Risk factors of peripheral arterial disease: a case control study in Sri Lanka

Background

Peripheral artery disease (PAD) is an important global health problem and contributes to notable proportion of morbidity and mortality. This particular manifestation of systemic atherosclerosis is largely under diagnosed and undertreated. For sustainable preventive strategies in a country, it is mandatory to identify country-specific risk factors. We intended to assess the risk factors of PAD among adults aged 40–74 years.

Methods

This case control study was conducted in 2012–2013 in Sri Lanka. Seventy-nine cases and 158 controls in the age group of 40–74 years were selected for the study in order to have case to control ratio 1:2. The criterion for selecting cases and control was based on Ankle brachial pressure index (ABPI). Cases were selected from those who had ABPI 0.85 or less (ABPI ≤0.85) in either lower limb. Controls were selected from those ABPI score between 1.18 and 1.28 in both lower limbs. Only newly identified individuals with PAD were selected as cases. Controls were selected from the same geographical location and within the 5 year age group as cases.

Results

The history of diabetes mellitus more than 10 years (OR 5.8, 95% CI 2.2–14.2), history of dyslipidemia for more than 10 years (OR 4.9, 95% CI 2.1–16.2), history of hypertension for more than 10 years (OR 3.8, 95% CI 1.8–12.7) and smoking (OR 2.9, 95% CI 1.2–6.9), elevated HsCRP (OR 3.7, 95% CI 1.2–12.0) and hyperhomocysteinemia (OR 3.0, 95% CI 1.1–8.1) were revealed as country specific significant risk factor of PAD.

Conclusions

Diabetes mellitus, hypertension, dyslipidemia, smoking as well as elevated homocysteine and HsCRP found as risk factors of PAD. Longer the duration or higher level exposure to these risk factors has increased the risk of PAD. These findings emphasis the need for routine screening of PAD among patients with the identified risk factors.

     

Molecular markers reveal a strong genetic differentiation between two European relic tree species: Zelkova abelicea (Lam.) Boissier and Z. sicula Di Pasquale, Garfì & Quézel (Ulmaceae)

Chloroplast (trnL) and ribosomal (ITS2)sequences and chloroplast DNA (PCR-RFLP andSSR) markers were analysed in two relicUlmaceae tree species: Zelkova abelicea,from Crete, and Z. sicula, from Sicily.The analysis of the plastidial trnLintron and of ITS2 ribosomal sequences revealedtheir divergence from the related speciesZ. carpinifolia, widespread in the Caucasianregion; one base substitution in the trnLintron was detected between the twoMediterranean species, thus suggesting theirrecent separation. Molecular markers(plastidial PCR-RFLP and SSR) showed an evidentgenetic differentiation between Z. siculaand Z. abelicea, the two species beingcharacterised by different haplotypes. Nowithin population variation was detected usingdifferent chloroplast markers inZ. abelicea and Z. sicula. Paleobotanicaldata proved that the genus Zelkova wasabundant and widespread in central Italy untilit became extinct in the continental part ofEurope during last glaciation events andsurvived only in two Mediterranean islands. Thesegregation of the two Mediterranean relicspecies might have occurred as a consequence ofthe strong reduction of their distribution andthe following geographic isolation. Geneticdrift may have determined the drastic reductionof within stand diversity as observed in othersmall, peripheral and geographically isolatedplant populations. The priorities forconservation programs are discussed in thelight of the different genetic resourcesrepresented by the two taxa.     

Variation at a chloroplast minisatellite locus reveals the signature of habitat fragmentation and genetic bottlenecks in the rare orchid Anacamptis palustris (Orchidaceae)

Geoclimatic changes during the Oligocene and more recent anthropogenic influences have shaped the current distribution and population structure of Mediterranean plant species. Anacamptis palustris (Orchidaceae) is a typical member of coastal wetlands, which have become increasingly fragmented and isolated. As a consequence, this orchid has become rare in the recent past. Length variation at a chloroplast minisatellite locus was used to estimate genetic variation within and between the largest extant populations of A. palustris. Genetic diversity was positively correlated with population size. Estimation of observed and expected gene diversity and analyses of haplotype number and haplotype frequency distributions provided evidence for population bottlenecks in the history of small populations. Comparison with an earlier study suggests that nuclear allozyme diversity was most likely lost during the Oligocene and could not recover subsequently due to low mutation rates, whereas genetic variation was restored at the highly variable chloroplast minisatellite locus. Population bottlenecks indicated by cpDNA variation occurred most likely as a consequence of more recent anthropogenic changes. The comparison of molecular markers with different levels of polymorphism provided valuable insights into the processes shaping genetic diversity and population structure in this rare orchid.     

Parameters of Metabolic Syndrome and Its Relationship with Zincemia and Activities of Superoxide Dismutase and Glutathione Peroxidase in Obese Women

