Use of CAR-T cells for the treatment of relapsed and refractory multiple myeloma: a systematic review / Uso de células CAR-T no tratamento de mieloma múltiplo recidivado e refratário: uma revisão sistemática

A systematic review of published articles based on randomized clinical trials was conducted to ascertain the efficacy or perspective of using CAR-T cell therapy for refractory multiple myeloma. The PubMed database was searched with the combination of terms "multiple myeloma", "refractory multiple myeloma", "CAR T-cell", and the PRISMA criteria were followed. Of the 78 articles found, only 5 were selected. The studies used different treatment protocols and four different types of CAR-T cells. All studies obtained interesting results in terms of increased progression-free survival and negative minimal residual disease responses. Some authors detected an expansion of CAR-T cells and noted dose-dependent relationship between treatment effectiveness and serum BCMA levels. Although the results were promising, a small number of patients still relapsed a few months after CAR-T cell infusion. Therefore, this new line of therapy should be further investigated, as it significantly increases progression-free survival and improves quality of life.

Uma revisão sistemática de artigos publicados com base em ensaios clínicos randomizados foi realizada para verificar a eficácia ou perspectiva do uso da terapia com células CAR-T para mieloma múltiplo refratário. Foi pesquisada a base de dados PubMed com a combinação dos termos "multiple myeloma", "refratory multiple myeloma", "CAR T-cell" e foram seguidos os critérios PRISMA. Dos 78 artigos encontrados, apenas 5 foram selecionados. Os estudos utilizaram diferentes protocolos de tratamento e quatro tipos diferentes de células CAR-T. Todos os estudos obtiveram resultados interessantes em termos de aumento da sobrevida livre de progressão e respostas negativas à doença residual mínima. Alguns autores detectaram uma expansão das células CAR-T e observaram uma relação dose-dependente entre a eficácia do tratamento e os níveis séricos de BCMA. Embora os resultados tenham sido promissores, um pequeno número de pacientes ainda apresentou recaída alguns meses após a infusão de células CAR-T. Portanto, esta nova linha de terapia deve ser mais investigada, pois aumenta significativamente a sobrevida livre de progressão e melhora a qualidade de vida.

Synergistic impact of -linolenic acid and -tocopherol on in vitro maturation and culture of buffalo oocytes

Abstract The objective of the current study was to investigate the synergistic impact of -Tocopherol and -Linolenic acid (100 µM) on IVM and IVC of Nili Ravi buffalo oocytes. Oocytes were obtained from the ovaries of slaughtered buffaloes within two hours after slaughter and brought to laboratory. Buffalo cumulus oocyte complexes were placed randomly in the five experimental groups included; GROUP 1: Maturation media (MM) + 100 µM ALA (control), GROUP 2: MM + 100 µM ALA + 50M -Tocopherol, GROUP 3: MM + 100 µM ALA + 100M -Tocopherol, GROUP 4: MM + 100 µM ALA + 200 M -Tocopherol and GROUP 5: MM + 100 µM ALA + 300 M -Tocopherol under an atmosphere of 5% CO2 in air at 38.5 °C for 22-24 h. Cumulus expansion and nuclear maturation status was determined (Experiment 1). In experiment 2, oocytes were matured as in experiment 1. The matured oocytes were then fertilized in Tyrodes Albumin Lactate Pyruvate (TALP) medium for about 20 h and cultured in synthetic oviductal fluid (SOF) medium to determine effect of -Linolenic acid (100 µM) and -Tocopherol in IVM medium on IVC of presumptive zygotes. To study the effect of -Linolenic acid (100 µM) in IVM media and increasing concentration of -tocopherol in the culture media on early embryo development (Experiment 3), the presumptive zygotes were randomly distributed into the five experimental groups with increasing concentration of -tocopherol in culture media. Higher percentage of MII stage oocytes in experiment 1(65.2±2.0), embryos at morula stage in experiment 2 (30.4±1.5) and experiment 3 (22.2±2.0) were obtained. However, overall results for cumulus cell expansion, maturation of oocyte to MII stage and subsequent embryo development among treatments remain statistically similar (P > 0.05). Supplementation of -tocopherol in maturation media having -Linolenic acid and/or in embryo culture media did not further enhance in vitro maturation of oocyte or embryo production.

Resumo O objetivo do presente estudo foi investigar o impacto sinérgico do -tocoferol e do ácido -linolênico (100 µM) na MIV e CIV de oócitos de búfala Nili Ravi. Os oócitos foram obtidos dos ovários de búfalos abatidos duas horas após o abate e levados ao laboratório. Complexos de oócitos cumulus de búfalo foram colocados aleatoriamente nos cinco grupos experimentais incluídos; GRUPO 1: Meio de maturação (MM) + 100 µM ALA (controle), GRUPO 2: MM + 100 µM ALA + 50 µM -tocoferol, GRUPO 3: MM + 100 µM ALA + 100 µM -tocoferol, GRUPO 4: MM + 100 µM ALA + 200 M -tocoferol e GRUPO 5: MM + 100 µM ALA + 300 M -tocoferol sob uma atmosfera de 5% de CO2 em ar a 38,5 °C por 22-24 h. A expansão cumulus e o estado de maturação nuclear foram determinados (Experimento 1). No experimento 2, os oócitos foram maturados como no experimento 1. Os oócitos maturados foram então fertilizados em meio de Tyrode's Albumina Lactato Piruvato (TALP) por cerca de 20 h e cultivados em meio de fluido oviductal sintético (SOF) para determinar o efeito do ácido -linolênico (100 µM) e -tocoferol em meio IVM em IVC de presumíveis zigotos. Para estudar o efeito do ácido -linolênico (100 µM) em meio IVM e aumentar a concentração de -tocoferol no meio de cultura no desenvolvimento inicial do embrião (Experimento 3), os presumíveis zigotos foram distribuídos aleatoriamente nos cinco grupos experimentais com concentração crescente de -tocoferol em meios de cultura. Maior porcentagem de oócitos em estágio MII no experimento 1 (65,2 ± 2,0), embriões em estágio de mórula no experimento 2 (30,4 ± 1,5) e experimento 3 (22,2 ± 2,0) foram obtidos. No entanto, os resultados gerais para a expansão das células do cumulus, maturação do oócito para o estágio MII e desenvolvimento embrionário subsequente entre os tratamentos permanecem estatisticamente semelhantes (P> 0,05). A suplementação de -tocoferol em meios de maturação com ácido -linolênico e / ou em meios de cultura de embriões não aumentou ainda mais a maturação in vitro de oócitos ou a produção de embriões.

