory 24-h SBP, instead of office SBP, also improved PAD risk discrimination., Conclusions: Increased CIMT and aortic stiffness are associated with greater risks of developing/progressing PAD, beyond traditional risk factors, in type 2 diabetes.

Cyclin-dependent kinases (CDKs) are frequently deregulated in cancer and represent promising drug targets. We provide evidence that CDK8 has a key role in B-ALL. Loss of CDK8 in leukemia mouse models significantly enhances disease latency and prevents disease maintenance. Loss of CDK8 is associated with pronounced transcriptional changes, whereas inhibiting CDK8 kinase activity has minimal effects. Gene set enrichment analysis suggests that the mTOR signaling pathway is deregulated in CDK8-deficient cells and, accordingly, these cells are highly sensitive to mTOR inhibitors. Analysis of large cohorts of human ALL and AML patients reveals a significant correlation between the level of CDK8 and of mTOR pathway members. We have synthesized a small molecule YKL-06-101 that combines mTOR inhibition and degradation of CDK8, and induces cell death in human leukemic cells. We propose that simultaneous CDK8 degradation and mTOR inhibition might represent a potential therapeutic strategy for the treatment of ALL patients.

Aims/hypothesis: The prognostic importance of the ankle-brachial index (ABI) in individuals with diabetes is controversial. We aimed to evaluate the relationship between the ABI and the occurrence of micro- and macrovascular complications in individuals with type 2 diabetes., Methods: The ABI was measured at baseline in 668 individuals with type 2 diabetes, and the individuals were followed-up for a median of 10 years. Multivariate Cox analysis was used to examine associations between the ABI and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration and peripheral neuropathy) and macrovascular (total cardiovascular events, major adverse cardiovascular events [MACE] and cardiovascular mortality) complications, and all-cause mortality. The improvement in risk stratification was assessed using the C statistic and the integrated discrimination improvement (IDI) index., Results: During follow-up, 168 individuals had a cardiovascular event (140 MACE) and 191 individuals died (92 cardiovascular deaths); 156 individuals newly developed or experienced worsening diabetic retinopathy, 194 achieved the renal composite outcome (122 with newly developed microalbuminuria and 93 with deteriorating renal function) and 95 newly developed or experienced worsening peripheral neuropathy. The ABI, either analysed as a continuous or as a categorical variable, was significantly associated with all macrovascular and mortality outcomes, except for non-cardiovascular mortality. Individuals with a baseline ABI of ≤0.90 had a 2.1-fold increased risk of all-cause mortality (95% CI 1.3, 3.5; p = 0.004), a 2.7-fold excess risk of cardiovascular mortality (95% CI 1.4, 5.4; p = 0.004) and a 2.5-fold increased risk of MACE (95% CI 1.5, 4.4; p = 0.001). The ABI improved risk discrimination over classical risk factors, with relative IDIs ranging from 6.3% (for all-cause mortality) to 31% (for cardiovascular mortality). In addition, an ABI of ≤0.90 was associated with the development or worsening of peripheral neuropathy (2.1-fold increased risk [95% CI 1.1, 4.3]; p = 0.033), but not with retinopathy or renal outcomes., Conclusions/interpretation: A low ABI is associated with excess risk of adverse cardiovascular outcomes, mortality and peripheral neuropathy development or worsening, and improves cardiovascular risk stratification. The ABI should therefore be routinely evaluated in individuals with type 2 diabetes.

