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1.
Nature ; 545(7653): 219-223, 2017 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-28467827

RESUMO

Although interactions between the thalamus and cortex are critical for cognitive function, the exact contribution of the thalamus to these interactions remains unclear. Recent studies have shown diverse connectivity patterns across the thalamus, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions is unknown. Here we show, by investigating the representation of two rules used to guide attention in the mouse prefrontal cortex (PFC), that the mediodorsal thalamus sustains these representations without relaying categorical information. Specifically, mediodorsal input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioural performance, whereas enhancing mediodorsal excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function, which is dissociable from categorical information relay, indicates that the thalamus has a much broader role in cognition than previously thought.


Assuntos
Atenção/fisiologia , Córtex Pré-Frontal/fisiologia , Tálamo/fisiologia , Animais , Cognição/fisiologia , Masculino , Camundongos , Vias Neurais , Optogenética , Córtex Pré-Frontal/citologia , Tálamo/citologia
2.
Antimicrob Agents Chemother ; 66(6): e0230221, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35603536

RESUMO

The objectives of this study were the identification in (morbidly) obese and nonobese patients of (i) the most appropriate body size descriptor for fosfomycin dose adjustments and (ii) adequacy of the currently employed dosing regimens. Plasma and target site (interstitial fluid of subcutaneous adipose tissue) concentrations after fosfomycin administration (8 g) to 30 surgery patients (15 obese/15 nonobese) were obtained from a prospective clinical trial. After characterization of plasma and microdialysis-derived target site pharmacokinetics via population analysis, short-term infusions of fosfomycin 3 to 4 times daily were simulated. The adequacy of therapy was assessed by probability of pharmacokinetic/pharmacodynamic target attainment (PTA) analysis based on the unbound drug-related targets of an %fT>MIC (the fraction of time that unbound fosfomycin concentrations exceed the MIC during 24 h) of 70 and an fAUC0-24h/MIC (the area under the concentration-time curve from 0 to 24 h for the unbound fraction of fosfomycin relative to the MIC) of 40.8 to 83.3. Lean body weight, fat mass, and creatinine clearance calculated via adjusted body weight (ABW) (CLCRCG_ABW) of all patients (body mass index [BMI] = 20.1 to 52.0 kg/m2) explained a considerable proportion of between-patient pharmacokinetic variability (up to 31.0% relative reduction). The steady-state unbound target site/plasma concentration ratio was 26.3% lower in (morbidly) obese than nonobese patients. For infections with fosfomycin-susceptible pathogens (MIC ≤ 16 mg/L), intermittent "high-dosage" intravenous (i.v.) fosfomycin (8 g, three times daily) was sufficient to treat patients with a CLCRCG_ABW of <130 mL/min, irrespective of the pharmacokinetic/pharmacodynamic indices considered. For infections by Pseudomonas aeruginosa with a MIC of 32 mg/L, when the index fAUC0-24h/MIC is applied, fosfomycin might represent a promising treatment option in obese and nonobese patients, especially in combination therapy to complement ß-lactams, in which carbapenem-resistant P. aeruginosa is critical. In conclusion, fosfomycin showed excellent target site penetration in obese and nonobese patients. Dosing should be guided by renal function rather than obesity status. (This study has been registered in the EU Clinical Trials Register under EudraCT no. 2012-004383-22.).


Assuntos
Fosfomicina , Obesidade Mórbida , Antibacterianos/farmacologia , Fosfomicina/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Obesidade Mórbida/tratamento farmacológico , Obesidade Mórbida/cirurgia , Estudos Prospectivos
3.
Phys Rev Lett ; 128(21): 212503, 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35687456

RESUMO

An unexplained >4σ discrepancy persists between "beam" and "bottle" measurements of the neutron lifetime. A new model proposed that conversions of neutrons n into mirror neutrons n^{'}, part of a dark mirror sector, can increase the apparent neutron lifetime by 1% via a small mass splitting Δm between n and n^{'} inside the 4.6 T magnetic field of the National Institute of Standards and Technology Beam Lifetime experiment. A search for neutron conversions in a 6.6 T magnetic field was performed at the Spallation Neutron Source which excludes this explanation for the neutron lifetime discrepancy.

