Surgical strategy for the treatment of sporadic medullary thyroid carcinoma: our experience

Background. Medullary thyroid carcinoma (MTC) is a rare disease which accounts for approximately 5-9% of all thyroid cancers and originates from the calcitonin-secerning parafollicular C cells. MTC can be divided into two subgroups: sporadic (75%) or inherited (25%). The majority of patients with invasive MTC have metastasis to regional lymph nodes at the time of diagnosis, as evidenced by the frequent finding of persistently elevated calcitonin levels after thyroidectomy and the high rates of recurrence in the cervical lymph nodes reported in retrospective studies. Objectives. The purpose of the study is to review our single institution's experience with MTC since 1998 and to evaluate surgical strategy, patterns of lymph node metastases and calcitonin response to compartment-oriented lymphadenectomy in patients with primary or recurrent sporadic medullary thyroid carcinoma. Methods. A retrospective review of 26 patients treated for MTC at the “Antonio Cardarelli” Hospital referral center, in Naples, between 1998 and 2012. There were 18 female and 8 male patients, median age at presentation was 55 years, and median follow-up for survivors was 5 years. Total thyroidectomy was performed in all 26 patients; central compartment (CC) node dissection (level VI) in 12 (46%) patients; central plus lateral compartment (LC) node dissection (levels II, III, and IV) in 7 (27%) patients. 4 patients (15%) underwent reoperation for loco-regional recurrent/persistent MTC. Results. After a median post-surgical follow-up of 5 years (range 1-10 years), 63 % of patients were living disease-free, 15% were living with disease and/or persistently elevated calcitonin levels after surgery, 11% were deceased due to MTC and 11 % were lost to follow-up. Conclusions. We agree with most authors advocating for a total thyroidectomy and prophylactic central neck dissection in the setting of clinically detected MTC. Lateral neck dissection may be best reserved for patients with positive preoperative imaging. Nevertheless MTC has a high rate of lymph node metastases that are sub optimally detected preoperatively in the central compartment by neck ultrasound or intra-operatively by the surgeon, and reoperation is associated with a higher rate of surgical complications. In our limited experience, patients with thyroid confined nodular pathology, without nodal disease and unknown preoperative diagnosis of MTC, underwent only total thyroidectomy with a good prognosis.

Use of Fibres Obtained from the Cashew (Anacardium ocidentale, L) and Guava (Psidium guayava) Fruits for Enrichment of Food Products

OLIVEIRA, E. L. et al. Use of Fibres obtained from the Cashew (Anacardium ocidentale, L) and Guava (Psidium guayava) Fruits for Enrichment of Food Products. Brazilian Archives of Biology and Technology, Curitiba, PR, v. 48, p. 143-150, 2005.

Nutrient fluxes on an intertidal mudflat in Marennes-Oleron Bay, and influence of the emersion period

Fluxes of nutrients (NH sub(4) super(+), NO sub(3) super(-), PO sub(4) super(3-) and Si(OH) sub(4)) were studied on an intertidal mudflat in Marennes-Oleron Bay, France, at two different seasons and at different times of the emersion period. Fluxes through the sediment-water interface were both calculated from vertical profiles of nutrient concentration in pore-water (diffusive fluxes, JD) and measured in light and dark benthic mini-chambers (measured fluxes, J sub(0)). Results indicate that ammonia was mainly released in summer while nitrate was mainly taken up in late winter. This uptake from the overlying water was probably due to the coupling of nitrification-denitrification within the sediment. The J sub(0) /J sub(D) ratio further indicates that bioturbation likely enhanced ammonia release in summer. Concerning phosphate, the comparison of diffusive and measured fluxes suggests that PO sub(4) super(3-) could be assimilated by the biofilm in winter while it was released in summer at a high rate due to both bioturbation and desorption because of the relative summer anoxic conditions. Silica was always released by the sediment, but at a higher rate in summer. Statistically significant differences in measured fluxes were detected in dark chambers at different times of low tide, thus suggesting a short-term variability of fluxes. Microphytobenthos preferred ammonia to nitrate, but assimilated nitrate when ammonia was not available. It also turned out that benthic cells could be limited in nitrogen during low tide in late winter. In summer, ammonia was not limiting and microphytobenthic activity significantly decreased the measured flux of NH sub(4) super(+) in the middle of low tide when its photosynthetic capacity was highest.

