A Localized, Quantitative Drug Delivery Tool for Neurotransmission Studies

Iontophoresis is the movement of charged molecules in solution under applied current using pulled multibarrel glass capillaries drawn to a sharp tip. The technique is commonly used in neuroscience as a localized drug delivery tool to target select brain regions. A major limitation of the technique is its non-quantitative nature and inherent variability between probes. In this dissertation, iontophoretic delivery has been coupled to fast-scan cyclic voltammetry for real-time monitoring of ejections. The ejection of charged and neutral species has been characterized with carbon-fiber microelectrodes coupled to iontophoresis barrels to reveal the mechanisms underlying drug delivery: iontophoretic and electroosmotic forces. With the use of the neutral, electroactive molecule 2-(4-nitrophenoxy) ethanol (NPE), which is only transported by electroosmotic flow (EOF), electroosmosis (EO) was identified as the major contributor to observed variability from probe to probe. In addition, differences in mobility for charged compounds were positively correlated to differences in electrophoretic mobility as determined by capillary electrophoresis (CE). Thus, CE can be used to predict the rate of transport for compounds that cannot be electrochemically monitored. With this information, quantitative iontophoresis is possible for electrochemically inactive drugs by using a marker molecule. This approach was validated in vivo in a well-understood biological system. Carbon-fiber/iontophoresis probes were used to measure and modulate electrically evoked dopamine release in the striatum of anesthetized rats. Dopamine release in this brain region is highly regulated by autoreceptors and the dopamine transporter. Iontophoretic ejections of an autoreceptor antagonist and a dopamine transporter inhibitor demonstrate that this technique can be used to locally modulate presynaptic release. Additionally, the experiments demonstrate that use of an internal marker molecule do not interfere with the biological results. The final chapters of this dissertation focus on the use of quantitative iontophoresis in novel applications, such as presynaptic regulation of norepinephrine and dopaminergic signaling in awake animals performing behaviors related to drug addiction

Imputación necesaria en delitos de patrocinio indebido y su incidencia al principio de responsabilidad penal, Juzgado Investigación Preparatoria – Tarapoto 2023

La investigación tuvo el objetivo en analizar si la imputación necesaria en los delitos de patrocinio indebido incide en el principio de responsabilidad penal, JIP - Tarapoto 2023. La imputación se define como la atribución, con mayor o menor sustento, de un acto presumiblemente delictivo a una persona, sin que esto necesariamente implique una acusación formal en su contra. La metodología fue de tipo básica, diseño de teoría fundamentada y enfoque cualitativo, la aplicación de los instrumentos fueron la guía de análisis documental y entrevista a expertos. El resultado principal, resulta vital asegurar que los procedimientos judiciales sean imparciales, que se respete los derechos que corresponder al ser humano y que se brinden oportunidades para la rehabilitación y reintegración social de los infractores. Concluyendo que al analizar si la imputación necesaria en los delitos de patrocinio indebido incide en el principio de responsabilidad penal en el Juzgado de Investigación Preparatoria de Tarapoto, se logró identificar múltiples dimensiones y consideraciones importantes que influyen en la comprensión de este tema complejo

Comparative study of surgical and oncologic outcomes in oncoplastic versus non-oncoplastic breast conservative surgery for breast cancer treatment