4.
Nature ; 532(7597): 58-63, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27007844

RESUMO

Developmental disabilities, including attention-deficit hyperactivity disorder (ADHD), intellectual disability (ID), and autism spectrum disorders (ASD), affect one in six children in the USA. Recently, gene mutations in patched domain containing 1 (PTCHD1) have been found in ~1% of patients with ID and ASD. Individuals with PTCHD1 deletion show symptoms of ADHD, sleep disruption, hypotonia, aggression, ASD, and ID. Although PTCHD1 is probably critical for normal development, the connection between its deletion and the ensuing behavioural defects is poorly understood. Here we report that during early post-natal development, mouse Ptchd1 is selectively expressed in the thalamic reticular nucleus (TRN), a group of GABAergic neurons that regulate thalamocortical transmission, sleep rhythms, and attention. Ptchd1 deletion attenuates TRN activity through mechanisms involving small conductance calcium-dependent potassium currents (SK). TRN-restricted deletion of Ptchd1 leads to attention deficits and hyperactivity, both of which are rescued by pharmacological augmentation of SK channel activity. Global Ptchd1 deletion recapitulates learning impairment, hyper-aggression, and motor defects, all of which are insensitive to SK pharmacological targeting and not found in the TRN-restricted deletion mouse. This study maps clinically relevant behavioural phenotypes onto TRN dysfunction in a human disease model, while also identifying molecular and circuit targets for intervention.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Deleção de Genes , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Núcleos Talâmicos/fisiopatologia , Agressão , Animais , Animais Recém-Nascidos , Atenção , Transtorno do Deficit de Atenção com Hiperatividade/genética , Comportamento Animal , Modelos Animais de Doenças , Condutividade Elétrica , Feminino , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/patologia , Humanos , Deficiências da Aprendizagem/genética , Deficiências da Aprendizagem/fisiopatologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Transtornos Motores/genética , Transtornos Motores/fisiopatologia , Inibição Neural , Canais de Potássio Cálcio-Ativados/metabolismo , Sono , Privação do Sono/genética , Privação do Sono/fisiopatologia , Núcleos Talâmicos/patologia
5.
Nature ; 526(7575): 705-9, 2015 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-26503050

RESUMO

How the brain selects appropriate sensory inputs and suppresses distractors is unknown. Given the well-established role of the prefrontal cortex (PFC) in executive function, its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection. To test this idea and, more generally, dissect the circuits underlying sensory selection, we developed a cross-modal divided-attention task in mice that allowed genetic access to this cognitive process. By optogenetically perturbing PFC function in a temporally precise window, the ability of mice to select appropriately between conflicting visual and auditory stimuli was diminished. Equivalent sensory thalamocortical manipulations showed that behaviour was causally dependent on PFC interactions with the sensory thalamus, not sensory cortex. Consistent with this notion, we found neurons of the visual thalamic reticular nucleus (visTRN) to exhibit PFC-dependent changes in firing rate predictive of the modality selected. visTRN activity was causal to performance as confirmed by bidirectional optogenetic manipulations of this subnetwork. Using a combination of electrophysiology and intracellular chloride photometry, we demonstrated that visTRN dynamically controls visual thalamic gain through feedforward inhibition. Our experiments introduce a new subcortical model of sensory selection, in which the PFC biases thalamic reticular subnetworks to control thalamic sensory gain, selecting appropriate inputs for further processing.


