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Background The variable relationship between the orbicularis supercilii and frontalis muscles may cause side effects with botulin toxin; steadily frowning is the usual recommendation. Eliminating the need to frown until all injections are over might enhance efficacy and lessen the neurotoxicity risks related to muscle exhaustion. Objectives The goal of this study was to investigate whether the digital caliper–assessed distances between the medial and lateral corrugator injection sites and the midline differed significantly in patients persistently frowning from patients resting. Methods Seventy-six individuals with glabellar wrinkles treated with botulinum toxin in the authors' private practices for glabellar lines voluntarily contributed their retrospective data about the positions of injection sites. The investigators had freely chosen to inject the medial and lateral sections of the corrugator supercilii during persistent maximum frown or at rest. Results The mean differences in distances between the medial and lateral injection points and the estimated midline were clinically trivial (1.0 ± 1.28 and 1.5 ± 2.53 mm, respectively), although the distances between the relaxed and contracted medial and lateral injection sites exceeded 1.8 and 2.5 mm in 33.9% and 46.4% of patients, respectively. Distance differences, not significant before 40 years old, were statistically significant only for the lateral injections in older patients (on average, 1.9 ± 3.01 mm). Conclusions The average distances from the medial and lateral injection points and the midline appear minimally different in patients who frown until all injections are over and, conversely, patients who rest. Persistently frowning might be advisable only in patients older than 40. Facial asymmetries may be a confounding factor. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]

Floral homeotic MADS-box transcription factors ensure the correct morphogenesis of floral organs, which are organized in different cell layers deriving from distinct meristematic layers. How cells from these distinct layers acquire their respective identities and coordinate their growth to ensure normal floral organ morphogenesis is unresolved. Here, we studied petunia (Petunia × hybrida) petals that form a limb and tube through congenital fusion. We identified petunia mutants (periclinal chimeras) expressing the B-class MADS-box gene DEFICIENS in the petal epidermis or in the petal mesophyll, called wico and star, respectively. Strikingly, wico flowers form a strongly reduced tube while their limbs are almost normal, while star flowers form a normal tube but greatly reduced and unpigmented limbs, showing that petunia petal morphogenesis is highly modular. These mutants highlight the layer-specific roles of PhDEF during petal development. We explored the link between PhDEF and petal pigmentation, a well-characterized limb epidermal trait. The anthocyanin biosynthesis pathway was strongly downregulated in star petals, including its major regulator ANTHOCYANIN2 (AN2). We established that PhDEF directly binds to the AN2 terminator in vitro and in vivo, suggesting that PhDEF might regulate AN2 expression and therefore petal epidermis pigmentation. Altogether, we show that cell layer–specific homeotic activity in petunia petals differently impacts tube and limb development, revealing the relative importance of the different cell layers in the modular architecture of petunia petals. The expression of B-class homeotic MADS-box transcription factor PhDEF in different cell layers drives petunia petal tube or limb development. [ABSTRACT FROM AUTHOR]

The native parasitoids Bracon cephi (Gahan) and B. lissogaster Muesebeck (Hymenoptera: Braconidae) reduce populations of Cephus cinctus Norton (Hymenoptera: Cephidae), a native grassland species, and major wheat pest on the Northern Great Plains of North America. Non-host feeding adults of these braconids increase longevity, egg load, and egg volume when provisioned carbohydrate-rich diets. Nutrition from nectar can enhance the success of natural enemies in pest management programs. Cowpea, Vigna unguiculata (L.) Walpers, is a potential cover-crop that could add resilient features to the landscape and has extrafloral nectaries (EFN), easy-access nectar sources for beneficial insects. If more cowpea was grown on the Northern Great Plains, would B. cephi and B. lissogaster benefit from foraging on putatively beneficial EFN? We investigated cowpea inflorescence stalk extrafloral nectars (IS-EFN) and leaf stipel extrafloral nectars (LS-EFN) as potential food sources for these parasitoids. Females were caged on EFN sources on living cowpea plants to assess longevity. Egg load and volume were measured at 2, 5, and 10 days after placement. Bracon cephi survived 10 days on water, 38 days on IS-EFN; B. lissogaster 6 days on water, 28 days on IS-EFN. Bracon lissogaster maintained a constant egg load and volume across treatments while B. cephi produced 2.1-fold more eggs that were 1.6-fold larger on IS-EFN. Y-tube olfactometry indicated adult females were attracted to airstreams containing cowpea volatiles. These results demonstrate that non-native, warm-season cowpea benefits these native parasitoids and may improve conservation biocontrol of C. cinctus. [ABSTRACT FROM AUTHOR]

On average, the genomes of Asteraceae display a high proportion of TEs (70%), representing an excellent system to study plant genome evolution ([11]). Keywords: Asteraceae; Database; Transposable elements annotation EN Asteraceae Database Transposable elements annotation 365 367 3 04/19/23 20230401 NES 230401 Transposable elements (TEs) are interspersed repetitive DNA sequences that can move independently within the genome through specific transposition mechanisms. Furthermore, given its size, detailed annotation, and user-friendly implementation, ASTER-REP will be a useful platform to study transposon variability, helping to unravel the genome structure and improving transposon annotation for other plant genomes. [Extracted from the article]

Background prior statin treatment has been shown to have favourable effects on short- and long-term prognosis in patients with acute coronary syndrome (ACS). There are limited data in older patients. The aim of this study was to investigate the association of previous statin therapy and presentation characteristics, infarct size and clinical outcome in older patients, with or without atherosclerotic cardiovascular disease (ASCVD), included in the Elderly-ACS 2 trial. Methods data on statin use pre-admission were available for 1,192 of the 1,443 patients enrolled in the original trial. Of these, 531 (44.5%) were already taking statins. Patients were stratified based on established ASCVD and statin therapy. ACS was classified as non-ST elevation or ST elevation myocardial infarction (STEMI). Infarct size was measured by peak creatine kinase MB (CK-MB). All-cause death in-hospital and within 1 year were the major end points. Results there was a significantly lower frequency of STEMI in statin patients, in both ASCVD and No-ASCVD groups. Peak CK-MB levels were lower in statin users (10 versus 25 ng/ml, P  < 0.0001). There was lower all-cause death in-hospital and within 1 year for subjects with ASCVD already on statins independent of other baseline variables. There were no differences in all-cause death for No-ASCVD patients whether or not on statins. Conclusions statin pretreatment was associated with more favourable ACS presentation and lower myocardial damage in older ACS patients both ASCVD and No-ASCVD. The incidence of all-cause death (in-hospital and within 1 year) was significantly lower in the statin treated ASCVD patients. [ABSTRACT FROM AUTHOR]

