Lactoferrin. A natural glycoprotein involved in iron and inflammatory homeostasis

Human lactoferrin (hLf), an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and by neutrophils, is a key element of host defenses. HLf and bovine Lf (bLf), possessing high sequence homology and identical functions, inhibit bacterial growth and biofilm dependently from iron binding ability while, independently, bacterial adhesion to and the entry into cells. In infected/inflamed host cells, bLf exerts an anti-inflammatory activity against interleukin-6 (IL-6), thus up-regulating ferroportin (Fpn) and transferrin receptor 1 (TfR1) and down-regulating ferritin (Ftn), pivotal actors of iron and inflammatory homeostasis (IIH). Consequently, bLf inhibits intracellular iron overload, an unsafe condition enhancing in vivo susceptibility to infections, as well as anemia of inflammation (AI), re-establishing IIH. In pregnant women, affected by AI, bLf oral administration decreases IL-6 and increases hematological parameters. This surprising effect is unrelated to iron supplementation by bLf (80 µg instead of 1-2 mg/day), but to its role on IIH. AI is unrelated to the lack of iron, but to iron delocalization: cellular/tissue overload and blood deficiency. BLf cures AI by restoring iron from cells to blood through Fpn up-expression. Indeed, anti-inflammatory activity of oral and intravaginal bLf prevents preterm delivery. Promising bLf treatments can prevent/cure transitory inflammation/anemia/oral pathologies in athletes

Addressing Youth Perceptions of Harm in Marijuana Prevention Programming

The inverse relationship between perception of harm and substance use is clearly supported by decades of research – youth are less likely to engage in substance use when it is seen as harmful. However, despite strong theoretical and practical reasons to focus on perception of harm as a change-producer in prevention programming, little is known about what is effective in impacting perception of harm for youth marijuana use. To investigate the impact of existing prevention efforts designed to influence youth perception of harm and, consequently, youth marijuana use, we reviewed seven privately- or federally-funded online registries (e.g., Blueprints for Healthy Youth Development, Substance Abuse and Mental Health Administration’s National Registry of Evidence Based Programs and Practices) to identify evidence-based programs with marijuana-related outcomes for youth. We found 36 registry-identified programs with demonstrated impact on youth marijuana use. Although many of these programs may have actively or passively sought to alter perception of harm, only ten measured marijuana- or drug-related perception of harm as an intermediate outcome. Drawing on the commonalities of evidence-based programs with significant impacts on youth marijuana perception of harm, as well as lessons learned from other health behavior change efforts, we recommend best practices to provide state and local decision-makers with information on altering youth perception of harm for marijuana and on evaluating the impact of these efforts

Efficacy of lactoferrin oral administration in the treatment of anemia and anemia of inflammation in pregnant and non-pregnant women: an interventional study

The discovery of the ferroportin-hepcidin complex has led to a critical review on the treatment of anemia and anemia of inflammation (AI). Ferroportin, the only known mammalian iron exporter from cells to blood, is negatively regulated by hepcidin, a hormone peptide able to bind to ferroportin, leading to its degradation. Therefore, new efficient therapeutic interventions acting on hepcidin and ferroportin are imperative to manage anemia and AI. Bovine milk derivative lactoferrin (bLf), a glycoprotein able to chelate two ferric ions per molecule, is emerging as a natural anti-inflammatory substance able to modulate hepcidin and ferroportin synthesis through the down-regulation of interleukin-6 (IL-6). Here, an interventional study (ClinicalTrials.gov Identifier: NCT01221844) was conducted by orally administering 100 mg of 20-30% iron-saturated bLf (corresponding to 70-84 μg of elemental iron) twice a day. This treatment was compared with the Italian standard therapy, consisting in the oral administration of 329.7 mg of ferrous sulfate once a day (corresponding to 105 mg of elemental iron). Treatments were carried out on 29 anemic women with minor ß-thalassemia (20 pregnant and 9 non-pregnant), 149 women with hereditary thrombophilia (HT) (70 pregnant and 79 non-pregnant) affected by AI and 20 anemic pregnant women suffering from various pathologies. In anemic pregnant and non-pregnant women with minor ß-thalassemia, presenting undetectable hepcidin levels, differently from ferrous sulfate management, bLf decreased IL-6 (from 25 ± 8 to 6 ± 3 pg/ml) and increased total serum iron (TSI) (from 54 ± 17 to 80 ± 9 μg/dl). BLf was also more efficient than ferrous sulfate in AI treatment in HT pregnant and non-pregnant women by decreasing both serum IL-6 (from 89 ± 8 to 58 ± 6 pg/ml) and hepcidin (from 115 ± 23 to 65 ± 10 ng/ml), thus increasing hematological parameters, such as the number of red blood cells (RBCs), the concentration of hemoglobin, TSI and serum ferritin. BLf was also efficient in treating anemia in other pathological pregnancies. Taken together all the results, bLf, showing a greater benefit and efficacy than the standard ferrous sulfate management, can be considered as a promising compound in treating anemia and AI through its ability to down-regulate IL-6, thus restoring ferroportin-mediated iron export from cells to blood in a hepcidin-dependent or independent way