Assuntos
Atenção/fisiologia , Células Receptoras Sensoriais/fisiologia , Tálamo/fisiologia , Estimulação Acústica , Animais , Giro do Cíngulo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Inibição Neural/fisiologia , Vias Neurais/fisiologia , Optogenética , Estimulação Luminosa , Córtex Pré-Frontal/fisiologia , Núcleos Talâmicos/citologia , Núcleos Talâmicos/fisiologia , Tálamo/citologia
6.
BMC Psychiatry ; 19(1): 262, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455302

RESUMO

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.


Assuntos
Psiquiatria Biológica/normas , Transtorno Depressivo Resistente a Tratamento/terapia , Prova Pericial/normas , Guias de Prática Clínica como Assunto/normas , Psiquiatria/normas , Psicofarmacologia/normas , Antidepressivos/uso terapêutico , Psiquiatria Biológica/métodos , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/epidemiologia , Transtorno Depressivo Resistente a Tratamento/psicologia , Prova Pericial/métodos , Feminino , Fundações/normas , França/epidemiologia , Humanos , Masculino , Psiquiatria/métodos , Psicofarmacologia/métodos
7.
BMC Psychiatry ; 19(1): 50, 2019 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-30700272

RESUMO

BACKGROUND: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.


Assuntos
Psiquiatria Biológica/normas , Transtorno Depressivo Maior/terapia , Prova Pericial/normas , Guias de Prática Clínica como Assunto/normas , Psiquiatria/normas , Psicofarmacologia/normas , Idoso , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Psiquiatria Biológica/métodos , Comorbidade , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Prova Pericial/métodos , Feminino , Fundações/normas , França/epidemiologia , Humanos , Masculino , Transtornos da Personalidade/epidemiologia , Transtornos da Personalidade/psicologia , Transtornos da Personalidade/terapia , Psicofarmacologia/métodos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/terapia
8.
Encephale ; 45(6): 506-512, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31521338

RESUMO

BACKGROUND: The update of the Post-Traumatic Stress Disorder (PTSD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM5) emphasizes the definition of psychological traumatism as an objective and external event. Nevertheless, the scientific debate about the criteriology of PTSD, its clinical pertinence for application and the role of subjective dimension appears still open. Although the relation between psychotrauma and psychosis has been well examined, in the way of trauma as a risk factor for the development of schizophrenia, the potential traumatism represented by the psychotic experience seems to be less known. OBJECTIVE: This paper aims to provide a state of the art about the PTSD in reaction to psychosis, defined as PTSD post psychosis (PTSD-PP), particularly in epidemiological and psychopathological terms. METHODS: We performed a bibliographic research on Pubmed using the keywords "post-traumatic stress disorder", "psychological trauma", "schizophrenia review", "psychosis", "first episode psychosis"« ¼, "recovery schizophrenia", with a first screening on titles and abstracts. An acute psychotic episode referred to a decompensation of any pathology of the DSM5-schizophrenia spectrum or other psychotic disorders or to a mood disorder with psychotic features. The articles exclusively interested in the traumatic impact of hospitalizations and treatment conditions were excluded. RESULTS: The literature noted that PTSD-PP affected about a quarter to a third of the psychotic patients interrogated during the recovery of an acute psychotic episode. The analytic epidemiology showed that the main validated risk factors for PTSD were also relevant in the development of PTSD-PP, including past traumatic history, childhood trauma and feeling of helplessness during the traumatic event. Criticizing the methodological heterogeneity through studies, the observational approach brought out the lack of clinical pertinence of the DSM5A criteria defining the traumatic event for PTSD. This criteriology failed to consider the subjective dimension of the threat to psychological integrity generated by a psychotrauma. Historical case studies presented a complete post-traumatic symptomatology in reaction to psychosis, suggesting that the supposed psychotic residual symptoms after acute phase could referr to actual traumatic reactions. The PTSD-PP process observed in descriptive research and patients' interviews appeared congruent with the cognitive model of PTSD elaborated by Ehlers and Clark. Indeed, psychotic patients developed negative appraisals about themselves, others and the world because of the occurrence and the content of their psychotic symptoms. Shame, fear of recurrence, intolerance to uncertainty and perception of losing control of one's mind were demonstrated as significantly related to PTSD-PP. A perception of current threat then settled, leading to adaptation strategies, possibly psychotic themselves, to avoid intrusions and others indices about their past psychotic episode. Thus, reliving syndrome, avoidance, emotional numbing could simulate a new psychotic exacerbation to an outer-observer. CONCLUSION: A psychotic experience could be traumatic for patients and lead to complete PTSD. Although it appears as a non-consensual clinical entity, from a likely epistemological slip of the definition of "psychotrauma", the consideration of potential PTSD-PP presents an undoubted clinical relevance. Indeed, it could help practioners to precise the semiological analysis of patients recovering from an acute psychotic episode; to impact the prognosis of psychosis, thinking about impairment on the quality of life and the affective and suicidal comorbidities; and to modify the therapeutic approach in the recovery of schizophrenia. In addition, the literature about psychotic recovery seems particularly related to the concept of "post-traumatic growth" (PTG). The inscription of a psychotic episode in a traumatic frame requires a clinical approach as close as possible to the subjectivity of the patient experience, beyond the evaluation of psychotic symptoms and its remission. The question of trauma-focused therapies applied to PTSD-PP opens the field for future research.


