Polycystic ovary syndrome: clinical and laboratory variables related to new phenotypes using machine-learning models.

PURPOSE: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. Machine learning (ML) is the area of artificial intelligence with a focus on predictive computing algorithms. We aimed to define the most relevant clinical and laboratory variables related to PCOS diagnosis, and to stratify patients into different phenotypic groups (clusters) using ML algorithms. METHODS: Variables from a database comparing 72 patients with PCOS and 73 healthy women were included. The BorutaShap method, followed by the Random Forest algorithm, was applied to prediction and clustering of PCOS. RESULTS: Among the 58 variables investigated, the algorithm selected in decreasing order of importance: lipid accumulation product (LAP); abdominal circumference; thrombin activatable fibrinolysis inhibitor (TAFI) levels; body mass index (BMI); C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c), follicle-stimulating hormone (FSH) and insulin levels; HOMA-IR value; age; prolactin, 17-OH progesterone and triglycerides levels; and family history of diabetes mellitus in first-degree relative as the variables associated to PCOS diagnosis. The combined use of these variables by the algorithm showed an accuracy of 86% and area under the ROC curve of 97%. Next, PCOS patients were gathered into two clusters in the first, the patients had higher BMI, abdominal circumference, LAP and HOMA-IR index, as well as CRP and insulin levels compared to the other cluster. CONCLUSION: The developed algorithm could be applied to select more important clinical and biochemical variables related to PCOS and to classify into phenotypically different clusters. These results could guide more personalized and effective approaches to the treatment of PCOS.

Chitosan-Calcium-Simvastatin Scaffold as an Inductive Cell-Free Platform.

The development of biomaterials based on the combination of biopolymers with bioactive compounds to develop delivery systems capable of modulating dentin regeneration mediated by resident cells is the goal of current biology-based strategies for regenerative dentistry. In this article, the bioactive potential of a simvastatin (SV)-releasing chitosan-calcium-hydroxide (CH-Ca) scaffold was assessed. After the incorporation of SV into CH-Ca, characterization of the scaffold was performed. Dental pulp cells (DPCs) were seeded onto scaffolds for the assessment of cytocompatibility, and odontoblastic differentiation was evaluated in a microenvironment surrounded by dentin. Thereafter, the cell-free scaffold was adapted to dentin discs positioned in artificial pulp chambers in direct contact with a 3-dimensional (3D) culture of DPCs, and the system was sealed to simulate internal pressure at 20 cm/H2O. In vivo experiments with cell-free scaffolds were performed in rats' calvaria defects. Fourier-transform infrared spectroscopy spectra proved incorporation of Ca and SV into the scaffold structure. Ca and SV were released upon immersion in a neutral environment. Viable DPCs were able to spread and proliferate on the scaffold over 14 d. Odontoblastic differentiation occurred in the DPC/scaffold constructs in contact with dentin, in which SV supplementation promoted odontoblastic marker overexpression and enhanced mineralized matrix deposition. The chemoattractant potential of the CH-Ca scaffold was improved by SV, with numerous viable and dentin sialoprotein-positive cells from the 3D culture being observed on its surface. Cells at 3D culture featured increased gene expression of odontoblastic markers in contact with the SV-enriched CH-Ca scaffold. CH-Ca-SV led to intense mineralization in vivo, presenting mineralization foci inside its structure. In conclusion, the CH-Ca-SV scaffold induces differentiation of DPCs into a highly mineralizing phenotype in the presence of dentin, creating a microenvironment capable of attracting pulp cells to its surface and inducing the overexpression of odontoblastic markers in a cell-homing strategy.

The influence of the transposed stomach through the posterior mediastinum on the respiratory forced expiratory volume and forced vital capacity in patients with resected esophageal cancer.

Although the use of the posterior mediastinum and the stomach as a reconstruction option after esophagectomy has large acceptance all over the world, there are concerns about the potential respiratory impairment it could cause. We prospectively studied 35 patients regarding the forced expiratory volume and vital capacity. The patients were studied preoperatively and between the 45th and 60th postoperative days. The value of both parameters decreased, although they were still within normal clinical ranges. We concluded that this type of reconstruction does not harm the patients regarding the respiratory flow rates.

