Microwave assisted synthesis of heterometallic 3d-4f M4Ln complexes

In this paper we describe the synthesis and magnetic properties of a series of 3d-4f complexes of general formula [M4Ln(OH)2(chp)4(SALOH)5(H2O)(MeCN)(Solv)] (Solv = MeOH, MeCN, H2O; chp stands for deprotonated 6-chloro-2-hydroxypyridine (C5H3ClNO), SALOH stands for monodeprotonated 3,5-ditert-butylsalicylic acid (C15H21O3)) obtained by a solvent-free microwave assisted synthesis method. The Ni(II) complexes (Ni4Gd, Solv = MeOH; Ni4Dy, Solv = MeCN) are not SMMs in the absence of an applied dc field. The replacement of Ni(II) by Co(II) (Co4La, Solv = MeOH; Co4Gd, Solv = H2O; Co4Gd-MeCN, Solv = MeCN; Co4Tb, Solv = MeOH; Co4Dy, Solv = H2O) results in improved SMM properties

Solvation-guided design of fluorescent probes for discrimination of amyloids

The deposition of insoluble protein aggregates in the brain is a hallmark of many neurodegenerative diseases. While their exact role in neurodegeneration remains unclear, the presence of these amyloid deposits often precedes clinical symptoms. As a result, recent progress in imaging methods that utilize amyloid-specific small molecule probes have become a promising avenue for antemortem disease diagnosis. Here, we present a series of amino-aryl cyanoacrylate (AACA) fluorophores that show a turn-on fluorescence signal upon binding to amyloids in solution and in tissue. Using a theoretical model for environmental sensitivity of fluorescence together with ab initio computational modeling of the effects of polar environment on electron density distribution and conformational dynamics, we designed, synthesized, and evaluated a set of fluorophores that (1) bind to aggregated forms of Alzheimer's-related beta-amyloid peptides with low micromolar to high nanomolar affinities and (2) have the capability to fluorescently discriminate different amyloids based on differences in amino acid composition within the binding pocket through exploitation of their solvatochromic properties. These studies showcase the rational design of a family of amyloid-binding imaging agents that could be integrated with new optical approaches for the clinical diagnosis of amyloidoses, where accurate identification of the specific neurodegenerative disease could aid in the selection of a proper course for treatment

Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) that express the F4ab and F4ac fimbriae is a major contributor to diarrhoea outbreaks in the pig breeding industry, infecting both newborn and weaned piglets. Some pigs are resistant to this infection, and susceptibility is inherited as a simple dominant Mendelian trait. Indentifying the genetics behind this trait will greatly benefit pig welfare as well as the pig breeding industry by providing an opportunity to select against genetically susceptible animals, thereby reducing the number of diarrhoea outbreaks. The trait has recently been mapped by haplotype sharing to a 2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes. FINDINGS: The coding regions of five candidate genes for susceptibility to ETEC F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5 Mb region, were investigated for the presence of possible causative mutations. A total of 34 polymorphisms were identified in either coding regions or their flanking introns. The genotyping data for two of those were found to perfectly match the genotypes at the ETEC F4ab/ac locus, a G to C polymorphism in intron 11 of TFRC and a C to T silent polymorphism in exon 22 of KIAA0226. Transcriptional profiles of the five genes were investigated in a porcine tissue panel including various intestinal tissues. All five genes were expressed in intestinal tissues at different levels but none of the genes were found differentially expressed between ETEC F4ab/ac resistant and ETEC F4ab/ac susceptible animals in any of the tested tissues. CONCLUSIONS: None of the identified polymorphisms are obvious causative mutations for ETEC F4ab/ac susceptibility, as they have no impact on the level of the overall mRNA expression nor predicted to influence the composition of the amino acids composition. However, we cannot exclude that the five tested genes are bona fide candidate genes for susceptibility to ETEC F4ab/ac infection since the identified polymorphism might affect the translational apparatus, alternative splice forms may exist and post translational mechanisms might contribute to disease susceptibility