A substantial number of chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) experience periprocedural myocardial injury or infarction. Accurate diagnosis of these PCI-related complications is required to guide further management given that their occurrence may be associated with increased risk of major adverse cardiac events (MACE). Due to lack of scientific data, the cut-off thresholds of post-PCI cardiac troponin (cTn) elevation used for defining periprocedural myocardial injury and infarction, have been selected based on expert consensus opinions, and their prognostic relevance remains unclear. In this Consensus Document from the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI), we recommend, whenever possible, the measurement of baseline (pre-PCI) cTn and post-PCI cTn values in all CCS patients undergoing PCI. We confirm the prognostic relevance of the post-PCI cTn elevation >5× 99th percentile URL threshold used to define type 4a myocardial infarction (MI). In the absence of periprocedural angiographic flow-limiting complications or electrocardiogram (ECG) and imaging evidence of new myocardial ischaemia, we propose the same post-PCI cTn cut-off threshold (>5× 99th percentile URL) be used to define prognostically relevant 'major' periprocedural myocardial injury. As both type 4a MI and major periprocedural myocardial injury are strong independent predictors of all-cause mortality at 1 year post-PCI, they may be used as quality metrics and surrogate endpoints for clinical trials. Further research is needed to evaluate treatment strategies for reducing the risk of major periprocedural myocardial injury, type 4a MI, and MACE in CCS patients undergoing PCI. [ABSTRACT FROM AUTHOR]

Aims The prognostic importance of cardiac procedural myocardial injury and myocardial infarction (MI) in chronic coronary syndrome (CCS) patients undergoing elective percutaneous coronary intervention (PCI) is still debated. Methods and results We analysed individual data of 9081 patients undergoing elective PCI with normal pre-PCI baseline cardiac troponin (cTn) levels. Multivariate models evaluated the association between post-PCI elevations in cTn and 1-year mortality, while an interval analysis evaluated the impact of the size of the myocardial injury on mortality. Our analysis was performed in the overall population and also according to the type of cTn used [52.0% had high-sensitivity cTn (hs-cTn)]. Procedural myocardial injury, as defined by the Fourth Universal Definition of MI (UDMI) [post-PCI cTn elevation ≥1 × 99th percentile upper reference limit (URL)], occurred in 52.8% of patients and was not associated with 1-year mortality [adj odds ratio (OR), 1.35, 95% confidence interval (CI) (0.84–1.77), P  = 0.21]. The association between post-PCI cTn elevation and 1-year mortality was significant starting ≥3 × 99th percentile URL. Major myocardial injury defined by post-PCI ≥5 × 99th percentile URL occurred in 18.2% of patients and was associated with a two-fold increase in the adjusted odds of 1-year mortality [2.29, 95% CI (1.32–3.97), P  = 0.004]. In the subset of patients for whom periprocedural evidence of ischaemia was collected (n  = 2316), Type 4a MI defined by the Fourth UDMI occurred in 12.7% of patients and was strongly associated with 1-year mortality [adj OR 3.21, 95% CI (1.42–7.27), P  = 0.005]. We also present our results according to the type of troponin used (hs-cTn or conventional troponin). Conclusion Our analysis has demonstrated that in CCS patients with normal baseline cTn levels, the post-PCI cTn elevation of ≥5 × 99th percentile URL used to define Type 4a MI is associated with 1-year mortality and could be used to detect 'major' procedural myocardial injury in the absence of procedural complications or evidence of new myocardial ischaemia. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Citrus canker type A is a serious disease caused by Xanthomonas citri subsp. citri (X. citri), which is responsible for severe losses to growers and to the citrus industry worldwide. To date, no canker-resistant citrus genotypes are available, and there is limited information regarding the molecular and genetic mechanisms involved in the early stages of the citrus canker development. Here, we present the CitrusKB knowledge base. This is the first in vivo interactome database for different citrus cultivars, and it was produced to provide a valuable resource of information on citrus and their interaction with the citrus canker bacterium X. citri. CitrusKB provides tools for a user-friendly web interface to let users search and analyse a large amount of information regarding eight citrus cultivars with distinct levels of susceptibility to the disease, with controls and infected plants at different stages of infection by the citrus canker bacterium X. citri. Currently, CitrusKB comprises a reference citrus genome and its transcriptome, expressed transcripts, pseudogenes and predicted genomic variations (SNPs and SSRs). The updating process will continue over time by the incorporation of novel annotations and analysis tools. We expect that CitrusKB may substantially contribute to the field of citrus genomics. CitrusKB is accessible at http://bioinfo.deinfo.uepg.br/citrus. Users can download all the generated raw sequences and generated datasets by this study from the CitrusKB website. [ABSTRACT FROM AUTHOR]

Background: A perfect smile is dictated by the balance among 3 parameters: the white (teeth), the pink (gum), and the lips: excessive gingival display while smiling has been a cause of esthetic embarrassment for many patients, thus affecting their psychosocial behavior. With respect to different etiologies, treatment of gummy smile must be properly planned: treatment options include facial surgery, oral surgery, or laser.Objectives: Given the growing demand for less invasive techniques and observed complications secondary to botulinum toxin injection, we present a novel treatment option aimed at correcting gummy smile using hyaluronic acid injection and review the published techniques and the anatomy of the involved facial muscles.Methods: The treatment was performed by infiltration in the paranasal area, in the location of the most cranial portion of the nasojugal fold, about 3 mm lateral to the alar cartilage wing, according to a vector perpendicular to the cutaneous plane, to gently compress the lateral fibers of the levator labii superioris alaeque nasi without invading it. A Vycross® technology filler was used for all the treatments.Results: All patients had an immediate improvement, with a maximum duration ranging from 186 to 240 days (mean, 213 days), according to parameters of the Global Aesthetic Improvement Scale (GAIS 4.06).Conclusions: This new, less invasive and safer technique to correct dynamic excessive gingival display was shown to be feasible and safe with a long-lasting result. This treatment could be a novel effective option for experienced injectors to treat aesthetic facial flaws.Level of Evidence4: [ABSTRACT FROM AUTHOR]

Background: The genus Potentilla is closely related to that of Fragaria, the economically important strawberry genus. Potentilla micrantha is a species that does not develop berries but shares numerous morphological and ecological characteristics with Fragaria vesca. These similarities make P. micrantha an attractive choice for comparative genomics studies with F. vesca. Findings: In this study, the P. micrantha genome was sequenced and annotated, and RNA-Seq data from the different developmental stages of flowering and fruiting were used to develop a set of gene predictions. A 327 Mbp sequence and annotation of the genome of P. micrantha, spanning 2674 sequence contigs, with an N50 size of 335,712, estimated to cover 80% of the total genome size of the species was developed. The genus Potentilla has a characteristically larger genome size than Fragaria, but the recovered sequence scaffolds were remarkably collinear at the micro-syntenic level with the genome of F. vesca, its closest sequenced relative. A total of 33,602 genes were predicted, and 95.1% of bench-marking universal single-copy orthologous genes were complete within the presented sequence. Thus, we argue that the majority of the gene-rich regions of the genome have been sequenced. Conclusions: Comparisons of RNA-Seq data from the stages of floral and fruit development revealed genes differentially expressed between P. micrantha and F. vesca. The data presented are a valuable resource for future studies of berry development in Fragaria and the Rosaceae and they also shed light on the evolution of genome size and organization in this family. [ABSTRACT FROM AUTHOR]

