Deciphering the Molecular Mechanisms behind Drug Resistance in Ovarian Cancer to Unlock Efficient Treatment Options.

Ovarian cancer is a highly lethal form of gynecological cancer. This disease often goes undetected until advanced stages, resulting in high morbidity and mortality rates. Unfortunately, many patients experience relapse and succumb to the disease due to the emergence of drug resistance that significantly limits the effectiveness of currently available oncological treatments. Here, we discuss the molecular mechanisms responsible for resistance to carboplatin, paclitaxel, polyadenosine diphosphate ribose polymerase inhibitors, and bevacizumab in ovarian cancer. We present a detailed analysis of the most extensively investigated resistance mechanisms, including drug inactivation, drug target alterations, enhanced drug efflux pumps, increased DNA damage repair capacity, and reduced drug absorption/accumulation. The in-depth understanding of the molecular mechanisms associated with drug resistance is crucial to unveil new biomarkers capable of predicting and monitoring the kinetics during disease progression and discovering new therapeutic targets.

Concern about the risk of aerosol contamination from ultrasonic scaler: a systematic review and meta-analysis.

BACKGROUND: Many instruments used in dentistry are rotary, such as handpieces, water syringes, and ultrasonic scalers that produce aerosols. The spray created by these instruments can carry, in addition to water, droplets of saliva, blood, and microorganisms, which can pose a risk of infections for healthcare professionals and patients. Due to the COVID-19 pandemic, this gained attention. OBJECTIVE: The aim was to carry out a systematic review of the evidence of the scope of the aerosol produced by ultrasonic scaler in environmental contamination and the influence of the use of intraoral suction reduction devices. DESIGN: Scientific literature was searched until June 19, 2021 in 6 databases: Pubmed, EMBASE, Web of science, Scopus, Virtual Health Library and Cochrane Library, without restrictions on language or publication date. Studies that evaluated the range of the aerosol produced by ultrasonic scaler during scaling/prophylaxis and the control of environmental contamination generated by it with the use of low (LVE) and high (HVE) volume evacuation systems were included. RESULTS: Of the 1893 potentially relevant articles, 5 of which were randomized controlled trials (RCTs). The meta-analysis of 3 RCTs showed that, even at different distances from the patient's oral cavity, there was a significant increase in airborne bacteria in the dental environment with the use of ultrasonic scaler. In contrast, when meta-analysis compared the use of HVE with LVE, there was no significant difference (P = 0.40/CI -0.71[-2.37, 0.95]) for aerosol produced in the environment. CONCLUSIONS: There is an increase in the concentration of bioaerosol in the dental environment during the use of ultrasonic scaler in scaling/prophylaxis, reaching up to 2 m away from the patient's mouth and the use of LVE, HVE or a combination of different devices, can be effective in reducing air contamination in the dental environment, with no important difference between different types of suction devices.

Asociación entre niveles de ansiedad y depresión en adultos con obesidad / Associação entre níveis de ansiedade e depressão em adultos com obesidade / Association between anxiety levels and depression in adults with obesity

Objetivo: Verificar la asociación entre los niveles de ansiedad y depresión en participantes de un Programa Multidisciplinario para el Tratamiento de la Obesidad, con variables antropométricas; composición corporal; parámetros bioquímicos y hemodinámicos; y aptitud física relacionada con la salud. Método: Estudio cuantitativo, correlacional, transversal, realizado con adultos participantes del Programa Multidisciplinario de Tratamiento de la Obesidad en un municipio del Noroeste de Paraná. Para la recolección de datos se aplicaron medidas antropométricas en julio de 2021; composición corporal; parámetros bioquímicos y hemodinámicos; pruebas de aptitud física relacionadas con la salud; y escala para evaluar los niveles de ansiedad y depresión. Resultados: Participaron del estudio 116 individuos, 87,94% mujeres, 12,06% hombres, con una edad media de 40 años. Hubo una correlación positiva considerable entre la hemoglobina y el hematocrito; colesterol total y LDL; glucosa y HbA1C1; peso e IMC; peso y perímetro abdominal; peso y circunferencia de la cintura; IMC y perímetro abdominal; IMC y perímetro de cintura; así como ansiedad y depresión. Conclusión: Los niveles de ansiedad y depresión de los participantes de Programa Multidisciplinario para el Tratamiento de la Obesidad no se correlacionaron significativamente con las variables de medición antropométricas; composición corporal; parámetros bioquímicos y hemodinámicos; y pruebas de evaluación de la aptitud física relacionadas con la salud. (AU)

