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Recent reports show a correlation between haemophilia and osteoporosis. HIV, HCV and their treatments are independently associated with an increased risk of osteoporosis. Vitamin D plays a pivotal role in bone mineralization. The aim of our study was to compare Vitamin D levels, bone metabolism markers and bone mineral density ( BMD) in patients with haemophilia with or without co-infections. Seventy-eight adult patients with severe or moderate haemophilia A or B were subdivided into three groups of 26 patients each ( HIV- HCV co-infected, HCV mono-infected and uninfected). The BMD was measured by dual energy X-ray absorptiometry ( DXA) at both the femoral area (F) and lumbar spine (L). This was correlated to laboratory values and haemophilic arthropathy was assessed using validated clinical and radiological scores. The DXA showed a homogeneous F- BMD reduction in all the three groups, whereas L- BMD was significantly lower in co-infected patients ( P < 0.05). The clinical score was higher in co-infected ( P < 0.002) and mono-infected ( P < 0.006). The radiological score was higher in mono-infected than in the other two groups ( P < 0.001). Overall 25-hydroxyvitamin D (25-OH Vit D) was reduced (87%). Bone-specific alkaline phosphatase (b- ALP) and telopeptide were increased in co-infected ( P < 0.001 and P < 0.01) and mono-infected ( P < 0.001 and P < 0.02). The result of the homogeneous F- BMD reduction in all groups could be explained by the pivotal role of arthropathy; the lower L- BMD in co-infected and the increase of b- ALP and telopeptide in co-infected and mono-infected groups suggest faster bone metabolism in case of infections. [ABSTRACT FROM AUTHOR]

Shear stress has been shown to influence endothelial cell gene expression and morphology. In particular, low and bi-directional shear stress, mimicking conditions at plaque-prone areas, down-regulates the expression of several atheroprotective genes, and up-regulates that of other genes considered as pro-inflammatory. Another mechanical situation thought to have a negative influence on vascular functions is arterial stiffness. Loss of arterial compliance occurs during ageing, in diabetic as well as in hypertensive patients. In this work we investigated the effects of these two particular hemodynamic environments (bi-directional shear stress and reduced compliance), using a recently developed perfusion system allowing to expose native arteries in vitro to complex hemodynamic environments. We were able to show that both plaque-prone shear stress and reduced compliance trigger endothelial dysfunction, but via different mechanisms. Only reduced compliance affected vascular contractility, inducing a dedifferentiation of smooth muscle cells and a consequent loss of norepinephrine sensitivity. [ABSTRACT FROM AUTHOR]

Human leishmaniasis is facing important epidemiological changes in Southern Europe, driven by increased urbanization, climate changes, emerging of new animal reservoirs, shifts in human behavior and a growing population of immunocompromised and elderly individuals. In this evolving epidemiological landscape, we analyzed the clinical and epidemiological characteristics of human leishmaniasis in the Tuscany region of Central Italy. Through a multicentric retrospective analysis, we collected clinical and demographic data about all cases of leishmaniasis recorded between 2018 and 2023. We observed 176 cases of human leishmaniasis, with 128 (72.7%) visceral leishmaniasis (VL) and 47 (26.7%) cutaneous leishmaniasis (CL). Among these, 92.2% of VL and 85.1% of CL cases were autochthonous. The cumulative incidence of autochthonous human leishmaniasis was 0.22 cases per 100,000 inhabitants in 2018, but reached 1.81/100,000 in 2023. We identified three main areas of transmission: around the city of Florence (North-East Tuscany), around Grosseto city (South-West Tuscany) and Elba Island. Our findings confirm that the epidemiology of leishmaniasis is undergoing significant changes in Central Italy. Awareness towards this emerging health threat and surveillance strategies need to be improved in order to reliably assess the disease's burden. Further research is needed in a "One-Health" perspective, to clarify the epidemiological dynamics at the environmental, reservoir, vector and human levels. The role of climate change and specific climatic factors affecting the epidemiological patterns of human leishmaniasis should be assessed. Further knowledge in these fields would promote targeted control and prevention strategies at regional and national levels.

