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CAPNS1 is essential for the stability and function of ubiquitous CAPN1 and CAPN2. Calpain modulates by proteolytic cleavage many cellular substrates and its activity is often deregulated in cancer cells, therefore calpain inhibition has been proposed as a therapeutical strategy for a number of malignancies. Here we show that CAPNS1 depletion is coupled to impairment of MCF7 and MCF10AT cell lines growth on plate and defective architecture of mammary acini derived from MCF10A cells. In soft agar CAPNS1 depletion leads to cell growth increase in MCF7, and decrease in MCF10AT cells. In both MCF7 and MCF10AT, CAPNS1 depletion leads to the enlargement of the stem cell compartment, as demonstrated by mammosphere formation assays and evaluation of stem cell markers by means of FACS and western blot analysis. Accordingly, activation of calpain by thapsigargin treatment leads to a decrease in the stem cell reservoir. The expansion of the cancer stem cell population in CAPNS1 depleted cells is coupled to a defective shift from symmetric to asymmetric division during mammosphere growth coupled to a decrease in NUMB protein level.

Background: Despite recent improvements, uptake and retention of mothers and infants in prevention of mother-to-child transmission (PMTCT) services remain well below target levels in many low- and middle-income countries (LMICs). Identification of effective interventions to support uptake and retention is the first step towards improvement. We aim to complete a systematic review and meta-analysis to evaluate the effectiveness of interventions at the patient, provider or health system level in improving uptake and retention of HIV-infected mothers and their infants in PMTCT services in LMICs., Methods/design: We will include studies comparing usual care or no intervention to any type of intervention to improve uptake and retention of HIV-infected pregnant or breastfeeding women and their children from birth to 2 years of age attending PMTCT services in LMICs. We will include randomized controlled trials (RCTs), cluster RCTs, non-randomized controlled trials, and interrupted time series. The primary outcomes of interest are percentage of HIV-infected women receiving/initiated on anti-retroviral prophylaxis or treatment, percentage of infants receiving/initiated on anti-retroviral prophylaxis, and percentage of women and infants completing the anti-retroviral regimen/retained in PMTCT care. The following databases will be searched from inception: Ovid MEDLINE and EMBASE, The WHO Global Health Library, CAB abstracts, EBM Reviews, CINAHL, HealthSTAR and Web of Science databases, Scopus, PsychINFO, POPLINE, Sociological Abstracts, ERIC, AIDS Education Global Information System, NLM Gateway, LILACS, Google Scholar, British Library Catalogue, DARE, ProQuest Dissertation & Theses, the New York Academy of Grey Literature, Open Grey, The Cochrane Library, WHO International Clinical Trials Registry, Controlled Clinical Trials, and clinicaltrials.gov. Reference lists of included articles will be hand searched and study authors and content experts contacted to inquire about eligible unpublished or in progress studies. Screening, data abstraction, and risk of bias appraisal using the Cochrane Effective Practice and Organization of Care criteria will be conducted independently by two team members. Results will be synthesized narratively and a meta-analysis conducted using the DerSimonian Laird random effects method if appropriate based on assessment of clinical and statistical heterogeneity., Discussion: Our findings will be useful to PMTCT implementers, policy makers, and implementation researchers working in LMICs., Systematic Review Registration: PROSPERO CRD42015020829.

Graphene, nanotubes and other carbon nanostructures have shown potential as candidates for advanced technological applications due to the different coordination of carbon atoms and to the possibility of π-conjugation. In this context, atomic-scale wires comprised of sp-hybridized carbon atoms represent ideal 1D systems to potentially downscale devices to the atomic level. Carbon-atom wires (CAWs) can be arranged in two possible structures: a sequence of double bonds (cumulenes), resulting in a 1D metal, or an alternating sequence of single-triple bonds (polyynes), expected to show semiconducting properties. The electronic and optical properties of CAWs can be finely tuned by controlling the wire length (i.e., the number of carbon atoms) and the type of termination (e.g., atom, molecular group or nanostructure). Although linear, sp-hybridized carbon systems are still considered elusive and unstable materials, a number of nanostructures consisting of sp-carbon wires have been produced and characterized to date. In this short review, we present the main CAW synthesis techniques and stabilization strategies and we discuss the current status of the understanding of their structural, electronic and vibrational properties with particular attention to how these properties are related to one another. We focus on the use of vibrational spectroscopy to provide information on the structural and electronic properties of the system (e.g., determination of wire length). Moreover, by employing Raman spectroscopy and surface enhanced Raman scattering in combination with the support of first principles calculations, we show that a detailed understanding of the charge transfer between CAWs and metal nanoparticles may open the possibility to tune the electronic structure from alternating to equalized bonds.

Background: Across Sub-Saharan Africa, the roll-out of antiretroviral treatment (ART) has contributed to shifting HIV care towards the management of a chronic health condition. While the balance of professional and lay tasks in HIV caregiving has been significantly altered due to changing skills requirements and task-shifting initiatives, little attention has been given to the effects of these changes on health workers' motivation and existing care relations., Methods: This paper draws on a cross-sectional, qualitative study that explored changes in home-based care (HBC) in the light of widespread ART rollout in the Lusaka and Kabwe districts of Zambia. Methods included observation of HBC daily activities, key informant interviews with programme staff from three local HBC organisations (n = 17) and ART clinic staff (n = 8), as well as in-depth interviews with home-based caregivers (n = 48) and HBC clients (n = 31)., Results: Since the roll-out of ART, home-based caregivers spend less time on hands-on physical care and support in the household, and are increasingly involved in specialised tasks supporting their clients' access and adherence to ART. Despite their pride in gaining technical care skills, caregivers lament their lack of formal recognition through training, remuneration or mobility within the health system. Care relations within homes have also been altered as caregivers' newly acquired functions of monitoring their clients while on ART are met with some ambivalence. Caregivers are under pressure to meet clients and their families' demands, although they are no longer able to provide material support formerly associated with donor funding for HBC., Conclusions: As their responsibilities and working environments are rapidly evolving, caregivers' motivations are changing. It is essential to identify and address the growing tensions between an idealized rhetoric of altruistic volunteerism in home-based care, and the realities of lay worker deployment in HIV care interventions that not only shift tasks, but transform social and professional relations in ways that may profoundly influence caregivers' motivation and quality of care.

In July 2011, Malawi introduced an ambitious public health program known as "Option B+," which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy, regardless of clinical stage or CD4 count. Option B+ is expected to have benefits for HIV-infected women, their HIV-exposed infants, and their HIV-uninfected male sex partners. However, these benefits hinge on early uptake of prevention of mother-to-child transmission, good adherence, and long-term retention in care. The Prevention of mother-to-child transmission Uptake and REtention (PURE) study is a 3-arm cluster randomized controlled trial to evaluate whether clinic- or community-based peer support will improve care-seeking and retention in care by HIV-infected pregnant and breastfeeding women, their HIV-exposed infants, and their male sex partners, and ultimately improve health outcomes in all 3 populations. We describe the PURE Malawi Consortium, the initial work conducted to inform the trial and interventions, the trial design, and the analysis plan. We then discuss concerns and expected contributions to Malawi and the region.

