Protein interacting with C kinase and neurological disorders

Best known for its interaction with the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor subunit GluA2 and for its influence on excitatory synapse activity, the protein interacting with C kinase, PICK1, is the focus of considerable attention from neurobiologists. Indeed, this PSD‐95/DlgA/ZO‐1 (PDZ) domain‐containing protein has been shown to interact with a wide variety of neurotransmitter receptors, transporters, and enzymes, including glutamate and nicotinic acetylcholine receptors, dopamine and glutamate transporters, and the enzyme serine racemase. Through its lipid binding domain, PICK1 is targeted to the inner surface of the cell membrane where it contributes to anchoring these partners and thereby influences their synaptic localization and function. Under pathological conditions, the regulation of some PICK1‐interacting partners is altered, pointing to an involvement of PICK1 in neurological disorders. Also, genetic or pharmacological manipulations of PICK1 expression, localization, or function have been shown to influence several physiological or pathological processes in which putative PICK1 partners are involved. This review will summarize recent experimental observations that highlight the involvement of PICK1 in neurological disorders, including schizophrenia, Parkinson's disease, epilepsy, chronic pain, drug abuse, and amyotrophic lateral sclerosis. Synapse 67:532–540, 2013. © 2013 Wiley Periodicals, Inc.     

A Randomized Controlled Trial of Brief Skills Training in Affective and Interpersonal Regulation (STAIR) for Veterans in Primary Care

This randomized controlled trial assessed the efficacy of a five-session version of Skills Training in Affective and Interpersonal Regulation (STAIR) among veterans obtaining treatment in primary care. Veterans who screened positive for either posttraumatic stress disorder (PTSD) or depression (N = 26) were enrolled and randomized into either five-session STAIR or treatment as usual (TAU). Assessments of PTSD symptoms (PTSD Checklist for DSM-5; PCL-5), depression (Beck Depression Inventory–II; BDI-II), emotion regulation (Difficulties in Emotion Regulation Scale; DERS), and social engagement difficulties (World Health Organization Disability Assessment 2.0; WHODAS-2) were assessed at pretreatment, posttreatment, and 3-month follow-up assessments. Participants assigned to the five-session STAIR condition reported significant improvements on all measures, whereas those assigned to TAU showed no change. Group × Treatment interactions were significant for all outcomes, and effect sizes for the interactions ranged from moderate to large, Hedge's gs = 0.81 for the PCL-5, 1.15 for the BDI-II, 0.75 for the DERS, and 0.81 for the WHODAS-2. The results indicate that five-session STAIR, a brief, skills-focused treatment, may be effective in reducing a range of symptoms and in improving social functioning among veterans treated in primary care settings.     

Genetic diversity of Streptococcus suis strains isolated from pigs and humans as revealed by pulsed-field gel electrophoresis

The genetic diversity of 123 Streptococcus suis strains of capsular types 2, 1/2, 3, 7, and 9, isolated from pigs in France and from humans in different countries, was evaluated by pulsed-field gel electrophoresis (PFGE) of DNA restricted with SmaI. The method was highly discriminative (D = 0.98), results were reproducible, and the PFGE analysis was easy to interpret. Among all S. suis strains, 74 PFGE patterns were shown. At 60% homology, three groups (A, B, and C) were identified, and at 69% homology, eight subgroups (a to h) were observed. Strains isolated from diseased pigs or from humans were statistically clustered in group B, especially in subgroup d. By contrast, S. suis strains isolated from clinically healthy pigs were preferentially included in subgroup b of group A. Relationships could be established between capsular types 1/2, 3, and 9 and groups A, e, and B, respectively. S. suis strains isolated from humans were homogeneous, and a very high level of association between these strains and four DNA patterns was observed. The PFGE used in this study is a very useful tool for evaluating the genetic diversity of S. suis strains, and it would be used for epidemiological investigations.     