Estudo do potencial antimicrobiano e citotóxico da espécie Pouteria venosa (Sapotaceae) / Study of antimicrobial and cytotoxic potential of Pouteria venosa species (Sapotaceae)

RESUMO Estudo experimental in vitro que objetivou investigar o potencial antimicrobiano e citotóxico de quatro frações e um extrato etanólico da espécie Pouteria venosa usada como planta medicinal. A atividade antimicrobiana foi determinada pelos testes de sensibilidade microbiana, como o método de difusão em disco e o método da microdiluição em caldo, para a determinação da Concentração Inibitória Mínima (CIM). Obteve-se a avaliação da citotoxicidade por meio do método colorimétrico do Metiltetrazolium. No estudo da atividade antimicrobiana, os principais resultados foram obtidos contra Staphylococus aureus para a fração AcOEt das cascas do caule, CIM de 125 µg/mL; Streptococcus pneumoniae e Proteus mirabilis para a fração AcOEt das cascas do caule, CIMde250 µg/mL; Staphylococus epidermidis, Pseudomonas aeruginosa para a fração AcOEt das folhas e cascas do caule, CIM de 250 µg/mL. Todas as amostras foram inativas para os fungos testados. A fração AcOEt das cascas do caule foi considerada atóxica, podendo ser utilizada em testes pré-clínicos in vivo

ABSTRACT Study of antimicrobial and cytotoxic potential of Pouteria venosa species (Sapotaceae). This experimental in vitro study aimed to investigate the antimicrobial and cytotoxic potential of four fractions and one ethanolic extract of the specie Pouteria venosa used as a medicinal plant. The antimicrobial activity was determined by microbial sensitivity tests, as the method of disk diffusion and the broth microdilution method for determination of Minimum Inhibitory Concentration (MIC). The evaluation of the cytotoxicity was obtained by the Metiltetrazolium colorimetric method. In the antimicrobial activity research, the main results were obtained against the Staphylococcus aureus for the AcOEt fraction of the stem bark MIC 125 µg/mL, Streptococcus pneumoniae and Proteus mirabilis for the AcOEt fraction from the stem bark, CIM 250 µg/mL, Staphylococcus epidermidis, Pseudomonas aeruginosa to the AcOEt fraction of the leaves and stem bark, MIC 250 µg/mL. All samples did not react for the fungi tested. The AcOEt fraction of the stem bark was considered non-toxic and can be used at in vivo pre-clinical testing

Role of red cell distribution width in screening for Hb E trait in population screening for hemoglobin disorders.

The national screening policy for hemoglobinopathies uses the cutoffs for red cell indices mean corpuscular volume >80 and mean corpuscular hemoglobin >27, a strategy known to miss some individuals with Hb E trait (EBT), the most common abnormal hemoglobin in Sri Lanka. We wanted to determine if red cell distribution width (RDW) cutoff values would help in increasing the sensitivity of screening for Hb E trait. High-performance liquid chromatography was carried out as the gold standard to detect hemoglobinopathies and red blood cell parameters with colter counter. Receiver operating characteristic curve was drawn to determine the cutoff value for EBT against ß-trait (BTT) and other anemias. Of the 504 patients, 246 had BTT, 110 had EBT, and 151 had other types of anemias. Mean (SD) RDW among patients with BTT was 16 (2.8), with EBT 14.5 (2.9), and with other anemias 15.8 (4.2) (P>0.001). With 14.45 as the cutoff for RDW and considering accepted values for mean corpuscular volume >80 and mean corpuscular hemoglobin >27, it gave a predictive sensitivity of 98.2% for EBT. By using RDW cutoff at 14.45 in addition to the accepted screening indices, sensitivity of Hb E trait detection went up to 98.2% from 86.6%. This study highlights the importance of taking RDW into consideration for screening.

Action of phosphorylated mannanoligosaccharides on immune and hematological responses and fecal consistency of dogs experimentally infected with enteropathogenic Escherichia coli strains.