Grapevine (Vitis vinifera L.) is a species well known for its adaptation to radiation. However, photomorphogenic factors related to UV-B responses have not been molecularly characterized. We cloned and studied the role of UV-B RECEPTOR (UVR1), ELONGATED HYPOCOTYL 5 (HY5), and HY5 HOMOLOGUE (HYH) from V. vinifera. We performed gene functional characterizations, generated co-expression networks, and tested them in different environmental conditions. These genes complemented the Arabidopsis uvr8 and hy5 mutants in morphological and secondary metabolic responses to radiation. We combined microarray and RNA sequencing (RNA-seq) data with promoter inspections to identify HY5 and HYH putative target genes and their DNA binding preferences. Despite sharing a large set of common co-expressed genes, we found different hierarchies for HY5 and HYH depending on the organ and stress condition, reflecting both co-operative and partially redundant roles. New candidate UV-B gene markers were supported by the presence of HY5-binding sites. These included a set of flavonol-related genes that were up-regulated in a HY5 transient expression assay. We irradiated in vitro plantlets and fruits from old potted vines with high and low UV-B exposures and followed the accumulation of flavonols and changes in gene expression in comparison with nonirradiated conditions. UVR1, HY5, and HYH expression varied with organ, developmental stage, and type of radiation. Surprisingly, UVR1 expression was modulated by shading and temperature in berries, but not by UV-B radiation. We propose that the UV-B response machinery favours berry flavonol accumulation through the activation of HY5 and HYH at different developmental stages at both high and low UV-B exposures. [ABSTRACT FROM AUTHOR]

The mitochondrial DNA A3243G mutation causes neuromuscular disease. To investigate the muscle-specific pathophysiology of mitochondrial disease, rhabdomyosarcoma transmitochondrial hybrid cells (cybrids) were generated that retain the capacity to differentiate to myotubes. In some cases, striated muscle-like fibres were formed after innervation with rat embryonic spinal cord. Myotubes carrying A3243G mtDNA produced more reactive oxygen species than controls, and had altered glutathione homeostasis. Moreover, A3243G mutant myotubes showed evidence of abnormal mitochondrial distribution, which was associated with down-regulation of three genes involved in mitochondrial morphology, Mfn1, Mfn2 and DRP1. Electron microscopy revealed mitochondria with ultrastructural abnormalities and paracrystalline inclusions. All these features were ameliorated by anti-oxidant treatment, with the exception of the paracrystalline inclusions. These data suggest that rhabdomyosarcoma cybrids are a valid cellular model for studying muscle-specific features of mitochondrial disease and that excess reactive oxygen species production is a significant contributor to mitochondrial dysfunction, which is amenable to anti-oxidant therapy. [ABSTRACT FROM AUTHOR]

The complement receptor 2 (CR2, CD21) is part of a complex (CD21/CD19/CD81) acting as a co-receptor to the B cell receptor (BCR). Simultaneous triggering of the BCR and CD21 lowers the threshold for B cell activation. Although CD21 is important, B cells that express low amounts or lack surface CD21 (CD21-/low) are increased in conditions with chronic inflammation, e.g. autoimmune diseases. However, little is known about the CD21-/low B cell subset in peripheral blood from healthy donors. Here, we show that CD21-/low cells represent approximately 5% of B cells in peripheral blood from adults but are barely detectable in cord blood, after excluding transitional B cells. The CD21-/low subset can be divided into CD38-24+ and CD38-24low cells, where most of the CD38-24+ are CD27+immunoglobulin (Ig)M+IgD+ and the CD38-24low are switched CD27-. Expression levels of additional markers, e.g. CD95 and CD62L, are similar to those on classical memory B cells. In contrast to naive cells, the majority of CD21-/low cells lack expression of the ABCB1 transporter. Stimulation with a combination of BCR, Toll-like receptor (TLR)−7/8 and interleukin (IL)−2 induces proliferation and differentiation of the CD21-/low B cells comparable to CD21+CD27+ memory B cells. The response excluding BCR agonist is not on par with that of classical memory B cells, although clearly above that of naive B cells. This is ascribed to a weaker response by the CD38-24low subset, implying that some memory B cells require not only TLR but also BCR triggering. We conclude that the CD21-/low cells in healthy donors are memory B cells. [ABSTRACT FROM AUTHOR]

Objective. Pain prevalence data for patients at various stages after stroke. Design. Repeated cross-sectional, observational epidemiological study. Setting. Hospital-based multicenter study. Subjects. Four hundred forty-three prospectively enrolled stroke survivors. Methods. All patients under went bedside clinical examination. The different types of post-stroke pain (central post-stroke pain, musculoskeletal pains, shoulder pain, spasticity-related pain, and headache) were diagnosed with widely accepted criteria during the acute, subacute, and chronic stroke stages. Differences among the three stages were analyzed with v2 -tests. Results. The mean overall prevalence of pain was 29.56% (14.06% in the acute, 42.73% in the subacute, and 31.90% in the chronic post-stroke stage). Time course differed significantly according to the various pain types (P< 0.001). The prevalence of musculoskeletal and shoulder pain was higher in the subacute and chronic than in the acute stages after stroke; the prevalence of spasticity-related pain peaked in the chronic stage. Conversely, headache manifested in the acute post-stroke stage. The prevalence of central post-stroke pain was higher in the subacute and chronic than in the acute post-stroke stage. Fewer than 25% of the patients with central post-stroke pain received drug treatment. Conclusions. Pain after stroke is more frequent in the subacute and chronic phase than in the acute phase, but it is still largely undertreated. [ABSTRACT FROM AUTHOR]

The sunflower (Helianthus annuus) genome contains a very large proportion of transposable elements, especially long terminal repeat retrotransposons. However, knowledge on the retrotransposon-related variability within this species is still limited. We used next-generation sequencing (NGS) technologies to perform a quantitative and qualitative survey of intraspecific variation of the retro-transposon fraction of the genome across 15 genotypes--7 wild accessions and 8 cultivars--of H. annuus. By mapping the Illumina reads of the 15 genotypes onto a library of sunflower long terminal repeat retrotransposons, we observed considerable variability in redundancy among genotypes, at both superfamily and family levels. In another analysis, we mapped Illumina paired reads to two sets of sequences, that is, long terminal repeat retrotransposons and protein-encoding sequences, and evaluated the extent of retro-transposon proximity to genes in the sunflower genome by counting the number of paired reads in which one read mapped to a retrotransposon and the other to a gene. Large variability among genotypes was also ascertained for retrotransposon proximity to genes. Both long terminal repeat retrotransposon redundancy and proximity to genes varied among retrotransposon families and also between cultivated and wild genotypes. Such differences are discussed in relation to the possible role of long terminal repeat retrotransposons in the domestication of sunflower. [ABSTRACT FROM AUTHOR]

