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.

A new model of classification of third molars development and its correlation with chronological age in a Brazilian subpopulation.

The present study correlated the mineralization of third molars to chronological age using a modified classification based on Demirjian's stages in a Brazilian subpopulation and compared with the original classification. A total of 1082 patients with age ranging from 6 to 26 years were included in the sample, with at least one third molar on panoramic radiographs. The third molars were classified according to the original Demirjian classification (8 stages) and a new model based on the Demirjian method, where the original stages were grouped into four stages: AB-enamel mineralization; CD-crown dentin mineralization; EFG-root formation; and H-complete development. Statistical analyses were performed by Kruskal-Wallis/Dunn tests (α = 0.05) and the multinomial logistic regression model. Data were analyzed according to percentiles for the probability of an individual being over 18 years old. The mean ages of the stages in both classifications did not present a significant difference between superior and inferior arches (p < 0.05). The differences in mean ages between all the stages of mineralization were statistically significant (p < 0.001) only for the 4-stage classification. Males attained root formation and complete formation earlier than females (p < 0.05) in the 4-stage classification. The modified classification system showed dependence between chronological age and mineralization stages of third molars, simplifying the age estimation process. At stage H, females present a 95.7% chance of being over 18, while for males, this probability is 89.6%. This modified classification system simplifies the dental age estimation process based on third molars and can be used as a reference for future studies.

Installing oncofertility programs for common cancers in limited resource settings (Repro-Can-OPEN Study): An extrapolation during the global crisis of Coronavirus (COVID-19) pandemic.

PURPOSE: The state of limited resource settings that Coronavirus (COVID-19) pandemic has created globally should be taken seriously into account especially in healthcare sector. In oncofertility, patients should receive their fertility preservation treatments urgently even in limited resource settings before initiation of anticancer therapy. Therefore, it is very crucial to learn more about oncofertility practice in limited resource settings such as in developing countries that suffer often from shortage of healthcare services provided to young patients with cancer. METHODS: As an extrapolation during the global crisis of COVID-19 pandemic, we surveyed oncofertility centers from 14 developing countries (Egypt, Tunisia, Brazil, Peru, Panama, Mexico, Colombia, Guatemala, Argentina, Chile, Nigeria, South Africa, Saudi Arabia, and India). Survey questionnaire included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. RESULTS: All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed different domestic standards for oncofertility practice in case of childhood cancer, breast cancer, and blood cancer in the developing countries under limited resource settings. CONCLUSIONS: Medical practice in limited resource settings has become a critical topic especially after the global crisis of COVID-19 pandemic. Understanding the resources necessary to provide oncofertility treatments is important until the current COVID-19 pandemic resolves. Lessons learned will be valuable to future potential worldwide disruptions due to infectious diseases or other global crises.

The Relationship between Intraocular Pressure and Optic Nerve Structural and Functional Damage in Patients with Optic Nerve Head Drusen.

The aim of this retrospective study was to evaluate if, in ocular normotensive patients, at the time of diagnosis of optic nerve head drusen (ONHD), perimetric mean deviation (PMD) on visual field (VF) examination and retinal nerve fibre layer (RNFL) thickness on optical coherence tomography correlated with intraocular pressure (IOP). There was a significant association between IOP and PMD (Spearman's rho = -0.863, p < .01) and between IOP and RNFL thickness (Spearman's rho = -0.630, p < .01). A higher IOP was associated with a greater functional loss in the VF and a reduction in the RNFL thickness. These results suggest that a clinical trial of IOP reduction should be considered in patients with ONHD to decrease the progression of optic nerve damage over time.

B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice.

