Heathland vegetation of the northern-central part of the Iberian Peninsula

Heathland vegetation of northern Spain, included in theCalluno-Ulicetea, was studied using a set of 802 phytosociological relevés. The existing syntaxonomy has been tested and most of the types (associations and subassociations) fit satisfactorily with the observed groupings. Two main problems were encountered within theUlex dominated communities of the Cantabrian fringe and the Castilian-Cantabrian heathland communities. Both groups of communities were subject to ordination in order to clarify relationships between them. For the former group, ordination suggests that three associations can be distinguished: theUlici-Ericetum vagantis (lowlands up to the submontane belt), theVaccinio-Ulicetum gallii for the communities of higher altitudes (montane belt) and theUlici-Ericetum ciliaris (hygrophilous heathlands). The Castilian-Cantabrian heathlands show a variable Mediterranean influence and have a dispersed distribution due to lithological conditions. This results in the distinction of two new associations, viz. theArctostaphylo crassifoliae-Daboecietum cantabricae (marly, water-retaining soils) and theEricetum scopario-vagantis (sandy soils). A complete classification of theCalluno-Ulicetea in the studied area and short ecological and biogeographical diagnoses are given.     

Etiologic and epidemiologic study of dermatomycoses in Navarra (Spain)

We review the etiology of the dermatophytosis in Navarra (Spain) over a 5-year period and it is compared with previous studies. We have isolated 312 strains of dermatophyte fungi in 285 patients (188 men and 97 women). Trichophyton rubrum was the most frequently isolated species (58.6%) followed by Trichophyton mentagrophytes (26.2%) and Microsporum canis (10.5%). Concerning the location of the lesions, tinea pedis was the clinical pattern found in the greatest number of patients, followed by tinea corporis, tinea unguium and tinea capitis. Twenty eight percent of the isolations were accomplished in October and November. More than half of those patients questioned had had epidemiological contact with animals or practiced sports. The rise of tinea pedis in our region is emphasised. The possible causes of this increment are analyzed and some recommendations for its control are made.     

Plasma aminopeptidase activities in Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by a progressive motor disorder, but frequently is accompanied by autonomic symptoms such as hypotension. Together with the decrease of dopamine, significant decreases in aminopeptidase activities have been reported in PD brains. However, up to date there are no studies about changes of aminopeptidase activities in plasma of PD patients. We studied plasma activities of alanyl-, aspartyl-(AspAP), cystinyl-(CysAP) and glutamyl-aminopeptidase (GluAP) in two groups of subjects: control (n=41) and PD (n=48). Plasma activities of AspAP, CysAP, and GluAP showed significant decreases of 24.9% (p<0.05), 39.4% (p<0.01) and 33.3% (p<0.01), respectively, in PD group. These aminopeptidases are involved in the metabolism of circulating peptides such as the ones of the renin-angiotensin system. The importance of aminopeptidases in striatal dopamine content and in neuroendocrine system in PD is discussed.     

S-adenosyl-L-methionine reverses the cholestatic effect of ethinylestradiol in rat hepatocytes by increasing its catabolism

In this study, ethinylestradiol inhibited the uptake of taurocholate by cultured rat hepatocytes, increasing the K_m1 while leaving the V_max unchanged. S-AdenosylL-methionine (SAMe) had no effect on taurocholate uptake or release, but was able to reverse the competitive inhibition induced by ethinylestradiol. S-Adenosyl-L-homocysteine did not reverse this inhibition, which suggests that the methyl group of SAMe affects its activity. Several possible mechanisms for the action of SAMe were investigated. The methylation of cell membrane phospholipids was eliminated as a possible mechanism. The presence of SAMe greatly increased the catabolism of ethinylestradiol by hepatocytes and reduced its covalent binding to hepatocyte macromolecules. In culture supernatants, both highly polar (conjugated) and non-conjugated metabolites could be detected. Moreover, most of the metabolites were methylated. This suggests that SAMe may revert the effects of ethinylestradiol of taurocholate uptake by increasing its catabolic rate by hepatocytes.Abbreviations SAMe, S-adenosyl-L-methionine - EE, 17-ethinylestradiol     

The ring finger protein 213 gene (Rnf213) contributes to Rift Valley fever resistance in mice

Mammalian Genome - Rift Valley fever (RVF) is an emerging viral zoonosis that primarily affects ruminants and humans. We have previously shown that wild-derived MBT/Pas mice are highly susceptible...     