Assuntos
Transtornos Psicóticos/complicações , Transtornos de Estresse Pós-Traumáticos/etiologia , Ciências Biocomportamentais , Cognição/fisiologia , Comorbidade , Humanos , Psicoterapia/métodos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/terapia , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/terapia
9.
Phys Rev Lett ; 120(14): 147203, 2018 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-29694132

RESUMO

The magnetic field induced rearrangement of the cycloidal spin structure in ferroelectric monodomain single crystals of the room-temperature multiferroic BiFeO_{3} is studied using small-angle neutron scattering. The cycloid propagation vectors are observed to rotate when magnetic fields applied perpendicular to the rhombohedral (polar) axis exceed a pinning threshold value of ∼5 T. In light of these experimental results, a phenomenological model is proposed that captures the rearrangement of the cycloidal domains, and we revisit the microscopic origin of the magnetoelectric effect. A new coupling between the magnetic anisotropy and the polarization is proposed that explains the recently discovered magnetoelectric polarization perpendicular to the rhombohedral axis.

10.
Mol Psychiatry ; 22(2): 183-191, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27725660

RESUMO

While localizing sensory and motor deficits is one of the cornerstones of clinical neurology, behavioral and cognitive deficits in psychiatry remain impervious to this approach. In psychiatry, major challenges include the relative subtlety by which neural circuits are perturbed, and the limited understanding of how basic circuit functions relate to thought and behavior. Neurodevelopmental disorders offer a window to addressing the first challenge given their strong genetic underpinnings, which can be linked to biological mechanisms. Such links have benefited from genetic modeling in the mouse, and in this review we highlight how this small mammal is now allowing us to crack neural circuits as well. We review recent studies of mouse thalamus, discussing how they revealed general principles that may underlie human perception and attention. Controlling the magnitude (gain) of thalamic sensory responses is a mechanism of attention, and the mouse has enabled its functional dissection at an unprecedented resolution. Further, modeling human genetic neurodevelopmental disease in the mouse has shown how diminished thalamic gain control can lead to attention deficits. This breaks new ground in how we untangle the complexity of psychiatric diseases; by making thalamic circuits accessible to mechanistic dissection; the mouse has not only taught us how they fundamentally work, but also how their dysfunction can be precisely mapped onto behavioral and cognitive deficits. Future studies promise even more progress, with the hope that principled targeting of identified thalamic circuits can be uniquely therapeutic.


