Prepuberal stimulation of 5-HT7-R by LP-211 in a rat model of hyper-activity and attention-deficit: permanent effects on attention, brain amino acids and synaptic markers in the fronto-striatal interface

The cross-talk at the prefronto-striatal interface involves excitatory amino acids, different receptors, transducers and modulators. We investigated long-term effects of a prepuberal, subchronic 5-HT7-R agonist (LP-211) on adult behaviour, amino acids and synaptic markers in a model for Attention-Deficit/Hyperactivity Disorder (ADHD). Naples High Excitability rats (NHE) and their Random Bred controls (NRB) were daily treated with LP-211 in the 5th and 6th postnatal week. One month after treatment, these rats were tested for indices of activity, non selective (NSA), selective spatial attention (SSA) and emotionality. The quantity of L-Glutamate (L-Glu), L-Aspartate (L-Asp) and L-Leucine (L-Leu), dopamine transporter (DAT), NMDAR1 subunit and CAMKIIα, were assessed in prefrontal cortex (PFC), dorsal (DS) and ventral striatum (VS), for their role in synaptic transmission, neural plasticity and information processing. Prepuberal LP-211 (at lower dose) reduced horizontal activity and (at higher dose) increased SSA, only for NHE but not in NRB rats. Prepuberal LP-211 increased, in NHE rats, L-Glu in the PFC and L-Asp in the VS (at 0.250 mg/kg dose), whereas (at 0.125 mg/kg dose) it decreased L-Glu and L-Asp in the DS. The L-Glu was decreased, at 0.125 mg/kg, only in the VS of NRB rats. The DAT levels were decreased with the 0.125 mg/kg dose (in the PFC), and increased with the 0.250 mg/kg dose (in the VS), significantly for NHE rats. The basal NMDAR1 level was higher in the PFC of NHE than NRB rats; LP-211 treatment (at 0.125 mg/kg dose) decreased NMDAR1 in the VS of NRB rats. This study represents a starting point about the impact of developmental 5-HT7-R activation on neuro-physiology of attentive processes, executive functions and their neural substrates

A vivência da amamentação em “mães de primeira viagem”

L'allaitement dépasse la limite du biologique, en nous insérant aussi de contextes social et psychologique. Cette étude, réalisée à la Clinique Obstétrique de ICHC-FMUSP, a utilisé la méthodologie qualitative pour interviewer en profondeur dix « mères de premier voyage », afin de comprendre des aspects psychologiques impliqués dans l'allaitement, dans la première semaine de vie du bébé, et comme ces mères traitent avec les orientations des arrivées de l'équipe de santé. Des entrevues individuelles et de l'analyse qualitative des données ont été réalisées. L'allaitement est apparu comme une expérience ambivalente, avec des sentiments de pouvoir et complétude, de féminité, mais aussi une expérience pénible. La moitié des interviewées a reçu des orientations de l'équipe de santé, senties comme une aide et une sécurité émotionnelle. Ainsi, l'allaitement, quand il n'est pas imposé, peut favoriser la rencontre de la mère avec son bébé et le contact avec elle-même. L'équipe de santé peut agir comme une facilitation, en utilisant des connaissances techniques mais en se maintenant ouverte à l'écoute de ces femmes.A amamentação ultrapassa o limite do biológico, inserindo-se também nos âmbitos social e psicológico. Esse estudo, realizado na Clínica Obstétrica do ICHC-FMUSP, utilizou a metodologia qualitativa para entrevistar em profundidade dez "mães de primeira viagem", a fim de compreender aspectos psicológicos envolvidos na amamentação, na primeira semana de vida do bebê, e como essas mães lidam com as orientações vindas da equipe de saúde. Foram realizadas entrevistas individuais e análise qualitativa dos dados. A amamentação apareceu como uma vivência ambivalente, com sentimentos de poder e completude, feminilidade, mas também uma experiência dolorosa. Metade das entrevistadas recebeu orientações da equipe de saúde, sentidas como um apoio e segurança emocional. Assim, a amamentação, quando não é imposta, pode favorecer o encontro da mãe com seu bebê e o contato com ela mesma. A equipe de saúde pode atuar como facilitadora, utilizando conhecimentos técnicos, mas mantendo-se aberta à escuta dessas mulheres.El amamantamiento sobrepasa el límite biológico, haciendo parte también de los ámbitos social y psicológico. Este estudio, realizado en la Clínica Obstétrica del ICHC-FMUSP, utilizó la metodología cualitativa para entrevistar con detenimiento a diez "madres de primer viaje", con la finalidad de comprender aspectos psicológicos vinculados al amamantamiento en la primera semana de vida del bebé, y cómo esas madres manejan las orientaciones recibidas del equipo de salud. Fueron realizadas entrevistas individuales y análisis cualitativo de los datos. El amamantamiento apareció como una experiencia ambivalente, con sentimientos de poder y sensación de plenitud, femineidad, pero también una experiencia dolorosa. La mitad de las entrevistadas recibió orientaciones del equipo de salud, las cuales fueron evaluadas como un apoyo y seguridad emocional. Así, el amamantamiento, cuando no es impuesto, puede favorecer el encuentro de la madre con su bebé y el contacto con ella misma. El equipo de salud puede actuar como facilitador, utilizando conocimientos técnicos pero manteniéndose de oídos abiertos hacia esas mujeres.Breast-feeding exceeds the boundaries of biology, inserting itself also in the social and psychological scopes. This study, taken place in the Obstetric Clinic of the ICHC-FMUSP, used the qualitative methodology to interview in depth ten "first-time mothers", in order to understand the psychological aspects involved in breast-feeding, during the baby’s first week of life, and how these mothers dealt with the guidance given by the health team. Individual interviews and qualitative analysis of the data has been carried through. Breast-feeding appeared as an ambivalent experience, with feelings of power and completeness, femininity, but also appeared as a painful experience. Half of the interviewed mothers received guidance from the health team, and felt it as an emotional support and security. Thus, breast-feeding, when it is not imposed, may favor the meeting of mother and child, as well as the contact of the mother with herself. The health team can act as a facilitator, using technical knowledge, but always keeping themselves opened to listening to these women

