IFNγ-dependent silencing of TFF1 during Helicobacter pylori infection.

Chronic Helicobacter pylori infection is the leading cause of intestinal-type adenocarcinoma, as prolonged Helicobacter colonization triggers chronic active gastritis, which may evolve into adenocarcinoma of the intestinal type. In this environment, cytokines play a significant role in determining the evolution of the infection. In combination with other factors (genetic, environmental and nutritional), the pro-inflammatory response may trigger pro-oncogenic mechanisms that lead to the silencing of tumour-suppressor genes, such as trefoil factor 1 (TFF1). The latter is known to play a protective role by maintaining the gastric mucosa integrity and retaining H. pylori in the mucus layer, preventing the progression of infection and, consequently, the development of gastric cancer (GC). Since TFF1 expression is reduced during chronic Helicobacter infection with a loss of gastric mucosa protection, we investigated the molecular pathways involved in this reduction. Specifically, we evaluated the effect of some pro-inflammatory cytokines on TFF1 regulation in GC and primary gastric cells by RT-qPCR and luciferase reporter assay analyses and the repressor role of the transcription factor C/EBPß, overexpressed in gastric-intestinal cancer. Our results show that, among several cytokines, IFNγ stimulates C/EBPß expression, which acts as a negative regulator of TFF1 by binding its promoter at three different sites.

A combined system for asbestos-cement waste degradation by dark fermentation and resulting supernatant valorization in anaerobic digestion.

The use of biological processes for the treatment of asbestos cement waste (ACW) has gained interest in recent years. Nevertheless, this methodology is not yet consolidated because of the incomplete ACW conversion during the biological treatment and the consequent need for further treatments that generally require a high amount of energy and chemicals. In this study, the efficiency of both mesophilic and thermophilic dark fermentation (DF) fed with glucose in fed-batch conditions was assessed for ACW biological treatment. Both thermophilic and mesophilic DF of glucose resulted in a partial conversion of glucose into organic acids that successfully degraded all the asbestos fibers contained in an ACW sample. A hydrogen-rich biogas was produced as well: at the end of the mesophilic DF treatment 0.14 LH2 gglucose-1 were obtained. In addition, the anaerobic digestion (AD) of the DF supernatants led to the production of 0.38 LCH4 gCOD-1.

An online Sexual Health and Rehabilitation eClinic (TrueNTH SHAReClinic) for prostate cancer patients: a feasibility study.

PURPOSE: The primary objective was to determine the feasibility of implementing the TrueNTH SHAReClinic as a pan-Canadian sexual health and rehabilitation intervention for patients treated for localized prostate cancer. METHODS: The feasibility study was designed to evaluate the accessibility and acceptability of the intervention. Participants from five institutions across Canada were enrolled to attend one pre-treatment and five follow-up online clinic visits over 1 year following their prostate cancer (PC) treatment. RESULTS: Sixty-five patients were enrolled in the intervention. Website analytics revealed that 71% completed the intervention in its entirety, including the educational modules, with an additional 10% completing more than half of the intervention. Five thousand eighty-three views of the educational modules were made along with 654 views of the health library items. Over 1500 messages were exchanged between participants and their sexual health coaches. At 12 months, the intervention received an overall average participant rating of 4.1 out of 5 on a single item satisfaction measure. CONCLUSION: Results support the TrueNTH SHAReClinic as highly acceptable to participants as defined by intervention adherence and engagement. The TrueNTH SHAReClinic demonstrated promise for being a feasible and potentially resource-efficient approach to effectively improving the sexual well-being of patients after PC treatment.

Automated finite element meshing of the lumbar spine: Verification and validation with 18 specimen-specific models.