Acid-Base Disorders in Patients with Chronic Obstructive Pulmonary Disease: A Pathophysiological Review

The authors describe the pathophysiological mechanisms leading to development of acidosis in patients with chronic obstructive pulmonary disease and its deleterious effects on outcome and mortality rate. Renal compensatory adjustments consequent to acidosis are also described in detail with emphasis on differences between acute and chronic respiratory acidosis. Mixed acid-base disturbances due to comorbidity and side effects of some drugs in these patients are also examined, and practical considerations for a correct diagnosis are provided

Biotimer assay: A reliable and rapid method for the evaluation of central venous catheter microbial colonization

Adherent bacteria and biofilm frequently colonize central venous catheters (CVCs). CVC colonization is correlated to infections and particularly to bloodstream ones. The classical microbiological methods to determine of CVC colonization are not fully reliable and are time-consuming. BioTimer Assay (BTA) is a biological method already used to count bacteria adherent to abiotic surfaces and biofilm without sample manipulation. BTA employs specific reagents whose color changed according to bacterial metabolism. BTA is based on the principle that a metabolic reaction will be faster when more bacteria are present in the sample. Therefore, the time required for color changes of BTA reagents determines the number of bacteria present in the sample through a correlation line. Here, for the first time, we applied BTA and a specifically developed laboratory procedure to evaluate CVC colonization in comparison with the routine microbiological method (RMM). 125 CVCs removed from patients for suspected catheter-related bloodstream infection (CRBSI) or at hospital discharge were examined. BTA was reliable in assessing sterility and CVC colonization (100% agreement with RMM) and in recognizing the presence of fermenting or non-fermenting bacteria (97.1% agreement with RMM) shortening the analytical time by between 2- and 3-fold. Moreover, the reliability of BTA as early alert of CRBSI was evaluated. The sensitivity, specificity, positive, and negative predictive values for BTA as an early alert of CRBSI were 100, 40.0, 88.8 and 100%, respectively. In conclusion, BTA and the related laboratory procedure should be incorporated into routine microbiological methods since it can be considered a reliable tool to evaluate CVC colonization in a very short time and a rapid alert for CRBSIs

A comparative study of models for the incident duration prediction

This study is intended to investigate the reliability of different incident duration prediction models for real time application with a view to contribute to the development of a decision aid tool within the incident management process context where rough incident duration estimates are currently provided by traffic operators or police on the basis of their skill and past experience. Five predictive models, ranging from parametric models, to non-parametric and neural network models, have been considered and compared evaluating their capacity of predicting incident duration. The data set used in this study for developing and testing the prediction models includes 237 incident events and contains information about the incident characteristics, the personnel and equipment involved to clear the incident and the related response times, including the beginning and ending time of the incident. Testing results have demonstrated that the proposed models are able to achieve good performance in terms of prediction accuracy especially for incidents with duration less than 90 min. This finding is partly due to the fact that the dataset has a relatively small number of severe incidents. Furthermore a linear combination of predictions from models was applied with negligible gain in accuracy. A deeper investigation is suggested for a future work to evaluate potential improvements from the application of other combination methods. Moreover each proposed model is able to reach best performance for incidents within a particular duration range. Thus a preliminary incident classification scheme could be more convenient in order to select the more appropriate prediction model

Primi dati zooarcheologici dal santuario della Malophoros a Selinunte (TP). Firts Results from the Archaeozoological Study at the Sanctuary of Malophoros in Selinunte (TP)

