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Acute porphyrias are a group of rare genetic metabolic disorders, caused by a defect in one of the enzymes involved in the heme biosynthesis, which results in an abnormally high accumulation of toxic intermediates. Acute porphyrias are characterized by potentially life-threatening attacks and, for some patients, by chronic manifestations that negatively impact daily functioning and quality of life. Clinical manifestations include a nonspecific set of gastrointestinal, neuropsychiatric, and/or cutaneous symptoms. Effective diagnostic methods are widely available, but due to their clinical heterogeneity and non-specificity, many years often elapse from symptom onset to diagnosis of acute porphyrias, delaying the treatment and increasing morbidity. Therefore, increased awareness of acute porphyrias among healthcare professionals is paramount to reducing disease burden. Treatment of acute porphyrias is centered on eliminating the potential precipitants, symptomatic treatment, and suppressing the hepatic heme pathway, through the administration of hemin or givosiran. Moreover, properly monitoring patients with acute porphyrias and their relatives is fundamental to preventing acute attacks, hospitalization, and long-term complications. Considering this, a multidisciplinary panel elaborated a consensus paper, aiming to provide guidance for an efficient and timely diagnosis of acute porphyrias, and evidence-based recommendations for treating and monitoring patients and their families in Portugal. To this end, all authors exhaustively reviewed and discussed the current scientific evidence on acute porphyrias available in the literature, between November 2022 and May 2023.

This study extensively analyzed campylobacteriosis surveillance in Portugal from 2009 to 2021, aiming to investigate demographic shifts, seasonal variations, and antimicrobial resistance (AMR) within Campylobacter isolates. Surveillance network and sentinel laboratory-based system data revealed a substantial under-notification of campylobacteriosis cases, suggesting an underestimated disease burden. Notification rates exhibited a paradigm shift, with a notable prevalence among the pediatric population, particularly in children aged 1–4 years, diverging from European reports. Additionally, an emerging trend of Campylobacter infections in younger adults (15–44 years) was observed. The study unveiled a unique seasonal distribution of cases, defying typical summer peaks seen elsewhere. AMR analysis revealed high resistance to ciprofloxacin and tetracycline, in both C. jejuni (93.7% and 79.2%, respectively) and C. coli (96.5% and 93.2%, respectively), stable throughout the studied period (2013–2021). C. coli exhibited significantly higher resistance to erythromycin, gentamicin, ampicillin and ertapenem compared to C. jejuni (p < 0.001). Multilocus Sequence Typing (MLST) data demonstrated the distribution of resistance markers across diverse sequence types, challenging the notion of a clonal origin for multidrug-resistant isolates. In conclusion, the study highlights the need for enhanced surveillance and raises concerns about alarming AMR levels, recommending the implementation of whole-genome sequencing (WGS)-based surveillance for a deeper comprehension of disease patterns and an evolving AMR landscape.

Gliomas are aggressive brain tumors with poor prognosis even after surgical removal and radio-chemotherapy, stressing the urgency to find alternative therapies. Several preclinical studies evaluating the anticancer effect of curcumin in animal models of glioma are reported, but a systematic review with meta-analysis of these studies, considering the different experimental conditions used, has not been made up to this date. A search in different databases (Pubmed, Web of Science, Scopus, and SciELO) following the PRISMA statement was conducted during November 2023 to systematically identify articles assessing the effect of curcumin in murine xenograft models of glioma and identified 15 articles, which were subdivided into 24 studies. Tumor volume before and after treatment with curcumin or vehicle was extracted and the efficacy of curcumin was evaluated by performing a random effects meta-analysis of the data. Publication bias and the impact of different experimental conditions on curcumin efficacy were assessed. Treatment with curcumin decreased tumor volume. Comparing curcumin with control groups, the overall weighted standardized difference in means was −2.079 (95% CI: −2.816 to −1.341; p-value < 0.001). The curcumin effect was observed for different animal models, types of glioma cells, administration routes, and curcumin formulations. Publication bias was identified but does not invalidate curcumin’s effectiveness. The findings suggest the potential therapeutic efficacy of curcumin against glioma.

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required.MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis.Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFNγ- and TNFα-dependent manner. IFNγ produced during infection enhanced macrophage TNFα secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.

Gliomas are aggressive malignant brain tumors, with poor prognosis despite available therapies, raising the necessity for finding new compounds with therapeutic action. Numerous preclinical investigations evaluating resveratrol’s anti-tumor impact in animal models of glioma have been reported; however, the variety of experimental circumstances and results have prevented conclusive findings about resveratrol’s effectiveness. Several databases were searched during May 2023, ten publications were identified, satisfying the inclusion criteria, that assess the effects of resveratrol in murine glioma-bearing xenografts. To determine the efficacy of resveratrol, tumor volume and animal counts were retrieved, and the data were then subjected to a random effects meta-analysis. The influence of different experimental conditions and publication bias on resveratrol efficacy were evaluated. Comparing treated to untreated groups, resveratrol administration decreased the tumor volume. Overall, the effect’s weighted standardized difference in means was −2.046 (95%CI: −3.156 to −0.936; p-value < 0.001). The efficacy of the treatment was observed for animals inoculated with both human glioblastoma or rat glioma cells and for different modes of resveratrol administration. The combined administration of resveratrol and temozolomide was more effective than temozolomide alone. Reducing publication bias did not change the effectiveness of resveratrol treatment. The findings suggest that resveratrol slows the development of tumors in animal glioma models.

The spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) relies on host cell surface glycans to facilitate interaction with the angiotensin-converting enzyme 2 (ACE-2) receptor. This interaction between ACE2 and the spike protein is a gateway for the virus to enter host cells and may be targeted by antiviral drugs to inhibit viral infection. Therefore, targeting the interaction between these two proteins is an interesting strategy to prevent SARS-CoV-2 infection. A library of glycan mimetics and derivatives was selected for a virtual screening performed against both ACE2 and spike proteins. Subsequently, in vitro assays were performed on eleven of the most promising in silico compounds to evaluate: (i) their efficacy in inhibiting cell infection by SARS-CoV-2 (using the Vero CCL-81 cell line as a model), (ii) their impact on ACE2 expression (in the Vero CCL-81 and MDA-MB-231 cell lines), and (iii) their cytotoxicity in a human lung cell line (A549). We identified five synthetic compounds with the potential to block SARS-CoV-2 infection, three of them without relevant toxicity in human lung cells. Xanthene 1 stood out as the most promising anti-SARS-CoV-2 agent, inhibiting viral infection and viral replication in Vero CCL-81 cells, without causing cytotoxicity to human lung cells.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are a recent targeted therapy approved for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer. Abemaciclib, palbociclib and ribociclib demonstrated great efficacy and safety during clinical studies. However, differences in their adverse-event profiles have been observed. This work aims to describe the suspected adverse drug reactions (ADRs), such as leukopenia and thrombocytopenia, reported for each CDK4/6 inhibitor in the EudraVigilance (EV) database. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. Information on concomitant drug therapy, including fulvestrant, letrozole, anastrozole and exemestane, was also analyzed. A total of 1611 ICSRs were collected from the EV database. Most reports of palbociclib and ribociclib were classified as serious cases for both suspected leukopenia and thrombocytopenia ADRs. However, most patients had their leukopenia and thrombocytopenia recovered/resolved. On the contrary, reports of abemaciclib were mostly characterized as non-serious cases. Abemaciclib and palbociclib were often combined with fulvestrant, while ribociclib was generally associated with letrozole. Pharmacovigilance studies are crucial for the early identification of potential ADRs and to better differentiate the toxicity profile of the different CDK4/6 inhibitors, particularly in a real-world setting.

