Tapping into Tapajos: antibacterial potential of fungal strains isolated from decaying wood in the Brazilian Amazon.

The emergence of bacterial resistance to antimicrobials poses a significant health threat. To address this issue, exploring the fungal diversity in freshwater environments in the Amazon Forest has potential in the search for new antimicrobials. This study aimed to investigate the production of antibacterial metabolites by aquatic fungi from Amazon lakes, specifically Lake Juá and Lake Maicá (Brazil-PA). The fungal isolates were obtained from wood fragments submerged in these lakes, and the ethyl acetate extracts were evaluated for antibacterial activity against Staphylococcus aureus ATCC 25923, S. aureus (MRSA), ATCC 43300, Escherichia coli ATCC 25922, and E. coli (ESBL) NCTC 13353. Additionally, toxicity of the extracts (EtOAc with antimicrobial activity) against human fibroblasts MRC-5 was investigated. The study identified 40 fungal strains with antimicrobial screening, and the ethyl acetate extracts of Fluviatispora C34, Helicascus C18, Monodictys C15, and Fusarium solani LM6281 exhibited antibacterial activity. F. solani LM6281 showed the lowest minimum inhibitory concentration (MIC) of 50 µg/mL against S. aureus strains and MIC of 100 µg/mL against E. coli strains including ESBL. The cytotoxicity (IC50) of the extract (EtOAc) of F. solani LM6281 was 34.5 µg/mL. Preliminary studies of the TLC culture and RNM-H from the extract (EtOAc) of F. solani suggested the presence of substances from the class of terpenes, quinones, phenolics, and flavonoids. This study highlights the potential of submerged wood fungi in the Amazon region to produce antibacterial substances, thus identifying them as sources of novel bioactive compounds with potential use in the pharmaceutical industry and regional bioeconomy.

Notes on the conservation threats to the western lesser spot-nosed monkey (Cercopithecus petaurista buettikoferi) in the Bijagós Archipelago (Guinea-Bissau, West Africa).

The lesser spot-nosed monkey (Cercopithecus petaurista) is a widely distributed West African guenon, which is generally considered less vulnerable to local extinctions than many sympatric primate species. Guinea-Bissau harbours the westernmost populations of the species, which is thought to be very rare or even extinct on the mainland, but to have putative populations on some islands of the Bijagós Archipelago. However, due to a lack of regional studies, baseline information on these insular populations is missing. We collected baseline data on the anthropogenic activities that possibly threaten the long-term conservation of this primate by using non-systematic ethnographic methodologies. The species was reported to be decreasing in number or rare by locals on two of the islands, and we identified two main conservation threats to it: generalised habitat loss/degradation, and hunting. While subsistence hunting has been recorded before in these areas, we report, to the best of our knowledge for the first time for these islands, the presence of a semi-organised commercial wild meat trade. The carcasses of western lesser spot-nosed monkeys were observed being stored and shipped from seaports to be sold at urban hubs (Bissau and Bubaque Island). The effect of commercial trade on the species could be severe, considering the small, naturally occurring, carrying capacities typical of insular ecosystems. The results of this study highlight the importance of understanding the leading social drivers of wild meat hunting of lesser spot-nosed monkeys on the Bijagós Archipelago, and the need to conduct baseline research on these insular populations, for which qualitative and quantitative methods could be combined.

A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe.

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety.

Utilising surface-level data to explore surface, tooth, individual and family influence on the aetiology of hypomineralised second primary molars.