Objetivo: Verificar associação entre níveis de ansiedade e depressão de participantes de um Programa Multiprofissional de Tratamento da Obesidade, com variáveis antropométricas; composição corporal; parâmetros bioquímicos e hemodinâmicos; e aptidão física relacionada à saúde. Método: Estudo transversal, realizado com adultos que participaram do programa em município do Noroeste do Paraná. Para a coleta de dados, aplicou-se em julho de 2021, avaliações de medidas antropométricas; composição corporal; parâmetros bioquímicos e hemodinâmicos; testes de aptidão física relacionada à saúde; e escala para avaliar os níveis de ansiedade e depressão. Resultados: Participaram do estudo 116 indivíduos, sendo 87,94% do sexo feminino, 12,06% do sexo masculino, com média de idade de 40 anos. Houve correlação positiva entre hemoglobinas e hematócritos; colesterol total e LDL; glicose e HbA1C1; peso, IMC e circunferências abdominal e de cintura; além de ansiedade e depressão. Conclusão: Os níveis de ansiedade e depressão não apresentaram correlação significativa com as variáveis estudadas. (AU)

Objective: To verify the association between levels of anxiety and depression of participants in a Multidisciplinary Program for the Treatment of Obesity, with anthropometric variables; body composition; biochemical and hemodynamic parameters; and health-related physical fitness. Method: Quantitative, correlational, cross-sectional study carried out with adults who participated in the Multidisciplinary Program for the Treatment of Obesity in a municipality in the Northwest of Paraná. For data collection, anthropometric measurements were applied in July 2021; body composition; biochemical and hemodynamic parameters; health-related physical fitness tests; and scale to assess levels of anxiety and depression. Results: 116 individuals participated in the study, 87.94% female, 12.06% male, with a mean age of 40 years. There was a considerable positive correlation between hemoglobin and hematocrit; total and LDL cholesterol; glucose and HbA1C1; weight and BMI; weight and abdominal circumference; weight and waist circumference; BMI and abdominal circumference; BMI and waist circumference; as well as anxiety and depression. Conclusion:The levels of anxiety and depression of the participants of the Multidisciplinary Program for the Treatment of Obesity did not present a significant correlation with the variables of anthropometric measurements; body composition; biochemical and hemodynamic parameters; and health-related physical fitness assessment tests. (AU)

Epidemiological, immunological, and treatment response profile of patients with lupus nephritis in Brazil.

BACKGROUND AND HYPOTHESIS: Brazil has the largest number of individuals of African descent outside Africa and a very admixed population. Among cases of lupus nephritis (LN) in the country, there are differences in incidence, and even in severity, depending on the location and characteristics of the population studied. The aim of this study was to describe the clinical and epidemiological characteristics of LN in Brazil, as well as to determine which of those characteristics would be risk factors for a poor renal prognosis. METHODS: This was a retrospective, descriptive observational study of patients diagnosed with LN who underwent kidney biopsy between 1999 and 2015 in the Nephrology Department of the Hospital das Clínicas, in São Paulo, Brazil. Data were collected from electronic medical records. RESULTS: We evaluated 398 patients, among who 94.1% and 77.7% tested positive for antinuclear antibodies and anti-DNA antibodies, respectively, whereas 33.7% showed the full-house pattern. The time from LN symptom onset to biopsy was <6 months in 47.5% (early biopsy group) and ≥6 months in 52.5% (late biopsy group). In the early biopsy group, the chronicity index was lower and the activity index was higher. Multivariate analysis showed that a higher chronicity index was the only independent risk factor for progression to requiring kidney replacement therapy. CONCLUSION: Late biopsy seems to be associated with negative renal outcomes in LN. However, it seems that a higher chronicity index is the main predictor of a poor renal outcome among patients with LN in Brazil.

Cdc42 activation is necessary for heterosynaptic cooperation and competition.

