Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells.

Diruthenium tetracarbonyl complexes of the type [Ru2(CO)4(l2-g2-O2CR)2L2] containing a Ru-Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo [3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1-3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying an LD50 between 1.5 and 6.5 J/cm2 in these two cell lines and more than 15 J/cm2 for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizers.

Copper, selenium, and zinc status and balances after major trauma.

To investigate the trace elements (TE) losses and status after trauma, 11 severely injured patients (Injury Severity Score: 29 +/- 6), admitted to the ICU were studied from the day of injury (D0) until D25. Balance studies were started within 24 hours after injury, until D7. Serum and urine samples were collected from D1 to D7, then on D10, 15, 20, and 25. Intravenous TE supplementation was initiated upon admission. SERUM: Selenium (Se) and zinc (Zn) levels were decreased until D7 and were normal thereafter. LOSSES: TE urinary excretions were higher than reference ranges until D20 in all patients. Fluid losses through drains contained large amounts of TE. BALANCES: Balances were slightly positive for copper (Cu) and Zn, and negative for Se from D5 to D7 despite supplements. Cu status exhibited minor changes compared to those observed with the Zn and Se status: Serum levels were decreased and losses increased. Considering the importance of Se and Zn in free radical scavenging, anabolism, and immunity, current recommendations for TE supplements in severely traumatized patients ought to be revised.

NanoImpactNet - Stakeholders' knowledge needs for research on the health and environmental impact of nanomaterials

NanoImpactNet (NIN) is a multidisciplinary European Commission funded network on the environmental, health and safety (EHS) impact of nanomaterials. The 24 founding scientific institutes are leading European research groups active in the fields of nanosafety, nanorisk assessment and nanotoxicology. This 4−year project is the new focal point for information exchange within the research community. Contact with other stakeholders is vital and their needs are being surveyed. NIN is communicating with 100s of stakeholders: businesses; internet platforms; industry associations; regulators; policy makers; national ministries; international agencies; standard−setting bodies and NGOs concerned by labour rights, EHS or animal welfare. To improve this communication, internet research, a questionnaire distributed via partners and targeted phone calls were used to identify stakeholders' interests and needs. Knowledge gaps and the necessity for further data mentioned by representatives of all stakeholder groups in the targeted phone calls concerned: potential toxic and safety hazards of nanomaterials throughout their lifecycles; fate and persistence of nanoparticles in humans, animals and the environment; risks associated to nanoparticle exposure; participation in the preparation of nomenclature, standards, methodologies, protocols and benchmarks; development of best practice guidelines; voluntary schemes on responsibility; databases of materials, research topics and themes. Findings show that stakeholders and NIN researchers share very similar knowledge needs, and that open communication and free movement of knowledge will benefit both researchers and industry. Consequently NIN will encourage stakeholders to be active members. These survey findings will be used to improve NIN's communication tools to further build on interdisciplinary relationships towards a healthy future with nanotechnology.

Amniotic fluid insulin-like growth factor binding protein 3 concentration as early indicator of fetal growth restriction.

OBJECTIVE: Insulin-like growth factor-I (IGF-I) is an important regulator of fetal growth and its bioavailability depends on insulin-like growth factor binding proteins (IGFBPs). Genes coding for IGF-I and IGFBP3 are polymorphic. We hypothesized that either amniotic fluid protein concentration at the beginning of the second trimester or genotype of one of these two genes could be predictive of abnormal fetal growth. STUDY DESIGN: Amniotic fluid samples (14-18 weeks of pregnancy) from 123 patients with appropriate for gestational age (AGA) fetuses, 39 patients with small for gestational age (SGA) fetuses and 34 patients with large for gestational age (LGA) were analyzed. Protein concentrations were evaluated by ELISA and gene polymorphisms by PCR. RESULTS: Amniotic fluid IGFBP3 concentrations were significantly higher in SGA compared to AGA group (P=0.030), and this was even more significant when adjusted to gestational age at the time of amniocentesis and other covariates (ANCOVA analysis: P=0.009). Genotypic distribution of IGF-I variable number of tandem repeats (VNTR) polymorphism was significantly different in SGA compared to AGA group (P=0.029). 19CA/20CA genotype frequency was threefold decreased in SGA compared to AGA group and the risk of SGA occurrence of this genotype was decreased accordingly: OR=0.289, 95%CI=0.1-0.9, P=0.032. Genotype distribution of IGFBP3(A-202C) polymorphism was similar in all three groups. CONCLUSIONS: High IGFBP3 concentrations in amniotic fluid at the beginning of the second trimester are associated with increased risks of SGA while 19CA/20CA genotype at IGF-I VNTR polymorphism is associated with reduced risks of SGA. Neither IGFBP3 concentrations, nor IGF-I/IGFBP3 polymorphisms are associated with modified risks of LGA.