The therapeutic action of phosphorylated mannanoligosaccharides (MOS) was investigated regarding its prebiotic activity on enteropathogenic Escherichia coli (EPEC). Diarrhea was induced in dogs by experimental infection with EPEC strains. Then MOS was supplied once a day, in water for 20 days. Immunological (IgA and IgG), hematological (lymphocytes, neutrophils and monocytes) and bacteriological variables (PCR detection of the eae gene of EPEC recovered from stool culture), as well as occurrence of diarrhea were evaluated. All strains caused diarrhea at 24, 48 and 72 h after infection. PCR results indicated that E. coli isolated from stool culture of all infected animals had the eae gene. There was no significant difference among groups as to number of blood cells in the hemogram and IgA and IgG production. MOS was effective in recovering of EPEC-infected dogs since prebiotic-treated animals recovered more rapidly from infection than untreated ones (p < 0.05). This is an important finding since diarrhea causes intense dehydration and nutrient loss. The use of prebiotics for humans and other animals with diarrhea can be an alternative for the treatment and prophylaxis of EPEC infections.

Desempenho produtivo e econômico do confinamento de bovinos zebuínos alimentados com três dietas de alto concentrado / Economic performance of zebu cattle under feedlot fed with three high concentrate diets

Estudaram-se o desempenho produtivo e a viabilidade econômica no confinamento de 24 bovinos, inteiros, com idade média de 23 meses, sendo 12 Nelore (NEL) e 12 F1 Nelore x Brahman (NBR), divididos em três dietas: SIL - silagem de milho e ração concentrada; PEL - exclusiva de pellets; GRN - milho grão inteiro e pellets. O experimento foi realizado em um delineamento inteiramente ao acaso, em esquema fatorial 2x3, com quatro repetições. Os animais NBR apresentaram resultados semelhantes aos da raça NEL quanto aos desempenhos alimentar e econômico, para todas as variáveis analisadas durante o confinamento. Entre as três dietas, a dieta PEL, apesar de não ser a de maior custo em R$/kg, obteve o menor desempenho, com maior COT/kg, menor RT e menores margens líquidas. A dieta SIL apresentou os menores COT/kg e custo/kg de carcaça, com maiores receitas e margens líquidas. A dieta GRN obteve resultados econômicos semelhantes à SIL, porém obteve menor GMD em relação à SIL, além de ter o custo de dieta (R$/kg) mais oneroso em relação aos três tratamentos. Todas as dietas foram economicamente viáveis ao final do experimento, com ML/Kg de carcaça médios de 2,12, 0,35 e 1,09 para SIL, PEL e GRN, respectivamente, no entanto a dieta SIL foi a de melhor desempenho produtivo e econômico.

The production performance and economic viability of a feedlot of 24 cattle, with an average age of 23 months, 12 Nellore (NEL) and 12 F1 Nellore x Brahman (NBR), divided into three diets: SIL - corn silage and concentrate diet; PEL - exclusive of pellets; GRN - corn and whole grain pellets were studied. The experiment was conducted in a completely randomized scheme in a 2x3 factorial with four replications. The NBR animals showed similar results to the NEL in performance and economic viability for all variables analyzed. Among the diets, the PEL diet, although not the highest diet cost in R$/kg, had the lowest performance with higher TOC/kg, lower TR and lower net margins. The SIL diet had the lowest TOC/kg and cost/kg of carcass, with higher revenues and net margins. The economic results obtained for the GRN diet were similar to SIL, but had lower ADG compared to SIL and highest diet cost (R$/kg) among all. The diets were economically viable at the end of the trial, with average net margin/kg carcass of 2.12, 0.35 and 1.09 for SIL, FEP and GRN, respectively; however the SIL diet presented better productive and economical performance.

Genetic variability in the ITS and IGS regions of the ribosomal DNA of Acremonium cavaraeanum exhibiting antimicrobial activity.