For a coordination of the supportive care for people affected by severe illnesses: proposition of organization in the public and private health care centres

The concept of continuous and global care is acknowledged today by all as inherent to modern medicine. A working group gathered to propose models for the coordination of supportive care for all severe illnesses in the various private and public health care centres. The supportive care are defined as: "all care and supports necessary for ill people, at the same time as specific treatments, along all severe illnesses". This definition is inspired by that of "supportive care" given in 1990 by the MASCC (Multinational Association for Supportive Care in Cancer): "The total medical, nursing and psychosocial help which the patients need besides the specific treatment". It integrates as much the field of cure with possible after-effects as that of palliative care, the definition of which is clarified (initial and terminal palliative phases). Such a coordination is justified by the pluridisciplinarity and hyperspecialisation of the professionals, by a poor communication between the teams, by the administrative difficulties encountered by the teams participating in the supportive care. The working group insists on the fact that the supportive care is not a new speciality. He proposes the creation of units. departments or pole of responsibility of supportive care with a "basic coordination" involving the activities of chronic pain, palliative care, psycho-oncology, and social care. This coordination can be extended, according to the "history" and missions of health care centres. Service done with the implementation of a "unique counter" for the patients and the teams is an important point. The structure has to comply with the terms and conditions of contract (Consultation, Unit or Centre of chronic pain, structures of palliative care, of psycho-oncology, of nutrition, of social care). A common technical organization is one of the interests. The structure has to set up strong links with the private practitioners, the networks, the home medical care (HAD) and the nurses services at home (SSIAD), when they exist, to guarantee the continuity of the supportive care under all its aspects and in order to take into account the preferences of the patients. According to Hospital 2007 propositions, the extended, flexible and general purpose Group of Sanitary Cooperation (GCS) meets the necessities inherent to the structures of supportive care within the territories of health because it can be established between one or several health care centres and the private health professionals, thus favouring the cooperation between public and private health care centres. PSPH and general medicine.     

Spontaneous vitiligo in an animal model for human melanoma: role of tumor-specific CD8+ T cells

Tumor antigen-reactive T cells can be detected in a large proportion of melanoma patients, but their efficacy on tumor control in vivo remains unclear. On the other hand, vitiligo, a skin disorder characterized by patchy depigmented macules, may occur spontaneously or after antitumor therapies. Moreover, vitiligo is significantly associated with positive clinical response, but the mechanism is not understood. Therefore, the establishment of a relevant animal model in which melanoma and vitiligo spontaneously develop stepwise may be useful for better understanding of the parameters involved in the destruction of both benign and malignant melanocytes. In a previous work, we established a mouse model for melanoma in which MT/ret transgenic mice express the ret oncogene fused to the metallothionein promoter. Here we report that melanoma leads to spontaneous vitiligo. We further investigate, for the first time in this model, the natural antitumor T-cell response and evaluate the role of cellular immunity in the development of the disease. Interestingly, the occurrence of spontaneous tumor nodules in MT/ret mice with melanoma-associated vitiligo is significantly delayed when compared in melanoma mice without vitiligo. Moreover, a significant proportion of mice with melanoma-associated vitiligo resisted a challenge with syngeneic melanoma cells in contrast to animals without vitiligo. Our results confirm that vitiligo is associated with clinical benefit and further demonstrate the crucial role of CD8+ T cells for tumor control in melanoma-associated vitiligo.     

Multidisciplinary approach decreases length of stay and reduces cost for ventricular assist device therapy

High implantation costs and long postoperative length of stay (LOS) in debilitated patients complicate ventricular assist device (VAD) therapy. Between July 2000 and February 2005, 30 patients received a VAD at our institution. Of those, 20 patients were successfully discharged from the hospital with VADs. In August 2003, a multidisciplinary team was formed consisting of all services for VAD patients to replace a single-discipline (cardiac surgery) system. This team evaluated potential VAD candidates and identified optimal timing for implantation. These 20 VAD patients were divided into two groups according to the initiation of multidisciplinary team; the traditional group (n=7, July 2000-July 2003) and the multidisciplinary group (n=13, August 2003-February 2005). Patient demographics were not different. The LOS decreased from 61 to 15 days (P<0.01), especially LOS on the floor decreased from 35 to 7 days (P=0.03). The floor cost was significantly reduced ($47,111 vs. $8742, P<0.01), leading to a decrease in total postoperative cost ($202,238 vs. $161,744, P<0.01). The 30-day readmission rate decreased (5/7 patients vs. 1/13 patients, P<0.01). A multidisciplinary approach significantly decreased LOS and cost after VAD therapy, mostly by decreasing the cost of routine non-ICU care, without increasing the readmission rate.