Metabolic and neurological consequences of the treatment with polyphenols: a systematic review in rodent models of noncommunicable diseases.

BACKGROUND: Noncommunicable diseases (NCDs) lead to drastic metabolic alterations with associated energy balance and body weight changes, two related physiological processes regulated by the brain. Polyphenol-based treatments for NCDs have emerged as a promising therapy, which seems to involve the energy balance modulation. However, it remains unclear what the most effective polyphenols-based treatment is to attenuate adverse effects in the energy balance of NCDs. OBJECTIVES: This systematic review aimed to evaluate the literature on the metabolic and neurological effects of polyphenols-based treatment in rodent models of NCDs. METHODS: Literature search was carried out in the following databases: CINAHL, Medline/PubMed, SCOPUS, and Web of Science. For title and abstract screening, original papers with polyphenols exposure in rodents were selected. For full-text screening, studies with models of NCDs that reported metabolic and neurological outcomes when treated with polyphenols were selected for inclusion in this review. RESULTS: 23 articles, using individual compound (11 articles) or polyphenols extracts (12 articles), were included in this review: 5 articles using tea polyphenols, 12 articles using grape-derived polyphenols, 3 articles using the polyphenol quercetin, and 3 articles using other polyphenol sources. Most results agree on the beneficial effect of polyphenols in attenuating alterations in energy balance and body weight. Such effects were associated with neuroprotective responses in different brain areas including hippocampus and hypothalamus. CONCLUSION: In conclusion, this review shows that the treatment with polyphenols, especially resveratrol or quercetin, attenuates the adverse effects of NCDs on energy balance and are associated with neuroprotective effects.

Analysis of Defense-Related Gene Expression in Citrus Hybrids Infected by Xylella fastidiosa.

Resistance to Xylella fastidiosa was evaluated in 264 hybrids of crosses between Murcott tangor (Citrus reticulata × Citrus sinensis) and Pera sweet orange (C. sinensis) under field conditions. Uninfected hybrids were grafted with buds collected from Pera sweet orange plants infected with X. fastidiosa, forming a plant with two scions (i.e., hybrid branches and Pera sweet orange branches). From these plants, we chose 10 genotypes with three biological replicates. We evaluated gene expression, bacterial multiplication, and citrus variegated chlorosis (CVC) symptom development in both scions. X. fastidiosa was not detected in most hybrid scions and none showed disease symptoms. In contrast, all Pera sweet orange scions were infected with X. fastidiosa and expressed symptoms of CVC. We quantified the expression of 12 defense-related genes by qPCR comparing resistant to susceptible scions. We suggest that some of these genes are involved in resistance of the hybrids to X. fastidiosa, since their expression was significantly higher in the resistant hybrid scions than in tolerant hybrids and scions originated from CVC symptomatic Pera sweet orange buds. However, we note that these data should be interpreted carefully, as the plant genotypes tested are related but necessarily distinct (hybrids of C. reticulata and C. sinensis, in relation to a C. sinensis control). A principal component analysis revealed a relationship between the expression of these genes and hybrid scions, and between scions that originated from infected buds and the presence of the bacteria and plant symptoms. Multiyear field trials are necessary to develop plant resistance to X. fastidiosa. While the experimental design used here had limitations, it allowed us to identify a set of genes potentially involved in Citrus sp. resistance to this pathogen. Future work on the role of these genes in plant defenses to X. fastidiosa infection is necessary to confirm their importance in the displayed resistance phenotype.

Perceived sources of stress amongst dental students: A multicountry study.

AIMS: The aim of this study was to explore the perceived sources of stress reported by dental students from fourteen different countries. METHODS: A total of 3568 dental students were recruited from 14 different dental schools. The dental environmental stress (DES) questionnaire was used including 7 domains. Responses to the DES were scored in 4-point Likert scale. Comparison between students was performed according to the study variables. The top 5 stress-provoking questions were identified amongst dental schools. Data were analysed using SPSS software program. Mann-Whitney and Kruskal-Wallis tests were used as appropriate. Logistic regression analysis was also conducted to determine the effect of the studied variables on the stress domains. The level of statistical significance was set at <.05. RESULTS: Internal consistency of the scale was excellent (0.927). Female students formed the majority of the total student population. The percentage of married students was 4.8%. Numbers of students in pre-clinical and clinical stages were close together. The most stress-provoking domain was "workload" with a score of 2.05 ± 0.56. Female students scored higher stress than male students did in most of the domains. Significant differences were found between participating countries in all stress-provoking domains. Dental students from Egypt scored the highest level of stress whilst dental students from Jordan scored the lowest level of stress. CONCLUSION: The self-reported stress in the dental environment is still high and the stressors seem to be comparable amongst the participating countries. Effective management programmes are needed to minimise dental environment stress.