Oxidized Single-Wall Carbon Nanohorns (o-SWCNHs) were used, for the first time, to assemble chemically modified Screen Printed Electrodes (SPEs) selective towards the electrochemical detection of Epinephrine (Ep), in the presence of Serotonine-5-HT (S-5HT), Dopamine (DA), Nor-Epineprhine (Nor-Ep), Ascorbic Acid (AA), Acetaminophen (Ac) and Uric Acid (UA). The Ep neurotransmitter was detected by using Differential Pulse Voltammetry (DPV), in a wide linear range of concentration (2-2500 μM) with high sensitivity (55.77 A M(-1) cm(-2)), very good reproducibility (RSD% ranging from 2 to 10 for different SPEs), short response time for each measurement (only 2s) and low detection of limit (LOD=0.1 μM). o-SWCNHs resulted in higher analytical performances when compared with other nanomaterials used in literature for electrochemical sensors assembly., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: In sub-Saharan Africa antiretroviral therapy (ART) is being decentralized from tertiary/secondary care facilities to primary care. The Lablite project supports effective decentralization in 3 countries. It began with a cross-sectional survey to describe HIV and ART services., Methods: 81 purposively sampled health facilities in Malawi, Uganda and Zimbabwe were surveyed., Results: The lowest level primary health centres comprised 16/20, 21/39 and 16/22 facilities included in Malawi, Uganda and Zimbabwe respectively. In Malawi and Uganda most primary health facilities had at least 1 medical assistant/clinical officer, with average 2.5 and 4 nurses/midwives for median catchment populations of 29,275 and 9,000 respectively. Primary health facilities in Zimbabwe were run by nurses/midwives, with average 6 for a median catchment population of 8,616. All primary health facilities provided HIV testing and counselling, 50/53 (94%) cotrimoxazole preventive therapy (CPT), 52/53 (98%) prevention of mother-to-child transmission of HIV (PMTCT) and 30/53 (57%) ART management (1/30 post ART-initiation follow-up only). All secondary and tertiary-level facilities provided HIV and ART services. In total, 58/81 had ART provision. Stock-outs during the 3 months prior to survey occurred across facility levels for HIV test-kits in 55%, 26% and 9% facilities in Malawi, Uganda and Zimbabwe respectively; for CPT in 58%, 32% and 9% and for PMTCT drugs in 26%, 10% and 0% of facilities (excluding facilities where patients were referred out for either drug). Across all countries, in facilities with ART stored on-site, adult ART stock-outs were reported in 3/44 (7%) facilities compared with 10/43 (23%) facility stock-outs of paediatric ART. Laboratory services at primary health facilities were limited: CD4 was used for ART initiation in 4/9, 5/6 and 13/14 in Malawi, Uganda and Zimbabwe respectively, but frequently only in selected patients. Routine viral load monitoring was not used; 6/58 (10%) facilities with ART provision accessed centralised viral loads for selected patients., Conclusions: Although coverage of HIV testing, PMTCT and cotrimoxazole prophylaxis was high in all countries, decentralization of ART services was variable and incomplete. Challenges of staffing and stock management were evident. Laboratory testing for toxicity and treatment effectiveness monitoring was not available in most primary level facilities.

Introduction: As adolescents living with HIV gain autonomy over their self-care and begin to engage in sexual relationships, their experiences of being informed about their HIV status and of telling others about their HIV status may affect their ability to cope with having the disease., Methods: In 2010, we conducted a qualitative study among adolescents aged 10-19 living with HIV in Zambia, and with their parents and health care providers. Through interviews and focus group discussions, we explored the disclosure of HIV status to adolescents living with HIV; adolescents' disclosure of their status to others; and the impact of both forms of disclosure on adolescents., Results: Our study identified three main barriers to disclosure of HIV status: local norms that deter parents from communicating with their children about sexuality; fear of HIV stigma; and an underlying presumption that adolescents would not understand the consequences of a HIV diagnosis on their lives and relationships. With regard to adolescents' disclosure of their HIV status to their sexual partners, our study identified fear of rejection as a common barrier. In rare cases, open family conversations about HIV helped adolescents come to terms with a HIV diagnosis. Findings indicated that disclosure had various outcomes at the individual and interpersonal levels. At the individual level, some adolescents described being anxious, depressed and blaming themselves after being told they had HIV. At the interpersonal level, disclosure created opportunities for adolescents to access adherence support and other forms of psychosocial support from family members and peers. At the same time, it occasionally strained adolescents' sexual relationships, although it did not always lead to rejection., Conclusions: There is a need for public health interventions that guide adolescents living with HIV, their parents and families through the disclosure process. Such interventions should help parents to assess and understand the evolving cognitive capacity and maturity of their adolescents in order to determine the appropriate time to inform them of their HIV-positive status. Such interventions should also mitigate the risk of HIV stigma, as well as local norms that may prevent discussions of sexuality within families. Adolescents who have been informed of their HIV status should be provided with on-going support to prevent disclosure from negatively affecting their psychological and sexual wellbeing. Further research is needed to explore the potential role of trusted family members in contributing to the disclosure process.

Background: Previous studies have reported an association between sun exposure and improved cutaneous melanoma (CM) survival. We analysed the association of UV exposure with prognostic factors and outcome in a large melanoma cohort., Methods: A questionnaire was given to 289 (42%) CM patients at diagnosis (Group 1) and to 402 CM patients (58%) during follow-up (Group 2). Analyses were carried out to investigate the associations between sun exposure and melanoma prognostic factors and survival., Results: Holidays in the sun two years before CM diagnosis were significantly associated with lower Breslow thickness (p=0.003), after multiple adjustment. Number of weeks of sunny holidays was also significantly and inversely associated with thickness in a dose-dependent manner (p=0.007). However when stratifying by gender this association was found only among women (p=0.0004) the risk of CM recurrence in both sexes was significantly lower in patients (n=271) who had holidays in the sun after diagnosis, after multiple adjustment including education: HR=0.30 (95%CI:0.10-0.87; p=0.03) conclusions: Holidays in the sun were associated with thinner melanomas in women and reduced rates of relapse in both sexes. However, these results do not prove a direct causal effect of sun exposure on survival since other confounding factors, such as vitamin D serum levels and socio-economic status, may play a role. Other factors in sun seeking individuals may also possibly affect these results.

Background: In 2011, Malawi initiated an ambitious program for the prevention of maternal to child transmission (PMTCT) of HIV, called 'Option B+,' which employs a universal test and life-long treatment strategy for all pregnant women. Priority setting should take place in defining a national research agenda for evaluating Option B + rollout in Malawi., Methods: In April 2011, a three-day workshop took place for all major stakeholders in PMTCT aiming to provide an update on current PMTCT operational research in Malawi, find consensus on key questions not yet being addressed, identify opportunities for collaboration, and develop multi-partner research proposals., Results: Overall, 24 participants attended the workshop including representatives from the Ministry of Health, the National AIDS Commission and 12 multilateral, non-governmental organizations and academic partners.Three interrelated clusters emerged as priorities for research: i) pregnancy intentions and family planning needs; ii) evaluation of models of care; and iii) determinants of uptake, adherence, and retention of women for Option B+. In addition, two cross-cutting themes arose: partner involvement in PMTCT services and cost-effectiveness as a guide to priority setting. Within each cluster a coordinator was designated and a proposed plan for research and potential collaborators were discussed. The results of the workshop were presented to the national technical working groups and the National AIDS Commission. Several large-scale, collaborative proposals have been developed and funded to address the research areas defined., Conclusions: Option B + represents a significant change in PMTCT policy in Malawi and the process for evaluation of the Malawi PMTCT strategy is outlined. This workshop contributed to defining and coordinating the national agenda for research priorities.

