Mathematical analysis and simulations involving chemotherapy and surgery on large human tumours under a suitable cell-kill functional response

Dosage and frequency of treatment schedules are important for successful chemotherapy. However, in this work we argue that cell-kill response and tumoral growth should not be seen as separate and therefore are essential in a mathematical cancer model. This paper presents a mathematical model for sequencing of cancer chemotherapy and surgery. Our purpose is to investigate treatments for large human tumours considering a suitable cell-kill dynamics. We use some biological and pharmacological data in a numerical approach, where drug administration occurs in cycles (periodic infusion) and surgery is performed instantaneously. Moreover, we also present an analysis of stability for a chemotherapeutic model with continuous drug administration. According to Norton & Simon [22], our results indicate that chemotherapy is less eficient in treating tumours that have reached a plateau level of growing and that a combination with surgical treatment can provide better outcomes.

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.

Single early prenatal lipopolysaccharide exposure impairs striatal monoamines and maternal care in female rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Patient Education and Self-Care for the Management of Jaw Pain upon Awakening: A Randomized Controlled Clinical Trial Comparing the Effectiveness of Adding Pharmacologic Treatment with Cyclobenzaprine or Tizanidine

Aims: To compare the effectiveness of adding cyclobenzaprine, tizanidine, or placebo to patient education and a self-care management program for patients with myofascial pain and specifically presenting with jaw pain upon awakening. Methods: Forty-five patients with a diagnosis of myofascial pain based on the guidelines of the American Academy of Orofacial Pain participated in this 3-week study. The subjects were randomly assigned into one of three groups: placebo group, TZA group (tizanidine 4 mg), or CYC group (cyclobenzaprine 10 mg). Patients were evaluated for changes in pain intensity, frequency, and duration by using the modified Severity Symptoms Index and changes in sleep quality with the use of the Pittsburgh Sleep Quality Index. Data were analyzed by ANOVA and post-hoc or nonparametric statistical tests as appropriate. Results: All three groups had a reduction in pain symptoms and improvement of sleep quality based on a comparison of pretreatment and treatment scores. However, no significant differences among the groups were observed at the posttreatment evaluation. Conclusion: The use of tizanidine or cyclobenzaprine in addition to self-care management and patient education was not more effective than placebo for the management of patients with myofascial jaw pain upon awakening.

Development of organic-inorganic polymeric film formers for controlled drug release and wound care

Film forming polymeric systems represents a new and unexplored technology of systems forskin or wounds protection and for controlled drug release. The aim of this work was to study the use of polymeric organic-inorganic ureasil-polyether hybrids synthesized by the sol-gel process as film forming system containing silver sulfadiazine as model drug. The film formationtime can be controlled by changing the precursor/catalyst ratio used during the step of hydrolysis and condensations. The results showed that the precursor/catalyst proportion influences both the visual characteristics and time required to form the film. The precursor/catalyst ratio equal to 20.8 m/v was considered ideal due to promote the homogeneous and transparent film formation in less than 5 minutes. The release profile of sulfadiazine is dependent on the characteristics of the matrixes: matrix more hydrophobic as ureasil-POP provided a slowed released mainly due to the low swelling of the matrix. The more hydrophilic ureasil-POE matrix presents a large capacity to swell and favors the faster release of the drug. The set of results showed the possibility of future use of these systems for treating wounds caused by burns.

Immunomodulatory effects of low dose chemotherapy and perspectives of combanation with immunotherapy

Nowadays cancer is one of the main causes of death and many efforts worldwide have been driven to find out new treatments and approaches in order to extinguish or reduce this group of disorder. Chemotherapy is the main treatment for cancer, however, conventional schedule based on maximum tolerated dose (MTD) show several side effects and frequently allow the development of drug resistance. In this review we present the evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics is as efficient as MTD and works better in some situations. 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 provide us the evidence that low concentrations of selected chemotherapeutics agents, rather than conventional high doses, should be chosen for combination with immunotherapy

SOCIAL MONOGAMY AND BIPARENTAL CARE OF THE NEOTROPICAL SOUTHERN BAMBOO RAT (KANNABATEOMYS AMBLYONYX)