Effect of influenza vaccination in patients with asthma

BACKGROUND:Although annual influenza vaccination is recommended for persons with asthma, its effectiveness in this patient population is not well described. We evaluated the effect of influenza vaccination in the current and previous seasons in preventing influenza among people with asthma.METHODS:Using population health data from the Navarre region of Spain for the 2015/16 to 2019/20 influenza seasons, we conducted a test-negative case–control study to assess the effect of influenza vaccination in the current and 5 previous seasons. From patients presenting to hospitals and primary health care centres with influenza-like illness who underwent testing for influenza, we estimated the effects of influenza vaccination among patients with asthma overall and between those presenting as inpatients or outpatients, as well as between patients with and without asthma.RESULTS:Of 1032 patients who had asthma and were tested, we confirmed that 421 had influenza and the remaining 611 were test-negative controls. We found that the average effect of influenza vaccination was 43% (adjusted odds ratio [OR] 0.57, 95% confidence interval [CI] 0.40 to 0.80) for current-season vaccination regardless of previous doses, and 38% (adjusted OR 0.62, 95% CI 0.39 to 0.96) for vaccination in previous seasons only. Effects were similar for outpatients and inpatients. Among patients with asthma and confirmed influenza, current-season vaccination did not reduce the odds of hospital admission (adjusted OR 1.05, 95% CI 0.51 to 2.18). Influenza vaccination effects were similar for patients with and without asthma.INTERPRETATION:We estimated that, on average, current or previous influenza vaccination of people with asthma prevented almost half of influenza cases. These results support recommendations that people with asthma receive influenza vaccination.

Influenza can lead to serious complications in people with risk factors, and the main preventive measure is vaccination. ¹ Influenza infection can exacerbate symptoms of asthma. Because people with asthma have an increased risk of severe complications and hospital admission when infected with influenza virus,^2–5 annual influenza vaccination is recommended worldwide for people with asthma.^1,5–8People who are targeted for influenza vaccination frequently accumulate several doses over successive years,⁹ and adherence to influenza vaccination has been found to be higher in those with asthma.¹⁰ Patients with asthma frequently receive long-term corticosteroid treatment (inhaled or oral), therefore, their systemic immunity may have a reduced response to vaccines.^5,11,12Effectiveness of influenza vaccines in preventing primary health care consultations or hospital admissions in people with asthma has been evaluated in observational studies,^13–15 but we are unaware of any studies that compared the effect in preventing outpatient and inpatient cases or assessed the effect of vaccination in previous seasons.^13,16 The test-negative design is the suggested method to evaluate effectiveness of influenza vaccines in preventing laboratory-confirmed influenza, because it achieves good comparability and control of bias.^17–19 Only 1 study used this method for people with asthma over several seasons.¹³ The pooled analysis of several seasons, the inclusion of inpatients and outpatients, and consideration of vaccination history would provide a complete view of the effect of influenza vaccination in people with asthma.Our objective was to assess the average effect of influenza vaccination status in the current and previous seasons on preventing laboratory-confirmed influenza among people with asthma. We also aimed to compare these estimates with those of the target population for influenza vaccination.     

The mineral dissolution function of osteoclasts is dispensable for hypertrophic cartilage degradation during long bone development and growth

During long bone development and post-natal growth, the cartilaginous model of the skeleton is progressively replaced by bone, a process known as endochondral ossification. In the primary spongiosa, osteoclasts degrade the mineralized cartilage produced by hypertrophic chondrocytes to generate cartilage trabeculae that osteoblasts embed in bone matrix. This leads to the formation of the trabecular bone network of the secondary spongiosa that will undergo continuous remodeling. Osteoclasts are specialized in mineralized tissue degradation, with the combined ability to solubilize hydroxyapatite and to degrade extracellular matrix proteins. We reported previously that osteoclasts lacking Dock5 could not degrade bone due to abnormal podosome organization and absence of sealing zone formation. Consequently, adult Dock5^−/− mice have increased trabecular bone mass. We used Dock5^−/− mice to further investigate the different functions of osteoclast during endochondral bone formation. We show that long bones are overall morphologically normal in developing and growing Dock5^−/− mice. We demonstrate that Dock5^−/− mice also have normal hypertrophic cartilage and cartilage trabecular network. Conversely, trabecular bone volume increased progressively in the secondary spongiosa of Dock5^−/− growing mice as compared to Dock5^+/+ animals, even though their osteoclast numbers were the same. In vitro, we show that Dock5^−/− osteoclasts do present acidic compartments at the ventral plasma membrane and produce normal amounts of active MMP9, TRAP and CtsK for matrix protein degradation but they are unable to solubilize minerals. These observations reveal that contrarily to bone resorption, the ability of osteoclasts to dissolve minerals is dispensable for the degradation of mineralized hypertrophic cartilage during endochondral bone formation.     

