Analyzing Neoadjuvant Chemotherapy Effects in HER2-Low Breast Cancer: Real World Data.

PURPOSE: Neoadjuvant chemotherapy (NAC) can be used as upfront therapy in aggressive breast cancer (BC). human epidermal growth factor receptor 2 (HER2)-low BC, defined as tumors scoring +1 or +2 on immunohistochemistry without HER2 gene amplification by in situ hybridization, lacks information on real-world data (RWD) outcomes, especially in the NAC setting. This subgroup, which does not reach the HER2 positive criteria due to its lower receptor expression, represents a distinct clinical category potentially requiring tailored therapeutic approaches. STUDY OBJECTIVE:  The objective of this study is to characterize patients with BC with HER2-low status who received NAC in a Brazilian public reference center for female tumors and key outcomes such as pathological complete response (pCR), overall survival (OS), and metastasis-free survival (MFS). METHODS: A retrospective cohort study based on a large BC database from a reference cancer center in Brazil. Patients with BC that received NAC, diagnosed between 2011 and 2020, were included if they presented HER2-low status (defined as tumors scoring +1 or +2 on immunohistochemistry without HER2 gene amplification by in situ hybridization) and had complete data on outcomes. Clinical and demographic data were collected, such as age, menopausal status, Ki-67, hormone receptor expression and others. Key outcomes from the study comprised pCR (defined as ypT0/TIs/ypN0), overall survival, and metastasis-free survival (MFS). Survival analyses were conducted through the semiparametric Kaplan-Meier method to assess OS and MFS by pCR status, considering BC diagnosis as the index date. RESULTS: Overall, 297 patients were eligible and 141 were included in the study after matching the HER2-low definition. The pCR was seen in 18 out of 141 patients (12.7%). The median overall survival was 8.2 years, and the median MFS was 2.7 years. The OS of pCR was 83.4% and non-pCR was 58.1%; the DFS of pCR was 55.5% and non-pCR 40.6%. CONCLUSION: This study gives updated insights on pCR, OS, and MFS in women with HER2-low BC exposed to NAC.

Sit4 Genetically Interacts with Vps27 to Regulate Mitochondrial Function and Lifespan in Saccharomyces cerevisiae.

The Sit4 protein phosphatase plays a key role in orchestrating various cellular processes essential for maintaining cell viability during aging. We have previously shown that SIT4 deletion promotes vacuolar acidification, mitochondrial derepression, and oxidative stress resistance, increasing yeast chronological lifespan. In this study, we performed a proteomic analysis of isolated vacuoles and yeast genetic interaction analysis to unravel how Sit4 influences vacuolar and mitochondrial function. By employing high-resolution mass spectrometry, we show that sit4Δ vacuolar membranes were enriched in Vps27 and Hse1, two proteins that are part of the endosomal sorting complex required for transport-0. In addition, SIT4 exhibited a negative genetic interaction with VPS27, as sit4∆vps27∆ double mutants had a shortened lifespan compared to sit4∆ and vps27∆ single mutants. Our results also show that Vps27 did not increase sit4∆ lifespan by improving protein trafficking or vacuolar sorting pathways. However, Vps27 was critical for iron homeostasis and mitochondrial function in sit4∆ cells, as sit4∆vps27∆ double mutants exhibited high iron levels and impaired mitochondrial respiration. These findings show, for the first time, cross-talk between Sit4 and Vps27, providing new insights into the mechanisms governing chronological lifespan.

The feasibility and technical aspects of trigemino-cervical reflex elicitation in humans under general anesthesia.

OBJECTIVE: To analyze the feasibility, neurophysiological aspects, stimulation patterns, and topographic distribution of trigemino-cervical reflex (TCR) components in humans under general anesthesia. METHODS: This prospective observational study enrolled 20 participants who underwent posterior fossa surgery, surgical proceduresin thecraniovertebral junction,or spinal cord surgery. TCR responses were simultaneously recorded in the sternocleidomastoid (SCM) and trapezius muscles after electrical stimulation of the supraorbital and infraorbital nerves. TCR responses were recorded preoperatively and intraoperatively using single-pulse and multipulse (trains of 2-7 electrical stimuli) stimulation, respectively. Two stimulus duration patterns were evaluated: 0.2-0.5 ms and 0.5-1.0 ms. RESULTS: Intraoperatively, short- and long-latency TCR components were obtained in the SCM ipsilateral to the stimulation with variable recordability. Short-latency responses were the most commonly recorded components. A longer stimulus duration (0.5-1.0 ms) seems to favor the elicitation of TCR responses under general anesthesia. CONCLUSIONS: Short-latency components recorded in the SCM ipsilateral to the stimulation could be regularly elicited under general anesthesia when a larger stimulus duration (0.5-1.0 ms) was applied. SIGNIFICANCE: This is the first study to demonstrate the elicitation of TCR components in humans under general anesthesia. This neurophysiological technique can potentially optimize intraoperative neurophysiological monitoring during brainstem surgery.