Este estudo analisou a produção de conhecimento da dança nos periódicos nacionais da Educação Física. Identificou a produção de artigos sobre dança por revista, instituição e região do país e as palavras-chave. O universo e a amostra foram constituídos pelos periódicos nacionais da Educação Física classificados de A2 a B2, que tematizam a área sociocultural da Educação Física. O tratamento dos dados seguiu a análise quantitativa simples. Foram analisados oito periódicos e encontrados 234 artigos. As três revistas com maior número de publicações foram a Pensar a Prática 61 artigos, a Revista Movimento 56 artigos e a Motriz com 30 artigos. A universidade com maior número de artigos publicados é a Universidade Federal de Santa Catarina e as regiões com maior produção sobre a dança são os estados de Santa Catarina, Rio Grande do Sul e São Paulo. As principais tematizações dos artigos analisados configuram-se no debate sobre o corpo, a educação escolar, a cultura, a estética e a arte. Os dados permitiram concluir um aumento na produção sobre a dança ao longo dos anos, embora sua representação seja muito pequena. Além disso, foi possível verificar que a maior preocupação da área da Educação Física sobre a dança está relacionada aos aspectos educacionais.

Petroleum-based plastics used in food packaging are not biodegradable. They accumulate in the environment in large amounts, causing a decrease in soil fertility, jeopardizing marine habitats, and causing serious problems to human health. Whey protein has been studied for applications in food packaging, either because of its abundant availability or because it confers transparency, flexibility, and good barrier properties to packaging materials. Taking advantage of whey protein to produce new food packaging materials is a clear example of the so-called circular economy. The present work focuses on optimizing the formulation of whey protein concentrate-based films to enhance their general mechanical properties applying the Box–Behnken experimental design. Foeniculum vulgare Mill. (fennel) essential oil (EO) was incorporated into the optimized films, which were then further characterized. The incorporation of fennel EO in the films leads to a significant increase (p < 0.05) in peak elongation (from 14.03 to 31.61%) and tensile index (from 0.40 to 0.50 N.m/g). The optimized whey protein films were yellowish and very transparent (>90%). The results of the bioactive activities of the optimized films showed their ability to be applied as active materials for food packaging to improve the shelf-life of food products and also to prevent foodborne diseases associated with the growth of pathogenic microorganisms.

Abstract Introduction: Type 1 diabetes mellitus is associated with an increased risk of coronary artery disease, which is frequently asymptomatic. This risk increases significantly in those with nephropathy. In selected patients, simultaneous pancreas-kidney transplantation is the renal and pancreatic replacement therapy of choice, as it increases longevity and stabilizes diabetic complications. Despite essential, universal screening protocols are still controversial for coronary artery disease in this population. Methods: We retrospectively analysed 99 simultaneous pancreas-kidney recipients from our centre from 2011 to 2018 and selected 77 patients who underwent coronary angiography during the pre-transplant evaluation. Our aim was to identify potential risk factors associated with significant lesions on coronary angiography. Results: Almost half of our cohort of 77 candidates submitted to coronary angiography had coronary artery disease. Of these, nearly 30% underwent revascularization, although only one of them reported symptoms of myocardial ischemia. In a univariate analysis, the presence of smoking habits was the only risk factor for coronary artery disease. We also found that 20 or more years of type 1 diabetes mellitus was significantly associated with the presence of coronaropathy. Discussion: Selection of diabetic candidates with acceptable cardiac risk before simultaneous pancreas-kidney transplantation is imperative. Given the impact of a correct diagnosis and a low procedural risk, we defend the routine use of coronary angiography as the initial screening method for coronary artery disease in this population. Particularly care must be taken in evaluating asymptomatic patients with long-term type 1 diabetes mellitus and smokers.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes. Methods In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis. Results Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0–18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7–35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4–17.8) (p≤0.001). SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency. Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF. Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function). Conclusion SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s

Cervical cancer (CC) is a disease that affects many women worldwide, especially in low-income countries. The human papilloma virus (HPV) is the main causative agent of this disease, with the E6 and E7 oncoproteins being responsible for the development and maintenance of transformed status. In addition, HPV is also responsible for the appearance of cervical intraepithelial neoplasia (CIN), a pre-neoplastic condition burdened by very high costs for its screening and therapy. So far, only prophylactic vaccines have been approved by regulatory agencies as a means of CC prevention. However, these vaccines cannot treat HPV-positive women. A search was conducted in several databases (PubMed, Scopus, Web of Science, and ClinicalTrials.gov) to systematically identify clinical trials involving therapeutic vaccines against CIN 3. Histopathological regression data, immunological parameters, safety, DNA clearance, and vaccine efficacy were considered from each selected study, and from the 102 articles found, 8 were selected based on the defined inclusion criteria. Histopathological regression from CIN 3 to CIN < 1 was 22.1% (95% CI: 0.627–0.967; p-value = 0.024), showing a vaccine efficacy of 23.6% (95% CI; 0.666–0.876; p-value < 0.001). DNA clearance was assessed, and the risk of persistent HPV DNA was 23.2% (95% CI: 0.667–0.885; p-value < 0.001). Regarding immunological parameters, immune responses by specific T-HPV cells were more likely in vaccinated women (95% CI: 1.245–9.162; p-value = 0.017). In short, these studies favored the vaccine group over the placebo group. This work indicated that therapeutic vaccines are efficient in the treatment of CIN 3, even after accounting for publication bias.

African history has been significantly influenced by the Sahara, which has represented a barrier for migrations of all living beings, including humans. Major exceptions were the gene flow events that took place between North African and sub-Saharan populations during the so-called African Humid Periods, especially in the Early Holocene (11.5 to 5.5 thousand years ago), and more recently in connection with trans-Saharan commercial routes. In this study, we describe mitochondrial DNA (mtDNA) diversity of human populations from both sides of the Sahara Desert, i.e., both from North Africa and the Sahel/Savannah belt. The final dataset of 7213 mtDNA sequences from 134 African populations encompasses 470 newly collected and 6743 previously published samples, which were analyzed using descriptive methods and Bayesian statistics. We completely sequenced 26 mtDNAs from sub-Saharan samples belonging to the Eurasian haplogroup N1. Analyses of these N1 mitogenomes revealed their possible routes to the Sahel, mostly via Bab el-Mandab. Our results indicate that maternal gene flow must have been important in this circum-Saharan space, not only within North Africa and the Sahel/Savannah belt but also between these two regions.