STUDY QUESTION: What are the effects of B lymphocyte inactivation or depletion on the progression of endometriosis? SUMMARY ANSWER: Skewing activated B cells toward regulatory B cells (Bregs) by Bruton's tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect. WHAT IS KNOWN ALREADY: A polyclonal activation of B cells and the presence of anti-endometrial autoantibodies have been described in a large proportion of women with endometriosis though their exact role in the disease mechanisms remains unclear. STUDY DESIGN, SIZE, DURATION: This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation. PARTICIPANTS/MATERIALS, SETTING, METHODS: After syngeneic endometrial transplantation, murine endometriotic lesions were compared between treated and control mice using volume, weight, ultrasonography, histology and target genes expression in lesions. Phenotyping of activated and regulatory B cells, T lymphocytes and macrophages was performed by flow cytometry on isolated spleen and peritoneal cells. Cytokines were assayed by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis. In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinib-treated mice compared to anti-CD20 and control mice. Depletion of B cells using an anti-CD20 antibody had no effect on activity and growth of endometriotic lesions and neither on the macrophages, compared to control mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: It is still unclear whether B cell depletion by the anti-CD20 or inactivation by Ibrutinib can prevent establishment and/or progression of endometriosis in humans. WIDER IMPLICATIONS OF THE FINDINGS: Further investigation may contribute to clarifying the role of B cell subsets in human endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant of Institut National de la Santé et de la Recherche Médicale and Paris Descartes University. None of the authors has any conflict of interest to disclose.

Electromyographic characterisation of abdominal wall trigger points developed after caesarean section and response to local anaesthesia: an observational study.

OBJECTIVE: This study examines the electromyography pattern of abdominal trigger points developed after a caesarean section, and the association between clinical response and local anaesthetic injection. DESIGN: Prospective cohort study. SETTING: A tertiary university hospital. POPULATION: Twenty-nine women with chronic pelvic pain associated with trigger points after a caesarean section were included in the study. METHODS: Participants received needle electromyography before treatment, then underwent a treatment protocol consisting of trigger-point injection of 2 ml of 1% lidocaine. The protocol was repeated once a week for 4 weeks. The clinical responses of the patients were compared 1 week after and 3 months after treatment. The clinical trial is registered with the Brazilian Clinical Trials Registry (REBEC) under RBR-42c6gz (www.ensaiosclinicos.gov.br/rg/RBR-42c6gz/). MAIN OUTCOME MEASURES: Needle electromyography and algometry results and pain reduction. RESULTS: Fifteen patients had abnormal electromyography findings; 14 had normal findings. The rates of response 1 week and 3 months after treatment within the abnormal electromyography group were 95 and 87%, respectively. In the normal group, the rate was 38% both 1 week after and 3 months after treatment. CONCLUSIONS: Trigger points developed after caesarean section, even without clinical symptoms or signs of neuralgia, may originate from neuropathies. Electromyographic abnormalities were associated with pain remission after anaesthesia injection; normal electromyography findings were associated with undiagnosed causes of pain, such as adhesions. TWEETABLE ABSTRACT: Trigger points developed after caesarean section are neuropathies, even in the absence of classical neuralgia.

Gonadotropin-releasing hormone agonists for ovarian protection during cancer chemotherapy: systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of gonadotropin-releasing hormone agonist (GnRHa) administration before and/or during cancer chemotherapy for the protection of ovarian reserve in premenopausal women without prior diagnosis of infertility. METHODS: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing administration of GnRHa before and/or during chemotherapy vs chemotherapy alone. Eligible participants were premenopausal women at any stage of cancer, without previous diagnosis of infertility. An electronic database search in MEDLINE, CENTRAL, LILACS and ClinicalTrials.gov was performed. After selecting eligible studies, the relative risk (RR) was assessed for primary ovarian insufficiency (POI)/amenorrhea and for spontaneous pregnancy after completion of treatment. RESULTS: Thirteen RCTs comparing concurrent use of GnRHa and chemotherapy (609 participants) with chemotherapy alone (599 participants) were eligible for meta-analysis. All trials were open-label and patients had been treated for breast cancer (n = 1099) or lymphoma (n = 109). GnRHa had a significant benefit on the risk of POI/amenorrhea (RR, 0.60; 95% CI, 0.45-0.79), which persisted in subgroup analysis for breast cancer (RR, 0.57; 95% CI, 0.43-0.77) but not for lymphoma patients (RR, 0.70; 95% CI, 0.20-2.47). The rate of spontaneous pregnancy after completion of treatment was higher in women receiving GnRHa plus chemotherapy compared with those receiving chemotherapy alone (RR, 1.43; 95% CI, 1.01-2.02). Overall, the quality of evidence was low due to the unclear risk of bias, short follow-up and lack of objective assessment of ovarian function and reserve. CONCLUSIONS: Evidence, albeit of low quality, supports the use of GnRHa before and/or during chemotherapy to reduce the risk of POI and increase the probability of spontaneous pregnancy in the short term. Further high quality RCTs with more accurate assessment of ovarian reserve are needed to support definitive recommendations for clinical practice. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Cystic fibrosis in Afro-Brazilians: XK haplotypes analysis supports the European origin of p.F508del mutation.