Análisis de Datos Antropométricos y Madurativos para la Selección de Talentos en Voleibol / Analysis of Anthropometric and Maturational Data for Talents Selection in Volleyball

El proceso madurativo tiene una gran influencia sobre los factores antropométricos y las capacidades físicas del atleta, y por tanto, sobre el proceso de selección de talentos deportivos. El objetivo de este trabajo fue analizar el estado madurativo y las características antropométricas junto con la comparación de estos datos por sexo en una muestra de 39 jugadores jóvenes de voleibol dentro de un proceso de selección de talentos (19 damas de 14,88±1,05 años y 13 varones de 15,1 años). Se obtuvieron datos de edad cronológica, altura, peso, altura sentado, altura de la madre y padre, la edad pico de crecimiento, el "timing" o periodo de tiempo por encima o por debajo de la edad pico, altura al final del proceso madurativo, el porcentaje actual de altura máxima, los centímetros restantes y el estado madurativo (pre-púber, púber o pos-púber). Los jugadores mostraron una mayor altura en el momento de las mediciones (179,92±6,87 vs 171,05±4,80; p<0,001), así como una mayor altura final calculada (189,46±3,73 vs 178,52±5,17; p<0,001), en comparación a las jugadoras. El pico en la velocidad de crecimiento también fue superior en los jugadores (14,56±0,44 vs 12,60±0,57; p<0,001), aunque su timing era inferior al de las jugadoras (0,531±1,19 vs 2,27±0,64; p<0,001). Esto se debió a un mayor porcentaje de jugadores masculinos en estados puberales, incluyendo un jugador en estadio pre-puberal, mientras que fue abundante la presencia de jugadoras en estado pospuberal. Estos datos reflejan la gran cantidad de jugadores que tienden a estar en periodos avanzados de maduración en procesos de selección de talentos. Por tanto, entrenadores y seleccionadores deben contemplar estas variables para evitar sesgos en el proceso de identificación del talento deportivo.

SUMMARY: The maturation process has a great influence on the anthropometric factors and physical capabilities of the athlete, and therefore, on the selection process of sporting talents. The objective of this work was to analyze the maturational state and anthropometric characteristics together with the comparison of these data by sex in a sample of 39 young volleyball players within a talent selection process (19 ladies of 14.88±1. 05 years old and 13 males aged 15.1 years). Data were obtained on chronological age, height, weight, sitting height, height of the mother and father, peak age of growth, timing or period of time above or below the peak age, height at the end of the process. maturation, the current percentage of maximum height, the remaining centimeters and the maturation status (pre-pubertal, pubertal or post-pubertal). The players showed a greater height at the time of the measurements (179.92±6.87 vs. 171.05±4.80; p<0.001), as well as a greater final calculated height (189.46±3.73 vs. 178.52±5.17; p<0.001), compared to the female players. The peak in growth speed was also higher in male players (14.56±0.44 vs 12.60±0.57; p<0.001), although their timing was lower than that of female players (0.531±1.19 vs 2.27±0.64; p<0.001). This was due to a higher percentage of male players in pubertal states, including one player in a pre-pubertal stage, while the presence of female players in a post-pubertal stage was abundant. These data reflect the large number of players who tend to be in advanced periods of maturation in talent selection processes. Therefore, coaches and selectors must consider these variables to avoid biases in the process of identifying sporting talent.

Validity of the Maturation Stage Method in the Individual Assessment of Midpalatal Suture Ossification Before Maxillary Expansion: A Systematic Review / Validez del Método de la Etapa de Maduración en la Evaluación Individual de la Osificación de la Sutura Palatina Mediana Previo a la Expansión Maxilar: Una Revisión Sistemática

In 2013, midpalatal suture maturation stage assessment was proposed for the evaluation of patients before performing maxillary expansion. In this study, we aimed to analyze the association between the midpalatal suture maturation stages assessed by CBCT, according to the method described by Angelieri et al., and other objective methods used to assess skeletal maturation or bone fusion. A computerized database search was conducted using PubMed, Cochrane Library, SciELO, LILACS, Web of Science, and Scopus, without language restriction. Unpublished literature was searched on ClinicalTrials.gov, the National Research Register, and Pro-Quest Dissertation Abstracts and Thesis database. Authors were contacted when necessary, and reference lists of the included studies were screened. Search terms included midpalatal suture, maturation, correlation, diagnostic performance, classification, evaluation, assessment, and relationship. Quality assessment was performed using the Observational Cohort and Cross-Sectional Studies tool developed by the National Heart, Lung, and Blood Institute. Eleven studies met the inclusion criteria. Of all the studies included, 81.9% had fair qualit y and 18.1% good quality, respectively. Eight out of eleven studies assessed the correlation between the midpalatal suture maturation method and the skeletal maturity evaluated by CVM method (Spearman's correlation coefficient: 0.244-0.908). Two out of eleven studies evaluated the correlation between midpalatal suture maturation method and the skeletal maturity assessed by HWM method (Spearman's correlation coefficient: 0.904-0.905) Even though midpalatal suture maturation stage assessment needs an exhaustive training and calibration process, it is a valid method to evaluate skeletal maturation or bone fusion. From a clinical perspective, for patients at CS4, CS5 and CS6, an assessment of the midpalatal suture on CBCT is indicated. A similar assessment should be done in patients at SMI 7-9.