P27/CDKN1B Translational Regulators in Pituitary Tumorigenesis.

In pituitary tumors, P27(CDKN1B) is underexpressed. We aimed to clarify whether translational regulation underlies this phenomenon. This study evaluated the expression of P27/CDKN1B, its targets (CCNE1, CDK2) and translational regulators (DKC1, RPS13, miR221, miR222) and screened for DKC1 variants in sporadic pituitary adenomas. Samples were obtained during transsphenoidal surgery from 48 patients with pituitary adenomas: 10 ACTH-, 17 GH-secreting, and 21 nonfunctioning (NFPA). The control group comprised 7 normal pituitaries (NP) obtained during autopsies. Gene expression was assessed by RT-PCR and protein expression by immunohistochemistry. The 15 exons of DKC1 were sequenced. P27 protein underexpression was observed in all adenomas subtypes (p=0.001). CCNE1 mRNA (p=0.01) overexpression, but not protein, was observed in NFPA. No differential gene expression among groups was observed in CDKN1B regulators RPS13 (p=0.23) and DKC1 (p=0.34). The expression of miR221 and miR222 was similar among tumors and NP. Frequent DKC1 variants (SNPs) were found in exon 14 and in the 3'-UTR in similar frequency to NCBI-dsSNP databases. We also observed rare DKC1 variants in 11% of the studied tumor samples, indicating a high prevalence in pituitary adenomas, however, in silico studies failed to indicate deleterious effects. The high frequency of DKC1 variants may influence, in some extent, pituitary tumors development, without clear role in its tumorigenesis. Our data reinforce the P27 underexpression in pituitary adenomas and provide further evidence of the post-translational machinery involvement, although this phenomenon cannot be explained either by mis-expression of P27 translational regulators - DKC1, RPS13, miR221, miR222 - or directly by DKC1 mutations.

Resistance exercise modulates lipid plasma profile and cytokine content in the adipose tissue of tumour-bearing rats.

Cancer cachexia is a multifactorial syndrome characterised by progressive weight loss, frequently accompanied by anorexia, sarcopenia, and chronic systemic inflammation. The white adipose tissue is markedly affected by cachexia and contributes to this syndrome throught the secretion of pro-inflammatory factors which reach the adjacent tissues and the circulation. A nonpharmacologic intervention that may attenuate cancer cachexia is chronic physical activity, but the effect of resistance training upon adipose tissue inflammation in cachexia has never been examined. For that purpose we designed a protocol in which animals were randomly assigned to a control group (CT, n=7), a Tumour bearing group (TB, n=7), a Resistance Trained group (RT, n=7) and a Resistance Trained tumour bearing group (RTTB, n=7). Trained rats climbed a vertical ladder with an extra load attached to the tail, representing 75-90% of total body mass, 3 times per week, for 8 weeks. In the 6 th week of resistance training, tumour cells (3 × 10(7) Walker 256 carcinosarcoma) were inoculated in the tumour groups. Body, adipose tissue, muscle and tumour mass was determined, as well a blood biochemical parameters, and the hormone and cytokine profile assessed. The glycogen content of the liver and muscle was measured. IL-10, IL-6 and TNF-α protein expression was evaluated in the mesenteric adipose tissue (MEAT) examined. Resistance training increased by 9% body weight gain in RTTB (final weight 310.8 ± 9.8 g), when compared with TB (final weight 288.3 ± 4.9 g). LDL-c levels were decreased in RTTB (0.28 ± 0.9 mmol/L) by 43% when compared with TB (0.57 ± 0.1 mmol/L). HDL-c levels were increased in RTTB (1.31 ± 0.12 mmol/L) by 15% in regard to CT (1.13 ± 0.7 mmol/L) and 22% as compared with TB (1.07 ± 0.07 mmol/L). RTTB testosterone levels (577 ± 131 ng/mL) were 55% higher when compared with CT (254 ± 41.3 ng/mL) and 63% higher when compared with TB (221 ± 23.1 ng/mL). Adiponectin levels were augmented in RT (23 µg/mL) by 43% when compared with TB (11 µg/mL). Protein expression of IL-6 was increased 38% in TB MEAT (5.95 pg/µg), as compared with CT (3.64 pg/µg) and 50% compared with RTTB (2.91 pg/µg). Similar results with respect to TNF-α TB (7.18 pg/µg) were observed: 39% and 46%, higher protein expression in comparison with CT (4.63 pg/µg) and RTTB (3.8 pg/µg), respectively. IL-10 protein expression was found to be increased in TB (4.4 pg/µg) and RTTB (3.2 pg/µg) 50% and 47%, respectively, in comparison with CT (1.2 pu/µg). The IL-10/TNF-α ratio was higher in RTTB in relation to all others experimental groups. The results show a robust effect of resistance exercise training in preventing important symptoms of cancer cachexia, thus strongly suggesting it may appear as an alternative to endurance exercise as a non-pharmacological therapy in the management of this syndrome.

