Practical oxygen therapy for newborn piglets.

Aims: To evaluate the effect of a novel method of practical oxygen therapy on physiological parameters related to survival, weaning weight and preweaning mortality of neonatal piglets under commercial farm conditions. Methods: Piglets from hyperprolific sows born with signs of asphyxia, (n = 109; <6 on a score of respiration, meconium staining and activity) or very low birth weight (VLBW; n = 112; <1.05 kg) were selected for the study. Approximately half of each group (n = 55 VLBW piglets and n = 57 piglets with asphyxia) received 100% oxygen immediately after birth using a specially designed facemask for 45 seconds (VLBW) or 1 minute (asphyxiated). Physiological parameters (peripheral blood oxygen saturation (SpO2) blood glucose concentration and rectal temperature) were measured before oxygen treatment 5 minutes after birth (SpO2) and 24 hours later (SpO2, blood glucose concentration, temperature). Weight at birth, at 24 hours and at 21 days of age, preweaning mortality, and estimated colostrum intake were also recorded. Results: A significant treatment effect on SpO2 was observed (p = 0.013 and p < 0.001 for VLBW and asphyxiated piglets respectively). VLBW and asphyxiated piglets that received oxygen treatment had higher SpO2 after treatment (measured 5 minutes after birth, 97.7 and 97.8% respectively) compared to immediately after birth (93.3 and 86.8% respectively) while untreated piglets showed no variation. Blood glucose concentrations increased in all piglets between birth and 24 hours of age (p = 0.003 and p < 0.001 for asphyxiated and VLBW piglets respectively) and this was higher in asphyxiated piglets that received oxygen than those that did not (5.6 (SE 0.2) mmol/L; p < 0.05). Estimated colostrum intake was higher in asphyxiated (401.6 (SD 24.4) g/kg) and VLBW (374.9 (SE 23.4 g/kg) piglets that received oxygen than those that did not (273.2 (SE 24.1) g/kg; p < 0.001 and 249.0 (SE 22.5) g/kg; p < 0.001 respectively). Similarly weight at weaning was higher in asphyxiated (5.8 (SE 0.2) kg) and VLBW (4.9 (SE 0.2) kg) piglets that received oxygen therapy than control animals (4.9 (SE 0.2) kg; = 0.005 and 4.1 (SE 0.2) kg; p = 0.008 respectively). Furthermore, oxygen treatment markedly reduced preweaning mortality from 9/52 (17%) untreated to 1/57 (1.7%) oxygen-treated piglets suffering asphyxia at birth (p = 0.006). Conclusions: Oxygen therapy improves physiological and productive parameters in piglets born with signs of asphyxia or VLBW. The incorporation of this strategy as part of the farrowing routine enhances the advantages of rearing hyperprolific sows.

1,2,3-Triazole Bridge as Conformational Constrain in ß-Hairpin Peptides: Analysis of Hydrogen-Bonded Positions.

Conformational constrained ß-hairpin peptides are useful tool to modulate protein-protein interactions. A triazole bridge in hydrogen-bonded positions between two antiparallel strands induces a conformational stabilization of the ß-hairpin peptide. The entity of the stability of the ß-hairpin peptide depends on the length of the bridge.

III Italian Consensus Conference on Malignant Mesothelioma of the Pleura. Epidemiology, Public Health and Occupational Medicine related issues.