Members of the family Arcobacteraceae are distributed widely in aquatic environments, and some of its species have been associated with human and animal illness. However, information about the diversity and distribution of Arcobacteraceae in different water bodies is still limited. In order to better characterize the health risk posed by members in the family Arcobacteraceae, a systematic review and meta-analysis-based method was used to investigate the prevalence of Arcobacteraceae species in aquatic environments based on available data published worldwide. The database search was performed using related keywords and considering studies up to February 2021. The pooled prevalence in aquatic environments was 69.2%, ranging from 0.6 to 99.9%. These bacteria have a wide geographical distribution, being found in diverse aquatic environments with the highest prevalence found in raw sewage and wastewater treatment plants (WWTP), followed by seawater, surface water, ground water, processing water from food processing plants and water for human consumption. Assessing the effectiveness of treatments in WWTP in eliminating this contamination, it was found that the wastewater treatment may not be efficient in the removal of Arcobacteraceae. Among the analyzed Arcobacteraceae species, Al. butzleri was the most frequently found species. These results highlight the high prevalence and distribution of Arcobacteraceae in different aquatic environments, suggesting a risk to human health. Further, it exposes the importance of identifying and managing the sources of contamination and taking preventive actions to reduce the burden of members of the Arcobacteraceae family.

Introduction: Apart from its economic impact, calf mortality is an important welfare indicator in beef calf farms. Objectives: Evaluate mortality rates in calves born from two indigenous cattle breeds dams in the Portalegre district. Methods: Records of births and deaths between birth and 180 days of calves born from Alentejana and Mertolenga dams in Portalegre district, from January 1, 2016, to December 31, 2018, were obtained from the national database. Mortality rates were calculated and the association between mortality period and age of the dam was evaluated. Results: Calves born from Alentejana and Mertolenga cows represented 11.6% and 2.9% of cattle births in the Portalegre district during this period, with a decrease in the number of births during the three considered years, more noticeable in the Alentejana breed. The average mortality rate was 3.2% for calves born from Alentejana dams and 2.3% for calves born from Mertolenga dams. The average age of dams was 8.68 and 7.37 years, for Alentejana and Mertolenga dams respectively. Perinatal death (from birth to 48 h) occurred in calves born from older cows (p=0.024). Conclusions: Mortality rates of calves born from the two studied indigenous breeds are low to moderate when compared to rates reported in other breeds.

Thyroid cancer therapy is based on surgery followed by radioiodine treatment. The incorporation of radioiodine by cancer cells is mediated by sodium iodide symporter (NIS) (codified by the SLC5A5 gene), that is functional only when targeted to the cell membrane. We aimed to evaluate if NIS expression in thyroid primary tumors would be helpful in predicting tumor behavior, response to therapy and prognosis. NIS expression was addressed by qPCR and immunohistochemistry. In order to validate our data, we also studied SLC5A5 expression on 378 primary papillary thyroid carcinomas from The Cancer Genome Atlas (TCGA) database. In our series, SLC5A5 expression was lower in carcinomas with vascular invasion and with extrathyroidal extension and in those harboring BRAFV600E mutation. Analysis of SLC5A5 expression from TCGA database confirmed our results. Furthermore, it showed that larger tumors, with locoregional recurrences and/ or distant metastases or harboring RAS, BRAF and/or TERT promoter (TERTp) mutations presented significantly less SLC5A5 expression. Regarding immunohistochemistry, 12/211 of the cases demonstrated NIS in the membrane of tumor cells, those cases showed variable outcomes concerning therapy success, prognosis and all but one were wild type for BRAF, NRAS and TERTp mutations. SLC5A5 mRNA lower expression is associated with features of aggressiveness and with key genetic alterations involving BRAF, RAS and TERTp. Mutations in these genes seem to decrease protein expression and its targeting to the cell membrane. SLC5A5 mRNA expression is more informative than NIS immunohistochemical expression regarding tumor aggressiveness and prognostic features.

Abstract Background The prognostic variability of thyroid carcinomas has led to the search for accurate biomarkers at the molecular level. Follicular thyroid carcinoma (FTC) is a typical example of differentiated thyroid carcinomas (DTC) in which challenges are faced in the differential diagnosis. Methods We used high-throughput paired-end RNA sequencing technology to study four cases of FTC with different degree of capsular invasion: two minimally invasive (mFTC) and two widely invasive FTC (wFTC). We searched by genes differentially expressed between mFTC and wFTC, in an attempt to find biomarkers of thyroid cancer diagnosis and/or progression. Selected biomarkers were validated by real-time quantitative PCR in 137 frozen thyroid samples and in an independent dataset (TCGA), evaluating the diagnostic and the prognostic performance of the candidate biomarkers. Results We identified 17 genes significantly differentially expressed between mFTC and wFTC. C1QL1, LCN2, CRABP1 and CILP were differentially expressed in DTC in comparison with normal thyroid tissues. LCN2 and CRABP1 were also differentially expressed in DTC when compared with follicular thyroid adenoma. Additionally, overexpression of LCN2 and C1QL1 were found to be independent predictors of extrathyroidal extension in DTC. Conclusions We conclude that the underexpression of CRABP1 and the overexpression of LCN2 may be useful diagnostic biomarkers in thyroid tumours with questionable malignity, and the overexpression of LCN2 and C1QL1 may be useful for prognostic purposes.

Afadin is a cytoplasmic protein of the adherens junctions, which regulates the formation and stabilization of both the adherens and the tight junctions. Aberrant expression of Afadin has been shown in cancer and its loss has been associated with epithelial-to-mesenchymal transition (EMT). EMT is characterized by the change from an epithelial to a mesenchymal phenotype, with modifications on the expression of adhesion molecules and acquisition of a migratory and invasive cell behavior. While it is known that Helicobacter pylori disrupts the tight and the adherens junctions and induces EMT, the effect of the bacteria on Afadin is still unknown. The aim of this study was to disclose the effect of H. pylori on Afadin and its impact in the induction of an EMT phenotype in gastric cells. Using two different cell lines, we observed that H. pylori infection decreased Afadin protein levels, independently of CagA, T4SS, and VacA virulence factors. H. pylori infection of cell lines recapitulated several EMT features, displacing and downregulating multiple proteins from cell–cell junctions, and increasing the expression of ZEB1, Vimentin, Slug, N-cadherin, and Snail. Silencing of Afadin by RNAi promoted delocalization of junctional proteins from the cell–cell contacts, increased paracellular permeability, and decreased transepithelial electrical resistance, all compatible with impaired junctional integrity. Afadin silencing also led to increased expression of the EMT marker Snail, and to the formation of actin stress fibers, together with increased cell motility and invasion. Finally, and in line with our in vitro data, the gastric mucosa of individuals infected with H. pylori showed decrease/loss of Afadin membrane staining at cell–cell contacts significantly more frequently than uninfected individuals. In conclusion, Afadin is downregulated by H. pylori infection in vitro and in vivo, and its downregulation leads to the emergence of EMT and to the acquisition of an aggressive phenotype in gastric cells, which can contribute to gastric carcinogenesis.