The current long-term treatment for leishmaniasis causes severe side effects and resistance in some cases. An evaluation of the anti-leishmanial potential of an HSP90-inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), demonstrated its potent effect against Leishmania spp. in vitro and in vivo . We have previously shown that 17-AAG can kill L. (L) amazonensis promastigotes with an IC 50 of 65 nM and intracellular amastigote at concentrations as low as 125 nM. As this compound presents low solubility and high toxicity in human clinical trials, we prepared an inclusion complex containing hydroxypropyl-β-cyclodextrin and 17-AAG (17-AAG:HPβCD) to improve its solubility. This complex was characterized by scanning electron microscopy, and X-ray diffraction. Liposomes-containing 17-AAG:HPβCD was prepared and evaluated for encapsulation efficiency (EE%), particle size, polydispersity index (PDI), pH, and zeta potential, before and after accelerated and long-term stability testing. An evaluation of leishmanicidal activity against promastigotes and intracellular amastigotes of L. (L) amazonensis was also performed. The characterization techniques utilized confirmed the formation of the inclusion complex, HPβCD:17-AAG, with a resulting 33-fold-enhancement in compound water solubility. Stability studies revealed that 17-AAG:HPβCD-loaded liposomes were smaller than 200 nm, with 99% EE. Stability testing detected no alterations in PDI that was 0.295, pH 7.63, and zeta potential +22.6, suggesting liposome stability, and suitability for evaluating leishmanicidal activity. Treatment of infected macrophages with 0.006 nM of 17-AAG:HPβCD or 17-AAG:HPβCD-loaded liposomes resulted in almost complete amastigote clearance inside macrophages after 48 h. This reduction is similar to the one observed in infected macrophages treated with 2 μM amphotericin B. Our results showed that nanotechnology and drug delivery systems could be used to increase the antileishmanial efficacy and potency of 17-AAG in vitro , while also resulting in reduced toxicity that indicates these formulations may represent a potential therapeutic strategy against leishmaniasis.

Aims: To investigate the associated factors with the vibration threshold perception (VPT) in patients with type 2 diabetes and to assess whether it is useful for detection of diabetic peripheral neuropathy (DPN)., Methods: VPTs were measured with Vibration Sensory Analyzer (VSA-3000) in 426 diabetic patients. The diagnosis of DPN was based on Neuropathy Symptom Score and Neuropathy Disability Score (NDS). ROC curve analysis and multiple linear and logistic regressions were performed to investigate the associations between VPT and DPN., Results: Values of VPT were progressively higher according to NDS stages. Age, height, diabetes duration, and mean cumulative HbA 1c exposure (partial correlation coefficients: 0.34; 0.27; 0.10; and 0.13; respectively) were the variables independently associated with VPT. Area under ROC curve of VPT for detection of DPN was 0.71 (95% CI: 0.66-0.75) and >8.9 μm was its best cut-off value. VPT, age, female sex, height, diabetes duration and mean HbA 1c levels were the independent correlates of the presence of DPN. An increased VPT triplicate the likelihood of having DPN (OR: 3.24; 95% CI: 2.05-5.11)., Conclusions: VPT, measured by an automatic device, shares common correlates with DPN and is strongly associated with its presence. VPT testing may be useful as a screening tool for DPN assessment., (Published by Elsevier Inc.)

Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34 + /CD38 - LSCs in patients with Ph + ALL (n = 22) and Ph - ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested. Moreover, in various subgroups of patients, LSCs also displayed CD20 (MS4A1) (10/41 = 24%), CD22 (12/20 = 60%), CD33 (Siglec-3) (20/48 = 42%), CD52 (CAMPATH-1) (17/40 = 43%), IL-1RAP (13/29 = 45%), and/or CD135 (FLT3) (4/20 = 20%). CD25 (IL-2RA) and CD26 (DPPIV) were expressed on LSCs in Ph + ALL exhibiting BCR/ABL1 p210 , whereas in Ph + ALL with BCR/ABL1 p190 , LSCs variably expressed CD25 but did not express CD26. In Ph - ALL, CD34 + /CD38 - LSCs expressed IL-1RAP in 6/18 patients (33%), but did not express CD25 or CD26. Normal stem cells stained negative for CD25, CD26 and IL-1RAP, and expressed only low amounts of CD52. In xenotransplantation experiments, CD34 + /CD38 - and CD34 + /CD38 + cells engrafted NSG mice after 12-20 weeks, and targeting with antibodies against CD33 and CD52 resulted in reduced engraftment. Together, LSCs in Ph + and Ph - ALL display unique marker- and target expression profiles. In Ph + ALL with BCR/ABL1 p210 , the LSC-phenotype closely resembles the marker-profile of CD34 + /CD38 - LSCs in chronic myeloid leukemia, confirming the close biologic relationship of these neoplasms. Targeting of LSCs with specific antibodies or related immunotherapies may facilitate LSC eradication in ALL., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment. By modeling ponatinib resistance and testing samples from these CML patients, it is hoped that an alternative drug target can be identified and inhibited with a novel compound., Methods: Two CML cell lines with acquired BCR-ABL-independent resistance were generated following culture in ponatinib. RNA sequencing and gene ontology (GO) enrichment were used to detect aberrant transcriptional response in ponatinib-resistant cells. A validated oncogene drug library was used to identify US Food and Drug Administration-approved drugs with activity against TKI-resistant cells. Validation was performed using bone marrow (BM)-derived cells from TKI-resistant patients (n = 4) and a human xenograft mouse model (n = 4-6 mice per group). All statistical tests were two-sided., Results: We show that ponatinib-resistant CML cells can acquire BCR-ABL-independent resistance mediated through alternative activation of mTOR. Following transcriptomic analysis and drug screening, we highlight mTOR inhibition as an alternative therapeutic approach in TKI-resistant CML cells. Additionally, we show that catalytic mTOR inhibitors induce autophagy and demonstrate that genetic or pharmacological inhibition of autophagy sensitizes ponatinib-resistant CML cells to death induced by mTOR inhibition in vitro (% number of colonies of control[SD], NVP-BEZ235 vs NVP-BEZ235+HCQ: 45.0[17.9]% vs 24.0[8.4]%, P = .002) and in vivo (median survival of NVP-BEZ235- vs NVP-BEZ235+HCQ-treated mice: 38.5 days vs 47.0 days, P = .04)., Conclusion: Combined mTOR and autophagy inhibition may provide an attractive approach to target BCR-ABL-independent mechanism of resistance.

Thymol is a monoterpene and acetylation form of this compound can reduce the toxicity and enhance its biological effects. The objective of this study was to evaluate the effect of thymol and thymol acetate (TA) on egg, larva and adult Haemonchus contortus and the cuticular changes, acute toxicity in mice and the efficacy on sheep gastrointestinal nematodes. In vitro tests results were analyzed by analysis of variance (ANOVA) and followed by comparison with Tukey test or Bonferroni. The efficacy of in vivo test was calculated by the BootStreet program. In the egg hatch test (EHT), thymol (0.5 mg/mL) and TA (4 mg/mL) inhibited larval hatching by 98% and 67.1%, respectively. Thymol and TA (8 mg/mL) inhibited 100% of larval development. Thymol and TA (800 µg/mL) reduced the motility of adult worms, by 100% and 83.4%, respectively. Thymol caused cuticular changes in adult worm teguments. In the acute toxicity test, the LD50 of thymol and TA were 1,350.9 mg/kg and 4,144.4 mg/kg, respectively. Thymol and TA reduced sheep egg count per gram of faeces (epg) by 59.8% and 76.2%, respectively. In in vitro tests thymol presented better anthelmintic activity than TA. However TA was less toxic and in in vivo test efficacy was similar.