OBJECTIVES: Hypomineralised second primary molars (HSPM) are common developmental enamel defects. The aims of this study were to use surface-level data to explore the clustering of HSPM at four levels (family, child, tooth, surface). METHODS: This study of 172 twin pairs was nested within the Peri/postnatal Epigenetic Twin Study. HSPM was measured by standardised oral examinations at age 6 years. Multilevel logistic regression models were fitted to assess the correlation structure of surface level data and variation in HSPM. The associations between surface level risk factors and HSPM were then explored using the multilevel logistic regression model using the best fitting correlation structure. RESULTS: The prevalence of HSPM was 68 (19.8%) children, with a total of 141 (10.3%) teeth and 264 tooth surfaces (6.3%) affected. Multilevel models revealed that a hierarchical structure accounting for correlation at the family, child and tooth level best accounted for the variation in HSPM. The estimated variances from the best fitting model (Model 3) were largest at the family level (12.27, 95% CI 6.68, 22.51) compared with 5.23 at the child level and 1.93 at the tooth level. Application of regression analysis utilising this three-level correlation structure identified tooth/surface level factors in addition to the previously identified familial and individual risk factors for HSPM. CONCLUSION: In addition to familial (environmental and genetic) and unique child-level factors, the aetiology of HSPM is likely to be influenced by local tooth-level factors.

Papel del bloqueo ecoguiado del plano del músculo serrato en el dolor neuropático crónico tras una cirugía de mama en una paciente de cáncer / The role of ultrasound guided serratus plane block on chronic neuropathic pain after breast surgery in cancer patient

Antecedentes: El cáncer de mama es el tipo de cáncer más frecuente entre las mujeres. Entre las secuelas de su tratamiento se encuentra el dolor neuropático crónico tras la cirugía de mama (CNPBS). El tratamiento del dolor es difícil y consiste normalmente en una terapia farmacológica aunque, sin embargo, los estudios recientes han defendido el uso de técnicas locorregionales como adyuvantes. El bloqueo del plano del músculo serrato (SPB) ha surgido recientemente como herramienta potencial para controlar el CNPBS. El objetivo de este estudio es evaluar la eficacia y papel potencial del SPB ecoguidado en el CNPBS. Métodos: Se realizó un análisis retrospectivo en 30 pacientes con CNPBS refractario a terapia farmacológica, sometidas a SPB entre 2017 y 2019. Se analizaron los parámetros siguientes: dolor basal, dolor a las 24 horas, una semana y un mes. Se aplicó la prueba de Mann-Whitney. Se consideró significación estadística al nivel de p < 0,05. Todos los análisis estadísticos se realizaron utilizando SPSS 20. Resultados: Tres pacientes fueron excluidas. Transcurridas 24 horas, reportamos mejora del dolor (al menos una reducción del 30% sobre la puntuación del dolor basal) en 20 pacientes, y en 12 transcurrida una semana. Al cabo de un mes, 22 pacientes habían experimentado mejora, de los cuales: 11 mejoraron sin ajuste terapéutico, 11 pacientes mejoraron con ajuste terapéutico (ocho con monoterapia de gabapentinoides, tres con introducción de politerapia), y cinco pacientes no experimentaron mejora. Conclusión: Nuestro estudio demostró que SPB es una alternativa válida para el tratamiento de CNPBS cuando la terapia farmacológica se ha mostrado insuficiente, no habiéndose reportado efectos secundarios. Son necesarios estudios aleatorios para evaluar la magnitud de SPB en CNPBS, e identificar a los pacientes que más se beneficiarían de SPB.(AU)

Background: Breast cancer is the most commonly occurring cancer among women. Among its treatment sequelae is chronic neuropathic pain after breast surgery (CNPBS). Pain management is difficult and classicaly consists in a pharmacological approach, however recent studies have advocated the use of locoregional techniques as adjuvants. Serratus plane block (SPB) has recently emerged as a potential tool for the control of CNPBS. This study aims to evaluate the efficacy and potencial role of the ultrasound-guided SPB on CNPBS. Methods: A retrospective analysis was performed on 30 patients with CNPBS refractory to drug therapy, who underwent SPB between 2017-2019. The following parameters were analyzed: basal pain, pain at 24 hours, 1 week and at 1 month. The Mann-Whitney test was applied. Statistical significance was considered at the level of p < 0.05. All statistical analysis was performed with SPSS 20. Results: 3 patients were excluded. At 24 hours, we report pain improvement (at least 30% reduction on basal pain score) on 20 patients and after 1 week on 12. At 1 month after, 22 patients had improved, from these: 11 improved with no therapeutic adjustment; 11 patients improved with therapeutic adjustment (8 in gabapentinoid monotherapy, 3 with introduction of polytherapy). 5 patients didn’t improve. Conclusión: Our study demonstrated SPB as a valid alternative for CNPBS management when pharmacologic therapy has been proven insufficient, with no side effects reported. Randomized studies are needed to assess the magnitude of SPB on CNPBS and to identify the patients who benefit the most from SPB.(AU)

