Variation in primary health care services after implementation of quality improvement policy in Brazil.

BACKGROUND: Brazil is the most populous country with a public, universal and free health care system. The National Program for Access and Quality Improvement in Primary Care (PMAQ) was created to improve the quality of primary health care (PHC). OBJECTIVE: To evaluated whether progress generally has been made within Brazil's PHC since PMAQ implementation, and if changes occurred uniformly in the country, while also identifying municipal characteristics that may have influenced the improvement. METHODS: This is an observational study using data from PMAQ external evaluation (2012 and 2014), a 1200-item survey used to evaluate Brazilian PHC quality. After confirming the groupings of items using factor analysis, we created 23 composed indexes (CIs) related to infrastructure and work process. RESULTS: On average, the large majority of CIs showed improvements between 2012 and 2014. Region and city size moderated changes in the PHC indices differently. Overall, there were better improvements in infrastructure in the Northeast compared with other country regions, and in smaller cities (10 000-20 000 people). Infrastructure indices appear to have improved equitably across the country. Work process improvements varied with city size and region. CONCLUSION: Despite similar support of PMAQ across the country, improvements are not predictable nor homogeneous. Non-uniform improvements were seen in Brazil's PHC. Though we do not directly evaluate the effectiveness of the PMAQ (financial reward) method, these initial findings suggest that it is a potentially useful tool to improve health systems, but additional support may be needed in regions that lag behind in quality improvements.

Cinnamyl Schiff bases: synthesis, cytotoxic effects and antifungal activity of clinical interest.

The aim of this study was to synthesize and investigate the in vitro antifungal properties of 23 cinnamyl Schiff bases. In addition, cytotoxic effects of such cinnamyl Schiff bases against human lung, kidney or red blood cells were also checked. The compounds were synthesized in a single-step, 2 min of reaction under microwave irradiation produced up to 97% yield. Six of the 23 cinnamyl Schiff bases possessed antifungal activities against strains of Candida, Aspergillus, Fonsecaea and, particularly, Cryptococcus species. Indeed, cinnamyl Schiff bases 1 and 23 exhibited minimum inhibitory concentration (MIC) values more than twofold lower than fluconazole (FCZ) against all the Cryptococcus neoformans strains (MIC = 1·33, 1·4 and 5·2 µg ml-1 , respectively) and Cryptococcus gattii strains (MIC = 5·3, 2·8 and 9·2 µg ml-1 , respectively) (12 strains of each species) while cinnamyl Schiff base 11 was as potent as FCZ against all strains from both Cryptococcus species. No significant cytotoxic effects were observed for Schiff bases against human lung, kidney or red blood cells, all presenting selective indexes higher than 10. In conclusion, this study revealed cinnamyl Schiff bases, especially 1 and 23, as new lead anticryptococcal agents for the discovery of novel antifungal drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The occurrence and severity of fungal infections have increased in recent decades due to resistance to available antifungal drugs and the appearance of new emerging pathogens. Thus, the search for new antifungal agents is mandatory. From a series of 23 cinnamyl Schiff bases, two compounds (1 and 23) were interrogated as new anticryptococcal agents without significant cytotoxicity against human lung, kidney or red blood cells. In turns, these new Schiff bases are lead compounds for the discovery of novel antifungal drugs.

Genome-wide association studies for heat stress response in Bos taurus × Bos indicus crossbred cattle.

