Frequency of perfume in 398 children's cosmetics

Abstract Objective: Perfume (Parfum) or fragrance is a natural or synthetic cosmetic ingredient added to emit a pleasant aroma or to improve the odor of a cosmetic formula. It is a mixture of substances, not revealed by the manufacturer, which may contain ingredients with allergenic potential, endocrine disruptors, and other possible harmful effects on human health. This study aims to analyze children's cosmetics labels to assess the presence of Perfume. Methods: The researchers randomly visited points of sale in Curitiba, the capital of a southern Brazilian state; in order to catalog the largest possible number of children's cosmetics items. Results: 398 children's cosmetics were analyzed and found Parfum on 295 (74.1 %) of the labels, including 90.4 and 79,1 % of the shampoos and wet wipes, respectively. Conclusion: Exposure of children's skin to fragrances can lead to local side effects such as allergies, but also to systemic effects, and the lack of knowledge of the general population and health professionals about its possible deleterious effects emphasizes the importance of changes in the regulation of cosmetics aiming to reduce the use of this ingredient.

Bisphenol A released and ultrastructural changes in dental composite resins

Dental composite resins may release bisphenol-A or similar molecules affecting patient health and the environment. This study measured bisphenol-A release from three commonly used in patients composite resins (Filtek™ Z350 XT, Filtek™ P60, Filtek™ Bulk Fill) immersed in three liquid mediums (artificial saliva, 0.001 M lactic acid and 15% ethanol) and assessed the changes in the surface micromorphology.The released BPA was measured by HPLC at basal time (t=0), 1 h, 1 d, 7 d and 30 d. Topographic analysis of specimens was performed by scanning electron microscopy (SEM). The data were analyzed using one-way ANOVA and Tukey post-hoc test (P < 0.05). BPA in solution increased significantly in the three DCRs immersed in 0.001 M lactic acid at all times. SEM micrographs of the specimen in 0.001 M lactic acid disclosed more structural defects than others. The surface of the three composite resins was morphologically affected by their immersion in all solutions. SEM evidenced that the dental materials underwent erosion and cracks with filler particles protruding from the surface. The morphological changes in tested dental materials produced by exposure to these solutions are potentially dangerous to patients by causing caries, infections, and partial loss of dental material.

Food packaging and endocrine disruptors

Abstract Objectives Narrative review evaluating food contamination by endocrine disruptors present in food packaging. Data source The terms "endocrine disruptors" and "food packaging" were used in combination in the PubMed, MEDLINE and SciELO databases, evaluating studies, in humans, published in Portuguese, English, French and Spanish between 1990 and 2023. Data synthesis Packaging, especially those made from plastic or recycled material, is an important source of food contamination by endocrine disruptors. Bisphenols and phthalates are the endocrine disruptors most frequently associated with food contamination from packaging. However, many unknown substances and even those legally authorized can cause harm to health when exposure is prolonged or when substances with additive effects are mixed. Furthermore, the discarding of packaging can cause contamination to continue into the environment. Conclusion Although packaging materials are essential for the transport and storage of food, many of them are associated with chemical contamination. As it is not possible to exclude them from our routine, it is important to develop research aimed at identifying the endocrine disruptors present in them, including the effects of chronic exposure; and that regulatory agencies and industry come together to reduce or prevent this risk. Additionally, consumers must be instructed on how to purchase products, handle them and prepare them to reduce the migration of chemical substances into food.

Cuidado ás pessoas com agravos endocrinos e metabólicos / Care for people with endocrine and metabolic problems

O objetivo desse trabalho é descrever a sistematização da Assistência de Enfermagem a pessoas com agravos endócrinos e metabólicos pautado na teoria de Calista Roy. Metodologia: Trata-se de um relato de experiência através da aplicação da Sistematização da Assistência de Enfermagem (SAE), voltado para pessoas com agravos endócrinos e metabólicos no contexto hospitalar. Resultados e discussão: Foi aplicado a teoria da adaptação nas seis fases da Teoria de Calista Roy e foi elaborado diagnósticos de enfermagem para os quatro modos de adaptação: fisiológico, interdependência, autoconceito e função de papel. Considerações finais: Ao aplicar a SAE no indivíduo com agravos endócrinos e metabólicos a enfermeira deve realizá-lo em todas as suas etapas, e utilizar os protocolos para oferecer um cuidado holístico e integral, visando a promoção da saúde, prevenção de risco potencial e adaptação diante das necessidades em saúde.(AU)

