Time-Dependent Changes in Muscle IGF1-IGFBP5-PAPP System after Sciatic Denervation.

Denervation-induced muscle atrophy is a frequent cause of skeletal muscle diseases. However, the role of the most important muscle growth factor, insulin-like growth factor (IGF-1), in this process is poorly understood. IGF-1 activity is controlled by six IGF-1 binding proteins (IGFBPs). In skeletal muscle, IGFBP-5 seems to have an important role in atrophic processes. Furthermore, pappalysins (PAPP-A) modulate muscle growth by increasing IGF-1 bioavailability through IGFBP cleavage. We aimed to study the time-dependent changes in the IGF1-IGFBP5-PAPP system and its regulators in gastrocnemius muscle after sciatic denervation. Gastrocnemius atrophy and overexpression of IGF-1 was observed from day 3 post-denervation. The proteolytic factors measured were elevated from day 1 post-denervation onwards. Expression of both IGFBP-5 and pappalysins were increased on days 1 and 3. Subsequently, on days 7 to 14 pappalysins returned to control levels while IGFBP-5 remained elevated. The ratio IGFBP-5/PAPP-A was correlated with the main proteolytic markers. All data suggest that the initial increase of pappalysins could facilitate the IGF-1 action on muscle growth, whereas their subsequent decrease could lead to further muscle wasting.

Pelvic floor rehabilitation for defecation disorders.

Pelvic floor rehabilitation is frequently recommended for defecation disorders, in both constipation and fecal incontinence. However, the lack of patient selection, together with the variety of rehabilitation methods and protocols, often jeopardize the results of this approach, causing difficulty in evaluating outcomes and addressing proper management, and above all, in obtaining scientific evidence for the efficacy of these methods for specific indications. The authors represent different gastroenterological and surgical scientific societies in Italy, and their aim was to identify the indications and agree on treatment protocols for pelvic floor rehabilitation of patients with defecation disorders. This was achieved by means of a modified Delphi method, utilizing a working team (10 members) which developed the statements and a consensus group (15 members, different from the previous ones) which voted twice also suggesting modifications of the statements.

Ostreid herpesvirus type 1 genomic diversity in wild populations of Pacific oyster Crassostrea gigas from Italian coasts.

Ostreid herpesvirus 1 (OsHV-1) is a significant pathogen affecting the young Pacific oyster Crassostrea gigas, worldwide. A new variant, OsHV-1 µVar, has been associated with recurrent mortality events in Europe since 2008. Epidemiological data collection is key for global risk assessment; however little is known about health status and genotypes present in European wild oyster beds. Most studies to date have involved only cultivated individuals during mortality events, and reported low genotype diversity. With this study, conducted along the Italian coasts, we investigated for the first time the presence of OsHV-1 in European natural oyster beds. Analysis of three genomic regions revealed the presence of at least nine different genotypes, including two variants close to the OsHV-1 reference, known since the early 1990s but with no European record reported since 2010, and highlights relevant genotype diversity in natural environment. Phylogenetic analysis distinguished two distinct clusters and geographical distribution of genotypes, with the exception of a variant very closely related to the µVar, which appeared the single genotype present in all the Adriatic sites. Interestingly, these wild symptom free populations could represent, in Europe, an accessible alternative to the import of OsHV-1-resistant oyster strains from the East Pacific, the native area of C. gigas, avoiding the high-risk of non-native marine species and new pathogen introductions.

Drinking and swimming around waterways: The role of alcohol, sensation-seeking, peer influence and risk in young people.

The role of individual and sociocultural factors contributing to drowning risk for young adults is complex and poorly understood. This study examined the relationship between behaviour in and around waterways and: 1) alcohol consumption; 2) resistance to peer influence; 3) sensation-seeking; 4) perception of risk among people aged 15-24 in Western Australia. A cross-sectional online survey was conducted at three time-points with a convenience sample. Predictor variables included: Alcohol Use Disorder Identification Test Consumption (AUDIT_C); Resistance to Peer Influence; Brief Sensation Seeking scale; Benthin's Perception of risk. Pearson chi-squared tests determined the association between demographic and predictor variables. Logistic regression explored influence of potential predictor variables on behaviour in and around water. The final sample (n = 730) participants, consisted of females (n = 537, 74.5%), metropolitan dwelling (n = 616, 84.4%), and attended university (n = 410, 56.9%). Significant associations were found for those who swum after drinking alcohol compared with those that had not by age, gender, education. For every 1-unit increase in AUDIT-C participants were 60% more likely to swim after drinking (OR 95% CI 1.60 1.44-1.78). Participants who considered an adverse event serious were 15% less likely to have swum after drinking alcohol (OR 0.85 95% CI 0.73-0.99). The complex relationship between social participation in activities in and around waterways, higher drowning rates, propensity for risk, and the meaning young adults attach to risk locations and practices present unique challenges for drowning prevention research. Findings should be used to improve the awareness and education components of future youth water safety strategies in high-income settings.