Orientadores: Luiz Carlos Zeferino, Fabrício Palermo BrenelliDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: A cirurgia conservadora associada à radioterapia é o tratamento de escolha para pacientes com câncer de mama em estadios iniciais. A cirurgia oncoplástica é uma importante ferramenta na ampliação da indicação de cirurgia conservadora no tratamento de tumores maiores, com localização desfavorável ou desproporção tumor-mama, possibilitando ressecções com margens mais amplas, melhores resultados estéticos e reduzindo a indicação de mastectomias. O objetivo deste estudo foi comparar as características das pacientes e do tumor e os desfechos cirúrgicos e oncológicos das pacientes submetidas à cirurgia conservadora com e sem oncoplástica para tratamento do câncer de mama. Métodos: foram incluídas 866 pacientes consecutivamente submetidas a cirurgia conservadora de 2011 a 2015 no CAISM (Hospital da Mulher Prof. Dr. José Aristodemo Pinotti - Centro de Atenção Integral à Saúde da Mulher). Foi realizada um estudo de coorte reconstituída baseada em amostra de conveniência. Os dados foram colhidos e gerenciados no REDCap® e exportados para o Excel® para análise estatística. Para comparar os grupos, foram utilizados Teste t de Student ou Mann-Whitney para variáveis contínuas e teste Qui-quadrado ou Exato de Fisher para variáveis categóricas e regressão logística binária para obtenção do Odds ratio (OR) e Intervalo de confiança (IC) de 95% foi considerado significativo. O estudo foi aprovado pelo Comitê de Ética em Pesquisa da instituição. Foram analisados: perfil da população e do tumor, complicações pós-operatórias, status de margem cirúrgica, taxa de ampliação de margem e de conversão em mastectomia, tempo para adjuvância e recidiva local. Resultados: O tempo médio de seguimento foi de 50,4 meses. Em 768 (88,7%) pacientes foi realizada cirurgia conservadora sem oncoplástica e em 98 (11,3%) cirurgia conservadora com oncoplástica. No grupo de cirurgia oncoplástica houve mais pacientes com menos de 50 anos (OR 3,19; IC 2,08-4,90) e foram submetidas com mais frequência à quimioterapia neoadjuvante (OR 2,67; IC 1,26-3,67). Menos pacientes apresentavam diabetes (OR 0,30; IC 0,13-0,70) e hipertensão (OR 0,41; IC 0,26-0,66). No grupo oncoplástica foram mais frequentes os tumores in situ (OR 3,15; IC 1,56-6,35), os invasores maiores do que 2cm (OR 3,40; IC 2,13-5,43) e os tumores multifocais (OR 2,15; IC 1,26-3,67), além de axila clinicamente comprometida (OR 2,03; IC 1,24-3,31) e maior peso de peça cirúrgica excisada (p<0,0001). Indicação de segunda cirurgia para ampliação de margens foi 2,72 vezes maior no grupo sem oncoplástica (OR 2,72; IC 1,07-6,85). Houve mais deiscência de cicatriz no grupo oncoplástica (OR 4,74; IC 2,32-9,65), mas não houve diferença significativa quanto à presença de complicações maiores precoces (OR 0,93; IC 0,45-1,93), conversão em mastectomia (OR 1,48; IC 0,70-3,12), tempo para adjuvância (p=0,32), ou recidiva local (OR 1,50; IC 0,55-4,07). Conclusão: A cirurgia oncoplástica, mesmo sendo utilizada no tratamento de tumores maiores e multifocais, levou a menos cirurgias para ampliação de margem e não levou a aumento de complicações maiores, conversão para mastectomia, atraso no tratamento adjuvante ou recidiva localAbstract: Breast conservative surgery with radiotherapy is the standard treatment for patients with early breast cancer. Oncoplastic surgery plays an important role in extending the indications of breast conservative surgery for larger tumors, unfavorable tumor location or breast-tumor rate, enabling large margin extensions, better cosmetic outcomes and reducing the indications of mastectomy. The aim of this study was to analyze the characteristics and both surgical and oncologic outcomes of patients submitted to oncoplastic and non-oncoplastic conservative surgery. Methods: Data was retrospectively collected from 866 patients consecutively submitted to oncoplastic and non-oncoplastic breast conservative surgery from 2011 to 2015 at CAISM (Women's Hospital Prof. Dr. José Aristodemo Pinotti - Center for Integral Attention to Women's Health). Data management and statistical analysis were done with REDCap® and Excel®. Mann-Whitney or t-Student test were used for comparison of continuous variables and Chi squared or Fisher Exact test for the categorical variables. For multivariate analysis, binary logistic regression was used to obtain the OR, with a 95% Confidence Interval (CI) considered to be statistically significant. The study was approved by the Research Ethics Committee of the institution. The variables analyzed were: population and tumor characteristics, postoperative complications and their risk factors, surgical margin status and factors associated with positive margins, margin extension and mastectomy conversion rates, time for adjuvant therapy and local recurrence. Results: The 866 patients had a median follow up of 50.4 months. Non-oncoplastic conservative surgery was performed in 768 (88.7%) patients and oncoplastic surgery in 98 (11.3%). The oncoplastic group had more young patients (OR 3.19; CI 2.08-4.90), more neoadjuvant chemotherapy (OR 2.67; CI 1.57-4.54) and fewer patients with diabetes (OR 0.30; CI 0.13-0.70) and hypertension (OR0.41; CI 0.26-0.66). The tumors in this group were more frequently in situ (OR 3.15; CI 1.56-6.35), larger invasive tumors (OR 3.40; CI 2.13-5.43) and multifocal (OR 2.15; CI 1.26-3.67), with compromised axilla (OR 2.03; CI 1,24-3.31) and greater weight of surgical specimen (p<0.0001). The indication for a second surgery for margin re-excision was 2.72 times higher in the non-oncoplastic group (OR 2.72; CI 1.07-6.85). There was more scar dehiscence in the oncoplastic group (OR 4.74; CI 2.32-9.65), but there was no significant difference in early major complications (OR 0.93; CI 0.45-1.93), conversion to mastectomy (OR 1.48; CI 0.70-3.12), time to adjuvant therapy (p=0.32) or local recurrence (OR 1.50; CI 0.55-4.07). Conclusion: Oncoplastic surgery, even when used in the treatment of larger and multifocal tumors, resulted in fewer surgeries for margin re-excision and did not increase the rate of early major complications, positive margins, conversion to mastectomy or local recurrenceMestradoOncologia Ginecológica e MamáriaMestra em Ciências da Saúd