The purpose of this study was to seek broad verification and validation of human lumbar spine finite element models created using a previously published automated algorithm. The automated algorithm takes segmented CT scans of lumbar vertebrae, automatically identifies important landmarks and contact surfaces, and creates a finite element model. Mesh convergence was evaluated by examining changes in key output variables in response to mesh density. Semi-direct validation was performed by comparing experimental results for a single specimen to the automated finite element model results for that specimen with calibrated material properties from a prior study. Indirect validation was based on a comparison of results from automated finite element models of 18 individual specimens, all using one set of generalized material properties, to a range of data from the literature. A total of 216 simulations were run and compared to 186 experimental data ranges in all six primary bending modes up to 7.8Nm with follower loads up to 1000N. Mesh convergence results showed less than a 5% difference in key variables when the original mesh density was doubled. The semi-direct validation results showed that the automated method produced results comparable to manual finite element modeling methods. The indirect validation results showed a wide range of outcomes due to variations in the geometry alone. The studies showed that the automated models can be used to reliably evaluate lumbar spine biomechanics, specifically within our intended context of use: in pure bending modes, under relatively low non-injurious simulated in vivo loads, to predict torque rotation response, disc pressures, and facet forces.

Automated finite element modeling of the lumbar spine: Using a statistical shape model to generate a virtual population of models.

Population-based modeling of the lumbar spine has the potential to be a powerful clinical tool. However, developing a fully parameterized model of the lumbar spine with accurate geometry has remained a challenge. The current study used automated methods for landmark identification to create a statistical shape model of the lumbar spine. The shape model was evaluated using compactness, generalization ability, and specificity. The primary shape modes were analyzed visually, quantitatively, and biomechanically. The biomechanical analysis was performed by using the statistical shape model with an automated method for finite element model generation to create a fully parameterized finite element model of the lumbar spine. Functional finite element models of the mean shape and the extreme shapes (±3 standard deviations) of all 17 shape modes were created demonstrating the robust nature of the methods. This study represents an advancement in finite element modeling of the lumbar spine and will allow population-based modeling in the future.

Enablers and barriers in delivery of a cancer exercise program: the Canadian experience.

BACKGROUND: Exercise is an important therapy to improve well-being after a cancer diagnosis. Accordingly, cancer-exercise programs have been developed to enhance clinical care; however, few programs exist in Canada. Expansion of cancer-exercise programming depends on an understanding of the process of program implementation, as well as enablers and barriers to program success. Gaining knowledge from current professionals in cancer-exercise programs could serve to facilitate the necessary understanding. METHODS: Key personnel from Canadian cancer-exercise programs (n = 14) participated in semistructured interviews about program development and delivery. RESULTS: Content analysis revealed 13 categories and 15 subcategories, which were grouped by three organizing domains: Program Implementation, Program Enablers, and Program Barriers. ■ Program Implementation (5 categories, 8 subcategories) included Program Initiation (clinical care extension, research project expansion, program champion), Funding, Participant Intake (avenues of awareness, health and safety assessment), Active Programming (monitoring patient exercise progress, health care practitioner involvement, program composition), and Discharge and Follow-up Plan.■ Program Enablers (4 categories, 4 subcategories) included Patient Participation (personalized care, supportive network, personal control, awareness of benefits), Partnerships, Advocacy and Support, and Program Characteristics.■ Program Barriers (4 categories, 3 subcategories) included Lack of Funding, Lack of Physician Support, Deterrents to Participation (fear and shame, program location, competing interests), and Disease Progression and Treatment. CONCLUSIONS: Interview results provided insight into the development and delivery of cancer-exercise programs in Canada and could be used to guide future program development and expansion in Canada.

Risk perception and psychological morbidity in men at elevated risk for prostate cancer.

OBJECTIVE: As prostate-specific antigen (psa) makes prostate cancer (pca) screening more accessible, more men are being identified with conditions that indicate high risk for developing pca, such as elevated psa and high-grade intraepithelial neoplasia (hgpin). In the present study, we assessed psychological well-being and risk perception in individuals with those high-risk conditions. METHODS: A questionnaire consisting of a psychological symptom survey, a trait risk-aversion survey, and a cancer-specific risk perception survey was administered to 168 patients with early-stage localized pca and 69 patients at high risk for pca (n = 16 hgpin, n = 53 psa > 4 ng/mL). Analysis of variance was used to examine differences in psychological well-being and appraisal of risk between the groups. RESULTS: Compared with the pca group, the high-risk group perceived their risk of dying from something other than pca to be significantly lower (p = 0.007). However, pca patients reported significantly more clinically important psychological symptoms. CONCLUSIONS: The identification of prostate conditions that predict progression to cancer might not result in the psychological symptoms commonly experienced by pca patients, but does appear to be related to a distorted perception of the disease's mortal risk. Patients with pca experience reduced psychological well-being, but better understand the risks of pca recurrence and death. Education on the risks and outcomes of pca can help at-risk men to view health assessments with reduced worry.