Neat ethyl oleate was ozonized in a bubble reactor and the progress of the ozonolysis was followed by infrared (FT-IR) spectroscopy and by the differential scanning calorimetry (DSC). The ozonolysis was conducted till a molar ratio O3/C=C≈1 when the exothermal reaction spontaneously went to completion. A specific thermochemical calculation on ethyl oleate ozonation has been made to determine the theoretical heat of the ozonization reaction using the group increment approach. A linear relationship was found both in the integrated absorptivity of the ozonide infrared band at 1110 cm(-1) and the ozonolysis time as well as the thermal decomposition enthalpy of the ozonides and peroxides formed as a result of the ozonation. The DSC decomposition temperature of ozonated ethyl oleate occurs with an exothermal peak at about 150-155 °C with a decomposition enthalpy of 243.0 kJ/mol at molar ratio O3/C=C≈1. It is shown that the decomposition enthalpy of ozonized ethyl oleate is a constant value (≈243 kJ/mol) at any stage of the O3/C=C once an adequate normalization of the decomposition enthalpy for the amount of the adsorbed ozone is taken into consideration. The decomposition enthalpy of ozonized ethyl oleate was also calculated using a simplified thermochemical model, obtaining a result in reasonable agreement with the experimental value., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Paper-based village registers were introduced 5 years ago in Malawi as a tool to measure vital statistics of births and deaths at the population level. However, usage, completeness and accuracy of their content have never been formally evaluated. In Traditional Authority Mwambo, Zomba district, Malawi, we assessed 280 of the 325 village registers with respect to (i) characteristics of village headmen who used village registers, (ii) use and content of village registers, and (iii) whether village registers provided accurate information on births and deaths. All village headpersons used registers. There were 185 (66%) registers that were regarded as 95% completed, and according to the registers, there were 115 840 people living in the villages in the catchment area. In 2011, there were 1753 births recorded in village registers, while 6397 births were recorded in health centre registers in the same catchment area. For the same year, 199 deaths were recorded in village registers, giving crude death rates per 100 000 population of 189 for males and 153 for females. These could not be compared with death rates in health centre registers due to poor and inconsistent recording in these registers, but they were compared with death rates obtained from the 2010 Malawi Demographic Health Survey that reported 880 and 840 per 100 000 for males and females, respectively. In conclusion, this study shows that village registers are a potential source for vital statistics. However, considerable inputs are needed to improve accuracy of births and deaths, and there are no functional systems for the collation and analysis of data at the traditional authority level. Innovative ways to address these challenges are discussed, including the use of solar-powered electronic village registers and mobile phones, connected with each other and the health facilities and the District Commissioner's office through the cellular network and wireless coverage., (© 2013 John Wiley & Sons Ltd.)

A series of non-proteinogenic amino acids, most of them found quite commonly in the meteorites known as carbonaceous chondrites, were subjected to solid state radiolysis in vacuum to a total radiation dose of 3.2 MGy corresponding to 23% of the total dose expected to be taken by organic molecules buried in asteroids and meteorites since the beginning of the solar system 4.6 × 109 years ago. The radiolyzed amino acids were studied by FT-IR spectroscopy, Differential Scanning Calorimetry (DSC) and by polarimety and Optical Rotatory Dispersion (ORD). It is shown that an important fraction of each amino acid is able to "survive" the massive dose of radiation, while the enantiomeric excess is partially preserved. Based on the results obtained, it is concluded that it is unsurprising to find amino acids even in enantiomeric excess in carbonaceous chondrites.

A series of 33 different polycyclic aromatic hydrocarbons (PAHs) were studied by far infrared spectroscopy (terahertz spectroscopy) in the spectral range comprised between 600 and 50 cm(-1). In addition to common PAHs like naphthalene, anthracene, phenanthrene, fluoranthene, picene, pyrene, benzo[α]pyrene, and perylene, also quite unusual PAHs were studied like tetracene, pentacene, acenaphtene, acenaphtylene, triphenylene, and decacyclene. A series of alkylated naphthalenes and anthracenes were studied as well as methypyrene. Partially or totally hydrogenated PAHs were also object of the present investigation, ranging from tetrahydronaphthalene (tetralin) to decahydronaphthalene (decalin), 9,10-dihydroanthracene, 9,10-dihydrophenanthrene, hexahydropyrene, and dodecahydrotriphenylene. Finally, the large and quite rare PAHs coronene, quaterrylene, hexabenzocoronene, and dicoronylene were studied by far infrared spectroscopy. The resulting reference spectra were used in the interpretation of the chemical structure of asphaltenes (as extracted from a heavy petroleum fraction and from bitumen), the chemical structures of other petroleum fractions known as DAE (distillate aromatic extract) and RAE (residual aromatic extract), and a possible interpretation of components of the chemical structure of anthracite coal. Asphaltenes, heavy petroleum fractions, and coal were proposed as model compounds for the interpretation of the emission spectra of certain proto-planetary nebulae (PPNe) with a good matching in the mid infrared between the band pattern of the PPNe emission spectra and the spectra of these oil fractions or coal. Although this study was finalized in an astrochemical context, it may find application also in the petroleum and coal chemistry., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The dynamics of excited states in α,ω-dinaphthylpolyyne, a class of linear sp-carbon chains, has been investigated by ultrafast transient absorption spectroscopy and DFT//TDDFT calculations. We show that the role of molecular conformers, in which end-capped naphthalene rings are planar or perpendicular to the polyyne plane, is fundamental for understanding both the steady state properties, such as UV-Vis absorption spectra and vibronic transitions, and the ultrafast transient absorption features. In particular, we observed in one of the conformers the ultrafast formation of a narrow photo-induced absorption band rising within 30 ps. This band can be assigned to an inter-system crossing event leading to the formation of triplet excited states.

Calpains regulate a wide spectrum of biological functions, including migration, adhesion, apoptosis, secretion, and autophagy, through the modulating cleavage of specific substrates. Ubiquitous microcalpain (μ-calpain) and millicalpain (m-calpain) are heterodimers composed of catalytic subunits encoded, respectively, by CAPN1 and CAPN2 and a regulatory subunit encoded by CAPNS1. Here we show that calpain is required for the stability of the deubiquitinating enzyme USP1 in several cell lines. USP1 modulates DNA replication polymerase choice and repair by deubiquitinating PCNA. The ubiquitinated form of the USP1 substrate PCNA is stabilized in CAPNS1-depleted U2OS cells and mouse embryonic fibroblasts (MEFs), favoring polymerase-η loading on chromatin and increased mutagenesis. USP1 degradation directed by the cell cycle regulator APC/C(cdh1), which marks USP1 for destruction in the G1 phase, is upregulated in CAPNS1-depleted cells. USP1 stability can be rescued upon forced expression of calpain-activated Cdk5/p25, previously reported as a cdh1 repressor. These data suggest that calpain stabilizes USP1 by activating Cdk5, which in turn inhibits cdh1 and, consequently, USP1 degradation. Altogether these findings point to a connection between the calpain system and the ubiquitin pathway in the regulation of DNA damage response and place calpain at the interface between cell cycle modulation and DNA repair.

