CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Muitas dificuldades sÃo encontradas na implementaÃÃo de classificaÃÃes de enfermagem na prÃtica clÃnica. Destaca-se a falta de familiaridade dos enfermeiros com os sistemas de classificaÃÃo e as dificuldades na tomada de decisÃo diagnÃstica associadas Ãs deficiÃncias no processo de raciocÃnio diagnÃstico. Assim, estudos que desenvolvam ferramentas tecnolÃgicas como as Ãrvores de decisÃo (AD) podem contribuir para agilizar a tomada de decisÃo diagnÃstica e facilitar o uso destes fenÃmenos. Objetivou-se gerar Ãrvores de decisÃo baseadas em probabilidades condicionais para auxÃlio na inferÃncia diagnÃstica de DesobstruÃÃo ineficaz de vias aÃreas (DIVA) e PadrÃo respiratÃrio ineficaz (PRI) em crianÃas com infecÃÃo respiratÃria aguda (IRA). Estudo transversal desenvolvido com o intuito de identificar dados para que pudessem ser utilizados na geraÃÃo de Ãrvores de decisÃo com boa aplicabilidade clÃnica. Realizou-se avaliaÃÃo respiratÃria de 249 crianÃas com diagnÃstico mÃdico de IRA no perÃodo de janeiro a abril de 2011. Estes dados serviram de base para determinaÃÃo das caracterÃsticas definidoras (CD) dos diagnÃsticos de enfermagem (DE) em estudo. As CD foram enviadas para dois enfermeiros diagnosticadores para o processo de inferÃncia diagnÃstica. A maior parte das crianÃas era do sexo masculino (55,8%). Pneumonia (79,9%) foi a principal IRA encontrada e Asma (17,7%), a principal comorbidade. DIVA esteve presente em 89,2% dos casos e PRI em 65,5%. As CD de DIVA com maior prevalÃncia foram: âTosse ineficazâ (91,3%), âRuÃdos adventÃcios respiratÃriosâ (77,1%), âDispneiaâ (69,3%), âMudanÃas na frequÃncia respiratÃriaâ (56,6%), âOrtopneiaâ (54,2%) e âExpectoraÃÃoâ (32,1%). Jà para PRI, as CD mais prevalentes foram: âAlteraÃÃes na profundidade respiratÃriaâ (73,9%), âDispneiaâ (68,3%), âTaquipneiaâ (57,0%),âOrtopneiaâ (54,2%) e âUso da musculatura acessÃria para respirarâ (51,8%). Utilizaram-se trÃs algoritmos para geraÃÃo de AD: CHi-square Automatic Interaction Detection (CHAID), Classification and Regression Trees (CRT) e Quick, Unbiased, Efficient Statistical Tree (QUEST). As AD foram submetidas à validaÃÃo cruzada para que se avaliasse o poder de prediÃÃo dessas. Desenvolveram-se trÃs AD para auxÃlio na inferÃncia diagnÃstica de DIVA, trÃs para PRI e trÃs para diferenciaÃÃo destes diagnÃsticos. Para DIVA, a AD com maior poder de prediÃÃo foi a desenvolvida pelo mÃtodo CHAID. Jà para PRI, os valores de prediÃÃo foram similares para os trÃs mÃtodos de crescimento das Ãrvores. Para diferenciaÃÃo diagnÃstica, a Ãrvore gerada pelo mÃtodo CRT obteve melhor poder de prediÃÃo (86,4%). Acredita-se que a implementaÃÃo das Ãrvores de decisÃo pode ajudar a tornar as inferÃncias destes dois diagnÃsticos mais acuradas. Entretanto esta relaÃÃo necessita ser aprofundada, aplicando-se as AD geradas em outras populaÃÃes. Conclui-se que a utilizaÃÃo de tecnologias como as AD pode ser valorosa tanto na prÃtica clÃnica como no ensino de diagnÃsticos de enfermagem.