Assuntos
Atenção/fisiologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Tálamo/fisiologia , Animais , Comportamento Animal , Humanos , Camundongos , Modelos Animais , Vias Neurais/fisiologia , Transtornos do Neurodesenvolvimento/metabolismo , Tálamo/metabolismo
11.
Lasers Med Sci ; 33(4): 765-772, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29218493

RESUMO

Molecular effects of various ablative and non-ablative laser treatments on human skin cells-especially primary effects on epidermal keratinocytes and dermal fibroblasts-are not yet fully understood. We present the first study addressing molecular effects of fractional non-sequential ultrapulsed CO2 laser treatment using a 3D skin model that allows standardized investigations of time-dependent molecular changes ex vivo. While histological examination was performed to assess morphological changes, we utilized gene expression profiling using microarray and qRT-PCR analyses to identify molecular effects of laser treatment. Irradiated models exhibited dose-dependent morphological changes resulting in an almost complete recovery of the epidermis 5 days after irradiation. On day 5 after laser injury with a laser fluence of 100 mJ/cm2, gene array analysis identified an upregulation of genes associated with tissue remodeling and wound healing (e.g., COL12A1 and FGF7), genes that are involved in the immune response (e.g., CXCL12 and CCL8) as well as members of the heat shock protein family (e.g., HSPB3). On the other hand, we detected a downregulation of matrix metalloproteinases (e.g., MMP3), differentiation markers (e.g., LOR and S100A7), and the pro-inflammatory cytokine IL1α.Overall, our findings substantiate the understanding of time-dependent molecular changes after CO2 laser treatment. The utilized 3D skin model system proved to be a reliable, accurate, and reproducible tool to explore the effects of various laser settings both on skin morphology and gene expression during wound healing.


Assuntos
Fibroblastos/efeitos da radiação , Queratinócitos/efeitos da radiação , Lasers de Gás/uso terapêutico , Modelos Biológicos , Pele/efeitos da radiação , Quimiocina CXCL12/metabolismo , Criança , Imunofluorescência , Perfilação da Expressão Gênica , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Cicatrização/efeitos da radiação
12.
Encephale ; 44(2): 106-110, 2018 Apr.
Artigo em Francês | MEDLINE | ID: mdl-27871719

RESUMO

BACKGROUND AND AIM: Psychiatric emergency services (PES) have recently occupied a new and growing place in the landscape of mental health services. However, few data are available on the way psychiatrists practice in the PES. Our aim was to survey psychiatrists working in PES, focusing on their job satisfaction and the theoretical models they use in their everyday practice. METHOD: We sent a survey to a sample of 508 psychiatrists working in PES in France. RESULTS: Two hundred and thirty-seven psychiatrists returned the survey, yielding a response rate of 47%. On a 0 to 10 scale, the mean level of job satisfaction was 6.7 (SD: 1.92). Participants reported that facing a variety of clinical situations and playing a key-coordinating role in the mental health system were the two most specific features of emergency psychiatry. The main sources of dissatisfaction were organizational issues and stressful clinical experiences, including violence or hostility. Sixty-three percent (n=150) of participants reported using more than two theoretical models in their practice, while the use of crisis models was reported by almost 40% of them. When assessed for suggestions to improve the PES, the majority of participants indicated that efforts should be focused on organizational factors. CONCLUSION: While emergency psychiatry could appear as an ungrateful practice, the majority of psychiatrists who responded to our survey reported satisfaction with their work and highlighted its unique particularities. Future research and collaborations are needed to identify organizational models of PES and their better integration in mental health networks.


