Resveratrol-Loaded Polydimethylsiloxane-Silica Hybrid Materials: Synthesis, Characterization, and Antitumoral Activity.

In this work, hybrid materials within the polydimethylsiloxane-silica (PDMS-SiO2) system, synthesized via the sol-gel method, were developed and characterized for their potential to incorporate and release the bioactive compound resveratrol (RES). RES was incorporated into the materials with a high loading efficiency (>75%) using the rotary evaporator technique. This incorporation induced the amorphization of RES, resulting in enhanced solubility and in vitro release when compared to the free polyphenolic compound. The release profiles displayed pH dependence, exhibiting notably faster release at pH 5.2 compared to pH 7.4. The gradual release of RES over time demonstrated an initial time lag of approximately 4 h, being well described by the Weibull model. In vitro cytotoxicity studies were conducted on human osteosarcoma cells (MG-63), revealing a concentration-dependent decrease in cell viability for RES-loaded samples (for concentrations >50 µg mL-1).

Constitutional and somatic methylation status of DMRH19 and KvDMR in Wilms tumor patients.

The most frequent epigenetic alterations in Wilms tumor (WT) occur at WT2, assigned to 11p15. WT2 consists of two domains: telomeric domain 1 (DMRH19) that contains the IGF2 gene and an imprinted maternally expressed transcript (H19) and centromeric domain 2 (KvDMR) that contains the genes KCNQ1, KCNQ1OT1 and CDKN1C. In this work, we used pyrosequencing and MS-MLPA to compare the methylation patterns of DMRH19/KvDMR in blood and tumor samples from 40 WT patients. Normal constitutional KvDMR methylation indicated that most of the epigenetic alterations in WT occur at DMRH19. Constitutional DMRH19 hypermethylation (HM DMRH19) was observed in two patients with Beckwith-Wiedemann syndrome. Pyrosequencing and MS-MLPA showed HM DMRH19 in 28/34 tumor samples: 16/34 with isolated HM DMRH19 and 12/34 with concomitant HM DMRH19 and KvDMR hypomethylation, indicating paternal uniparental disomy. With the exception of one blood sample, the MS-MLPA and pyrosequencing findings were concordant. Diffuse or focal anaplasia was present in five tumor samples and was associated with isolated somatic HM DMRH19 in four of them. Constitutional 11p15 methylation abnormalities were present in 5% of the samples and somatic abnormalities in the majority of tumors. Combined analysis of DMRH19/KvDMR by pyrosequencing and MS-MLPA is beneficial for characterizing epigenetic anomalies in WT, and MS-MLPA is useful and reliable for estimation of DNA methylation in a clinical setting.

Variants in the new E1' cryptic exon of the VHL gene associated with congenital erythrocytosis-Description of three cases.

Congenital erythrocytosis (CE) represents a rare and heterogeneous group of hereditary disorders. The molecular basis of VHL gene mutations related to CE. Recently, Lenglet et al. reported a discovery of a novel cryptic exon in the VHL gene. Mutations in the first intronic region resulting in the creation of a cryptic exon termed E1' were found in seven families with CE and one family with VHL disease. We report three patients with prolonged CE with the aetiology being clarified several years later by sequencing of intronic region 1 of the VHL gene. This work addresses the first cases reported at the clinical level of VHL-associated CE due to the E1' cryptic exon.

The Effect of Weaning and Slaughter Age on the Physicochemical and Sensory Characteristics of Arouquesa Beef-A PDO Portuguese Meat.