Heat stress is an important issue in the global dairy industry. In tropical areas, an alternative to overcome heat stress is the use of crossbred animals or synthetic breeds, such as the Girolando. In this study, we performed a genome-wide association study (GWAS) and post-GWAS analyses for heat stress in an experimental Gir × Holstein F2 population. Rectal temperature (RT) was measured in heat-stressed F2 animals, and the variation between 2 consecutive RT measurements (ΔRT) was used as the dependent variable. Illumina BovineSNP50v1 BeadChip (Illumina Inc., San Diego, CA) and single-SNP approach were used for GWAS. Post-GWAS analyses were performed by gene ontology terms enrichment and gene-transcription factor (TF) networks, generated from enriched TF. The breed origin of marker alleles in the F2 population was assigned using the breed of origin of alleles (BOA) approach. Heritability and repeatability estimates (± standard error) for ΔRT were 0.13 ± 0.08 and 0.29 ± 0.06, respectively. Association analysis revealed 6 SNP significantly associated with ΔRT. Genes involved with biological processes in response to heat stress effects (LIF, OSM, TXNRD2, and DGCR8) were identified as putative candidate genes. After performing the BOA approach, the 10% of F2 animals with the lowest breeding values for ΔRT were classified as low-ΔRT, and the 10% with the highest breeding values for ΔRT were classified as high-ΔRT. On average, 49.4% of low-ΔRT animals had 2 alleles from the Holstein breed (HH), and 39% had both alleles from the Gir breed (GG). In high-ΔRT animals, the average proportion of animals for HH and GG were 1.4 and 50.2%, respectively. This study allowed the identification of candidate genes for ΔRT in Gir × Holstein crossbred animals. According to the BOA approach, Holstein breed alleles could be associated with better response to heat stress effects, which could be explained by the fact that Holstein animals are more affected by heat stress than Gir animals and thus require a genetic architecture to defend the body from the deleterious effects of heat stress. Future studies can provide further knowledge to uncover the genetic architecture underlying heat stress in crossbred cattle.

Genome-wide association studies for tick resistance in Bos taurus × Bos indicus crossbred cattle: A deeper look into this intricate mechanism.

Rhipicephalus (Boophilus) microplus is the main cattle ectoparasite in tropical areas. Gir × Holstein crossbred cows are well adapted to different production systems in Brazil. In this context, we performed genome-wide association study (GWAS) and post-GWAS analyses for R. microplus resistance in an experimental Gir × Holstein F2 population. Single nucleotide polymorphisms (SNP) identified in GWAS were used to build gene networks and to investigate the breed of origin for its alleles. Tick artificial infestations were performed during the dry and rainy seasons. Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA) and single-step BLUP procedure was used for GWAS. Post-GWAS analyses were performed by gene ontology terms enrichment and gene transcription factors networks, generated from enriched transcription factors, identified from the promoter sequences of selected gene sets. The genetic origin of marker alleles in the F2 population was assigned using the breed of origin of alleles approach. Heritability estimates for tick counts were 0.40 ± 0.11 in the rainy season and 0.54 ± 0.11 in the dry season. The top ten 0.5-Mbp windows with the highest percentage of genetic variance explained by SNP markers were found in chromosomes 10 and 23 for both the dry and rainy seasons. Gene network analyses allowed the identification of genes involved with biological processes relevant to immune system functions (TREM1, TREM2, and CD83). Gene-transcription factors network allowed the identification of genes involved with immune functions (MYO5A, TREML1, and PRSS16). In resistant animals, the average proportion of animals showing significant SNPs with paternal and maternal alleles originated from Gir breed was 44.8% whereas the proportion of animals with both paternal and maternal alleles originated from Holstein breed was 11.3%. Susceptible animals showing both paternal and maternal alleles originated from Holstein breed represented 44.6% on average, whereas both paternal and maternal alleles originated from Gir breed animals represented 9.3%. This study allowed us to identify candidate genes for tick resistance in Gir × Holstein crossbreds in both rainy and dry seasons. According to the origin of alleles analysis, we found that most animals classified as resistant showed 2 alleles from Gir breed, while the susceptible ones showed alleles from Holstein. Based on these results, the identified genes may be thoroughly investigated in additional experiments aiming to validate their effects on tick resistance phenotype in cattle.

Curcumin enhances the activity of fluconazole against Cryptococcus gattii-induced cryptococcosis infection in mice.