Avoidance behaviour and anxiety in rats irradiated with a sublethal dose of gamma-rays.

The aim of this study was to assess, whether a sublethal dose of gamma-rays will influence the avoidance behaviour and anxiety in rats and whether the response to radiation depends on time of day of its application. Adult male Wistar rats were tested in elevated plus-maze, in hot plate test and in the light/dark box in 4 regular intervals during a day. After two weeks the animals were irradiated with a whole-body dose 6 Gy of gamma-rays. One day after irradiation the animals were repeatedly tested in the same way, as before irradiation. In the plus-maze test an increased level of anxiety was established. The irradiation significantly decreased the locomotor activity of rats, but the extent of exploratory and comfortable behaviour were not altered. After irradiation, an elevated aversion to the thermal stimulus was observed in the hot plate test. The effects of radiation were more pronounced in the light period of the day, than in the dark one. No significant differences in aversion to light were detected after irradiation. The obtained results indicate, that sublethal doses of ionizing radiation can markedly influence the reactivity of animals to adverse stimuli, their motoric activity and emotional status, as well.

[Biogenic amines in epigeal spontaneous mushrooms: indicators of quality and freshness?]. / Ammine biogene in funghi epigei spontanei: possibili indi- catori di qualità e freschezza?

Purpose of the present study is to determine the qualitative and quantitative composition of nine biogenic amines (BA) in 153 samples of epigeal spontaneous mushrooms (Boletus edulis and Amanita Caesarea), sampled at large and small food retail shops in the Florence area. Each BA has been identified and quantified using a liquid chromatography system with a reversed phase, C18 column and post-column derivatization with o-oftalaldeide. The results have shown a widespread presence of each amine, although with varying frequency and concentration, and an increasing concentration of tyramine and putrescine in samples with poor organoleptic quality than those in good conditions.

Measurement of D{0}-D[-over]{0} mixing from a time-dependent amplitude analysis of D{0}-->K+pi{-}pi{0} decays.

We present evidence of D{0}-D[-over ]{0} mixing using a time-dependent amplitude analysis of the decay D{0}-->K+pi{-}pi;{0} in a data sample of 384 fb{-1} collected with the BABAR detector at the PEP-II e+e{-} collider at the Stanford Linear Accelerator Center. Assuming CP conservation, we measure the mixing parameters x{Kpipi{0}}{'}=[2.61{-0.68}{+0.57}(stat)+/-0.39(syst)]%, y{Kpipi;{0}}{'}=[-0.06{-0.64}{+0.55}(stat)+/-0.34(syst)]%. This result is inconsistent with the no-mixing hypothesis with a significance of 3.2 standard deviations. We find no evidence of CP violation in mixing.

Evidence for the eta(b)(1S) meson in radiative Upsilon(2S) decay.

We have performed a search for the eta_{b}(1S) meson in the radiative decay of the Upsilon(2S) resonance using a sample of 91.6x10(6) Upsilon(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at Egamma=609.3(-4.5)(+4.6)(stat)+/-1.9(syst) MeV, corresponding to an eta(b)(1S) mass of 9394.2(-4.9)(+4.8)(stat)+/-2.0(syst) MeV/c2. The branching fraction for the decay Upsilon(2S)-->gamma(eta)b(1S) is determined to be [3.9+/-1.1(stat)-0.9+1.1(syst)]x10(-4). We find the ratio of branching fractions B[Upsilon(2S)-->gamma(eta)b(1S)]/B[Upsilon(3S)-->gamma(eta)b(1S)]=0.82+/-0.24(stat)(-0.19)(+0.20)(syst).