Treatment of Chronic Viral Hepatitis in Woodchucks by Prolonged Intrahepatic Expression of Interleukin-12

Chronic hepatitis B is a major cause of liver-related death worldwide. Interleukin-12 (IL-12) induction accompanies viral clearance in chronic hepatitis B virus infection. Here, we tested the therapeutic potential of IL-12 gene therapy in woodchucks chronically infected with woodchuck hepatitis virus (WHV), an infection that closely resembles chronic hepatitis B. The woodchucks were treated by intrahepatic injection of a helper-dependent adenoviral vector encoding IL-12 under the control of a liver-specific RU486-responsive promoter. All woodchucks with viral loads below 10¹⁰ viral genomes (vg)/ml showed a marked and sustained reduction of viremia that was accompanied by a reduction in hepatic WHV DNA, a loss of e antigen and surface antigen, and improved liver histology. In contrast, none of the woodchucks with higher viremia levels responded to therapy. The antiviral effect was associated with the induction of T-cell immunity against viral antigens and a reduction of hepatic expression of Foxp3 in the responsive animals. Studies were performed in vitro to elucidate the resistance to therapy in highly viremic woodchucks. These studies showed that lymphocytes from healthy woodchucks or from animals with low viremia levels produced gamma interferon (IFN-γ) upon IL-12 stimulation, while lymphocytes from woodchucks with high viremia failed to upregulate IFN-γ in response to IL-12. In conclusion, IL-12-based gene therapy is an efficient approach to treat chronic hepadnavirus infection in woodchucks with viral loads below 10¹⁰ vg/ml. Interestingly, this therapy is able to break immunological tolerance to viral antigens in chronic WHV carriers.Hepatitis B virus (HBV) infection is estimated to cause approximately 1 million deaths per year (http://www.who.int/emc). Current therapies against chronic HBV include pegylated alpha interferon (IFN-α) and nucleoside/nucleotide analogs, such as lamivudine, entecavir, adefovir, and tenofovir (16). Sustained antiviral responses are achieved in only one-third of the patients treated with pegylated IFN-α (16, 32). Nucleoside/nucleotide analogs are effective, but treatment must be continued for many years, resulting in high costs, the emergence of drug-resistant variants, and frequent relapses after the discontinuation of therapy (32).Chronic HBV infection is associated with defects in antiviral immunity (3). Patients with an acute self-limiting HBV infection develop neutralizing anti-HBs antibodies and multispecific CD4⁺ and CD8⁺ T-cell responses with a type 1 cytokine profile (3). In contrast, patients with chronic HBV infection show no protective humoral immunity and a weak or undetectable virus-specific T-cell response (5). The precise mechanism responsible for this immunotolerance is still unknown. Recently, several studies have indicated that regulatory T cells (Tregs), immunosuppressive cytokines, and inhibitory receptor-ligand interactions, such as PD1-PDL1, contribute to the impairment of virus-specific T-cell responses in chronic HBV infection (1, 17, 23, 26, 28).Interleukin-12 (IL-12) is a cytokine produced by antigen-presenting cells that is essential for the induction of effective cell-mediated immunity against viruses and other pathogens (30). IL-12 promotes Th1-type responses, enhances cytotoxic-T-cell activity, and stimulates T lymphocytes and NK cells to produce IFN-γ (30). The administration of recombinant IL-12 (rIL-12) to HBV-transgenic mice resulted in the inhibition of HBV replication in the liver (8). In vitro studies demonstrated that IL-12 was able to enhance HBV-specific T-cell responses in chronic HBV carriers (15, 22, 31). Moreover, the upregulation of IL-12 production has been shown to be associated with HBe seroconversion, indicating an important role for this cytokine in the control of HBV infection (22). In two studies, rIL-12 administered to patients with chronic HBV infection once per week as monotherapy (7) or twice weekly in combination with lamivudine (21) increased virus-specific T-cell reactivity and exerted significant antiviral activity. However, in both studies, a rebound of viremia occurred following drug withdrawal. The antiviral effects of rIL-12 were dose dependent, but the therapy was limited by severe toxicity when high doses of the cytokine were used (7, 21).Gene therapy can significantly increase cytokine expression in the target organ without excessively elevating systemic cytokine levels, which leads to an increased efficacy/toxicity ratio. In the present study, we tested the antiviral potential of IL-12-mediated gene therapy using a high-capacity adenovirus (HC-Ad) encoding murine IL-12 (mIL-12) under the control of a liver-specific inducible promoter that is responsive to the progesterone antagonist RU486 (30). HC-Ad is a nonintegrating vector characterized by strong hepatotropism, low toxicity, long-term transgene expression, and high cloning capacity (13). All these properties make HC-Ad a useful tool for therapeutic applications in human liver diseases.As an animal model of chronic HBV infection, we used woodchucks that were chronically infected with woodchuck hepatitis virus (WHV). WHV is a hepadnavirus with a genomic organization, biological properties, and a replicative strategy that are essentially identical to those of HBV. When WHV infects woodchucks in the perinatal period of life, the infection causes chronic hepatitis in most animals. This condition resembles the pathological features and natural history of chronic hepatitis B (18). Here, we demonstrate that prolonged intrahepatic expression of IL-12 overcomes immunological tolerance for WHV antigens and induces sustained antiviral effects in woodchucks with chronic WHV infection and viral loads below 10¹⁰ viral genomes (vg)/ml. These observations indicate that IL-12 gene therapy is an alternative approach for the treatment of chronic HBV infection.     