The role of ultrasound guided serratus plane block on chronic neuropathic pain after breast surgery in cancer patient.

BACKGROUND: Breast cancer is the most commonly occurring cancer among women. Among its treatment sequelae is chronic neuropathic pain after breast surgery (CNPBS). Pain management is difficult and classicaly consists in a pharmacological approach, however recent studies have advocated the use of locoregional techniques as adjuvants. Serratus plane block (SPB) has recently emerged as a potential tool for the control of CNPBS. This study aims to evaluate the efficacy and potencial role of the ultrasound-guided SPB on CNPBS. METHODS: A retrospective analysis was performed on 30 patients with CNPBS refractory to drug therapy, who underwent SPB between 2017-2019. The following parameters were analyzed: basal pain, pain at 24 h, 1 week and at 1 month. The Mann-Whitney test was applied. Statistical significance was considered at the level of p < 0.05. All statistical analysis was performed with SPSS 20. RESULTS: 3 patients were excluded. At 24 h, we report pain improvement (at least 30% reduction on basal pain score) on 20 patients and after 1 week on 12. At 1 month after, 22 patients had improved, from these: 11 improved with no therapeutic adjustment; 11 patients improved with therapeutic adjustment (8 in gabapentinoid monotherapy, 3 with introduction of polytherapy). 5 patients didn't improve. CONCLUSION: Our study demonstrated SPB as a valid alternative for CNPBS management when pharmacologic therapy has been proven insufficient, with no side effects reported. Randomized studies are needed to assess the magnitude of SPB on CNPBS and to identify the patients who benefit the most from SPB.

The role of ultrasound guided serratus plane block on chronic neuropathic pain after breast surgery in cancer patient. / Papel del bloqueo ecoguiado del plano del músculo serrato en el dolor neuropático crónico tras una cirugía de mama en una paciente de cáncer.

BACKGROUND: Breast cancer is the most commonly occurring cancer among women. Among its treatment sequelae is chronic neuropathic pain after breast surgery (CNPBS). Pain management is difficult and classicaly consists in a pharmacological approach, however recent studies have advocated the use of locoregional techniques as adjuvants. Serratus plane block (SPB) has recently emerged as a potential tool for the control of CNPBS. This study aims to evaluate the efficacy and potencial role of the ultrasound-guided SPB on CNPBS. METHODS: A retrospective analysis was performed on 30 patients with CNPBS refractory to drug therapy, who underwent SPB between 2017-2019. The following parameters were analyzed: basal pain, pain at 24 hours, 1 week and at 1 month. The Mann-Whitney test was applied. Statistical significance was considered at the level of p < 0.05. All statistical analysis was performed with SPSS 20. RESULTS: 3 patients were excluded. At 24 hours, we report pain improvement (at least 30% reduction on basal pain score) on 20 patients and after 1 week on 12. At 1 month after, 22 patients had improved, from these: 11 improved with no therapeutic adjustment; 11 patients improved with therapeutic adjustment (8 in gabapentinoid monotherapy, 3 with introduction of polytherapy). 5 patients didn't improve. CONCLUSIóN: Our study demonstrated SPB as a valid alternative for CNPBS management when pharmacologic therapy has been proven insufficient, with no side effects reported. Randomized studies are needed to assess the magnitude of SPB on CNPBS and to identify the patients who benefit the most from SPB.

NF-κB-mediated effects on behavior and cartilage pathology in a non-invasive loading model of post-traumatic osteoarthritis.