Thesis (M.Pharm. (Pharmaceutics) -- University of Limpopo, 2018 / Griseofulvin is an antibiotic fungistatic drug used in the treatment of dermatophyte and ringworm infections. About 50% of a dose of griseofulvin passes the gastro- intestinal tract unabsorbed and is excreted in faeces. Since griseofulvin is highly soluble in acidic pH, a gastro-retentive floating matrix system was developed to control dissolution rate and thereby enhance solubility in an effort to develop an improved and convenient dosage form. Preformulation studies included selection of excipients and evaluation of their compatibility with griseofulvin. Using the chosen excipients, floating tablets of griseofulvin were formulated. Floating tablets containing 100 mg of griseofulvin were prepared by wet granulation technique with varying ratios of Methocel™, Accurel MP and Polyvinylpyrrolidone as determined by Design Expert software. Pre and post-compression studies, buoyancy capability and dissolution studies were carried out to assess the influence of the tablet components. Results obtained revealed that a density of less than 0.00091 g/cm3 was necessary for tablet floatation. Tablets that float immediately upon contact with dissolution medium and continue floating for over 12 hours were achieved with at least 28% Accurel MP by mass of the tablet. Dissolution studies revealed that an increase in tablet hardness reduced the rate of griseofulvin release only up to 120 minutes. From 120 minutes onwards, tablet hardness had no significant influence on griseofulvin release from tablets. Methocel™ had the most significant influence on griseofulvin release. The amount of Methocel™ included in the formulation was indirectly proportional to the rate of griseofulvin release. Using Design Expert software, optimized formulation was achieved with 1% Polyvinylpyrrolidone, 30% Methocel™, 60% Accurel MP and hardness ranging between 8 – 9 N. Pre and post-compression parameters of the optimized tablets were found to be within pharmacopoeial limits and thus compressed tablets were of acceptable quality. Tablets produced floated immediately upon contact with the medium and remained floating for at least 12 hours. Griseofulvin was released from the optimized tablets in a near zero order fashion, with a total of 80.8% griseofulvin released at the end of the 12 hour dissolution test period. Results of accelerated stability studies indicated potential stability of the manufactured tablets months.

An examination of previously unaccessioned and overlooked specimens has added 16 species to the vascular flora of the 3800 ha Rocky Fork Tract in northeastern Tennessee. One species was deleted because of a prior misidentification for a net gain of 15 species and a total of 764 species. One species, Solidago lancifolia (Torr. ex A. Gray) Chapm., is listed as Endangered in Tennessee. All additions except two, represent county records. ©2018 Botanical Research Institute of Texas.

Pediatric acute respiratory tract infections (ARTIs) are a leading cause of morbidity and mortality. The objectives of this study were to describe the epidemiology of polymicrobial ARTI in a hospital-based pediatric population and to investigate the association of polymicrobial infection and severity of illness. We conducted a retrospective study of 559 archived respiratory specimens from 421 children under the age of 10 years collected from March 28, 2008 through June 30, 2009 and stored by the University of Iowa Hospital and Clinics Clinical Microbiology Laboratory. Specimens were tested by immunofluorescence assay and/or viral culture at the time of collection (influenza A and B, parainfluenza [PIV] 1-3, respiratory syncytial virus [RSV], adenovirus [Ad]) and uniformly by RT-PCR (human metapneumovirus [hMPV], rhinovirus [HRV], human bocavirus [HBoV]) and PCR (Ad) for the current study. Demographic and clinical data were abstracted from electronic medical records. Results from this study suggest that polymicrobial respiratory tract infections are common in this population. A virus was identified in 61.3% of 349 respiratory specimens from children with confirmed or suspected ARTI. HRV (27.5%), RSV (18.9%), HBoV (8.3%), hMPV (7.7%), and PIV (6.6%) were the most common viruses detected. A viral coinfection was identified in 21.5% of the 214 virus-positive specimens and was most often detected for Ad (53.3% of 15 Ad-positive specimens), HBoV (51.7% of 29 HBoV-positive specimens), PIV (43.5% of 23 PIV-positive specimens), HRV (35.4% of 96 HRV-positive specimens), and RSV (34.8% of 66 RSV-positive specimens). Among the 46 specimens with dual or triple viral coinfections detected, the most frequent virus-virus combination was HRV-RSV (n=12). We hypothesized that certain host-specific risk factors were associated with the likelihood of viral coinfection. While none of the covariates in the final model were significant, the results were suggestive. Male gender (OR 1.70, 95% CI 0.83-3.46), age between 6 months to 1 year (as compared to children less than 6 months old, OR 2.15, 95% CI 0.75-6.19), and history of any chronic condition that may result in immunosuppression (OR 2.05, 95% CI 0.99-4.23) were each associated with increased odds of viral coinfection (p > 0.05). We also hypothesized that children with coinfections would be more likely to have severe ARTI. Children with viral-bacterial coinfection, as compared to children with viral mono-infection, were more likely to be admitted to an intensive care unit (OR 6.00, 95% CI 2.51-14.33) even after controlling for age, history of prematurity, urban/rural residence, and leukocytosis. This study will inform medical and public health professionals with regard to the epidemiology of polymicrobial infections and their potential importance as a cause of severe acute respiratory tract infection in children. Furthermore, results of this study may contribute to the ongoing discussion of the importance of diagnostic ability to reliably detect multiple concurrent pathogens in a single individual.