Anthocyanins are flavonoid compounds responsible for red/purple colors in the leaves, fruit, and flowers of many plant species. They are produced through a multistep pathway that is controlled by MYB transcription factors. VvMYBA1 and VvMYBA2 activate anthocyanin biosynthesis in grapevine (Vitis vinifera) and are nonfunctional in white grapevine cultivars. In this study, transgenic grapevines with altered VvMYBA gene expression were developed, and transcript analysis was carried out on berries using a microarray technique. The results showed that VvMYBA is a positive regulator of the later stages of anthocyanin synthesis, modification, and transport in cv Shiraz. One up-regulated gene, ANTHOCYANIN 3-O-GLUCOSIDE-699-O-ACYLTRANSFERASE (Vv3AT), encodes a BAHD acyltransferase protein (named after the first letter of the first four characterized proteins: BEAT [for acetyl CoA:benzylalcohol acetyltransferase], AHCT [for anthocyanin O-hydroxycinnamoyltransferase], HCBT [for anthranilate N-hydroxycinnamoyl/benzoyltransferase], and DAT [for deacetylvindoline 4-O-acetyltransferase]), belonging to a clade separate from most anthocyanin acyltransferases. Functional studies (in planta and in vitro) show that Vv3AT has a broad anthocyanin substrate specificity and can also utilize both aliphatic and aromatic acyl donors, a novel activity for this enzyme family found in nature. In cv Pinot Noir, a red-berried grapevine mutant lacking acylated anthocyanins, Vv3AT contains a nonsense mutation encoding a truncated protein that lacks two motifs required for BAHD protein activity. Promoter activation assays confirm that Vv3AT transcription is activated by VvMYBA1, which adds to the current understanding of the regulation of the BAHD gene family. The flexibility of Vv3AT to use both classes of acyl donors will be useful in the engineering of anthocyanins in planta or in vitro. [ABSTRACT FROM AUTHOR]

Autophagy is a process that sequesters and degrades organelles and macromolecular constituents of cytoplasm for cellular restructuring and repair and as a source of nutrients for metabolic use in early starvation. The effects of two antiaging dietary regimens (initiated in rats at the age of 2 months), namely, 40% dietary restriction (DR) and every-other-day ad-libitum feeding, that exhibited different effects on metabolism and similar effects on longevity on the age-related changes in the regulation of autophagic proteolysis were studied by monitoring the rate of valine release in the incubation medium from isolated liver cells of male albino Sprague-Dawley rats aged 2, 6, 12, 18, 24, and 27 months. (The liver cells were incubated in vitro with added amino acids and 10(-7) M insulin or glucagon.) Age-matched male albino Sprague-Dawley rats fed ad libitum served as a control. Results show that in ad-libitum-fed rats, after a transient increase by age 6 months, autophagic proteolysis and regulation by amino acid exhibit a dramatic age-related decline, and that the age-related changes are prevented by dietary antiaging intervention. A comparison shows that the protective effects of DR and every-other-day ad-libitum feeding are partially different in 24-month-old rats (but the beneficial effects of the two diets on regulation of autophagic proteolysis are always similar). With regard to endocrine regulation, results confirm that the liver cell response to glucagon (but not to insulin) declines with increasing age, and they show that antiaging DRs significantly improve the effects of glucagon (and have no effect on the response to insulin). The interactions of age by diet, glucagon (and in older rats, insulin), and amino acids are significant. It is concluded that DR significantly improves the susceptibility of liver cells to lysosomal degradation, and it prevents decline with increasing age. It is suggested that improved liver autophagy and lysosomal degradation might be part of the antiaging mechanisms of DR. [ABSTRACT FROM AUTHOR]

During intervals between meals, autophagy is a major source of nutrients and may remove damaged organelles and membranes. Age-related changes in the regulation of autophagic proteolysis were studied by monitoring the rate of valine release from liver cells of 2-, 6-, 12-, 18-, and 24-month-old male Sprague-Dawley rats fed ad libitum, and incubated in vitro with added amino acids and 10(-7) M of insulin or glucagon. The maximum rate of proteolysis and its maximum inhibition by amino acids were reached at 6 months and declined thereafter. In contrast, the rate of protein degradation in the presence of high concentrations of amino acids was not affected by aging. The inhibitor effect of insulin was additive to that of amino acids and was not altered significantly by age. The conclusion is that altered regulation of autophagic proteolysis decreases susceptibility of older cells to lysosomal degradation, and it may lead to the accumulation of altered organelles and membranes. [ABSTRACT FROM AUTHOR]

We determined the applicability of deriving the stature from knee height in an older Italian population, and, in the same population, we assessed longitudinally the change in stature over a 6-year interval. The standing stature and knee height in a supine position were measured in the entire home-dwelling older (65 + years) population of a small Italian town (N = 606). Stature measured in 1989 and in 1995 was used to assess longitudinal changes in 258 subjects of the same population. Stature derived from knee height was greater than measured stature in this population and in the two sexes. This difference disappeared when subjects with evident kyphosis were excluded. From 1989 to 1995, stature decreased by 1.7+/-3.0 cm, with women showing a larger decrement than men. Stature estimated from knee height is more accurate than measured stature in subjects with kyphosis. In accordance with previous studies, stature decreases with aging, and such height loss is greater in women than in men. [ABSTRACT FROM AUTHOR]

Because of the vast range of functions that phenylpropanoids possess, their synthesis requires precise spatiotemporal coordination throughout plant development and in response to the environment. The accumulation of these secondary metabolites is transcriptionally controlled by positive and negative regulators from the MYB and basic helix-loop-helix protein families. We characterized four grapevine (Vitis vinifera) R2R3-MYB proteins from the C2 repressor motif clade, all of which harbor the ethylene response factor-associated amphiphilic repression domain but differ in the presence of an additional TLLLFR repression motif found in the strong flavonoid repressor Arabidopsis (Arabidopsis thaliana) AtMYBL2. Constitutive expression of VvMYB4a and VvMYB4b in petunia (Petunia hybrida) repressed general phenylpropanoid biosynthetic genes and selectively reduced the amount of small-weight phenolic compounds. Conversely, transgenic petunia lines expressing VvMYBC2-L1 and VvMYBC2-L3 showed a severe reduction in petal anthocyanins and seed proanthocyanidins together with a higher pH of crude petal extracts. The distinct function of these regulators was further confirmed by transient expression in tobacco (Nicotiana benthamiana) leaves and grapevine plantlets. Finally, VvMYBC2-L3 was ectopically expressed in grapevine hairy roots, showing a reduction in proanthocyanidin content together with the down-regulation of structural and regulatory genes of the flavonoid pathway as revealed by a transcriptomic analysis. The physiological role of these repressors was inferred by combining the results of the functional analyses and their expression patterns in grapevine during development and in response to ultraviolet B radiation. Our results indicate that VvMYB4a and VvMYB4b may play a key role in negatively regulating the synthesis of small-weight phenolic compounds, whereas VvMYBC2-L1 and VvMYBC2-L3 may additionally fine tune flavonoid levels, balancing the inductive effects of transcriptional activators. [ABSTRACT FROM AUTHOR]

Improved knowledge of genome composition, especially of its repetitive component, generates important information for both theoretical and applied research. The olive repetitive component is made up of two main classes of sequences: tandem repeats and retrotransposons (REs). In this study, we provide characterization of a sample of 254 unique full-length long terminal repeat (LTR) REs. In the sample, Ty1-Copia elements were more numerous than Ty3-Gypsy elements. Mapping a large set of Illumina whole-genome shotgun reads onto the identified retroelement set revealed that Gypsy elements are more redundant than Copia elements. The insertion time of intact retroelements was estimated based on sister LTR’s divergence. Although some elements inserted relatively recently, the mean insertion age of the isolated retroelements is around 18 million yrs. Gypsy and Copia retroelements showed different waves of transposition, with Gypsy elements especially active between 10 and 25 million yrs ago and nearly inactive in the last 7 million yrs. The occurrence of numerous solo-LTRs related to isolated full-length retroelements was ascertained for two Gypsy elements and one Copia element. Overall, the results reported in this study show that RE activity (both retrotransposition and DNA loss) has impacted the olive genome structure in more ancient times than in other angiosperms. [ABSTRACT FROM PUBLISHER]