Cystic fibrosis (CF) is a common autosomal recessive disorder, being the p.F508del the most frequent mutation. Also, a nearby restriction fragment length polymorphism (RFLP) named XK (KM19 and XV2C) is non-randomly associated with specific CF alleles. Our aim was to analyze the occurrence of the p.F508del mutation and XK haplotypes in Afro-Brazilians CF patients and controls, since these data is available for the other two main ethnic groups found in Brazil (Euro-Brazilians and Brazilian Amerindians), contributing for the whole comprehension of these haplotypes in the Brazilian population. A total of 103 patients and 54 controls were studied. PCR and PCR-RFLP methodologies were used to identify the presence of the p.F508del and the XK haplotype in the subjects. The combined data show that 84.2% of p.F508del mutation is associated with haplotype B and only 15.8% with haplotype A; no other haplotypes were found to be associated with this mutation. Our data suggest that the occurrence of p.F508del mutation and haplotype B in Afro-Brazilian patients occurs probably due to admixture with Euro-descendants. Therefore this mutation and haplotype could be used as a admixture marker.

Magnetic resonance imaging in neuropsychiatric systemic lupus erythematosus: current state of the art and novel approaches.

Systemic lupus erythematosus is a chronic, inflammatory, immune-mediated disease affecting 0.1% of the general population. Neuropsychiatric manifestations in systemic lupus erythematosus have been more frequently recognized and reported in recent years, occurring in up to 75% of patients during the disease course. Magnetic resonance imaging is known to be a useful tool for the detection of structural brain abnormalities in neuropsychiatric systemic lupus erythematosus patients because of the excellent soft-tissue contrast observed with MRI and the ability to acquire multiplanar images. In addition to conventional magnetic resonance imaging techniques to evaluate the presence of atrophy and white matter lesions, several different magnetic resonance imaging techniques have been used to identify microstructural or functional abnormalities. This review will highlight different magnetic resonance imaging techniques, including the advanced magnetic resonance imaging methods used to determine central nervous system involvement in systemic lupus erythematosus.

Wernicke's encephalopathy mimicking neuropsychiatric symptoms in patients with systemic lupus erythematosus: a report of three cases and literature review.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that involves many organs and systems. Nervous system involvement in SLE encompasses neurological and psychiatric disorders, and remains a diagnostic and therapeutic challenge. Wernicke's encephalopathy (WE) is a neurological disorder that occurs as a consequence of thiamine deficiency, and its clinical presentation resembles the neuropsychiatric events attributed to SLE (NPSLE). Differentiation between these two entities is crucial because their treatment differs greatly and can change prognosis. We describe three cases of patients with SLE who presented with initial clinical findings suggestive of NPSLE that, at the end of a thorough clinical investigation, were actually found to represent WE. In all of these cases, treatment with thiamine resulted in significant improvement. WE should be considered as a differential diagnosis in SLE patients with neuropsychiatric signs and symptoms, especially when risk factors for thiamine deficiency are present.

Analysis of differential genetic expression in endometrial polyps of postmenopausal women.

OBJECTIVES: To evaluate the expression of four genetic markers (PTEN, BCL2, MLH1, and CTNNB1), linked to endometrial carcinogenesis, in endometrial polyps of patients with and without postmenopausal bleeding in order to determine whether symptomatic endometrial polyps have a genetic phenotype similar to that of endometrial cancer. METHODS: Samples were obtained hysteroscopically from endometrial polyps of postmenopausal patients, and the expression of genetic markers involved in the pathogenesis of endometrial cancer (PTEN, BCL2, MLH1, and CTNNB1) was analyzed. The expression of these markers was then compared between patients with and without symptoms, which was characterized as postmenopausal bleeding. Other clinical characteristics of the patients, such as duration of menopause, polyp size, presence of systemic hypertension, diabetes mellitus, and smoking habits were also analyzed. RESULTS: Samples from a total of 60 patients were obtained, as calculated for a test power of 0.80. No statistical differences (p > 0.05) were observed between the two groups concerning the expression of the studied endometrial cancer risk factor genes, or with regard to the clinical aspects evaluated. CONCLUSION: The study found no evidence that symptomatic endometrial polyps have a similar phenotype to type 1 endometrial cancer; further studies are needed in order to establish whether endometrial polyps are in fact true cancer precursors, or simply raise cancer incidence due to a detection bias.

Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: systematic review and meta-analysis.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is an insidious pathologic condition that can manifest from simple steatosis to steatohepatitis (NASH) with potential progression to cirrhosis. Like the polycystic ovary syndrome (PCOS), NAFLD is associated with obesity, diabetes mellitus, insulin resistance and metabolic syndrome. PCOS women have an increased risk of NAFLD, but it is debatable which features of PCOS, either specific (androgen excess) or unspecific (metabolic derangements) affect the NAFLD risk. METHODS: We performed a systematic review and meta-analysis of studies that addressed the association of PCOS and NAFLD. We selected 17 studies published between 2007 and 2017 that included 2734 PCOS patients and 2561 controls of similar age and body mass index (BMI). RESULTS: PCOS patients have increased prevalence of NAFLD (odds ratio 2.54, 95% confidence interval 2.19-2.95). PCOS women with hyperandrogenism (classic phenotype) have a higher prevalence of NAFLD compared to women with PCOS without hyperandrogenism, even after correction for confounding variables. Among women with PCOS, those with NAFLD have higher serum total testosterone (mean difference 0.40 nmol/L, 95% CI 0.29-0.50 nmol/L) and free androgen index (mean difference 4.46, 95% CI 3.53-5.39) than those without NAFLD. The studies that used multivariate analysis controlling for age, BMI, triglycerides, and insulin resistance index confirmed that serum androgens are independent predictors of NAFLD in women with PCOS. CONCLUSION: The prevalence of NAFLD is increased in women with PCOS and the presence of NAFLD is associated with high serum androgen levels, in addition to obesity and insulin resistance.

A rare case of a boy with de novo microduplication at 5q35.2q35.3 from central Brazil.

Genomic disorders are genetic diseases that are caused by rearrangements of chromosomal material via deletions, duplications, and inversions of unique genomic segments at specific regions. Such rearrangements could result from recurrent non-allelic homologous recombination between low copy repeats. In cases where the breakpoints flank the low copy repeats, deletion of chromosomal segments is often followed by reciprocal duplication. Variations in genomic copy number manifest differently, with duplication and deletions of the same genomic region showing opposite phenotypes. Sotos syndrome is caused by alterations in the dosage of NSD1 on human chromosome 5 by either deletions or mutations, such as microdeletion of 5q35.2q35.3. In general, patients carrying reciprocal microduplication at 5q35.2q35.3 present no clinical phenotype or milder phenotype than do patients with microdeletion at the same locus. We report the first case of 5q35.2q35.3 microduplication encompassing NSD1 in a patient from central Brazil. We identified a genomic imbalance corresponding to a de novo 0.45 Mb microduplication at 5q35.2q35.3 by chromosomal microarray analysis and study of low-copy repeats. The proband had microduplication in the chromosomal region containing NSD1, which resulted in a Sotos syndrome reversed phenotype, and this duplication was associated with microcephaly, short stature, and developmental delay. Analysis of the genomic structure of the rearranged 5q35.2q35.3 chromosomal region revealed two major low-copy repeat families, which caused the recurrent rearrangements. Chromosomal microarray analysis is a potential tool to identify microrearrangements and guide medical diagnosis, which has to be followed by a non-directive genetic counseling approach to improve the quality of life of the patient.

Posterior reversible encephalopathy syndrome and association with systemic lupus erythematosus.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a neurological complex disorder with many clinical associations and causative factors. It is important to recognize this condition because early diagnosis and treatment usually result in its complete resolution, radiological imaging becoming the key for the correct diagnosis. METHODS: We retrospectively reviewed charts and magnetic resonance imaging findings in the University of Campinas from January 2005 to July 2015, selecting three cases of patients with systemic lupus erythematosus syndrome who developed PRES, for whom risk factors, characteristics, magnetic resonance imaging findings and neurological resolution were analyzed. We also conducted a review of the English-language literature. RESULTS: The three cases had neurological symptoms like acute onset of headache, altered mental status, cortical blindness and seizures. Brain magnetic resonance imaging demonstrated posterior cortical and white matter alterations involving posterior brain territories, which were more conspicuous on T2-weighted and fluid-attenuated inversion recovery. Spectroscopy, diffusion-weighted imaging and susceptibility-weighted imaging were also important for neuroradiological evaluation. Immunosuppressive drugs were taken in all cases. Partial clinical and radiological recovery was observed in two cases, and complete resolution was observed in the third patient. LITERATURE REVIEW: We found 52 cases of PRES in systemic lupus erythematosus patients. Almost all patients were women 94%, ranging from 8 to 62 years old. Posterior brain territory involvements were found in 98% of patients. Hemorrhagic complications involved 26% of patients, becoming a risk factor for clinical sequels. The total percentage of patients with no complete resolution of radiological findings on follow-up images was 27.5%. DISCUSSION: In patients with autoimmune disorders, endothelial dysfunction may occur secondary to autoimmunity and the use of cytotoxic drugs, supposedly facilitating the occurrence of more severe PRES. The hypothesis that patients with autoimmune diseases have a propensity to develop non-reversible lesions has been raised.