How does the brain develop differently to support nocturnality in some mammals, but diurnality in others? To answer this question, one might look to the suprachiasmatic nucleus (SCN), the pacemaker of the mammalian brain, which is required for all circadian biological and behavioral rhythms. Light arriving at the retina entrains the SCN to the daily light-dark cycle via the retinohypothalamic tract (RHT). However, in all mammals studied thus far, whether nocturnal or diurnal, the SCN exhibits a rhythm of increased activity during the day and decreased activity at night. Therefore, structures downstream of the SCN are likely to determine whether a species is nocturnal or diurnal. From an evolutionary perspective, nocturnality appears to be the primitive condition in mammals, with diurnality having reemerged independently in some lineages. However, it is unclear what mechanisms underlie the development of one or the other circadian phase preference. In adult Norway rats (Rattus norvegicus), which are nocturnal, the RHT also projects to the ventral subparaventricular zone (vSPVZ), an adjacent region that expresses an in-phase pattern of SCN-vSPVZ neuronal activity (in other words, activity in the SCN and vSPVZ increase and decrease together). In contrast, in adult Nile grass rats (Arvicanthis niloticus), a diurnal species that is closely related to Norway rats, an anti-phase pattern of SCN-vSPVZ neuronal activity is expressed (in other words, activity in the SCN increases as activity in the vSPVZ decreases, and vice versa). We hypothesized that these species differences in activity pattern result in part from a weak or absent RHT-to-vSPVZ projection in grass rats. Using a developmental comparative approach, we assessed differences in behavior, hypothalamic activity, and RHT and SCN connectivity to the vSPVZ between these two species. We report that a robust retina-to-vSPVZ projection develops in Norway rats around the end of the second postnatal week when nocturnal wakefulness and the in-phase pattern of SCN-vSPVZ activity emerge. In grass rats, however, such a projection does not develop and the emergence of the anti-phase SCN-vSPVZ activity pattern during the second postnatal week is accompanied by increased diurnal wakefulness. When considered within the context of previously published reports on RHT projections in a variety of other nocturnal and diurnal species, our current findings suggest that how and when the retina connects to the hypothalamus differentially shapes brain and behavior to produce animals that occupy opposing temporal niches.