En 2013, se propuso un nuevo método para la evaluación del estadio de maduración de la sutura palatina mediana para la evaluación de los pacientes antes de realizar la expansión maxilar. En este estudio, nuestro objetivo fue analizar la asociación entre las etapas de maduración de la sutura palatina mediana evaluada en CBCT, según el método descrito por Angelieri et al., y otros métodos objetivos utilizados para evaluar la maduración esquelética o la fusión ósea. Se realizó una búsqueda en las bases de datos PubMed, Cochrane Library, SciELO, LILACS, Web of Science y Scopus, sin restricción de idioma. Se buscó literatura no publicada en ClinicalTrials.gov, el Registro Nacional de Investigación y la base de datos Pro-Quest Dissertation Abstracts and Thesis. Se estableció contacto con los autores cuando fue necesario y se revisaron las listas de referencias de los estudios incluidos. Los términos de búsqueda incluyeron sutura palatina mediana, maduración, correlación, rendimiento diagnóstico, clasificación, evaluación, valoración y relación. La evaluación de la calidad se realizó mediante la herramienta de Estudios transversales y de cohortes observacionales desarrollada por el Instituto Nacional del Corazón, los Pulmones y la Sangre. Once estudios cumplieron con los criterios de inclusión. Del total de estudios incluidos, el 81.9% tuvo calidad regular y el 18.1% calidad buena, respectivamente. Ocho de once estudios evaluaron la correlación entre el método de maduración de la sutura palatina mediana y la madurez esquelética evaluada por el método CVM (coeficiente de correlación de Spearman: 0.244-0.908). Dos de once estudios evaluaron la correlación entre el método de maduración de la sutura palatina mediana y la madurez esquelética evaluada por el método HWM (coeficiente de correlación de Spearman: 0.904-0.905). Aunque la evaluación del estado de maduración de la sutura palatina mediana necesita un proceso exhaustivo de entrenamiento y calibración, es un método válido para evaluar la maduración esquelética o la fusión ósea. Desde una perspectiva clínica, para pacientes en CS4, CS5 y CS6, está indicada una evaluación de la sutura palatina mediana en CBCT. Se debe realizar una evaluación similar en pacientes con SMI 7-9.

Body morphology and bone age in girls with obesity and without obesity aged 8 to 15 years: a cross-sectional study / Morfologia corporal e idade óssea em meninas com obesidade e sem obesidade de 8 a 15 anos: um estudo transversal

Introduction: childhood obesity is one of the main public health problems worldwide, leading to health status repercussions and growth and maturation process implications in both children and adolescents. Objective: the aim of this study was to verify body morphology and bone age variations in girls with obesity and without obesity. Methodology: this comprises a cross-sectional study conducted with 140 girls aged 8 to 15 years old, 70 with obesity and 70 without obesity. Hip and waist circumferences, body mass, height and and Body Mass Index (BMI) were determined. For maturation status determinations, bone ages were determined by a left wrist and hand radiography employing the Fels method. Results: the findigs indicate significant correlations between nutritional and maturation statuses (r=0.80; p˂0.01). Girls with obesity presented higher weight and BMI values, larger waist and hip circumferences and more advanced bone age compared to girls without obesity (p˂0.01). The same significant differences (p˂0.01) were noted in the contrasting maturational group analysis, where girls presenting advanced maturation always exhibited the highest parameter values. Conclusion: nutritional status is associated to maturation status, and girls with obesity exhibit more advanced bone age than girls without obesity.

Introdução: a obesidade infantil é um dos principais problemas de saúde pública mundial, com repercussões no estado de saúde e implicações no processo de crescimento e maturação de crianças e adolescentes. Objetivo: verificar a variação da morfologia corporal e da idade óssea em meninas com e sem obesidade. Metodologia: estudo transversal conduzido com 140 meninas de 8 a 15 anos de idade, sendo 70 meninas com obesidade e 70 sem obesidade. Foram mensuradas as circunferências do quadril e da cintura, massa corporal, altura e o Índice de Massa Corporal (IMC). Para o status maturacional foi determinada a idade óssea por meio de radiografia de punho e mão esquerdos pelo Método Fels. Resultados: os resultados apontaram a existência de correlação entre o status nutricional e o status maturacional (r=0,80; p˂0,01). As meninas com obesidade apresentaram maior peso, IMC mais elevado, circunferências maiores e idade óssea mais avançada quando comparadas às meninas sem obesidade (p˂0,01). Na análise dos grupos maturacionais contrastantes as mesmas diferenças se apresentaram com valores significativos (p˂0,01), sendo as meninas avançadas maturacionalmente sempre com valores superiores. Conclusão: o status nutricional apresentou correlação com o status maturacional, e as meninas com obesidade apresentam idade óssea mais avançada que aquelas sem obesidade

Effects of Abacus Training on Auditory Spatial Maturation in Children with Normal Hearing

