Kikuchi-Fujimoto - an enigmatic and rare disease: a report of 3 cases and brief review of the literature.

Kikuchi-Fujimoto disease (KFD) is a rare and benign condition mainly characterized by fever and lymphadenopathies. Although many studies have been carried out over time, its aetiology remains unclear, with infectious and autoimmune processes being hypothesized as the main causes. We report three cases of Kikuchi-Fujimoto disease. All patients were female and presented with fever and cervical lymphadenopathies. Extensive work up was performed, in order to rule out infectious, autoimmune and lymphoproliferative diseases. The diagnosis was established through lymph node excisional biopsy and histopathological examination. All patients were followed-up in a medical appointment, with one developing systemic lupus erythematosus (SLE).

Golden lion tamarin metapopulation dynamics five years after heavy losses to yellow fever.

The golden lion tamarin (GLT) is an Endangered primate endemic to Brazil's lowland Atlantic Forest. After centuries of deforestation and capture for the pet trade, only a few hundred individuals survived, all in isolated forest fragments 85 km from Rio de Janeiro city. Intensive conservation actions, including reintroduction of zoo-born tamarins, increased numbers to about 3700 in 2014. The most severe yellow fever epidemic/epizootic in Brazil in 80 years reduced two of the largest GLT populations by over 90%. Herein we report the results of a 2023 survey of GLTs designed to examine the dynamics of population recovery following yellow fever. Results indicate that populations hard hit by yellow fever are recovering due in part to immigration from adjacent forest fragments. No local extirpations were observed. About 4800 GLTs live in the survey area. This represents a 31% increase since the baseline survey completed in 2014. Two factors explain most of the increase: four large areas that had no GLTs or very low-density populations in 2014 are now at moderate density (three areas) or low density (one area), explaining 71% of overall increase since 2014. Increase in forest area within our survey area may explain up to 16% of the increase in GLT numbers since 2014. Results of computer simulations suggest that strengthening forest connectivity will facilitate metapopulation resilience in the face of mortality factors such as yellow fever.

PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families.

Childhood-onset osteoporosis is a rare but clinically significant condition. Studies have shown pathogenic variants in more than 20 different genes as causative for childhood-onset primary osteoporosis. The X-chromosomal PLS3, encoding Plastin-3, is one of the more recently identified genes. In this study, we describe five new families from four different European countries with PLS3-related skeletal fragility. The index cases were all hemizygous males presenting with long bone and vertebral body compression fractures. All patients had low lumbar spine bone mineral density (BMD). The age at the first clinical fracture ranged from 1.5 to 13 years old. Three of the identified PLS3 variants were stop-gain variants and two were deletions involving either a part or all exons of the gene. In four families the variant was inherited from the mother. All heterozygous women reported here had normal BMD and no bone fractures. Four patients received bisphosphonate treatment with good results, showing a lumbar spine BMD increment and vertebral body reshaping after 10 months to 2 years of treatment. Our findings expand the genetic spectrum of PLS3-related osteoporosis. Our report also shows that early treatment with bisphosphonates may influence the disease course and reduce the progression of osteoporosis, highlighting the importance of early diagnosis for prompt intervention and appropriate genetic counseling.