Background: In the last years Italy is confronting with massive migratory movements from developing countries where hemoglobinopathies are widespread. This is causing a large diffusion and a changing spectrum in the epidemiology of hemoglobin disorders in Italy., Methods: Investigations recently published in Italy on hemoglobinopathies among immigrants were revised in order to appreciate the impact of immigration from developing countries on epidemiology of these pathologies and to outline adequate guidelines of prevention., Results: Although in Italy there is a limited number of investigations regarding the relation between immigration and hemoglobin disorders, published data show that in our Nation there is a changing and increasing spectrum of hemoglobinopathies linked to immigration., Conclusions: Prospective and retrospective actions of public healthy preventive policy are requested, based upon information (health educational programs for immigrants and caregivers), screenings among immigrants (school screening, pre-marital, preconception and early pregnancy screening, newborn screening), counseling for foreign at-risk couples and healthy carriers.

Background: Current antiretroviral treatment (ART) models in Africa are labour intensive and require a high number of skilled staff. In the context of constraints in human resources for health, task shifting is considered a feasible alternative for ART service delivery. In 2006, Dignitas International in partnership with the Malawi Ministry of Health trained a cadre of expert patients at the HIV Clinic at a tertiary referral hospital in Zomba, Malawi. Expert patients were trained to assist with clinic tasks including measurement of vital signs, anthropometry and counseling., Methods: A descriptive observational study using mixed methods was conducted two years after the start of program implementation. Semi-structured interviews were conducted with 20 patients, seven expert patients and six formal health care providers to explore perceptions towards the expert patients' contributions in the clinic. Structured exit interviews with 81 patients, assessed whether essential ART information was conveyed during counseling sessions. Vital signs and anthropometry measurements performed by expert patients were repeated by a nurse to assess accuracy of measurements. Direct observations quantified the time spent with each patient., Results: There were minor differences in measurement of patients' weight, height and temperature between the expert patients and the nurse. The majority of patients exiting a counseling session reported, without prompting, at least three side effects of ART, correct actions to be taken on observing a side-effect, and correct consequences of non-adherence to ART. Expert patients carried out 368 hours of nurse tasks each month, saving two and a half full-time nurse equivalents per month. Formal health care workers and patients accept and value expert patients' involvement in ART provision and care. Expert patients felt valued by patients for being a 'role model', or a 'model of hope', promoting positive living and adherence to ART., Conclusions: Expert patients add value to the ART services at a tertiary referral HIV clinic in Malawi. Expert patients carry out shifted tasks acceptably, saving formal health staff time, and also act as 'living testimonies' of the benefits of ART and can be a means of achieving greater involvement of People Living with HIV in HIV treatment programs.

In response to the human resource challenges facing African health systems, there is increasing involvement of informal care providers in HIV care. Through social and institutional interactions that occur in the delivery of HIV care, linkages between formal and informal systems of care often emerge. Based on a review of studies documenting the relationships between formal and informal HIV care in sub-Saharan Africa, we suggest that linkages can be conceptualised as either 'actor-oriented' or 'systems-oriented'. Studies adopting an actor-oriented focus examine hierarchical working relationships and communication practices among health systems actors, while studies focusing on systems-oriented linkages document the presence, absence or impact of formal inter-institutional partnership agreements. For linkages to be effective, the institutional frameworks within which linkages are formalised, as well as the ground-level interactions of those engaged in care, ought to be considered. However, to date, both actor- and system-oriented linkages appear to be poorly utilised by policy makers to improve HIV care. We suggest that linkages between formal and informal systems of care be considered across health systems, including governance, human resources, health information and service delivery in order to improve access to HIV services, enable knowledge transfer and strengthen health systems.

Immunogenicity of tumour cells, immunomodulation and direct targeting of signalling pathways are promising avenues and matter of dated and innovative research in melanoma. Unfortunately, tumour cells are considered to be antigenic, but not immunogenic, either due to presentation of weakly recognized antigens or to the inability of the immune system to recognize them. However, spontaneous complete remission can be rarely observed in patients affected by melanoma, which are mainly attributed to the immune response against the tumour. Also, an elevated frequency of spontaneous humoral immune responses against tumour antigens was occasionally found in patients. These data confirm the existence of an interaction of the immune system with the tumour which can be used as a promising pathway for intervention and incorporates all portions of the immune system. The cancer immunotherapy approach is based on artificial activation of the immune system against the tumour and groups several types of treatments including immunization/vaccination but also modulation of immunity by cytokines or antibodies. Immunization approaches could either be based on undefined tumour antigens (e.g. whole tumour cells, tumour cell lysates, or tumour-antigen enriched fractions) or aimed at eliciting T-cell responses against specific tumour antigens. Novel and contemporary antigen-targeted therapy strategies, mainly directed to Cancer Testis and Heat Shock Proteins, leading to a possible active immunization against melanoma through T-cell specific activation, are discussed in this review., (© 2012 Bentham Science Publishers)

We perform a systematic investigation of the resonance and vibrational properties of naphthyl-terminated sp carbon chains (dinaphthylpolyynes) by combined multi-wavelength resonant Raman (MWRR) spectroscopy, ultraviolet-visible spectroscopy, and Fourier-transform infrared (FT-IR) spectroscopy, plus ab initio density functional theory (DFT) calculations. We show that the MWWR and FT-IR spectroscopies are particularly suited to identify chains of different lengths and different terminations, respectively. By DFT calculations, we further extend those findings to sp carbon chains end-capped by other organic structures. The present analysis shows that combined MWRR and FT-IR provide a powerful tool to draw a complete picture of chemically stabilized sp carbon chains.

Purpose: Prognosis in patients with sentinel node (SN)-positive melanoma correlates with several characteristics of the metastases in the SN such as size and site. These factors reflect biologic behavior and may separate out patients who may or may not need additional locoregional and/or systemic therapy., Patients and Methods: Between 1993 and 2008, 1,080 patients (509 women and 571 men) were diagnosed with tumor burden in the SN in nine European Organisation for Research and Treatment of Cancer (EORTC) melanoma group centers. In total, 1,009 patients (93%) underwent completion lymph node dissection (CLND). Median Breslow thickness was 3.00 mm. The median follow-up time was 37 months. Tumor load and tumor site were reclassified in all nodes by the Rotterdam criteria for size and in 88% by the Dewar criteria for topography., Results: Patients with submicrometastases (< 0.1 mm in diameter) were shown to have an estimated 5-year overall survival rate of 91% and a low nonsentinel node (NSN) positivity rate of 9%. This is comparable to the rate in SN-negative patients. The strongest predictive parameter for NSN positivity and prognostic parameter for survival was the Rotterdam-Dewar Combined (RDC) criteria. Patients with submicrometastases that were present in the subcapsular area only, had an NSN positivity rate of 2% and an estimated 5- and 10-year melanoma-specific survival (MSS) of 95%., Conclusion: Patients with metastases < 0.1 mm, especially when present in the subcapsular area only, may be overtreated by a routine CLND and have an MSS that is indistinguishable from that of SN-negative patients. Thus the RDC criteria provide a rational basis for decision making in the absence of conclusions provided by randomized controlled trials.