Aims In the HORIZONS trial, in-hospital treatment with bivalirudin reduced bleeding and mortality in primary percutaneous coronary intervention (PCI) compared with heparin and routine glycoprotein IIb/IIIa inhibitors (GPI). It is unknown whether this advantage of bivalirudin is observed in comparison with heparins only with GPI used as bailout. Methods and results In the EUROMAX study, 2198 patients with ST-segment elevation myocardial infarction (STEMI) were randomized during transport for primary PCI to bivalirudin or to heparins with optional GPI. Primary and principal outcome was the composites of death or non-CABG-related major bleeding at 30 days. This pre-specified analysis compared patients receiving bivalirudin (n = 1089) with those receiving heparins with routine upstream GPI (n = 649) and those receiving heparins only with GPI use restricted to bailout (n = 460). The primary outcome death and major bleeding occurred in 5.1% with bivalirudin, 7.6% with heparin plus routine GPI (HR 0.67 and 95% CI 0.46–0.97, P = 0.034), and 9.8% with heparins plus bailout GPI (HR 0.52 and 95% CI 0.35–0.75, P = 0.006). Following adjustment by logistic regression, bivalirudin was still associated with significantly lower rates of the primary outcome (odds ratio 0.53, 95% CI 0.33–0.87) and major bleeding (odds ratio 0.44, 95% CI 0.24–0.82) compared with heparins alone with bailout GPI. Rates of stent thrombosis were higher with bivalirudin (1.6 vs. 0.6 vs. 0.4%, P = 0.09 and 0.09). Conclusion Bivalirudin, started during transport for primary PCI, reduces major bleeding compared with both patients treated with heparin only plus bailout GPI and patients treated with heparin and routine GPI, but increased stent thrombosis. [ABSTRACT FROM PUBLISHER]

Analyzing genome structure in different species allows to gain an insight into the evolution of plant genome size. Olive (Olea europaea L.) has a medium-sized haploid genome of 1.4 Gb, whose structure is largely uncharacterized, despite the growing importance of this tree as oil crop. Next-generation sequencing technologies and different computational procedures have been used to study the composition of the olive genome and its repetitive fraction. A total of 2.03 and 2.3 genome equivalents of Illumina and 454 reads from genomic DNA, respectively, were assembled following different procedures, which produced more than 200,000 differently redundant contigs, with mean length higher than 1,000 nt. Mapping Illumina reads onto the assembled sequences was used to estimate their redundancy. The genome data set was subdivided into highly and medium redundant and nonredundant contigs. By combining identification and mapping of repeated sequences, it was established that tandem repeats represent a very large portion of the olive genome (∼31% of the whole genome), consisting of six main families of different length, two of which were first discovered in these experiments. The other large redundant class in the olive genome is represented by transposable elements (especially long terminal repeat-retrotransposons). On the whole, the results of our analyses show the peculiar landscape of the olive genome, related to the massive amplification of tandem repeats, more than that reported for any other sequenced plant genome. [ABSTRACT FROM AUTHOR]

Flavonoids play a key role in grapevine physiology and also contribute substantially to the quality of berries and wines. VvMYB5a and VvMYB5b are R2R3-MYB transcription factors previously proposed to control the spatiotemporal expression of flavonoid structural genes during berry development. We investigated the functions of these two proteins in detail by heterologous expression in a petunia an2 mutant, which has negligible anthocyanin levels in the petals because it lacks the MYB protein PhAN2. We also expressed VvMYBA1, the grapevine ortholog of petunia PhAN2, in the same genetic background. The anthocyanin profiles induced by expressing these transgenes in the petals revealed that VvMYBA1 is the functional ortholog of PhAN2 and that, unlike VvMYB5a, VvMYB5b can partially complement the an2 mutation. Transcriptomic analysis of petals by microarray hybridization and quantitative PCR confirmed that VvMYB5b up-regulates a subset of anthocyanin structural genes, whereas VvMYB5a has a more limited impact on the expression of genes related to anthocyanin biosynthesis. Furthermore, we identified additional specific and common targets of these two regulators, related to vacuolar acidification and membrane remodeling. Taken together, these data provide insight into the role of VvMYB5a and VvMYB5b in flavonoid biosynthesis and provide evidence for additional regulatory roles in distinct pathways. [ABSTRACT FROM AUTHOR]

Background. Stroke severely affects walking ability, and assessment of gait kinematics is important in defining diagnosis, planning treatment, and evaluating interventions in stroke rehabilitation. Although observational gait analysis is the most common approach to evaluate gait kinematics, tools useful for this purpose have received little attention in the scientific literature and have not been thoroughly reviewed. Objectives. The aims of this systematic review were to identify tools proposed to conduct observational gait analysis in adults with a stroke, to summarize evidence concerning their quality, and to assess their implementation in rehabilitation research and clinical practice. Methods. An extensive search was performed of original articles reporting on visual/observational tools developed to investigate gait kinematics in adults with a stroke. Two reviewers independently selected studies, extracted data, assessed quality of the included studies, and scored the metric properties and clinical utility of each tool. Rigor in reporting metric properties and dissemination of the tools also was evaluated. Results. Five tools were identified, not all of which had been tested adequately for their metric properties. Evaluation of content validity was partially satisfactory. Reliability was poorly investigated in all but one tool. Concurrent validity and sensitivity to change were shown for 3 and 2 tools, respectively. Overall, adequate levels of quality were rarely reached. The dissemination of the tools was poor. Conclusions. Based on critical appraisal, the Gait Assessment and Intervention Tool shows a good level of quality, and its use in stroke rehabilitation is recommended. Rigorous studies are needed for the other tools in order to establish their usefulness. [ABSTRACT FROM AUTHOR]

Hyaluronidases, a family of enzymes that are able to degrade hyaluronic acid (HA), are employed in medicine to increase drug diffusion and reverse the effects of HA filler injections. Hyaluronidases are able to dissolve subcutaneous nodules or to correct excessive quantities of injected filler. Knowledge of the use, methods of application, and adverse effects of hyaluronidases is essential for the aesthetic practitioner. Therefore, we performed an extensive review of the available literature from 1928 to 2011 and compared the different enzymes available, recording each author’s indications regarding usage and side effects. [ABSTRACT FROM PUBLISHER]

