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BACKGROUND AND PURPOSE: Designer ß-keto amphetamines (e.g. cathinones, 'bath salts' and 'research chemicals') have become popular recreational drugs, but their pharmacology is poorly characterized. EXPERIMENTAL APPROACH: We determined the potencies of cathinones to inhibit DA, NA and 5-HT transport into transporter-transfected HEK 293 cells, DA and 5-HT efflux from monoamine-preloaded cells, and monoamine receptor binding affinity. KEY RESULTS: Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors, similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and other entactogens. Cathinone, methcathinone and flephedrone, similar to amphetamine and methamphetamine, acted as preferential DA and NA uptake inhibitors and induced the release of DA. Pyrovalerone and 3,4-methylenedioxypyrovalerone (MDPV) were highly potent and selective DA and NA transporter inhibitors but unlike amphetamines did not evoke the release of monoamines. The non-ß-keto amphetamines are trace amine-associated receptor 1 ligands, whereas the cathinones are not. All the cathinones showed high blood-brain barrier permeability in an in vitro model; mephedrone and MDPV exhibited particularly high permeability. CONCLUSIONS AND IMPLICATIONS: Cathinones have considerable pharmacological differences that form the basis of their suggested classification into three groups. The predominant action of all cathinones on the DA transporter is probably associated with a considerable risk of addiction.

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We investigate the local static molecular orientational behavior in zeolite L inclusion compounds by polarimetric two-photon fluorescence microscopy. This technique, based on the polarized read-out of the signal under a tunable incident polarization state, provides refined information on molecular disorder that is not achievable using traditional fluorescence anisotropy. Moreover, the polarimetric microscopy imaging scheme permits a spatial investigation of possible heterogeneities, with a submicrometric resolution. The study performed on different fluorescent molecules inserted in zeolite L channels evidence a degree of disorder for either small or flexible structures.

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CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the National Federation of Comprehensive Cancer Centres (FNCLCC), the 20 French Cancer Centers and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for nutritional support in adult patients with advanced or terminal cancer. METHODS: Data were identified by searching Medline, web sites and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 95 independent reviewers. RESULTS: The main recommendations for nutritional support in adult patients with advanced or terminal cancer are: 1) Palliative care has been defined in a consensual way and is governed by the law (standard). Nutritional support is a palliative care which aim is to maintain and restore the "well-being" of the patient (standard). 2) Digestive symptoms and nutritional troubles are frequently noted in patients with advanced or terminal cancer (standard, level of evidence B2). Karnofsky index (KPS) and performance status (PS) are functional scores with a prognostic value and have to be used (standard, level of evidence B2). 3) Anorexia has a bad predictive value in patients with advanced or terminal cancer (standard, level of evidence B2). 4) In France, patients with advanced or terminal cancer are referred to medical institutions, palliative care units or remained at home (standard). Patients need a multidisciplinary follow-up (standard). An active participation of patients and/or their family circle is very important and physicians have to pay attention for their opinions (standard). 5) Dietetic counseling can help patients to improve their alimentation and its drawbacks (standard). 6) Palliative nutritional care often includes medicinal treatments (standard). 7) Artificial nutrition can slow down nutritional degradation, avoid dehydration and improve quality of life in patients with advanced stage cancer (especially head and neck cancer for enteral nutrition and digestive occlusions for parenteral nutrition) and unable to eat adapted meals (standard, level of evidence C). 8) When life expectancy is below 3 months with a KPS 3/4 50% (or PS > 2), artificial nutrition is not recommended (recommendation, expert agreement). 9) The assessment of nutritional care in patients with advanced or terminal cancer has to include functional scores measurement, quality of life and satisfaction degree of the patient and/or their family (standard, expert agreement).

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CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the French National Federation of Comprehensive Cancer Centers (FNCLCC), the 20 French Cancer Centers and specialists from French Public University or General Hospitals, and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome of cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of the main tumor markers in colorectal cancer and their potential role in the management of patients with this malignancy. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 117 independent reviewers, and to the medical committees of the 20 French Cancer Centers. RESULTS: The main recommendations for the tumor markers in colorectal cancer are: 1) The carcinoembryonic antigen (CEA) is the reference serum marker (standard). 2) All the analyses for a given patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 3) CEA or CA 19-9 should not be used for screening or diagnosis (standard, level of evidence B2). 4) High initial serum concentration of CEA is of bad predictive value (standard, level of evidence C). CEA is an independent prognostic factor of survival in colorectal cancers with lymph node metastases (standard, level of evidence B2). 5) CEA is the most sensitive biological parameter for the screening of hepatic metastases (standard, level of evidence B2). 6) CEA serum concentration before palliative chemotherapy is an independent prognostic factor of survival (standard, level of evidence B2). The combination of CEA assay with imagery techniques and clinical examination can help monitor the response to palliative chemotherapy (standard), in particular in non measurable disease (standard, expert agreement). 7) In 65% of the cases, CEA is the first indicator of relapse (standard, level of evidence B2). CEA is the choice marker for monitoring patients with colorectal cancer (standard, level of evidence B2). 8) A sustained biological follow-up including CEA assay can be used to predict the operability of recurring tumors (standard, level of evidence B2). Nevertheless, no survival advantage has been shown (standard).

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