OBJECTIVE: This study aimed to examine the temporal activation of NF-κB and its relationship to the development of pain-related sensitivity and behavioral changes in a non-invasive murine knee loading model of PTOA. METHOD: Following knee injury NF-κB activity was assessed longitudinally via in vivo imaging in FVB. Cg-Tg (HIV-EGFP,luc)8Tsb/J mice. Measures of pain-related sensitivity and behavior were also assessed longitudinally for 16 weeks. Additionally, we antagonized NF-κB signaling via intra-articular delivery of an IκB kinase two antagonist to understand how local NF-κB inhibition might alter disease progression. RESULTS: Following joint injury NF-κB signaling within the knee joint was transiently increased and peaked on day 3 with an estimated 1.35 p/s/cm2/sr (95% CI 0.913.1.792 p/s/cm2/sr) fold increase in signaling when compared to control joints. Furthermore, injury resulted in the long-term development of hindpaw allodynia. Hyperalgesia withdrawal thresholds were reduced at injured knee joints, with the largest reduction occurring 2 days following injury (estimate of between group difference 129.1 g with 95% CI 60.9,197.4 g), static weight bearing on injured limbs was also reduced. Local delivery of an NF-κB inhibitor following joint injury reduced chondrocyte death and influenced the development of pain-related sensitivity but did not reduce long-term cartilage degeneration. CONCLUSION: These findings underscore the development of behavioral changes in this non-invasive loading model of PTOA and their relationships to NF-κB activation and pathology. They also highlight the potential chondroprotective effects of NF-κB inhibition shortly following joint injury despite limitations in preventing the long-term development of joint degeneration in this model of PTOA.

Use of sugar cane to feed lactating dairy goats / [Uso da cana-de-açúcar na alimentação de cabras leiteiras em lactação]

The aim of the present study was to assess the effects of replacing corn silage with sugarcane in the diet of lactating Saanen goats and to determine their intake and digestibility of nutrients, ingestive behavior, milk yield and composition. The experimental diets were composed of increasing levels (0, 33, 66 and 100%) of substitution in dry matter (DM). Twelve multiparous Saanen goats, with an average body weight of 45.2kg, average milk yield of 3.0kg day-1, distributed in a triple latin square experimental design (4 × 4) were used. The dry matter intake (DMI) and other nutrients were estimated through the difference between the total nutrient in the food offered and its total in the leftovers. The DMI, crude protein, neutral detergent fiber (NDF) and total digestible nutrients were not influenced, but the apparent digestibility of DM and NDF decreased. Feeding time and feeding efficiency were not influenced, the rumination and total chewing times increased, and the leisure time decreased, both linearly. Milk yield was not influenced by substitution levels, but corrected milk yield to 3.5% fat decreased. Sugar cane represents a dietary alternative for goats with medium milk yield in critical periods of forage, since it does not change the consumption of DM and milk yield, even with the apparent declining digestibility of some nutrients, influencing the ingestive behavior of the animals.(AU)

O objetivo do presente estudo foi avaliar os efeitos da substituição da silagem de milho por cana-de-açúcar na dieta de cabras Saanen em lactação e determinar a ingestão e a digestibilidade de nutrientes, o comportamento ingestivo, a produção e a composição do leite. As dietas experimentais foram compostas de níveis crescentes (0, 33, 66 e 100%) de substituição na matéria seca (MS). Doze cabras Saanen multíparas, com peso corporal médio de 45,2kg, produção média de leite de 3,0kg dia-1, foram distribuídas em delineamento experimental triplo quadrado latino (4 × 4). A ingestão de matéria seca (IMS) e de outros nutrientes foi estimada por meio da diferença entre o total de nutrientes nos alimentos oferecidos e o total nas sobras. A IMS, a proteína bruta, a fibra em detergente neutro (FDN) e os nutrientes digestíveis totais não foram influenciados, mas a digestibilidade aparente da MS e da FDN diminuiu. A produção de leite não foi influenciada pelos níveis de substituição, mas a produção de leite corrigida para 3,5% de gordura diminuiu. A cana-de-açúcar representa uma alternativa alimentar para cabras com produção média de leite em períodos críticos de forragem, pois não altera o consumo de MS e a produção de leite, mesmo diminuindo a digestibilidade aparente de alguns nutrientes e influenciando o comportamento ingestivo dos animais.(AU)