Aims Pre-treating placenta-derived human mesenchymal stem cells (FMhMSCs) with a hyaluronan mixed ester of butyric and retinoic acid (HBR) potentiates their reparative capacity in rodent hearts. Our aim was to test FMhMSCs in a large-animal model by employing a novel combination of in vivo and ex vivo analyses. Methods and results Matched regional quantifications of myocardial function and viability were performed by magnetic resonance imaging (MRI) and positron emission tomography (PET) 4weeks after myocardial infarction combined with intramyocardial injection of FMhMSCs (n = 7), or HBR-pre-treated FMhMSCs (HBR-FMhMSCs, n = 6), or saline solution (PBS, n = 7). Sham-operated pigs (n = 4) were used as control animals. Despite no differences in the ejection fraction and haemodynamics, regional MRI revealed, in pigs treated with HBR-FMhMSCs compared with the other infarcted groups, a 40% smaller infarct scar size and a significant improvement of the end-systolic wall thickening and circumferential shortening of the infarct border zone. Consistently, PET showed that myocardial perfusion and glucose uptake were, respectively, 35 and 23% higher in the border zone of pigs treated with HBR-FMhMSCs compared with the other infarcted groups. Histology supported in vivo imaging; the delivery of HBR-FMhMSCs significantly enhanced capillary density and decreased fibrous tissue by approximately 68%. Moreover, proteomic analysis of the border zone in the HBR-FMhMSCs group and the FMhMSCs group indicated, respectively, 45 and 30% phenotypic homology with healthy tissue, while this homology was only 26% in the border zone of the PBS group. Conclusion Our results support a more pronounced reparative potential of HBR-pre-treated FMhMSCs in a clinically relevant animal model of infarction and highlight the necessity of using combined diagnostic imaging to avoid underestimations of stem cell therapeutic effects in the heart. [ABSTRACT FROM AUTHOR]

BackgroundElevated neutrophil count, a marker of systemic inflammation, has been suggested as a prognostic marker of cardiovascular disease in postmenopausal women with hypertension. We tested the hypothesis that an association exists between elevated neutrophil count and increased arterial stiffness, as reflected by a wide pulse pressure (PP), in this population of women. We also tested PP as predictor of cardiovascular adverse events in this population.MethodsWe analyzed data relating to 886 postmenopausal women with hypertension, consecutively enrolled in a prospective registry. Ambulatory blood pressure monitoring was carried out at entry in all the subjects. The median duration of follow-up was 7.4 years (range: 1-21 years).ResultsThere was a direct relationship between neutrophil count and 24-h ambulatory PP (P < 0.0001) and this association remained significant after adjusting for age, serum glucose, and left ventricular (LV) hypertrophy at electrocardiogram (ECG) (all P < 0.01). During follow-up there were 121 first-time major cardiovascular (CV) events. The rate (× 100 patient-years) of CV events was 1.02, 1.36, and 3.75, respectively in the three tertiles of the distribution of 24-h PP (P < 0.0001). In a multivariate analysis, 24-h ambulatory PP and neutrophil count were independent predictors of total CV events after adjusting for the influence of other risk markers. In particular, for each 10 mm Hg increase in 24-h PP, there was a 73% higher risk for total CV events (P = 0.015). Office-recorded PP did not achieve significance when forced in the same model.ConclusionsIncreased arterial stiffness, as reflected in high values of 24-h ambulatory PP, is an adverse prognostic marker in postmenopausal women with hypertension, possibly as an additional correlate of systemic inflammation.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.18 [ABSTRACT FROM AUTHOR]

Pneumocystis spp. are fungi that are able to infect a variety of host species and, occasionally, lead to severe pneumonia. Porcine circovirus type 2 (PCV2) is an important viral pathogen which affects both swine and wild boar herds worldwide. Co-infection between PCV2 and other pathogens has been reported, and the secondary immunodeficiency caused by the virus may predispose to these co-infections. In the present study, postmortem tissue samples obtained from wild boar herds in Southern Brazil were analyzed by histopathology, ultra-structural observation, and immunohistochemistry. Forty-seven out of seventy-eight (60%) wild boars showed clinical signs, gross, and histopathological lesions characteristic of infection by PCV2. Pneumocystis was detected by immunohistochemistry in 39 (50%) lungs and viral antigens of PCV2 were found in 29 (37.2%) samples. Concomitant presence of Pneumocystis and PCV2 were observed in 16 (20.5%) of the wild boars. Cystic and trophic forms of Pneumocystis were similar to previously described ultra-structural observations in other mammals. [ABSTRACT FROM AUTHOR]

Background: To estimate the incidence of aneuploidy in relation to patients' characteristics, the type of hormonal stimulation and their response to induction of multiple follicular growth, 4163 first polar bodies (PB1s) were analyzed.Methods: Five hundred and forty four infertile couples underwent 706 assisted conception cycles (640 with poor prognosis indications and 66 controls) in which chromosomal analysis of PB1 for the chromosomes 13, 15, 16, 18, 21 and 22 was performed. Results were evaluated in a multivariate analysis.Results: The proportion of normal oocytes was directly correlated (P < 0.01) with (i) the number of mature oocytes and (ii) the establishment of a clinical pregnancy; and inversely correlated (P < 0.01) with (i) female age, (ii) causes of female infertility (endometriosis, abortions, ovulatory factor), (iii) poor prognosis indications (female age, number of previous cycles, multiple poor prognosis indications), (iv) number of FSH units per oocyte and (v) number of FSH units per metaphase II oocyte. There was a weak significance of frequency (P < 0.05) between type of abnormality (originated by chromatid predivision, chromosome non-disjunction or combined mechanisms in the same oocyte) and groups of the studied variables, rather than to a specific abnormality or a specific chromosome.Conclusions: The type of infertility had a significant effect on errors derived from the first meiotic division, whose incidence was significantly higher in the presence of endometriosis or of an ovulatory factor, and in women that experienced repeated abortions. Each aneuploidy event was found to be dependent not on a specific variable, but on groups of variables. In addition, the tendency of chromosomal abnormalities to occur simultaneously implies that the deriving aneuploidies can be of any type. [ABSTRACT FROM AUTHOR]

Aims: It has been demonstrated that, in comparison with bare-metal stents (BMS), sirolimus-eluting stents (SES) reduce restenosis after the percutaneus revascularization of small coronary arteries, but the long-term clinical outcomes of this treatment have not yet been investigated. [ABSTRACT FROM PUBLISHER]

Aim of the project was to evaluate behavioral and productive variations of dairy cows detected by automatic monitoring systems, during different seasons. Environmental data (Temperature (T, °C), Relative Humidity, (RH, %) and Temperature and Humidity Index (THI)), were recorded inside the pens by electronic probes during 4 periods over 2 years, for a total of 473 days. Fans and sprinklers were activated at THI >60. Hundred lactating and dry cows were equipped with monitoring tag (Heatime-Pro, SCR Engineers Ltd.) that recorded continuously time (min/d) spent ruminating (RT), panting (PT) and feeding (FT). Daily PT and FT data were recorded as group average [lactating (LC) or dry], while RT and milk production were extracted as individual data. Four classes of environmental stress were identified based on maximum THI: comfort (C, THI < 60, 101d), moderate stress (MS, 60< THI >69, 92d), stress (S, 70< THI >75, 102d), severe stress (SS, THI >75, 178d). Behavioral and productive data were compared between classes. Data were analyzed by mixed model with repeated measures, with environmental class, group (dry or lactating), parity and interactions as fixed effect. Cow was included as random effect for RT and milk production. Means comparison was performed by Tukey post hoc test. All behavioral outcomes were influenced by heat stress (P < .001, table 1). Panting increased linearly with maximum THI recorded, being highest during SS days in LC (49.6 min/d, P < .001). FT and RT (min/d) were lowest (P < .001) during S days (206.9, FT and 473.1, RT) and RT reached the lowest values in cows within 15 DIM (456.4). Milk production was affected in multiparous cows, with a linear reduction from C to SS days (P < .001). Heat stress deeply affected cows behavior and performances, despite cooling systems. Automatic monitoring of these parameters can effectively help in detecting heat stress and consequently adopt strategies to improve animal welfare. [ABSTRACT FROM AUTHOR]