Western blot expression of 5-lipoxygenase in the brain from striped dolphins (stenella coeruleoalba) and bottlenose dolphins (tursiops truncatus) with or without encephalitis/meningo-encephalitis of infectious nature.

Dolphin Morbillivirus (DMV), Toxoplasma gondii and Brucella ceti are pathogens of major concern for wild cetaceans. Although a more or less severe encephalitis/meningo-encephalitis may occur in striped dolphins (Stenella coeruleoalba) and bottlenose dolphins (Tursiops truncatus) infected by the aforementioned agents, almost no information is available on the neuropathogenesis of brain lesions, including the neuronal and non-neuronal cells targeted during infection, along with the mechanisms underlying neurodegeneration. We analyzed 5-lipoxygenase (5-LOX) expression in the brain of 11 striped dolphins and 5 bottlenose dolphins, affected or not by encephalitic lesions of various degrees associated with DMV, T. gondii and B. ceti. All the 8 striped dolphins with encephalitis showed a more consistent 5-LOX expression than that observed in the 3 striped dolphins showing no morphologic evidence of brain lesions, with the most prominent band intensity being detected in a B. ceti-infected animal. Similar results were not obtained in T. gondii-infected vs T. gondii-uninfected bottlenose dolphins. Overall, the higher 5-LOX expression found in the brain of the 8 striped dolphins with infectious neuroinflammation is of interest, given that 5-LOX is a putative marker for neurodegeneration in human patients and in experimental animal models. Therefore, further investigation on this challenging issue is also needed in stranded cetaceans affected by central neuropathies.

Histone deacetylase inhibitors in the treatment of hematological malignancies.

Histone deacetylases (HDACs) play a central role in the epigenetic regulation of gene expression. Aberrant activity of HDACs has been found in several human cancers leading to the development of HDAC inhibitors (HDACi) as anti-tumors drugs. In fact, over the last years, a number of HDACi have been evaluated in clinical trials; these drugs have the common ability to hyperacetylate both histone and non-histone targets, resulting in a variety of effects on both cancer cells and immune responses. Clinical trials of HDACi conducted in solid tumors and hematological malignancies have shown a better clinical efficacy of these drugs in hematological malignancies. In this review, will be highlighted the mechanisms of action underlying the clinical responses obtained with these drugs and the doubts regarding the use of HDACi in cancer therapy.

Alterations of hepatic ATP homeostasis and respiratory chain during development of non-alcoholic steatohepatitis in a rodent model.

BACKGROUND: Mitochondrial dysfunction is considered a key player in non-alcoholic steatohepatitis (NASH) but no data are available on the mitochondrial function and ATP homeostasis in the liver during NASH progression. In the present paper we evaluated the hepatic mitochondrial respiratory chain activity and ATP synthesis in a rodent model of NASH development. MATERIALS AND METHODS: Male Wistar rats fed a High Fat/Methionine-Choline Deficient (MCD) diet to induce NASH or a control diet (SHAM), and sacrificed after 3, 7 and 11 weeks. The oxidative phosphorylation, the F(0)F(1)ATPase (ATP synthase) and the ATP content were assessed in liver mitochondria. RESULTS: NASH mitochondria exhibited an increased rate of substrate oxidation at 3 weeks, which returned to below the normal level at 7 and 11 weeks, concomitantly with the coupling between the phosphorylation activity and the mitochondrial respiration (ADP/O). Uncoupling of NASH liver mitochondria did not allow the recovery of the maximal respiration rate at 7 and 11 weeks. The ATPase (ATP synthase) activity was similar in NASH and SHAM rats, but the mitochondrial ATP content was significantly lower in NASH livers. CONCLUSIONS: The loss of hepatic ATP stores is not dependent on the F(0)F(1)-ATPase but resides in the respiratory chain. Dysfunction of both Complex I and II of the mitochondrial respiratory chain during NASH development implies a mitochondrial adaptive mechanism occurring in the early stages of NASH.