Abstract Introduction The spatial auditory system, though developed at birth, attains functional maturity in the late childhood (12 years). Spatial changes during childhood affect navigation in the environment and source segregation. Accommodation of a new skill through learning, especially during childhood, can expedite this process. Objective To explore the auditory spatial benefits of abacus training on psychoacoustic metrics in children. The study also aimed to identify the most sensitive metric to abacus training related changes in spatial processing, and utilize this metric for a detailed spatial error profiling. Methods A standard group comparison analysis with 90 participants divided into three groups: I: children with abacus training (C-AT); II: children with no training (C-UT); III: adults with no training (A-UT). The groups underwent a series of psychoacoustic tests, such as interaural time difference (ITD), interaural level difference (ILD), and virtual auditory space identification (VASI), as well as perceptual tests such as the Kannada version of the speech, spatial, and quality questionnaire (K-SSQ). Results Significant group differences were observed in the multivariate analysis of variance (MANOVA) and post-hoc tests, with the C-AT group showing significantly lower ILD scores (p = 0.01) and significantly higher VASI scores (p < 0.001) compared to the CUT group, which is indicative of better spatial processing abilities in the former group. The discriminant function (DF) analyses showed that the VASI was the most sensitive metric for training-related changes, based on which elaborate error analyses were performed. Conclusions Despite the physiological limits of the immature neural framework, the performance of the C-AT group was equivalent to that of untrained adults on psychoacoustic tests, which is reflective of the positive role of abacus training in expediting auditory spatial maturation.

A rationally designed cancer vaccine based on NIR-II fluorescence image-guided light-triggered remote control of antigen cross-presentation and autophagy

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.

Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Assessment of dehydroepiandrosterone sulphate (DHEAS) and cortisol levels in saliva and their correlation to cervical vertebrae maturation method in males and females at different growth stages: a clinical study

ABSTRACT Objective: The aim of this in-vivo study was to assess the salivary dehydroepiandrosterone sulphate (DHEAS) and cortisol levels, and their correlation to the Cervical Vertebrae Maturation method (CVM) in males and females at pre-pubertal, pubertal and post-pubertal growth stages. Methods: 48 patients (24 males, 24 females) who were to undergo routine orthodontic treatment were screened according to the inclusion and exclusion criteria. Then subjects were grouped according to CVM stages, using lateral cephalogram, in pre-pubertal, pubertal and post-pubertal groups. Unstimulated saliva from the selected subjects was collected. DHEAS and cortisol levels in the salivary samples were estimated by Enzyme-Linked Immunosorbent assay (ELISA). Then they were compared to Cervical Vertebrae Maturation Method stages. One-way ANOVA test followed by Tukey's post-hoc test was used to compare the salivary DHEAS and cortisol levels between different CVM stages in males and females. Independent Student t-test was used to compare the mean salivary DHEAS and cortisol levels between different males and females in each CVM stage. Result: There was a progressive increase in salivary DHEAS and cortisol concentration as skeletal maturation progressed from CVM stages 1 and 2, CVM stages 3 and 4, reaching the highest value at CVM stages 5 and 6. Their levels were higher in males than females. Conclusion: The salivary DHEAS and cortisol levels can be useful as a potential indicator of skeletal maturation, to aid in the assessment of pubertal status.

RESUMO Objetivo: O objetivo deste estudo in vivo foi avaliar os níveis salivares de sulfato de dehidroepiandrosterona (DHEAS) e de cortisol, e sua correlação com o método de maturação das vértebras cervicais (CVM) em homens e mulheres nas fases de crescimento pré-puberal, puberal e pós-puberal. Métodos: 48 pacientes (24 homens, 24 mulheres) que se submeteriam a tratamento ortodôntico de rotina foram selecionados de acordo com os critérios de inclusão e exclusão. Em seguida, usando telerradiografia lateral, os indivíduos foram agrupados de acordo com os estágios CVM, em grupos pré-puberal, puberal e pós-puberal. Foi feita coleta de saliva não estimulada nos indivíduos selecionados. Os níveis de DHEAS e cortisol nas amostras salivares foram avaliados pelo teste ELISA (Enzyme-Linked Immunosorbent assay). Em seguida, foram comparados aos estágios do método CVM. O teste ANOVA de uma via seguido pelo teste post-hoc de Tukey foi usado para comparar o DHEAS salivar e os níveis de cortisol entre os diferentes estágios de CVM em homens e mulheres. O teste t de Student independente foi usado para comparar a média de DHEAS salivar e os níveis de cortisol entre diferentes homens e mulheres em cada estágio de CVM. Resultados: Houve um aumento progressivo no DHEAS salivar e na concentração de cortisol à medida que a maturação esquelética progrediu dos estágios CVM 1 e 2, para os estágios CVM 3 e 4, atingindo o valor mais alto nos estágios CVM 5 e 6. Seus níveis foram maiores nos homens do que nas mulheres. Conclusões: Os níveis salivares de DHEAS e cortisol podem ser úteis como um potencial indicador de maturação esquelética, para auxiliar na avaliação do estado puberal.

A bolt from the blue in a testicular mass - continuous Splenogonadal fusion with maturation arrest

ABSTRACT Splenogonadal fusion is an infrequent cause of testicular or scrotal swelling with less than 250 cases reported. We report the case of a 27-year-old male who presented with painless scrotal swelling. The sonography showed a homogeneous, well-encapsulated left extratesticular mass, which was surgically removed. The gross examination revealed a grey-brown tissue below the left testis. The microscopy of the grey-brown mass revealed splenic tissue, and the testis showed maturation arrest, resulting in the diagnosis of splenogonadal fusion. These can be easily mistaken for a tumor, especially in this age group. Reporting such an entity increases awareness among clinicians, radiologists and pathologists, which will aid in preventing an orchiectomy for these patients.