The continuous characterization of genome-wide diversity in population and case–cohort samples, allied to the development of new algorithms, are shedding light on host ancestry impact and selection events on various infectious diseases. Especially interesting are the long-standing associations between humans and certain bacteria, such as the case of Helicobacter pylori, which could have been strong drivers of adaptation leading to coevolution. Some evidence on admixed gastric cancer cohorts have been suggested as supporting Homo-Helicobacter coevolution, but reliable experimental data that control both the bacterium and the host ancestries are lacking. Here, we conducted the first in vitro coinfection assays with dual human- and bacterium-matched and -mismatched ancestries, in African and European backgrounds, to evaluate the genome wide gene expression host response to H. pylori. Our results showed that: (1) the host response to H. pylori infection was greatly shaped by the human ancestry, with variability on innate immune system and metabolism; (2) African human ancestry showed signs of coevolution with H. pylori while European ancestry appeared to be maladapted; and (3) mismatched ancestry did not seem to be an important differentiator of gene expression at the initial stages of infection as assayed here.

Psilocybin is a naturally occurring tryptamine known for its psychedelic properties. Recent research indicates that psilocybin may constitute a valid approach to treat depression and anxiety associated to life-threatening diseases. The aim of this work was to perform a systematic review with meta-analysis of clinical trials to assess the therapeutic effects and safety of psilocybin on those medical conditions. The Beck Depression Inventory (BDI) was used to measure the effects in depression and the State-Trait Anxiety Inventory (STAI) was used to measure the effects in anxiety. For BDI, 11 effect sizes were considered (92 patients) and the intervention group was significantly favored (WMD = −4.589; 95% CI = −4.207 to −0.971; p-value = 0.002). For STAI-Trait, 11 effect sizes were considered (92 patients), being the intervention group significantly favored when compared to the control group (WMD = −5.906; 95% CI = −7.852 to −3.960; p-value ˂ 0.001). For STAI-State, 9 effect sizes were considered (41 patients) and the intervention group was significantly favored (WMD = −6.032; 95% CI = −8.900 to −3.164; p-value ˂ 0.001). The obtained results are promising and emphasize the importance of psilocybin translational research in the management of symptoms of depression and anxiety, since the compound may be effective in reducing symptoms of depression and anxiety in conditions that are either resistant to conventional pharmacotherapy or for which pharmacologic treatment is not yet approved. Moreover, it may be also relevant for first-line treatment, given its safety.

The human gastrointestinal tract harbors approximately 100 trillion microorganisms with different microbial compositions across geographic locations. In this work, we used RNASeq data from stomach samples of non-disease (164 individuals from European ancestry) and gastric cancer patients (137 from Europe and Asia) from public databases. Although these data were intended to characterize the human expression profiles, they allowed for a reliable inference of the microbiome composition, as confirmed from measures such as the genus coverage, richness and evenness. The microbiome diversity (weighted UniFrac distances) in gastric cancer mimics host diversity across the world, with European gastric microbiome profiles clustering together, distinct from Asian ones. Despite the confirmed loss of microbiome diversity from a healthy status to a cancer status, the structured profile was still recognized in the disease condition. In concordance with the parallel host-bacteria population structure, we found 16 human loci (non-synonymous variants) in the European-descendent cohorts that were significantly associated with specific genera abundance. These microbiome quantitative trait loci display heterogeneity between population groups, being mainly linked to the immune system or cellular features that may play a role in enabling microbe colonization and inflammation.

Julbernardia paniculata and Pterocarpus angolensis are two plant species with important application in African traditional medicine, particularly in Angola, in the treatment of several diseases. However, scientific studies concerning these species are scarce. The goal of this work was to know better which medicinal approaches are used by the Huíla population in Angola by means of ethnobotanical surveys. Furthermore, extracts of both plants were phytochemically characterized. Antioxidant, anti-inflammatory, wound-healing activities, and potential cytotoxicity were also studied. With this study it was possible to verify that 67% of the individuals that use medicinal plants are women, and their main therapeutic uses are the treatment of problems of the digestive system and skin disorders. Barks of J. paniculata and leaves of P. angolensis are the most often used plant parts. Through high-performance liquid chromatography coupled to diode-array detector (HPLC-DAD) and GC-MS it was possible to characterize the chemical composition of the two species, which are rich in phenolic compounds, terpenes, terpenoids, sesquiterpenoids and fatty acids. Both plants showed to possess antioxidant, anti-inflammatory proprieties, and wound-healing activity. To the best of our knowledge, this is the most comprehensive study of these two species and the first ethnobotanical and ethnopharmacological study of medicinal plants from this region of Angola.

In colon cancer, the prognostic value of macrophages is controversial, and it is still unknown how hypoxia modulates macrophage–cancer cell crosstalk. To unravel this, co-cultures of human primary macrophages and colon cancer cells were performed at 20% and 1% O2, followed by characterization of both cellular components. Different colon cancer patient cohorts were analyzed for hypoxia and immune markers, and their association with patient overall survival was established. A positive correlation between HIF1A and CD68 in colon cancer patients was identified but, unexpectedly, in cases with higher macrophage infiltration, HIF1A expression was associated with a better prognosis, in contrast to breast, gastric, and lung cancers. Under hypoxia, co-cultures’ secretome indicated a shift towards a pro-inflammatory phenotype. These alterations occurred along with increased macrophage phagocytic activity and decreased SIRPα expression. Cancer cells were more invasive and exhibited higher CD47 expression. We hypothesize that the better prognosis associated with HIF1AHighCD68High tumors could occur due to macrophagic pro-inflammatory pressure. Indeed, we found that tumors HIF1AHighCD68High expressed increased levels of CD8A, which is positively correlated with HIF1A. In conclusion, we show that in colon cancer, hypoxia drives macrophages into a pro-inflammatory phenotype, concomitant with increased infiltration of anti-tumor immune cells, favoring better disease outcome.

Carcinoid pulmonary tumors occur in the fourth to sixth decades of life. Usually, typical carcinoid arise a decade earlier when compared to atypical carcinoid (45 years and 55 years, respectively). Typical carcinoid tumors are the most common primary lung neoplasm in children and late adolescents, but there are less than 40 cases described in the literature. The clinical presentation is nonspecific and usually the symptoms are due to bronchial obstruction, sometimes with recurrent pneumonia. Its rarity may delay diagnosis but in most cases a favorable course after treatment is observed. The authors describe the case of a 13-year-old girl diagnosed with a carcinoid tumor located on the intermediate bronchus. The treatment approach included endoscopic laser resection, for obstruction resolution, followed by a right inferior bilobectomy with mediastinal lymph node dissection as definitive treatment. Histopathology confirmed a typical carcinoid tumor with mediastinal ipsilateral lymph node involvement.