The III Italian Consensus Conference on Pleural Mesothelioma (MM) convened on January 29th 2015. This report presents the conclusions of the 'Epidemiology, Public Health and Occupational Medicine' section. MM incidence in 2011 in Italy was 3.64 per 100,000 person/years in men and 1.32 in women. Incidence trends are starting to level off. Ten percent of cases are due to non-occupational exposure. Incidence among women is very high in Italy, because of both non-occupational and occupational exposure. The removal of asbestos in place is proceeding slowly, with remaining exposure. Recent literature confirms the causal role of chrysotile. Fibrous fluoro-edenite was classified as carcinogenic by IARC (Group 1) on the basis of MM data. A specific type (MWCNT-7) of Carbon Nanotubes was classified 2B. For pleural MM, after about 45 years since first exposure, the incidence trend slowed down; with more studies needed. Cumulative exposure is a proxy of the relevant exposure, but does not allow to distinguish if duration or intensity may possibly play a prominent role, neither to evaluate the temporal sequence of exposures. Studies showed that duration and intensity are independent determinants of MM. Blood related MM are less than 2.5%. The role of BAP1 germline mutations is limited to the BAP1 cancer syndrome, but negligible for sporadic cases. Correct MM diagnosis is baseline; guidelines agree on the importance of the tumor gross appearance and of the hematoxylin-eosin-based histology. Immunohistochemical markers contribute to diagnostic confirmation: the selection depends on morphology, location, and differential diagnosis. The WG suggested that 1) General Cancer Registries and ReNaM Regional Operational Centres (COR) interact and systematically compare MM cases; 2) ReNaM should report results presenting the diagnostic certainty codes and the diagnostic basis, separately; 3) General Cancer Registries and COR should interact with pathologists to assure the up-to-date methodology; 4) Necroscopy should be practiced for validation. Expert referral centres could contribute to the definition of uncertain cases. Health surveillance should aim to all asbestos effects. No diagnostic test is recommended for MM screening. Health surveillance should provide information on risks, medical perspective, and smoking cessation. The economic burden associated to MM was estimated in 250,000 Euro per case.

A universal DNA extraction and PCR amplification method for fungal rDNA sequence-based identification.

Accurate identification of fungal pathogens using a sequence-based approach requires an extraction method that yields template DNA pure enough for polymerase chain reaction (PCR) or other types of amplification. Therefore, the objective of this study was to develop and standardise a rapid, inexpensive DNA extraction protocol applicable to the major fungal phyla, which would yield sufficient template DNA pure enough for PCR and sequencing. A total of 519 clinical and culture collection strains, comprised of both yeast and filamentous fungi, were prepared using our extraction method to determine its applicability for PCR, which targeted the ITS and D1/D2 regions in a single PCR amplicon. All templates were successfully amplified and found to yield the correct strain identification when sequenced. This protocol could be completed in approximately 30 min and utilised a combination of physical and chemical extraction methods but did not require organic solvents nor ethanol precipitation. The method reduces the number of tube manipulations and yielded suitable template DNA for PCR amplification from all phyla that were tested.

Antimicrobial peptides from plants: stabilization of the γ core of a tomato defensin by intramolecular disulfide bond.

Cysteine-containing antimicrobial peptides of diverse phylogeny share a common structural signature, the γ core, characterized by a strong polarization of charges in two antiparallel ß sheets. In this work, we analyzed peptides derived from the tomato defensin SolyC07g007760 corresponding to the protein γ core and demonstrated that cyclization of the peptides, which results in segregation of positive charges to the turn region, produces peptides very active against Gram negative bacteria, such as Salmonella enterica and Helicobacter pylori. Interestingly, these peptides show very low hemolytic activity and thus represent a scaffold for the design of new antimicrobial peptides.

GIS-based pollution hazard mapping and assessment framework of shallow lakes: southeastern Pampean lakes (Argentina) as a case study.