AIM: The aim of this study was to investigate the in vitro and in vivo activities of pure curcumin, as well as its combination with fluconazole, against Cryptococcus gattii. METHODS AND RESULTS: The minimal inhibitory concentrations (MIC) of curcumin and its interactions with fluconazole against C. gattii were assessed in vitro using standard methods. This same combination was used to treat C. gattii-induced cryptococcosis in mice. The behavioural and functional assessment of the mice during treatment was also performed. The average MIC for curcumin was 19·8 µg ml(-1) . Its combination with fluconazole resulted in FICΣ (fractional inhibitory concentration index) values between 0·79 and 2·29. Curcumin (alone or combined with fluconazole) significantly reduced pulmonary damage and fungal burden in the brain. No colonies were found in the brain following combination treatment, which was also confirmed by the improved behaviour of mice. CONCLUSIONS: The combination therapy with curcumin and fluconazole was the most effective among the treatments tested, as in addition to reducing the fungal burden and damage on lung tissues, it was able to eliminate the fungal burden in the brain, enhancing the survival of mice. SIGNIFICANCE AND IMPACT OF THE STUDY: This study points to the possibility of using curcumin in combination with fluconazole as a clinical treatment of cryptococcosis.

Total Fluoride Intake by Children from a Tropical Brazilian City.

The main sources of fluoride intake by children are fluoridated water and toothpaste. Little has been studied regarding fluoride intake from these sources in regions with tropical climates and high temperatures throughout the year. This study aimed to determine the amount of fluoride ingested from diet and tooth brushing by children who live in a city with a tropical climate. Sixty-seven children from Teresina, Piauí, Brazil, took part in this study. The city's water supply was optimally fluoridated. The duplicate-diet method was used to determine the fluoride intake from diet. The intake of fluoride from dentifrice was determined by subtracting the amount of fluoride placed on the toothbrush and that recovered after brushing. The concentration of fluoride was measured using an ion-specific electrode and is expressed as milligrams/kilogram of body weight/day. The mean (±SD) total amount was 0.071 ± 0.036 mg F/kg body weight/day, and the relative contributions of diet and toothpaste were 0.025 ± 0.010 and 0.046 ± 0.035, respectively. The factors associated with fluoride intake from toothpaste were: use of children's toothpaste (p = 0.003), use of large amounts of toothpaste (p < 0.001), and a high frequency of tooth brushing (p = 0.003). Sixty-four percent of children had an intake of less than 0.07 mg F/kg body weight/day, which is considered the upper limit for an aesthetically tolerable fluorosis risk. The results suggest that the amount of fluoride ingested by most children who live in a Brazilian city with a tropical climate is considered safe in terms of the risk of dental fluorosis.

Hydroxyaldimines as potent in vitro anticryptococcal agents.

UNLABELLED: Cryptococcosis, a fungal infection that affects both immunocompromised and immunocompetent individuals, contributes to increasing indices of mortality and morbidity. The development of resistance by Cryptococcus spp., the limited number of commercial antifungal drugs and the various side effects of these drugs cause the treatment of cryptococcosis to be a challenge. The in vitro anticryptococcal activity of nine hydroxyaldimines was evaluated against 24 strains of Cryptococcus spp. Antifungal susceptibility was evaluated using a broth microdilution assay following the Clinical and Laboratory Standards Institute guidelines, using fluconazole as a positive control. Parameters such as the minimum inhibitory concentration and the minimum fungicidal concentration (MIC and MFC, respectively) were also determined. Antiproliferative activity on the normal cell line VERO was assessed 48 h post-compound exposure to determine the selectivity index (SI) of the hydroxyaldimines and fluconazole. All hydroxyaldimines were active against Cryptococcus spp. strains. Compounds 3A9 and 3B7 were the most potent against the Cryptococcus gattii and Cryptococcus neoformans strains. Selectivity indices also revealed that 3B10, 3C3, 3D3 and 3D9 are good candidates for in vivo studies. The in vitro anticryptococcal activity of hydroxyaldimines against various strains of C. gattii and C. neoformans indicates the potential of this class of molecules as lead compound for the development of selective and efficient anticryptococcal agents. SIGNIFICANCE AND IMPACT OF THE STUDY: The effectiveness of hydroxyaldimines for inhibition of Cryptococcus spp. growth and their low toxicity against healthy monkey kidney epithelial cells makes them promising lead compounds for the design of new anticryptococcal agents.