The aim of this study is to describe the systematization of nursing care for people with endocrine and metabolic disorders, based on Calista Roy's theory. Methodology: This is an experience report on the application of the Systematization of Nursing Care (SNC) to people with endocrine and metabolic disorders in a hospital setting. Results and discussion: The theory of adaptation was applied in the six phases of Calista Roy's theory and nursing diagnoses were drawn up for the four modes of adaptation: physiological, interdependence, self-concept and role function. Final considerations: When applying the SNC to individuals with endocrine and metabolic disorders, the nurse must carry it out in all its stages, and use the protocols to offer holistic and comprehensive care, aimed at promoting health, preventing potential risks and adapting to health needs.(AU)

El objetivo de este estudio es describir la sistematización de los cuidados de enfermería a personas con trastornos endocrinos y metabólicos, basándose en la teoría de Calista Roy. Metodología: Se trata de un informe de experiencia sobre la aplicación de la Sistematización de los Cuidados de Enfermería (SNC) a personas con trastornos endocrinos y metabólicos en un entorno hospitalario. Resultados y discusión: Se aplicó la teoría de la adaptación en las seis fases de la teoría de Calista Roy y se elaboraron diagnósticos de enfermería para los cuatro modos de adaptación: fisiológica, interdependencia, autoconcepto y función de rol. Consideraciones finales: Al aplicar el SNC a individuos con trastornos endocrinos y metabólicos, la enfermera debe llevarlo a cabo en todas sus fases, y utilizar los protocolos para ofrecer cuidados holísticos e integrales, dirigidos a promover la salud, prevenir riesgos potenciales y adaptarse a las necesidades de salud.(AU)

Occupational exposure to pesticides deregulates systemic cortisol levels in women with breast cancer and correlates with poor prognosis features

Pesticides have been pointed out as hormone disruptors and may significantly affect the prognosis of hormone-dependent diseases such as breast cancer (BC). Here, we investigated the impact of occupational pesticide exposure on systemic cortisol levels in female rural workers diagnosed with BC. Occupational exposure was assessed by interviews with a standardized questionnaire. Plasma samples (112 from pesticide-exposed women and 77 from unexposed women) were collected in the afternoon, outside the physiological cortisol peak, and analyzed by a chemiluminescent paramagnetic immunoassay for the quantitative determination of cortisol levels in serum and plasma. The results from both groups were categorized according to patients' clinicopathological and exposure data. BC pesticide-exposed women presented higher levels of cortisol than the unexposed. Higher cortisol levels were also detected in the exposed group with more aggressive disease (triple-negative BC), with tumors over 2 cm, with lymph node metastases, and with high risk of disease recurrence and death. These findings demonstrated that there is an association between pesticide exposure and BC that affected cortisol levels and correlated to poor disease prognosis.

Adrenal morphology and cortical function in patients with extrapulmonary tuberculosis: response to antituberculosis treatment

ABSTRACT Objective: Enlargement of the adrenal glands and variable adrenocortical function have been reported in patients with pulmonary tuberculosis and, in a few studies, in patients with extrapulmonary tuberculosis (EPTB). However, none of the studies have evaluated the course of the adrenal morphology in these patients. Subjects and methods: Prospective study including 37 patients with EPTB and 37 healthy age- and sex-matched controls. The adrenal function was evaluated by measurement of cortisol levels at baseline and after stimulation with ACTH (Acton Prolongatum) before and 6 months after antituberculosis treatment. The size of both adrenal glands was evaluated using 64-slice computed tomography (CT) scanning before and 6 months after treatment. The findings were compared with those in a group of healthy matched controls. Results: Clinical and biochemical parameters were comparable between groups. The mean baseline serum cortisol level was significantly lower in the EPTB group (397.1 ± 184.9 nmol/L) compared with the control group (696.3 ± 101.8 nmol/L). Compared with controls, patients with EPTB had significantly lower mean cortisol levels at baseline and 1 hour after ACTH, both before (397 ± 184.9 nmol/L and 750.7 ± 176.8 nmol/L, respectively) and after (529.7 ± 100.4 nmol/L and 1017.2 ± 119.7 nmol/L, respectively) antituberculosis treatment. Both the length and thickness of the right and left adrenal glands were greater in patients with EPTB than in controls but became comparable to those in controls after treatment completion. Conclusions: Patients with EPTB have an enlarged adrenal size and low baseline and stimulated serum cortisol levels. After treatment completion, cortisol levels increased significantly, and the adrenal size normalized in these patients.