Community health workers for ART in sub-Saharan Africa: learning from experience – capitalizing on new opportunities

Low-income countries with high HIV/AIDS burdens in sub-Saharan Africa must deal with severe shortages of qualified human resources for health. This situation has triggered the renewed interest in community health workers, as they may play an important role in scaling-up antiretroviral treatment for HIV/AIDS by taking over a number of tasks from the professional health workers. Currently, a wide variety of community health workers are active in many antiretroviral treatment delivery sites

Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study

BACKGROUND: Several countries are discussing new legislation on the ban of smoking in public places, and on the acceptable levels of traffic-related air pollutants. It is therefore useful to estimate the burden of disease associated with indoor and outdoor air pollution. METHODS: We have estimated exposure to Environmental Tobacco Smoke (ETS) and to air pollution in never smokers and ex-smokers in a large prospective study in 10 European countries (European Prospective Investigation into Cancer and Nutrition)(N = 520,000). We report estimates of the proportion of lung cancers attributable to ETS and air pollution in this population. RESULTS: The proportion of lung cancers in never- and ex-smokers attributable to ETS was estimated as between 16 and 24%, mainly due to the contribution of work-related exposure. We have also estimated that 5-7% of lung cancers in European never smokers and ex-smokers are attributable to high levels of air pollution, as expressed by NO2 or proximity to heavy traffic roads. NO2 is the expression of a mixture of combustion (traffic-related) particles and gases, and is also related to power plants and waste incinerator emissions. DISCUSSION: We have estimated risks of lung cancer attributable to ETS and traffic-related air pollution in a large prospective study in Europe. Information bias can be ruled out due to the prospective design, and we have thoroughly controlled for potential confounders, including restriction to never smokers and long-term ex-smokers. Concerning traffic-related air pollution, the thresholds for indicators of exposure we have used are rather strict, i.e. they correspond to the high levels of exposure that characterize mainly Southern European countries (levels of NO2 in Denmark and Sweden are closer to 10-20 ug/m3, whereas levels in Italy are around 30 or 40, or higher).Therefore, further reduction in exposure levels below 30 ug/m3 would correspond to additional lung cancer cases prevented, and our estimate of 5-7% is likely to be an underestimate. Overall, our prospective study draws attention to the need for strict legislation concerning the quality of air in Europe

Prevalence of urinary incontinence in Andorra: impact on women's health.

BACKGROUND: Urinary incontinence (UI) is a frequent public health problem with negative social consequences, particularly for women. Female susceptibility is the result of anatomical, social, economic and cultural factors. The main objectives of this study are to evaluate the prevalence of UI in the female population of Andorra over the age of 15 and, specifically, to determine the influence of socio-demographic factors. A secondary aim of the study is to measure the degree of concern associated with UI and whether the involved subjects have asked for medical assistance, or not. METHODS: Women aged 15 and over, answered a self-administered questionnaire while attending professional health units in Andorra during the period November 1998 to January 2000. A preliminary study was carried out to ensure that the questionnaire was both understandable and simple. RESULTS: 863 completed questionnaires were obtained during a one year period. The breakdown of the places where the questionnaires were obtained and filled out is as follows: 32.4% – medical specialists' offices; 31.5% – outpatient centres served exclusively by nurses; 24% – primary care doctors' offices; 12% from other sources. Of the women who answered the questionnaire, 37% manifested urine losses. Of those,45.3% presented regular urinary incontinence (RUI) and 55.7% presented sporadic urinary incontinence (SporadicUI). In those women aged between 45 and 64, UI was present in 56% of the subjects. UI was more frequent among parous than non-parous women. UI was perceived as a far more bothersome and disabling condition by working, middle-class women than in other socio-economic groups. Women in this particular group are more limited by UI, less likely to seek medical advice but more likely to follow a course of treatment. From a general point of view, however, less than 50% of women suffering from UI sought medical advice. CONCLUSION: The prevalence of UI in the female population of Andorra stands at about 37%, a statistic which should encourage both health professionals and women to a far greater awareness of this condition