[SAMHD1 acts at stalled replication forks to prevent interferon induction]. / SAMHD1 agit sur les fourches de réplication bloquées pour empêcher l'induction d'interféron.

DNA replication is an extremely complex process, involving thousands of replication forks progressing along chromosomes. These forks are frequently slowed down or stopped by various obstacles, such as secondary DNA structures, chromatin-acting proteins or a lack of nucleotides. This slowing down, known as replicative stress, plays a central role in tumour development. Complex processes, which are not yet fully understood, are set up to respond to this stress. Certain nucleases, such as MRE11 and DNA2, degrade the neo-replicated DNA at the level of blocked forks, allowing the replication to restart. The interferon pathway is a defense mechanism against pathogens that detects the presence of foreign nucleic acids in the cytoplasm and activates the innate immune response. DNA fragments resulting from genomic DNA metabolism (repair, retrotransposition) can diffuse into the cytoplasm and activate this pathway. A pathological manifestation of this process is the Aicardi-Goutières syndrome, a rare disease characterized by chronic inflammation leading to neurodegenerative and developmental problems. In this encephalopathy, it has been suggested that DNA replication may generate cytosolic DNA fragments, but the mechanisms involved have not been characterized. SAMHD1 is frequently mutated in the Aicardi-Goutières syndrome as well as in some cancers, but its role in the etiology of these diseases was largely unknown. We show that cytosolic DNA accumulates in SAMHD1-deficient cells, particularly in the presence of replicative stress, activating the interferon response. SAMHD1 is important for DNA replication under normal conditions and for the processing of stopped forks, independent of its dNTPase activity. In addition, SAMHD1 stimulates the exonuclease activity of MRE11 in vitro. When SAMHD1 is absent, degradation of neosynthesized DNA is inhibited, which prevents activation of the replication checkpoint and leads to failure to restart the replication forks. Resection of the replication forks is performed by an alternative mechanism which releases DNA fragments into the cytosol, activating the interferon response. The results obtained show, for the first time, a direct link between the response to replication stress and the production of interferons. These results have important implications for our understanding of the Aicardi-Goutières syndrome and cancers related to SAMHD1. For example, we have shown that MRE11 and RECQ1 are responsible for the production of DNA fragments that trigger the inflammatory response in cells deficient for SAMHD1. We can therefore imagine that blocking the activity of these enzymes could decrease the production of DNA fragments and, ultimately, the activation of innate immunity in these cells. In addition, the interferon pathway plays an essential role in the therapeutic efficacy of irradiation and certain chemotherapeutic agents such as oxaliplatin. Modulating this response could therefore be of much wider interest in anti-tumour therapy.