Assuntos
Serviços de Emergência Psiquiátrica , Satisfação no Emprego , Fadiga Mental/psicologia , Psiquiatria , Adulto , Esgotamento Profissional , Feminino , França , Humanos , Masculino , Fadiga Mental/etiologia , Pessoa de Meia-Idade , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Inquéritos e Questionários , Local de Trabalho/psicologia
13.
Osteoarthritis Cartilage ; 25(7): 1046-1054, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28232097

RESUMO

OBJECTIVE: To determine compartment-specific loading patterns during gait, quantified as joint reaction forces (JRF), of individuals with knee articular cartilage defects (ACD) compared to healthy controls (HC). METHODS: Individuals with ACDs and HC participated. Individuals with ACDs were divided into groups according to ACD location: PF (only a patellofemoral ACD), TF (only a tibiofemoral ACD), and MIX (both PF and TF ACDs). Participants underwent three-dimensional gait analysis at self-selected speed. TF joint reaction force (TF-JRF) was calculated using inverse dynamics. PF joint reaction force (PF-JRF) was derived from estimated quadriceps force (FQUAD) and knee flexion angle. Primary variables of interest were the PF- and TF-JRF peaks (body weight [×BW]). Related secondary variables (gait speed, quadriceps strength, knee function, activity level) were evaluated as covariates. RESULTS: First peak PF-JRF and TF-JRF were similar in the TF and MIX groups (0.75-1.0 ×BW, P = 0.6-0.9). Both peaks were also similar in the PF and HC groups (1.1-1.3 ×BW, P = 0.7-0.8), and higher than the TF and MIX groups (P = 0.004-0.02). For the second peak PF-JRF, only the HC group was higher than the TF group (P = 0.02). The PF group walked at a similar speed as the HC group; both groups walked faster than the TF and MIX groups (P < 0.001). With gait speed and quadriceps strength as covariates, no differences were observed in JRF peaks. CONCLUSIONS: The results suggest the presence of a TF ACD (TF and MIX groups), but not a PF ACD (PF group), may affect joint loading patterns during walking. Walking slower may be a protective gait modification to reduce load.


Assuntos
Doenças das Cartilagens/fisiopatologia , Cartilagem Articular/fisiopatologia , Marcha/fisiologia , Adolescente , Adulto , Fenômenos Biomecânicos/fisiologia , Feminino , Humanos , Articulação do Joelho/fisiologia , Masculino , Força Muscular/fisiologia , Osteoartrite do Joelho/fisiopatologia , Articulação Patelofemoral/fisiologia , Músculo Quadríceps/fisiologia , Amplitude de Movimento Articular/fisiologia , Tíbia/fisiologia , Caminhada/fisiologia , Adulto Jovem
14.
Mediators Inflamm ; 2017: 2786427, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28831207

RESUMO

Transient receptor potential vanilloid-1 (TRPV1) is a nonselective cation channel, predominantly expressed in sensory neurons. TRPV1 is known to play an important role in the pathogenesis of inflammatory and neuropathic pain states. Previous studies suggest interactions between tumor necrosis factor- (TNF-) alpha and TRPV1, resulting in a modulation of ion channel function and protein expression in sensory neurons. We examined the effect of intrathecal administration of the ultrapotent TRPV1 agonist resiniferatoxin (RTX) on TNF-induced pain-associated behavior of rats using von Frey and hot plate behavioral testing. Intrathecal injection of TNF induces mechanical allodynia (2 and 20 ng/kg) and thermal hyperalgesia (200 ng) 24 h after administration. The additional intrathecal administration of RTX (1.9 µg/kg) alleviates TNF-induced mechanical allodynia and thermal hyperalgesia 24 h after injection. In addition, TNF increases the TRPV1 protein level and number of TRPV1-expressing neurons. Both effects could be abolished by the administration of RTX. These results suggest that the involvement of TRPV1 in TNF-induced pain offers new TRPV1-based experimental therapeutic approaches and demonstrates the analgesic potential of RTX in inflammatory pain diseases.


Assuntos
Canais de Cátion TRPV/metabolismo , Animais , Diterpenos/uso terapêutico , Hiperalgesia/induzido quimicamente , Imuno-Histoquímica , Injeções Espinhais , Masculino , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPV/agonistas , Fator de Necrose Tumoral alfa/farmacologia
15.
Proc Natl Acad Sci U S A ; 111(38): 13811-6, 2014 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-25114234

RESUMO

The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury.