The activity of hsp90 alpha promoter is regulated by NF-kappa B transcription factors.

Heat-shock proteins (HSP) 90 exert a relevant role in the survival and response to therapy of many neoplastic cell types. Here, we show that the promoter of hsp90alpha gene, that encodes the inducible form of HSP90, is regulated by nuclear factor-kappaB (NF-kappaB) activity. Indeed, we found that NF-kappaB factors bound to one of the two putative consensus sequences present in the hsp90alpha-flanking region; mutation of such motif hampered the phorbol-myristate-13-acetate-stimulated expression of a luciferase reporter gene under the control of the hsp90alpha promoter. Furthermore, the downmodulation of NF-kappaB (p65) levels by a specific small interfering (si) RNA resulted in reducing the levels of endogenous HSP90alpha protein. These findings disclose a previously unrecognized mechanism that contributes to connect NF-kappaB factors and HSPs in cell defence machinery.

[Prevalence of symptoms of sleep apnea syndrome. Study of a French middle-aged population]. / Prévalence des symptômes du syndrome d'apnées du sommeil. Etude dans une population française d'âge moyen.

OBJECTIVE: To study the prevalence of symptoms of sleep apnoea syndrome (SAS) in a large French middle-aged population and to establish what proportion have symptoms that justify further investigation with a sleep study. METHODS: We performed a cross-sectional study of 2,195 men and 2,247 women, 33 to 69 year old (DESIR. cohort) recording responses to a self-administered "sleep" questionnaire and a general questionnaire including socio-economic characteristics and lifestyle factors. RESULTS: The prevalence of symptoms in men and women were respectively: snoring frequently (28%, 14%), frequent daytime sleepiness (14%, 18%) and frequent apnoeas (5%, 2%). Overall, 8.5% of men and 6.3% of women reported a pattern of symptoms suggestive of OSA, as they snored and had daytime sleepiness and/or apnoeas. This pattern was associated, for both sexes, with age, body mass index and after adjustment on these two factors, to a mediocre self-reported health status and treatment with benzodiazepines or other sedatives. For men only, the OSA pattern of symptoms was also associated with, hypertension, alcohol consumption and smoking. CONCLUSION: Snoring, daytime hypersomnolence and witnessed apnoeas are symptoms frequently observed in the general population. Subjects with a combination of these abnormalities suggesting a high probability of sleep apnoea syndrome and in whom a sleep study is warranted represent 7.5% of the adult population.

Annexin-1 downregulation in thyroid cancer correlates to the degree of tumor differentiation.

We investigated the expression of annexin-1 (ANXA1) in thyroid carcinoma cell lines and in thyroid cancers with a different degree of differentiation. The highest level of ANXA1 expression examined by Western blotting was detected in the papillary carcinoma cells (NPA) and in the follicular cells (WRO). On the other hand, the most undifferentiated thyroid carcinoma cells (ARO and FRO) presented the lowest level of ANXA1 expression. In surgical tissue specimens from 32 patients with thyroid cancers, we found high immunoreactivity for ANXA1 in papillary (PTC) and follicular (FTC) thyroid cancers while in undifferentiated thyroid cancers (UTC) the expression of the protein was barely detectable. Control thyroid tissue resulted positive for ANXA1. In summary, 70% of UTC examined weakly expressed ANXA1, whereas 65% of PTC or FTC specimens tested showed high expression of the protein. Thus ANXA1 expression may correlate with the tumorigenesis suggesting that the protein may represent an effective differentiation marker in thyroid cancer.