Research progress on food-derived antioxidants for alleviating toxicity of endocrine disrupting chemicals / 环境与职业医学

Endocrine disrupting chemicals (EDCs) are a class of chemical substances widely present in daily-life environment, and can enter human body through various pathways, posing a threat to reproductive development and health. Oxidative stress (OS) is one of the most important fundamental mechanisms underlying the reproductive toxicity of EDCs. Numerous studies have found that exposure to EDCs can increase the levels of reactive oxygen species (ROS) in human reproductive system and reduce the activity and quantity of multiple enzymatic antioxidants, leading to oxidative stress and inducing damage to the reproductive system at various levels such as DNA and cells. Many research results have shown that supplementing food-derived non-enzymatic antioxidants can reduce ROS levels and increase the activity of enzymatic antioxidants, thereby reduce OS levels, and further repair EDCs-induced reproductive damage. In addition, many food-derived antioxidants are important elements involved in reproductive physiological activities and have protective effects on reproductive health. This paper summarized the reproductive toxicity of EDCs, including damage to reproductive cells, interference with hormone action, and influence on reproductive-related epigenetic regulation, elaborated the relationship between OS and reproductive toxicity of EDCs, and further summarized the alleviating effects and related mechanisms of food-derived antioxidants such as vitamins, trace elements, and plant polyphenols and pigments against reproductive toxicity of EDCs, aiming to provide a theoretical and scientific basis for prevention and treatment against reproductive toxicity of EDCs.

Clinical Efficacy of Qingxin Zishen Decoction on Hot Flashes After Endocrine Therapy for Prostate Cancer and Its Preliminary Mechanism / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of Qingxin Zishen decoction on hot flashes after endocrine therapy for prostate cancer and explore its therapeutic mechanism. MethodA total of 60 patients who met the criteria and were admitted to Jiangsu Province Hospital of Chinese Medicine from December 2021 to December 2022 were collected and randomly divided into a treatment group and a control group， with 30 cases in each group. The treatment group was treated with Qingxin Zishen decoction， while the control group was only given routine nursing. The observation period of this study was eight weeks. The improvement of hot flash frequency， hot flash degree， hot flash score， ISS score， and TCM syndrome score were observed in the two groups before and after treatment. The changes of serum endothelin-1 （ET-1）， nitric oxide （NO）， calcitonin gene-related peptide （CGRP）， prostate specific antigen （PSA）， and testosterone were detected. ResultIn terms of efficacy， after treatment， the frequency， degree， and score of hot flashes， ISS score， and TCM syndrome score decreased in the treatment group （P<0.05）. Compared with the control group， all indicators were better in the treatment group （P<0.05）. In terms of laboratory indicators， after treatment， the serum NO level in the treatment group was increased. ET-1 level was decreased. The ratio of ET-1/NO was decreased， and the CGRP level was decreased （P<0.05）. However， testosterone and PSA levels were not significantly changed . Compared with the control group， after treatment， the serum NO level in the treatment group was higher， and the level of ET-1 was lower. The ratio of ET-1/NO and the CGRP level were lower （P<0.05）. There were no significant differences in testosterone and PSA levels between the two groups. ConclusionQingxin Zishen decoction can significantly improve hot flashes in patients with prostate cancer after endocrine therapy. The mechanism of Qingxin Zishen decoction may be to improve the vasomotor function by regulating the expression level of vasomotor factors， so as to treat hot flashes.