Coordination of thiosemicarbazones and bis(thiosemicarbazones) to bismuth(III) as a strategy for the design of metal-based antibacterial agents.

Complexes [Bi(2Fo4Ph)Cl(2)] (1), [Bi(2Ac4Ph)Cl(2)] (2), [Bi(2Bz4Ph)Cl(2)] (3), [Bi(H(2)Gy3DH)Cl(3)] (4), [Bi(H(2)Gy4Et)(OH)(2)Cl] (5), and [Bi(H(2)Gy4Ph)Cl(3)] (6) were prepared with pyridine-2-carbaldehyde 4-phenylthiosemicarbazone (H2Fo4Ph), 1-(pyridin-2-yl)ethanone 4-phenylthiosemicarbazone (H2Ac4Ph), phenyl(pyridin-2-yl)methanone 4-phenylthiosemicarbazone (H2Bz4Ph), as well as with glyoxaldehyde bis(thiosemicarbazone) (H(2)Gy4DH) and its 4-Et (H(2)Gy4Et) and 4-Ph (H(2)Gy4Ph) derivatives. The complexes exhibited antibacterial activities against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Pseudomonas aeruginosa. Coordination to Bi(III) proved to be an effective strategy to increase the antibacterial activity of the thiosemicarbazones and bis(thiosemicarbazones).

[Prevalence of grade retention and associated factors among adolescents from the 1993 Pelotas, Brazil, birth cohort]. / Prevalência de retenção escolar e fatores associados em adolescentes da coorte de nascimentos de 1993 em Pelotas, Brasil.

OBJECTIVE: To evaluate the occurrence of grade retention until 11 years of age and the factors associated with retention. METHODS: This prospective study included 4 452 adolescents from the 1993 city of Pelotas birth cohort (state of Rio Grande do Sul, Brazil). This sample represents 87.5% of the original cohort. Grade retention was defined as the repetition of at least one school grade until the date of the interview. The following independent variables were analyzed: sex, skin color, birth weight, ownership of goods, age, maternal schooling, type of school (private, state, or city), age at school entry, and employment. RESULTS: The overall frequency of grade retention was 36.3%, vs. 42.8% for boys and 30.0% for girls. The adjusted analysis showed that the lower the level of maternal schooling, ownership of goods, and birth weight, the higher the risk of grade retention for both boys and girls. Black/brown adolescents, those studying in public schools, and those who were 7 years of age or older at school entry had a higher risk of grade retention. For boys, childhood labor was associated with grade retention. CONCLUSIONS: Low socioeconomic and low maternal schooling levels were the factors most strongly associated with grade retention. Strategies to reduce this situation must take into account demographic and socioeconomic characteristics.

Curcumin as a promising antifungal of clinical interest.

OBJECTIVES: The antifungal activity of curcumin was evaluated against 23 fungi strains and its in vitro inhibitory effect on the adhesion of Candida species to human buccal epithelial cells (BEC) was also investigated. METHODS: The antifungal susceptibility was evaluated by broth microdilution assay following the CLSI (formerly the NCCLS) guidelines. The inhibitory effect of curcumin on the cell adhesion was performed with Candida species and BEC. RESULTS: Paracoccidioides brasiliensis isolates were the most susceptible to curcumin while the growth of Aspergillus isolates was not affected. Curcumin was much more efficient than fluconazole in inhibiting the adhesion of Candida species to BEC, particularly those strains isolated from the buccal mucosa of AIDS patients. CONCLUSIONS: The lack of antifungal compounds with reduced side effects highlights the importance of studying natural products for this purpose. Curcumin was a more potent antifungal than fluconazole against P. brasiliensis, the causal agent of the neglected disease paracoccidioidomycosis. Curcumin dramatically inhibited the adhesion of Candida species isolated from AIDS patients to BEC, demonstrating that curcumin is a promising lead compound that warrants further investigation into its therapeutical use in immunocompromised patients.