Artificial intelligence and statistical methods for stratification and prediction of progression in amyotrophic lateral sclerosis: A systematic review.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive loss of motor neurons in the brain and spinal cord. The fact that ALS's disease course is highly heterogeneous, and its determinants not fully known, combined with ALS's relatively low prevalence, renders the successful application of artificial intelligence (AI) techniques particularly arduous. OBJECTIVE: This systematic review aims at identifying areas of agreement and unanswered questions regarding two notable applications of AI in ALS, namely the automatic, data-driven stratification of patients according to their phenotype, and the prediction of ALS progression. Differently from previous works, this review is focused on the methodological landscape of AI in ALS. METHODS: We conducted a systematic search of the Scopus and PubMed databases, looking for studies on data-driven stratification methods based on unsupervised techniques resulting in (A) automatic group discovery or (B) a transformation of the feature space allowing patient subgroups to be identified; and for studies on internally or externally validated methods for the prediction of ALS progression. We described the selected studies according to the following characteristics, when applicable: variables used, methodology, splitting criteria and number of groups, prediction outcomes, validation schemes, and metrics. RESULTS: Of the starting 1604 unique reports (2837 combined hits between Scopus and PubMed), 239 were selected for thorough screening, leading to the inclusion of 15 studies on patient stratification, 28 on prediction of ALS progression, and 6 on both stratification and prediction. In terms of variables used, most stratification and prediction studies included demographics and features derived from the ALSFRS or ALSFRS-R scores, which were also the main prediction targets. The most represented stratification methods were K-means, and hierarchical and expectation-maximisation clustering; while random forests, logistic regression, the Cox proportional hazard model, and various flavours of deep learning were the most widely used prediction methods. Predictive model validation was, albeit unexpectedly, quite rarely performed in absolute terms (leading to the exclusion of 78 eligible studies), with the overwhelming majority of included studies resorting to internal validation only. CONCLUSION: This systematic review highlighted a general agreement in terms of input variable selection for both stratification and prediction of ALS progression, and in terms of prediction targets. A striking lack of validated models emerged, as well as a general difficulty in reproducing many published studies, mainly due to the absence of the corresponding parameter lists. While deep learning seems promising for prediction applications, its superiority with respect to traditional methods has not been established; there is, instead, ample room for its application in the subfield of patient stratification. Finally, an open question remains on the role of new environmental and behavioural variables collected via novel, real-time sensors.

Knowledge and Beliefs about Herb/Supplement Consumption and Herb/Supplement-Drug Interactions among the General Population, including Healthcare Professionals and Pharmacists: A Systematic Review and Guidelines for a Smart Decision System.

The increased consumption of a variety of herbs/supplements has been raising serious health concerns. Owing to an inadequate understanding of herb/supplement-drug interactions, the simultaneous consumption of these products may result in deleterious effects and, in extreme cases, even fatal outcomes. This systematic review is aimed at understanding the knowledge and beliefs about the consumption of herbs/supplements and herb/drug-supplement interactions (HDIs). The study follows the PRISMA guidelines. Four online databases (Web of Science; PubMed; Cochrane; and EBSCOhost) were searched, and a total of 44 studies were included, encompassing 16,929 participants. Herb and supplement consumption is explained mostly by the reported benefits across multiple conditions and ease of use. Regarding HDIs, most people take both herbs/supplements and prescription drugs simultaneously. Only a small percentage of participants have knowledge about their interaction effects, and many reported adverse interactions or side effects. Nevertheless, the main reason for stopping the prescribed drug intake is the perceived lack of its effect, and not due to interactions. Therefore, it is important to increase the knowledge about supplement use so that further strategies can be elaborated to better detect or be alert for whenever a potentially dangerous reaction and/or interaction may occur. This paper raises awareness regarding the need for developing a decision support system and ends with some considerations about the development of a technological solution capable of detecting HDIs and, thereby, aiding in the improvement of pharmacy services.

Reliability of the Coimbra Reactive Agility Soccer Test (CRAST).

Agility is a fitness-skill-related component that should be a part of the standard physiological testing for soccer players and one of the key performance indicators in soccer. The present study aimed to assess the reliability of the CRAST as a research tool in the study of soccer skills. Twenty-one university soccer players (chronological age: 19.3 ± 1.4 years; body mass: 69.6 ± 8.2 kg; stature: 173.5 ± 6.5 cm; federated training experience: 9.7 ± 3.6 years) volunteered for the testing protocol. The CRAST requires players to complete random courses six times as quickly as possible. In addition, the CRAST requires players to control and dribble the markers (four different colors: green, yellow, blue, and red). The soccer players completed three trials, each separated by one week. The first trial accounted for familiarization; the second and third were considered for analysis. The correlation for overall performance was very strong. The reliability of the CRAST was slightly better for total time than that for the penalty score (0.95 vs. 0.93). The TEM and the associated CV range of 7.04%-7.54% were for the penalty score and the total time, respectively. For both measurements, the ICC values also represent excellent reliability, as both values were over 0.900. The CRAST is a reliable protocol for assessing agility in soccer players.