Implantable cardioverter-defibrillators in the elderly: rationale and specific age-related considerations

Despite the increasingly high rate of implantation of cardioverter-defibrillators (ICD) in elderly patients, data supporting their clinical and cost-effectiveness in this age stratum are ambiguous and contradictory. We comprehensively reviewed the state-of-the-art data regarding the applicability, safety, clinical- and cost-effectiveness of the ICD in elderly patients, and analysed which patients in this age stratum are more likely to get a survival benefit from this therapy. Although peri-procedural risk may be slightly higher in the elderly, this procedure is still relatively safe in this age group. In terms of correcting potentially life-threatening arrhythmias, the effectiveness of ICD therapy is comparable in older and younger individuals. However, the assumption of persistent ICD benefit in the elderly population is questionable, as any advantage of the device on arrhythmic death may be largely attenuated by a higher total non-arrhythmic mortality. While septuagenarians and octogenarians have higher annual all-cause mortality rates, ICD therapy may remain effective in highly selected patients at high risk of arrhythmic death and with minimum comorbidities despite advanced age. ICD intervention among the elderly, as a group, may not be cost-effective, but the procedure may reach cost-effectiveness in those expected to live >5-7 years after implantation. Biological age rather than chronological age per se should be the decisive factor in making a decision on ICD selection for survival benefit.

Melanoma maligno da mucosa da cabeça e pescoço: casuística do IPO de Lisboa

Introdução: O melanoma maligno da mucosa (MMM) é uma doença rara com mau prognóstico. Material e Métodos: Estudo retrospetivo de 32 doentes do Instituto Português de Oncologia Francisco Gentil de Lisboa com MMM da cabeça e pescoço, no período de 1998 a 2012. Resultados: Dos 32 casos analisados a idade média foi de 70 anos. O tumor primário localizou-se na cavidade nasal e seios peri-nasais em 24 doentes e na cavidade oral em 8 casos. A maioria dos doentes (23) foi submetida a tratamento cirúrgico. Destes, 16 foram propostos para terapêutica complementar com Radioterapia. O tempo de seguimento variou de 26 dias a 10 anos. A sobrevida aos 5 anos foi de 18%. Conclusões: A maioria dos doentes apresentou um estadio avançado na altura do diagnóstico e, apesar dos tratamentos instituídos, verificou-se uma elevada mortalidade. O tratamento de escolha é a cirurgia. O papel da radioterapia continua a ser controverso.

The metabolic and epigenetic effects of the isocitrate dehydrogenase-1 mutation in glioma