A discinesia ciliar primária é uma doença genética e clinicamente heterogénea, cuja patogénese assenta em compromisso da estrutura e função ciliares. Cursa habitualmente com infecções respiratórias recorrentes, infertilidade e ainda situs inversus total em cerca de metade dos doentes. Dada a raridade e heterogeneidade fenotípica desta patologia o seu diagnóstico implica frequentemente um elevado índice de suspeição. Com este artigo os autores procuraram rever os aspectos fundamentais relativos à etiopatogénese, quadro clínico e abordagens diagnóstica e terapêutica da discinesia ciliar primária, contextualizando-os na discussão de três casos clínicos. Descrevem-se três doentes cujo quadro clínico inaugural foi marcado por síndroma de dificuldade respiratória neonatal associada, em dois doentes, a situs inversus total. A evolução clínica subsequente cursou com sintomatologia respiratória em dois doentes (tosse produtiva crónica num doente e episódios recorrentes de pneumonia e sibilância noutro) e atingimento do aparelho respiratório superior nos três. À data do diagnóstico de discinesia ciliar primária, os doentes apresentavam idades distintas (8 meses, 5 e 12 anos), sendo que os dois doentes com idades de diagnóstico mais tardias apresentavam nessa altura compromisso funcional respiratório do tipo obstrutivo. Os autores discutem os diferentes padrões de apresentação clínica, a abordagem terapêutica e a evolução clínica subsequente, os factores potencialmente implicados no diagnóstico tardio e as suas repercussões prognósticas. O objectivo primordial é alertar para manifestações clínicas precoces e/ou frequentes de discinesia ciliar primária, procurando deste modo influenciar o prognóstico pela melhoria do reconhecimento precoce desta patologia.Primary ciliary dyskinesia is a genetically and clinically heterogeneous disorder. Its pathogenesis reflects structural and functional compromise of the cilia. Common clinical manifestations include recurrent upper and lower respiratory tract infections and infertility, as well as situs inversus totalis in half of the affected patients. Besides its rarity and phenotypic heterogeneity its diagnosis usually requires a high suspicion index. The main purpose of this paper is to review the pathogenesis, clinical features, diagnostic and therapeutic approaches of primary ciliary dyskinesia beyond the discussion of three clinical reports. We report the cases of three patients all with a past history of neonatal respiratory distress and two with situs inversus totalis. The subsequent clinical manifestations included lower airway symptoms in two patients (chronic productive cough and recurrent pneumonia and wheezing) and upper respiratory tract disease in all patients. Age at primary ciliary dyskinesia diagnosis differed considerably among patients (8 months, 5 and 12 years). The two patients with later diagnosis had already obstructive lung function compromise at the time of diagnosis. The authors discuss the different clinical patterns presented, therapeutic strategies and the clinical progression that ensued, factors possibly implicated in late diagnosis and its prognostic consequences. The main goal is to emphasize early and/or prevalent clinical features of primary ciliary dyskinesia in order to promote clinical awareness and early recognition of the disease.

Introdução: Ao Staphylococcus aureus resistente à meticilina (MRSA) é lassicamente reconhecido um papel patogénico no âmbito da fibrose quística (FQ). Objectivos: Avaliação da evolução da prevalência e incidência da colonização por MRSA, impacto clínico no ano após o primeiro isolamento, factores de risco e padrão de resistência antimicrobiana. Métodos: Estudo retrospectivo dos doentes pediátricos colonizados por MRSA seguidos no centro de FQ do Hospital de Santa Maria de 2003 a 2007. Resultados: O MRSA foi isolado em secreções respiratórias de 12 dos 60 doentes seguidos durante este período (colonização crónica em 3 doentes). A idade média à data do primeiro isolamento foi de 9 anos e 10 meses e o tempo médio entre o diagnóstico de FQ e a aquisição de MRSA de 5 anos e 7 meses. Verificou-se um aumento da prevalência e incidência de colonização por MRSA, com um máximo atingido em 2007 (prevalência 14,3% e incidência 8,9%). Quatro doentes cumpriram antibioticoterapia profiláctica antiestafilocócica com flucloxacilina. No ano após o primeiro isolamento de MRSA, constatou -se um aumento do número de dias de internamento em 4 doentes (2 com colonização crónica) e deterioração da função pulmonar em 5, incluindo a totalidade dos doentes com colonização crónica. Apenas um doente apresentou diminuição de percentil de índice de massa corporal. As resistências mais frequentemente encontradas foram à rifampicina e à clindamicina.Conclusões: Este estudo revelou ocorrência de deterioração clínica relevante em doentes com colonização crónica por MRSA, reforçando a importância da implementação de estratégias eficazes e precoces de erradicação.Background: Methicillin-resistant Staphylococcus aureus (MRSA) plays a well-recognised pathogenic role in cystic fibrosis (CF). Aims: To evaluate the prevalence and incidence of colonisation by MRSA, clinical impact of MRSA colonisation (year after first MRSA isolation), risk factors and pattern of antimicrobial resistance. Methods: Retrospective review of paediatric CF patients colonised with MRSA followed-up at the CF Unit of Hospital de Santa Maria 2003-2007. Results: Twelve of the 60 patients followed-up during this period were MRSA-positive at some time (chronic colonisation in 3 patients). Mean age at acquisition was 9 years 10 months and mean time interval between CF diagnosis and MRSA acquisition 5 years 7 months. An important rise in MRSA colonisation prevalence and incidence was observed, with the highest rate seen in 2007 (prevalence 14.3% and incidence 8.9%). Four patients had received anti-staphylococcal prophylaxis with flucloxacillin. An increase in the total number of in-patient days was observed in four patients (two with chronic colonisation). Deterioration in lung function was seen in five patients (including the three patients with chronic colonisation). Only one patient had a decrease in body mass index percentile. Resistance to clindamycin and rifampin was the most frequently seen. Conclusions: This study revealed significant clinical deterioration in patients with chronic colonisation by MRSA, reinforcing the importance of effective and timely decolonisation strategies.

Newborn screening (NBS) for cystic fibrosis (CF) has been shown to be advantageous for children with CF, and has thus been included in most NBS programs using various algorithms. With this study, we intend to establish the most appropriate algorithm for CF-NBS in the Portuguese population, to determine the incidence, and to contribute to elucidating the genetic epidemiology of CF in Portugal. This was a nationwide three-year pilot study including 255,000 newborns (NB) that were also screened for congenital hypothyroidism (CH) and 24 other metabolic disorders included in the Portuguese screening program. Most samples were collected in local health centers spread all over the country, between the 3rd and 6th days of life. The algorithm tested includes immunoreactive trypsinogen (IRT) determination, pancreatitis associated protein (PAP) as a second tier, and genetic study for cases referred to specialized clinical centers. Thirty-four CF cases were confirmed positive, thus indicating an incidence of 1:7500 NB. The p.F508del mutation was found in 79% of the alleles. According to the results presented here, CF-NBS is recommended to be included in the Portuguese NBS panel with a small adjustment regarding the PAP cut-off, which we expect to contribute to the improvement of the CF-NBS performance. According to our results, this algorithm is a valuable alternative for CF-NBS in populations with stringent rules for genetic studies.

