PO 8608 Established partnerships of the University of Cape Verde with the University of Leicester, UK and the Institute of Hygiene and Tropical Medicine, Portugal

Background The University of Cape Verde (Uni-CV) was founded in 2006 and since then has developed an effective international strategy that is enhancing the teaching and research culture of the university. To build capacity in the public health field, Uni-CV has established collaborations with the University of Leicester (UoL), UK, and with the Institute of Hygiene and Tropical Medicine (IHTM – NOVA University), Portugal. These follow different approaches. Methods Different type of capacity building initiatives focused on researchers and postgraduate students. Results The collaboration with UoL was established in 2016 and builds on funded research programmes in infectious disease and evolution of antimicrobial drug resistance (AMR). These programmes have allowed technology development and transfer, which offer the opportunity for undergraduate students to lead laboratory–based research projects at Uni-CV. In these two years, we have successfully characterised the epidemiology and patterns of AMR underlying Helicobacter pylori infections in Cape Verde. Beyond the research outputs, we have trained four undergraduates in laboratory-based microbiology at Uni-CV. From this experience, we are currently designing new sustainable higher education programmes aligned with the MSc in Public health at Uni-CV that aim to support Uni-CV lecturers in the supervision of postgraduate students, either independently or in collaboration with UoL researchers. The collaboration with IHTM was established in 2008 with the main aim of developing the research capacity of Cape Verde researchers and health professionals in infection and vector-born diseases and in bioethics. These activities have also led to collaborative research in these areas. Since then, six training courses were taught that benefited ∼20 Uni-CV lecturers and ∼100 government professionals. Conclusion Although these collaborative approaches are different in nature, they have been successful in the training of health professionals, researchers and technicians in Cape Verde and have contributed to the establishment of mutually beneficial research programmes.publishersversionpublishe

cis-Regulatory Changes in Kit Ligand Expression and Parallel Evolution of Pigmentation in Sticklebacks and Humans

SummaryDramatic pigmentation changes have evolved within most vertebrate groups, including fish and humans. Here we use genetic crosses in sticklebacks to investigate the parallel origin of pigmentation changes in natural populations. High-resolution mapping and expression experiments show that light gills and light ventrums map to a divergent regulatory allele of the Kit ligand (Kitlg) gene. The divergent allele reduces expression in gill and skin tissue and is shared by multiple derived freshwater populations with reduced pigmentation. In humans, Europeans and East Asians also share derived alleles at the KITLG locus. Strong signatures of selection map to regulatory regions surrounding the gene, and admixture mapping shows that the KITLG genomic region has a significant effect on human skin color. These experiments suggest that regulatory changes in Kitlg contribute to natural variation in vertebrate pigmentation, and that similar genetic mechanisms may underlie rapid evolutionary change in fish and humans

Benefits on Hematological and Biochemical Parameters of a High-Intensity Interval Training Program for a Half-Marathon in Recreational Middle-Aged Women Runners

(1) Background: half-marathon races are popular among recreational runners, with increases in participation among middle-aged and women. We aimed to determine the effects of two half-marathon training programs on hematological and biochemical markers in middle-aged female recreational runners; (2) Methods: ten women (40 ± 7 years) followed moderate intensity continuous training (MICT), based on running volume below 80% VO2max, and another ten women followed high intensity interval training (HIIT) at 80-100% VO2max, with less volume, and combined with eccentric loading exercise. Hematology, plasma osmolality, and plasma markers of metabolic status, muscle damage, inflammatory, and oxidative stress were measured before (S1) and after (S2) training and 24 h after the half-marathon (S3); (3) Results: both training programs had similar moderate effects at S2. However, the acute response at S3 induced different alterations. There was a greater decrease in cholesterol and triglyceride levels in MICT and reductions in markers of damage and inflammation in HIIT. Greater variability in some plasma markers at S3 in MICT suggests that there is inter-individual variability in the response to training; (4) Conclusions: HIIT led to better adaptation to the competition maybe because of the repeated exposure to higher oxygen consumption and eccentric loading exercise

Genome-wide Association and Population Genetic Analysis of C-Reactive Protein in African American and Hispanic American Women