Estimation of the predictive effect of body mass index-percentile on skeletal maturation in a Nigerian population

To determine the predicting the effect of BMI-index percentile on the skeletal maturation of Nigerian children. Design: A prospective cross-sectional study. Setting: This study was conducted in a tertiary health care facility in North-Central Nigeria. Participants: Children between the ages of 5-17 years consisting of 44 males and 30 females that presented in the Child Dental clinic over a period of eight months were recruited for the study. Main outcome measured: Skeletal maturation was assessed using the middle phalanx of the third finger (MP3) while the standard WHO growth chart specific for age (2-20 years) and gender was used for grading BMI-percentile. The unpaired t-test was used to compare mean chronological age of the stages of MP3 according to gender. Multinomial logistic regression used to determine the predictive effect of age, gender and BMI percentile on pubertal growth spurt. Results: The BMI-percentile had weak correlation with the pubertal growth spurt (r=0.089, p=0.448). Gender (p=0.004) and chronological age had significant (p<0.001) predictive effect on the skeletal maturation. A one-percentile increase in the BMI-percentile decreases the likelihood of healthy children to be in the peak-pubertal by 1.504 when compared to obese children (p=0.305). Conclusions: This study showed that BMI-percentile is a weak predictor of skeletal maturation. However, obese children had a tendency towards advanced skeletal maturation than healthy participants. It is therefore suggested that orthodontists should consider early implementation of jaw modification treatments among obese children.

Predictive factors of autogenous arteriovenous fistula maturation and preliminary study on assisted maturation intervention timing / 中华肾脏病杂志

Objective:To analyze the predictive factors of autogenous arteriovenous fistula (AVF) maturation and tentatively discuss the intervention timing of assisted maturation.Methods:It was a retrospective study. The data of patients with newly established AVF and regular follow-up in Haidian Hospital, the Third Hospital of Peking University from August 1, 2018 to March 31, 2022 were analyzed. The patients were divided into mature group and immature group based on whether they met clinical maturity or ultrasonic maturity criteria 3 months after AVF establishment.The general data, preoperative laboratory examination and postoperative ultrasonic examination parameters were compared between the two groups. Logistic regression analysis model was used to analyze the related factors of AVF maturation, and receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of each factor for AVF maturation and intervention timing.Results:A total of 568 patients were included, with age of (56.86±13.82) years old, 339 males (59.68%), and 229 females (40.32%). There were 380 patients in the maturation group and 188 patients in the immature group. The total rate of AVF maturation was 66.90% (380/568). The anastomosis diameter ( t=9.732, P < 0.001), ln(anastomosis artery diameter)( t=10.116, P < 0.001), anastomosis vein diameter ( t=13.961, P < 0.001), ln(brachial artery diameter)( t=9.362, P < 0.001) and brachial artery blood flow ( t=16.542, P < 0.001) of postoperation one month, and anastomosis diameter ( t=7.356, P < 0.001), anastomosis artery diameter ( t=11.117, P < 0.001), anastomosis vein diameter ( t=12.332, P < 0.001), ln(brachial artery diameter) ( t=7.956, P < 0.001) and brachial artery blood flow ( t=13.803, P < 0.001) of postoperation three months in the mature group were significantly higher than those in the immature group. Logistic regression analysis models showed anastomosis vein diameter at 1 month after surgery ( OR=0.577, 95% CI 0.342-0.975, P=0.040), brachial arterial blood flow at 1 month after surgery ( OR=0.988, 95% CI 0.996-1.000, P=0.043) and brachial arterial blood flow at 3 months after surgery ( OR=0.997, 95% CI 0.995-0.999, P=0.002) were the independent relevant factors of AVF maturation. When the anastomosis vein diameter ≥ 3.90 mm at 1 month after AVF surgery ( AUC=0.842, 95% CI 0.809-0.871, P < 0.001), the blood flow of brachial artery ≥ 446.90 ml/min at 1 month after AVF surgery ( AUC=0.880, 95% CI 0.850-0.906, P < 0.001), the critical value of the combined index of anastomotic vein diameter and blood flow of brachial artery at 1 month after fitting ≥ 0.44 ( AUC=0.889, 95% CI 0.860-0.914, P < 0.001) and brachial arterial blood flow ≥ 595.00 ml/min ( AUC=0.857, 95% CI 0.822-0.888, P < 0.001), the unassisted maturation of AVF could be predicted. Conclusions:The anastomosis vein diameter ≥ 3.90 mm at 1 month after AVF surgery, and the blood flow of brachial artery ≥ 446.90 ml/min at 3 months after AVF surgery, or the critical value of combined index of both after fitting ≥ 0.44 can predict the unassisted maturation of AVF, and one month after surgery may be the opportunity for early intervention to promote maturation.

A Critical Review on Physiological Changes during Growth Maturation and Ripening of Citrus Fruits

Citrus is one of the major fruit crops in the world and widely recognized by their nutritional, organoleptic and health-related benefits of fresh fruit. The genetic diversity among the genus and independent changes in peel and pulp, make the definition of standard maturity indexes of fruit quality. Commercial maturity indexes in the citrus industry are usually based on peel coloration, soluble solids, pH but their relevance may differ among varieties and the specific requirements of the markets. Citrus fruits are excellent source of many phytochemical, including ascorbic acid, antioxidant, tannin, etc., which greatly contribute to the health-related benefits of citrus fruits. Criteria and definition of the main maturity indexes for citrus fruit worldwide are described, as well as changes during fruit maturation in key components affecting organoleptic and nutritional properties. Citrus fruits were analyzed at different maturity stages. This review is aimed to characterize the physiological maturity of the fruit across the different developmental stage which has not been well reported in literature till now.

