Chronic administration of risperidone in a rat model of schizophrenia: A behavioural, morphological and molecular study

In the present work we analyzed the effect of the chronic administration of risperidone (2mg/kg over 65 days) on behavioural, morphological and molecular aspects in an experimental model of schizophrenia obtained by bilateral injection of ibotenic acid into the ventral hippocampus of new-born rats. Our results show that during their adult lives the animals with hippocampal lesions exhibit different alterations, mainly at behavioural level and in the gene expression of dopamine D2 and 5-HT2A receptors. However, at morphological level the study performed on the prefrontal cortex did not reveal any alterations in either the thickness or the number of cells immunoreactive for c-Fos, GFAP, CBP or PV. Overall, risperidone administration elicited a trend towards the recovery of the values previously altered by the hippocampal lesion, approaching the values seen in the animals without lesions. It may be concluded that the administration of risperidone in the schizophrenia model employed helps to improve the altered functions, with no significant negative effects. © 2013.

A heuristic algorithm based on multi-assignment procedures for nurse scheduling

This paper tackles a Nurse Scheduling Problem which consists of generating work schedules for a set of nurses while considering their shift preferences and other requirements. The objective is to maximize the satisfaction of nurses' preferences and minimize the violation of soft constraints. This paper presents a new deterministic heuristic algorithm, called MAPA (multi-assignment problem-based algorithm), which is based on successive resolutions of the assignment problem. The algorithm has two phases: a constructive phase and an improvement phase. The constructive phase builds a full schedule by solving successive assignment problems, one for each day in the planning period. The improvement phase uses a couple of procedures that re-solve assignment problems to produce a better schedule. Given the deterministic nature of this algorithm, the same schedule is obtained each time that the algorithm is applied to the same problem instance. The performance of MAPA is benchmarked against published results for almost 250,000 instances from the NSPLib dataset. In most cases, particularly on large instances of the problem, the results produced by MAPA are better when compared to best-known solutions from the literature. The experiments reported here also show that the MAPA algorithm finds more feasible solutions compared with other algorithms in the literature, which suggest that this proposed approach is effective and robust. © 2013 Springer Science+Business Media New York.

Cost-effectiveness comparison between pituitary down-regulation with a gonadotropin-releasing hormone agonist short regimen on alternate days and an antagonist protocol for assisted fertilization treatments

Objective: To compare cost-effectiveness between pituitary down-regulation with a GnRH agonist (GnRHa) short regimen on alternate days and GnRH antagonist (GnRHant) multidose protocol on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcome. Design: Prospective, randomized. Setting: A private center. Patient(s): Patients were randomized into GnRHa (n = 48) and GnRHant (n = 48) groups. Intervention(s): GnRHa stimulation protocol: administration of triptorelin on alternate days starting on the first day of the cycle, recombinant FSH (rFSH), and recombinant hCG (rhCG) microdose. GnRHant protocol: administration of a daily dose of rFSH, cetrorelix, and rhCG microdose. Main Outcome Measure(s): ICSI outcomes and treatment costs. Result(s): A significantly lower number of patients underwent embryo transfer in the GnRHa group. Clinical pregnancy rate was significantly lower and miscarriage rate was significantly higher in the GnRHa group. It was observed a significant lower cost per cycle in the GnRHa group compared with the GnRHant group ($5,327.80 ± 387.30 vs. $5,900.40 ± 472.50). However, mean cost per pregnancy in the GnRHa was higher than in the GnRHant group ($19,671.80 ± 1,430.00 vs. $11,328.70 ± 907.20). Conclusion(s): Although the short controlled ovarian stimulation protocol with GnRHa on alternate days, rFSH, and rhCG microdose may lower the cost of an individual IVF cycle, it requires more cycles to achieve pregnancy. Clinical Trial Registration Number: NCT01468441. © 2013 by American Society for Reproductive Medicine.

Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy

Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy. Copyright © 2012 UICC.