Invasive management of significant tricuspid regurgitation in clinical practice.

BACKGROUND: Tricuspid regurgitation (TR) is a prevalent condition inside valvular heart disease (VHD) with relevant prognosis implications. However, concordance between real management in clinical practice and invasive treatment recommendations of European Society of Cardiology (ESC) guidelines is unknown. METHODS: A substudy of ESC VHD II survey was performed to evaluate the real treatment of TR compared to the clinical ESC guidelines recommendations published in 2012, 2017 and 2021 was performed. TR cases with surgical indication were divided in 3 groups: 1: severe isolated TR without previous left VHD; 2: moderate/severe TR and concomitant severe left VHD; 3: severe TR plus previous left VHD surgery. RESULTS: Of 902 patients assessed, 123 had significant TR. Fifty (41%) cases demonstrated ESC guidelines 2012-2017 Class I or IIa recommendations for invasive treatment: 9(18%) of group 1, 37(74%) of group 2 and 4(8%) of group 3. Surgery was performed in 24 patients (48%); 1 in group 1(4%), 22 in group 2(92%) and 1 in group 3(4%). Overall concordance was 48% (group 1: 11%; group 2: 59%; group 3: 25%). Regarding the 2021 ESC guidelines only one patient changed groups with an overall concordance of 47% (group 1: 10%; group 2: 59%; group 3: 25%). CONCLUSION: Concordance between 2012, 2017 and 2021 ESC guidelines recommendations and clinical practice for TR surgical intervention is low, especially in those without concomitant severe left VHD. These results suggest the need to improve further guideline implementation and alternative treatments, such as percutaneous, which could resolve potential discrepancies in those clinical scenarios.

A training plan to implement lung ultrasound for diagnosing pneumonia in children.

BACKGROUND: Lung ultrasound (LUS) for critical patients requires trained operators to perform them, though little information exists on the level of training required for independent practice. The aims were to implement a training plan for diagnosing pneumonia using LUS and to analyze the inter-observer agreement between senior radiologists (SRs) and pediatric intensive care physicians (PICPs). METHODS: Prospective longitudinal and interventional study conducted in the Pediatric Intensive Care Unit of a tertiary hospital. Following a theoretical and practical training plan regarding diagnosing pneumonia using LUS, the concordance between SRs and the PICPs on their LUS reports was analyzed. RESULTS: Nine PICPs were trained and tested on both theoretical and practical LUS knowledge. The mean exam mark was 13.5/15. To evaluate inter-observer agreement, a total of 483 LUS were performed. For interstitial syndrome, the global Kappa coefficient (K) was 0.51 (95% CI 0.43-0.58). Regarding the presence of consolidation, K was 0.67 (95% CI 0.53-0.78), and for the consolidation pattern, K was 0.82 (95% CI 0.79-0.85), showing almost perfect agreement. CONCLUSIONS: Our training plan allowed PICPs to independently perform LUS and might improve pneumonia diagnosis. We found a high inter-observer agreement between PICPs and SRs in detecting the presence and type of consolidation on LUS. IMPACT: Lung ultrasound (LUS) has been proposed as an alternative to diagnose pneumonia in children. However, the adoption of LUS in clinical practice has been slow, and it is not yet included in general clinical guidelines. The results of this study show that the implementation of a LUS training program may improve pneumonia diagnosis in critically ill patients. The training program's design, implementation, and evaluation are described. The high inter-observer agreement between LUS reports from the physicians trained and expert radiologists encourage the use of LUS not only for pneumonia diagnosis, but also for discerning bacterial and viral patterns.

Population structure from NOS genes correlates with geographical differences in coronary incidence across Europe.

OBJECTIVES: The population analysis of cardiovascular risk and non-risk genetic variation can help to identify adaptive or random demographic processes that shaped coronary incidence variation across geography. MATERIAL AND METHODS: In this study, 114 single nucleotide polymorphisms and 17 tandem repeat polymorphisms from Nitric Oxide Synthases (NOS) regions were analyzed in 1686 individuals from 35 populations from Europe, North Africa, and the Middle East. NOS genes encode for key enzymes on nitric oxide availability, which is involved in several cardiovascular processes. These genetic variations were used to test for selection and to infer the population structure of NOS regions. Moreover, we tested whether the variation in the incidence of coronary events and in the levels of classical risk factors in 11 of these European populations could be explained by the population structure estimates. RESULTS: Our results supported, first, the absence of clear signs of selection for NOS genetic variants associated with cardiovascular diseases, and second, the presence of a continuous genetic pattern of variation across European and North African populations without a Mediterranean barrier for gene flow. Finally, population structure estimates from NOS regions are closely correlated with coronary event rates and classical risk parameters (explaining 39-98%) among European populations. CONCLUSION: Our results reinforce the hypothesis that genetic bases of cardiovascular diseases and associated complex phenotypes could be geographically shaped by random demographic processes.