The assessment of water vulnerability and pollution hazard traditionally places particular emphasis on the study on groundwaters more than on surface waters. Consequently, a GIS-based Lake Pollution Hazard Index (LPHI) was proposed for assessing and mapping the potential pollution hazard for shallow lakes due to the interaction between the Potential Pollutant Load and the Lake Vulnerability. It includes easily measurable and commonly used parameters: land cover, terrain slope and direction, and soil media. Three shallow lake ecosystems of the southeastern Pampa Plain (Argentina) were chosen to test the usefulness and applicability of this suggested index. Moreover, anthropogenic and natural medium influence on biophysical parameters in these three ecosystems was examined. The evaluation of the LPHI map shows for La Brava and Los Padres lakes the highest pollution hazard (≈30 % with high to very high category) while Nahuel Rucá Lake seems to be the less hazardous water body (just 9.33 % with high LPHI). The increase in LPHI value is attributed to a different loading of pollutants governed by land cover category and/or the exposure to high slopes and influence of slope direction. Dissolved oxygen and biochemical oxygen demand values indicate a moderately polluted and eutrophized condition of shallow lake waters, mainly related to moderate agricultural activities and/or cattle production. Obtained information by means of LPHI calculation result useful to perform a local diagnosis of the potential pollution hazard to a freshwater ecosystem in order to implement basic guidelines to improve lake sustainability.

A novel synthetic peptide from a tomato defensin exhibits antibacterial activities against Helicobacter pylori.

Defensins are a class of cysteine-rich proteins, which exert broad spectrum antimicrobial activity. In this work, we used a bioinformatic approach to identify putative defensins in the tomato genome. Fifteen proteins had a mature peptide that includes the well-conserved tetradisulfide array. We selected a representative member of the tomato defensin family; we chemically synthesized its γ-motif and tested its antimicrobial activity. Here, we demonstrate that the synthetic peptide exhibits potent antibacterial activity against Gram-positive bacteria, such as Staphylococcus aureus A170, Staphylococcus epidermidis, and Listeria monocytogenes, and Gram-negative bacteria, including Salmonella enterica serovar Paratyphi, Escherichia coli, and Helicobacter pylori. In addition, the synthetic peptide shows minimal (<5%) hemolytic activity and absence of cytotoxic effects against THP-1 cells. Finally, SolyC exerts an anti-inflammatory activity in vitro, as it downregulates the level of the proinflammatory cytokines TNF-α and IFN-γ.

Isolation and characterization of a new fungal species, Chrysosporium ophiodiicola, from a mycotic granuloma of a black rat snake (Elaphe obsoleta obsoleta).

Isolation and characterization of the new species Chrysosporium ophiodiicola from a mycotic granuloma of a black rat snake (Elaphe obsoleta obsoleta) are reported. Analysis of the sequences of different fragments of the ribosomal genes demonstrated that this species belongs to the Onygenales and that this species is genetically different from other morphologically similar species of Chrysosporium. This new species is unique in having both narrow and cylindrical-to-slightly clavate conidia and a strong, pungent odor.

Interlaboratory reproducibility of a single-locus sequence-based method for strain typing of Aspergillus fumigatus.

Seven international laboratories tested the recently proposed single-locus typing strategy for Aspergillus fumigatus subtyping for interlaboratory reproducibility. Comparative sequence analyses of portions of the locus AFUA_3G08990, encoding a putative cell surface protein (denoted CSP), was performed with a panel of Aspergillus isolates. Each laboratory followed very different protocols for extraction of DNA, PCR, and sequencing. Results revealed that the CSP typing method was a reproducible and portable strain typing method.

Weekly paclitaxel for advanced aggressive classic Kaposi sarcoma: experience in 17 cases.

BACKGROUND: Paclitaxel has proved to be highly effective in the treatment of severe AIDS-related Kaposi sarcoma (KS), for which it is now considered as a second-line monotherapy. Taxanes were recently shown to be active also in classic, endemic and post-transplantation KS. OBJECTIVES: To evaluate the clinical efficacy and tolerability of standardized paclitaxel treatment (100 mg weekly, intravenously) in a homogeneous group of 17 patients with advanced aggressive and refractory classic KS (cKS). METHODS: Seventeen patients with aggressive refractory cKS (stage IIIBc-IVBcv) were treated with intravenous paclitaxel 100 mg weekly. The response to the therapy was evaluated after 12 weeks. A maintenance treatment every 2 weeks was introduced for most of the patients and a final evaluation was made. RESULTS: A partial/complete response was achieved in 14 of 17 patients. Two patients had allergic reactions, for which treatment was discontinued. One patient had progression of disease despite initial improvement. Patients received a mean of 16.8 courses. The treatment was generally well tolerated. Mean time to recurrence was 4.5 months from the end of the therapy and 7.35 months from the 12th course. In four of 10 patients who relapsed at follow-up, the recurrence was mild and responsive to local treatment, while the other six relapsing patients repeated paclitaxel with good response in five of them. CONCLUSIONS: This study shows that low-dose paclitaxel proved to be effective and well tolerated in patients with aggressive refractory cKS, controlling the aggressiveness of the disease. The treatment can be repeated with good response.