Gli aspetti religiosi ricoprivano un ruolo essenziale nella vita degli antichi greci. Tale ritualità si esprimeva attra- verso un’articolazione multiforme e diversif icata, spesso di diff icile lettura per gli archeologi. Tuttavia, è possibile identif icare all’interno di queste pratiche religiose un denominatore comune nella presenza degli animali come principale offerta sacrif icale. Il presente lavoro riguarda i primi dati zooarcheologici provenienti dalle recenti ricerche che hanno interessato l’area del santuario della Malophoros a Selinunte. La nostra indagine si pone come obiettivo principale l’esplora- zione delle modalità sacrif icali utilizzate dagli antichi frequentatori del santuario, ponendo particolare attenzione su tutti quegli elementi tafonomici riferibili ad un particolare trattamento subito dall’animale a scopo rituale. Le analisi f ino ad ora effettuate hanno riguardato un totale di 2299 resti faunistici di cui 805 attribuiti a livello specif ico. L’analisi incrociata dei reperti combusti e della distribuzione dei diversi elementi anatomici all’interno del campione ha mostrato che durante i riti che prevedevano la combustione dell’animale veniva preferita una particolare porzione: la coscia o le sue ossa. Sebbene si tratti di dati preliminari, le informazioni provenienti dallo studio delle faune sembrerebbero evidenzia- re la presenza di diversi utilizzi dell’animale a scopo rituale (olocausto, moirocausto, θυσία) che ben si accorda con la generale complessa articolazione del santuario selinuntino.Rituals played an essential role in the life of the ancient Greeks. These rituals were often expressed through multifaceted and diverse ways that are often diff icult to read in the archaeological record. However, it is possible to identify a common denominator in the use of animals as the main sacrif icial offering within these religious practices. We are presenting here the f irst zooarchaeology data from recent excavations in the area of the sanctuary of Malophoros at Selinunte. The main aim of our investigation, which is still ongoing, is the exploration of ancient sacrif icial rituals. We are paying particular attention to taphonomic aspects that are indicative of any specif ic treatment of animals for ritual purposes. The analysis carried out has included a total of 2,299 animal remains, of which 805 are attributed to species level. The combined analysis of burnt remains and that of the distribution of body parts showed that the preferred part offered to some deities was the thigh bone. The preliminary results of our data seem to highlight the presence of different uses of the animals for ritual purposes (holocaust, moirocaust, θυσία). The evidence is consistent with the articulation of the sanctuary

Enhanced osteogenic differentiation in zoledronate-treated osteoporotic patients

Bisphosphonates are well known inhibitors of osteoclast activity and thus may be employed to influence osteoblast activity. The present study was designed to evaluate the in vivo effects of zoledronic acid (ZA) on the proliferation and osteoblastic commitment of mesenchymal stem cells (MSC) in osteoporotic patients. We studied 22 postmenopausal osteoporotic patients. Densitometric, biochemical, cellular and molecular data were collected before as well as after 6 and 12 months of ZA treatment. Peripheral blood MSC-like cells were quantified by colony-forming unit fibroblastic assay; their osteogenic differentiation potential was evaluated after 3 and 7 days of induction, respectively. Circulating MSCs showed significantly increased expression levels of osteoblastic marker genes such as Runt-related transcription factor 2 (RUNX2), and Osteonectin (SPARC) during the 12 months of monitoring time. Lumbar bone mineral density (BMD) variation and SPARC gene expression correlated positively. Bone turnover marker levels were significantly lowered after ZA treatment; the effect was more pronounced for C terminal telopeptide (CTX) than for Procollagen Type 1 N-Terminal Propeptide (P1NP) and bone alkaline phosphatase (bALP). Our findings suggest a discrete anabolic activity supported by osteogenic commitment of MSCs, consequent to ZA treatment. We confirm its anabolic effects in vivo on osteogenic precursors

Models and Materials for Generalized Kitaev Magnetism

The exactly solvable Kitaev model on the honeycomb lattice has recently received enormous attention linked to the hope of achieving novel spin-liquid states with fractionalized Majorana-like excitations. In this review, we analyze the mechanism proposed by G. Jackeli and G. Khaliullin to identify Kitaev materials based on spin-orbital dependent bond interactions and provide a comprehensive overview of its implications in real materials. We set the focus on experimental results and current theoretical understanding of planar honeycomb systems (Na$_2$IrO$_3$, $\alpha$-Li$_2$IrO$_3$, and $\alpha$-RuCl$_3$), three-dimensional Kitaev materials ($\beta$- and $\gamma$-Li$_2$IrO$_3$), and other potential candidates, completing the review with the list of open questions awaiting new insights.Comment: updated references, published versio

Medication-related osteonecrosis of the jaw (MRONJ): are antiresorptive drugs the main culprits or only accomplices? The triggering role of vitamin D deficiency

Osteonecrosis of the jaw (ONJ) is a severe clinical condition characterized mostly but not exclusively by an area of exposed bone in the mandible and/or maxilla that typically does not heal over a period of 6-8 weeks. The diagnosis is first of all clinical, but an imaging feedback such as Magnetic Resonance is essential to confirm clinical suspicions. In the last few decades, medication-related osteonecrosis of the jaw (MRONJ) has been widely discussed. From the first case reported in 2003, many case series and reviews have appeared in the scientific literature. Almost all papers concerning this topic conclude that bisphosphonates (BPs) can induce this severe clinical condition, particularly in cancer patients. Nevertheless, the exact mechanism by which amino-BPs would be responsible for ONJ is still debatable. Recent findings suggest a possible alternative explanation for BPs role in this pattern. In the present work we discuss how a condition of osteomalacia and low vitamin D levels might be determinant factors