(1) Background: Autochthonous breeds meat is well accepted due to its sensory characteristics, perceived low environmental impact, and animal welfare. We aimed to evaluate the effect of weaning and slaughter age on the physicochemical and sensory characteristics of Arouquesa, a Portuguese Protected Designation of Origin (PDO) meat and to evaluate the psychological effect of knowing the weaning age on the consumer's hedonic evaluation. (2) Methods: Meat from 26 animals was assigned to 4 groups, with combinations of weaning (W) at 9 or 5 months and slaughter (S) at 9 or 12 months: W9-S9, W9-S12, W5-S9, and W5-S12. The meat was analysed for pH24h, colour (L*a*b*), cooking losses and shear force. A Check All that Apply test was made with 70 consumers; they were also asked to punctuate the hedonic appreciation of anonymous and weaning age-identified meat. (3) Results: W9-S9 were more tender, had lower shear force, and was juicier than W5-S9. When animals were slaughtered at 12 months, there were no differences in the physicochemical and sensory characteristics between the weaning ages. The effect of information about the weaning age influences the consumer's hedonic evaluation, as revealed by the comparison between the anonymous and identified samples. (4) Later weaning resulted in more tender meat when the slaughter was at 9 months and positively impacted consumer perception.

Growth Performance, Carcass and Meat Traits of Autochthonous Arouquesa Weaners Raised on Traditional and Improved Feeding Systems.

Arouquesa is an autochthonous bovine breed known for its Arouquesa PDO beef labeling. There are several production systems under the definition of PDO labeling. This study aimed to compare the effect of different production systems on carcass and meat traits for the Arouquesa breed. Two trials differing in diet and weaning age were conducted. The first trial included a TF group fed the traditional way and weaned at 9 months; a TF + S1 group, equal to TF, but with a starter supplement; and finally, a S1 + S2 group that was fed with a starter and a growth supplement and weaned at 5 months. The second trial was composed of a TF + S3 group fed like the TF + S1 group but reared until 12 months with a finishing supplement, and finally, the S3 group fed like the S1 + S2 group but reared until 12 months. In the first trial, the TF + S1 and S1 + S2 groups showed higher final live weight and average daily gain. In the second trial, we observed differences in the subcutaneous fat that was higher in the S3 group. Regarding meat traits, we observed differences in exudative and cooking losses in the first trial. In general, supplementation improved meat production without affecting meat quality parameters.

Age-related testosterone decline in a Brazilian cohort of healthy military men.

INTRODUCTION: Androgen decline in the aging man has become a topic of increasing clinical relevance worldwide, as the reduction in testosterone levels has been reported to be accompanied by loss of muscle mass, accumulation of central adiposity, impaired mobility and increase risk of bone fractures. Although well-established in studies conducted in developed countries, progressive decline in serum testosterone levels with age has been poorly investigated in Brazil. AIM: To determine the pattern of blood testosterone concentrations decline with age in a cohort of Brazilian healthy military men. MATERIALS AND METHODS: We retrospectively reviewed data on serum testosterone measurements of healthy individuals that had undergone a routine check-up at the Military Biology Institute. Blood samples were obtained early in the morning, and total testosterone concentration was determined using a commercial chemoluminescent immunoassay. Mean values were analyzed in five age groups: ≤ 40, 41 to 50, 51 to 60, 61 to 70, and > 70 years. MAIN OUTCOME MEASURE: Mean total testosterone levels. RESULTS: 1,623 subjects were included in the analysis; mean age was 57 years (24 to 87), and mean testosterone level was 575.5 ng/dL (25.0 to 1308.0 ng/dL). The evaluation of age-related changes in total testosterone levels revealed a progressive reduction in serum levels of this hormone with increasing age. Testosterone levels below 300 ng/dL were reported in 321 participants, a prevalence of nearly 20% in the study population. CONCLUSION: In agreement with other findings, a reduction of total testosterone levels with age was reported for healthy Brazilian men.

Cellular Response to Sol-Gel Hybrid Materials Releasing Boron and Calcium Ions.