Pertussis vaccination coverage in the Marche region is one of the lowest in Italy, with the province of Pesaro-Urbino remaining stable below 95% coverage since at least 2013. In this paper, we retrospectively analyzed all whooping cough notification cards arriving at the prevention department of the Area Vasta 1 Health Office in the Marche region and relating to the Pesaro-Urbino province (Italy). Between 2012 and 2017, there were 28 reported cases of pertussis with a peak in 2016 (11 cases, of which seven were in Urbino). The 28 patients were mostly male (65%), and had a mean age of 9 years. Three of these were not Italian. Between 2012 and 2017, the district of Pesaro reported the highest number of cases (almost 46.5% of the total), followed by Urbino (28.5%) and Fano (25%). The average incidence in the province in the period in question, still under 2 cases/100,000 inhabitants, arrived in 2016 at 4 cases/100,000 inhabitants. In particular, in Urbino there was an unforeseen incidence >8 cases/100,000 inhabitants. There were no deaths, although two children (both under 12 months of age) were hospitalized. Our data confirm that in 2016 there was a pertussis epidemic in Urbino (Italy).

Pertussis is a contagious, infectious disease that affects mainly children and is caused by Bordetella pertussis. The pertussis vaccine has changed the epidemiology of the disease up to the point when it almost vanished, with a minimum number of cases recorded in Italy (2008) when vaccination coverage was 97%. For the same reason the natural history of the disease was also modified. Indeed, in high-income countries the lack of immunity acquired with the vaccine causes adolescents and adults to become an important source of infection for unvaccinated subjects, the newborn and children who have not completed their primary education. The reduction in the vaccinated pediatric population and the loss of acquired immunity could be the cause of the re-emergence of a disease which, in developing countries, has a 4% mortality rate among children under one year of age. In this work we describe three cases of pertussis that are apparently unrelated. They occurred in the area of Urbino in a period of slightly under a month. Italy is going through a historical moment of great suspicion regarding pediatric vaccination, despite scientific evidence that should allay such suspicion. To increase people's awareness of vaccinations with a view to comments made regarding older children and adults it is our view that more effective intervention methods are needed.

Background: Since the Commission on Health Research for Development (COHRED) published its flagship report, more attention has been focused on strengthening national health research systems (NHRS). This paper evaluates the contribution of a regional project that used a participatory approach to strengthen NHRS in four post-conflict West African countries - Guinea-Bissau, Liberia, Sierra Leone and Mali., Methods: The data from the situation analysis conducted at the start of the project was compared to data from the project's final evaluation, using a hybrid conceptual framework built around four key areas identified through the analysis of existing frameworks. The four areas are governance and management, capacities, funding, and dissemination/use of research findings., Results: The project helped improve the countries' governance and management mechanisms without strengthening the entire NHRS. In the four countries, at least one policy, plan or research agenda was developed. One country put in place a national health research ethics committee, while all four countries could adopt a research information management system. The participatory approach and support from the West African Health Organisation and COHRED were all determining factors., Conclusion: The lessons learned from this project show that the fragile context of these countries requires long-term engagement and that support from a regional institution is needed to address existing challenges and successfully strengthen the entire NHRS.

Background: Identifying research priorities is key to innovation and economic growth, since it informs decision makers on effectively targeting issues that have the greatest potential public benefit. As such, the process of setting research priorities is of pivotal importance for favouring the science, technology, and innovation (STI)-driven development of low- and middle-income countries., Methods: We report herein on a major cross-sectoral nationwide research priority setting effort recently carried out in Tanzania by the Tanzania Commission for Science and Technology (COSTECH) in partnership with the Council on Health Research for Development (COHRED) and the NEPAD Agency. The first of its type in the country, the process brought together stakeholders from 42 sub-sectors in science, technology, and health. The cross-sectoral research priority setting process consisted of a 'training-of-trainers' workshop, a demonstration workshop, and seven priority setting workshops delivered to representatives from public and private research and development institutions, universities, non-governmental organizations, and other agencies affiliated to COSTECH., Results: The workshops resulted in ranked listings of research priorities for each sub-sector, totalling approximately 800 priorities. This large number was significantly reduced by an expert panel in order to build a manageable instrument aligned to national development plans that could be used to guide research investments., Conclusions: The Tanzania experience is an instructive example of the challenges and issues to be faced in when attempting to identify research priority areas and setting an STI research agenda in low- and middle-income countries. As countries increase their investment in research, it is essential to increase investment in research management and governance as well, a key and much needed capacity for countries to make proper use of research investments.