We analyzed social patterns indicative of the mating system and parental care in a population of the southern bamboo rat (Kannabateomys amblyonyx). This arboreal rodent feeds exclusively on bamboo stems and leaves. We conducted fieldwork from August 2003 to October 2004 in southern Brazil (30 degrees 20`-30 degrees 27`S, 50 degrees 50`-51 degrees 05`W), in patches of introduced Chinese bamboo (Bambusa tuldoides). We captured 18 individuals, 7 of which were adults that received radiotransmitters and were followed from 1 to 12 months. Another 5 animals (adults or subadults) received colored collars. We observed paternal care, delayed juvenile dispersal, and reduced degree of sexual dimorphism, all of which are traits typical of social monogamy. Mated males showed a direct parental behavioral repertoire similar to that of females (with the obvious exception of nursing), including grooming, huddling, and food provisioning. Potential monogamy in this species seems to be a flexible strategy linked to low density of bamboo patches. Females were confined to widely spaced., small home ranges, decreasing the possibility of male defense of and access to > 1 female. The arboreal habits of the species possibly increase the risk of inexperienced young falling from trees or else being depreciated when moving exposed through branches. This risk is probably reduced by the extensive biparental care observed, including the providing of low-energy plant food to young in the nest.

Diversity and Adaptation of Human Respiratory Syncytial Virus Genotypes Circulating in Two Distinct Communities: Public Hospital and Day Care Center

HRSV is one of the most important pathogens causing acute respiratory tract diseases as bronchiolitis and pneumonia among infants. HRSV was isolated from two distinct communities, a public day care center and a public hospital in Sao Jose do Rio Preto - SP, Brazil. We obtained partial sequences from G gene that were used on phylogenetic and selection pressure analysis. HRSV accounted for 29% of respiratory infections in hospitalized children and 7.7% in day care center children. On phylogenetic analysis of 60 HRSV strains, 48 (80%) clustered within or adjacent to the GA1 genotype; GA5, NA1, NA2, BA-IV and SAB1 were also observed. SJRP GA1 strains presented variations among deduced amino acids composition and lost the potential O-glycosilation site at amino acid position 295, nevertheless this resulted in an insertion of two potential O-glycosilation sites at positions 296 and 297. Furthermore, a potential O-glycosilation site insertion, at position 293, was only observed for hospital strains. Using SLAC and MEME methods, only amino acid 274 was identified to be under positive selection. This is the first report on HRSV circulation and genotypes classification derived from a day care center community in Brazil.

The profile of women who have experienced cesarean section and obstetric care at a public maternity hospital in Ribeirao Preto

The present paper presents the social and obstetric profile of women undergoing cesarean childbirth at a public maternity hospital in the interior of Sao Paulo state. This is a quantitative, retrospective, descriptive study performed using documental research. The collected data refer to the period between July and December 2005, and between January and June 2006. A total of 670 records were reviewed. A 23% rate of cesarean births was identified at the institution studied during the aforementioned period. The studied population was characterized as having a low level of education, living in a common-law relationship, and not having a paid occupation. The main indications for cesarean sections were iterativity and acute fetal distress. The findings revealed an emphasis on obstetric nursing in the low-risk normal childbirth scenario, considering the non-interventionist character inherent to their education and training.

Burden of maternal bipolar disorder on at-risk offspring: A controlled study on family planning and maternal care