Synapses change their weights in response to neuronal activity and in turn, neuronal networks alter their response properties and ultimately allow the brain to store information as memories. As for memories, not all events are maintained over time. Maintenance of synaptic plasticity depends on the interplay between functional changes at synapses and the synthesis of plasticity-related proteins that are involved in stabilizing the initial functional changes. Different forms of synaptic plasticity coexist in time and across the neuronal dendritic area. Thus, homosynaptic plasticity refers to activity-dependent synaptic modifications that are input-specific, whereas heterosynaptic plasticity relates to changes in non-activated synapses. Heterosynaptic forms of plasticity, such as synaptic cooperation and competition allow neurons to integrate events that occur separated by relatively large time windows, up to one hour. Here, we show that activation of Cdc42, a Rho GTPase that regulates actin cytoskeleton dynamics, is necessary for the maintenance of long-term potentiation (LTP) in a time-dependent manner. Inhibiting Cdc42 activation does not alter the time-course of LTP induction and its initial expression but blocks its late maintenance. We show that Cdc42 activation is involved in the phosphorylation of cofilin, a protein involved in modulating actin filaments and that weak and strong synaptic activation leads to similar levels on cofilin phosphorylation, despite different levels of LTP expression. We show that Cdc42 activation is required for synapses to interact by cooperation or competition, supporting the hypothesis that modulation of the actin cytoskeleton provides an activity-dependent and time-restricted permissive state of synapses allowing synaptic plasticity to occur. We found that under competition, the sequence in which synapses are activated determines the degree of LTP destabilization, demonstrating that competition is an active destabilization process. Taken together, we show that modulation of actin cytoskeleton by Cdc42 activation is necessary for the expression of homosynaptic and heterosynaptic forms of plasticity. Determining the temporal and spatial rules that determine whether synapses cooperate or compete will allow us to understand how memories are associated.

Partial Implant Rehabilitations in the Posterior Regions of the Jaws Supported by Short Dental Implants (7.0 mm): A 7-Year Clinical and 5-Year Radiographical Prospective Study.

Background: Short implants have been used in the restoration of edentulous jaws in the past several years. However, some studies have suggested that short implants are less successful than standard implants. The aim of this study is to investigate the outcome of short implants placed in the posterior maxilla or mandible following one-stage or immediate-function protocols with a follow-up of 7 years (clinically) and 5 years (radiographically). Methods: This study included 127 patients rehabilitated with 217 implants measuring 7 mm and supporting 157 fixed prostheses in the posterior segments of both jaws. Final abutments were delivered at the surgery stage and were loaded after 4 months in 116 patients (199 implants). The primary outcome measure was implant survival measured through life tables. Secondary outcome measures were marginal bone loss and the incidence of biological and mechanical complications at the patient level and implant level (evaluated through descriptive statistics). Results: Twenty-four patients (18.9%) with 45 implants (20.7%) were lost to the follow-up. In total, 32 implants failed (14.8%) in 22 patients (17.3%), resulting in a cumulative survival rate at 7 years of 81.2% for 7 mm implants in the rehabilitation of the posterior regions of the maxilla and mandible. The average (standard deviation) marginal bone loss was 1.47 mm (0.99 mm) at 5 years. The incidence rate of biological complications was 12.6% and 10.6% at the patient and implant levels, respectively. The incidence rate of mechanical complications was 21.3% for patients and 16.1% for implants. A higher failure rate was registered in smokers and in implant arrangements with a sequence of three fixtures in proximity. Conclusions: Within the limitations of this study, it can be concluded that the placement of 7 mm long implants for the partial implant-supported rehabilitation of atrophic posterior jaws is possible in the long term, judging by the survival rate and stable average marginal bone loss. Nevertheless, strict case selection should be performed, especially in smokers and with implant arrangements that provide a minimum of one unit in inter-implant distance.

The influence of carvedilol posology timing on clinically significant portal hypertension: insights from elastography measurements.

BACKGROUND AND AIMS: Carvedilol has emerged as the preferred ß-blocker for treating portal hypertension. However, there is still a debate in dosing regimen, with a potential lower bioavailability in once-daily regimens. The aim of this study is to assess the acute effects of carvedilol posology in patients with clinically significant portal hypertension (CSPH), as a surrogate marker of bioavailability. METHODS: In this experimental study, 34 patients with CSPH receiving carvedilol twice daily were asked to suppress the night dose of carvedilol, creating a standardized 24-hour dose interval. Spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by transient elastography (TE) were performed, with the exact interval between the last carvedilol administration and TE measurements consistently maintained at 24 hours and compared with values prior and under treatment. RESULTS: Thirty-four patients were included, predominantly male (82.9%). SSM after suspending carvedilol for 24 hours [mean, 73.9kPa (SD, 17.0)] was significantly higher ( P < 0.001) than under treatment [mean, 56.3kPa (SD, 13.2)] and was not significantly different ( P = 0.908) from SSM prior to introduction of carvedilol [mean, 74.5kPa (SD, 12.4)]. Differences were also found in stratified analysis for carvedilol dosage, D'Amico classification stages, MELDNa scores, MELD3.0 scores, Child-Pugh class A and CSPH due to alcoholic cirrhosis. LSM after suspension was not significantly different from both under treatment and prior to treatment. CONCLUSION: The differences in SSM after skipping one dose of carvedilol show both the importance of strict adherence to the prescribed dosing regimen to achieve the expected therapeutic benefits and the impact of twice daily prescription in bioavailability throughout the day.

