N-Adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as Fluorescent Probes to Detect Microglia Activation through the Imaging of Cannabinoid Receptor Subtype 2 (CB2R).

Cannabinoid receptor subtype 2 (CB2R) is emerging as a pivotal biomarker to identify the first steps of inflammation-based diseases such as cancer and neurodegeneration. There is an urgent need to find specific probes that may result in green and safe alternatives to the commonly used radiative technologies, to deepen the knowledge of the CB2R pathways impacting the onset of the above-mentioned pathologies. Therefore, based on one of the CB2R pharmacophores, we developed a class of fluorescent N-adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives spanning from the green to the near-infrared (NIR) regions of the light spectrum. Among the synthesized fluorescent ligands, the green-emitting compound 55 exhibited a favorable binding profile (strong CB2R affinity and high selectivity). Notably, this ligand demonstrated versatility as its use was validated in different experimental settings such as flow cytometry saturation, competitive fluorescence assays, and in vitro microglia cells mimicking inflammation states where CB2R are overexpressed.

Diabetes mellitus in patients with acromegaly: pathophysiology, clinical challenges and management.

Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications.

EGFR and HER2 hyper-activation mediates resistance to endocrine therapy and CDK4/6 inhibitors in ER+ breast cancer.

In patients with ER + metastatic breast cancer (mBC), the first-line treatment involves the combination of endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i). However, a significant group of patients experiences disease progression, emphasizing the urgent clinical need to identify novel anti-tumor therapies. We previously generated breast cancer cells resistant to the combination of fulvestrant (ER downregulator) and abemaciclib (CDK4/6 inhibitor) from MCF7 and T47D (MCF7-FAR and T47D-FAR). RNA-seq-based Gene Set Enrichment Analysis (GSEA) revealed hyper-activation of EGFR, HER2, and AKT signaling in both MCF7-FAR and T47D-FAR. Modulating EGFR or ERBB2 expression through loss- and gain-of-function experiments altered tumor sensitivity to fulvestrant and abemaciclib in parental and FAR spheroids, affecting ERK and AKT/S6 pathways. Cetuximab treatment overcame tumor resistance to fulvestrant and abemaciclib in FAR and EGFR-overexpressing breast cancer spheroids and xenografts. Likewise, patient-derived organoids (PDOs) from individuals with ER + mBC, progressing on palbociclib, exhibited up-regulation of EGFR and HER2 pathways. In conclusion, our findings suggest that inhibiting EGFR and HER2 pathways might overcome resistance to ET + CDK4/6i in selected patients with ER + mBC.

Androgen deficiency in hypopituitary women: its consequences and management.

Women with hypopituitarism have various degrees of androgen deficiency, which is marked among those with combined hypogonadotrophic hypogonadism and secondary adrenal insufficiency. The consequences of androgen deficiency and the effects of androgen replacement therapy have not been fully elucidated. While an impact of androgen deficiency on outcomes such as bone mineral density, quality of life, and sexual function is plausible, the available evidence is limited. There is currently no consensus on the definition of androgen deficiency in women and it is still controversial whether androgen substitution should be used in women with hypopituitarism and coexisting androgen deficiency. Some studies suggest beneficial clinical effects of androgen replacement but data on long-term benefits and risk are not available. Transdermal testosterone replacement therapy in hypopituitary women has shown some positive effects on bone metabolism and body composition. Studies of treatment with oral dehydroepiandrosterone have yielded mixed results, with some studies suggesting improvements in quality of life and sexual function. Further research is required to elucidate the impact of androgen deficiency and its replacement treatment on long-term outcomes in women with hypopituitarism. The lack of transdermal androgens for replacement in this patient population and limited outcome data limit its use. A cautious and personalized treatment approach in the clinical management of androgen deficiency in women with hypopituitarism is recommended while awaiting more efficacy and safety data.