Chronic rhinosinusitis is a common disorder of chronic inflammation of the upper respiratory tract. It is associated with significant symptoms and impairment of the quality of life of sufferers. Despite recent advances in the medical and surgical management of chronic rhinosinusitis, there remains a population of patients who fail to obtain relief from their symptoms. Chronic inflammation of the mucosa of the nasal cavity and paranasal sinuses is one of the hallmarks of chronic rhinosinusitis. This inflammation is demonstrated by an increased number of chronic inflammatory cells, elevated levels of pro-inflammatory cytokines, increased expression of adhesion molecules and metaplastic changes in the epithelium. The current medical treatments for chronic sinusitis aim to reduce this inflammation and consequently improve symptoms. In recent years, evidence has emerged that macrolide antibiotics have an anti-inflammatory effect that is separate from their anti-bacterial effect. This effect was first described in the treatment of diffuse panbronchiolitis, a disorder of chronic inflammation of the lower respiratory tract. Following the success of macrolides in treating this condition it was trialed in chronic rhinosinusitis. Several open-label trials have subsequently demonstrated a beneficial effect. Laboratory studies have investigated the mechanism of the anti-inflammatory effect of macrolides. These have shown that macrolides effect cytokine production, inflammatory cell apoptosis, expression of adhesion molecules, neutrophil oxidative burst, bacterial virulence and mucociliary function. In this thesis we report a series of experiments designed to further investigate the mechanism of action and clinical effect of macrolides. In vitro studies using whole sections of chronic rhinosinusitis mucosa cultured for 24 hours in macrolide, prednisolone or control showed that macrolide and prednisolone produced significant reductions in the production of interleukin-5, interleukin-8 and granulocyte-macrophage colony stimulating factor. The same cultured specimens also showed a reduction in expression of transforming growth factor-?. No reduction was seen in the expression of the key pro-inflammatory nuclear transcription factor Nuclear factor-?B. In our in vivo experiments, biopsies were taken from chronic rhinosinusitis patients who had received a 3-month course of macrolide. These biopsies showed a reduction in the number of neutrophils present following treatment. There was no reduction in the number of other inflammatory cells or in the expression of TGF-? and NK-?B. We have performed the first ever double-blinded, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis. Patients receiving macrolide showed significant improvements in saccharine transit time, nasal endoscopic scoring and symptom scores following a 12 week course. Patients with low levels of serum immunoglobulin E showed significantly improved outcomes compared to those with high levels. Interleukin-8 levels in nasal lavage fluid were significantly reduced in the patients with low levels of IgE following macrolide treatment. No improvements in any of the objective or subjective outcome measures were seen in the placebo-treated patients. We have performed a series of experiments investigating the anti-inflammatory effect of macrolide antibiotics from 'the bench to the bedside'. These experiments have provided insight into the mechanism of action of macrolides in the laboratory setting and evidence of a beneficial effect in the treatment of chronic rhinosinusitis patients.

<p>The lungs and upper airways are mucosal surfaces that are common site for infection with an enormous variety of inhaled pathogens. Therefore, induction of immune responses in the respiratory tract is crucial for protection against respiratory diseases.</p><p>One of the pathogens infecting the host via the respiratory tract is <i>Mycobacterium Tuberculosis</i>. The reported efficacy of the currently used Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis is highly variable, ranging from 50% against pulmonary tuberculosis to 80% against disseminated tuberculosis. Recently, the current route of vaccination (intradermal) has been considered as a possible factor influencing the protective capacity of the BCG vaccine. In this regard, intradermal route most likely induces protective systemic responses while it fails to induce optimal responses in the lungs. Therefore, our working hypothesis is that vaccination should be directed towards the respiratory mucosal immunity in order to improve the degree of host protection in the lungs.</p><p>In this thesis we studied the effect of the route of immunization as well as of different mucosal adjuvants on the induction of mucosal immune responses against the mycobacterial surface antigen PstS-1. We found that, the intranasal (i.n.) route of immunization was a more favorable route inducing strong local immune responses, than intraperitoneal (i.p.) route. Indeed, i.n. route immunization, unlike the i.p. route, elicited strong IgA responses in the lungs accompanied by a major influx of CD4⁺ T cells and a significant local production of IFN-gamma.