Empowering Nursing Staff to Activate Rapid Response Teams: Using In Situ Simulation to Bolster Knowledge and Confidence

Purpose: To examine the impact of in situ simulation (ISS) with scripting on nursing staff’s knowledge and confidence to initiate rapid response teams (RRTs) immediately after identifying patient condition deterioration. Background/Significance: Failure to rescue (FTR) related to delays in activation of RRT is on the rise, leading to poor patient outcomes. Lack of confidence, knowledge, and empowerment are associated with delayed activation of RRTs. As such, the nursing staff’s confidence is integral in activating RRTs and FTR prevention. In situ simulation may help nurses increase their confidence, thus empowering timely RRT initiation. Methods: This quantitative pretest–posttest study used a convenience sample of nurses and nursing assistants. First, participants completed the Rapid Response Team Survey (RRTS) pretest. Then, they participated in the ISS scenario. Lastly, they completed debriefing and the RRTS posttest. Results: Pearson\u27s correlation results showed no significant relationships between the variables. Dependent t-test results showed statistically significant increases between the pretest and posttest means (Part l, t = -5.51, p \u3c .001, MD = 1.32; Part 2, t = -1.04, p \u3c .01, MD = 3.1). These results suggest that ISS with scripting increased participants\u27 knowledge and confidence in early activation of RRTs. Additionally, staff reported feeling more confident and empowered regarding future RRT decision-making and communication with other healthcare colleagues. Discussion: Early activation of RRTs prevents FTR. The results of this study suggest ISS with scripting increases staff\u27s knowledge, confidence, and empowerment to activate RRTs. We recommend that hospital organizations adopt ISS with scripting to empower nurses to activate RRTs to prevent FTR

Deletion of GPIHBP1 causing severe chylomicronemia

Lipoprotein lipase (LPL) is a hydrolase that cleaves circulating triglycerides to release fatty acids to the surrounding tissues. The enzyme is synthesized in parenchymal cells and is transported to its site of action on the capillary endothelium by glycophosphatidylinositol (GPI)-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). Inactivating mutations in LPL; in its cofactor, apolipoprotein (Apo) C2; or in GPIHBP1 cause severe hypertriglyceridemia. Here we describe an individual with complete deficiency of GPIHBP1. The proband was an Asian Indian boy who had severe chylomicronemia at 2 months of age. Array-based copy-number analysis of his genomic DNA revealed homozygosity for a 17.5-kb deletion that included GPIHBP1. A 44-year-old aunt with a history of hypertriglyceridemia and pancreatitis was also homozygous for the deletion. A bolus of intravenously administered heparin caused a rapid increase in circulating LPL and decreased plasma triglyceride levels in control individuals but not in two GPIHBP1-deficient patients. Thus, short-term treatment with heparin failed to attenuate the hypertriglyceridemia in patients with GPIHBP1 deficiency. The increasing resolution of copy number microarrays and their widespread adoption for routine cytogenetic analysis is likely to reveal a greater role for submicroscopic deletions in Mendelian conditions. We describe the first neonate with complete GPIHBP1 deficiency due to homozygosity for a deletion of GPIHBP1

The Student Movement Volume 109 Issue 1: Cardinals Migrate Back to Berrien for \u2724 School Year