Anesthetic-induced transient hyperglycemia and insulin resistance do not depend on the sympathoadrenal axis.

AIM: Glucose homeostasis is maintained under strict physiological control in which the central nervous system is very important. Ketamine/xylazine mixture induces hyperglycemia, although the mechanism involved is unknown. We aimed to study the role of sympathoadrenal axis on glycemia and insulinemia in adult rats. METHODS: NInety-day-old male Wistar rats were used. Half of the rats underwent removal of the adrenal gland medullae (adrenodemedullation, ADM). After overnight fasting, all rats were given the intravenous glucose tolerance test (ivGTT), which was performed in six groups: awake, ketamine/xylazine (KX) and thiopental (Thiop) anesthetized intact rats, and the same groups of ADM rats. The intraperitoneal insulin tolerance test (1U/kg BW) was performed in an additional animal group to record the rate constant of plasma glucose disappearance (Kitt). Tissue insulin sensitivity was also evaluated by the homeostasis model assessment (HOMA). RESULTS: Ketamine/xylazine increased basal glycemia by 110.6% (P<0.001) in intact rats. In the ADM group, KX rats had a reduction of 36.6% (P<0.05) basal glycemia. Thiop caused a decrease of 70.3% (P<0.05) in basal insulinemia in intact rats. ADM reduced fasting insulin in all groups. Insulin sensitivity was elevated in intact Thiop rats, while insulin resistance was observed in intact KX rats. Both anesthetics induced glucose intolerance during ivGTT in the intact group, but not in ADM rats. Insulin secretion was reduced for both anesthetics in intact and ADM rats. CONCLUSION: Sympathoadrenal axis activity is not involved with the hyperglycemia induced by thiopental or ketamine/xylazine.

Analysis of GATA1 mutations and leukemogenesis in newborns with Down syndrome.

It has been reported that patients with Down syndrome (DS) frequently develop transient myeloproliferative disorder (TMD) and less commonly myeloid leukemia in DS (ML-DS). We examined the pathogenetic relationship of these conditions with somatic mutations of the GATA1 gene in children with both TMD and ML-DS. To determine the incidence of GATA1 mutations in a cohort of DS patients and the applicability of these mutations as a clonal marker to detect minimal residual disease, we screened 198 samples of 169 patients with DS for mutations in GATA1 exon 2 by direct sequencing. Novel mutations were detected in four of the 169 DS patients (2 with TMD and 2 with ML-DS). We examined spontaneous remission and response to therapy in TMD and ML-DS patients and concluded that these mutations can be used as stable markers in PCR analysis to monitor these events.

Early exposure to a high-fat diet has more drastic consequences on metabolism compared with exposure during adulthood in rats.