Replacing oxamniquine by praziquantel against Schistosoma mansoni infection in a rural community from the sugar-cane zone of Northeast Brazil: an epidemiological follow-up

A group of 52 villagers was followed-up for three years regarding Schistosoma mansoni infection. All villagers were periodically surveyed by the Kato-Katz method. In March 1997 and March 1998 the positives were treated with oxamniquine (15-20 mg/kg), and in March 1999, with praziquantel (60 mg/kg). All infection indices decreased substantially between March 1999 and March 2000: prevalence of infection (from 32.7% to 21.2%), prevalence of moderate/heavy infection (from 7.7% to 1.9%), intensity of infection (from 23.1 epg to 7.4 epg) and reinfection (from 35.7% to 14.3%). Negativation increased from 53.8 to 82.4. An optimistic prognostic is assumed in the short term for the introduction of praziquantel in the study area.

The effects of temperature change on the infection rate of Biomphalaria glabrata with Schistosoma mansoni

The aim of this study was to investigate the influence of temperature on the development of Schistosoma mansoni infections in Biomphalaria glabrata. The snails were infected at 15, 20, and 30ºC, and the cercarial release was analyzed after 30 and 60 days post-infection. Our results showed that a decrease in the temperature has a substantial influence on the development of S. mansoni infection in B. glabrata, with significant differences (p < 0.05) between 15 and 30ºC. These data could provide a better understanding of the epidemiological aspects of schistosomiasis.

Cervical screening: Frequently asked questions (FAQs)

Testing for high-risk human papillomavirus (HR-HPV) as triage and test of cure was introduced into the Northern Ireland Cervical Screening Programme on Monday 28 January 2013. This policy change will significantly alter the screening pathway for women with a mild dyskaryosis or borderline smear result. The link between HR-HPV infection and the development of cervical cancer has now been clearly established, with almost 100% of cervical cancers containing HPV DNA. Women with no evidence of HR-HPV infection are extremely unlikely to develop cervical cancer in the short to medium term. HPV triage is the process whereby HR-HPV testing is used to manage women with low grade cervical abnormalities. Only 15-20% of women with a borderline or mild smear result have a significant abnormality that needs treatment. HR-HPV testing is effective in identifying which women may need treatment and allows colposcopy resources to be allocated more effectively. The test of cure process is being introduced because it is now known that women with a normal or low grade smear test, and who are HR-HPV negative at six months after treatment, are at very low risk of residual disease. These women do not need to be recalled for another screening appointment for three years. The test of cure process means all post-treatment smears (at six months) that are reported as normal, borderline or mild dyskaryosis will be tested for HR-HPV. Those women who are HR-HPV positive will remain at colposcopy. HR-HPV negative women can be safely returned to recall in three years. It is estimated that the HR-HPV test of cure will allow approximately 80% of women who have been through treatment to avoid undergoing annual smear tests. These FAQs answer the most common and important queries in relation to HPV and the new screening process, and were distributed to all GPs in Northern Ireland. They can be downloaded as a PDF from this website.

Cervical screening programme: HPV triage and test of cure protocol

Testing for high-risk human papillomavirus (HR-HPV) as triage and test of cure was introduced into the Northern Ireland Cervical Screening Programme on Monday 28 January 2013. This policy change will significantly alter the screening pathway for women with a mild dyskaryosis or borderline smear result. The link between HR-HPV infection and the development of cervical cancer has now been clearly established, with almost 100% of cervical cancers containing HPV DNA. Women with no evidence of HR-HPV infection are extremely unlikely to develop cervical cancer in the short to medium term. HPV triage is the process whereby HR-HPV testing is used to manage women with low grade cervical abnormalities. Only 15-20% of women with a borderline or mild smear result have a significant abnormality that needs treatment. HR-HPV testing is effective in identifying which women may need treatment and allows colposcopy resources to be allocated more effectively.The test of cure process is being introduced because it is now known that women with a normal or low grade smear test, and who are HR-HPV negative at six months after treatment, are at very low risk of residual disease. These women do not need to be recalled for another screening appointment for three years.The test of cure process means all post-treatment smears (at six months) that are reported as normal, borderline or mild dyskaryosis will be tested for HR-HPV. Those women who are HR-HPV positive will remain at colposcopy. HR-HPV negative women can be safely returned to recall in three years. It is estimated that the HR-HPV test of cure will allow approximately 80% of women who have been through treatment to avoid undergoing annual smear tests. This flowchart poster outlines the new triage and test of cure process. It was distributed to all GPs in Northern Ireland and is available to download as a PDF from this website.�

Kälteresistenz und reversible Hypothermie der Etrskerspitzmaus (Suncus etruscus, Soricidae, Insectivora)

On a testé la sensibilité présumée aux basses températures de Suncus etruscus, le plus petit mammifère connu. Nourri à profusion, cette espèce a supporté des températures inférieures à 0° C. L'activité de l'animal (=absence du nid) à une température ambiante de 0-10° C s'élève en moyenne de 303min/24 h contre 358 min24 h à des températures de 15°-20° C. Si on retire toute nourriture à la musaraigne étrusque, celle-ci entre en hypothermie réversible et léthargique, de laquelle elle sort de temps en temps à la recherche de nourriture. En léthargie, la température corporelle est d'environ 2° C au dessus de la température ambiante. Avec 1 1/2 à 2 g de nourriture par jour et à la température ambiante de 16° à 18° C, les phases de léthargie durent de 1 1/2 à 2 h avec un maximum de 7 1/2h. En 24 h, un animal insuffisamment nourri montrait une activité totale de 205 min seulement. Pendant 696 min l'animal a dormi en conservant sa température "normale", et pendant 539 min il était en léthargie. L'hypothermie réversible chez un représentant des Soricidae s'explique probablement par une insuffisance de son métabolisme par rapport à sa taille minuscule. Comme les espèces du genre Sorex de taille voisine n'ont pas la possibilité d'entrer en léthargie réversible, cette adaptation particulière peut être considérée comme un indice d'un métabolisme relativement bas chez les Crocidurinae

Styles de vie, besoins de santé et utilisation des services de soins des adolescents porteurs d'affections chroniques