Analysis of Genomic Regions Associated With Coronary Artery Disease Reveals Continent-Specific Single Nucleotide Polymorphisms in North African Populations.

BACKGROUND: In recent years, several genomic regions have been robustly associated with coronary artery disease (CAD) in different genome-wide association studies (GWASs) conducted mainly in people of European descent. These kinds of data are lacking in African populations, even though heart diseases are a major cause of premature death and disability. METHODS: Here, 384 single nucleotide polymorphisms (SNPs) in the top four CAD risk regions (1p13, 1q41, 9p21, and 10q11) were genotyped in 274 case-control samples from Morocco and Tunisia, with the aim of analyzing for the first time if the associations found in European populations were transferable to North Africans. RESULTS: The results indicate that, as in Europe, these four genetic regions are also important for CAD risk in North Africa. However, the individual SNPs associated with CAD in Africa are different from those identified in Europe in most cases (1p13, 1q41, and 9p21). Moreover, the seven risk variants identified in North Africans are efficient in discriminating between cases and controls in North African populations, but not in European populations. CONCLUSIONS: This study indicates a disparity in markers associated to CAD susceptibility between North Africans and Europeans that may be related to population differences in the chromosomal architecture of these risk regions.

X-Chromosome Alu Insertions in Bahía Blanca, Argentina: Assessment of Population Information from Varied Genetic Markers and Usefulness of X-Chromosome Markers to Trace Sex-Biased Parental Contributions.

Bahía Blanca is an urban city in a historically and geographically strategic location for the mixture of different populations in Argentina. In the present study, 10 Alu elements from the X chromosome are analyzed to characterize the genetic composition of the city's population, to compare it with other worldwide populations, and to explore the usefulness of X-chromosome markers for human population genetics purposes. In the Bahía Blanca sample, 7 of 10 Alu insertion frequencies are polymorphic. X-chromosome Alu results in Bahía Blanca are compared with eight different populations from Africa, Europe, and America. Genetic distance analysis indicates that the Bahía Blanca sample is closer to the European and North African samples (average distances of 0.106 and 0.113) than to the Native American (0.163) and sub-Saharan African samples (0.247). Genetic relationships shown by multidimensional scaling illustrate the intermediate position of Bahía Blanca compared with groups in other regions (European, Native American, and African). Admixture results of the Bahía Blanca sample for X-chromosome markers indicate similar proportions of Native American (0.472) and European parental contributions (0.479) and a minor sub-Saharan African contribution (0.049). These results are consistent with the past decade's genetic studies of Argentinean populations that reported higher Native American and sub-Saharan African contributions than previous data.

Potential Signals of Natural Selection in the Top Risk Loci for Coronary Artery Disease: 9p21 and 10q11.

BACKGROUND: Coronary artery disease (CAD) is a complex disease and the leading cause of death in the world. Populations of different ancestry do not always share the same risk markers. Natural selective processes may be the cause of some of the population differences detected for specific risk mutations. OBJECTIVE: In this study, 384 single nucleotide polymorphisms (SNPs) located in four genomic regions associated with CAD (1p13, 1q41, 9p21 and 10q11) are analysed in a set of 19 populations from Europe, Middle East and North Africa and also in Asian and African samples from the 1000 Genomes Project. The aim of this survey is to explore for the first time whether the genetic variability in these genomic regions is better explained by demography or by natural selection. RESULTS: The results indicate significant differences in the structure of genetic variation and in the LD patterns among populations that probably explain the population disparities found in markers of susceptibility to CAD. CONCLUSIONS: The results are consistent with potential signature of positive selection in the 9p21 region and of balancing selection in the 9p21 and 10q11. Specifically, in Europe three CAD risk markers in the 9p21 region (rs9632884, rs1537371 and rs1333042) show consistent signals of positive selection. The results of this study are consistent with a potential selective role of CAD in the configuration of genetic diversity in current human populations.

Genetic diversity of CYP3A4 and CYP3A5 polymorphisms in North African populations from Morocco and Tunisia.