Alterations in antioxidant defense in obese people with metabolic syndrome can contribute to oxidative stress. This study assessed the relationship between the parameters of metabolic syndrome and the zincemia, activity of superoxide dismutase, and glutathione peroxidase enzymes in obese women. Seventy-three premenopausal women, aged between 20 and 50 years, were divided into two groups: case group, composed of obese (n = 37), and control group, composed of no obese (n = 36). Analyses of zinc intake, parameters of metabolic syndrome, plasma, and erythrocyte zinc, and activities of superoxide dismutase and glutathione peroxidase were carried out. The mean values of body mass index of obese women and control group were 34.5 ± 3.4 and 21.7 ± 1.9 kg/m², respectively (p < 0.05). In the study, body mass index, waist circumference, and zinc intake were higher in obese women than control group (p < 0.05). The plasma zinc and activity of superoxide dismutase did not show significant differences between obese and controls (p > 0.05). The values of erythrocyte zinc was 36.4 ± 15.0 μg/gHb and 45.4 ± 14.3 μg/gHb and of glutathione peroxidase was 46.4 ± 19.4 U/gHb and 36.7 ± 13.6 U/gHb in obese women and controls, respectively (p < 0.05). The study shows that there are alterations in biochemical parameters of zinc in obese women, with low zinc concentrations in erythrocytes. Regression analysis demonstrates that the erythrocyte zinc and activity of superoxide dismutase enzyme is influenced by components of the metabolic syndrome, and the plasmatic glucose, body mass index, and waist circumference have a negative correlation with this enzyme.     

Differential toxicity of TAR DNA‐binding protein 43 isoforms depends on their submitochondrial localization in neuronal cells

TAR DNA ‐binding protein 43 (TDP ‐43) is an RNA ‐binding protein and a major component of protein aggregates found in amyotrophic lateral sclerosis and several other neurodegenerative diseases. TDP ‐43 exists as a full‐length protein and as two shorter forms of 25 and 35 kD a. Full‐length mutant TDP ‐43s found in amyotrophic lateral sclerosis patients re‐localize from the nucleus to the cytoplasm and in part to mitochondria, where they exert a toxic role associated with neurodegeneration. However, induction of mitochondrial damage by TDP ‐43 fragments is yet to be clarified. In this work, we show that the mitochondrial 35 kD a truncated form of TDP ‐43 is restricted to the intermembrane space, while the full‐length forms also localize in the mitochondrial matrix in cultured neuronal NSC ‐34 cells. Interestingly, the full‐length forms clearly affect mitochondrial metabolism and morphology, possibly via their ability to inhibit the expression of Complex I subunits encoded by the mitochondrial‐transcribed mRNA s, while the 35 kD a form does not. In the light of the known differential contribution of the full‐length and short isoforms to generate toxic aggregates, we propose that the presence of full‐length TDP ‐43s in the matrix is a primary cause of mitochondrial damage. This in turn may cause oxidative stress inducing toxic oligomers formation, in which short TDP ‐43 forms play a major role.

     

Measuring expansion from macro‐ to nanoscale using NPC as intrinsic reporter

Expansion microscopy is a super‐resolution method that allows expanding uniformly biological samples, by increasing the relative distances among fluorescent molecules labeling specific components. One of the main concerns in this approach regards the isotropic behavior at the nanoscale. The present study aims to determine the robustness of such a technique, quantifying the expansion parameters i.e. scale factor, isotropy, uniformity. Our focus is on the nuclear pore complex (NPC), as well‐known nanoscale component endowed of a preserved and symmetrical structure localized on the nuclear envelope. Here, we show that Nup153 is a good reporter to quantitatively address the isotropy of the expansion process. The quantitative analysis carried out on NPCs, at different spatial scales, allows concluding that expansion microscopy can be used at the nanoscale to measure subcellular features with an accuracy from 10 to 5 nm. Therefore, it is an excellent method for structural studies of macromolecular complexes.     

In vitro production of interleukin 1 by normal and malignant human B lymphocytes

In this study, the capacity of normal and neoplastic B lymphocytes to release interleukin 1 (IL 1) has been investigated. Peripheral blood B cells from normal donors were isolated by depletion of E rosetting cells and by positive selection of cells expressing surface immunoglobulin (sIg) or the B1 marker. Peripheral blood B cells from patients with B cell chronic lymphocytic leukemia (B-CLL) were purified by removal of E rosetting cells followed by complement-mediated cytotoxicity with selected monoclonal antibodies. All of the normal B cell suspensions and the large majority of the B-CLL cells produced in culture high amounts of IL 1 in the absence of any apparent stimulus. Control experiments ruled out that small numbers of monocytes in the B cell suspensions could represent the source of IL 1. These data support the contention that B cells participate to the immune response as accessory cells for T cell activation not only by physically presenting antigen, but also by releasing IL 1.     

Generation of Fbn1 conditional null mice implicates the extracellular microfibrils in osteoprogenitor recruitment

Loss-of-function experiments in mice have yielded invaluable mechanistic insights into the pathogenesis of Marfan syndrome (MFS) and implicitly, into the multiple roles fibrillin-1 microfibrils play in the developing and adult organism. Unfortunately, neonatal death from aortic complications of mice lacking fibrillin-1 (Fbn1(-/-) mice) has limited the scope of these studies. Here, we report the creation of a conditional mutant allele (Fbn1(fneo) ) that contains loxP sites bordering exon1 of Fbn1 and an frt-flanked neo expression cassette downstream of it. Fbn1(fneo/+) mice were crossed with FLPeR mice and the resulting Fbn1(Lox/+) progeny were crossed with Fbn1(+/-) ;CMV-Cre mice to generate Fbn1(CMV-/-) mice, which were found to phenocopy the vascular abnormalities of Fbn1(-/-) mice. Furthermore, mating Fbn1(Lox/+) mice with Prx1-Cre or Osx-Cre mice revealed an unappreciated role of fibrillin-1 microfibrils in restricting osteoprogenitor cell recruitment. Fbn1(Lox/+) mice are, therefore, an informative genetic resource to further dissect MFS pathogenesis and the role of extracellular fibrillin-1 assemblies in organ development and homeostasis.