Allopurinol-Induced Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis (TEN) is a rare and life-threatening cutaneous disease, frequently triggered by drugs. Allopurinol is one of the most frequent drugs associated with TEN, which implies detachment of a significant amount of the body surface area (BSA) and has a high morbidity and mortality associated with it. We present the case of a 68-year-old female with a recent diagnosis of hyperuricemia who started treatment with allopurinol. A week later, she presented to the emergency department with an extensive maculopapular exanthema with blisters and skin detachment. After the exclusion of other etiologies, the diagnosis of allopurinol-induced TEN was made, with 35% of BSA involvement. Due to the severity of the clinical condition, she was admitted to intensive care and treated with corticoids that had no response. So, she was started on immunoglobulins and transferred to a burn unit. She developed sepsis with multiorgan failure and required supportive treatment. She was discharged after a month, and physical rehabilitation was needed. This clinical case highlights the severity of allopurinol hypersensitivity that may happen and the importance of an accurate diagnosis and treatment for this rare disease.

Dynamics of Lateral Habenula-Ventral Tegmental Area Microcircuit on Pain-Related Cognitive Dysfunctions.

Chronic pain is a health problem that affects the ability to work and perform other activities, and it generally worsens over time. Understanding the complex pain interaction with brain circuits could help predict which patients are at risk of developing central dysfunctions. Increasing evidence from preclinical and clinical studies suggests that aberrant activity of the lateral habenula (LHb) is associated with depressive symptoms characterized by excessive negative focus, leading to high-level cognitive dysfunctions. The primary output region of the LHb is the ventral tegmental area (VTA), through a bidirectional connection. Recently, there has been growing interest in the complex interactions between the LHb and VTA, particularly regarding their crucial roles in behavior regulation and their potential involvement in the pathological impact of chronic pain on cognitive functions. In this review, we briefly discuss the structural and functional roles of the LHb-VTA microcircuit and their impact on cognition and mood disorders in order to support future studies addressing brain plasticity during chronic pain conditions.

Faunistic Analysis of Calliphoridae and Mesembrinellidae (Diptera: Oestroidea) at Different Stages of Bovine Liver Decomposition in the State of Rio de Janeiro.

Performing quantitative sampling and determining faunistic analyses of dipterans is of fundamental importance in the analysis of ecological behavior, such as population dynamics and diversity, among other factors, for exotic and native species of necrophagous dipterans, so it is important to observe the type of bait used in traps to capture these dipteran species. This work aims to study structural parameters and faunistic indices of the diversity of Calliphoridae and Mesembrinellidae species as well as the abundance and diversity of species attracted to liver in two stages of decomposition: fresh liver and liver at 48 h of putrefaction. A total of 2826 dipterans were collected during the period from May 2021 to February 2022. We observed that liver in decomposition for 48 h was more attractive in the forest and rural environments, while fresh liver showed greater attractiveness in the urban environment; however, no statistical difference was evidenced between the attractiveness in the different environments. The Mesembrinellidae family and the species Lucilia eximia (Wiedemann, 1819) were collected mostly from deteriorated liver, while Cochliomyia macellaria (Fabricius, 1775) showed no preference for any liver decomposition stage. The Wilcoxon test indicated that there is a significant difference between the preferences for putrefied bait in Mesembrinellidae, while in Calliphoridae, there was no preference for type of bait. The faunistic analysis showed that richness in the forest area was always higher when compared to the urban and rural areas. Laneela nigripes (Guimarães, 1977) and Mesembrinella bellardiana (Aldrich, 1922) were abundant and exclusive in the preserved environment, showing themselves to be good environmental bioindicators.

Associação de métodos de imagem no desafio diagnóstico da drenagem anômala total das veias pulmonares do tipo mista / Association of imaging methods in the diagnostic challenge of mixed total anomalous pulmonary vein drainage

