1) To perform the first comprehensive systematic review of genetic association studies (GASs) in idiopathic recurrent spontaneous abortion (IRSA); 2) to analyze studies according to recurrent ...spontaneous abortion (RSA) definition and selection criteria for patients and control subjects; and 3) to perform meta-analyses for the association of candidate genes with IRSA.
Systematic review and meta-analysis.
Not applicable.
Couples with IRSA and their spontaneously aborted embryos.
Summary odds ratios (ORs) were calculated by means of fixed- or random-effects models.
Association of genetic variants with IRSA.
The systematic review included 428 case-control studies (1990–2015), which differed substantially regarding RSA definition, clinical evaluation of patients, and selection of control subjects. In women, 472 variants in 187 genes were investigated. Meta-analyses were performed for 36 variants in 16 genes. Association with IRSA defined as three or more spontaneous abortions (SAs) was detected for 21 variants in genes involved in immune response (IFNG, IL10, KIR2DS2, KIR2DS3, KIR2DS4, MBL, TNF), coagulation (F2, F5, PAI-1, PROZ), metabolism (GSTT1, MTHFR), and angiogenesis (NOS3, VEGFA). However, ORs were modest (0.51–2.37), with moderate or weak epidemiologic credibility. Minor differences in summary ORs were detected between IRSA defined as two or more and as three or more SAs. Male partners were included in 12.1% of studies, and one study included spontaneously aborted embryos.
Candidate gene studies show moderate associations with IRSA. Owing to large differences in RSA definition and selection criteria for participants, consensus is needed. Future GASs should include both partners and spontaneously aborted embryos. Genome-wide association studies and large-scale replications of identified associations are recommended.
In this research we aimed to (1) develop and validate a new questionnaire examining attitudes and knowledge towards medical genetics, (2) examine the knowledge and attitudes towards medical genetics ...in students of the Medical Faculty in Rijeka, Croatia and (3) evaluate the impact of education from the mandatory course Medical Genetics on the change of knowledge and attitudes. The study was conducted on 191 fifth- and sixth-year students of the Integrated Undergraduate and Graduate University Study of Medicine in the academic year 2019/2020. Students completed the validated online questionnaire anonymously and voluntarily. Fifth-year students completed the questionnaire twice (beginning/end of the course), while sixth-year students completed the questionnaire once, 3 months after completing the course. The education was carefully designed for medical students according to the CoreCompetences in Genetics for Health Professionals in Europe issued by the European Society of Human Genetics. Using the Kruskal-Wallis test, a statistically significant difference was found between fifth year before and after education and between the fifth year before education and sixth year for (a) total knowledge (P < 0.001), (b) total attitudes (P < 0.001) and (c) personal assessment of knowledge in medical genetics (P < 0.001). Moreover, positive attitudes were associated with higher levels of knowledge. In conclusion, our results emphasise the importance of needs-based education in medical genetics for medical students, which is indispensable for the increase in the level of knowledge and development of positive attitudes in order to provide better health care for patients with genetic disorders.
Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) gene polymorphisms have been extensively evaluated as predisposing factors to human reproductive disorders. However, ...the evidence available is inconsistent. Therefore, we performed a systematic review and meta-analysis to provide the first comprehensive synopsis of case-control studies that investigated the association of MMP and TIMP gene polymorphisms with disorders that influence fertility and pregnancy complications. Literature search was performed using PubMed and Scopus databases. We included 42 case-control studies in the systematic review for the following disorders: adenomyosis, endometriosis, hypertensive disorders of pregnancy, preterm birth and recurrent spontaneous abortion. Although a large number of MMP and TIMP gene polymorphisms were tested, no exclusive and unambiguous risk factors were identified for any of the disorders. The majority of statistically significant associations were confirmed in just one study. Additionally, we performed two meta-analyses for MMP9 rs3918242 polymorphism in endometriosis/adenomyosis and preeclampsia but found no association with either disorder. Considering the modest associations and conflicting results between individual case-control studies, new data is needed for further research of this subject.