Relação entre maturação sexual e indicadores antropométricos e pressóricos em adolescentes / Relationship between sexual maturation and anthropometric and blood pressure indicators in teenagers

Resumo Objetivou-se investigar a relação entre a maturação sexual com indicadores antropométricos e pressóricos de adolescentes. Estudo transversal de base populacional, realizado entre 2018 e 2020, com 345 adolescentes de 10 a 19 anos. Coletou-se variáveis sociodemográficas e antropométricas, pressão arterial e maturação sexual. A análise dos dados foi feita por meio da Análise de Componentes Principais, que gerou três componentes e, posteriormente, testou-se a correlação entre a maturação sexual e os componentes gerados. A maioria dos adolescentes eram do sexo feminino (53%), normotensos (66,1%) e com peso normal (73%). Houve correlação positiva entre o desenvolvimento das mamas com o componente 1 e o componente 2, e correlação negativa entre mamas e o componente 3. Nos meninos, o desenvolvimento dos genitais e pelos pubianos estiveram positivamente correlacionados com o componente 2 e inversamente correlacionados com o componente 3. Conclui-se que existe relação entre a maturação sexual e os indicadores antropométricos e pressóricos, sendo variáveis representativas de risco cardiovascular em adolescentes, mesmo que não em sua totalidade.

Abstract This study aimed to investigate the relationship between sexual maturation and anthropometric and blood pressure indicators in teenagers. This was a population-based cross-sectional study, conducted with 345 teenagers, aged 10 to 19 years, between 2018 and 2020. In this study, data referent to sociodemographic and anthropometric variables, blood pressure, and sexual maturation were collected. The data analysis was performed by applying the Principle Component Analysis (PCA), which generated three components and then tested the correlation between sexual maturation and the generated components. Most of the teenagers were female (53%), normotensive (66.1%), and with a normal weight (73%). A positive correlation was found between breast development and component 1 and component 2, as well as a negative correlation between the breasts and component 3. In the boys, the development of genitals and pubic hair was positively correlated with component 2 and inversely correlated with component 3. It could therefore be concluded that there is a relationship between sexual maturation and the anthropometric and blood pressure indicators, which proved to be representative variables for cardiovascular risk in teenagers, even if not in their entirety.

Maduración pulmonar fetal en diabetes mellitus pregestacional y complicaciones crónicas / Fetal lung maturation in pregestational diabetes mellitus and chronic complications

Las pacientes embarazadas con diabetes mellitus (DM) pregestacional y complicaciones micro y macroangiopáticas tienen mayor riesgo de empeoramiento de las mismas y de presentar otros trastornos asociados al embarazo. La progresión de la retinopatía diabética ocurre durante el embarazo y el posparto. La nefropatía se asocia con un mayor riesgo de preeclampsia, parto prematuro, restricción del crecimiento fetal y mortalidad perinatal. Cuando hay enfermedad de arterias coronarias o gastroparesia se observa un aumento de la morbilidad materna y fetal. El parto prematuro es una condición prevalente en pacientes con DM. La maduración pulmonar fetal con corticosteroides fue extensamente estudiada, con numerosas pruebas controladas, hasta convertirse en una de las más importantes terapias prenatales basadas en evidencias para reducir la mortalidad perinatal y el síndrome de dificultad respiratoria, la hemorragia intraventricular y la enterocolitis necrosante en los niños prematuros. Sin embargo, en dicha evidencia no se han incluido a embarazadas con DM, por lo cual no se conocen resultados perinatales en este grupo de pacientes.

Pregnant patients with pregestational diabetes mellitus (DM) and micro and macroangiopathic complications have a higher risk of their worsening and of presenting other pregnancyassociated disorders. The progression of diabetic retinopathy occurs during pregnancy and postpartum. Nephropathy is associated with an increased risk of preeclampsia, preterm delivery, fetal growth restriction, and perinatal mortality. When there is coronary artery disease or gastroparesis, an increase in maternal and fetal morbidity is observed Preterm delivery is a prevalent condition in diabetic patients. Corticosteroid fetal lung maturation has been extensively studied, with numerous controlled trials, to become one of the most important evidence-based prenatal therapies to reduce perinatal mortality and decrease respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis, in premature infants. Nevertheless, this evidence did not include patients with DM, for this reason perinatal results are not known in this group of patients.

Rendimiento de atletas de levantamiento de potencia (Powerlifting) durante su vida / The Performance of Powerlifting Athletes During Their Lifetime

Resumen Esta investigación realizó una minería de datos de hombres y mujeres atletas de levantamiento de potencia (comúnmente conocido como powerlifting), para las clases: Levantamiento de potencia equipado, Levantamiento de potencia clásico, Press de banca equipado y Press de banca clásico, reconocidas por la Federación Internacional de Powerlifting (IPF). Se realizó un análisis de regresión no lineal basado en la edad versus la media de los puntajes: Wilks Points, IPF Points o IPF GoodLift Points. Se obtuvo la curva mejor ajustada y la edad con el máximo rendimiento para cada clase. En general, el rendimiento para todas las clases de hombres y mujeres en Levantamiento de potencia y Press de banca comienza con un crecimiento exponencial desde la juventud hasta cerca de la tercera década, y muestra un rendimiento máximo entre 27,67 a 31,50 años, y luego una disminución lineal durante la edad madura y edad avanzada. La comparación entre hombres y mujeres, o grupos de atletas equipados y clásicos no muestra diferencias significativas para la edad del rendimiento máximo, lo que sugiere el mismo reloj de envejecimiento biológico. El deporte de levantamiento de potencia es un modelo útil para estudiar el crecimiento, la maduración y el envejecimiento del ser humano.

Abstract This research performed data mining for men and women powerlifters for the categories of Equipped Powerlifting, Classic Powerlifting, Equipped Bench Press, and Classic Bench Press, recognized by the International Powerlifting Federation (IPF). It then conducted a nonlinear regression analysis based on age versus mean scores in terms of Wilks Points, IPF Points, and IPF GoodLift Points to obtain the fitted curve and the age of peak performance for each category. Overall, the performance for all categories of men and women in powerlifting and bench press starts with exponential growth from youth until close to the third decade, showing a peak performance between 27.67 to 31.50 years of age, and then a linear decrease during maturation and older age. Comparisons between men and women and between equipped and classic athletes do not show meaningful differences in age of peak performance, suggesting the same biological clock in terms of aging. The sport of powerlifting offers a useful model to study human beings' growth, maturation, and aging.