Endophytic microorganisms represent promising alternatives for obtaining new drugs of biotechnological importance. In this study, the endophytic species Acremonium cavaraeanum (A1a) isolated from Cocos nucifera was cultivated for the production of secondary metabolites, and its extracts and fractions were evaluated by the dilution method (MIC). The EtOAc extracts and MeOH fractions were tested against Gram-positive and -negative bacteria, and had an MIC of 125 µg/mL when evaluated in the EtOAc extract (EBI). The EtOAc extract (EBII) had an MIC of 62.25 µg/mL for Staphylococcus aureus and an MIC between 125 and 250 µg/mL for Gram-negative bacteria. The methanolic fractions showed activity with MIC between 125 and 250 µg/mL for all bacteria tested. The IGS region of the rDNA repeat unit of genomic DNA was analyzed by PCR/RFLPs, including endonucleases PstI, BamHII, HinfI, and EcoRI. The physical maps showed different restriction sites for the 6 Acremonium sp isolates, and revealed 5 RFLP patterns. The results showed that isolates of the same Acremonium species exhibited variation in this specific region. The sequences of ITS1-5.8S-ITS2 regions were aligned by Clustal W using the neighbor joining method, which grouped the isolates into 5 distinct clusters. This study aimed to evaluate the genetic diversity of A. cavaraeanum crops exhibiting antibacterial activity. The results of this study indicate that different fungal genetic isolates have biotechnological potential for the production of active bio-compounds against several human pathogens.

Action of phosphorylated mannanoligosaccharides on immune and hematological responses and fecal consistency of dogs experimentally infected with enteropathogenic Escherichia coli strains

The therapeutic action of phosphorylated mannanoligosaccharides (MOS) was investigated regarding its prebiotic activity on enteropathogenic Escherichia coli (EPEC). Diarrhea was induced in dogs by experimental infection with EPEC strains. Then MOS was supplied once a day, in water for 20 days. Immunological (IgA and IgG), hematological (lymphocytes, neutrophils and monocytes) and bacteriological variables (PCR detection of the eae gene of EPEC recovered from stool culture), as well as occurrence of diarrhea were evaluated. All strains caused diarrhea at 24, 48 and 72 h after infection. PCR results indicated that E. coli isolated from stool culture of all infected animals had the eae gene. There was no significant difference among groups as to number of blood cells in the hemogram and IgA and IgG production. MOS was effective in recovering of EPEC-infected dogs since prebiotic-treated animals recovered more rapidly from infection than untreated ones (p < 0.05). This is an important finding since diarrhea causes intense dehydration and nutrient loss. The use of prebiotics for humans and other animals with diarrhea can be an alternative for the treatment and prophylaxis of EPEC infections.

Influence of transposed stomach on cardiac function in patients with resected esophageal cancer.

Although the use of the posterior mediastinum and the stomach as a reconstruction option after esophagectomy has wide acceptance, there are concerns about the potential cardiac impairment it could cause. We prospectively studied 27 patients regarding the function and the systolic diameter, diastolic diameter, shortening fraction, ejection fraction and the presence of extrinsic compression. The patients were studied preoperatively and between the 45th and 60th postoperative days. The parameters were still within normal clinical ranges. We concluded that this type of reconstruction does not harm the patients in terms of their cardiac function.

Comparative anatomical study of the anterior and posterior mediastinum as access routes after esophagectomy.

Esophagectomy is the main option for treatment of esophageal cancer. Among the subjects of surgical interest is the use of anterior versus posterior mediastinum to permit reconstruction of the alimentary tract. We performed postmortem measurements in order to analyze the lengths of both routes. For each route (anterior and posterior) we performed two measurements. The first one was called anatomical route and the second was named as surgical route. Both routes begin at the cricoid cartilage. The anatomical route goes to the celiac axis and the surgical route goes to the gastroduodenal artery. Our results show that in both routes the posterior mediastinum is a shorter way to reach the cervical region.

Androgen-induced cell growth and c-myc expression in human non-transformed epithelial prostatic cells in primary culture.