Nos últimos anos tem sido descrita, no mundo ocidental, uma redução da incidência da pneumonia aguda da comunidade (PAC) nas crianças, parodoxalmente associada a maior gravidade dos casos internados. O presente estudo pretendeu caracterizar os casos de PAC internados e compará-los com um estudo anterior a 2001. Recolhemos dados referentes a 63 internamentos, durante seis meses. Houve predomínio do grupo dos 0-2 anos. Na radiografia torácica, em 58 casos (92,1%) detectou-se condensação/atelectasia e em 17 (27,0%) derrame pleural (DP). Onze dos DP corresponderam a empiema (17,4% dos internamentos). Isolou-se agente bacteriano em cinco casos: Streptococcus pyogenes (dois, líquido pleural), Streptococcus pneumoniae (dois, hemocultura) e Haemophilus influenzae (um, hemocultura). Foi prescrita antibioticoterapia em 61 (96,8%) crianças. A duração mediana de internamento foi de cinco dias. Constatou-se, nos casos de DP, idade superior, maior duração de febre, proteína C reactiva mais alta e maior duração de internamento e de antibioticoterapia endovenosa. Comparativamente com o estudo anterior, constatou-se haver maior gravidade dos casos internados, traduzida por maior incidência de DP e empiema; paradoxalmente, registou-se menor duração da febre em meio hospitalar e menor duração do internamento. No estudo actual houve menor prescrição antibiótica prévia à admissão e maior prescrição de ampicilina durante o internamento. Na literatura, a maior gravidade das pneumonias internadas nos últimos anos tem sido associada à emergência de serotipos mais agressivos de Stretococcus pneumoniae não integrados na vacina heptavalente, assumindo interesse crescente a introdução de vacinas que os incluam. As pneumonias complicadas devem ser orientadas para centros de referência com experiência no seu diagnóstico e tratamento.The past few years have seen a decline in community acquired pneumonia (CAP) in children in the western world, although this has gone hand-in-hand with more serious cases needing hospital admission. Our study characterises cases of CAP admitted to hospital and compares this data with a 2001 study. We collected data on 63 admissions over a six-month period. The majority were aged 0-2 years old. Chest X-ray showed consolidation/atelectasy in 58 (92.1%) and pleural effusion (PE) in 17 (27.0%), of which 11 were empyema (17.4% of all admissions). The bacterial agent was isolated in five cases: Streptococcus pyogenes (two, pleural fluid), Streptococcus pneumoniae (two, blood culture) and Haemophilus influenzae (one, blood culture). Sixty-one children (96.8%) were prescribed antibiotherapy. The median length of hospital stay was five days. Patients with PE were older, had a longer course of fever, higher inflammatory parameters, longer hospital stay and longer course of iv antibiotics. Compared to the prior study we found greater severity of CAP, with higher prevalence of PE and empyema. Nevertheless there was a shorter course of fever during hospital stay and shorter hospital stay. We also noticed less antibiotic prescription prior to admission and greater prescription of ampicillin during hospital stay. In the literature, the higher severity of CAP has been partially attributed to the emergence of more aggressive serotypes of Stretococcus pneumoniae not included in the heptavalent vaccine. There is therefore a greater interest in new vaccines containing them. Complicated CAP should be referred to centres specialising in its diagnosis and management.

A síndroma de Marfan é uma doença do tecido conjuntivo de transmissão autossómica dominante, com manifestações esqueléticas, oculares e cardiovasculares típicas. Com menor frequência, verifica -se envolvimento pulmonar, nomeadamente pneumotórax espontâneo. Este é habitualmente recorrente, surgindo em 4 -11% dos casos. Descreve -se um adolescente de 14 anos, sem diagnóstico anterior de doença, internado por pneumotórax espontâneo unilateral, com fenótipo de síndroma de Marfan. A investigação subsequente conduziu ao diagnóstico de prolapso da válvula mitral e dilatação da raiz da aorta. Houve resolução do pneumotórax através de drenagem activa e excluíram -se, por tomografia computorizada, lesões bolhosas subpleurais. O doente foi reinternado, dois meses depois, por novo pneumotórax espontâneo, com idêntica localização, procedendo -se a ressecção cirúrgica de bolha enfisematosa então identificada e pleurodese. Dois anos depois encontra-se assintomático. Realça -se a importância do diagnóstico precoce e acompanhamento multidisciplinar destes doentes. A monitorização da progressão da doença e a prevenção de complicações graves, nomeadamente cardiovasculares, são imprescindíveis.Marfan syndrome is an autosomal dominant illness of the connective tissue, with typical skeletal, ocular and cardiovascular manifestations. Less frequently, pulmonary involvement occurs, namely spontaneous pneumothorax, which generally is recurrent and occurs in 4 -11% of cases. The authors describe a 14 -year -old boy, previously healthy, admitted with a unilateral spontaneous pneumothorax, and clinical phenotype of Marfan syndrome. The subsequent investigation led to the diagnosis of mitral valve prolapse and dilatation of the root of aorta. Pneumothorax resolved through active drainage and a computerised tomography scan excluded subpleural blebs. The patient was readmitted two months later with a new spontaneous pneumothorax, with an identical localization. Surgical resection of a newly identified enfisematous bleb and pleurodesis were performed. Two years later he is asymptomatic. We highlight the importance of an early diagnosis of and a multidisciplinary approach to these patients. Monitoring illness progression and prevention of serious complications, namely cardiovascular, are essential.