•A large number of MMP and TIMP SNPs were tested as predisposing factors to fertility disorders.•The aim of the study was to conduct a systematic review and meta-analysis of MMP and TIMP SNPs.•No unambiguous risk factors were identified for any of the disorders.
Summary
To examine the knowledge, behavior, and attitudes toward medical genetics among obstetrics and gynecology, pediatrics, and neurology residents and specialists, who encounter the highest ...number of patients with specific genetic disorders, in their everyday practice. The cross-sectional study involved 182 nongenetic residents and specialists in the Republic of Croatia, who completed a validated online questionnaire anonymously and voluntarily. The questionnaire consisted of five groups of questions: general information, knowledge, behavior in practice, attitude toward genetic testing, and additional education in medical genetics. The median score for overall knowledge of medical genetics was 70.2% among obstetrician-gynecologists, 80.5% among pediatricians, and 76.7% among neurologists (
P
< 0.001, lowest median in obstetrician-gynecologists). When asked about their behavior in daily practice, around 90% of respondents admitted the possibility of not recognizing patients with genetic disorders, which is why more than 90% emphasized the need for additional education in medical genetics. In addition, the respondents showed a positive attitude toward genetic testing, but they did not feel educated enough to interpret the results of genetic testing. The results highlight the need for further genetic education of non-genetic health professionals, which would lead to greater confidence and ability to recognize patients with genetic disorders, select the appropriate genetic testing method and achieve more efficient communication with patients.
Abstract In the last three decades it has become quite common to evaluate local muscle fatigue by means of surface electromyographic (sEMG) signal processing. A large number of studies have been ...performed yielding signal-based quantitative criteria of fatigue in primarily static but also in dynamic tasks. The non-invasive nature of this approach has been particularly appealing in areas like ergonomics and occupational biomechanics, to name just the most prominent ones. However, a correct appreciation of the findings concerned can only be obtained by judging both the scientific value and practical utility of methods while appreciating the corresponding advantages and limitations. The aim of this paper is to serve as a state of the art summary of this issue. The paper gives an overview of classical and modern signal processing methods and techniques from the standpoint of applicability to sEMG signals in fatigue-inducing situations relevant to the broad field of biomechanics. Time domain, frequency domain, time–frequency and time-scale representations, and other methods such as fractal analysis and recurrence quantification analysis are described succinctly and are illustrated with their biomechanical applications, research or clinical alike. Examples from the authors’ own work are incorporated where appropriate. The future of this methodology is projected by estimating those methods that have the greatest chance to be routinely used as reliable muscle fatigue measures.
Recurrent pregnancy loss (RPL) is a reproductive disorder defined as the loss of two or more pregnancies before 24 weeks of gestation. Despite the fact that several mechanisms have been previously ...described for the pathogenesis of RPL, the causes of ∼50% of cases remain unknown. However, recent studies indicate association of vitamin D deficiency with adverse pregnancy outcome, including RPL. The vitamin D receptor (VDR) is a crucial mediator of the pleiotropic cellular effects of vitamin D. Its function is influenced by several single nucleotide polymorphisms (SNPs). The main objective of this study is to assess whether maternal VDR SNPs are associated with the risk of RPL in Slovenian and Croatian women.
A case-control study including 320 women with RPL and control women is designed to examine the potential association of VDR polymorphisms (FokI rs222857, Cdx2 rs11568820, and Taq1 rs731236) with RPL. Genotyping is performed using polymerase chain reaction and restriction fragment length polymorphism methods.
We find a statistically significant higher frequency of the rs222857 CC genotype (χ
2
= 6.61, p = .036) and C allele (χ
2
= 5.93, p = .015) in RPL women compared to controls. Subsequently, the odds for RPL for the rs222857 are increased under the recessive (CCvsCT + TT: OR = 1.78; 95% CI = 1.12-2.82; p = .015) and the codominant (CCvsTT: OR = 2.21; 95% CI = 1.08-4.53; p = .029; CCvsCT: OR = 1.68; 95% CI = 1.04-2.72; p = .036) genetic models. The other two analyzed polymorphisms did not show any statistical significant result.