Poly(dimethylsiloxane) (PDMS)-SiO2-CaO-based hybrid materials prepared by sol-gel have proved to be very promising materials for tissue engineering applications and drug-delivery systems. These hybrids are biocompatible and present osteogenic and bioactive properties supporting osteoblast attachment and bone growth. The incorporation of therapeutic elements in these materials, such as boron (B) and calcium (Ca), was considered in this study as an approach to develop biomaterials capable of stimulating bone regeneration. The main purpose of this work was thus to produce, by sol-gel, bioactive and biocompatible hybrid materials of the PDMS-SiO2-B2O3-CaO system, capable of a controlled Ca and B release. Different compositions with different boron amounts were prepared using the same precursors resulting in different monolithic materials, with distinct structures and microstructures. Structural features were assessed by Fourier transform infrared (FT-IR) spectrometry and solid-state nuclear magnetic resonance (NMR) techniques, which confirmed the presence of hybrid bonds (Si-O-Si) between organic (PDMS) and inorganic phase (tetraethyl orthosilicate (TEOS)), as well as borosiloxane bonds (B-O-Si). From the 11B NMR results, it was found that Ca changes the boron coordination, from trigonal (BO3) to tetrahedral (BO4). Scanning electron microscopy (SEM) micrographs and N2 isotherms showed that the incorporation of boron modifies the material's microstructure by increasing the macroporosity and decreasing the specific surface area (SSA). In vitro tests in simulated body fluid (SBF) showed the precipitation of a calcium phosphate layer on the material surface and the controlled release of therapeutic ions. The cytocompatibility of the prepared hybrids was studied with bone marrow stromal cells (ST-2 cell line) by analyzing the cell viability and cell density. The results demonstrated that increasing the dilution rate of extraction medium from the hybrids leads to improved cell behavior. The relationship between the in vitro response and the structural and microstructural features of the materials was explored. It was shown that the release of calcium and boron ions, determined by the hybrid structure was crucial for the observed cells behavior. Although not completely understood, the encouraging results obtained constitute an incentive for further studies on this topic.

A rare histiocytosis with severe cardiac involvement: Erdheim-Chester disease.

The term histiocytosis covers various disorders that lead to primary proliferation, infiltration and accumulation of cells of the mononuclear-phagocytic system within the affected tissues. Its pathophysiology is still unclear and the clinical course variable, which explains the lack of specific treatment and the need for a high level of suspicion to arrive at the diagnosis. The authors present the case of a patient with a complex cardiological clinical history, recently referred for surgical treatment of severe mitral insufficiency. Severe thickening of both atrial walls made it impossible to proceed with the intervention. After a complex etiological evaluation, a diagnosis of Erdheim-Chester disease was made. This is a rare, non-Langerhans cell histiocytosis and, to our knowledge, this represents the first case reported in Portugal. The authors also review the literature, particularly of the few cases with cardiac involvement.

Does clarifyng the digital rectal examination to the elderly reduce the discomfort in its first execution?

OBJECTIVE: To assess the degree of discomfort reported by elderly men when first submitted to digital rectal examination (DRE) in the prevention of prostate cancer and the effect of previous explanations on this complaint. METHODS: A prospective, randomized study in 120 men aged 60 to 80 years, divided into two groups: group A (routine medical appointment) and group B (medical appointment with educational intervention). In group B, the information tools were informal talk with explanations of DRE and prostate cancer, visualization of model of the male pelvis and the anatomical relations with the prostate, DRE simulator and DVD with three-dimensional animation of the pelvic organs. The degree of discomfort was measured by visual scale of pain. We used the chi-square test, with significance at 0.05. RESULTS: There were significant differences between the degree of discomfort mentioned in DRE between the two groups; 81% of group B reported it as mild, while 80% of group A referred it as moderate or intense, with significant p=0.01. The signs and symptoms were the main reason for consultation in 35% of patients; 78% went to be consulted alone and 81% commented on their own examination with their spouses. With no statistical difference, 94.2% in group A and 97.8% in group B repeated the examination the following year and 91.6% in group A and 96.6% in group B reported that the exam was not worse than imagined. All would recommend DRE for relatives or friends. CONCLUSION: Patients who did the first DRE after urological consultation with prior educational clarification on the issue reported significantly less discomfort.

Cytogenetic and molecular studies of an X;21 translocation previously diagnosed as complete monosomy 21.