Technical Aspects of Eliciting Trigeminocervical and Trigeminospinal Reflexes in Humans: A Scoping Review.

SUMMARY: This scoping review aims to summarize the technical strategies for obtaining trigeminocervical reflex (TCR) and trigeminospinal reflex (TSR) responses. Studies published on TCR or TSR elicitation in humans through electrical stimulation of trigeminal nerve branches were eligible for this scoping review. The data of interest included stimulation parameters, site of stimulation, recording parameters, and the feasibility of TCR and TSR elicitation, in healthy participants. Short-latency TCR responses were regularly obtained in both anterior and posterior neck muscles after electrical stimulation of the supraorbital and infraorbital nerves under voluntary muscle activation. However, without voluntary muscle activation, we found evidence of elicitation of short-latency TCR components only in the posterior neck muscles after supraorbital or infraorbital nerve stimulation. Long-latency TCR responses were regularly obtained in the anterior and posterior neck muscles in studies that evaluated this technique, regardless of the trigeminal branch stimulation or muscle activation status. Short-latency TSR components were not obtained in the included studies, whereas long-latency TSR responses were regularly recorded in proximal upper limb muscles. This scoping review revealed key heterogeneity in the techniques used for TCR and TSR elicitation. By summarizing all the methodological procedures used for TCR and TSR elicitation, this scoping review can guide researchers in defining optimized technical approaches for different research and clinical scenarios.

Construção de um aplicativo: promoção à saúde do idoso com incapacidade e dor lombar / Building an app: promoting the health of elderly people with disabilities and low back pain

Introdução: A incapacidade funcional e o desempenho físico são definidos pela dificuldade ou necessidade de ajuda para o indivíduo executar tarefas diárias, podendo repercutir na capacidade adaptativa das atividades diárias, tanto nas suas capacidades físicas quanto mentais. O processo de envelhecimento acarreta incapacidade funcional, comprometendo a qualidade de vida. Objetivo geral: Construir um aplicativo em saúde com foco na saúde do idoso com incapacidade na lombar. Métodos: Trata-se de um estudo do tipo construção de um aplicativo, desenvolvido durante o período de agosto de 2021 a maio de 2022 em Fortaleza-CE, na página https://fabricadeaplicativos.com.br e será disponibilizado com um instrumento composto pelo índice de Oswestry 2.0 de Incapacidade. Resultados: Telas explicativas para download e acesso ao aplicativo desenvolvido para facilitar o alcance de informações relevantes aos idosos que sofrem limitações no seu dia a dia, provenientes do processo de envelhecimento. Conclusão: Tendo visto que existem poucos estudos e aplicativos sobre esse assunto, se faz necessário a criação de um aplicativo voltado ao tema.(AU)

Introduction: Functional disability and physical performance are defined by the difficulty or need for help for the individual to perform daily tasks. It can have repercussions on the adaptive capacity of daily activities, both in their physical and mental capacities. The aging process causes functional disability, thus compromising quality of life. General objective: To build a health application focused on the health of the elderly with disabilities in the lumbar. Methods: This is a study of the type of construction of an application, developed during the period from August 2021 to May 2022 in Fortaleza-Ceará, on page https://fabricadeaplicativos.com.br and will be made available with an instrument composed of the Oswestry 2.0 Disability Index. Results: Explanatory screens for download and access to the application that was developed to facilitate the reach of relevant information to the elderly who suffer limitations in their day-to-day coming from the aging process. Conclusion: Having seen that there are few studies and applications on this subject, it is necessary to create an application focused on the subject.(AU)

