Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy.

BACKGROUND: The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response. in vivo. Lasers Surg. Med. 47:323-330, 2015. © 2015 Wiley Periodicals, Inc. METHODS: Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group). RESULTS: Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls. CONCLUSIONS: Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics. Lasers Surg. Med. 47:323-330, 2015.

Handwriting and pre-frailty in the Lausanne cohort 65+ (Lc65+) study

BACKGROUND: Frailty is detected by weight loss, weakness, slow walking velocity, reduced physical activity or poor endurance/exhaustion. Handwriting has not been examined in the context of frailty, despite its functional importance. OBJECTIVE: Our goal was to examine quantitative handwriting measures in people meeting 0, 1, and 2 or more (2+) frailty criteria. We also examined if handwriting parameters were associated with gait performance, weakness, poor endurance/exhaustion and cognitive impairment. METHODS: From the population-based Lc65+, 72 subjects meeting 2+ frailty criteria with complete handwriting samples were identified. Gender-matched controls meeting 1 criterion or no criteria were identified. Cognitive impairment was defined by a Mini-Mental State Examination score of 25 or less or the lowest 20th percentile of Trail Making Test Part B. Handwriting was recorded using a writing tablet and measures of velocity, pauses, and pressure were extracted. RESULTS: Subjects with 2+ criteria were older, had more health problems and need for assistance but had higher education. No handwriting parameter differed between frailty groups (age and education adjusted). Writing velocity was not significantly slower among participants from the slowest 20th percentile of gait velocity but writing pressure was significantly lower among those from the lowest 20th percentile of grip strength. Poor endurance/exhaustion was not associated with handwriting measures. Low cognitive performance was related to longer pauses. CONCLUSIONS: Handwriting parameters might be associated with specific aspects of the frailty phenotype, but not reliably with global definitions of frailty at its earliest stages among subjects able to perform handwriting tests.

Educational intervention for parents of adolescents with chronic illness: a pre-post test pilot study.

OBJECTIVE: This pilot experimental study tested the feasibility and intended effect of an educational intervention for parents to help them assist their adolescent child with chronic illness (CI) in becoming autonomous. METHODS: A two-phase pre-post pilot intervention study targeting parents of adolescents with CI was conducted. Parents were allocated to group 1 and 2 and received the four-module intervention consecutively. Intended effect was measured through online questionnaires for parents and adolescents before, at 2 months after, and at 4-6 months after the intervention. Feasibility was assessed through an evaluation questionnaire for parents. RESULTS: The most useful considered modules concerned the future of the adolescent and parents and social life. The most valued aspect was to exchange with other parents going through similar problems and receiving a new outlook on their relationship with their child. For parents, improvement trends appeared for shared management, parent protection, and self-efficacy, and worsening trends appeared for coping skills, parental perception of child vulnerability, and parental stress. For adolescents, improvement trends appeared for self-efficacy and parental bonding and worsening trends appeared for shared management and coping skills. CONCLUSION: Parents could benefit from peer-to-peer support and education as they support the needed autonomy development of their child. Future studies should test an online platform for parents to find peer support at all times and places.

Pre-dispersal predation effect on seed packaging strategies and seed viability.

An increased understanding of intraspecific seed packaging (i.e. seed size/number strategy) variation across different environments may improve current knowledge of the ecological forces that drive seed evolution in plants. In particular, pre-dispersal seed predation may influence seed packaging strategies, triggering a reduction of the resources allocated to undamaged seeds within the preyed fruits. Assessing plant reactions to pre-dispersal seed predation is crucial to a better understanding of predation effects, but the response of plants to arthropod attacks remains unexplored. We have assessed the effect of cone predation on the size and viability of undamaged seeds in populations of Juniperus thurifera with contrasting seed packaging strategies, namely, North African populations with single-large-seeded cones and South European populations with multi-small-seeded cones. Our results show that the incidence of predation was lower on the single-large-seeded African cones than on the multi-small-seeded European ones. Seeds from non-preyed cones were also larger and had a higher germination success than uneaten seeds from preyed cones, but only in populations with multi-seeded cones and in cones attacked by Trisetacus sp., suggesting a differential plastic response to predation. It is possible that pre-dispersal seed predation has been a strong selective pressure in European populations with high cone predation rates, being a process which maintains multi-small-seeded cones and empty seeds as a strategy to save some seeds from predation. Conversely, pre-dispersal predation might not have a strong effect in the African populations with single-large-seeded cones characterized by seed germination and filling rates higher than those in the European populations. Our results indicate that differences in pre-dispersal seed predators and predation levels may affect both selection on and intraspecific variation in seed packaging.

Aux sources de l'orthopédie clinique : l'histoire revisitée de Jean-André Venel, "père de l'orthopédie" (fin XVIIIe-début XIXe siècle)

(ENGLISH VERSION BELOW) En 1780, le médecin Jean-André Venel fonde à Orbe, dans le canton de Vaud, le premier institut orthopédique connu dans le monde, proposant une version clinique d'un savoir-faire médical ancestral. A travers des sources qui réactualisent les travaux consacrés à Venel, cet article retrace les origines de son institution et de sa pensée médicale, dans un contexte de production et de diffusion d'un savoir particulier en termes de technique du corps et de médecine de l'enfant. Revisitant la figure légendaire - ou mythique ? - de ce que l'histoire de la médecine a retenu comme étant le « père de l'orthopédie », l'article s'interroge par la même occasion sur les conditions d'émergence d'une spécialité médicale au sortir de l'Ancien Régime, et de son impact dans les premières décennies du XIXe siècle. In 1780, the physician Jean-André Venel creates in Orbe (canton of Vaud) the first orthopedic institute of the world, offering a clinical version of an ancient medical savoir-faire. By using sources that enable us to update the scholarship on Venel, this article traces the origins of his institute and of his medical thought, in the context of the production and diffusion of a specialized knowledge on the body and on children. With this new perspective on the legendary, if not mythical, figure, whom the history of medicine has canonized as the "father of orthopedia", this article also examines the conditions of emergence of a medical specialization at the end of the Ancien Régime and its impact in the first decades of the nineteenth century.

Pre-existing astrocytes form functional perisynaptic processes on neurons generated in the adult hippocampus.

The adult dentate gyrus produces new neurons that morphologically and functionally integrate into the hippocampal network. In the adult brain, most excitatory synapses are ensheathed by astrocytic perisynaptic processes that regulate synaptic structure and function. However, these processes are formed during embryonic or early postnatal development and it is unknown whether astrocytes can also ensheathe synapses of neurons born during adulthood and, if so, whether they play a role in their synaptic transmission. Here, we used a combination of serial-section immuno-electron microscopy, confocal microscopy, and electrophysiology to examine the formation of perisynaptic processes on adult-born neurons. We found that the afferent and efferent synapses of newborn neurons are ensheathed by astrocytic processes, irrespective of the age of the neurons or the size of their synapses. The quantification of gliogenesis and the distribution of astrocytic processes on synapses formed by adult-born neurons suggest that the majority of these processes are recruited from pre-existing astrocytes. Furthermore, the inhibition of astrocytic glutamate re-uptake significantly reduced postsynaptic currents and increased paired-pulse facilitation in adult-born neurons, suggesting that perisynaptic processes modulate synaptic transmission on these cells. Finally, some processes were found intercalated between newly formed dendritic spines and potential presynaptic partners, suggesting that they may also play a structural role in the connectivity of new spines. Together, these results indicate that pre-existing astrocytes remodel their processes to ensheathe synapses of adult-born neurons and participate to the functional and structural integration of these cells into the hippocampal network.