Our results suggest that variations in the maternal VDR FokI gene might be associated with RPL in Slovenian and Croatian women.
Parkinson's disease is a neurological disorder that affects motor function, autonomic functions, and cognitive abilities. It is likely that both genetic and environmental factors, along with age, ...contribute to the cause. However, there is no comprehensive guideline for genetic testing for Parkinson's disease, and more research is needed to understand genetic variations in different populations. There has been no research on the genetic background of Parkinson's disease in Croatia so far. Therefore, with the GiOPARK project, we aimed to investigate the genetic variants responsible for Parkinson's disease in 153 Croatian patients with early onset, familial onset, and sporadic late-onset using whole-exome sequencing, along with multiplex ligation-dependent probe amplification and Sanger sequencing in select patients. We found causative variants in 7.84% of the patients, with GBA being the most common gene (4.58%), followed by PRKN (1.96%), ITM2B (0.65%), and MAPT (0.65%). Moreover, variants of uncertain significance were identified in 26.14% of the patients. The causative variants were found in all three subgroups, indicating that genetic factors play a role in all the analyzed Parkinson's disease subtypes. This study emphasizes the need for more inclusive research and improved guidelines to better understand the genetic basis of Parkinson's disease and facilitate more effective clinical management.
Problem
Aberrant DNA methylation has been suggested as a potential cause of recurrent spontaneous abortion (RSA). Considering the growing evidence on the important roles of DNA methylation in ...gametogenesis and early pregnancy, we investigated the potential association of DNA methyltransferase gene polymorphisms (DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686) with RSA in Slovenian reproductive couples.
Method of study
A total of 146 couples with ≥3 consecutive spontaneous abortions and 149 control women and men with ≥2 normal pregnancies were included. Genotyping was performed using PCR‐RFLP methods.
Results
We found a statistically significant higher frequency of the DNMT3B rs1569686 GG genotype (X2=7.37;P = .025) and G allele (X2 = 6.33;P = .012) in RSA women compared with controls. Moreover, the odds for RSA in women were increased under the recessive genetic model (GGvsTG+TT: OR=1.92; 95% CI=1.18‐3.09; P = .008).
Conclusion
DNMT3B rs1569686 gene polymorphism in women might be a genetic marker for the susceptibility to RSA.
In this study we aimed to perform the first research on the current state of compulsory basic and clinical courses in genetics for medical students offered at medical faculties in six Balkan ...countries with Slavic languages (Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, Serbia, and Slovenia).
The study was conducted from June to September 2021. One representative from each country was invited to collect and interpret the data for all medical faculties in their respective country. All representatives filled a questionnaire, which consisted of two sets of questions. The first set of questions was factual and contained specific questions about medical faculties and design of compulsory courses, whereas the second set of questions was more subjective and inquired the opinion of the representatives about mandatory education in clinical medical genetics in their countries and internationally. In addition, full course syllabi were analysed for course aims, learning outcomes, course content, methods for student evaluation and literature.
Detailed analysis was performed for a total of 22 medical faculties in Bosnia and Herzegovina (6), Croatia (4), Montenegro (1), North Macedonia (3), Serbia (6), and Slovenia (2). All but the two medical faculties in Slovenia offer either compulsory courses in basic education in human genetics (16 faculties/courses) or clinical education in medical genetics (3 faculties/courses). On the other hand, only the medical faculty in Montenegro offers both types of education, including one course in basic education in human genetics and one in clinical education in medical genetics. Most of the basic courses in human genetics have similar aims, learning outcomes and content. Conversely, clinical courses in medical genetics are similar concerning study year position, number of contact hours, ECTS (European Credit Transfer and Accumulation System) and contents, but vary considerably regarding aims, learning outcomes, ratio of types of classes, teaching methods and student evaluation.
Our results emphasise the need for future collaboration in reaching a consensus on medical genetics education in Balkan countries with Slavic languages. Further research warrants the analysis of performance of basic courses, as well as introducing clinical courses in medical genetics to higher years of study across Balkan countries.
PDF