AS602868, a dual inhibitor of IKK2 and FLT3 to target AML cells.

Acute myeloid leukemia (AML) cells carry molecular defects that promote their leukemic proliferation, resistance to apoptosis and defect in differentiation. Pharmacological targeting of the nuclear factor kappaB (NF-kappaB) pathway has been shown to promote apoptosis of primary AML cells and to sensitize blasts to neoplastic drugs (Frelin, Blood 2005, 105, 804). The Fms-like tyrosine kinase 3 (FLT3), which sustains proliferation of normal hematopoietic progenitors is frequently overexpressed or mutated in AML patients. Using Ba/F3 murine pre-B cells transfected with various mutants of FLT3 (ITD, D835V, D835Y) and the MV4-11 human AML line, we show that normal or oncogenic stimulation of FLT3 led to activation of NF-kappaB. Pharmacological inhibition of either FLT3 with AG1296 or NF-kappaB with the small molecule inhibitor of IkappaB kinase-2 AS602868 reduced viability and triggered cell death. Moreover, AS602868 was also found to interfere directly with FLT3 kinase activation. AS602868 thus appears to target two different kinases that play a crucial role in the pathogenesis of AML, making it particularly attractive as a new therapeutical approach for AML.

Fractional dynamics in the Lévy quantum kicked rotor.

We investigate the quantum kicked rotor in resonance subjected to momentum measurements with a Lévy waiting-time distribution. We find that the system has a sub-ballistic behavior. We obtain an analytical expression for the exponent of the power law of the variance as a function of the characteristic parameter of the Lévy distribution. We also connect the anomalous diffusion found with a fractional dynamics.

Ribosomal S6 kinase 1 (RSK1) activation requires signals dependent on and independent of the MAP kinase ERK.

BACKGROUND: The rsk1 gene encodes the 90 kDa ribosomal S6 kinase 1 (RSK1) protein, which contains two kinase domains. RSK1, which is involved in regulating cell survival and proliferation, lies at the end of the signaling cascade mediated by the extracellular signal-regulated kinase (ERK) subfamily of mitogen-activated protein (MAP) kinases. ERK activation and subsequent phosphorylation of the RSK1 carboxy-terminal catalytic loop stimulates phosphotransferase activity in the RSK1 amino-terminal kinase domain. When activated, RSK1 phosphorylates both nuclear and cytoplasmic substrates through this amino-terminal catalytic domain. It is thought that stimulation of the ERK/MAP kinase pathway is sufficient for RSK1 activation, but how ERK phosphorylation activates the RSK1 amino-terminal kinase domain is not known. RESULTS: The individual isolated RSK1 kinase domains were found to be under regulatory control. In vitro kinase assays established that ERK phosphorylates RSK1 within the carboxy-terminal kinase domain, and the phosphoinositide-dependent kinase 1 (PDK1) phosphorylates RSK1 within the amino-terminal kinase domain. In transiently transfected HEK 293E cells, PDK1 alone stimulated phosphotransferase activity of an isolated RSK1 amino-terminal kinase domain. Nevertheless, activation of full-length RSK1 in the absence of serum required activation by both PDK1 and ERK. CONCLUSIONS: RSK1 is phosphorylated by PDK1 in the amino-terminal kinase-activation loop, and by ERK in the carboxy-terminal kinase-activation loop. Activation of phosphotransferase activity of full-length RSK1 in vivo requires both PDK1 and ERK. RSK1 activation is therefore regulated by both the mitogen-stimulated ERK/MAP kinase pathway and a PDK1-dependent pathway.