Acute lymphoblastic leukemia (ALL) is characterized by leukemic expansion of lymphoid blasts in hematopoietic tissues. Despite improved therapy only a subset of patients can be cured. Therefore, current research is focusing on new drug-targets. Members of the BCL-2 family and components of the PI3-kinase/mTOR pathway are critically involved in the regulation of growth and survival of ALL cells. We examined the effects of the pan-BCL-2 blocker obatoclax and the PI3-kinase/mTOR-inhibitor BEZ235 on growth and survival of ALL cells. In 3 H-thymidine uptake experiments, both drugs suppressed the in vitro proliferation of leukemic cells in all patients with Philadelphia chromosome-positive (Ph + ) ALL and Ph - ALL (obatoclax IC 50 : 0.01-5 μM; BEZ235, IC 50 : 0.01-1 μM). Both drugs were also found to produce growth-inhibitory effects in all Ph + and all Ph - cell lines tested. Moreover, obatoclax and BEZ235 induced apoptosis in ALL cells. In drug-combination experiments, obatoclax and BEZ235 exerted synergistic growth-inhibitory effects on ALL cells. Finally, we confirmed that ALL cells, including CD34 + /CD38 - stem cells and all cell lines express transcripts for PI3-kinase, mTOR, BCL-2, MCL-1, and BCL-xL. Taken together, this data shows that combined targeting of the PI3-kinase/mTOR-pathway and BCL-2 family-members is a potent approach to counteract growth and survival of ALL cells., Competing Interests: CONFLICTS OF INTEREST The authors of this manuscript have the following conflicts of interest to declare: P.V. received honoraria from Novartis and Ariad. W.R.S. received a research grant from Amgen and honoraria from Novartis, Amgen, and Ariad. G.H. received research funding from Gilead and honoraria from Novartis, Ariad, and Amgen. U.J. received honoraria from Novartis and Abbvie. A.W.H. received honoraria from Amgen, Ariad and Jazz Pharmaceuticals.

Purpose: The objective of this study was to investigate whether the potentially inappropriate medication (PIM) use is a predictor for mortality in a community-based population of older adults., Methods: A cohort study was performed between January 1, 1997, and December 31, 2011, based on data from a representative sample of the population aged 60 years or older living in Bambuí, Brazil. Univariate and multivariate analyses of the association between the variable of interest (use of PIM or pharmacological groups of PIM) and mortality were based on the extended Cox model for proportional hazards. The extended model was adopted to include the measurement of the exposure of interest throughout the follow-up period and not only at baseline. Adjustment variables included sociodemographic characteristics, health status, and use of health care services and medications. A level of significance of 5% was adopted for all analyses., Results: The prevalence of PIM use was 56.0% (95%CI 53.4-58.6). After multiple adjustments, the risk of death among users of at least one PIM was 44% higher (HR = 1.44; 95%CI 1.21 to 1.71) than among those who did not use any PIM. Among the PIM groups analyzed, antipsychotics were the most strongly associated with mortality (HR = 2.33; 95%CI 1.72 to 3.17)., Conclusions: The study revealed a high prevalence of PIM use among the community-based aged population. It also identified PIM use as a predictor for mortality in this group of individuals. This indicates the need for selection of safer drug therapy alternatives in this patient group.

This study analyzed indicators for health behaviors and use of preventive services in two probabilistic samples of adults, one in 2003 (n = 13,757) and the other in 2010 (n = 12,983), with and without private health insurance in Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil. After adjusting for demographic variables, temporal variation, and source of care, there was a reduction in smoking prevalence, similar between individuals with and without private health insurance, from 2003 to 2010. During this same period the prevalence of excessive alcohol intake and sedentary lifestyle increased in both groups; with the same magnitude, there was a decrease in the prevalence of leisure-time physical activity. No changes were observed in the prevalence of blood pressure measurement, but the prevalence of cholesterol testing, mammogram, and Pap smear increased more sharply in individuals without health insurance.

Babassu oil extraction is the main income source in nut breakers communities in northeast of Brazil. Among these communities, babassu oil is used for cooking but also medically to treat skin wounds and inflammation, and vulvovaginitis. This study aimed to evaluate the anti-inflammatory activity of babassu oil and develop a microemulsion system with babassu oil for topical delivery. Topical anti-inflammatory activity was evaluated in mice ear edema using PMA, arachidonic acid, ethyl phenylpropiolate, phenol, and capsaicin as phlogistic agents. A microemulsion system was successfully developed using a Span® 80/Kolliphor® EL ratio of 6 : 4 as the surfactant system (S), propylene glycol and water (3 : 1) as the aqueous phase (A), and babassu oil as the oil phase (O), and analyzed through conductivity, SAXS, DSC, TEM, and rheological assays. Babassu oil and lauric acid showed anti-inflammatory activity in mice ear edema, through inhibition of eicosanoid pathway and bioactive amines. The developed formulation (39% A, 12.2% O, and 48.8% S) was classified as a bicontinuous to o/w transition microemulsion that showed a Newtonian profile. The topical anti-inflammatory activity of microemulsified babassu oil was markedly increased. A new delivery system of babassu microemulsion droplet clusters was designed to enhance the therapeutic efficacy of vegetable oil.