Resumo Esta pesquisa realizou uma garimpagem de dados de atletas masculinos e femininos do levantamento de peso (comumente conhecido como powerlifting), para as classes: levantamento de peso equipado, levantamento de peso clássico, Press de banco equipado e Press de banco clássico, reconhecidos pela Federação Internacional de Powerlifting (IPF). Uma análise de regressão não linear foi realizada com base na idade versus pontuação média: Wilks Points, IPF Points ou IPF GoodLift Points. Foi obtida a melhor curva ajustada e idade com o melhor desempenho para cada classe. Em geral, o desempenho para todas as classes de homens e mulheres em levantamento de potência e Press de banco começa com um crescimento exponencial da juventude até próximo a terceira década, mostrando um desempenho máximo entre 27,67 a 31,50 anos, e depois uma diminuição linear durante a idade madura e a idade avançada. A comparação entre homens e mulheres, ou atletas equipados e clássicos, não mostra diferenças significativas para a idade do melhor desempenho, sugerindo o mesmo relógio do envelhecimento biológico. O esporte de levantamento de peso é um modelo útil para estudar o crescimento, a maturação e o envelhecimento humano.

O estágio da concernência e a elaboração do complexo de Édipo: revisitando Winnicott e o caso Piggle / The stage of concern and the elaboration of the Oedipus complex: revisiting Winnicott and the Piggle case / La etapa de preocupación y la elaboración del complejo de Edipo: revisando Winnicott y el caso Piggle

O nosso texto toma como ideia central o referencial winnicottiano, salientando a importância de um bom atravessamento do estágio da concernência (stage of concern) ­ etapa que, a nosso ver, é indispensável para constituir os pilares de um psiquismo relativamente saudável, capaz de enfrentar as mazelas oriundas do conflito edipiano. Para tanto, iniciaremos o trabalho com uma breve descrição do estágio da concernência, seguida das questões relativas à ambivalência característica do Édipo propriamente dito. Por fim, tecemos algumas considerações que objetivam relacionar uma análise do caso Piggle (The Piggle), uma menina de dois anos e meio, cujo tratamento, realizado por D. W. Winnicott, ocorreu em dezesseis encontros, constituindo uma espécie de análise, de acordo com a demanda, tratando, sobretudo, questões ligadas à intensidade de sentimentos ambivalentes não elaborados pela paciente, que anteciparam o seu ingresso no complexo de Édipo antes que ela passasse, fundamentalmente, pelo estágio da concernência.

Our text makes as its central idea the Winnicott's approach, emphasizing the importance of a good crossing of the stage of concern - a stage that, in our view, is essential to constitute the pillars of a relatively healthy psyche, capable of coping with ailments arising from the oedipal conflict. Therefore, we will begin our work with a brief description of the stage of concern, followed by questions relating to the characteristic ambivalence of Oedipus himself. Finally, we make some considerations that aim to connect with an analysis of the Piggle case (The Piggle), a two and a half year old girl, whose treatment, carried out by D.W. Winnicott, occurred during sixteen meetings, constituting a kind of analysis according to demand, dealing with, above all, issues related to the intensity of ambivalent feelings not elaborated by the patient, which anticipated her entry into the Oedipus complex before she went, fundamentally, through the stage of concern.

Nuestro texto toma como idea central el marco winnicottiano, enfatizando la importancia de un buen cruce de la etapa de la preocupación, etapa que, a nuestro juicio, es fundamental para constituir los pilares de una psique rela-tivamente sana, capaz de hacer frente a las dolencias que surgen. del conflicto edípico. Por lo tanto, comenzaremos el trabajo con una breve descripción de la etapa de preocupación, seguida de preguntas relacionadas con la ambiva-lencia característica del propio Edipo. Finalmente, hacemos algunas consi-deraciones que pretenden relacionar un análisis del caso Piggle (The Piggle), una niña de dos años y medio, cuyo tratamiento, realizado por DW Winnicott, ocurrió en dieciséis encuentros, constituyendo una especie de análisis según demanda, abordando, sobre todo, cuestiones relacionadas con la intensidad de sentimientos ambivalentes no elaborados por la paciente, que anticipaban su entrada en el complejo de Edipo antes de pasar, fundamentalmente, por la etapa de la preocupación.

Organoides: fundamentos, presente y futuro / Organoids: fundamentals, present and future

RESUMEN Los organoides son estructuras miniaturizadas, generadas principalmente a partir de células madre pluripotentes inducidas, que se cultivan en el laboratorio conservando sus características innatas o adquiridas. Tienen el potencial de reproducir procesos de desarrollo biológico, modelar procesos patológicos que permitirán el descubrimiento de nuevos fármacos y propicien la medicina regenerativa. Sin embargo, estas experiencias requieren perfeccionamiento constante porque pueden haberse realizado variaciones en la constitución de estos órganos. Por ello, el presente artículo tiene como objetivo revisar la información actualizada sobre organoides y sus procesos experimentales básicos y recientes, empezando por la gastrulación, para tratar de imitar, en lo posible, la formación de las tres capas: ectodermo, mesodermo y endodermo, incluyendo los factores que intervienen en la inducción, diferenciación y maduración en la generación de estos organoides. Asimismo, el diseño y preparación de medios de cultivo altamente especializados que permitan obtener el órgano seleccionado con la mayor precisión y seguridad. Se realizó una búsqueda de artículos originales y de revisión publicados en PubMed, Nature y Science. Los artículos se seleccionaron por sus resúmenes y por su texto completo. Las conclusiones de este articulo destacan las ventajas futuras en el uso y aplicaciones de los organoides.