Angiotensin receptor/Neprilysin inhibitor effects in CRTd non-responders: From epigenetic to clinical beside

We evaluated whether Angiotensin receptor/Neprilysin inhibitors (ARNI) reduce heart failure (HF) hospitalizations and deaths in cardiac resynchronization therapy with defibrillator (CRTd) non-responders patients at 12 months of follow-up, modulating microRNAs (miRs) implied in adverse cardiac remodeling

Measurement of Warfarin in the Oral Fluid of Patients Undergoing Anticoagulant Oral Therapy

BACKGROUND: Patients on warfarin therapy undergo invasive and expensive checks for the coagulability of their blood. No information on coagulation levels is currently available between two controls. METHODOLOGY: A method was developed to determine warfarin in oral fluid by HPLC and fluorimetric detection. The chromatographic separation was performed at room temperature on a C-18 reversed-phase column, 65% PBS and 35% methanol mobile phase, flow rate 0.7 mL/min, injection volume 25 µL, excitation wavelength 310 nm, emission wavelength 400 nm. FINDINGS: The method was free from interference and matrix effect, linear in the range 0.2-100 ng/mL, with a detection limit of 0.2 ng/mL. Its coefficient of variation was <3% for intra-day measurements and <5% for inter-day measurements. The average concentration of warfarin in the oral fluid of 50 patients was 2.5±1.6 ng/mL (range 0.8-7.6 ng/mL). Dosage was not correlated to INR (r = -0.03, p = 0.85) but positively correlated to warfarin concentration in the oral fluid (r = 0.39, p = 0.006). The correlation between warfarin concentration and pH in the oral fluid (r = 0.37, p = 0.009) confirmed the importance of pH in regulating the drug transfer from blood. A correlation between warfarin concentration in the oral fluid and INR was only found in samples with pH values ≥7.2 (r = 0.84, p = 0.004). CONCLUSIONS: Warfarin diffuses from blood to oral fluid. The method allows to measure its concentration in this matrix and to analyze correlations with INR and other parameters

A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control

Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed

Modelling skeletal pain harnessing tissue engineering

Bone pain typically occurs immediately following skeletal damage with mechanical distortion or rupture of nociceptive fibres. The pain mechanism is also associated with chronic pain conditions where the healing process is impaired. Any load impacting on the area of the fractured bone will stimulate the nociceptive response, necessitating rapid clinical intervention to relieve pain associated with the bone damage and appropriate mitigation of any processes involved with the loss of bone mass, muscle, and mobility and to prevent death. The following review has examined the mechanisms of pain associated with trauma or cancer-related skeletal damage focusing on new approaches for the development of innovative therapeutic interventions. In particular, the review highlights tissue engineering approaches that offer considerable promise in the application of functional biomimetic fabrication of bone and nerve tissues. The strategic combination of bone and nerve tissue engineered models provides significant potential to develop a new class of in vitro platforms, capable of replacing in vivo models and testing the safety and efficacy of novel drug treatments aimed at the resolution of bone-associated pain. To date, the field of bone pain research has centred on animal models, with a paucity of data correlating to the human physiological response. This review explores the evident gap in pain drug development research and suggests a step change in approach to harness tissue engineering technologies to recapitulate the complex pathophysiological environment of the damaged bone tissue enabling evaluation of the associated pain-mimicking mechanism with significant therapeutic potential therein for improved patient quality of life