Cancer cells have been noted to have an altered metabolic phenotype for over ninety years. In the presence of oxygen, differentiated cells predominately utilise the tricarboxylic acid (TCA) cycle and oxidative phosphorylation to efficiently produce energy and the metabolites necessary for protein and lipid synthesis. However, in hypoxia, this process is altered and cells switch to a higher rate of glycolysis and lactate production to maintain their energy and metabolic needs. In cancer cells, glycolysis is maintained at a high rate, even in the presence of oxygen; a term described as “aerobic glycolysis”. Tumour cells are rapidly dividing and have a much greater need for anabolism compared to normal differentiated cells. Rapid glucose metabolism enables faster ATP production as well as a greater redistribution of carbons to nucleotide, protein, and fatty acid synthesis, thus maximising cell growth. Recently, other metabolic changes, driven by mutations in genes related to the TCA cycle, indicate an alternative role for metabolism in cancer, the “oncometabolite”. This is where a particular metabolite builds up within the cell and contributes to the tumorigenic process. One of these genes is isocitrate dehydrogenase (IDH) IDH is an enzyme that forms part of the tricarboxylic acid (TCA) cycle and converts isocitrate to α-ketoglutarate (α-KG). It exists in three isoforms; IDH1, IDH2 and IDH3 with the former present in the cytoplasm and the latter two in the mitochondria. Point mutations have been identified in the IDH1 and IDH2 genes in glioma which result in a gain of function by converting α-KG to 2-hydroxyglutarate (2HG), an oncometabolite. 2HG acts as a competitive inhibitor of the α-KG dependent dioxygenases, a superfamily of enzymes that are involved in numerous cellular processes such as DNA and histone demethylation. It was hypothesised that the IDH1 mutation would result in other metabolic changes in the cell other than 2HG production, and could potentially identify pathways which could be targeted for therapeutic treatment. In addition, 2HG can act as a potential competitive inhibitor of α-KG dependent dioxygenases, so it was hypothesised that there would be an effect on histone methylation. This may alter gene expression and provide a mechanism for tumourogenesis and potentially identify further therapeutic targets. Metabolic analysis of clinical tumour samples identified changes associated with the IDH1 mutation, which included a reduction in α-KG and an increase in GABA, in addition to the increase in 2HG. This was replicated in several cell models, where 13C labelled metabolomics was also used to identify a possible increase in metabolic flux from glutamate to GABA, as well as from α-KG to 2HG. This may provide a mechanism whereby the cell can bypass the IDH1 mutation as GABA can be metabolised to succinate in the mitochondria by GABA transaminase via the GABA shunt. JMJ histone demethylases are a subset of the α-KG dependent dioxygenases, and are involved in removing methyl groups from histone tails. Changes in histone methylation are associated with changes in gene expression depending on the site and extent of chemical modification. To identify whether the increase in 2HG and fall in α-KG was associated with inhibition of histone demethylases a histone methylation screen was used. The IDH1 mutation was associated with an increase in methylation of H3K4, which is associated with gene activation. ChiP and RNA sequencing identified an increase in H3K4me3 at the transcription start site of the GABRB3 subunit, resulting in an increase in gene expression. The GABRB3 subunit forms part of the GABA-A receptor, a chloride channel, which on activation can reduce cell proliferation. The IDH1 mutation was associated with an increase in GABA and GABRB3 subunit of the GABA-A receptor. This raises the possibility of GABA transaminase as a potential therapeutic target. Inhibition of this enzyme could reduce GABA metabolism, potentially reducing any beneficial effect of the GABA shunt in IDH1 mutant tumours, and increasing activation of the GABA-A receptor by increasing the concentration of GABA in the brain. This in turn may reduce cell proliferation, and could be achieved by using Vigabatrin, a GABA transaminase inhibitor licensed for use in epilepsy.

Modelagem aplicada ao processo de biofixação de CO2 por microalgas

A fixação biológica de dióxido de carbono por microalgas é considerada a melhor forma de fixar CO2. Dentre os microrganismos utilizados destaca-se Spirulina platensis devido às suas altas taxas de fixação de CO2 e variedade de aplicações da biomassa gerada. A aplicação de modelos e simulações pode auxiliar na previsão de custos e na escolha das condições ideais de cultivo. Este trabalho teve como objetivo etsabelecer um modelo cinético no qual a iluminância é o fator limitante para o crescimento da microalga Spirulina platensis. A fim de validar o modelo proposto foi utilizada a microalga S. platensis, cultivada em meio Zarrouk modificado (NaHCO3 1,0 g.L-1 ), em biorreator aberto tipo raceway de 200L, mantido a 30°C, sob iluminação natural. A concentração celular variou de 0,19 a 0,34 g.L-1 e a velocidade específica de crescimento celular obtida a partir da regressão exponencial das curvas de crescimento de cada período iluminado variou de 0,55 a 0,59 d-1 . O modelo proposto gerou dados estimados satisfatórios (r2 =0,97). De acordo com os dados obtidos 16,2% da biomassa é consumida durante o período não iluminado.