O complexo Burkholderia cepacia (Bcc) é um grupo constituído por nove espécies de bactérias patogénicas oportunistas na fibrose quística (FQ), associadas a prognóstico mais reservado e a infecção cruzada entre os doentes. Existe grande heterogeneidade na deterioração pulmonar dos doentes colonizados/infectados com Bcc, evoluindo, por vezes, de forma fulminante - síndroma da cepacia. Com o objectivo de avaliar a relação entre a colonização/infecção com as diferentes espécies do Bcc e a evolução clínica, os autores analisaram, retrospectivamente, 31 doentes com FQ acompanhados no Hospital de Santa Maria com isolamentos entre Janeiro de 1995 e Março de 2006. Os doentes foram divididos nos grupos: Grupo I - isolamento intermitente (15 doentes) e Grupo II - isolamento crónico (16 doentes). A prevalência das espécies do Bcc foi: B. cepacia 57%, B. cenocepacia 43%, B. multivorans 7%, B. stabilis 13%. Três doentes faleceram com síndroma da cepacia. As espécies B. cepacia e B. stabilis, pouco frequentes nas populações de FQ caracterizadas na Europa e na América do Norte, foram isoladas de uma percentagem importante dos doentes estudados, não tendo sido possível estabelecer uma correlação entre a espécie e a evolução clínica. Nos doentes deteriorados, mas não nos estáveis, do grupo II, em quem foi possível analisar retrospectivamente a função respiratória (FEV1) e os períodos de internamento por exacerbação pulmonar, encontraram-se algumas diferenças relevantes antes e após o isolamento de Bcc. Perante a incapacidade actual de orientar as medidas de profilaxia através da caracterização molecular dos isolados de Bcc, há que manter as medidas de controlo recomendadas.Bacteria of the Burkholderia cepacia complex (Bcc), a group of nine related species, are opportunistic pathogens in cystic fibrosis (CF) patients, associated with a poor prognosis and patient-to-patient transmissibility. The pulmonary deterioration in Bcc-colonised/infected patients has a heterogeneous pattern leading, sometimes, to a fulminant development - the cepaciasyndrome. To evaluate the relationship between colonisation/infection by the different Bcc species and the clinical course, the authors carried out a retrospective study of 31 CF patients with Bcc bacteria isolations followed at Hospital de Santa Maria from January 1995 to March 2006. Patients were categorised into two groups: Group I, with intermittent isolations and Group II with chronic isolations. The prevalence of Bcc species was as follows: B. cepacia 57%, B. cenocepacia 43%, B. multivorans 7%, B. stabilis 13%. Three of the patients died of cepacia syndrome. The species B. cepacia and B. stabilis, usually less frequent in CF populations of Europe and America, were isolated in a considerable percentage of the patients examined. No correlation could be established between the species and the clinical outcome. Deteriorated but not stable patients from group II, whose lung function and pulmonary exacerbationcaused hospitalisation could be retrospectively analysed, exhibited significant differences in the number of hospitalisations and pulmonary function (FEV1) in the year prior to and the years following Bcc isolation. Based on the available data, it is not currently possible to outline preventive measures through the molecular characterisation of Bcc isolates, reinforcing the notion that the recommended control measures must be followed.

A abordagem do derrame pleural parapneumónico complicado, em idade pediátrica, permanece controversa. As opções terapêuticas incluem antibioticoterapia e drenagem pleural contínua, instilação intrapleural de fibrinolíticos, videotoracoscopia e toracotomia com descorticação. O objectivo deste estudo foi rever, avaliar e actualizar a abordagem ao derrame pleural complicado. Procedeu-se à revisão retrospectiva dos processos clínicos das crianças internadas na UPP por derrame pleural complicado entre 1992 e 2003. Foram incluídos 25 doentes, com idade média (±DP): 37,4 (± 37,0) meses, sendo 15/25 (60%) do sexo masculino. A identificação do agente foi possível em 17/25 (68%) casos [S. Aureus 6/17 (35%), St. pneumoniae 5/17 (29%)], no líquido pleural em 16/17 (94%) casos. Todos os doentes realizaram toracocentese e antibioticoterapia sistémica. A drenagem pleural contínua foi instituída em 22/25 (88%) casos com duração média (±DP): 14,2 (± 7,8) dias; em 1 caso houve instilação de fibrinolíticos intrapleurais e em 11/25 (44%) realizou-se toracotomia com descorticação. Um doente foi submetido a videotoracoscopia primária. A duração média de internamento (±DP) foi de 30,4 (± 15,1) dias e não ocorreram óbitos. A experiência do centro é determinante na abordagem escolhida e na rapidez de actuação. Provavelmente ambas influenciam o prognóstico imediato.Pediatric management of complicated pleural effusion (CPE) remains controversial. Different approaches include antibiotics and chest tube drainage alone or the use of fibrinolitics, videothorascoscopy (VTC) and surgical decortication through thoracotomy. The aim of the present study was to review, evaluate and update technical approach to CPE. We retrospectively reviewed the clinical files of children admitted to the Pediatric Respiratory Ward between 1992 and 2003 with the diagnosis of CPE. Twenty-five patients were included [15 male (60%)]. Mean (±SD) age was 37,4 (±37,0) months. Bacteria were identified in 17/25 (68%) [S. aureus in 6/17 (35%), St. pneumoniae in 5/17 (29%)], 16/17 (94%)in the pleural fluid. Twenty-five children were treated with antibiotics and thoracocentesis (100%). Chest tube drainage was required in 22/25 (88%) with mean (±DP) duration of 14,2 (±7,8) days. Fibrinolitics were employed in 1 only case and surgical decortication in 11/25 (44%). One patient (4%) was submitted to primary VTC. Median length of stay was 30,4 (±15,1) days and no deaths were recorded. Center skills in CPE management are critical on the choice of the technique and the timing of approach. This seems to influence immediate prognosis

At the crossroads between Africa and Eurasia, Arabia is necessarily a melting pot, its peoples enriched by successive gene flow over the generations. Estimating the timing and impact of these multiple migrations are important steps in reconstructing the key demographic events in the human history. However, current methods based on genome-wide information identify admixture events inefficiently, tending to estimate only the more recent ages, as here in the case of admixture events across the Red Sea (~8-37 generations for African input into Arabia, and 30-90 generations for "back-to-Africa" migrations). An mtDNA-based founder analysis, corroborated by detailed analysis of the whole-mtDNA genome, affords an alternative means by which to identify, date and quantify multiple migration events at greater time depths, across the full range of modern human history, albeit for the maternal line of descent only. In Arabia, this approach enables us to infer several major pulses of dispersal between the Near East and Arabia, most likely via the Gulf corridor. Although some relict lineages survive in Arabia from the time of the out-of-Africa dispersal, 60 ka, the major episodes in the peopling of the Peninsula took place from north to south in the Late Glacial and, to a lesser extent, the immediate post-glacial/Neolithic. Exchanges across the Red Sea were mainly due to the Arab slave trade and maritime dominance (from ~2.5 ka to very recent times), but had already begun by the early Holocene, fuelled by the establishment of maritime networks since ~8 ka. The main "back-to-Africa" migrations, again undetected by genome-wide dating analyses, occurred in the Late Glacial period for introductions into eastern Africa, whilst the Neolithic was more significant for migrations towards North Africa.

Background: The last decades have seen an increased awareness by the scientific community of the extent of resistance to conventional antibiotics, particularly with respect to the emerging multidrug-resistant pathogenic microbes. Additionally, natural antioxidants have received significant attention among food professionals and consumers because of their assumed safety and potential therapeutic value. The aim of this work was to assess the antioxidant activities of eight selected commercial essential oils (EOs), together with the evaluation of their antibacterial and anti-quorum sensing properties. Methods: The chemical profiling of the EOs was performed using gas chromatography-mass spectrometry (GC-MS) analysis. The antioxidant properties of the EOs were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and by β-carotene bleaching test. Disc diffusion assays were employed to evaluate the anti-bacterial and anti-quorum sensing activities of the EOs. Results: It was observed that EOs from three Eucalyptus species are rich in eucalyptol. Generally, linalool is abundant in EOs from four Lavandula species. The oil of Cymbopogon citratus is the one with the best capacity to scavenge the DPPH free radicals and presented great antibacterial activity. Conclusions: The geographical origins of the plant species are determinant factors in the EO composition and in the corresponding biological activities.