Objective: Understand and analyze procedures used to create national integrated research agendas from 2007 to 2011 in Argentina, Guatemala, Mexico, Panama, and Paraguay., Methods: Descriptive, cross-sectional study using an online survey of agenda preparation processes; specifically, development, integration, implementation, and use and dissemination of the agenda., Results: The 45 respondents reported following specific methodologies for agenda construction and had a good opinion of organizational aspects with regard to prior information provided and balance among disciplines and stakeholders. Some 60% considered the coordinators impartial, although 25% mentioned biases favoring some subject; 42% received technical support from consultants, reading matter, and methodological guidelines; 40% engaged in subject-matter priority-setting; and 55% confirmed dissemination and communication of the agenda. However, only 22% reported inclusion of agenda topics in national calls for research proposals., Conclusions: In the countries studied, development of the health research agenda was characterized by prior planning and appropriate organization to achieve - consensus-based outcomes. Nevertheless, the agendas were not used in national calls for research proposals, reflecting lack of coordination in national health research systems and lack of connection between funders and researchers. It is recommended that stakeholders strengthen integration and advocacy efforts to modify processes and structures of agenda-based calls for research proposals.

Background: There is a keen interest to develop research systems and increase research output in the 14 Pacific Island Forum Countries (PIFC) to support development of policies and practice based on locally relevant research evidence., Aims: To assess the quantity and characteristics of reproductive health research output by each country (14 PIFC) from 2000 to 2011 using New Zealand's reproductive research outputs as the reference., Methods: A systematic search of the literature using a broad definition of reproductive health., Results: There were 174 papers published in the PIFC from 2000 to 2011 compared with 628 papers published in New Zealand (NZ). Most (57%) of the PIFC papers were from Papua New Guinea (PNG), although Samoa had the most papers by population (10/100,000). Five of the countries did not have a single publication. The majority of papers from both the PIFC and NZ were observational studies (72 vs 36%). Authors from Australia were responsible for 34% of PIFC publications followed by 25% from PNG. Sixty-three per cent of papers by PIFC sole and first authors were published in local journals, whereas 86% of non-PIFC authors published in international journals., Conclusion: There is a need for reproductive research in PIFC. PNG had the most publications on the back of a well-funded dedicated research institute and a significant collaboration with Australian researchers. The large number of papers in PIFC countries without PIFC authors raises the question about the need to require non-PIFC researchers to enter into genuine research partnerships in order to build research capacity in the PIFC., (© 2013 The Authors ANZJOG © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Hemodynamic forces play an active role in vascular pathologies, particularly in relation to the localization of atherosclerotic lesions. It has been established that low shear stress combined with cyclic reversal of flow direction (oscillatory shear stress) affects the endothelial cells and may lead to an initiation of plaque development. The aim of the study was to analyze the effect of hemodynamic conditions in arterial segments perfused in vitro in the absence of other stimuli. Left common porcine carotid segments were mounted into an ex vivo arterial support system and perfused for 3 days under unidirectional high and low shear stress (6 +/- 3 and 0.3 +/- 0.1 dyn/cm(2)) and oscillatory shear stress (0.3 +/- 3 dyn/cm(2)). Bradykinin-induced vasorelaxation was drastically decreased in arteries exposed to oscillatory shear stress compared with unidirectional shear stress. Impaired nitric oxide-mediated vasodilation was correlated to changes in both endothelial nitric oxide synthase (eNOS) gene expression and activation in response to bradykinin treatment. This study determined the flow-mediated effects on native tissue perfused with physiologically relevant flows and supports the hypothesis that oscillatory shear stress is a determinant factor in early stages of atherosclerosis. Indeed, oscillatory shear stress induces an endothelial dysfunction, whereas unidirectional shear stress preserves the function of endothelial cells. Endothelial dysfunction is directly mediated by a downregulation of eNOS gene expression and activation; consequently, a decrease of nitric oxide production and/or bioavailability occurs.