C-reactive protein (CRP) is a systemic inflammation marker that predicts future cardiovascular risk. CRP levels are higher in African Americans and Hispanic Americans than in European Americans, but the genetic determinants of CRP in these admixed United States minority populations are largely unknown. We performed genome-wide association studies (GWASs) of 8,280 African American (AA) and 3,548 Hispanic American (HA) postmenopausal women from the Women's Health Initiative SNP Health Association Resource. We discovered and validated a CRP-associated variant of triggering receptors expressed by myeloid cells 2 (TREM2) in chromosomal region 6p21 (p = 10−10). The TREM2 variant associated with higher CRP is common in Africa but rare in other ancestral populations. In AA women, the CRP region in 1q23 contained a strong admixture association signal (p = 10−17), which appears to be related to several independent CRP-associated alleles; the strongest of these is present only in African ancestral populations and is associated with higher CRP. Of the other genomic loci previously associated with CRP through GWASs of European populations, most loci (LEPR, IL1RN, IL6R, GCKR, NLRP3, HNF1A, HNF4A, and APOC1) showed consistent patterns of association with CRP in AA and HA women. In summary, we have identified a common TREM2 variant associated with CRP in United States minority populations. The genetic architecture underlying the CRP phenotype in AA women is complex and involves genetic variants shared across populations, as well as variants specific to populations of African descent

Asymmetries of the Muscle Mechanical Properties of the Pelvic Floor in Nulliparous and Multiparous Women, and Men: A Cross-Sectional Study

This study aimed to identify if the muscle mechanical properties (MMPs) of both sides of pelvic floor muscles (PFMs) are symmetrical in different populations of both sexes. Between-sides comparisons of MMPs of PFMs, assessed with manual myotonometry, were performed in three groups, with 31 subjects each, composed of healthy nulliparous women (without any type of delivery or pregnancy), multiparous women (with at least two vaginal deliveries), and healthy adult men. Intra-group correlations between MMPs and age, body mass index (BMI), or clinical state of pelvic floor were also obtained. The nulliparous women and the men showed no between-sides differences in any MMP of PFMs. However, the multiparous women showed that the right side displayed less frequency (−0.65 Hz, 95% CI = −1.01, −0.20) and decrement (0.5, 95% CI = 0.11, 0.01), and more relaxation (1.00 ms, 95% CI = 0.47, 1.54) and creep (0.07 De, 95% CI = 0.03, 0.11), than the left side. Further, MMPs were related to age, sex, and BMI, also depending on the population, with the multiparous women being the only group with some between-sides asymmetries, which in this case were positive and of fair intensity for the left side of the PFMs, between BMI, and frequency and stiffness (rho Spearman coefficient: 0.365 and 0.366, respectively). The symmetry of MMPs of the PFMs could depend on the subject’s condition. Multiparous women show a higher tendency to asymmetries than nulliparous women and men, which should be considered in research and clinical settings

Prolegomenon to the Comparison of Stylistic Features of Hungarian and Croatian Manor Houses in Historicism

Bogate hrvatsko-mađarske kulturne i arhitektonske veze proizlaze iz više od osam stoljeća dugog suživota unutar istoga kraljevstva. U članku koji je rezultat istraživanja ladanjske arhitekture Mađarske i Hrvatske, autori donose pregled dvoraca obiju zemalja, ponajprije onih izgrađenih u doba historicizma. Dvorci su analizirani, strukturirani i predstavljeni prema glavnim stilskim tendencijama toga doba.Croatian-Hungarian cultural and architectural relations are the result of more than eight centuries long cohabitation in the same kingdom. In the paper, which is the result of a research on country house building in Hungary and in Croatia, the authors present an overview of manors built in both countries, focusing on those built in the age of historicism. The manors are analysed, sorted, and presented according to the main stylistic trends of that period

Streptococcus pneumoniae serotypes that frequently colonise the human nasopharynx are common recipients of penicillin-binding protein gene fragments from Streptococcus mitis