Materiais educacionais acessíveis ­ tradução para linguagem fácil e validação de folheto informativo de apoio à reabilitação respiratória / Accessible educational materials - translation into easy language and validation of information leaflet to support respiratory rehabilitation

Em Portugal a literacia em saúde é particularmente baixa em faixas específicas da população nomeadamente nas pessoas com baixa escolaridade e, dentro destas, nas pessoas com deficiência e incapacidade intelectual/cognitiva. A esta população, com evidentes dificuldades em aceder e compreender informações complexas, juntam-se as pessoas cuja língua materna não é o português como é o caso da população migrante. Torna-se, portanto, imperioso que toda a informação lhes seja fornecida de forma acessível. Os Enfermeiros de Reabilitação no âmbito do exercício na comunidade confrontam-se, muitas vezes, com esta realidade. Os materiais educacionais acessíveis são fundamentais para garantir a eficácia da componente educacional dos programas de reabilitação e pode assegurar a sua realização autónoma no domicílio. Objetivos: Traduzir para linguagem fácil um folheto informativo de apoio à Reabilitação Respiratória. Validar essa tradução em três grupos específicos. Metodologia: Utilizou-se uma metodologia de tradução e validação por rondas com recurso a um painel de consultores, selecionado por conveniência, que incluiu pessoas com deficiência e incapacidade intelectual/cognitiva, pessoas cuja língua materna não é o português e pessoas com baixa escolaridade. Foi, ainda, usado o software de Análise de Legibilidade Textual disponível online. Resultados: O painel de consultores foi constituído por 27 pessoas com média de idade de 35,6 anos. Relativamente à escolaridade, as pessoas cuja língua materna não é o português frequentavam o 1o ano do ensino superior, as pessoas com baixa escolaridade frequentam o 2o ciclo no ensino profissional e as pessoas com deficiência e incapacidade intelectual/cognitiva variam entre 1o ciclo (2), 2o ciclo (2) e ensino secundário (1). Nas sucessivas rondas verificou-se a necessidade de introduzir a explicação de palavras complexas que não podem ser substituídas nem retiradas como por exemplo termos técnicos, de reduzir frases longas, usar palavras mais simples e de usar um registo de língua informal para o leitor. Foram ainda substituídos os desenhos dos exercícios por fotografias da sequência dos movimentos. Da versão original para a final a análise da legibilidade textual baixou de nível 14 ‒ Média legibilidade, Dificuldade média, para nível 9 ‒ Alta legibilidade, Texto simples. Conclusões: Envolver as pessoas nos processos de criação de materiais educacionais acessíveis é reconhecido como boas práticas na promoção da Literacia em Saúde. Esta estratégia permitiu identificar as reais dificuldades e necessidades das pessoas a que a informação se destina. A componente educacional dos programas de enfermagem de reabilitação deve incluir toda a informação necessária de forma acessível tendo em consideração a população-alvo dos cuidados de Enfermagem de Reabilitação.