Neoplasia endocrina múltiple tipo 1 en paciente con diagnóstico de nesidioblastosis. Presentación de un caso

Las neoplasias endocrinas múltiples engloban una serie de síndromes caracterizados por su origen genético y la afectación de una o más glándulas. Se describe el caso de un paciente masculino, de 23 años, con antecedentes de salud de nesidioblastosis diagnosticado a los 16 años de edad, quien acudió al Hospital General Docente Ambato por presentar convulsiones tónico clónicas, e hipoglucemia severa con posterior estatus epiléptico. Los estudios de laboratorio mostraron hiperparatiroidismo primario, y los de imagen identificaron lesiones sugerentes de adenoma paratiroideo e insulinoma de cabeza de páncreas. Después de analizar el caso, se identificaron dos criterios para plantear una neoplasia endocrina múltiple tipo 1: presencia de insulinoma e hiperparatiroidismo primario. Además de tratamiento con bifosfonato, se planificó interconsulta con el servicio de Genética, para estudio del paciente y familiares; y con Cirugía General, para programación de resolución quirúrgica. Debido a la poca frecuencia de esta enfermedad, resulta de interés describir el caso, con el objetivo de exponer las principales manifestaciones clínicas y conducta a seguir. Constituye una prioridad el diagnóstico de su causa en cada paciente.

Multiple endocrine neoplasias encompass a series of syndromes characterized by their genetic origin and the involvement of one or more glands. A 23-years-old male patient with a health history of nesidioblastosis diagnosed at 16 years of age, who attended the Ambato General Teaching Hospital with tonic-clonic seizures and severe hypoglycemia with subsequent epileptic status, is described. Laboratory studies showed primary hyperparathyroidism, and imaging identified lesions suggestive of parathyroid adenoma and insulinoma of the head of the pancreas. After analyzing the case, two criteria were identified to suggest multiple endocrine neoplasia type 1: presence of insulinoma and primary hyperparathyroidism. In addition to treatment with bisphosphonate, consultation with the Genetics service was planned for study of the patient and family members; and with General Surgery, for scheduling surgical resolution. Due to the infrequency of this disease, it is of interest to describe the case, with the aim of exposing the main clinical manifestations and conduct to follow. Diagnosing its cause in each patient is a priority.

Protective Effects and Mechanisms of Huangqi Decoction Against Radiation-Induced Bystander Effects / Efectos Protectores y Mecanismos de la Decocción de Huangqi Contra los Efectos Secundarios Inducidos por la Radiación

SUMMARY: The 12C6+ heavy ion beam irradiation can cause bystander effects. The inflammatory cytokines, endocrine hormones and apoptotic proteins may be involved in 12C6+ irradiation-induced bystander effects. This study characterized the protective effects and mechanisms of Huangqi decoction (HQD) against 12C6+ radiation induced bystander effects. Wistar rats were randomly divided into control, 12C6+ heavy ion irradiation model, and high-dose/medium-dose/low-dose HQD groups. HE staining assessed the pathological changes of brain and kidney. Peripheral blood chemical indicators as well as inflammatory factors and endocrine hormones were detected. Apoptosis was measured with TUNEL. Proliferating cell nuclear antigen (PCNA) expression was determined with real-time PCR and Western blot.Irradiation induced pathological damage to the brain and kidney tissues. After irradiation, the numbers of white blood cells (WBC) and monocyte, and the expression of interleukin (IL)-2, corticotropin-releasing hormone (CRH) and PCNA decreased. The damage was accompanied by increased expression of IL-1β, IL-6, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) as well as increased neuronal apoptosis. These effects were indicative of radiation-induced bystander effects. Administration of HQD attenuated the pathological damage to brain and kidney tissues, and increased the numbers of WBC, neutrophils, lymphocyte and monocytes, as well as the expression of IL-2, CRH and PCNA. It also decreased the expression of IL-1β, IL-6, CORT and ACTH as well as neuronal apoptosis. HQD exhibits protective effects against 12C6+ radiation-induced bystander effects. The underlying mechanism may involve the promotion of the production of peripheral blood cells, inhibition of inflammatory factors and apoptosis, and regulation of endocrine hormones.