In vitro studies of anticandidal activity of goniothalamin enantiomers.

AIMS: The antifungal activity of (R)-goniothalamin (1) and (S)-goniothalamin (ent-1) was evaluated against six Candida species. The in vitro effect of these compounds on yeast adhesion to human buccal epithelial cells (BEC) and Candida albicans and C. dubliniensis biofilms progression were also investigated. METHODS AND RESULTS: Yeast susceptibility was evaluated by broth microdilution assay and showed that ent-1 exhibited higher potency against all fungal clinical isolated when compared to compound 1. Compounds 1 and ent-1 were as potent as fluconazole in inhibiting the adhesion of C. albicans and C. dubliniensis to BEC. XTT-reducing assay and scanning electron microscopy revealed that 1 and ent-1 were twice as potent as fluconazole in the inhibition of yeast biofilms progression. CONCLUSIONS: Our findings indicate that compounds 1 and ent-1 are potent anticandidal agents. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights goniothalamin enantiomers as promising lead compounds for the design of new antifungal with inhibitory activity on yeast adhesion and biofilm progression.

Evolution of X-ray machine quality control acceptance indices.

The quality assurance (QA) of radiographic images based on the operating conditions of X-ray equipment is essential for good image quality, accurate medical diagnostics and for the prevention of health professionals and patients to unnecessary doses of ionizing radiation. This paper presents a historical analysis of 1,635 Quality Assurance Technical Reports of Health Institutions in the state of São Paulo, Brazil, over a seven-year period. Based on acceptable limits for variations between nominal and measured parameters as the variable to determine the quality of X-ray equipment operating conditions, a significant improvement was found in the percentage of acceptance of the overall parameters described in the QA technical reports over this period. As expected, we found a strong concentration in the categories of conventional and portable X-ray equipment, which represent 72% and 84%, respectively, of the total number of equipments. A mechanical parameter such as half-value layer (HVL), which is important not only for image quality but also for radiation protection, showed significant improvements. Again, only 58% of portable X-ray equipment showed HVL values recommended for 80 kVp (above 2.3 mm Al), a percentage that improved to 76% in 2006. With regard to mammographers, which are newer machines, all the analyzed systems presented acceptable HVL values. Conventional X-ray machines showed an increase of this conformity index from 89% in 2000 to 94% in 2006. All this improvement was attributed to the continuous and extensive enforcement of Regulation Act 453 in the state of São Paulo. The improvement in equipment quality control standards is expected to result in the improvement of diagnostic quality, as well as in the reduction of exam repetitions, and thereby reducing the patient's exposure to radiation.

First report of Meloidogyne graminis on golf courses turfgrass in Brazil.

Plant-parasitic nematodes of the genus Meloidogyne, known as root-knot nematodes (RKN), have an important economic impact on golf course turfgrasses. The most prevalent RKN species associated with grasses are M. chitwoodi, M. graminicola, M. graminis, M. incognita, M. marylandi, M. microtyla, M. minor, M. naasi and M. sasseri. In 2010, slight thickening of the roots and RKN females with unusual features were observed in turfgrass roots on golf courses in Araras, São Paulo state, Brazil. This population (MgARA) was maintained in the lab and studied including morphological, morphometrical, biochemical and molecular markers. Morphology and morphometry were variable and not useful for identification, although perineal pattern morphology showed highly similarity with M. graminis description. Concerning to biochemical characterisation, the esterase phenotype Mg1, characterised by a very slow and fainter band, was detected in some protein homogenates. Regarding to molecular analysis, D2-D3 region of 28S rDNA gene and cytochrome oxidase subunit II region from mitochondrial DNA were amplified by PCR and sequenced. Phylogenetic analysis revealed that the Brazilian isolate, found associated with turfgrass, grouped with M. graminis isolates (98-99% bootstrap; variation of 8-11 and 0-24 bp, respectively), close to M. marylandi, supporting its identification as M. graminis. This is the first report of M. graminis on golf courses in Brazil.