</p><p>IgA, being the predominant Ig isotype at mucosal tissues, is considered a major effector molecule involved in defense mechanisms against viral and bacterial pathogens at these sites. Therefore, we investigated the possible role of IgA in the protection of the respiratory mucosa against mycobacterial infections, using mice deficient in IgA and in the polymeric Ig receptor. We show that, deficient mice are more susceptible to mycobacterial infections than wild type mice, thereby demonstrating a role for IgA in protection against mycobacteria. Importantly, our studies revealed a reduced production of protective factors, such as INF-gamma and TNF-alpha in the lungs of deficient mice that was associated with the higher susceptibility seen in these mice compared to wild-type mice. We also conducted challenge experiments against another respiratory pathogen, <i>Chlamydia pneumoniae</i>, using IgA deficient mice. Likewise to mycobacteria, our data support a role for IgA in the protection of the respiratory tract against <i>C. pneumoniae</i> infection.</p><p>Finally, we investigated the possible mechanisms explaining the reduced pro-inflammatory responses in IgA deficient mice. Our data indicated that IgA deficient mice present a defective response to stimulation with LPS or 19kDa which appears to be both, essentially due to suboptimal stimulation of macrophages and restricted to the lungs.</p>

A new model for an adult human gastrointestinal tract (GIT) has been developed for use in internal dose estimations to the wall of the GIT and to the other organs and tissues of the body from radionuclides deposited in the lumenal contents of the five sections of the GIT. These sections were the esophagus, stomach, small intestine, upper large intestine, and the lower large intestine. The wall of each section was separated from its lumenal contents. Each wall was divided into many small regions so that the histologic and radiosensitive variations of the tissues across the wall could be distinguished. The characteristic parameters were determined based on the newest information available in the literature. Each of these sections except the stomach was subdivided into multiple subsections to include the spatiotemporal variations in the shape and characteristic parameters. This new GIT was integrated into an anthropomorphic phantom representing both an adult male and a larger-than-average adult female. The current phantom contains 14 different types of tissue. This phantom was coupled with the MCNP 4C Monte Carlo simulation package. The initial design and coding of the phantom and the Monte Carlo treatment employed in this study were validated using the results obtained by Cristy and Eckerman (1987). The code was used for calculating specific absorbed fractions (SAFs) in various organs and radiosensitive tissues from uniformly distributed sources of fifteen monoenergetic photons and electrons, 10 keV - 4 MeV, in the lumenal contents of the five sections of the GIT. The present studies showed that the average photon SAFs to the walls were significantly different from that to the radiosensitive cells (stem cells) for the energies below 50 keV. Above 50 keV, the photon SAFs were found to be almost constant across the walls. The electron SAF at the depth of the stem cells was a small fraction of the SAF routinely estimated at the contents-mucus interface. Electron studies showed that the “self-dose” for the energies below 300 keV and the “cross-dose” below 2 MeV were only from bremsstrahlung and fluorescent radiations at the depth of the stem cells and were not important.

Sarcomas of the female genital tract are rare tumors and account for less than 5% of gynecologic malignancies. Traditionally, gynecologic sarcomas have been divided into different tumor types according to their histopathological features. The most common are leiomyosarcoma (LMS), malignant mixed Müllerian tumors (MMMT), endometrial stromal sarcoma (ESS) and (Müllerian) adenosarcoma. The different tumor types are highly aggressive with early lymphatic and/or hematogenous spread. Treatment is difficult and it is believed that sarcomas have a low radio-and chemosensitivity, and the mainstay in treatment is surgical removal of the tumor. The most important prognostic feature has been tumor stage. Nevertheless, there are some early-stage tumors that run a biological course different from that expected and additional prognostic factors indicating high-risk tumors are desirable. The study cohort consists of 49 uterine LMS, 44 uterine MMMTs, 17 uterine ESS, 11 uterine adenosarcomas and 26 ovarian MMMTs. The tumors were analyzed in a retrospective manner for DNA ploidy, S-phase fraction (SPF), p53 and mdm-2 expression, as well as traditional clinical and pathological prognostic factors, such as tumor stage. grade, atypia and mitotic index. Of the 49 LMS, 36 (86%) were non-diploid and 13 (27%) were p53-positive. Among the 44 uterine MMMTs, 30 (68%) were non-diploid and 27 (61%) had an SPF&gt;10%. Twenty-seven (61%) overexpressed p53 and 11 (25%) were mdm-2 positive. Furthermore, 40 (91%) of the uterine MMMTs had a high mitotic count and 42 (95%) had high grade cytologic atypia. All low-grade ESS were DNA diploid and had a low SPF. Among the four high-grade ESS, three (75%) were DNA aneuploid and three (75%) were p53-positive. Among 1 1 adenosarcomas, eight (73%) were non-diploid. All ovarian MMMTs were non-diploid and all but two had an SPF&gt;10%. 