MHC class II molecules: transport pathways for antigen presentation.

During biosynthesis, MHC class II molecules travel through the endocytic pathway and interact with antigenic peptides before their stable insertion in the plasma membrane. The process of class II association with these peptides and their final deposition at the cell surface are essential steps in boosting specific antibody responses. Therefore, the study of class II molecules is important in understanding how cell-biological events can direct an immune response.

Intestinal cell migration damage induced by enteropathogenic Escherichia coli strains.

Epithelial cell migration is an essential response to enteric pathogens such as enteropathogenic Escherichia coli (EPEC). This study aimed to investigate the effects of EPEC infection on intestinal epithelial cell migration in vitro, as well as the involvement of type III secretion system (T3SS) and Rho GTPases. Crypt intestinal epithelial cells (IEC-6) were infected with EPEC strains (E2348/69, ΔescF, and the LDI001 strain isolated from a malnourished Brazilian child) and commensal E. coli HS. Wound migration and cell death assays were performed at different time-points. Transcription and expression of Rho GTPases were evaluated using real-time PCR and western blotting. Overall, EPEC E2348/69 reduced migration and increased apoptosis and necrosis levels compared to EPEC LDI001 and E. coli HS strains. Moreover, EPEC LDI001 impaired cell migration at a higher level than E. coli HS and increased necrosis after 24 hours compared to the control group. The different profiles of virulence genes between the two wild-type EPEC strains, characterized by the absence of espL and nleE genes in the LDI001, might explain the phenotypic results, playing significant roles on cell migration impairment and cell death-related events. Moreover, the type III secretion system is determinant for the inhibition of intestinal epithelial cell migration by EPEC 2348/69, as its deletion prevented the effect. Active Rac1 concentrations were increased in E2348/69 and LDI001-infected cells, while the T3SS-deficient strain did not demonstrate this activation. This study contributes with valuable insight to characterize the mechanisms involved in the impairment of intestinal cell migration induced by EPEC.

Search for the rare decay B-->pil+ l-.

We have performed a search for the flavor-changing neutral-current decays B-->pil+ l-, where l+ l- is either e+ e- or mu+ mu-, using a sample of 230 x 10(6) Upsilon(4S)-->BB decays collected with the BABAR detector. We observe no evidence of a signal and measure the upper limit on the isospin-averaged branching fraction to be B(B-->pil+ l-)<9.1 x 10(-8) at 90% confidence level. We also search for the lepton-flavor-violating decays B-->pie+/- mu-/+ and measure an upper limit on the isospin-averaged branching fraction of B(B-->pie+/- mu-/+)<9.2 x 10(-8) at 90% confidence level.

A cost-effectiveness analysis of artemether lumefantrine for treatment of uncomplicated malaria in Zambia.

BACKGROUND: Malaria remains a leading cause of morbidity, mortality and non-fatal disability in Zambia, especially among children, pregnant women and the poor. Data gathered by the National Malaria Control Centre has shown that recently observed widespread treatment failure of SP and chloroquine precipitated a surge in malaria-related morbidity and mortality. As a result, the Government has recently replaced chloroquine and SP with combination therapy as first-line treatment for malaria. Despite the acclaimed therapeutic advantages of ACTs over monotherapies with SP and CQ, the cost of ACTs is much greater, raising concerns about affordability in many poor countries such as Zambia. This study evaluates the cost-effectiveness analysis of artemether-lumefantrine, a version of ACTs adopted in Zambia in mid 2004. METHODS: Using data gathered from patients presenting at public health facilities with suspected malaria, the costs and effects of using ACTs versus SP as first-line treatment for malaria were estimated. The study was conducted in six district sites. Treatment success and reduction in demand for second line treatment constituted the main effectiveness outcomes. The study gathered data on the efficacy of, and compliance to, AL and SP treatment from a random sample of patients. Costs are based on estimated drug, labour, operational and capital inputs. Drug costs were based on dosages and unit prices provided by the Ministry of Health and the manufacturer (Norvatis). FINDINGS: The results suggest that AL produces successful treatment at less cost than SP, implying that AL is more cost-effective. While it is acknowledged that implementing national ACT program will require considerable resources, the study demonstrates that the health gains (treatment success) from every dollar spent are significantly greater if AL is used rather than SP. The incremental cost-effectiveness ratio is estimated to be 4.10 US dollars. When the costs of second line treatment are considered the ICER of AL becomes negative, indicating that there are greater resource savings associated with AL in terms of reduction of costs of complicated malaria treatment. CONCLUSION: This study suggests the decision to adopt AL is justifiable on both economic and public health grounds.