La irradiación con haz de iones pesados 12C6+ puede provocar efectos secundarios. Las citoquinas inflamatorias, las hormonas endocrinas y las proteínas apoptóticas pueden estar involucradas en los efectos secundarios inducidos por la irradiación 12C6+. Este estudio caracterizó los efectos y mecanismos protectores de la decocción de Huangqi (HQD) contra los efectos externos inducidos por la radiación 12C6+. Las ratas Wistar se dividieron aleatoriamente en grupos control, modelo de irradiación de iones pesados 12C6+ y grupos de dosis alta/media/baja de HQD. La tinción con HE evaluó los cambios patológicos del cerebro y el riñón. Se detectaron indicadores químicos de sangre periférica, así como factores inflamatorios y hormonas endocrinas. La apoptosis se midió con TUNEL. La expresión del antígeno nuclear de células en proliferación (PCNA) se determinó mediante PCR en tiempo real y transferencia Western blot. La irradiación indujo daños patológicos en los tejidos cerebrales y renales. Después de la irradiación, disminuyó el número de glóbulos blancos (WBC) y monocitos, y la expresión de interleucina (IL)-2, hormona liberadora de corticotropina (CRH) y PCNA. El daño estuvo acompañado por una mayor expresión de IL-1β, IL-6, corticosterona (CORT) y hormona adrenocorticotrópica (ACTH), así como un aumento de la apoptosis neuronal. Estas alteraciones fueron indicativas de efectos inducidos por la radiación. La administración de HQD atenuó el daño patológico a los tejidos cerebrales y renales, y aumentó el número de leucocitos y monocitos, así como la expresión de IL-2, CRH y PCNA. También disminuyó la expresión de IL-1β, IL-6, CORT y ACTH, así como la apoptosis neuronal. HQD exhibe mecanismos protectores contra los efectos externos inducidos por la radiación 12C6+. El mecanismo subyacente puede implicar la promoción de la producción de células sanguíneas periféricas, la inhibición de factores inflamatorios y la apoptosis y la regulación de hormonas endocrinas.

An Interesting Endocrine Cause of Pyrexia of Unknown Origin: A Case Report and Review of Literature

Pyrexia of unknown origin (PUO) is one of the most challenging medical problems. Endocrine causes of PUO are rare. Fever is common in a few endocrine disorders (e.g., thyroid storm, adrenal crisis and pheochromocytoma). However, PUO as the sole presenting feature is very rare with only a few reported cases in the literature. We present the case of a middle-aged male who came to us with PUO, weight loss and loss of appetite. The unusual symptomatology like loss of appetite, altered bowel habits made diagnosis difficult. This case highlights the importance of considering thyroid disorder in the differential diagnosis of PUO. Abnormal thyroid function may be an early clue for diagnosis.

Thyroid Dysfunction in Adults with Newly Detected Type 2 Diabetes Mellitus: A Study in a Tertiary Care Hospital, Dhaka, Bangladesh

Background: Thyroid disorders and diabetes mellitus are common endocrine disorders that often coexist and can significantly impact each other’s management. The American Diabetes Association recommends that people with diabetes be periodically screened for thyroid dysfunction due to the strong link between the two conditions. It is important for individuals to be aware of the risk factors for both conditions and to seek appropriate medical care if necessary, and for healthcare providers to consider testing for thyroid dysfunction in adults with newly detected type 2 diabetes mellitus. The aim of the study was to find out thyroid dysfunction in adults with newly detected type 2 diabetes mellitus. Material & Methods: This cross-sectional, descriptive study was conducted at the Departments of Medicine and Endocrinology at Sir Salimullah Medical College and Mitford Hospital in Dhaka. The study period lasted six months, from May to October 2019. A total of 102 adult patients (above 20 years old) with newly diagnosed type 2 diabetes mellitus who were attending the Endocrinology and Medicine Outpatient Department participated in the study. Results: Out of 102 adults with newly detected type 2 diabetes mellitus, the majority (86.3%) had normal thyroid function (euthyroid), while a smaller number (13.7%) had thyroid dysfunction. The most common subgroup of thyroid dysfunction was subclinical hypothyroidism (7.8%), followed by hypothyroidism (3.9%), subclinical thyrotoxicosis (1.0%), and hyperthyroidism (1.0%). The majority of the study population was male (66%) and from urban areas (88%), with a mean age of 45.1 years, a mean BMI of 25.0 kg/m2, and a mean waist circumference of 98.4 cm. About 45% had a family history of diabetes mellitus and 37% were smokers. The blood pressure of the study population was within normal limits. A minority (30%) had co-morbidities such as hypertension, dyslipidemia, and ischemic heart disease. The predictors of thyroid dysfunction were observed Age (OR=0.785), F/H of thyroid disorder (OR=0.495) BMI (OR=1.059), Anti-TPO Ab(OR= 0.021). Conclusion: Thyroid dysfunction and diabetes are commonly associated with each other and can impact clinical presentation and laboratory results. It is important to routinely screen for thyroid function in all patients with type 2 diabetes mellitus to detect, treat, and prevent complications of both these conditions.