APRESENTAÇÃO DO CASO: Lactente sem diagnósticos prévios, internado com dispneia e baixo débito cardíaco aos dois meses de vida. Transferido para serviço de referência em cardiopatias congênitas em ventilação mecânica e em uso de drogas vasoativas. Realizado ecocardiograma que demonstrou drenagem anômala total das veias pulmonares (DATVP) do tipo mista, com as veias pulmonares esquerdas drenando em veia vertical ascendente, que desemboca na veia inominada, e então na veia cava superior (VCS) e as veias pulmonares direitas drenando no seio coronário, que desemboca no átrio direito. O exame também demonstrou comunicações interatriais tipo ostium secundum não restritivas com fluxo do átrio direito para o esquerdo, dilatação importante das cavidades direitas, ventrículo direito com hipertrofia importante e disfunção sistólica, além de hipertensão pulmonar. Submetido a angiotomografia de coração corroborando o diagnóstico, com melhor visualização de todo o trajeto da veia vertical. Realizada cirurgia com redirecionamento das veias pulmonares e ligadura da veia vertical, com sucesso. DISCUSSÃO: A DATVP é uma cardiopatia congênita cianótica rara na qual todas as veias pulmonares se conectam com o sistema venoso sistêmico. Resulta da persistência das conexões embrionárias do plexo venoso pulmonar. O tipo IV da classificação de Darling e colaboradores ou drenagem mista é a associação entre duas ou mais dentre as formas supracardíaca, infracardíaca ou intracardíaca. Neste caso, houve combinação da drenagem supracardíaca das veias pulmonares esquerdas (que por meio da veia vertical drenavam na VCS), com a drenagem intracardíaca das veias pulmonares direitas (que drenavam no átrio direito através do seio coronário). Esta associação é uma variante rara com apenas alguns relatos. O ecocardiograma realizado por profissional experiente em cardiopatias congênitas dá o diagnóstico, mas a associação com outros métodos de imagem como a tomografia é especialmente importante nas variantes mistas para permitir um plano cirúrgico adequado e o redirecionamento completo, evitando lesões residuais. COMENTÁRIOS FINAIS: Apresentamos um caso de DATVP com drenagem cardíaca e supracardíaca, forma rara e de diagnóstico desafiador, definido pelo ecocardiograma e confirmado por tomografia computadorizada com reconstrução 3D. Devido à grande variabilidade da DATVP, é essencial detalhar bem o trajeto, as conexões dos vasos e o local de drenagem de cada um deles para um manejo adequado.

Synanthropy and ecological aspects of Calliphoridae and Mesembrinellidae (Diptera: Oestroidea) in three ecological areas in Rio de Janeiro State, Brazil.

The determination of the synanthropic index is essential to evaluate the degree of association between species, such as diptera and man, based solely on their degree of preference for urban areas. This research aimed to study the synanthropic behavior of Calliphoridae and Mesembrinellidae flies in Rio de Janeiro, Brazil. The experiment was conducted between 2021 and 2022 in three areas, where four traps containing 300 g of fresh liver or with 48 h of putrefaction were installed, remaining exposed for 48 h; after collection the dipterans were sacrificed and taxonomically identified. A total of 2,826 dipterans were collected, represented by nine species of Calliphoridae (89.24%) and ten of Mesembrinellidae (10.76%), with the first record of Mesembrinella currani in this biome. The Kruskal-Wallis test showed that the abundance of individuals did not differ among the three analyzed environments. The Mesembrinellidae family was exclusively asynanthrope, along with two species of Calliphoridae: Hemilucilia benoisti (Séguy 1925) and Paralucilia nigrofacialis (Mello 1969) which were exclusive of the forest area, while Calliphoridae had varied synanthropy. Lucilia eximia (Wiedemann 1819) alone represented 57.18% of the total sampled, being the most abundant in all environments except the urban area where Hemilucilia segmentaria (Fabricius 1805) totaled 55.73%. No species were exclusive to the urban area, however Cochliomyia hominivorax (Coquerel 1858) and Lucilia cuprina (Wiedemann 1830) were exclusive to the rural area. The most synanthropic species were Chrysomya megacephala (Fabricius 1794) and Chrysomya albiceps (Wiedemann 1819).

Role of Glutamatergic Projections from Lateral Habenula to Ventral Tegmental Area in Inflammatory Pain-Related Spatial Working Memory Deficits.

The lateral habenula (LHb) and the ventral tegmental area (VTA), which form interconnected circuits, have important roles in the crucial control of sensory and cognitive motifs. Signaling in the LHb-VTA pathway can be exacerbated during pain conditions by a hyperactivity of LHb glutamatergic neurons to inhibit local VTA DAergic cells. However, it is still unclear whether and how this circuit is endogenously engaged in pain-related cognitive dysfunctions. To answer this question, we modulated this pathway by expressing halorhodopsin in LHb neurons of adult male rats, and then selectively inhibited the axonal projections from these neurons to the VTA during a working memory (WM) task. Behavioral performance was assessed after the onset of an inflammatory pain model. We evaluated the impact of the inflammatory pain in the VTA synapses by performing immunohistochemical characterization of specific markers for GABAergic (GAD65/67) and dopaminergic neurons (dopamine transporter (DAT), dopamine D2 receptor (D2r) and tyrosine hydroxylase (TH)). Our results revealed that inhibition of LHb terminals in the VTA during the WM delay-period elicits a partial recovery of the performance of pain animals (in higher complexity challenges); this performance was not accompanied by a reduction of nociceptive responses. Finally, we found evidence that the pain-affected animals exhibit VTA structural changes, namely with an upregulation of GAD65/67, and a downregulation of DAT and D2r. These results demonstrate a role of LHb neurons and highlight their responsibility in the stability of the local VTA network, which regulates signaling in frontal areas necessary to support WM processes.