HUMANS Believe the Promise Through the Storms, Interviewed by Savannah Tyler A Sit-Down with New Associate Chaplain Pitcher, Esther Martin Dean Fitting on Lamson\u27s Refreshing , Interviewed by Alyssa Caruthers What Happened to Change Day?, Andrew Francis ARTS & ENTERTAINMENT Farewell, Brat Summer, Joel Pelletier Believe the Promise Musical Review, Joel Pelletier Got What You Wanted, So Stop Feeling Sorry: An Opinion on Chappell Roan\u27s Request for Privacy, Melanie Webb Helping Through Books: A Review of Welcome to the Hyunam-dong Bookshop , Aiko J. Ayala Rios NEWS Sophomores Win Big at AUlmost Anything Goes, Melissa Moore AUSA Hosts The Nest, Natalie Mendonça Fostering Student Involvement: Highlights From AU\u27s Club Fair, Callie Carlsen IDEAS How to Ace This School Year, Natalie Reid No More Change Day, Timi Olatunde Returning Home: Adjusting After Serving Abroad, Katherine Pierre PULSE International Camporee: Gillette, Wyoming, Anna Rybachek On the Presidential Debate, Nora Martin Can Happiness Be Chosen?, Anna Rybachek Tips on How to Combat Stress, Lexie Dunham LAST WORD Overcoming the Goliath , Amelia Stefanescuhttps://digitalcommons.andrews.edu/sm-109/1000/thumbnail.jp

Reflexões sobre dieta vegetariana na adolescência

A dieta vegetariana consiste em uma alimentação que exclui o consumo de carnes, em diferentes níveis e formas. Por se caracterizar como uma fase de intenso crescimento e desenvolvimento, a adolescência demanda necessidades nutricionais específicas para adequado funcionamento e desenvolvimento dos processos biológicos. Diante do exposto, o objetivo deste trabalho foi contribuir com reflexões a respeito da dieta vegetariana à saúde do adolescente. Foi realizada uma revisão narrativa de literatura, a partir de buscas nas bases de dados PubMed e Biblioteca Virtual em Saúde (BVS), utilizando os seguintes descritores: (Adolescent) AND (Diet, Vegetarian) para buscas na PubMed e os descritores (Adolescente) AND (Dieta Vegetariana) para buscas na BVS, cujas publicações tenham ocorrido nos últimos 5 anos (2018-2023). Aspectos éticos, morais, de saúde, ecológicos e religiosos, têm sido apontados como os principais fatores de influência a adesão de um padrão alimentar vegetariano entre adolescentes, além da influência familiar e/ou necessidade de distanciamento de comportamentos entre os adolescentes em relação a seus pais. A dieta vegetariana pode apresentar diversos benefícios relacionados ao maior consumo de frutas, verduras e legumes, proporcionando maior aporte de fibras, micronutrientes e antioxidantes, reduzindo consideravelmente o risco de doenças cardiovasculares. A adoção do padrão alimentar vegetariano balanceado é considerado seguro para crianças e adolescentes e&nbsp; pode ser facilmente obtido a partir da elaboração e adesão a um bom planejamento e acompanhamento dietético individualizado realizado com apoio do profissional nutricionista com expertise no atendimento a indivíduos vegetarianos

Global evidence of gender equity in academic health research: a scoping review

Objectives: To chart the global literature on gender equity in academic health research. Design: Scoping review. Participants: Quantitative studies were eligible if they examined gender equity within academic institutions including health researchers. Primary and secondary outcome measures: Outcomes related to equity across gender and other social identities in academia: (1) faculty workforce: representation of all genders in university/faculty departments, academic rank or position and salary; (2) service: teaching obligations and administrative/non-teaching activities; (3) recruitment and hiring data: number of applicants by gender, interviews and new hires for various rank; (4) promotion: opportunities for promotion and time to progress through academic ranks; (5) academic leadership: type of leadership positions, opportunities for leadership promotion or training, opportunities to supervise/mentor and support for leadership bids; (6) scholarly output or productivity: number/type of publications and presentations, position of authorship, number/value of grants or awards and intellectual property ownership; (7) contextual factors of universities; (8) infrastructure; (9) knowledge and technology translation activities; (10) availability of maternity/paternity/parental/family leave; (11) collaboration activities/opportunities for collaboration; (12) qualitative considerations: perceptions around promotion, finances and support. Results: Literature search yielded 94 798 citations; 4753 full-text articles were screened, and 562 studies were included. Most studies originated from North America (462/562, 82.2%). Few studies (27/562, 4.8%) reported race and fewer reported sex/gender (which were used interchangeably in most studies) other than male/female (11/562, 2.0%). Only one study provided data on religion. No other PROGRESS-PLUS variables were reported. A total of 2996 outcomes were reported, with most studies examining academic output (371/562, 66.0%). Conclusions: Reviewed literature suggest a lack in analytic approaches that consider genders beyond the binary categories of man and woman, additional social identities (race, religion, social capital and disability) and an intersectionality lens examining the interconnection of multiple social identities in understanding discrimination and disadvantage. All of these are necessary to tailor strategies that promote gender equity. Trial registration number: Open Science Framework: https://osf.io/8wk7e/