Calidad de vida en pacientes con enfermedades tiroideas

Introducción: Las enfermedades del tiroides son relativamente frecuentes, constituyen un importante grupo dentro de las enfermedades crónicas no transmisibles. Objetivo: Determinar la calidad de vida en pacientes con enfermedades tiroideas. Métodos: Se realizó un estudio observacional, descriptivo y transversal. El universo estuvo constituido por 210 pacientes con diagnóstico de enfermedades tiroideas, que cumplieron con los criterios de inclusión y exclusión previstos en el estudio, previo consentimiento informado y la muestra no probabilística de 198 pacientes. Se utilizaron las variables: edad, sexo, enfermedad tiroidea diagnosticada (hipertiroidismo, hipotiroidismo, bocio difuso eutiroideo) y calidad de vida (facetas según dimensiones, según la clasificación de expertos y enfermedades tiroideas y la calidad de vida integral según enfermedades tiroideas). Se utilizó el cuestionario World Health Organization Quality of Life. Resultados: Predominó el hipotiroidismo como afección tiroidea más frecuente en las féminas entre 50 a 59 años. Las manifestaciones clínicas que puntuaron las medias más bajas fueron el dolor y malestar, seguido de indicaciones médicas y sentimientos negativos; las dimensiones físicas y psicológicas puntuaron con medias bajas, al igual que el ambiente, valores considerados como deficientes. Conclusiones: Predominó una calidad de vida integral media en el mayor por ciento de los pacientes, estas enfermedades deben ser identificadas a tiempo, para evitar otras complicaciones en diferentes sistemas del organismo que pudieran comprometer la vida del paciente.

Introduction: Thyroid diseases are relatively frequent; they constitute an important group within chronic non-communicable diseases. Objective: To determine the quality of life in patients with thyroid diseases. Methods: An observational, descriptive and cross-sectional study was carried out. The universe (210 patients) with a diagnosis of thyroid diseases, who met the inclusion and exclusion criteria provided for in the study, prior informed consent, and the non-probabilistic sample (198 patients). The variables used were: age, sex, diagnosed thyroid disease (hyperthyroidism, hypothyroidism, diffuse euthyroid goiter) and quality of life (facets according to dimensions, according to expert classification and thyroid diseases and comprehensive quality of life according to diseases thyroid). The World Health Organization Quality of Life questionnaire was used. Results: Hypothyroidism predominated as the most frequent thyroid condition in women between 50 and 59 years of age. The clinical manifestations that scored the lowest average were pain and discomfort, followed by medical indications and negative feelings; the physical and psychological dimensions scored with low averages, as well as the environment, values ​​considered deficient. Conclusions: An average comprehensive quality of life prevailed in the highest percentage of patients; these diseases must be identified in time, to avoid other complications in different body systems that could compromise the patient's life.

Does bisphenol A (BPA) participates in the pathogenesis of Polycystic Ovary Syndrome (PCOS)?

Abstract PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erβ, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.

Comparative efficacy & safety of buparlisib plus fulvestrant, fulvestrant plus dalpiciclib, and ribociclib plus letrozole for postmenopausal, hormone receptor-positive, and HER2-negative breast cancer

Abstract Objectives: This study aimed to compare progression-free survival, overall survival, clinical benefits, and adverse effects in postmenopausal women with hormone receptor-positive and HER2-negative breast cancer who received buparlisib plus fulvestrant against those of women who received dalpiciclib plus fulvestrant, considering ribociclib plus letrozole treatment as the reference standard. Methods: Women received buparlisib plus fulvestrant (BF cohort, n = 108), dalpiciclib plus fulvestrant (DF cohort, n = 132), or ribociclib plus letrozole (RL cohort, n = 150) until unacceptable toxicity was observed. Results: A total of 117 (89 %), 80 (74 %), and 84 (56 %) women in the BF, DF, and RL cohorts, respectively, had clinical benefits. After treatment, the clinical benefits for women and after 42 months of follow-up progression-free survival and overall survival were higher in the DF cohort than in the BF and RL cohorts (p < 0.05 for all). Neutropenia, vomiting, constipation, nausea, diarrhea, and anorexia were reported higher in women of the DF and BF cohorts than in women of the RL cohort. Leukopenia and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the RL cohort than in women in the DF and BF cohorts. Depression, anxiety, and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the BF cohort than in women in the DF and RL cohorts. Conclusions: Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