Introducción: La discapacidad funcional y el rendimiento físico se definen por la dificultad o necesidad de ayuda del individuo para realizar las tareas diarias, lo que puede repercutir en la capacidad adaptativa de las actividades diarias, tanto en sus capacidades físicas como mentales. El proceso de envejecimiento conduce a una discapacidad funcional, comprometiendo la calidad de vida. Objetivo general: Construir una aplicación de salud centrada en la salud de personas mayores con discapacidad lumbar. Métodos: Se trata de un estudio del tipo constructivo de una aplicación, desarrollado durante el período de agosto de 2021 a mayo de 2022 en Fortaleza-CE, en la página https://fabricadeaplicativos.com.br y estará disponible con un instrumento compuesto. por el Índice de Discapacidad Oswestry 2.0. Resultados: Pantallas explicativas de descarga y acceso a la aplicación desarrollada para facilitar el acceso a información relevante a personas mayores que sufren limitaciones en su vida diaria, derivadas del proceso de envejecimiento. Conclusión: Dado que existen pocos estudios y aplicaciones sobre este tema, es necesario crear una aplicación enfocada en el tema.(AU)

Combinatorial analysis of ACE and ACE2 polymorphisms reveals protection against COVID-19 worsening: A genetic association study in Brazilian patients.

Since angiotensin-converting enzyme 2, ACE2, was identified as the receptor for SARS-CoV-2 and considering the intense physiological interplay between the two angitensinases isoforms, ACE and ACE2, as counter-regulatory axis of the renin-angiotensin system, we proposed the evaluation of polymorphisms in these two key regulators in relation to COVID-19 severity. A genetic association study involving 621 COVID-19 hospitalized patients from Brazil was performed. All subjects had a confirmed diagnosis of COVID-19 via RT-PCR. Patients were categorized into two groups: the "mild" group (N = 296), composed of individuals hospitalized in ward beds who progressed to cure, and the "severe" group (N = 325), composed of individuals who required hospitalization in an intensive care unit (ICU), or who died. Blood samples were genotyped for ACE I/D polymorphism and ACE2 G8790A polymorphism by real-time PCR via TaqMan assay. The analysis of combined polymorphisms revealed a protective role for genotypic profile II/A_ (ORA = 0,26; p = 0,037) against the worsening of COVID-19 in women. The results indicate a protection profile to COVID-19 progression, in which the II/A_ carriers have almost four times less chance of a severe outcome. It is proposed that a decreased activity of ACE (deleterious effects) in conjunction with an increased ACE2 activity (protective effects), should be the underlying mechanism. The findings are unprecedented once other studies have not explored the genotypic combination analysis for ACE and ACE2 polymorphisms and bring perspectives and expectations for dealing with the COVID-19 pandemic based on definitions of genetically-based risk groups within the context of personalized medicine.

Tolerability of endometriosis medical treatment: a comparison between combined hormonal contraceptives and progestins.

Endometriosis is a chronic inflammatory disease that occurs in women of reproductive age. Much of the treatment involves hormone therapy that suppresses the proliferation of endometriosis lesions.Objective To compare discontinuation rates of pharmacological treatment with estrogen-progestins and progestins medications. The secondary objective is to evaluate the main side effects of these drugs in patients with endometriosis.Methods This retrospective study analyzed data from 330 patients who attended the Hospital of the State Public Servant of São Paulo from August 1999 to September 2020 and received pharmacological treatment for endometriosis. The data were obtained by review of the files of medical appointments with specialized staff.Results The median treatment time was 18 months, ranging from 1 to 168 months, and 177 patients interrupted the proposed treatment. The combined contraceptives with estrogens and progestins were significantly linked to treatment interruption, with a relative risk of 1,99 (p = 0,005). The most important side effects that resulted in treatment interruption were pain persistence (p = 0,043), weight gain (p = 0,017) and spotting (p < 0,001).

Impact of the COVID-19 pandemic on the breast cancer early diagnosis program in Brazil.