Cloning of the complete gene for carcinoembryonic antigen: analysis of its promoter indicates a region conveying cell type-specific expression.

Carcinoembryonic antigen (CEA) is a widely used tumor marker, especially in the surveillance of colonic cancer patients. Although CEA is also present in some normal tissues, it is apparently expressed at higher levels in tumorous tissues than in corresponding normal tissues. As a first step toward analyzing the regulation of expression of CEA at the transcriptional level, we have isolated and characterized a cosmid clone (cosCEA1), which contains the entire coding region of the CEA gene. A close correlation exists between the exon and deduced immunoglobulin-like domain borders. We have determined a cluster of transcriptional starts for CEA and the closely related nonspecific cross-reacting antigen (NCA) gene and have sequenced their putative promoters. Regions of sequence homology are found as far as approximately 500 nucleotides upstream from the translational starts of these genes, but farther upstream they diverge completely. In both cases we were unable to find classic TATA or CAAT boxes at their expected positions. To characterize the CEA and NCA promoters, we carried out transient transfection assays with promoter-indicator gene constructs in the CEA-producing adenocarcinoma cell line SW403, as well as in nonproducing HeLa cells. A CEA gene promoter construct, containing approximately 400 nucleotides upstream from the translational start, showed nine times higher activity in the SW403 than in the HeLa cell line. This indicates that cis-acting sequences which convey cell type-specific expression of the CEA gene are contained within this region.

The concept of quality of life in organ transplantation.

The goal of organ transplantation is not only to ensure the survival of individuals with end-stage heart, lung, liver, kidney, pancreas, and small bowel diseases, but also to offer patients the health they enjoyed before the disease, achieving a good balance between the functional efficacy of the graft and the patient's psychological and physical integrity. Quality of life (QoL) assessments are used to evaluate the physical, psychological, and social domains of health, seen as distinct areas that are influenced by a person's experiences, beliefs, expectations, and perceptions, and QoL is emerging as a new medical indicator in transplantation medicine too.

Unburnt carbon from coal fly ashes as a precursor of activated carbon for nitric oxide removal.

The aim of this work is to evaluate the characteristics of an activated carbon obtained from unburnt carbon in coal fly ashes to be used in the removal of NO. Carbon-rich fraction was obtained by mechanical sieving of fly ashes. The mineral matter was removed by conventional HCl and HF demineralization procedure. Activation was carried out with steam at 900 degrees C in order to develop porosity onto the sample. Characterization of samples was performed by several techniques with a main objective: to follow the mineral matter content, composition and distribution on the samples in order to better understand how to remove it from unburnt carbon in fly ashes. To study the use of this unburnt carbon as a precursor for the preparation of activated carbons for gas cleaning, the NO removal by ammonia using activated carbon as a catalyst at low temperature was performed. Results show a good performance of activated carbon in this reaction that is in relationship with BET surface area.

Melanocortin-4 receptor agonist (RO27-3225) ameliorates soleus but not gastrocnemius atrophy in arthritic rats.