Stone-Wales operators interchange four adjacent hexagons with two pentagon-heptagon 5|7 pairs that, graphically, may be iteratively propagated in the graphene layer, originating a new interesting structural defect called here Stone-Wales wave. By minimization, the Wiener index topological invariant evidences a marked anisotropy of the Stone-Wales defects that, topologically, are in fact preferably generated and propagated along the diagonal of the graphenic fragments, including carbon nanotubes and graphene nanoribbons. This peculiar edge-effect is shown in this paper having a predominant topological origin, leaving to future experimental investigations the task of verifying the occurrence in nature of wave-like defects similar to the ones proposed here. Graph-theoretical tools used in this paper for the generation and the propagation of the Stone-Wales defects waves are applicable to investigate isomeric modifications of chemical structures with various dimensionality like fullerenes, nanotubes, graphenic layers, schwarzites, zeolites.

Oleum (fuming sulphuric acid), a well known superacid, was used as medium for the generation of the radical cation of a series of selected PAHs. The resulting radical cation spectra were studied by electronic absorption spectroscopy. Not only common PAHs like naphthalene, anthracene, tetracene, pentacene, perylene, pyrene, benzo[a]pyrene, phenanthrene and picene were studied but also the less common and very large PAHs relevant also for the astrochemical research, like coronene, hexabenzocoronene, quaterrylene, dicoronylene and a coronene oligomer. A correlation between the first ionization potential (IP1) of the PAHs studied and the energy to the so-called A-type band of the radical cations observed in oleum has led to the equation IP1=1.30EA+4.39 (in eV) which permits to estimate the energy of the PAHs radical cation transition (EA) in the VIS-NIR knowing the relative ionization potential or vice versa., (Copyright © 2010 Elsevier B.V. All rights reserved.)

We report a combined study on the synthesis, spectroscopic characterization, and theoretical modeling of a series of α,ω-dinaphthylpolyynes. We synthesized this family of naphthyl-terminated sp carbon chains by reacting diiodoacetylene and 1-ethynylnaphthalene under the Cadiot-Chodkiewicz reaction conditions. By means of liquid chromatography (HPLC), we separated the products and recorded their electronic absorption spectra, which enabled us to identify the complete series of dinaphthylpolyynes Ar-C(2n)-Ar (with Ar = naphthyl group and n = number of acetilenic units) with n ranging from 2 to 6. The longest wavelength transition (LWT) in the electronic spectra of the dinaphthylpolyynes red shifts linearly with n away from the LWT of the bare termination. This result is also supported by DFT-LDA simulations. Finally, we probed the stability of the dinaphthylpolyynes in a solid-state precipitate by Fourier-transform infrared spectroscopy and by differential scanning calorimetry (DSC).

Electroporation uses pulsed, high-intensity electric fields to temporarily increase cell membrane permeability by creation of pores, through which small molecules, such as chemotherapeutic agents, can diffuse inside cells before they reseal. The combination of electroporation with the administration of otherwise low-permeant cytotoxic drugs is known as electrochemotherapy (ECT). The two most commonly used drugs are bleomycin and cisplatin. ECT has already been proven to be effective in diverse tumor histotypes, including melanoma and basal and squamous cell carcinoma, Kaposi sarcoma, and breast cancer, also in those cases nonresponding to classical chemotherapies or other loco-regional treatment modalities, with a good safety profile. ECT can be proposed as loco-regional therapy for disseminated cutaneous and subcutaneous tumor lesions as alternative treatment modality to conventional therapies or as palliative care, in order to improve patients' quality of life., (© 2010 Wiley Periodicals, Inc.)

Home-based care (HBC) programmes in low- and middle-income countries have evolved over the course of the past two decades in response to the HIV epidemic and wider availability of antiretroviral therapy (ART). Evidence is emerging from small-scale and well-resourced studies that ART delivery can be effectively incorporated within HBC programmes. However, before this approach can be expanded, it is necessary to consider the lessons learned from implementing routine HBC programmes and to assess what conditions are required for their roll-out in the context of ART provision. In this paper, we review the literature on existing HBC programmes and consider the arguments for their expansion in the context of scaling up ART delivery. We develop a framework that draws on the underlying rationale for HBC and incorporates lessons learned from community health worker programmes. We then apply this framework to assess whether the necessary conditions are in place to effectively scale up HBC programmes in the ART era. We show that the most effective HBC programmes incorporate ongoing support, training and remuneration for their workers; are integrated into existing health systems; and involve local communities from the outset in programme planning and delivery. Although considerable commitment has so far been demonstrated to delivering comprehensive HBC programmes, their effectiveness is often hindered by weak linkages with other HIV services. Top-down donor policies and a lack of sustainable and consistent funding strategies represent a formidable threat to these programmes in the long term. The benefits of HBC programmes that incorporate ART care are unlikely to be replicated on a larger scale unless donors and policymakers address issues related to human resources, health service linkages and community preparedness. Innovative and sustainable funding policies are needed to support HBC programmes if they are to effectively complement national ART programmes in the long term.

Unsaturated lipids when exposed to air at room temperature undergo a slow autoxidation. When fullerene C(60) was dissolved in selected lipids (ethyl oleate, ethyl linoleate, linseed oil and castor oil) the spectrophotometric analysis shows that the oxidation is concentrated to C(60) which is converted to an epoxide C(60)O. Thus, fullerene C(60) displays antioxidant activity not only when dissolved in unsaturated lipids but also, more generally, when dissolved in unsaturated solvents subjected to autoxidation like, for example, in cyclohexene. The behaviour of C(60) in ethyl oleate has been compared with that of the known antioxidant TMPPD (N,N',N,N,'-tetramethyl-p-phenylenediamine) in ethyl oleate. The mechanism of the antioxidant action of C(60) in lipids has been proposed. The kinetics of C(60) oxidation in lipids was determined spectrophotometrically both at room temperature in the dark and under UV irradiation. The oxidized products derived from C(60) photo-oxidation in lipids have been identified., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Senescence represents an important barrier against cellular transformation. Here we show that CAPNS1 depletion impairs senescence induction both in BJ-ET H-Ras(v12) inducible human fibroblasts upon Ras induction and in HT1080 targeted to senescence by treatment with low doses of doxorubicin. We further show that CAPNS1 depletion is coupled to reduced levels of H2AX phosphorylation, not only in Ras(v12) induced BJ-ET fibroblasts, but also in a number of cellular systems upon genotoxic stress. In particular CAPNS1 depletion affects gamma-H2AX appearance or persistence in U2OS osteosarcoma cells 24 hours after MMC addition or UV light exposure; in HT1080 upon camptothecin treatment for 4 hours and 48 hours after addition of MMC; in MDA-MB-231, 24 hours after UV light exposure and 2 hours after bleomycin addition. Overall this study unveils a novel link between calpain, cellular senescence and DNA damage response.