The aim of this study was determine whether the introduction of a high-fat diet during the peripubertal phase induces significant changes in body weight control, glucose homeostasis and the parasympathetic tonus compared with the administration of this diet to adult rats. High-fat diet was offered to male Wistar rats at weaning or during adulthood. A group of rats received high-fat diet for 60 days, from weaning to 81-day-old (HF81) or from 60 to 120-day-old (HF120), whereas 2 other groups received a normal-fat diet (i. e., NF81 and NF120). We analyzed adiposity, glucose homeostasis, insulin sensitivity, and vagal nerve activity. High-fat diet increased the accumulation of adipose tissue in all of the rats, but the difference was greater in the rats that were fed the high-fat diet since weaning (p<0.001). The HF rats showed glucose intolerance with high levels of insulin secretion during the glucose tolerance test (p<0.01). Rats that were fed the high-fat diet presented severe insulin resistance, indicated by a low K itt (p<0.01). Interestingly, the HF81 rats exhibited greater insulin resistance compared with the HF120 rats (p<0.05). The recordings of vagus nerve activity showed that the HF rats had higher parasympathetic activity than the NF rats irrespective of age (p<0.01). Our results show that a high-fat diet offered to rats just after weaning or in adulthood both cause impairment of glycemic homeostasis and imbalance in parasympathetic activity. Importantly, the consumption of high-fat diet immediately after weaning has more drastic consequences compared with the consumption of the same diet during adulthood.

Maternal morbidity and near miss in the community: findings from the 2006 Brazilian demographic health survey.

OBJECTIVE: To obtain an estimate of the prevalence of potentially life-threatening maternal conditions and near-miss events in Brazil, and to explore the factors associated with these complications. DESIGN: A demographic health survey (DHS) focusing on reported maternal complications. SETTING: Data from the five geographical regions of Brazil. POPULATION: A total of 5025 women with at least one live birth in the 5-year reference period preceding their interview in the DHS. METHODS: A secondary analysis of the 2006 Brazilian DHS database was carried out using a validated questionnaire to evaluate the occurrence of maternal complications and related key interventions. According to a pragmatic definition, any woman reporting the occurrence of eclampsia, hysterectomy, blood transfusion or admission to the intensive care unit was considered as having experienced a near-miss event. Associations between the sociodemographic characteristics of the women and severe maternal morbidity were evaluated. MAIN OUTCOME MEASURES: Proportions and ratios of complications and related interventions defined as maternal near miss in pregnancy, and estimated risk factors for maternal morbidities. RESULTS: Around 22% of women reported complications during pregnancy. The prevalence of maternal near miss in Brazil, using the pragmatic definition, was 21.1 per 1000 live births. An increased risk of severe maternal morbidity was found in women aged ≥40 years and in those with low levels of education. CONCLUSIONS: Nearly 70,000 maternal near-miss cases and approximately 750,000 cases with potentially life-threatening conditions are estimated to occur in Brazil per year. A pragmatic definition of maternal near miss was useful to obtain more reliable information at the community level. This approach could be used to gather information on maternal morbidity in settings in which such data are not routinely collected.

Longitudinal Study of Foraging Networks in the Grass-Cutting Ant Atta capiguara Gonçalves, 1944.

Colonies of leaf-cutting ants of the genus Atta need to collect large quantities of vegetal substrate in their environment to ensure their growth. They do so by building and extending over time a foraging network that consists of several underground tunnels extending above ground by physical trails. This paper presents a longitudinal study of the foraging network of two mature colonies of the grass-cutting ant Atta capiguara (Gonçalves) located in a pasture in central Brazil. Specifically, we investigated whether the extension of the foraging area of the colonies required to reach new resources occurs by building new and longer underground tunnels or by building new and longer physical trails. Each nest was surveyed at intervals of approximately 15 days during 1 year. At each survey we mapped the position of the tunnel entrances and foraging trails at which activity was observed. In addition, we assessed the excavation effort of the colonies since the last survey by the number and distance to the nest of new tunnel entrances, and the physical trail construction effort by the number and length of newly built physical trails. Our study reveals that in A. capiguara the collection of new resources around the nest required to ensure the continuous growth of the colonies is achieved mainly through the excavation of new underground tunnels, opening at greater distance from the nest, not through the building of longer aboveground physical trails.

Fat-Soluble Substance Flow During Symbiotic Fungus Cultivation by Leaf-Cutter Ants.