We studied a child with apparent monosomy of chromosome 21. Cytogenetic, FISH and microsatellite analyses revealed a 45,X,-21,+der(X)t(X;21)(q25;q21.1) karyotype resulting from a de novo, unbalanced, X;21 non-reciprocal translocation of paternal origin, with partial monosomy of chromosomes 21 and X. An extreme, skewed X-inactivation pattern of the der(X) chromosome was demonstrated. Skewed inactivation probably accounted for a mild phenotype with respect to Xq25-->qter deletion while propagation of inactivation to the adjacent 21q region may account for mild clinical features associated to distal 21q monosomy.

Age-related testosterone decline in a Brazilian cohort of healthy military men

INTRODUCTION: Androgen decline in the aging man has become a topic of increasing clinical relevance worldwide, as the reduction in testosterone levels has been reported to be accompanied by loss of muscle mass, accumulation of central adiposity, impaired mobility and increase risk of bone fractures. Although well-established in studies conducted in developed countries, progressive decline in serum testosterone levels with age has been poorly investigated in Brazil. AIM: To determine the pattern of blood testosterone concentrations decline with age in a cohort of Brazilian healthy military men. MATERIALS AND METHODS: We retrospectively reviewed data on serum testosterone measurements of healthy individuals that had undergone a routine check-up at the Military Biology Institute. Blood samples were obtained early in the morning, and total testosterone concentration was determined using a commercial chemoluminescent immunoassay. Mean values were analyzed in five age groups: < 40, 41 to 50, 51 to 60, 61 to 70, and > 70 years. MAIN OUTCOME MEASURE: Mean total testosterone levels. RESULTS: 1,623 subjects were included in the analysis; mean age was 57 years (24 to 87), and mean testosterone level was 575.5 ng/dL (25.0 to 1308.0 ng/dL). The evaluation of age-related changes in total testosterone levels revealed a progressive reduction in serum levels of this hormone with increasing age. Testosterone levels below 300 ng/dL were reported in 321 participants, a prevalence of nearly 20 percent in the study population. CONCLUSION: In agreement with other findings, a reduction of total testosterone levels with age was reported for healthy Brazilian men.

Esclarecer o idoso sobre o exame digital retal diminui o desconforto na sua primeira realização? / Does clarifyng the digital rectal examination to the elderly reduce the discomfort in its first execution?

OBJETIVO: Verificar o grau de desconforto referido por homens idosos que realizam pela primeira vez o exame digital retal (EDR) na prevenção do câncer de próstata e o efeito de esclarecimentos prévios sobre essa queixa. MÉTODOS: Estudo prospectivo e aleatório em 120 homens, com idade de 60 a 80 anos, distribuídos em dois grupos: grupo A (consulta médica rotineira) e grupo B (consulta médica com intervenção educativa). No grupo B, os instrumentos de informação foram: palestra informal com esclarecimentos sobre EDR e câncer de próstata, visualização de maquete da pelve masculina, mostruário com as relações anatômicas prostáticas, simulador do EDR e DVD com animação tridimensional dos órgãos pélvicos. O grau de desconforto foi medido através da escala visual de dor. Utilizou-se o teste do qui-quadrado, com significância de 0,05. RESULTADOS: Houve diferença significativa entre o grau de desconforto referido no EDR entre os dois grupos, 81 por cento do grupo B referiram-no como leve e 80 por cento do grupo A, como moderado ou intenso, com p significativo de 0,01. Os sinais e sintomas foram a principal razão da consulta em 35 por cento dos pacientes, 78 por cento foram à consulta sozinhos e 81 por cento comentaram o exame com a parceira. Sem diferença estatística, 94,2 por cento no grupo A e 97,8 por cento no grupo B repetiriam o exame no ano seguinte e 91,6 por cento no grupo A e 96,6 por cento no grupo B relataram que o exame não foi pior do que imaginavam. Todos recomendariam o EDR para parentes ou amigos. CONCLUSÃO: Os pacientes que fizeram o EDR pela primeira vez após consulta urológica com esclarecimentos educativos prévios sobre o tema referiram significativamente menor desconforto.