Résumé Contexte et objectifs Le premier volet a comme objectif d'évaluer la prévalence de l'affection chronique (AC) parmi les adolescents en Suisse, de décrire leurs comportements (loisirs, sexualité, conduites à risque) et de les comparer aux adolescents non porteur d'AC afin d'évaluer l'impact de l'AC sur leur bien-être. Le second volet a comme objectif d'explorer leur réseau de soutien, leur mode d'adaptation et leur perception de la prise en charge dont ils bénéficient par les équipes soignantes. Chacun des objectifs est traité dans un article : - « Chronic illness, life style and emotional health in adolescence: results of a cross-sectional survey on the health of 15-20-year-olds in Switzerland » Eur J Pediatr (2003) 162: 682-689 - « Adolescents porteurs d'affections chroniques: la parole aux patients » Med Hyg 2004 ; 62 : 2224-9. Méthode Première partie: les données ont été obtenues par analyse secondaire de l'enquête sur la santé des adolescents en Suisse, réalisée en 1993-1994 auprès d'un échantillon de 9268 jeunes de 15 à 20 ans (6% de la population visée), à l'aide d'un questionnaire auto administré de 100 questions environ. Le programme SPSS a été utilisé pour effectuer les analyses bi- et multi-variées. Seconde partie: la commission d'éthique de la Faculté de médecine de l'Université de Lausanne a donné son accord permettant la réalisation d'un focus group (discussion en petit groupe) de 12 jeunes. Ils ont participé à une discussion de 2 heures, conduite par un modérateur entraîné à cette méthode. Résultats Premier volet : 11.4% des filles et 9.6% des garçons se déclarent porteurs d'une AC. 25% des filles porteuses d'une AC (versus 13% de non porteur; p=0.007) et 38% des garçons porteurs d'une AC (versus 25% de non porteur; p=0.002) déclarent ne pas utiliser la ceinture de sécurité quand ils conduisent. 6.3% des filles (versus 2.7% ; p= 0.000) disent avoir conduit en étant ivres. 43% des filles (versus 36% ; p= 0.004) et 47% des garçons (versus 39% ; p=0.001) sent fumeurs de cigarettes. 32% des garçons (versus 27% p=0.02) rapportent avoir consommé du cannabis. 17% des filles (versus 13°h ; p=0.013) et 43% des garçons (versus 36% ; p= 0.002) disent boire de l'alcool. Le fait d'être porteur d'AC a aussi des conséquences psychologiques : 7.7% des filles (versus 3.4% ; p= 0.000) et 4.9% des garçons (versus 2% ; p=0.000) ont effectué un tentamen durant les 12 mois précédents. Deuxième volet: Sur oui peuvent-ils compter ? Avant tout sur eux-mêmes, puis sur leurs parents ou leurs amis. Les pairs, l'équipe soignante, les autres malades et les enseignants ont chacun des rôles à jouer à des moments précis de l'évolution de l'AC. Leurs modes d'adaptation: prendre du recul, faire preuve d'humour et demander de l'aide à leurs proches. Ils s'évadent dans l'écriture, les pensées ou la musique. Demande aux médecins une prise en charge globale qui permette une compréhension de l'ensemble de leurs besoins plutôt que focalisée seulement sur leur AC. Le respect, la possibilité d'un soutien et d'explications précises leur paraissent importants. Conclusions Les conduites dites à risque ne sont pas moins fréquentes chez les adolescents porteurs d'AC que chez leurs pairs Elles peuvent être expliquées par le besoin de tester leurs limites tant sur le plan des consommations que du comportement. Une prévention et une attention spécifiques des équipes soignantes sont nécessaires. Un réseau social diversifié paraît nécessaire aux jeunes souffrant d'AC. Les médecins devraient avoir une vision globale de leur patient, les aider à se situer dans le monde de l'adolescence, leur permettre de nommer leurs émotions et anticiper les questions difficiles à poser. Abstract The objective was to evaluate the prevalence of chronic conditions (CC) in adolescents in Switzerland; interval to describe their behaviour (leisure, sexuality, risk taking behaviour) and to compare them to those in adolescents who do not have CC in order to evaluate the impact of those conditions on their well-being. The data were obtained from the Swiss Multicentre Adolescent Survey Introduction on Health, targeting a sample of 9268 in-school adolescents aged 15 to 20 years, who answered a self-administered questionnaire. Some 11.4% of girls and 9.6% of boys declared themselves carriers of a CC. Of girls suffering from a CC, 25% (versus 13% of non carriers; P = 0.007) and 38% of boys (versus 25%; P=0.002) proclaimed not to wear a seatbelt whilst driving. Of CC girls, 6.3% (versus 2.7%; P= 0.000) reported within the last 12 months to have driven whilst drunk. Of the girls, 43% (versus 36%; P=0.004) and 47% (versus 39%; P=0.001) were cigarette smokers. Over 32% of boys (versus 27%; P=0.02) reported having ever used cannabis and 17% of girls (versus 13%; P=0.013) and 43% of boys (versus 36%; P=0.002) admitted drinking alcohol. The burden of their illness had important psychological consequences: 7.7% of girls (versus 3.4%; P=0.000) and 4.9% of boys (versus 2.0%; P=0.000) had attempted suicide during the previous 12 months. Conclusion: Experimental behaviours are not rarer in adolescents with a chronic condition and might be explained by a need to test their limits both in terms of consumption and behaviour. Prevention and specific attention from the health caring team is necessary.

Duality of the murine CD8 compartment.

CD8αβ plays crucial roles in the thymic selection, differentiation, and activation of some, but not all, CD8(+) T cells, whereas CD8αα does not. To investigate these roles, we produced mice that expressed transgene P14 T-cell receptor β (TCRβ) chain and CD8β or did not (WT and KO mice, respectively). The primary CD8(+) T-cell response to acute lymphocytic choriomeningitis virus (LCMV) infection was predominantly D(b)/GP33 specific and CD8 independent in KO mice and was mostly CD8 dependent in WT mice. Cytotoxic T lymphocytes (CTL) from KO mice failed to mobilize intracellular Ca(2+) and to kill via perforin/granzyme. Their strong Fas/FasL-mediated cytotoxicity and IFN-γ response were signaled via a Ca(2+)-independent, PI3K-dependent pathway. This was also true for 15-20% of CD8-independent CTL found in WT mice. Conversely, the perforin/granzyme-mediated killing and IFN-γ response of CD8-dependent CTL were signaled via a Ca(2+), p56(lck), and nuclear factor of activated T cells-dependent pathway. Deep sequencing of millions of TCRα chain transcripts revealed that the TCR repertoires of preimmune CD8(+) T cells were highly diverse, but those of LCMV D(b)/GP33-specific CTL, especially from KO mice, were narrow. The immune repertoires exhibited biased use of Vα segments that encoded different complementary-determining region 1α (CDR1α) and CDR2α sequences. We suggest that TCR from WT CD8-independent T cells may engage MHC-peptide complexes in a manner unfavorable for efficient CD8 engagement and Ca(2+) signaling but permissive for Ca(2+)-independent, PI3K-dependent signaling. This duality of the CD8 compartment may provide organisms with broader protective immunity.