Metástasis cutáneas de adenocarcinoma renal. A propósito de un caso / Cutaneous metastases of renal adenocarcinoma About a case

El carcinoma de células renales convencional o de células claras constituye la variedad más frecuente de todos los carcinomas de células renales, aproximadamente el 80 %. Es uno de los tumores urológicos más agresivos. Produce metástasis cutánea con una baja incidencia, siendo la misma de presentación infrecuente y en etapa avanzada de la enfermedad. Presentamos el caso clínico de un paciente con metástasis en tronco y cuero cabelludo secundarias a un adenocarcinoma renal. Dichas lesiones fueron el primer indicio del tumor primario (AU)

Conventional renal cell carcinoma or clear cell carcinoma is the most common type of all renal cell carcinomas (80%). It is one of the most aggressive urological tumors. Cutaneous metastasis is unusual and appears at an advanced stage of the disease. A male patient with trunk and scalp metastases secondary to renal adenocarcinoma is reported. These cutaneous lesions were the first manifestation of the primary tumor (AU)

Caracterização do uso do cicloergômetro para auxiliar no atendimento fisioterapêutico em pacientes críticos / Characterization of the use of a cycle ergometer to assist in the physical therapy treatment of critically ill patients

OBJETIVO: Analisar as alterações cardiorrespiratórias de pacientes durante o exercício ativo com um cicloergômetro e verificar a aceitação dos pacientes para realizar esse tipo de atividade. MÉTODOS: Foi realizada uma única intervenção de exercício ativo de membros inferiores no cicloergômetro (sem carga) durante 5 minutos. As variáveis frequência cardíaca, pressão arterial, frequência respiratória, saturação periférica de oxigênio e escala de dispneia de Borg foram avaliadas em três momentos: antes, durante e imediatamente após o exercício. Ao final, o paciente respondia um questionário avaliando sua satisfação em relação a esse tipo de atividade. RESULTADOS: Participaram do estudo 38 pacientes (65% masculino) com 48±16 anos e SOFA=2 (0-5). Durante o exercício, 55% estavam em ar ambiente e 16% utilizaram algum tipo de suporte ventilatório. Comparando-se os valores iniciais e finais das variáveis analisadas, verificou-se um aumento apenas nas variáveis frequência cardíaca (92±17 e 95±18; p<0,05), frequência respiratória (19±8 e 23±8; p<0,05) e Borg (1,3±1,8 e 2,8±2,2; p<0,05). Além disso, 85% dos pacientes gostaram muito de realizar esse tipo de atividade. Apenas 25% dos pacientes relataram algum tipo de desconforto, entretanto 100% dos pacientes gostariam de repetir esse tipo de atividade em um próximo atendimento. CONCLUSÃO: Nos pacientes estudados, verificaram-se pequenas alterações cardiorrespiratórias durante o exercício com o cicloergômetro. Os pacientes avaliados relataram alta satisfação com esse tipo de atividade.

OBJECTIVE: The objective of this study was to use a cycle ergometer to assess cardiorespiratory changes during active exercise and to verify patients' satisfaction with this type of activity. METHODS: A single intervention involving active lower limb exercise was performed with a cycle ergometer (without load) for 5 minutes. The following variables were measured before, during and immediately after exercise: heart rate, blood pressure, respiratory rate, peripheral oxygen saturation and the Borg dyspnea scale score. Following the exercise, the patients answered a questionnaire to evaluate their satisfaction with this type of activity. RESULTS: A total of 38 patients (65% male) with a mean age of 48 ± 16 years old participated in the study. Enrolled patients presented a sequential organ failure assessment (SOFA) score of 2 (0 - 5 scale). During the exercise, 16% of the patients used ventilation support and 55% of them were breathing at room air. A comparison of the initial and final values of the variables indicated increases in the heart rate (92±17 beats/min vs. 95±18 beats/min; p<0.05), the respiratory rate (19 ± 8 breaths/min vs. 23±8 breaths/min; p<0.05) and the Borg dyspnea scale score (1.3±1.8 vs. 2.8±2.2; p<0.05). In addition, 85% of the patients reported enjoying the activity. Only 25% of the patients reported some discomfort, and 100% of the patients wanted to repeat this type of activity in future treatments. CONCLUSION: During the cycle ergometer exercises, minor cardiorespiratory changes were observed in the patients. The evaluated patients reported high satisfaction with this type of activity.

Motivação e educação odontológica em pacientes especial / Dental health education and the special patient

O presente trabalho relata o caso clínico de um paciente portador de deficiência mental e auditiva atendido na Disciplina de Paciente Especiais da Faculdade de Odontologia da UNIBAN, apresentando higiene bucal precária, em que a utilização de figuras como meio para movimentacao imposta pelas patologias melhorando a condição imposta pelas patologias bucal do paciente