Diagnosis of endometriosis in women with chronic pelvic pain.

PURPOSE OF INVESTIGATION: To assess the accuracy of CA-125 determination associated with clinical history and of the neutrophil/lymphocyte (N/L) ratio for a presumptive diagnosis of endometriosis in women with chronic pelvic pain (CPP). MATERIALS AND METHODS: This was a cross-sectional study of data from the medical records of women with CPP submitted to laparoscopy from August 1999 to January 2009 at the University Hospital. The performance of the evaluation of CA-125 and of the N/L ratio for the prediction of endometriosis was compared based on the corresponding ROC curves and their 95% confidence intervals. RESULTS: CA-125 levels were significantly higher in women with CPP and endometriosis and their association with a complaint of dysmenorrhea improved their sensitivity. For a cut-off of 20 IU/ml, the predictive value for a diagnosis of endometriosis in women with CPP was 97.6%. Dyspareunia, subfertility, and N/L ratio were not useful for a diagnosis of endometriosis in women with CPP. CONCLUSION: The association of elevated CA-125 levels with a complaint of dysmenorrhea is adequate in a presumptive and accurate diagnosis of endometriosis in this specific group of women with CPP, permitting an early institution of clinical treatment without the need of previous laparoscopic confirmation.

Characterization of neovascular age-related macular degeneration patients with outer retinal tubulations.

PURPOSE: To characterize the neovascular lesions of patients with age-related macular degeneration (AMD) and outer retinal tubulations (ORTs). METHODS: A retrospective study of 377 eyes with exudative AMD, submitted to intravitreal anti-angiogenic treatment. Patients were divided into 2 groups according to the presence or absence of ORTs on spectral-domain optical coherence tomography (SD-OCT; group 1 - with ORTs; group 2 - without ORTs). Age, best corrected visual acuity (BCVA), fluorescein angiography characteristics, presence of subretinal fibrosis and subfoveal photoreceptor integrity on SD-OCT were analyzed. RESULTS: Although both groups had a BCVA gain during the follow-up period, initial and final BCVA were lower in group 1 (p = 0.020 and p = 0.042, respectively). There was no statistically significant difference in the BCVA variation between the 2 groups (p = 0.907). Regarding the initial angiographic lesion type, there was a statistically significant difference between the 2 groups (p = 0.008): group 1 had more lesions with a classic component and group 2 had more occult lesions with no classic component. There was a statistically significant difference concerning the loss of subfoveal photoreceptor integrity (p = 0.0007). CONCLUSIONS: Even though AMD patients with ORTs were associated with poor visual outcomes, we reported BCVA improvement. AMD patients with a classical component in their lesions are prone to develop ORTs.

Influence of reciprocating single-file and rotary instrumentation on bacterial reduction on infected root canals.

AIM: To compare the bacterial reduction achieved with reciprocating and rotary systems during root canal preparation. METHODOLOGY: Sixty distobuccal root canals of maxillary molars were contaminated with Enterococcus faecalis broth culture. After an incubation period of 21 days, bacterial samples were collected and cultured on m-Enterococcus agar plates. The root canals were divided into five groups, according to the system used for instrumentation: WaveOne, Reciproc, ProTaper, Mtwo and manual instrumentation. The negative controls consisted of five uncontaminated root canals that were subjected to the same instrumentations as each of the experimental groups. Bacterial samples were collected immediately and 7 days after instrumentation. Statistical analysis was performed by paired t-tests and anova tests. RESULTS: Compared with the samples before instrumentation, the bacterial count was significantly reduced after instrumentation in all groups, with no significant difference in bacterial count reduction amongst the reciprocating, rotary and manual techniques. However, the samples tested 7 days after instrumentation showed significantly higher bacterial counts than the samples tested immediately after instrumentation. CONCLUSIONS: All systems tested reduced bacterial counts to a similar level.