Autophagy is a process that sequesters and degrades altered organelles and macromolecular cytoplasmic constituents for cellular restructuring and repair, and as a source of nutrients for metabolic use in early starvation it may be involved in anti-aging mechanisms of caloric restriction. The effects of 40% daily dietary restriction (DR) and intermittent feeding (EOD) on the age-related changes in the endocrine regulation of autophagic proteolysis were studied by monitoring the rate of valine release from isolated rat liver cells. Results show that in ad libitum-fed rats sensitivity of autophagy to glucagon and insulin declines by one order of magnitude in older rats. Both DR and EOD maintain the sensitivity to glucagon at juvenile levels, whereas only EOD can fully maintain response to insulin. It is concluded that changes in the sensitivity to glucagon may have a role in the aging process. [ABSTRACT FROM AUTHOR]

The genus Pneumocystis is composed of opportunistic fungi currently considered as specific pulmonary pathogens in humans and other mammals. In pigs, Pneumocystis pneumonia (PcP) could create significant economical losses due to its detrimental effects on growth, food conversion, and carcass/viscera condemnation. This study revealed that Pneumocystis organisms could be detected by Grocott's staining or immunohistochemistry in 36.9% of 564 slaughtered pigs from two geographic regions of Brazil. The prevalence of positive cases was 39.9% and 33.9% in pigs slaughtered in Rio Grande do Sul (RS) and Mato Grosso (MT) states, respectively. Among the positive cases in RS, Pneumocystis organisms were observed in 41.9% of 33 histologically normal lungs, and in 58.0% of lungs presenting with histological lesions. In contrast, the prevalence in MT in normal and abnormal lungs was 36.3% and 63.5%, respectively. Major histopathological findings in lungs of infected animals were bronchointerstitial pneumonia (47.6%), suggestive of enzootic pneumonia, and interstitial pneumonia (37.9%), compatible with PcP. The results of this survey strengthened the interest of detecting fungal pathogens, in addition to other infectious agents, and evaluating their financial impact on Brazilian pig industry. Preventive and/or therapeutic strategies should be developed in order to minimize the incidence of respiratory fungal infections in pigs and associated economic losses. [ABSTRACT FROM AUTHOR]

In the beginnings of mechanical refrigeration, at the end of the nineteenth century, carbon dioxide was one of the first refrigerants to be used in compression-type refrigerating machines, later gaining widespread application mainly onboard refrigerated ships, but common in other sectors of refrigeration as well. It was only immediately after World War II that CO2 was rapidly eclipsed as a refrigerant, due to the advent of the synthesised halogenated working fluids, addressed as safe and ideal refrigerants at that time. Because of the stratospheric Ozone depletion environmental issue, CFC and HCFC working fluids are now in the process of being phased out of use under the Montreal Protocol. The Global Warming environmental issue casts concern over the use of the new HFC fluids as substitute refrigerants, because of their high GWP values, which make them subject to regulations under the Kyoto Protocol. In this mixed situation, CO2 is being revisited as a fully environmentally friendly and safe refrigerant. An intense research activity on its prospective applications is underway in many research establishments in Europe, Japan and North America, and important results have already been reached in exploiting the peculiar characteristics of this high-pressure fluid operated with a transcritical cycle. In some applications CO2 systems have already been commercialised; this applies to heat pump water heaters, as a brine in indirect systems and in the low temperature stage of cascade systems. The paper critically analyses the prospects for the future return of CO2 as a working fluid, or sometimes as a brine with change of phase, in important application areas. These include air conditioning and heat pump systems in the residential and commercial sectors, commercial and transport refrigeration and mobile air conditioning. [ABSTRACT FROM AUTHOR]

We describe a self-monitoring approach for improving older adult learning that older adults can use in conjunction with more traditional mnemonic-based interventions. According to the self-monitoring approach, older adults can improve the effectiveness of learning by accurately monitoring their progress toward a learning goal and by using the output from such monitoring to allocate study time and to inform strategy selection. We review current evidence, which includes outcomes from two previously unpublished interventions, relevant to the efficacy of this approach. Both interventions demonstrated performance gains in memory performance after self-monitoring training, although these training gains did not exceed gains obtained through standard mnemonic training. Our discussion highlights both successes and failures of self-monitoring to enhance learning as well as challenges for future research. [ABSTRACT FROM AUTHOR]

In this paper we evaluate the characteristics observed both on a crime sample and on individuals included in a database to assess the probability of alternative hypotheses concerning identification. The problem is first addressed by considering a generic characteristic and we demonstrate the problem via a computationally efficient Bayesian network. Then we turn our attention to a heritable DNA trait to show how to evaluate the hypotheses that some individuals, genetically related to the members of the database, are the donors of the crime sample. Then the network is extended to cope with many loci. Applications of the method are provided as well as details of computational requirements. [ABSTRACT FROM AUTHOR]

BACKGROUND: A protocol for the chromosomal analysis of sperm samples with a severely reduced number of sperm cells was designed. METHODS: A severe male factor condition was the main cause of infertility for 38 couples: 27 were oligoasthenoteratospermic (OAT) and 11 with non-obstructive azoospermia underwent testicular sperm extraction (TESE). A two-round fluorescence in situ hybridization (FISH) protocol was performed with probes specific for the chromosomes X, Y, 13, 15, 16, 17, 18, 21 and 22. The recording of the position of each sperm cell at the microscope allowed diagnosis of each spermatozoon for the nine tested chromosomes. RESULTS: A mean number of 12278.5 sperm were diagnosed per patient with an incidence of total abnormalities corresponding to 13.4%. ?2-tests for the observed frequencies and goodness-of-fit test were highly significant in all cases. A significantly higher proportion of total aneuploidy was detected in 79% of the tested samples compared to the normal population. Testicular sperm were significantly more prone to aneuploidy than ejaculated sperm. CONCLUSIONS: The designed FISH protocol for the analysis of severe OAT and TESE sperm samples is reliable, implying that the studied sample is representative of the original population. In view of the high incidence of aneuploidy in most severe OAT and TESE sperm, the FISH analysis of pathological sperm samples can be routinely performed in order to estimate the chances of the paternal contribution to aneuploidy in the resulting embryos. [ABSTRACT FROM AUTHOR]

Aims Retrospective studies and post hoc analyses have suggested that mild elevations in the creatine kinase-MB (CK-MB) isoenzyme following percutaneous coronary intervention (PCI) may be associated with an increased risk of death in the long term. However, this finding is still controversial, and the prognostic significance of elevations of more sensitive markers of myocardial damage, such as the cardiac troponins, has not been established. In this multicentre prospective cohort study, we evaluated the influence of post-procedural elevations of CK-MB and troponin I (cTnI) on long-term mortality. [ABSTRACT FROM PUBLISHER]