The genes CYP3A4 and CYP3A5 form part of a cluster of cytochrome P450 genes involved in drug metabolism reactions. The allelic variants of these genes CYP3A4*1B, CYP3A4*3, CYP3A4*17 and CYP3A5*3 have been linked both to the reduced catalytic activity of cytochromes and to prostate cancer risk in whites, though scarce data exist for North African populations. The main objective of this study was to describe CYP3A4*3, CYP3A4*17, CYP3A4*1B and CYP3A5*3 allele frequencies and haplotype variation in Moroccan Berbers and the general Tunisian population. The data obtained for the Tunisian participants were consistent with the European allele frequency ranges described, while Moroccan Berbers showed high frequencies of CYP3A4*17 (1.8%), CYP3A4*3 (8.5%) and the CYP3A4*1B/CYP3A5*3 haplotype (18.4%). This haplotype, linked to an increased risk of prostate cancer, was detected at a much higher frequency compared with the present Tunisian population (8.4%) or with reported frequencies for populations such as whites (0.6%) or African Americans (5.3%).

Human diversity in Jordan: polymorphic Alu insertions in general Jordanian and Bedouin groups.

Jordan, located in the Levant region, is an area crucial for the investigation of human migration between Africa and Eurasia. However, the genetic history of Jordanians has yet to be clarified, including the origin of the Bedouins today resident in Jordan. Here, we provide new genetic data on autosomal independent markers in two Jordanian population samples (Bedouins and the general population) to begin to examine the genetic diversity inside this country and to provide new information about the genetic position of these populations in the context of the Mediterranean and Middle East area. The markers analyzed were 18 Alu polymorphic insertions characterized by their identity by descent, known ancestral state (lack of insertion), and apparent selective neutrality. The results indicate significant genetic diffferences between Bedouins and general Jordanians (p = 0.038). Whereas Bedouins show a close genetic proximity to North Africans, general Jordanians appear genetically more similar to other Middle East populations. In general, these data are consistent with the hypothesis that Bedouins had an important role in the peopling of Jordan and constitute the original substrate of the current population. However, migration into Jordan in recent years likely has contributed to the diversity among current Jordanian population groups.

Genetic risk score of NOS gene variants associated with myocardial infarction correlates with coronary incidence across Europe.

Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65-85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition.

Results from screening immigrants of low-income countries: data from a public primary health care.

BACKGROUND: A total of 3,132 immigrants from low- and middle-income countries were involved in a cross-sectional observational study to screen for infectious diseases among immigrants attending public primary health care (PHC) centers. The study was conducted to clarify the degree of demographic differences and risk predictors of these diseases. METHODS: Demographic and clinical variables, screening for infectious diseases [hepatitis B and C, human immunodeficiency virus infection, syphilis, and tuberculosis (TB)], and analytical data (anemia, hematuria, and liver function) were recorded from immigrants attending a public PHC unit in Barcelona. RESULTS: Global hepatitis B, including chronic and previous, reached 18.1%; Morocco as the country of origin [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.07-4.14] and gastrointestinal symptoms (OR 1.9, CI 1.18-3.02) were risk factors. Hepatitis C prevalence was 3.3% with elevated hepatic transaminase levels as a risk factor (OR 26.1, CI 8.68-78.37). Positive syphilis was 3.1%; latent and active TB rates were 28.1 and 5.8%, respectively. Concerning TB, we found remarkable differences both among WHO regions of origin (the Eastern Mediterranean region showed the highest rate of active TB, 8%) and the three categories of years of residence in Spain (6.5% for <1 year, 12.8% for 1-5 years, and 10% for >5 years). CONCLUSIONS: The data allowed recommendation of a minimal screening of TB in immigrants from low-income countries regardless of the years of residence in Spain, hepatitis C in patients with altered transaminase levels, and hepatitis B in patients with gastrointestinal symptoms and/or from Morocco.

Ethnic composition and genetic differentiation of the Libyan population: insights on Alu polymorphisms.