Assuntos
Córtex Cerebral/metabolismo , Neurônios/metabolismo , Engenharia Tecidual/métodos , Animais , Lesões Encefálicas/terapia , Córtex Cerebral/citologia , Neurônios/citologia , Ratos , Ratos Sprague-Dawley
16.
Encephale ; 43(2): 154-159, 2017 Apr.
Artigo em Francês | MEDLINE | ID: mdl-27265566

RESUMO

AIMS: Historically, there is a strong link between depression and epilepsy. Patients with epilepsy are four to five times more likely to develop a depressive syndrome. It seems that the link between epilepsy and depression is bidirectional. There is little data on mood disorders secondary to epilepsy surgery. The goal of epilepsy surgery is to reduce the number and frequency of attacks, which in turn would allow improvements in mood disorders and cognitive impairment. METHODS: A systematic search of the international literature was performed using the bibliographic search engines PubMed and Embase. The following MESH terms were used: epilepsy surgery AND (depression OR depressive disorder OR mood disorder). We also used the "related articles" of PubMed, bibliography surveys, conference abstracts and Google Scholar to identify additional relevant papers. RESULTS: Of the 130 studies found by the systematic search, 112 are excluded because they did not take into account the mood disorders secondary to epilepsy surgery. Fifteen studies are included in this review of the literature with a case study. Depression is the psychopathological condition that is the most frequently studied. According to several studies, the prevalence of depression is approximately 30% with nearly 70% of cases diagnosed during the first three months following epilepsy surgery. The majority of patients presented depressive symptoms during the first 3 to 12months after epilepsy surgery. In these studies, the risk of developing depression is correlated with the existence of previous depressive elements relative to the epilepsy surgery. A small number of studies reported cases of de novo depression. Studies have shown a correlation between very good to excellent control of epileptic seizures and a persistent improvement of mood disorders. It would seem that depressive symptoms post-surgery are more common when the surgical intervention concerns the temporal lobe and in particular mesial resections. There are only very few cases of maniac episodes. Hamid et al. showed an increased risk of suicide waning after the epilepsy surgery over a period of 5years. CONCLUSION: Mood disorders are common psychiatric comorbidities in epilepsy surgery. The detection, prevention, and treatment of these symptoms in patients eligible for epilepsy surgery pose major challenges for psychiatrists and neurologists, requiring their close collaboration.


Assuntos
Epilepsia/complicações , Epilepsia/cirurgia , Transtornos do Humor/complicações , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Transtorno Bipolar/complicações , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Comorbidade , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Epilepsia/epidemiologia , Epilepsia/psicologia , Humanos , Transtornos do Humor/epidemiologia , Transtornos do Humor/psicologia , Procedimentos Neurocirúrgicos/efeitos adversos
17.
Encephale ; 43(4S): S1-S24, 2017 Sep.
Artigo em Francês | MEDLINE | ID: mdl-28822460

RESUMO

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease.


Assuntos
Antidepressivos/uso terapêutico , Psiquiatria Biológica/normas , Transtorno Depressivo Resistente a Tratamento/terapia , Neuropsicologia/normas , Comitês Consultivos/organização & administração , Comitês Consultivos/normas , Antipsicóticos/uso terapêutico , Psiquiatria Biológica/organização & administração , Comorbidade , Consenso , Transtorno Depressivo Resistente a Tratamento/classificação , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/epidemiologia , Quimioterapia Combinada , Prova Pericial , França/epidemiologia , Humanos , Neuropsicologia/organização & administração , Qualidade de Vida , Sociedades Médicas/normas
18.
Encephale ; 42(1): 112-5, 2016 Feb.
Artigo em Francês | MEDLINE | ID: mdl-25526814