Background: The aim of this study was to analyze the arterial wall response to plaque-prone hemodynamic environments, known to occur mainly in areas of arterial trees such as bifurcations and branching points. In these areas, the vasculature is exposed to cyclically reversing flow that induces an endothelial dysfunction predisposing thus arteries to local development of atherosclerotic plaques., Methods: We used an ex vivo perfusion system that allows culturing arterial segments under different hemodynamic conditions. Porcine carotid arteries were exposed for 3 days to unidirectional high and low shear stress (6 +/- 3 and 0.3 +/- 0.1 dyn/cm(2)) as well as to oscillatory shear stress (0.3 +/- 3 dyn/cm(2)). This latter condition mimics the hemodynamics present at plaque-prone areas. At the end of the perfusion, the influence of different flow patterns on arterial metabolism was assessed in terms of matrix turnover as well as of smooth muscle cell function, differentiation and migration., Results: Our results show that after 3 days of perfusion none of the applied conditions influence smooth muscle cell phenotype retaining their full contraction capacity. However, an increase in the expression level of matrix metalloproteinase-2 and -9, as well as a decrease in plasminogen activator inhibitor-1 expression were observed in arteries exposed to oscillatory shear stress when compared to arteries exposed to unidirectional shear stress., Conclusion: These observations suggest that plaque-prone hemodynamic environment triggers a vascular wall remodelling process and promotes changes in arterial wall metabolism, with important implication in atherogenesis.

Objective: Vascular remodeling is an adaptive response to variations in the hemodynamic environment acting on the arterial wall. Remodeling translates into changes of structure, geometry and mechanical properties of the artery. Our aim was to study the remodeling response of pig right common carotid arteries in vitro., Methods: In vivo right carotid arteries are exposed to a non-uniform hemodynamic environment and exhibit a strong wall asymmetry in the circumferential direction that allows the study of two regions separately, as the artery remodels under in vitro perfusion. Porcine right common carotid arteries were cultured during 1 day (n = 6), 3 days (n = 6) or 8 days (n = 6) in an in vitro organ culture system, at a constant perfusion pressure of 100 mmHg. Geometrical, histological, biomechanical and biological analysis of the perfused segments was performed at the end of each study., Results: Smooth muscle cell nuclei density and wall thickness remain constant along the culture periods. Elastin and collagen are significantly redistributed to equilibrate their relative content along the vessel circumference. The distensibility profile is significantly different at day 8. Matrix metalloproteinase-2 expression and activity increase significantly at days 3 and 8., Conclusion: The non-axisymmetric arterial wall adapts to a uniform hemodynamic environment by redistributing the structural components of the extracellular matrix. The changes of collagen and elastin density may result from a vascular remodeling process involving matrix metalloproteinase-2 up-regulation and enzymatic activity. The remodeling response results in a new vascular wall configuration that is more distensible at physiological pressures (30-120 mmHg) and stiffer at higher pressures.

Previous research in arterial remodeling in response to changes in blood pressure seldom included both hyper- and hypotension. To compare the effects of low and high pressure on arterial remodeling and vascular smooth muscle tone and performance, we have utilized an in vitro model. Porcine carotid arteries were cultured for 3 days at 30 and 170mmHg and compared to controls cultured at 100mmHg for 1 and 3 days. On the first and last day of culture, pressure-diameter and pressure-wall thickness curves were measured under normal smooth muscle tone using a high-resolution ultrasonic device. Last-day experiments included measurements where vascular smooth muscle was contracted or totally relaxed. From the data wall cross-sectional area, Hudetz elastic modulus and a contraction index related to the diameter reduction under normal smooth muscle tone were calculated. We found that although wall cross-sectional area (indicating wall mass) did not change much, Hudetz elastic modulus was significantly reduced in the 3-day hypotension group. Inspection of the wall contraction index suggests that this is due to a reduction in the vascular smooth muscle tone. Further, the peak of contraction index was found to be shifted to higher pressures in the 3-day 170mmHg group. We conclude that vascular smooth muscle performance adapts to both hypo- and hypertension at short time scales and can alter the biomechanics of the vascular wall in vitro.