Do species distribution models explain spatial structure within tree species ranges?

Aim To evaluate the ability of species distribution models (SDMs) to predict the spatial structure of tree species within their geographical ranges (how trees are distributed within their ranges). Location Continental Spain. Methods We used an extensive dataset consisting of c. 90,000 plots (1 plot km^?2) where presence/absence data for 23 common Mediterranean and Atlantic tree species had been surveyed. We first generated SDMs relating the presence or absence of each species to a set of 16 environmental predictors, following a stepwise modelling process based on maximum likelihood methods. Superimposing spatial correlograms generated from the predictions of the SDMs over those generated from the raw data allowed a model–observation comparison of the nature, scale and intensity (level of aggregation) of spatial structure with the species ranges. Results SDMs predicted accurately the nature and scale of the spatial structure of trees. However, for most species, the observed intensity of spatial structure (level of aggregation of species in space) was substantially greater than that predicted by the SDMs. On average, the intensity of spatial aggregation was twice that predicted by SDMs. In addition, we also found a negative correlation between intensity of aggregation and species range size. Main conclusions Standard SDM predictions of spatial structure patterns differ among species. SDMs are apparently able to reproduce both the scale and intensity of species spatial structure within their ranges. However, one or more missing processes not included in SDMs results in species being substantially more aggregated in space than can be captured by the SDMs. This result adds to recent calls for a new generation of more biologically realistic SDMs. In particular, future SDMs should incorporate ecological processes that are likely to increase the intensity of spatial aggregation, such as source–sink dynamics, fine‐scale environmental heterogeneity and disequilibrium.     

Sexual dysfunction in the elderly. Pathophysiological and medical issues. Treatment of erectile dysfunction

Erectile dysfunction (ED) is a very distressing condition that not only negatively affects the elderly man's sexual ability, but also his overall quality of life and that of his partner. Encouraging men, alone or as a couple, to seek professional help is a major educational challenge which needs to be met by medical, social and political initiatives. The exact pathogenesis of ED remains unknown, but is presumed to be multifactorial; vascular disease is the most frequent cause with endothelial dysfunction being the common denominator. It has been postulated that ED is a sentinel symptom of cardiovascular clinical events and should prompt investigation and intervention for cardiovascular risk factors. Therefore, when a patient presents with ED, a thorough history and physical examination should be performed, as well as appropriate laboratory tests aimed at detecting associated diseases.