Effects of Feed Supplementation on Mineral Composition,Mechanical Properties and Structure in Femurs of Iberian Red Deer Hinds (Cervus elaphus hispanicus)

Few studies in wild animals have assessed changes in mineral profile in long bones and their implications for mechanical properties. We examined the effect of two diets differing in mineral content on the composition and mechanical properties of femora from two groups each with 13 free-ranging red deer hinds. Contents of Ca, P, Mg, K, Na, S, Cu, Fe, Mn, Se, Zn, B and Sr, Young’s modulus of elasticity (E), bending strength and work of fracture were assessed in the proximal part of the diaphysis (PD) and the mid-diaphysis (MD). Whole body measures were also recorded on the hinds. Compared to animals on control diets, those on supplemented diets increased live weight by 6.5 kg and their kidney fat index (KFI), but not carcass weight, body or organ size, femur size or cortical thickness. Supplemental feeding increased Mn content of bone by 23%, Cu by 9% and Zn by 6%. These differences showed a mean fourfold greater content of these minerals in supplemental diet, whereas femora did not reflect a 5.4 times greater content of major minerals (Na and P) in the diet. Lower content of B and Sr in supplemented diet also reduced femur B by 14% and Sr by 5%. There was a subtle effect of diet only on E and none on other mechanical properties. Thus, greater availability of microminerals but not major minerals in the diet is reflected in bone composition even before marked body effects, bone macro-structure or its mechanical properties are affected.     

Human Papillomavirus Infection in a Male Population Attending a Sexually Transmitted Infection Service

Objective

Human Papillomavirus (HPV) infection in men may produce cancer and other major disorders. Men play an important role in the transmission of the virus and act as a reservoir. The aim of this study was to determine the HPV-genotypes and their prevalence in a group of men attending a Sexually Transmitted Infection service.

Patients and Samples

Between July 2002 and June 2011, 1392 balanopreputial, 435 urethral, 123 anal, and 67 condyloma lesions from 1551 men with a mean age of 35.8±11.3 years old (range: 17–87) were collected for HPV-DNA testing.

Methods

A fragment of the L1-gene and a fragment of the E6/E7-genes were amplified by PCR. Positive samples were typed by hybridization.

Results

The HPV genome was detected in 36.9% (486/1318) balanopreputial and in 24.9% (101/405) urethral (p<0.0001) swabs from 38.1% (538) of 1469 men. Co-infections were present in 5.4% (80/1469) of cases. HPV was found in 43.9% (373/850) of men younger than 35 vs. 31.7% (187/589) of men aged >35. HPV was found in 59.4% (104) of 165 men with lesions (macroscopic or positive peniscopy), and in 22.8% (61/267) without clinical alterations. HPV was also detected in 71.4% (40/56) men with condylomata and in 58.7% (64/109) of men with positive peniscopy.

Conclusions

HPV prevalence in men was high and decreased with age. HPV was found more frequently in balanopreputial than in urethral swabs. There was a low rate of co-infections. Low-risk HPV vaccine genotypes were the most recurrent especially in younger. Although HPV has been associated with clinical alterations, it was also found in men without any clinical presentation. Inclusion of men in the national HPV vaccination program may reduce their burden of HPV-related disease and reduce transmission of the virus to non-vaccinated women.     

Landscape Genetics of Leaf-Toed Geckos in the Tropical Dry Forest of Northern Mexico