This study compared the use of health services and medication, screening test coverage, characteristics of primary care, and health behaviors in 370 diabetics 45 years or older according to sources of care: private health policyholders regardless of place of residence; residents in areas covered by the Family Health Strategy; and individuals covered by a "traditional" Primary Care Unit. The study used data from the 2nd Adult Health Survey in Belo Horizonte Metropolitan Region (2010), Minas Gerais State, Brazil. Use of health services, use of medication, coverage of follow-up tests, alcohol abuse, and smoking did not differ significantly according to source of care. Prevalence rates for insufficient leisure-time physical exercise and sedentary lifestyle were higher among individuals covered by the Family Health Strategy or "traditional" Primary Care Unit. The primary care characteristics (access, comprehensiveness, continuity, and family focus) performed better among individuals with private health insurance, even after adjusting for age, sex, and schooling. The study identified two main challenges for the Brazilian Unified National Health System in managing patients with diabetes in the city of Belo Horizonte: the promotion of physical exercise and reorganization to improve performance in primary care, especially in access to medical appointments.

Objective: To assess the prevalence of disability and its association with social capital among community-dwelling elderly., Methods: The study was based on 2nd Health Survey of Belo Horizonte Metropolitan Region - 2010, that included 1,995 community-dwelling elderly, randomly sampled. The exposure of interest was social capital, measured by confidence in neighborhood, perception of the physical environment, sense of cohesion in housing, and neighborhood perception of help. Socio-demographic variables, health conditions and use of health services were considered in the analysis with the purpose of adjustment., Results: Approximately one third of participants (32.6%) were unable to at least one instrumental activity of daily living (IADL) and/or basic activity of daily living (ADL); the prevalence of disability in ADL/IADL was 18.1%, and only in IADL was 14.6%. Elderly with functional disabilities had higher odds of poor social capital, but only the sense of cohesion in housing neighborhood showed to be independently associated with functional disability (OR = 1.80; 95%CI 1.12 - 2.88)., Conclusions: Our results show the importance of social capital in research on associated factors of functional disability and indicate the need to implement public policies for social and environmental areas, since the needs of the elderly require measures beyond those typical of the health sector.

Background: The aim of this study was to evaluate the psychometric properties of the Brazilian version of the Oral Anticoagulation Knowledge (OAK) Test., Methods: This study, conducted in an anticoagulation clinic, included 201 Brazilian participants aged over 18 years, who had been using warfarin for more than two months. The reliability of the instrument was evaluated by assessing internal consistency (Kuder-Richardson coefficient) and reproducibility (test-retest reliability). The validity was evaluated by hypothesizing that there would be a positive correlation of moderate to strong intensity between the correctness levels of the OAK Test and time within therapeutic range (TTR) values, which is a measure used to evaluate the quality of oral anticoagulation., Results: The instrument exhibited good psychometric properties. The total a Kuder-Richardson coefficient value was 0.818 and intraclass correlation coefficient was 0.967. The validity revealed a strong positive correlation between the values of the level of knowledge, as measured by the OAK Test and the TTR values (rs = 0.780)., Conclusion: The instrument proved to be a reliable and valid tool for evaluating the knowledge of Brazilian patients on oral anticoagulation therapy with warfarin. This instrument may be incorporated into the practice of health care for substantiating the structuring of educational activities to ensure the improvement of knowledge about the use of warfarin, thereby increasing the effectiveness and safety of treatment.