p70 S6 kinase is regulated by protein kinase Czeta and participates in a phosphoinositide 3-kinase-regulated signalling complex.

p70 S6 kinase (p70S6K) is an important regulator of cell proliferation. Its activation by growth factor requires phosphorylation by various inputs on multiple sites. Data accumulated thus far support a model whereby p70S6K activation requires sequential phosphorylations at proline-directed residues in the putative autoinhibitory pseudosubstrate domain, as well as threonine 389. Threonine 229, a site in the catalytic loop is phosphorylated by phosphoinositide-dependent kinase 1 (PDK-1). Experimental evidence suggests that p70S6K activation requires a phosphoinositide 3-kinase (PI3-K)-dependent signal(s). However, the intermediates between PI3-K and p70S6K remain unclear. Here, we have identified PI3-K-regulated atypical protein kinase C (PKC) isoform PKCzeta as an upstream regulator of p70S6K. In coexpression experiments, we found that a kinase-inactive PKCzeta mutant antagonized activation of p70S6K by epidermal growth factor, PDK-1, and activated Cdc42 and PI3-K. While overexpression of a constitutively active PKCzeta mutant (myristoylated PKCzeta [myr-PKCzeta]) only modestly activated p70S6K, this mutant cooperated with PDK-1 activation of p70S6K. PDK-1-induced activation of a C-terminal truncation mutant of p70S6K was also enhanced by myr-PKCzeta. Moreover, we have found that p70S6K can associate with both PDK-1 and PKCzeta in vivo in a growth factor-independent manner, while PDK-1 and PKCzeta can also associate with each other, suggesting the existence of a multimeric PI3-K signalling complex. This work provides evidence for a link between a phorbol ester-insensitive PKC isoform and p70S6K. The existence of a PI3-K-dependent signalling complex may enable efficient activation of p70S6K in cells.

Sub-ballistic behavior in quantum systems with Lévy noise.

We investigate the quantum walk and the quantum kicked rotor in resonance subjected to noise with a Lévy waiting time distribution. We find that both systems have a sub-ballistic wave function spreading as shown by a power-law tail of the standard deviation.

[ELF-MF occupational exposure: repeated measures on workers]. / Campi magnetici ELF ed esposizione professionale: misure ripetute della esposizione individuale in lavoratori addetti a varie mansioni.

The aim of our study was to estimate occupational exposure to Extremely Low Frequency-Magnetic Fields (ELF-MF). Using personal dosimeters we evaluated occupational exposure in 543 workers employed in 9 occupational settings (about 150 jobs), representative of the main occupational activities in Emilia-Romagna region. In the whole sample, the median Time-Weighted Average (TWA) exposure resulted 0.14 microT (5 degrees - 95 degrees percentiles: 0.04 - 2.50 microT); Tile production presented the highest occupational setting TWA (0.46 +/- 1.83 microT), while the lower job TWA was Stock Clerk in Tile Production and Stock Clerk in Garment Production. After 6-9 months we repeated measurement in about 10% of the original sample (about 48 subjects) to verify the resulted obtained. At repeated measurement analysis with SPSS 12.0 no variation was found compared the previous monitoring. Individual occupational exposure to ELF-MF evaluated in a relatively large group of workers engaged in the main occupational activities proved low values compared to the proposed occupational limit.

Clinical and endoscopic presentation of primary gastric lymphoma: a multicentre study.