Introduction: Bipolar disorder (BD) is a highly incapacitating disease typically associated with high rates of familial dysfunction. Despite recent literature suggesting that maternal care is an important environmental factor in the development of behavioral disorders, it is unclear how much maternal care is dysfunctional in BD subjects. Objective: The objective of this study was to characterize maternal care in DSM-IV/SCID diagnosed BD type I subjects compared to healthy controls with (PD) and without (NPD) other psychiatric diagnoses. Materials and methods: Thirty-four BD mothers and 106 controls underwent an interview about family planning and maternal care, obstetrical complications, and mother-child interactions. K-SADS-PL questions about violence exposure were used to ascertain domestic violence and physical/sexual abuse. Results: BD mothers were less likely to have stable unions (45.5%; p < 0.01) or to live with the biological father of their children (33.3%; p < 0.01), but had higher educational level and higher rates of social security use/retirement. They also had fewer children and used less contraceptive methods than controls. Children of BD women had higher rates of neonatal anoxia, and reported more physical abuse (16.1%; p = 0.02) than offspring of NPD mothers. Due to BD mothers' symptoms, 33.3% of offspring suffered physical and/or psychological abuse. Limitations: Post hoc analysis, and the use of questions as a surrogate of symptoms as opposed to validated instruments. Conclusion: This is one of few reports confirming that maternal care given by BD women is dysfunctional. BD psychopathology can lead to poor maternal care and both should be considered important environmental risk factors in BD, suggesting that BD psychoeducation should include maternal care orientation. (C) 2012 Elsevier B.V. All rights reserved.

Qualifying instrument for evaluation of food and nutritional care in hospital

Establishing criteria for hospital nutrition care ensures that quality care is delivered to patients. The responsibility of the Hospital Food and Nutrition Service (HFNS) is not always well defined, despite efforts to establish guidelines for patient clinical nutrition practice. This study describes the elaboration of an Instrument for Evaluation of Food and Nutritional Care (IEFNC) aimed at directing the actions of the Hospital Food and Nutrition Service. This instrument was qualified by means of a comparative analysis of the categories related to hospital food and nutritional care, published in the literature. Elaboration of the IEFNC comprised the following stages: (a) a survey of databases and documents for selection of the categories to be used in nutrition care evaluation, (b) a study of the institutional procedures for nutrition practice at two Brazilian hospitals, in order to provide a description of the sequence of actions that should be taken by the HFNS as well as other services participating in nutrition care, (c) design of the IEFNC based on the categories published in the literature, adapted to the sequence of actions observed in the routines of the hospitals under study, (d) application of the questionnaire at two different hospitals that was mentioned in the item (b), in order to assess the time spent on its application, the difficulties in phrasing the questions, and the coverage of the instrument, and (e) finalization of the instrument. The IEFNC consists of 50 open and closed questions on two areas of food and nutritional care in hospital: inpatient nutritional care and food service quality. It deals with the characterization and structure of hospitals and their HFNS, the actions concerning the patients' nutritional evaluation and monitoring, the meal production system, and the hospital diets. "This questionnaire is a tool that can be seen as a portrait of the structure and characteristics of the HFNS and its performance in clinical and meal management dietitian activities." (Nutr Hosp. 2012;27:1170-1177) DOI:10.3305/nh.2012.27.4.5868

Gauging food and nutritional care quality in hospitals

Background: Food and nutritional care quality must be assessed and scored, so as to improve health institution efficacy. This study aimed to detect and compare actions related to food and nutritional care quality in public and private hospitals. Methods: Investigation of the Hospital Food and Nutrition Service (HFNS) of 37 hospitals by means of structured interviews assessing two quality control corpora, namely nutritional care quality (NCQ) and hospital food service quality (FSQ). HFNS was also evaluated with respect to human resources per hospital bed and per produced meal. Results: Comparison between public and private institutions revealed that there was a statistically significant difference between the number of hospital beds per HFNS staff member (p = 0.02) and per dietitian (p < 0.01). The mean compliance with NCQ criteria in public and private institutions was 51.8% and 41.6%, respectively. The percentage of public and private health institutions in conformity with FSQ criteria was 42.4% and 49.1%, respectively. Most of the actions comprising each corpus, NCQ and FSQ, varied considerably between the two types of institution. NCQ was positively influenced by hospital type (general) and presence of a clinical dietitian. FSQ was affected by institution size: large and medium-sized hospitals were significantly better than small ones. Conclusions: Food and nutritional care in hospital is still incipient, and actions concerning both nutritional care and food service take place on an irregular basis. It is clear that the design of food and nutritional care in hospital indicators is mandatory, and that guidelines for the development of actions as well as qualification and assessment of nutritional care are urgent.

