The postmarsupial development of Porcellio siculoccidentalis, with some data on reproductive biology (Crustacea, Isopoda, Oniscidea)

In the broader context of research on the Sicilian Porcellio imbutus-complex, the postmarsupial development of Porcellio siculoccidentalis Viglianisi, Lombardo & Caruso, 1992 was studied in detail. This research was conducted in the laboratory under controlled conditions, allowing us to follow the stages of development, from the formation of the marsupium in ovigerous females until the larval stages and development of the seventh pair of legs. The timing of developmental stages and the morphological modifications of appendages in the postmarsupial manca stages (M I-M III) are described. The manca stage M I had a duration of about one hour. Ovigerous females were collected and reared separately, and the number of parturial molts in the absence of males was counted. The results showed a maximum of four successive parturial molts. Fecundity and fertility were evaluated as the number of eggs and embryos, respectively, inside the marsupium of the ovigerous females. Both parameters were positively correlated with the size of the females. The maximum numbers of eggs and embryos in the marsupium were 113 and 141, respectively. Data describing the total number of postmarsupial mancas released per month indicated that the highest release occurred in April.     

Appraising Hospital Performance by Using the JCHAO/CMS Quality Measures in Southern Italy

Objectives

The main objective of the present study was to estimate the uptake to quality indicators that reflect the current evidence-based recommendations and guidelines.

Methods

A retrospective review of medical records of patients admitted to two hospitals in the South of Italy was conducted. For the purposes of the analysis, a sets of quality indicators has been used from the Joint Commission on Accreditation of Hospital Organizations and Centers for Medicare & Medicaid Services. Four areas of care were selected: acute myocardial infarction (AMI), heart failure (HF), pneumonia (PN), and surgical care improvement project (SCIP). Frequency or median was calculated, as appropriate, for each indicator. A composite score was calculated to estimate the overall performance for each area of care.

Results

A total of 1772 medical records were reviewed. The adherence rates showed a wide-ranging variability among the selected indicators. The use of aspirin and angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for AMI, the use of ACEI or ARB for HF, the use of appropriate thromboembolism prophylaxis and appropriate hair removal for surgical patients almost approached optimal adherence. At the other extreme, rates regarding adherence to smoking-cessation counseling in AMI and HF patients, discharge instructions in HF patients, and influenza and pneumococcal vaccination in pneumonia patients were noticeably intangible. Overall, the recommended processes of care among eligible patients were provided in 70% for AMI, in 32.4% for HF, in 46.4% for PN, and in 46% for SCIP.

Conclusions

The results show that there is still substantial work that lies ahead on the way to improve the uptake to evidence-based processes of care. Improvement initiatives should be focused more on domains of healthcare than on specific conditions, especially on the area of preventive care.     

Increased Serum Hepcidin Levels in Subjects with the Metabolic Syndrome: A Population Study

The recent discovery of hepcidin, the key iron regulatory hormone, has changed our view of iron metabolism, which in turn is long known to be linked with insulin resistant states, including type 2 diabetes mellitus and the Metabolic Syndrome (MetS). Serum ferritin levels are often elevated in MetS (Dysmetabolic hyperferritinemia - DHF), and are sometimes associated with a true mild-to-moderate hepatic iron overload (dysmetabolic iron overload syndrome - DIOS). However, the pathophysiological link between iron and MetS remains unclear. This study was aimed to investigate, for the first time, the relationship between MetS and hepcidin at population level. We measured serum hepcidin levels by Mass Spectrometry in 1,391 subjects from the Val Borbera population, and evaluated their relationship with classical MetS features. Hepcidin levels increased significantly and linearly with increasing number of MetS features, paralleling the trend of serum ferritin. In multivariate models adjusted for relevant variables including age, C-Reactive Protein, and the HFE C282Y mutation, ferritin was the only significant independent predictor of hepcidin in males, while in females MetS was also independently associated with hepcidin. Overall, these data indicate that the fundamental iron regulatory feedback is preserved in MetS, i.e. that hepcidin tends to progressively increase in response to the increase of iron stores. Due to recently discovered pleiotropic effects of hepcidin, this may worsen insulin resistance and contribute to the cardiovascular complications of MetS.     

Biomarkers of Good EULAR Response to the B Cell Depletion Therapy in All Seropositive Rheumatoid Arthritis Patients: Clues for the Pathogenesis

Objective

To find out whether a high number of auto-antibodies can increase the probability of a “good-EULAR response” and to identify the possible biomarkers of response in seropositive rheumatoid arthritis (RA) patients undergoing the B cell depletion therapy (BCDT).