BACKGROUND: Although the stomach is the most frequent site of intestinal lymphomas, few data are available on both clinical endoscopic presentation of gastric lymphoma and possible differences between low-grade and high-grade lymphomas. METHODS: Clinical, histological and endoscopic records of consecutive patients with primary low-grade or high-grade lymphoma diagnosed were retrieved. Symptoms were categorized as 'alarm' or 'not alarm'. The endoscopic findings were classified as 'normal' or 'abnormal'. RESULTS: Overall, 144 patients with primary gastric lymphoma were detected, including 74 low-grade and 70 high-grade lymphoma. Alarm symptoms, particularly persistent vomiting and weight loss, were more frequently present in patients with high-grade lymphoma than in those with low-grade lymphoma (54% vs. 28%; P = 0.002). Low-grade lymphomas presented as 'normal' appearing mucosa (20% vs. 0%; P = 0.0004) or petechial haemorrhage in the fundus (9% vs. 0%; P = 0.02) more frequently than high-grade lymphomas, being also more often confined to the antrum (47% vs. 27%, P = 0.03) and associated with Helicobacter pylori infection (88% vs. 52%, P < 0.0001). On the contrary, high-grade lymphomas presented more commonly as ulcerative type (70% vs. 52%; P = 0.03), being also more frequently diagnosed in stage >I when compared with low-grade lymphomas (70% vs. 21%, P < 0.0001). CONCLUSIONS: The overall prevalence of alarm symptoms is quite low and may be absent in more than 70% of patients with low-grade lymphoma.

A case of Smith-Lemli-Opitz Syndrome, defect of cholesterol biosynthesis.

We report the case of a child with Smith-Lemli-Opitz Syndrome. The pregnancy was complicated by prenatal growth retardation. The baby was admitted to the Neonatal Intensive Care Unit of Chieti when she was five months old. She showed postnatal growth retardation, trouble sucking and swallowing, microcephaly and multiple major and minor malformations, including characteristic facial features and 2-3 syndactyly of the toes. We found correlations between multiple congenital malformations, failure to thrive and low plasmatic cholesterol measurement.

Rett syndrome: a wide clinical and autonomic picture.

BACKGROUND: Rett Syndrome is a neurodevelopmental disorder almost exclusively affecting females, characterized by a broad clinical spectrum of signs and symptoms and a peculiar course. The disease affects different body systems: nervous, muscolo-skeletal, gastro-enteric. Moreover, part of the symptoms are related to the involvement of the autonomic nervous system. In the Tuscany Rett Center at Versilia Hospital, we collected data from 151 subjects with a clinical diagnosis of classical or variant RTT syndrome. For each subject, we assessed the severity of the condition with clinical-rating scales (ISS, PBZ), we quantified the performance of the autonomic nervous system, and we performed genetic analysis. We used multivariate statistical analysis of the data to evaluate the relation between the different clinical RTT forms, the cardiorespiratory phenotype, the different genetic mutations and the severity of the clinical picture. Individuals were classified according to existing forms: Classical RTT and three atypical RTT: Z-RTT, Hanefeld, Congenital. A correlation between C-Terminal deletions and lower severity of the clinical manifestations was evident, in the previous literature, but, considering the analysis of autonomic behaviour, the original classification can be enriched with a more accurate subdivision of Rett subgroups, which may be useful for early diagnosis. RESULTS: Present data emphasize some differences, not entirely described in the literature, among RTT variants. In our cohort the Z-RTT variant cases show clinical features (communication, growth, epilepsy and development), well documented by specific ISS items, less severe, if compared to classical RTT and show autonomic disorders, previously not reported in the literature. In this form epilepsy is rarely present. In contrast, Hanefeld variant shows the constant presence of epilepsy which has an earlier onset In Hanefeld variant the frequency of apneas was rare and, among the cardiorespiratory phenotypes, the feeble type is lacking. CONCLUSION: A quantitative analysis of the different autonomic components reveals differences across typical and atypical forms of RTT that leads to a more accurate classification of the groups. In our cohort of RTT individuals, the inclusion of autonomic parameter in the classification leads to an improved diagnosis at earlier stages of development.