ABSTRACT Organoids are tiny structures, mainly generated from induced pluripotent stem cells, which are cultured in the laboratory while retaining their innate or acquired characteristics. They have the potential to reproduce biological development processes, model pathological processes that will enable the discovery of new drugs and promote regenerative medicine. However, these processes require constant improvement because variations may have occurred in the constitution of the organs. Therefore, this article aims to review updated information on organoids and their basic and recent experimental processes, starting with gastrulation, in an attempt to mimic, as much as possible, the formation of the three layers: ectoderm, mesoderm and endoderm; as well as the information regarding the factors involved in the induction, differentiation and maturation during the generation of organoids. Likewise, the design and preparation of highly specialized culture media that allow obtaining the selected organ with the highest precision and safety. We searched for original and review articles published in PubMed, Nature and Science. Articles were selected for their abstracts and full text. The conclusions of this article highlight the future advantages in the use and applications of organoids.

Ethical aspects of age estimation for forensic purposes in Saudi Arabia / Aspectos éticos de la estimación de la edad para propósitos forenses en Arabia Saudita / Aspectos éticos da estimativa de idade para propósitos forenses na Arábia Saudita

Abstract: In forensic and legal contexts, an assessment of skeletal maturation is required to predict the chronological age in certain circumstances in which the chronological age is undocumented or unable to be proven. Carrying such medical examinations will always pose an ethical concern, especially in cases of assessing sexual maturity as well as examinations involving ionizing radiation. The cultural and religious barriers are also discussed concerning the ethical standards set in Saudi Arabia. Several ethical issues concerning age estimation examinations including issues related to consent forms, privacy, and radiation hazards have been documented. While ethical issues regarding radiation hazards are more likely to be overcome by introducing other imaging modalities without radiation hazards, ethics related to consent forms and privacy are still to be improved.

Resumen: En contextos forenses y legales, se requiere la evaluación de la maduración del esqueleto para predecir la edad cronológica en ciertas circunstancias en que la edad cronológica no está documentada o no es posible de probar. Realizar tales exámenes médicos siempre significa una preocupación ética, especialmente en casos de evaluación de madurez sexual así como en exámenes que involucran radiaciones ionizantes. Se discuten también las barreras culturales y religiosas relacionadas con el contexto de estándares éticos en Arabia Saudita. Entre los varios temas éticos relacionados con la estimación de la edad, se documentan temas relacionados con los formularios de consentimiento, privacidad y riesgos de radiación. Mientras que los temas éticos relacionados con riesgos de radiación pueden ser resueltos al introducir otras modalidades de examen sin radiación, los problemas éticos relacionados con los formularios de consentimiento y privacidad todavía necesitan mejorarse.

Resumo: Em contextos forenses e legais, uma avaliação de maturação esquelética é requerida para predizer a idade cronológica em certas circunstâncias nas quais a idade cronológica não é documentada ou impossível de ser provada. Conduzir tais exames médicos sempre irá suscitar uma preocupação ética, especialmente em casos para avaliar maturidade sexual bem como exames envolvendo radiação ionizante. As barreiras culturais e religiosas também são discutidas no que diz respeito a padrões éticos estabelecidos na Arábia Saudita. Diversos aspectos éticos concernentes a exames de estimativa de idade incluindo aspectos relacionados a formulários de consentimento, privacidade e risco de radiação foram documentados. Ao passo que aspectos éticos que dizem respeito a risco de radiação serem mais provavelmente superáveis pela introdução de outras modalidades de exames de imagem sem risco de radiação, a ética relacionada a formulários de consentimento e privacidade ainda estão por serem melhorados.

Maduración pulmonar fetal en diabetes mellitus pregestacional y complicaciones crónicas / Fetal lung maturation in pregestational diabetes mellitus and chronic complications

Resumen Las pacientes embarazadas con diabetes mellitus (DM) pregestacional y complicaciones micro y macroangiopáticas tienen mayor riesgo de empeoramiento de las mismas y de presentar otros trastornos asociados al embarazo. La progresión de la retinopatía diabética ocurre durante el embarazo y el posparto. La nefropatía se asocia con un mayor riesgo de preeclampsia, parto prematuro, restricción del crecimiento fetal y mortalidad perinatal. Cuando hay enfermedad de arterias coronarias o gastroparesia se observa un aumento de la morbilidad materna y fetal. El parto prematuro es una condición prevalente en pacientes con DM. La maduración pulmonar fetal con corticosteroides fue extensamente estudiada, con numerosas pruebas controladas, hasta convertirse en una de las más importantes terapias prenatales basadas en evidencias para reducir la mortalidad perinatal y el síndrome de dificultad respiratoria, la hemorragia intraventricular y la enterocolitis necrosante en los niños prematuros. Sin embargo, en dicha evidencia no se han incluido a embarazadas con DM, por lo cual no se conocen resultados perinatales en este grupo de pacientes.

Abstract Pregnant patients with pregestational diabetes mellitus (DM) and micro and macroangiopathic complications have a higher risk of their worsening and of presenting other pregnancyassociated disorders. The progression of diabetic retinopathy occurs during pregnancy and postpartum. Nephropathy is associated with an increased risk of preeclampsia, preterm delivery, fetal growth restriction, and perinatal mortality. When there is coronary artery disease or gastroparesis, an increase in maternal and fetal morbidity is observed Preterm delivery is a prevalent condition in diabetic patients. Corticosteroid fetal lung maturation has been extensively studied, with numerous controlled trials, to become one of the most important evidence-based prenatal therapies to reduce perinatal mortality and decrease respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis, in premature infants. Nevertheless, this evidence did not include patients with DM, for this reason perinatal results are not known in this group of patients.