RESUMO

BACKGROUND: In times of fiscal restraint for health structures, apart from the clinical input, it seems important to discuss the economic impact of liaison psychiatry. There are only a few studies on the economic added value provided by a liaison psychiatry team. In addition to this, only a few psychiatric pathologies are coded as they should be, hence we make the assumption of an additional development provided by a specialised team. METHODS: Over a short period of 4months, in three departments of the Toulouse University Hospital Centre, the added value to the general pricing system of liaison psychiatry was studied. The population was represented by all the consecutive requests for consultations from patients over 18years old, men and women, hospitalised at that time. These three departments frequently request consultations with the psychiatry liaison team. They set a diagnostic, and if this is associated with a higher Homogeneous Group of Patients (HGP), it provides added value. RESULTS: Fifty-two patients benefited from a psychiatric consultation over 4months. The results highlight a development of € 8630.43 for the traumatology department, € 3325.03 for the internal medicine department, and € 513.61 for the haematology department over the study period. The overall development over this period was € 12,469.07. CONCLUSION: To our knowledge, this approach is one of the first in France to highlight an economic impact of the intervention of liaison psychiatry in the claiming departments.


Assuntos
Unidade Hospitalar de Psiquiatria/economia , Unidade Hospitalar de Psiquiatria/organização & administração , Psiquiatria/economia , Psiquiatria/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , França , Hospitais Universitários/organização & administração , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/economia , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/economia , Encaminhamento e Consulta , Adulto Jovem
19.
Phys Rev Lett ; 114(3): 036401, 2015 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-25659009

RESUMO

Using inelastic neutron scattering, we map a 14 meV coherent resonant mode in the topological Kondo insulator SmB6 and describe its relation to the low energy insulating band structure. The resonant intensity is confined to the X and R high symmetry points, repeating outside the first Brillouin zone and dispersing less than 2 meV, with a 5d-like magnetic form factor. We present a slave-boson treatment of the Anderson Hamiltonian with a third neighbor dominated hybridized band structure. This approach produces a spin exciton below the charge gap with features that are consistent with the observed neutron scattering. We find that maxima in the wave vector dependence of the inelastic neutron scattering indicate band inversion.

20.
Conserv Biol ; 29(6): 1704-14, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26171679

RESUMO

Islands present a unique scenario in conservation biology, offering refuge yet imposing limitations on insular populations. The Kimberley region of northwestern Australia has more than 2500 islands that have recently come into focus as substantial conservation resources. It is therefore of great interest for managers to understand the driving forces of genetic structure of species within these island archipelagos. We used the ubiquitous bar-shouldered skink (Ctenotus inornatus) as a model species to represent the influence of landscape factors on genetic structure across the Kimberley islands. On 41 islands and 4 mainland locations in a remote area of Australia, we genotyped individuals across 18 nuclear (microsatellite) markers. Measures of genetic differentiation and diversity were used in two complementary analyses. We used circuit theory and Mantel tests to examine the influence of the landscape matrix on population connectivity and linear regression and model selection based on Akaike's information criterion to investigate landscape controls on genetic diversity. Genetic differentiation between islands was best predicted with circuit-theory models that accounted for the large difference in resistance to dispersal between land and ocean. In contrast, straight-line distances were unrelated to either resistance distances or genetic differentiation. Instead, connectivity was determined by island-hopping routes that allow organisms to minimize the distance of difficult ocean passages. Island populations of C. inornatus retained varying degrees of genetic diversity (NA = 1.83 - 7.39), but it was greatest on islands closer to the mainland, in terms of resistance-distance units. In contrast, genetic diversity was unrelated to island size. Our results highlight the potential for islands to contribute to both theoretical and applied conservation, provide strong evidence of the driving forces of population structure within undisturbed landscapes, and identify the islands most valuable for conservation based on their contributions to gene flow and genetic diversity.


Assuntos
Distribuição Animal , Conservação dos Recursos Naturais , Fluxo Gênico , Variação Genética , Lagartos/fisiologia , Animais , Ilhas , Lagartos/genética , Repetições de Microssatélites , Austrália Ocidental
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