Avaliação do potencial da macrófita Pistia stratiotes na exposição de íon cromo (VI): biossorção e tolerância

The environmental pollution caused by industries has increased the concentration of pollutants in the environment, especially in water. Among the most diverse contaminants, there is the metals, who may or may not to be heavy/toxic, causing effluent of difficult treatment when in low concentrations. The search for alternative measures of wastewater effluent treatment has led to studies using phytoremediation technique through the various matrices (plant, fungi, bacteria) as means of polishing treatment to remove contaminants by means of biosorption/bioaccumulation. In order to use the phytoremediation technique for removing metals of the environmental, it have been performed bioassay with the macrophyte Pistia stratiotes. The bioassays were realized with healthy plants of P. stratiotes acclimatized in a greenhouse, at room temperature and lighting conditions during 28 days of cultivate. The cultivations were performed in glass vessels containing 1 L of the hydroponic solution with chromium (VI) in the potassium dichromate form with concentration range 0.10 to 4.90 mg L-1. The experiments were performed by Outlining Central Composite Rotational (OCCR), where the kinetics of bioaccumulation and chlorophyll a fluorescence were monitored in plants of P. stratiotes during cultivation. The collections of the samples and cultive solution were performed according to the OCCR. The chromium levels were measured in samples of P. stratiotes and the remaining solutions by the methodology of atomic absorption spectrometry by flame. The tolerance of P. stratiotes in relation to exposure to chromium (VI) was analyzed by parameters of physiological activity by means of chlorophyll a fluorescence, using the portable fluorometer PAM (Pulse Amplitude Modulation). The development of P. stratiots and their biomass were related to the time factor, while bioaccumulation capacities were strongly influenced by factors of time and chromium concentration (VI). The chlorophyll fluorescence parameters were affected by chromium and the exposure time at the bioassays. It was obtained an higher metal removal from the root in relation to the sheet, reaching a high rate of metal removal in solution. The experimental data removal kinetics were represented by kinetic models Irreversibly Langmuir, Reversible Langmuir, Pseudo-first Order and Pseudo-second Order, and the best fit for the culture solution was the Reversible Langmuir model with R² 0.993 and for the plant the best model was Pseudo-second order with R² 0.760.

Intratumoral heterogeneity in glioblastoma: don't forget the peritumoral brain zone

International audience

Atribuições causais de alunos do 9ºano de escolaridade face ao (in)sucesso a matemática

Dissertação de Mestrado apresentada no Instituto Superior de Psicologia Aplicada para obtenção de grau de Mestre na especialidade de Psicologia Educacional

Ocular injuries and eye care seeking patterns following injuries among cocoa farmers in Ghana.

Background: The work environment of cocoa farmers exposes them to several ocular hazards that predispose them to eye diseases and injuries. However, the extent of ocular injuries and health seeking patterns following these injuries are unknown among cocoa farmers in Ghana. Objectives: To determine the prevalence of ocular injuries and health seeking behaviour following injury among cocoa farmers in Ghana. Methods: Five hundred and fifty six participants were recruited through simple random sampling using a multistage approach from four cocoa growing districts in Ghana. A structured questionnaire was used to collect relevant information such as demography, ocular hazards and injuries experienced. An ocular examination was also conducted to assess the eye health of the participants. Descriptive and regression statistics were used to analyze the data. The rate of ocular injuries was calculated by using the number of injuries reported that resulted in lost work time/days divided by the number of worker years at risk of injury (sum of years worked in cocoa farms for all the participants). Results: The rate of ocular injuries was 11.3/1000 worker years (95% CI: 9.4 - 31) which led to lost work time of 37.3/1000 worker years (95% CI: 34.1 - 40.8). The major causes of ocular injury were plants/branches (n=73, 51.1%), chemicals (n=27, 18.9%), cocoa pod/husk (n=14, 9.8%) and occurred mostly during weeding, harvesting and chemical spraying. Few (n=34, 6.1%) participants reported the use of ocular protection. Fifty-five (38.5%) participants visited the local chemical shops, while 37 (25.9%) visited hospitals/clinics for ocular treatment of their injuries. Conclusion: There is a high rate of ocular injuries among cocoa farmers who make insufficient use of appropriate eye care services. There is the need for eye health education among cocoa farmers in Ghana. Keywords:

Doença trofoblástica gestacional

A Doença Trofoblástica Gestacional (DTG) resulta sempre de uma fertilização anormal e, apesar de este tumor representar menos de 1% das neoplasias ginecológicas, é importante conhecer a sua história natural e abordagem, não só porque podem colocar em risco a vida das mulheres em idade fértil, mas também pela sua alta taxa de cura se tratados atempadamente. Os exames radiológicos podem sugerir o diagnóstico numa fase precoce e têm um papel na avaliação da doença metastática. A ecografia é habitualmente o exame de primeira linha, mas a ressonância magnética também tem um papel na detecção da DTG e na avaliação da sua extensão.

REDUCING TEACHER ATTRITION: THE ROLES AND RESPONSIBILITIES OF BUILDING PRINCIPALS IN A LARGE URBAN DISTRICT TO SUPPORT TEACHER RETENTION

The high rate of teacher attrition in urban schools is well documented. While this does not seem like a problem in Carter County, this equates to hundreds of teachers that need to be replaced annually. Since school year (SY) 2007-08, Carter County has lost over 7,100 teachers, approximately half of (50.1%) of whom resigned, often going to neighboring, higher-paying jurisdictions as suggested by exit survey data (SY2016-2020 Strategic Plan). Included in this study is a range of practices principals use to retain teachers. While the role of the principal is recognized as a critical element in teacher retention, few studies explore the specific practices principals implement to retain teachers and how they use their time to accomplish this task. Through interviews, observations, document analysis and reflective notes, the study identifies the practices four elementary school principals of high and relatively low attrition schools use to support teacher retention. In doing so, the study uses a qualitative cross-case analysis approach. The researcher examined the following leadership practices of the principal and their impact on teacher retention: (a) providing leadership, (b) supporting new teachers, (c) training and mentoring teaching staff, (d) creating opportunities for collaboration, (d) creating a positive school climate, and (e) promoting teacher autonomy. The following research questions served as a foundational guide for the development and implementation of this study: 1. How do principals prioritize addressing teacher attrition or retention relative to all of their other responsibilities? How do they allocate their time to this challenge? 2. What do principals in schools with low attrition rates do to promote retention that principals in high attrition schools do not? What specific practices or interventions are principals in these two types of schools utilizing to retain teachers? Is there evidence to support their use of the practices? The findings that emerge from the data revealed the various practices principals use to influence and support teachers do not differ between the four schools.

Proyecto de creación e implementación de una revista socio cultural en la parroquia San Miguel de Porotos del cantón Azogues

El presente proyecto Creación e Implementación de una Revista Sociocultural en la parroquia San Miguel de Porotos del cantón Azogues, fue creado por dos estudiantes de la carrera de comunicación social con el principal objetivo de crear un vínculo comunicacional en la parroquia, y como un aporte a la conservación y difusión de la cultura. En su desarrollo se pone de manifiesto la combinación de los saberes teóricos adquiridos en la universidad con la práctica e inclusión en el campo de estudio, basado en investigación teórica complementada con la historia de la parroquia en estudio. Culturas y Tradiciones San Migueleñas, revista que abarca temas de índole cultural, religioso, social y deportivo, recoge historias innatas de los habitantes del lugar y pone en manifiesto la riqueza ancestral que posee su gente, la alfarería, el tejido de paja toquilla y su alto índice de catolicismo fueron las principales características para la elaboración de los artículos y fotografías publicados en la primera edición de este medio de comunicación. La apertura y colaboración de las autoridades parroquiales y pobladores permitieron la realización de este trabajo periodístico, el mismo que se forjó a base de entrevistas directas e involucramiento con la comunidad en diferentes espacios sociales y familiares.