Streptococcus pneumoniae is an important global pathogen that causes bacterial pneumonia, sepsis and meningitis. Beta-lactam antibiotics are the first-line treatment for pneumococcal disease, however, their effectiveness is hampered by beta-lactam resistance facilitated by horizontal genetic transfer (HGT) with closely related species. Although interspecies HGT is known to occur among the species of the genus Streptococcus, the rates and effects of HGT between Streptococcus pneumoniae and its close relatives involving the penicillin binding protein (pbp) genes remain poorly understood. Here we applied the fastGEAR tool to investigate interspecies HGT in pbp genes using a global collection of whole-genome sequences of Streptococcus mitis, Streptococcus oralis and S. pneumoniae. With these data, we established that pneumococcal serotypes 6A, 13, 14, 16F, 19A, 19F, 23F and 35B were the highest-ranking serotypes with acquired pbp fragments. S. mitis was a more frequent pneumococcal donor of pbp fragments and a source of higher pbp nucleotide diversity when compared with S. oralis. Pneumococci that acquired pbp fragments were associated with a higher minimum inhibitory concentration (MIC) for penicillin compared with pneumococci without acquired fragments. Together these data indicate that S. mitis contributes to reduced β-lactam susceptibility among commonly carried pneumococcal serotypes that are associated with long carriage duration and high recombination frequencies. As pneumococcal vaccine programmes mature, placing increasing pressure on the pneumococcal population structure, it will be important to monitor the influence of antimicrobial resistance HGT from commensal streptococci such as S. mitis

47 patients with FLNA associated periventricular nodular heterotopia

Background: Heterozygous loss of function mutations within the Filamin A gene in Xq28 are the most frequent cause of bilateral neuronal periventricular nodular heterotopia (PVNH). Most affected females are reported to initially present with difficult to treat seizures at variable age of onset. Psychomotor development and cognition may be normal or mildly to moderately impaired. Distinct associated extracerebral findings have been observed and may help to establish the diagnosis including patent ductus arteriosus Botalli, progressive dystrophic cardiac valve disease and aortic dissection, chronic obstructive lung disease or chronic constipation. Genotype-phenotype correlations could not yet be established. Methods: Sanger sequencing and MLPA was performed for a large cohort of 47 patients with Filamin A associated PVNH (age range 1 to 65 years). For 34 patients more detailed clinical information was available from a structured questionnaire and medical charts on family history, development, epileptologic findings, neurological examination, cognition and associated clinical findings. Available detailed cerebral MR imaging was assessed for 20 patients. Results: Thirty-nine different FLNA mutations were observed, they are mainly truncating (37/39) and distributed throughout the entire coding region. No obvious correlation between the number and extend of PVNH and the severity of the individual clinical manifestation was observed. 10 of the mutation carriers so far are without seizures at a median age of 19.7 years. 22 of 24 patients with available educational data were able to attend regular school and obtain professional education according to age. Conclusions: We report the clinical and mutation spectrum as well as MR imaging for a large cohort of 47 patients with Filamin A associated PVNH including two adult males. Our data are reassuring in regard to psychomotor and cognitive development, which is within normal range for the majority of patients. However, a concerning median diagnostic latency of 17 to 20 years was noted between seizure onset and the genetic diagnosis, intensely delaying appropriate medical surveillance for potentially life threatening cardiovascular complications as well as genetic risk assessment and counseling prior to family planning for this X-linked dominant inherited disorder with high perinatal lethality in hemizygous males

Novel Multilocus Sequence Typing and Global Sequence Clustering Schemes for Characterizing the Population Diversity of Streptococcus mitis

Streptococcus mitis is a common oral commensal and an opportunistic pathogen that causes bacteremia and infective endocarditis; however, the species has received little attention compared to other pathogenic streptococcal species. Effective and easy-to-use molecular typing tools are essential for understanding bacterial population diversity and biology, but schemes specific for S. mitis are not currently available. We therefore developed a multilocus sequence typing (MLST) scheme and defined sequence clusters or lineages of S. mitis using a comprehensive global data set of 322 genomes (148 publicly available and 174 newly sequenced). We used internal 450-bp sequence fragments of seven housekeeping genes (accA, gki, hom, oppC, patB, rlmN, and tsf) to define the MLST scheme and derived the global S. mitis sequence clusters using the PopPUNK clustering algorithm. We identified an initial set of 259 sequence types (STs) and 258 global sequence clusters. The schemes showed high concordance (100%), capturing extensive S. mitis diversity with strains assigned to multiple unique STs and global sequence clusters. The tools also identified extensive within- and between-host S. mitis genetic diversity among isolates sampled from a cohort of healthy individuals, together with potential transmission events, supported by both phylogeny and pairwise single nucleotide polymorphism (SNP) distances. Our novel molecular typing and strain clustering schemes for S. mitis allow for the integration of new strain data, are electronically portable at the PubMLST database (https://pubmlst.org/smitis), and offer a standardized approach to understanding the population structure of S. mitis. These robust tools will enable new insights into the epidemiology of S. mitis colonization, disease and transmission