In Portugal, health literacy is somewhat low in the general population, and especially so in groups that have low literacy and, among these, in people with intellectual and cognitive impairments. This subgroup shows clear difficulties in accessing and understanding complex information, as well as people whose mother tongue is not Portuguese, as the case of migrants. It is then of the utmost importance that all information is given to them in accessible formats. Rehabilitation nurses often come across this reality when working within the community. The production of accessible educational materials is essential for guaranteeing the effectiveness of the pedagogy underlying rehabilitation programmes and for ensuring that patients repeat them autonomously at home. Aims: Translating into easy language an information brochure to support Respiratory Rehabilitation. Validating this translation with 3 different groups. Methodology: A methodology of translation was conducted, as well as validation in rounds that resorted to a group of consultants. This group was chosen for convenience and included people with intellectual and cognitive impairments, people speaking Portuguese as a foreign language and people with low literacy. The online software for the analysis of text readability was also used. Results: The group of consultants comprehended 27 people with an average age of 35.6 years. In terms of their schooling, people whose language is not Portuguese were attending the 1st year in higher education, people with low literacy attended the 2nd cycle of professional education and people with intellectual and cognitive impairments varied between the 1st cycle of Basic Education (2), the 2nd cycle of Basic Education (2) and secondary school (1). In the successive rounds, it was necessary to introduce the explanation of complex words that could not be neither replaced nor removed, such as technical terms, to reduce long sentences, use simpler words and use a direct language register. The drawings of the exercises were also replaced by photos illustrating the sequence of movements. Between the original version and the final one, the analysis of text readability dropped from level 14 ­ Medium readability, medium difficulty, to level 9 ­ High readability, simple text. Conclusions: Involving people in the process of creating accessible educational materials is regarded as a good practice in the promotion of Health Literacy. This strategy allowed to identify the real difficulties and needs of the people to whom information is directed. The educational component of pulmonary rehabilitation programmes ought to include all necessary information in accessible formats considering the target groups of pulmonary rehabilitation.

Characterization of Novel Pathogenic Variants Leading to Caspase-8 Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome.

Pathogenic RIPK1 variants have been described as the cause of two different inborn errors of immunity. Biallelic loss-of-function variants cause the recessively inherited RIPK1 deficiency, while monoallelic variants impairing the caspase-8-mediated RIPK1 cleavage provoke a novel autoinflammatory disease (AID) called cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome. The aim of this study was to characterize the pathogenicity of two novel RIPK1 variants located at the cleavage site of caspase-8 detected in patients with dominantly-inherited, early-onset undefined AID. RIPK1 genotyping was performed by Sanger and next-generation sequencing. Clinical and analytical data were collected from medical charts, and in silico and in vitro assays were performed to evaluate the functional consequences. Genetic analyses identified two novel heterozygous RIPK1 variants at the caspase-8 cleavage site (p.Leu321Arg and p.Asp324Gly), which displayed a perfect intrafamilial phenotype-genotype segregation following a dominant inheritance pattern. Structural analyses suggested that these variants disrupt the normal RIPK1 structure, probably making it less accessible to and/or less cleavable by caspase-8. In vitro experiments confirmed that the p.Leu321Arg and p.Asp324Gly RIPK1 variants were resistant to caspase-8-mediated cleavage and induced a constitutive activation of necroptotic pathway in a similar manner that previously characterized RIPK1 variants causing CRIA syndrome. All these results strongly supported the pathogenicity of the two novel RIPK1 variants and the diagnosis of CRIA syndrome in all enrolled patients. Moreover, the evidences here collected expand the phenotypic and genetic diversity of this recently described AID, and provide interesting data about effectiveness of treatments that may benefit future patients.

Learning Prognostic Models Using Disease Progression Patterns: Predicting the Need for Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis is a devastating neurodegenerative disease causing rapid degeneration of motor neurons and usually leading to death by respiratory failure. Since there is no cure, treatment's goal is to improve symptoms and prolong survival. Non-invasive Ventilation (NIV) is an effective treatment, leading to extended life expectancy and improved quality of life. In this scenario, it is paramount to predict its need in order to allow preventive or timely administration. In this work, we propose to use itemset mining together with sequential pattern mining to unravel disease presentation patterns together with disease progression patterns by analysing, respectively, static data collected at diagnosis and longitudinal data from patient follow-up. The goal is to use these static and temporal patterns as features in prognostic models, enabling to take disease progression into account in predictions and promoting model interpretability. As case study, we predict the need for NIV within 90, 180 and 365 days (short, mid and long-term predictions). The learnt prognostic models are promising. Pattern evaluation through growth rate suggests bulbar function and phrenic nerve response amplitude, additionally to respiratory function, are significant features towards determining patient evolution. This confirms clinical knowledge regarding relevant biomarkers of disease progression towards respiratory insufficiency.