During the COVID-19 pandemic, several screening exams were postponed, including mammograms. The aim of this study was to evaluate the impact of COVID-19 in mammographic screening in Brazil, considering 2015 to 2021. This was descriptive ecologic study based on the retrospective data of Brazil's mammographic screening program. A Brazilian national screening database (DATASUS - SISCAN (Cancer System Information)) was used as the data source, and the data in this database are publicly available for download and analysis. We report the number of screening rate from January 2015 to December 2021, using 2020 as reference year for COVID-19. From 2015 to 2021, 10,763,894 mammograms were performed and included in the analysis. Reductions of 39.6% and 13.3% were found in 2020 in 2021, respectively. During the pandemic's peak, the reduction was more pronounced, with maximum reductions of 82.4% in May 2020 and 34.8% in April 2021. There was an increase in the number of mammograms performed on high-risk patients from 11.2% in 2020 to 13.9% in 2021. This research demonstrated a decline in the breast cancer screening rate during the two years of the COVID-19 pandemic; this reduction will increase the burden of advanced breast cancer, potentially impacting morbidity and mortality related to this neoplasm.

Does Pink October really impact breast cancer screening?

Objective: This study aims to evaluate the impact of the Pink October Campaign on the increase in mammographic screening in Brazil. Study design: Ecological observational study, based on retrospective data. Methods: Brazilian national screening database (DATASUS/SISMAMA/Information System on Breast Cancer) was used as a data source and is publicly available for download and analysis. We report screening numbers and outcome rates from January 2017 to December 2021 comparing statistically (ANOVA test, post-Tukey test), age groups, regions of Brazil, and the four quarters of the year. Results: During the study period, the average number of exams performed monthly over the five years was 137,400.117. An increase in the number of mammograms performed in October was identified, as well as in the two following months, respectively 33%, 39%, and 22%, with statistical significance (p = 0.000) in relation to the three quarters of the year. In addition, in the other months, we found values below the monthly average. Statistical difference was not found in the increase in mammograms considering age groups (p = 0.5) and different regions of the country (p = 0.6). Conclusions: This study showed an increase in mammographic screening in the three months following the Pink October Campaign, so we should intensify similar actions throughout the year and not just in October.

Dysregulation in erythrocyte dynamics caused by SARS-CoV-2 infection: possible role in shuffling the homeostatic puzzle during COVID-19

Abstract Introduction The evolving COVID-19 pandemic became a hallmark in human history, not only by changing lifestyles, but also by enriching scientific knowledge on viral infection and its consequences. Objective Although the management of cardiorespiratory changes is pivotal to a favorable prognosis during severe clinical findings, dysregulation of other systems caused by SARS-CoV-2 infection may imbalance erythrocyte dynamics, such as a bidirectional positive feedback loop pathophysiology. Method and Results Recent evidence shows that SARS-CoV-2 is capable of affecting the genetics and dynamics of erythrocytes and this coexists with a non-homeostatic function of cardiovascular, respiratory and renal systems during COVID-19. In hypothesis, SARS-CoV-2-induced systematical alterations of erythrocytes dynamics would constitute a setpoint for COVID-19-related multiple organ failure syndrome and death. Conclusion The present review covers the most frequent erythrocyte-related non-homeostatic findings during COVID-19 capable of providing mechanistic clues of SARS-CoV-2-induced infection and inspiring therapeutic-oriented scientific evidence.

Dysregulation in erythrocyte dynamics caused by SARS-CoV-2 infection: possible role in shuffling the homeostatic puzzle during COVID-19.

Introduction: The evolving COVID-19 pandemic became a hallmark in human history, not only by changing lifestyles, but also by enriching scientific knowledge on viral infection and its consequences. Objective: Although the management of cardiorespiratory changes is pivotal to a favorable prognosis during severe clinical findings, dysregulation of other systems caused by SARS-CoV-2 infection may imbalance erythrocyte dynamics, such as a bidirectional positive feedback loop pathophysiology. Method and Results: Recent evidence shows that SARS-CoV-2 is capable of affecting the genetics and dynamics of erythrocytes and this coexists with a non-homeostatic function of cardiovascular, respiratory and renal systems during COVID-19. In hypothesis, SARS-CoV-2-induced systematical alterations of erythrocytes dynamics would constitute a setpoint for COVID-19-related multiple organ failure syndrome and death. Conclusion: The present review covers the most frequent erythrocyte-related non-homeostatic findings during COVID-19 capable of providing mechanistic clues of SARS-CoV-2-induced infection and inspiring therapeutic-oriented scientific evidence.