AIDS mortality, "race or color", and social inequality in a context of universal access to highly active antiretroviral therapy (HAART) in Brazil, 1999-2004.

Highly active antiretroviral therapy (HAART) has led to a substantial increase in the survival of people living with AIDS, despite heterogeneities among individuals from different socioeconomic strata. The present paper analyzes AIDS deaths in Brazil during a period in which HAART became a key treatment regimen, exploring the hypothesis that "race or color" defines one dimension of socioeconomic inequality in Brazil. AIDS mortality, stratified by gender and "race or color", was calculated using data from the National Mortality System. The rates were highest among individuals classified as "black" and lower among those classified as "mixed-race", with a continuous increase among the later from 1999 to 2004 for men and women. Among individuals classified as "white", mortality rates remained stable among men, but not women. Median age at death among "mixed-race" individuals was lower for both men and women. Differential trends according to gender and "race or color" were highlighted by the present study, indicating the pressing need to further explore the underlying factors that might explain different mortality rates in a context of universal access.

Styryl lactones and their derivatives: biological activities, mechanisms of action and potential leads for drug design.

Nature is an inexhaustible source of natural compounds with interesting biological activities. In general, natural products are an important source of new compounds with a variety of structural arrangements and singular properties. Styryl lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess interesting biological properties, in particular antiproliferative activity against cancer cells. In general, the cytotoxicity of styryl lactones appears to be specific against cancer cells since insignificant effects of these compounds on normal cells are reported. A large body of evidence suggests that the antiproliferative activity of styryl lactones is associated with the induction of apoptosis in target cells. In the first part of this review we discuss the biological activities of styryl lactones focusing on cancer cells, the causal agent of Chagas' disease and the vectors for yellow fever and human lymphatic filariasis. Stru described in detail for ninety styryl lactones. The last part describes the molecular targets of styryl lactones for inducing apoptosis, as well as immunosuppressive and inflammatory processes. Overall, understanding how these compounds exert their activities in biological system is essential for future development and application of styryl lactones for human health.

[Food insecurity perception in families with elderly in Campinas, São Paulo, Brazil]. / A percepção de insegurança alimentar em famílias com idosos em Campinas, São Paulo, Brasil.

The aim of this study was to determine the prevalence of food insecurity (FI) in families with elderly members and to describe their socio-demographic profile. The study focused on families with members aged 65 years or more (n = 195) participating in a household survey in Campinas, São Paulo, Brazil, in 2003. The Brazilian Food Insecurity Scale, an adaptation of the USDA FI module, was used to diagnose food security/insecurity (FS/FI). Mild FI was present in 33.0% of families, moderate in 11.8%, and severe in 7.2%. The elderly had no income in < 5.0% of the families. Families with FI, as in the United States, had a greater proportion of elderly with low income and low level of education (no schooling or incomplete primary schooling). A significantly higher proportion of daily qualitative food intake was observed in FS families (vegetables 92.3 vs. 61.8%; OR = 7.4; 95%CI: 2.9-19.6; meat 74.2 vs. 43.1%; OR = 3.8; 95%CI: 1.9-7.3; fruit 77.4 vs. 49.0%; OR = 3.6; 95%CI: 1.8-6.9). The elderly contribute to family income and thus do not pose a burden to their families.

Effects of Water-Based Training on Static and Dynamic Balance of Older Women.