19 (73%) ovarian MMMTs were p53positive. The 5-year survival rate was 33% for LMS, 38% for uterine MMMT, 57% for ESS, 69% for adenosarcoma and 30% for ovarian MMMT. Thirty-five (71%) patients with LMS died of disease and two of intercurrent disease. Stage was found to be the most important factor for survival (p=0.007); in addition DNA ploidy (p=0.045) and SPF (p=0.041) had prognostic significance. Twenty-seven (61%) patients with uterine MMMT died of disease and six (14%) died of intercurrent disease. Stage was the only prognostic factor for survival. Nine (53%) patients with ESS died of disease. There was a significant correlation of survival to tumor grade (p=0.007), DNA ploidy (p=0.026), SPF (p=0.048) and stage (p=0.026). Of the 11 patients with adenosarcoma, four (36%) patients died of disease and three (27%) patients died of intercurrent disease. There were no variables that correlated with survival. Eighteen (69%) patients with ovarian MMMT died of disease and two (8%) patients died of intercurrent disease. In a multivariate analysis, only stage reached independent prognostic significance for survival (p=0.023). In summary, stage represents the most important prognostic factor for survival for uterine and ovarian sarcomas. DNA flow cytometry is useful in gaining additional prognostic information for LMS and ESS. P53-and mdm-2 overexpression had no prognostic value for survival rate. Most of the MMMT overexpressed p53 and were non-diploid. Treatment of sarcomatous neoplasms is difficult and the mainstay remains surgical removal of the tumor. For patients with early stage sarcoma there was a high recurrence rate, which suggests that a large proportion of patients may have systemic micrometastasic disease at the time of diagnosis. Recurrent and metastatic uterine sarcoma remains an incurable disease, and treatment must be considered palliative. / On the day of the public defence the status of the articles III and IV was: Accepted for publication. ; Bild/Image 1=p53/mdm-2 interaction ; Bild/Image 2=Leiomysarcoma stage I ; Bild/Image 3=Survival in uterine sarcoma.

Despite the advances made in our understanding of the molecular mechanistic actions of general anesthetics very little is known about the in vivo neural circuits involved in creating the state of general anesthesia. To date the common consensus is that general anesthetics act ubiquitously within the CNS. Recently, (Devor and Zalkind, 2001) have reported that microinjections of pentobarbital (PB) into a discrete brainstem focal area of conscious rats induced a classical, reversible general anesthesia-like behavioral state. The authors concluded that this area, termed the mesopontine tegmental anesthesia area (MPTA), may be important for the induction of general anesthesia. The purpose of the present project was to study the neurophysiological basis of the analgesia, which accompanied the state of general anesthesia induced by PB microinjections into the MPTA that was reported by (Devor and Zalkind, 2001). Here, sensory inflow via the spinothalamic tract (STT), a classical spinal nociceptive pathway in the rat, was assessed using single neuron extracellular recording techniques before, during and after microinjections of PB into the MPTA. Spontaneous firing rate (SFR), antidromic firing index (FI) and sciatic as well as sural nerve-evoked responses (Sc-, Su-ER) of STT neurons in isoflurane-anesthetized rats were quantified before as well as 2, 15, 30 and 60 min following bilateral microinjections of either PB (200 micrograms/side) or vehicle control solution (Vh, 1 microliter/side) into the MPTA. The group mean SFR, FI as well as magnitudes of Sc-, Su-ER of STT neurons were significantly and reversibly reduced following PB microinjections compared to corresponding baseline measurements. There were no significant changes in any of the three parameters following microinjections of Vh compared to the pre-microinjection baseline responses. The results from this study indicate that analgesia, which occurs during the anesthesia-like state following microinjections of PB into the MPTA, may be due to attenuation of sensory inflow through the STT. The suppression of STT neurons likely occurs via direct and/or indirect descending pathways from the MPTA to the spinal cord. This study provides the first direct electrophysiological evidence for the analgesia caused by PB microinjections into the rat MPTA.