In the context of rolling out antiretroviral treatment programmes in resource-constrained settings, "expert patients" are hailed as an important step towards greater involvement of people living with HIV (PLHIV) in HIV care, and in addressing the human resources crisis. The rise of the "expert patient" in HIV care partly echoes the move towards greater patient agency and self-management that informs health services delivery in industrialised countries. However, the "expert patient" also represents a particular moment in the trajectory of PLHIVs' quest for greater access to treatment and health care. In this paper, we examine the unique evolution and 'instrumentalisation' of PLHIV in public health in relation to shifts in the epidemiology, interventions and socio-political response related to HIV since the 1980s. Synthesised broadly as "risk-based", "empowerment", "structural" and "activist" approaches, four key paradigms are identified that attribute different levels of citizenship for PLHIV, that is the motivation, agency and responsibility to act not only on their own interests, but also on behalf of collective interests in HIV prevention and care. We problematise the concept of the patient-citizen by drawing attention to the context-specificity of such notions as patient identity, capacity and rights as well as the structural realities of access to treatment, and broader engagement with the health system. We conclude by offering some thoughts on the applicability of 'expert patient' approaches across a broad range of settings.

The seroprevalence of Human Herpes Virus 8 (HHV8) and its transmission pattern were assessed testing serum samples of 120 internationally adopted children (aged 1-15 years) coming from Eastern Europe. Determinations of IgG antibodies against both latent and lytic HHV-8 antigens were performed by indirect immunofluorescence assay. Antibodies were detected only for lytic antigen of the virus in 12.5% of children with a seroprevalence significatively higher (19.6%) in young children (age 1-6). No correlation was observed between HHV8 seropositivity and serological markers for hepatitis A, B and C viruses and Human Immunodeficiency virus. In conclusion, our findings suggest that HHV8 infection is widespread in some populations from the East Europe, and that person to person contacts among children could be considered the predominant mode of HHV8 transmission in younger age.

Brazil has received praise internationally for its national health policy against HIV. Whilst the ethical stance of the Brazilian programme has been widely applauded, there is a lack of empirical data on how the commitment to equitable and universal HIV prevention and treatment works in practice among the poorest population groups. The aim of this paper is to explore the broad ethics of the Brazilian AIDS programme by investigating how universal access to HIV treatment is being implemented within a favela (shanty town). Data collected through anthropological research show that in settings such as the favelas, the universal character of this public health programme is challenged by a number of issues such as local definitions of illness, problems related to the understanding of and adherence to treatment, structural violence, political alienation, and lack of perspectives about the future. It is also argued that such health intervention has contributed to the promotion of novel attitudes towards individual notions of socio-political participation. These are explored with reference to the notion of therapeutic citizenship, which in the context of a favela neighbourhood translates into a new set of concerns around free access to and availability of treatment, the right to health care and the sustainability of public health policies.

Gelatin, the lower molecular weight derivative of collagen, was treated with ozone and the structural changes were studied with polarimetry, electronic absorption and FT-IR spectroscopy. The resulting ozonized gelatins were studied by thermal analysis (DSC and TGA) in comparison to a reference gelatin. It has been found that at relatively low ozone dose, for instance at ozone/gelatin molar ratios between 0.1 and 0.35 the structural damage introduced by ozone oxidation of gelatin is minimal to negligible and this may facilitate the industrial utilization of ozone in the cold sterilization of gelatin as well as in its bleaching processes required for certain applications. At higher O(3)/gelatin molar ratios the gelatine damage is evident both polarimetrically as suggested by the drop of its specific optical rotation and by spectrophotometrical analyses.

In the past, celiac disease was believed to be a chronic enteropathy, almost exclusively affecting people of European origin. The availability of new, simple, very sensitive and specific serological tests (anti-gliadin, anti-endomysium and anti-transglutaminase antibody assays) have shown that celiac disease is common not only in Europe and in people of European ancestry but also in the developing countries where the major staple diet is wheat (Southern Asia, the Middle East, North West and East Africa, South America), both in the general population and in the groups at risk. Gluten intolerance thus appears to be a widespread public health problem and an increased level of awareness and clinical suspicion are needed in the New World where physicians must learn to recognize the variable clinical presentations (classical, atypical and silent forms) of celiac disease. In the developing countries, both serological screening in the general population and serological testing in groups at risk are necessary for an early identification of celiac patients. The gluten-free diet poses a challenging public health problem in the developing countries, especially since commercial gluten-free products are not available.

The exposure of powdered crystals of C60 and C70 fullerenes to ozone with an O3/O2 ratio of 9.7% w/w causes their immediate oxidation. The FT-IR spectroscopy shows the formation of CO2 and the accelerated disappearance of ozone. The infrared spectra of crystalline C60 and C70 powders that were exposed to ozone show absorption bands indicating that oxidation was accompanied by formation of alpha,beta-unsaturated carboxylic groups, aldehyde and other ketonic moieties. The spontaneous decay of O3 in the O3/O2 atmosphere monitored by FT-IR spectroscopy was found to follow a pseudofirst order kinetic law with k0 = 6.9 x 10(-5) s(-1). When powdered C60 is present in the system a k(C60)(1) = 2.0 x 10(-4) s(-1); k(C70)(1) = 1.4 x 10(-4) s(-1) for C70. The accelerated disappearance of O3 is due to its adsorption/reaction with the powdered fullerenes. After about approximately 1000 s the reaction enters in a second step wherein the disappearance of O3 slows down significantly due to the lack of further reaction sites on the powdered fullerene surfaces and due to accumulated CO2 in the gas phase which exerts an inhibitory effect in the ozone spontaneous decomposition.

Synthetic graphite particles 0.2 microns in diameter react with O3 at room temperature with evolution of CO2. Graphite is less reactive with ozone than carbon blacks having different surface area ranging from 120 to 8 m2/g, but graphite reactivity is comparable to that shown by powdered solid C60 and C70 fullerenes. The kinetic rate constant derived from the ozone consumption k appears in relation with the rate of CO2 evolution suggesting a very simple reaction stoichiometry at the early stages. The reaction between ozone and graphite or carbon blacks essentially involves two stages: the gasification of the surface to CO2 and its functionalization with oxygenated chemical groups, mainly as COOH but also other oxygenated chemical moieties. The pseudofirst order kinetics appears adequate to describe the heterogeneous reaction between ozone and the selected carbon materials. The discussion of the results is focused on the role played by fullerene-like carbon nanostructures, present in graphene sheets to explain the observed gasification rates and surface functionalization.

The treatment of the terpene beta(-)pinene with gamma radiation (at dose level: 150, 300 and 600 kGy) causes its polymerization into a resin and into a dimer. The yield of the resin and of the dimer appears to be linearly dependent to the radiation dose. The structure of the products was studied by FT-IR spectroscopy also in comparison to a reference beta(-)pinene resin prepared by cationic polymerization. A highly ordered structure was found in the case of the radiopolymer in comparison to the resin from cationic polymerization. Polarimetric measurements have shown astonishing enhancement in the optical activity of the radiopolymer and radiodimer in comparison to the starting optical activity of the beta(-)pinene monomer. Also DSC (differential scanning calorimetry) data supports the unexpected highly ordered structure for the beta(-)pinene radiopolymer in comparison to the resin prepared by cationic polymerization. The results have been discussed in terms of amplification of chirality caused by gamma radiation and the implications of this fact on the mechanism of chiral amplification on prebiotic molecules.