Long-term outcome of congenital aortic valve stenosis: predictors of reintervention.

OBJECTIVES: To evaluate long-term outcome of initial aortic valve intervention in a paediatric population with congenital aortic stenosis, and to determine risk factors associated with reintervention. PATIENTS AND METHODS: From 1985 to 2009, 77 patients with congenital aortic stenosis and a mean age of 5.8±5.6 years at diagnosis were followed up in our institution for 14.8±9.1 years. RESULTS: First intervention was successful with 86% of patients having a residual peak aortic gradient 1 regurgitation increased by 7%. Long-term survival after the first procedure was excellent, with 91% survival at 25 years. At a mean interval of 7.6±5.3 years, 30 patients required a reintervention (39%), mainly because of a recurrent aortic stenosis. Freedom from reintervention was 97, 89, 75, 53, and 42% at 1, 10, 15, 20, and 25 years, respectively. Predictors of reintervention were residual peak aortic gradient (p=0.0001), aortic regurgitation post-intervention >1 (p=0.02), prior balloon aortic valvuloplasty (p=0.04), and increased left ventricular posterior wall thickness (p=0.1). CONCLUSIONS: Aortic valve intervention is a safe and effective procedure for congenital aortic stenosis with excellent survival results. However, rate of reintervention is high and influenced by increased left ventricular posterior wall thickness pre-intervention, prior balloon valvuloplasty, higher residual peak systolic valve gradient, and more than mild regurgitation post-intervention. The study highlights that long-term follow-up is recommended for these patients.

Interchange of callosal and association projections in the developing visual cortex.

Neurons projecting transitorily into the corpus callosum from area 17 of the cat were retrogradely labeled by the fluorescent tracer Fast Blue (FB) injected into contralateral areas 17 and 18 on postnatal days 1-5. During the second postnatal month these neurons were still labeled by the early injection, although they had eliminated their callosal axon. At this time, 15-20% of these neurons could be retrogradely relabeled by injections of Diamidino Yellow (DY) into ipsilateral areas 17 and 18, but few or none by similar injections in the other areas that receive from area 17 (19, 21a, PMLS, 20a, 20b, DLS). Similarly, area 17 neurons projecting transitorily to contralateral area PMLS during the first postnatal week could be relabeled by DY injections in ipsilateral areas 17 and 18 but not in PMLS. Already around birth, many transitorily callosal neurons in area 17 send bifurcating axons both to contralateral areas 17 and 18 and ipsilateral area 18. It is probable that during postnatal development some of these neurons selectively eliminate their callosal axon collaterals and maintain the projection to ipsilateral area 18. In fact, some transitorily callosal neurons in area 17 can be double-labeled by simultaneous perinatal injections of FB in contralateral areas 17 and 18 and of a new long-lasting retrograde tracer, rhodamine-conjugated latex microspheres, in ipsilateral area 18. The same neurons can then be relabeled by reinjecting ipsilateral area 18 with DY during the second postnatal month. This finding, however, does not exclude the possibility that some transitorily callosal neurons send an axon to ipsilateral area 18 after eliminating their callosal axon. In conclusion, area 17 neurons that project transitorily through the corpus callosum later participate, probably permanently, in ipsilateral corticocortical projections but selectively to areas 17-18. The mechanism responsible for this selectivity is unknown, but it may be related to the differential radial distribution (i.e., to birth date) of area 17 neurons engaged in the various corticocortical projections. The problems raised by the use of long-lasting retrograde fluorescent tracers in neurodevelopmental studies and by the quantification of results of double- and triple-labeling paradigms are also discussed.