Habitat fragmentation due to both natural and anthropogenic forces continues to threaten the evolution and maintenance of biological diversity. This is of particular concern in tropical regions that are experiencing elevated rates of habitat loss. Although less well-studied than tropical rain forests, tropical dry forests (TDF) contain an enormous diversity of species and continue to be threatened by anthropogenic activities including grazing and agriculture. However, little is known about the processes that shape genetic connectivity in species inhabiting TDF ecosystems. We adopt a landscape genetic approach to understanding functional connectivity for leaf-toed geckos (Phyllodactylus tuberculosus) at multiple sites near the northernmost limit of this ecosystem at Alamos, Sonora, Mexico. Traditional analyses of population genetics are combined with multivariate GIS-based landscape analyses to test hypotheses on the potential drivers of spatial genetic variation. Moderate levels of within-population diversity and substantial levels of population differentiation are revealed by F _ST and D _est. Analyses using structure suggest the occurrence of from 2 to 9 genetic clusters depending on the model used. Landscape genetic analysis suggests that forest cover, stream connectivity, undisturbed habitat, slope, and minimum temperature of the coldest period explain more genetic variation than do simple Euclidean distances. Additional landscape genetic studies throughout TDF habitat are required to understand species-specific responses to landscape and climate change and to identify common drivers. We urge researchers interested in using multivariate distance methods to test for, and report, significant correlations among predictor matrices that can impact results, particularly when adopting least-cost path approaches. Further investigation into the use of information theoretic approaches for model selection is also warranted.     

Effect of Statin Therapy in the Outcome of Bloodstream Infections Due to Staphylococcus aureus: A Prospective Cohort Study

Introduction

Statins have pleiotropic effects that could influence the prevention and outcome of some infectious diseases. There is no information about their specific effect on Staphylococcus aureus bacteremia (SAB).

Methods

A prospective cohort study including all SAB diagnosed in patients aged ≥18 years admitted to a 950-bed tertiary hospital from March 2008 to January 2011 was performed. The main outcome variable was 14-day mortality, and the secondary outcome variables were 30-day mortality, persistent bacteremia (PB) and presence of severe sepsis or septic shock at diagnosis of SAB. The effect of statin therapy at the onset of SAB was studied by multivariate logistic regression and Cox regression analysis, including a propensity score for statin therapy.

Results

We included 160 episodes. Thirty-three patients (21.3%) were receiving statins at the onset of SAB. 14-day mortality was 21.3%. After adjustment for age, Charlson index, Pitt score, adequate management, and high risk source, statin therapy had a protective effect on 14-day mortality (adjusted OR = 0.08; 95% CI: 0.01–0.66; p = 0.02), and PB (OR = 0.89; 95% CI: 0.27–1.00; p = 0.05) although the effect was not significant on 30-day mortality (OR = 0.35; 95% CI: 0.10–1.23; p = 0.10) or presentation with severe sepsis or septic shock (adjusted OR = 0.89; CI 95%: 0.27–2.94; p = 0.8). An effect on 30-day mortality could neither be demonstrated on Cox analysis (adjusted HR = 0.5; 95% CI: 0.19–1.29; p = 0.15).

Conclusions

Statin treatment in patients with SAB was associated with lower early mortality and PB. Randomized studies are necessary to identify the role of statins in the treatment of patients with SAB.     

Statistical Basis for Predicting Technological Progress

Forecasting technological progress is of great interest to engineers, policy makers, and private investors. Several models have been proposed for predicting technological improvement, but how well do these models perform? An early hypothesis made by Theodore Wright in 1936 is that cost decreases as a power law of cumulative production. An alternative hypothesis is Moore''s law, which can be generalized to say that technologies improve exponentially with time. Other alternatives were proposed by Goddard, Sinclair et al., and Nordhaus. These hypotheses have not previously been rigorously tested. Using a new database on the cost and production of 62 different technologies, which is the most expansive of its kind, we test the ability of six different postulated laws to predict future costs. Our approach involves hindcasting and developing a statistical model to rank the performance of the postulated laws. Wright''s law produces the best forecasts, but Moore''s law is not far behind. We discover a previously unobserved regularity that production tends to increase exponentially. A combination of an exponential decrease in cost and an exponential increase in production would make Moore''s law and Wright''s law indistinguishable, as originally pointed out by Sahal. We show for the first time that these regularities are observed in data to such a degree that the performance of these two laws is nearly the same. Our results show that technological progress is forecastable, with the square root of the logarithmic error growing linearly with the forecasting horizon at a typical rate of 2.5% per year. These results have implications for theories of technological change, and assessments of candidate technologies and policies for climate change mitigation.     