Rhabdomyosarcoma of the oral cavity in children aged 0-2 years: A scoping review.

BACKGROUND: The aim of this study was to collect, synthesize, and analyze the clinic-demographic data of rhabdomyosarcoma affecting the oral cavity of young children. METHODS: The clinical question was "What are the clinical characteristics of oral rhabdomyosarcoma in children aged zero to two years?" Two independent reviewers selected the studies, extracted data, and assessed the methodological quality through the Joanna Briggs Institute Checklist. Descriptive statistics were performed in SPSS. (protocol: osf.io/b9hvy). RESULTS: Thirty case reports with 41 patients were included (22 males; mean age at diagnosis: 15 months). All studies had some methodological limitations, mainly due to the lack of clarity for a final judgment. More than 70% of the cases affected the tongue or lips. Tumors had a fast growth (mean 2.5 months), usually with red coloration, and variable shape and consistency. Embryonal (63.41%) and alveolar (29.27%) were the most common histological subtypes. Treatment was quite variable but usually included surgery. Most patients (53.66%) were alive without disease at follow-up. CONCLUSION: Oral rhabdomyosarcoma is rare in children aged 0-2 years without a marked gender predilection. The tumor presents as a fast and infiltrative growth leading to local and/or systemic symptoms, and a favorable prognosis for most patients.

Tumor cardíaco na infância: quando pensar em fibroma? Relato de caso / Heart tumor in childhood: when to think about fibroma? Case report

INTRODUÇÃO E/OU FUNDAMENTOS: Introdução: Cerca de 90% dos tumores cardíacos na faixa etária pediátrica são classificados como primários benignos representados majoritariamente pelos rabdomiomas. Os fibromas, por sua vez, constituem um tipo bastante raro na infância, sendo caracterizados por massa tumoral única, bem delimitada, não contrátil, ecogênica e heterogênea no interior do miocárdio, frequentemente localizados no septo interventricular (SIV) e parede livre ventricular. Diferentemente dos rabdomiomas, podem apresentar calcificações centrais típicas e não costumam regredir espontaneamente. Em caso de repercussão hemodinâmica (obstrução ao fluxo, insuficiência cardíaca congestiva (ICC) ou arritmia ventricular), a depender da extensão da massa neoplásica para o interior da cavidade ventricular, a única opção terapêutica possível é ressecção total ou parcial do tumor, além do transplante cardíaco. RELATO DO CASO: Relato de caso: Lactente do sexo feminino, nascida a termo, encaminhada ao centro de referência com 11 meses de idade. História de sopro cardíaco ao nascimento. À admissão, genitora negou queixas cardiovasculares. Exame físico: sopro sistólico 2+/4 em BEEM, B2 fisiológica, SatO2 de 98%, sem sinais de ICC. Radiografia de tórax: aumento da área cardíaca (ICT 0,75) e da trama vascular pulmonar. Eletrocardiograma: sobrecarga ventricular direita e desvio extremo do SÂQRS à -144º. Ecocardiograma (ECO): massa extensa única, medindo 48x54mm, aderida ao SIV com centro calcificado e sem vascularização, com redução luminal dos ventrículos e obstrução dinâmica na via de saída do ventrículo direito gerando gradiente sistólico máximo de 30mmHg. O diagnóstico de fibroma foi corroborado pela ressonância magnética cardíaca (RMC). Paciente segue estável, assintomática do ponto de vista cardiovascular, em acompanhamento ambulatorial. CONCLUSÕES: Conclusão: Atualmente, o diagnóstico e a classificação dos tumores cardíacos na infância, mesmo os mais raros como o fibroma, podem ser definidos pela análise clínica e, sobretudo, das imagens do ECO e da RMC, permitindo também a diferenciação de diagnósticos importantes como cistos, trombos e vegetações. Inegavelmente, a despeito do prognóstico inicial, a investigação precoce, a intervenção oportuna (clínica e/ou cirúrgica) e o seguimento especializado regular são essenciais para um desfecho mais favorável a longo prazo.

Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action.

Drug combination and drug repurposing are two strategies that allow to find novel oncological therapies, in a faster and more economical process. In our previous studies, we developed a novel model of drug combination using antineoplastic and different repurposed drugs. We demonstrated the combinations of doxorubicin (DOX) + artesunate, DOX + chloroquine, paclitaxel (PTX) + fluoxetine, PTX + fluphenazine, and PTX + benztropine induce significant cytotoxicity in Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. Furthermore, it was found that 5-FU + thioridazine and 5-fluorouracil (5-FU) + sertraline can synergistically induce a reduction in the viability of human colorectal adenocarcinoma cell line (HT-29). In this study, we aim to (1) evaluate the biosafety profile of these drug combinations for non-tumoral cells and (2) determine their mechanism of action in cancer cells. To do so, human fetal lung fibroblast cells (MRC-5) fibroblast cells were incubated for 48 h with all drugs, alone and in combination in concentrations of 0.25, 0.5, 1, 2, and 4 times their half-maximal inhibitory concentration (IC50). Cell morphology and viability were evaluated. Next, we designed and constructed a cell microarray to perform immunohistochemistry studies for the evaluation of palmitoyl-protein thioesterase 1 (PPT1), Ki67, cleaved-poly (ADP-ribose) polymerase (cleaved-PARP), multidrug resistance-associated protein 2 (MRP2), P-glycoprotein (P-gp), and nuclear factor-kappa-B (NF-kB) p65 expression. We demonstrate that these combinations are cytotoxic for cancer cells and safe for non-tumoral cells at lower concentrations. Furthermore, it is also demonstrated that PPT1 may have an important role in the mechanism of action of these combinations, as demonstrated by their ability to decrease PPT1 expression. These results support the use of antimalarial and central nervous system (CNS) drugs in combination regimens with chemotherapeutic agents; nevertheless, additional studies are recommended to further explore their complete mechanisms of action.

Pitavastatin and Ivermectin Enhance the Efficacy of Paclitaxel in Chemoresistant High-Grade Serous Carcinoma.

Chemotherapy is a hallmark in high-grade serous carcinoma management; however, chemoresistance and side effects lead to therapeutic interruption. Combining repurposed drugs with chemotherapy has the potential to improve antineoplastic efficacy, since drugs can have independent mechanisms of action and suppress different pathways simultaneously. This study aimed to explore whether the combination of Paclitaxel with repurposed drugs led to a therapeutic benefit. Thus, we evaluated the cytotoxic effects of Paclitaxel alone and in combination with several repurposed drugs (Pitavastatin, Metformin, Ivermectin, Itraconazole and Alendronate) in two tumor chemoresistant (OVCAR8 and OVCAR8 PTX R P) and a non-tumoral (HOSE6.3) cell lines. Cellular viability was assessed using Presto Blue assay, and the synergistic interactions were evaluated using Chou-Talalay, Bliss Independence and Highest Single Agent reference models. The combination of Paclitaxel with Pitavastatin or Ivermectin showed the highest cytotoxic effect and the strongest synergism among all combinations for both chemoresistant cell lines, resulting in a chemotherapeutic effect superior to both drugs alone. Almost all the repurposed drugs in combination with Paclitaxel presented a safe pharmacological profile in non-tumoral cells. Overall, we suggest that Pitavastatin and Ivermectin could act synergistically in combination with Paclitaxel, being promising two-drug combinations for high-grade serous carcinoma management.

Surgical sterilization of free-ranging capybaras (Hydrochoerus hydrochaeris): "Passos Nunes" uterine horn ligature.

Capybaras are the primary hosts of Amblyomma sculptum tick, vectors of Rickettsia rickettsia bacteria, and the zoonotic agent of Brazilian Spotted Fever (BSF). In this context, contraceptive methods have been suggested for population control in order to reduce the number of free-ranging capybaras cohabiting with humans in urban and rural areas and acting as disease amplifiers. To maintain the group's expected behavior and social hierarchy, sterilization techniques that preserve the gonads are recommended. On 126 female capybaras in the Brazilian state of São Paulo, a new surgical technique named "Passos Nunes" uterine horn ligature was performed after adequate general anesthesia. It achieved effective surgical sterilization, with an incision length of about 3 cm in the periumbilical linea alba, cranial to the pubis. After entering the abdominal cavity, the urinary bladder is pulled laterally to access the uterine horns and the cervix. The uterine horn is folded up, forming a strap; the distal portion of the strap is ligated and its distal end sectioned. The exact process is performed on the opposite horn. After the surgical procedure, the musculature is sutured in a sultan pattern and the subcutaneous tissue with a horizontal mattress pattern. The skin is sutured in a separate simple format, using nylon 2.0 for all steps. The wide exposure of the uterine horns facilitates the confirmation of pregnancy, allowing the surgeon to choose between salpingo hysterectomy or ligature of the uterine horns. The present study presents a new technique of surgical sterilization that can be used in female free-ranging mammals in which maintenance of the gonads is recommended, and births of offspring should not occur.