BACKGROUND: It is thought that the ancient population of Libya was mainly composed of Saharan Berbers. Socio-geographic conditions and historical events have exerted some changes on the composition of the present-day Libyan population. AIM: To screen a set of autosomal Alu markers in a representative sample of the general Libyan population in order to study its ethnic and genetic structure and to re-examine its genetic relationships with Mediterranean and Middle Eastern groups. SUBJECTS AND METHODS: A sample of 190 Libyans was analysed for 17 Alu insertions. The sample was divided according to the Arabic or Berber origin of individuals' surnames. RESULTS: The current general Libyan population is homogeneous and shows considerable genetic diversity compared with other North Mediterranean and North African populations. It shows intermediate genetic distances between Moroccans, Algerians and Tunisians on one side and Egyptian Siwa Berbers on the other. No particular affinities with Middle Eastern groups were detected. CONCLUSION: Alu insertions are useful markers to contribute to the reconstruction of human population history at a microgeographic scale, in particular when the analyses include anthropologically well sampled populations. The present results provide new information to improve understanding some aspects of the complex peopling of North Africa.

Close genetic relationships in vast territories: autosomal and X chromosome Alu diversity in Yakuts from Siberia.

Twelve autosomal and 8 X chromosome Alu markers were genotyped for the first time in 161 Central and West Yakuts to test their ability to reconstruct the genetic history of these populations, the northernmost Turkic-speaker ethnic group living in Siberia. Autosomal data revealed that both groups showed extremely close genetic distances to other populations of Siberian origins that occupied areas from Lake Baikal, the ancestral place of origin of Yakuts, to North Siberia, their current territories. Autosomal and X chromosome data revealed some discrepancies on the genetic differentiation and the effective sizes of Central and West Yakuts. Such discrepancies could be related to the patrilineal and occasionally polygamous structure of these populations. Autosomal and X Alu markers are informative markers to reconstruct population past demography and history, but their utility is limited by the available data. This study represents a contribution for further investigations on these populations.

Genetic position of Bahrain natives among wider Middle East populations according to Alu insertion polymorphisms.

BACKGROUND: The genetic differentiation of Bahrain natives is unclear because of the absence of adequate genetic studies. AIM: Eight Alu insertion polymorphisms have been analysed in Bahrainis and southern Iranians to examine the origins of Bahrainis and to determine their genetic position among wider Middle East populations. SUBJECTS AND METHODS: Two representative samples of 97 Bahrainis and 65 southern Iranians have been determined. Genetic relationships among populations have been estimated by a principal component plot based on the R-matrix software. Mantel tests have been used to check the statistical significance of correlation between genetic and geographic distances. RESULTS: The results show that Bahrainis are in an intermediate genetic position between Emirians and Southern Iranians. Although a general significant correlation between genetic and geographic distances was found between the 16 populations included in the analysis, a lack of this correlation may occur in some particular situations such as the case of populations from southern Iran, United Arab Emirates (UAE) and Bahrain, separated by the Persian Gulf. CONCLUSION: The results support the idea that Bahrainis ancestors were mainly emigrants from Arabia and Iran. In addition the results show that the Iranian component may reach 69.2% of the current genetic pool of Bahrainis.

Apolipoprotein E/C1/C4/C2 gene cluster diversity in two native Andean populations: Aymaras and Quechuas.

The APOE/C1/C4/C2 gene cluster presents high relevance in lipid metabolism and, therefore, has important epidemiological implications. Here, we study for the first time the variation patterns of 25 polymorphisms (10 short tandem repeats, STRs, and 15 single nucleotide polymorphismas, SNPs) in two native Andean samples from Bolivia (45 Aymaras and 45 Quechuas) as well as one European sample (n = 41) as external reference. We estimated diversity parameters, linkage disequilibrium patterns, population structure, and possible selective effects. In general, diversity was low and could be partly attributed to selection (probably due to its physiological importance), since the APOE/C1/C4/C2 region was highly conserved compared to the flanking genes in both Bolivians and Europeans. Moreover, the lower gene diversity in Bolivians compared to Europeans for some markers might indicate different demographic histories. Regarding the APOE isoforms, in addition to ɛ3 (94%) and ɛ4 (5%), isoform ɛ2 (1%) was also detected in Bolivians. In relation to previous hypotheses, our results support that genetic drift or founder effects rather than selection for increased cholesterol absorption are the main factors that have shaped the distribution of APOE isoforms observed in South America.

Genetic differentiation and origin of the Jordanian population: an analysis of Alu insertion polymorphisms.