Germline Allele-Specific Expression of DAPK1 in Chronic Lymphocytic Leukemia

We previously reported a rare germline variant (c.1-6531) that resulted in allele–specific expression (ASE) of death-associated protein kinase 1 (DAPK1) and predisposition to chronic lymphocytic leukemia (CLL). We investigated a cohort of CLL patients lacking this mutation for the presence of ASE of DAPK1. We developed a novel strategy that combines single-nucleotide primer extension (SNuPE) with MALDI-TOF mass spectrometry, and detected germline DAPK1 ASE in 17 out of 120 (14.2%) CLL patients associated with a trend towards younger age at diagnosis. ASE was absent in 63 healthy controls. Germline cells of CLL patients with ASE showed increased levels of DNA methylation in the promoter region, however, neither genetic nor further epigenetic aberrations could be identified in the DAPK1 5′ upstream regulatory region, within distinct exons or in the 3′-UTR. We identified B-lymphoid malignancy related cell line models harboring allelic imbalance and found that allele-specific methylation in DAPK1 is associated with ASE. Our data indicate that ASE at the DAPK1 gene locus is a recurrent event, mediated by epigenetic mechanisms and potentially predisposing to CLL.     

Antigenic Proteins Involved in Occupational Rhinitis and Asthma Caused by Obeche Wood (Triplochiton Scleroxylon)

Background

Obeche wood dust is a known cause of occupational asthma where an IgE-mediated mechanism has been demonstrated.

Objective

To characterize the allergenic profile of obeche wood dust and evaluate the reactivity of the proteins by in vitro, ex vivo and in vivo assays in carpenters with confirmed rhinitis and/or asthma

Materials and methods

An in-house obeche extract was obtained, and two IgE binding bands were purified (24 and 12 kDa) and sequenced by N-terminal identity. Specific IgE and IgG, basophil activation tests and skin prick tests (SPTs) were performed with whole extract and purified proteins. CCD binding was analyzed by ELISA inhibition studies.

Results

Sixty-two subjects participated: 12 with confirmed occupational asthma/rhinitis (ORA+), 40 asymptomatic exposed (ORA−), and 10 controls. Of the confirmed subjects, 83% had a positive SPT to obeche. There was a 100% recognition by ELISA in symptomatic subjects vs. 30% and 10% in asymptomatic exposed subjects and controls respectively (p<0.05). Two new proteins were purified, a 24 kDa protein identified as a putative thaumatin-like protein and a 12 kDa gamma-expansin. Both showed allergenic activity in vitro, with the putative thaumatin being the most active, with 92% recognition by ELISA and 100% by basophil activation test in ORA+ subjects. Cross-reactivity due to CCD was ruled out in 82% of cases.

Conclusions

Two proteins of obeche wood were identified and were recognized by a high percentage of symptomatic subjects and by a small proportion of asymptomatic exposed subjects. Further studies are required to evaluate cross reactivity with other plant allergens.     

HSP-72 Accelerated Expression in Mononuclear Cells Induced In Vivo by Acetyl Salicylic Acid Can Be Reproduced In Vitro when Combined with H2O2

Background

Among NSAIDs acetyl salicylic acid remains as a valuable tool because of the variety of benefic prophylactic and therapeutic effects. Nevertheless, the molecular bases for these responses have not been complete understood. We explored the effect of acetyl salicylic acid on the heat shock response.

Results

Peripheral blood mononuclear cells from rats challenged with acetyl salicylic acid presented a faster kinetics of expression of HSP-72 messenger RNA and protein in response to in vitro heat shock. This effect reaches its maximum 2 h after treatment and disappeared after 5 h. On isolated peripheral blood mononuclear cells from untreated rats, incubation with acetyl salicylic acid was ineffective to produce priming, but this effect was mimicked when the cells were incubated with the combination of H₂O₂+ ASA.