Mevalonate Kinase Deficiency: A Cause of Severe Very-Early-Onset Inflammatory Bowel Disease.

Mevalonate kinase deficiency should be considered in patients with severe very-early-onset inflammatory bowel disease (IBD), especially in patients with a history of recurrent or chronic fever, peritoneal adhesions, and atypical IBD pathology. Anti-interleukin-1 therapy may be efficacious in these patients with monogenic very-early-onset IBD.

Oral gallic acid improves metabolic profile by modulating SIRT1 expression in obese mice brown adipose tissue: A molecular and bioinformatic approach.

AIMS: The aim of the presente study was to examine the effects of oral gallic acid (GA) administration on the brown adipose tissue of obese mice fed with high-fat diet. New mechanisms and interactions pathways in thermogenesis were accessed through bioinformatics analyses. MAIN METHODS: Swiss male mice were divided into four groups and fed during 60 days with: standard diet, standard diet combined with gallic acid, high-fat diet and high-fat diet combined with gallic acid. Body weight, food intake, and blood parameters (glucose tolerance test, total-cholesterol, high-density low-c, triglyceride and glucose levels) were evaluated. Brown and subcutaneous white adipose tissue histological analysis were performed. SIRT1 and PGC1-α mRNA expression in the brown adipose tissue were assessed. KEY FINDINGS: Our main findings showed that the gallic acid improved glucose tolerance and metabolic parameters. These results were accompanied by bioinformatics analyses that evidenced SIRT1 as main target in the thermogenesis process, confirmed as increased SIRT1 mRNA expression was evidenced in the brown adipose tissue. SIGNIFICANCE: Together, the data suggest that the gallic acid effect in brown adipose tissue may improve body metabolism, glucose homeostasis and increase thermogenesis.

Yellow fever in Brazil threatens successful recovery of endangered golden lion tamarins.

The golden lion tamarin is an endangered primate endemic to Brazil's Atlantic Forest. Centuries of deforestation reduced numbers to a few hundred individuals in isolated forest fragments 80 km from Rio de Janeiro city. Intensive conservation action including reintroduction of zoo-born tamarins into forest fragments 1984-2000, increased numbers to about 3,700 in 2014. Beginning in November 2016, southeastern Brazil experienced the most severe yellow fever epidemic/epizootic in the country in 80 years. In May 2018, we documented the first death of a golden lion tamarin due to yellow fever. We re-evaluated population sizes and compared them to results of a census completed in 2014. Tamarin numbers declined 32%, with ca. 2,516 individuals remaining in situ. Tamarin losses were significantly greater in forest fragments that were larger, had less forest edge and had better forest connectivity, factors that may favor the mosquito vectors of yellow fever. The future of golden lion tamarins depends on the extent of additional mortality, whether some tamarins survive the disease and acquire immunity, and the potential development of a vaccine to protect the species against yellow fever.

[Live Vaccine in Children with DiGeorge/22q11.2 Deletion Syndrome]. / Vacinas Vivas em Crianças com Síndrome de DiGeorge/ Deleção 22q11.2.