Prescreening tools for diabetes and obesity-associated dyslipidaemia: comparing BMI, waist and waist hip ratio. The D.E.S.I.R. Study.

OBJECTIVE: To compare the sensitivities of BMI, waist circumference and waist hip ratio (WHR) in identifying subjects who should be screened for diabetes and/or for obesity-associated dyslipidaemia. DESIGN: Cross-sectional study. SETTING: Central-western France. PARTICIPANTS: More than 3000 men and women, aged 40-64 years, from the French study: data from an epidemiological study on the insulin resistance syndrome (D.E.S.I.R.). MAIN OUTCOME MEASURES: Sensitivity and specificity for screened diabetes (fasting plasma glucose>or=7.0 mmol/l) and screened dyslipidaemia (triglycerides>or=2.3 mmol/l and/or HDL-cholesterol <0.9/1.1 mmol/l (men/women)) according to BMI, waist circumference and WHR. RESULTS: Sensitivities increased as more corpulent subjects were screened, but they increased slowly after screening the top 30%: body mass index (BMI)>or=27/26 kg/m(2) (men/women) or waist >or=96/83 cm or WHR>or=0.96/0.83. These values were chosen as thresholds. In men, BMI had a nonsignificantly higher sensitivity than waist or WHR for both diabetes and dyslipidaemia (77 vs 74 and 66% P<0.3, 0.09; 56 vs 54 and 49% P<0.5, 0.16). For women, waist had a slightly higher sensitivity than BMI or WHR (82 vs 77 and 77% P<0.8, 0.7) for diabetes; for dyslipidaemia, waist and WHR had similar sensitivities, higher than for BMI (65 and 67 vs 54% P<0.16, 0.13). CONCLUSIONS: We propose that for screening in a French population 40-64 years of age, the more obese 30% of the population, identified either by BMI, waist or WHR be screened for diabetes and obesity-associated dyslipidaemia.

Misregulation of poly(ADP-ribose) polymerase-1 activity and cell type-specific loss of poly(ADP-ribose) synthesis in the cerebellum of aged rats.

Protein modification by ADP-ribose polymers is a common regulatory mechanism in eukaryotic cells and is involved in several aspects of brain physiology and physiopathology, including neurotransmission, memory formation, neurotoxicity, ageing and age-associated diseases. Here we show age-related misregulation of poly(ADP-ribose) synthesis in rat cerebellum as revealed by: (i) reduced poly(ADP-ribose) polymerase-1 (PARP-1) activation in response to enzymatic DNA cleavage, (ii) altered protein poly(ADP-ribosyl)ation profiles in isolated nuclei, and (iii) cell type-specific loss of poly(ADP-ribosyl)ation capacity in granule cell layer and Purkinje cells in vivo. In particular, although PARP-1 could be detected in virtually all granule cells, only a fraction of them appeared to be actively engaged in poly(ADP-ribose) synthesis and this fraction was reduced in old rat cerebellum. NAD(+), quantified in tissue homogenates, was essentially the same in the cerebellum of young and old rats suggesting that in vivo factors other than PARP-1 content and/or NAD(+) levels may be responsible for the age-associated lowering of poly(ADP-ribose) synthesis. Moreover, PARP-1 expression was substantially down-regulated in Purkinje cells of senescent rats.

Photoelectrochemical study on photosynthetic pigments-sensitized nanocrystalline ZnO films.

Hetero-structures formed by quantum-sized ZnO nanocrystals and photosynthetic pigments were prepared by adsorbing either chlorophyll a, carotenoids or their mixture onto a film of organic-capped ZnO nanoparticles. Photoelectrochemical measurements were comparatively performed on both bulk and nanocrystalline ZnO films after dye-covering in order to probe the photosensitization process occurring at the hetero-junction. The photoconversion process was found to be greatly enhanced at the nanocrystalline electrodes upon sensitization with a dye mixture. The sensitization process is discussed on the basis of the aggregation state of chlorophyll a, and of the specific photoprotective action played by carotenoids.