AIM: Although much of Jordan is covered by desert, its north-western region forms part of the Fertile Crescent region that had given a rich past to Jordanians. This past, scarcely described by historians, is not yet clarified by sufficient genetic data. Thus in this paper we aim to determine the genetic differentiation of the Jordanian population and to discuss its origin. METHODS: A total of 150 unrelated healthy Jordanians were investigated for ten Alu insertion polymorphisms. Genetic relationships among populations were estimated by a principal component (PC) plot based on the analyses of the R-matrix software. RESULTS: Statistical analysis showed that the Jordanian population is not significantly different from the United Arab Emirates population or the North Africans. This observation, well represented in PC plot, suggests a common origin of these populations belonging respectively to ancient Mesopotamia, Arabia, and North Africa. CONCLUSION: Our results are compatible with ancient peoples' movements from Arabia to ancient Mesopotamia and North Africa as proposed by historians and supported by previous genetic results. The original genetic profile of the Jordanian population, very likely Arabian Semitic, has not been subject to significant change despite the succession of several civilizations.

Research of the origin of a particular Tunisian group using a physical marker and Alu insertion polymorphisms.

The aim of this study was to show how, in some particular circumstances, a physical marker can be used along with molecular markers in the research of an ancient people movement. A set of five Alu insertions was analysed in 42 subjects from a particular Tunisian group (El Hamma) that has, unlike most of the Tunisian population, a very dark skin, similar to that of sub-Saharans, and in 114 Tunisian subjects (Gabes sample) from the same governorate, but outside the group. Our results showed that the El Hamma group is genetically midway between sub-Saharan populations and North Africans, whereas the Gabes sample is clustered among North Africans. In addition, The A25 Alu insertion, considered characteristic to sub-Saharan Africans, was present in the El Hamma group at a relatively high frequency. This frequency was similar to that found in sub-Saharans from Nigeria, but significantly different from those found in the Gabes sample and in other North African populations. Our molecular results, consistent with the skin color status, suggest a sub-Saharan origin of this particular Tunisian group.

Genetic differences among North African Berber and Arab-speaking populations revealed by Y-STR diversity.

Y-chromosome STR polymorphisms are inherited in a haploid state which makes them a powerful tool for easy tracing of paternal lineage and for use in human population evolutionary studies. North-African Y chromosomal diversity has traditionally been studied in order to find genetic and geographic associations as well as to test how natural and cultural barriers have affected the degree of genetic flow not only within North Africa but also in a wider Mediterranean context. The degree of Berber/Arab genetic differentiation in the Moroccan population has been tested for a complete set of forensic markers as sixteen Y-chromosomal short tandem repeats (STRs) (DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and GATA H4.1). The results suggest considerable population heterogeneity in North Africa.

Research of the origin of a particular Tunisian group using a physical marker and Alu insertion polymorphisms

The aim of this study was to show how, in some particular circumstances, a physical marker can be used along with molecular markers in the research of an ancient people movement. A set of five Alu insertions was analysed in 42 subjects from a particular Tunisian group (El Hamma) that has, unlike most of the Tunisian population, a very dark skin, similar to that of sub-Saharans, and in 114 Tunisian subjects (Gabes sample) from the same governorate, but outside the group. Our results showed that the El Hamma group is genetically midway between sub-Saharan populations and North Africans, whereas the Gabes sample is clustered among North Africans. In addition, The A25 Alu insertion, considered characteristic to sub-Saharan Africans, was present in the El Hamma group at a relatively high frequency. This frequency was similar to that found in sub-Saharans from Nigeria, but significantly different from those found in the Gabes sample and in other North African populations. Our molecular results, consistent with the skin color status, suggest a sub-Saharan origin of this particular Tunisian group.

Mixed origin of the current Tunisian population from the analysis of Alu and Alu/STR compound systems.

During successive historical periods, Tunisia has been a crossroads of multiple civilizations and their corresponding key population movements. The aim of this study was to provide genetic information relating to the mixed origin of the Tunisian population, and to analyze its genetic relationship with other North African and Mediterranean populations. A set of 16 Alu and 3 Alu/STR compound systems has been analyzed in 268 autochthonous Tunisians from the north-center and the south of the country. Our two sampled populations showed no significant differentiation from one another in any of the three Alu/STR compound systems, whereas the analysis of the 16 Alu markers revealed a significant genetic differentiation between them. A sub-Saharan component shown by the three Alu/STR combinations is more noticeable in our north-center sample than in that of the south. The presence of two Alu/STR combinations specific to North African ancestral populations also suggests that the ancient Berber component is relatively more substantial in the north and center regions than in the south. Our Tunisian samples cluster together with other Berber samples from Morocco and Algeria, underpinning the genetic similarity among North Africans regardless of their current linguistic status (Berber or Arabic).