Adjuvant-induced arthritis in rats decreases body weight and muscle mass. Melanocyte stimulating hormone administration to arthritic rats decreases inflammation and skeletal muscle wasting. In this study, we investigate whether activation of melanocortin-4 receptor by RO27-3225 administration is able to prevent the effect of arthritis on the expression of muscle-specific E3 ubiquitin ligases and MyoD in two different muscles, gastrocnemius (a mainly fast type muscle) and soleus (slow type). Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected with RO27-3225 (180 µg/kg i.p. twice a day) or saline, for 8 days. Body weight change, food intake and arthritis index were assessed daily. After sacrifice, serum insulin-like growth factor -1 (IGF-1) and corticosterone, as well as nuclear factor-κB(p65), cyclooxygenase-2 (COX-2), atrogene and MyoD in gastrocnemius and soleus were analysed. Administration of RO27-3225 to arthritic rats decreased arthritis scores, hind paw volume as well as nuclear factor-κB(p65) phosphorylation in gastrocnemius and soleus. However, RO27-3225 was not able to modify the effects of arthritis on serum IGF-1 and corticosterone. RO27-3225 ameliorates arthritis-induced decrease in food intake, body weight gain, epidydimal white adipose tissue and soleus weight, but not in gastrocnemius weight. Arthritis increased COX-2, atrogin-1 and MuRF1 expression in gastrocnemius and soleus, whereas RO27-3225 prevented this increase in soleus but not in gastrocnemius. Arthritis also increased MyoD expression in gastrocnemius and soleus (P < 0.01). RO27-3225 decreased MyoD expression in gastrocnemius but not in soleus of arthritic rats. In control rats RO27-3225 did not modify MyoD expression in gastrocnemius or soleus. In conclusion, our data suggest that in arthritic rats, RO27-3225 treatment decreases inflammation and muscle atrophy, preventing atrogene upregulation in slow type muscle but not in gastrocnemius. The lack of effect in the gastrocnemius can be related to the inability of RO27-3225 to prevent arthritis-induced corticosterone upregulation as well as IGF-1 downregulation.

Capsule endoscopy findings in patients with suspected Crohn's disease and biochemical markers of inflammation.

BACKGROUND: Because it provides a direct view of superficial lesions in the small bowel, capsule endoscopy is a promising diagnostic tool for studying patients with suspected Crohn's disease undetected by conventional modalities. AIM: To assess the role of capsule endoscopy in the diagnosis of patients with suspected Crohn's disease. PATIENTS AND METHODS: Thirty-eight patients (16 males, mean age 46.2 years) with suspected Crohn's disease but negative at conventional imaging were examined using capsule endoscopy. They were divided into 2 groups: 12 patients with ongoing symptoms (Group 1), and 26 with ongoing symptoms and biochemical markers of inflammation (Group 2). Capsule endoscopy findings were classified as diagnostic (multiple erosions/ulcerations), suspicious (

Costing of Paediatric Treatment alongside Clinical Trials under Low Resource Constraint Environments: Cotrimoxazole and Antiretroviral Medications in Children Living with HIV/AIDS.

Introduction. Costing evidence is essential for policy makers for priority setting and resource allocation. It is in this context that the clinical trials of ARVs and cotrimoxazole provided a costing component to provide evidence for budgeting and resource needs alongside the clinical efficacy studies. Methods. A micro based costing approach was adopted, using case record forms for maintaining patient records. Costs for fixed assets were allocated based on the paediatric space. Medication and other resource costs were costed using the WHO/MSH Drug Price Indicators as well as procurement data where these were available. Results. The costs for cotrimoxazole and ARVs are significantly different. The average costs for human resources were US$22 and US$71 for physician costs and $1.3 and $16 for nursing costs while in-patient costs were $257 and $15 for the cotrimoxazole and ARV cohorts, respectively. Mean or average costs were $870 for the cotrimoxazole cohort and $218 for the ARV. The causal factors for the significant cost differences are attributable to the higher human resource time, higher infections of opportunistic conditions, and longer and higher frequency of hospitalisations, among others.

Spectral and catalytic properties of cytochrome oxidase in organic solvents.

Isolated bovine heart cytochrome oxidase has been extracted into n-hexane, probably in reverse micelles, by the use of asolectin and calcium. The diluted extracts are composed of particles with the hydrodynamic radius of 42 nm. Spectral characteristics of the extracted oxidase are similar to those in aqueous solutions. At the high molar ratio of water to phospholipid (W0 = 8) in an organic solvent both cytochrome a and a3 are reducible and oxygen uptake is observed. However, at low W0 (W0 = 1.8) the rate of cytochrome a reduction is decreased and reduction of cytochrome a3 is inhibited.

Spectrophotometric detection of the interaction between cytochrome c and heparin.

Heparin inhibits transport of electrons from reduced cytochrome c to cytochrome c oxidase. The effect is due to the interaction of heparin with cytochrome c. It has been observed that binding of heparin to the reduced or oxidized cytochrome c changes the spectrum of cytochrome c at the Soret region. Affinity chromatography of heparin in cytochrome c immobilized to thiol-Sepharose shows that commercial heparin is eluted in the low-affinity and high-affinity fractions. Both participate in the interaction with cytochrome c. Polylysine induces decay of the cytochrome c-heparin complex.