INTRODUCTION: Children with DiGeorge syndrome/chromosome 22q11.2 deletion syndrome might have a variable degree of immunodeficiency, which may limit the use of live vaccines. The aim of this study was to review the adverse effects of live vaccines and possible relation with immune status in patients with DiGeorge Syndrome/partial 22q11.2 deletion syndrome. MATERIAL AND METHODS: Retrospective study with analysis of the clinical records of children with chromosome 22q11.2 deletion syndrome and DiGeorge syndrome phenotype, followed in a Primary Immunodeficiency center. Data were collected on: demographic characteristics; medical and vaccination history with live vaccines; T-CD4+ lymphocyte counts and lymphocyte proliferative responses to antigens and mitogens; adverse reactions; vaccine failure. RESULTS: Twenty three children with DiGeorge syndrome/22q11.2 deletion syndrome were included, 65.2% male, with average age at diagnosis of 11.3 months. Eighteen children (78%) received bacillus Calmette-Guérin vaccine: all with evidence of thymic activity; three presented moderate T-CD4+ lymphopenia and abnormal lymphocyte proliferative responses; one had abnormal lymphocyte proliferative responses for mitogens, four for purified protein derivative and one for tetanus toxoid. Measles, mumps and rubella vaccine was administered to 15 children, three of them with moderate immunosuppression and abnormal lymphocyte proliferative responses. Live attenuated polio vaccine was administered to 4 children without immunosuppression and the rotavirus vaccine to three children, one with moderate immunosuppression. No significant adverse reactions were reported. DISCUSSION: These data are in line with the findings of other international studies. CONCLUSION: In our sample, live vaccines were well-tolerated, even in children with moderate T-CD4+ lymphopenia and abnormal lymphocyte proliferative responses to antigens/mitogens.

Introdução: A síndrome de DiGeorge/deleção 22q11.2 pode apresentar um grau variável de imunodeficiência, condicionando a utilização de vacinas vivas. Este estudo teve como objetivo documentar os efeitos adversos de vacinas vivas e possível relação com alterações imunitárias em crianças com síndrome de DiGeorge/deleção 22q11.2 parcial. Material e Métodos: Foi realizado um estudo retrospetivo por revisão dos processos clínicos das crianças com deleção do cromossoma 22q11.2 e fenótipo de síndrome de DiGeorge, seguidos num centro de referência de imunodeficiências primárias. Foi realizada colheita de dados, incluindo: características demográficas; história médica; historial de vacinação com vacinas vivas; contagem de linfócitos T-CD4+ e respostas proliferativas linfocitárias a antigénios e mitogénios; reações adversas; falências vacinais. Resultados: Foram incluídas 23 crianças com síndrome de DiGeorge/deleção 22q11.2, 65,2% do sexo masculino e idade média de diagnóstico de 11,3 meses. Destas, 18 crianças (78%) receberam a vacina bacillus Calmette-Guérin: todas com evidência de atividade tímica; três apresentaram linfopénia T-CD4+ moderada e respostas proliferativas linfocitárias anormais; uma com respostas proliferativas linfocitárias anormais para mitogénios, quatro para derivado de proteína purificada e uma para toxóide tetânico. A vacina tríplice contra o sarampo, parotidite e rubéola foi administrada a 15 crianças, três com imunossupressão moderada e respostas proliferativas linfocitárias anormais. A vacina viva atenuada contra poliomielite foi administrada a quatro crianças sem imunossupressão e a vacina contra o rotavírus a três crianças, uma com imunossupressão moderada. Não foram reportadas reações adversas. Discussão: Estes dados estão de acordo com as conclusões de outros estudos internacionais. Conclusão: Na nossa amostra, as vacinas vivas atenuadas foram bem toleradas, incluindo em crianças com linfopénia T-CD4+ moderada e com respostas proliferativas linfocitárias a antigénios/mitogénios anormais.

Estimating population sizes to evaluate progress in conservation of endangered golden lion tamarins (Leontopithecus rosalia).

Efforts to reverse the decline of endangered golden lion tamarin monkeys have been relatively successful because the Brazilian organization dedicated to the species' conservation (Associação Mico-Leão-Dourado, AMLD) relies on science-based computer modeling to determine the number of tamarins necessary to achieve demographic and genetic goals, and a process of strategic planning to achieve those goals. Accurate estimates of the numbers of tamarins in forest fragments are essential to evaluate progress in achieving goals and adapt strategies as necessary. In this report we present the results of a new method to survey the number of tamarins in the wild, a modification of the point transect with lures procedure. Using this method, we estimate that in 2014 there were approximately 3,700 golden lion tamarins in 41,400 hectares of Atlantic Forest. Of these, 59% are from remnant wild populations, 34% are descendants of captive-born reintroduced animals and 7% are descendants of wild translocated groups. The number of tamarins and amount of forest estimated in this survey exceeded values necessary to meet AMLD's definition of a viable population, determined to be 2,000 tamarins in 25,000 hectares of connected and protected forest. However, the seven forest blocks and their tamarin populations are not yet adequately connected and protected. AMLD's strategic plan to achieve a viable population of golden lion tamarins includes 12 strategies that mitigate these and other threats or contribute directly to the conservation goal. The point transect with lures survey method provides a way to evaluate progress in achieving that goal and adapt strategies as appropriate.

