A cross-continental analysis of weight gain, psychiatric diagnoses and medication use during inpatient psychiatric treatment. The international study on physical illness in mentally ill.

Weight gain among psychiatric inpatients is a widespread phenomenon. This change in body mass index (BMI) can be caused by several factors. Based on recent research, we assume the following factors are related to weight gain during psychiatric inpatient treatment: psychiatric medication, psychiatric diagnosis, sex, age, weight on admission and geographic region of treatment. 876 of originally recruited 2328 patients met the criteria for our analysis. Patients were recruited and examined in mental health care centres in Nigeria (N = 265), Japan (N = 145) and Western-Europe (Denmark, Germany and Switzerland; N = 466). There was a significant effect of psychiatric medication, psychiatric diagnoses and geographic region, but not age and sex, on BMI changes. Geographic region had a significant effect on BMI change, with Nigerian patients gaining significantly more weight than Japanese and Western European patients. Moreover, geographic region influenced the type of psychiatric medication prescribed and the psychiatric diagnoses. The diagnoses and psychiatric medication prescribed had a significant effect on BMI change. In conclusion, we consider weight gain as a multifactorial phenomenon that is influenced by several factors. One can discuss a number of explanations for our findings, such as different clinical practices in the geographical regions (prescribing or admission strategies and access-to-care aspects), as well as socio-economic and cultural differences.

Reactivating p53 and Inducing Tumor Apoptosis (RITA) Enhances the Response of RITA-Sensitive Colorectal Cancer Cells to Chemotherapeutic Agents 5-Fluorouracil and Oxaliplatin.

Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract with frequently dysregulated intracellular signaling pathways, including p53 signaling. The mainstay of chemotherapy treatment of CRC is 5-fluorouracil (5FU) and oxaliplatin. The two anticancer drugs mediate their therapeutic effect via DNA damage-triggered signaling. The small molecule reactivating p53 and inducing tumor apoptosis (RITA) is described as an activator of wild-type and reactivator of mutant p53 function, resulting in elevated levels of p53 protein, cell growth arrest, and cell death. Additionally, it has been shown that RITA can induce DNA damage signaling. It is expected that the therapeutic benefits of 5FU and oxaliplatin can be increased by enhancing DNA damage signaling pathways. Therefore, we highlighted the antiproliferative response of RITA alone and in combination with 5FU or oxaliplatin in human CRC cells. A panel of long-term established CRC cell lines (n=9) including p53 wild-type, p53 mutant, and p53 null and primary patient-derived, low-passage cell lines (n=5) with different p53 protein status were used for this study. A substantial number of CRC cells with pronounced sensitivity to RITA (IC50<3.0 µmol/l) were identified within established (4/9) and primary patient-derived (2/5) CRC cell lines harboring wild-type or mutant p53 protein. Sensitivity to RITA appeared independent of p53 status and was associated with an increase in antiproliferative response to 5FU and oxaliplatin, a transcriptional increase of p53 targets p21 and NOXA, and a decrease in MYC mRNA. The effect of RITA as an inducer of DNA damage was shown by a strong elevation of phosphorylated histone variant H2A.X, which was restricted to RITA-sensitive cells. Our data underline the primary effect of RITA, inducing DNA damage, and demonstrate the differential antiproliferative effect of RITA to CRC cells independent of p53 protein status. We found a substantial number of RITA-sensitive CRC cells within both panels of established CRC cell lines and primary patient-derived CRC cell lines (6/14) that provide a rationale for combining RITA with 5FU or oxaliplatin to enhance the antiproliferative response to both chemotherapeutic agents.

Tremor, olfactory and motor changes in Italian adolescents exposed to historical ferro-manganese emission.

BACKGROUND AND OBJECTIVE: Increased prevalence of Parkinsonism was observed in Valcamonica, Italy, a region impacted by ferroalloy plants emissions containing manganese and other metals for a century until 2001. The aim of this study was to assess neurobehavioral functions in adolescents from the impacted region and the reference area of Garda Lake. METHODS: Adolescents age 11-14 years were recruited through the school system for neuro-behavioral testing. Metals including manganese, lead, iron, zinc, copper were measured in airborne particulate matter collected with 24-h personal samplers, and in soil, tap water, blood, urine and hair. Independent variables included parental education and socio-economic status, children's body mass index, number of siblings, parity order, smoking and drinking habits. RESULTS: A total of 311 subjects (49.2% females), residing in either the exposed (n=154) or the reference (n=157) area participated. Average airborne and soil manganese were respectively 49.5 ng/m(3) (median 31.4, range 1.24-517) and 958 ppm (median 897, range 465-1729) in the impacted area, and 27.4 ng/m(3) (median 24.7, range 5.3-85.9) ng/m(3) and 427 ppm (median 409 range 160-734) in the reference area. Regression models showed significant impairment of motor coordination (Luria-Nebraska test, p=0.0005), hand dexterity (Aiming Pursuit test, p=0.0115) and odor identification (Sniffin' task, p=0.003) associated with soil manganese. Tremor intensity was positively associated with blood (p=0.005) and hair (p=0.01) manganese. CONCLUSION: Historical environmental exposure to manganese from ferroalloy emission reflected by the concentration in soil and the biomarkers was associated with sub-clinical deficits in olfactory and motor function among adolescents.