Patients and Methods

One hundred and thirty-eight patients with long standing RA (LSRA), 75% non or poorly responsive to one or more TNFα blockers, all seropositive for at least one autoantibody (AAB) (RF-IgM, RF-IgA, RF-IgG, anti-MCV, ACPA-IgG, ACPA-IgA, ACPA-IgM) received one full course of BCDT. The major outcomes (moderate or good-EULAR response) were assessed after 6 months of therapy. The IL6 and BAFF levels were also determined.

Results

At a 6-month follow-up, 33 (23.9%) of the RA patients achieved a good EULAR response. Having up to 5-AABs positivity increased the chances for treatment response. After a logistic regression analysis, however, only 4 baseline factors arose as associated with a good-EULAR response: no steroid therapy (OR = 6.25), a lymphocyte count <1875/uL (OR = 10.74), a RF-IgG level >52.1 IU/ml (OR = 8.37) and BAFF levels <1011 pg/ml (OR = 7.38). When all the AABs, except for RF-IgM and ACPA-IgG, were left in the analysis, the two final predictors were no-steroid therapy and low lymphocyte count.

Discussion

The number of AABs increased the chances of being a “good-EULAR” responder. The only predictors, however, at the baseline of a good response in this seropositive cohort of RA patients were 2 simple variables – no steroids and lymphocyte count – and two laboratory assays – IgG-RF and BAFF.     

Human chorionic villus mesenchymal stromal cells reveal strong endothelial conversion properties

Chorion, amnion and villi are reservoirs of mesenchymal stromal cells (StC) and the hypothesis that StC from fetal tissues retain higher plasticity compared to adult StC has been suggested. Aimed at investigating this aspect, a series of in vitro experiments were performed with StC isolated from first trimester human chorionic villi (CVStC). CVStC were cultured in: (i) standard mesenchymal medium (MM) and (ii) AmniomaxII? (AM), specifically designed to grow amnion-derived cells in prenatal diagnostic procedures. Cells were then exposed to distinct differentiation treatments and distinguished according to morphology, immunophenotype and molecular markers. Human StC obtained from adult bone marrow (BMStC) were used as control. CVStC cultured either in MM or AM presented stromal morphology and immunophenotype, were negative for pluripotency factors (Nanog, Oct-4 and Sox-2), lacked detectable telomerase activity and retained high genomic stability. In AM, however, CVStC exhibited a faster proliferation rate compared to BMStC or CVStC kept in MM. During differentiation, CVStC were less efficient than BMStC in acquiring adipocytes and osteocytes features; the cardiomyogenic conversion occurred at low efficiency in both cell types. Remarkably, in the presence of pro-angiogenic factors, CVStC reprogrammed toward an endothelial-like phenotype at significantly higher efficiency than BMStC. This effect was particularly evident in CVStC expanded in AM. Mechanistically, the reduced CVStC expression of anti-angiogenic microRNA could support this process. The present study demonstrates that, despite of fetal origin, CVStC exhibit restricted plasticity, distinct from that of BMStC and predominantly directed toward the endothelial lineage.     

Buxus in Europe: Late Quaternary dynamics and modern vulnerability

The suggested location of broadleaved evergreen trees in Europe during the last full-glacial has traditionally favoured a southerly refugial model, which proposes survival in the Mediterranean peninsulas and recolonization of central and northern Europe during the Holocene. This hypothesis is not always substantiated by thorough reviews of original past and modern occurrence data, or considered in the light of plant traits and autoecology. Our approach focuses on the genus Buxus with the aim of exploring (i) the relationship between the location of refugia and post-glacial population dynamics, (ii) past processes determining density, fragmentation and local extinctions of modern populations, and (iii) the vulnerability of Buxus in the context of the undergoing environmental changes. We compiled a database of over 3600 modern occurrences and 676 fossil sites to reconstruct the distribution of Buxus in Europe since 30 ka cal BP. The location of fossil finds and the plant traits of Buxus indicate that it persisted widely across its modern distribution through the last glacial period with modes varying from region to region. The E Pyrenees, W Alps, and Jura Mts hosted dense populations, which expanded exponentially during the whole Holocene, and resulted in a modern continuous distribution area. In contrast, the Mediterranean Peninsulas hosted sparse populations, which increased exponentially only during the first half of the Holocene, clearly decreased in the last 4.5 ka BP and resulted in a highly fragmented modern distribution area, most likely in relation to the climate trends towards dry conditions of the last few millennia. These results challenge the common view that the Mediterranean regions are the exclusive and most important refuge areas for evergreen broadleaved trees and stress the importance of considering long-term population dynamics based on fossil data to evaluate the vulnerability of modern fragmented plant populations in view of conservation actions.     