Sexual selection in Pomatoschistus – nests, sperm competition, and paternal care

Sexual selection arises through variation in reproductive success. This thesis investigates different aspects important in sexual selection, namely nest building, sperm competition, paternity and paternal care, and their mutual interrelationships. In the studied species, the sand goby (Pomatoschistus minutus) and the common goby (Pomatoschistus microps), sperm competition did arise when small males, so called sneakers, sneaked into other males nests and released sperm. They seemed to use female behaviour as their prime cue for a sneaking opportunity. However, also nest-holders, both with and without eggs, were found to fertilize eggs in the nests of other males. Clearly, nest-holding males tried to prevent other males from spreading their sperm in their nests, since they showed aggression towards such males. A nest building experiment indicated that the small nest-openings found in the sneaker male treatment were sexually selected through protection against sneaking or by female choice. Yet, no behavioural or genetical support for the hypothesis that the nest functions as a physical or visual defence, or that sneaker males prefer to sneak upon nests with wide nest-openings, were found in the other studies. Still, individual nest-holding males showed a higher mucus preparation effort inside the nest in the presence of a sneaker male than when alone. In close relatives, such mucus contains sperm, suggesting an importance in sperm competition. However, the mucus may also have pheromone and anti-bacterial functions and may constitute a mating effort, as found in other gobies. Both a behavioural and a mate choice experiment suggested that the males were not less eager to spawn in the presence of a sneaker male. Sneak intrusion did not affect nest defence, fanning or filial cannibalism, nor had paternity an effect on filial cannibalism. This and various life history aspects, together with the fact that the parasitic male only fertilized a fraction of the clutches, would predict females to ignore sneaker males. This was also the case, as the presence of sneaker males was found not to affect female spawning decision. Still, several females spawned in two nests, which coincided with parasitic spawnings, suggesting a cost of disturbance for the females and thus a substantial cost to the nest-holding males in terms of lost mating success. However, females paid attention to other traits in their choice of mate since spawning was associated with sand volume of the nest, but not with nest-opening width. Also, female (but not male) courtship was correlated with partial clutch filial cannibalism, indicating that females are able to anticipate future male cannibalism. In a partial correlation of nest opening, sand volume, male courtship display, displacement fanning and male size, a large number of traits were correlated both positively and negatively with regard to how we may expect them to be appreciated by females. For instance, males which fan well also build large nests or display intensely (but not both). Together with all the other results of this thesis, this shows the entangled selection pressures working on breeding animals, as well as the different male and female tactics employed to maximize their reproduction.

Essays in Applied Health Economics: Evidence on Health and Health Care in Italy and UK

This thesis is the result of my experience as a PhD student taking part in the Joint Doctoral Programme at the University of York and the University of Bologna. In my thesis I deal with topics that are of particular interest in Italy and in Great Britain. Chapter 2 focuses on the empirical test of the existence of the relationship between technological profiles and market structure claimed by Sutton’s theory (1991, 1998) in the specific economic framework of hospital care services provided by the Italian National Health Service (NHS). In order to test the empirical predictions by Sutton, we identify the relevant markets for hospital care services in Italy in terms of both product and geographic dimensions. In particular, the Elzinga and Hogarty (1978) approach has been applied to data on patients’ flows across Italian Provinces in order to derive the geographic dimension of each market. Our results provide evidence in favour of the empirical predictions of Sutton. Chapter 3 deals with the patient mobility in the Italian NHS. To analyse the determinants of patient mobility across Local Health Authorities, we estimate gravity equations in multiplicative form using a Poisson pseudo maximum likelihood method, as proposed by Santos-Silva and Tenreyro (2006). In particular, we focus on the scale effect played by the size of the pool of enrolees. In most of the cases our results are consistent with the predictions of the gravity model. Chapter 4 considers the effects of contractual and working conditions on selfassessed health and psychological well-being (derived from the General Health Questionnaire) using the British Household Panel Survey (BHPS). We consider two branches of the literature. One suggests that “atypical” contractual conditions have a significant impact on health while the other suggests that health is damaged by adverse working conditions. The main objective of our paper is to combine the two branches of the literature to assess the distinct effects of contractual and working conditions on health. The results suggest that both sets of conditions have some influence on health and psychological well-being of employees.