Criteria for defining biomarkers have been suggested. Accumulation of dolichol in tissues of older animals meets the following criteria: (a) levels of dolichol exhibit a quantitative correlation with age in all tissues and are not altered by several age-dependent diseases in the same direction as that of aging; (b) accumulation is not secondary to metabolic changes of aging and is altered appropriately by factors that modulate the aging rate like caloric restriction and physical exercise; (c) biomarker is applicable to different tissues across mammalian species, including humans, and to trisomy 21 and its hypothalamic digoxin-mediated model. Reliable changes in tissue dolichol levels are seen in relatively short intervals of time compared to over a life span, and levels can be tested on a small amount of tissue without causing death of the animal. In this article, we show applications to the study of host-graft interaction and detection of gender-related differences in biological age, and we discuss mechanism(s) of accumulation. [ABSTRACT FROM AUTHOR]

Seagrasses such as Posidonia oceanica (L.) Delile are marine phanerogams, widespread in various seas, where they form large prairies representing dynamic substrates exceeding the area of the sediment surface several times over and allowing settlement of epiphyte organisms. Studying mechanisms involved in water transport in marine plants, we isolated two aquaporin-encoding genes, PoPIP1;1 and PoTIP1;1, showing high similarity to plasma membrane- and tonoplast-intrinsic protein-encoding genes, respectively. PoPIP1;1 is unique in the genome of P. oceanica, while PoTIP1;1 belongs to an aquaporin subfamily of at least four members. PoPIP1;1 and PoTIP1;1 encode functional proteins, as indicated by expression experiments in Xenopus oocytes. Both genes are constitutively expressed in the leaves, with higher levels of transcripts in young than in differentiated leaf tissues. Variations of salt concentration in aquarium determined different PoPIP1;1 and PoTIP1;1 transcript accumulation, indicating the existence of adaptation mechanisms related to gene expression also in marine plants, i.e. adapted to very high salt concentrations. Hyposalinity induced lower levels of PIP1 transcripts, while hypersalinity determined more PIP1 transcripts than normal salinity. TIP1 transcripts increased in response to both hypo- and hypersalinity after 2 days of treatment and went back to control levels after 5 d. [ABSTRACT FROM PUBLISHER]

Background Intracranial haemorrhage is an important limitation to pharmacologic reperfusion therapy for acute myocardial infarction. The combination of a glycoprotein IIb/IIIa inhibitor, half-dose plasminogen activator and reduced-dose heparin has been evaluated as an alternative to standard fibrinolytic therapy in this setting.Methods and results We evaluated the relation between univariate and multivariate predictors of intracranial haemorrhage and the effect of treatment with either reteplase alone (10U bolus twice, 30min apart) with standard-dose heparin (5000U bolus followed by an infusion of 1000Uh−1for patients ≥80kg and 800Uh−1for those <80kg) or combination therapy with abciximab (0.25mg/kg bolus and 0.125μg/kg/min for 12h) and half-dose reteplase (two boluses of 5U 30min apart) with reduced-dose heparin (60Ukg−1bolus, maximum 5000U, followed by an infusion of 7Ukg−1h−1) in the 16 588 patients randomized in the GUSTO V trial. Overall, the incidence of intracranial haemorrhage was similar in the two groups (0.6% vs 0.6%; OR 1.05, 95% CI 0.71, 1.56). The median (25th–75th) time from drug administration to intracranial haemorrhage was 5.5 (3.4–11) hours with combination therapy and 9.2 (5.9–22) hours with reteplase (P=0.048). Among the multivariable predictors of intracranial haemorrhage, only age showed a significant interaction with treatment effect (age per treatment interaction chi-square 4.60, P=0.032) with a lower risk of combination therapy for younger patients and a higher risk for the elderly.Conclusions Although no additional risk of intracranial haemorrhage has been observed with combination therapy in the whole population, a significant age pertreatment interaction exists, with a lower risk with combination therapy in younger patients, and a higher risk in the elderly. [ABSTRACT FROM PUBLISHER]

Supraventricular arrhythmias are often observed in patients before and after atrial septal defect repair. Although several papers report different incidences of sustained supraventricular arrhythmias, postoperative ‘incisional’ macrore-entrant tachycardias have not been systematically investigated.Methods We reviewed 136 consecutive patients (79 female, 57 male, mean age 36·8±17·8 years) who underwent atrial septal defect repair at our institutions between January 1990 and January 1999. Coexisting valve disease requiring surgical intervention was noted in 13 patients (9·5%). The mean follow-up period was 78·8±30·1 months. Results Sustained supraventricular arrhythmias occurred in 12 patients (8·8%) before surgery (atrial fibrillation in 11 patients). Using multivariate analysis the occurrence of arrhythmia significantly correlated with the presence of coexisting heart disease (P< 0·001) and age at surgery (P=0·011) After surgery sustained supraventricular arrhythmias were recorded in 16 patients (11·7%). Eleven of them had atrial fibrillation, permanent in 8 cases, 4 ‘incisional’ macroreentrant atrial tachycardia and 1 atrioventricular re-entry tachycardia. There was a significant correlation between pre and postoperative arrhythmia (P< 0·001). Two of the 4 patients with macroreentrant atrial tachycardia underwent successful radiofrequency catheter ablation, whereas the arrhythmia was controlled medically in the remaining 2 patients. Conclusions Atrial fibrillation remains the most frequent form of arrhythmia before and after surgical closure of atrial septal defects in adulthood, and relates to age at the time of repair and coexisting heart disease. Incisional macroreentrant atrial tachycardia is an identifiable, albeit less common, form of tachycardia, which can be treated by transcatheter ablation. [ABSTRACT FROM PUBLISHER]

Features a study on the effects of hepatitis C virus (HCV) genotypes on patients with cirrhosis in southern Italy. Details on HCV genotypes; Methods of the study; Results; Discussion.

Background: Hepatitis C virus (HCV) is a common cause of chronic liver diseases but the degree to which these diseases contribute to liver-related mortality is not well established. The aim of this study was to estimate the absolute and relative effects of HCV infection on liver-related mortality.Methods: A population random sample of 2472 subjects aged > or = 30 years was enrolled and followed up from 1985 to 1996. At enrollment, a structured interview and a clinical evaluation were performed. Serum samples were tested using HCV ELISA and RIBA HCV. Outcomes were overall and liver-related mortality and tracing procedures included review of office and hospital records, death certificates, and interviews with general practitioners, attending hospital and next of kin. Statistical analysis was performed using Poisson and binomial prospective data regression.Results: Crude overall and liver-related mortality rates were 7.66 (95% CI : 6.68-8.79) and 0.9 (95% CI : 0.3-2.2) per 10(3) person-years, respectively. For HCV infection effect, incidence rate ratio and difference (per 10(3) person-year), risk ratio and difference were 27.5 (95% CI : 6.5-115.6), 4 (95% CI : 3-7), 33.1 (95% CI : 7.8- 139.3) and 0.06 (95% CI : 0.04-0.08), respectively; all measures were adjusted for age at death, sex and daily alcohol intake.Conclusions: The results show a strong relative but weak absolute effect of HCV infection on liver-related mortality in the 10-year period considered. Poisson and binomial models are virtually equivalent, but the choice of the summarizing measure of effect may have a different impact on health policy. [ABSTRACT FROM AUTHOR]