La réplication de l'ADN est un processus extrêmement complexe, impliquant des milliers de fourches de réplication progressant le long des chromosomes. Ces fourches sont fréquemment ralenties ou arrêtées par différents obstacles, tels que des structures secondaires de l'ADN, des protéines agissant sur la chromatine ou encore un manque de nucléotides. Ce ralentissement, qualifié de stress réplicatif, joue un rôle central dans le développement tumoral. Des processus complexes, qui ne sont pas encore totalement connus, sont mis en place pour répondre à ce stress. Certaines nucléases, comme MRE11 et DNA2, dégradent l'ADN néorépliqué au niveau des fourches bloquées, ce qui permet le redémarrage des réplisomes. La voie interféron est un mécanisme de défense contre les agents pathogènes qui détecte la présence d'acides nucléiques étrangers dans le cytoplasme et active la réponse immunitaire innée. Des fragments d'ADN issus du métabolisme de l'ADN génomique (réparation, rétrotransposition) peuvent diffuser dans le cytoplasme et activer cette voie. Une manifestation pathologique de ce processus est le syndrome d'Aicardi-Goutières, une maladie rare caractérisée par une inflammation chronique générant des problèmes neurodégénératifs et développementaux. Dans le cadre de cette encéphalopathie, il a été suggéré que la réplication de l'ADN pouvait générer des fragments d'ADN cytosoliques, mais les mécanismes impliqués n'avaient pas été caractérisés. SAMHD1 est fréquemment muté dans le syndrome d'Aicardi-Goutières ainsi que dans certains cancers, mais son rôle dans l'étiologie de ces maladies était jusqu'à présent largement inconnu. Nous montrons que de l'ADN cytosolique s'accumule dans les cellules déficientes pour SAMHD1, particulièrement en présence de stress réplicatif, activant la réponse interféron. Par ailleurs, SAMHD1 est important pour la réplication de l'ADN en conditions normales et pour le processing des fourches arrêtées, indépendamment de son activité dNTPase. De plus, SAMHD1 stimule l'activité exonucléase de MRE11 in vitro. Lorsque SAMHD1 est absent, la dégradation de l'ADN néosynthétisé est inhibée, ce qui empêche l'activation du checkpoint de réplication et entraine un défaut de redémarrage des fourches de réplication. De plus, la résection des fourches de réplication est réalisée par un mécanisme alternatif qui libère des fragments d'ADN dans le cytosol, activant la réponse interféron. Les résultats obtenus montrent, pour la première fois, un lien direct entre la réponse au stress réplicatif et la production d'interférons. Ces résultats ont des conséquences importantes dans notre compréhension du syndrome d'Aicardi Goutières et des cancers liés à SAMHD1. Par exemple, nous avons démontré que MRE11 et RECQ1 sont responsables de la production des fragments d'ADN qui déclenchent la réponse inflammatoire dans les cellules déficientes pour SAMHD1. Nous pouvons donc imaginer que bloquer l'activité de ces enzymes pourrait diminuer la production des fragments d'ADN et, in fine, l'activation de l'immunité innée dans ces cellules. Par ailleurs, la voie interférons joue un rôle essentiel dans l'efficacité thérapeutique de l'irradiation et de certains agents chimiothérapiques comme l'oxaliplatine. Moduler cette réponse pourrait donc avoir un intérêt beaucoup plus large en thérapie anti-tumorale.

Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell models.

Food products can be contaminated by several fungi species and each species may produce different mycotoxins, leading to human combined exposure. Although predictions about the joint toxic effects of mycotoxins can be made from their individual toxicities, experimental data is still limited to allow a reliable hazard assessment. Thus, this study aimed to characterize the combined cytotoxic and genotoxic effects of ochratoxin A (OTA) and fumonisin B1 (FB1) in cell lines representative of their target organs, kidney and liver. Interactions were ascertained using mathematical extensions to the reference models of concentration addition and independent action. Cytotoxicity (MTT assay) data modeling revealed a synergistic pattern for low doses of both FB1 and OTA shifting to antagonism at higher concentration levels, irrespectively of the reference model applied. Concerning genotoxicity assessment, neither OTA nor FB1, individually or in combination, induced a prominent increase in DNA damage (comet assay) or oxidative DNA damage (FPG-comet assay). In conclusion, this study revealed a synergistic cytotoxic effect for OTA and FB1 at low concentration levels. Given that human co-exposure to these two mycotoxins is probable to occur at low doses, these results raise concerns regarding their potential health outcomes that seem to differ from those predicted by an additive model.

A twin study of body mass index and dental caries in childhood.