Conclusions

Administration of acetyl salicylic acid to rats alters HSP-72 expression mechanism in a way that it becomes more efficient in response to in vitro heat shock. The fact that in vitro acetyl salicylic acid alone did not induce this priming effect implies that in vivo other signals are required. Priming could be reproduces in vitro with the combination of acetyl salicylic acid+H₂O₂.     

Use of RT-Defective HIV Virions: New Tool to Evaluate Specific Response in Chronic Asymptomatic HIV-Infected Individuals

Background

Generation of new reagents that can be used to screen or monitor HIV-1-specific responses constituted an interesting field in the development of HIV vaccines to improve their efficacy.

Methods

We have evaluated the specific T cell response against different types of NL4-3 virions (including NL4-3 aldrithiol-2 treated, NL4-3/ΔRT and R5 envelopes: NL4-3/ΔRT/ΔEnv[AC10] and NL4-3/ΔRT/ΔEnv[Bal]) and against pools of overlapping peptides (15 mer) encompassing the HIV-1 Gag and Nef regions. Cryopreserved PBMC from a subset of 69 chronic asymptomatic HIV positive individuals have been employed using different techniques including IFN-γ ELISPOT assay, surface activation markers and intracellular cytokine staining (ICS) by flow cytometry.

Results

The differential response obtained against NL4-3 aldrithiol-2 treated and NL4-3/ΔRT virions (25% vs 55%, respectively) allow us to divide the population in three groups: “full-responders” (positive response against both viral particles), “partial-responders” (positive response only against NL4-3/ΔRT virions) and “non-responders” (negative responses). There was no difference between X4 and R5 envelopes. The magnitude of the total responses was higher against NL4-3/ΔRT and was positively correlated with gender and inverse correlated with viral load. On the contrary CD4+ T cell count was not associated with this response. In any case responses to the viruses tended to be lower in magnitude than those detected by the overlapping peptides tested. Finally we have found an increased frequency of HLA-B27 allele (23% vs 9%) and a significant reduction in some activation markers (CD69 and CD38) on T cells surface in responders vs non-responders individuals.

Conclusions

In summary these virions could be considered as alternative and useful reagents for screening HIV-1-specific T cell responses in HIV exposed uninfected people, HIV infected patients and to assess immunogenicity of new prototypes both in vitro and in vaccine trials, by a feasible, simply, effective and low cost assay.     

Smokers with CT Detected Emphysema and No Airway Obstruction Have Decreased Plasma Levels of EGF,IL-15, IL-8 and IL-1ra

Rationale

Low-grade inflammation and emphysema have been shown to be associated with an increased risk of lung cancer. However, the systemic inflammatory response in patients with emphysema is still unknown.

Objective

To compare the plasma cytokine profiles in two groups of current or former smokers without airway obstruction: a control group of individuals without computed tomography (CT) detected emphysema vs. a study group of individuals with CT detected emphysema.

Methods

Subjects underwent a chest CT, spirometry, and determination of EGF, IL-15, IL-1ra, IL-8, MCP-1, MIP-1β, TGFα, TNFα, and VEGF levels in plasma. Cytokine levels in each group were compared adjusting for confounding factors.

Results

160 current smokers and former smokers without airway obstruction participated in the study: 80 without emphysema and 80 subjects with emphysema. Adjusted group comparisons revealed significant reductions in EGF (−0.317, p = 0.01), IL-15 (−0.21, p = 0.01), IL-8 (−0.180, p = 0.02) and IL-1ra (−0.220, p = 0.03) in subjects with emphysema and normal spirometry.

Conclusions

Current or former smokers expressing a well-defined disease characteristic such as emphysema, has a specific plasma cytokine profile. This includes a decrease of cytokines mainly implicated in activation of apoptosis or decrease of immunosurveillance. This information should be taken into account when evaluated patients with tobacco respiratory diseases.