Leaf-cutter ants perform a series of specialized behaviors in preparing plant substrates for their symbiotic fungus. This process may be related to contamination of workers by substances such as insecticides, leading us to hypothesize that substances are spread among workers through behaviors they perform to grow the fungus. To test this hypothesis, we analyzed the behavioral acts of workers during the processing of the pellets by using a fat-soluble tracing dye, since the active ingredient that composes toxic baits, used for control of leaf-cutter ants, is fat-soluble. The frequencies of performed behaviors were recorded and the number of dyed workers was assessed after fungus cultivation. The most frequent behavior is allogrooming and corresponds to 45.87% of the contamination process in workers, followed by holding, licking, and cutting pellets, which account for 40.22% of the process. After pellet processing, the workers had their external and internal morphological structures marked by the tracing dye-93.75% and 79.25%, respectively. These results confirm that behaviors performed during fungus cultivation contribute to dispersing substances such as insecticides, causing the contamination of workers.

Do Workers from Subspecies Acromyrmex subterraneus Prepare Leaves and Toxic Baits in Similar Ways for Their Fungus Garden?

Toxic baits are the most efficient method to control leaf-cutter ants in eucalyptus forests for paper and cellulose production. For the proper use of these baits, insecticide compounds must reach workers and contaminate them. Thus, understanding how these baits are processed inside the nests is vital for a successful control, especially when it comes to genus Acromyrmex. Lack of information on toxic baits and on contamination of Acromyrmex workers raises the question: do workers from subspecies Acromyrmex subterraneus (Forel) prepare leaves and toxic baits in similar ways for their fungus garden? To answer it, this study described and analyzed the behavioral repertoire executed by A. subterraneus workers during the preparation of leaf disks and baits and their incorporation into the fungus garden. Results show that the act of licking the substrate was the most frequently executed behavior, regardless of subspecies or size categories. Moreover, additional behaviors have been observed when workers processed the baits, such as licking and scraping their jaws on the surface of the bait pellet, as well as licking and biting fragments of bait pellets, moistening them. Thus, it is concluded that the preparation of baits is different from that of leaves; baits are more processed and can therefore contribute to contaminating workers via insecticides.

Mucosal leishmaniasis: description of case management approaches and analysis of risk factors for treatment failure in a cohort of 140 patients in Brazil.

BACKGROUND: Mucosal leishmaniasis is caused mainly by Leishmania braziliensis and it occurs months or years after cutaneous lesions. This progressive disease destroys cartilages and osseous structures from face, pharynx and larynx. OBJECTIVE AND METHODS: The aim of this study was to analyse the significance of clinical and epidemiological findings, diagnosis and treatment with the outcome and recurrence of mucosal leishmaniasis through binary logistic regression model from 140 patients with mucosal leishmaniasis from a Brazilian centre. RESULTS: The median age of patients was 57.5 and systemic arterial hypertension was the most prevalent secondary disease found in patients with mucosal leishmaniasis (43%). Diabetes, chronic nephropathy and viral hepatitis, allergy and coagulopathy were found in less than 10% of patients. Human immunodeficiency virus (HIV) infection was found in 7 of 140 patients (5%). Rhinorrhea (47%) and epistaxis (75%) were the most common symptoms. N-methyl-glucamine showed a cure rate of 91% and recurrence of 22%. Pentamidine showed a similar rate of cure (91%) and recurrence (25%). Fifteen patients received itraconazole with a cure rate of 73% and recurrence of 18%. Amphotericin B was the drug used in 30 patients with 82% of response with a recurrence rate of 7%. The binary logistic regression analysis demonstrated that systemic arterial hypertension and HIV infection were associated with failure of the treatment (P < 0.05). CONCLUSION: The current first-line mucosal leishmaniasis therapy shows an adequate cure but later recurrence. HIV infection and systemic arterial hypertension should be investigated before start the treatment of mucosal leishmaniasis. Conflicts of interest The authors are not part of any associations or commercial relationships that might represent conflicts of interest in the writing of this study (e.g. pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).

Contamination Route of Leaf-Cutting Worker Ants Analyzed Through a Fat-Soluble Tracer Dye in Toxic Bait.

