Multibiomarker approach to assess the magnitude of occupational exposure and effects induced by a mixture of metals.

Metals and metalloids including lead (Pb), arsenic (As) and manganese (Mn) can occur as mixtures in occupational contexts, such as mines. These chemicals are all known to be neurotoxic and provoke changes in heme metabolism also known to induce neurotoxicity. The objective of this work was to propose a multi-biomarker (BM) methodology to screen subjects exposed to the mixture of Pb, As and Mn and assess the severity of their exposure/effects, in an individual basis. The urinary levels of the metals, dela-aminolevulinic acid (ALA) and porphyrins were determined in Portuguese miners and in a control group. The combination of Pb and As urinary levels had the highest capability to identify subjects occupationally exposed to this mixture in mines, as evaluated through Receiver Operating Characteristic (ROC) (A = 98.2%; p < 0.05), allowing that 94.2% of 86 studied subjects were properly identified and the generation of an equation indicating the odd of a subject be considered as exposed to the metal mixture. The combination of urinary ALA and porphyrins revealed to be best one to be applied in the assessment of subjects with high, intermediate, and low magnitudes of exposure/effects, with 95.7% of 46 miners classified correctly according to their severity sub-group and allowing to generate equations, which can be applied in new subjects. The proposed methodology showed a satisfactory performance, evaluating in an integrated manner the magnitude of exposure/effects of the exposed workers, may contributing to improve the control of their health.

Assessment of occupational exposures to multiple metals with urinary porphyrin profiles.

Chronic occupational exposures to low levels of metal mixtures necessitates biomonitoring of exposed workers. However, a single biomarker (BM) is rarely sufficient to ascertain the exposure of an individual to a complex mixture, with multiparameter analysis of the same sample considered recently as a preferred approach. Porphyrins are formed as intermediates of heme biosynthesis and different metals can exert their effects at different points of this metabolic pathway, leading to changed urinary porphyrins excretion profiles. The aim of this work was to develop a model that could serve to identify, on an individual basis, multiple metal exposure resulting from mining work, by using urinary porphyrin profiles. Urine samples of workers were obtained from a Portuguese mining company and a non-occupationally exposed group was used as control. The levels of uro-, hepta-, hexa-, penta-, copro- and protoporphyrins were determined by HPLC. It was observed that only heptaporphyrin levels in miners were significantly (p<0.05) different from controls. However, when the concentrations of all porphyrins were combined by binary logistic regression, their ability to discriminate between miners and controls was higher than each one of the porphyrins alone, as indicated by a greater curve' area under a ROC curve. Moreover, when the combined porphyrins were used to calculate the probability of each subject fit in the occupationally exposed group, 83% of 47 individuals were correctly identified with respect to their type of exposure. These results suggest that the integration of the urinary porphyrin profile is a promising tool for the detection of subjects exhibiting biochemical modifications due to occupational exposure to metals in mines.

'We were our parents' ears and mouths': reflecting on the language brokering experiences of hearing children born to deaf parents

Background. Hearing children born to deaf parents, or children of deaf adults (CODAs), are often bicultural and bilingual members of the deaf and hearing communities. They are often expected to fulfil very adult roles, especially as the communication link between their deaf parents and the hearing society. Assuming adult roles may place CODAs in difficult situations, potentially affecting their wellbeing and development. In SA, little is known about CODAs and the dynamics of growing up hearing in deaf-parented homes. Objective. To reflect on the childhood experiences of language brokering in deaf-parented families. Methods. Two male and eight female participants (21 - 40 years), identified through purposive and snowball sampling, participated in this study. A phenomenological, qualitative approach was employed using semi-structured, open-ended interviews. Thematic analysis revealed inductive themes. Results. The findings indicate that the interviewed CODAs acted as language brokers and interpreters between their families and the hearing community from a very young age. As children, they were placed in demanding situations, for which they were not developmentally ready. CODAs found balancing the demands from both communities emotionally draining, especially at a young age. Conclusion. A multidisciplinary approach is suggested to address the mental health, wellbeing and development of young CODAs

Self-spreading of the wetting ridge during stick-slip on a viscoelastic surface.

Dynamic wetting behaviors on soft solids are important to interpret complex biological processes from cell-substrate interactions. Despite intensive research studies over the past half-century, the underlying mechanisms of spreading behaviors are not clearly understood. The most interesting feature of wetting on soft matter is the formation of a "wetting ridge", a surface deformation by a competition between elasticity and capillarity. Dynamics of the wetting ridge formed at the three-phase contact line underlies the dynamic wetting behaviors, but remains largely unexplored mostly due to limitations in indirect observation. Here, we directly visualize wetting ridge dynamics during continuous- and stick-slip motions on a viscoelastic surface using X-ray microscopy. Strikingly, we discover that the ridge spreads spontaneously during stick and triggers contact line depinning (stick-to-slip transition) by changing the ridge geometry which weakens the contact line pinning. Finally, we clarify 'viscoelastic-braking', 'stick-slipping', and 'stick-breaking' spreading behaviors through the ridge dynamics. In stick-breaking, no ridge-spreading occurs and contact line pinning (hysteresis) is enhanced by cusp-bending while preserving a microscopic equilibrium at the ridge tip. We have furthered the understanding of spreading behaviors on soft solids and demonstrated the value of X-ray microscopy in elucidating various dynamic wetting behaviors on soft solids as well as puzzling biological issues.