Sub-optimal nutrition and dental caries are both common with significant short and long-term implications for child health and development. We applied twin statistical methods to explore the relationship between body mass index (BMI) and dental caries. We measured BMI at 18 months and six years of age and cumulative dental caries experience at six years in 344 twin children. Dental caries in primary teeth was categorised into 'any' or 'advanced' and BMI was analysed as both a continuous and categorical variable. Statistical analyses included multiple logistic regression using generalized estimating equations and within/between-pair analyses. There was no association between BMI and 'any' dental caries experience at either time-point, neither overall nor in within/between pair analyses. However, 'advanced' dental caries at six years was associated with a within-pair difference in BMI of -0.55 kg/m2 (95% CI -1.00, -0.11, p = 0.015). A within-pair increase of 1 kg/m2 in BMI was associated with a lower within-pair risk of advanced dental caries (OR 0.68, 95% CI 0.52, 0.90, p = 0.007). These findings reveal a possible causal relationship between lower BMI and dental caries. As dental outcomes were only measured at one time point, the direction of this potentially causal relationship is unclear.

Experimental evidences that P21 protein controls Trypanosoma cruzi replication and modulates the pathogenesis of infection.

P21 is a protein secreted by Trypanosoma cruzi (T. cruzi). Previous studies have shown a spectrum of biological activities performed by P21 such as induction of phagocytosis, leukocyte chemotaxis and inhibition of angiogenesis. However, the activity of P21 in T. cruzi infection remains unknown. Here, we reported the role of P21 in mice harboring late T. cruzi infection. Treatment with recombinant P21 protein (rP21) reduced parasite load and angiogenesis, and induced fibrosis in the cardiac tissue of infected mice. In addition, rP21 reduced the growth of epimastigotes, inhibited intracellular replication of amastigotes and modulated the parasite cell cycle. Our data suggest that P21 controls parasite replication in the host, supporting the survival of both parasite and host.

Getting ahead of the oral health game: it starts before we're born?

Dental caries is one of the most common chronic diseases affecting individuals of all ages. Caries in the primary dentition is one of the main risk factors for caries in the permanent dentition. Preventing the development of the first carious lesion is fundamental not only to long term health and wellbeing but to reducing the burden of this disease on individuals, families and the community. Described as the developmental origins of health and disease, events from the prenatal period are increasingly recognised as having a significant impact on later health outcomes. While social and behavioural factors from this period have long been linked with oral health, emerging evidence of the influence of epigenetics and early life programming of microbiome and host response suggests that the prenatal period provides a timely opportunity for preventive interventions. Pregnancy is an ideal time to focus on health promoting activities as most women have regular interaction with health care professionals who can target risk factors before the onset of disease. This paper summarizes contemporary understanding of the role of pre- and perinatal factors on child oral health and describes how this evidence might be used by all health professionals to ensure infants start life ahead in the oral health game.

[Health literacy in patients with type 2 diabetes: A cross-sectional study using the HLS-EU-Q47 questionnaire]. / Alfabetización en salud en pacientes con diabetes tipo 2: un estudio transversal con el cuestionario HLS-EU-Q47.

OBJECTIVE: The aim of this study was to determine the level of health literacy of diabetic patients aged 50 to 75 years, from Ourense, Spain, as well as its relationship with the glycated haemoglobin (HbA1c) concentration and cardiovascular risk of the patient. MATERIAL AND METHODS: Cross-sectional study using a self-completed questionnaire. From a multi-stage sampling, urban, type 2 diabetic patients were randomly included. The level of health literacy, using the HLS-EU-Q47 questionnaire, the last concentration of HbA1c, and both total and fatal cardiovascular risk at 10 year follow-up, measured using the UKPDS (U.K. Prospective Diabetes Study) algorithm, were determined. The age, gender, level of education, level of social support, social class, and comorbidities were used as covariates. RESULTS: A total of 103 patients were analysed. Out of all the patients, 81.5% (84) had an unsuitable health literacy level (29.1% had an inadequate level and 52.4% had a problematic level). A clear association was seen between a higher level of health literacy and higher levels of education. Moreover, the level of health literacy was seen to be inversely related to the level of control of the patients' diabetes measured on the basis of their HbA1c (P=.03) concentration. However, no such association was found with the cardiovascular risk (P=.3). CONCLUSIONS: The results of the present study show that the level of literacy of the analysed population was insufficient, and that its improvement could result in a better outcome in the treatment of diabetic patients.

