De l’agressivité à la maternité. Étude longitudinale sur 30 ans auprès de filles agressives devenues mères : trajectoires de leur agressivité durant l’enfance, indicateurs de leurs caractéristiques parentales et développement de leurs enfants

L’agressivité chez les filles tend à ne pas se manifester de la même façon que chez les garçons ; de plus, elle suit une trajectoire longitudinale particulière. Les filles agressives envers leurs pairs ne se caractérisent pas tant par leurs manifestations de délinquance et de criminalité ; elles s’orientent plutôt vers une trajectoire de troubles sociaux et de santé mentale qui, à terme, compromet leur avenir scolaire, social et professionnel, de même que leur état de santé physique. Les compétences parentales des filles agressives, de même que le fonctionnement de leur famille, peuvent aussi être affectées ; dans ce cas, c’est la socialisation, la santé et le développement de toute une nouvelle génération d’enfants qui sont menacés. La Concordia Longitudinal Risk Project (Enquête longitudinale sur les risques, Université Concordia) suit un échantillon intergénérationnel de 1 770 sujets vivant à Montréal, dont un sous-échantillon de plus de 200 filles dites très agressives, et le compare avec un échantillon de garçons agressifs et un groupe témoin composé d’enfants des deux sexes. Les participants sont suivis de l’enfance à l’âge adulte sur une période de 30 ans. Le présent article décrit les trajectoires à long terme des filles agressives et les conséquences de cette agressivité sur une large variété d’éléments psychosociaux et de santé comme la maternité et la transmission des risques à la prochaine génération. Plus particulièrement, nous souhaitons : (1) établir les trajectoires des filles qui mènent de l’agressivité dans l’enfance au développement négatif à l’âge adulte, (2) établir les indicateurs de santé et les facteurs physiologiques connexes qui comportent des risques pour les filles agressives et leurs enfants et (3) évaluer comment l’agressivité à l’enfance se répercute sur le rôle maternel et le développement de la prochaine génération. Enfin, les retombées de nos conclusions seront discutées.Childhood aggression in girls may take different forms and follow different longitudinal trajectories from those typical of aggressive boys. Even when overt delinquency and criminality are avoided, girls who are aggressive towards their peers may follow a life course involving continuing social and mental health problems. From a longterm perspective, academic, social, health, and occupational achievement are likely to be negatively affected. Family functioning and parenting abilities may also be compromised, placing the offspring of these girls, a subsequent generation, at risk for social, health, and developmental problems. The Concordia Longitudinal Risk Project, which follows an intergenerational sample of 1770 inner-city Montrealers, includes a sub-sample of over 200 highly aggressive girls, with comparison groups of aggressive boys and normative children of both genders. Participants have been followed over a 30-year period, from childhood into adulthood. The present paper describes the long-term trajectories and sequelae of girlhood aggression in the context of a broad range of negative psychosocial and health outcomes, including parenting and the inter generational transfer of risk to offspring. More specifically, (1) trajectories by which childhood aggression places girls at risk for negative developmental outcomes are outlined, (2) health behaviours and physiological correlates that signify risk to aggressive girls and their offspring are delineated, and (3) pathways through which girlhood aggression influences parenting and offspring development are elucidated. Implications of these findings are discussed

Polymeric glabrescione B nanocapsules for passive targeting of Hedgehog-dependent tumor therapy in vitro

Aim: With the purpose of delivering high doses of glabrescione B (GlaB) to solid tumors after systemic administration, long-circulating GlaB-loaded oil-cored polymeric nanocapsules (NC-GlaB) were formulated. Materials & methods: Synthesis of GlaB and its encapsulation in nanocapsules (NCs) was performed. Empty and GlaB- loaded NCs were assessed for their physico-chemical properties, in vitro cytotoxicity and in vivo biodistribution. Results: GlaB was ef ciently loaded into NCs (~90%), which were small (~160 nm), homogeneous and stable upon storage. Further, GlaB and NC-GlaB demonstrated speci c activities against the cancer stem cells. Preliminary studies in tumor-bearing mice supported the ability of NC to accumulate in pancreatic tumors. Conclusion: This study provides early evidence that NC-GlaB has the potential to be utilized in a preclinical setting and justi es the need to perform therapeutic experiments in mice

In vitro potency, in vitro and in vivo efficacy of liposomal alendronate in combination with γδ T cell immunotherapy in mice

Nitrogen-containing bisphosphonate (N-BP), including zoledronic acid (ZOL) and alendronate (ALD), have been proposed as sensitisers in γδ T cell immunotherapy in pre-clinical and clinical studies. Therapeutic efficacy of N-BPs is hampered by their rapid renal excretion and high affinity for bone. Liposomal formulations of N-BP have been proposed to improve accumulation in solid tumours. Liposomal alendronate (L-ALD) has been suggested as a suitable alternative to liposomal ZOL (L-ZOL), due to unexpected mice death experienced in pre-clinical studies with the latter. Only one study so far has proven the therapeutic efficacy of L-ALD, in combination with γδ T cell immunotherapy, after intraperitoneal administration of γδ T cell resulting in delayed growth of ovarian cancer in mice. This study aims to assess the in vitro efficacy of L-ALD, in combination with γδ T cell immunotherapy, in a range of cancerous cell lines, using L-ZOL as a comparator. The therapeutic efficacy was tested in a pseudo-metastatic lung mouse model, following intravenous injection of γδ T cell, L-ALD or the combination. In vivo biocompatibility and organ biodistribution studies of L-BPs were undertaken simultaneously. Higher concentrations of L-ALD (40–60 μM) than L-ZOL (3–10 μM) were required to produce a comparative reduction in cell viability in vitro, when used in combination with γδ T cells. Significant inhibition of tumour growth was observed after treatment with both L-ALD and γδ T cells in pseudo-metastatic lung melanoma tumour-bearing mice after tail vein injection of both treatments, suggesting that therapeutically relevant concentrations of L-ALD and γδ T cell could be achieved in the tumour sites, resulting in significant delay in tumour growth

Solvent-Free Click-Mechanochemistry for the Preparation of Cancer Cell Targeting Graphene Oxide

Polyethylene glycol-functionalized nanographene oxide (PEGylated n-GO) was synthesized from alkyne-modified n-GO, using solvent-free click-mechanochemistry, i.e., copper­(I)-catalyzed azide–alkyne cycloaddition (CuAAC). The modified n-GO was subsequently conjugated to a mucin 1 receptor immunoglobulin G antibody (anti-MUC1 IgG) via thiol–ene coupling reaction. n-GO derivatives were characterized with Fourier-transformed infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), Bradford assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and atomic force microscopy (AFM). Cell targeting was confirmed in vitro in MDA-MB-231 cells, either expressing or lacking MUC1 receptors, using flow cytometry, confocal laser scanning microscopy (CLSM) and multiphoton (MP) fluorescence microscopy. Biocompatibility was assessed using the modified lactate dehydrongenase (mLDH) assay

Engineering hepatitis B virus core particles for targeting HER2 receptors in vitro and in vivo

We acknowledge funding from Biotechnology and Biological Sciences Research Council (BBSRC; (BB/J008656/1)) and the EU FP7-ITN Marie-Curie Network programme RADDEL (290023). NH is a recipient of Graduate School King's Health Partner's scholarship. RK is a Marie-Curie Fellow. S.B. acknowledges funding from the European Research Council under the 7th Framework Program (FP7), ERC Starting Grant No. 335078 COLOURATOMS, and the Integrated Infrastructure Initiative No. 262348European Soft Matter Infrastructure, ESM