Estudo de caso intrínseco de um recém-nascido prematuro: procedimentos dolorosos / Intrinsic case study of a premature newborn: painful procedures / Estudio de caso intrínseco de un recién nacido prematuro: procedimientos dolorosos

Objetivo: identificar e descrever os procedimentos invasivos/dolorosos e as medidas analgésicas aplicadas em um recém-nascido prematuro extremo durante o período de internação em uma Unidade de Terapia Intensiva Neonatal. Método: trata-se de uma pesquisa observacional, tipo estudo de caso de caráter intrínseco, quantitativo, descritivo e analítico. Os dados foram coletados do prontuário de um lactente que nasceu com idade gestacional de 26 semanas e com seguimento no Ambulatório Canguru, de um hospital escola, do interior do Estado do Paraná. Resultados: o recém-nascido foi submetido a 368 procedimentos invasivos e dolorosos durante todo o período de internação (73 dias), sendo a aspiração de vias aéreas o procedimento prevalente realizado 217 vezes. Destes procedimentos, 64% foram realizados com o uso de analgesia e 36% sem medidas analgésicas. Considerações Finais: os procedimentos dolorosos aos quais o RN foi submetido, durante o período de internação foram expressivos. Por meio de uma ação efetiva e segura foi prescrito o método farmacológico para minimizar a dor.

Objective: identifying and describing the invasive/painful procedures and the analgesic measures applied inan extremely premature newborn baby during the period of hospitalization in a Neonatal Intensive Care Unit. Method: it is an observational search, a case studyof an intrinsic, quantitative, descriptive and analytical character. The data were collected from the medical records of a baby who was born at the gestational age of 26 weeks, with follow-up in Medical Clinic Canguru, which belongs to a teaching hospitalin the countryside of Paraná State. Results: the newborn baby was submitted to 368 invasive andpainful procedures during the whole period of hospitalization (73 days), being airway aspiration the prevalent procedure, performed 217 times. Of these procedures, 64% were carried out with the use of analgesia and 36% without any analgesic measures. Final Considerations: the painful procedures to which the newborn baby was submitted during the hospitalization period were expressive. By means of an effective andsafe action, the pharmacological method was prescribed in order to minimize pain.

Objetivo: identificar y describir los procedimientos invasivos/dolorosos y las medidas analgésicas aplicadas a un recién nacido extremadamente prematuro durante el período de hospitalización en una Unidad de Cuidados Intensivos Neonatales. Método: se trata de una investigación observacional, tipo estudio de caso, de carácter intrínseco, cuantitativo, descriptivo y analítico. Los datos fueron recolectados de la historia clínica de un niño que nació con edad gestacional de 26 semanas y seguido en el Ambulatorio Canguro de un hospital escuela del interior del estado de Paraná. Resultados: el recién nacido fue sometido a 368 procedimientos invasivos y dolorososdurante todo el período de hospitalización (73 días), siendo la aspiración de las vías aéreas el procedimiento predominante realizado 217 veces. De estos procedimientos, el 64% se realizaron con el uso de analgesia y el 36% sin medidas analgésicas. Consideraciones finales: los procedimientos dolorosos a los que fue sometido el RN durante el período de hospitalización fueron significativos. A través de una acción eficaz y segura, se prescribió el método farmacológico para minimizar el dolor.

InfectionCMA: A Cell MicroArray Approach for Efficient Biomarker Screening in In Vitro Infection Assays.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the scientific community to acquire knowledge in real-time, when total lockdowns and the interruption of flights severely limited access to reagents as the global pandemic became established. This unique reality made researchers aware of the importance of designing efficient in vitro set-ups to evaluate infectious kinetics. Here, we propose a histology-based method to evaluate infection kinetics grounded in cell microarray (CMA) construction, immunocytochemistry and in situ hybridization techniques. We demonstrate that the chip-like organization of the InfectionCMA has several advantages, allowing side-by-side comparisons between diverse cell lines, infection time points, and biomarker expression and cytolocalization evaluation in the same slide. In addition, this methodology has the potential to be easily adapted for drug screening.