Probing Novel Microstructural Evolution Mechanisms in Aluminum Alloys Using 4D Nanoscale Characterization.

Dispersions of nanoscale precipitates in metallic alloys have been known to play a key role in strengthening, by increasing their strain hardenability and providing resistance to deformation. Although these phenomena have been extensively investigated in the last century, the traditional approaches employed in the past have not rendered an authoritative microstructural understanding in such materials. The effect of the precipitates' inherent complex morphology and their 3D spatial distribution on evolution and deformation behavior have often been precluded. This study reports, for the first time, implementation of synchrotron-based hard X-ray nanotomography in Al-Cu alloys to measure kinetics of different nanoscale phases in 3D, and reveals insights behind some of the observed novel phase transformation reactions. The experimental results of the present study reconcile with coarsening models from the Lifshitz-Slyozov-Wagner theory to an unprecedented extent, thereby establishing a new paradigm for thermodynamic analysis of precipitate assemblies. Finally, this study sheds light on the possibilities for establishing new theories for dislocation-particle interactions, based on the limitations of using the Orowan equation in estimating precipitation strengthening.

Molecular dynamics simulations of T-2410 and T-2429 HIV fusion inhibitors interacting with model membranes: Insight into peptide behavior, structure and dynamics.

T-2410 and T-2429 are HIV fusion inhibitor peptides (FI) designed to present a higher efficiency even against HIV strains that developed resistance against other FIs. Similar peptides were shown to interact with model membranes both in the liquid disordered phase and in the liquid ordered state. Those results indicated that such interaction is important to function and could be correlated with their effectiveness. Extensive molecular dynamics simulations were carried out to investigate the interactions between both T-2410 and T-2429 with bilayers of pure 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and a mixture of POPC/cholesterol (Chol) (1:1). It was observed that both peptides interact strongly with both membrane systems, especially with the POPC/Chol systems, where these peptides show the highest number of H-bonds observed so far. T-2410 and T-2429 showed higher extent of interaction with bilayers when compared to T-20 or T-1249 in previous studies. This is most notable in POPC/Chol membranes where, although able to form H-bonds with Chol, they do so to a lesser extent than T-1249 does, the latter being the only FI peptide so far that was observed to form H-bonds with Chol. This behavior suggests that interaction of FI peptides with rigid Chol rich membranes may not be as dependent from peptide/Chol H-bond formation as previous results of T-1249 behavior led to believe. As in other similar peptides, the higher ability to interact with membranes shown by T-2410 and T2429 is probably correlated with its higher inhibitory efficiency.

Nanoscale Three-Dimensional Microstructural Characterization of an Sn-Rich Solder Alloy Using High-Resolution Transmission X-Ray Microscopy (TXM).

Three-dimensional (3D) nondestructive microstructural characterization was performed using full-field transmission X-ray microscopy on an Sn-rich alloy, at a spatial resolution of 60 nm. This study highlights the use of synchrotron radiation along with Fresnel zone plate optics to perform absorption contrast tomography for analyzing nanoscale features of fine second phase particles distributed in the tin matrix, which are representative of the bulk microstructure. The 3D reconstruction was also used to quantify microstructural details of the analyzed volume.

What do we mean by multimorbidity? An analysis of the literature on multimorbidity measures, associated factors, and impact on health services organization.

BACKGROUND: Multimorbidity is a consequence of both epidemiological and demographic transition. Unlike comorbidity, it currently has no consensus definition, making it difficult to assess its epidemiological and socioeconomic burden, to organize healthcare services rationally, and to determine the skills needed for patient self-reliance. The aim of this study is to define the spectrum of multimorbidity and to discuss current implications for the organization of care. METHODS: Two independent readers analyzed the literature indexed in PubMed, Embase, CINAHL, and Scopus. RESULTS: The bibliographic search conducted on July 16, 2013, retrieved 2287 articles (670 in PubMed, 666 in Embase, 582 in Scopus, and 369 in CINAHL). Of these, 108 articles were retained. Multimorbidity is designated by a variety of terms, none of them being MeSH terms. There is no single measure of multimorbidity, as this entity is usually studied for its functional or economic impact, rather than its causes. The prevalence varies considerably, depending on the measure used and the population studied. Factors associated with multimorbidity are age, gender, and socioeconomic characteristics of the populations studied. Studies evaluating the organization-of-care are inconclusive or insufficient. CONCLUSIONS: Multimorbidity serves as an avatar for the fundamental, recurrent problems of modern medicine and the organization-of-care. It may be defined by its causes or its consequences and reflects our concept of both individual health and its collective management. Tools that would allow a more appropriate measurement of this entity are available; we should use them to match medical reality to the needs of patients.