‘Failure to maintain’: care rationing and the clinical and financial burden of nurse sensitive hospital-acquired complications in complex older patients

Background: The ageing population, with concomitant increase in chronic conditions, is increasing the presence of older people with complex needs in hospital. People with dementia are one of these complex populations and are particularly vulnerable to complications in hospital. Registered nurses can offer simultaneous assessment and intervention to prevent or mitigate hospital-acquired complications through their skilled brokerage between patient needs and hospital functions. A range of patient outcome measures that are sensitive to nursing care has been tested in nursing work environments across the world. However, none of these measures have focused on hospitalised older patients. Method: This thesis explores nursing-sensitive complications for older patients with and without dementia using an internationally recognised, risk-adjusted patient outcome approach. Specifically explored are: the differences between rates of complications; the costs of complications; and cost comparisons of patient complexity. A retrospective cohort study of an Australian state’s 2006–07 public hospital discharge data was utilised to identify patient episodes for people over age 50 (N=222,440) where dementia was identified as a primary or secondary diagnosis (N=44,422). Extra costs for patient episodes were estimated based on length of stay (LOS) above the average for each patient’s Diagnosis Related Group (DRG) (N=157,178) and were modelled using linear regression analysis to establish the strongest patient complexity predictors of cost. Results: Hospitalised patients with a primary or secondary diagnosis of dementia had higher rates of complications than did their same-age peers. The highest rates and relative risk for people with dementia were found in four key complications: urinary tract infections; pressure injuries; pneumonia, and delirium. While 21.9% of dementia patients (9,751/44,488, p<0.0001) suffered a complication, only 8.8% of non-dementia patients did so (33,501/381,788, p<0.0001), giving dementia patients a 2.5 relative risk of acquiring a complication (p<0.0001). These four key complications in patients over 50 both with and without dementia were associated with an eightfold increase in length of stay (813%, or 3.6 days/0.4 days) and double the increased estimated mean episode cost (199%, or A$16,403/ A$8,240). These four complications were associated with 24.7% of the estimated cost of additional days spent in hospital in 2006–07 in NSW (A$226million/A$914million). Dementia patients accounted for 22.0% of these costs (A$49million/A$226million) even though they were only 10.4% of the population (44,488/426,276 episodes). Hospital-acquired complications, particularly for people with a comorbidity of dementia, cost more than other kinds of inpatient complexity but admission severity was a better predictor of excess cost. Discussion: Four key complications occur more often in older patients with dementia and the high rate of these complications makes them expensive. These complications are potentially preventable. However, the care that can prevent them (such as mobility, hydration, nutrition and communication) is known to be rationed or left unfinished by nurses. Older hospitalised people who have complex needs, such as those with dementia, are more likely to experience care rationing as their care tends to take longer, be less predictable and less curative in nature. This thesis offers the theoretical proposition that evidence-based nursing practices are rationed for complex older patients and that this rationed care contributes to functional and cognitive decline during hospitalisation. This, in turn, contributes to the high rates of complications observed. Thus four key complications can be seen as a ‘Failure to Maintain’ complex older people in hospital. ‘Failure to Maintain’ is the inadequate delivery of essential functional and cognitive care for a complex older person in hospital resulting in a complication, and is recommended as a useful indicator for hospital quality. Conclusions: When examining extra length of stay in hospital, complications and comorbid dementia are costly. Complications are potentially preventable, and dementia care in hospitals can be improved. Hospitals and governments looking to decrease costs can engage in risk-reduction strategies for common nurse sensitive complications such as healthy nursing work environments that minimise nurses’ rationing of functional and cognitive care. The conceptualisation of complex older patients as ‘business as usual’ rather than a ‘burden’ is likely necessary for sustainable health care services of the future. The use of the ‘Failure to Maintain’ indicators at institution and state levels may aid in embedding this approach for complex older patients into health organisations. Ongoing investigation is warranted into the relationships between the largest health services expense (hospitals), the largest hospital population (complex older patients), and the largest hospital expense (nurses). The ‘Failure to Maintain’ quality indicator makes a useful and substantive contribution to further clinical, administrative and research developments.