Unraveling the dispersal patterns and the social drivers of natal emigration of a cooperative breeding mammal, the golden lion tamarin.

The study of the social drivers of animal dispersal is key to understanding the evolution of social systems. Among the social drivers of natal emigration, the conspecific attraction, aggressive eviction, and reduced social integration hypotheses predict that sexually mature individuals who receive more aggressive behavior and are engaged in less affiliative interactions are more likely to disperse. Few reports have explored these proximate factors affecting emigration in cooperatively breeding species, particularly of Neotropical primates. In this study, we investigated the dispersal patterns and tested the social drivers of natal emigration in the golden lion tamarin (Leontopithecus rosalia) - an endangered species inhabiting Atlantic rainforests fragments in Brazil. We used behavioral and demographic data collected during 7 years from 68 groups of tamarins inhabiting 20 forest fragments. Our analyses from the 160 dispersing individuals showed that dispersal success is higher for males and for those engaged in parallel dispersal, but that males and females use different strategies to enhance their dispersal success, males immigrate into established groups while females form new groups. We did not find high levels of agonistic behavior among group members before natal emigration. Instead we found that conspecific attraction drives natal emigration in both sexes, while additionally the low level of affiliative interactions within the natal group triggers male emigration. We discuss natal emigration in the broader perspective of the cooperative breeding system and the implications of these findings for the conservation of the species.

Arthritis in Kawasaki disease: A poorly recognised manifestation.

AIM: To determine the prevalence of arthritis in Kawasaki disease (KD) and the clinical characteristics of children with KD and arthritis. METHODS: This was a single-centre, 15-year, retrospective study of children admitted with KD. Clinical features (including coronary involvement), laboratory results and treatment response were evaluated. RESULTS: Of 63 children with KD, 60.3% were male, with a median of age of 2.0 years. Complete KD was found in 68.3%. The time from symptom onset to treatment was 7.0 days (median); 30.7% had coronary artery aneurysms, from which 82.5% responded to intravenous immunoglobulin. During the course of their illness, eight children developed arthritis (12.7%), which was early onset in six (75%) and oligoarticular in five (62.5%). The median number of joints was 3.5 (P25 = 1.3, P75 = 17.0), and at least one large joint was affected. In all cases, the arthritis was self-limited and left no sequelae, lasting a median of 14 days and no longer than 22 days. KD children with arthritis were older (P = 0.025), and those with early-onset arthritis responded to first-line therapy, unlike the late-onset group (P = 0.018). CONCLUSIONS: This study emphasises the value of a systematic articular examination of joints in KD. Refractory KD was observed in children with late-onset arthritis.

A Helical Short-Peptide Fusion Inhibitor with Highly Potent Activity against Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus.