Effects of a moderate physical training on the leptin synthesis by adipose tissue of adult rats submitted to a perinatal low-protein diet.

The aim of the study was to verify if moderate physical training affects leptin content in visceral and subcutaneous adipose tissue of adult rats subjected to a low-protein diet during the perinatal period. Male Wistar rats were divided into 2 groups according to their mother's diet during gestation and lactation: control (17% casein, C, n=12) and low-protein (8% casein, LP, n=12). On postnatal day 60, half of each group was submitted to moderate physical training (8 wks, 5 d · wk - 1, 60 min · d - 1, at 70% of VO2max, T) or not. After the physical training period, visceral and subcutaneous adipose tissues were removed. Leptin content was evaluated by western blotting. Starting from the fifth week on, T pups showed a reduction in the body weight. Similarly, LP+T offspring showed a lower body weight starting from the sixth week on. Western blotting analysis showed that leptin content in the visceral tissue was higher in the LP rats (p<0.01) and it was reversed in LP+T. No difference was found in the subcutaneous tissue. Moderate physical training attenuated the effects of a perinatal low-protein diet on the leptin content in visceral adipose tissue in adult offspring.

Protective effects of the dipeptidyl peptidase IV inhibitor sitagliptin in the blood-retinal barrier in a type 2 diabetes animal model.

AIM: The aim of this study was to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV inhibitor (DPP-IV), in preventing the deleterious effects of diabetes on the blood-retinal barrier in male Zucker Diabetic Fatty (ZDF) rats. METHODS: ZDF rats at 20 weeks of age were treated with sitagliptin (10 mg/kg/day) during 6 weeks. The effect of the drug on glycaemia was assessed by evaluating glycated haemoglobin (HbA1c). The content and/or distribution of tight junction (TJ) proteins occludin and claudin-5, as well as nitrotyrosine residues, interleukin (IL)-1ß, BAX and Bcl-2 was evaluated in the retinas by western blotting and/or immunohistochemistry. Retinal cell apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay. The number of CD34+ cells present in peripheral circulation was assessed by flow cytometry, and endothelial progenitor cells (EPC) adhesion ability to the retinal vessels was evaluated by immunohistochemistry. RESULTS: Sitagliptin improved glycaemic control as reflected by a significant decrease in HbA1c levels by about 1.2%. Treatment with sitagliptin prevented the changes in the endothelial subcellular distribution of the TJ proteins induced by diabetes. Sitagliptin also decreased the nitrosative stress, the inflammatory state and cell death by apoptosis in diabetic retinas. Diabetic animals presented decreased levels of CD34+ cells in the peripheral circulation and decreased adhesion ability of EPC to the retinal vessels. Sitagliptin allowed a recovery of the number of CD34+ cells present in the bloodstream to levels similar to their number in controls and increased the adhesion ability of EPC to the retinal vessels. CONCLUSIONS: Sitagliptin prevented nitrosative stress, inflammation and apoptosis in retinal cells and exerted beneficial effects on the blood-retinal barrier integrity in ZDF rat retinas.

Interface collisions with diffusive mass transport.

We report on a linear Langevin model that describes the evolution of the roughness of two interfaces that move towards each other and are coupled by a diffusion field. This model aims at describing the closing of the gap between two 2D material domains during growth, and the subsequent formation of a rough grain boundary. We assume that deposition occurs in the gap between the two domains and that the growth units diffuse and may attach to the edges of the domains. These units can also detach from edges, diffuse, and reattach elsewhere. For slow growth, the edge roughness increases monotonously and then saturates at some equilibrium value. For fast growth, the roughness exhibits a maximum just before the collision between the two interfaces, which is followed by a minimum. The peak of the roughness can be dominated by statistical fluctuations or by edge instabilities. A phase diagram with three regimes is obtained: Slow growth without peak, peak dominated by statistical fluctuations, and peak dominated by instabilities. These results reproduce the main features observed in kinetic Monte Carlo simulations.