Carvacrol is a compound isolated from some essential oils. It has been reported to possess anthelmintic activity. Acetylation of this monoterpene has been proposed as a potential way to reduce the toxicity and enhance the pharmacological effects of carvacrol. This study aimed to evaluate the effect of carvacryl acetate (CA) using in vitro and in vivo assays with gastrointestinal nematodes of small ruminants. The egg hatching test (EHT), larval development test (LDT) and adult worm motility (AWM) assessment were conducted to evaluate the effect of the acetylated product and pure carvacrol on Haemonchus contortus eggs, larvae and adults. The structural changes induced in adult H. contortus were assessed using scanning electron microscopy (SEM). CA and carvacrol acute toxicity was evaluated in mice. Finally, the efficacy of 250 mg/kg CA and 2.5mg/kg monepantel (positive control) were evaluated in 30 sheep naturally infected with gastrointestinal nematodes by the fecal egg count reduction test (FECRT). In vitro tests were analyzed by analysis of variance (ANOVA) followed by comparison with Tukey's test. The efficacy was calculated by the Boot Street program using the arithmetic average. The number of eggs in feces (epg) of the groups were transformed to log (x+1) and subjected to ANOVA to compare differences among the groups by Tukey's test. The level of significance was P<0.05. CA and carvacrol inhibited larval hatching by 89.3 and 97.7% at doses of 8.0 and 1.0mg/ml, respectively. At the concentration of 2mg/ml, CA and carvacrol inhibited 100% of larval development. At a concentration of 200 μg/ml, CA and carvacrol inhibited the motility of adult worms by 100% and 58.3% at 24h post-exposure, respectively. CA caused cuticle and vulvar flap wrinkling and bubbles to emerge from the tegument. Carvacrol caused more discreet effects on the cuticle and vulvar flap. The LD10 and LD50 of CA were 566.7 mg/kg and 1544.5mg/kg, respectively. The LD10 and LD50 of carvacrol were 546.8 mg/kg and 919 mg/kg, respectively. CA and monepantel reduced the epg of sheep by 65.9 and 96.4%, respectively, at 16 days post-treatment. CA showed in vitro and in vivo anthelmintic activity and was less toxic than carvacrol., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Durable responses to imatinib monotherapy are rarely seen in aggressive forms of Philadelphia chromosome positive (Ph+) leukemias. To investigate the possible cause of treatment failure we examined the role of protein kinase C epsilon (PKCE), an oncogene highly implicated in the development of solid tumors and resistance to chemotherapy. We found high levels of PKCE transcripts in Ph+ acute lymphoblastic leukemia (ALL) cells from patients and cell lines, and imatinib resistant chronic myeloid leukemia, which were also less responsive to imatinib-induced apoptosis than Ph+ cells with lower PKCE expression. Furthermore, the siRNA-mediated knockdown or peptide inhibition of PKCE in Ph+ cells increased imatinib-induced apoptosis while overexpression of PKCE reduced imatinib-induced apoptosis, with concomitant increase in the pro-survival factor AKT. Our results suggest PKCE plays a protective role against apoptosis induced by BCR-ABL inhibition in Ph+ leukemias with high PKCE expression, such as Ph+ ALL.

Background: Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification., Materials/methods: We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians. We also examined whether genomic ancestry and ethnoracial self-classification affect the predictive value of SRH for subsequent mortality., Results: European ancestry predominated among participants, followed by African and Native American (median = 84.0%, 9.6% and 5.3%, respectively); the prevalence of Non-White (Mixed and Black) was 39.8%. Persons at higher levels of African and Native American genomic ancestry, and those self-identified as Non-White, were more likely to report poor health than other groups, even after controlling for socioeconomic conditions and an array of self-reported and objective physical health measures. Increased risks for mortality associated with worse SRH trajectories were strong and remarkably similar (hazard ratio ~3) across all genomic ancestry and ethno-racial groups., Conclusions: Our results demonstrated for the first time that higher levels of African and Native American genomic ancestry--and the inverse for European ancestry--were strongly correlated with worse SRH in a Latin American admixed population. Both genomic ancestry and ethnoracial self-classification did not modify the strong association between baseline SRH or SRH trajectory, and subsequent mortality.