Our study seeks to discover contamination routes of leaf-cutting worker ants during chemical control by formicide baits. To do so, toxic baits containing fat-soluble tracer dye were provided to colonies of three subspecies of Acromyrmex under laboratory conditions, in order to assess the proportion of dyed workers by size category, as well as dyed internal morphological structures. Results showed that nearly 50% of the workers come into contact with the active ingredient, since the internal structures of their bodies are dyed by the fat-soluble tracer dye within the first 24 h from contact with the toxic bait. In addition, the three subspecies of leaf-cutting ants present a similarity as to the contamination of their workers, probably due to their specialized behavior performed during the growth of the fungus garden with the baits. We conclude that the workers' pattern of behavior during fungus garden growth was the main means for dispersion of a fat-soluble substance among approximately half of the nest mates in our experiments, serving as a model for further studies on contamination of worker ants with insecticides.

Congenital hypothyroid goiter with deficient thyroglobulin. Identification of an endoplasmic reticulum storage disease with induction of molecular chaperones.

Recent advances in understanding the molecular pathogenesis of congenital hypothyroid goiter in cog/cog mice, have raised important questions concerning the maturation of thyroglobulin (the thyroid prohormone) in certain human kindreds with congenital goiter. We have now examined affected siblings from two unrelated families that synthesize an apparently normally glycosylated, > 300 kD immunoreactive thyroglobulin, yet have a reduced quantity of intraglandular thyroglobulin and that secreted into the circulation. From thyroid tissues of the four patients, light microscopic approaches demonstrated presence of intracellular thyroglobulin despite its absence in thyroid follicle lumina, while electron microscopy indicated abnormal distention of the endoplasmic reticulum (ER). We have confirmed biochemically that most intrathyroidal thyroglobulin fails to reach the (Golgi) compartment where complex carbohydrate modification takes place. Moreover, the disease in the affected patients is associated with massive induction of specific ER molecular chaperones including the hsp90 homolog, GRP94, and the hsp70 homolog, BiP. The data suggest that these patients synthesize a mutant thyroglobulin which is defective for folding/assembly, leading to a markedly reduced ability to export the protein from the ER. Thus, these kindreds suffer from a thyroid ER storage disease, a cell biological defect phenotypically indistinguishable from that found in cog/cog mice.

Effects of extremely low frequency electromagnetic fields on in-vitro cellular cultures HeLa and CHO.

This paper presents the cellular proliferation effects of the exposure to extremely low frequency electromagnetic fields (ELF-EMF) on in-vitro cellular cultures HeLa and CHO. Through the magnetic stimulation system (MSS) the cells were exposed to magnetic fields with sinusoidal waveform at 50 Hz; initially for 40 minutes at intensities of 0.4 mT, 1.4 mT, 2.13 mT, 2.49 mT and 2.53 mT in parallel and perpendicular directions to the culture plates. Subsequently, the repetitive electromagnetic field (rEMF) was applied to 2.49 mT in parallel direction (for 40 minutes every twelve hours during 4 days) with which the highest cellular proliferation rate was obtained at 66.6 %. The results show a greater effect on proliferation in radiated cell lines, particularly in the application of rEMF a greater effect of ELF-EMF was observed in the proliferation rate of HeLa cells than in CHO cells, in contrast to the respective control cells. These results supported by other studies serve as a reference in the search for alternatives for the treatment of cervical cancer and the maintenance and preservation of cell lines.

Mechanical behavior of a Y-TZP ceramic for monolithic restorations: effect of grinding and low-temperature aging.

This study aimed to investigate the effects of grinding with diamond burs and low-temperature aging on the mechanical behavior (biaxial flexural strength and structural reliability), surface topography, and phase transformation of a Y-TZP ceramic for monolithic dental restorations. Disc-shaped specimens (Zirlux FC, Ivoclar Vivadent) were manufactured according to ISO 6872 (2008) and divided in accordance with two factors: "grinding - 3 levels" and "LTD - 2 levels". Grinding was performed using a contra-angle handpiece under constant water-cooling with different grit-sizes (extra-fine and coarse diamond burs). LTD was simulated in an autoclave at 134°C, under a pressure of 2 bar, over a period of 20h. Surface topography analysis showed an increase in roughness based on surface treatment grit-size (Coarse>Xfine>Ctrl), LTD did not influence roughness values. Both grinding and LTD promoted an increase in the amount of m-phase, although different susceptibilities to degradation were observed. According to existing literature the increase of m-phase content is a direct indicative of Y-TZP degradation. Weibull analysis showed an increase in characteristic strength after grinding (Coarse=Xfine>Ctrl), while for LTD, distinct effects were observed (Ctrl