OBJECTIVE: To assess the degree of discomfort reported by elderly men when first submitted to digital rectal examination (DRE) in the prevention of prostate cancer and the effect of previous explanations on this complaint. METHODS: A prospective, randomized study in 120 men aged 60 to 80 years, divided into two groups: group A (routine medical appointment) and group B (medical appointment with educational intervention). In group B, the information tools were informal talk with explanations of DRE and prostate cancer, visualization of model of the male pelvis and the anatomical relations with the prostate, DRE simulator and DVD with three-dimensional animation of the pelvic organs. The degree of discomfort was measured by visual scale of pain. We used the chi-square test, with significance at 0.05. RESULTS: There were significant differences between the degree of discomfort mentioned in DRE between the two groups; 81 percent of group B reported it as mild, while 80 percent of group A referred it as moderate or intense, with significant p=0.01. The signs and symptoms were the main reason for consultation in 35 percent of patients; 78 percent went to be consulted alone and 81 percent commented on their own examination with their spouses. With no statistical difference, 94.2 percent in group A and 97.8 percent in group B repeated the examination the following year and 91.6 percent in group A and 96.6 percent in group B reported that the exam was not worse than imagined. All would recommend DRE for relatives or friends. CONCLUSION: Patients who did the first DRE after urological consultation with prior educational clarification on the issue reported significantly less discomfort.

Geleophysic dysplasia - Report on two sibs

Os autores descrevem dois novos casos de displasia Geleofísica em irmäos, uma doença autossômica recessiva rara do metabolismo de glicoproteínas cujo defeito básico ainda näo foi determinado.

Chromosome 6q deletion: report of a new case and review of the literature

Os autores descrevem um novo caso de monossomia parcial do braço longo do cromossomo 6[46,XY,del(6)(q22 qter)]. A ocorrência de retardo psicomotor severo é esperada em funçäo do paciente apresentar um dos maiores segmentos deletados além da banda 6q25.

Clinical and molecular studies in a mother and son with Xp22.3 deletion

Estudamos um paciente que apresentava baixa estatura, retardo mental moderado, convulsöes, ictiose, anosmia e hipogonadismo hipogonadotrópico (Síndrome de Kallmann). A análise citogenética identificou a translocaçäo X;Y (Xp22.3;Yq11) de origem materna. Os resultados do estudo molecular foram compatíveis com uma síndrome de genes contíguos. A diminuiçäo do ângulo carpal na mäe e as deformidades do côndilo medial da tibia em ambos relacionam essas anormalidades ao segmento cromossômico perdido do cromossomo X.

Síndrome de Noonan: Estudo clínico-genético de 30 pacientes / Noonan syndrome: clinical-genetic study of 30 patients

A síndrome de Noonan (SN), entidade genética de herança autossômica dominante, subdiagnosticada em funçäo da expressividade extremamente variável do quadro clínico, é possivelmente uma das síndromes mendelianas mais freqüentes. Em um estudo prospectivo foram avaliados 30 pacientes a partir de um protocolo de investigaçäo clínico-laboratorial. Entre os critérios clínicos descritos na SN os mais importantes para o diagnóstico foram: ptose palpebral, micrognatia, fendas anti-down, raiz nasal deprimida, base nasal larga, hipertelorismo mamilar, criptorquidia e ptergium colli. Retardo mental era presente ou questionável em 14 pacientes. Os achados laboratoriais mais freqüentes foram: cardiopatia (predominando estenose pulmonar e comunicaçäo inter-atrial), anomalias renais, atraso de idade óssea, anomalias de coluna cervical, alteraçöes oftalmológicas, alteraçöes de audiçäo e coagulograma alterado. Apenas três pacientes (10 porcento) apresentaram displasia linfática, sugerindo possivelmente uma mortalidade aumentada neste grupo. Dois pacientes têm a reconhecida associaçäo da SN com neurofibromatose. Dois casos familiais foram confirmados e há nove casos familiais suspeitos. A idade paterna avançada nos casos näo familiais seria compatível com a mutaçäo nova para gen autossômico dominante. Os dados apresentados ressaltam a importância da sistematizaçäo do protocolo de investigaçäo e acompanhamento, visando a antecipaçäo e prevençäo de complicaçöes, bem como subsídios para o aconselhamento genético