Acústicas bioquímicas semi-automatizadas por processamento de imagem Dipstick com base em arduino / Biochemical semi-automated acoustics by Dipstick image processing based on arduino

Apesar da ampla disponibilidade de dispositivos para leitura de tiras reativas para análise de urina, falhas potenciais persistem na rotina baseada na interpretação humana. O objetivo deste estudo foi desenvolver e avaliar o desempenho de um dispositivo baseado em Arduino para a leitura semi-automática de parâmetros de fitas reativas. O parâmetro glicose de um modelo de tira reativa comercial foi analisado pelo sistema, que prevê a concentração do analito submetendo a cor observada na tira a um modelo de regressão, ajustado a um banco de dados de padrões de cores. O sistema foi avaliado através da leitura de 80 tiras com 16 amostras de concentrações aleatórias de glicose. O menor coeficiente de variação após cinco leituras replicadas foi de 4,5% e o mais alto foi de 16,6% (MSE = 68,7 mg / dL; r = 0,979). O dispositivo apresentou resultados satisfatórios mais baixos custos. Para torná-lo útil na rotina laboratorial, seriam necessárias novas experiências com outros parâmetros e outras classes de tiras reativas para análise de urina.

Although many devices are available to read urinalysis reactive strips, potential failure, based on human interpretation, persists in routine tasks. Current study develops and evaluates the performance of an Arduino-based device for the semi-automated reading of reactive strip parameters. The glucose parameter of a commercial reactive strip model was analyzed by the system, which predicts analyte concentration by submitting the color observed in the strip to a regression model, adjusted to a database of color patterns. The system was assessed by reading of 80 strips with 16 samples of random glucose concentrations. The lowest coefficient of variation after five replicated readings was 4.5% and the highest was 16.6% (MSE=68.7 mg/dL; r=0.979). The device featured satisfactory results plus low costs. To make it useful in the laboratory routine, further experiments with other parameters and other classes of urinalysis reactive strips would be necessary.

Difficulty producing high-pitched sounds in singing: correlations with laryngostroboscopy and electromyographic findings / Dificuldade na produção de sons agudos no canto: correlações com a laringoestroboscopia e achados eletromiográficos

Abstract Introduction: Difficulties or limitations in producing high-pitched sounds while singing may be due to the vocal technique used or organic factor. The observation of such difficulty or limitation by singing teachers is one of the main reasons affected individuals are referred to otolaryngologists. Objective: To evaluate the laryngostroboscopic and electromyographic changes in the cricothyroid muscles of singers with difficulties or limitations producing high-pitched sounds. Methods: This is a cross-sectional study. Ten singers with difficulty producing high-pitched sounds underwent voice, laryngostroboscopic, and electromyographic evaluations. Results: None of the evaluated singers presented signs of impairment of the superior laryngeal nerve on laryngostroboscopy. The electromyographic findings for the cricothyroid muscle were normal for all singers. Six singers presented vocal fold lesions, seven had signs suggestive of laryngopharyngeal reflux, and two presented vascular changes. Conclusion: No signs suggestive of superior laryngeal nerve paresis or paralysis were observed on laryngostroboscopy and electromyography of the cricothyroid muscle in singers with difficulties or limitations producing high-pitched sounds. The presence of vocal fold lesions should be investigated in this population.

Resumo Introdução: Dificuldades ou limitações na produção de sons agudos durante o canto podem ser decorrentes da técnica vocal utilizada ou de fatores orgânicos. A observação dessa dificuldade ou limitação pelos professores de canto é uma das principais razões pelas quais os indivíduos afetados são encaminhados aos otorrinolaringologistas. Objetivo: Avaliar as alterações laringoestroboscópicas e eletromiográficas no músculo cricotireóideo de cantores com dificuldades ou limitações na produção de sons agudos. Método: Estudo de coorte transversal. Dez cantores com dificuldade de produzir sons agudos foram submetidos a avaliações de voz, laringoestroboscópicas e eletromiográficas. Resultados: Nenhum dos cantores avaliados apresentou sinais de comprometimento do nervo laríngeo superior na laringoestroboscopia. Os achados eletromiográficos para o músculo cricotireóideo foram normais para todos os cantores. Seis cantores apresentaram lesões nas pregas vocais, sete apresentaram sinais sugestivos de refluxo laringofaríngeo e dois apresentaram alterações vasculares. Conclusão: Não foram observados sinais sugestivos de paresia ou paralisia do nervo laríngeo superior na laringoestroboscopia e eletromiografia do músculo cricotireóideo em cantores com dificuldades ou limitações na produção de sons agudos. A presença de lesões nas pregas vocais deve ser investigada nessa população.