The triglyceride-glucose index as an indicator of insulin resistance and cardiometabolic risk in Brazilian adolescents

ABSTRACT Objective: To set cutoff points for the triglyceride and glucose index (TyG) as a marker of insulin resistance (IR) for the pediatric population. Subjects and methods: This was a cross-sectional study with schoolchildren population-based data using data of 377 schoolchildren age 10 to 17 years of both sexes. We studied metabolic variables associated with IR indicators, such as fasting insulin and blood glucose, to calculate the homeostatic model assessment (HOMA-IR), and we studied triglycerides (TG) to determine the TyG index. We obtained TyG cutoff values for IR using the receiver operation characteristic (ROC), with definitions of sensitivity (Sen), specificity (Spe), and area under the ROC curve (AUC), with the HOMA-IR as reference. Results: The cutoff points of the TyG index for IR in adolescents are 7.94 for both sexes, 7.91 for boys, and 7.94 for girls, indicating moderate discriminatory power. When we also considered anthropometric variables of excess weight [TyG-BMI (body mass index)] and visceral fat [TyG-WC (waist circumference)], these indexes reached AUC values higher than 0.72, enhancing their potential use for a good diagnosis. Conclusion: TyG has proven to be a useful instrument for identifying IR in adolescent health screening, with high discrimination capacity when added to anthropometric variables, making it a feasible and inexpensive option.

Immune checkpoint inhibitor-induced endocrinopathies: a possible indicator of improved survival

ABSTRACT Objective: To evaluate the association between the patients' characteristics and the development of endocrine toxicity and to assess the association between endocrine-related adverse effects (ERAE) development and mortality. Subjects and methods: A retrospective observational study was conducted in 98 patients submitted to immunotherapy in our centre since its introduction in 2015 until March 2021. We excluded patients for which data regarding the corticotroph axis evaluation was missing. We used linear and logistic regression models to address our aims. Results: We observed a significant negative association between ERAE development and death (OR 0.32; p = 0.028). We detected no associations between ERAE and the following characteristics: age at immune checkpoint inhibitors (ICI) initiation, sex, diabetes mellitus, medical history, immunotherapy duration and ICI type. Conclusion: The development of an ERAE may be associated with a better overall survival rate in advanced oncologic disease, supporting the role of an unleashed immune system response to malignant cells.

Mechanisms of endocrine-resistance and therapeutic breakthroughs in hormone receptor-positive, HER2-negative breast cancer / 中国临床药理学与治疗学

Breast cancers that are positive for hormone receptor but negative for human epidermal growth factor receptor 2 (abbreviated as HR+/HER2-) account for approximately 60% of total cases. Targeting estrogen signaling is one of the most important therapeutic strategies for HR+/HER2- breast cancer. However, the management of endocrine-resistant HR+/HER2- breast cancer remains a difficult issue in clinical practice. Previous multi-omic analysis and translational research have identified the mechanisms underlying endocrine-resistance including genomic alteration and abnormal epigenetic modification. To overcome endocrine-resistance, we have established a comprehensive and coherent therapeutic strategy. In addition, several novel therapies have shown promising efficacy in previous clinical trials and will emerge as alternative options for targeting endocrine-resistant HR+/HER2- breast cancer. In this review, we will introduce the mechanisms of endocrine-resistance, explain the current therapeutic strategy for endocrine-resistant HR +/HER2 - breast cancer and discuss the possible targeted therapies in the future.

Discovery of novel covalent selective estrogen receptor degraders against endocrine-resistant breast cancer

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα+) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα+ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

Short chain fatty acid: a messenger of gut-organ axis for disease regulation / 药学学报

Gut microbiota is a complex and dynamic system, and is essential for the health of the body. As the "second genome" of the body, it can establish communication with the important organs by regulating intestinal nerves, gastrointestinal hormones, intestinal barrier, immunity and metabolism, thus affecting host′s physiological functions. Short chain fatty acid (SCFA), known as one important metabolite of intestinal microbiota, is regarded as a significant messenger of the gut-organ communication, due to its extensive regulation in the body′s immunity, metabolism, endocrine and signal transduction. In this review, we summarize the interaction between gut-liver/brain/kidney/lung axis and diseases, and focus on the role and mechanism of SCFA in the gut-organ communication, hoping to provide new ideas for the treatment of the related diseases.