Oxidative stress in mice treated with antileishmanial meglumine antimoniate.

In order to improve the understanding of the toxicity of pentavalent antimony (Sb(V)), we investigated the acute effects of meglumine antimoniate (MA) on the oxidative stress in heart, liver, kidney, spleen and brain tissue of mice. Levels of lipoperoxidation and protein carbonylation were measured to evaluate the oxidative status, whereas superoxide dismutase/catalase activity and glutathione levels were recorded to examine the antioxidative status. We observed that MA caused significant protein carbonylation in the heart, spleen and brain tissue. Increased lipoperoxidation was found in the liver and brain tissue. An imbalance between superoxide dismutase and catalase activities could be observed in heart, liver, spleen and brain tissue. Our results suggest that MA causes oxidative stress in several vital organs of mice. This indicates that the production of highly reactive oxygen and nitrogen species induced by MA might be involved in some of its toxic adverse effects.

Emotional behavior in middle-aged rats: Implications for geriatric psychopathologies.

Clinical findings reveal that middle-aged patients are more susceptible to suffer from psychiatric disorders than older ones. However, little is known about the emotional behavior of aging rodents. This study aimed to investigate behavioral alterations in male middle-aged Wistar rats in the open-field (OF) test (at illuminated and dimly light conditions), elevated plus maze (EPM), forced swimming (FST) and inhibitory avoidance task (IA). In the EPM, middle-aged rats displayed reduced percentages of the time spent in and entries into open arms. The ambulatory activity measured in the OF under dimly light conditions was identical among groups. However, under illuminated conditions, a reduction in the number of crossings was detected in older rats, reinforcing that aged animals display a genuine anxiogenic-like phenotype. Additionally, aged rats showed an increase in the immobility time in the FST, and a reduction in the latency to step down the platform in the IA. A negative correlation was found between the immobility time and latency to step down the platform, suggesting a relationship between depressive-behavior and cognitive impairment in old rats. Altogether, male middle-aged rats are more anxious, depressed, and display aversive memory impairments. These observations contribute to investigate biological mechanisms and therapeutic interventions for geriatric anxiety and depression.

[Factors associated with household and family in leprosy transmission in Rio de Janeiro, Brazil]. / Fatores associados ao domicílio e à família na determinação da hanseníase, Rio de Janeiro, Brasil.

A cross-sectional study was carried out to characterize the contribution of several household characteristics to the transmission of leprosy. Households with diagnosed cases of illness were compared to two healthy groups. All randomly selected households were located in the municipality of Sao Goncalo, in the State of Rio de Janeiro. Using an aerial map with the description of the census tract, 2,412 cases were marked. Three groups were established, while the household was the analytical unit: group I - households with cases; group II - neighboring households; and group III - households located in tracts with no reported case of illness, that is, outside disease foci. Group I was compared with that of neighboring households using a multiple logistic regression model by conditional methods. Unconditional methods were used to compare groups I and III. Group I as compared to Group II showed an association with age and educational level for households and heads of families. Comparison of characteristics of the heads of families and households with cases of leprosy with those located outside the focus showed that the differential factors were age, type of dwelling, and availability of running water. This is probably due to more recent settlement in a peripheral region where water resources are not available yet. Households are the basic ecological unit, and age and educational level are determinant factors for leprosy morbidity in this area.

[Location of single skin lesions of paucibacillary leprosy]. / Localisation des lésions cutanées uniques de lèpre paucibacillaire.

In this paper the authors study the sites of single lesions in 317 paucibacillary patients registered at the outpatient units of the CMS Jorge Saldanha and the Curupaiti State Hospital in Rio de Janeiro, Brazil. The preferential sites of lesions in the population studied, their relation with age and sex and factors likely to influence their distribution are discussed. The findings are compared with other similar studies performed in Asia and Africa.

[Efficacy of multidrug therapy in treatment of paucibacillary leprosy patients--preliminary results]. / Eficácia da MDT no tratamento de pacientes hansenianos paucibacilares--resultados preliminares.

The efficaciousness evaluation of the polychemotherapics regimens recommended by WHO to the hansenian paucibacillary patients, is carried out mainly by the suitable follow up of patients after therapeutic discharge. The criterion for inclusion of patients as paucibacillary ones is another point of importance. The authors based on the follow up of 66 patients that completed treatment and in the absence of relapses until the moment, advise that together with the clinical classification it should be considered factors like: the Mitsuda test, the number of lesions and the bacilloscopy result.