The predictive role of serum and bronchoalveolar lavage cytokines and adhesion molecules for acute respiratory distress syndrome development and outcome

BACKGROUND: The predictive role of many cytokines and adhesion molecules has not been studied systematically in acute respiratory distress syndrome (ARDS). METHODS: We measured prospectively tumour necrosis factor alpha (TNF-α), interleukin (IL)-1, soluble vascular adhesion molecule-1 (VCAM-1) and soluble intercellular adhesion molecule-1 (ICAM-1) in serum and bronchoalveolar lavage fluid (BALF) within 2 hours following admission, in 65 patients. The patients were divided into: those fulfilling the criteria for ARDS (n = 23, group A), those who were pre-ARDS and who developed ARDS within 24 hours (n = 14, group B), and those on pre-ARDS but who never developed ARDS (n = 28, group C). RESULTS: All the measured molecules were only found at higher levels in the serum of patients that died either with or without ARDS (P < 0.05 – P < 0.0001). Patients at risk exhibited a good negative predictive value (NPV) of the measured molecules for ARDS development both in their serum (89 to 95%) and BALF (86 to 92%) levels. In contrast to BALF, serum levels of IL-1 and adhesion molecules exhibited a good NPV (68 to 96%), sensitivity (60 to 88%) and survival specificity (74 to 96%) in all groups. All molecules in serum and BALF IL-1 were correlated with the APACHE II (P < 0.05 – P < 0.0001). Serum and BALF IL-1 as well as BALF TNF-α were negatively correlated to PaO(2)/FiO(2) (all P < 0.05). CONCLUSIONS: The studied molecules have good NPV for ARDS development both in serum and BALF. Serum rather than BALF levels seem to be related to outcome

History of adversity, health and psychopathology among prisoners: comparison between men and women

Adversity in childhood, risk behaviors and psychopathology are highly prevalent phenomena in inmate populations and have a strong impact on health. Knowing the differences in these variables between the sexes is most important in order to develop appropriate intervention strategies in a prison context. By administering the Socio-demographic and Life History Questionnaire and the Brief Symptoms Inventory, we sought to characterize adverse childhood experiences and relate them to risk behaviors and to psychopathological symptoms, and study the differences between the 65 male and 42 female detainees in Portuguese prison establishments. Men and women report a complex web of adversity in childhood. In a range of ten possible categories, a medium value of 5.05 (DP = 2.63) in total adversity for women and 2.63 (DP = 2.18) for men was encountered, with the prevalence being significantly higher within the female population (Z = -4.33; p = .000). A high prevalence of risk behaviors and psychopathological symptoms was found in both groups, the latter being higher among females. We concluded that the differences between men and women calls for in depth studies in order to provide guidelines for intervention projects in specific populations.Adversidade na infância, comportamentos de risco e psicopatologia são fenómenos muito prevalentes na população reclusa e com forte impacto na saúde. Conhecer as diferenças entre sexos, no que diz respeito a tais variáveis, é de elevada importância no sentido de adequar estraté- gias de intervenção em contexto prisional. Utilizando o Questionário Sociodemográfico e Histó- ria de Vida, o Questionário de Adversidade na Infância e o Brief Symptons Inventory, procuramos caracterizar a adversidade na infância, os comportamentos de risco e as dimensões psicopatológicas, e averiguar as diferenças entre 65 homens e 42 mulheres reclusos em estabelecimentos prisionais Portugueses. Homens e mulheres relatam um quadro complexo de adversidade na infância. Num total possível de dez categorias, verificamos uma média de adversidade total de 5.05 (DP = 2.63) para as mulheres e de 2.63 (DP = 2.18) para os homens, sendo a prevalência significativamente mais elevada junto da população feminina (Z = -4.33; p = .000). Foi ainda encontrada uma elevada prevalência de comportamentos de risco e de sintomatologia psicopatológica em ambos os grupos, sendo esta última superior nas mulheres. Concluímos que as diferenças entre sexos devem ser estudadas para guiarem a adequação dos projetos

Human Papillomavirus Type 16 Entry: Retrograde Cell Surface Transport along Actin-Rich Protrusions

The lateral mobility of individual, incoming human papillomavirus type 16 pseudoviruses (PsV) bound to live HeLa cells was studied by single particle tracking using fluorescence video microscopy. The trajectories were computationally analyzed in terms of diffusion rate and mode of motion as described by the moment scaling spectrum. Four distinct modes of mobility were seen: confined movement in small zones (30–60 nm in diameter), confined movement with a slow drift, fast random motion with transient confinement, and linear, directed movement for long distances. The directed movement was most prominent on actin-rich cell protrusions such as filopodia or retraction fibres, where the rate was similar to that measured for actin retrograde flow. It was, moreover, sensitive to perturbants of actin retrograde flow such as cytochalasin D, jasplakinolide, and blebbistatin. We found that transport along actin protrusions significantly enhanced HPV-16 infection in sparse tissue culture, cells suggesting a role for in vivo infection of basal keratinocytes during wound healing

Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice

<p>Abstract</p> <p>Background</p> <p>Histone deacetylase (HDAC) inhibitors, developed as promising anti-tumor drugs, exhibit their anti-inflammatory properties due to their effects on reduction of inflammatory cytokines.</p> <p>Objective</p> <p>To investigate the protective effect of butyrate, a HDAC inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.</p> <p>Methods</p> <p>ALI was induced in Balb/c mice by intratracheally instillation of LPS (1 mg/kg). Before 1 hour of LPS administration, the mice received butyrate (10 mg/kg) orally. The animals in each group were sacrificed at different time point after LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain and lung wet/dry weight ratios were observed. Concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF) and concentrations of nitric oxide (NO) and myeloperoxidase (MPO) activity in lung tissue homogenates were measured by enzyme-linked immunosorbent assay (ELISA). Expression of nuclear factor (NF)-κB p65 in cytoplasm and nucleus was determined by Western blot analysis respectively.</p> <p>Results</p> <p>Pretreatment with butyrate led to significant attenuation of LPS induced evident lung histopathological changes, alveolar hemorrhage, and neutrophils infiltration with evidence of reduced MPO activity. The lung wet/dry weight ratios, as an index of lung edema, were reduced by butyrate administration. Butyrate also repressed the production of TNF-α, IL-1β and NO. Furthermore, the expression of NF-κB p65 in nucleus was markedly suppressed by butyrate pretreatment.</p> <p>Conclusions</p> <p>Butyrate had a protective effect on LPS-induced ALI, which may be related to its effect on suppression of inflammatory cytokines production and NF-κB activation.</p

Depurated fish as an alternative reference for field-based biomarker monitoring

The whole of the Swan-Canning Estuary, in the south-west of Australia, is impacted by human activity, and the selection of a local reference site to assess the impact of environmental contamination on the health of biota is not possible. To determine whether fish depurated under laboratory conditions could be used as an alternative to a reference site; adult black bream (Acanthopagrus butcheri) were collected from the estuary and maintained in clean water (S24) for 3 months. A suite of biomarkers of fish health were assessed, and the results were compared with field-captured black bream from three sites within the estuary (Ascot, Claisebrook, and Riverton). Comparisons of a subset of biomarkers were also made between hatchery-bred juvenile fish and the depurated fish. Biomarker levels were up to 3.8 times higher in field captured fish compared with depurated fish, while DNA integrity was lower. EROD activity was comparable in the hatchery-bred black bream to the depurated fish while s-SDH levels were two times higher in the hatchery fish. From the results obtained, field-captured black bream depurated for 3 months are suitable to determine reference/baseline levels for biomarker of health studies in estuarine environments

Conventionally assessed voluntary activation does not represent relative voluntary torque production

The ability to voluntarily activate a muscle is commonly assessed by some variant of the twitch interpolation technique (ITT), which assumes that the stimulated force increment decreases linearly as voluntary force increases. In the present study, subjects (n = 7) with exceptional ability for maximal voluntary activation (VA) of the knee extensors were used to study the relationship between superimposed and voluntary torque. This includes very high contraction intensities (90–100%VA), which are difficult to consistently obtain in regular healthy subjects (VA of ∼90%). Subjects were tested at 30, 60, and 90° knee angles on two experimental days. At each angle, isometric knee extensions were performed with supramaximal superimposed nerve stimulation (triplet: three pulses at 300 Hz). Surface EMG signals were obtained from rectus femoris, vastus lateralis, and medialis muscles. Maximal VA was similar and very high across knee angles: 97 ± 2.3% (mean ± SD). At high contraction intensities, the increase in voluntary torque was far greater than would be expected based on the decrement of superimposed torque. When voluntary torque increased from 79.6 ± 6.1 to 100%MVC, superimposed torque decreased from 8.5 ± 2.6 to 2.8 ± 2.3% of resting triplet. Therefore, an increase in VA of 5.7% (from 91.5 ± 2.6 to 97 ± 2.3%) coincided with a much larger increase in voluntary torque (20.4 ± 6.1%MVC) and EMG (33.9 ± 6.6%max). Moreover, a conventionally assessed VA of 91.5 ± 2.6% represented a voluntary torque of only 79.6 ± 6.1%MVC. In conclusion, when maximal VA is calculated to be ∼90% (as in regular healthy subjects), this probably represents a considerable overestimation of the subjects’ ability to maximally drive their quadriceps muscles

A retrospective analysis of noise-induced hearing loss in the Dutch construction industry

Purpose Noise exposure is an important and highly prevalent occupational hazard in the construction industry. This study examines hearing threshold levels of a large population of Dutch construction workers and compares their hearing thresholds to those predicted by ISO-1999. Methods In this retrospective study, medical records of periodic occupational health examinations of 29,644 construction workers are analysed. Pure-tone audiometric thresholds of noise-exposed workers are compared to a non-exposed control group and to ISO-1999 predictions. Regression analyses are conducted to explore the relationship between hearing loss and noise intensity, noise exposure time and the use of hearing protection. Results Noise-exposed workers had greater hearing losses compared to their non-noise-exposed colleagues and to the reference population reported in ISO-1999. Noise exposure explained only a small proportion of hearing loss. When the daily noise exposure level rose from 80 dB(A) towards 96 dB(A), only a minor increase in hearing loss is shown. The relation of exposure time and hearing loss found was similar to ISO-1999 predictions when looking at durations of 10 years or more. For the first decade, the population medians show poorer hearing than predicted by ISO-1999. Discussion Duration of noise exposure was a better predictor than noise exposure levels, probably because of the limitations in noise exposure estimations. In this population, noise-induced hearing loss was already present at the beginning of employment and increased at the same rate as is predicted for longer exposure duration