Carbon vapour generated from a carbon arc or by laser ablation of graphite is reactive with simple molecules and atoms producing end-capped polyyne chains. With these techniques both hydrogen-terminated polyynes as well as monocyano- and dicyanopolyynes have been produced. Experiments based on arcing graphite electrodes can reproduce the molecular distribution of polyynes existing around carbon-rich AGB stars. In fact, it has been found that the relative abundances of the polyynes produced in carbon arc in vacuum decreases by a factor between 3 and 5 as the chain length increases by a C(2) unit. An analogous trend has been observed both for polyynes and cyanopolyynes in the circumstellar environment around carbon-rich stars. This fact suggests that the mechanism of formation of the polyynes in the carbon arc may be similar to that occurring in the surroundings of the carbon-rich stars. Polyynes and cyanopolyynes represent authentic prebiotic molecules which appear quite ubiquitous in the cosmos and should have played a role in the early organic chemistry preceding the appearance of life.

There are not available data concerning the occurrence, the clinical features and the environmental risk factors for food intolerances and allergies in immigrant children. The aim of the study was to evaluate rates, distribution, clinical features and environmental risk factors for food intolerances and allergies in immigrant children. Hospital records of 4,130 patients with celiac disease (CD), cow milk protein intolerance (CMPI) and food allergies (FA) diagnosed in 24 Italian Centres from 1999 to 2001 were retrospectively reviewed, comparing immigrant patients with Italian ones. 78/4,130 (1.9%) patients were immigrant: 36/1,917 (1.9%) had CD, 24/1,370 (1.75%) CMPI and 18/843 (2.1%) FA. They were evenly distributed across Italy and their native areas were: East Europe (23/78), Northern Africa (23/78), Southern Asia (14/78), Saharan and Sub-Saharan Africa (9/78), Southern America (4/78), Far East (3/7), Middle East (2/78). Despite differences in their origin, the clinical features of immigrant children were similar to the ones of Italian patients and among each ethnic group. The majority of them were born in Italy (57/78) or have been residing in Italy since several years (19/78). All of them had lost dietary habits of the native countries and had acquired those of the Italian childhood population. Food intolerances and allergies are present also in children coming from developing countries, and paediatricians will need to have a full awareness of them because the number of immigrant children in Italy is quickly increasing. The clinical features of food intolerances and allergies appear the same in each ethnic group, despite differences in races. Sharing of dietary habits with the Italian childhood population seems to be an important environmental risk factor.

DNA was ozonized in solution and the reaction was followed with polarimetry and with iodimetry. Polarimetry was used to determine the molar ratio DNA/O(3) when the DNA optical activity vanishes completely. At a molar ratio DNA/O(3)=2.3 the supramolecular structure of DNA collapses completely. Instead, iodimetry shows that the ozonolysis proceeds until all the nucleobases have been destroyed, an event which occurs at a molar ratio DNA/O(3)=1.1. The ozonolysis of DNA was also followed spectrophotometrically. DNA is reactive with ozone also in the solid state, as fixed bed. Clear indication about its oxidation derives from the FT-IR spectra from polarimetric measurements and from thermal analysis performed by thermogravimetric analysis (TGA), differential thermogravimetric analysis (DTG) and from differential thermal analysis (DTA). Particular remarkable is the fact that RNA has been found much less reactive toward ozone in the solid state than DNA.

An increasing number of internationally adopted children is coming to Italy, and their immunization status is unknown. We evaluated the immunization status of such children in Palermo, Italy. We searched for the presence of a BCG scar in 88 children, 49 boys and 39 girls (mean age 76+/-32 months), most of whom (98%) came from Eastern Europe. Presence of BCG scar was observed in 59 (67.1%) of them, included five children without any pre-adoptive medical records. Twenty-three out of 29 children without any evidence of BCG scar were tested by Mantoux. Seven (30.4%) of 23 were tuberculin positive and diagnosed as having latent tuberculosis infection. We also examined immunization status against poliovirus 1-3, tetanus, diphtheria, pertussis, measles, mumps, rubella and hepatitis B of 70 internationally adopted children and we compared it with the pre-adoptive immunization records of their birth country. Protective titers (>1:8) against poliovirus 1-3, were found respectively in 67.1%, 91.4%, 42.8% of 70 immunized children, and only 38.5% of them had at the same time full protection against all three types of poliovirus. Protective titers against tetanus and diphtheria were found in 91.4% and 95.7% of 70 vaccinated children. Presence of antibodies against pertussis, measles, mumps and rubella was observed respectively in 16 (32.6%) of 49, 40 (62.5%) of 64, 28 (56%) of 50 and 24 (85.7%) of 28 children who had received the vaccine. As regards hepatitis B, only 20 of 29 vaccinated children had detectable hepatitis B surface antibodies, while four of 29 vaccinated and two of 41 not vaccinated children were positive for both hepatitis B surface antibodies and hepatitis B core antibodies. Finally three of 41 not vaccinated children were both hepatitis B surface antigen and hepatitis B core antibodies positive. No relation was found between health status and immunization and between age and antibody positiveness of vaccinated children except for hepatitis B, therefore the youngest immunized children were more likely to be hepatitis B surface antibodies positive. Our data suggest that internationally adopted children should be tested for their immunization status on arrival in the adopting country, because they are not protected in a sufficient way against vaccine-preventable diseases and their pre-adoptive immunization records sometimes are lacking and frequently are scarcely reliable.

The authors have recently reported that celiac patients show a proinflammatory cytokine genetic profile characterized by the contemporaneous presence of both the tumour necrosis factor-alpha-308A and the interferon-gamma +874T allele-positive genotypes. The same alleles are considered risk factors for aging associated disease, whereas an anti-inflammatory cytokine genotype profile might be associated with an extended life expectancy. This paper reports data on the 1249-1250InsACAA/Non-Ins transforming growth factor (TGF)-beta2, a multifunctional anti-inflammatory cytokine, polymorphism distribution in 88 celiac disease (CD) patients, 99 age- and sex-matched controls, and 28 >95-year-old healthy subjects living in western Sicily. These data demonstrate that genotype frequencies of CD patients are not different from that of age-matched and >95-year-old healthy control subjects. These data might suggest that TGF-beta2 polymorphism is not involved in the complex genotypes associated with successful or unsuccessful aging. In addition, one can speculate that the genotype profile associated with CD susceptibility might be detrimental for longevity, and studies of this CD genetic asset might point to a candidate gene for antiaging strategies.

Children adopted from abroad by Italian families have increased during the last years. Since 2001 to 2004 they have been more than 10,000, mainly from Eastern Europe, and all indications suggest that they will continue to increase. Most of the internationally adopted children reside in orphanage before adoption where they may experience malnutrition, exposure to infectious diseases, environmental deprivation, neglect. Moreover, their pre-adoptive records are scarcely reliable and their immunization status is not always adequate. The most common long-term problems of internationally adopted children concern developmental and scholastic delay especially if they come from a long and severely deprived institutional setting, precocious puberty and, during adolescence, depressive disorders as well as antisocial behaviours. Inter-country adopted children are at increased risk for health and social problems and have to be recognized as a group of subjects requiring special medical attentions. Specialized centres for internationally adopted children where they could receive medical evaluations upon arrival and a prolonged health follow-up should be set up.