We assessed androgen-induced cell growth and c-myc expression in human non-transformed epithelial prostatic (HNTEP) cells in primary culture. Prostatic tissue was obtained from 48 retropubic prostatectomy patients (age: 61-77years) with benign prostatic hyperplasia (malignant tumors excluded). HNTEP cells were treated with testosterone or DHT, alone or in association with hydroxyflutamide. DHT action on c-myc mRNA was examined using Northern blots and RT-PCR. RT-PCR also was used to verify if HNTEP cells expressed the androgen receptor gene. Cell proliferation was assessed on days 3 and 6. Testosterone (2 x 10(-11) M) and DHT (10(-13)M) caused a significant increase (P < 0.05) in cell proliferation on both days. Addition of hydroxyflutamide (10(-6) M) to DHT abolished cell proliferation. HNTEP cells expressed androgen receptor (AR) gene and the treatment with DHT increased AR mRNA levels. C-myc expression was maximal at 30 min and 1 h with DHT (10(-13) M). C-myc seems to play a key role in the control of hormone responsiveness and cell proliferation in epithelial prostatic cells. The detection of androgen receptor gene expression and the increase in this expression with the addition of androgen shows that the HTNEP cells maintain functional characteristics and hormone dependence, and that they are a fruitful in vitro model for studying steroid hormone action mechanisms.

Spectrophotometric determination of acid volatile sulfide in river sediments by sequential injection analysis exploiting the methylene blue reaction.

This paper demonstrates the application of sequential injection analysis to perform sulfide determination using the methylene blue chemistry, based on two reagents: 3.63 mmol l(-1)N,N dimethyl-p-phenylene diamine hydrochloride in 1.1 mol l(-1) HCl solution and 19 mmol l(-1) FeCl(3), also in 1.1 mol l(-1) HCl. These solutions are aspirated inside the holding coil of the sequential injection system as two reagent zones sandwiching the sample zone. Under optimized conditions, the detection limit was calculated at 40 mug l(-1) S(2-), with a linear dynamic range from 0.05 to 2 mg l(-1) S(2-). This linear range can be extended up to 32 mg l(-1) using in-line dilution for sulfide concentrations greater than 2 mg l(-1). The robust characteristic of the SI system with syringe pump leads to very stable analytical curves (precision of 4%), minimizing the laborious preparation of sulfide standards. The method was applied in the determination of acid volatile sulfide in river sediments.

Birthweight, childhood growth and risk of breast cancer in a British cohort.

We have examined the relationship between birthweight and risk of breast cancer, taking into account growth in childhood, using data on a total of 2221 women born in 1946 and followed up to 1997. Thirty-seven breast cancers occurred during follow-up. There was evidence of greater risk of breast cancer with greater birthweight (rate ratio = 1.76 (95% CI: 0.92, 3.35) for birthweight >/= 3.5 kg vs birthweight < 3.5 kg), which was more marked at pre-menopausal ages (RR = 2.31, 95% CI: 0.93, 5.74). The relation with birthweight was not substantially confounded by any of the measured adult risk factors. A significant interaction was observed between the effects of birthweight and height at age 7 years. Relative to those born lighter than 3.5 kg, women who were heavy at birth (>/= 3.5 kg) and short or average at 7 years (< 1.22 m) had a 21% increase in breast cancer rates (RR = 1.21; 95% CI = 0.49-2.99), while women who were heavy at birth (>/= 3.5 kg) but tall at 7 years (>/= 1.22 m) had a four-fold increase (RR = 4.01; 95% CI = 1.82-8.83). These results suggest that the effect of birthweight on breast cancer risk may be modulated by childhood growth.

Bioavailability of once- and twice-daily regimens of didanosine in human immunodeficiency virus-infected children.

The bioavailability of didanosine at 180 mg/m(2) once daily was compared to that at 90 mg/m(2) twice daily in 24 children with advanced human immunodeficiency virus infection. Children were studied at steady state using optimal sampling and prior pharmacokinetic parameter estimates. Relative bioavailability was 0. 95 +/- 0.49, supporting the potential clinical adequacy of once-daily dosing.

The influence of the transposed stomach through the posterior mediastinum on the respiratory forced expiratory volume and forced vital capacity in patients with resected esophageal cancer.

Although the use of the posterior mediastinum and the stomach as a reconstruction option after esophagectomy has large acceptance all over the world, there are concerns about the potential respiratory impairment it could cause. We prospectively studied 35 patients regarding the forced expiratory volume and vital capacity. The patients were studied preoperatively and between the 45th and 60th postoperative days. The value of both parameters decreased, although they were still within normal clinical ranges. We concluded that this type of reconstruction does not harm the patients regarding the respiratory flow rates.