Etiology of Hypomineralized Second Primary Molars: A Prospective Twin Study.

The etiology of hypomineralized second primary molars (HSPM) is unclear, but genetic and environmental factors have been proposed. The aim of this study was to investigate the relative contribution of genes and environment to the etiology of HSPM and to identify potential environmental risk factors in a longitudinal twin cohort. Children from twin pregnancies ( N = 250) were recruited antenatally, and detailed demographic, health, and phenotypic data were collected at recruitment, 24- and 36-wk gestation, birth, and 18 mo of age. 25-Hydroxyvitamin D was quantified for mothers at 28-wk gestation and infants at birth. Dental examinations were conducted on the twins at 6 y of age to determine the presence, severity, and extent of HSPM per standardized criteria. To investigate associations of environmental risk factors with HSPM, multiple logistic regression models were fitted with generalized estimating equations to adjust for twin correlation. Within- and between-pair analyses were performed for unshared continuous variables: birthweight and birth 25-hydroxyvitamin D. Twin-twin concordance for monozygotic (MZ) and dizygotic (DZ) pairs was calculated and compared after adjusting for identified risk factors. A total of 344 twins underwent the 6-y-old dental assessment; HSPM occurred in 68 (19.8%). After adjusting for potential confounders, vitamin D levels at birth, infantile eczema, dizygosity, in vitro fertilization, socioeconomic position, and maternal smoking beyond the first trimester of pregnancy demonstrated the strongest associations with HSPM. Overall concordance for HSPM was 0.47 (95% CI, 0.32 to 0.62) with weak evidence ( P = 0.078) of higher concordance in MZ twins (0.63; 95% CI, 0.38 to 0.89) as compared with DZ twins (0.41; 95% CI, 0.24 to 0.58). After adjusting for known risk factors, there was no evidence ( P = 0.172) for an additive genetic influence. These findings suggest that shared and unshared environmental factors, such as maternal smoking later in pregnancy and infantile eczema, are important in the etiology of HSPM.

Evaluation of apoptosis/necrosis and cytokine release provoked by three root canal sealers in human polymorphonuclears and monocytes.

AIM: To evaluate the in vitro cytotoxicity and cytokine release of three fresh root canal sealers and to determine the type of cell death they induce. METHODOLOGY: The sealers tested were Sealer 26 (S26), AH Plus (AHP), and Endosequence BC Sealer (END). Fresh sealers were cultivated in contact with monocytes and polymorphonuclears (PMNs) obtained from the peripheral blood of humans. Cell viability, apoptosis and necrosis were analysed at 4 h (PMNs) or 24 h (monocytes) using Annexin-V and propidium iodide in a cytometer. The supernatants were used to quantify Interleukin (IL)-4, IL-6, IL-10, IL-12 and tumour necrosis factor-α (TNF-α) in monocytes and IL-8 in PMNs by ELISA. One-way ANOVA and the Tukey post-test were used to compare data for cytotoxicity, and the multiple T-test was used to determine the differences between sealers in the release of cytokines that were statistically significant. RESULTS: After 4 h of treatment, S26 was associated with greater cell viability than the other sealers (P < 0.05) in the PMN culture and had similar values of necrosis as END (P > 0.05). After 24 h of treatment, AHP and END had greater monocyte cell viability than S26 (P < 0.05), which had more necrosis (P < 0.05). END had the lowest levels of IL-12 compared to the other sealers (P < 0.05) and higher levels of IL-6 compared to S26 (P < 0.05). The tested sealers did not differ in the release of IL-8, IL-10, TNF-α and IL-4 (P > 0.05). CONCLUSIONS: The effect of toxic agents released varied depending on the cell type studied. The composition of the sealers appeared to alter the form of self-regulation in the production of these cytokines by cells.