Background: In Down syndrome there is an increased prevalence of coeliac disease, but the reasons for this association are yet unknown., Aims: To evaluate a possible correlation between TNFalpha, IFNgamma and IL-10 genotype polymorphisms with the susceptibility to coeliac disease in Down syndrome patients., Methods: Single nucleotide polymorphisms of TNFalpha (-308G-->A promoter region), IFNgamma (+874T-->A promoter region) and IL-10 (-1082G-->A promoter region) have been studied in 10 Down patients with coeliac disease, in 40 Down patients without coeliac disease and in 220 healthy controls. Clinical features were also studied in coeliac disease-Down syndrome patients., Results: The 10 coeliac disease-Down syndrome patients had a biopsy proven coeliac disease afterward a serological testing positive to antigliadin, antiendomysium and antitransglutaminase antibodies. Intestinal biopsy showed total atrophy in 6/10 and partial villous atrophy in 4/10 of them. All coeliac disease-Down syndrome patients had silent forms of coeliac disease and classical trisomy 21. No significant differences were observed for the IFNgamma and IL-10 polymorphisms in the studied groups. A significant trend for increase of TNFalpha -308A positive frequency was observed in coeliac disease-Down syndrome patients compared to healthy controls (p=0.043)., Conclusions: Single nucleotide polymorphisms of IFNgamma and IL-10 do not play a role in predisposing Down syndrome patients to coeliac disease, while the TNFalpha -308 allele could be an additional genetic risk factor for coeliac disease in trisomy 21.

Background: Coeliac disease is associated with DQ2 and DQ8 alleles, but other genes also confer an additional genetic risk., Aims: Defining whether the genetic profiles of interleukin-10, tumour necrosis factor alpha and interferon gamma are associated with an increased coeliac disease risk., Patients and Methods: The functionally gene polymorphisms of tumour necrosis factor alpha (-308G/A), interferon gamma (+874T/A) and interleukin-10 (-1082G/A) were typed using sequence specific primer-polymerase chain reaction in 110 Sicilian coeliac disease patients and in 220 Sicilian healthy controls., Results: No differences in genotype frequencies of interleukin-10 polymorphisms were found between coeliac disease patients and healthy controls. A significant increase of -308A (p<0.033; OR: 1.72; CI: 1.27-2.33) and of +874T (p: 0.0045; OR: 3.02; CI: 1.47-6.21) allele frequencies, both in hetero- and homozygosis, was observed in coeliac patients in comparison with healthy controls. In addition, simultaneous significant higher percentages of -308A and +874T alleles (p: 0.0066; OR: 2.33; CI: 1.42-3.82) as well as simultaneous significant lower percentages of -308A and +874T alleles (p: 0.003; OR: 0.23; CI: 0.10-0.60) were observed in coeliac patients compared with healthy controls., Conclusions: Genetically determined higher frequencies of -308A tumour necrosis factor alpha and +874T interferon gamma alleles, both in hetero and in homozygosis and mostly whether simultaneous, may play a role in predisposing to gluten intolerance. Subjects positive for -308A tumour necrosis factor alpha and +874T interferon gamma alleles have an increased risk for coeliac disease.

The pseudofirst-order ozonization rate constant of whole bovine blood has been measured in comparison to that of free haemin. The free prosthetic group haemin (which has also the central iron atom in the oxidized form) shows k values in the range of 0.20-0.03 s(-1) while the haeme groups inside haemoglobin protein and contained in the whole blood sample show slightly lower k values, just in the range of 0.10-0.02 s(-1). It has been found that ozone even with whole blood reacts specifically with haemoglobin of the red cells because it is adsorbed selectively on the iron atoms of the haeme prosthetic groups of haemoglobin. The absorption implies the oxidation of the central iron atom of the haeme groups with formation of methaemoglobin followed by an oxidative fission of the haeme rings. The other blood components do not exert any significant protection to the reaction between ozone and haemoglobin, which appear extremely specific and selective like the reaction between CO or HCN and haemoglobin. By analogy with the behaviour of these other gases ozone may be classified as a blood poison. The results of this work are discussed in the frame of the risks connected to the ozonotherapy and autohaemotherapy involving the blood ozonization of human or animal subjects and the re-injection of ozonized blood into the bodies.

Background: There are no available data concerning the incidence and the clinical pattern of coeliac disease in immigrant children coming to Italy from developing countries., Aims: To evaluate the epidemiological and clinical features of coeliac immigrant children coming to Italy., Patients and Methods: Hospital records of 1917 children diagnosed in 22 Italian Centres from 1999 to 2001 as having coeliac disease were retrospectively reviewed, comparing immigrant patients versus Italian ones., Results: 36/1917 (1.9%) coeliac children were immigrant. This prevalence was similar to that of the immigrant children among the whole paediatric population living in Italy. Prevalence was influenced by geographical factors, being higher in Northern Italy (1.7%) and in Central Italy (2.5%) than in Southern-Insular Italy (1.5%), as consequence of a higher proportion of immigrants in these regions. The native areas of the immigrant children were East Europe (15/36), Northern Africa (14/36), Southern Asia (4/36), West Africa (1/36), East Africa (1/36) and the Middle East (1/36). The clinical spectrum and dietary habits in immigrant patients were similar to those of the Italian children., Conclusions: Coeliac disease among the immigrant children coming from developing countries is an emerging problem, and physicians need to be fully aware of it. An important risk factor for coeliac disease in immigrant children appears to be sharing of the same dietary habits with the Italian population. The finding of coeliac disease in children coming from many countries worldwide suggests that coeliac disease is a global public health problem.

Background: In Burkina Faso, in contrast with high rates of Helicobacter pylori infection from an early age, the prevalence of H. pylori-associated diseases (ulcer and gastric cancer) is low., Aims: To look for the prevalence of H. pylori in healthy natives of Burkina Faso, both children and adults., Methods: We studied the prevalence of H. pylori infection in 258 healthy natives of Burkina Faso (70 children aged 6 months-15 years and 188 adults aged 16-65 years), using a serological screening (IgA and IgG H. pylori antibodies). All the studied subjects underwent a questionnaire regarding their life-style, socio-economic status, dietary habits and hygienic sanitary conditions. Data concerning the questionnaire were compared between H. pylori positive and negative subjects., Results: The rates of H. pylori positivity in children were significantly higher than in adults, and in adults the positivity for H. pylori infection decreased with increasing age. The comparison of the questionnaire's data between H. pylori seropositive and seronegative subjects showed that poor socio-economic status and hygienic sanitary conditions were similar in the two groups. Instead, a higher prevalence of H. pylori positivity was observed in subjects belonging to families living in close contact with sheep, because of their labour and agro-pastoral tradition (shepherds and sedentary farmers)., Conclusion: H. pylori infection in Burkina Faso is acquired early in life and is related not only to some yet well-known risk factors (poor socio-economic and hygienic status), but also to a close contact with sheep. The gradually decreasing H. pylori seropositivity in adult population of Burkina Faso represents an unexplained enigma, which needs further studies.