Human immunodeficiency virus type 2 (HIV-2) has already spread to different regions worldwide, and currently about 1 to 2 million people have been infected, calling for new antiviral agents that are effective on both HIV-1 and HIV-2 isolates. T20 (enfuvirtide), a 36-mer peptide derived from the C-terminal heptad repeat region (CHR) of gp41, is the only clinically approved HIV-1 fusion inhibitor, but it easily induces drug resistance and is not active on HIV-2. In this study, we first demonstrated that the M-T hook structure was also vital to enhancing the binding stability and inhibitory activity of diverse CHR-based peptide inhibitors. We then designed a novel short peptide (23-mer), termed 2P23, by introducing the M-T hook structure, HIV-2 sequences, and salt bridge-forming residues. Promisingly, 2P23 was a highly stable helical peptide with high binding to the surrogate targets derived from HIV-1, HIV-2, and simian immunodeficiency virus (SIV). Consistent with this, 2P23 exhibited potent activity in inhibiting diverse subtypes of HIV-1 isolates, T20-resistant HIV-1 mutants, and a panel of primary HIV-2 isolates, HIV-2 mutants, and SIV isolates. Therefore, we conclude that 2P23 has high potential to be further developed for clinical use, and it is also an ideal tool for exploring the mechanisms of HIV-1/2- and SIV-mediated membrane fusion. IMPORTANCE: The peptide drug T20 is the only approved HIV-1 fusion inhibitor, but it is not active on HIV-2 isolates, which have currently infected 1 to 2 million people and continue to spread worldwide. Recent studies have demonstrated that the M-T hook structure can greatly enhance the binding and antiviral activities of gp41 CHR-derived inhibitors, especially for short peptides that are otherwise inactive. By combining the hook structure, HIV-2 sequence, and salt bridge-based strategies, the short peptide 2P23 has been successfully designed. 2P23 exhibits prominent advantages over many other peptide fusion inhibitors, including its potent and broad activity on HIV-1, HIV-2, and even SIV isolates, its stability as a helical, oligomeric peptide, and its high binding to diverse targets. The small size of 2P23 would benefit its synthesis and significantly reduce production cost. Therefore, 2P23 is an ideal candidate for further development, and it also provides a novel tool for studying HIV-1/2- and SIV-mediated cell fusion.

A genotypic method for determining HIV-2 coreceptor usage enables epidemiological studies and clinical decision support.

BACKGROUND: CCR5-coreceptor antagonists can be used for treating HIV-2 infected individuals. Before initiating treatment with coreceptor antagonists, viral coreceptor usage should be determined to ensure that the virus can use only the CCR5 coreceptor (R5) and cannot evade the drug by using the CXCR4 coreceptor (X4-capable). However, until now, no online tool for the genotypic identification of HIV-2 coreceptor usage had been available. Furthermore, there is a lack of knowledge on the determinants of HIV-2 coreceptor usage. Therefore, we developed a data-driven web service for the prediction of HIV-2 coreceptor usage from the V3 loop of the HIV-2 glycoprotein and used the tool to identify novel discriminatory features of X4-capable variants. RESULTS: Using 10 runs of tenfold cross validation, we selected a linear support vector machine (SVM) as the model for geno2pheno[coreceptor-hiv2], because it outperformed the other SVMs with an area under the ROC curve (AUC) of 0.95. We found that SVMs were highly accurate in identifying HIV-2 coreceptor usage, attaining sensitivities of 73.5% and specificities of 96% during tenfold nested cross validation. The predictive performance of SVMs was not significantly different (p value 0.37) from an existing rules-based approach. Moreover, geno2pheno[coreceptor-hiv2] achieved a predictive accuracy of 100% and outperformed the existing approach on an independent data set containing nine new isolates with corresponding phenotypic measurements of coreceptor usage. geno2pheno[coreceptor-hiv2] could not only reproduce the established markers of CXCR4-usage, but also revealed novel markers: the substitutions 27K, 15G, and 8S were significantly predictive of CXCR4 usage. Furthermore, SVMs trained on the amino-acid sequences of the V1 and V2 loops were also quite accurate in predicting coreceptor usage (AUCs of 0.84 and 0.65, respectively). CONCLUSIONS: In this study, we developed geno2pheno[coreceptor-hiv2], the first online tool for the prediction of HIV-2 coreceptor usage from the V3 loop. Using our method, we identified novel amino-acid markers of X4-capable variants in the V3 loop and found that HIV-2 coreceptor usage is also influenced by the V1/V2 region. The tool can aid clinicians in deciding whether coreceptor antagonists such as maraviroc are a treatment option and enables epidemiological studies investigating HIV-2 coreceptor usage. geno2pheno[coreceptor-hiv2] is freely available at http://coreceptor-hiv2.geno2pheno.org .