Efficiency of scat-analysis lab procedures for bear dietary studies: The case of the Apennine brown bear

Bear food habits are often quantified using scat analysis, mainly due to its non-invasiveness and because samples are relatively easy to collect. However, lab processing time can be daunting and may end up competing with other field activities. Sub-sampling a bear scat to analyze its contents may reduce the lab processing time, but the number of subsamples per scat is usually chosen arbitrarily. We investigated the effect of the number of subsamples per bear scat on the estimatation of the diet composition of the Apennine brown bear in the Abruzzo Lazio and Molise National Park. Based on a sample of 328 bear scats collected in 2006, and from 5 to 1 subsamples (10 ml) per scat, dietary analysis showed qualitative and quantitative stability at a decreasing number of subsamples, and only food items of negligible importance were occasionally missed using 1–2 subsamples per scat. We concluded that 2 subsamples can be used without significant loss in accuracy, corresponding to a 60% reduction in lab time, and to more than 50 days of lab work for one operator to process our entire bear scat sample. By assessing the effect of sub-sampling a bear scat for dietary analysis, we also present preliminary data on the seasonal food habits of the Apennine brown bear population.     

Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia

The association of type 2 diabetes with elevated plasma triglyceride (TG) and very low-density lipoproteins (VLDL), and intrahepatic lipid accumulation represents a pathophysiological enigma and an unmet therapeutic challenge. Here, we uncover a link between insulin action through FoxO1, bile acid (BA) composition, and altered lipid homeostasis that brings new insight to this longstanding conundrum. FoxO1 ablation brings about two signature lipid abnormalities of diabetes and the metabolic syndrome, elevated liver and plasma TG. These changes are associated with deficiency of 12α-hydroxylated BAs and their synthetic enzyme, Cyp8b1, that hinders the TG-lowering effects of the BA receptor, Fxr. Accordingly, pharmacological activation of Fxr with GW4064 overcomes the BA imbalance, restoring hepatic and plasma TG levels of FoxO1-deficient mice to normal levels. We propose that generation of 12α-hydroxylated products of BA metabolism represents a signaling mechanism linking hepatic lipid abnormalities with type 2 diabetes, and a treatment target for this condition.     

New retinoid derivatives as back-ups of Adarotene

Adarotene belongs to the so-called class of atypical retinoids. The presence of the phenolic hydroxyl group on Adarotene structure allows a rapid O-glucuronidation as a major mechanism of elimination of the drug, favoring a fast excretion of its glucuronide metabolite in the urines. A series of ether, carbamate and ester derivatives was synthesized. All of them were studied and evaluated for their stability at different pH. The cytotoxic activity in vitro on NCI-H460 non-small cell lung carcinoma and A2780 ovarian tumor cell lines was also tested. A potential back-up of Adarotene has been selected to be evaluated in tumor models.     

Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study

Introduction

Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question.

Methods

European SLE patients, 1444, recruited at 17 centres from 10 countries were analyzed. Genotypes for 26 SLE associated SNPs were compared between patients with and without each of 11 clinical features: ten of the American College of Rheumatology (ACR) classification criteria (except ANAs) and age of disease onset. These analyses were adjusted for centre of recruitment, top ancestry informative markers, gender and time of follow-up. Overlap of samples with previous studies was excluded for assessing replication.

Results

There were three new associations: the SNPs in XKR6 and in FAM167A-BLK were associated with lupus nephritis (OR = 0.76 and 1.30, P_corr = 0.007 and 0.03, respectively) and the SNP of MECP2, which is in chromosome X, with earlier age of disease onset in men. The previously reported association of STAT4 with early age of disease onset was replicated. Some other results were suggestive of the presence of additional associations. Together, the association signals provided support to some previous findings and to the characterization of lupus nephritis, autoantibodies and age of disease onset as the clinical features more associated with SLE loci.

Conclusion

Some of the SLE loci shape the disease phenotype in addition to increase susceptibility to SLE. This influence is more prominent for some clinical features than for others. However, results are only partially consistent between studies and subphenotype specific GWAS are needed to unravel their genetic component.