OBJECTIVE: The aim of this study was to evaluate the effects of a water-based exercise program on static and dynamic balance. METHOD: Thirty-six older women were randomly assigned to a water-based training (3 days/week for 12 weeks) or control group. Water level was kept at the level of the xiphoid process and temperature at ∼28-30°C. Each session included aerobic activities and lower limb strength exercises. The medial-lateral, the anterior-posterior amplitude, and displacement of the center of pressure (CP-D) were measured in a quiet standing position (60 sec eyes opened and closed). The dynamic balance and 8-Foot Up-and-Go tests were also applied. Group comparisons were made using two-way analysis of variance (ANOVA) with repeated measures. RESULTS: No differences were found in the center of pressure variables; however, the WBT group showed better performance in the 8 Foot Up-and-Go Test after training (5.61±0.76 vs. 5.18±0.42; p<0.01). CONCLUSION: The water-based training was effective in improving dynamic balance, but not static balance.

Phenotypic and genotypic characterization of VanA Enterococcus isolated during the first nosocomial outbreak in Brazil.

We report the phenotypic and genotypic characterization of 50 VanA Enterococcus clinical isolates from infected patients and 97 isolates from colonized patients obtained during a nosocomial outbreak in a single hospital in São Paulo, Brazil during 1998. The identification of strains to the species level by conventional biochemical and phenotypic tests and by multiplex PCR assay had 100% agreement. Both E. faecalis and E. faecium were isolated from patients during this outbreak. The vanA genotype was confirmed by PCR. Antibiotic susceptibility testing showed that E. faecium isolates are generally less susceptible to antibiotics than E. faecalis. By PCR, 24 of 26 VRE strains tested carried the Tn1546 element. Pulsed-field gel electrophoresis identified five distinct patterns for E. faecalis (A, B, C, D, E) and three for E. faecium (M, N, and O). A single PFGE pattern was identified in the majority of strains of each species and does not discriminate between case and carrier isolates.

(S)-Goniothalamin induces DNA damage, apoptosis, and decrease in BIRC5 messenger RNA levels in NCI-H460 cells.

(R)-Goniothalamin (R-GNT) is a secondary metabolite isolated from the plants of the genus Goniothalamus. This molecule has attracted the attention of researchers because of its selective cytotoxicity against tumor cells and its ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic enantiomer of R-GNT, and its mechanism of action is largely unknown. In this study, we investigated the activity of S-GNT in a human non-small cell lung cancer NCI-H460 cells. We observed that the cells exposed to this compound exhibited cytotoxicity in a concentration-dependent manner. Based on the data obtained through the assessment of apoptosis induction in situ and the comet assay, we suggest that this cytotoxicity occurs due to the potential ability of this molecule to induce DNA damage with the consequent induction of cell death via apoptosis. A significant reduction in the messenger RNA levels of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene that encodes the survivin protein was found. This novel finding may explain the inhibition of cell proliferation and induction of apoptosis in tumor cells caused by this compound.

Long-lasting effects of undernutrition.

Undernutrition is one of the most important public health problems, affecting more than 900 million individuals around the World. It is responsible for the highest mortality rate in children and has long-lasting physiologic effects, including an increased susceptibility to fat accumulation mostly in the central region of the body, lower fat oxidation, lower resting and postprandial energy expenditure, insulin resistance in adulthood, hypertension, dyslipidaemia and a reduced capacity for manual work, among other impairments. Marked changes in the function of the autonomic nervous system have been described in undernourished experimental animals. Some of these effects seem to be epigenetic, passing on to the next generation. Undernutrition in children has been linked to poor mental development and school achievement as well as behavioural abnormalities. However, there is still a debate in the literature regarding whether some of these effects are permanent or reversible. Stunted children who had experienced catch-up growth had verbal vocabulary and quantitative test scores that did not differ from children who were not stunted. Children treated before 6 years of age in day-hospitals and who recovered in weight and height have normal body compositions, bone mineral densities and insulin production and sensitivity.