Difficulty producing high-pitched sounds in singing: correlations with laryngostroboscopy and electromyographic findings.

INTRODUCTION: Difficulties or limitations in producing high-pitched sounds while singing may be due to the vocal technique used or organic factor. The observation of such difficulty or limitation by singing teachers is one of the main reasons affected individuals are referred to otolaryngologists. OBJECTIVE: To evaluate the laryngostroboscopic and electromyographic changes in the cricothyroid muscles of singers with difficulties or limitations producing high-pitched sounds. METHODS: This is a cross-sectional study. Ten singers with difficulty producing high-pitched sounds underwent voice, laryngostroboscopic, and electromyographic evaluations. RESULTS: None of the evaluated singers presented signs of impairment of the superior laryngeal nerve on laryngostroboscopy. The electromyographic findings for the cricothyroid muscle were normal for all singers. Six singers presented vocal fold lesions, seven had signs suggestive of laryngopharyngeal reflux, and two presented vascular changes. CONCLUSION: No signs suggestive of superior laryngeal nerve paresis or paralysis were observed on laryngostroboscopy and electromyography of the cricothyroid muscle in singers with difficulties or limitations producing high-pitched sounds. The presence of vocal fold lesions should be investigated in this population.

The combination of ACE I/D and ACE2 G8790A polymorphisms revels susceptibility to hypertension: A genetic association study in Brazilian patients.

BACKGROUND: Systemic arterial hypertension (SAH) is a multifactorial condition that already affects one third of the worldwide population. The identification of candidate genes for hypertension is a challenge for the next years. Nevertheless, the small contribution of each individual genetic factor to the disease brings the necessity of evaluate genes in an integrative manner and taking into consideration the physiological interaction of functions. Angiotensin I-converting enzymes, ACE and ACE2, are key regulators of blood pressure that have counterbalance roles by acting on vasoactive peptides from Renin-Angiotensin-Aldosterone System (RAAS). Insertion/deletion (I/D) polymorphism of ACE gene and single nucleotide polymorphism G8790A of ACE2 gene have been associated with susceptibility to SAH, but the literature is controversial. We proposed to evaluate these two polymorphisms jointly exploring the combined effects of ACE and ACE2 genotypes on SAH susceptibility, an approach that have not been done yet for ACE and ACE2 polymorphisms. METHODS AND FINDINGS: This genetic association study included 117 hypertensive (mean age 59.7 years) patients and 123 normotensive and diabetes-free controls (mean age 57.5 years). ACE and ACE2 polymorphisms were genotyped by SYBR Green real-time PCR and RFLP-PCR, respectively. Crude and adjusted odds ratio (OR) values were calculated to estimate the susceptibility to SAH development. It was obtained homogeneity regarding distribution by sex, age range, smoking, alcohol consumption and body mass index (BMI) between case and control groups. No-association was verified for each gene individually, but the combination of ACE and ACE2 polymorphisms on female gender revealed a significative association for DD/G_ carriers who had a 3-fold increased risk to SAH development (p = 0.03), with a stronger susceptibility on DD/GG carriers (7-fold increased risk, p = 0.01). The D allele of ACE showed association with altered levels of lipid profile variables on case group (VLDL-cholesterol, p = 0.01) and DD genotype in all individuals analysis (triglycerides, p = 0.01 and VLDL-cholesterol, p = 0.01). CONCLUSION: These findings indicate that the combination of ACE and ACE2 polymorphisms effects may play a role in SAH predisposition been the DD/G_ genotype the susceptibility profile. This result allowed us to raise the hypothesis that an increased activity of ACE (prohypertensive effects) in conjunction with reduced ACE2 activity (antihypertensive effects) could be the underlining mechanism. The association of ACE D allele with lipid alterations indicate that this can be a marker of poor prognostic on SAH evolution and contribute to CVD development. Although these preliminary findings must be confirmed by further researches with larger sample size, we could observe that the integrative analysis of ACE and ACE2 can be an informative tool in hypertension understanding that needs to be explored in new studies.