Mitochondrial DNA (mtDNA), the circular DNA molecule inside the mitochondria of all eukaryotic cells, has been shown to be under the effect of purifying selection in several species. Traditional testing of purifying selection has been based simply on ratios of nonsynonymous to synonymous mutations, without considering the relative age of each mutation, which can be determined by phylogenetic analysis of this non-recombining molecule. The incorporation of a mutation time-ordering from phylogeny and of predicted pathogenicity scores for nonsynonymous mutations allow a quantitative evaluation of the effects of purifying selection in human mtDNA. Here, by using this additional information, we show that purifying selection undoubtedly acts upon the mtDNA of other mammalian species/genera, namely Bos sp., Canis lupus, Mus musculus, Orcinus orca, Pan sp. and Sus scrofa. The effects of purifying selection were comparable in all species, leading to a significant major proportion of nonsynonymous variants with higher pathogenicity scores in the younger branches of the tree. We also derive recalibrated mutation rates for age estimates of ancestors of these various species and proposed a correction curve in order to take into account the effects of selection. Understanding this selection is fundamental to evolutionary studies and to the identification of deleterious mutations.

The emergence of more refined chronologies for climate change and archaeology in prehistoric Africa, and for the evolution of human mitochondrial DNA (mtDNA), now make it feasible to test more sophisticated models of early modern human dispersals suggested by mtDNA distributions. Here we have generated 42 novel whole-mtDNA genomes belonging to haplogroup L0, the most divergent clade in the maternal line of descent, and analysed them alongside the growing database of African lineages belonging to L0's sister clade, L1'6. We propose that the last common ancestor of modern human mtDNAs (carried by "mitochondrial Eve") possibly arose in central Africa ~180 ka, at a time of low population size. By ~130 ka two distinct groups of anatomically modern humans co-existed in Africa: broadly, the ancestors of many modern-day Khoe and San populations in the south and a second central/eastern African group that includes the ancestors of most extant worldwide populations. Early modern human dispersals correlate with climate changes, particularly the tropical African "megadroughts" of MIS 5 (marine isotope stage 5, 135-75 ka) which paradoxically may have facilitated expansions in central and eastern Africa, ultimately triggering the dispersal out of Africa of people carrying haplogroup L3 ~60 ka. Two south to east migrations are discernible within haplogroup LO. One, between 120 and 75 ka, represents the first unambiguous long-range modern human dispersal detected by mtDNA and might have allowed the dispersal of several markers of modernity. A second one, within the last 20 ka signalled by L0d, may have been responsible for the spread of southern click-consonant languages to eastern Africa, contrary to the view that these eastern examples constitute relicts of an ancient, much wider distribution.

The forensic genetics field is generating extensive population data on polymorphism of short tandem repeats (STR) markers in globally distributed samples. In this study we explored and quantified the informative power of these datasets to address issues related to human evolution and diversity, by using two online resources: an allele frequency dataset representing 141 populations summing up to almost 26 thousand individuals; a genotype dataset consisting of 42 populations and more than 11 thousand individuals. We show that the genetic relationships between populations based on forensic STRs are best explained by geography, as observed when analysing other worldwide datasets generated specifically to study human diversity. However, the global level of genetic differentiation between populations (as measured by a fixation index) is about half the value estimated with those other datasets, which contain a much higher number of markers but much less individuals. We suggest that the main factor explaining this difference is an ascertainment bias in forensics data resulting from the choice of markers for individual identification. We show that this choice results in average low variance of heterozygosity across world regions, and hence in low differentiation among populations. Thus, the forensic genetic markers currently produced for the purpose of individual assignment and identification allow the detection of the patterns of neutral genetic structure that characterize the human population but they do underestimate the levels of this genetic structure compared to the datasets of STRs (or other kinds of markers) generated specifically to study the diversity of human populations.

A Síndrome da Imunodeficiência Adquirida se configura nos dias de hoje como uma pandemia mundial de acentuada propagação e passou a atingir muitas mulheres em idade fértil, fenômeno conhecido como feminização da epidemia. Conseqüentemente, as crianças passaram a constituir um grupo também crescente para a infecção do vírus da imunodeficiência humana através da transmissão vertical, ocasionando a infantilização do agravo. Para evitar tal fato foram instituídas medidas de prevenção, entre elas o impedimento do aleitamento materno, conhecido como reverso da amamentação. Frente isto foi traçado como objetivo discutir as implicações do reverso da amamentação imposto pela condição sorológica da mãe e descrever a forma de enfrentamento desta condição. Trata-se de uma pesquisa de abordagem qualitativa realizada no Serviço de Assistência Especializada da Secretaria Municipal de Juiz de Fora, local em que é desenvolvido o Programa de Doenças Sexualmente Transmissíveis. O instrumento utilizado para a obtenção dos dados foi um questionário semi-estruturado aplicado á gestantes e mães com sorologia positiva para o HIV. Na análise e discussão dos dados foram enfatizados padrões relevantes para atingir os objetivos propostos destacando os depoimentos importantes que levem a compreensão do contexto estudado. A guisa da conclusão evidencia-se que é imprescindível o profissional de saúde se aproximar da realidade dessas mulheres, ouvindo-as e permitindo que elas expressem todos os seus sentimentos e dúvidas. Assim, será capaz de esclarecer todos os seus anseios, perceber possíveis riscos para a saúde da mulher e do filho, além de criar medidas que torne mais branda a vivencia dessa realidade.

Let X(i) ={Xgi(n)}n≥1, i= 1, 2, be sequences of random variables, where {gi(n)}n≥1 are disjoint and strictly increasing sequences of integer numbers such that {g1(n)}n≥1 ∪ {g2(n)}n≥1 = N. Using superposition of point processes, we study the extremal behaviour of a superposed sequence {Xn}n≥1 = {Xg1(n)}n≥1 ∪ {Xg2(n)}n≥1 , where we consider the proportion of variables superposed from each sequence asymptotically constant and {Xn}n≥1 verifying some dependence conditions. We apply the obtained results in the computation of the bivariate extremal index.

When infants with recurrent wheezing have a clinical course inconsistent with a common diagnosis, anatomic malformations should be considered in diagnostic workup, followed by medical stabilization and early therapy. A careful history and physical examination could reveal important diagnostic clues that indicate the need to perform a fiberoptic bronchoscopy, which in the reported case showed tracheal stenosis in the transition between the first and second third of the trachea. Chest CT scan revealed a long funnel-shaped tracheal stenosis and along with an echocardiogram, excluded associated cardiovascular malformations. Surgical correction by sliding tracheoplasty under extra-corporeal circulation was successfully performed at the Hospital Gregório Marañon in Madrid. The surgical complications that have occurred (mediastinitis and pulmonary embolism) were resolved. After a two-year follow-up, that included endoscopic control, the patient was found to be free of symptoms of wheezing or post-surgical complications. The authors emphasize the need for early diagnosis and surgical treatment to be performed in an experienced reference center.